ASA Refresher 2012

2012 Refresher Course Lectures
Washington District of Columbia
October 13-17, 2012
© American Society of Anesthesiologists. All rights reserved.

Note: This publication contains material copyrighted by others. Individual
refresher course lectures are reprinted by ASA with permission. Reprinting
or using individual refresher course lectures contained herein is strictly
prohibited without permission from the authors/copyright holders.
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Current Controversies in Adult Outpatient Anesthesia
Jeffrey L. Apfelbaum, M.D. Chicago, Illinois
Introduction
The fast paced world of ambulatory anesthesiology continues to present anesthesiologists with an ever-
changing array of challenges. This Refresher Course will provide an update on current controversial issues in adult
outpatient anesthesia, including fast tracking; preoperative assessment, evaluation, and preparation; recent changes
to ASA Basic Anesthesia Monitoring Standards; ramifications of recent changes to Interpretative Guidelines issued
by the Center for Medicare and Medicaid Services (CMS) on our practice; and computer assisted personalized
sedation. Additionally we will consider a variety of “breaking news” areas of controversy which may include topics
such as patients with obesity/modified metabolic syndrome; advances in and recommendations to enhance
perioperative communication; treatment decisions for patients with coronary artery stents; opportunities to
incorporate one’s personal outcomes data into your patient care plan; choice of anesthetic on cancer recurrence
rates; and the effects of drug shortages on ambulatory surgical care.
Fast Tracking: Eliminating Intensive Post-Operative Care in Same Day Surgery Patients Using
Short Acting Fast Emergence Anesthetics
Many anesthetics have the pharmacokinetic and pharmacodynamic advantages of a shorter duration of
action and a more rapid rate of recovery which permit a faster emergence from anesthesia compared with their
predecessors. Showing the value of these agents is required to increase their acceptance and foster further
development. Less than 30 years ago, it was unthinkable that patients would be able to return home on the day of
surgery. Today, advances in surgery and anesthesiology make it possible to perform the vast majority of all surgical
procedures, safely and effectively on an ambulatory basis, with many patients ready to be reunited with their
families within minutes of emergence from anesthesia. In today’s cost sensitive healthcare environment, the
processes of ambulatory surgical care must be continually re-evaluated to take advantage of advances in medicine
and to optimize the efficiency of the surgical center without detriment to patient safety and satisfaction.
Traditionally, ambulatory surgical patients go from the operating room to the postanesthesia care unit or recovery
unit ( a highly specialized intensive care unit) for their immediate postoperative recovery from anesthesia and then
to a second stage recovery unit (SSRU) for preparation for home readiness. By its very nature as a specialized ICU,
the PACU is an expensive, labor-intensive environment. After a set of recovery criteria 1, 2, 3 are met in the PACU,
the patient is usually transferred to the SSRU. In the SSRU, the patient-to-nurse ratio is considerably higher (i.e.,
nursing care in the SSRU is less labor intensive) than in the PACU. Only basic monitoring and observation are
performed as the patient and his or her escort are prepared for home readiness. Because of the rapid recovery of
patients undergoing anesthesia with the shorter acting, faster emergence anesthetics, some have questioned if all
ambulatory surgical patients need to receive intensive postoperative care in the PACU setting or whether “first
stage” recovery from anesthesia can be achieved safely while still in the operating room (at least for some patients),
thereby resulting in enormous potential savings.
The “SAFE” study evaluates the impact of selective patient bypass of the PACU on both the outcomes of
ambulatory surgical patients and the use of resources in the surgical arena.4 This study was designed to evaluate the
rapid recovery of patients undergoing ambulatory surgery using short-acting, fast emergence anesthetic agents and
to determine if policies and procedures could be developed that would allow patients to safely bypass first stage
post-anesthesia care units (PACU) and whether such changes in the recovery paradigm would result in financial
savings for the surgical center. Five community based facilities (hospitals or surgery centers) participated in this
prospective observational study. While in the operating room at the end of the surgical procedure, anesthesiologists
were asked to assess all ambulatory surgical patients for recovery using standardizing discharge criteria typically
Refresher Course Lectures Anesthesiology 2012 © American Society of Anesthesiologists. All rights reserved.
Note: This publication contains material copyrighted by others. Individual refresher course lectures are reprinted by ASA with permission.
Reprinting or using individual refresher course lectures contained herein is strictly prohibited without permission from the authors/copyright
holders.
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used at the end of a PACU stay (Table 1). If the patient met the discharge criteria, they were transferred from the
OR directly to the less labor intensive second stage recovery unit (SSRU). Financial data were provided from all
five sites detailing all costs associated with the recovery process. Clinical data on every elective ASA 1, 2 and 3
ambulatory surgical patient were collected over a three month period. During month one, data collected established
a baseline of case mix, time stamps, adverse events, bypass rates, and financial profile. During month two, an
educational intervention was provided on a multi-disciplinary basis to all units in the surgical center discussing the
implications of the bypass paradigm. After implementation of the paradigm (month three) weekly feedback reports
were provided to the site featuring the key outcomes of the study, and these reports were distributed to the health
care providers. Nearly 5,000 patients were entered into the study. The overall bypass rate increased from 15.9% in
the baseline month to 58.9% in the month following the educational intervention (p < 0.0001). The change in
process in this study went beyond reducing time spent in the PACU to eliminating the time spent in the PACU while
not increasing the time spent in the operating room or SSRU. In fact, the average (SD) time spent in the SSRU was
significantly shorter for patients who bypassed the PACU than for those who did not bypass the PACU. There were
no significant differences in other parameters of patient outcome. Annualized savings ranged from $50,000 to
$160,000 per site.
The Hows And Whys Of Preoperative Evaluation
The continued growth of outpatient surgery has created new roles for the anesthesiologist which seemingly
demands skills in addition to "giving a good anesthetic." The times from induction to emergence are no longer the
only important role for the perioperative physician. Particularly in the freestanding and office environments, it is
often the anesthesiologist who is most involved in the direct medical care of the patient; we are the physicians who
must insure that the patient is appropriately screened, evaluated, and informed prior to the day of surgery. Indeed,
the anesthesiologist/patient relationship which sometimes develops often takes on a primary care quality. Although
sometimes difficult to arrange, the preoperative interview and evaluation by a consultant anesthesiologist
(particularly in high risk patients) can be extraordinarily beneficial. In addition to lessening anxiety about the
surgery and anesthesia, in most cases, the anesthesiologist will be able to identify potential medical problems in
advance, determine their etiology, and if indicated, initiate appropriate corrective measures. In most facilities, the
goal is to resolve preoperative problems well in advance of the day of surgery, thereby minimizing the numbers of
both cancellations and complications.
At the present time, there are several commonly used approaches to screening patients for ambulatory
surgery. These include: (1) facility visit prior to the day of surgery, (2) office visit prior to the day of surgery, (3)
telephone interviews/no visit, (4) review of health survey/no visit, (5) preoperative screening and visit on the
morning of surgery, (6) computer assisted information gathering, and (7) the use of telemedicine technology. Each
system has its own advantages and disadvantages.
Should Patient Age or ASA Physical Status Influence Case Selection?
Although the vast majority of individuals scheduled for outpatient surgery are relatively healthy (ASA
Physical Status 1 and 2), practitioners are constantly being pressured by third party payors to consider "simple
outpatient surgery" for patients with significant baseline co-morbidities. A survey of members of the Society for
Ambulatory Anesthesia (SAMBA) revealed that half the respondents felt that their practice “pushes the envelope of
patient safety by performing outpatient surgery on patients with serious pre-existing conditions,” and that 40% of
respondents felt that their practice “pushes the envelope of patient safety by performing complex or lengthy surgical
procedures on outpatients.” In the past, many individuals had arbitrarily stated that freestanding ambulatory surgical
facilities were severely limited in the type of patients they could anesthetize, particularly with regard to age and
physical status. Clinical experience, however, suggests otherwise. In a retrospective study of over 1,500 cases of
patients anesthetized for ambulatory surgery, Meridy5 was unable to demonstrate an age-related effect on the
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duration of recovery or the incidence of postoperative complications. Additionally, a retrospective review of cases
performed at the Methodist Ambulatory Surgicare Center in Peoria, Illinois between 1981 and 1985 demonstrated an
unanticipated admission rate of 1.1% for patients over the age of 60 compared to an overall unanticipated admission
rate of 0.8%. With regard to the issue of physical status, in a prospective study involving over 13,000 patients at a
freestanding ambulatory surgical center, Natof 6 concluded that ASA 3 patients whose systemic diseases were well
controlled preoperatively were at no higher risk for postoperative complications than ASA 1 or 2 patients.
Furthermore, in 1987, the Federated Ambulatory Surgery Association (FASA) published the results of a survey
involving over 87,000 patients and concluded that there appeared to be little or no cause and effect relationship
between pre-existing disease and the incidence of perioperative complications7 Chung examined predictors of
adverse events in ambulatory surgery in the elderly, as well as factors contributing to prolonged stay after
ambulatory surgery in elderly patients. This data demonstrated that outpatient surgery is safe in this patient
population, with elderly patients sustaining more minor cardiovascular events than their younger counterparts, and
less postoperative nausea and vomiting, pain, and drowsiness.8, 9. It is clear that geriatric and higher risk (physical
status 3 and 4) patients may be considered acceptable candidates for outpatient surgery if their systemic diseases are
well controlled and the patient’s medical condition is optimized preoperatively.
The Inappropriate Patient - Who's OK And Who's Not
There are few data to reliably categorize the inappropriate adult surgical outpatient. As anesthesiologists
have become more experienced with the anesthetic management of the problem surgical outpatient, the list of
"inappropriate" patients has dwindled. We must individualize our decision with regard to each patient; with few
exceptions, the appropriateness of a case for outpatient surgery is determined by a combination of factors including
patient considerations, surgical procedure, anesthetic technique, and anesthesiologist's comfort level.
At the University of Chicago Medical Center, we have distinguished several groups of patients who may
not be appropriate candidates for ambulatory surgery. As one might expect, this list is frequently modified to adapt
to the ever-changing conditions of our social and medicolegal environment.
• Unstable ASA Physical Status 3 and 4: At the present time we are reluctant to proceed with elective ambulatory
surgery in a medically unstable patient. Instead, we use our anesthesia perioperative medicine clinic (APMC) to
screen these patients, and together with the primary care surgeon or interventionalist, establish a plan to proceed
with the surgery or intervention after medical stabilization. Contrary to the original "ground rules" of ambulatory
surgery, studies involving hundreds of thousands of patients seem to suggest that neither increasing age nor the
presence of stable pre-existing disease affect the incidence of postoperative complications in the surgical outpatient.
• Malignant Hyperpyrexia: In our facility, overnight hospitalization and observation is usually indicated for patients
with a history of malignant hyperpyrexia or with identified susceptibility to malignant hyperpyrexia. However,
patients who are well educated, have a good understanding of their disease process, and have ready access to
medical care may be treated as outpatients by some centers.
• Complex Morbid Obesity/Complex Sleep Apnea: Although patients who have a history of sleep apnea or who
are morbidly obese without systemic disease are acceptable candidates for ambulatory surgery, we prefer overnight
hospitalization and postoperative observation for morbidly obese surgical patients with significant pre-existing
cardiac, pulmonary, hepatic or renal compromise or those patients with a history of complex sleep apnea. Practice
guidelines for the perioperative management of patients with obstructive sleep apnea have recently been developed
by the American Society of Anesthesiologists and offer recommendations for preoperative evaluation, preoperative
preparation, intraoperative management, postoperative management, and “site” of surgery (inpatient vs.
outpatient).10
• Acute Substance Abuse: Because of the increased likelihood of acute untoward cardiovascular responses when
one administers an anesthetic to a patient who has recently abused illicit drugs, we preoperatively counsel these
patients and inform them that any sign of recent drug abuse on the day of surgery will result in immediate
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cancellation of their anesthetic. We tell them that no elective surgical procedure "is worth dying for" and encourage
their preoperative participation in a rehabilitation program.
Anesthesiology directed perioperative medicine clinics are used to optimize the medical condition of a
patient in preparation for surgery. These clinics have been shown to enhance patient safety11, improve patient
satisfaction 12,13, minimize preoperative consultation14, and reduce day of surgery case cancellations and case
postponements.15
Changes to the ASA Standards for Basic Anesthesia Monitoring
For the first time in nearly a decade, there has been a significant change to the ASA Standards for Basic
Anesthesia Monitoring.16 The standard for monitoring of ventilation has undergone significant revision:
V ENTILA TION: 3.2.4: During regional anesthesia (with no sedation) or local anesthesia (with no sedation), the
adequacy of ventilation shall be evaluated by continual observation of qualitative clinical signs. During moderate or
deep sedation the adequacy of ventilation shall be evaluated by continual observation of qualitative clinical signs
and monitoring for the presence of exhaled carbon dioxide unless precluded or invalidated by the nature of the
patient, procedure, or equipment. Many physicians have asked if these standards apply to cases where sedation is
administered in “out of operating room” locations. The Centers for Medicare and Medicaid (CMS) Revised Hospital
Anesthesia Services Interpretative Guidelines seemingly provide guidance on this issue. The first section in these
Interpretative Guidelines is entitled “Types of Anesthesia Services” and the first “bullet” in this section begins as
follows: A nesthesia services, which include both anesthesia and analgesia, are provided along a continuum, ranging
from the application of local anesthetics for minor procedures to general anesthesia for patients who require loss of
consciousness as well as control of vital body functions in order to tolerate invasive operative procedures. This
continuum also includes minimal sedation, moderate sedation/analgesia (“conscious sedation”), monitored
anesthesia care (MA C), and regional anesthesia.
CMS Issues Revised Hospital Anesthesia Services Interpretive Guidelines
CMS has recently issued significant revisions to the Anesthesia Services Interpretive Guidelines.16 These
included significant revisions to the CMS compliance requirements for both pre and post anesthesia evaluations, as
well as a requirement that heretofore, ALL anesthesia and sedation services (including mild, moderate, and deep
sedation) , regardless of providers MUST be organized into a single anesthesia service under the direction of a
qualified doctor of medicine or doctor of osteopathy. Specific portions of these Interpretive Guidelines will be
addressed during the presentation.
Computer- Assisted Personalized Sedation (CAPS)
Ethicon Endo-Surgery, Inc. has recently developed a computer-assisted personalized sedation system (trade
name SEDASYS®) According to the manufacturer, “the SEDASYS® System is the first computer-assisted
personalized sedation (CAPS) system designed for physician/nurse teams to provide minimal-to-moderate sedation
levels with propofol. By integrating drug delivery and patient monitoring, the SEDASYS® System enables
physician/nurse teams to deliver personalized sedation. It automatically detects and responds to signs of over-
sedation (oxygen desaturation and low respiratory rate/apnea) by stopping or reducing delivery of propofol,
increasing oxygen delivery and automatically instructing patients to take a deep breath. The device is currently an
investigational device limited by U.S. law to investigational use only.”17
On May 28, 2009, the Anesthesia and Respiratory Therapy Devices Advisory Committee of the US Food and
Drug Administration (FDA) concluded its deliberations and recommended to the FDA that the SEDASYS® device
be approvable for the administration of propofol by physician/nurse teams for the initiation and maintenance of
minimal to moderate sedation during screening and diagnostic procedures in patients undergoing colonoscopy and
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esophagoduodenoscopy procedures with the following conditions:

1) The device may only be used in adult patients (ASA I, II, and III) 70 years old or younger;
2) The device may only be used in the presence of a 3 person clinical team where one person shall have the sole
responsibility of monitoring the patient, the device and managing the patient's airway. This dedicated person must
have advanced training and at least the skills of a nurse;
3) Physicians utilizing the device must complete training in advanced airway management, pharmacology of
propofol and opioids, patient selection, monitor training (such as SpO2 monitoring), device set-up and maintenance
with the training provided by a clinician with credentials to provide deep sedation to general anesthesia. In addition,
there needs to be a program established for ongoing maintenance of training;
4) The manufacturer must complete all post-marketing studies as proposed at the time of the Advisory Panel
hearing.
5) The product launch is “controlled.”
On several occasions, representatives of the company have suggested that the device is compliant with
ASA guidelines on sedation/analgesia by non-anesthesiologists; as a result of this claim both medical professionals
and lay people have occasionally erroneously concluded that the device is consistent with ASA standards,
guidelines, statements and/or policies.18 Indeed, some individuals have mistakenly concluded that ASA has
“endorsed” the product. However, this conclusion is erroneous. In the AANA-ASA Joint Statement Regarding
Propofol Administration (April 14, 2004) the ASA position regarding the use of propofol is clearly stated as
follows:19
“W henever propofol is used for sedation/anesthesia, it should be administered only by persons trained in the
administration of general anesthesia, who are not simultaneously involved in these surgical or diagnostic procedures.
This restriction is concordant with specific language in the propofol package insert, and failure to follow these
recommendations could put patients at increased risk of significant injury or death.”
In April, 2010, Johnson & Johnson, the parent company of Ethicon-Endo Surgery, Inc., announced that the
FDA sent the company a “not approvable” letter for the SEDASYS® Computer Assisted Personalized Sedation
System. The company has recently appealed this decision. During the session, we will review many of the specifics
of this device and present an update on its current approval status.
Summary
Today there is a continued trend to expand the indications for ambulatory surgery. Because outpatient
anesthesia is a break from our traditional training, we are constantly being confronted with the need for change in
our clinical practice patterns. We have recognized that the needs of the surgical outpatient may be very different
from the inpatient and are now trying to adapt our practice patterns to meet the psychologic and pharmacologic
requirements of the compacted perioperative management the outpatient receives. This Refresher Course has
focused on some of the controversial problems which we as practicing clinicians must deal with every day in our
practice of ambulatory anesthesia for adult patients.
REFERENCES
1. Chung F: Are discharge criteria changing? J Clin Anesth 1993; 5:64S-68S.
2. Chung F: Recovery pattern and home-readiness after ambulatory surgery. Anesth Analg 1995; 80:896-902.
3. Aldrete JA: J Perianes Nurs 1998; 13(3):148-55.
4. Apfelbaum JL, et al: Anesthesiology 2002; 97:66-74.
5. Meridy HW. Anesth Analg 1982, 61:921-6.
6. Natof HE. Ambulatory surgery: Patients with pre-existing medical problems. Ill Med J 1984; 166(2):101.
7. FASA Special Study 1. Federated Ambulatory Surgery Association. Alexandria, Virginia, 1987.
8. Chung F, Mezeu G, Tong D. BJA 1999, 83(2): 262-70.
9. Chung F, Mezei G. Anesth Analg 1999, 89(6): 1352-9.
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10. Gross JB, et al. Anesthesiology 2006; 104(5):1081-1093.

11. Parsa P, et al. Anesth Analg 2004; 100:S-147.
12. Parker BM, et al. J Clin Anesth 2000; 12:350-6.
13. Harnett, et al. Anesthesiology 2010; 112:66
14. Fischer SP. Anesthesiology 1996; 85:190-206.
15. Ferschl MB, et al. Anesthesiology 103(4):855-859.
16. http://www.asahq.org/For-Members/Clinical-Information/Standards-Guidelines-and-Statements.aspx
17. http://www.medicalnewstoday.com/articles/151976.php
18. Pambianco, et al: GI Endoscopy 2008;68: 542-547
19. http://www.asahq.org/publicationsAndServices/standards/37.pdf
TABLE 1. DISCHARGE CRITERIA
• Awake, alert, oriented, responsive (or return to baseline)

• Minimal pain
• No active bleeding
• Vital signs stable (not likely to require pharmacologic intervention)
• Minimal nausea
• No vomiting
• If nondepolarizing neuromuscular blocking agent used, patient can perform sustained five second head lift
• Oxygen saturation of 94% on room air (three minutes or longer) OR return of oxygen saturation to baseline
or higher in order to be eligible to bypass Phase I recovery (PACU), the patient must meet ALL of the
above criteria, and in the judgment of the anesthesiologist, be capable of transfer to the step-down unit,
with appropriate care and facility for patient management at that location
DISCLOSURE
This speaker has indicated that he or she has no significant financial relationship with the manufacturer of a
commercial product or provider of a commercial service that may be discussed in this presentation.
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The Adult Patient With Morbid Obesity and/or Obstructive Sleep Apnea For Ambulatory Surgery
Girish P. Joshi, MB BS, MD, FFARCSI Dallas, Texas
Introduction
The prevalence of obesity is rapidly increasing worldwide. Morbidly obese have an increased risk of
comorbidities (Table 1) [1,2], and therefore pose considerable challenges to the anesthesiologist (Table 2). One of
the major co-morbidities associated with obesity includes obstructive sleep apnea (OSA), reported in 60-70% of
morbidly obese [3-5]. Because approximately 60-70% of all surgical procedures performed on an outpatient basis, it
is inevitable anesthesiologists will encounter morbidly obese patients with or without OSA in an ambulatory setting.
This update discusses the current literature related to perioperative care of the morbidly obese, with emphasis on
patients with OSA, scheduled for ambulatory surgery.
Table 1: Comorbidities Associated With Obesity

Respiratory: Restrictive pulmonary disease, obstructive sleep apnea, asthma, pulmonary
hypertension
Cardiac: Systemic hypertension, coronary artery disease, dysrhythmias, cardiomyopathy, CHF
Neurologic: Stroke
Renal: Renal dysfunction
Metabolic: Metabolic syndrome, type 2 diabetes mellitus, hypothyroidism
Abdominal: Hiatal hernia, gastroesophageal reflux, fatty liver infiltration
Others: Airway abnormalities, deep vein thrombosis, primary open-angle glaucoma
Table 2: Challenges in the patients with morbid obesity and/or OSA undergoing ambulatory surgery.
Intraoperative Difficult/failed mask ventilation and/or tracheal intubation
Difficulty in ventilation and/or maintaining adequate oxygen saturation
Difficulty in positioning
Exacerbation of cardiac co-morbidities: hypertension, arrhythmias,
myocardial ischemia and infarction, pulmonary hypertension, heart failure
Immediate Delayed extubation
postoperative Obstruction and/or desaturation after extubation
Post-obstructive pulmonary edema
Need for tracheal reintubation
Exacerbation of cardiac comorbidities
Cerebrovascular disorders (e.g., stroke)
Postoperative delirium
Prolonged PACU stay
Delayed discharge home
Unanticipated hospital admission
Post-discharge Readmission after discharge
Hypoxic brain death and death
Selection of Adult Patients Morbidly Obesity and/or OSA For Ambulatory Surgery
The scientific literature regarding the safety of ambulatory surgery in the obese and/or OSA patients is sparse
and of limited quality. Therefore, the suitability of ambulatory surgery in these patients remains controversial. A
recent systematic review revealed that BMI alone might not influence perioperative complications or unplanned
admissions (Society For Ambulatory Anesthesia [SAMBA] Committee on Clinical Practice Guidelines). A recent
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large observational trial of patients undergoing gastric banding (n=26,002) revealed that the 30-day readmission
rates were low (1.2%) and mortality was rare [6]. The authors concluded that this study does not support excluding
patients with certain comorbidities because any reductions in overall readmission rates would be very small on the
absolute risk scale. Therefore, BMI should not be considered the sole patient selection criterion for ambulatory
surgery. Overall, the patient selection for ambulatory surgery should depend upon the severity of comorbidities, the
surgical procedure, and the anesthetic technique.
With respect to suitability of OSA patients for ambulatory surgery, the ASA-OSA practice guidelines propose a
scoring system that may be used to estimate the perioperative risk of complications [5]. However, this scoring
system is not yet validated. Preliminary studies have failed to validate the scoring system. In addition, these
guidelines also recommend that patients undergoing intra-abdominal and upper airway procedures are not suitable
for ambulatory surgery. However, numerous large observational case series have reported that laparoscopic
adjustable gastric banding (LABG) can be safely performed on an outpatient basis [6-8]. Thus, invalidating the
recommendation that intra-abdominal procedures are not suitable for ambulatory surgery. A survey of
anesthesiologists from Germany found that respiratory tract surgery is routinely performed on an ambulatory basis
in patients with moderate or severe OSA suggesting that the current practice does not conform to the ASA-OSA
guidelines [9].
A recent systematic review of published studies assessed the perioperative complications in patients with OSA
undergoing ambulatory surgery [8]. Patients with OSA had greater number of comorbidities including hypertension,
diabetes, and obesity and higher ASA physical status score. Although more frequent oxygen desaturation requiring
oxygen supplementation was documented in patients with OSA, there were no differences between the OSA and
non-OSA patients with respect to anesthesia-related complciations, unanticipated hospital admission, and mortality.
It appears that mild OSA, based on a sleep study, is not a predictor of perioperative complications in patients
undergoing ambulatory surgery. The predictors for surgical morbidity and mortality include age, male gender,
coexisting medical conditions, surgical characteristics (i.e., degree of invasiveness), surgeon’s experience, and
postoperative opioid dose. Thus, preoperative optimization of medical conditions and limiting opioid use is critical
for patient safety.
Overall, patients with inadequately treated co-morbid conditions are not suitable for ambulatory surgery.
However, it appears that postoperative CPAP use may be protective. Also, it is imperative that all surgical patients
are evaluated for presence of OSA, preoperatively. Patients with known diagnosis of moderate-to-severe OSA and
optimized comorbid conditions can be considered for ambulatory surgery, if they are able to use the CPAP device in
the postoperative period. Patients with presumed diagnosis of OSA and optimized comorbid conditions can be
considered for ambulatory surgery, if postoperative pain can be managed predominantly with non-opioid analgesic
techniques. In addition, the ability of the facility to manage these patients should also be taken into consideration.
Preoperative Considerations
Morbidly obese patients (BMI ≥40 kg/m2) suffer from numerous chronic medical conditions (Table 1). The
comorbidities associated with obesity and OSA should be optimized preoperatively. A focused preoperative
evaluation includes assessment of the airway, cardiovascular, respiratory, and endocrine systems. In addition to
assessment of functional status, patients should be questioned to determine symptoms of angina, paroxysmal
nocturnal dyspnea, orthopnea, and arrhythmia (i.e., palpitations). Because OSA is undiagnosed in an estimated 60-
70% of patients, screening for OSA should be part of routine preoperative evaluation. The STOP-BANG screening
tool is a user-friendly questionnaire that could be included in routine preoperative evaluation to identify
unrecognized OSA (Table 3) [10]. Two recent studies have validated the STOP-BANG questionnaire and found that
a higher STOP-BANG score identified patients with high probability of moderate/severe OSA [11,12].
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Table 3: STOP-BANG Scoring System

S = Snoring. Do you snore loudly (louder than talking or loud enough to be heard through closed doors)?
T = Tiredness. Do you often feel tired, fatigued, or sleepy during daytime?
O = Observed Apnea. Has anyone observed you stop breathing during your sleep?
P = Pressure. Do you or are you being treated for high blood pressure?
B = BMI > 35 kg/m2
A = Age > 50 years
N = Neck circumference > 40 cm
G = Male Gender
High risk of OSA: 3 or more questions answered yes
Moderate-to-severe OSA: 6 or more questions answered yes
Preoperative Testing
It is well recognized that preanesthesia tests should be based on clinical indications and the invasiveness of the
surgical procedure. The American college of Cardiology (ACC) and American Heart Association (AHA) proposed
recommendations for perioperative care of morbidly obese patients undergoing surgery [13]. It is recommended that
ECG be obtained in patients with at least one risk factor for CHD and/or poor exercise tolerance. ECG signs of right
ventricular hypertrophy including right-axis deviation and right bundle-branch block would suggest pulmonary
hypertension, while a left bundle-branch block may suggest occult CHD. In addition, chest X-ray should be obtained
on all morbidly obese patients as it may suggest undiagnosed heart failure, cardiac chamber enlargement, or
abnormal pulmonary vascularity suggestive of pulmonary hypertension, which warrants further cardiovascular
investigation. Further testing, such as exercise and/or pharmacological stress echocardiography, may be performed
in presence of ≥3 risk factors of CAD (i.e., history of CHD, history of congestive heart failure, history of cerebro-
vascular disease, preoperative treatment with insulin, and preoperative serum creatinine levels >2 mg/dL). Although
obesity can influence pulmonary function (e.g., reduced expiratory reserve volume, forced expiratory volume
[FEV], and functional residual capacity [FRC]), pulmonary function tests (e.g., spirometry), are of no added benefit
unless COPD is suspected [14]. Patients should be assessed for obesity-induced hypoventilation syndrome.
A sleep study confirms the diagnosis and provides the severity of OSA based upon the apnea-hypopnea index
(AHI). Because an overnight-attended sleep study may not always be available, and is associated with high costs,
unattended portable screening home-based devices have been explored. The Agency for Healthcare Research and
Quality (AHRQ) suggested that multichannel (e.g., recording airflow, respiratory effort, and blood oxygenation)
portable monitoring might be used as an alternative to a sleep study [15]. If OSA is suspected during preoperative
evaluation, one could proceed with a presumptive diagnosis of severe OSA or obtain a sleep study. It is unclear if a
routine sleep study would improve perioperative outcome. Also, the optimal duration of CPAP therapy before
proceeding with elective surgical procedures is unknown.
Patient Information
Patients who use CPAP devices at home should be advised to bring their device for perioperative use. Because
there is a possibility that OSA patients may not always meet criteria for safe home discharge, the option of
admission should be discussed with the patient prior to surgery.
Preoperative Medications
Obese patients may be on multiple medications including prescription and non-prescription (i.e., over-the-
counter or herbal diet drugs) that might have detrimental cardiopulmonary effects as well as adversely interact with
anesthetic drugs. Patients should be asked to continue their preoperative medications until the day of surgery, except
for antidiabetic therapy that might need some modification [16]. Because morbid obesity is one of the major risk
factors for the development of pulmonary embolism, prophylaxis for deep vein thrombosis, low dose heparin in
combination with intermittent pneumatic compression, are recommended [17].
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Preoperative prophylaxis against acid aspiration (e.g., H2-receptor antagonists and proton pump inhibitors) is
commonly used. However, their routine use is questioned, as the risk of regurgitation of gastric contents for the
morbidly obese and the non-obese appears to be similar [18]. Midazolam (1-2 mg, IV) has been used to provide
anxiolysis; however, it is prudent to avoid midazolam, if possible.
Intraoperative Considerations
Although the surgical procedure and the need for postoperative opioids, rather than the choice of anesthetic
technique appear to be more important determinants of perioperative complications in the morbidly obese
particularly those with OSA, local or regional anesthesia should be preferred. Local/regional anesthesia obviates the
need for airway manipulation as well as avoids hypnotic-sedatives, opioids, and muscle relaxants. In addition, these
techniques provide postoperative analgesia and reduce postoperative opioid requirements.
Sedation and Analgesia in the Obese and OSA Patients

Patients with OSA are more sensitive to sedative-hypnotics and opioids, which cause dose-dependent upper
airway collapse, respiration depression, and reduced respiratory responses to hypoxia and hypercapnia. Of note,
during sedation OSA may develop in previously unrecognized patients. Therefore, monitoring should include
continuous capnography as it allows detection of upper airway obstruction much prior to oxygen desaturation.
Because CPAP counteracts sedation-induced airway closure, it should be considered during moderate sedation,
particularly in patients using CPAP preoperatively.
Midazolam and propofol have a similar propensity for upper airway obstruction at similar levels of sedation
[19]. However, respiratory problems disappear more quickly (within 15 min) with propofol. Dexmedetomidine, a
highly selective alpha-2 adrenergic agonist with sedative, amnestic, analgesic, and sympatholytic properties with no
respiratory depression, can be used to provide sedation/analgesia. In addition, it reduces salivary secretions through
sympatholytic and vagomimetic effects. Of note, it is generally assumed that dexmedetomidine is a short-acting
drug; however, it may have prolonged sedative effects. Addition of low-dose ketamine (up to 1 mg/kg) to
dexmedetomidine may potentiate the analgesics effects and reduce the hemodynamic adverse effects with
influencing respiration [20].
General Anesthesia
The optimal general anesthetic technique would allow rapid and clear-headed recovery including early return of
the patient’s protective airway reflexes, which would allow maintenance of a patent airway. In addition, early
recovery should reduce postoperative cardiac complications due to residual anesthetic effects.
Pre-induction Considerations
Alterations in pulmonary function (e.g., reduced FRC and oxygen reserves) in the obese may result in severe
hypoxemia even after short periods of apnea. Positioning of the patient in the head elevated laryngoscopy position
(HELP), which can be achieved by “stacking” with blankets or a specially designed foam pillow, structurally
improves maintenance of the passive pharyngeal airway and may be beneficial for mask ventilation as well as
improve the success of tracheal intubation. Other techniques used to avoid post-induction hypoxemia include
preoxygenation with 100% oxygen until the end-tidal oxygen is at least 90% and use of 10 cm H2O CPAP with the
patient in head-up position [21]. Preinduction techniques followed by 10 cm H2O PEEP during mask ventilation and
after intubation have been shown to reduce post-intubation atelectasis and improve arterial oxygenation [22].
Airway Management
Because BMI alone is not a predictor of difficult intubation [23], ‘awake’ tracheal intubation may not always be
necessary. Nevertheless, OSA has been reported to be a predictor of difficult airway [3-5]. Predictors of difficult
tracheal intubation include high Mallampati score (III or IV), neck circumference ≥40 cm, limited mandibular
protrusion, and severe OSA (AHI ≥40). The availability of videolaryngoscopes has increased the success of tracheal
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intubation. A recent study in morbidly obese reported that the awake videolaryngoscopy after topical anesthesia can
be considered as an alternate to awake fiberoptic tracheal intubation [24]. If ‘awake’ intubation is necessary,
sedatives and opioids must be utilized judiciously as they may cause airway obstruction before the airway is
secured. Of note, oropharyngeal and upper airway topicalization necessary for ‘awake’ tracheal intubation may
impair the upper airway protective reflexes and increase the frequency of apneic episodes, which may lead to post-
extubation airway obstruction if the surgical procedure is short.
Induction of General Anesthesia

Because of concerns of regurgitation and difficult tracheal intubation, rapid sequence induction (RSI) of general
anesthesia is commonly performed in the morbidly obese. However, the need for RSI is increasing questioned [25].
Recent studies, in morbidly obese patients, have shown than the barrier pressure (lower esophageal pressure - gastric
pressure) remains positive throughout induction of anesthesia. This suggests that the risk of gastric regurgitation in
the morbidly obese is similar to that in the non-obese patients. Controlled induction of anesthesia should allow
adequate ventilation prior to intubation attempt and avoid hypoxia between induction and tracheal intubation. Most
anesthesia drugs including intravenous anesthetic drugs and opioids should be dosed according to lean body weight
(not actual body weight), except for neuromuscular blocking drugs, which should be dosed according ideal body
weight [26].
Maintenance of General Anesthesia

There is lack of evidence for superiority of a specific maintenance technique (e.g., inhalation vs. total
intravenous anesthesia). Nevertheless, inhalation anesthesia remains the mainstay of current anesthesia practice
because of the ease of titratibility. In addition, inhaled anesthetics exert some neuromuscular blocking effect, which
may reduce the need for muscle relaxants.
The overall clinical differences between newer inhaled anesthetics (i.e., desflurane and sevoflurane) appear to
be small. However, several studies have reported that in the morbidly obese, desflurane allows earlier emergence
compared with sevoflurane. Compared with sevoflurane, desflurane allows earlier ability to swallow water without
coughing or drooling, suggesting an earlier return of protective airway reflexes [27]. In addition, increasing duration
of anesthesia further delayed the recovery of protective airway reflexes after sevoflurane. In these studies the inhaled
anesthetics were not titrated down towards the end of the surgery. It is possible that titration of sevoflurane
concentrations towards the end of surgery may have allowed similar recovery. A recent study used anesthesia
information management system as well as metaanalysis of 29 randomized controlled trials comparing desflurane
and sevoflurane to determine the time from end of surgery to tracheal extubation [28]. They found that compared
with sevoflurane, desflurane reduced the mean extubation time by 25% as well as reduced the variability of
extubation time by 20-25%.
Because of its amnestic and analgesic properties, nitrous oxide (N2O) reduces anesthetic and analgesic
requirements and facilitates recovery. Nevertheless, the use of N2O is questioned due to concerns of increased
incidence of postoperative nausea and vomiting (PONV) and pressure effects through expansion of closed spaces.
However, a recent systematic review concluded that use of propofol for induction of anesthesia and antiemetic
prophylaxis (current standard of care for ambulatory surgery) [29]. There is no convincing reason to avoid N2O.
Opioids continue to play an important role in anesthesia practice; however, opioid-related sedation, airway
obstruction, and respiratory depression are of concern in this patient population [30]. Therefore, opioids should be
used sparingly. Remifentanil (titrated to hemodynamics) may be preferable in the obese because of its unique
pharmacokinetics and ultra-short duration. It is suggested that recurrent hypoxia, which typically occurs in patients
with OSA, may affect endogenous opioid mechanisms that may alter responsiveness to exogenous opioid
administration [31]. One study found that opioid requirements of patients with preoperative hypoxia (e.g., those with
OSA) were lower than those without preoperative hypoxemia suggesting an increased sensitivity to opioids in this
patient population. Because lower opioid doses may be sufficient to achieve adequate analgesia, opioid therapy in
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OSA patients should be individualized and carefully titrated. Importantly, opioids should be administered according
to lean body weight NOT actual body weight [26].
Because even minor degree of residual neuromuscular blockade (usually not appreciated clinically), particularly
the obese and OSA patients, can increase postoperative morbidity such as inadequate ventilation, hypoxia, and the
need for reintubation, muscle relaxants should be used sparingly. In addition, reversal with neostigmine (in
appropriate doses) should be utilized without hesitation [32, 33].
Mechanical Ventilation
Obesity is associated with changes in pulmonary function (e.g., reduction in lung volumes, increase in peak
inspiratory pressures, and decrease in pulmonary compliance). Lung protective ventilation strategies in the obese
would include the use of pressure-controlled ventilation with low tidal volumes (8-10 ml/kg IBW) and PEEP of 5-10
cmH2O [34]. Recruitment maneuvers are beneficial in obese patients and should be applied, particularly before and
after laparoscopic surgery. Unfortunately the effects of recruitment maneuvers are short lasting and often limited by
hemodynamic instability. It is important to avoid hyperventilation (and hypocapnia), as this may result in metabolic
alkalosis and lead to postoperative hypoventilation. Mild hypercapnia (i.e., ETCO2 of 40 mmHg) can improve tissue
oxygenation through improved tissue perfusion resulting from increased cardiac output and vasodilatation as well as
increased oxygen off-loading from the shift of the oxyhemoglobin dissociation curve to the right.
Pain Prophylaxis
Because opioid-related sedation, airway obstruction, and respiratory depression are of concern in this patient
population, opioids should be used sparingly. Preventive analgesia with non-opioids (e.g., local/regional anesthetic
techniques, acetaminophen, and NSAIDs/COX-2 specific inhibitors) should reduce perioperative opioid
requirements and lower opioid-related side effects as well as improve postoperative pain relief. Recently, there is
increasing interest in using analgesic adjuncts such as corticosteroids (e.g., dexamethasone 4-8 mg), ketamine 25-50
mg, and dexmedetomidine to provide improved pain relief.
Nausea and Vomiting Prophylaxis

Patients undergoing ambulatory surgery are at a higher risk of PONV and should receive prophylactic
multimodal antiemetic therapy (e.g., combinations of 5-HT3-receptor antagonists, droperidol, and dexamethasone).
Although it is recommended that the number of antiemetics be based on the patient’s level of risk as determined by
risk factor assessment, double or triple antiemetic prophylaxis is optimal for this patient population.
Intraoperative Fluid Management

Adequate preoperative hydration (i.e., encourage patients to consume water until 2 h preoperatively) and higher
intraoperative fluid administration (20-40 ml/kg) have been reported to reduce postural hypotension, postoperative
dizziness, drowsiness, nausea, and fatigue. In addition, because the morbidly obese are at a high risk of
rhabdomyolysis [35], administration of higher fluid volumes may reduce the potential for myoglobinuric acute renal
failure associated with rhabdomyolysis.
Emergence From Anesthesia

In contrast to traditional practice, the primary aim at the end of the surgery should be to washout the inhaled
anesthetic rather than increase the CO2 levels. Adequate ventilation (probably with the use of pressure support
ventilation) during recovery from anesthesia and muscle relaxants should allow washout of inhaled anesthetics and
facilitate emergence as well as reduce postoperative pulmonary atelectasis and hypoxemia.
One of the major concerns in obese patients, particularly those with OSA, is the risk of airway obstruction after
tracheal extubation [36]. Thus, prior to tracheal extubation the patient must be fully awake, alert, and follow verbal
commands (i.e., deep extubation is not advisable). Importantly, coughing and reflex movements of the hand towards
the tracheal tube should not be confused as purposeful movements. Extubation should be performed in a semi-
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upright (25-30º head-up) position, when possible. Also, use of a nasal airway, placed before tracheal extubation,
may avoid postextubation airway obstruction. A recent study suggests that a nasal airway is more effective than a
combination of oral and nasal airway [37]. A recent study reported that CPAP instituted immediately after tracheal
extubation is superior in maintaining lung function at 24 h after laparoscopic bariatric surgery than CPAP initiated
later in the recovery room [38].
Postoperative Considerations
Potential postoperative complications include airway obstruction, respiratory failure, need for reintubation, life
threatening hypoxia as well as systemic hypertension, ischemia, and cardiac arrhythmia. Once in the PACU, patients
should be maintained in a semi-upright (25-30º head-up) position, if possible.
Postoperative CPAP/BiPAP
Patients who use CPAP preoperatively should use CPAP postoperatively. Although supplemental oxygen is
beneficial for most patients, it should be administered with caution as it may reduce hypoxic respiratory drive and
increase the incidence and duration of apneic episodes. Because obese patients might have unrecognized OSA,
recurrent hypoxemia may be better treated with CPAP or bi-level positive airway pressure (BiPAP) along with
oxygen rather than oxygen alone.
Because determination of optimal CPAP settings may be difficult in patients who have not previously used the
device, use of automatic self-adjusting or auto-adjusting positive airway pressure (APAP) devices may be preferred
in the postoperative period. The APAP devices change the pressure level based on feedback from various patient
measures such as airflow, pressure fluctuations, or measures of airway resistance. The pressure titration with APAP
devices allows for the changes in upper airway pressures that might occur in the immediate postoperative period due
to varying degrees of residual anesthetic and muscle relaxant effects. Of note, the potential benefits of APAP in the
postoperative period need to be confirmed in future trials. Anesthesiologists involved in the management of OSA
patients should familiarize themselves with CPAP devices.
Post-PACU Discharge Care

Prior to discharge from the PACU the oxygen saturation on room air should return to baseline and the patient
should not become hypoxic or develop airway obstruction when left undisturbed in the recovery area. It has been
suggested that most significant postoperative complications in OSA patients usually occur within 2 hours after
surgery. Therefore, it may be worthwhile to observe these patients in the recovery room for at least 2 h. Of note,
complaints of postoperative shoulder, hip, or buttock pain along with unexplained elevations in serum creatinine and
creatine phosphokinase (>5000 IU/L) levels should raise suspicion of rhabdomyolysis [32].
Discharge home might be considered if the patient can maintain baseline oxygen saturation on room air, and the
propensity to develop airway compromise and respiratory depression no longer exists. The ASA-OSA Practice
Guidelines suggest that OSA patients be monitored for a median of 3 hours longer than their non-OSA counterparts
before discharge from the facility [5]. In addition, the monitoring should continue for a median of 7 hours after the
last episode of airway obstruction or hypoxemia while breathing room air in an unstimulated environment.
Unfortunately, the recommendation for longer postoperative stays are not based upon any scientific evidence, and
may be the major limitation of performing surgical procedures in an ambulatory setting.
Care After Discharge Home

One of the major concerns after ambulatory surgery is nocturnal apnea with catastrophic consequences. The risk
of respiratory complications may last for several days after surgery because postoperative surgical stress response,
anxiety, pain, and opioid use cause sleep deprivation and fragmentation, which may reduce REM sleep and
exacerbate sleep disorders. This period is followed by a rebound REM sleep that makes patients with OSA even
more vulnerable to airway obstruction and life-threatening apnea. Of note, postoperative sleep disturbances appear
to be related to the location and invasiveness of the surgical procedure and opioid usage. Fewer sleep disturbances
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occur after mild-to-moderately invasive surgery, commonly performed on an outpatient basis than inpatient surgical
procedures. It is important that the post-discharge instructions emphasize the potential for aggravation of OSA and
the need to use opioids judiciously.
Summary
Obese patients, particularly those with OSA, are at a high risk of perioperative complications and pose several
challenges to the anesthesiologist including difficult tracheal intubation, intraoperative cardiopulmonary
complications, and life threatening airway obstruction and respiratory depression that might last for several days
after surgery. Because undiagnosed OSA is common and failure to recognize OSA preoperatively is one of the
major causes of perioperative complications, a focused history and physical examination can help identify patients
with OSA. It is unclear if routine preoperative sleep studies would influence perioperative outcome. Nevertheless,
when a sleep study is not available, it is prudent to treat the patients as though they have severe OSA. There is
uncertainty regarding scheduling and management of OSA patients for outpatient surgery. With limited
understanding of their postoperative (particularly post-discharge) course, any recommendations remain speculative.
Prudent perioperative management should be guided by the awareness of the potential complications based on
the severity of comorbidities, invasiveness of diagnostic or therapeutic procedure, and requirement of postoperative
opioids. Use of fast-track anesthesia techniques with pain and PONV prophylaxis should allow rapid emergence,
reduce postoperative cardiopulmonary complications, and hasten recovery. Patients should be educated regarding
the deleterious effects of opioids and asked to limit their use. Patients on preoperative CPAP should be instructed to
use CPAP at night for several days postoperatively. Patients who are placed on OSA protocol based on clinical
indicators should be asked to follow-up with their primary physician for possible sleep study. Finally, developing
and implementing protocols (clinical pathways) is the best way to avoid adverse events and improve postoperative
outcome [39].
References
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36. Popat M, et al. Difficult Airway Society guidelines for the management of tracheal extubation. Anaesthesia
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38. Neligan PJ, et al. Continuous positive airway pressure via the Boussignac system immediately after extubation
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DISCLOSURE
Pfizer, Honoraria, Baxter, Funded Research, Honoraria, Eisai, Consulting Fees, Cadence, Honoraria
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Preoperative Evaluation of the Adult Outpatient

Barbara S. Gold, M.D. Minneapolis, Minnesota
Introduction
Preoperative evaluation is a fundamental component of anesthetic delivery because it guides anesthetic management
and postoperative care. This is especially true in the ambulatory surgical setting where preoperative evaluation also
informs patient selection. Patient selection, in turn, is the cornerstone for safe and efficient ambulatory anesthesia
care.
In the outpatient setting the preoperative anesthesia assessment – which exists in a variety of forms - is a key tool for
both optimizing medical and administrative outcomes. Proactive identification and management of medical
problems avoids last minute surprises that at best interrupt ambulatory surgery center patient flow and at worst
contribute to adverse medical outcomes. This lecture will review: 1) the basic requirements for preoperative
evaluation as determined by payers and regulators 2) models of preoperative evaluation and their merits and 3)
preanesthetic evaluation of selected co-morbidities which are particularly relevant to the outpatient setting such as
obesity, sleep apnea, cardiac disease, and insulin requiring diabetes.
Ground Rules
The ground rules which govern US hospitals as set forth by the Joint Commission state that prior to any operative or
other high risk procedure the patient receives a medical history and physical examination no more than 30 days prior
to surgery. (Standard: RC.02.01.03, PC.01.02.03, EP 5) The American Society of Anesthesiologists has adopted
standards (last amended in 2010) for preanesthesia care which is more specific http://www.asahq.org/For-
Healthcare-Professionals/Standards-Guidelines-and-Statements.aspx; accessed 5/12)
Basic Standards for Preanesthesia Care
The anesthesiologist, before the delivery of anesthesia care, is responsible for:
1. Reviewing the available medical record.
2. Interviewing and performing a focused examination of the patient to:
a. Discuss the medical history, including previous anesthetic experiences and medical therapy.
b. Assess those aspects of the patient’s physical condition that might affect decisions regarding perioperative
risk and management.
3. Ordering and reviewing pertinent available tests and consultations as necessary for the delivery of anesthesia care.
4. Ordering appropriate preoperative medications.
5. Ensuring that consent has been obtained for the anesthesia care.
6. Documenting in the chart that the above has been performed.
Furthermore the ASA Statement on Documentation (last amended in 2008) lists specific elements of the
preanesthesia evaluation that should be recorded and further states that this is the responsibility of an
anesthesiologist. (www.asahq.org/publicationsAndServices/sgstoc.htm, accessed 5-12) The content of this
evaluation is to include medical history, anesthetic history, medications, appropriate physical exam including vital
signs and documentation of airway assessment, review of objective diagnostic data and medical records, medical
consultations when applicable, assignment of ASA physical status, formulation of anesthetic plan and
documentation of risks and benefits of the plan “including discharge issues when indicated”. The Center for
Medicare and Medicaid Services (CMS) issued “Revised Hospital Anesthesia Services Interpretive Guidelines” in
December 2009 (with a clarification in January 2011) which reflect the ASA Statement for documenting
preoperative assessment.
What then is the best approach for satisfying these minimum requirements and professional society expectations?
Clearly, the answer depends on the type of facility, patient population and procedures. Patient selection criteria, and
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hence evaluation paradigms, for a free-standing or office based practice will undoubtedly differ from a hospital
based practice in a tertiary care center. In spite of these differences, there are some unifying guiding principles that
apply to all settings.
For starters, the basic requirements as outlined above need to be satisfied in a manner that is consistent and efficient.
The goal is to determine who is fit for outpatient surgery and then to optimize those candidates. The extent and
focus of the preanesthesia assessment is determined by the patient’s co-morbidities and type of surgical procedure.
Secondly, a plethora of studies indicate that laboratory exams should be obtained for medical indication only and
that “routine” testing is of no value, especially in the ambulatory setting. (1-3) However, the information gained
from a thorough history and physical exam and clear communication with members of the perioperative team is of
considerable benefit. Investigators of the Australian Incident Monitoring Study database identified poor airway
assessment, communication problems, and inadequate preoperative evaluation as contributing factors in 197
preventable major adverse events (incidence 3.1%) including death and major morbidity. (4) While laboratory
exams may not be useful, basic patient evaluation and communication of salient features are still essential.
Over the past few decades, several models have been developed to facilitate preoperative communication,
triaging, and medical evaluation. All of these models have their strengths and weaknesses, depending on the facility
(free-standing center, office, hospital, etc.) and the patient population.
Models for Systematic Preoperative Evaluation

Patients can be evaluated on the day of surgery or seen in a preoperative evaluation clinic, or some hybrid version.
The preferred model depends on patient demographics and type of facility. Patients evaluated the day of surgery
have usually had a screening telephone interview with a preoperative nurse several days in advance of the procedure
with anesthesiologist consultation as necessary. This method can be quite effective and efficient if relevant patient
records (i.e., history and physical, laboratory values) are available at the time of the telephone screen, the nurses are
well trained at interviewing, and have algorithms for seeking physician consultation. At the other end of the
spectrum are preoperative evaluation clinics where patients are seen well in advance of surgery by an
anesthesiologist and/or advanced practice nurse. These clinics are usually found in larger tertiary medical centers
and face-to-face visits are reserved for patients with extensive co-morbidities. These clinics require institutional
support and delineated organizational infrastructure. (5)
Regardless of the method used, preoperative screening is cost effective and has the potential to yield
substantial dividends by minimizing delays, cancellations, and opportunity costs. (6-8) While data for ambulatory
surgery are limited, in a large urban medical center Ferschl and colleagues found same day surgery patients seen in
the preoperative evaluation clinic had a cancellation rate of 8.4% as compared with a cancellation rate of 16% for
same day patients who were not evaluated in clinic. Cancelations have significant negative financial impact, with
estimates of over $1500/hr of lost revenue for every hour the OR sits idle (contribution margin).
Data are beginning to emerge using preoperative assessment to predict future hospital costs. In the
National Surgical Quality Improvement Program (NSQIP), 51 preoperative risk factors such as Cr > 1.2 or previous
cardiac surgery, predicted post-operative cost variation due to complications and extended hospital stay. (9) The
authors speculate that preoperative optimization of these risk factors would mitigate the occurrence of postoperative
complications and hospital costs. This remains to be determined.
Whether telephone screens or preoperative clinic visits are used, the model chosen for ambulatory
anesthesia evaluation needs to emphasize patient selection using evidence-based algorithms developed by
anesthesiologists and broadly shared with surgeons and their offices. This will permit effective triaging of patients
and optimization of medical conditions preoperatively. For example, a patient with a drug-eluting cardiac stent
placed within the year who abruptly discontinued clopidigrel would not be an appropriate candidate for elective
surgery, irrespective of the venue. However, the same patient a year later may be perfectly appropriate for a
hospital-based surgery center but not an office setting, depending on the procedure and other co-morbidities.
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Medical Evaluation
This discussion will encompass medical co-morbidities that have considerable relevance to the outpatient setting due
to the associated perioperative risks and dilemmas posed by discharging the patient within a few hours of surgery
and anesthesia. Areas of focus include cardiac disease with an emphasis on stents and implantable cardiac rhythm
devices, obesity and obstructive sleep apnea, and diabetes and perioperative glycemic control.
Cardiac
There is an abundance of data, guidelines and opinions to guide preoperative evaluation of cardiac risk. This section
will focus on key studies and guidelines which are applicable to outpatients since the type of surgery is usually
limited in scope, with minimal fluid shifts. However, most studies which form the backbone of current guidelines
were extrapolated from (in) patients having extensive procedures.
In guideline parlance, outpatient procedures are generally considered “low risk” however, lumping these
procedures can be misleading (i.e., a cataract repair is not equivalent to a rigid bronchoscopy). Consequently, it
becomes incumbent on the anesthesiologist to sort out which patients are at risk and require more extensive
evaluation. Risk stratification methods are useful but they all have their limitations, namely they are often
observational studies at a single institution. Nevertheless, common themes emerge.
A landmark study of 4315 patients over 50 years having noncardiac elective surgery was used to identify
independent risk factors, comprising the Revised Cardiac Risk Index (RCRI). (10) Although major cardiac
complications were rare (2%) six independent risk factors were identified:
• High risk surgery (intraperitoneal, intrathoracic, or suprainguinal vascular)
• History if ischemic heart disease
• History of congestive heart failure
• History of cerebrovascular disease
• Preoperative treatment with insulin
• Preoperative serum creatinine > 2.0 mg/dL
The authors specifically note that “(T)he Index is of uncertain generalizability in lower-risk populations, such as
patients who undergo minor procedures….”. However, data specifically examining that population is lacking so this
risk index is widely used.
While risk indices can be quite useful, Reilly used a simple – and practical - screening tool to predict
perioperative risk, namely self-reported exercise tolerance. Poor exercise tolerance, such as the inability to walk 3
blocks or climb 2 flights of stairs (< 4 METS), is an independent predictor of serious perioperative complications
(OR 1.94, CI 1.19-3.17). Moreover the likelihood of serious complications is inversely related to the number of
blocks walked or flights of stairs climbed. (11)
A decade later, in a single-center observational study, Kheterpal used NSQIP data to identify preoperative
and intraoperative predictors of adverse cardiac events. (12) Their findings are consistent with findings from a
decade earlier, with some modifications. Those independent predictors are:
• Age > 68 yrs
• Active CHF
• BMI > 30 kg/m2
• Emergency surgery
• Previous cardiac intervention
• Cerebrovascular disease
• Hypertension
• Operative duration > 3.8 hrs
• Administration of one or more units of PRBCs
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All of the aforementioned predictors except for two (emergency surgery and administration of > 1 unit of PRBC) are
commonly encountered in the ambulatory setting. On a related note, a supporting study by Correll and colleagues
found that age > 65 was an independent predictor of preoperative electrocardiogram abnormalities. (13)
The findings from the aforementioned studies and many, many others led to the most recent (2007)
American Heart Association/American College of Cardiology guidelines on perioperative evaluation for patients
having noncardiac surgery. (14) (These guidelines were updated in 2009 with respect to perioperative beta-
blockade.) There are some key points in these guidelines as they relate to ambulatory surgery. First, ambulatory
surgery is considered as one entity and all ambulatory procedures are considered low risk with reported cardiac
mortality < 1%. Secondly, in the absence of “active cardiac conditions”, “interventions based on cardiovascular
testing in stable patients would rarely result in a change in management and it would be appropriate to proceed with
the planned surgery.” In other words, in the absence of active cardiac conditions (unstable coronary syndromes,
decompensated heart failure, significant arrhythmias, and severe valvular disease), additional interventions would
rarely alter perioperative risk for low risk procedures. However, although additional testing may not be warranted
(because it would rarely lead to a meaningful intervention), a complete and thorough history and physical exam
which can probe the presence or absence of active cardiac conditions is essential. The AHA/ACC guidelines
recognize that there are clinical risk factors (which are based on Lee’s Revised Cardiac Risk Index cited earlier).
However, in the absence of active cardiac conditions, further action is rarely needed.
Previous Coronary Interventions: Stents and Cardiac Rhythm Devices

Stents
Approximately two million patients per year in Western countries have cardiac stents placed and 90% of
those stents are drug eluting stents which will require long term antiplatelet therapy. About 5% of stented patients
will present for noncardiac surgery within the first year of stent placement. (15,16) The implications of cardiac
stents and antiplatelet therapy on preoperative assessment requires a clinical understanding of the associated risks
and well defined preoperative policies to guide patient selection and evaluation.
With any coronary stent, there are risks, especially during the period of re-endothelialization. Until the
period of re-endothelialization is complete, patients need to remain on dual antiplatelet therapy (i.e., aspirin and
clopidigrel). Bare metal stents (BMS) are layered with endothelial cells after about 4-6 weeks. However, there is a
risk that these stents are vulnerable to restenosis over time hence the development of drug eluting stents (DES).
DES are coated with agents which impair cellular proliferation. This can prevent restenosis but also results in a
longer period of time to stent re-endothelialization. During this period, patients must remain on dual antiplatelet
therapy.
Premature discontinuation of dual antiplatelet therapy, especially in the perioperative period, can be
catastrophic due to stent thrombosis. (17-22) If noncardiac surgery is performed immediately after stent placement
and without antiplatelet therapy, there is a 30% risk of perioperative MI and 20-40% of those are fatal. The risk of
MI and death is 5-10 times higher than waiting the appropriate amount of time.
Practice guidelines are unequivocal in stating that elective surgery be postponed until patients have
completed an appropriate course of antiplatelet therapy. (14,18,22) The duration of antiplatelet therapy is currently
estimated at minimum of 4 weeks for BMS and 12 months for DES, with aspirin continued indefinitely. However,
some patients may be more prone to thrombosis and may need to remain on antiplatelet therapy for longer periods.
Predictors of stent thrombosis are: bifurcated lesions, long stents, diabetes, renal failure and low ejection fractions.
However, until more data are available, the practice guidelines are unequivocal.
The ACC/AHA 2007 Perioperative Guidelines state: “Elective procedures for which there is significant
risk of perioperative or postoperative bleeding should be deferred until patients have completed an appropriate
course of thienopyridine therapy (12 months after DES implantation if they are not at high risk of bleeding and a
minimum of 1 month for bare-metal stent implantation).”(14) Similarly, the ASA Practice Alert issued in 2009
affirms the position of the ACC/AHA Perioperative Guidelines. (22)
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Since ambulatory surgery procedures are usually elective, patients need to defer surgery until 4-6 weeks
after placement of a BMS and one year after DES. Aspirin should be continued in the perioperative period if at all
possible. To avoid confusion and compromised patient care, it is extremely useful for surgery centers to have
policies which reflect these guidelines.
Cardiac Rhythm Devices

The perioperative assessment management of the adult surgical outpatient with a cardiac implantable
electronic device (CIED) – either a pacemaker, an implantable defibrillator or both, is common place in 2011. This
poses clinical and administrative challenges. (23-25) Indeed, perioperative management of these devices is the topic
of an updated ASA Practice Advisory. (25)
The indications for the CIED should be fully appreciated, as this often reflects significant underlying
cardiac disease. (23) Permanent pacemakers are indicated for symptomatic third-degree heart block, type II second-
degree heart block, sinus node dysfunction, recurrent neurally mediated syncope as well as some forms of
cardiomyopathy. For example, biventricular pacemakers, are considered in patients with significant heart failure
(ejection fraction <35%) despite medical therapy. Implantable Cardiac Defibrillators (ICDs) are indicated in
patients who have had a cardiac arrest that is not due to a temporary condition. This includes a wide array of
problems including ischemia, long QT syndrome, hypertrophic cardiomyopathy or familial cardiomyopathy. Thus
the first question to be asked is: WHY was THIS device placed? The second question is whether the patient (and
procedure) are appropriate for outpatient surgery given the status of the cardiac disease.
If the patient and procedure are appropriate for the facility, then basic information about the devices should
be obtained either during a preoperative visit or telephone call. This should be done well in advance of surgery, so
that there is time to 1) decide if device interrogation or reprogramming by appropriate personnel will be necessary
and 2) have enough time to coordinate personnel for preoperative and postoperative care.
Preoperatively, the following information should be obtained (ASA Practice Advisory):

1. Indication for CIED
2. Is patient device dependent?
3. Type of device and manufacturer (available from manufacturer’s identification card)
4. Assess CIED function
Date of last interrogation and results
Current setting
Does the device capture when it paces?
Effect of magnet on pacemaker function (ie, defaults to DOO at # bpm)
Does CIED automatically reset to preoperative settings when a magnet is removed?
5. Likelihood of device interference

• Will electromagnetic interference (EMI) be likely during the procedure? (EMI is unlikely if the
device is < 10 years old and bipolar cautery is > 15 cm from device lead or generator)
• Based on the likelihood of EMI, is reprogramming the CIED to asynchronous mode or disabling
rate responsive function with a magnet or reprogramming indicated?
• Should antitachyarrhythmia functions be suspended? (By whom?)
Appropriate arrangements need to be made preoperatively so that the device can be reprogrammed (if necessary) in
advance of the procedure and immediately after the procedure, without unduly inconveniencing patients or
providers. If the device required reprogramming by the cardiology service/manufacturer’s representative
preoperatively then original settings will need to be restored postoperatively and before discharge from PACU.
Until those settings are restored, patients need to have cardiac monitoring with the capability to defibrillate
immediately (i.e., defibrillator pads in place).
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Obesity
Approximately 34% of the adult US population is obese and ~ 68% are overweight and obese
(http://www.cdc.gov/nchs/fastats/overwt.htm, accessed 5/12). Obesity poses considerable perioperative challenges,
and this is especially true in the outpatient setting where patients are expected to be discharged within a few hours
after surgery. Associated co-morbidities such as obstructive sleep apnea and pulmonary dysfunction impact
postoperative recovery/discharge and hence the patient selection process. A thorough understanding of the common
obesity associated co-morbidities is useful to help formulate not only ambulatory anesthetic management but also
patient selection criteria.
Cardiovascular
There is a direct and independent relationship between obesity and hypertension. (26-28) Furthermore,
obese patients without documented hypertension are prone to occult diastolic dysfunction, probably secondary to
increased circulating blood volume and chronic LV wall stress. (29) Systolic dysfunction associated with obesity is
a later development, and is most often seen among obese patients with body mass index (BMI) > 40kg/m2 for > 10
years. (30) Cardiac function can be difficult to assess preoperatively due to diminished functional capacity.
Consequently, non-invasive testing with appropriate modalities (such as stress echocardiography) may be required if
patients have multiple risk factors or have limited functional capacity. (31, 32)
Reconciling the AHA/ACC cardiac evaluation and care algorithm for non-cardiac surgery in obese patients
having ambulatory surgery requires clinical judgment. Indeed, this issue was highlighted in the recent advisory
from the AHA regarding the cardiac evaluation of severely obese patients: “(T)hese categorizations (low,
intermediate and vascular surgery) are used in the decision algorithm for further testing but it is unknown if obesity
influences these categorizations.” (33) Consequently, this AHA advisory recommends a preoperative ECG in
severely obese patients (BMI > 40 kg/m2) with one risk factor for heart disease. If there are signs of CV disease
(e.g., CAD, RVH consistent with pulmonary hypertension), additional workup based on functional capacity be
pursued – if it will change management.
Obesity and obstructive sleep apnea are associated with pulmonary hypertension which poses considerable
perioperative risk. However, diagnostic criteria (such as signs of right heart failure) in the absence of an
echocardiogram are vague, especially in the morbidly obese. The associated postoperative mortality in patients with
pulmonary hypertension across several different inpatient procedures is estimated to be 7-10%. (35,36) Due to
several factors, including intense intra and postoperative monitoring, these patients may not be candidates for the
vast majority of ambulatory procedures and need to be carefully evaluated on a case by case basis.
Obstructive Sleep Apnea (OSA)
The prevalence of OSA in obese patients presenting for bariatric surgery is 71% -77%, depending on (BMI). (37)
OSA is usually not a solitary diagnosis in an obese patient; associated co-morbidities include:
hypertension and increased risk of cardiovascular disease, including stroke and sudden death. (38-40) Sudden
cardiac death in (non-surgical) obese patients is associated with a nocturnal pattern which is distinctly different than
in other populations. A review of polysomnograms and death certificates from 112 persons who experienced sudden
cardiac death demonstrated that those with OSA had peak in sudden death from cardiac causes during sleeping hours
(midnight to 6am). In contrast, those without OSA had peak incidence of sudden death after 6am. (41)
In the perioperative setting, patients with OSA have an increased incidence of postoperative complications:
Hwang measured home nocturnal desaturations preoperatively in 172 subjects. Patients with > 5 desaturations/hr
had significantly higher rate of postop complications (15%) vs. those with < 5 events/hour (3%). Complications
were primarily respiratory. (42) Chung evaluated 177 patients deemed at risk for OSA by various screening tools
and then performed polysomnography. (43) Those with apnea-hypopnea index (AHI) >5 as confirmed by
polysomnography had postoperative complication rate that was more than double those with AHI < 5 (27% vs.
12%).
Discerning who actually has OSA is challenging, as the diagnostic “gold standard” is polysomnography,
which many patients do not obtain. Diagnosis based on screening questionnaires is unreliable. A meta-analysis of
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clinical screening tests for OSA illustrates that it is possible to predict severe OSA with a high degree of accuracy.
However, aside from severe OSA, false negative rates range from 14-38% which will miss a significant proportion
of patients. (44)
Nevertheless, simple screening methods have been developed for preoperative use including the STOP-
BANG questionnaire which has a sensitivity from 84% (AHI>5) to 100% (AHI >30). Patients who answer yes to
three or more items are considered to be at high risk of OSA. (43) Other similar validated tools incorporate upper
airway anatomy to enhance predictive modeling. (45)
STOP-BANG (Chung 2008)

1. Snoring 5. BMI
Do you snore loudly (louder than talking or loud enough to be heard BMI more than 35 kg/m2?
through closed doors)?
2. Tired Do you often feel tired, fatigued, or sleepy during daytime? 6. Age over 50 yr old?
3. Observed 7. Neck circumference greater than 40 cm?

Has anyone observed you stop breathing during your sleep?
4. Blood pressure 8. Male gender?
Do you have or are you being treated for high blood pressure?
A main concern for patients with OSA is their suitability for ambulatory surgery. Is it safe to send these patients
home to an unmonitored setting after anesthesia and surgery? Data are scant since important determinants such as
severity of OSA, type of anesthetic and type of procedure have not been individually examined. Instead, we have
expert opinions extrapolated from inpatient setting and used as guide. The ASA Practice Guidelines for the
Perioperative Management of Patients with OSA (approved by ASA HOD October 2005) state that literature is
insufficient to make recommendations and those guidelines are based on consultant opinion. (46) Moreover, the
clinical screening tool suggested in ASA Guideline has not been clinically validated. The ASA Guidelines
recommend that anesthesiologists determine whether a given surgical procedure and individual patient with (or at
risk for) OSA is appropriate for outpatient setting. Factors to consider include:
(1) severity of sleep apnea status
(2) anatomical and physiologic abnormalities
(3) status of coexisting diseases
(4) nature of surgery
(5) type of anesthesia
(6) need for postoperative opioids
(7) patient age
(8) adequacy of postdischarge observation
(9) capabilities of the outpatient facility
Specifically in reference to outpatients, the ASA Guidelines recommends: “These patients should not be
discharged from the recovery area to an unmonitored setting (i.e., home or unmonitored hospital bed) until they are
no longer at risk for postoperative respiratory depression.” The Guidelines also recommend observing patients
while breathing room air in an unstimulated environment and note that this may require a longer ambulatory stay
(i.e., 3 hours longer than non-OSA counterparts and median of 7h after last episode of airway obstruction or
hypoxemia while breathing room air in an unstimulating environment). Practical application has been challenging
because patients frequently do not have formal preoperative diagnosis of OSA and severity is difficult to estimate.
Most likely, recommendations in this arena will continue to evolve as more relevant data become available.
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Diabetes
Approximately 15% of US adults aged >20 years and ~27% of individuals >65years have diabetes or impaired
fasting glucose. (http://www.cdc.gov, accessed 5/12) In order to evaluate potential end-organ damage and maintain
metabolic homeostasis these patients require a focused assessment to a) gauge appropriateness for procedure on an
outpatient basis, with a focus on potentially difficult airway in patients with long-standing Type I diabetes and b)
guide preoperative fasting and insulin instructions.
Cardiovascular disease is the major cause of morbidity and mortality amongst patients with diabetes, with
the most common conditions being hypertension and dyslipidemias. The most recent American Diabetes
Association guidelines recommend that patients with diabetes be treated to a blood pressure < 130 mm Hg systolic
and < 80 mmHg diastolic. Furthermore, it is recommended that all patients with diabetes have serum creatinine
measured and cardiovascular risk factors such as dyslipidemia, hypertension, smoking, positive history of coronary
disease and presence of micro- or macroalbuminemia assessed annually. This is part of routine health maintenance
and is independent of surgical need. Further cardiac testing – irrespective of the need for surgery - should be
considered in diabetics with typical or atypical anginal symptoms or an abnormal resting ECG. (47)
Patients with diabetes may be on complicated regimens to achieve glycemic goals in order to reduce the
risk of micro and macrovascular complications. In addition to insulin and conventional oral hypoglycemic agents,
treatment may include relatively new classes of gastrointestinal hormones – namely incretions and amylin – which
impact glucose homeostasis. (48) In adults glycemic goals are: A1C < 7 % and preprandial glucose 70-130mg/dl
and peak postprandial glucose < 180 mg/dl. (47) Due to concerns about perioperative hypoglycemia as delineated in
the NICE-SUGAR study, perioperative glycemic goals as suggested by the ADA are in the range of 120 – 180
mg/dl. (47, 51)
To achieve those targets and simplify preoperative instructions, ambulatory surgery centers usually have
protocols which address the type and quantity of insulin (and other hypoglycemic agents) to be administered
preoperatively, recommendations for monitoring blood sugar preoperatively and treating hypoglycemia while
adhering to NPO guidelines. A common feature in these protocols is to include a basal form of insulin on the day of
surgery (usually as a fraction of the typical intermediate acting insulin or long acting insulin) and withhold oral
hypoglycemic agents and incretions. (48-50) A basic understanding of the time course of commonly used insulin’s,
as outlined below, is integral to developing effective preoperative instructions.
Insulin Comparison
Action Generic name Onset Peak Duration
Rapid Insulin Aspart 15 min 45-90 min 3-5 hrs

Short Regular Human Insulin 30 min 2.5-5 hrs 8 hrs
Intermediate NPH Insulin 1.5 hrs 4-12 hrs ~24 hrs
Long Insulin Glargine ~1 hr - up to 24 hrs
Long Insulin Detemir ~3 hrs ~6-8 hrs up to 24 hrs
Mixtures Insulin Aspart Protamine, Insulin Aspart 60 min 1-4 hrs up to 24 hrs
Mixtures Insulin NPH/ Regular, 70/30 ~30 min 2-12 hrs ~24 hrs
Summary
Outpatient evaluation is the basis for patient selection, which is fundamental for safe and efficient ambulatory
anesthetic management. Models of evaluation include: assessment on the day of surgery, telephone triage, or
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preoperative clinic visit. Each model has its advantages, and adoption depends on the facility and patient
demographics. Irrespective of the method, patients are evaluated with discharge planning in mind. Patients should
be suitable for elective surgery with the expectation that they can be safely discharged home within a few hours of
their procedure. Several co-morbidities affect this process and serve to refine patient assessments and selection
criteria.
References
1) Chung F, Yuan H, et al. Elimination of preoperative testing in ambulatory surgery. Anesth Analg 2009; 108:467-75
2) Finegan B, et al. Selective ordering of preoperative investigations by anesthesiologist reduces the number and cost of tests. Can J Anesth 2005;
52:575-80
3) Schein OD, et al. The value of routine preoperative medical testing before cataract surgery. N Engl J Med 2000; 342:168-75
4) Kluger M, Tham E, et al. Inadequate pre-operative evaluation and preparation. Anaesthesia 2000; 55:1173-1178
5) Bader AM, Correll DJ. Organizational infrastructure of the preoperative evaluation center. Preoperative Assessment and Management. 2nd
edition. Editor: BobbieJean Sweitzer, M.D. Lippincott Williams & Wilkins/Wolters Kluwer. 2008
6) Correll D, Bader A, et al. Value of preoperative clinic visits in identifying issues with potential impact on operating room efficiency.
Anesthesiology 2006; 105:1254-9
7) Ferschl M, Tung A, et al. Preoperative clinic visits reduce operating room cancellations and delays. Anesthesiology 2005; 103:855-9
8) Gibby G. How preoperative assessment programs can be justified financially to hospital administrators. Int Anesthesiol Clin 2002; 40:17-30
9) Davenport D, Henderson W. et al. Preoperative risk factors and surgical complexity are more predictive of costs that postoperative
complications. Annals of Surgery 2005; 242:463-471
10) Lee T, et al. Derivation and prospective validation of a simple index for prediction of cardiac risk of major noncardiac surgery. Circulation
1999; 100:1043-1049
11) Reilly D, et al. Self-reported exercise tolerance and the risk of serious perioperative complications Arch Intern Med 1999; 159:2185-2192
12) Kheterpal S, O’Reilly M, et al. Preoperative and Intraoperative predictors of cardiac adverse events after general, vascular, and urological
surgery. Anesthesiology 2009; 110:58-66
13) Correll D, Hepner D, et al. Preoperative Electrocardiograms. Anesthesiology 2009; 110:1217-22
14) Fleisher L, Beckman, et al. ACC/AHA Guidelines on perioperative cardiovascular evaluation for noncardiac surgery. Circulation 2007; 116
15) Vicenzi M, Meislitzer T, et al. Coronary artery stenting and non-cardiac surgery. Br. J Anaesth 2006; 96:686-93
16) Spaulding C, et al. A pooled analysis of data comparing sirolimus-eluting stents with bare-metal stents. N Engl J Med 2007; 356:989-97
17) Chassot P-G, Delabays A, et al. Perioperative antiplatelet therapy. Br J Anaesth 2007; 99:316-28
18) Grimes C, Bonow R, et al. Prevention of premature discontinuation of dual antiplatelet therapy in patients with coronary artery stents.
Circulation 2007; 115:813-818
19) Mehta S, Yusuf S. et al. PCI-Cure Study. Lancet 2001; 358:527-33
20) Rabbits J, Nuttall G, et al Cardiac risk of noncardiac surgery after percutaneous coronary intervention with durg-eluting stents.
21) Nuttall G, Brown M, et al. Time and cardiac risk of surgery after bare-metal stent percutaneous coronary intervention. Anesthesiology 2008;
109:588-95
22) Practice alert for the perioperative management of patients with coronary artery stents. Anesthesiology 2009; 110:22–3
23) Myerberg R. Implantable cardioverter-debrillators after myocardial infarction. N Engl J Med 2008; 359:2245-53
24) Stone M, Apinis A. Current perioperative management of the patient with a cardiac rhythm management device. Semin Cardiothorac Vasc
Anesth 2009; 13:31-43
25) Practice Advisory: preoperative management of cardiac implantable electronic devices: pacemakers and implantable cardioverter-
defibrillators. Anesthesiology 2011; 114:247–61
26)Kannel WB, Brand N, Skinner J, Dawber T, McNamara P. The relation of adiposity to blood pressure and development of hypertension
Annals Int Med 1967; 67:48-59
27) Havlik R, Hubert H, et al. Weight and hypertension. Annals of Internal Medicine 1983; 98:855-859
28) Jones D, Kim J, Andrew M. Kim S. Hong Y. Body mass index and blood pressure in Korean men and women. J Hypertension 1994; 12:1433
29) Pascual M, Pascual D, Soria F, et al. Effects of isolated obesity on systolic and diastolic left ventricular function. Heart 2003; 89:1152-1156
30) Alpert M. Obesity cardiomyopathy: Pathophysiology and evolution of the clinical syndrome. Am J Medical Sciences 2001; 321:225-236
31) Gugliotti D, Grant P, et al. Challenges in cardiac risk assessment in bariatric surgery patients. Obes Surg 2008; 18:129-133
32) Kuruba R, Koche L, Murr M. Preoperative assessment and perioperative care of patients undergoing bariatric surgery. Med Clin N Am 2007;
339-351
33) CV evaluation and management of severely obese patients undergoing surgery: A science advisory from the American Heart Association.
Circulation 2009; 120:86-95
34) Subramaniam K, Yared J, Management of pulmonary hypertension in the operating room. Semin Cardiothorac Vasc Anesth 2007; 11:119
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35) Lai H-C, et al. Severe pulmonary hypertension complicates postoperative outcome of non-cardiac surgery. Br J Anaesth 2007; 99:184-90
36) Ramadrishna G, Sprung J, et al. Impact of pulmonary hypertension on the outcomes of noncardiac surgery: Predictors for preoperative
morbidity and mortality. J Am Coll Cardiol 2005; 45:1691-9
37) Lopez P, et al. Prevalence of sleep apnea in morbidly obese patients who presented for weight loss surgery evaluation. Am Surgeon 2008;
74:834-38
38) Isono S. Obstructive sleep apnea of obese adults. Anesthesiology 2009; 110:908-21
39) Lawate N, et al. Epidemiology, risk factors, and consequences of OSA and short sleep duration. Prog CV Dis 2009; 51:285-293
40) Yaggi H, Concata J, et al. Obstructive sleep apnea as a risk factor for stroke and death. N Engl J Med 2005; 353:2034-41
41) Gami A, Howard D, Olson E, Somers V. Day-night pattern of sudden death in obstructive sleep apnea. N Engl Med 2005; 352:1206-14
42) Hwang D, Shakir N, et al. Association of sleep-disordered breathing with postoperative complications. Chest 2008; 133:1128-1134
43) Chung F, Yegneswaran B, et al. Validation of the Berlin questionnaire and ASA checklist as screening tools for obstructive sleep apnea in
surgical patients. Anesthesiology 2008; 108:822-30
44) Ramachandran S, Josephs L. A meta-analysis of clinical screening tests for obstructive sleep apnea. Anesthesiology 2009; 110:928–39
45) Ramachandran S, et al. Derivation and validation of a simple perioperative sleep apnea prediction score. Anesth Analg 2010; 110:1007-15
46) Practice guidelines for the perioperative management of patients with obstructive sleep apnea. Anesthesiology 2006; 104:1081–93
47) Standards of Medical Care in Diabetes - 2009. Diabetes Care 2009; 32:513-561
48) Chen D, Lee S, et al. New therapeutic agents for diabetes mellitus: implications for anesthetic management. Anesth Analg 2009; 108:1803-10
49) Mooradian A, Bernbaum M. Narrative review: a rational approach to starting insulin therapy. Ann Intern Med 2006; 145:125-134
50) Clements S, Briathwaite S, et al. Management of diabetes and hyperglycemia in hospitals. Diabetes Care 2004; 27:553
51) Intensive versus conventional glucose control in critically ill patients. N Engl J Med 2009; 360:1283-97
DISCLOSURE
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Management of MH and MH-Susceptible Patients in the Ambulatory Setting

Ronald S. Litman, D.O. Philadelphia, Pennsylvania
In this refresher course lecture, we will review basic principles of MH pathophysiology, susceptibility,
diagnosis, and treatment. We will also discuss unique aspects of treating acute MH in the ambulatory setting,
preparing your free-standing ambulatory center for potential MH, and anesthetizing the known MH susceptible
patient in a free-standing ambulatory center. Even in this current era of sophisticated means of detecting, diagnosing
and treating MH, mortality from MH in unsuspected individuals is not zero. In the past several years, at least ten
cases of MH-related death in ambulatory surgery patients are known to the Malignant Hyperthermia Association of
the United States (MHAUS). The incidence of acute MH in the general population is approximately 1:30,000
general anesthetics, but this doesn’t account for unreported cases, or unrecognized, mild, or atypical reactions.
Furthermore, MH-susceptible patients may not develop the acute syndrome during any given anesthetic exposure.
Although acute MH may develop during the patient’s first exposure to a triggering agent, many MH-susceptible
patients will trigger upon subsequent anesthetic exposures.
Between 1996 and 2006, the rate of surgical procedures in a free-standing ambulatory surgery center
increased 300 percent. In 2006, approximately 53 million procedures were performed during 35 million ambulatory
surgery visits. Almost half of these visits occurred in a free-standing center.1 Since malignant hyperthermia (MH)
susceptibility almost always occurs in phenotypically normal individuals, it is impossible to predict the risk of MH
in any given seemingly healthy ambulatory surgery patient.
MH Pathophysiology
MH susceptibility results from a familial or spontaneous mutation in a gene that encodes for one of the
components of a muscle cell that plays a role in regulation of intracellular calcium. The most commonly affected
structure is the ryanodine receptor, which regulates the movement of calcium from the sarcoplasmic reticulum into
the intracellular space of the myocyte.2 The inheritance is autosomal dominant with variable penetrance. Affected
individuals are often healthy appearing, and, except for extremely rare cases of heat- or stress-related MH,3 will only
develop signs of acute MH when exposed to one of the anesthetic triggering agents (i.e., volatile anesthetics or
succinylcholine). The specific mechanism by which anesthetics interact with these abnormal receptors to trigger an
MH crisis is unknown.
During an acute MH crisis, abnormal levels of calcium accumulate inside the muscle cell. This results in a
massive overload of actin-myosin cross-bridging, which leads to sustained muscle contracture, cellular hypoxia,
ATP depletion, and cell death (rhabdomyolysis). Hyperthermia results from the sustained muscle contraction, which
generates more heat than the body is able to dissipate.
Diseases Associated with MH

The gene for the ryanodine receptor, RY R1, is located on chromosome 19. The diseases that are known to
be linked with MH susceptibility are invariably also caused by mutations on chromosome 19 in the same region as
that which encodes for ryanodine. These are relatively rare and include central core myopathy,4,5 multiminicore
myopathy,6 King-Denborough syndrome,7 Native American myopathy,8 and possibly hypokalemic periodic
paralysis.9
An interesting group of patients with possible MH susceptibility are those individuals with a history of
exercise- or heat-induced rhabdomyolysis.10,11 Although many of these patients will not test positive, those with a
convincing history of severe heat- or exercise-induced rhabdomyolysis should probably be considered to be MH
susceptible unless proven negative by contracture testing.
A number of other diseases have been erroneously linked with MH susceptibility because patients have
developed rhabdomyolysis upon exposure to triggering agents. These include Duchene’s and Becker’s myopathy,12
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McArdle’s disease (glycogen storage disease, type V),13 myoadenylate deaminase deficiency,14 and carnitine
palmitoyltransferase type 2 (CPT-2) deficiency.15 The mechanism of the relationship between these diseases and
anesthetic-induced rhabdomyolysis is unknown.16
Additional diseases that are not associated with MH susceptibility include the mitochondrial myopathies,
Noonan’s syndrome, arthrogryposis, osteogenesis imperfecta, and neuroleptic malignant syndrome.
Clinical Features of Acute MH

MH manifests clinically as signs and symptoms of hypermetabolism and the sequelae of muscle
breakdown. An early important sign of hypermetabolism is hypercapnia that is out of proportion to increases in
minute ventilation. Tachycardia and hypertension may also occur. Spontaneously breathing patients will develop
marked tachypnea in an attempt to compensate for respiratory acidosis. Signs of ongoing rhabdomyolysis include
metabolic acidosis, localized or generalized rigidity (with or without neuromuscular blockade), hyperkalemia-
induced arrhythmias, myoglobinuria (tea-colored urine), and rapid temperature elevation. In some patients, masseter
muscle spasm in response to administration of succinylcholine is a harbinger of acute MH.17 Death from MH almost
always results from acute hyperkalemia or hyperthermia-induced disseminated intravascular coagulation (DIC).
Muscular individuals appear to have the greatest risk of severe complications from MH, presumably because of the
relatively larger amount of muscle damage that contributes to hyperkalemia and hyperthermia.18 They are also more
susceptible to recrudescence of MH following initial treatment with dantrolene.19
Intraoperative or postoperative hyperthermia without additional signs of hypermetabolism is not an
observed presentation of acute MH.20 In fact, the notion of acute MH first presenting several hours after completion
of the general anesthetic is unproven. Postoperative hyperthermia, even if striking, should prompt a search for other
causes unless accompanied by muscle rigidity or rhabdomyolysis. The most common mimic of acute MH is
hypercapnia caused by hypoventilation, from any one of a number of causes related to impaired ventilation.
Treatment of Acute MH
When clinical signs indicate a strong possibility of acute MH, the diagnosis should be confirmed by blood
gas analysis (when available), which shows the characteristic mixed respiratory and metabolic acidosis. In some
cases of severe acute MH, such as that seen with marked hypercapnia along with generalized rigidity, metabolic
acidosis may not yet be evident. Nevertheless, triggering agents should be immediately discontinued and the surgical
procedure should be aborted or completed as quickly as possible while administering intravenous (nontriggering)
anesthetics. An endotracheal tube should be placed if not already present, the minute ventilation should be increased
to offset respiratory acidosis, and the inspired oxygen should be increased to 100 percent. Simultaneously, all
available personnel are summoned, and the MH emergency cart (Table 1) is brought into the room. If the surgery is
being performed in a free-standing facility, plans for transport to the nearest full-service medical center should be
arranged. The concentration of the volatile gas remaining in the patient can be decreased most rapidly by increasing
fresh gas flows and by inserting into the anesthesia circuit a charcoal filter.21
Immediate administration of dantrolene is the most important aspect of treatment of acute MH – all
personnel should be focused on its administration as quickly as possible. Dantrolene is supplied as a lyophilized
powder (20 mg) and also contains 3 g of mannitol. It is reconstituted with sterile water, which when warmed will
enhance solubility.22 A newer formulation manufactured by JHP Pharmaceuticals will solubilize within 20 seconds.
The initial dose of dantrolene is 2.5 mg/kg; subsequent bolus doses of 1 mg/kg should be administered until the
signs of acute MH begin to reverse. Some patients (eg muscular males) may require initial doses approaching 10
mg/kg; however, the need for higher than usual doses should prompt an exploration for alternative diagnoses. As
soon as feasible, the MH hotline should be called to speak with a knowledgeable expert who can assist with
diagnosis, treatment, and follow-up care (1-800-MH-HYPER).
The most important aspects of treatment of acute MH are listed in Table 2.

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Preparing Your Ambulatory Surgery Center for Unexpected Acute MH

Since patients with significant neuromuscular disease are usually excluded from receiving general anesthesia in
an ambulatory facility, it is most likely that any patient that develops MH will be otherwise healthy. Therefore, each
facility should be optimally prepared to treat patients that unexpectedly develop acute MH. Each facility should have
a completely stocked MH cart (Table 1) and a readily available source of ice and cold intravenous fluids. A full
component of dantrolene (36 vials) should be available at every ambulatory facility that uses any anesthetic
triggering agent, and the facility should proactively identify a mechanism to rapidly attain additional dantrolene in
the event that the patient requires more than is immediately available. MH treatment drills should be performed at
least yearly. An in-service video and manual for management of MH in ambulatory centers is available from
MHAUS.
Anesthesia for MH Susceptible Patients in the Ambulatory Setting

MH susceptible patients are eligible for outpatient surgery in a free-standing facility. A non-triggering
technique should be used for general anesthesia after properly preparing the anesthetic machine according to the
manufacturer’s recommendations. Insertion of a charcoal filter into the anesthesia machine circuit allows rapid
clearance of residual anesthetic gases without prolonged flushing with fresh gas.21 The patient should be carefully
monitored, especially with a focus on end-tidal carbon dioxide and core temperature. Prophylactic dantrolene is not
indicated. MH susceptible patients that receive a non-triggering anesthetic technique do not require extended
postoperative monitoring as long as their anesthetic course was uneventful. Following discharge, the patient is
instructed to call their physician or go to the emergency room if they develop elevated temperature or brownish
discoloration of their urine, which indicates myoglobinuria.
Case Example
During the RCL, I will discuss this real case from our practice that I had previously presented for
discussion at the annual meeting of the Society for Ambulatory Anesthesia (Baltimore, May 2010): A healthy 5 yr
old girl presented for T&A. Her paternal aunt (father’s sister) had a suspicious episode of MH in 1981 and has been
treated as if she is MH susceptible ever since. The aunt never had a biopsy or genetic testing. No one else in the
family has ever been tested but they have always considered themselves MH susceptible.
Questions:
Does the pt need a non-triggering technique?
Should she receive prophylactic dantrolene?
Postoperatively, do standard discharge criteria apply?
Can she have her surgery at a freestanding ASU?
Who should now be tested, and how?
What are the advantages/disadvantages of always considering the aunt (and family) MH susceptible?
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Table 1. Suggested Emergency MH Cart Supplies
Drugs
Dantrolene 20 mg vials 36 vials
Sterile water 2 1-liter bags
Sodium bicarbonate 8.4 percent, 50 mL 5 prefilled syringes or vials
Dextrose 50 percent, 50 mL 2 vials
Furosemide 10 mg/mL, 10 mL 2 vials
Calcium chloride 10 percent, 10 mL 2 vials
Lidocaine 2 percent, 5 mL 4 prefilled syringes or vials
Amiodarone 50 mg/mL, 3 mL 2 vials
Refrigerated drugs and solutions

Insulin regular 100 units/mL, 10 mL 1 vial
0.9% normal saline, 1000 mL for IV cooling 4 bags and sterile pour bottles
Cold packs 8 (freezer)
General equipment
Syringes, 60 mL to dilute dantrolene 5
Mini-spike® or similar IV additive pins and transfer set to reconstitute 2
dantrolene.
IV catheters: 16G, 18G, 20G 2 inch, 22 g 1 inch, 24G ¾ inch (for IV 4 each
access and arterial line)
NG tubes Various sizes
60 cc irrigation syringes 2
Drip IV set, chamber, extension 4
Syringes (insulin, ABG, 60 mL, 10 mL, 3 mL) 4 to 6 each
18G needles 6
Charcoal filter (Vapor-Clean, Dynasthetics LLC, Salt Lake City, UT) 2
Monitoring equipment
Esophageal or tympanic temperature probes 2
Rectal or bladder and skin temperature probes 2
Nursing supplies
Large sterile Steri-Drape 1
Urine meter 1
Irrigation tray with piston (60 cc irrigation) syringe 1
Small and large clear plastic bags for ice 4 each
Bucket for ice 1
Test strips: urine analysis for hemoglobin and finger stick glucose 1 vial
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Table 2. Treatment of Acute MH
Initial Steps:
Call for help, dantrolene, and MH emergency supply cart.
Notify surgeon to abort or complete procedure rapidly.
Discontinue triggering agents and switch to non-triggering intravenous anesthetics if surgery ongoing.
Hyperventilate with 100% oxygen, place charcoal filter into breathing circuit; endotracheal intubation.
Administer dantrolene: dissolve 20 mg dantrolene in 60 mL sterile water; 2.5 mg/kg IV rapid push, and then 1
mg/kg every 10-15 minutes until reversal of acute signs of MH.
Place bladder catheter to monitor urine output and color.
If feasible, call MH Hotline during any part of treatment process: 1-800-644-9737 (1-315-464-7079 outside U.S.).
Ongoing Monitoring and Treatment:

Potassium, ABG, glucose levels at least every 20 minutes, CK levels every 6 hours for first 48 hours.
Treat hyperkalemia with hyperventilation, calcium chloride (10 - 20 mg/kg) or calcium gluconate (50 - 100 mg/kg).
Additional treatment of hyperkalemia: 10 units insulin IV push with 50 mL 50% dextrose glucose (for adults); 0.1
units insulin/kg IV push with 2 mL/kg 25% dextrose glucose (for pediatric patients).
Treat metabolic acidosis with sodium bicarbonate, 1-2 mEq/kg, IV push over 5 to 10 minutes.
Treat hyperthermia with cooling methods such as IV cold saline, ice to body surface, or cold lavage to open body
cavities; stop cooling when core body temperature decreases to 38oC.
Life-threatening dysrhythmias usually caused by hyperkalemia. Do not administer calcium channel
blockers (contraindicated with dantrolene treatment).
Maintenance dantrolene: 1 mg/kg every 4 to 6 hours, or 0.25 mg/kg/hr continuous infusion. Maintain for 24-48 hrs
after last sign of acute MH.
Treat myoglobinuria with induced diuresis (furosemide 1 mg/kg/dose) and sodium bicarbonate to alkalinize urine if
CK >10,000 IU/L.
Monitor coagulation studies for disseminated intravascular coagulation if rhabdomyolysis or hyperthermia severe.
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References
1. Cullen KA, Hall MJ, Golosinskiy A: Ambulatory surgery in the United States, 2006. Natl Health Stat Report
2009; 1-25
2. Sei Y, Sambuughin NN, Davis EJ, Sachs D, Cuenca PB, Brandom BW, Tautz T, Rosenberg H, Nelson TE,
Muldoon SM: Malignant hyperthermia in North America: genetic screening of the three hot spots in the type I
ryanodine receptor gene. Anesthesiology 2004; 101: 824-30
3. Groom L, Muldoon SM, Tang ZZ, Brandom BW, Bayarsaikhan M, Bina S, Lee HS, Qiu X, Sambuughin N,
Dirksen RT: Identical de novo mutation in the type 1 ryanodine receptor gene associated with fatal, stress-
induced malignant hyperthermia in two unrelated families. Anesthesiology 2011; 115: 938-45
4. Robinson R, Carpenter D, Shaw MA, Halsall J, Hopkins P: Mutations in RYR1 in malignant hyperthermia
and central core disease. Hum Mutat 2006; 27: 977-89
5. Wu S, Ibarra MC, Malicdan MC, Murayama K, Ichihara Y, Kikuchi H, Nonaka I, Noguchi S, Hayashi YK,
Nishino I: Central core disease is due to RYR1 mutations in more than 90% of patients. Brain 2006; 129:
1470-80
6. Mathews KD, Moore SA: Multiminicore myopathy, central core disease, malignant hyperthermia
susceptibility, and RYR1 mutations: one disease with many faces? Arch Neurol 2004; 61: 27-9
7. D'Arcy CE, Bjorksten A, Yiu EM, Bankier A, Gillies R, McLean CA, Shield LK, Ryan MM: King-
denborough syndrome caused by a novel mutation in the ryanodine receptor gene. Neurology 2008; 71: 776-7
8. Stamm DS, Aylsworth AS, Stajich JM, Kahler SG, Thorne LB, Speer MC, Powell CM: Native American
myopathy: congenital myopathy with cleft palate, skeletal anomalies, and susceptibility to malignant
hyperthermia. Am J Med Genet A 2008; 146A: 1832-41
9. Marchant CL, Ellis FR, Halsall PJ, Hopkins PM, Robinson RL: Mutation analysis of two patients with
hypokalemic periodic paralysis and suspected malignant hyperthermia. Muscle Nerve 2004; 30: 114-7
10. Capacchione JF, Muldoon SM: The relationship between exertional heat illness, exertional rhabdomyolysis,
and malignant hyperthermia. Anesth Analg 2009; 109: 1065-9
11. Tobin JR, Jason DR, Challa VR, Nelson TE, Sambuughin N: Malignant hyperthermia and apparent heat
stroke. JAMA 2001; 286: 168-9
12. Gurnaney H, Brown A, Litman RS: Malignant hyperthermia and muscular dystrophies. Anesth Analg 2009;
109: 1043-8
13. Bollig G, Mohr S, Raeder J: McArdle's disease and anaesthesia: case reports. Review of potential problems
and association with malignant hyperthermia. Acta Anaesthesiol Scand 2005; 49: 1077-83
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14. Fricker RM, Raffelsberger T, Rauch-Shorny S, Finsterer J, Muller-Reible C, Gilly H, Bittner RE: Positive
malignant hyperthermia susceptibility in vitro test in a patient with mitochondrial myopathy and
myoadenylate deaminase deficiency. Anesthesiology 2002; 97: 1635-7
15. Wieser T, Kraft B, Kress HG: No carnitine palmitoyltransferase deficiency in skeletal muscle in 18 malignant
hyperthermia susceptible individuals. Neuromuscul Disord 2008; 18: 471-4
16. Litman RS, Rosenberg H: Malignant hyperthermia-associated diseases: state of the art uncertainty. Anesth
Analg 2009; 109: 1004-5
17. O'Flynn RP, Shutack JG, Rosenberg H, Fletcher JE: Masseter muscle rigidity and malignant hyperthermia
susceptibility in pediatric patients. An update on management and diagnosis. Anesthesiology 1994; 80: 1228-
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18. Larach MG, Brandom BW, Allen GC, Gronert GA, Lehman EB: Cardiac arrests and deaths associated with
malignant hyperthermia in north america from 1987 to 2006: a report from the North American Malignant
Hyperthermia Registry of the Malignant Hyperthermia Association of the United States. Anesthesiology
2008; 108: 603-11
19. Burkman JM, Posner KL, Domino KB: Analysis of the clinical variables associated with recrudescence after
malignant hyperthermia reactions. Anesthesiology 2007; 106: 901-6
20. Litman RS, Flood CD, Kaplan RF, Kim YL, Tobin JR: Postoperative malignant hyperthermia: an analysis of
cases from the North American Malignant Hyperthermia Registry. Anesthesiology 2008; 109: 825-9
21. Birgenheier N, Stoker R, Westenskow D, Orr J: Activated charcoal effectively removes inhaled anesthetics
from modern anesthesia machines. Anesthesia & Analgesia 2011; 112: 1363-70
22. Mitchell LW, Leighton BL: Warmed diluent speeds dantrolene reconstitution. Can J Anaesth 2003; 50: 127-
30
DISCLOSURE
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Outcomes and the ASC: the Role of the Medical Director and Measurement
in Improving Clinical and Business Outcomes
Douglas G. Merrill M.D. MBA Lebanon, New Hampshire
Introduction
Measurements and analysis of financial and functional performance to support the achievement of individual and
organizational goals are required tools of management for any business enterprise. The use of outcomes to direct
strategic management decisions to attain goals is integral to the theory of knowledge management, a core aspect
of modern business management.1 The advent of the “learning organization” theory has grown out of the need
to respond to customer demand with rapid process improvement. Defined by one writer2 as “the process whereby
organizations understand and manage their experiences”, it includes the use of customer-focused data collection and
assessment, employee-centric management, benchmarking and best practice implementation and process re-
engineering in response to data.3 This methodology is what Argyris and Schon defined as the employees’ response
when they4
…experience a surprising mismatch between expected and actual results of action and
respond to that mismatch through a process of thought and further action that leads them
to modify their images of organization or their understandings of organizational
phenomena and to restructure their activities so as to bring outcomes and expectations
into line…
In the past 50 years, this “management by measurement” has become an integral tactic to the administration of the
health care enterprise and has stimulated the large body of literature on healthcare quality as represented by
Donabedian’s work on quality improvement.5 6These techniques are now widely applied in healthcare.7 8Indeed,
outcome measurement is critical to quality improvement.9 However, collection of data and sharing with providers so
that they can ‘experience a surprising mismatch’ is not widespread in perioperative practice. Here, we will examine
the value of such measurement and discuss the role of the Medical Director and her or his team in the management
of that data and its use in altering care, process, business and accreditation outcomes for the better. Finally, we will
discuss the potential salutary impact of measurement as a means of changing the elusive concept of the “culture” of
an institution.
The Role of the Medical Director

Inherent in this lecture is the assumption that the Medical Director serves as a leader in the ASC’s management. In
most cases, the Medical Director in an ambulatory surgery center (ASC) has long since become an integral part both
of the medical team and the business team that manages the ASC. Gone are the days we hope of the medical director
merely filling a daily role of waiting on site for the discharge of the last patient. Instead, he or she is expected to
fully participate in the creating of policies and procedures that will improve the safety of the patients and the high
quality of their surgical, anesthesia and nursing care. As well, the Medical Director is most often accountable for
decisions regarding marketing to and credentialing of surgeons, a significant part of the strategic management of the
ASC.
In this regard, the role of Medical Director shares much with that of the Chief Medical Officer of any size healthcare
enterprise. Both are charged with supporting and/or directing initiatives intended to improve the quality and safety
of care, but also to be an integral member of the business team that moves the entity towards excellence in
operational and financial performance. Strategic decisions required to create such improvement are heavily
dependent upon data access and evaluation. Too often, the Medical Director or even the CMO are not provided the
access to financial and process data necessary to advance the mission of the enterprise. It is the intent here to show
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the value of including the Medical Director in such decision making and the reason that physicians should demand
such access, if offered the opportunity to serve in such a capacity.
Evidence Based Medicine and Clinical Outcome Measurement

Two complaints raised about the directives of “Evidence-Based Medicine” (EBM) are that it stymies care innovation
by encouraging standardized practice (care pathways) and is of little value in guiding much of routine clinical
practice, because the randomized controlled trials it ‘requires’ have not or cannot be performed in many clinical
situations. However, the proponents of EBM actually stated that, “the practice of evidence based medicine means
integrating individual clinical expertise with the best available external clinical evidence from systematic
research.”10 In reality, EBM is actually a construct of expertise garnered locally, combined with the best that the
literature can offer. The cornerstone of EBM is actually its de-emphasis of ‘expert’ opinion in favor of the lessons of
local experience. The appropriate means to garner accurate local experience in a useful format is the copious
collection of outcomes in a database. Then, the application of EBM is accomplished by the careful scrutiny of those
data, assessment for trends and linkages between practice and outcome, and a resulting focus on quality
improvement efforts unencumbered by anecdote or defensiveness.11 Done well, with objective, equanimous and
open sharing of data, exchange of ideas and decisions on action followed by careful re-assessment and open
discussion of outcomes, this measurement can form the cornerstone of effective quality improvement efforts in any
perioperative environment. It is particularly useful in the ambulatory setting, where patients have relatively fewer
procedures performed, by a smaller number of practitioners and on patients that tend to have a smaller range of co-
morbidities than may be found in a hospital setting.
Requirements of Measurement
To meet the needs and to support the goals discussed here, the metrics chosen must meet certain criteria: accuracy,
risk adjustment, regular presentation to all stakeholders, and that those providers who are being held accountable for
the outcomes must actually be able to control them. As well, there must be an ongoing tailoring of the metrics to
meet changes in strategic goals of the organization.
The concept of publishing data and identifying responsible caregivers has been done with post-cardiac surgery
mortality data, but no effect upon improving outcomes was shown.12 Mortality is a complex outcome, however,
created by a multiplicity of treatment and co-morbidity factors such that simply reporting it would be unlikely to
decrease its incidence. Of course, complex measures like mortality, stroke, MI and transfers are recorded to comply
with accreditation and licensing requirements in the outpatient surgery venue, but they otherwise rarely are caused
by variation in practice nor are they – thankfully – frequent. Therefore, they have little value as metrics to guide
quality improvement in an ASC.
However, attaching names to providers’ data has been successful in this author’s practice as a means of generating
process improvement through the ‘magic’ of friendly competition that is aimed at the universal success of all team
members in the ASC. The metrics shared should include process outcomes (e.g., time in recovery room, time of
turnover, first case start on time history, etc.). Frequently that is the only type of information collected and shared
because it is easy to obtain. However, one should not shy away from true clinical outcomes. Posting PONV and
PDNV outcome data with names attached has been particularly useful as a means of reducing this negative outcome
that is so pernicious to outpatients.
Posting of identified data should be done in a protected site (the clean core, med room, etc.) in a locked “trophy
case” where patients and families cannot see it and others cannot obtain it. It should not be emailed. There will be
initial resistance to the concept of such data sharing and so it is ideal to discuss it in advance with staff and
physicians, giving an opportunity to discuss the reasons for its use. Some will feel that ‘embarrassment’ is the goal
of such sharing, but repeated public emphasis on emulation of the best, rather than to worry about past outcomes
will – over time, and in combination with improved outcomes – typically convince most disbelievers.
This approach is different from that required for de-identified or Center outcome data, such as the Center’s waiting
times, PONV rates, patient satisfaction, etc. These may be placed in a site where patients and families can see the
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information (although still in a trophy case, so it can’t be taken). Staff rightfully takes pride in accomplishment of
excellent outcomes and such transparency is of course welcomed by patients and families.
Matching chosen metrics to goals

Our goals are threefold:
A. to exceed patient and family expectations,
B. to achieve superb clinical and financial outcomes, and
C. to create high provider (surgeon and staff) satisfaction.
To accomplish these, we craft our systems and improvement processes to focus on them. Thus, the metrics we
choose to measure and share must reflect them, as well.
Surveying patient and family satisfaction is a primary means of assessing customer satisfaction in
healthcare and is related to - but may not precisely reflect - the quality of outcomes delivered.13 Given their baseline
expectation of safety in the ASC venue, patients and families value excellent service, the absence of PONV and
PDNV, and respect for their time.1415 Measures that examine their satisfaction with each stage of their care and the
people who provided it, time measures (on-time starts, accuracy in scheduling case durations, and the absence of
delays in turnover) and PONV and PDNV are appropriate to choose, to be sure that the staff are keeping patient
expectations in the forefront of their daily work.
Clinical outcomes we measure include PDNV, PONV and pain scores, and adequacy of home pain medication.
Post-operative infection, unplanned transfers, unplanned urinary catheter placement, use of opioid or benzodiazepine
reversal agents, spinal headache, failed regional or neuraxial block, and prolonged stays in the PACU are relatively
easy to measure and are significant as indicators of quality of care. Individual practitioners vary in their techniques
of care and that will result in variation on these metrics and so the process of identifying and emulating best practice
can be applied.
Financial measures include cost per case, including supplies, implants and cost of FTE. Including the latter is
reasonable to help all practitioners to concentrate on decreasing that cost over time. However, when comparing
surgeon to surgeon on same-case data, eliminating the cost of FTE is reasonable as it should be considered
equivalent, unless overtime is being routinely engendered by one or more practitioners. An exception would be if the
facility sends staff home without pay when the work is done. In that case, minutes in the O.R. should be tracked by
surgeon. Contribution margin (CM) is an excellent measure to track and useful for strategic planning as well as
focusing all on cost reduction. More than utilization, CM is a reasonable metric upon which to base allocation of
O.R. time16, but the measurement of income and expense must be absolutely dependable and should be shared solely
with the surgeon and/or department involved. The measurements of capacity and utilization, combined with cost will
generate a pathway for reducing cost while increasing capacity.17
Staff and provider satisfaction can be measured overtly by surveys, but also (for surgeons) by the case
volumes they bring to you (vs. those at competitor facilities, if you have those) and staff retention rates. Peer
reviews can be of great value in helping practitioners understand if they are outliers in comportment or collegiality.
This data is of great value in one-to-one counseling sessions.
Risk Stratification
In the simplest construct, risk stratification for clinical measures can be accomplished by categorizing outcomes by
surgical specialty. For instance, the PONV rate for an anesthesiologist or surgeon who performs pediatric cases
under general anesthesia cannot fairly be compared to the PONV generated by cataract cases done under local with
I.V. sedation or with that which is created in a practice of knee arthroscopy under epidural. As the electronic health
record (EHR) reaches more ASCs, the opportunities increase to use more, and more discrete metrics to stratify risk:
e.g., ASA status, co-morbidities, age, CPT, duration of the case, etc. These metrics can be automatically downloaded
into local and national databases from an increasing number of EHRs (see Table 1).
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Process Improvement and Benchmarking: AQI and SCOR!

As noted, measurement of the ‘right’ outcomes can lead to improvement in the quality of practice.1819 Measurement
of outcomes can reveal repetitive error in care choices, even leading to changing indications for surgery with
resulting decreases in morbidity and mortality.20 A great tool in gaining consensus for improvement of care is
benchmarking with external but similar facilities. A single ASC’s practice will most often not be large enough to
meet statistical significance when assessing trends, particularly for individual physicians.21 Using external
benchmarks can provide risk stratified targets for the individual ASC’s quality improvement when insufficient
numbers of a particular procedure or patient populations prevent identification of ‘best practice’ within the Center’s
own data. This can best be managed by joining a national database overseen by a professional society, such as
SAMBA’s SCOR! (www.scordata.org ) or ASA’s AQI (http://www.aqihq.org ), or both. The AQI has been
accepting data of all kinds for two years, with an early emphasis on administrative data but now taking clinical data
as well. SCOR! is exclusively collecting data describing outpatient surgical and anesthesia care. In SCOR!,
outcomes for individual caregivers can be monitored by the ASC, as well as aggregate reports. AQI and SCOR! are
working with several electronic health record vendors to provide direct download capability between a Center’s
system and the AQI database. SCOR! and AQI are now linked with one another, so that entry of data into SCOR!
will allow measurement against the many outpatient cases in AQI, but with stratification by similar facility size and
type (and vice versa). It is anticipated that SAMBA will provide primary oversight of reporting all ambulatory data
coming into both entities. Each is available to members of ASA and SAMBA, respectively, free of charge.
Business Decision Making

As noted above, metrics such as contribution margin should guide decisions regarding allocation of scarce resources,
including operating rooms and equipment purchases. An ASC can also make it clear to staff and physicians alike
that ‘citizenship’ metrics are as important those that indicate income to the Center (such as APCs (Ambulatory
Payment Classifications) or RVUs (Relative Value Units)) in determining the ASC’s willingness to provide
investment support. Providing resources to the practice of a surgeon who values teamwork and respects the staff is a
far safer investment than supporting a surgeon who is disrespectful of staff or patients’ time, showing up late or
without paperwork done in advance, for instance. The latter will not make a good long-term partner for the ASC.
Counseling of such a surgeon is made far easier with his or her personal data in hand.
Accreditation
The various accreditation organizations and CMS all value evidence of a cohesive quality assessment and
improvement program.22 Showing that staff are provided with individual outcomes is particularly positive in the
eyes of an inspector who is seeking evidence of a patient-centric, employee-empowered ‘just culture’. As well,
proving that an ASC’s administration is intent upon meeting its stated goals and supports this by matching metrics to
those goals is a significant positive to portray at the time of assessment. Professional ‘accreditation’ (e.g., MOCA)
should also be supported by the practitioner’s access to such data.
Culture Change
When physicians complete their residencies and embark upon careers, they have been imbued with a body of
knowledge that includes facts like medication doses and expected ranges of patient physiologic responses to
interventions. What is not always in place is the knowledge that these facts will change, and that co-workers of all
kinds can be of value in the life-long learning process so necessary to provision of excellent care. There is also little
emphasis on the need to re-assess via outcome measurement to be sure that patients respond to care in the ways we
were taught they would. In fact, for many physicians and other caregivers, it is a large leap to the conclusion that the
‘facts’ we were taught are not actually correct and that the best means to discover these new ‘facts’ is to
continuously review the literature and to monitor our local outcomes. By not emphasizing the need to “experience
surprising mismatches”, our educational process has supported anecdotal care delivery. I still have not met a newly
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graduated surgeon who does not have at least one particular “need” for an instrument or implant or O.R. table
without which he or she “cannot do” a particular procedure. Often that same procedure has been done in our facility
for years by other surgeons using the equipment we already own. I could easily cite similar examples in anesthesia
and nursing practice.
Sadly, whether due to intent, apathy or a lack of resources, and despite the general approbation afforded EBM since
the late 1990s, the monitoring of individual practitioners’ outcomes of care provision has been relatively rare over
the years. This has yielded a lack of progress in care pathway creation, discovery of best practice, and self-discovery
and accountability. At one lecture I gave a couple of years ago on the value of knowing your own PONV rate, an
anesthesiologist responded, “I don’t have to measure patient outcomes on PONV because I know I don’t have a
problem with PONV. If I did, the recovery room nurses would tell me.” After spending a few moments with that
physician afterward, I was pretty certain that no one would ever approach her with any bad news if they could avoid
it.
As Nonaka has stated, “…knowledge is justified true belief. Individuals justify the truthfulness of their beliefs based
on their interactions with the world.”23 If our interactions with the world include no information about the outcomes
of our actions, then we lack justification for our beliefs. In business, it would be unacceptable to make an investment
in a particular service line or product without an understanding of its profitability and ongoing assessment of its
performance in the market place. However, that expectation of assessment has not made its way to healthcare in a
uniform fashion. As a result, some of the safety assessment techniques long accepted in business are only nascent in
healthcare, including assessment of data and outcomes regarding practice techniques, even though these are of clear
value in improved patient safety.24
The literature on the topic of organizational culture is extensive, particularly in business but also in healthcare where
the topics of “patient-centered’, ‘change-oriented’, and ‘just culture’ behaviors and techniques are well reviewed.25
26
Inherent to all of these methodologies is the timely assessment and feedback to providers of the outcomes of their
actions, acceptance of personal responsibility in a blame-free environment, empowerment to make change in your
domain of influence, and patient-centric behavior. These all hinge on the accurate and risk-adjusted monitoring and
sharing of individual and group outcomes. In my management practice, the Holy Grail of successful change creation
is repetitive and congenial decisions to alter beliefs about medical practice ‘facts’. These moments have been
reached only when I provided data to caregivers that portray the outcomes of their actions, either in one-to-one
counseling sessions (if personal trends are negative and far outside the norm) or in a team environment. In general
and over time, providers have come to accept that data is provided to support targeted assessment and improvement,
not as a source of blame. This epiphany has often triggered the change in individual approaches to care and self-
conduct that make up the above-noted elements of a ‘positive’ culture change in even the most inveterate
‘autonomous anecdotist’.
Conclusions
The use of local outcomes combined with national benchmarking and review of the literature allows and ASC to use
the best evidence to identify best practice and to use that as a template to create care pathways. In the management
of individual patients, the evidence and pathways must be further leavened by patient choice and by the individual
practitioner’s skill and judgment. Outcome measures should be chosen to reflect the goals of the Center including
clinical, financial and ‘citizenship’ metrics. In addition to guiding best practice, the collection of outcomes can allow
the Medical Director to focus investment and process improvement projects on those care systems that yield the
most value to patients and the Center. It is the ideal tool to manage a busy and complex care delivery system.
Bill James, the noted writer, mathematician and baseball statistician, once observed that “Education is the process of
opening minds to possibilities, souls to justice, and bodies to implementation.”27 Observing our own work is the
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epitome of ‘life-long learning’ that is the attribute often cited in the definition of a physician. The difference
between children and adults, the difference between an educated and an uneducated populous is openness to or even
the ability to conceive of change. By observing the outcomes of our work, discussing them openly, and by crafting
means of improvement as a result of that data, we can educate ourselves. That education will improve the care
delivered to patients and the experience of its delivery for caregivers, and will create an environment that is the
safest and most efficient that it can be.
Table 1: Useful Outcome Metrics to Consider for an Ambulatory Surgery Center
PATIENT
Would you refer a friend or family member to use our facility if they needed surgery and could have it here?
Would you return for surgery here if you were given the choice of another facility?
How would you rate your care today? (poor, fair, average, good, excellent) – we only count “excellent” towards our
“satisfaction rate”.
Did anyone in particular provide notably excellent service to you or your family while you were here?
Did anyone in particular provide less than satisfactory service to you or your family while you were here?
Did you feel that we valued your time?
What could we do differently that would have made your experience here more positive?
FINANCIAL
Days in accounts receivable and (if a stand-alone ASC) Days Cash on Hand.
Projected vs Actual Net profit (gross income less expenditure) by week, by month, by quarter
Cost (total operating expense) per case or per 100 O.R. minutes (used and available)
Full time equivalent (FTE) per case, or per 100 O.R. minutes (used and available)
Cost per FTE (total operating expense per month/total no. of FTEs per month) – it may be useful to track both paid
hours and worked hours to elicit the burden of vacation and leaves.
Cost of supplies, implants, instruments, etc.
Total operating expenses (rolled up from Personnel vs. Non-personnel expense)
Cases per month (actual vs budgeted)
Gross charges (day, week, month, quarter, year to date)
Collection rate (budgeted vs actual)
OPERATIONAL MEASURES
Cases per day (average) – actual vs. budget (take the overall case budget and divide by 252 working days/year) –
this is a number that works well to help staff get a general sense of a ‘good day’ vs. a slow day.
Turnover time, average, same surgeon following self (“wheels out to wheels in”)
Turnover time, average, all cases
Incidence of delay: location and causes – ask Pre-op and O.R. RNs to keep a log (Excel) with delays and pre-chosen
categories (e.g., ‘patient’ would refer to patient late arrival or lack of ride; “paperwork”, “surgeon delay”,
“anesthesia delay”, “equipment or supply delay”)
Minutes patient in room (MPIR) per room per day
Minutes of operation (MOO) (skin to skin) per room per day
MOO/MPIR
Minutes from room entry to skin incision
Minutes from skin closure to room exit
Utilization (MPIR/Blocked time allocated) by service or surgeon
Case time estimation accuracy: estimates that are either too long or too short (> <15% of actual case time)
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CLINICAL MEASURES – while the list below is large (and not exhaustive), only a few should be collected in the
absence of an electronic record. The Center should choose the measures in a collective and multidisciplinary
manner. Be willing to change those decisions if little is gained by the ones chosen (e.g., occurrence is too rare).
ASA Score
BMI
Smoker – current or recent past (quit < 3mos ago)
CHF
CAD
Previous MI
AICD
Pacemaker
COPD
CRF
Previous difficult airway
OSA
Neurologic disease, pre-existing
HTN
CVA or TIA
Mental alteration pre-op
New Mental alteration PACU
On site nausea or vomiting
Post discharge nausea or vomiting
Highest pain score in PACU
Highest pain core in the first 48 hours
Did pain medication provided for home provide you sufficient relief?
Use of opioid or benzodiazepine reversal agent – OR
Use of opioid or benzodiazepine reversal agent – PACU
Use of opioid pre- or intra-op
Use of IV/IM/SQ atropine or epinephrine
Arrival in PACU with LMA or ET in place
RR below 10 in PACU
Failed intubation
Return to the OR
Re-intubation or airway device replacement
Requirement for nebulizer treatment in PACU, unplanned
Unexpected need to call or visit a physician in the first 48 hours after surgery
Unexpected admission to the E.D. or hospital in the 30 days following discharge
Infection of the wound site in the 30 days following discharge
Unexpected need for urinary catheter in the PACU
Unexpected need for urinary catheter at home
Did you experience any mental fogginess, memory loss or dizziness that lasted longer than the day of surgery?
CVA, TIA, PE or MI in the 30 days following discharge
Unexpectedly prolonged numbness or dysfunction after regional or neuraxial blockade
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1 Nonaka, I. A Dynamic Theory of Organizational Knowledge Creation. Organ. Sci. 1994; 5(1) 14–37.
2 Wang CL, Ahmed PK. Organisational Learning; a critical review. The Learning Org 2003; 10:8-17.
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Argyris C, Schon D. Organisational Learning: A theory of action perspective. 1978 Addison-Wesley, NY, NY.
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Schiff GD, Rucker TD. Beyond Structure-Process-Outcome: Donabedian’s seven pillars and eleven buttresses of
quality. Jt Comm J. Qual Imp. 2001; 27(3):169-174.
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de Lusigna S, Pritchard K, Chan T. A knowledge management model for clinical practice. J Postgrad Med.
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Kuo AMH et al. A healthcare lean six sigma system for post-anesthesia care unit workflow improvement. Q
Manage Health Care 2011; 20: 4–14.
10 Sackett DL et al. Evidence based medicine: what it is and what it isn't. BMJ 1996; 1996; 312:71.
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Ting HH et al. Quality improvement: science and action. Circulation. 2009; 119:1962-1974.
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Sequist TD, et al. Quality monitoring of physicians: linking patients’ experiences of care to clinical quality and
outcomes. J Gen Intern Med. 2008; 23(11):1784-1790.
14
Macario A. et al. Which Clinical Anesthesia Outcomes Are Important to Avoid? The Perspective of Patients.
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Saila T. et al. Measuring patient assessments of the quality of outpatient care: a systematic review. J. Evaluation in
Clinical Practice ISSN 1356-1294.
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Wachtel R and Dexter F. Tactical Increases in Operating Room Block Time for Capacity Planning Should Not Be
Based on Utilization. Anesth Analg 2008; 106:215–26.
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Kaplan RS, Porter ME How to solve the cost crisis in health care. Harv Bus Rev 2011; 89:46-52.
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Tremper KK. Anesthesiology: from patient safety to population outcomes. Anesthesiology 2011; 114:755-70.
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Shortell SM, et al. Improving patient care by linking evidence-based medicine and evidence-based management.
JAMA 2007; 298(6):673-6.
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Moonesinghe SR et al. High-Risk Surgery: Epidemiology and Outcomes. Anesth Analg 2011; 112:891–901.
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Berwick DM. Measuring Physicians’ Quality and Performance: adrift on Lake Wobegon. JAMA 2009; 302:2485-
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Garcia JL, Wells KK. Knowledge-Based Information to Improve the Quality of Patient Care. J. Healthcare
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McDonald TB et al. Responding to patient safety incidents: the “seven pillars”. Quality & Safety in Health Care.
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27
http://www.jpods.com/bill/LetterOnEducation.pdf
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DISCLOSURE
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Ultrasound-guided Regional Anesthesia for Ambulatory Patients

Meg A. Rosenblatt, M.D. New York, New York
Introduction
Outpatient surgeries now account for more than two-thirds of all surgeries performed in the United States and after
GI endoscopies, and ophthalmologic procedures, orthopedic operations (surgery of the muscle, tendon, fascia and
bursa) are the next most frequently performed .1 The advantages that regional anesthesia (RA) confers over general
anesthesia (GA), especially in the outpatient setting, are numerous. Specifically, orthopedic patients are the group
of ambulatory patients with the highest incidence (16.1%) of pain in the PACU.2 Peripheral nerve blocks (PNBs)
offer predictable intraoperative anesthesia, as well as provide analgesia into the postoperative period, the
opportunity to bypass Phase I recovery, and the avoidance of airway manipulations. Ultrasound (US) imaging
permits direct visualization of peripheral nerves, needle location and distribution of local anesthetic. The use of US-
guidance to perform nerve blocks is associated with decreased time to onset and quality of block which is equal to or
better than PNBs performed with nerve stimulator (NS) techniques, 3, 4 and the use of US facilitates the placement
of blocks in patients who are obese, may be on anticoagulants and those with challenging external anatomy.
Since the mastery of US-guided PNBs frequently does not occur during residency, their successful incorporation
into practice requires that an anesthesiologist continues to acquire skills while often having to work in a rapid
turnover environment and meet high surgeon and patient expectations. Performing US-guided nerve blocks requires
an entirely new skill set for practitioners. Firstly, one must learn to operate ultrasound equipment and then use this
to identify anatomy as it appears on a two-dimensional screen. Secondly, one must be able to simultaneously use
both hands (one holding the ultrasound transducer and the other holding the block needle), watch the display screen,
and manipulate the needle into the nerve sheath. Lastly, it is necessary to learn to identify patterns of local
anesthetic spread that are associated with optimal plexus blockade. Smith designed a learner-centered curriculum
which describes the three elements that need to be acquired. They are the use of the US equipment (management of
the machine, choice of probe, medical record documentation), scanning techniques and sonoanatomy (performing
the exam, distinguishing anatomical elements, recognizing artifacts) and sonographic needle guidance
(understanding needle/probe orientation, optimizing needle visualization). 5
Enlisting the surgeon to introduce the concept of PNBs when they offer patients their preoperative instructions will
improve patient acceptance. Local anesthetics should be chosen to minimize onset times and limit the use of GA in
order to prevent operating room delays. Meticulous follow-up until resolution of all blocks along with
communication with the surgeons can add to overall satisfaction.
Local Anesthetics and Adjuvants

Local anesthetic (LA) agents should be chosen according to the desired duration of action and the required degree of
motor blockade. An insensate extremity in a patient whose procedure may not produce much post-operative
discomfort may be at risk for injury secondary to the loss of protective reflex to pain, or place the patient at risk
secondary to a loss of proprioception—blocks of the longest possible duration are not always the wisest choice.
Whereas some practitioners combine LAs to decrease onset time while providing long duration, combining
chloroprocaine 2% and bupivacaine 0.5% causes pH changes that create a block that resembles one produced by
bupivacaine alone. Galindo concluded that mixing LAs leads to unpredictable blockade characteristics.6 Gratenstein
looked at US-guided interscalene blocks with 30 mL in 3 different solutions—mepivacaine 1.5%, bupivacaine0.5%
and a 50:50 mixture of the two, and found that mixing the short and long-acting agents does not result in a
significant difference in onset time compared with either solution alone.7 LAs diffuse into nerves and the rate of
diffusion is determined by the concentration, therefore higher concentrations of LAs result in more rapid onset of
blockade. Ropivacaine 0.75% has been shown to have similar or shorter onset times for femoral, sciatic and
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interscalene blocks, while providing significantly longer postoperative analgesia than mepivacaine and
bupivacaine.8,9 The effect of alkalinization of agents on the speed of onset of the block is unclear. It has been shown
to offer no advantage in perivascular blocks with 0.5% bupivacaine,10 but improvement in onset and quality of
analgesia in axillary blocks with 1.25% mepivacaine,11 and in femoral and sciatic blocks with 2% mepivacaine has
been demonstrated.12 Adding sodium bicarbonate to lidocaine has been shown to have no effect on the onset of
axillary block,13 and in rats it has been shown to decrease the intensity and duration of the block.14 In one study
fentanyl improved the sensory blockade achieved with an axillary block using 1.5% lidocaine, but the pH changes it
conferred delayed the onset of analgesia.15 Other studies have not shown efficacy of either fentanyl or morphine in
the improvement of onset or quality of axillary blocks.16,17 Clonidine, an α2-agonist, is known to prolong the
duration of sensory and motor blockade, particularly when added to local anesthetics of intermediate duration. One
study of 56 patients undergoing carpal tunnel release under axillary block with 1% lidocaine and varying amounts of
clonidine, showed a reduction in block onset time. However, even with doses as small as 30µg, patients experienced
sedation. More than 50% of patients were reported to fall asleep intermittently at 140 minutes after performance of
the block.18
Recently the utility of adding dexamethasone to upper extremity blocks. The addition of dexamethasone 8 mg to 30
mL mepivaciane has been shown to significantly prolong the duration of a supraclavicular block.19 Eight mg of
dexamethasone was shown to prolong the duration of action of ropivacaine (11.8 vs 22.2 hrs) and bupivacaine (14.8
vs 22.4 hrs) when added to 30 mL of local anesthetic for interscalene anesthesia.20 Tando and colleagues found no
difference in the duration of analgesia between adding 4 mg and 8 mg doses of dexamethasone to interscalene
blocks using 40mL bupivacaine.21 There exact mechanism of this prolongation of action is yet to be elucidated.
The 5 US-Guided PNBs Every Ambulatory Practitioner Needs and When to Use Them
The following is a discussion of useful blocks and their specific applications for outpatients. Mastery of the
interscalene (ISB), supraclavicular, femoral, popliteal and transverses abdominis plane (TAP) blocks will be
adequate for almost all of the needs of the anesthesiologist who has an ambulatory-based practice. Learning the
infraclavicular block may be advantageous if the practitioner will be providing continuous postoperative analgesia
after surgery of the elbow, forearm or hand. All can be performed with a linear array probe which is 13 to 16 mHz
and 25 mm wide and a 22g, 50 mm needle.
Upper Extremity US-Guided Peripheral Nerve Blocks

This author is of the belief that one needs to master only two single-shot PNBs to be able to adequately anesthetize
the entire upper extremity for ambulatory surgery—ISB and supraclavicular block. Both of these blocks can be
accomplished by learning a simple scanning technique. The patient is placed in the supine position with his or her
head flat on the bed (without pillows) and turned towards the contralateral shoulder. The region to be blocked is
sterilely prepped:22
1) Identify the carotid artery and internal jugular vein, with the probe in the horizontal position, just above
the clavicle.
2) Moving the probe laterally along the clavicle and aiming the beam caudad, towards the first rib, the
subclavian artery is identified as the next pulsatile structure that is visualized. The brachial plexus at the level of the
divisions appears as a “bag of grapes” located lateral to the artery. To perform a supraclavicular block at that level, a
22 gauge block needle is inserted in-plane (parallel to the probe), until it reaches the location that is bordered by the
subclavian artery medially, the first rib inferiorly, and the divisions of the brachial plexus superior laterally--the
“eight ball in the corner pocket” position.23 This block is ideal for all procedures of the elbow and distally. 30- 40 ml
of local anesthetic will be more than adequate to provide a block.
3) It is then possible to choose the largest of the nerves, appearing as a radiolucent circle and trace it
cephalad, as the probe is kept in the horizontal position. When the C-6 level is reached, this nerve and the others of
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the brachial plexus are seen in a vertical orientation, between the anterior and middle scalene muscles. The 22-
gauge block needle is inserted either in-plane or out-of-plane and directed towards the previously identified nerve,
within the sheath. The out-of-plane approach may be preferable to an in-plane one for practitioners who have
experience with using a vessel finder for central venous line placement. Again, 30-40 ml of local anesthetic will
provide adequate anesthesia. In a study looking at 170 patients undergoing shoulder surgery, Spence sought to
describe the ideal location to inject LA—either peri-plexus (between the middle scalene muscle and brachial
plexus), or intra-plexus (injection within the brachial plexus sheath). After injecting 30 mL bupivacaine 0.5%, they
looked for loss of shoulder abduction. Onset times and block quality were equal, but the intra-plexus blocks resulted
in statistically significantly longer block duration (2.6 hrs, p=0.03). 24
Data show that when 5mL vs. 20 ml of ropivacaine are used for in ISB combined with GA for the surgical
procedure, patients have fewer respiratory and other complications with no change in postoperative analgesia.25
More recently this group showed that with the use of US, the minimum effective analgesic volume of ropivacaine
0.5% in an ISB required to provide analgesia in the immediate post op period is 0.9mL.26 Although studies show
that much less LA can be used, the effect on the adequacy of these smaller volumes as the sole anesthetic for surgery
has not been described. Interestingly, 61 patients were undergoing US-guided ISB performed with insulated needles
for ambulatory shoulder surgery. After the needle tip was determined to be in the interscalene groove the nerve
stimulator was turned on and the lowest current eliciting a response was noted. The sensory analgesia achieved
between the groups with responses at <0.5 mA and >0.5 mA was similar, thus confirming that US-guided blocks
produce successful analgesia regardless of the motor stimulation evoked.27
The use of US has been shown to speed the execution and improve the quality of supraclavicular blocks.28 Perlas et
al described their experience with 510 consecutive US-guided supraclavicular blocks, and reported a 94.6% success
at achieving surgical anesthesia with a single attempt. Complications included symptomatic hemidiaphragmatic
paresis (1%), Horner syndrome (1%), vascular puncture (0.4%) and transient sensory deficit (0.4%). They
concluded that this US-guided block is a safe and effective technique.29 A prospective registry of 1,169 US-guided
ISB and supraclavicular blocks for shoulder surgeries shows a 0% incidence of vascular puncture, 0.4%incidence of
short-term postoperative neurologic symptoms and a 0% incidence of permanent nerve injury.30
Since Sauter used MRI to define the anatomic location of the cords of the infraclavicular brachial plexus, we know
that needle placement at the “VIII o’clock” position adjacent to the axillary artery in the cranioposterior quadrant
and observing satisfactory spread of local anesthetic between the “III o’clock and IX o’clock” positions will predict
a successful infraclavicular block.31 The use of US-guidance (with the probe in a sagital position medial to the
corticoid process and employing an in-plane technique) for single shot infraclavicular blocks yields high success
rates and trends toward improved block quality.32
Practitioners who perform US-guided axillary blocks find that there is a greater success rate for achieving surgical
anesthesia and shorter performance times than when nerve stimulation or transarterial techniques are used. 33 Thirty
to 40 ml of local anesthesia is injected to ensure circumferential spread around the axillary artery. Mccairre
described using US-guided median and ulnar nerve blocks at the wrist to provide anesthesia for endoscopic carpal
tunnel release. Through a single injection site located 5 to 10 cm proximal to the wrist crease in the anterior
forearm, both nerves are blocked under direct vision, each with 4 ml of 1.5% mepivacaine. This is supplemented
with 1-2 ml of local anesthetic at the level of incision in the wrist crease in order to block the palmaris ramus of the
median nerve.34
Lower Extremity US-guided Peripheral Nerve Blocks

US-guided blocks of the lower extremity that are useful in ambulatory practice include femoral, saphenous and
popliteal blocks. The femoral nerve is located by placing the linear probe in the inguinal crease. It is the dense
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white structure, lateral to the hypoecoic pulsatile femoral artery and deep to both the fascia lata and fascia iliaca.
This can be blocked with a 22g needle in an in- or out- of plane approach and a successful block is anticipated when
local anesthesia spread is seen surrounding the nerve. This block is particularly useful for patients undergoing
repairs of the anterior cruciate ligament or surgical procedures involving the patella. Performing a fascia iliaca
block is an alternative to the femoral nerve block, and may be more successful for blocking the lateral femoral
cutaneous nerve and occasionally the obturator nerve. A line drawn between the anterior superior iliac spine and
pubic tubercle is divided in thirds. At the junction between the middle and lateral thirds an ultrasound probe is
placed in a transverse position and the fascia lata and iliaca are identified. The needle is placed under the fascia
iliaca, and 30 ml of local anesthetic is injected. Spread of local anesthetic in medial and lateral directions under the
fascia iliaca is evidence of correct needle placement.
For surgical procedures below the knee, the sciatic nerve in the popliteal fossa can be blocked either from a posterior
or lateral approach. The posterior approach requires placing the patient in a prone position and the hyperechoic
nerve is located at the midpoint between the tendons of the biceps femoris and the semitendinosus/semimembranosis
muscles. The popliteal artery is located medial and deep to the nerve, and is an excellent landmark from which to
begin scanning superior and laterally. It is essential to identify the point of division of the sciatic nerve into the
common peroneal and anterior tibial nerves, and place the needle proximal to this point to ensure that both divisions
are blocked. US-guidance has been shown to increase success of block and decrease onset time compared to a NS
technique.35 For the lateral approach, the patient remains in the supine position and it is helpful to have the patient’s
leg placed on a bolster, with the US probe placed underneath. A 100 mm needle is inserted parallel to the probe and
directed towards the hyperechoic nerve, again insuring that it has not yet divided. For either approach, 30 ml of local
anesthetic will ensure an adequate block.
To provide complete analgesia of the lower extremity with the popliteal block, anesthesia of the saphenous
distribution (medial side of the lower extremity) is necessary. And, in order to preserve quadriceps muscle function
(which would not be possible with a femoral nerve block), the saphenous nerve can be blocked at the level of the
tibial tuberosity. This can be accomplished by locating the saphenous vein in the short axis view, and then
delivering 5 ml of local anesthesia both medial and lateral to the vessel.36 Because it may be difficult to identify the
saphenous nerve at this level, it may be easier to identify the nerve as it travels deep to the sartorius muscle, adjacent
to a descending branch of the femoral artery. With the patient’s lower extremity externally rotated at the hip, the
probe is placed perpendicular to the extremity 7 cm proximal to the popliteal crease. Using an in-plane approach, 10
ml of local anesthesia is deposited deep to the sartorious muscle anterior and superior to the artery, where the nerve
is visualized.37
US is now being used to improve the success rate of PNBs nerve blocks at the ankle. The sural nerve has been
shown to lie adjacent to the lesser saphenous vein. Redborg placed his patients in a prone position with a tourniquet
around the proximal tibia, to allow easy identification of the vein, and using a 27 gauge needle in an out-of-plane
technique, injected 5 ml of local anesthetic. The endpoint was to observe the spread of local anesthesia completely
around the lesser saphenous vein. Although the US blocks took longer to perform than anatomically based ones
(172 sec vs. 70 sec), they were considered to be denser in quality.38 She also described using US to block the tibial
nerve at the ankle. Again, patients were placed in the prone position, and the probe was placed in a horizontal plane
posterior to the medial malleolus. The nerve can be identified posterior to the posterior tibial artery. The flexor
hallucis longus tendon travels with the neurovascular structures at that level and may look like the nerve; therefore
the author suggests demonstrating motion of the tendon with movement of the great toe in order to differentiate it
from the nerve. Using 5 ml of local anesthetic and demonstrating circumferential spread around the nerve is
associated with block success.39
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Truncal Blocks
The TAP block is gaining popularity as a method for postoperative analgesia for procedures of the abdomen,
including laparoscopic appendectomy40and cholecystectomy.41 The block is accomplished by placing a linear array
probe horizontally at the T10 level and moving laterally until it is possible to identify the following abdominal
layers: skin/subcutaneous tissue, external oblique muscle, internal oblique muscle, and transversus abdominis
muscle (below which is peritoneal cavity). Using a 22 gauge block needle and an in-plane approach, 20 ml of
0.25% bupivacaine is deposited on one or both sides, depending upon the location of the surgical incisions. This
block has been shown to reduce both the intraoperative and postoperative use of narcotic analgesics. US-guidance
has also been described to place ilioinguinal and iliohypogastric blocks to provide analgesia following outpatient
inguinal herniorrhaphy. After identifying the anterior superior iliac spine, the anterior abdominal muscle layers, and
the peritoneum, a needle is inserted into the fascial plane between the internal oblique muscle and transversus
abdominis muscle. Occasionally it is possible to identify the iliohypogastric nerve. Lastly, the rectus sheath block
has been described to block the lower thoracic nerves and provide analgesia for midline incisions and procedures
around the umbilicus. Needles are inserted 5 cm above and below the umbilicus and 5 cm bilaterally, and injecting
10 ml of local anesthetic in each quadrant between the anterior and posterior rectus sheaths.42
Indwelling Catheter Techniques

For ambulatory practitioners who place indwelling catheters, US-guidance has proven to provide analgesia equal to
that achieved when a NS technique is employed, with statistically significant shorter time from needle placement
under to catheter insertion and lower catheter insertion pain scores.43 For interscalene catheters, some advocate a
posterior approach to the interscalene groove, which provides postoperative analgesia and offers the advantages of
avoidance of the external jugular vein and placement of the catheter further away from the surgical field.44 However
the use of GA is necessary since the nerves of the superficial cervical plexus and the skin around the shoulder are
not anesthetized. When placing catheters for forearm and hand procedures, an infraclavicular approach offers the
advantage of a more secure position under both the pectoralis major and minor muscles. In this position there is less
leakage around the catheter than from more superficially placed ones (i.e., supraclavicular and interscalene
catheters). And US-guided infraclavicular catheters result in higher primary block success and decreased secondary
catheter failure when compared to traditional insertion techniques.45
There are conflicting data regarding the ideal solutions for ambulatory catheters. For example, Lee found that low
concentrations of anesthetic at higher basal rate provided superior analgesia to patients with interscalene catheters.46
Conversely, Ilfeld showed that for continuous popliteal-sciatic nerve blocks, concentrated solutions of small volume
provided excellent analgesia, with a lower incidence of insensate limbs.47
Interestingly, Clendenen just reported a series of 5 cases of difficult removal of stimulating catheters placed in the
interscalene groove of ambulatory patients. In each case the polyurethane sheath sheared from stainless steel coil
and the coil was retained, requiring 4 of the patients to return to the hospital. Therefore, it may be prudent to avoid
the use of stimulating catheters in the ambulatory population.48
Patient Instructions and Follow-Up

Whenever a regional anesthetic is performed, detailed instructions must be given to the patient, 49 offering an
expectation of the duration and extent of their block, the requirement to protect the insensate limb, and the need to
begin analgesic medications prior to his/her experiencing severe pain. Timely follow-up must be conducted to
ensure complete block resolution. Borgeat specifies in his study following 521 patients after interscalene block, that
sulcus ulnaris syndrome, carpal tunnel syndrome or complex regional pain syndrome must be excluded in the
presence of persistent paresthesia, dysesthesia or pain not related to the surgery, because specific interventions may
be necessary to treat those conditions.45 Should any persistent neurologic deficit be discovered during a
postoperative interview, the patient should be reassured that it will resolve, and that the anesthesiologists’
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participation in the follow-up is certain. Discussion with the surgeon should include a plan for neurologic
evaluation.
Conclusions
The use of PNBs is associated with shortened post-procedure operating room, PACU and discharge times, provision
of postoperative analgesia, and a high level of patient satisfaction. Numerous techniques have been described in
order to provide anesthesia and analgesia for ambulatory surgical procedures. The introduction of US into the
practice of regional anesthesia offers new and exciting challenges for today’s regionalists. Regional techniques
should be both encouraged and employed for procedures in outpatients.
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DISCLOSURE
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Office Based Anesthesia: Success and Challenges

Rebecca S. Twersky, M.D., MPH Brooklyn, New York
Introduction
Office-based surgery (OBS) accounted for 10 million of all elective procedures performed in the United States,
doubling over the past decade. Although there are no good national registries to accurately determine the amount of
surgery done in office, the projections have ranged from 17-24% of all elective ambulatory surgery [1,2]. This
phenomenon has paralleled and was certainly driven by the huge increase in demand for cosmetic surgery over the
past ten years. Newer surgical and anesthetic techniques have allowed more invasive procedures to be performed in
non-hospital settings. Economic advantages and physician and patient convenience have driven the rapid growth of
OBS and office-based anesthesia (OBA). Other advantages of OBS include ease of scheduling, greater privacy,
lower cost, no risk for nosocomial infection, increased efficiency, and consistency in nursing personnel [3]. Despite
these advantages, OBS is not for every surgeon nor is it appropriate for every patient or every surgical procedure. In
addition, OBA requires a different approach than that is used in hospitals and ambulatory surgery centers (ASCs).
This venue may not be suited for all anesthesia providers. The rapid growth of OBA has not been uniformly
accompanied by adherence to safety standards used in hospitals or ASCs. This lecture will address the current status
of OBA from recent reports and challenges faced by the office-based anesthesiologists relative to patient safety,
patient and procedure selection, and anesthesia management for adult patients.
Facility Considerations
Is OBS/OBA as safe as that is done at hospitals or ASCs? Media coverage of high profile liposuction deaths and
other tragic mishaps exposed OBA as the “Wild, Wild West of Health Care” [4]. Such press is more powerful than
the medical literature in the minds of patients. Lack of regulatory oversight of OBA is the fundamental difference
between OBS and surgery done at hospitals or ASCs. With minimal safety standards, OBS may be performed in an
environment with limited or outdated equipment, inadequate emergency resources, too few qualified healthcare
providers, or insufficient policies and procedures. In addition, quality of care plans for performance improvement,
peer review and emergency preparedness are often lacking in OBS. Office personnel may be untrained and
providers of anesthesia care may have varying levels of skill – ranging from physician anesthesiologists, nurse
anesthetists, surgeons, dental anesthetists, to personnel without anesthesia training. Only 2% of Anesthesiology
residency programs provide formal training in OBA leaving a void in properly educating anesthesiologists on how
to prepare themselves for offices [5].
In response to this gap, ASA has established a framework from which clinicians can establish their own practice.
The ASA Guidelines for OBA underscore that the level of care in an office should be equal to that in a hospital [6].
Together with the ASA guidelines, the ASA-SAMBA OBA Manual on Office Based Anesthesia: Considerations
for Anesthesiologists in Setting Up and Maintaining a Safe Office Anesthesia Environment has addressed major
administrative and clinical aspects on OBA such as facility and safety, quality improvement and professional
liability, controlled medications, practice management, patient and procedure selection, perioperative care,
monitoring and equipment, pediatric and dental anesthesia, emergencies and transfers [7]. All ASA documents are
relevant to OBA practice, with 12 in particular very relevant (www.asahq.org/publicationsAndServices/sgstoc.htm
accessed May 25, 2012).
Anesthesiologists must examine each practice with vigilance, and discuss with surgeons about steps needed to
provide safe perioperative care. Before agreeing to provide anesthesia, anesthesiologists should allow time to inspect
the office and evaluate the anesthesia work area and space requirements with focus on adequacy of facility design,
medication, equipment and supplies, perioperative patient flow, hospital transfer arrangement, emergency equipment
and protocols, competency and designated responsibilities of staff including credentialing and licensure of providers,
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malpractice coverage, and ongoing peer review and quality assurance (Table). The practice should comply with all
applicable federal, state and local laws, building codes and regulation. Environmental safety features that are often
taken for granted should be verified in the office. These include fire safety, air handling, electrical systems and
alternate back-up power, inspection and preventive maintenance of all operative equipment, setup and maintenance
of medical gases, handling of controlled drugs, equipment disinfection and biohazardous waste and sharps [8].
The OBS infrastructure should support the safe delivery of anesthesia and surgery. In particular, anesthesiologists
and surgeons need to come to terms of agreement regarding the clinical and fiscal responsibilities of common
aspects of the practice. No anesthesiologist should provide services for a facility that demonstrates disregard for
standard of care for surgery, anesthesia and nursing care. Anesthesiologists would set a high bar for safety if they
practice only in accredited or licensed facilities. When not accredited, their anesthetic practice should at least reflect
accreditation and professional society standards. Anesthesiologists can distinguish themselves by assisting the
practice in becoming accredited.
Rules/Regulations/Accreditation
Improved state regulations may help to address patient safety problems in OBA, however, there are still many states
lacking any type of oversight of OBS/OBA and the regulations vary significantly from state to state. At present, 29
states have statutes, regulations or guidelines regarding OBA, and several states also require the reporting of adverse
events (www.asahq.org/Washington/rulesregs.htm,
www.fsmb.org/pdf/GRPOL_Regulation_Office_Based_Surgery.pdf accessed May 10, 2012). Accreditation is
another option to address OBA patient safety and is voluntary in most US states. Many third-party payers will only
reimburse the facility fee for procedures performed in accredited offices. Medicare reimburses professional fees but
not facility fees. Accreditation of office-based practices is conducted by three major accrediting organizations: The
Joint Commission (TJC, http://www.jointcommission.org/ accreditation/ accreditation_main.aspx), The
Accreditation Association for Ambulatory Healthcare (AAAHC, http://www.aaahc.org/en/accreditation/office-
based-surgery-centers/), and the American Association for Accreditation of Ambulatory Surgery Facilities
(AAAASF, http://www.aaaasf.org/pub/site/index-4.html) similarly address key components of OBS, however, they
differ in their requirements for adverse event (AE) reporting, peer review process, credentialing and privileging of
practitioners without hospital privileges and enforcement [9]. In addition, the American Medical Association (AMA,
www.ama-assn.org/ama/) identifies 10 core principles for establishing safety standards in offices, which has been
embraced by medical specialties and state medical boards.
Practice Management
Successful OBA practices hinge on certain business sense, even more so than in other venues. Anesthesiologists that
assume a management role will be in a better position to align the financial incentives of surgeons with
anesthesiologists. Providing extra services includes helping with facility operations, providing drugs and supplies,
staffing, and/or helping with accreditation issues, or including everything as a “turn-key” approach. Competition
will dictate which services to provide and how much to charge for them. Anesthesiologists should be sensitive to
potential kickback issues in connection with providing extra services and ensure that they receive fair market value
compensation for the extra services they provide, not a “bonus”. Examples of problematic practices include
providing services at below-market rates or paying above-market rates to rent an office in the surgeon’s building.
Whether or not providing anesthesia drugs/supplies would be deemed to be an illegal kickback depends upon the
intent of the parties, and whether or not the person providing anesthesia drugs/supplies received fair market value
payment for such items [7]. Understanding federal and state regulations affecting anesthesia practice and billing
prior to starting an OBA practice is essential. Legal counsel should be sought where appropriate. Probably one of the
best known federal laws is Stark II which prohibits physicians from making referrals to an entity that they, or a
family member, has financial interest in. Other legal issues to consider are exclusive contracts with hospitals, which
may contain non-compete clauses [7].
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Payment for services rendered is a key component of a successful OBA practice. There is no one single model for
reimbursement of anesthesia services, allowing each practice to determine the optimum arrangement. Billing for
anesthesia services should be clear to all participating parties during initial negotiations to provide service. The
anesthesia provider will need to decide which method to bill for its services and how much to charge.
Patient Safety in Office-Based Anesthesia

Notwithstanding the often-repeated advantages, death rates associated with OBA still precipitated significant
professional and public concern about the level of safety in this setting. Quality and safety in anesthesia is usually
monitored by analysis of perioperative morbidity-mortality (M & M) and incidents. Patient perioperative M & M
are not always related to anesthesia. Incidents largely rely on the willingness of staff members to report them. Most
of the earlier reports are surveys, questionnaires or chart review based on limited populations and small sample
sizes. Often the definitions for M&M are different (e.g. 24 hrs, 7-30 days). To date, the largest QI database (over 1
million outpatient procedures) from accredited facilities reports a mortality rate of 0.002%, with PE the most
common cause of death (56.5%) [10]. In reviewing ASA closed claims analysis of 63 office-based claims 1990-
2009, Domino reported that the severity of injury for office-based claims was greater than for other ambulatory
anesthesia claims: 40% of office-based claims were for death, compared to 25% of ambulatory anesthesia claims.
Respiratory events airway obstruction, bronchospasm, inadequate oxygenation-ventilation and esophageal intubation
were the most frequent (29%), with the trends in complications changing. There has been a reduction in the claims
for medication error yet nearly three-fold increase for equipment reasons (17%) [Personal communication,
K. Domino, MD, MPH May 2012]. These events were judged to be preventable by monitoring, especially in the
postoperative period [11]. This report points to several areas for improvement relevant to office based anesthesia
safety: oversedation during MAC with failure to recognize and treat respiratory depression in a timely fashion,
hazards of anesthesia in nonoperating room locations, prevention of cautery-induced burns, and management of the
difficult airway particularly at extubation. Analysis of these rare events can improve practice and patient safety [12].
Data derived from the Florida Board of Medicine report causes of death due to poorly-trained personnel, inadequate
resuscitation equipment, deep venous thrombosis (DVT)/pulmonary embolus with inadequate prophylaxis, local
anesthetic overdose, airway mishap, and or failure to vigilantly maintain the same anesthetic monitoring techniques
used in the ASC or hospital [13]. More recent published reviews of the 10 years of prospective, independently
collected verifiable data on office surgery mortality in Florida concluded that office and other outpatient surgery are
safe if performed in an accredited facility by American Board of Medical Specialties, certified surgeons who are
credentialed for the same procedures in a hospital [14]. An NIH-funded conference concluded that evidence speaks
to the safety of OBS with even lower rates of adverse events and mortality (adverse event rate of 0.24/100,000 and
death rate of 0.41/100,000 procedures)[15]. This is supported further by Fleisher et al., in a comparative study of
outcomes in Medicare patients (> 65 yrs) by location of ambulatory surgery. They reported a death rate on day of
surgery /100,000 procedures of zero in offices, compared to 2.3 deaths in ASCs and 2.5 in hospital-based units.
Comparative admission rate/1000 procedures were 91 in office-based settings 8.4 for ASCs, and 21 in the hospital-
based ambulatory setting [16]. An extensive review of patient safety in OBS identified risk factors for adverse
events [17], urging more prospective research.
Anesthesiologists’ Role in Patient Safety

Much of the work on patient safety is reported from dentistry and oral and maxillofacial surgery, and focuses on
surgical outcomes, with almost no mention of anesthetic complications such as nausea and vomiting, pain, delayed
discharge, patient satisfaction or post-discharge symptoms. Recent data compiled from the SAMBA Committee on
OBA reported outcomes and complications in a database of 50,520 OBA cases from 6 practices for 2008-10. Deep
sedation without an airway device accounted for 84% of cases. Only 6% of cases required intubation, most from a
single, primarily dental OBA practice. Overall complication rates were very low with cancelations being the most
frequent event (3.3%). This higher rate than ASCs reflects more conservative approach for safe practice. The rates
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for minor complications were all below 1%. Unplanned admission rates were 0.07%. Of note, there were 11
incidents of medication error, 4 aspirations, 2 wrong site surgeries, and 2 patients discharged without escort. No
deaths were reported. These sites showed that OBA compared favorably with safety and outcome data from
ambulatory, hospital-based practices [18, personal communication Michael T. Walsh, MD, May 2012]. An OBA
specific checklist has been tested in several office sites and was reported to improve safety, documentation, and
assessment of patient satisfaction [19]. It is anticipated that with more participation in anesthesia registries, i.e.
SAMBA Clinical Outcome Registry (SCOR) (http://www.scordata.org) and ASA Anesthesia Quality Institute (AQI)
Data Registry (http://www.aqihq.org) comparative benchmarks of anesthesia outcomes will become available.
The challenges for anesthesiologists are to collaborate with their surgical colleagues to improve the culture of safety
including educating patients to seek out the safest venue to have their surgery. The ASA-SAMBA OBA Manual
serves as a good companion for a quality driven and patient-safety oriented practice [7]. Familiarity with
professional guidelines of OBS specialties is helpful to ensure consistency with our clinical approach.
Anesthesiologists should actively participate in the OBS quality improvement (QI) plan. A review of anesthesia and
surgical morbidity and "adverse" or "sentinel" or outcome events should be integral to the plan. Examples include
patient deaths within 30 days, postop infection, transferring to a hospital/ ED for more than 24 hours, unscheduled
hospital admission within 72 hours of procedure, wrong site surgery or other serious or life threatening events [7].
AE reporting should be standardized and registered on a national level to allow risk assessment by large scaled
studies. The low rate of anesthesia AE can be attained by ensuring trained anesthesia providers; careful patient
selection; utilizing full preoperative evaluation, intraoperative care and monitoring consistent with ASA standards;
and sufficient postoperative care to enable safe discharge.
Facility Readiness
As different anesthesiologists and surgeons might be providing care in the same offices on either a rotating or
permanent basis, all personnel, should be properly oriented to policies, procedures, physical layout, and the location
of emergency equipment. Facilities must establish written protocols for emergency management of rare but
catastrophic events and conduct regular drills that include the anesthesiologists and surgeons. Critical management
of emergencies most likely will require stabilization of the patient and quick transfer of the patient to an acute care
facility [7,20]. Anesthesiologists should be comfortable with the qualifications of surgeon providers, especially
when performing the newer high-tech procedures. The office must be equipped to deliver positive pressure
ventilation with self-inflating ambu-bag and there must be an identifiable source of oxygen. Suction may be
delivered via a portable or installed system. All anesthesia equipment should have a reliable back-up power source
in the event of equipment failure. Functioning resuscitation equipment and defibrillator, emergency airway
equipment, ACLS drugs and trained personnel must be available in the event of any emergency. Dantrolene must be
readily available to treat MH if triggering anesthetics are used [21]. Equipment should be maintained and inspected
according to manufacturer’s specifications. There should be sufficient space to accommodate all the necessary
equipment, adequate lighting and expeditious access to the patient. In locations administering only local anesthesia,
Intralipid 20%, other appropriate drugs, monitors and equipment should be on hand in the event of untoward
reaction [7]. Patients receiving oxygen under MAC for facial procedures are at risk for surgical fires and
anesthesiologists should take precautions to reduce airway fires [22].
Patient Selection
As with all ambulatory anesthesia venues, not all patients or procedures are suitable for the office setting. When
evaluating patients to determine suitability for office procedures, surgeons should be alerted to those high risk
medical conditions. that would exclude patients from OBA. Criteria of excluding patients from OBA include
unstable ASA 3 or greater, MI within 6 months; severe cardiomyopathy; uncontrolled HTN; brittle or poorly-
controlled diabetes mellitus; active multiple sclerosis; acute substance intoxication (drugs and alcohol); history of
malignant hyperthermia (MH); morbid obesity with poorly controlled comorbidities, severe COPD or obstructive
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sleep apnea, pacemaker or AICD, end-stage renal disease, sickle cell disease, patient on transplant list, dementia (not
oriented), psychologically unstable (rage/anger problems), stroke within 3 months, myasthenia gravis or lack of
adult escort [20,23,24]. A list of exclusions from OBA should be shared with surgeons, and screening questionnaires
should be completed by patients. Office staff should confirm suitability of the patient for this venue and forward all
evaluations to be reviewed by anesthesiologists, preferably before the day of surgery.A review of prescription, non
prescription drugs and use of herbal and dietary supplements are important as drug interactions may occur.
Preoperative tests and consultations should be requested when indicated. Anesthesiologists, assuming the role of
medical consultant, remain the best qualified professional to evaluate patients’ overall risk for OBA. However, since
most patients are seen for the first time by anesthesiologists on the morning of the procedure, surgeons must ensure
that patients have been adequately evaluated and undergone appropriate preoperative testing beforehand.
Oftentimes, this falls to the office staff, which needs clear direction from the surgeon providers.
Good communication between surgeons and anesthesiologists is crucial in determining accurate risk for patients
with older age or comorbidities. Surgeons should screen patients for potential difficult airway and the need for
further medical optimization. OBS staff should also ensure that patients receive proper preoperative instructions
regarding NPO and continuation of any chronic medications. The office surgeons should pay specific attention to
instructions for discontinuation of antiplatelets or other anticoagulation treatment; or whether perioperative
antibiotics are need, as the anesthesiologists will only evaluate the patient face-to-face on the morning of surgery.
Types of Procedures
OBA procedures should be of duration and degree of complexity that will permit patients to recover and be
discharged from the facility as soon as possible. Anesthesiologists should ensure that OBA procedures are within the
scope of the physician’s practice as well as the capabilities of the facility. As several OBA procedures are not
commonly done in the hospitals or ASCs, anesthesiologists must familiarize themselves with the physiological and
anesthetic implications of the newer and technologically updated surgical procedures. Among the procedures
considered appropriate for OBA are cosmetic surgeries (liposuction, rhytidectomies, breast augmentation/reduction,
and rhinoplasty), ophthalmology, dental, gynecology, orthopedic, urologic and GI endoscopies. Procedures with
potential risk of significant blood loss such as major intra-abdominal, intrathoracic and intracranial surgeries are
inappropriate for OBA [8, 23,25]. There are few prospective studies about using duration of surgery as a predictor of
adverse outcomes and results are still controversial. Some recommended that procedures not to exceed 6 hours to
decrease the risk of hypothermia and DVT, especially during high volume liposuction (> 5000 ml) combined with
other procedures [25, 26]. However, duration of surgery and anesthesia was not demonstrated to be an indicator of
patient morbidity and mortality in facial plastic surgery performed on 1200 patients lasting more than 4 hours in an
accredited OBS facility with board certified anesthesiologists [27].
Perioperative Care
The definition of appropriate level of anesthesia remains debatable in the non-anesthesia literature, though several
publications identify it as any safe technique provided by appropriate anesthesia professional in accredited facilities
[10, 28,29]. However, there is no one preferred technique. Choice of agents and techniques should be appropriate to
patients’ health and surgical procedures, the equipment, which might depend on whether the platform in the office is
fixed or mobile; and whether it allows a rapid recovery to normal function with minimal postoperative pain, nausea
and other side-effects. The same anesthetic techniques that are used in hospitals and ASCs can be used in OBA
(including local, monitored anesthesia care or MAC, regional or general anesthesia). MAC with or without local
anesthesia is more commonly used [30-33], though with increasing complexity there is growing demand for general
anesthesia (GA). GA may be preferable in complex or extended procedures because of safety provided by airway
protection, consistent level of anesthesia and the ability of allowing surgeons to concentrate on procedures.
Commonly utilized sedatives and anesthetics include midazolam, ketamine, fentanyl and propofol, either alone or
combined. IV Acetaminophen ,ketorolac, IV Ibuprofen, and other nonsteroidal anti-inflammatory agents (NSAIDs)
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can be used as adjuvant non-opioid analgesics. Sevoflurane and desflurane are used for inhalation anesthesia [34-
36]. Adjuvant treatment with clonidine or dexmedetomidine has been reported to be beneficial in plastic surgery
procedures [37]. In general, opioid use is minimized and substituted with generous use of local anesthetic and
NSAIDs to augment analgesia through the recovery period and avoid opioid-induced postoperative nausea and
vomiting (PONV).
For GA, some practitioners prefer total intravenous anesthesia (TIVA) over inhalation agents for several reasons:
lack of capacity to deliver inhalation agents or nitrous oxide and need for adequate waste scavenging system;
avoidance of MH-triggering agents that would otherwise require the immediate availability of Dantrolene; improved
infusion pumps and computerized TIVA delivery systems. TIVA for OBA generally consists of propofol, preferably
with none or minimal opioids, with spontaneous or assisted patient ventilation, either with or without laryngeal mask
airway or other supraglottic device. Avoiding muscle relaxation permits muscle tone in the extremities which can
reduce DVT and subsequent PE. Generally, muscle relaxants and endotracheal intubation are used sparingly,
although airway equipment for intubation must always be available during all cases of GA. It is important that the
equipment and machines used are maintained, tested and inspected on a regular basis and not become a repository
for obsolete equipment (http://www.asahq.org/For-Members/Standards-Guidelines-and-Statements.aspx
ASA_Publications_-_Anesthesia_Machine_Obsolescence_-_2004[1].pdf, accessed May 11, 2012). The bispectral
index (BIS) system has been used in OBA to guide timing of intubation without neuromuscular blockers [38].
Office-based practice, perhaps even more than others, has zero tolerance for PONV. Therefore, interventions against
PONV should be aggressively implemented [39]. My recipe for OBA is premedication with antiemetics,
intraoperative use of long acting local anesthetics, use of anesthesia agents that minimize PONV and pain and target
toward a rapid emergence and ambulation. Multimodal approaches that use multiple drugs and combinations of
techniques to improve pain relief and minimize side effects are growing in popularity [40]. Clinical studies have
shown preoperative oral or intravenous co-administration of acetaminophen or nonsteroidal anti-inflammatory drugs
(NSAIDs) can decrease the use of opioids and opioid-related adverse effects and can be safely used for the treatment
of postoperative pain after ambulatory surgery [41-43].
Patients must transition through the standard postoperative care following OBA regardless of the type of office
procedure. Traditional stretchers are not used in the office setting; therefore patients must transfer directly from the
operating table to a lounge chair, wheelchair or walk with assistance to the designated recovery area. While the
objective is to have the patient fully awake to walk off the stretcher, sometimes this is not feasible, given patients’
diverse age and baseline condition [44]. Nonetheless, fast-tracking patients are met by selecting an intraoperative
anesthetic technique that maximizes rapid emergence with minimal side-effects. Postoperative recovery of patients
in the office should be provided by a qualified PACU nurse, freeing up the anesthesiologists to return to the
procedure room; although the anesthesiologists should remain responsible for overall postoperative recovery and
discharge. Discharge criteria for the office setting should use the same standards as for all ambulatory surgery
settings.
Conclusion
OBA has undergone tremendous growth in the last ten years and is slowly becoming regulated and standardized.
As technology progresses, surgical techniques become less invasive and more cost conscious. Office-based facilities
will continue to perform more outpatient procedures. While safety has been questioned in the past, most OBA is
probably safe when performed by properly trained physicians working within their scope of practice and following
the standards and guidelines developed by professional societies. We should continue to advocate for outcomes
registries, uniform reporting of adverse events (AEs), allowing proper analysis and ongoing assessments of patient
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outcomes. In the hands of skilled professionals, and with proper patient selection and perioperative care,
anesthesiologists can serve as pivotal leaders in ensuring that OBA can be as a safe as those done at hospitals or
ASCs.
References:
1. AHA, TrendWatch issue from July 2006. The Migration of Care to Non-hospital Settings: Have Regulatory
Structures Kept Pace with Care Delivery?
http://www.aha.org/research/reports/tw/twjuly2006migration.ppt#256,1 (Accessed May 31, 2012)
2. AHA. Trendwatch Chartbook 2011.Trends affecting hospitals and health systems Chapter 3: Utilization and
Volume, p.36. Available at: http://www.aha.org/research/reports/tw/chartbook/2012/chart3-14.ppt. (Accessed
May 31, 2012).
3. Byrd HS, Barton FE, Orenstein HH, et al. Safety and efficacy in an accredited outpatient plastic surgery
facility: A review of 5316 consecutive cases. Plast Reconstr Surg 2003; 112 (2) 636-641.
4. Quattrone MS. Is physician office the wild, Wild West of health care? J A mbul Care Manage 2000;23:64.
5. Hausman LM, Levine AI, Rosenblatt MA: A survey evaluating the training of anesthesiology residents in
office-based anesthesia. J Clin A nesth 2006; 18 (7): 499-503.
6. ASA Guidelines for office-based anesthesia. Affirmed on October 19, 2009. Available at:
http://www.asahq.org/Home/For-Members/Clinical-Information/Standards-Guidelines-and-Statements
(Accessed May 2012)
7. Twersky RS et al. ASA Committee on Ambulatory Surgical Care and the SAMBA Committee on Office-Based
Anesthesia. Office-based Anesthesia: Considerations for Anesthesiologists in setting up and maintaining a safe
office anesthesia environment. https://ecommerce.asahq.org/p-319-office-based-anesthesia-considerations-in-
setting-up-and-maintaining-a-safe-office-anesthesia-environment.aspx (Accessed May 2012).
8. Kurrek MM, Twersky RS. Office-based anesthesia: how to start an office-based practice. A nesth Clin
2010;28(2):353-67.
9. Kurrek MM, Twersky RS. Office-based anesthesia. Can J A nesth 2010;57:256-272.
10. Keyes G, Singer R, Iverson R, et al. Mortality in Outpatient Surgery. Plast Reconstr Surg 2008; 122: 245-250.
11. Domino KB. Office based anesthesia: Lessons learned from the closed claims database. ASA Newsletter
2001; 65(6): 9-11. Available at: Closed Claims: Office-Based Anesthesia: Lessons Learned Accessed May 25,
2012.
12. Metzner J, Posner KL, Lam MS, et al. Closed claims’ analysis. Best Pract Res Clin A nesthesiol
2011;25(2):263-76.
13. Vila H, Soto R, Cantor AB, Mackay D. Comparative outcome analysis of procedures performed in physician
offices and ambulatory surgery center. A rch Surg 2003; 138: 991-5.
14. Starling J 3 rd, Thosani MK, Coldiron BM: Determining the safety of office-based surgery: What 10 years of
Florida data and 6 years of Alabama data reveal. Dermatol Surg 2012; 38: 171-7.
15. Balkrishnan R, Hill A, Feldman SR, Graham GF: Efficacy, safety and cost of office-based surgery: A
multidsciplinary perspective. Dermatol Surg 2003; 29(1): 1-6.
16. Fleisher LA, Pasternak LR, Herbert R, et al. Inpatient hospital admission and death after outpatient surgery in
elderly patients. A rch Surg 2004; 139 (1):67-72.
17. Lorincz CY, Drazen E, Sokol PE, et al: Research in Ambulatory Patient Safety 2000–2010: A 10-Year Review.
Chapter IV:Ambulatory safety in office-based surgery and anesthesia research. p 51-56. American Medical
Association, Chicago IL 2011. Available at: www.ama-assn.org/go/patientsafety. Accessed May 2012
18. Walsh MT, Kurrek MM, Desai M. Anesthesia outcomes in office-based anesthesia. Proceedings of the 2010
Annual meeting of the American Society Anesthesiologists. A798.
19. Rosenberg NM, Gallagher S, Stenglein J, Urman RD, Shapiro FE The effects of a customizable, office-based
surgical safety checklist on the rates of key patient safety indicators.” IARS May 2012 Poster S-03,
Ambulatory Anesthesia.
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20. Ahmad S. Office based-is my anesthetic care any different? Assessment and management. A nesth Clinics
2010;28(2):369-84.
21. Larach MG, Dirksen SJ, Belani KG et al: Creation of a Guide for the Transfer of Care of the Malignant
Hyperthermia Patient from Ambulatory Surgery Centers to Receiving Hospital Facilities. Anesth Analg 2012;
114: 94-100.
22. Caplan RA, Barker SJ, Connis RT et al. Practice Advisory for the prevention and management of operating
room fires: Anesth 2008; 108:786-801.
23. Vila, H, Desai M, Miguel R “Office-Based Anesthesia” In: Twersky RS, Philip BK, eds. The Ambulatory
Anesthesia Handbook, 2nd edition. New York: Springer, Inc, 2008, p 283-324.
24. Iverson RE, Lynch DJ, Twersky RS and the ASPS Task Force on Patient Safety in Office-Based Surgery
Facilities. Patient safety in office-based surgery facilities: II. Patient Selection. Plast Reconstr Surg 2002; 110:
1785-90.
25. Iverson RE, Twersky RS, and the ASPS Task Force on Patient Safety in Office-based Surgery Facilities. Patient
safety in office-based surgery facilities: I. Procedures in the office-based surgery setting. Plast Reconstr Surg
2002; 110:1337-42.
26. Iverson RE, Lynch DJ, and the ASPS Committee on Patient Safety. Practice advisory on liposuction. Plast
Reconstr Surg 2004; 113(5):1478-90.
27. Gordon NA, Koch ME: Duration of anesthesia as an indicator of morbidity and mortality in office-based facial
plastic surgery: A review of 1200 consecutive cases. A rch Facial Plast Surg 2006; 8: 47-53.
28. Hoefflin SM, Bornstein JB, Gordon M. General anesthesia in an office-based plastic surgery facility: a report on
more than 23,000 consecutive office-based procedures under general anesthesia with no significant anesthetic
complications. Plast Reconstr Surg 2001; 107: 243-51.
29. Blake, D. Office-Based Anesthesia: Dispelling Common Myths. A esthetic Surg J 2008; 28:564–570.
30. Badrinath S, Avramov M, Shadrick M. The use of a ketamine-propofol combination during monitored
anesthesia care. A nesth A nalg 2000; 90: 858-862.
31. Jourdy DN, Kacker A: Regional anesthesia for office-based procedures in otorhinoloaryngology. Anesthesiol
Clin 2012; 28: 457-68.
32. Olabi NF, Jones JE, Saxen MA et al. The use of office-based sedation and general anesthesia by board certified
pediatric dentists practicing in the United States. Anesth Prog 2012; 49: 12-7.
33. Hausman LM, Eisenkraft JB, Rosenblatt MA. The Safety and Efficacy of regional Anesthesia in an office-based
setting. J Clin A nesth 2008; 20 (4): 271-5.
34. Shapiro FE. Manual of office-based anesthesia procedures, ed. Lippincott Williams & Wilkins: Philadelphia,
PA, 2007, p.40-51.
35. Tang J et al. Use of propofol for office-based anesthesia. Effect of nitrous oxide on recovery profile. J Clin
A nesth 1999; 11: 226-230.
36. Tang J, White PF, Wender RH, et al: Fast-track Office Based Anesthesia: A comparison of propofol vs.
desflurane with antiemetic prophylaxis in spontaneously breathing patients. A nesth A nalg 2001; 92: 95-99.
37. Taghinia AH, Liao EC, May JW Jr. Randomized controlled trials in plastic surgery: a 20-year review of
reporting standards, methodologic quality, and impact. Plast Reconstr Surg. 2008; 122 (4):1253-63.
38. Messieha ZS, Guirguis A, Hanna S. Bispectral index monitoring (BIS) as a guide for intubation without
neuromuscular blockade in office-based pediatric general anesthesia: a retrospective evaluation. A nesth Prog
2011; 58(1):3-7
39. Tang J, Chen X, White PF, et al: Antiemetic prophylaxis for office-based surgery; are the 5-HT3 receptor
antagonists beneficial? A nesthesiology 2003; 98(2): 293-8.
40. Elvir-Lazo OL, White PF. The role of multimodel analgesia in pain management after ambulatory surgery. Curr
Opin A nesthesiol. 2010;23(6):697-703
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41. Wininger SJ, Miller H, Minkowitz HS, et al: A randomized, double-blind, placebo-controlled, multicenter,
repeat-dose study of two intravenous acetaminophen dosing regimens for the treatment of pain after abdominal
laproscopic surgery. Clin Ther. 2010;32(14):2348-69
42. White PF, Tang J, Wender RH, et al. The effects of oral ibuprofen and celecoxib in preventing pain, improving
recovery outcomes and patient satisfaction after ambulatory surgery. A nesth A nalg. 2011,112(2):323-329
43. Bookstaver PB, Miller AD, Rudisill CN, et al. Intravenous ibuprofen: the first injectable product for the
treatment of pain and fever. J Pain Res. 2010,25;3:67-79
44. Twersky RS, Sapozhnikova S, Toure B. Risk factors associated with fast-track ineligibility after monitored
anesthesia care in ambulatory surgery patients. A nesth A nalg 2008;106(5):1421-6.
Table . Office-based Anesthesia Checklist
 Facility design:
Date
Completed
Comments
• Sufficient work and storage areas

• Recovery area
• Meets building codes
• Sufficient electrical outlets
• Backup power
• Visual access to patient at all times during
surgery/proper lighting
 Equipment and supplies:

Date
Completed
Comments
• Procurement of anesthesia medications

• Reliable O2 source with backup
• Adequate source of suction and catheters
• Self-inflating (Ambu) resuscitation bag capable of
administering at least 90 percent O2 with back-up bag
• Appropriate sized airways; laryngoscope blade,
masks/LMAs
• Communication device (telephone, intercom within
reach)
• Scavenging system for waste gas
• BP, EKG, stethoscope, pulse oximeter, capnogram
• Functioning resuscitation equipment and defibrillator
• Emergency cart/airway equipment/ACLS drugs for
population(s) served (i.e., adult, pediatric)
• Dantrolene when using triggering agents
 General preparedness:
Date
Completed
Comments
• Credentialed and licensed MDs, malpractice coverage

• ACLS and/or pediatric ACLS trained staff on premises
until patient discharge
• Hospital transfer agreement
• QA policies/initiatives and peer reviews
Adapted from Twersky RS, Philip BK, eds. The Ambulatory Anesthesia Handbook, 2nd edition. New York:
Springer, Inc, 2008 with permission.
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DISCLOSURE
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Effective Management of Pain, Postoperative Nausea and Vomiting and

Opioid Related Side Effects in Ambulatory Surgical Patients
Tong J. Gan, M.D., M.H.S. Durham, North Carolina
Postoperative nausea and vomiting (PONV) and pain are two of the most common and unpleasant side effects
following anesthesia and surgery. Although both are predictable part of the postoperative experience, inadequate
management of these symptoms is common and can have profound implications. Unrelieved postoperative pain may
result in clinical and psychological changes that increase morbidity, mortality, costs as well as decrease quality of
life and potentially increase the incidence of chronic pain1. Negative clinical outcomes resulting from ineffective
postoperative pain management include deep vein thrombosis and pulmonary embolism, coronary ischemia and
myocardial infarction, pneumonia, poor wound healing, insomnia and demoralization2,3. Associated with these
complications are economic and humanistic implications such as extended lengths of stay, readmissions, and patient
dissatisfaction with medical care.4,5 A recent study suggests that pain in ambulatory surgical patients is still
undermanaged and the incidence of moderate to severe pain remains high.6
The overall incidence of PONV has decreased from 60 % when ether and cyclopropane were used, to approximately
30% more recently.7 However, in certain high-risk patients the incidence is still as high as 70%. It is estimated that
an episode of vomiting prolongs PACU stay by about 30 min.8 Furthermore, it is estimated that approximately 0.2%
of all patients may experience intractable PONV, leading to unanticipated hospital admission following ambulatory
surgery, thereby increasing medical costs. The estimated cost of PONV to a busy ambulatory surgical unit was
estimated to range from $0.25 million to $1.5 million per year in lost surgical revenue.9
The results of several studies suggest that patients not only rank the absence of PONV and pain as being important10
but also rank it more important than an earlier discharge from an ambulatory surgical unit.11 Because patients
convalesce at home after surgery, pain and nausea and vomiting must be effectively assessed, monitored, and treated
within the surgical setting and anticipated during the recovery at home. This article will discuss the management of
PONV and pain following ambulatory surgery, the use of an effective, multimodal and novel therapy as well as
recommendations for the prophylaxis and treatment of PONV and pain.
Management of Postoperative Pain

Pharmacological Options
Opioids
Opioids are effective analgesics for moderate to severe pain. They act on opioid receptors in the peripheral 12,13 and
central nervous system. However their efficacy is limited by side effects. Opioids and/or NSAIDs combined with
local anesthetic infiltration or regional block has proven to be a useful technique for controlling pain in patients after
ambulatory surgery and should be considered whenever possible. In most studies local anesthetic infiltration with
systemic opioids or NSAIDs showed improvement in analgesia, better recovery 14 and shortening of discharge time
from day surgery unit. 15,16
Acetaminophen
Acetaminophen (Paracetamol) is an effective analgesic for mild to moderate pain with favorable side effect profile.
17
It is an effective adjuvant to opioid analgesia and a reduction in opioid requirement by 20-30% can be achieved
when combined with a regular regimen of IV, oral or rectal acetaminophen. It has been shown that 1 g of
propacetamol results in significant reduction in postoperative morphine consumption over 6 h period. 18 A meta-
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analysis of analgesic efficacy suggested that acetaminophen and tramadol is an effective analgesic combination in
dental and post surgical pain. However, more patients experienced side effects like dizziness, nausea and vomiting
with this combination.19 IV acetaminophen, commonly used in Europe, has the flexibility of being able to be used in
the perioperative period and may be a viable alternative to NSAIDs in minor surgery and a useful adjunct in
conjunction with other analgesics.18,20
Non-Steroidal Anti-inflammatory Drugs and Cyclo-oxygenase (COX-2) Inhibitors

Non-steroidal anti-inflammatory drugs (NSAIDs) have become the cornerstone in the treatment of acute pain in the
early postoperative period because of its opioid sparing effect.21 Administration of ibuprofen and oxycodone in
combination provides superior and effective analgesia in the postoperative period.22 The combination of ibuprofen
and acetaminophen has also been reported to reduce the need for early analgesia up to 34% in children undergoing
tonsillectomy.23 The use of COX-2 inhibitors have been shown to be an effective opioid adjunct in the perioperative
period without the increased risk of bleeding. Recently data suggest that oral regimen of ibuprofen (1200 mg/d) or
celecoxib (400 mg/d) improves analgesia and quality of recovery in ambulatory patients.24 The recent availability of
IV ibuprofen may provide further option of administration in the perioperative setting.
Tramadol and Tapentadol

Tramadol is a synthetic, centrally acting analgesic with a weak opioid action. It also inhibits serotonin and
noradrenaline reuptake. 25 The tramadol metabolite, O-desmethyl tramadol is a more potent analgesic than tramadol.
26
Unlike other opioids, it lacks the respiratory depressant effects and exhibits lower risk of bowel dysfunction 27 at
conventional doses. A meta-analysis 28 of acetaminophen and tramadol combination confirmed superior analgesia
without additional toxicity. The most common adverse effects noted were dizziness, headache, nausea and vomiting.
Combination of tramadol with acetaminophen increases tolerability. 29 More recently, tapentadol has been approved
in the US for the treatment of acute pain, It acts on opioid receptors as well as by inhibiting norepineprine pathway.
More studies are needed to define its clinical utility in an ambulatory setting.
Ketamine
Ketamine acts as an antagonist on the NMDA receptor. Used more widely as an anesthetic before the availability of
newer induction and maintenance agents, it has received renewed interest for its role in enhancing postoperative
analgesia. Several studies have focused on demonstrating use of subanesthetic doses of ketamine for various surgical
procedures to enhance pain relief and reduce total analgesic consumption. 30-35 Central excitatory neurotransmitters
acting on N-methyl-D aspartate receptor (NMDA) have been identified in the development and perpetuation of
pathologic pain states causing hyperalgesia and allodynia.36
There is ample evidence to suggest that ketamine has opioid sparing effect and may confer advantage in patients
where large amount of postoperative opioid consumption is anticipated. At low doses ketamine can provide
analgesia in opioid resistant pain. 37 Continuous infusion of ketamine has been used perioperatively. Adam et al.,
evaluated IV ketamine with an initial bolus (0.5 mg/kg) followed by continuous infusion of 3 mcg/kg/min
intraoperatively in combination with continuous femoral nerve block in patients undergoing total knee arthroplasty.
In this multimodal approach, ketamine group required significantly less morphine and tolerated early mobilization of
knee.38 These drugs have to be used with caution in the ambulatory setting due to its potential side effects including
sedation and hallucinatory effects in some individuals, though administering only a bolus dose and avoiding the
infusion regimen can reduce the incidence of adverse events.
Wound infiltration with local anesthetics

Infiltration of surgical wound with local anesthetics is probably the simplest method of achieving wound analgesia.
This method has been shown to be effective in providing analgesia in patients undergoing inguinal hernia repair and
other ambulatory procedures. There is lack of evidence for any clinically useful effect for other more extensive
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abdominal procedures. 39 For example, wound infiltration does not provide beneficial effect on pulmonary function
after surgery in one study. 40 Inadequate dosing and relatively short duration of action of the local anesthetics may
explain the poor results in some trials. Prolonged release technology of local anesthetics (e.g. depobupivacaine) has
recently approved for clinical use. In two pivotal studies, depobupivacine (Exparel®) would infiltration has been
shown to improve postoperative analgesia and reduced opioid consumption in bunionectomy and hemorrhoidectomy
surgery.41,42 The role of other adjuvants to local anesthetics is unclear. For example, wound infiltration of
bupivacaine and ketamine has not shown a decrease in pain score or the need for rescue analgesia but the duration of
analgesia has been reported to be prolonged by the addition of ketamine.43
Intra-articular analgesics
There are conflicting reports about the efficacy of intra-articular analgesics in the literature. 44-46. In a systematic
review Moiniche S et al. 47 observed that the effect of intra-articular local anesthetics seemed to provide moderate
pain relief of short duration. Although the pain relief in the early postoperative period was statistically significant,
evidence was not overwhelming in favor of intra-articular local anesthetics because majority of the studies did not
demonstrate improved pain relief beyond the immediate postoperative period.
Peripheral Nerve Blocks (PNB)

Appropriate nerve blocks depending on the site of surgery are useful in providing short to intermediate-term pain
relief after surgery. Direct visualization of neural tissue with ultrasound technology and the utility of stimulating
catheters has made placement of indwelling catheters safer and more accurate. Continuous infusion of local
anesthetics through a peripheral nerve catheter is becoming increasingly popular in both hospital and ambulatory
setting to achieve prolonged analgesia.48,49 For example, continuous femoral nerve block has been shown to reduce
duration of hospital stay and the frequency of serious complications. 50 Similarly, several other studies have
demonstrated the benefits of PNB including reduced length of stay and costs, 49 decreased incidence of PONV 51
and lower rates of unexpected hospital admissions after ambulatory surgery. 49,50,52 Systemic agents co-administered
during PNB such as opioids and clonidine have been found to enhance intraoperative and postoperative analgesia.
Two systematic reviews of 15 studies that used opioids as adjuvant, six reported a statistically significant benefit in
analgesia. Of the six studies that evaluated clonidine, 53 five found improvement in analgesia.
Other Pharmacological and Non-Pharmacological Options

Numerous other adjunctive analgesia including gabapentin, pregabalin, corticosteroids, neostigmine, magnesium
have some usefulness in an ambulatory settings but more evidence need to be gathered to determine their specific
roles. A recent study suggests that patients anesthetized with propofol was associated with less pain compared to
sevoflurane anesthesia although the exact mechanism is not known.54 Non-pharmacological therapy should be
considered as complimentary to pharmacological options for postoperative pain management. They may provide
additional benefits in reducing the total dose of analgesics required and therefore minimizing the adverse effects of
the analgesics. Techniques include acupuncture, hypnosis, relaxation, music therapy, etc. 55,56
Rationale for multimodal analgesia

The ideal analgesic regimen would provide effective pain relief, reduce opioid related side effects and surgical stress
response and improve clinical outcome e.g. morbidity, mortality and hospital stay. The concept of multimodal
analgesia was introduced to achieve these goals by combining various analgesic techniques and different classes of
drugs to improve postoperative outcome. 57 However, available data are conflicting and do not necessarily resulted
in improved outcome and concomitant reduction in adverse effects of opioids. 58-60 The failure to improve clinical
outcome may be due to inappropriate combination and dosing of analgesics. Apart from adequate analgesia,
postoperative morbidity and hospital stay depend on other factors such as initiation of early nutrition, mobilization
and comprehensive rehabilitation program. 61 Although, there is insufficient evidence to recommend pre-emptive
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analgesia routinely it is prudent to attenuate postoperative pain as effectively as possible during the intraoperative
period and initiating effective analgesic therapy in the early phase of perioperative period.
The effectiveness of individual analgesics is enhanced by the additive or synergistic effect of two or more drugs
acting by different mechanisms. For example, the synergism between alpha-adrenergic and opioid systems has been
demonstrated. 62 Similarly, combination of acetaminophen and non-steroidal anti-inflammatory drugs provides
additive analgesic effect in mild to moderate acute pain. 63 The addition of COX-2 inhibitors or NSAIDs reduces
opioid requirements by 20-30% with the reduction of opioid related side effects and better analgesia. Similarly,
ketamine has been shown to reduce the pain scores and lower analgesic requirement when added to a multimodal
epidural analgesia. 64 Adding ketamine in patient controlled epidural analgesia along with morphine, bupivacaine
and epinephrine has been demonstrated to result in enhanced analgesic effect. Chia et al., 65 showed that the mean
visual analogue score in the ketamine group during movement and cough were lower than the control group. The
cumulative total analgesic consumption in the ketamine group was lower by 30% than the control group 24 h
following surgery. In another study, it was demonstrated that the combination of intraoperative ketamine and
epidural analgesia may confer a long-term benefit in reducing incidence of chronic pain.66
Management of PONV
Risk factors for PONV
Identification of patients at high risk for PONV enables targeting prophylaxis to those who will benefit most from it.
Universal PONV prophylaxis is not cost effective, is unlikely to benefit patients at low risk for PONV and would
put them at risk from the potential side effects of antiemetic agents. Patient, anesthesia, and surgery related risk
factors have been identified. Anesthesia related risk factors include the use of volatile agents 67, nitrous oxide68,
opioids67,69 and high doses of neostigmine (>2.5 mg) for the reversal of neuromuscular blockade.70 Patient related
factors include female gender69,71, history of PONV or motion sickness 69,71,72, and non-smoking status.69,71 High
levels of anxiety and postoperative pain, especially of pelvic or visceral origin, may also be associated with a higher
incidence of PONV.73-75
A recent systematic review of the results of all available studies suggest that the phase of the menstrual cycle has no
impact on the occurrence of PONV.76 An increased Body Mass Index (BMI) is not a risk factor for PONV.77
However, long surgical duration71 and certain types of surgery also carry a greater risk of PONV. 71,78,79 In adults,
high incidences of PONV are found in intra-abdominal surgery, major gynecological surgery, laparoscopic surgery,
breast surgery, neurosurgery, eye and ENT surgery. Pediatric operations at high risk for PONV include strabismus,
adenotonsillectomy, hernia repair, orchidopexy, penile surgery and middle ear procedures.80-82 However, in a
prospective validation study, an association between type of surgery and the risk of PONV was not apparent.69 It
was suggested that the high incidence of PONV after certain operations might be caused by the involvement of high
risk patients. The incidence of PONV increases after the age of 3 years with a peak incidence of about 40 % in the
11 –14 year age group.69,83,84 Prior to puberty, gender differences for postoperative vomiting have not been
identified. 85 A recent study suggests black South African as an independent factor in reducing PONV risk.86
A number of PONV risk scoring systems have been developed. Apfel et al developed a simplified risk score
consisting of four predictors: female gender, history of motion sickness or PONV, non-smoking status and the use of
opioids for postoperative analgesia.69 A recent study identifies five independent predictors for postdischarge nausea
and vomiting: female sex, age<50 years, history of PONV, opioid use in the PACU, and nausea in the PACU.87
Reduction of Baseline Risks

There are several effective strategies which can be easily employed to reduce the baseline risk for PONV. Adequate
hydration is simple and inexpensive and has been shown to reduce the incidence of PONV.88 Liberal fluid regimen
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is associated with a lower incidence of vomiting and improved pulmonary function in patients undergoing knee
arthroplasty compared with restricted fluid regimen.89 While earlier studies suggest a protective effect of higher
concentration of oxygen, a recent meta-analysis concluded that 80% FiO2 should no longer be considered an
effective or reliable method to reduce overall PONV. 90 Reducing the use of opioid by adding other adjunctive
analgesia, e.g. NSAID, COX-2 inhibitor, acetaminophen, local anesthetic infiltration, gabapentin etc can lower
incidence of PONV.91 Avoidance of deep inhalational anesthesia guided by bispectral index has also been shown to
reduce the risk of PONV. Dexmedetomidine infusion (0.2–0.8 µg · kg–1 · h–1) has recently been shown to reduce
rescue antiemetic use in bariatric surgical patients.92 Most importantly, the use of propofol as the maintenance
anesthetic have the greatest impact in further reducing the incidence.93
Combination Antiemetic Therapy

There are at least four major receptor systems involved in the etiology of PONV. The concept of combination
antiemetic therapy was first introduced in 1988 in chemotherapy induced nausea and vomiting (CINV).94 Its success
prompted similar research in the field of PONV. Over 100 randomized controlled trials have been published
comparing the relative efficacy of combination versus single agent antiemetic prophylaxis. Most of these studies
suggested better efficacies against PONV can be achieved by the use of two or more antiemetics acting at different
receptors compared with monotherapy.95-97 The choice of combination is not critical. In a meta-analysis, Habib et al.
found no statistically significant difference in the incidence PONV when a 5-HT3 receptor antagonist was combined
with either droperidol or dexamethasone. Both combination regimens provided significantly better PONV
prophylaxis compared with 5-HT3 receptor antagonists alone.98.
In a large prospective study using a multifactorial design, Apfel et al. evaluated 3 antiemetic interventions
(ondansetron 4 mg, droperidol 1.25 mg, dexamethasone 4 mg) and 3 anesthetic interventions (TIVA with propofol,
omitting nitrous oxide, and substituting remifentanil for fentanyl) for the prophylaxis of PONV. The data suggest
that antiemetics with different mechanisms of action have additive rather than synergistic effects on the incidence of
PONV. Each antiemetic reduced the risk of PONV by about 25 %. When combinations of interventions were used,
the benefit of each subsequent intervention was always less than that of the first intervention.95. Interestingly, a
recent study showed superior efficacy in reducing vomiting when aprepitant was combined with dexamethasone
instead of ondansetron-dexamethasone combination in neurosurgical patients.99
Multimodal Approach
In addition to using a combination of anti-emetics acting at different receptor sites, the multifactorial etiology of
PONV might be better addressed by the adoption of a multimodal approach other than pharmacotherapy. This is
especially important in patients at high risk for PONV.
Scuderi et al reported a multimodal approach to the management of PONV in females undergoing outpatient
laparoscopy. Their multimodal algorithm consisted of total intravenous anesthesia with propofol and remifentanil,
avoiding nitrous oxide and neuromuscular blockade, aggressive intravenous hydration (25 ml/kg), triple
prophylactic antiemetics (ondansetron 1 mg, droperidol 0.625 mg and dexamethasone 10 mg), and ketorolac 30 mg.
Multimodal management resulted in a 98% complete response rate (no PONV and no antiemetic rescue) in
PACU.100 More recently, a multimodal approach incorporating TIVA with propofol, a combination of ondansetron
and droperidol, and omitting nitrous oxide, was associated with a higher complete response rate and greater patient
satisfaction in the PACU, compared to similar antiemetic prophylaxis with isoflurane/nitrous oxide based
anesthetic.98 A combination of ondansetron and transdermal scopolamine (TDS) proves to be effective in reducing
PONV up to 48 hours after ambulatory surgery.101 A recent meta-analysis suggests a similar effective reduction in
PONV with both early (the night before surgery) and late patch (same day of surgery) application. Apart from a
higher prevalence of visual disturbances after surgery with TDS, there was no difference in the other anticholinergic
side effects when compared to placebo.102
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Droperidol
Following the FDA “black box” warning on droperidol due to concerns of prolonged QTc interval, its use has
declined dramatically. A recently published pro and con debate weighed the justification of the FDA’s action 103,104.
Increasingly, clinicians begin to use haloperidol, another drug in the butyrophenone class, due to its lack of “black
box” warning”. Haloperidol in doses of 1 mg has been shown to be effective without significant side effects.105,106
Its efficacy is enhanced when combined with dexamethasone. 107
Novel Antiemetics
Neurokinin-1 A ntagonists
Substance P, a member of the tachykinin family of neuropeptides, is an important neurotransmitter in afferent
pathways of emesis.108 Substance P may be released from enterochromaffin cells in the stomach and intestine (e.g.
postoperative trauma) or from sensory neurons (e.g. radiation, chemotherapeutic agents).108 Tachykinin peptide
activity is tied to at least three G-protein–coupled receptor subtypes found in the peripheral or central nervous tissue:
neurokinin receptor subtype 1 (NK1), type 2 (NK2), and subtype 3 (NK3). The NK1 receptors are located in the area
postrema and are thought to play a particularly important role in emesis. However, NK1 receptor antagonists (NK1
RAs) are thought to exert their mechanism of action on neurons in the “afferent relay station” situated between the
medial NTS and the central pattern generator for vomiting.108 The potential NK1 receptor blocking activity located
deeper in the brain stem is thought to prevent both acute and delayed emesis, whereas 5-HT3 RAs are largely
effective against acute emesis,108 leading to considerable interest in the use of NK1 RAs for prophylaxis of PONV.
NK1 receptor antagonists are effective for the prophylaxis and treatment of PONV.109,110 In one study in females
undergoing gynecologic surgery, an NK1 receptor antagonist, CP-122,721 provided better prophylaxis against
vomiting compared with ondansetron. The combination of both agents also significantly prolonged the time to the
need for rescue compared with either drug alone, and was associated with a low incidence of emesis (2 %).110
Aprepitant is the only NK-1 receptor antagonist currently approved by the FDA for the prophylactic management
for PONV. It is available in oral capsule in 40 mg to be administered between 1-3 hours before surgery. It has a long
half-live of about 48 hours. It appears to have better efficacy in the prevention of PONV when compared with
ondansetron. In two identically designed, randomized, double-blind, active-controlled studies, patients scheduled for
mostly major gynecological surgery under general anesthesia were randomized to either aprepitant 40 mg, aprepitant
125 mg or ondansetron 4 mg. In the combined analysis, aprepitant 40 mg was superior to ondansetron for no nausea
(39.6% v 33.1%), no vomiting (86.7% v 72.4%), and no nausea, no vomiting, and no use of rescue (37.9% v 31.2%)
(p<0.05 for the odds ratio for each comparison).111,112 Rolapitant, with a half-life of 180 h, also has superior efficacy
in the reduction of postoperative emesis when compared with ondansetron.113 There are a number of other NK-1
antagonists currently under development.114
Long A cting Serotonin A ntagonist

Palonosetron has the longest elimination half-life of all the currently available serotonin antagonists at about 40
hours.115 Its long duration of action can also be explained by its high binding affinity for 5-HT3 receptors.116
Polanosetron was first introduced into the US market in for the management of (CINV) and it is also recently
approved for PONV. Recent studies suggest palonosetron 0.075 mg i.v. is effective for the reduction of the
incidence of nausea and vomiting in patients up to 72 h postoperatively. Palonosetron also reduces nausea severity
and interference in postoperative patient functioning due to PONV117. It would be interesting to see if the longer
half-life of this drug translates into prolonged clinical efficacy when compared with other serotonin antagonists.
Recommended strategy for PONV prophylaxis

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The risk of PONV should be estimated for each patient. No prophylaxis is recommended for patients at low risk for
PONV except if they are at risk for medical consequences from vomiting e.g. patients with wired jaws, aesthetic
procedures or at patient’s request. For patients at moderate to high risk for PONV, regional anesthesia should be
considered. If this is not possible or contraindicated and a general anesthetic is used, strategies to minimize the
baseline risk of PONV should be adopted, e.g. minimize the use of opioids, avoid high dose neuromuscular reversal
drugs and the use of propofol maintained anesthesia. The use of combination antiemetic therapy and more
appropriately a multimodal approach in high-risk patients is recommended. However, the best available combination
and the optimum doses of antiemetic agents when used in combination are yet to be established. Ondansetron should
be considered in any prophylactic regimen as it is now generic and hence has a low acquisition cost.
Recommendations for the treatment of established PONV

There is a paucity of data on the use of antiemetics for the treatment of PONV in patients who failed prophylaxis or
did not receive prophylaxis. This is due to the difficulty in performing such studies since a large number of patients
would need to be recruited in order to obtain the required number of patients who eventually experience PONV.
The 5-HT3 receptor antagonists were the most commonly tested drugs in rescue clinical trials. Similar to their use in
PONV prophylaxis, the anti-vomiting efficacy of the 5-HT3 receptor antagonists is more pronounced than their anti-
nausea efficacy. There is no evidence of dose-responsiveness for these agents when used for rescue. As ondasnetron
is now generic, a 4 mg dose is recommended.
In patients who fail ondansetron prophylaxis, there is evidence to suggest that the use of ondansetron for rescue is no
more effective than placebo. A drug acting at a different receptor might be more effective in this case.118 Droperidol
was not different from ondansetron when used for the treatment of established PONV.119 On the other hand,
ondansetron 4 mg was more effective than metoclopramide 10 mg in this setting.120,121
When evaluating PONV following surgery, the role of medication and mechanical factors should be considered first.
Such contributing factors might include opioids, blood draining down the throat, or bowel obstruction. Then rescue
therapy should be initiated as soon as possible. If PONV occurs within 6 hours postoperatively, patients should not
receive a repeat dose of the prophylactic antiemetic; a drug from a different class should be used for rescue. Beyond
6 hours, PONV can be treated with any of the antiemetics used for prophylaxis except dexamethasone and
scopolamine, which are longer acting.
In summary, PONV and pain are very common following ambulatory surgery and should be managed aggressively.
The thorough understanding of the mechanism of these common symptoms and a careful assessment of risk factors
provide a rationale for appropriate management of PONV and pain. The adoption of a comprehensive and
multimodal approach for both symptoms will likely ensure success in the management.
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DISCLOSURE
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The Geriatric Outpatient: Cognitive Dysfunction and Other Concerns

Kathryn E. McGoldrick, M.D. Valhalla, New York
Introduction
The elderly (≥65 yr) are a rapidly growing demographic segment in the United States as well as in many other parts
of the developed world. This reality has profound implications for anesthesiologists and surgeons. Aging, for
example, increases the probability that an individual will require a surgical procedure. Whereas approximately 12%
of those aged 45 to 60 yr undergo surgery annually, this number increases to >21% in the elderly (1). Although
operative mortality has decreased in the geriatric population in recent decades, perioperative morbidity continues to
be more common in the elderly and perioperative mortality rates, especially in the presence of co-existing disease,
remain higher than those encountered with younger patients. Using the Cox proportional hazards model, the risk of
postoperative long-term mortality increases 1.42 times per decade of age (2). Clearly, as an ever-increasing
proportion of the surgical outpatient population falls into the geriatric category, anesthesiologists are becoming
geriatric subspecialists to a certain extent. Thus, it seems appropriate to summarize our current knowledge about the
physiology of aging and to discuss the implications of these issues for the perioperative management of the elderly
outpatient.
Physiology and Pathophysiology of Aging

Age alters both the pharmacokinetic and pharmacodynamic aspects of anesthetic management. As an individual
ages, he or she experiences a loss of reserve and a diminished ability to tolerate stress. The functional capacity of
organs declines and co-existing disease further contributes to this decline. Advanced age, in conjunction with
comorbidity, is a risk factor for increased perioperative mortality, and age itself may further amplify the negative
prognostic value of impaired physical status (3).
The effects of aging at the subcellular level are ubiquitous, and these effects are apparent when one considers organ
function in the elderly. In terms of cardiac function, it is well known that geriatric patients have reduced beta-
adrenergic responsiveness, and they experience an increased incidence of bradyarrhythmias and hypertension.
Fibrotic infiltration of cardiac conduction pathways and replacement of myocardial elastic fibers render the elderly
individual vulnerable to conduction delay and to atrial and ventricular ectopy. It is well known that postoperative
atrial arrhythmias, and atrial fibrillation (AF) and flutter specifically, are seen in 6.1% of elderly patients undergoing
noncardiothoracic surgery and in 10% to 40% of patients after cardiothoracic operations (4-7). Because reliance on
atrial “kick” is critically important for older adults, should we prophylactically treat high-risk patients to prevent
postoperative AF? If so, should we use rate control or rhythm control drugs? Elderly patients also have an increased
reliance on the Frank Starling mechanism for cardiac output. It is important, therefore, to consider fluid as a drug
that the elderly individual may or may not need. In the noncompliant older heart, small changes in venous return will
produce large changes in ventricular preload and cardiac output. Owing to reduced diastolic myocardial function,
baroreceptor-mediated heart rate control, adrenergic receptor responsiveness, and vascular compliance, the elderly
person compensates poorly for hypovolemia. Similarly, overtransfusion is also poorly tolerated.
COPD, pneumonia, and sleep apnea are common in the elderly. Closing volume increases with age, and FEV1
declines 8% to 10% per decade owing to reduced pulmonary compliance and muscle power (8). Arterial oxygen
tension decreases progressively with age-induced V/Q mismatch, diffusion block, and anatomical shunt (9). [Owing
to these abnormalities in gas exchange, it is recommended that elderly patients be transported to the PACU with 2-4
L/min of oxygen via nasal cannula, even after relatively minor ambulatory surgery (10)]. Given these deleterious
changes, it is not surprising that postoperative respiratory complications are common in geriatric patients. However,
the most important clinical predictor of adverse pulmonary outcome is the site of surgery, with thoracic and upper
abdominal surgery having the highest pulmonary complication rates (11, 12).
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Because the central nervous system is the target for so many of our drugs, age-related alterations in nervous system
function have extremely compelling implications for anesthetic management. Indeed, aging universally produces a
reduction in total nervous system tissue mass, neuronal density, and concentration of neurotransmitters, as well as
various receptors. Drug interactions are a very real concern in the elderly because senior citizens typically undergo
physiologic changes related to disease as well as to normal aging. Moreover, although elders represent
approximately 13% of the population in the United States, they consume one-third of all medications and are seven
times more likely to experience an adverse drug reaction than their younger counterparts. In fact, the elderly account
for 50% of all medication-related deaths. Important to an understanding of geriatric pharmacokinetics is an
appreciation of the role that reduced drug excretion plays in adverse interactions. With advancing age, the number of
functioning glomeruli declines, as do glomerular filtration rate and renal blood flow.
Intraoperative Management
Because of the pulmonary changes discussed previously, it is imperative to appreciate that desaturation occurs faster
in older adults. Additionally, elderly patients are more vulnerable to desaturation-related cardiac events. Therefore,
proper preoxygenation is critical. Benumof points out that maximal preoxygenation is achieved with 8 large breaths
of 100% oxygen within 60 sec with an oxygen flow of 10 L/min (13).
Advanced age is associated with a reduction in median effective dose requirements for all agents that act within the
central nervous system regardless of whether these drugs are administered via the oral, parenteral, or inhalational
route. Indeed, the ED50 equivalent for anesthetics falls linearly with age, such that the “typical” healthy 80-yr-old
will require only about two-thirds of the anesthetic dose needed to produce comparable effects in a young adult. An
octagenarian with notable comorbidities will require even lower doses. This reduction in anesthetic requirement is
agent-independent and probably reflects fundamental neurophysiologic changes in the brain, such as reduced
neuronal density or altered concentrations of neurotransmitters. Elderly patients require less propofol (and other
agents) for induction, and it is also important to appreciate that the concurrent use of midazolam, ketamine, and/or
opioids with propofol synergistically increases the depth of anesthesia. Even with an appropriate dose reduction of
propofol, hypotension is common. Less hypotension has been reported with appropriately titrated administration of
mask sevoflurane for induction compared with a propofol infusion (14). Interestingly, gender differences have been
described in the pharmacokinetics of propofol given by continuous infusion in elderly patients (15).
Several neuromuscular blocking agents, including vecuronium and rocuronium, have an increased onset time in
elderly patients, possibly as a result of a less dynamic circulation and, thus, an increased transfer time to the effector
site (16). The time required for clinical recovery from neuromuscular blockade is markedly increased in older adults
for nondepolarizing agents that undergo organ-based clearance from plasma, but is minimally different for
atracurium, cisatracurium, or mivacurium because they undergo hydrolysis in plasma. Those neuromuscular
blockers with prolonged duration of action in the elderly are associated with delayed elimination, which may be a
result of the reduced total body water and decreased liver mass that often accompany aging. The likelihood of
postoperative respiratory complications after long-acting muscle relaxants increases with advanced age. It is not
unusual for patients who meet rigorous extubation criteria in the OR to deteriorate in the PACU. Hence, it seems
advisable to administer a short- or intermediate-acting muscle relaxant to any elderly patient for whom extubation is
planned at the end of the surgical procedure. Importantly, sugammadex has been shown to facilitate rapid reversal
from moderate rocuronium-induced neuromuscular blockade in adults of all ages, but recovery to a train-of-four
ratio of 0.9 is 0.7 min faster in young and middle-aged adults compared with patients ≥65 yr (17).
In planning an expeditious emergence, anesthesiologists should be aware that end-tidal gas monitoring
underestimates the brain concentration of the more soluble agents. Failure to appreciate this hysteresis effect leads to
prolonged emergence. Moreover, MAC awake is more favorable if the vaporizer is turned down gradually rather
than turned off abruptly (18). Not surprisingly, it has been reported that use of shorter-acting drugs (propofol,
desflurane, sevoflurane), in conjunction with BIS monitoring, can provide more rapid emergence in geriatric patients
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and facilitate PACU bypass (19). Whether this approach will have a favorable effect on longer-term outcomes
remains to be determined.
When one considers selection of anesthetic technique, it is important to appreciate that there are no controlled,
randomized studies in elderly patients to show that regional anesthesia is clearly superior to general anesthesia for
ambulatory surgery. In fact, neuraxial, plexus, or peripheral nerve blocks (PNBs) in the elderly may be associated
with an increased risk of persistent numbness, nerve palsies, and other neurological complications. It has recently
been demonstrated that age is a major determinant of duration of complete motor and sensory blockade with PNB,
perhaps reflecting increased sensitivity to conduction failure from local anesthetic agents in peripheral nerves in the
elderly (20). That said, PNBs offer some appealing features, especially in terms of postoperative pain control.
Clonidine is a valuable adjunct that enhances both local anesthetic and narcotic efficacy, and its addition to the local
anesthetic mixture may afford some hemodynamic advantages compared with epinephrine. However, one should
select a dose of clonidine that will not produce postoperative sedation or hypotension. When administering epidural
blockade to elderly patients, it is important to remember that a given dose will produce a higher level of block in
seniors, and is typically accompanied by a greater incidence and degree of hypotension and bradycardia as well as a
longer duration of anesthesia (21). Sedation requirements are dramatically reduced under conditions of central
neuraxial block. Sensory input to the brain is attenuated and the BIS50 is shifted to a higher index. Although recent
data have supported a relaxation of the requirement for voiding before discharge after outpatient neuraxial blockade
with short-acting drugs for low-risk surgical procedures in low-risk patients, it is important to appreciate that elderly
patients do not meet these criteria (22). Current thinking is that elderly (≥70 yr) patients who received neuraxial
block, regardless of the duration of the block, should be required to void before discharge.
Postoperative Management
Perioperative hypothermia is prevalent in both young and elderly surgical patients, but it is more frequent,
pronounced, and prolonged in the elderly, who have compromised ability to regain thermoregulatory control
quickly. Adverse consequences of postoperative hypothermia include cardiac ischemia, arrhythmias, increased
blood loss, wound infection, decreased drug metabolism, and prolonged hospitalization. Indeed, it has been shown
that maintaining normothermia decreases cardiac morbidity by 55 percent (23).
Postoperative pain increases the risk of adverse outcome in geriatric patients by contributing to tachycardia,
hypertension, cardiac ischemia, and hypoxemia. Effective analgesia can decrease the incidence of myocardial
ischemia and pulmonary complications, accelerate recovery, promote early mobilization, shorten hospital stay, and
reduce medical costs. However, postoperative pain control often is inadequate in the elderly because of concerns
about drug overdose, adverse response, drug interactions, and other issues. Pain control is further complicated by the
fact that the patient’s perception and expression of pain may be affected by changes in mental status. Current
postoperative analgesic techniques include the use of opioids by various routes, nonsteroidal anti-inflammatory
drugs, local anesthetic techniques (neuraxial, intra-articular, PNB, etc), and nonpharmacologic (transcutaneous or
percutaneous electrical nerve stimulation, acupuncture, acupressure, etc) methods. Pre-emptive, multimodal
approaches have been favored to minimize the risk of such opioid-related side effects as hypoxemia, constipation,
and pruritus. However, the recent discovery of data fabrication by a major researcher in the area of pre-emptive
analgesia has far-reaching and serious consequences. There is, for example, no longer unequivocal evidence
supporting the pre-emptive effect of nonsteroidal anti-inflammatory drugs and cyclooxygenase-2 inhibitors.
Additionally, the ability of a multimodal pre-emptive analgesic regimen to prevent the development of chronic pain
after major orthopedic surgery remains unproven (24).
Postoperative Cognitive Impairment

Reports of postoperative cognitive deterioration in elderly patients surfaced several decades ago, and anesthesia
had often been implicated as a possible cause or contributing factor. Although improvements in surgical techniques
and anesthetic agents and methods have led to improved outcomes in the elderly, a troubling proportion of these
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patients experience postoperative cognitive impairment (25-28), at least on a short-term (~3 months) basis.
The syndrome of postoperative cognitive impairment can be classified into two main categories: postoperative
delirium and postoperative cognitive dysfunction (POCD)(29). Delirium is defined as an acute change in cognitive
function that develops over a brief period of time, often lasting for a few days to a few weeks and typically having a
fluctuating course. It is characterized by inattention, as well as either disorganized thinking and/or altered
level of consciousness. Prospective studies have cited an incidence of delirium that ranges from 3% to >50% and is
dependent upon the type of surgery, the patient's preoperative physical and cognitive status, and the age of the
patient (29). Recently, Rudolph and Marcantonio reported an incidence of postoperative delirium ranging from 35%
to 65% for hip fracture repair, down to 4% for cataract surgery. Delirium is a costly complication that has been
associated with increased postoperative morbidity and mortality. Although the risk factors for postoperative delirium
vary among studies, greater preoperative age, alcohol use, major comorbidities, and cognitive impairment are
generally thought to confer a higher risk of postoperative delirium. Recently, Smith et al (31) reported that
preoperative executive dysfunction and depression are independent risk factors for postoperative delirium.The
etiology of delirium is probably multifactorial and may include drug intoxication or withdrawal, drug interactions,
anticholinergic agents, metabolic disturbances, hypoxia, abnormal carbon dioxide levels, sepsis, inadequate
analgesia, and organic brain disease (32). Neurotransmitter imbalances involving acetylcholine, dopamine, and
gamma-aminobutyric acid appear to be heavily involved in the multifactorial pathophysiology of delirium. Recent
evidence suggests that deregulation in the homeostasis of tryptophan, the precursor to serotonin, may have a critical
role in the pathogenesis of postoperative delirium (33). Because abnormalities in the regulation of serotonin have
consistently been linked with depression (34), this may have important implications for explaining the association of
depression with delirium. It has also been suggested that occult white matter damage to the frontal-striatal areas of
the brain predisposes some patients to develop delirium (31). It is perhaps possible that this mild loss of white matter
could manifest preoperatively as impaired executive performance and/or greater levels of depression (31).
Interestingly, the use of melatonin to treat delirium has produced some benefit, presumably by resetting the
circadian sleep-awake cycle of older surgical patients (35). Although common in the elderly, the incidence of
postoperative delirium may be reduced by protocol-driven perioperative treatment. Marcantonio and colleagues
reported a reduction in postoperative delirium in hospitalized patients by more than one-third, and of severe delirium
by more than one-half, by adherence to multifaceted recommendations that included elimination or minimization of
benzodiazepines, anticholinergics, antihistaminics, and meperidine, as well as encouraging early mobilization and
providing appropriate environmental stimuli (36).
POCD is defined as a deterioration of intellectual function in one or more neuropsychological domains that
often presents as impaired memory or concentration. Other neuropsychological domains, including executive
function, perceptual organization, language, attention, and psychomotor function, may be affected. Moller and
colleagues (25) evaluated cognitive function in patients aged 60 yr or older after major abdominal and orthopedic
surgery. These investigators found that approximately 25% of the patients had measurable cognitive dysfunction a
week after their surgery and 10% had cognitive changes 3 months postoperatively. This finding contrasted with a
3% incidence of cognitive deterioration in healthy control subjects in the same age range who did not undergo
anesthesia and surgery. Interestingly, neither perioperative hypoxemia nor hypotension correlated with the
occurrence of prolonged cognitive dysfunction. The identified risk factors for early (1 week) postoperative cognitive
dysfunction were increasing age and duration of anesthesia, low education level, a need for a second operation,
postoperative infection, and respiratory complications. The major risk factor for late (3 months) postoperative
cognitive dysfunction was age. Although the incidence of late postoperative cognitive dysfunction was 14% for
patients >70 yr, this rate decreased to only 7% for patients between the ages of 60 to 70 yr.
An additional large, prospective study conducted by Monk and colleagues evaluated the relationship of age to
POCD (28). Using the same methodology as the first multinational study (25), Monk and colleagues reported that
cognitive decline occurred in 16% of patients aged 60 yr or older at 3 months after major noncardiac surgery, but
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was present in only 3% to 5% of younger patients (28). This study also determined that rates of cognitive decline
were higher in those >70 yr compared with younger elderly patients. More recently (2008), Monk explored the
predictors of cognitive dysfunction after major noncardiac surgery (37). Independent risk factors for POCD at 3
months after surgery were increasing age, lower educational level, a history of previous CVA without residual
impairment, and POCD at hospital discharge. Patients who had POCD at both hospital discharge and 3 months
after surgery were more likely to die in the first year after surgery, but whether this suggests a causal link or is
related to patients’ comorbidities is unknown (37).
There are few prospective studies on long-term cognitive outcomes after outpatient surgery, but an analysis of
cognitive recovery after major and minimally invasive surgery exists. Monk classified the type of surgical procedure
as minimally invasive (laparoscopic or superficial surgery), major intra-abdominal surgery, or orthopedic surgery
(28). The incidence of POCD was significantly greater for patients undergoing major abdominal or orthopedic
procedures compared with minimally invasive surgery. Because outpatient surgery is usually minimally invasive,
these results suggest that outpatients may have a better cognitive outcome than patients who require hospitalization.
The International Study of Postoperative Cognitive Dysfunction (ISPOCD) group, however, recently conducted a
longitudinal study comparing the incidence of POCD after inpatient versus outpatient surgery in patients older than
60 yr (38). At 7 days after surgery, the incidence of POCD was substantially lower in the outpatient group, but this
difference was not detected 3 months later. These results suggest that elderly outpatients have better cognitive
outcomes at discharge than elderly inpatients, but we currently have no explanation for the difference. Possible
explanations for the improved early outcome in outpatients include the healthier status of patients who qualify for
outpatient surgery, the briefer surgical and anesthesia times, the minimally invasive nature of most outpatient
procedures, or avoidance of hospitalization. Interestingly, a recent (2011) study by Evered et al found that POCD
was independent of the type of surgery and anesthetic (39). Specifically, at 3 months post procedure, 21% of
geriatric patients having coronary angiography under sedation had POCD. The incidence of POCD in geriatric
patients who underwent either total hip replacement or CABG surgery was 16% in each group.
It is important to understand that full return of cognitive function to preoperative levels may require several days,
even after ambulatory surgery in young, healthy patients (32, 40). Indeed, Lichtor (41) has suggested that even
young adults may be sleepy for 8 hr after receiving IV sedation with midazolam and fentanyl, and the elderly
outpatient suffering from balance disturbances or age-related gait impairment may be at high risk of falling owing to
residual drowsiness. Nonetheless, it remains unclear which patient populations are most vulnerable and what the
causative factors might be for the serious problem of POCD. Although we have much to learn about postoperative
delirium and cognitive decline, it is clear that pre-existing subclinical decrements in functional status may become
evident during the perioperative period. Indeed, if a cognitive deficit is noted preoperatively, it may be a harbinger
of further postoperative decline. The data on the predictive value of preoperative cognitive status for the
development of delirium (42) and the ability of that assessment to result in successful intervention (as may be the
case with delirium) (36) offer compelling reasons to conduct a simple, brief mental status examination as part of the
preoperative interview. Indeed, Evered and colleagues recently identified that 20% of patients ≥60 hr having total
hip replacement had preexisting cognitive impairment, and 22% had amnestic mild cognitive impairment (MCI); 7%
had both (43). These findings underscore the need for a robust, reproducible, practical tool to assess preoperative
cognitive function in our elderly patients (44). Additionally, Vaurio and colleagues recently demonstrated that
elevated levels of preoperative pain and a postoperative increase in pain levels are independent predictors of
postoperative delirium in elderly surgical patients (45). These findings suggest that elderly surgical patients with
substantial preoperative pain should be targeted for more intensive pain control postoperatively.
Our current understanding of POCD suggests the etiology is multifactorial and may include the preoperative
status of the patient, as well as intraoperative events related to surgery (e.g., microemboli), and anesthetic factors.
The potential roles of inflammation and anesthetic depth remain to be more fully determined. Although we currently
have no reliable neuroprotective intervention to offer our patients, a marker for POCD might influence the decision
to have such elective procedures as cosmetic surgery. Hopefully, future studies will lead to a clearer definition of the
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incidence, mechanisms, and prevention of POCD (46).

Finally, it should be mentioned that interest has grown recently in exploring a potential relationship between
anesthesia and the onset and progression of such neurodegenerative conditions as Alzheimer’s disease (47). Our
knowledge in this area is limited, and anesthesia has been both implicated and exonerated. There is, however, some
laboratory evidence that anesthesia may affect the processing of amyloid beta peptide. It has also been speculated
that risk factors for POCD may overlap with those for Alzheimer’s disease, although any shared mechanism remains
conjectural. Available human studies on anesthesia and Alzheimer’s disease are inconclusive because they are
under-powered or confounded by coexisting disorders, independent risk factors for dementia, and, of course, surgery
(48-50). Increasingly, we are realizing that many of our elderly patients have MCI at baseline. The cognitive loss of
some of these patients may not be readily apparent preoperatively, and is unmasked by the perioperative experience.
Perhaps the concerning cognitive changes that are identified postoperatively indicate more about our patients than
about our anesthetic agents.
Interestingly, in April 2011, the first new diagnostic guidelines released in 27 years in the United States for
Alzheimer’s disease recognized MCI as a precursor to Alzheimer’s disease. The National Institute on Aging and the
Alzheimer’s Association now describe the disorder as a disease that occurs gradually over many years, starting with
changes in the brain, then mild memory problems, and finally progressing to florid dementia. This preclinical stage,
happening about a decade before dementia develops, may be the best place to intervene in the disease, with many
researchers believing that most Alzheimer’s drugs have been disappointing because they were tried in people whose
disease was too advanced to be halted or reversed. Although not yet ready for prime time, the development of new
imaging agents for PET scans, spinal fluid tests, and other biomarkers that predict or detect Alzheimer’s in its
earliest stages will be increasingly important to researchers, drug companies, and clinicians.
Summary
Elderly patients are uniquely vulnerable and particularly sensitive to the stresses of trauma, hospitalization, and
surgery/anesthesia in ways that are only partially understood. The ambulatory environment offers many potential
benefits for geriatric patients having elective procedures. Accordingly, minimizing perioperative risk in the
elderly population requires thoughtful preoperative assessment of organ function and reserve, meticulous
intraoperative management of coexisting disorders, maintenance of normothermia, and vigilant postoperative
monitoring and pain control.
References
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2. Manku K, Bacchetti P, Leung JM. Prognostic significance of postoperative in-hospital complications in elderly
patients. I. Long-term survival. Anesth Analg 2003;96:583-9.
3. Forrest JB, Rehder K, Cahalan MK, Goldsmith CH. Multicenter study of general anesthesia III : Predictors of
severe adverse outcomes. Anesthesiology 1992;76:3-15.
4. Polanczyk CA, Goldman L, Marcantonio ER, et al. Supraventricular arrhythmias in patients having noncardiac
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Predictors, outcomes, and resource utilization. JAMA 1996;276:300-6.
8. Knudson RJ, Lebowitz MD, Holberg CJ, Burrows B. Changes in the normal maximal expiratory
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9. Sorbini CA, Grassi V, Solinas E, Muiesan G. Arterial oxygen tension in relation to age in healthy
subjects. Respiration 1968;25:3-13.
10. Mathes DD, Conaway MR, Ross WT. Ambulatory surgery: Room air versus nasal cannula oxygen
during transport after general anesthesia. Anesth Analg 2001;93:917-21.
11. Klotz HP, Candinas D, Platz A, et al. Preoperative risk assessment in elective general surgery. Br J
Surg 1996;83:1788-91.
12. Vodinh J, Touboul C, Lefloch JP, et al. Risk factors of postoperative pulmonary complications after vascular
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13. Benumof J. Preoxygenation: Best method for both efficacy and efficiency (editorial). Anesthesiology 1999;
91:603-5.
14. Kirkbride DA, Parker JL, Williams GD, Buggy DJ. Induction of anesthesia in the elderly ambulatory
patient: A double-blind comparison of propofol and sevoflurane. Anesth Analg 2001;93:1185-7.
15. Vuyk J, Oostwouder CJ, Vletter AA, Burm AGL, Bovill JG. Gender differences in the
pharmacokinetics of propofol in elderly patients during and after continuous infusion. Br J Anaesth
2001;86:183-8.
16. Matteo RS, Ornstein E, Schwartz AE, et al. Pharmacokinetics and pharmacodynamics of rocuronium (Org
9426) in elderly surgical patients. Anesth Analg 1993;77:1193-7.
17. McDonagh DL, Benedict PE, Kovac AL, et al. Efficacy, safety, and pharmacokinetics of sugammadex for the
reversal of rocuronium-induced neuromuscular blockade in elderly patients. Anesthesiology 2011;114:318-29.
18. Katoh T, Suguro Y, Kimura T, Ikeda K. Cerebral awakening concentration of sevoflurane and
isoflurane predicted during slow and fast alveolar washout. Anesth Analg 1993;77:1012-7.
19. Fredman B, Sheffer O, Zohar E, et al. Fast-track eligibility of geriatric patients undergoing short
urologic procedures. Anesth Analg 2002;94:560-4.
20. Pagueron X, Boccara G, Bendahou M, Coriat P, Riou B. Brachial plexus nerve block exhibits
prolonged duration in the elderly. Anesthesiology 2002;97:1245-9.
21. Simon MJG, Veering BT, Stienstra R, van Kleek JW, Burm AGL. The effects of age on neural
blockade and hemodynamic changes after epidural anesthesia with ropivacaine. Anesth Analg
2002;94:1325-30.
22. Mulroy MF, Salinas FV, Larkin KL, Polissar NL. Ambulatory surgery patients may be discharged
before voiding after short-acting spinal and epidural anesthesia. Anesthesiology 2002;97:315-9.
23. Frank SM, Higgins MS, Breslow MJ, et al. The catecholamine, cortisol, and hemodynamic responses
to mild perioperative hypothermia: A randomized clinical trial. Anesthesiology 1995;82:83-93.
24. White PF, Kehlet H, Liu S. Perioperative analgesia: What do we still know? (editorial). Anesth Analg 2009;
108:1364-7.
25. Moller JT, Cluitmans P, Rasmussen LS, et al. Long-term postoperative cognitive dysfunction in the
elderly: ISPOCD1 study. The Lancet 1998;351:857-61.
26. Williams-Russo P, Sharrock NE, Mattis S, Szatowski TP, Charlson ME. Cognitive effects after
epidural vs. general anesthesia in older adults. JAMA 1995;274:44-50.
27. Dodds C, Allison J. Postoperative cognitive deficit in the elderly surgical patient. Br J Anaesth
1998;81:449-62.
28. Monk TG, Garvin CW, Dede DE, van der Aa MT, Gravenstein JS. Predictors of postoperative
cognitive dysfunction following major surgery (abstract). Anesthesiology 2001;95:A50.
29. Moller JT. Cerebral dysfunction after anaesthesia. Acta Anaesthesiol Scan (supp) 1997;110:13-6.
30. Rudolph JL, Marcantonio ER. Postoperative delirium: acute change with long-term implications. Anesth Analg
2011; 112:1202-11.
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31.Smith PJ, Attix DK, Weldon BC, Greene NH, Monk TG. Executive function and depression as independent risk
factors for postoperative delirium. Anesthesiology 2009;110:781-7.
32. O’Keefe ST, Chonchubhair AN. Postoperative delirium in the elderly. Br J Anaesth 1994;73:673-87.
33. Lewis MC, Barnett SR. Postoperative delirium: the tryptophan dysregulation model. Med Hypotheses
2004;63:402-6.
34. Nestler EJ, Barrot M, DiLeone RJ, et al. Neurobiology of depression. Neuron 2002;34:13-25.
35. Hanania M, Kitain E. Melatonin for the treatment and prevention of postoperative delirium. Anesth
Analg 2002;94:338-9.
36. Marcantonio ER, Flacker JM, Wright RJ, Resnick NM. Reducing delirium after hip fracture: A
randomized trial. J Am Geriatr Soc 2001;49:516-22.
37. Monk TG, Weldon BC, Garvan CW, et al. Predictors of cognitive dysfunction after major noncardiac surgery.
Anesthesiology 2008;108:18-30.
38. Canet J, Rasmussen LS, Raeder J, et al. Cognitive dysfunction after minor surgery in the elderly. Acta
Anaesthesiol Scand 2003;47:1204-10.
39. Evered L, Scott DA, Silbert B, Maruff P. Postoperative cognitive dysfunction is independent of type of surgery
and anesthetic. Anesth Analg 2011;112:1179-85.
40. Tzabar Y, Asbury AJ, Millar K. Cognitive failure after general anaesthesia for day-case surgery. Br J
Anaesth 1996;76:194-7.
41. Lichtor JL, Alessi R, Lane BS. Sleep tendency as a measure of recovery after drugs used for
ambulatory surgery. Anesthesiology 2002;96:878-83.
42. Inouye SK. Predisposing and precipitating factors for delirium in hospitalized older patients. Dement
Geriatr Cogn Disorders 1999;10:393-400.
43. Evered LA, Silbert BS, Scott DA, et al. Preoperative cognitive impairment and mild cognitive impairment in
subjects presenting for total hip joint replacement. Anesthesiology 2011;114:1297-304.
44. Crosby G, Culley DJ, Hyman B. Preoperative cognitive assessment of the elderly surgical patient: A call for
action (editorial). Anesthesiology 2011;114:1265-8.
45. Vaurio L, Sands L, Wang Y, Mullen EA, Leung JM. Postoperative delirium: the importance of pain and pain
management. Anesth Analg 2006;102:1267-73.
46. Newman S, Stygall J, Hirani S, et al. Postoperative cognitive dysfunction after noncardiac surgery: A systematic
review. Anesthesiology 2007;106:572-90.
47. Baranov D, Bickler PE, Crosby GJ, et al. Consensus statement: International workshop on anesthetics and
Alzheimer’s disease. Anesth Analg 2009; 108:1627-30.
48. Bohnen N, Warner MA, Kokmen E, et al. Alzheimer’s disease and cumulative exposure to anesthesia: A case-
control study. J Am Geriatr Soc 1994;42:198-201.
49. Bohnen N, Warner MA, Kokmen E, Kurland LT. Early and midlife exposure to anesthesia and age of onset of
Alzheimer’s disease. Intern J Neurosci 1994;77:181-5.
50. Knopman DS, Petersen RC, Cha RH, et al. Coronary artery bypass grafting is not a risk factor for dementia or
Alzheimer disease. Neurology 2005;65:986-90.
DISCLOSURE
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TEE for the Occasional Cardiac Anesthesiologist

Michael K. Cahalan, M.D. Salt Lake City, Utah
Introduction and Overview. Transesophageal Echocardiography (TEE) has transformed the practice of cardiac
anesthesia rendering it far more demanding and influential than before TEE’s wide adoption. With the information provided
by TEE, cardiac anesthesiologists can help direct the course of cardiac surgery and improve outcome for patients. As a
result, routine intraoperative TEE is an expectation in most cardiac surgical practices. However, many anesthesiologists who
practice cardiac anesthesia do so only occasionally and, therefore they have little opportunity to hone their skills in TEE. To
assist the occasional cardiac anesthesiologist in his/her use of TEE, this refresher course will review four related topics: 1)
recently published TEE guidelines 2) the most common and best-established applications of TEE in cardiac surgical
patients, 3) a basic TEE examination and 4) TEE certification opportunities.
Recent TEE Guidelines. In 2010, the ASA House of Delegates approved updated guidelines for TEE. For cardiac
surgery, the recommendations are quite straightforward:
“For adult cardiac patients without contraindications, TEE should be used in all open heart (e.g. valvular procedures)
and thoracic aortic surgical procedures, and should be considered in CABG surgeries as well, to: (1) confirm and refine
the preoperative diagnosis, (2) detect new or unsuspected pathology, (3) adjust the anesthetic and surgical plan
accordingly, and (4) assess results of the surgical intervention. In small children, the use of TEE should be considered
on a case-by-case basis because of risks unique to these patients (e.g. bronchial obstruction.”1
However, as an important qualifying statement, these ASA guidelines state that their recommendations do not apply if the
practitioner is “not prepared to perform TEE properly or safely nor do they apply when TEE equipment or skilled examiners
are unavailable.”1 The 2010 European Society on TEE update concludes simply that TEE “is reasonable for use in all adult
patients who are undergoing either cardiac surgery or thoracic aortic surgical procedures under general anaesthesia.”2 The
2011 American College of Cardiology and American Heart Association guidelines for CABG surgery state that TEE is
“reasonable for monitoring hemodynamic status, ventricular function, regional wall motion, and valvular function in
patients undergoing CABG.”3
Established Applications.
New Diagnoses. TEE can reveal new diagnostic findings prior to cardiopulmonary bypass (CPB) that prompt
changes in surgical management. Skinner et al. reviewed 797 intraoperative TEEs to determine the cause of 46 unexpected
new intraoperative findings: 20 were present in the preoperative echocardiography studies but undiagnosed (reporting
errors), 14 were due to limitations of transthoracic echocardiography relative to TEE, 10 due to progression of disease, and 2
due to inter-observer variability.4 Surgical management changed significantly in 18/20 patients with reporting errors.
However, the reported incidence of new intraoperative diagnoses with TEE varies widely (3.4% to 27% of cardiac cases)
depending on the patient population, selected or consecutive use of TEE, and surgical practices, especially the treatment of
patent foramen ovale (PFO) and ischemic mitral regurgitation (IMR). 5-8 Two recent studies help clarify the correct
approach to these two variable surgical practices. First, Krasuski et al. reviewed the intraoperative TEE studies of 13,092
patients without prior diagnosis of PFO undergoing cardiac surgery.9 A new diagnosis of PFO was made intraoperatively in
2277 of these patients and 639 of them underwent surgical closure. The patients who had PFO closure had a 2.5 times
greater odds of having a postoperative stroke compared with a matched group of patients who did not have PFO closure. No
long-term survival advantage resulted from PFO closure. Thus, the new diagnosis of PFO during cardiac surgery should not
prompt its closure without careful consideration of the additional risk of stroke. Second, Fattouch et al. randomly assigned
patients with moderate IMR undergoing coronary artery surgery (CABG) to receive CABG alone (N=54) or CABG plus
mitral valve repair (MVR) (N=48).10 Overall hospital mortality was 3% (1 in the CABG group and 2 in the CABG+MVR
group). Five-year survival rates were not statistically different between the groups (CABG=88% vs. CABG+MVR=94%).
However, patients in the CABG+MVR group had better postoperative exercise capacity and less cardiac distension than
those in the CABG alone group. Only 40% of the patients in the CABG alone group had a decrease in their IMR while 25%
Note: This publication contains material copyrighted by others. Individual refresher course lectures are reprinted by ASA with permission. Reprinting or
using individual refresher course lectures contained herein is strictly prohibited without permission from the authors/copyright holders.
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remained stable and 35% worsened. No patient in the CABG+MVR group had greater than mild IMR during the 5-year
follow-up. Thus, repairing moderate IMR appears to have significant benefit when CABG is planned. However,
hemodynamic changes caused by general anesthesia
alter the degree of mitral regurgitation (usually lessening it) thereby complicating surgical decision-making.
Restoring intraoperative blood pressure with phenylephrine to preoperative levels improves the concordance between
preoperative and intraoperative assessment of mitral regurgitation but discrepancies remain.11 In coronary surgery patients,
even mild mitral regurgitation identified by intraoperative TEE predicts a significantly greater likelihood of death or
hospitalization for heart failure over the subsequent three years compared to coronary surgical patients without mitral
regurgitation.12 The decision to repair a regurgitant mitral valve during CABG surgery is complex and depends on many
factors including the mechanism and degree of regurgitation, the ability of the patient to survive the additional surgery and
the skill of the surgeon.
Aortic Diseases. TEE can have a crucial role in the management of surgical diseases of the aorta. The 2010
multidisciplinary guidelines on the management of thoracic aortic disease cite an 88-98% sensitivity and a 90-95%
specificity for detection of proximal aortic dissection.13 In this true surgical emergency, speed is of the essence and TEE
takes considerably less time than alternative diagnostic techniques. To limit the time to surgery further, one center employs
a regional strategy of direct admission to the operating room for patients with diagnosed or suspected acute aortic
dissections.14 TEE is performed there under general anesthesia and the decision to proceed with surgery is based on the
results. Nevertheless, important TEE limitations should be noted including: TEE may miss dissections confined to the upper
ascending aorta where TEE imaging is partially obstructed by the trachea and TEE will not reveal coincident coronary
lesions that should be bypassed during surgery. However, TEE can delineate the mechanisms and severity of any associated
aortic regurgitation, thereby identifying patients in whom valve repair is likely to be successful.15 Similarly, TEE detected
aortic atheromas have important implications. In 130 patients older than 65 years undergoing coronary artery bypass
grafting, TEE detection of protruding atheroma of the ascending aorta proved to be the only independent predictor of
stroke.16 When these atheroma are detected by TEE, alteration of the aortic cannulation technique or raising the blood
pressure during cardiopulmonary bypass may reduce the incidence of stroke.17, 18 Although TEE is not as sensitive as
epiaortic scanning for detection of atheromas of the aortic arch, it is a good screening tool: if TEE reveals no significant
atheromas in the ascending or descending aorta, none are likely to be present in the arch.19 When intraoperative TEE reveals
severe atheromatous disease of the aorta, off-pump coronary surgery results in lower risk of death and stroke than on-pump
surgery.20
Valvular Diseases. TEE has profoundly affected valvular heart surgery. For example, in 205 consecutive patients
undergoing posterior mitral leaflet quadrangular resection (the most common mitral repair technique) for treatment of mitral
regurgitation, TEE revealed immediate failures in 24 patients (11%).21 In 20 of these patients, TEE identified the mechanism
of the failure and guided immediate further repair while one patient required valve replacement. In a different study, 437
patients underwent mitral valve repair by a variety of techniques.22 During a mean follow-up period of 29 months, 41
patients (9%) required reoperation for repair failure. Successful initial repair as assessed by intraoperative TEE was the most
important predictor of repair durability. Systolic anterior motion (SAM) of the mitral leaflet diagnosed with intraoperative
TEE is a known complication of mitral repair surgery. In a study of 2,076 patients undergoing mitral repair, TEE identified
SAM in 174 patients (8.4%).23 Four of these patients required immediate reoperation to relieve severe persistent SAM. In
the others, it was managed medically. During a median follow-up period of 5.4 years, echocardiograms were available in 93
of these patients. SAM was present in 13 of them; and in 4 patients, it was severe enough to cause partial LV outflow tract
obstruction. Thus, when TEE reveals SAM immediately after mitral repair, it can be managed medically in most patients:
preload augmentation, arterial vasoconstriction, and/or beta blockade.24 Landoni et al. have reported a stepwise approach to
this strategy.25 In patients with aortic regurgitation, TEE provides a highly reliable assessment of the underlying cause and is
predictive of the repairability of the valve and of postoperative outcome.26 During valve replacement surgery, TEE reliably
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detects periprosthetic leaks (surprisingly common). While moderate or severe periprosthetic leaks should almost always
undergo immediate repair, almost half of the small leaks resolve with the administration of protamine. However, surgically
correctable prosthesis malfunction occurs in other patients and will be missed without the use of TEE. In a study of 417
patients undergoing valve replacement, immediate surgical correction was required in 15 patients (3.6%): periprosthetic leak
(N=8), immobilized leaflet (N=4), coronary obstruction (N=2), and xenograft incompetence (N=1).27 In a more recent study
limited to patients undergoing elective aortic valve replacement (N=604), TEE revealed new information influencing
surgery in 104 patients prior to CPB: changes regarding the mitral valve were the most frequent.28 After CPB, TEE revealed
unexpected findings requiring a second bypass run in 20 patients. In the future, the incremental value of 3-D TEE in
valvular heart surgery, especially mitral repair, may prove significant, but there is no doubt that properly performing and
interpreting 3-D TEE requires substantial additional operator expertise.29
Coronary Disease. In a study of 82 high-risk patients undergoing coronary artery surgery, the investigators used
staged blindings of the cardiac surgeons and anesthesiologists at critical points during surgery to document the clinical
impact of TEE. After these clinicians documented their planned management at each stage, the TEE results were revealed
and led to at least one significant change in anesthetic management in 51% of patients and surgical management in 33% of
patients including: additional unplanned or revised grafts (15%) and unplanned valve procedures (7%).30 These high-risk
patients had postoperative infarction and mortality rates below predicted (1% versus 3% predicted, difference not
statistically significant). In a different study involving 474 consecutive patients undergoing coronary artery surgery, TEE
identified 71 new findings in 13% of patients. The new finding resulted in a change in surgical management in 6% of
patients. Following bypass, surgical management changed in 10 patients including graft revision and mitral repair.8
Congenital Heart Surgery. Pediatric TEE probes are used in infants as small as 3 kg. Stevenson et al. reported that
intraoperative TEE reliably detected residual cardiac defects in 17 (7%) of 230 consecutive patients undergoing congenital heart
surgery.31 These patients were reoperated immediately for revision of the residual defects. However, a subsequent publication from
the same center found that the number of residual defects missed by intraoperative TEE increased from 2% to 13% when the
attending anesthesiologist and not a separate echocardiographer performed TEE.32 This study generated considerable controversy.
Although it does not resolve the issue of whether a separate echocardiographer is required to adequately perform TEE in patients
undergoing congenital heart repairs, it does amply demonstrate that patients can suffer severe consequences when intraoperative TEE
is not expertly performed, interpreted, and acted upon. In this study, the deaths of seven patients may have been related to the delayed
recognition of residual defects. With progress in pediatric congenital heart surgery, more and more children with palliated congenital
heart disease will survive to adulthood and will present for cardiac and other kinds of surgery. For an excellent update on TEE in
adult congenital heart disease, please see the review by Russell et al.33
Hemodynamic Assessment. TEE reveals changes in LV preload more reliably than filling pressures. In 30 patients
scheduled for cardiac surgery, Cheung et al. removed 15% of each patient's blood volume in 6 equal aliquots prior to
bypass.34 TEE demonstrated a significant decrease in EDA after removal of the first aliquot (about 200 ml) and a linear
decrease with subsequent aliquots. The pulmonary artery occlusion and central venous pressures also declined but correlated
poorly with EDA. In most adults, an EDA of less than 12 cm2 indicates hypovolemia but values between 12-15 cm2 may not
because of variations in patient size and diastolic compliance. However, when a volume challenge increases EDA, then
stroke volume also increases.35 Although quantitative TEE measurements of ventricular preload are well validated as noted
above, they are tedious and impractical to perform intraoperatively. Instead, clinicians assess LV filling and function
subjectively using the “trained eye." This approach is a valid method to guide fluid administration; and in patients with
concentric hypertrophy, it may identify the need for higher than normal filling pressures to achieve optimal LV filling and
function.36 In addition to estimating LV filling volume, TEE provides practical ways to estimate LV filling pressure and
cardiac output.37-39 Appropriately performed TEE estimates of cardiac output should fall within 0.3-0.8 liter/minute of
thermodilution estimates except in patients with severe tricuspid regurgitation when thermodilution may underestimate
output.40
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Ventricular Function Assessment. Fractional area change (FAC) during systole is a commonly used measure of
global LV systolic function using the simple formula (EDA-ESA)/EDA where EDA is the cross-sectional area at end
diastole and ESA at end systole. Marked changes in FAC are apparent by simply viewing the real-time images. Thus, severe
LV systolic depression is easy to detect with TEE. Although FAC correlates reasonably well with other approximations of
systolic ventricular function, significant limitations apply. First, TEE often underestimates the LV long axis (it foreshortens
the left ventricle). Second, the mid-ventricular short-axis view may be a poor guide to overall ventricular ejection, if other
areas of the ventricle have markedly different function. And third, FAC, like other traditional echocardiographic indices of
systolic function, is load dependent: changes in preload and afterload markedly alter FAC without changing the intrinsic
function of the ventricle. Measurement of right ventricular (RV) systolic function is more difficult than LV systolic function
because of the right ventricle’s complex shape and response to changes in loading. However, severe RV systolic dysfunction
is not difficult to recognize: severe hypokinesis or akinesis of the RV free wall, enlargement of the right ventricle to exceed
the size of the left ventricle, and a change in shape of the right ventricle from crescent to round. When RV systolic
dysfunction is due to acute pulmonary hypertension, as occurs in pulmonary embolism, the intra-ventricular septum flattens
or bulges leftward during systole. Additionally, detection of LV diastolic dysfunction is important because it
is the primary cause of congestive heart failure in one third of all patients with this problem. Although considered an
advanced application of TEE, Doppler findings diagnostic of diastolic dysfunction are readily obtained with TEE.41
Detection of Myocardial Ischemia. Within seconds after the onset of myocardial ischemia, affected segments of the
heart cease contracting normally. In 50 patients undergoing cardiovascular surgery, new intraoperative segmental wall
motion abnormalities (SWMA) diagnostic of myocardial ischemia (see below) occurred in 24 patients and ischemic ST-
segment changes in only six.42 Three patients who sustained intraoperative myocardial infarctions (MI) developed SWMA
in the corresponding area of myocardium which persisted until the end of surgery, but only one of these three had ischemic
ST-segment changes intraoperatively. Subsequent studies in comparable patients confirmed these advantages of TEE over
ECG monitoring43 as well as the superiority of intraoperative TEE over preoperative dobutamine testing for the prediction of
myocardial infarction.44 Moreover, when multiple TEE cross sections are monitored (not just the one cross section as was
done in the above studies), the detection rate of SWMA more than doubles.45 Limitations of TEE in the detection of
ischemia should be recognized. When an area of myocardium is clearly in view, segmental contraction can be difficult to
evaluate if the heart rotates or translates markedly during systole or if discoordinated contraction occurs due to bundle
branch block or ventricular pacing. Consequently, a valid system for SWMA assessment must evaluate both regional
endocardial motion and myocardial thickening. A marked worsening of segmental wall motion and wall thickening (in the
absence of similar global changes) is required to make the diagnosis of ischemia; even experts do not consistently interpret
less pronounced changes. Not all SWMAs are indicative of myocardial ischemia. Myocarditis, myocardial infarction, and
myocardial stunning cause SWMA. In coronary surgery, differentiating infarction, stunning, and ischemia is vitally
important. When TEE reveals LV wall thickness of less than 0.6 cm, an old infarction in that thinned area is almost
certain.46 If inotopic stimulation improves segmental motion of a SWMA, then stunning, not ischemia, is likely.47 One other
cause of SWMA is severe hypovolemia in patients with preexisting SWMA.48 However, with the exception of myocardial
stunning and severe hypovolemia as noted above, a sudden, severe decrease of segmental contraction is almost certainly due
to myocardial ischemia.
TEE During Life-Threatening Hypotension. Ultimately, hypotension has only two possible causes: inadequate
cardiac output or inappropriately low systemic vascular resistance. TEE is remarkably well suited for addressing this
differential diagnosis. During severe hypotension, qualitative TEE estimates of ventricular filling and function serve as the
practical guides for administration of fluids, inotropes, and vasopressors. An experienced observer can differentiate
immediately severe ventricular dysfunction from other life-threatening causes of hypotension. In severe left-ventricular
failure, ventricular filling (as assessed by end-diastolic area) is increased and ejection is decreased. While in inappropriately
low systemic vascular resistance, ventricular filling is usually normal or slightly decreased and ejection is markedly
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increased. Hypovolemia is easily recognized as a marked decrease in ventricular filling and a marked increase in ejection.
Although inappropriately low systemic vascular resistance, severe aortic regurgitation, severe mitral regurgitation, and
ventricular septal defect can manifest the same LV filling and ejection pattern at the transgastric short-axis cross section,
distinguishing these etiologies of hypotension is not difficult using other cross sections and color Doppler. A dramatic
example of the use of TEE in hypotensive patients is provided by a study of 60 consecutive patients with severe, persistent
hypotension following cardiac surgery despite intensive therapy guided by invasive monitors.49 TEE confirmed the
presumed etiology of the hypotension in only 30 of these patients. In two patients, TEE revealed unsuspected cardiac
tamponade and in six others unsuspected hypovolemia. In five patients, TEE prevented unnecessary reoperations by proving
that tamponade was not present despite hemodynamic data suggesting it. In another study, unstable cardiac surgical patients
in the operating room (n=57) or intensive care unit (n=83) underwent emergent TEE.50 Based on the TEE findings alone, 22
of these patients had urgent surgical interventions. The average time to diagnosis was 11 minutes. In still another study
involving critically ill surgical patients, TEE was proven more cost effective than transthoracic echocardiography because
the latter fails so often to reveal diagnostic images.51
Basic TEE Examination. Because of time constraints and relatively narrow diagnostic goals, anesthesiologists often
perform a more limited intraoperative examination than described in the recommendations for a comprehensive TEE
examination.52, 53 However, even when time is critical, the examination performed should allow at least the basic
applications of TEE as outlined in the original guidelines for perioperative TEE: to detect markedly abnormal ventricular
filling or function, extensive myocardial ischemia or infarction, large air embolism, severe valvular dysfunction, large
cardiac masses or thrombi, large pericardial effusions, and major lesions of the great vessels.54 A minimum of eight different
cross sections drawn from the 20 cross sections delineated in the
comprehensive examination are required to meet these diagnostic goals. Four of the cross sections are imaged in both 2-D
and color Doppler to assess valvular function. The next paragraph will describe the probe manipulations required to achieve
these cross sections.
This
figure
was
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53
adapted with permission from Shanewise et al.
After the TEE probe is introduced safely into the esophagus, it is advanced to the mid-esophageal (ME) level (28-
32 cm measured at the upper incisors), and the aortic valve (AV) is imaged in the short axis (SAX) by turning the probe,
adjusting its depth in the esophagus, and rotating the multiplane transducer to 25-45 degrees until the three cusps of the
valve are seen as approximately equal in size and shape (ME AV SAX). Image depth is set to 10-12 cm as required to
position the AV in the center of the video screen. This cross section is ideal for detection of aortic stenosis. Digitally record
this and all the subsequent cross sections. Next, the probe is turned slightly to position the AV in the center of the video
screen and then the multiplane angle is rotated forward to 110-130 degrees to bring the long axis (LAX) of the AV in view
(ME AV LAX). This cross section is best for detection of ascending aortic abnormalities including type I aortic dissection.
Color Doppler is used for assessment of aortic valve competence. For detection of valvular stenosis and regurgitation, set
the Nyquist limit to 50-60cm/sec.55 Next, the Doppler is discontinued and the probe is turned rightward until the ME bicaval
cross section comes into view (ME Bicaval). This cross section is seen best usually at a multiplane angle between 90 and
110 degrees and is ideal for assessing caval abnormalities as well as compression of the right atrium from anteriorly located
masses or effusions and the left atrium from posteriorly located masses or effusions. In addition, the bicaval cross section
may reveal collections of air located anteriorly in the left or right atrium, as well as the structure of the interatrial septum
including the foramen ovale. Next, the multiplane angle is rotated back to 60-80 degrees and the probe is turned leftward
just past the aortic valve to bring the ME right ventricular (RV) inflow and outflow cross section into view (ME RV In-
Outflow). Usually, an image depth of 12-14 cm is required to position the RV outflow track in the center of the video
screen. This cross section reveals the contractile function of the RV, the outflow tract, as well as
the pulmonary valve function with the application of color Doppler. Next, the transducer is rotated back to 0 degrees, the
probe advanced 4-6 millimeters into the esophagus, and gently retroflex it until all four cardiac chambers are visualized (ME
4-Chamber). Often, rotating the transducer 10-15 degrees will enhance the view of the tricuspid annulus. In 2-D imaging,
the free wall of the RV and the lateral and septal LV wall segments are evaluated for contractile function. With color
Doppler, both the mitral and tricuspid valves are assessed. Stenotic and regurgitant lesions can be diagnosed. During this
assessment, the image depth is decreased to 10-12 cm to afford a
magnified view of the valves and color Doppler flow patterns. Next, color Doppler is discontinued, the left ventricle is
positioned in the center of the screen, and the multiplane angle is rotated forward to 90 degrees to bring into view the ME 2-
chamber cross section (ME 2-Chamber). The image depth is returned to 14-16 cm. This cross section is best for revealing
the function of the basal and apical segments of the anterior and inferior LV walls as well as anterior and inferior pericardial
collections. When air emboli collect in the left ventricle, they can be seen best usually in this view as very echogenic areas
located along the anterior apical endocardial surface. Then, the transducer is rotated forward to 135 degrees to reveal the
ME LAX cross section that is best for assessment of the anteroseptal and posterior wall function (ME LAX). Together, the
ME 4-chamber, 2-chamber, and LAX cross sections reveal all 16 segments of the left ventricle. However, the next and last
of the basic cross sections provides a second look at the mid-ventricular segments as well as other benefits. To achieve this
cross section, the transducer is rotated back to 0 degrees, the left ventricle centered in the screen and the probe advanced 4-6
cm into the stomach. Then, it is flexed gently anteriorly to reveal the transgastric (TG) mid-ventricular SAX cross section
(TG mid SAX ). This cross section is ideal for monitoring LV filling and contractile function. All major coronary arteries
supplying the myocardium are viewed in this cross section. More, changes in preload cause greater changes in the LV short-
axis than in the long-axis dimension, and movement of the probe from this cross section is readily apparent because the
papillary muscles provide prominent landmarks. Since this cross section is used to judge filling and ejection, image depth is
consistently set to 12 cm so that the size and function of the heart are judged easily relative to previously examined hearts.
Even this basic examination requires some time to master. If you have no experience in TEE, you should work with
another physician who has advanced training in TEE until you have performed at least 50 TEE examinations and are
prepared to function at the basic practitioner level. As you use TEE in your cardiac practice, be sure to record your
examinations and interpretations. Archive these data either in a collaborative fashion with your hospital’s echocardiography
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laboratory, or, when this is not possible, archive them independently. They are important medical records and must be
available for comparison with other cardiac studies and subsequent echocardiograms. A standardized interpretation form is
available from the website of the Society of Cardiovascular Anesthesiologists (http://www.scahq.org/) along with billing
codes.
Certification Opportunities. The National Board of Echocardiography (NBE) offers an examination and
certification process for basic and advanced perioperative TEE (http://www.echoboards.org/content/verification-physicians-
certification). At the basic level, the requirements are: 1) passage of the NBE’s basic perioperative echocardiography
examination (basic PTeXAM), 2) current and unrestricted license to practice medicine, 3) board certification in
anesthesiology, and 4) specific training in perioperative TEE. “Specific training” has two pathways: “supervised” and
“practice experienced.” The “practice experience” pathway is the one most likely to apply to most occasional cardiac
anesthesiologists. It requires “at least 150 TEE examinations within the four (4) consecutive years immediately preceding
the application with no less than 25 in any year.” In addition, this pathway requires at least 40 hours of AMA category 1
continuing medical education devoted to perioperative TEE. Of special note is the clear limitation the NBE has placed on
basic TEE certification:
“The primary purpose of this certification is to provide anesthesiologists who use TEE as a monitor during general
anesthesia an opportunity to demonstrate their competence with this technique. Certification in basic perioperative TEE
is NOT intended to qualify an individual to use TEE as a diagnostic tool to direct or assess cardiac surgical
interventions; the board certification in perioperative transesophageal echocardiography offered by the NBE since 2003
remains unchanged and still serves this purpose and from this point on will be referred to as Advanced PTE
Certification.
In reality, most anesthesiologists practice somewhere between the basic and advanced levels. Regardless of your level of
practice, anticipate the need for consultation whenever the demands of anesthetic management, TEE interpretation, or both
will be more than you can manage alone.
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DISCLOSURE
This speaker has indicated that he or she has no significant financial relationship with the manufacturer of a commercial
product or provider of a commercial service that may be discussed in this presentation.
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Anesthesia for Cardiac Patients Outside of the Operating Room
Douglas Shook, M.D. Boston, Massachusetts
RCL outline not available at the time of publication
holders.
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New Developments in Thoracic Anesthesia

Edmond Cohen, M.D. New York, NewYork
A variety of thoracic surgical procedures, such as lobectomy, pneumonectomy, esophago-gastrectomy, pleural

decortication, bullectomy and bronchopulmonary lavage are commonly performed. Customarily they are
classified either as absolute or as relative. THE ABSOLUTE INDICATIONS include life-threatening
complications, such as massive bleeding, sepsis and pus, where the non diseased contra lateral lung, must be
protected from contamination. Broncho-pleural and broncho-cutaneous fistulae are absolute indications since they
offer a low resistance pathway for the delivered tidal volume during positive pressure ventilation. Giant unilateral
bullae may rupture under positive pressure and ventilatory exclusion is mandatory. Finally, during
bronchopulmonary lavage for alveolar proteinosis or cystic fibrosis, prevention of the contra lateral lung from
drowning is necessary. Video assisted thoracoscopy (VAT) brought to the practice of surgery for diagnostic and
therapeutic procedures required a well collapse lung and should be included in the absolute indication for OLV
category. RELATIVE INDICATIONS which includes lobectomies (particularly right upper), pneumonectomy,
and thoracic aortic aneurysm repair, are primarily for surgical exposure. Lower or middle lobectomy and
esophageal resection are of lower priority. In practice, the majority of the procedures where DLT is used, are in
essence relative indication, and only a small fraction are absolute. The use of OLV for relative indications rely on
the surgeon-anesthesiologist practice and preference.
METHODS OF LUNG SEPARATION :In the past, bronchial blockers and the single-lumen endobronchial
tubes have been utilized to achieve lung isolation. These tubes are seldom used today due to technical obstacle,
inability to remove secretions from the non-ventilated lung, and less than satisfactory performance. In modern
practice, endobronchial double-lumen tubes (DLTs) are most widely employed. These tubes have a fixed
curvature, are without a carinal hook to avoid tracheal laceration, and reduce the likelihood of kinking. The
original non-disposable Robertshaw red rubber tubes are presently available in small, medium and large sizes.
Numerous manufacturers produce clear disposable PVC Robertshaw design DLTs, which are available in French
sizes 35-41. (Mallinckrodt, Rusch, Sheridan). Essentially, they consist of similar features and modify in cuff
shape and location. A colored bronchial cuff, commonly blue, permits easy identification by fiberoptic
bronchoscopy. The right endobronchial cuff is donut-shaped, and allows the right upper lobe ventilation slot to
ride over the right upper lobe orifice. Most authors refrain from using right-sided DLT simply to avoid potential
obstacle. A 37Fr DLT can be used in most adult female, while 39 Fr are used in the average adult male. These
types of PVC tubes are currently considered the foremost and are most extensively used to obtain lung separation.
In recent years, 28 F and 32F DLT’s were introduced for small adults.
Positioning of Double-Lumen Tubes: Following intubation the

tracheal cuff should be inflated first and equal breath sounds
should be confirmed. To ensure from mucosal damage from
excessive pressure applied by the bronchial cuff, the cuff is
inflated with incremental volume to seal air leaks around the
bronchial cuff into the tracheal lumen. Inflation of the bronchial
cuff seldom requires more than 2 ml of air. Bilateral breath
sounds should be re-checked to confirm that the bronchial cuff is
not herniating over to impede the ipsilateral lung ventilation.
An important step is to verify that the tip of the bronchial lumen
is located in the designated bronchus. One simple way to check
is to first clamp the tracheal lumen (always at the level of the
connector!), observe and auscultate. Usually, inspection will
reveal unilateral ascent of the ventilated hemithorax. Following
proper auscultation, the bronchial lumen is clamped to ventilate the tracheal lumen. Each time a right-sided DLT
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is used, appropriate ventilation of the right upper lobe should be ensured. This can be accomplished by careful
auscultation over the right upper lung field or more accurately by fiberoptic bronchoscope. When a left-sided
DLT is used, the risk of occluding the left upper lobe bronchus by the bronchial tip advanced far into the left main
bronchus should be kept in mind. If peak airway pressure is of 20 cm H2O during two-lung ventilation, for the
same tidal volume, that pressure should not exceed 40cm H2O on OLV.
Perhaps the most important advancement in confirming the proper positioning of DLTs is the introduction of
fiberoptic bronchoscopy to clinical practice. It has been recently shown that DLTs, thought to be correctly
positioned by inspection and auscultation, subsequent fiberoptic bronchoscopy revealed malposition in 20-48%.
The simplest method to evaluate proper positioning of a left sided DLT is bronchoscopy via the tracheal lumen.
The carina is then visualized, while only the proximal edge of the endobronchial cuff should be identified just
below the tracheal carina. Herniation of the bronchial cuff over the carina to partially occlude the ipsilateral main
bronchus should be excluded. The bronchial blue cuff of the clear disposable PVC DLT is easily visualized, while
the non-disposable rubber DLTs contains yellow bronchial cuffs somewhat more difficult to recognize.
Bronchoscopy should then be performed via the bronchial lumen to identify the patent left upper lobe orifice.
When using a right-sided DLT, the carina is visualized through the tracheal lumen. More importantly, the right
upper lobe bronchial orifice must be identified while the bronchoscope is passed through the right upper lobe
ventilating slot This is somewhat complex to accomplish and requires a relatively skilled endoscopist. Several
sizes of bronchoscope are available for clinical use: 5.6, 4.9, and 3.9 mm of external diameter (Olympus Co.).
The 3.9mm-diameter bronchoscope can easily pass through a 37 Fr or larger tube, while it a tight fit through a 35
Fr tube
An airway may be termed difficult when onventional laryngoscopy reveals a grade III view (just epiglottis) or a
grade IV view (just soft palate). Furthermore, depending on the type and the length of surgery, the degree of fluid
shift during surgery, an airway that initially was not classified as difficult may become difficult secondary to
facial edema, the presence of secretion and laryngeal trauma from the initial intubation. A logical approach to
lung separation is described in Figure 1. When the separation of the lung is strictly indicated, use of tubes that are
difficult to insert such as DLT or a Univent tube cannot be avoided despite the presence of a difficult airway. If
the patient has a recognized difficult airway awake Intubation with fiberoptic bronchoscopy (FOB) can be
attempted using DLT / Univent /or a SLT. The same approach may be use for the patient with an unrecognized
difficult airway and a failure to intubate with conventional laryngoscopy. When using a DLT over a fiberoptic
bronchoscope (FB) one should keep in mind that it is a bulky tube with a large external diameter, and because the
length of the DLT, only a limited part of the FB is available for manipulation. In addition, the mismatch between
the flexibility of the FOB and the rigidity of the DLT make it harder to pass over the FOB. (5) The Univent tube
has the same bulky external diameter and is also often hard to pass through the vocal cords particularly in an
awake patient. In some cases advancing the bronchial blocker of the Univent tube can serve as an introducer to
facilitate the passage through the larynx. Following a successful intubation with a DLT or a Univent tube, OLV
can be immediately established. If these difficult tubes cannot be inserted over a FOB, than a SLT should be use
to establish an airway.
The use of a tube exchanger: Several tube exchangers are available: (Cook Critical Care, Bloomington, IN.).
All of these airway guides are commercially made, are depth marked in centimeters, are available in a wide range
DLT/Airway Exchange Catheter Figure 2 of ODs, and are easily adapted for either oxygen insulation or jet
SMALL
(N 11)
MEDIUM
(N 14)
LARGE
(N 18)
ventilation. The airway guide may be used for inserting an SLT,
DLT Size
changing an SLT to one of the difficult tubes, or simply inserting a
35F
difficult tube. Critical details to keep in mind to maximize benefit
SATISFACTORY
37F BORDERLINE
and minimize risk of airway guides are as follows: First, the size of
IMPOSSIBLE the airway guide and the size of the difficult tube must be determined
39F and should be tested in vitro before the use of the airway guide.
Second, the airway guide should never be inserted against a
41F resistance; the clinician must always be cognizant of the depth of
insertion. Two reported perforations of the tracheobronchial tree
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have occurred. Third, a jet ventilator should be immediately available in case the new tube does not follow the
airway guide into the trachea, and the jet ventilator should be preset at 25 psi by the use of an additional in-line
regulator. Finally, when passing any tube over an airway guide, a laryngoscope should be used, to facilitate
passage of the tube over the airway guide past supraglottic tissues. Because of the potential injury to the bronchial
tree from the stiff tip of the tube exchanger, a new catheter is been designed that have a soft tip to reduce the risk
of trauma.
ENDOBRONCHIAL BLOCKERS Over time, it has become clear that modern thoracic anesthesiologists
need an alternative to DLT’s. In the past, Fogarty embolectomy catheters were used to achieve lung isolation.
Placement may be difficult, due to its lack of directing mechanism and communication channel in the center;
therefore suctioning or oxygen
insufflation is unachievable.
INDICATION FOR THE USE OF ENDOBRONCHIAL BLOCKERS Finally, due to the high
 Lung Isolation Vs Lung Separation pressure low volume spherical
Video Assisted Thoracoscopy ; Increase the Number of Patients Who Required OLV
Avoid the Need for Tube Exchange
shaped cuff, the elliptic shape
of the bronchus is poorly
The Difficult Airway occluded. Today, Fogarty
Patients With a Difficult Airway ( Mllampatti 3 or 4)
 Patients Post Laryngeal/Pharyngeal surgery catheters have no use in
 Patients with Tracheotomy thoracic anesthesia practice
Patients with Distorted Bronchial anatomy from aneurysm compression or intraluminal tumor
 Patients who Requires Nasotracheal Intubation

 Patients with a Immobility or Kypjhoscoliosis
Surgical Procedure Non-Evolving the Lung

 Esophageal surgery
 Spine Surgery that Required Transthoracic Approach
 Minimally Invasive Cardiac Surgery
Management:
 VAT procedures where a quick look or simple wedge of chest exploration is planned
 Possible Segmental blockade in patient intolerable to OLV
 Morbidly obese
 Small size adult or pediatrics
 Patients who requires intraoperative lung isolation
 Patients who arrive intubated to the OR from the ICU
The need to teach the new generation and for practice for the present generation
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In modern thoracic anesthesia, three independent 9F endobronchial blockers (EBB) were introduced to clinical
practice. The clinical indications for the use of endobronchial blockers are out line in a recent Pro debate by
Cohen. (See table). The Arndt blocker (Ardnt , Cook Inc., Bloomington IN). The FB is passed through the loop
and guided into the desired bronchus than the BB is slide over the FB into the select bronchus. Bronchoscopic
visualization confirms blocker placement and occlusion. The string may than removed and a 1.8mm lumen may
be used as a suction port or for oxygen insufflation. In the first generation of this device it was not possible to
reinsert the string once it have been pulled out losing the ability to redirect the BB if necessary. A recent
modification in the string design overcomes the problem. Finally,
ARNDT ENDOBRONCHIAL BLOCKER
the external diameter is somewhat larger which requires a large
size SLT (at list 8.0 mm) to be able to accommodate the BB. Te
Ardnt blocker is available in 7F and in a pediatric size . More
recently a new endobronchial blocker has been approved by the
FDA for clinical use. The Cohen Flexitip Endobronchial
Blocker is designed for use as independent BB through a standard
ET with a small 4.0 mm fiberoptic bronchoscope. The most
important feature of the blocker is that it uses a flexible soft tip
that can be deflected to more than 90 degrees and easily directed
into the desired bronchus
needed to be blocked. As
demonstrated by the
figure, the deflection of
COOK the tip is achieved by
Tip Straight rotation of the wheel that
Turning the Wheel
Tip Flexed
3cm 60cm
is located at the proximal
Soft flexible tip part of the BB. The
COOK
blocker cuff is a high
volume, low-pressure
balloon that have appear
shape that provides
adequate seal of the
bronchus. The blocked contain a lumen (1.6mm) that allow suctioning of the lung to facilitate deflation, a limited
suctioning of secretion and insufflation of oxygen to the collapsed lung in case of hypoxia. (Cook Inc.,
Bloomington Indiana)
The Univent Tube: The Univent tube (Univent, Fuji Systems Corp., Tokyo, Japan) is a novel, relatively new
means of achieving bronchial blockade. The bronchial blocker technique has been modified so that the bronchial
blocker is passed along a single-lumen endobronchial tube. The bronchial blocker is housed in a small anterior
lumen containing a thin (2 mm internal diameter) tube with a distal balloon (blocker tube). The Univent tube has
the advantage of using a single lumen tube instead of a DLT, and there no need to change over at the end of the
procedure if postoperative ventilatory support is required. It is also possible to suction through the blocker lumen
or to apply CPAP to improve oxygenation in case of hypoxia. The disadvantages of the tube are: The enteral
diameter is relatively large, the blocker can dislocate during surgical manipulation, and satisfactory bronchial seal
and lung separation are sometimes hard to achieve. Finally, like other endobronchial blockers, the relative small
diameter of the blocker lumen makes it more difficult to remove secretion, and prolong the time required to
achieve a complete deflation of the non-dependent lung. The new generations TCB Univent (Torque control
blocker) are made out of silicone are easier to manipulate to the selected bronchus. The Univent tube blocker is
now available as an independent blocker to be inserted through a standard ET tube (Uniblocker), which is
available in 9F and 5F for pediatric patients.
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MANAGEMENT OF OLV: Once the patient has been placed in the lateral decubitus position, proper DLT
position should be re-checked, since dislocation during position change is not uncommon. Two-lung ventilation
should be maintained for as long as possible. When OLV is required, a Fi02 of 1.0 provides a high margin of
safety to protect against possible hypoxemia. With a FiO2 of 1.0, assuming an intact hypoxic pulmonary
vasoconstriction (HPV) response, PaO2 during OLV should be between 150-210 mmHg. The patient should be
ventilated with a tidal volume of 10-12 ml/kg at a ventilatory rate to maintain a PaCO2 of 35+3 mmHg that can be
estimated from the end-tidal CO2 value. Low tidal volume might produce atelectasis in the ventilated lung
(reduced FRC) and increases in the degree of shunt. High tidal volume might shift blood flow into the non-
dependent lung (similar to the application of PEEP) to increase the transpulmonary shunt. Following the initiation
of OLV, PaO2 can continue to decrease for up to 45 minutes, hence, close monitoring of arterial blood gases
and/or the use of a pulse oximeter are indispensable. Should hypoxia occur, proper positioning of the DLT should
be re-conform by fiberoptic bronchoscopy. Several techniques can be employed to improve oxygenation. The
most effective maneuver for improving PaO2 is the application of a continuous positive airway pressure of 10 cm
H2O (CPAP10) to the non-dependent lung. It consists of insufflation of oxygen under positive pressure to keep a
“quiet” lung, while preventing it from collapsing completely. The beneficial effect of CPAP10 is not secondary to
the positive pressure effect, potentially causing blood flow diversion to the dependent perfused lung, but from
distending the alveoli with oxygen to allow gas exchange. Hyperinflation of nitrogen under positive pressure into
the non-dependent lung failed to improve PaO2. Most studies confirmed that dramatic improvement in PaO2
values with the application of CPAP10. PEEP may be added to the dependent lung, or in combination with
CPAP10 to the non-dependent lung. PEEP10 alone added to the dependent lung, resulted in either no change or in
a decrease in PaO2 values. Most probably, the beneficial effects of PEEP to the dependent lung, assumed to be
subsequent to expansion of atelectatic alveoli, are offset by the increased blood flow diverted to the non-ventilated
lung from the continuous positive pressure. In summary, the preferred method to manage hypoxemia during OLV
is by application of CPAP to the non-dependent lung with a search for an optimal combination of PEEP and
CPAP (between 5-10 cm of H2O). In exceptional cases, despite all of these maneuvers, PaO2 will fail to improve
and intermittent ventilation of the non-dependent lung should be reinstituted with the surgeon’s collaboration.
Depending on the stage of the surgery, if a pneumonectomy is planed, ligation of the pulmonary artery will
eliminate the shunt through that lung. Should doubt arise as to the stability of the patient, (patient becomes
hypotensive, dusky, or tachycardic), two-lung ventilation should be resumed until the problem is settled.
Recently, more attention is directed toward the protection of the ventilated lung. Data form studies conducted in
the ICU recommended the use of low tidal volume (TV) to avoid acute lung injury (ALI). That concept stimulated
a debate over the optimal TV that should be used during OLV. A recent Pro and Con editorial argued that large
TV of 12ml/Kg during OLV may cause over distention and stretching of the lung parenchyma and therefore
would increase the risk of ALI. On the other hand, low TV of 6ml/Kg would predispose the formation of
atelectasis in the depended lung. Furthermore, low TV with PEEP may cause dynamic hyperinflation secondary to
the increase in respiratory rate to maintain PaCO2.
Other important issues are: the use of frequent recruiting maneuvers to reduce the amount of atelectasis in the
dependent lung. The limitations of fluid administration during the procedure to avoid fluid overload which may
increase lung capillary permeability. The risk of ALI and fluid overload increases proportionally to the extension of
the lung parenchyma resection. Finally, total intravenous anesthesia (TIVA) would least inhibit the protective effect
of hypoxic pulmonary vasoconstriction and decrease the transpulmonary shunt through the ventilated lung. A
recent study by Yang et al, compared a group of patients who were ventilated using protective lung ventilation
regime ( TV 6/ml/kg , PEEP 5 Cm H2O, pressure-controlled, Fio2 0.5) compared to conventional ventilation ( FiO2
1.0, TV 10 ml/Kg, Zero PEEP, Volume–controlled.). They found a better oxygenation intra and pos-operatively and
less post operative pulmonary complications in the protective lung ventilation group.
A recent review by Karzai W, addressed the, prediction prevention and treatment of hypoxemia during one lung
ventilation.
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VIDEO ASSISTED THORACOSCOPY

The improvements in video endoscopic surgical equipment and a growing enthusiasm for minimally invasive
surgical approaches brought VAT to the practice of surgery for diagnostic and therapeutic procedures. Most of these
procedures required a well-collapsed lung and should be included in the absolute indication for OLV category. The
patient population tends to be either very healthy, undergoing diagnostic procedures, or high-risk patients who are
undergoing VAT to avoid the stress of a thoracotomy. The patients with advanced cardiopulmonary disease should
have an extensive pre-operative evaluation and interaoperative monitoring the same as for thoracotomy. Small
incision in the chest wall permits the insertion of the video camera and the surgical instruments. In most cases
general anesthesia with one lung ventilation is required. The lung should be well collapsed to allow the surgeon an
optimal view of the surgical field and to palpate the lesion in the lung parenchyma. Because it may take 30 minute
for the lung to collapse it is advisable to initiate OLV immediately following endobronchial intubation. In some
cases, CO2 is insufflated to facilitate visualization, at pressure <10 mm H2O with a flow of less than 2 L/min.
Higher pressure may cause mediastinal shift with cardiovascular compromise. In a very small selected group of
patients to avoid the need for endobronchial intubation, VAT may be performed under regional anesthesia using an
intercostals block or epidural. The patients for regional VAT should be carefully selected and the risk benefit should
be considered.
NITRIC OXIDE AND ONE LUNG VENTILATION

Nitric oxide (NO) is an important endothelium-derived relaxing factor. Clinically used nitrovasodilatators such as
nitroprusside and nitroglycerin exert their effects by releasing NO intracellulary. Inhaled NO (5-80 ppm) has been
shown to decrease pulmonary vascular resistance. NO have selective dilating effects on the pulmonary circulation
without effect on the systemic circulation. The half-life of NO is between 110-130 ms, thus exogenous inhaled NO
may diffuse from the alveoli to pulmonary vascular smooth muscle and produce pulmonary vasodilatation, but any
NO that diffuses into blood will be inactivated before it can produce systemic vasodilatation. Since NO distributes
directly into the alveoli, it is a selective microvasodilator only of those capillaries adjacent to ventilated alveoli, and
therefore improve V/Q matching. This effect is in contrast to NTP or NTG, that when given IV, cause a non-
selective capillary dilatation of poorly ventilated alveoli, which result in deterioration of oxygenation.
The concept that the pulmonary circulation can be modulated by the administration of NO to selective areas of the
lung may be important during one lung ventilation. In theory, the administration of NO during OLV will cause
vasodilatation of that lung, that will enhance the effect of HPV in the non-dependent lung to increase blood flow to
the dependent lung and reduce the degree of shunt. Preliminary studies during OLV presents mixed results. Booth et
al, administered NO at 40 ppm to 9 patients during OLV reported improvement in oxygenation during OLV
compared to a control group of 6 patients (26.8 Pka vs 12.6 Pka). Wilson et al, found no improvement in 6 patients
with the administration of NO at 40 ppm. Os/Qt did not changed in these patients with a normal PVR. The beneficial
effect of NO is limited in the absence of hypoxemia and pulmonary vasoconstriction. Most likely those patients with
hypoxemia and elevated pulmonary pressure during OLV will benefit from the application of NO.
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One of the most interesting future concepts to keep adequate oxygenation during OLV is the ability to modulate
the lung circulation. Almitrine bimesylate a peripheral chemoreceptor agonist increases pulmonary hypoxic
vasoconstriction in low doses. In fact inhaled NO and intravenous Almitrine have been combined with additive
FIG.6 : Almitrine bimesylate effects on gas exchange. In case of OLV using that
combination will maximize the HPV of the non-
Low dose (0.3 ug /Kg)
dependent lung while dilate the dependent lung to
High dose (14 ug/Kg)
95% N2 LLL (Nakanishi) practically eliminate the transpulmonary shunt (Fig.6).
13% O2 , OLV
(Chen) Moutafis et al tested that theory, in 20 patients
Enhance HPV undergoing thoracoscopic lung resection. The group of
Inhibit HPV
patients that received the combination of Almitrine and
IV Almitrine
Enhance HPV
NO has almost no decrease in PaO2 during OLV. That
( low dose) is important for those patients with a marginal
Reduce respiratory reserve who are unable to maintain
shunt oxygenation on OLV. Finally, it would be useful during
no no VAT where the application of CPAP to the non-
Nitric oxide no no Vasodilation
dependent lung interferes with the surgeon’s ability to
Chen L: Ansthesiology ,1987
Nakanishi S: Respir Physio 1988
view the surgical field.
Protective lung ventilation with a TV less than that used for two lung ventilation and accomplishing ventilation
with the lowest feasible peak airway pressure, I: E ratio of 1:1, with a rapid respiratory rate. Alternatively, one
may use pressure control ventilation. Patients with COPD may have difficulties if PEEP leads to dynamic
hyperinflation secondary to the increase in respiratory rate to maintain a satisfactory PaCO2.Recruiting maneuvers
should be used to reduce the amount of atelectasis in the dependent lung. They should be applied with sustained
peak pressure of 40 cm H20 to be effective. One should limit fluid administration during thoracic surgery
procedures to avoid fluid overload. Finally, a balanced anesthetic technique with inhalational agents and adjuvants
(propofol infusion, opioids) to reduce the required concentration of potent inhaled agent, appears the best choice
during OLV. In an interesting recent prospective randomized study by De Conno et al., 58 patients undergoing
thoracic surgery were divided to receive either propofol of sevoflurane. The sevoflurane group showed not only an
attenuated inflammatory reaction at the organ level in the lung undergoing OLV, but also an improved
postoperative course with significantly lower overall number of adverse events. A recent review by Karzai W et
al., discussed prevention and treatment of hypoxemia during one lung ventilation.
Clinical approach to OLV management

1. Use Fio2 of 1.0
2. Ventilate with a TV of 6-8 ml\Kg with PEEP 5 cm H2O
3. Respiratory rate to maintain PaCO2 between 35-40 mmHg
4. Check the DLT/endobronchial blocker position subsequent to the lateral decubitus

positioning
5. If peak airway pressure exceeds 40 mmHg during OLV, DLT/endobronchial blocker

malposition should be excluded.
6. For hypoxemia, apply CPAP10 cm H2O to the non-dependent lung. (not during
VAT)
7. If additional correction of hypoxemia is necessary add PEEP 5-10 cmH2O to the

ventilated lung.
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8. Frequent recruiting maneuvers
9. Avoid fluid over-load
10. TIVA may be preferable to inhalation anesthetics
11. If necessary, intermittently inflate and deflate the operated lung
REFERENCES:
-Benumof JL, et al. Margin of safety in positioning modern double-lumen endotracheal tube. Anesthesiology.
67:729,1985.
-McKenna MJ, et al. Right upper lobe obstruction with right-sided double-lumen Endobronchial tubes: A
comparison of two types. Anesthesiology 63:734-740, 1988.
-Smith G, et al. Sight and sound. Can double-lumen endotracheal tubes be placed accurately without fiberoptic
bronchoscopy? Br J Anaesth 58:1317, 1987.
-Cohen, E, et al. Fiberoptic Evaluation of Endobronchial tube position: red rubber vs. polyvinylchloride. Anesth
Analg 68: S1-S321, 1989.
-Cohen, E, et al. Oxygenation and hemodynamic changes during one-lung ventilation. J Cardiothoracic Anesthesia:
2:134-40, 1988.
-Karande SV. A new tube for single lung ventilation. Chest 92:761-763, 1987.
-Campos JH, et al. Is there a better right-sided tube for one-lung ventilation? A comparison of the right-sided
double-lumen tube with the single-lumen tube with right-sided enclose bronchial blocker Anesth Analg. 86 (4) 696-
700, 1998.
-Arndt GA, Kramer PW, Rusy DA, et al: Single lung ventilation in a critically ill patient using a fiberoptically
directed wire-guided endobronchial blocker. Anesthesiology. 90: 1484-6, 1999.
- Prabhu MR, Smith JH. Use of the Arndt wire-guided endobronchial blocker: Anesthesiology 97: 1325, 2002.
-Campos JH, Kernstine KH. A comparison of a left-sided Bronco-Cath with the torque control blocker Univent and
the wire-guided blocker. Anesth Analg. 96: 283-9, 2003.
-Campos JH: Progress in lung separation. Thorac Surg Clin. 15, 71-83, 2005.
-Cohen E: The Cohen flexitip endobronchial blocker: an alternative to a double lumen tube. Anesth Analg.
101(6):1877-9, 2005.
- Cohen E; The New Bronchial Blockers are Preferable to Double-Lumen Tubes for Lung Isolation J Cardiothor asc
Anesth December, 2008
-Cohen, E, et al. Oxygenation and Hemodynamics changes during one-lung ventilation. J Cardiothoracic
Anesth.2:134-40, 1988.
-Capan LM, et al. Optimization of arterial oxygenation during one-lung anesthesia. Anesth Analg. 59:847, 1980.
-Rees DI, et al. One-lung anesthesia and arterial oxygen tension during continuous insufflation of oxygen to the
non-ventilated lung. Anesth Analg. 61:501, 1982.
Alfery D, et al. Improving oxygenation during one lung ventilation: The effects of PEEP and blood flow
restoration of the non-ventilated lung. Anesthesiology 55:381, 1981.
--Benumof JL, et al: : Halothane and isoflurane only slightly impair arterial oxygenation during one-lung
ventilation in patients undergoing thoracotomy. Anesthesiology. 67:910, 1987.
-Katz JA, et al. Pulmonary oxygen exchange during endobronchial anesthesia: Effect of tidal volume and
PEEP. Anesthesiology 56:164, 1982.
-Allen MS. Video-Assisted thoracic surgical procedures: The Mayo experience. Mayo Clin Proc. 71:351, 1996.
-Rodney J, et al. Video-Assisted Thoracoscopic Surgery: Basic Technical Concepts and Intercostal Approach
Strategies. Ann Thorac Surg. 54:800-7, 1992.
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-Slinger P, Low tidal volume is indicated during one-lung ventilation: Anesth & Analg. 103(2):268-270, 2006
-Gal T. Low tidal volume is not indicated during one lung ventilation: Anesth & Analg. 103(2):271-273, 2006
-Duggan M, -Duggan M, Kavanagh BP. Pulmonary atelectasis. Anesthesiology 102: 838-54, 2005
-Tusman G, Bohm SH, Sipmann FS, Maisch S. Lung recruitment improves the efficiency of ventilation and gas
exchange during one-lung ventilation anesthesia. Anesth Analg. 98:1604-9, 2004
-Fernandez ER, Keegan MT, Brown DR. Intraoperative tidal volume as a risk factor for respiratory failure after
pneumonectomy. Chest 128:129, 2005.
-Nakata M, Saeki H, Yokoyama N, et al. Pulmonary function after lobectomy: video-assisted thoracic surgery versus
thoracotomy. Ann Thorac Surg. 70:938-41, 2000
-Ferson PF. The Role of Video-Assisted Thoracoscopy in Pulmonary Metastases: Chest Clin N Am. 8:59-76, 1998.
-Mukaida T, et al. Thoracoscopic operation for secondary pneumothorax under local and epidural anesthesia in high
risk patients. Ann. Thorac Surg. 65:924-926, 1998.
-Booth J, et al. Effect of unilateral inhaled NO during selective ventilation in anesthetized human (abstract).
Anesthesiology. 81:A1457, 1994.
-Wilson WC, et al. Inhaled nitric oxide (40 ppm) during one-lung ventilation, in the lateral decubitus position, does
not decrease pulmonary vascular resistance or improve oxygenation in normal patients. J Cardiothorac
Vasc Anesth. 11:172-6, 1997.
-Moutafis M, et al. The effect of inhaled nitric oxide and its combination with intravenous Almotrine on PaO2
during one-lung ventilation in patients undergoing thoracoscopic procedures. Amnesty Analg. 85:1130-5, 1998.
-.Wiedemann HP: A perspective on the fluids and catheters treatment trial (FACTT). Fluid restriction is superior in
acute lung injury and ARDS. Cleve Clin J Med 2008: 75:42-48.
-. De Conno E, Steurer MP, Wittlinger M, et al: Anesthetic induced improvement of the inflammatory
response to one-lung ventilation. Anesthesiology 2009: 110:1316-1326.
-Yang M, Ahn HJ, Kim K, Kim JA Et al,: Does a protective ventilation strategy reduce the risk of pulmonary
complications after lung cancer surgery? A randomized controlled trail. Chest 2011: 139: 530-537.
Karzai W, Schwarzkopf K : Hypoxemia during OLV: Prediction, prevention and treatment. Anesthesiology 110:6
2009, 1402-1411
DISCLOSURE
Cook Critical, Honoraria
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Central Venous Pressure and Pulmonary Artery Pressure Monitoring

Jonathan B. Mark, M.D. Durham, North Carolina
Complications of Central Venous Catheterization
Central venous catheterization (CVC) remains a common procedure for the care of intensive care and high-
risk surgical patients. The complications are well recognized, and the more common include:
1. Bleeding (adjacent arterial injury, hematoma formation, airway compromise, or cardiac tamponade)
2. Pneumothorax, hemothorax, and chylothorax
3. Nerve injury
4. Infection (bacteremia, sepsis, endocarditis)
5. Venous thromboembolism
6. Venous (and paradoxical) air embolism
Numerous other complications have been reported, and a recent ASA Closed Claims Analysis (Domino 2004)
suggested that nearly 2% of claims in the database pertain to CVC-associated injuries. Compared to other claims in
this database, CVC claims were associated with a higher average severity of injury and increased fatality. The most
common claim related to catheter or wire embolism, undoubtedly the result of a medical error, and other common
complications described were as noted above. Perhaps of greatest importance, the authors determined that nearly
half of these injuries were preventable by use of pressure waveform monitoring (Ezaru 2009), chest radiography, or
ultrasound-guided cannulation. Growing use of ultrasound for CVC (Ortega 2010) is based on clinical evidence of
reduced failure rates and complications compared to standard techniques that are based on surface anatomy and
palpation (Randolph 1996). Consequently, the recently published ASA practice guideline for central venous
catheterization (Rupp 2012) recommends ultrasound guidance for all elective internal jugular vein catheterization,
based on unequivocal level A1 evidence. Inexpensive ultrasound devices are widely available, easy to use, and
should be considered routinely for all internal jugular cannulation procedures. For example, a thrombosed jugular
vein can be identified prior to prepping and draping, the easily compressible internal jugular vein can be rapidly
identified and distinguished from the adjacent carotid artery, and successful placement of the guidewire can be
confirmed.
IJ
CA
Transverse ultrasound image of right internal Long axis ultrasound image of right internal jugular
jugular (IJ) vein lying slightly lateral and superficial vein showing the guidewire in the lumen (arrow).
to the right carotid artery (CA).
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Pulmonary artery catheterization carries additional risks beyond those associated with central venous
catheterization, including risks associated with catheter flotation through the right heart chambers and prolonged
catheter residence in the pulmonary artery (Roizen, ASA Task Force on PAC 2003). During passage of a
pulmonary artery catheter (PAC) through the right heart chambers, non-sustained atrial and ventricular dysrhythmias
are common and of no clinical significance. Less frequent but more life threatening complications include right
bundle branch block leading to complete heart block in patients with pre-existing left bundle branch block or
sustained ventricular dysrhythmias, including ventricular fibrillation, particularly in patients with myocardial
ischemia involving the right ventricle (Lopez-Sendon 1990). Catheter residence within the pulmonary artery for
hours or days can be complicated by infection (endocarditis and sepsis), pulmonary infarction, and pulmonary artery
rupture, conditions that are often fatal.
The infectious risks of both PAC and CVC placement can be reduced by adherence to practice guidelines
for catheter placement promulgated by JCAHO and the Institute for Healthcare Improvement (IHI) (Berwick 2006).
The IHI 100,000 Lives Campaign has identified six areas for improving patient care, including prevention of CVC-
related infection by proper hand hygiene, maximal barrier precaution (including a large patient drape), chlorhexidine
skin preparation, optimal catheter site selection, and prompt removal of unnecessary catheters. As anesthesiologists,
we need to be concerned with complications that may result from our care but not clinically manifest for days after
surgery. The above-mentioned ASA practice guideline (Rupp 2012) supports these recommendations.
Technical Considerations for Measuring Intravascular Pressures
Prior to initiating pressure monitoring, the transducers must be “zeroed” and “leveled.” While often done
at the same time, these are distinct procedures, both of which are required for accurate pressure measurement.
Zeroing refers to the procedure in which the transducer is exposed to ambient atmospheric pressure through an
attached stopcock open to air, and the atmospheric pressure is assigned a pressure of 0 mmHg when the monitor
zero button is pushed. Note that this means that all intravascular pressure measurements are referenced to ambient
atmospheric pressure.
The second step in transducer setup is to
determine the proper external reference level for the
pressure transducer, or leveling the transducer.
Although the mid-chest position is chosen commonly,
this level has no consistent relation to the position of
the heart (or right atrium) within the thorax.
Positioning the transducer in this location may produce
a significant hydrostatic error, which causes
overestimation of central vascular pressures by more
than 5 mmHg in the average patient. Cogently
summarized, "the only factor that contributes to
measured hydrostatic pressure with a fluid-filled
catheter system is the position of the transducer with
respect to the uppermost fluid level in the … chamber
in which pressure is being measured." (Courtois 1995)
It follows that the preferred position for an external
transducer is the top of the right atrium, which is
estimated best at a point approximately 5-cm below the sternal border at the 4th intercostal space. Transducers for
measuring central venous pressure (CVP) and pulmonary artery pressure (PAP) should be placed in this position.
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Physiologic Basis for CVP and PAC Waveforms and Interpretation of Cardiac Filling Pressures
The normal CVP waveform consists of three peaks (a, c, v) and two descents (x, y). The most prominent
wave is the a wave, which results from atrial contraction following the ECG P wave at end-diastole. This atrial
contraction provides the end-diastolic atrial kick, which loads the right ventricle through the open tricuspid valve.
Atrial pressure decreases following the a wave, as the atrium relaxes. This decline in atrial pressure is interrupted
by the c wave at the beginning of systole. The c wave results from isovolumic right ventricular contraction, which
closes the tricuspid valve, causing it to bow back toward the right atrium in early systole and produce an increase in
atrial pressure. The c wave must follow onset of the ECG QRS, since it is an early systolic event. Atrial pressure
continues its decline in mid-systole, owing to ongoing atrial relaxation and changing atrial geometry produced by
ventricular contraction and ejection. This is the x descent or systolic collapse in atrial pressure. The x descent can
be divided into x and x' descents, denoting the portions before and after the c wave. However, the x descent
generally should be considered to be the systolic decline in atrial pressure. The last atrial pressure peak is the v
wave, caused by venous filling of the right atrium, through the vena cava, during late systole while the tricuspid
valve remains closed. The v wave peaks just after the ECG T wave. Atrial pressure then decreases as the tricuspid
valve opens and blood flows from atrium to ventricle. This is the y descent or diastolic collapse in atrial pressure.
During flotation of a PAC through the right heart chambers, typical pressure waveforms are recorded from
the right atrium, right ventricle, and pulmonary artery. Note that right atrial (RA) pressure is equal to CVP and of
similar waveform morphology. As the PAC crosses the tricuspid valve, the increase in systolic pressure identifies
arrival of the catheter in the right ventricle (RV),
and flotation across the pulmonic valve is ECG
identified by an increase in diastolic pressure in
the pulmonary artery (PA). Occasionally,
distinguishing RV from PA pressure is difficult, RV
but careful examination of the diastolic portion
of these two pressure waveforms clarifies these 30- RA
different catheter tip locations. During diastole,
RV filling results in a pressure increase in the -
RV, while diastolic flow from the PA toward the
lung results in a pressure decrease (Red Arrows). 0-
Advancing the balloon tipped PAC

further into the PA will allow the catheter to
“wedge” and record the PA wedge pressure or
PA occlusion pressure. When the PAC is PA
wedged, the pressure recorded from the catheter PA Wedge
tip is isolated from the proximal PA pressure by 30-
the occluding balloon, and the tip records
downstream pulmonary venous and left atrial -
pressure. Normal PA wedge pressure
waveforms display the same characteristic peaks 0-
and descents previously described for CVP or RA pressure waveforms. However, PA wedge pressure is an indirect
measure of left atrial pressure. Left atrial pressure waves (a, c, and v) must be transmitted in a retrograde fashion,
from the left atrium, through the pulmonary veins, capillaries, and arteries to arrive at the wedged PAC. As a result,
PA wedge pressure is a delayed, damped reflection of left atrial pressure. Left atrial pressure a and v waves are
recorded in a pulmonary artery wedge pressure trace approximately 150-200 msec after they are inscribed in the left
atrial pressure trace, largely owing to the transmission time through the interposed pulmonary vascular bed. In
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general, the wedge pressure a wave follows the ECG R wave owing to this delay (compare CVP and PA wedge
pressures in red box). If these a and v waves are prominent, they can be detected in the unwedged PA pressure
trace, the a wave distorting the systolic upstroke, and the v wave obscuring the dicrotic notch.
ECG
R R
120- -30
ART
- -
PA
- PA Wedge -
CVP
0- -0
A wide variety of hemodynamic abnormalities can be identified through careful analysis of CVP and PAC
waveforms. Dysrhythmias have characteristic signatures. In atrial fibrillation the CVP a wave disappears, and
the c wave becomes more prominent, since atrial volume is greater at end-diastole and onset of systole, owing to the
absence of atrial contraction. Isorhythmic atrioventricular dissociation or junctional rhythm alters the
normal sequence of atrial and ventricular contraction. When there is retrograde conduction of the pacemaker
impulse from AV node to the atrium, atrial contraction occurs during ventricular systole, when the tricuspid valve is
closed, thereby inscribing a tall cannon a wave in the CVP waveform. Absence of normal atrioventricular synchrony
during ventricular pacing can be identified in similar fashion by searching for venous cannon waves. In these
instances, the CVP helps diagnosis the cause of arterial hypotension since loss of the normal end-diastolic ECG P
wave may not be as clearly evident as the cannon a waves in the CVP trace. Valvular heart disease may also be
identified, particularly AV valve regurgitation. Tricuspid regurgitation produces abnormal systolic filling of
the right atrium through the incompetent valve. A broad, tall systolic c-v wave is inscribed, which begins in early
systole and obliterates the systolic x descent in atrial pressure. The CVP trace is said to be ventricularized,
resembling RV pressure. This regurgitant wave differs in onset, duration and magnitude from a normal CVP v
wave caused by end-systolic atrial filling from the vena cavae. Right ventricular end-diastolic pressure is
overestimated by the numeric readout on the bedside monitor, which reports a single mean value for CVP. Instead,
right ventricular end-diastolic pressure is estimated best by measuring the CVP value at the time of the ECG R
wave, prior to the regurgitant systolic wave. In a similar manner, a tall systolic c-v wave noted in the PA wedge
pressure trace is the typical hallmark of severe mitral regurgitation. As noted above, a tall v can be noted to
distort the PA waveform in the unwedged PA pressure trace.
Tricuspid Regurgitation
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ECG Mitral Regurgitation
200- R R
- 90- v
ART - v
-
-
0- -
20- v 45-
c
-
CVP -
-
- y PA
-
0- PA Wedge
0-
Perhaps the most clinically important pressure waveform abnormalities are those introduced during the
respiratory cycle and caused by cyclic variations in intrathoracic pressure. During spontaneous breathing,
inspiration causes a decrease in pleural and pericardial pressures that is transmitted to the RA and produces a decline
in transduced CVP (as well as other measured central vascular pressures). Note that the decrease in the transduced
CVP measured during inspiration may actually reflect an increase in transmural CVP, which is calculated as the
difference between the pressure measured inside the RA and pericardial pressure outside the atrium. In clinical
practice, transmural pressures are rarely determined owing to the difficulties in assessing pleural or pericardial
pressures. Instead, end-expiratory pressure should always be recorded to provide the best estimate for
transmural filling pressures. Since pleural and pericardial
pressures approach atmospheric pressure at end-
expiration whether the patient is breathing spontaneously
or receiving positive pressure mechanical ventilation,
pressures recorded at this point in the respiratory cycle
will provide the best estimate for transmural pressure and
cardiac preload. End-expiratory pressure values can be
determined by visual inspection of the CVP, PA, and
wedge waveforms on a calibrated monitor screen or paper
recording.
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Measurement of CVP
at End-Expiration
An understanding of transmural pressure is the key to proper interpretation of intravascular pressure

recordings and their relationship to cardiac filling volume or preload (Gelman 2008). Increased filling pressure can
result from increased chamber volume, increased chamber wall stiffness, or increased pressure surrounding the heart
(pericardial or intrathoracic pressure). This is the physiologic basis for recording intravascular pressures at end-
expiration and explains why high CVP or PA wedge pressures may not always indicate hypervolemia or increased
chamber volume. For example, when there is diastolic left ventricular dysfunction from myocardial ischemia
(impaired relaxation) or hypertrophy (increased wall stiffness), the shape of the ventricular pressure-volume
relationship is shifted up and to the left. Under normal conditions, a fluid challenge would increase ventricular
preload with little change in filling pressure (Point A  Point B). Owing to the curvilinear relationship between
chamber pressure and volume, marked increases in chamber filling will be accompanied by an increased filling
pressure (Point C). On the other hand, when there is diastolic dysfunction, the same elevated filling pressure may
not reflect increased preload, but rather abnormal chamber stiffness or increased surrounding pressure (Point D). It
is likely that these physiologic considerations confound simple interpretation of PAC-derived data and contribute to
the limited value of PAC monitoring found in many clinical trials.
Pulmonary Artery Catheterization and Patient Outcome
The PAC has been surrounded by controversy since its introduction into clinical medicine by Swan and
Ganz more than 40 years ago (Swan 1970). A number of early clinical trials identified excess mortality in patients
receiving PAC monitoring, but these studies were criticized for their retrospective design and other shortcomings.
The SUPPORT Trial was perhaps the most widely publicized of these studies, as it was a large trial conducted in
critically ill medical and surgical patients from five major medical centers. The patients with PAC monitoring were
carefully matched to other ICU patients through use of a propensity score, but still had increased hospital length of
stay, increased hospital costs, and higher mortality than patients who were not monitored with PACs (Connors
1996). Widespread use of these catheters continued, in part owing to concerns that randomized prospective clinical
trials were still not available. However, several studies in the past few years have provided new and important data.
Sandham et. al. randomized PAC usage in nearly 2,000 ASA III and IV patients undergoing urgent or
elective major surgery and found identical survival in patients with and without PAC monitoring (Sandham 2003).
Although the authors did not identify excess mortality associated with PAC usage, there were more pulmonary
complications in the PAC group, including pulmonary embolism, hemorrhage, and infarction. Another seminal
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randomized prospective investigation was conducted in 1,041 patients from 65 intensive care units in the United
Kingdom. This PAC-Man Trial showed no difference in hospital mortality in patients monitored with PACs
compared with control patients (Harvey 2005). A third randomized prospective study, the ESCAPE Trial, evaluated
PAC use in hospitalized patients with severe congestive heart failure and found no effect on mortality or days alive
out of hospital (ESCAPE 2005). And perhaps of greatest clinical impact, a meta-analysis of 13 randomized clinical
trials conducted between 1985 and 2005 in 5,051 patients, half of whom were surgical, showed that PAC monitoring
had NO EFFECT on mortality or days hospitalized (Shah 2005).
Taken together, these most recent publications suggest that we have little clinical evidence that PAC
monitoring benefits our patients. Consequently, it is not surprising that use of PACs is decreasing. Between 1993
and 2004, data derived from the National Inpatient Sample (part of the Agency for Healthcare Research and Quality
[AHRQ] Healthcare Cost and Utilization Project) demonstrated a 65% reduction in use of PACs in hospitalized
medical patients and a similar reduction in surgical patients (Wiener 2007). A similar trend has been identified in a
recent review of PAC use in 27,000 critically ill patients, which showed a 68% reduction in PAC monitoring in
intensive care (Berthiaume 2009).
Notwithstanding these practice trends, many critical care experts and anesthesiologists still use PACs in
high-risk patients and believe they are needed to manage complex hemodynamic conditions (Chatterjee 2009).
Furthermore, despite recent randomized controlled trials that have failed to demonstrate benefit from PAC
monitoring, it is quite possible that trials have not been conducted in patient cohorts likely to reap these benefits,
such as complex cardiac surgical patients or those with the most severe cardiopulmonary disorders. A recent report
from the ESCAPE Trial investigators showed that patients who were excluded from randomization but included in a
parallel trial registry of PAC monitoring had a higher mortality than randomized trial patients who received PACs
(Allen 2008). In the words of these authors, “ESCAPE investigators enrolled quite different patients into the
randomized trial compared with those relegated to the registry… The perceived need for hemodynamic
measurement itself identified a high-risk population.” Perhaps more relevant for the typical clinical practice of
anesthesiologists, the most recent American College of Cardiology/American Heart Association practice guideline
for coronary artery bypass graft surgery recommends PAC monitoring for patients presenting in cardiogenic shock
(Class I, Level C Evidence) and patients with acute hemodynamic instability (Class IIa, Level B Evidence), and
possibly for coronary bypass surgery in otherwise stable patients (Class IIb, Level C Evidence) (Hillis 2012).
Strong evidence derived from robust clinical trials for the use of PACs in this population remains unavailable.
The 40-year saga of the PAC is not likely at an end. These observations have important implications for
training and maintenance of competency (Rubenfeld 2007). For years, many have argued that clinicians, both
doctors and nurses, who use PACs are inadequately trained in their use and have inadequate knowledge to use these
devices safely (Iberti 1990). This problem may be even greater today. If we are to continue using this invasive
monitoring tool, we must understand its limitations, the physiologic principles underlying interpretation of the data
provided, and recognize the potential associated complications before they harm patients.
All figures modified courtesy of Jonathan B. Mark, Atlas of Cardiovascular Monitoring, 1998 (Churchill Livingstone)
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References and Additional Reading
1. Allen LA, Rogers JG, Warnica JW, et al. High mortality without ESCAPE: The registry of heart failure
patients receiving pulmonary artery catheters without randomization. J Cardiac Failure 2008;14:661-9.
2. Berthiaume LR, Peets AD, Schmidt U, et al. Time series analysis of use patterns for common invasive
technologies in critically ill patients. Journal of Critical Care 2009;xx:xxxx.
3. Berwick DM, Calkins DR, McCannon CJ, Hackbarth AD. The 100 000 Lives Campaign: Setting a Goal and a
Deadline for Improving Health Care Quality. JAMA 2006;295:324-7.
4. Braner DAV, Lai S, Eman S, Tegtmeyer K. Central venous catheterization -- subclavian vein. N Engl J Med
2007;357:e26.
5. Chatterjee K. The Swan-Ganz Catheters: Past, present, and future. A viewpoint. Circulation 2009;119:147-52.
6. Connors AF, Speroff T, Dawson NV, et al. The effectiveness of right heart catheterization in the initial care of
critically ill patients. JAMA 1996;276:889-97.
7. Courtois M, Fattal PG, Kovacs SJ, Tiefenbrunn AJ, Ludbrook PA. Anatomically and physiologically based
reference level for measurement of intracardiac pressures. Circulation 1995;92:1994-2000.
8. Domino KB, Bowdle TA, Posner KL, Spitellie PH, Lee LA, Cheney FW. Injuries and liability related to central
vascular catheters: a closed claims analysis. Anesthesiology 2004;100:1411-8.
9. ESCAPE I. Evaluation study of congestive heart failure and pulmonary artery catheterization effectiveness.
The ESCAPE Trial. JAMA 2005;294:1625-33.
10. Ezaru CS, Mangione MP, Oravitz TM, Ibinson JW, Bjerke RJ. Eliminating arterial injury during central venous
catheterization using manometry. Anesth Analg 2009;109:130-4.
11. Gelman S. Venous function and central venous pressure: a physiologic story. Anesthesiology 2008;108:735-48.
12. Gnaegi A, Feihl F, Perret C. Intensive care physicians' insufficient knowledge of right-heart catheterization at
the bedside: Time to act? Crit Care Med 1997;25:213-20.
13. Gordon AC, Saliken JC, Johns D, Owen R, Gray RR. Ultrasound-guided puncture of the internal jugular vein:
Complications and anatomic considerations. Journal of Vascular and Interventional Radiology 1998;9:333-8.
14. Graham AS, Ozment C, Tegtmeyer K, Lai S, Braner DAV. Central venous catheterization. N Engl J Med
2007;356:e21.
15. Harvey S, Harrison DA, Singer M, et al. Assessment of the clinical effectiveness of pulmonary artery catheters
in management of patients in intensive care (PAC-Man): a randomised controlled trial. Lancet 2005;366:472-7.
16. Hillis LD, Smith PK, Anderson JL, et al. 2011 ACCF/AHA guideline for coronary artery bypass graft surgery:
Executive Summary. Anesth Analg 2012;114:11-45.
17. Iberti TJ, Daily EK, Leibowitz AB, et al. Assessment of critical care nurses' knowledge of the pulmonary artery
catheter. Crit Care Med 1994;22:1674-8.
18. Iberti TJ, Fischer EP, Leibowitz AB, et al. A multicenter study of physicians' knowledge of the pulmonary
artery catheter. JAMA 1990;264:2928-32.
19. Jacka MJ, Cohen MM, To T, Devitt JH, Byrick R. Pulmonary artery occlusion pressure estimation: How
confident are anesthesiologists? Crit Care Med 2002;30:1197-203.
20. Lopez-Sendon J, Lopez de Sa E, Maqueda IG, et al. Right ventricular infarction as a risk factor for ventricular
fibrillation during pulmonary artery catheterization using Swan-Ganz catheters. Am Heart J 1990;119:207-9.
21. Marik PE, Baram M, Vahid B. Does central venous pressure predict fluid responsiveness? A systematic review
of the literature and the Tale of Seven Mares. Chest 2008;134:172-8.
22. Mark JB. Central venous pressure monitoring: clinical insights beyond the numbers. J Cardiothorac Vasc
Anesth 1991;5:163-73.
23. Mark JB. Atlas of cardiovascular monitoring. New York: Churchill Livingstone; 1998.
24. McGee DC, Gould MK. Preventing complications of central venous catheterization. N Engl J Med
2003;348:1123-33.
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25. Ortega R, Song M, Hansen CJ, Barash P. Ultrasound-guided internal jugular vein cannulation. N Engl J Med
2010;362:e57.
26. Randolph AG, Cook DJ, Gonzales CA, Pribble CG. Ultrasound guidance for placement of central venous
catheters: A meta-analysis of the literature. Crit Care Med 1996;24:2053-8.
27. Roizen MF, Berger DL, Gabel RA, et al. Practice guidelines for pulmonary artery catheterization. An updated
report by the American Society of Anesthesiologists Task Force on Pulmonary Artery Catheterization.
28. Rubenfeld GD, McNamara-Aslin E, Rubinson L. The pulmonary artery catheter, 1967-2007: rest in peace?
Jama 2007;298:458-61.
29. Rupp SM, Apfelbaum JL, Blitt C, et al. Practice Guidelines for Central Venous Access. A report by the
American Society of Anesthesiologists Task Force on Central Venous Access. Anesthesiology 2012;116:539-73.
30. Sandham JD, Hull RD, Brant RF, et al. A randomized, controlled trial of the use of pulmonary-artery catheters
in high-risk surgical patients. N Engl J Med 2003;348:5-14.
31. Schroeder RA, Barbeito A, Bar-Yosef S, Mark JB. Cardiovascular monitoring. In: Miller RD, ed. Miller's
Anesthesia. Seventh Edition. Philadelphia: Churchill Livingstone Elsevier; 2010:1267-328.
32. Shah MR, Hasselblad V, Stevenson LW, et al. Impact of the pulmonary artery catheter in critically ill patients:
meta-analysis of randomized clinical trials. JAMA 2005;294:1664-70.
33. Sharkey SW. Beyond the wedge: Clinical physiology and the Swan-Ganz catheter. Am J Med 1987;83:111-22.
34. Sharkey SW. A guide to interpretation of hemodynamic data in the coronary care unit. Philadelphia, PA:
Lippincott-Raven; 1997.
35. Squara P, Bennett D, Perret C. Pulmonary artery catheter. Does the problem lie in the users? Chest
2002;121:2009-15.
36. Swan HJC, Ganz W, Forrester J, Marcus H, Diamond G, Chonette D. Catheterization of the heart in man with
use of a flow-directed balloon-tipped catheter. N Engl J Med 1970;283:447-51.
37. Teplick RS. Measuring central vascular pressures: a surprisingly complex problem. Anesthesiology
1987;67:289-91.
38. Trottier SJ, Taylor RW. Physicians' attitudes toward and knowledge of the pulmonary artery catheter: Society
of Critical Care Medicine Membership Survey. New Horizons 1997;5:201-6.
39. Tsui JY, Collins AB, White DW, Lai J, Tabas JA. Placement of a femoral venous catheter. N Engl J Med
2008;358:e30.
40. Wiener RS, Welch HG. Trends in the use of the pulmonary artery catheter in the United States, 1993-2004.
JAMA 2007;298:423-9.
DISCLOSURE
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Postoperative Acute Kidney Injury in Cardiac Surgery

Madhav Swaminathan, M.D., FASE, FAHA Durham, North Carolina
Introduction
Acute kidney injury (AKI) is a significant cause of morbidity and mortality among hospitalized patients, especially
in the postoperative setting. In addition, it remains a significant complication of cardiac surgery throughout the
world.1-5 Consequences of AKI include an increase in mortality risk which can exceed 60% among patients
requiring dialysis.3 Even when serum creatinine values remain within the normal range, modest increases from
baseline values are associated with increased odds of death and end-stage renal disease, as well as longer hospital
stays and increased costs.2,5,6 In general, there have neither been any associated improvements in incidence nor
mortality despite many recent advances in our understanding of the etiology and pathophysiology of AKI.7
Incidence
Nearly 500,000 coronary artery
bypass graft (CABG) surgeries are
performed each year in the US.8 AKI
is a common complication following
cardiac surgery that appears to be
increasing in frequency independent
of increasing severity of patient case-
mix, perhaps related to changing
diagnostic criteria (Figure 1).9
Common risk factors include age,
diabetes, hypertension, and metabolic
syndrome, and chronic kidney disease.
In addition to the substantial increase
in short-term mortality associated with
AKI following cardiac surgery, long-
term mortality may be mediated by
persistent chronic kidney disease
among AKI survivors.10 Figure 1: Trends in acute renal failure (ARF) and a subset requiring
concurrent dialysis (ARF-D). Unadjusted values over an estimated US
Pathophysiology population of 7.4 million CABG cases over 16 years from 1988-2003.
Perioperative AKI is the net result of (Swaminathan, M, et al. Crit Care Med. 2007 Oct;35(10):2286-91)
several possible insults. Common to
all AKI though, are tubular and vascular cell dysfunction, necrosis, and apoptosis. Although details of the trigger
mechanisms for AKI are unclear, there is better understanding of some insults specific to cardiac surgery, the field
in which it has been comprehensively studied. Cardiac surgery is an ideal model for studying the AKI phenomenon
– a non-physiological insult and exposure to a pro-inflammatory, frequently hypothermic and ischemic
cardiopulmonary bypass (CPB) circulation in a patient with cardiovascular disease already at risk for renal injury.
Inflammation
Circulating proinflammatory cytokines are part of the systemic inflammatory response to surgical trauma and CPB.
Additionally, local release of cytokines related to renal ischemia/reperfusion is mediated by nuclear factor kappa B
(NF-κB) activation. Renal dysfunction also influences the inflammatory responses since filtration is a primary
clearance mechanism for many cytokines.
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Ischemia Reperfusion
Embolism, low-output syndrome, and exogenous catecholamines can all contribute to renal ischemia/reperfusion
during cardiac surgery, leading to phosphate depletion, calcium accumulation, oxygen free radical generation, local
leukocyte activation, and NF-κB activation. These changes cause necrosis, and apoptotic cell death through caspase
activation. Experimentally, caspase or NF-κB inhibition attenuates ischemia-reperfusion mediated AKI.11
Embolism
Renal atheroembolism can be a major cause of postoperative AKI. Aortic atheroma burden and intraoperative
emboli counts predict AKI. Aortic plaque disruption due to intra-aortic balloon pump counterpulsation is likely also
a significant contributor to AKI. Anti-atheroembolism strategies have been widely adopted into the conduct of
cardiac surgery, including aortic avoidance and use of devices that limit aortic manipulation, but none have proved
effective tools at preventing postoperative AKI.
Nephrotoxins
Nephrotoxic agents blamed in the pathogenesis of AKI include pigments and drugs such as antifibrinolytics.
Myoglobin and hemoglobin avidly bind nitric oxide, causing AKI through direct cytotoxicity, vasoconstrictor
effects, and tubular obstruction. Leg ischemia from femoral artery cannulation has been blamed for myoglobinuric
AKI. Although statins have been associated with myopathy, they have not been associated with increased renal risk
in vascular and major non-cardiac surgery patients.
While both aprotinin and the lysine analogues (tranexamic acid, epsilon aminocaproic acid) are freely filtered by the
glomerulus and attach to the same brush border receptors in the proximal tubule (megalin/cubilin), understanding of
subsequent metabolism of these agents is incomplete. Aprotinin is taken up into proximal tubular cells, where it
remains for many hours. In contrast, epsilon aminocaproic acid and tranexamic acid, both of which resemble amino
acids in size, block these same receptors,
causing minor tubular proteinuria. While
proteinuria would normally be evidence of
tubular injury, this type can also be elicited
by doses of lysine or arginine, and
completely resolves 15 minutes after the
agent is discontinued.
A single retrospective analysis of epsilon
aminocaproic acid in 1502 patients did not
find an increase in AKI.12 Controversial
retrospective studies comparing renal and
other consequences of aprotinin,
tranexamic acid, and epsilon aminocaproic
acid in large cardiac surgery populations
found increased AKI and mortality with
aprotinin.13,14 Concerns persist that a bias
towards sicker patients receiving aprotinin
cannot be adequately addressed by
statistical methods in these studies. Other Figure 2: The difference between a creatinine-based biomarker and novel
studies on AKI have also used exposure to early biomarker-based diagnostic approach for postoperative AKI. (Hudson,
aprotinin as models of investigating better C et al. Semin Cardiothorac V asc A nesth. 2008 Dec;12(4):320-30.)
creatinine profiles for AKI prediction.15
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Biomarkers
Given the limitations of using serum creatinine and urine output for detecting AKI, there is a need for better
biomarkers that can more reliably help diagnose AKI that is specifically caused by acute tubular necrosis, the most
common renal injury among post-cardiac surgery patients. If such a diagnosis could be accurately detected early
after the injury, then the ‘window of opportunity’ for effective therapies may shift dramatically (figure 2). In
addition, earlier and more reliable detection of AKI would facilitate better risk stratification. Examples of outcomes
that could be estimated include the degree of AKI including dialysis requirement, duration of AKI, subsequent
chronic kidney disease, or mortality.
Several new biomarkers have been identified while those previously known have been more intensely studied.
Although there have been over 20 unique biomarkers of AKI identified or under investigation, most of the current
interest has focused on a handful of promising biomarkers: neutrophil gelatinase-associated lipocalin, cystatin C,
interleukin-18, and kidney injury molecule–1.16
In the setting of cardiac surgery, NGAL has been demonstrated to be a highly sensitive and specific biomarker of
postoperative AKI. Its gene is one of the earliest and the most upregulated in the kidney after ischemic injury.17 In
a study of 81 adult cardiac patients, 20% of the patients developed postoperative AKI. NGAL was higher in patients
with AKI at 1 hour, 3 hours, and 18 hours post-CPB when compared with their non-AKI counterparts. A more
recent study found that the use of aprotinin versus epsilon amino-caproic acid in patients undergoing cardiac surgery
resulted in a two-fold incidence of AKI in the aprotinin group. Urinary NGAL was significantly higher at both 0 and
3 hours post CPB in patients receiving aprotinin.18
Interleukin-18 (IL-18) is a proinflammatory cytokine that belongs to the IL-1 superfamily, and has been shown to be
both a mediator and biomarker of ischemic AKI. Kidney injury molecule-1 (KIM-1) is an immunoglobulin
superfamily transmembrane protein normally present at low levels in proximal renal tubular cells that dramatically
increases in expression following acute ischemic or nephrotoxic insult. Several studies among non-cardiac patients
have demonstrated that KIM-1 is a very sensitive indicator of AKI. However, fewer studies exist in the cardiac
surgery literature.
It has been suggested that cystatin C is an ideal molecule for measuring GFR because it is freely filtrated by the
glomerulus, completely reabsorbed by the proximal convoluted tubules, and is not secreted. Unlike creatinine, it is
not affected by age, gender, sex, or body mass. There have only been a few studies to date that have explored
cystatin C as a biomarker for AKI post-cardiac surgery. In one prospective study, both serum cystatin C and NGAL
were measured in 129 pediatric patients following CPB for corrective congenital heart surgery.19 Both cystatin C
and NGAL were very strong independent predictors of AKI when compared to creatinine. In the 41 patients who
developed AKI, NGAL levels were elevated 2 hours postoperatively while cystatin C levels were elevated at 12
hours postoperatively.
In the largest cardiac surgery AKI biomarker study performed so far, the Translational Research Investigating
Biomarker Endpoints (TRIBE) AKI consortium gathered detailed plasma and urinary biomarker data in 1,219 adults
undergoing cardiac surgery at high risk for postoperative AKI.20 These investigators found that the highest quintiles
of plasma NGAL and urinary IL-18 were associated with 6.8 and 5 fold greater odds of developing AKI, in addition
to being at higher risk for dialysis, longer hospital stay and overall mortality. The addition of these novel biomarkers
significantly improved the AKI risk predictive capability of conventional models inclusive of only clinical
variables.20
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Renal Protective Strategies

Advances in identifying individuals at-risk for
AKI early are of limited value if they cannot
be used to meaningfully improve patient
outcomes. To date, attempts to prevent and
attenuate renal injury have met with limited
success. Current renal protective strategies
involve optimization of renal perfusion,
avoidance of nephrotoxic agents, and the use
of several pharmaceutical agents. Despite
decades of trying to mitigate the severity of
renal injury, none of these strategies have
shown a consistent benefit in improving
outcomes such as reduced incidence of AKI
requiring dialysis or death.
Although these biomarkers are still early in
the process of being validated, several are
likely to be used in clinical trials. Some
current trials are revisiting previously tested
renal protective agents while others are Figure 3: The association between early recovery of renal function as
testing newer ones. Nonetheless, there are characterized by the percentage decrease in creatinine 24 hours after its
several exciting trials under way in post- peak value (PD24) and long-term adverse outcome. Significant
cardiac surgical AKI. For example, differences exist in event-free survival among patients grouped according
erythropoeitin has been shown to have to magnitude of early recovery, with superior survival among those with a
diverse effects on nonhematopoeitic tissues higher PD24. (Swaminathan, M et al. A nn Thorac Surg. 2010)
that may be beneficial in the prevention of A pr;89(4):1098-104.)
AKI. Another promising treatment currently under investigation for the prevention of AKI is minocyline. A second
generation tetracycline, this antibiotic has both anti-inflammatory and antiapoptotic properties. It has been shown in
rat models to reduce nephrogenic inflammation and cell death. Currently, there is a randomized, double-blind
placebo control study under way to evaluate its efficacy preoperatively in patients with pre-existing renal
insufficiency undergoing cardiac surgery.21
Intrarenal infusion of medication is another emerging therapy proposed to improve efficacy and decrease the
systemic effects of renal protective therapies. For instance, while systemic administration of a vasodilator may be
detrimental in a hypotensive post-surgical patient, selective renal vasodilation via intrarenal catheter infusion may be
beneficial in preventing AKI. Other therapies being investigated or revisited in AKI post cardiac surgery are sodium
bicarbonate, N-acetylcysteine, and tight glucose control.
Another phenomenon that is appears promising for management of AKI is recovery of renal function.22 We have
recently shown that patients that recover renal function early after AKI may have reduced risk of mortality
compared to those who do not recover as well, given the same magnitude of injury (figure 3).22 The repair and
regenerative potential of the kidneys may therefore be crucial to overall survival. With our failure to significantly
prevent postoperative AKI, salvage of renal function by targeting regenerative potential may the interventional
strategy that should be assessed next.
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Summary
Acute kidney injury in the postoperative cardiac surgery population remains a significant cause of perioperative
morbidity and mortality. Despite extensive research in the prediction and treatment of this disease, there has been
limited success in altering patient outcomes. With advances in our understanding of underlying clinical and genetic
risk, as well as the development of more sensitive and specific biomarkers, we may be on the cusp of a new era of
AKI treatment. Once promising therapies are identified, customized approaches would harness information from
individuals’ own genetic profiles and biomarker
responses following cardiac surgery in order to
identify specific personalized interventions. For
example, preoperative evaluation may include a
genetic panel that stratifies patients into
categories of risk and targets them for
preventive therapies. For some high-risk
patients, this may also assist with the decision
whether to proceed with surgery or to use more
conservative medical management for their
cardiovascular disease. During the
perioperative period, urinary and serum
biomarkers could be used to detect AKI in the
earliest stages, confirm the appropriate
phenotype warranting intervention, and discern Figure 4: A suggested strategy for post-AKI targeted intervention
anticipated responses to available agents in stratified using a combination of biomarkers and genomic methods
order to deliver tailored therapy to each to stratify those at risk of adverse outcome. (Hudson, C et al. Semin
individual patient (figure 4). Targeting renal Cardiothorac V asc A nesth. 2008 Dec;12(4):320-30.)
salvage to reduce mortality risk may offer hope
in those already affected by AKI. Although such a future hinges on many advances from the current state, we
believe that this multifaceted, individualized approach will finally lead to meaningful improvements in postoperative
AKI.
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20. Parikh CR, Coca SG, Thiessen-Philbrook H, et al. Postoperative biomarkers predict acute kidney injury and
poor outcomes after adult cardiac surgery. J A m Soc Nephrol. Sep 2011;22(9):1748-1757.
21. http://clinicaltrials.gov/ct2/show/NCT00556491. Minocycline to Prevent Acute Kidney Injury After
Cardiac Surgery. Clinicaltrials.gov 2008; http://clinicaltrials.gov/ct2/show/NCT00556491, 2008.
22. Swaminathan M, Hudson CC, Phillips-Bute BG, et al. Impact of early renal recovery on survival after
cardiac surgery-associated acute kidney injury. A nn Thorac Surg. Apr 2010;89(4):1098-1104.
DISCLOSURE
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Cerebral Protection During Cardiac Surgery

Charles W. Hogue, M.D. Baltimore, Maryland
Cerebral injury from cardiac surgery continues to adversely impact patient survival, quality of life, and health care
costs.1-3 Clinical manifestations of this complication include stroke, which occurs in 1–3% of patients; delirium,
which occurs in 15–30% of patients; and postoperative cognitive dysfunction (POCD), which affects 15–40% of
patients 1 month after surgery.1,3-6 The relationship between POCD and long-term cognitive decline and dementia
has been the focus of several longitudinal studies. Newman et al6 found an association between POCD after CABG
surgery and cognitive impairment 5 years later. In contrast, Selnes et al7 found similar rates of decrement in
cognition over 6 years of follow-up between patients who underwent CABG surgery and a control group treated
medically for known coronary artery disease. The latter findings are supported by data from Van Dijk et al,8 who
compared cognition in patients 5 years after CABG surgery (performed with or without cardiopulmonary bypass,
CPB) to that in a group of subjects without cardiac disease. More recently, Evered et al9 reported that the incidence
of POCD was similar for patients 3 months after coronary angiography (21%), total hip joint replacement surgery
(16%), and CABG surgery (16%; p=0.13). Thus, a preponderance of data suggest that POCD resulting primarily
from cardiac surgery resolves by 3 to 6 months after surgery in most patients and that further cognitive decline likely
results from the progression of coexisting cerebrovascular disease.
Proposed Mechanisms
Two mechanisms have been proposed for cerebral injury from cardiac surgery: cerebral macro/microembolism and
cerebral hypoperfusion.3,5 It is hypothesized that the clinical manifestations depend on the size and location of the
injury (e.g., motor areas vs. areas involved with cognition). Importantly, embolism and hypoperfusion do not
necessarily occur in isolation; they can co-exist in the same or different areas in a given patient.10 Although, primary
cerebral hemorrhage is believed to be a rare cause of cerebral injury, sensitive magnetic resonance imaging (MRI)
methods suggest that punctuate hemorrhages can occur after surgery in some patients, such as those with
endocarditis.11 Inflammatory processes resulting from CPB, organ ischemia/reperfusion, and genetic susceptibility
may further contribute to injury.3,12-14
Atherosclerosis of the ascending aorta is a potential source of cerebral macro- and micro- (<200 µm) emboli,
according to prospective ultrasound investigations, intraoperative transcranial Doppler (TCD) monitoring, and
autopsy studies.5,15 Autopsy studies of adults after cardiac surgery also have implicated lipogenous emboli as a
source of microemboli.16 Canine experiments suggest that fat arising from the cardiotomy suction aspirate is the
major source of these lipid emboli. Some small studies have implicated cerebral microemboli as a cause of POCD
by correlating the number of TCD-detected cerebral embolic signals with cognitive decline after CABG surgery.17,18
These results were not confirmed in subsequent studies of patients undergoing open-chamber valvular surgery,
where more emboli are present.19,20 It is likely that the composition and not the number of microemboli is more
important for the manifestations of cerebral injury. Cerebral injury from hypoperfusion may be more common in
contemporary practice because of a growing number of patients with preexisting, and typically clinically
asymptomatic, cerebrovascular disease.5 This concern is reinforced by data showing that as many as 27–43% of
patients experience regional or global cerebral O2 desaturations during CPB, indicating cerebral O2 demand/delivery
mismatch.21 Further, one study found that 68% of strokes that occurred after cardiac surgery were hypoperfusion-
type watershed strokes based on diffusion-weighted MRI.22 Cerebral hypoperfusion might be of particular concern
during “off-pump” surgery, when displacement of the heart results in systemic hypotension and cerebral venous
hypertension. One study showed that 15% of patients undergoing off-pump CABG surgery exhibited EEG evidence
of cerebral hypoxemia and near infrared spectroscopy (NIRS) desaturations.23
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Approaches to Cerebral Protection

Cerebral ischemic injury is broadly classified as global or regional. Brain energy stores are rapidly depleted during
ischemia, leading to depolarization and release of excitatory neurotransmitters. Cerebral ischemia triggers activation
of multiple pathways (“ischemic cascade”) over a period of hours to days that determine the ultimate extent of injury
and functional outcome.24 Other injury pathways activated lead to altered calcium homeostasis, free radical
production, activation of proteases, and initiation of apoptosis. Vulnerability to injury varies between cell subtypes,
with particular susceptibility occurring in neurons located in the hippocampus, cortex, cerebellum, corpus striatum,
and thalamus.25 The central area of ischemic injury is surrounded by viable tissue that is vulnerable to infarction
(“the ischemic penumbra”) from the secondary events that follow the initial injury. Prevention of cerebral injury
from cardiac surgery is distinguished from “rescue” therapies for patients who present with a stroke in progress such
as those in non-surgical settings. That is, the timing of the potential injurious event is known beforehand, allowing
the potential for implementation of proactive strategies. These cerebral protective measures can be categorized into
several basic strategies: 1) prevent injury from cerebral emboli; 2) ensure cerebral O2 delivery/demand balance; and
3) prevent secondary brain injury to the ischemic penumbra.
Reducing Cerebral Emboli

Performing CABG surgery off pump has been suggested as a means for reducing the injurious consequences of
CPB, including the introduction of microemboli into the systemic circulation.26 However, several prospectively
randomized trials comparing off- and on-pump CABG surgery have failed to demonstrate that avoiding CPB
provides a clear reduction in stroke rate.27 In a prospectively randomized study of low-risk patients undergoing
CABG surgery, there were no differences in the frequency of cognitive dysfunction 3 months or 5 years after
surgery between patients randomized to on- or off-pump surgery.28 In the VA Randomized On/Off Bypass Study,
there was no difference between surgery groups in the rate of the composite outcome of death or complications
(reoperation, new mechanical support, cardiac arrest, coma, stroke, or renal failure) within 30 days of surgery.29 The
rate of graft patency at 1 year based on angiography was lower in the off-pump group (82.6% vs. 87.8%, p<0.01). In
a review of 6665 patients followed for an average of 4.5 years, off-pump CABG was associated with an increased
risk of repeat revascularization and major vascular events (cardiac death, repeat revascularization, MI, or stroke)
compared with on-pump surgery.30 It has been argued that high-risk patients may benefit the most from CPB
avoidance. In a randomized study of 341 high-risk CABG surgery patients (Euroscore ≥ 5), however, avoiding CPB
did not affect the frequency of stroke (4.0% vs. 3.7%; RR, 1.08; 95% CI, 0.37–3.14; p=1.0).27 The decision to carry
out CABG surgery off pump must be individualized, but the current data do not indicate that this surgical approach
substantially improves neurologic outcomes.
Atherosclerosis of the ascending aorta is a known source of cerebral emboli that may cause stroke and possibly
POCD.5 In patients presenting with stroke, aortic atherosclerosis is associated with blood hypercoagulability, which
increases the risk for recurrent stroke and death.31 Detection and surgical management are fundamental clinical
issues related to atherosclerosis of the aorta. Epiaortic ultrasound is more sensitive than direct palpation or TEE for
detecting atherosclerosis of the ascending aorta.32,33 This method allows the surgeon to identify and avoid atheroma
during aortic cannulation and cross-clamping. Approaches to surgical management of patients who have been found
to have an atherosclerotic aorta include: a) converting to off-pump surgery; b) using alternative sites for CPB
cannulation; c) using the single cross-clamp technique to avoid partial aortic occlusion clamping for proximal
bypass graft anastamosis; d) using fibrillatory arrest rather than cardioplegic arrest to avoid cross-clamping; e)
avoiding proximal anastomosis by using arterial grafts; and f) replacing the ascending aorta under circulatory arrest.5
Improved neurologic outcomes have been reported with epiaortic ultrasound-guided surgery and with practices that
minimize the risk for embolization.34-36 A meta-analysis of 7 studies found that the rate of stroke was 0.31% for
patients undergoing off-pump CABG with minimal aortic manipulations but 1.35% for patients undergoing off-
pump CABG with a side-clamp or proximal graft anastomosis device (p=0.003).37
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Insufflation of CO2 into the mediastinum may increase the rate of absorption of intravascular emboli by
substituting the more soluble CO2 for air in the surgical wound, thus reducing the number of arterial emboli.5 In a
study of 80 patients undergoing open chamber cardiac surgery, P300 auditory evoked potentials (believed to be a
sensitive marker for subtle cognitive changes) were better preserved in patients whose surgical field was flooded
with CO2 than in patients who did not receive this intervention.38 However, neurocognitive outcomes did not differ
between the two groups. Cardiotomy suction aspirate is high in lipid content and is a source of cerebral lipid
microemboli in experimental canine CPB.5,39 Based on animal data and inferential data from humans, many centers
have adopted a practice of either discarding cardiotomy suction aspirate or processing it before returning it to the
CPB circuit. As platelets and coagulation factors are lost with either approach, these practices might increase the
frequency of blood transfusions when the suction volume is high. This possibility is an important consideration, as
transfusion of allogeneic packed red blood cells and platelets is associated with increased risk for stroke after cardiac
surgery.40 Rubens et al41 reported no difference in the frequency of POCD 1 week or 3 months after CABG and/or
aortic valve surgery between patients whose cardiotomy blood was processed with a cell saver and those who had
direct return to the CPB circuit. However, Djaiani et al42 found that processing cardiotomy blood with a continuous-
flow cell saver led to a significantly lower rate of POCD 6 weeks after CABG surgery. This benefit was not
sustained at 1-year follow-up.43 Neither study showed a difference in the number of TCD embolic signals between
cell-saver and control groups. In both studies, patients in the cell-saver group had higher rates of transfusion than did
controls. Of note, the median volume of aspirated cardiotomy blood in the Djaiani et al43 study (800 mL; range,
175–3840 mL) was higher than that in the study by Rubens et al41 (636 mL; 95% CI, 566–706 mL). Thus, the data
are conflicting on whether routine processing of cardiotomy suction aspirate with a cell saver improves neurologic
outcomes. Any benefits might depend on the volume of aspirated blood and/or the type of device used. Therefore,
when large blood loss is not expected, avoiding the return of unprocessed cardiotomy suction aspirate to the CPB
circuit is reasonable.
Improving Cerebral Oxygen Balance

Blood Pressure Management: A basic tenet of patient care during CPB is that cerebral blood flow (CBF)
autoregulation remains functional when alpha-stat pH management is used. Thus, low mean arterial pressure (MAP)
is believed to be tolerated because CBF is ensured to blood pressures of 50 mmHg or even lower.44 Whether this
practice is appropriate for the rising proportion of patients with cerebrovascular disease is not clear. Gottesman et
al,22 for example, found a relationship between a decrease in MAP by ≥10 mmHg from baseline during CPB and a
risk for watershed stroke detected by MRI. More recent data suggest that maintaining MAP between 80 and 90
mmHg during CPB is associated with less delirium and less early cognitive dysfunction.45 Our group has reported in
animal and clinical studies that real-time continuous monitoring of CBF autoregulation with TCD or NIRS may
provide a novel approach for individualizing MAP targets during CPB.46,47 That is, this method allows for MAP to
be optimized within an individual’s autoregulatory range, thus reducing the potential for cerebral hypoperfusion. In
a cohort of 232 patients, we found that the average MAP at the lower limit of CBF autoregulation was 66 mmHg
(95% CI, 65–58 mmHg). The range of pressures, though, at the autoregulation threshold was 40 to 90 mmHg.
Women tended to have a lower autoregulatory threshold than men, but the appropriate MAP for CPB could not be
predicted accurately based on demographic data, including preoperative MAP. Importantly, patients with stroke had
a higher MAP at the autoregulatory threshold than did patients without stroke (CVA, 74±15 mmHg; no CVA, 66±12
mmHg, p=0.054). We have also found a link between the product of the magnitude and duration that the MAP is
below the lower limit of CBF autoregulation and acute kidney injury as defined by the RIFLE criteria. In that
analysis of 348 patients, every 5 mmHg unit of the product of MAP and minutes below the lower limit of
autoregulation during CPB increased the risk for kidney injury by 10%. Regardless, our growing experience
suggests that monitoring CBF autoregulation in real-time might be necessary to identify the optimal MAP for CPB.
Further, individualizing MAP with this approach may lead to better organ perfusion and possibly better patient
outcomes.
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Red Cell Transfusion: In retrospective analyses, preoperative and intraoperative anemia has been linked to adverse
outcomes, including stroke, particularly when Hct is <21% during CPB.48,49 In a prospectively randomized study,
hemodilution to a Hct of 15–18% during CPB was associated with increased neurocognitive impairment in elderly
patients compared with a Hct ≥27%.50 The TRACS study examined whether treatment of anemia with transfusion of
packed red blood cells (PRBC) improves patient outcome in a prospectively randomized clinical trial of 502 patients
undergoing cardiac surgery with CPB.51 Patients were randomly assigned to a liberal or restrictive transfusion group
(Hct ≥30% or ≥ 24%, respectively). The hemoglobin level in the liberal transfusion group (10.5 g/dL; 95% CI, 10.4–
10.6) was higher than that in the restrictive group (9.1 g/dL; 95% CI, 9.0–9.2; p<0.001). The frequency of the
primary composite endpoint of 30-day all-cause mortality or severe morbidity (cardiogenic shock, ARDS, or acute
renal injury requiring dialysis or hemofiltration) was similar between groups [10% liberal vs. 11% restrictive;
between-group difference, 1% (95% CI,−6% to 4%); p=0.85]. Non-leukocyte-depleted blood was used in this study,
but the PRBC units were stored for a median of 3 days before transfusion. These variables have been associated with
reduced risk from PRBC transfusion.52,53 Further, cell salvage was not used in the study patients. The number of
transfused PRBC units was an independent risk factor for clinical complications or death at 30 days [hazard ratio for
each additional unit transfused, 1.2 (95% CI, 1.1–1.4); p=0.002]. Transfusion of ≥5 units of PRBC was associated
with mortality. The authors concluded that for patients undergoing cardiac surgery, outcomes do not differ with use
of a liberal or restrictive transfusion strategy. The Society of Thoracic Surgeons and Society of Cardiovascular
Anesthesiologists clinical practice guidelines opine that “For patients on CPB with risk for critical end-organ
ischemia/injury, it is not unreasonable to keep hemoglobin level at 7 g/dL or more.”54
Temperature Management: Extensive laboratory data have demonstrated that hypothermia provides neuronal
protection from ischemic injury via multiple mechanisms.5 Clinically, hypothermia has been shown to improve
neurologic recovery in comatose survivors of cardiac arrest.25 Hypothermia may extend the time that circulatory
arrest is tolerated during complex aortic surgery, but there is little clinical evidence that it provides robust
neuroprotection during routine cardiac surgery.55 The ineffectiveness of hypothermia might be explained by the
absence of hypothermia during all periods of cerebral risk or inadvertent hyperthermia with re-warming.5 The latter
might result from the proximity of the aortic cannula (returning warm blood) to cerebral vessels and/or inaccurate
patient temperature monitoring that underestimates brain temperature. Rapid re-warming and postoperative
hyperthermia are associated with risk for neurologic complications.56,57 Re-warming to 34oC rather than to 37oC
resulted in improved neurocognitive outcome after CABG surgery.58 However, at 3 months after CABG surgery, the
rates of POCD did not differ among patients who were maintained at 37oC (with a circulating warming blanket)
during CPB and those who were maintained at 34oC without rewarming.59 Our group has shown that CPB re-
warming is associated with impaired CBF autoregulation in a high proportion of patients.60 These results indicate
that CBF is pressure-passive in some patients during re-warming at a time when systemic vascular resistance is
typically low and cerebral metabolic rate is elevated. These conditions might lead to a CBF that is inadequate for
metabolic demand. In that study, there was an association between impaired CBF autoregulation and stroke.
Neuromonitoring: NIRS is increasingly used to monitor regional cerebral O2 saturation (rScO2) during cardiac
surgery. We have recently performed a systematic review of PubMed, Embase, and Cochrane library to evaluate the
evidence on the relationship between rScO2 desaturations and POCD and stroke. Several case reports and many
observational studies offered anecdotal evidence that rScO2 monitoring has value for identifying CPB cannula
malposition. Nine observational studies evaluated the potential association between acute rScO2 desaturation and
POCD based on the Mini-Mental Status Examination (n=3 studies) or more detailed cognitive testing (n=6 studies).
Six of the studies found an association, but three did not. Two retrospective studies reported a relationship between
rScO2 desaturation and stroke or type I and II neurologic deficits after surgery compared with historical controls.
The observational studies had many limitations, including small sample size, assessments only during the immediate
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postoperative period, and failure to perform risk-adjustments. Moreover, these studies have failed to distinguish that
the relationship between rScO2 desaturation represents a modifiable risk factor for poor neurologic outcome or
whether it is an epiphenomenon identifying patients generally of higher risk for poor outcome.61 Two randomized
intervention studies attempted to answer the question of whether interventions for rScO2 desaturation improve
patient outcomes. The results of one are difficult to interpret owing to poor adherence with the protocol for treating
rScO2 desaturations. In the other study of 200 CABG surgical patients, NIRS-guided interventions were associated
with less major organ injury (death, MI, stroke) and shorter ICU length of stay compared to standard care.62
Algorithms have been proposed for treating cerebral O2 desaturation.63 Interventions include ensuring adequate CPB
flow or cardiac output when patients are not on CPB, increasing MAP, avoiding hypocarbia (decreasing gas-inflow),
deepening anesthesia, increasing the FiO2, instituting pulsatile CPB flow, considering transfusion if indicated,
administering anticonvulsant drugs when indicated, and considering hypothermia.
Protecting the Ischemic Penumbra

Areas of brain infarction are surrounded by viable but vulnerable tissue termed the ischemic penumbra. The viability
of the ischemic penumbra is threatened by the multiple injury pathways that comprise the ischemic cascade
referenced earlier. Microcirculatory changes resulting from brain injury, particularly inflammatory and hemostatic
activation, can contribute to cerebral hypoperfusion due to the “no reflow” phenomenon. Thus, measures aimed at
neuroprotective hemodynamic management may be critical to protection from secondary brain injury. Other
measures for protecting the ischemic penumbra are mostly pharmacologic, including avoidance of hyperglycemia.
Blood Glucose Control: Hyperglycemia worsens experimental cerebral injury and is associated with poor neurologic
outcome after stroke in humans.64 Hyperglycemia worsens ischemic damage by multiple mechanisms. The
relationship between serum glucose and stroke severity appears to be “U” shaped. Experimentally, the nadir glucose
level associated with best neurologic outcome appears to be around 120 mg/dL.65 Initial results showing that
intensive insulin treatment improves outcomes of critically ill patients were rapidly extrapolated to patients
undergoing cardiac surgery.66 More recent data (the NICE-SUGAR study) demonstrated in a multicenter,
randomized trial that a glucose target of 81 to 108 mg/dL was associated with higher mortality compared with a
target of ≤180 mg/dL in adult critically ill patients. Importantly, these trials were conducted in the ICU.67 Data in
cardiac surgery patients have not supported intensive insulin therapy for improving neurologic outcomes. In a
randomized trial of 400 patients undergoing cardiac surgery, the frequency of the composite outcome of death,
cardiac morbidity, stroke, or renal failure was higher for patients given an insulin infusion to maintain intraoperative
glucose between 80 and 100 mg/dL than for patients who received conventional treatment [insulin given when
glucose was >200 mg/dL (p=0.02)].68 A prospectively randomized trial found no difference in the frequency of
neurologic complications 6 weeks or 6 months after CABG surgery between patients who received intraoperative
insulin when glucose was >100 mg/dL and those who received insulin when glucose was >200 mg/dL.69 A recent
meta-analysis identified 7 randomized studies of intravenous insulin administration for acute stroke.70 The authors
concluded that “the administration of intravenous insulin with the objective of maintaining serum glucose within a
specific range in the first hours of acute ischemic stroke does not provide benefit in terms of functional outcome,
death, or improvement in final neurologic deficit and significantly increased the number of hypoglycemic episodes.”
Administration of insulin when glucose is >140 mg/dL is recommended for nonsurgical patients with stroke.71
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Drugs for Cerebral Protection: Despite exhaustive efforts, little progress has been made in the clinical translation of
pharmacologic agents that target key pathways of the ischemic cascade as a clinically relevant approach for cerebral
protection. Agents that showed promising effects in vitro via multiple mechanisms but failed to provide clinical
protection against ischemic cerebral injury include barbiturates, propofol, Ca2+ channel blockers, NMDA receptor
antagonists, anti-inflammatory agents, anti-oxidants, GABA receptor blockers, 17β-estradiol, piracetam, and
others.5,72-75 Volatile anesthetics and xenon have laboratory-proven cerebral protective effects. However, based on a
systematic literature review, Schifilliti et al76 concluded that evidence was insufficient to choose one anesthetic over
another for the purposes of cerebral protection. Magnesium was investigated as a cerebral protectant in a
randomized, blinded, placebo-controlled trial of 350 patients undergoing cardiac surgery.77 At a dose that increased
serum levels to 1½ to 2 times normal, Mg2+ use was associated with improved cognitive performance compared with
placebo 24 to 96 hours after surgery, but these benefits were not present 3 months after cardiac surgery.
Experimentally, ketamine protects against ischemic neuronal injury by blocking NMDA receptors and by
attenuating inflammation.78 In a small randomized pilot study (n=52), the frequency of POCD 1 week after cardiac
surgery was lower in patients who received ketamine than in those who received placebo (33% vs. 81%, p<0.001).74
Likewise, the frequency of delirium was lower for patients given ketamine during surgery than for those given
placebo.79 Early data have been promising for use of erythropoietin (EPO). Thirty-two patients undergoing CABG
surgery were randomized to receive one of two doses of EPO or placebo starting the day before surgery.80 Two
months after surgery, there was a trend toward a lower frequency of POCD in patients who received EPO (p=0.085).
In contrast, EPO failed to provide cerebral protective benefits and was associated with higher mortality and
thromboembolic events compared with placebo in a large trial of patients with acute ischemic stroke.81 In a placebo-
controlled, double-blinded trial of 242 patients undergoing cardiac surgery with CPB, investigators found no
difference in the frequency of POCD between patients prospectively randomized to receive lidocaine and those who
received placebo (45.5% vs. 45.7%, respectively, p=0.97). 73 Diabetic patients who received lidocaine had a higher
frequency of POCD than did those who received placebo (p=0.004).
Table. Evidence-based recommendations for cerebral protection during cardiac surgery
Strategies Supported by Clinical Investigations

Epiaortic ultrasound for detection of atherosclerosis of the ascending aorta
Avoidance of hyperthermia during CPB re-warming
Strategies With Reasonable Level of Clinical Evidence
The use of a membrane oxygenator and an arterial line filter (≤40 µm) during CPB
α-stat pH management during CPB
Single cross-clamp technique for proximal CABG anastamosis patients at risk for atheroembolism
Arterial blood pressure kept >70 mmHg during CPB in high-risk patients
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Strategies That Are Acceptable and Considered Reasonable Treatment by Most Experts
NIRS monitoring, especially in high-risk patients
Serum glucose should be kept <140 mg/dL with an infusion of insulin
Consider processing cardiotomy suction aspirate with a cell-saver device
Transfusion of packed red blood cells should be considered in high-risk patients when hemoglobin is ≤7 g/dL or
higher depending on other patient-specific considerations.
Hyperbaric O2 was evaluated as a potential neuroprotective strategy in a study of 64 patients undergoing surgery
with CPB.83 This therapy reduces inflammation and ischemic infarct volume in animals. Patients who received
hyperbaric O2 in three sessions 24, 12, and 4 hours before CPB had lower levels of inflammatory marker and a
lower frequency of POCD 4 months after surgery compared with controls who received pressurized atmospheric air.
Another exciting approach for cerebral protection that is in the preliminary phase of clinical investigations is remote
limb transient ischemia. In a study of 33 patients with subarachnoid hemorrhage, limb preconditioning consisting of
three 5-minute inflations of a blood pressure cuff every 24 to 48 hours for 14 days was found to be safe and well
tolerated.84
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Conclusions
A comprehensive approach to cerebral protection that includes interventions to reduce cerebral embolism and ensure
cerebral O2 supply/demand balance may result in improved neurologic outcomes.5 Strategies for improving
neurologic outcomes from cardiac surgery are summarized in the Table.
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83. J Thorac Cardiovasc Surg 130:1623-30, 2005.

84. Stroke 42:1387-91, 2011.
DISCLOSURE
Covidien, Self Funded Research ; Ornim, Self,
Consulting Fees ; Merck, Self, Consulting Fees
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Rethinking Acute Blood Pressure Management

Solomon Aronson, M.D. Durham, North Carolina
INTRODUCTION
Death due to anesthesia has become rare. Worldwide, the mortality due to general anesthesia is now estimated in the
range 0.5 to 28 per 10,000 anesthetics, with the highest mortality rates reported by clinical investigators from
developing countries (Anaesthesia 56:1141-1153, 2001). By contrast, morbid events related to anesthetic care are
more prevalent and difficult to classify. Hemodynamic changes may signal morbid events during anesthesia. A
decrease in blood pressure (BP), enabling detection of occult hemorrhage, is an obvious example of how
hemodynamic monitoring contributes to the diagnosis of a morbid state; however, monitoring for BP variability
outside acceptable target thresholds, because it may contribute to postoperative 30-day mortality, is a much more
subtle example. It is estimated that 500 million surgeries will be performed worldwide annually by the year 2050,
with approximately 2% of these in patients at high risk for the development of cardiovascular complications.3 In the
United States alone, 30 million noncardiac surgical procedures are performed annually (N Engl J Med 335:1713-
1720, 1996) and 2.5% to 10% of these procedures are associated with perioperative cardiovascular morbidity and
mortality.
What do we mean by ‘Blood Pressure?” Are we referring to systolic, diastolic, mean, ambulatory, intraoperative,
postoperative? What about white coat hypertension? “Hypertension” accounts for 14% of cardiovascular deaths
worldwide, and yet nearly one third of the population in the United States (70 million) has some form of the disease.
In general, among the hypertensive population, approximately 25% are not treated, 50% are poorly treated, and 25%
are undiagnosed. Data from NHANES/NCHS 2005–2006 showed that of those with hypertension ≥20 years of age,
78.7% were aware of their condition, 69.1% were under current treatment, 45.4% had it under control, and 54.6%
did not have it controlled.7 According to several estimates, 90% of people in the United States will be diagnosed
with hypertensive disease by their sixth to seventh decade of life, which coincidentally is the group constituting the
fastest growing segment of the general population.
It has been estimated that the annual cost of hypertension management is nearly 70 billion dollars per year in the
Unites States alone and that intensive blood pressure (BP) control saves approximately $2000 per quality-adjusted
life year. Cardiovascular disease, a cause and consequence of hypertension, accounts for ~30% of all deaths
worldwide and is expected to remain the most serious public health challenge in the decades to come. It is estimated
that there are as many deaths and hospital readmissions attributable to acute BP crises (8.8% and 37.2%,
respectively) as to acute coronary syndromes (ACS; 5%–7% and 21%, respectively) and congestive heart failure
(CHF; 8.5% and 25.7%, respectively). Taking into account the fact that up to 64 million people per year in the
United States have surgery requiring anesthesia, and that hypertension is an established risk factor for adverse
outcome following surgery, it should come as no surprise that poorly controlled hypertension remains one of the
most common medical indications for deferring elective surgery.
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Prevalence of high blood pressure (BP) in adults aged ≥20 years by age and sex (NHANES: 2005 to 2006).
Hypertension is defined as systolic BP ≥140 mm Hg or diastolic BP ≥90 mm Hg, taking antihypertensive
medication, or being told twice by a physician or other professional that one has hypertension.
While some investigators have suggested acceptable ranges for MAP (55 to 100 mm Hg), and SBP (80 to 160 mm
Hg) in surgical patients,37 there are few data to support such recommendations, and only recently have studies
focused on the association and relationship between hemodynamic targets and outcomes.
UNDERSTANDING THE RISK

Preexisting hypertension exists in over two-thirds of all patients undergoing cardiac surgery. None the less a target
threshold for perioperative blood pressure is not clearly defined and optimal blood pressure management strategy in
high-risk patients is even less well understood. Preexisting hypertension introduces further challenges, as it has
been shown that the autoregulatory capacity of the brain 26,27 and kidney, is impaired, potentially influencing end-
organ tolerance of high or low blood pressures. As a result, the therapeutic window of acceptable blood pressure is
narrowed and shifted to the right in these patients.,21
The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High
Blood Pressure (JNC-7) classifies BP as normal, prehypertension, and stages 1 and 2 hypertension. Prehypertension
(formally known as “high normal” BP) is also associated with increased cardiovascular morbidity and mortality, as
well as subclinical atherosclerosis and target-organ damage.
Classification of Hypertension Subtypes

Systolic BP (mm Hg) Diastolic BP (mm Hg) Category
<120 and <80 Normal
120–139 or 80–89 Prehypertension
140–159 or 90–99 Stage 1 hypertension
>160 or >100 Stage 2 hypertension
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Physiologic stress associated with surgical procedures may be associated with adverse perioperative cardiovascular
events (ie, cardiac death, nonfatal MI, nonfatal cardiac arrest) (CMAJ 173:627-634, 2005). These events both cause
and are precipitated by decreased fibrinolytic activity, hypercoagulability, decreased vasomotor reactivity,
vulnerable plaque rupture, catecholamine surges, decreased coronary perfusion, shorter diastolic intervals,
tachycardia, and a heightened inflammatory state (Am J Med 122:222-229, 2009, Pharmacotherapy 18:911-914,
1998) . Hypertension represents a major risk factor for coronary artery disease (CAD), dyslipidemia, CHF, renal
dysfunction, cerebral dysfunction, dementia and diabetes. Studies have established that cardiovascular morbidity and
mortality risk increases continuously with increasing BP at levels well below thresholds for standard definitions of
hypertension. The higher the BP, the higher the risk, such that between the ages of 40 and 69 years, for each 20-mm
Hg increase in systolic BP (SBP) or 10-mm Hg increase in diastolic BP (DBP), the chance of developing
cardiovascular disease doubles across the BP range of 115/75 to 185/115.
Over the years, much has been learned about the characterization of hypertensive states, associated morbidity and
mortality, and efficacy and safety of antihypertensive therapy. During this time, the understanding of the relative
importance of mean, systolic, diastolic, and pulse pressure (PP) has evolved. Whereas traditionally diastolic
hypertension was presumed to represent the hypertension state currently all hypertension subtypes have been
appreciated to reflect specific manifestations of underlying cardiovascular disease status. There is strong evidence
that isolated systolic BP and PP are independently associated with adverse cardiovascular outcomes.
JAMA 2010;304:61-68.
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Pathogenesis of systolic and diastolic hypertension.
Isolated systolic hypertension (ISH) increases in prevalence with age and as the prevalence of isolated diastolic
hypertension (IDH) decreases. Combined ISH and IDH also decreases with age. Evidence also indicates that adverse
ischemic cardiac and cerebral vascular disease increase with age-adjusted increasing SBP. Systolic hypertension is
more prevalent than diastolic hypertension, particularly in individuals aged ≥60 years, and is associated with greater
risk of both fatal and nonfatal outcomes, including cerebral and cardiac dysfunction. Evidence now indicates that the
specific BP subtype also conveys an independent risk to perioperative outcome.
Mean arterial pressure (MAP) has also been extensively evaluated as an intraoperative index of perioperative
risk during non-cardiac and cardiac surgery involving cardiopulmonary bypass (CPB). It has been reported that
high-risk patients who experience a drop in MAP >20 mm Hg for more than 1 hour or the same in addition to an
increase in MAP >20 mm Hg for more than 15 minutes from baseline while undergoing elective non-cardiac surgery
had the greatest risk of complications. Additionally, a drop in MAP in patients undergoing cardiac surgery from
baseline during CPB has been reported to be associated with an increased risk of cognitive dysfunction and bilateral
watershed strokes.
Data on the relationship of preoperative ISH to perioperative outcome have been reported in cardiac and noncardiac
surgery. It was concluded that ISH was associated with a 40% increase in perioperative cardiovascular morbidity
following coronary artery bypass graft. Interestingly, this risk remained, regardless of preoperative antihypertension
medication, anesthetic techniques, or other perioperative cardiovascular risk factors.
AKI After Cardiac Surgery Is Proportionate to preoperative PP

Preoperative Risk Score Intraoperative Risk Factors Score
Factors
Age >75 years 7 >2 Inotropes 10
PP (mm Hg) Intra-aortic balloon pump 15
40 0
41-60 4
61-80 8
81-100 12
>100 16
History Cardiopulmonary bypass ≥122 min 6
CHF 9
MI 6
Renal disease 13
Among patients undergoing cardiac surgery, the mean PP was greater in those patients who suffered a stroke (81 vs
65 mm Hg) with each additional 10 mm Hg contributing additive risk (odds ratio [OR], 1.35; confidence interval
[CI], 1.13–1.62; P=0.001). It was also noted in an independent observation that death from cardiac and cerebral
causes was directly associated to preoperative PP among this patient population. Stroke after cardiac surgery is
proportionate to pulse pressure.
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Preop Pulse pressure and postop adverse events (Eur J Cardiothorac Surg 2008;33:971-976)
The Changing Paradigm in Acute Hypertension Management
Although preexisting hypertension is a significant risk factor for perioperative risk, it is important to recognize that
acute hypertension syndrome per se, typically seen during surgery or post-surgery as well as in other
conditions such as acute stroke, ACS, or acute decompensated heart failure, may differ in mechanism and treatment
responsiveness from chronic preexisting hypertension pathology. Acute hypertension syndrome is not necessarily
the same as hypertensive emergencies either, with the latter representing 1% to 2% of the overall manifestation of
hypertensive disease (ie, 700,000 out of 70 million cases).
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Prevalence of hypertension (HTN) type.
Pathophysiology of Acute Hypertension
BP consists of a steady component (MAP) and a pulsatile component (PP). The fluid-pressure dynamic of BP is
determined by different parameters depending on its component subtype; for example, the determinants of MAP are
left ventricular (LV) ejection and peripheral vascular resistance (PVR), whereas the determinants of SBP are stroke
volume, LV ejection, distensibility, and wave reflection. The determinants of PP are LV ejection, viscoelasticity,
and wave reflection. The actual observed pulse contour that is displayed on a monitor is a summation of forward and
returning pressure waves.
Observed arterial pulse wave contour is the aggregate of forward and reflected waves
Adaptive changes in the vessel wall are dependent on BP load. The lumen to wall ratio is decreased in diastolic
hypertension with inward (eutrophic) remodeling in small vessels. Vascular remodeling, characterized by outward
hypertrophy, on the other hand occurs with PP hypertension, a disease of large conduit vessels (eg, aorta).
The conditions that cause an acute change in systemic hemodynamics during surgery are common and include acute
changes in systemic vascular resistance due to anesthesia depth, surgical stimulation, aortic occlusive clamping and
unclamping, fluid shifts, hemorrhage, secondary drug effects, and many other examples. These changes commonly
occur in the setting of insufficient intravascular volume and likely effect patients differently, depending on their
underlying vascular physiology and compliance. Arterial compliance relates to the change in volume (stroke
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volume) and inversely to the ensuing change in pressure. PP, the difference between SBP and DBP, is an index of
conduit vessel stiffness and the rate of pressure wave propagation within the arterial tree. When stiffening of the
aorta occurs, propagated and reflected waves within the arterial tree travel much more rapidly, resulting in an early
return of the propagated wave to the central aorta during late systole as opposed to early diastole. This augmented
systolic component thereby effectively increases afterload, and the ensuing loss of DBP augmentation may decrease
organ perfusion, including coronary, cerebral, and renal perfusion pressure.
There is a tight relationship between aging, long-standing arterial hypertension, vascular disease, and PP—all acting
in concert to limit organ flow and reserve. The combination of such preexisting vasculopathy and aortic-wall injury
from surgical manipulation (aortic clamping/declamping, cannulation and decannulation), as well as the
inflammatory response associated with CPB, provide a compelling pathophysiologic basis for the increased
postoperative vascular complications observed in patients with noncompliant arteries manifested by increased PP
undergoing cardiac or major vascular surgery. Stiff vessels have altered vascular smooth muscle cell phenotypes
with arterial remodeling of the blood vessels in vital organs. It is possible that the autoregulatory range is distinctly
different across individuals with different vascular properties and with different types of superimposed surgery and
anesthesia. An altered autoregulatory range might lead to organ hypoperfusion in some individuals, despite what
may be deemed to be a “clinically acceptable” BP. Moreover, an increased systolic load, along with a lower diastolic
perfusion pressure combined with relative intravascular volume depletion, may set up a unique pathophysiologic
basis for perioperative vascular injury. It has been postulated that changes in strain and shear stress on the
endothelial wall in the setting of endothelial plaque may contribute to inflammation and the destabilization of
vulnerable plaque. This procoagulation effect may be further enhanced by low and oscillatory shear stress forces that
are exacerbated in noncompliant arteries. Importantly, the pulsatile stress that conduit vessels are exposed to may
cause the elastic elements in the vessel wall to break down, thereby producing further vessel dilation and stiffening.
As the vessel dilates, the stress on the wall worsens. Remodeling changes lead to vessel-wall medial necrosis,
stiffening, increased vascular resistance, and reduced organ perfusion. Whereas the effects of laminar shear stress in
normal vessels are atheroprotective, the effects of oscillatory and low shear stress promote atherosclerosis and
plaque rupture.
Hypertension and Cardiovascular Surgery
The behavior to actively manage high BP during cardiovascular surgery is a frequent occurrence (88% of all cases).
Perhaps this behavior reflects that poorly controlled BP during surgery is not tolerated in part because of easily
recognized safety concerns related to ischemia modulation, the need for aortovascular stress-strain modulation (eg,
clamping, unclamping), maintaining adequate perfusion conditions during CPB, and balancing these pressure-
perfusion requirements with surgical bleeding concerns throughout surgery. This is especially true during the
postoperative period, when requirements for weaning from mechanical ventilation and analgesia are additional
stresses for poor BP control. It is well understood that perioperative hypertension increases myocardial oxygen
consumption and left ventricular end-diastolic pressure and contributes to sub-endocardial hypoperfusion and
myocardial ischemia. It also increases the risk of stroke, neuron-cognitive dysfunction, and renal dysfunction and
contributes to surgical bleeding from anastomotic sites. In addition, it is now understood that poorly controlled BP
during surgery can trigger hyper-inflammatory and procoagulation conditions, including platelet activation, which
may compromise microvascular blood flow.
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BP Control and Outcomes

Defining goals for BP control should depend on patient factors such as the presence of preexisting hypertensive
disease, the specific acute-care situation that is being managed, and the vulnerable end organ. Specific BP goals
need to be defined for each patient in each instance, recognizing the situation (type of surgery, CHF, stroke, etc),
the type of hypertension (ie, phenotype: DBP, SBP, MAP, PP), and the condition (treatment effectiveness).
As few data support an association between blood pressure variability and clinical outcomes during cardiac surgery
we tested the hypothesis that intraoperative systolic blood pressure variability outside a targeted blood pressure
range predicts 30-day mortality in patients undergoing cardiac surgery. 3.1 million intraoperative blood pressure
evaluations were analyzed. Systolic blood pressure variability was derived in 5038 patients and validated in 2466
patients. It was observed that mean duration of systolic excursion [outside a range of 105-130mmHg] was most
predictive of 30 day mortality (OR =1.03 per minute, 95% CI [1.02-1.39], P<0.0001).
Hence it was concluded that intra-operative blood pressure variability is associated with 30 day post-operative
mortality in patients undergoing aortocoronary bypass surgery. Although an odds ratio of 1.03 represents a modest
effect; it is important a) to realize that this effect size is a per minute effect; such that for every minute outside the
105-130mmHg range, the odds ratio for 30 day mortality increases by 0.03 and b) intraoperative blood pressure is a
modifiable risk factor.
Unadjusted data of 30 day mortality within each tertiles of dataset, based on blood pressure variability
(minutes per episode spent outside the range).
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Duration of blood pressure lability and risk of 30-day mortality.
The percent change of intraoperative systolic BP below baseline BP is associated with the percent increase change
from baseline in creatinine observed following cardiac surgery. 7,247 patients were evaluated from Sept. 1996 to
Dec. 2005 with systolic blood pressure variability determined for each patient and characterized by frequency,
magnitude (mmHg), duration (min), area under curve (mmHg*min), and % change from baseline. The study sample
was randomly divided into a development cohort (2/3) and a validation cohort (1/3). Each of these was evaluated
separately in a linear regression model predicting % delta creatinine, adjusting for covariates (aprotinin use, age, chf,
previous mi, baseline creatinine, bypass time, diabetes, weight, valve surgery, gender, and pulse pressure).
The measure most highly associated with % delta creatinine based on model r2 value in the developmental sample
was % change from baseline SBP to the lowest SBP, p< 0.006 (model r2 value =0.005). Multivariable linear
regression demonstrated an association between % change in SBP below baseline to % delta creatinine (p< 0.0016)
in the validation data set.
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Systolic BP excusion outside upper and lower thresholds during cardiac surgery predicts 30 day mortality and is
associated with the magnitude and duration of excursion
50
40
Percent Delta Creatinine
30
20
10
0
–80 –70 –60 –50 –40 –30 –20 –10 0
Percent Decrease Systolic (mmHg)
Percent change in serum creatinine (baseline to peak value post surgery) as a function of %
decrease in systolic blood pressure (baseline to lowest value during surgery) in the combined
study sample (n=7504)
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BP Control and Outcomes in non cardiac surgery
Bijker et al (Anesthesiology: 2012 - Volume 116 - Issue 3 - p 658–664) investigated the incidence of stroke in
48,241 pts who underwent non-cardiac & non-neurosurgical procedures (2002 to 2009) . They found 42 ischemic
strokes (0.09%) within 10 days after surgery (matched to 252 control pts) and concluded that the duration
intraoperative MAP was decreased > 30% from baseline was assoc with postop stroke. They concluded that
although, the most widely proposed mechanism of a postoperative stroke is arterial embolism, hypotension can also
influence the evolution of a postoperative stroke by compromising (collateral) blood flow to ischemic areas. In this
context, hypotension is best defined as a decrease in mean blood pressure relative to a preoperative baseline, rather
than an absolute low blood pressure value. In another study Davis et al (Anesthesiology: 2012 ;116 , 396–405)
reviewed 120 charts and found that independent predictors for good neurologic following non cardiac
surgeryoutcome were local anesthesia, systolic BP >140 mmHg, and low baseline stroke scores.
Safety Events (ECLIPSE) trial was performed to compare the safety and efficacy of clevidipine (CLV) with
nitroglycerin (NTG), sodium nitroprusside (SNP), and nicardipine (NIC) in the treatment of perioperative acute
hypertension. In ECLIPSE, the largest randomized perioperative hypertension management trial (over 1500 patients
undergoing cardiac surgery), an overall treatment-independent evaluation of BP control to 30-day mortality was also
conducted. BP control was assessed by area under the curve (AUC) analysis. AUC was defined as the summation of
the integrated SBP-time curve excursions (AUCSBP-D), capturing the magnitude (mm Hg) times duration (minutes)
of BP outside the predefined ranges (65–135 mm Hg intraoperatively [from chest incision through chest closure]
and 75–145 mm Hg pre- and postoperatively). AUC was calculated based on BP recorded from the initiation of
study drug infusion through either the permanent removal of the arterial line or 24 hours after drug initiation,
whichever occurred first. AUC was normalized per hour and expressed as mm Hg × min/h. The total area of the
SBP-time curve outside (either above or below) the predefined SBP ranges (AUCSBP-D) was calculated, as well as by
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treatment group as the SBP range was narrowed by incrementally increasing the lower SBP limit by 10, 20, and 30
mm Hg.
Results from ECLIPSE also demonstrated that BP excursion outside a target systolic range was associated with
increased post operative mortality and increased postoperative renal injury
ECLIPSE: Predictors of 30-Day Mortality

P Value OR 95% CI
Surgery duration (hour) <0.0001 1.517 1.240–1.856
Age (year) 0.0003 1.070 1.031–1.110
Pre-op creatinine ≥1.2 mg/dL 0.0031 2.670 1.392–5.122
AUC (area outside the range) 0.0069 1.003 1.001–1.004
Additional surgical procedures 0.0089 2.409 1.246–4.655
Pre-op Hgb (g/dL) 0.0135 0.824 0.707–0.961
Pre-op SBP >160 or DBP >105 0.0228 2.386 1.147–4.963
History of COPD 0.0228 2.326 1.125–4.812
History of recent MI (<6 months prior) 0.0312 2.197 1.073–4.497
SUMMARY
Pre-op HTN subclass predicts (postop) risk in patients undergoing cardiac surgery. Intra-op SBP variability predicts
(postop) risk in patients undergoing cardiac surgery. BP goals remain an area for further investigation and depend on
the patient, situation & condition. There is much to be learned about integrating observational data for individual
patients in specific situations with specific conditions when establishing BP management strategies.
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DISCLOSURE
The Medicines company, Consulting Fees ; Acute care medical education, Ownership ; Baxter, Funded Research ;
nonin, Funded Research ; dynamic medical education, Ownership
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Massive Bleeding Post Bypass: Rational Approach to Management

Edwin G. Avery, IV, M.D. Cleveland, Ohio
Introduction
The use of extracorporeal circulation, also termed cardiopulmonary bypass (CPB), allows clinicians to
perform invasive surgical procedures on the heart and vascular system that would otherwise not be possible without
compromising vital organ perfusion. Despite the great surgical advantages offered by the use of CPB there are also
several physiologic insults that accompany its use. One of the more important and potentially life threatening insults
that is associated with CPB is a variable degree of post-CPB bleeding. Post-CPB related hemorrhage accompanies
every surgical procedure to some extent and is not always predictable. The study of this clinical problem reveals a
number of potentially contributory variables that include the following: small body habitus, antecedent
administration of antiplatelet and/or antithrombotic drugs, noncardiac comorbidities (e.g., hepatic insufficiency and
renal insufficiency), sepsis, pre-existing blood dyscrasias, dilutional coagulopathy, hypothermia and prolonged CPB
time (i.e.> 2.5 hours).
The multifactorial nature of post-CPB related bleeding often causes frustration among perioperative
clinicians, especially when bleeding is excessive and thus clinicians may respond by transfusing all available
allogeneic blood products as well as administering pharmacological based blood components or blood conservation
drugs. The literature has firmly established that the transfusion of allogeneic blood and blood products is associated
with increased morbidity and mortality and the relationship of the quantity of transfused allogeneic blood products
and observed negative outcomes appears to be progressive (i.e. the more one is transfused the more likely one is to
experience an undesirable outcome). It is for this reason that clinicians are compelled to employ a rationale approach
to the management of post-CPB bleeding and hence is the subject of this monograph.
Assessment of Coagulopathy
Post-CPB bleeding is often multifactorial and to some extent is predictable if one is aware of the presence
of any pertinent preoperative variables as detailed in the introduction section of this document. In some cases by
working with the patient’s primary cardiologist these variables can be favorably modified (e.g., discontinuing an
antiplatelet or antithrombotic drug at an appropriate interval before an elective surgery). Additionally, preoperative
coagulation screening can identify patients that are at greater risk for massive bleeding. Consider that a healthy
coagulation system is composed of up to three times the soluble coagulation proteins that are required to achieve
hemostasis under normal clinical conditions. A patient that presents for a procedure involving CPB that has
abnormal central laboratory coagulation studies (i.e. elevated international normalized ratio, elevated activated
partial thromboplastin time, hypofibrinogenemia, thrombocytopenia or abnormal thromboelastography or rotational
thromboelastometry parameters) is likely at higher risk for massive bleeding.
CPB is known to universally reduce measured concentrations of all soluble coagulation proteins through
both hemodilution and consumption related to subclinical activity of the coagulation cascade that cannot be
prevented regardless of the administered dose of unfractionated heparin. Thus these “double jeopardy” patients with
a known preoperative laboratory verified coagulation defect who undergo CPB should have blood products available
immediately upon separation from CPB to decrease the time interval during which the patient’s coagulopathy is
untreated as many blood banks require an ample “heads up” notification to appropriately process (i.e. thaw as well
as type and cross match) ordered blood products. Under such circumstances clinicians are left to with only
crystalloid or commercially available colloid solutions to replace blood volume which can lead to exacerbation of
the coagulopathy via additional hemodilution or as is the case with some colloids direct antagonism of essential
elements of the coagulation system (e.g., synthetic starch has a known reproducible platelet anti-aggregatory effect
as well as an anti-factor VIII effect). Further, the risk of massive hemorrhage for an individual with significant
synthetic hepatic dysfunction and the associated reduced concentrations of soluble coagulation proteins can be
mitigated by priming the CPB circuit with fresh frozen plasma in place of crystalloid. This practice will mitigate the
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hemodilution associated with CPB and provide a “head start” on managing the massive bleeding that patients with
advanced synthetic hepatic dysfunction often demonstrate.
Optimization of known isolated coagulation protein defects can also be undertaken preoperatively and can
be expected to reduce the potential for massive hemorrhage. For example, an individual with either congenital or
acquired hypofibrinogenemia or dysfibrinogenemia can now be treated preoperatively with fibrinogen concentrate
(RIASTAP®). Similar steps can be taken to optimize patients with hemophilia A or B in that purified pooled human
or recombinant factors can be administered to provide 100% of normal protein levels. Preoperative optimization of
such patients is best done in conjunction with hematology consultation.
Defining Massive Post-CPB Bleeding
Often times despite appropriate preoperative optimization of the coagulation system patients will still
demonstrate massive post-CPB bleeding. It can be helpful to quantify the degree of hemorrhage and there is some
guidance on this question in the literature. Spiess et al defined > 300 mLs of chest tube drainage in the first hour
following chest closure as excessive hemorrhage. Other published criteria include ≥ 8 mLs/kg in any two successive
hours or > 20 mLs/kg in the first four hours following CPB separation. Additional criteria to define excessive post-
CPB bleeding are those that are applied as endpoints in clinical trials and involve assigning threshold definitions
(e.g., the recently published BRIDGE trial of cangrelor in cardiac surgery defined post-CPB massive hemorrhage as
occurring when patients received > 4 units of red blood cells, underwent surgical re-exploration for hemorrhage or
had chest tube drainage > 1.5 L within 24 hours of CPB separation). However, in practice massive post-CPB
bleeding is usually identified before chest closure and well in advance of connecting the chest tubes to the blood
collection system. Certainly for experienced clinicians the phrase “I know it when I see it” is used as the metric to
identify massive post-CPB bleeding. This degree of hemorrhage is always accompanied by hemodynamic instability
and an ongoing volume requirement.
Treating Massive Post-CPB Bleeding
There are three key clinical elements (W .A .R. - WARM, ASSESS, RESTORE/RECYCLE ) that form the
foundation of successfully treating massive post-CPB hemorrhage, 1) WARM - employ fluid warming devices on
administered IV fluids/blood products (except platelets) and use active patient warming systems (e.g., forced
convective warming blankets), 2) ASSESS - perform frequent assessments of the coagulation cascade regardless of
whether you rely upon central laboratory tests (i.e. fibrinogen concentration, platelet count, hemoglobin
concentration, international normalized ratio, activated partial thromboplastin time) or point-of-care testing [POCT]
(e.g., thromboelastography [TEG], rotational thromboelastometry [ROTEM]), 3) RESTORE/RECYCLE - have
ample blood products ready and available for immediate administration (i.e. activate your massive transfusion
protocol if available) and insure adequate access to pharmacologic blood conservation agents (e.g., antifibrinolytics
and recombinant activated factor VII); during massive hemorrhage use of a blood collection system that permits
centrifugal washing and re-transfusion of the shed blood is essential to keep up with ongoing volume loss and can
minimize the transfusion of allogeneic red blood cells.
Serial assessments of the coagulation cascade are vital to the success of the W A R strategy. These
assessments are performed to monitor the severity of the coagulopathy as well as the effectiveness of ongoing
interventions undertaken to mitigate bleeding. The published literature strongly supports the fact that both central
laboratory and/or POCT guided blood product (non-red cell) algorithms are superior to physician discretion in the
treatment of post-CPB hemorrhage. Compared to POCT the use of central laboratory based assessments may have a
longer turn-around time for both sample processing and result reporting but often these times can be reduced by
direct communication with the laboratory that life threatening hemorrhage is occurring. Even if the information that
is reported from the processed samples does not appear temporally relevant it does establish positive or negative
trends in the effectiveness of the blood product administration strategy. There are several published algorithms
available for review that have been proven to reduce the amount of bleeding when compared to physician discretion.
Optimally, individual institutions should develop customized POCT or laboratory guided blood product transfusion
algorithms based upon assessment of their own institutional data.
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The availability of blood products and timely coagulation assessments are often not sufficient to abate
massive hemorrhage. In such clinical scenarios the administration of pharmacologic adjuncts such as recombinant
activated factor VII (NovoSeven®), fibrinogen concentrate, antifibrinolytics and desmopressin are indicated. While
none of these products are US FDA cleared for the treatment of massive post-CPB bleeding there is published data
to support their use. Care should be taken with making the decision to administer any of these agents, especially
recombinant activated factor VII as its use has been associated with a significantly increased incidence of stroke. In
practice, experienced clinicians will only administer this agent when there is no evidence of significant progress
with coagulopathy reversal after the first two rounds of blood product administration.
Summary
While massive post-CPB hemorrhage is not common in most practices the clinicians who treat cardiac
surgical patients must be ready to identify and treat this life threatening problem when it occurs. Preoperative
optimization combined with use of the W A R strategy provides a rational and effective approach to treating this
clinically challenging scenario.
DISCLOSURE
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Preoperative Cardiac Evaluation for Noncardiac Surgery

Lee A. Fleisher, M.D. Philadelphia, Pennsylvania
The past several years has seen a dramatic increase in the number and quality of randomized and prospective studies
to define the optimal and most cost-effective approach to preoperative cardiovascular evaluation and management
for noncardiac surgery, including studies evaluating the role of coronary revascularization before noncardiac surgery
and perioperative beta-blockers. In 2009, the American Heart Association/American College of Cardiology
(AHA/ACC) Guidelines on Perioperative Cardiovascular Evaluation before Noncardiac Surgery were updated
which included a new algorithm (2007) and new recommendations regarding perioperative beta-blockade usage.[1]
In addition, the European Society of Cardiology (ESC) has also produced Guidelines for pre-operative cardiac risk
assessment and perioperative cardiac management in non-cardiac surgery: the Task Force for Preoperative Cardiac
Risk Assessment and Perioperative Cardiac Management in Non-cardiac Surgery, which has been endorsed by the
European Society of Anaesthesiology (ESA).[2] These recommendations are similar to the AHA/ACC
recommendations with an algorithm, although the beta-blocker recommendations are slightly different.
Additionally, the conclusions of the ESC Guidelines have been questioned because of concerns regarding the studies
published by one of the authors. That said, the basic tenet in preoperative evaluation remains that information
regarding the extent and stability of disease will effect patient management and lead to improved outcome. In the
case of cardiovascular disease, the preoperative evaluation attempts to define the extent of coronary artery disease
and the left ventricular function.
Perioperative interventions based upon preoperative cardiac evaluation

Decision to forego surgery
Modification of surgical procedure
Delay case for treatment of unstable symptoms
Modification of perioperative medical therapy
Initiation of beta-blockers, statins, alpha-2 agonists
Modification of postoperative monitoring (eg. Intensive Care Unit)
Coronary revascularization before noncardiac surgery
Modification of location of care
Appropriate allocation of transplant organs
Clinical Assessment
Since the original manuscript by Goldman and colleagues in 1977 describing a Cardiac Risk Index, multiple
investigators have validated various clinical risk indices for their ability to predict perioperative cardiac
complications.[3] The most recent index was developed in a study of 4315 patients aged 50 years or greater
undergoing elective major noncardiac procedures in a tertiary-care teaching hospital. Six independent predictors of
complications were identified, and included in a Revised Cardiac Risk Index (RCRI): high-risk type of surgery,
history of ischemic heart disease, history of congestive heart failure, history of cerebrovascular disease, preoperative
treatment with insulin, and preoperative serum creatinine >2.0 mg/d, with increasing cardiac complication rates
noted with increasing number of risk factors.[4] The RCRI has become the standard tool in the literature in
assessing the prior probability of perioperative cardiac risk in a given individual and has been used to direct the
decision to perform cardiovascular testing and implement perioperative management protocols, and has recently
been validated for both short- and long-term outcomes.[5] A primary issue with all of these indices from the
anesthesiologist’s perspective is that a simple estimate of risk does not help in refining perioperative management,
and therefore it is important that the anesthesiologist determine the extent and stability of the patient’s coronary
artery disease through obtaining information from the primary caregiver or cardiologist or through a thorough
history or physical examination.
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A thorough history should focus on cardiovascular risk factors and symptoms or signs of unstable cardiac disease
states, such as myocardial ischemia with minimal exertion, active congestive heart failure, symptomatic valvular
heart disease, and significant cardiac arrhythmias. In patients with symptomatic coronary disease, the preoperative
evaluation may lead to the recognition of a change in the frequency or pattern of anginal symptoms. In virtually all
studies, the presence of active congestive heart failure preoperatively has been associated with an increased
incidence of perioperative cardiac morbidity.[6] Stabilization of ventricular function and treatment for pulmonary
congestion is prudent prior to elective surgery. Also, it is important to determine the etiology of the left heart failure
since the type of perioperative monitoring and treatments would be different.
Patients with a prior MI have coronary artery disease, although a small group of patients may sustain an MI from a
nonatherosclerotic mechanism. Since the publication of the original Guidelines in 1996, there has been a consensus
that the traditional recommendation to wait 6 months for elective surgery has been modified.[7] Instead, patients
should be evaluated from the perspective of their risk for ongoing ischemia. A recent analysis using Medicare
Claims data suggests that the risk of reinfarction remains high for at least 2 months after an MI, and that coronary
artery bypass grafting (CABG) may reduce that risk while coronary stent placement soon after an MI does not.[8, 9]
For those patients without overt symptoms or history, the probability of CAD varies with the type and number of
atherosclerotic risk factors present. Diabetes mellitus is common in the elderly and represents a disease that impacts
on multiple organ systems. Diabetes accelerates the progression of atherosclerosis, which can frequently be silent in
nature, leading many clinicians to assume coronary artery disease in this population and treating them as such.
Diabetes is an independent risk factor for perioperative cardiac morbidity and the preoperative treatment with insulin
has been included in the RCRI. In attempting to determine the degree of this increased probability, the treatment
modality, length of the disease and other associated end-organ dysfunction should be taken into account, including
autonomic neuropathy. Hypertension has also been associated with an increased incidence of silent myocardial
ischemia and infarction. Those hypertensive patients with left ventricular hypertrophy and who are undergoing
noncardiac surgery are at a higher perioperative risk than nonhypertensive patients.[10] There is a great deal of
debate regarding a trigger to delay or cancel a surgical procedure in a patient with poorly or untreated hypertension.
In the absence of end-organ changes, such as renal insufficiency or left ventricular hypertrophy with strain, it would
seem appropriate to proceed with surgery. A randomized trial of treated hypertensive patients without known CAD
who presented the morning of surgery with an elevated diastolic blood pressure was unable to demonstrate any
difference in outcome between those who were actively treated versus those in whom surgery was delayed.[11] In
contrast, a patient with a markedly elevated blood pressure and the new onset of a headache should have surgery
delayed for further evaluation and potential treatment. For the purpose of the Guidelines, a list of active cardiac
conditions and clinical risk factors were defined.
Active Cardiac Conditions Clinical Risk Factors

• Unstable coronary syndromes • Ischemic heart disease
-Unstable angina • H/O CHF
-Recent MI (consider w/in 2 mon) • H/O Cerebrovascular disease
• Decompensated Heart Failure • Diabetes mellitus
• Significant arrhythmias • Preop Cr>2.0mg/dl
• Significant valvular disease
Importance of Surgical Procedure

The surgical procedure influences the extent of the preoperative evaluation required by determining the potential
range of changes in perioperative management. There is little hard data to define the surgery specific incidence of
complications, and the rate may be very institution dependent. Eagle et. al. published data on the incidence of
perioperative myocardial infarction and mortality by procedure for patients enrolled in the coronary artery surgery
study (CASS).[12] Higher risk procedures for which coronary artery bypass grafting reduced the risk of noncardiac
surgery compared to medical therapy include major vascular, abdominal, thoracic, and orthopedic surgery.
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Ambulatory procedures denote low risk. Vascular surgery represents a unique group of patients in whom there is
extensive evidence regarding preoperative testing and perioperative interventions. Endovascular stent placement is
associated with lower perioperative risk, particularly the risk of death, but similar long-term mortality compared to
open procedures. There is evidence to suggest that the rate of surgical mortality is correlated with hospital surgery-
specific volume and therefore higher volume hospitals may have better outcomes which can impact the decision to
perform preoperative testing. Locations with less intensive resources, eg. smaller hospitals, may actually perform
testing to determine who to refer to larger Centers.
Importance of exercise tolerance

Exercise tolerance is one of the most important determinants of perioperative risk and the need for invasive
monitoring. If a patient can walk a mile without becoming short of breath, than the probability of extensive coronary
artery disease is small. Alternatively, if patients become dyspneic associated with chest pain during minimal
exertion, then the probability of extensive coronary artery disease is high. Reilly and colleagues demonstrated that
the likelihood of a serious complication occurring was inversely related to the number of blocks that could be
walked or flights of stairs that could be climbed.[13] Exercise tolerance can be assessed with formal treadmill
testing or with a questionnaire that assesses activities of daily living. There is some suggestion that
cardiopulmonary testing is useful for more accurately predicting risk.
Approach to the Patient
The figure presents in

algorithmic
form a framework for
determining which patients are
candidates for cardiac testing.
Given the availability of this
evidence, the AHA/ACC
Writing Committee chose to
include the level of the
recommendations and strength
of evidence for many of the
pathways. Importantly, the
value of adopting the algorithm
depends upon local factors such
as current perioperative risk and
rate of utilization of testing.
Step 1: The individual should
determine the urgency of
noncardiac surgery. In many
instances, patient- or surgery-
specific factors dictate an
obvious strategy (eg, emergent surgery) that may not allow for further cardiac assessment or treatment.
Step 2: Does the patient have 1 of the active cardiac conditions? In patients being considered for elective noncardiac
surgery, the presence of unstable coronary disease, decompensated heart failure, or severe arrhythmia or valvular heart
disease usually leads to cancellation or delay of surgery until the cardiac problem has been clarified and treated
appropriately. Examples of unstable coronary syndromes include previous MI with evidence of important ischemic risk
by clinical symptoms or noninvasive study, unstable or severe angina, and new or poorly controlled ischemia-mediated
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heart failure. Depending on the results of the test or interventions and the risk of delaying surgery, it may be appropriate
to proceed to the planned surgery with maximal medical therapy.
Step 3: Is the patient undergoing low-risk surgery? In these patients, interventions based on cardiovascular testing in
stable patients would rarely result in a change in management, and it would be appropriate to proceed with the
planned surgical procedure. Step 4: Does the patient have moderate functional capacity without symptoms? In
highly functional asymptomatic patients, management will rarely be changed on the basis of results of any further
cardiovascular testing and it is therefore appropriate to proceed with the planned surgery.. If the patient has poor
functional capacity, is symptomatic, or has unknown functional capacity, then the presence of clinical risk factors
will determine the need for further evaluation. If the patient has no clinical risk factors, then it is appropriate to
proceed with the planned surgery, and no further change in management is indicated.
If the patient has 1 or 2 clinical risk factors, then it is reasonable either to proceed with the planned surgery, with
heart rate control, or to consider testing if it will change management. In patients with 3 or more clinical risk factors,
if the patient is undergoing vascular surgery, recent studies suggest that testing should only be considered if it will
change management. In nonvascular surgery in which the perioperative morbidity related to the procedures ranges
from 1% to 5% (intermediate-risk surgery), there are insufficient data to determine the best strategy (proceeding
with the planned surgery with tight heart rate control with beta blockade or further cardiovascular testing if it will
change management).
Choice of Diagnostic Test

There are multiple noninvasive diagnostic tests which have been proposed to evaluate the extent of coronary artery
disease before noncardiac surgery. Although exercise electrocardiogram has been the traditional method of
evaluating individuals for the presence of coronary artery disease, patients with a good exercise tolerance will rarely
benefit from further testing. Therefore, pharmacologic stress testing has become popular, particularly as a
preoperative test in vascular surgery patients.
Several authors have shown that the presence of a redistribution defect on dipyridamole thallium imaging in patients
undergoing peripheral vascular surgery is predictive of postoperative cardiac events. In order to increase the
predictive value of the test, several strategies have been suggested. Lung uptake, left ventricular cavity dilation, and
redistribution defect size have all been shown to be predictive of subsequent morbidity.[14] The appearance of new
or worsened regional wall motion abnormalities is considered a positive test. The advantage of this test is that it is a
dynamic assessment of ventricular function. Dobutamine echocardiography has also been studied and was found to
have among the best positive and negative predictive values. Poldermans et al. demonstrated that the group at
greatest risk were those who demonstrated regional wall motion abnormalities at low heart rates.[15] The presence
of 5 or more segments of new regional wall motion abnormalities denotes a high risk group who did not benefit
from perioperative beta blockade in one trial.[16] Beattie and colleagues demonstrate that stress echocardiography
has better negative predicative characteristics than thallium imaging.[17] They found that moderate-to-large
perfusion defect by either test predicts postoperative MI and death.
Interventions for patients with documented CAD

There is increasing evidence that coronary revascularization before noncardiac surgery does not reduce the
incidence of perioperative cardiac morbidity. McFalls and colleagues reported the results of a multi-center
randomized trail in the Veterans Administration Health System in which patients with documented coronary artery
disease on coronary angiography (CARP), excluding those with left main disease or severely depressed ejection
fraction (<20%), were randomized to coronary artery bypass grafting (CABG)(59%) or percutaneous coronary
interventions (PCI)(41%) versus routine medical therapy.[18] At 2.7 years after randomization, mortality in the
revascularization group was not significantly different (22%) percent compared to the no-revascularization group
(23%) percent. Within 30 days after the vascular operation, a postoperative myocardial infarction, defined by
elevated troponin levels, occurred in 12 percent of the revascularization group and 14 percent of the no-
revascularization group (P=0.37). In a follow-up analysis, Ward and colleagues reported improved outcome in the
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subset who underwent CABG compared to PCI.[19] When patients who underwent coronary angiography in both
the randomized and nonrandomized portion of the CARP trial, only the subset of patients with unprotected left main
disease showed a benefit with preoperative coronary artery revascularization.[20] Poldermans and colleagues
randomized 770 patients having major vascular surgery and considered as having intermediate cardiac risk, defined
as the presence of 1 or 2 cardiac risk factors to either undergo further risk stratification with stress imaging or
proceed right to surgery.[21] All patients received preoperative bisoprolol with a targeted heart rate (HR) of 60-65
initiated before, and continued after surgery. The 30 day incidence of cardiac death and non-fatal MI was similar in
both groups (1.8% in the no testing group versus 2.3% in the tested group). The conclusion of the authors was that
further risk stratification in this group of patients considered at intermediate risk based on clinical history alone was
unnecessary as long as perioperative beta-blockers were used, and testing only delayed necessary vascular surgery.
In a pilot study (DECREASE V), 101 patients with 3 or more risk factors and a markedly positive stress test were
randomized to coronary revascularization versus medical therapy. In those patients in whom there was successful
revascularization, there was significant improvement in long-term outcome.[22]
The current evidence does not support the use of percutaneous transluminal coronary angioplasty (PTCA) beyond
established indications for nonoperative patients, since the incidence of perioperative complications does not appear
to be reduced in those patients in whom PTCA was performed less than 90 days prior to surgery.[23] Coronary stent
placement may be a unique issue and several studies suggest that a minimum of 30 days is required before the rate
of perioperative complications is low.[24-27] Several reports suggest that drug-eluting stents may represent an
additional risk over a prolonged period (up to 12 months), particularly if antiplatelet agents are discontinued.[28]
However, a recent case series suggests that an elevated risk continues beyond 1 year.[29] The new Guidelines
suggest continuing aspirin therapy in all patients with a coronary stent and discontinuing clopidogrel for as short a
time interval as possible for patients with bare-metal stents <30 days or drug-eluting stents <1 year. Based upon the
non-perioperative literature, there is a suggestion that hold clopidogrel for the traditional 8 days may actually
increase risk associated with a hypercoagulable rebound suggesting a shorter period of time may be optimal. A
recent cohort study suggests that withdrawal of anti-platelet agents >5 days is associated with increased major
adverse cardiac events.
There is now a great deal of evidence to suggest that perioperative medical therapy can be optimized in those
patients with coronary artery disease as a means of reducing perioperative cardiovascular complications. Multiple
studies have demonstrated improved outcome in patients given perioperative beta-blockers, especially if heart rate is
controlled.[30, 31] However, newer studies have demonstrated that beta blockers may not be effective if heart rate
is not well controlled, or in lower risk patients.[32-34] The POISE trial was published in which 8351 high-risk beta-
blocker naive patients were randomized to high dose metoprolol CR versus placebo.[35] There was a significant
reduction of the primary outcome of cardiovascular events, associated with a 30% reduction in MI rate, but with a
significantly increased rate of 30-day all-cause mortality and stroke. Patients at intermediate risk were randomized
to statin therapy, beta-blocker therapy, both (started on average 30 days in advance) or double placebo. Beta-
blocker therapy was associated with significantly decreased cardiovascular events, while statin therapy was not.[36]
The current AHA/ACC Guidelines on perioperative beta-blockade advocate that perioperative beta-blockade is a
Class I indication and should be used in patients previously on beta-blockers. The new recommendations advocate
that beta blockers titrated to heart rate and blood pressure are probably recommended for patients undergoing
vascular surgery who are at high cardiac risk owing to coronary artery disease or the finding of cardiac ischemia on
preoperative testing (Class IIa). The ESC Guidelines continue to advocate that both recommendations are Class I.
Flu et al. demonstrated that β-blocker treatment initiated >1 week before surgery is associated with improved
outcome, compared with treatment initiated <1 week pre-operative which is associated with an increased risk of
stroke.[37] Wallace et al. reported that perioperative β-blockade administered according to the Perioperative
Cardiac Risk Reduction protocol is associated with a reduction in 30-day and 1-yr mortality. [38]Perioperative
withdrawal of β-blockers is associated with increased mortality. Atenolol is associated with improved outcome
compared to metoprolol is several large administrative datasets.[39]
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Other pharmacologic agents have also been shown to improve perioperative cardiac outcome. Alpha-2 agonists
have been shown to improve both perioperative mortality and 6 month event-free survival.[40] Most recently,
perioperative statins have been shown to improve cardiac outcome. Durazzo and colleagues published a randomized
trial of 200 vascular surgery patients in which statins were started an average of 30 days prior to vascular
surgery.[41] A significant reduction in cardiovascular complications was demonstrated using this protocol. Le
Manach and colleagues demonstrated that statin withdrawal greater than 4 days was associated with a 2.9 odds ratio
of increased risk of cardiac morbidity in vascular surgery.[42] Most recently, a total of 250 patients were assigned
to fluvastatin, and 247 to placebo, a median of 37 days before vascular surgery.[43] Perioperative fluvastatin therapy
was associated with an improvement in postoperative cardiac outcome. However, a recent small randomized trial
questions the value of statin therapy in reducing perioperative inflammation. The recent Guidelines advocate
continuing statin therapy in patients currently taking statins as a Class I indication. A multi-modal approach to
medical management should be taken in high risk patients.
Summary
Preoperative evaluation should focus on identifying patients with symptomatic and asymptomatic coronary artery
disease and the exercise capacity of the patient. The decision to perform further diagnostic evaluation depends upon
the interactions of patients and surgery specific factors, as well as exercise capacity and should be reserved for those
at moderate risk undergoing major or intermediate surgery with poor exercise capacity. The indications for coronary
interventions are the same in the perioperative period as for the non-operative setting.
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(MaVS) study, a randomized controlled trial. Am Heart J, 2006. 152(5): p. 983-90.
35.Devereaux, P.J., et al., Effects of extended-release metoprolol succinate in patients undergoing non-cardiac
surgery (POISE trial): a randomised controlled trial. Lancet, 2008. 371(9627): p. 1839-47.
36.Goei, D., et al., The interrelationship between preoperative anemia and N-terminal pro-B-type natriuretic peptide:
the effect on predicting postoperative cardiac outcome in vascular surgery patients. Anesth Analg, 2009. 109(5): p.
1403-8.
37.Flu, W.J., et al., Timing of pre-operative Beta-blocker treatment in vascular surgery patients: influence on post-
operative outcome. Journal of the American College of Cardiology, 2010. 56(23): p. 1922-9.
38.Wallace, A.W., S. Au, and B.A. Cason, Association of the pattern of use of perioperative beta-blockade and
postoperative mortality. Anesthesiology, 2010. 113(4): p. 794-805.
39. Wallace, A. W., et al. Perioperative beta-blockade: atenolol is associated with reduced mortality when compared
to metoprolol. Anesthesiology 2011.114(4): 824-836.
40.Wallace, A.W., et al., Effect of clonidine on cardiovascular morbidity and mortality after noncardiac surgery.
Anesthesiology, 2004. 101(2): p. 284-93.41.Durazzo, A.E., et al., Reduction in cardiovascular events after vascular
surgery with atorvastatin: a randomized trial. J Vasc Surg, 2004. 39(5): p. 967-75.
42.Le Manach, Y., et al., The impact of postoperative discontinuation or continuation of chronic statin therapy on
cardiac outcome after major vascular surgery. Anesth Analg, 2007. 104(6): p. 1326-33, table of contents.
43.Schouten, O., et al., Fluvastatin and perioperative events in patients undergoing vascular surgery. N Engl J Med,
2009. 361(10): p. 980-9.
DISCLOSURE
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Utility of TEE in the Integrated Management of Patients Undergoing Valvular Heart Surgery
Robert Savage, M.D. Cleveland, Ohio
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Wellness in Anesthesiologists
John E. Ellis, M.D. Philadelphia, Pennsylvania
Slides available after the presentation at vascularanesthesia.com
Stress and burnout may occur in health care professionals. This review will examine these issues in general. It will
also examine causes of mortality in anesthesiologists. The occupational risks of anesthesia practice include: drug
dependence, ergonomic risks, radiation risks, and infection risks. Tools to combat stress and reduce chronic disease
in health care professionals will also be reviewed.
Stress and burnout in health care professionals

• Sources of stress
o Production pressure
o Periop catastrophes/lawsuits
o Financial
o Personal
o Circadian rhythms (call)
Production pressure
A survey by Gaba et al. looked at the internal and external pressures on anesthesiologists, and reported that
respondents placed the highest pressures on themselves to avoid delays to surgery, avoid litigation, and get along
with surgeons.1 The survey reported that anesthesiologists faced relatively high pressure from surgeons to proceed
with a case rather than cancel it; and from administrators to reduce turnover time. An alarming 63% of respondents
suggested that they had made errors because of workload.1
Consequences of Physician Stress and Burnout

Stress and burnout have dire consequences for physicians both personally and professionally. Personal consequences
include depression; anxiety; suicide; broken relationships with family, friends and colleagues; addiction to alcohol
and/or drugs; marital dysfunction and divorce; and early retirement. Professional consequences include
disengagement; poor judgment in patient care decision-making; hostility towards patients; medical errors; adverse
patient events; diminished commitment and dedication to optimal patient care; and difficult relationships with co-
workers.2
Predictors of Burnout3
• Spending < 20% time on most meaningful activity
• Age < 55 y
• Generalist
• Total hrs worked/wk
Medical errors
A Balch et al. study of surgeons reported that those who experience burnout, or have been screened positive for
depression, are at an increased risk of perceived medical error. Retired surgeons, plastic surgeons, those who spend
> 50% of their time dedicated to nonpatient care, and older surgeons are at a lower risk of perceived medical error.3
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Periop catastrophes/lawsuits
Respondents of a study by Gazoni et al. chose death, cardiac arrest, myocardial infarction, stroke or other brain
injury, perioperative visual loss, and wrong site/wrong patient as events that qualify most as perioperative
catastrophes.4
Anesthesiologists who experience perioperative catastrophes undergo deep emotional trauma that may affect their
ability to provide subsequent patient care.4 Most respondents of the Gazoni et al. study required time to recover
emotionally from perioperative catastrophes. 21% of respondents required a week to recover and 19% never fully
recovered.4 67% of respondents felt that their ability was compromised when they provided care 4 hours after the
periop catastrophe, and 16% felt their ability was comprised more than a week after.4
Financial Stress
Financial stress is among the top 5 sources of stress for anesthesiologists. Financial stress persists before residency,
through residency and in practice.5 Impatience (years of training = shorter working time), faith (physicians are
marks), and (over) confidence are the common factors that result in physicians’ financial mistakes.6
Circadian rhythms (call): Sleep deprivation

Sleep deprivation is one of the most impactful consequences of physician call schedules. It elevates stress hormones
and promotes over eating. Studies of sleep deprivation have shown that long distance pilots have smaller temporal
lobes.
Causes of mortality in anesthesiologists

• Overall statistics
• Suicide
• Drug addiction
• Exposure to anesthetic gases?
• Infectious risks
Mortality in Anesthesiologists:
Death rates for anesthesiologists decreased between 1957-1976 after the introduction of fluorinated anesthetic
agents, but are similar to rates between 1930-1946 and 1947-1956. 7This suggests that fluorinated agents do not
adversely affect the health of anesthesiologists.
The main health problem among American anesthesiologists is the high suicide rate at ages <55 years.8
Anesthesiologists have higher rates of suicide and drug-related deaths than internists. Male anesthesiologists had a
higher death rate from HIV and viral hepatitis, which may be explained by lifestyle. 9
Research by Kain et al. concluded that only minor acute physiological stress occurs in anesthesiology during the
perioperative process. 10
The incidence of coronary artery disease among anesthesiologists is not alarming in context to the general male
population or in comparison to a similar socioeconomic group. 11 This may be, in part, because smoking is rare,
except in anesthesiologists who are also opiate addicts; physicians with opioid addiction have the higher rates of
tobacco and marijuana use than physicians in general, as well as the general population.12
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Occupational risks of anesthesia practice

Occupational risks include drug dependence; and ergonomic, radiation, and infection risks.
Drug dependence
Anesthesiologists are over-represented in Florida drug treatment programs. 13 Some have suggested that this may
be, in part, due to drug exposures in operating room. Second-hand exposure to drugs like fentayl and propofol in the
operating room may influence drug dependence on opioids. This environmental exposure may be a more reasonable
explanation - than mere access - for the high drug dependence among anesthesiologists.14
Drug/Chemical dependence recovery among anesthesiologists

Anesthesiologists who received treatment from PHPs with strict regulations and guidelines for return to workplace
had similar recovery results as other physicians.15
The Disabled Anesthesiologist

Three general categories of questions related to disability: “1) an anesthesiologist who has suffered an injury or
illness and wants to return to practice; 2) an anesthesiologist with an established impairment who is seeking support
in his/her attempt to receive disability insurance benefits; or 3) colleagues who are questioning whether an
anesthesiologist with particular limitations should be permitted to continue practicing.”16
Ergonomic risks: musculoskeletal disorders

A study of professional nurses in Mainland China reported a 70% prevalence of musculoskeletal disorders, with the
following breakdown: lower back (56.7%), neck (42.8%), shoulders (38.9%) and upper back (38.9%).17 A study
showed that anesthesia trainees often have poor ergonomics. 18 Body posture and work clothing (lead apron, foot
wear, etc - clothing that causes physical discomfort) are among the factors that affect ergonomics for
anesthesiologists.19
Radiation exposure
Radiation exposure to anesthesiologist’s face was six times greater during an angiography and three times greater
than that of a radiologist according to Anastasian et al. study. A recommendation for anesthesiologists who spend
significant time performing such procedures is to wear protective eyewear.20
Infectious risks
Researchers from Robin Medical Center and Tel Aviv University conducted a study during a 3-month strike of
anesthesiologists. They measured induced cytokine production and lymphocytes proliferative responses in the blood
samples of 10 anesthesiologists before and after the strike. Proliferative responses were much lower at the end of the
strike, and the study concluded that anesthesiologist work environments correlate to certain immune changes.21
Steps to promote personal well-being

Identifying personal values and priorities, nurturing wellness strategies (relationships, spiritual, hobbies), enhancing
areas of work that are personally meaningful, rest and reflection, and self care are among steps to promote personal
well-being.2
REFERENCES
1
Leedal JM, Smith AF. Methodological approaches to anaesthetists' workload in the operating theatre. Br J
Anaesth. 2005 Jun;94(6):702-9.
2
Balch CM, Shanafelt T. Combating stress and burnout in surgical practice: a review. Adv Surg. 2010;44:29-47.
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3
Shanafelt TD, West CP, Sloan JA, Novotny PJ, Poland GA, Menaker R, Rummans TA, Dyrbye LN.
Career fit and burnout among academic faculty. Arch Intern Med. 2009 May 25;169(10):990-5.
4
Gazoni FM, Amato PE, Malik ZM, Durieux ME. The impact of perioperative catastrophes on anesthesiologists:
results of a national survey. Anesth Analg. 2012 Mar;114(3):596-603. Epub 2011 Jul 7.
5
Lutsky I, Hopwood M, Abram SE, Jacobson GR, Haddox JD, Kampine JP. Psychoactive substance use among
American anesthesiologists: a 30-year retrospective study. Can J Anaesth. 1993 Oct;40(10):915-21.
6
Ron Lieber. Investment Advice for Doctors: First, Do No Harm. New York Times. Online. August 26, 2011.
http://goo.gl/AVGDc
7
Linde HW, Mesnick PS, Smith NJ. Causes of Death among Anesthesiologists: 1930-1946. Anesthesia and
Analgesia 60:1-7, 1981.
8
Edward L. Mortality Experience among Anesthesiologists, 1954-1976. Anesthesiology 51:195-199, 1979.
9
Alexander BH, Checkoway H, Nagahama SI, Domino KB. Cause-specific mortality risks of anesthesiologists.
Anesthesiology. 2000 Oct;93(4):922-30.
10
Kain ZN, Chan KM, Katz JD, Nigam A, Fleisher L, Dolev J, Rosenfeld LE. Anesthesiologists and acute
perioperative stress: a cohort study. Anesth Analg. 2002 Jul;95(1):177-83
11
Bruce DL, Eide KA, Linde HW, Eckenhoff JE. Causes of Death among Anesthesiologists: A 20-Year Survey.
Anesthesiology May/June 1968 – Volujme 29 – Issue 3.
12
Merlo LJ, Goldberger BA, Kolodner D, Fitzgerald K, Gold MS. Fentanyl and propofol exposure in the operating
room: sensitization hypotheses and further data. J Addict Dis. 2008;27(3):67-76.
13
McAuliffe PF, Gold MS, Bajpai L, et al. Second-hand exposure to aerosolized intravenous anesthetics propofol
and fentanyl may cause sensitization and subsequent opiate addiction among anesthesiologists. Med
Hypotheses 2006; 66: 874-882.
14
Gold MS, Graham NA, Goldberger BA. Second-hand and third-hand drug exposures in the operating room: a
factor in anesthesiologists' dependency on fentanyl. J Addict Dis. 2010 Jul;29(3):280-1.
15
Gold MS, Melker RJ, et al. Fentanyl Abuse and Dependence. Journal of Addictive Diseases, Vol. 25 (1) 2006.
16
Jonathan D. Katz. The Disabled Anesthesiologist. ASA Volume 71, Number 5, May 2007.
http://old.asahq.org/Newsletters/2007/05-07/katz05_07.html
17
Smith DR, Wei N, Kang L, Wang RS. Musculoskeletal disorders among professional nurses in mainland China. J
Prof Nurs. 2004 Nov-Dec;20(6):390-5.
18
Ajmal M, Power S, Smith T, Shorten GD.Ergonomic task analysis of ultrasound-guided femoral nerve block: a
pilot study. J Clin Anesth. 2011 Feb;23(1):35-41.
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19
Veelen MA, et al. Ergonomic problems encountered by the medical team related to products used for minimally
invasive surgery. Surg Endosc (2003) 17: 1077–1081
20
Anastasian ZH, Strozyk D, Meyers PM, Wang S, Berman MF. Radiation exposure of the anesthesiologist in the
neurointerventional suite. Anesthesiology. 2011 Mar;114(3):512-20.
21
Beilin B, Greenfeld K, Abiri N, Yardeni IZ, Bessler H, Ben-Eliyahu S. Anesthesiologists at work: an increase in
pro-inflammatory and Th2 cytokine production, and alterations in proliferative immune responses. Acta
Anaesthesiol Scand. 2006 Nov;50(10):1223-8.
DISCLOSURE
Baxter, Self, Consulting Fees, Honoraria
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Hypoxia During Thoracic Surgery

Practical Advice for the Anesthesiologist
Javier H. Campos, M.D. Iowa City, Iowa
Learning Objectives:
The learner will be able to:

1. Describe the risk stratification in patients undergoing thoracic surgery that may develop hypoxia.
2. Describe the pathophysiology of hypoxia during one-lung ventilation.
3. Describe the effects of hypoxia on inflammatory response and cytokine release during one-lung ventilation.
4. Describe the influence of protective ventilation, continuous positive airway pressure (CPAP), positive end
expiratory pressure (PEEP), and selective lobar ventilation in the management of hypoxia during thoracic
surgery.
5. Describe the influence of anesthetics on hypoxia during the intraoperative period and potential complications in
the postoperative period.
Introduction
Lung separation with the use of a double-lumen tube (DLT) or bronchial blocker (BB) is used to provide one-lung
ventilation (OLV) in patients undergoing thoracic, mediastinal, cardiac, vascular or esophageal procedures. [1-2]
During OLV, an intrapulmonary shunt, related in part to collapse of the non-dependent lung and increased
atelectatic areas in the dependent lung, results in hypoxemia. [3] Hypoxemia by definition is a decrease in arterial
hemoglobin oxygen saturation (SaO2) to less than 90% [4], or a PaO2 <60 mmHg when the patient is being
ventilated with a FiO2 1.0. [5]
The incidence of hypoxemia during OLV has been reported to be 1-5%. This is partially related to advances with
routine use of a fiberoptic bronchoscope for optimal placement of lung isolation devices, as well as with the
introduction of newer volatile anesthetics that cause less inhibition of hypoxic pulmonary vasoconstriction (HPV)
and less shunting during OLV. [6-8]
The Risk Stratification in Patients Undergoing Thoracic Surgery that may Develop Hypoxia During OLV
Slinger, et al [9], using regression analysis in 80 patients undergoing OLV, showed that the three most significant
predictors for PaO2 were: right-sided operation [because the right lung is larger than the left lung, oxygenation is
better during left thoracotomy (i.e. when the larger right lung is the dependent and ventilated lung)], preoperative
FEV1 % and intraoperative PaO2 during two lung ventilation. Others [10-11] have shown better oxygenation during
left-sided thoracic surgery as compared to right-sided surgeries when FiO2 of 1.0 is used.
Morbidly obese patients (BMI >30 Kg-m2) undergoing thoracic surgical procedures under OLV have been shown to
develop intraoperative hypoxemia and an increase in alveolar arterial oxygen difference. [12] In a study by
Schwarzkopf, et al [10], they found that patients undergoing lobectomy and pneumonectomy had better oxygenation
during OLV than patients undergoing video thoracoscopic metastasectomy. Lung perfusion studies in these patients
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showed that perfusion of the non-ventilated lung was more impaired in patients presenting for lobectomy and
pneumonectomy than in patients presenting for metastasectomy. Patients with previous lobectomy requiring
another surgery in the contralateral lung may be at risk of developing hypoxemia during total lung collapse.
Effects on Arterial Oxygen Tension (PaO2) in Supine or Lateral Decubitus Position in Thoracic Surgery
In general, for thoracic surgical patients undergoing OLV, the most common practice is to operate in a lateral
decubitus position. Therefore, gravity is a major determinant of shunt fraction and perfusion. [13] Recent studies
[14-15] have examined the changes in arterial oxygen tension (PaO2) during procedures requiring OLV. In the
Watanabe, et al study [14], patients were ventilated with a FiO2 of 1.0 and divided into three groups. One group
was supine, another group was positioned in a left semi-lateral decubitus position and the third group was placed in
left full–lateral position. In the supine position group, 9 out of 11 patients had arterial oxyhemoglobin saturation
<90%; in the other two groups (semi lateral and full lateral), only one patient in each group developed hypoxemia.
The study by Bardoczky, et al [15], compared the positional effects and the inspired fraction of oxygen during OLV.
The patients, randomly assigned, received FiO2 of 0.4, 0.6 or 1.0 during two lung ventilation and thereafter OLV in
the supine and lateral position. PaO2 decreased more during OLV compared to two lung ventilation regardless of
the position. However, in all three groups, PaO2 was significantly higher during OLV in the lateral than the supine
position. These studies clearly demonstrated that during OLV in a lateral decubitus position, the gravitational effect
augments the redistribution of perfusion to the ventilated (dependent) lung, improving V/Q match. Therefore, in
patients requiring OLV who are placed in supine position, it is possible to experience more transient episodes of
hypoxemia.
Pathophysiology of Hypoxia During One-Lung Ventilation

Hypoxemia during OLV is caused by venous admixture through shunts and areas of low ventilation-perfusion ratio
(V/Q) gas exchanging units. During OLV, the collapsed non-dependent lung is an obligate shunt while the
dependent lung also causes a venous admixture through shunt and areas of low V/Q. This is primarily through
atelectatic areas of the lung seen with general anesthesia and is perhaps increased with the lateral decubitus position
through the weight of the mediastinum, abdominal organs, retractors, excessive packing of the thorax and low
compliance of the chest wall in the dependent position.[16]
The determinants of arterial oxygen content include: hemoglobin concentration, hemoglobin dissociation curve
(P50), oxygen consumption, total cardiac output, inspired oxygen fraction (FiO2), arterial carbon dioxide level
(PaCO2), blood flow through the unventilated lung and unventilated or low V/Q areas of the ventilated lungs. The
last two factors are often associated together as shunt (Q) or shunt fraction (Qs/Qt). [17]
Effects of Hypoxia on Inflammatory Response and Cytokine Release During One-Lung Ventilation
When considering the effects of ventilation on arterial oxygenation during OLV, it is better to consider the blood
flow through the unventilated lung (V/Q = O) separately from the ventilation of the low V/Q areas of the ventilated
lung. In general, the Qs/Qt fraction seen during anesthesia and OLV ranges from 20-40%.
During OLV, the non-dependent (operated) lung remains atelectatic and hypoperfused because of hypoxic
pulmonary vasoconstriction (HPV). Thus, the HPV in the non-dependent lung ameliorates the pulmonary
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ventilation/perfusion relationship, preserving the systemic oxygenation by constricting pulmonary vessels in poorly
ventilated or atelectatic hypoxic lung regions to divert the pulmonary blood flow to better aerated areas.[18]
Although HPV decreases the shunt fraction and attempts to resolve hypoxemia[19], it is a serious aggravating factor
when ventilation is restored because pulmonary re-expansion promotes the re-entry of oxygen through the airways,
causing the release of excessive oxidative radicals.[20] The re-expansion of a previously collapsed lung is
accompanied by an ischemia/reperfusion like response resulting in the release of cytokines from the collapsed lung
and the contralateral lung. Through this mechanism, OLV increases the risk of developing acute lung injury (ALI).
[21]
During OLV, inflammatory response reactions can be produced by multiple factors such as mechanical damage due
to surgical manipulation, OLV induced atelectasis and re-expansion, atelectasis, and damage by high oxygen tension
or by the use of high peak inspiratory pressure during mechanical ventilation. [22-25] Inflammatory cytokines,
tumor necrosis factor, interleukin (IL) – IB, IL-6 and IL-8 are important chemoattractants that affect the recruitment
of neutrophils and alveolar macrophages. Alveolar macrophages secrete biologically active products and thereby
play a significant role in regulating pulmonary inflammatory reactions. An increase in these inflammatory cytokines
can be clinically relevant to pulmonary complications and impairment of oxygenation during or following thoracic
surgery.
One study [25] has shown that the epithelial lining fluid contained significantly increased levels of interleukins in
the dependent or ventilated lung and the non-dependent lung at the end of thoracic surgery. The inflammatory
response was even greater in the dependent lung. The peak inspiratory pressures used in this study were below 30
cmH2O, tidal volume of 6 ml/Kg and FiO2 of 0.6-1.0. Misthos, et al [26], has shown that patients with non-small cell
lung cancer have a higher production level of oxygen free radicals than the normal population; mechanical
ventilation and surgical trauma are weak free radical generators. Manipulated lung tissue is also a source of free
radicals in the intra or postoperative period and lung re-expansion provoked severe oxidative stress. Interestingly,
this study also showed that the degree of generated oxygen free radicals was associated with the duration of OLV.
Oxygen toxicity is a well-recognized consequence of prolonged exposure to high FiO2 characterized by

histopathologic changes similar to ALI. Oxygen toxicity occurs during OLV and involves ischemia-reperfusion
injury and oxidative stress. [27] Collapse of the operative lung and surgical manipulation result in relative organ
ischemia and reperfusion at the time of lung expansion, which leads to the production of radical oxygen species.
Increasing the duration of OLV and the presence of tumor also increases the markers of oxidative stress. Lung re-
expansion should likely occur at a lower FiO2 as hypoxemic reperfusion has been shown to attenuate reperfusion
syndrome.
Influence of Protective Ventilation, Continuous Positive Airway Pressure (CPAP), Positive End Expiratory
Pressure (PEEP) and Selective Lobar Ventilation in the Management of Hypoxia During OLV
Malposition of lung isolation devices is a common cause of hypoxemia. A study by Inoue, et al [5], has shown that
patients who experience DLT malposition after turning the patient into lateral decubitus position had more
malpositions during OLV and more hypoxemia. Also, this study showed that after correction of the malposition, the
patients required more interventions (i.e. CPAP or apneic oxygen insufflation) to treat the hypoxemia.
If during OLV the patient experiences hypoxemia, the first step is to ventilate the patient’s lung with FiO2 1.0 and
restore two lung ventilation. Once oxygenation improves, reassessment of the lung isolation device takes
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precedence (expands the non-ventilated lung and re-assesses the position of the DLT or a bronchial blocker with the
flexible fiberoptic bronchoscope). [28] After the correct position is obtained, aspiration of secretions follows. In
addition, it is important to maintain the patient under OLV normocarbic, normotensive and normothermic. Any
alteration of these factors will also contribute to the development of hypoxemia. In cases where hypoxemia is
present, despite the fact that tube position is optimal, during thorascopic surgery where the application of CPAP can
interfere with surgical exposure, a selective ipsilateral segmental insufflation of oxygen with a fiberoptic
bronchoscope has been shown to improve oxygenation without interfering with surgical exposure. [29]
An alternative to improve oxygenation to the non-dependent lung is to use intermittent positive airway pressure
during OLV. One study [30] has shown that slow inflation of 2 l/min of oxygen into the non-dependent lung for 2
seconds at different interval periods improves oxygenation and saturation. In the 10 patients reported, the mean
oxygenation rose from 67±12 to 99±20 mmHg during OLV.
Use of CPAP has been traditionally used to treat hypoxemia due to the obligatory shunt developed by the non-
dependent (collapsed) lung. The application of CPAP has been suggested to be used in the deflation phase of a tidal
volume breath. It is prudent to start with 5 cmH2O of CPAP and progressively increase to no more than 10 cmH2O
CPAP. If necessary CPAP can be easily applied to a DLT or a bronchial blocker. See Figure 1
Figure 1
Another alternative to improve oxygenation and treatment of hypoxemia in patients who have previous lobectomy is
the use of a selective lobar blockade. In some instances, it will only be necessary to partially collapse one lobe
segment while the rest is being ventilated. [31-32] It is estimated that after a lobe resection, the loss of lung function
is approximately 24%. [33] Patients with previous lobectomy requiring another surgery in the contralateral lung may
be at risk of developing hypoxemia during total lung collapse. One alternative is to use selective lobar collapse to
improve oxygenation with or without CPAP. [34] Higher levels of CPAP (i.e. >10 cmH2O) to the non-dependent
lung will interfere with surgical exposure and may compromise venous return. Always, when applying CPAP to the
non-dependent lung, it is advisable to observe the direct distention of the collapsed lung.
Should PEEP be used Routinely in all Patients Undergoing OLV
In some patients, the application of PEEP to the dependent (ventilated) lung is beneficial through the restoration of
functional residual capacity close to normal values. [35] This ventilatory maneuver will prevent atelectasis when its
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value is titrated along the static compliance curve. [36] However, not all patients will tolerate the routine use of
PEEP in the dependent lung during OLV. Many patients, particularly those with emphysema, develop auto-PEEP
during OLV. [37] However, patients with normal lung parenchyma or those with restrictive lung disease tend to fall
below their functional residual capacity at the end-expiration during OLV and may benefit from the application of
external PEEP to the dependent lung. [37]
Outcomes research studies performed in patients undergoing thoracic surgical procedures have shown that one of the
factors that is independently associated with acute lung injury is the high intraoperative ventilatory pressure index.
[38] Recent research has recommended the use of low tidal volumes during thoracic surgical procedures and during
OLV. One study [39] has shown that low tidal volume of 6 ml/kg during OLV with the use of FiO2 = 0.6-0.7 and
CPAP 5 cmH2O to the non-dependent lung lead to a higher PaO2 (141±82 vs 112±49) mmHg when compared to low
tidal volumes and PEEP 5 cmH2O to the dependent lung.
Also, alveolar recruitment maneuvers have been recommended to improve oxygenation during OLV. Tusman, et al
[40], have shown the beneficial effects with an alveolar recruitment maneuver with pressure controlled ventilation.
They reported that PaO2 values were similar to the ones obtained during two lung ventilation.
During OLV it is not uncommon to alternate from volume controlled ventilation to pressure controlled ventilation in
order to improve oxygenation. One study has demonstrated that a better oxygenation is achieved when pressure
controlled ventilation is used during OLV. [41] However, another study [42] in a crossover experiment involving
thoracic surgical patients requiring OLV showed that arterial oxygenation was similar in the groups that received
volume controlled ventilation when compared to pressure controlled ventilation. Also, this study observed a
decrease in peak plateau pressure in the patients that received pressure controlled ventilation. The use of pressure
controlled ventilation would be more beneficial in the morbidly obese patient undergoing OLV. (Personal report this
study is underway) to demonstrate the advantage of this mode of ventilation to maintain optimal oxygenation during
OLV.
Pharmacologic interventions have been studied to control pulmonary blood flow during OLV. [43-46] Some studies
have shown that the use of a respiratory stimulant, such as almitrine intravenously and with an infusion, improved
oxygenation during OLV, probably due to the molecular mechanisms of action on the pulmonary vessels combined
with direct stimulation of chemoreceptors and direct pulmonary vasoconstrictive action. [43] Also, others have
shown no effect on oxygenation when inhaled nitric oxide has been used in patients requiring OLV. [44] However,
the combination of inhaled nitric oxide with intravenous almitrine has shown promising results while improving
PaO2 during OLV. [45-46] At the present time, I believe these drugs are in the experimental phase to recommend
routine use to improve oxygenation during OLV.
Influence of Anesthetics on Hypoxia During the Intraoperative Period and Potential Complications in the
Postoperative Period
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In the 1980’s, special attention was given to the effects of anesthetics and HPV during OLV. However, in the past
10 years more attention has been given to the effects on ventilation, and the inflammatory response and their
potential complications after OLV, which is the development of ALI. Some of the studies have included very
limited samples of studied patients. One study [24] has shown that the use of small tidal volumes (5 ml/kg) during
OLV had lower levels of interleukin (IL-8, 10, and TNF) when compared to high tidal volumes of 10 ml/kg. Others
have shown a protective effect in modulating the inflammatory response when inhalational agents are used during
OLV compared to pure total intravenous anesthesia. [47-49] Reduction of inflammatory mediators had significantly
better clinical outcomes defined by postoperative adverse events such as atelectasis or systemic inflammatory
response syndrome. [48] As part of the intervention to manage hypoxemia and inflammatory response during OLV,
I recommend the use of inhalational agents during the management of these patients.
Another area that deserves special attention is the effects of hypoxia during OLV in relationship to cerebral oxygen
saturation. One study [50] involving thoracic surgical patients has shown a significant decrease in cerebral oxygen
saturation measured by absolute cerebral oximetry during OLV. Unfortunately, cognitive mental tests were not used
to correlate the significance of a cerebral desaturation with cognitive functions. Other investigators [51] have
studied the jugular bulb venous oxygen saturation during OLV comparing sevoflurane versus propofol. This study
reported more cerebral oxygen desaturation episodes using propofol anesthesia during OLV. Once again, clinical
outcomes or significance of cognitive function was not evaluated.
Summary
Hypoxemia during OLV is an infrequent finding, ventilatory maneuvers to optimize and improve oxygenation is
listed in table I. Inhalational agents appear to have a protective effect in controlling inflammatory response during
OLV. Low tidal volumes with PEEP in the dependent lung along with CPAP in the non-dependent lung appear to
be the most common intervention to treat hypoxemia.
Table 1: Treatment of Hypoxia During One-Lung Ventilation

• Increase FiO2 1.0 • Adjust ventilation according to patient needs pressure
control vs volume control?
• Re-expand the collapsed lung • If a DLT is being used in video thoracoscopic
surgery, consider selective O2 insufflation to the non-
ventilated lung with fiberoptic bronchoscope
• Convert to two lung ventilation • If a bronchial blocker is used, consider selective lobar
blockade in patients with previous contralateral
lobectomy
• Confirm position with fiberoptic bronchoscope for • Intermittent O2 insufflation with 2 l/min for short
optimal position of lung isolation device intervals to the non-dependent lung
• After SPO2 >98%, convert to OLV and apply CPAP • Recruitment ventilatory maneuvers during OLV
5 cmH2O to non-dependent lung
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• Unless contraindicated (i.e. auto PEEP >10), use • Clamping of pulmonary vessel during
PEEP 5 cm H2O routinely to the dependent lung pneumonectomy cases will reduce the shunt fraction
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6. Slinger P. Pro: low tidal volume is indicated during one-lung ventilation. Anesth Analg 2006; 103:268-70.
7. Klein U, Karzai W, Bloos F, et al. Role of fiberoptic bronchoscopy in conjunction with the use of double-
lumen tubes for thoracic anesthesia: a prospective study. Anesthesiology 1998; 88:346-50.
8. Campos JH. Current techniques for perioperative lung isolation in adults. Anesthesiology 2002; 97:1295-1301
9. Slinger P, Suissa S, Triolet W. Predicting arterial oxygenation during one-lung anaesthesia. Can J Anaesth
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10. Schwarzkopf K, Klein U, Schreiber T, et al. Oxygenation during one-lung ventilation: the effects of inhaled
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11. Lewis JW Jr, Serwin JP, Gabriel FS, et al. The utility of a double-lumen tube for one-lung ventilation in a
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12. Suemitsu R, Sakoguchi T, Morikawa K, et al. Effect of body mass index on perioperative complications in
thoracic surgery. Asian Cardiovasc Thorac Ann 2008; 16:463-7
13. Brodsky JB. Approaches to hypoxemia during single-lung ventilation. Curr Opin Anaesthesiol 2001; 14:71-6.
14. Watanabe S, Noguchi E, Yamada S, et al. Sequential changes of arterial oxygen tension in the supine position
during one-lung ventilation. Anesth Analg 2000; 90:28-34.
15. Bardoczky GI, Szegedi LL, d'Hollander AA, et al. Two-lung and one-lung ventilation in patients with chronic
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16. Larsson A, Malmkvist G, Werner O. Variations in lung volume and compliance during pulmonary surgery. Br
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17. Ward DS. Intra-operative ventilation strategies for thoracic surgery. Chapter 21 in Principles and Practice of
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18. Leite CF, Calixto MC, Toro IF, et al. Characterization of Pulmonary and Systemic Inflammatory Responses
Produced by Lung Re-expansion After One-Lung Ventilation. Cardiothorac Vasc Anesth 2012; 26:427-32
19. Lohser J. vidence-based management of one-lung ventilation. Anesthesiol Clin 2008; 26:241-72
20. Cheng YJ, Chan KC, Chien CT, et al. Oxidative stress during 1-lung ventilation. J Thorac Cardiovasc Surg
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21. Tsai JA, Lund M, Lundell L, et al. One-lung ventilation during thoracoabdominal esophagectomy elicits
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22. Baudouin SV. Lung injury after thoracotomy. Br J Anaesth 2003; 91:132-42
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24. Schilling T, Kozian A, Huth C, et al. The pulmonary immune effects of mechanical ventilation in patients
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36. Slinger PD, Kruger M, McRae K, et al. Relation of the static compliance curve and positive end-expiratory
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40. Tusman G, Böhm SH, Sipmann FS, et al. Lung recruitment improves the efficiency of ventilation and gas
exchange during one-lung ventilation anesthesia. Anesth Analg 2004; 98:1604-9
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42. Unzueta MC, Casas JI, Moral MV. Pressure-controlled versus volume-controlled ventilation during one-lung
ventilation for thoracic surgery. Anesth Analg 2007; 104:1029-33
43. Dalibon N, Moutafis M, Liu N, et al. Treatment of hypoxemia during one-lung ventilation using intravenous
almitrine. Anesth Analg 2004; 98:590-4
44. Rocca GD, Passariello M, Coccia C, et al. Inhaled nitric oxide administration during one-lung ventilation in
patients undergoing thoracic surgery. J Cardiothorac Vasc Anesth 2001; 15:218-23.
45. Moutafis M, Liu N, Dalibon N, et al. The effects of inhaled nitric oxide and its combination with intravenous
almitrine on Pao2 during one-lung ventilation in patients undergoing thoracoscopic procedures. Anesth Analg
1997; 85:1130-5.
46. Silva-Costa-Gomes T, Gallart L, Vallès J, et al. Low- vs high-dose almitrine combined with nitric oxide to
prevent hypoxia during open-chest one-lung ventilation. Br J Anaesth 2005; 95:410-6
47. Schilling T, Kozian A, Kretzschmar M, et al. Effects of propofol and desflurane anaesthesia on the alveolar
inflammatory response to one-lung ventilation. Br J Anaesth 2007; 99:368-75
48. De Conno E, Steurer MP, Wittlinger M, et al. Anesthetic-induced improvement of the inflammatory response
to one-lung ventilation. Anesthesiology 2009; 110:1316-26.
49. Mahmoud K, Ammar A. Immunomodulatory Effects of Anesthetics during Thoracic Surgery. Anesthesiol Res
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50. Kazan R, Bracco D, Hemmerling TM. Reduced cerebral oxygen saturation measured by absolute cerebral
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51. Iwata M, Inoue S, Kawaguchi M, et al. Jugular bulb venous oxygen saturation during one-lung ventilation
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DISCLOSURE
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Perioperative Management of Cardiovascular Implantable Electronic Devices

(CIEDs)
Annemarie Thompson, M.D. Nashville, Tennessee
OVERVIEW
The rapidly expanding technology of cardiovascular implantable electronic devices (CIEDs) as well as their
widespread use not only for bradyarrhythmia and tachyarrhythmia management, but also for congestive heart failure
management has ushered in an era where patients who experience long-term benefit from such therapy are
presenting for both cardiac and noncardiac surgery. With approximately one million patients worldwide receiving a
pacemaker or implantable cardioverter defibrillator (ICDs) every year, patients with CIEDs are a growing
population in the perioperative arena. As “internists of the operating room” who routinely manage complex, life-
threatening medical illnesses such as diabetes, anesthesiologists are increasingly asked to address the perioperative
management of patients with CIEDs. Until recently, there was little guidance, confusing literature, and frank
misinformation regarding the perioperative management of CIEDs.
The July 2011 Heart Rhythm Society (HRS)/American Society of Anesthesiologists (ASA) Expert Consensus
Statement on the perioperative management of patients with CIEDs has sought to inform perioperative physicians
and encourage responsible communication between the CIED team that typically manage patients with devices and
the perioperative team. 1 The HRS/ASA Expert Consensus Statement on the perioperative management of CIEDs
has also been endorsed by the AHA, ACC, and STS. Due to its relatively recent publication in the leading
electrophysiology journal, most anesthesiologists are not familiar with the document or its details. Additionally, due
to the technical complexity of CIEDs, the rapidly evolving field, and the dearth of education regarding these devices
in clinical training programs, many advanced perioperative physicians find it challenging to learn about the
perioperative management of CIEDs.
PERIOPERATIVE CONSIDERATIONS
Preoperative assessment
Basic terminology/codes for pacemakers and ICDs are reviewed in Tables 1 and 2 respectively.
The need for two-way communication between the CIED team that usually cares for the patient and the operative
team was emphasized by the Heart Rhythm Society (HRS)/American Society of Anesthesiologists (ASA) Expert
Consensus Statement published in July 2011. The most effective means of caring for the patient with a CIED will
occur when the CIED team that usually manages the patient’s device is given the necessary details of the operative
procedure in order to create an individualized, perioperative prescription. The details are summarized in Tables 3
and 4.
Electromagnetic interference
Pacemakers and ICDs present challenges in the perioperative setting due to electromagnetic interference (EMI),
which is external interference with pacemaker or ICD function. Although there are several potential sources of
electromagnetic interference, the major source is monopolar electrocautery, particularly if the source of EMI is
within 6 inches (15 cm) of the generator. Bipolar electrocautery is usually not a concern, as the electrical current is
limited to the two poles at the end of the stylus. Monopolar electrocautery is the most frequently used type of
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electrocautery, as it has both cutting as well as coagulation capabilities. Modern CIEDs have evolved to produce
better shielding from EMI. The importance of EMI is not the potential to induce a “reset’ mode, but rather the
potential to induce oversentsing in the CIED. Oversensing in a pacemaker means the pacemaker “sees” the EMI as
intrinsic cardioelectrical activity and therefore, does not initiate a paced rhythm. Such failure to initiate a paced
rhythm can
negatively affect hemodynamics in a pacemaker-dependent patient. If oversensing occurs in an ICD, EMI may be
misinterpreted by the ICD as a malignant tachyarrhythmia, which may cause the patient to receive an inappropriate
shock.
In contrast to the ASA Practice Advisory2, the HRS/ASA Consensus Statement suggests that due to the unlikelihood
of EMI when surgery is below the umbilicus, the patient should proceed to surgery with no magnet application to
the device or reprogramming. However, there should be a magnet available with the magnet function of the device
known in case of a change in surgical plan or unexpected EMI. Alternatively, a magnet can be applied if
perioperative physicians feel more comfortable with that approach, provided the perioperative team is aware of the
magnet function for that particular device.
Magnets
Interestingly, magnets were never developed for perioperative use, although they are now widely considered for
shielding of EMI or treatment of CIED emergencies. Magnets were initially used to determine battery life in
CIEDs. However, both magnet application and reprogramming are options for eliminating EMI. The choice of
reprogramming versus magnet application largely depends on the type of surgery, patient position, accessibility of
programmer, and knowledge of magnet function of a particular patient’s device. It should be emphasized that
magnet application to an ICD generally inhibits tachyarrhythmia therapy (shocks), but does not change the mode of
the underlying pacemaker. Therefore, a magnet placed over an ICD will not induce asynchronous mode in the
underlying pacemaker. For patients with an ICD who are pacemaker-dependent, reprogramming is the preferred
option if EMI is a significant concern.
For a few ICDs, notably the PRIZM series (Boston Scientific – Guidant), the magnet mode can be changed to induce
suspension of tachyarrhythmia therapy only after the magnet is applied for 30 seconds. Tachytherapy will be
reactivated when the magnet is reapplied for 30 seconds. For any device, the magnet response should be confirmed
with the CIED team prior to magnet application. While most pacemakers will convert to asynchronous mode when
a magnet is applied to the generator, some devices have a programmable magnet function that can prevent
conversion to asynchronous mode when a magnet is placed over the generator. For this reason, it
is important to consult with the patient’s CIED team to determine a particular device’s magnet response.
Electrical reset
One of the most misunderstood issues is the concept of electrical reset. In the perioperative setting, this is thought to
very rarely occur when an energy surge directly contacts the pulse generator, resulting in a major hardware/software
failure. The reset mode is unique to each manufacturer and serves as a safety backup in the case of catastrophic
failure. The most common cause of electrical reset is therapeutic radiation, not electrocautery or external
cardioversion/defibrillation. Neither magnet application nor reprogramming will prevent electrical reset. The best
prevention of electrical reset is to direct energy away from the pulse generator (>15 cm) and to place the dispersive
electrode (“Bovie pad”) to prevent current flow across the generator.
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Emergency protocol
Patients with CIEDs may present for urgent/emergent surgery, leaving little to no time for device interrogation or
CIED team consultation. In such instances, identification of the device is important. If the patient does not know
the type of device (pacemaker, ICD, Biventricular pacemaker, Biventricular ICD, etc.), then chest radiography can
be used to help identify the device.
An electrocardiogram or rhythm strip should be examined for pacing spikes. If pacing spikes are noted before most
or all of either p-wave or qrs complexes, then the patient should be treated as if pacemaker dependent. All
pacemaker-dependent patients and patients with ICDs should have transcutaneous pacing and defibrillator pads
placed during emergency cases. A magnet should always be available and its use is recommended in the
pacemaker-dependent patient as well as the patient with an ICD. Regardless of the type of device, interrogation of
the CIED under the direction of a physician knowledgeable in the function of devices should occur as soon as
possible. The emergency protocol is described in the HRS/ASA Expert Consensus Statement.
Table 1: NASPE/BPEG Generic Pacemaker Code
I II III IV V
Response to
Chamber Sensed Chamber Paced Rate Responsive Multisite Pacing
Sensing
O = None O = None O = None O = None O = None
A = Atrium A = Atrium T = Triggered R= Rate Modulation A = Atrium
V = Ventricle V = Ventricle I = Inhibited V = Ventricle
D = Dual (A+V) D = Dual (A+V) D = Dual (T+I) D = Dual (A+V)
S = Single (A or V) S = Single (A or V)
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Table 2: NASPE/BPEG Generic Defibrillator Code
I II III IV
Antitachycardia Pacing Tachycardia Antibradycardia
Shock Chamber
Chamber Detection Pacing Chamber
O = None O = None E = Electrogram O = None
A = Atrium A = Atrium H = Hemodynamic A = Atrium
V = Ventricle V = Ventricle V = Ventricle
D = Dual (A+V) D = Dual (A+V) D = Dual (A+V)
Table 3: Essential information to be given to the CIED team by the perioperative team
1) Type of procedure
2) Anatomic location of procedure
3) Patient position during procedure
4) If and where monopolar electrocautery will be used
5) Any other sources of EMI
6) Any planned cardioversion or defibrillation
7) Surgical venue (operating room, office-based procedure, etc.)
8) Postprocedural plan (hospital admission, discharge within 12 hours, etc.)
9) Unusual circumstances (surgery encroaching upon device leads or generator, etc.)
Table 4: Essential elements to be communicated to the perioperative team by the CIED team
1) Date of last device interrogation -- recommend within 6 months for ICD or cardiac resynchronization
therapy (CRT) device, 12 months for pacemaker
2) Device type, manufacturer, and model
3) Indication for device placement
4) Battery longevity
5) Any leads placed within the last 3 months
6) Current programming
7) Is the patient pacemaker-dependent?
8) Device response to magnet placement
9) Any alert status on device? (such as manufacturing issues)
10) Last pacing threshold
11) Individualized perioperative recommendation/prescription based on patient information, device
characteristics, and surgical factors
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References
1. Crossley GH, Poole JE, Rozner MA, et al. The Heart Rhythm Society (HRS)/American Society of
Anesthesiologists (ASA) Expert Consensus Statement on the perioperative management of patients with implantable
defibrillators, pacemakers and arrhythmia monitors: facilities and patient management this document was developed
as a joint project with the American Society of Anesthesiologists (ASA), and in collaboration with the American
Heart Association (AHA), and the Society of Thoracic Surgeons (STS). Heart Rhythm 2011;8:1114-54.
2. Practice advisory for the perioperative management of patients with cardiac implantable electronic devices:
pacemakers and implantable cardioverter-defibrillators: an updated report by the american society of
anesthesiologists task force on perioperative management of patients with cardiac implantable electronic devices.
DISCLOSURE
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Perioperative Care of the Adult with Congenital Heart Disease

Francis X. McGowan, Jr., M.D. Charleston, South Carolina
The population of children and adults who have undergone successful palliation of various forms of congenital heart
disease (CHD) continues to increase and live longer. Factors contributing to this success include expanded surgical
and catheterization-based option, early, more definitive surgery and other interventional techniques, and improved
surgical, interventional, catheterization, electrophysiological, and intensive care management. The estimates are
based upon certain assumptions, but currently indicate that there are at least 1.5 million adults (>16 years) living
with various forms of CHD (ACHD) in the U.S.; of these, >100,000 have complex forms (defined as lesions other
than repaired secundum or sinus venosus ASD without residuae [e.g no pulmonary hypertension or dysrhythmias],
Current birth, incidence, and survival rates predict an annual increase in the CHD population of between 10,000 to
30,000 patients/year, and include a doubling in the survival of patients with complex physiology. Data from at large
ACHD centers (Mayo Clinic, Toronto, and London) show that as many as 50% of these patients with complex
physiology are 40 years of age or older, and that overall ~60-70% can be categorized as medium or high risk
(significant risk for premature death, reoperation, ventricular dysfunction, severe dysrhythmias, and complications).
These data have led to far-reaching and in some quarters what are controversial recommendations about who and
where should provide care for ACHD patients (1). In summary, these recommendations include: 1)complex ACHD
patients should be followed in, and have all of their care coordinated by, regional/supraregional centers that have
multi-disciplinary ACHD programs and staff; such centers would be expected to serve ~5-10 million in population;
2)every adult cardiology/cardiac surgery program and medical cardiologist should affiliate with a specialized,
dedicated ACHD program; 3)every pediatric cardiology program should identify a specialized, dedicated ACHD
program for the transition of their patients; 4)patients with moderate or severe ACHD should be transferred to a
dedicated ACHD program for urgent or acute care, most cardiac catheterization and electrophysiology procedures,
and both cardiac and non-cardiac surgery. Facilities and expertise required at the regional/supraregional level
include 1)several/group ACHD specialists; 2)pediatric cardiologists; 3)medical cardiologists and internists;
4)congenital cardiac surgeon(s) [each with > 100 cases/year]; 5)cardiac anesthesiologists*; 6)echocardiography,
including TEE and intraoperative TEE*; 7)diagnostic and non-coronary interventional catheterization*;
8)electrophysiology* including pacemakers, ICDs, VT/VF management, EP surgery, complex ablations for atrial
dysrhythmias and VT; 9)exercise testing; 10)cardiac, lung, heart-lung transplantation; 11)nuclear medicine, cardiac
CT*, cardiac MRI*; 12)cardiac pathology; 13)high-risk OB, genetics, rehab services, social services, database [*
these modalities must be supervised and performed by physicians with specific skills and knowledge in CHD]. Of
particular note, the guidelines for anesthesia include the presence of a dedicated cardiac anesthesia team with
expertise in the management of CHD and ACHD, performs consultative services, interacts at all levels with other
members of the ACHD team, and anesthetizes patients with CHD.
Who is actually repaired? Very few types of congenital heart disease are truly “fixed”, if one defines fixed as
having a high likelihood of minimal or no significant residual problems. Lesions in this category are likely to
include PDA ligation, uncomplicated repair of secundum ASD (within the first decade), and uncomplicated repair of
isolated VSD (within the first couple of years of life). Virtually all other forms carry substantial risk of residual and
potentially progressive structural, contractile, hemodynamic, electrophysiologic, and/or end-organ abnormalities.
Key Pathophysiological Consequences Overall, the chronic presence and/or potential to develop or exacerbate
low systemic cardiac output is probably the single most important consideration in approaching the care of these
patients; this is especially true in the perioperative setting. The ways for this to occur are multiple and to some extent
lesion-specific. However, there are a number of related themes associated with various forms of congenital disease
that are likely to carry increased perioperative risk. Some prominent ones include:1) progressive contractile
dysfunction; 2) the pressure- and/or volume-loaded ventricle(s);3)pulmonary hypertension;4)end-organ dysfunction.
Note: This publication contains material copyrighted by others. Individual refresher course lectures are reprinted by ASA with
permission. Reprinting or using individual refresher course lectures contained herein is strictly prohibited without permission from the
authors/copyright holders.
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In summary, most lesions are palliated, and not completely repaired. Palliated lesions will frequently continue to
have some aspect(s) of abnormal hemodynamics and circulation, along with other consequences such as CHF,
hypoxemia, cyanosis, polycythemia, and pulmonary vascular disease. Lesions that may be classified as “successfully
palliated” or “corrected” can still have significant residual problems that can either be static or, more likely,
associated with progressive dysfunction over time. Prominent risk factors include, ventricular dysfunction, residual
shunts, residual obstructive and/or regurgitant lesions, arrhythmias, and pulmonary hypertension.
Preoperative Optimization/Effective Use of the Consultant Cardiologist I personally believe that “clearance”
from a pediatric or adult cardiologist is not a useful concept. The anesthesiologist caring for these patients for
noncardiac surgery needs to have a comprehensive understanding of the pathophysiology of the lesion, the type and
natural history of its repair, and the likely interactions of all of these with the planned procedure. He/she needs to be
able to use this knowledge to assess existing information, order and interpret new tests, and initiate and coordinate
operative and perioperative planning. Few cardiologists have sufficient understanding of what is actually involved
surgically or anesthetically and need to be gently educated in these issues in order to provide the best assessment and
advice. The cardiologist can be used to better define pathophysiologic issues specific to the particular lesion and that
particular patient, but again, the consulting anesthesiologist needs to have a pretty good idea of what questions to
ask for this to be most effective, and may also need to clearly explain the surgical and perioperative risks in order to
justify additional investigations. The cardiologist can and should be used to 1)help assess the likelihood, severity,
and complications of issues such as CHF, pulmonary overcirculation, valvar regurgitation and obstruction,
contractile dysfunction, potential dysrhythmias, in addition to the overall functional status of the patient;
2)recommend and help evaluate tests to better clarify these issues; 3)recommend medical interventions to better
optimize the patient (e.g. increased diuresis or other CHF therapies, dobutamine or milrinone “tune-up” (dilated
cardiomyopathy), anti-arrhythmic therapies, response to pulmonary vasodilators (e.g. inhaled NO), etc. We have
found the diagnostic and interventional catheterization laboratory to be particularly useful improve patient status
prior to major procedures. Key examples will be provided.
Outcomes of Common CHD Lesions and Repairs Long-term complications are less likely following anatomic
repair if the heart is structurally normal and the procedure was done in a timely fashion with a structurally and
functionally successful outcome (e.g. PDA, ASD, VSD). On the other hand, late and progressive complications are
likely if a complex procedure (e.g. baffle, conduit, outflow tract reconstruction, arterial or AV valve repair) was
required.
Aortic Coarctation Problems in these patients can include residual or recurrent stenosis at the coarct site, which
can frequently be addressed by balloon dilation in the catheterization laboratory. Persistent systemic hypertension
(independent of any residual obstruction and at times difficult to manage) and LV hypertrophy can be found in
approx. 25-35% of repaired coarct patients. The incidence is higher in patients repaired later in childhood. An
increased risk of sudden death may also present in this subset of patients.
Atrial Septal Defects: As noted previously, most successful ASD repairs carry little risk of late complications.
However, there is a modest but increasing risk of the development of pulmonary hypertension, beginning around the
second or third decade of life, if the defect is closed late. Persistent atrial arrhythmias (flutter and fibrillation) are
also more likely if closure is delayed until after 10-12 years of age.
Ventricular Septal Defects: If the VSD is repaired early (first few months to year or two of life), myocardial and
pulmonary function are likely to be normal subsequently, assuming that there are no residual VSDs of significance
(Qp/Qs < 1.5), and no outflow obstruction, subaortic membrane formation, or heart block. However, in a small
number of patients, LV dysfunction and/or pulmonary hypertension may be late problems. These are more likely
following repair of a large defect, especially if closure was delayed to later in childhood.
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Atrioventricular Canal Defects: These patients have large left-to-right shunts, excessive pulmonary blood flow,
and hence CHF and are at risk for pulmonary hypertension. The repair of the most frequent types involves dividing
the common AV valve and closing the ASD and VSD with either one or two patches. Frequently, the mitral valve
(and sometimes the tricuspid valve) require additional approximation and suspension of the divided valve apparatus.
The most common problems after AV canal repair include valvar regurgitation (especially mitral), residual VSD,
and occasionally pulmonary hypertension; the last is more likely Down syndrome patients.
Tetralogy of Fallot: TOF is perhaps the classic example of a lesion that is “fixed but not cured”. The majority of
problems relate to abnormal RV loading (both pressure and volume) and to problems associated with RV outflow
tract (RVOT) reconstruction. Many of these issues are shared by other lesions that require RVOT reconstruction or
the placement of an RV-PA conduit (that can subsequently develop obstruction), such as truncus arteriosus,
pulmonary atresia, and the Rastelli procedure for transposition of the great arteries with pulmonary stenosis.
Progressive RV dysfunction, along with the development of ventricular arrhythmias and increased risk of sudden
death, are the major problems following TOF repair. Factors that have been associated with these problems and
reduced long-term survival include older age (>4 years) at repair, initial palliative shunting procedures (especially
central shunts), and significant residual RV hypertension (RV:LV pressure ratio >0.5-0.75; often due to residual
RVOT obstruction or distal PA stenoses) and/or volume loading of the RV (e.g. PR following attempted relief of
RVOTO with a transannular patch). Overall, recent long-term outcome data indicate that both pressure and volume
loading of the RV are poorly tolerated over time. Progressive systolic RV dysfunction can occur as a maladaptation
to chronic pressure overload alone, although it is more likely to occur when combined with volume load due to
pulmonary regurgitation. RV dysfunction is a predictor of late morbidity and mortality. It may be manifest as
clinically decreased exercise tolerance and signs of right-sided congestion, or may only be detected by exercise
testing (decreased maximal aerobic capacity and endurance),or stress echocardiographic or radionuclide techniques
(revealing decreased RVEF). Cardiac MRI has become particularly useful to quantify RV systolic function, RV
volume, the degree of PR (not readily quantified by any other technique), and image potential sites of RVOT
obstruction. The development of significant TR in these patients should trigger concern for the presence of
substantial RV dysfunction. The incidence of ventricular arrhythmias on ambulatory Holter or exercise testing is
significant and increases with age; however, the exact prognostic significance is not known (these findings have not
predicted sudden death in most series, although they almost certainly are linked to RV dysfunction). The ability to
induce VT during programmed electrophysiologic stimulation, particularly in a symptomatic (palpitations, syncope)
patient, is believed at the present time to be significant and an indication for ablation, antiarrhythmic agents, or an
implantable cardioversion/defibrillator (ICD). As with all of these situations, it is difficult to accurately predict
patients who will respond poorly to anesthesia and surgery. There is very little objective information or study of this
problem. It is therefore impossible to prescribe an algorithm or recipe for every patient. However, some concepts
and approaches would seem to be valid in these patients. First, defining their risk factors for and their degree of RV
dysfunction, as outlined above, is essential. Consideration should be given to interventional catheterization for
significant lesions that appear to be amenable to improvement (e.g. RVOT or PA obstruction, residual VSD,
collaterals causing LV volume loading, ventricular arrhythmias). The potential for positive pressure ventilation
(which mechanically increases RV afterload and decreases RV filling by increasing intrathoracic pressure) to
decrease cardiac output in patients with significant PR and RV dysfunction should be recognized, as should the
ability of the acutely dysfunctional RV to compromise systemic cardiac output (via decreased RV output, as well as
via ventricular interdependence causing decreased LV filling and function). Thus, initial considerations are directed
at optimizing and maintaining RV function. Factors that increase PVR should be avoided, especially in the setting of
free PR and RV dilation. RV filling should be maintained, understanding that excessive volume loading may also be
poorly tolerated. Drugs that significantly diminish RV contractility should be avoided if contractile dysfunction is a
prominent feature. Factors that are detrimental to RV myocardial supply:demand relationship need to be optimized;
this is true of all types, but may need to be specifically pointed out in the patients with restrictive physiology, as
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their stiff, non-compliant RVs may be particularly susceptible to reductions in subendocardial oxygen delivery.
From a practical standpoint, this means maintaining contractility and filling volumes (while attempting to avoid
overdistention), keeping heart rate approximately normal, and maintaining RV oxygen delivery by maintaining
blood pressure and oxygen carrying capacity (e.g. the combination of tachycardia, hypotension, acidosis, and anemia
is particularly detrimental). Based upon the severity of preexisting dysfunction and the magnitude of the planned
procedure, one should have a low threshold for invasive monitoring and postoperative care in an ICU setting.
“Prophylactic” or early administration of inotropes to improve RV contractile performance should be considered.
Transposition of the Great Arteries (TGA): There are two distinct methods to correct TGA, an atrial switch
procedure (Mustard or Senning operation) or an arterial switch. In the former, a fairly complex intra-atrial baffle
redirects pulmonary venous return across the atrium to the tricuspid valve (and hence to the RV and the aorta);
another section of the atrial baffle carries systemic venous return across to the mitral valve (and hence to the LV and
out the PA). Again, this is a prime example of a physiologic repair, where the circulation is established in series and
cyanosis is removed; however, the RV and tricuspid valve are left in series with the aorta for life, and thus must
work at systemic pressure and against systemic levels of afterload. The arterial level switch operation was pursued
and perfected in large part due to the long-term and late complications of atrial baffle procedures (see below). In the
arterial switch, which is usually performed in the neonatal period, the great arteries are divided distal to their
respective valves and reattached to the opposite, anatomically correct ventricle; in addition, the coronaries must be
excised and reimplanted into the proximal neoaorta (formerly the pulmonary root). Functional Outcome of the
Atrial Switch: these patients have their RV as the systemic ventricle in a 2-ventricle physiologic repair. Many of
these patients will self-report a reasonable functional status and are able to lead fairly normal lives into their 3rd and
4th decade; the 15-20 year survival approaches 80-85%. However, the long-term prognosis for cardiac function is
not good, and progressive deterioration of RV function, development of TR (here functioning as the systemic AV
valve), and signs and symptoms of right heart failure, arrhythmias, and sudden death are likely. In patients both with
and without significant functional complaints, exercise testing demonstrates moderate to severe limitations in RV
function and exercise response and hence abnormal exercise and aerobic capacity and peak heart rate and blood
pressure responses in anywhere from 50-75% of adult patients. In addition to ventricular arrhythmias, these patients
are likely (50-60 percent have non-sinus rhythm by 10-20 years after the repair) to develop significant atrial
tachyarrhythmias as well as sick sinus syndrome as they age; these may be preceded by the development of RV
dysfunction or initially occur as an independent finding (presumable due to the extensive atrial suture lines and atrial
distention). Subendocardial ischemia is being seen with increasing frequency in many of these patients. Pacemaker
insertion may be indicated for sick sinus syndrome and as an adjunct to aggressive antiarrhythmic drug therapy.
Radiofrequency ablation is may be useful, although the success rate is less than with many other lesions (e.g. WPW)
as the anatomy and mechanisms of these arrhythmias are often complex and multiple. Problems with the atrial baffle
can be present or develop. Baffle leaks can result in intra-atrial shunting and hypoxemia. Baffle obstruction of the
systemic venous return can cause superior vena cava syndrome, hepatic congestion, ascites, and peripheral edema.
Protein-losing enteropathy (PLE) can occur occasionally in these patients. PLE is defined as an albumin < 3 mg/dL
in the absence of liver or renal disease; other features include ascites, peripheral edema, abdominal pain, diarrhea,
and lymphopenia. Hemodynamic features in many PLE patients include decreased RV function, decreased cardiac
index, and increased systemic venous pressure (although intuitively attractive, it is not clearly always related to the
degree of systemic venous hypertension). Obstruction of the pulmonary venous side of the baffle can result in
pulmonary edema (if severe) or the development of pulmonary hypertension. End-organ dysfunction appears to be
more likely due to chronic low output, and the other issues. Functional Outcome of the
Arterial Switch Procedure for Transposition: In centers with extensive experience, the early hospital mortality is
now less than 3% (<1-2% in many), and actuarial analyses indicate 5-10 year survival >97-98%. It is these results
and the numerous problems and poor long-term outcome with the atrial switch operations described previously that
have made the arterial switch operation the preferred procedure. Longer-term follow-up is just beginning to accrue,
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but intermediate results (teenagers) suggest that complications after the arterial switch is are, unfortunately, possible.
There is a modest incidence of supravalvar pulmonary arterial and aortic stenoses at the anastomotic sites; these are
less common in the current era due to improved surgical techniques, and can frequently be addressed by balloon
dilatation. However, at least 2 longer-term complications will bear watching as this group of patients ages:
1)neoartic valve (the anatomic pulmonary valve) regurgitation, and 2)coronary ostial lesions. At present, a 25-30%
incidence of neoartic valve regurgitation, usually trivial to mild, has been reported; the development so far of severe
regurgitation has been limited. On the other hand, experience with the Ross procedure (which autografts the
pulmonary root into the aortic position) might suggest that progressive incompetency of the pulmonary valve in the
aortic position could be a problem over the long haul. The significance of the coronary ostial lesions, occurring in 3-
10% of patients based upon coronary angiographic findings, is also unclear at present. There has been no evidence
of infarction, and Holter, exercise testing, and echocardiography rarely show evidence of myocardial ischemia.
However, it is possible that the coronary reimplantation establishes abnormal regional flow patterns or other
responses that promote the development of ostial stenosis; for now, I believe that one should have an increased
index of suspicion for the possibility of coronary stenosis and potential for myocardial ischemia, especially as these
patients age.
Anesthesia and Fontan Physiology: The Fontan operation (in all of its iterations) passively routes systemic venous
return to the pulmonary arteries. Pulmonary blood flow and cardiac output are thus largely the result of the pressure
differential between systemic venous return and the pulmonary artery (the “upstream” driving pressure) and the
“downstream” pulmonary venous atrium/systemic ventricle (kinetic energy in the return of vensou blood is the other
major “driving force” for pulmonary blood flow and hence ventricular filling. In the “ideal” Fontan circulation, the
systemic venous or baffle pressure is approx. 10-15 mm Hg, and the pulmonary venous atrial (the functional left
atrium) pressure is approximately 5-10 mm Hg; this leads to a transpulmonary gradient, or TPG, driving pressure of
5-8 mm Hg. At the most upstream point, optimal Fontan physiology depends upon unobstructed systemic venous
return, adequate preload, patent anastomotic connections, and low intrathoracic pressure. At the level of the lungs
and pulmonary circulation, it requires low mean pulmonary artery pressure (<15-20 mm Hg), low PVR (ideally <2
Wood units), unobstructed pulmonary arteries, normal lung parenchyma and alveolar ventilation, and minimal or no
pulmonary vascular disease or pulmonary venous obstruction. At the level of the systemic ventricle, good Fontan
function depends upon sinus rhythm (primarily to maintain ventricular function and cardiac output), a competent
AV valve, normal systolic and diastolic function, and no outflow obstruction. Any significant departure from these
requirements can result in severe compromise. For example, ventricular dysfunction leading to an EDP of 15 mm
Hg mandates a venous pressure of 20-25 mm Hg to achieve comparable pulmonary blood flow, ventricular filling,
and cardiac output. Alternatively, an infectious pneumonitis that increases PVR will acutely decrease cardiac output
(due to decreased filling of the ventricle) and subsequently require a significantly increase in the TPG to restore
ventricular filling and cardiac output toward normal. The use of mechanical ventilation in Fontan patients derives
from similar considerations. There is little doubt that the majority of pulmonary blood flow in spontaneously
ventilating Fontan patients occurs during inspiration, and that it (and cardiac output) can be further augmented
during negative pressure (iron lung) ventilation; in contrast, one can demonstrate either no flow or even a reversal of
flow in the pulmonary arteries of Fontan patients during the administration of a positive pressure breath. Positive
pressure ventilation at relatively high lung volumes can directly increase PA pressures via transmission of increased
intrathoracic pressure, and also by airway and alveolar distention (which compress adjacent blood vessels);
excessive lung stretch may also induce a myogenic contractile response in pulmonary arterioles. On the other hand,
hypoventilation (as might be expected to occur during anesthesia and also due to procedures associated with
abdominal or thoracic compression) increases PVR via alveolar hypoxia, hypercarbia, and atelectasis; surgical stress
responses may also increase PVR. The effects of positive pressure ventilation to decrease afterload on the systemic
ventricle (via the Law of LaPlace) and thereby improve cardiac output, particularly of the dysfunctional ventricle,
also need to be kept in mind. Therefore, for most surgical situations, I believe that the sum of these considerations
favors judicious use of positive pressure ventilation in order to provide an effective anesthetic while maintaining
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lung volumes and normal gas exchange. Although most patients report normal functional status with moderate
exercise tolerance, this is not born out by more objective measures. Systemic ventricular dysfunction, perhaps more
likely with a systemic right ventricle (e.g. HLHS), is not uncommon. With longer term follow-up, progressive
decline in NYHA class, as well as decreased exercise tolerance, endurance, maximal aerobic capacity, heart rate
response, and delayed recovery from peak exercise have all been described; overall as a group, their exercise reserve
capacity is 50% or less that of age- matched control subjects. This inability to significantly increase pulmonary
blood flow and cardiac output in response to exercise stress is due to several factors, including limited ventricular
function reserve, inability to increase heart rate (sinus node dysfunction and other conduction abnormalities), and the
inability to achieve preload augmentation; the last of these would appear to be the result of Fontan patients having
high resting venous (and arterial) tone. Fontan patients are thus very dependent upon the status of the pulmonary
vascular bed for ventricular filling; the limited contractile and preload reserves increase dependency upon heart rate
to increase cardiac output. The implications of these findings for anesthesia and surgery have not been formally
evaluated but are probably significant in light of the potential for anesthesia and surgery to be associated with
increased PVR (hypoxia, hypercarbia, acidosis, stress hormones), myocardial depression (e.g. inhaled anesthetics),
vasodilation (causing a critical decrease in preload), and hypovolemia (blood loss, etc.).There are other important
complications and limitations in these patients. PLE (see above) may occur in 3-15% of Fontan patients. There is an
increased incidence of thromboembolism, with reports of up to 20-30% having one or more such events during the
course of their life, and a stroke rate of 2-3%. Numerous abnormalities of pro- and anti coagulant factors have been
measured, including increased factor VIII and decreased protein C and S; however, these are often accompanied by
reduced levels of pro-coagulant factors, and it is unclear whether the measured abnormalities have any causal
relationship to the observed incidence of thromboembolism. Other risk factors in these patients include increased
venous pressure and stasis of flow in the right atrium or through the right atrial baffle, atrial dysrhythmias, and
perhaps increased resting venous tone. The routine use of long-term anticoagulation and specifically which drug(s)
remain controversial. Perioperatively, bleeding may be more significant in Fontan patients due to the presence of
collaterals and high venous pressures, in addition to any deficiencies in procoagulant factors. Arrhythmias such as
atrial flutter, sick sinus syndrome, sinus bradycardia, and heart block occur in more than 20% of Fontan patients by
10 years after surgery. By 15-20 years, especially with older versions of the operation (extensive atrial suture lines,
damaged SA node artery, chronic atrial hypertension) and in patients who were older at the time of Fontan
operation, the probability of being free from atrial arrhythmias is less than 40-50%. Recent data on the lateral tunnel
version of the operation suggests that the incidence of atrial flutter, other tachyarrhythmias, as well as severe
ventricular dysfunction, is substantially lower; interestingly, the incidence of sinus bradycardia and sick sinus
syndrome was till around 10-15%; it of course remains to be seen whether the outcome will worsen with longer
follow-up. The preoperative assessment and planning for Fontan patients follows directly from the above
considerations. In addition to standard non-invasive tests, echocardiography is useful to assess ventricular function
and Fontan pathway patency; cardiac catheterization may be indicated in patients with poor or deterioration in
function, and radiofrequency ablation should be considered prior to major elective surgery in appropriate patients.
Invasive monitoring should be considered based upon the individual patient and the planned procedure. Central
venous cannulation facilitates monitoring of venous filling and pulmonary artery pressure, as well as mixed venous
oxygen saturation. One must, however, be aware of the risk of thrombosis and serious impairment to venous return.
In operations with the potential for major fluid shifts and/or cardiopulmonary embarrassment (e.g. spinal fusion), we
have found it helpful to place a balloon tipped pulmonary artery catheter, particularly because it can be wedged and
thus the transpulmonary gradient measured directly. Placement is best done in the catheterization laboratory under
fluoroscopic guidance (and with the availability of special guide wires) due to the abnormal anatomy and absence of
pulsatile waveforms. Here again, no specific anesthetic regimen can be recommended. General principles include
maintenance of adequate preload, ensuring normal gas exchange while minimizing mechanical effects upon PVR
and PBF, limiting significant increases in the stress response, preserving sinus rhythm and ventricular filling and
contractility, and avoiding large increases in afterload. As might be inferred, appropriate afterload reduction (as long
as myocardial perfusion is maintained) is usually well-tolerated and perhaps even beneficial to this circulation.
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Support of ventricular function, perhaps preferably with an inodilator such as milrinone, or otherwise with
dopamine, should be considered in patients with evidence of ventricular dysfunction and/or in whom the surgery and
its consequences are extensive. As mentioned previously, end-organ dysfunction can be a major postoperative
complication in older Fontan patients. Contributing factors presumable include chronic low organ perfusion due to
limited cardiac output and high venous pressures, with superimposed acute deterioration due to anesthetics, blood
loss, etc. The liver and kidneys seem particularly susceptible. This problem is a further reason to make all attempts
to optimize Fontan pathway flow and myocardial performance; agents such as fenoldopam, which even at very low
doses increase mesenteric and renal blood flow, are theoretically attractive. Because of the apparent increased risk of
DVT or thrombus formation in the baffle or atrial appendage, consideration should be given after surgery to the use
of subcutaneous heparin or low molecular weight heparin, along with adequate hydration and early mobilization.
Facilities for pacing (external, esophageal, and overdrive for tachyarrhythmias), and external cardioversion should
be immediately available in the operating room.
Selected Bibliography
1. J Am Coll Cardiol 2001;37:1166-1198 (series of 5 articles from expert panels on various aspects of care of adults
with congenital heartdisease)
2. Studer et al. Determinants of early and late results of repair of atrioventricular septal defects. J Thorac Cardiovasc
Surg 1982;84:523.
3. Rizzoli et al. Does Down syndrome affect prognosis of surgically managed atrioventricular canal defects? J
Thorac Cardiovasc Surg 1992;104:945.
4. Murphy et al. Long-term outcome in patients undergoing repair of tetralogyof Fallot. N Engl J Med
1993;329:593.
5. Nollert et al. Long term survival in patients with repair of tetralogy of Fallot. J Am Coll Cardiol 1997;30:1374
6. Pigula F et al. Repair of tetralogy of Fallot in neonates and young infants. Circulation 1999;100:57.
7. Gatzoulis et al. Risk factors for arrhythmia after and sudden cardiac death late after repair of tetralogy of allot: a
multicentre study. Lancet 2000;356:975.
8. Bove, et al. The influence of pulmonary insufficiency on ventricular function following repair of tetralogy of
Fallot. J Thorac Cardiovasc Surg 1983;85:691.
9. Merlo et al. Long-term results after atrial correction of complete transposition of the great arteries. Ann Thorac
Surg 1991;51:227.
10. Helbing et al. Long-term results of atrial correction for transposition of the great arteries: comparison of Mustard
and Senning operations. J Thorac Cardiovasc Surg 1994;108:363.
11. Deanfield et al. Arrhythmia and late mortality after Mustard and Senning operation for transposition. J Thorac
Cardiovasc Surg 1988;96:569.
12. Yacoub MH. The case for anatomic correction of transposition of the great arteries. J Thorac Cardiovasc Surg
1979;78:3.
13. Jenkins et al. Function of the anatomic pulmonary valve in the systemic circulation. Circulation 1991;84:173. 14.
Tanel et al. Coronary artery abnormalities detected at cardiac catheterization following the arterial switch operation
for transposition of the great arteries. Am J Cardiol 1995;76:153.
15. Formigari et al. Prevalance and predictors of neoaortic regurgitation after arterial switch operation for
transposition of the great arteries. J Thorac Cardiovasc Surg 2003;126:1753.
16. Williams WG et al. Outcomes of 829 neonates with complete transposition of the great arteries 12-17 years after
repair. Eur JCardiothorac Surg 2003;24:1.
17. Hovels-Gurich et al. Long-term results of cardiac and general health status in children after neonatal arterial
switch operation. Ann Thorac Surg 2003;75:935.
18. Stamm et al. Long-term results of the lateral tunnel Fontan operation. J Thorac Cardiovasc Surg 2001;121:28 19.
Driscoll et al. Five- to fifteen year follow-up after Fontan operation. Circulation 1992;85:468.
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20. Gentles et al. Fontan operation in five hundred consecutive patients: factors influencing early and late outcome. J
Thorac Cardiovasc Surg 1997;114:376.
21. Penny et al. Doppler echocardiographic evaluation of pulmonary blood flow after Fontan operation: the role of
the lungs. Br Heart J 1991;66:372.
22. Harrison et al. Cardiopulmonary function in adults late after Fontan repair. J Am Coll Cardiol 1995;26:1016. 23.
Fishberger et al. Factors that influence the development of atrial flutter after the Fontan operation. J Thorac
Cardiovasc Surg 1997;113:80.
24. Gewillig et al. Exercise responses in patients with congenital heart disease after Fontan repair: patterns and
determinants of performance. J Am Coll Cardiol 1990;15:1424.
25. Shachar et al. Rest and exercise hemodynamic results after Fontan operation for tricuspid atresia. Circulation
1982;65:1043
26. DuPlessis et al. Cerebrovascular accidents following the Fontan procedure. Pediatr Neurol 1995;12:230.
27. Odegard et al. Procoagulant and anticoagulant factor abnormalities following the Fontan procedure: increased
factor VIII may predispose to thrombosis. J Thorac Cardiovasc Surg 2003;125:1260.
28. Kussman BD and McGowan FX. Anesthesia for Congenital Cardiac Surgery, In Davis PJ, Motoyama EK,
Claddis FK (eds): Smith’s Textbook of Pediatric Anesthesia 2010.
DISCLOSURE
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Introducing Blood Conservation Into Clinical Practice:

Can the New Guidelines Lead Us?
Colleen G. Koch, M.D., MS, MBA Cleveland, Ohio
Objectives
• Understand the role practice guidelines in the clinical practice setting.
• Become aware of the issues and controversies involved with adoption and implementation of practice
guidelines.
• Recognize that guidelines represent one component to comprehensive blood conservation and blood
management programs.
• Become aware of components to effective blood conservation and blood management through examples of
an institutional blood management program whose outcomes involve more effective use of blood and
product management.
Practice guidelines serve to aide physicians in making patient care decisions and in particular, in the setting of
considerable practice variation, serve as useful tools to more effectively manage and guide patient care. Guidelines
are meant to provide the ‘best evidence’ for decision-making from currently available research with the ultimate
goal of providing a more methodological approach to evidence-based patient care along with the most efficient use
of healthcare resources. Whether practice guidelines in general, and more specifically the current: ‘Perioperative
blood transfusion and blood conservation in cardiac surgery: the Society of Thoracic Surgeons (STS) and the
Society of Cardiovascular A nesthesiologists (SCA ) clinical practice guidelines’ have been widely accepted and
implemented into clinical practice by caregivers is under debate. While development of practice guidelines follows
formal well-described procedures, the actual adoption and implementation is reportedly variable in a number of
practice settings. A recent investigation reported on the effect of the perioperative blood transfusion and blood
conservation in cardiac surgery clinical practice guidelines by the STS and SCA on clinical practice. Among the
groups surveyed were members of the SCA, the American Academy of Cardiovascular Perfusion, Canadian Society
of Clinical Perfusion and the American Society of Extracorporeal Technology. The authors used a standardized
survey instrument to evaluate the change to clinical practice based on the available STS/SCA guidelines. Responses
were received from 891 institutions; 78% of anesthesiologists and 67% of perfusionists who responded reported
reading the all/ part of the guideline document however overall little change to clinical practices was attributed to
the guidelines. Of note, among reasons put forth for poor adoption of the clinical practice guidelines were that the
number of recommendations were based on limited/very limited scientific evidence. It is the lack of evidence on
when and who to transfuse RBC that limits adoption of guidelines that are based on ‘expert opinion’ rather than
results of randomized controlled trials.
Blood and component therapy are limited and costly resources and have been associated with an increased morbidity
risk following surgical and interventional procedures and in the intensive care unit settings. A recent investigation
reported considerable variation on a national level with red blood cell (RBC) use from a large national surgical
database. Despite similar surgical procedures and patient population comorbidity, there was wide variability in RBC
and component product use-- despite the availability of the STS/SCA updated guidelines. This investigation and
other investigations on RBC transfusion and patient outcomes highlight a number of issues: 1). We continue to be
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challenged in our ability to identify specific patients who will and will not benefit from RBC transfusion, 2). There
is continued lack of sufficient high-level evidence to form the foundation for evidence-based guidelines on
transfusion thresholds and 3). Insufficient availability of bedside technology to determine tissue oxygenation to
access need for RBC transfusion.
Blood management programs serve as multidisciplinary programs with the aim of appropriately allocating blood
products, ensuring safety and providing value to the patient and institution. Guidelines may be a component to blood
management however only in so much as they provide sound evidence for evidence-based practice decisions. Local
educational initiatives, physician and nursing engagement and accountability, culture change and process
improvements are all important components to a successful blood management program. Blood management
performance outcome measures may soon be part of formal measurement tools to gauge success of blood
management programs.
References
1. Ferraris V et al. Perioperative blood transfusion and blood conservation in cardiac surgery: the Society of
Thoracic Surgeons and the Society of Cardiovascular Anesthesiologists clinical practice guidelines. Ann Thorac
Surg 2007;83:S27-86.
2. Woolf S et al. Clinical guidelines: potential benefits, limitations and harms of clinical guidelines. BMJ
1999;318:527-30.
3. Grol R et al. Attributes of clinical guidelines that influence use of guidelines in general practice: observational
study. BMJ 1998:317:858-61.
4. Grilli R et al. Evaluating the message: the relationship between compliance rate and the subject of a practice
guideline. Med Care 1994;32:202-213.
4. Timmermans S. From autonomy to accountability: the role of clinical practice guidelines in professional power.
Perspect Biol Med 2005;48:490-501.
5. Likosky D et al. Effect of perioperative blood transfusion and blood conservation in cardiac surgery clinical
practice guidelines of the Society of Thoracic Surgeons and the Society of Cardiovascular Anesthesiologists upon
clinical practice. Anesth Analg 2010;111:316-23.
6. Koch CG, et al. Morbidity and mortality risk associated with red blood cell and blood-component transfusion in
isolated coronary artery bypass grafting. Critical Care Medicine 2006;34:1608-1616.
7. Koch CG, et al. Persistent effect of red cell transfusion on health-related quality of life after cardiac surgery.
Annals of Thoracic Surgery 2006;82:13-20.
8. Murphy G, et al. Increased mortality, postoperative morbidity and cost after red blood cell transfusion in patients
having cardiac surgery. Circulation 2007;116:2544-2552.
9. Koch CG, et al. Duration of red-cell storage and complications after cardiac surgery. New England Journal of
Medicine. 2008;358:15-25.
10. Koch C, Li L, Figueroa P, Mihaljevic T, Svensson L, Blackstone EH. Role of Transfusion in Lung Injury and
Pulmonary Morbidity after Cardiac Surgery, Annals of Thoracic Surgery 2009;88:1410-8.
11. Koch CG, Li L, Duncan A, Mihalijvec T, Starr N, Blackstone E. Perioperative red blood cell transfusion is
associated with reduced long-term survival in isolated coronary artery bypass grafting, A nnals of Thoracic Surgery
2006;81:1650-7.
12. Vivacqua A, Koch CG, Nowicki E, Houghtaling P, Blackstone EH, Sabik J. Morbidity of Bleeding after Cardiac
Surgery: Is It Blood Transfusion, Reoperation for Bleeding or Both? Annals of Thoracic Surgery 2011;91:1780-
1790.
13. Kumar A, Figueroa P, Gowans LK, Parker B, Proctor A, Benitez Santana SM, Koch CG. An Evolution in Blood
Management: Past, Present and Future. Quality Management in Healthcare 2011;20(4):311-321.
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14. Bennett-Guerrero E, et al. Variation in use of blood transfusion in coronary artery bypass graft surgery. JAMA
2010;304:1568-1575.
DISCLOSURE
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Update on Strategies for Blood Conservation and

Hemostasis in Cardiac Surgery
C. David Mazer, M.D. Toronto, Ontario, Canada
Introduction: The management of perioperative bleeding with cardiac surgery is an important clinical challenge.
Cardiopulmonary bypass (CPB) predisposes to perioperative bleeding by causing thrombocytopenia, functional
platelet defects, activation of fibrinolysis, hemodilution and depletion of coagulation factors. As a result, up to 30%
of patients develop significant microvascular bleeding after cardiac surgery, accounting for 10 % of all red cell
transfusions. Although there is much variability in transfusion practice, the following factors have been
independently associated with increased risk of transfusion: age, anemia, female gender, body size, preoperative use
of anticoagulant and antiplatelet therapy, significant systemic disease, CPB time, and type and urgency of
procedure1-11.
Rationale for Blood Conservation: The cost and risks associated with allogeneic transfusion are significant12.
Several studies have shown that bleeding, anemia and transfusion of allogeneic blood are all important predictors of
adverse outcome13. Multi-disciplinary blood conservation programs have been shown to reduce red blood cell
transfusion and associated adverse outcomes including infection and length of hospital stay in CABG patients14.
Thus, blood conservation can reduce risks associated with transfusion. “Blood conservation” is but one part of an
overall blood management program, the goals of which are to improve patient outcomes with appropriate use of
blood products15. The focus of most blood management programs is optimization of red cell mass and avoidance or
reduction of allogeneic red blood cell transfusion, but other blood components should be considered as well. Blood
management spans the entire perioperative period, and has the goals of optimizing preoperative hemoglobin levels
and hematopoiesis, correcting underlying coagulopathy, minimizing intra- and post-operative blood loss, and
maximizing tissue oxygen delivery. All institutions can benefit, even those with below average transfusion rates.
Risks of Anemia: The physiological and clinical consequences of anemia are well documented, with several
studies demonstrating an association between decreasing hemoglobin concentration and adverse outcome.
Preoperative anemia has also been recognized as a significant risk factor for adverse outcome and mortality8,9,16,13.
More recent studies have suggested that even mild degrees of anemia are associated with increased perioperative
morbidity and mortality17,18. While preoperative anemia may identify a patient at risk, it remains to be determined
whether or not treating anemia prior to surgery with either transfusion or hemapoetic therapy improves outcome.
As the degree of anemia increases, the normal physiologic response is to increase cardiac output (CO) and
vital organ blood flow (brain, heart) and increase oxygen extraction. At some point, these compensatory
mechanisms become exhausted and a state of inadequate oxygen delivery for tissue needs is reached19. Although
some older studies have suggested that tissue hypoxia does not occur in the brain and heart until the hemoglobin
(Hb) is below 4 gm/dL, newer studies utilizing non-invasive oxygen sensing probes have demonstrated that brain
microvascular PO2 decreases progressively below Hb values of 9 g/dL20. In addition, there is clear evidence that
tissue hypoxia occurs earlier in tissues such as the kidney and liver, relative to the brain and heart21,22. Activation of
hypoxic mechanisms have been observed near a hemoglobin thresholds near 6-7 gm/dL23,24. There are limited
options for treating anemia, and transfusion of stored red blood cells (RBCs) has been the cornerstone of
management of patients with life-threatening anemia. RBC transfusions are usually administered to improve tissue
oxygen delivery but whether or not they do so depends on a variety of factors, including the conditions and length of
storage, and the clinical circumstances in which they are administered. Transfusion decisions should always be
based on an evaluation of whether the risks of transfusion outweigh the risks of anemia25,13. The balance of risk may
be influenced by physiologic, pathophysiologic and pharmacologic factors. For example, patients with neurotrauma
and acute coronary syndrome (ACS) may benefit from a higher Hb than other patients. Also, recent data have
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suggested that bleeding increases the risk of stroke and mortality in beta blocked patients, possibly due to inadequate
oxygen delivery26,27,27,21. Thus, treatment is dependent on the individual patient and clinical parameters.
Transfusion Risks: Over the last 60 years, a wide variety of bacterial, viral and parasitic agents have been spread
via blood transfusion causing hepatitis, HIV, malaria, syphilis, West Nile, and other infectious diseases28. Although
transmission of infection is widely cited as a common risk of transfusion, modern screening and testing procedures
have significantly reduced these risks to approximately 1 in 2-10 million for viral agents. Current literature suggests
that the most common transfusion related side-effects include TRALI (Transfusion Associated Lung Injury), febrile
non-hemolytic transfusion reactions and other immunologic reactions15,29. Over the last 10 years, TRALI (30%) has
eclipsed ABO Incompatibility (20%) and Transfusion Associated Sepsis as the leading cause of known and reported
allogeneic blood transfusion related death. Donor plasma from multiparous women is thought to be an important
risk factor for TRALI and it has recently been suggested that the preferential use of male donor plasma has resulted
in a significant reduction in the incidence of TRALI 30. On the other hand, Welsby et al reported that female donor
plasma recipients had a lower incidence of pulmonary dysfunction and a lower incidence of prolonged
hospitalization compared to male donor recipients 31, suggesting the potential for other mechanisms being involved.
Risks of Transfusion
Infectious Non-infectious
HIV 1:2-10 million Febrile reaction 1:1,000
Hepatitis B 1:155,000-350,000 TRALI 1:2,000-5,000
Hepatitis C 1:2-2.3 million Transfusion error 1:38,000
HTLV 1:3-4.3 million Hemolysis 1:100,000
Bacterial contamination 1:500,000 Graft vs Host Disease 1:1 million
Other (eg Yersinia, West Nile, malaria) 1:1 million Death 1:1.8-5.6 million
Sources: SHOT, NHLBI, O’Brien et al32, Vamvakas et al33
Costs of Transfusion: There are many costs associated with transfusion, including recruitment and donor
collection, infectious agent testing, manufacturing, shipping, handling, labeling, pre-transfusion testing, transfusion
costs, post-transfusion sequelae and regulatory and legal costs. The overall cost for a hospital to administer one unit
of blood to a patient may be more than 3 times the cost of its actual acquisition. An activity-based costing model in
surgical patients from 2 US and 2 European hospitals found the per-unit RBC cost to be USD$ 760.82 (+/-
$293.74)34. The total annual per hospital expenditures for blood and transfusion related activities ranged from
$1,618,780 to $6,030,589 just for surgical patients.
While the range of options for blood conservation may be similar for most hospitals, each institution should pick its
own combination of approaches to produce the best solution. It is important to remember that the options are not
mutually exclusive: each option may result in up to 1-2 units of blood saved per patient, and some options may, in
fact, be better in combination. The incremental benefit of individual strategies varies between institutions.
Similarly, although expert opinion and outside advice may be helpful, an internal and institution-specific approach
to blood management is usually best. A database or data management system is essential to provide accurate
baseline institution-specific data. An institution-specific estimate to predict risk of transfusion for different types of
procedures can be developed or previously published prediction rules can be adapted3,7,35,36.
It is extremely useful to engage the administrative leadership of the hospital in the process. In addition to the
benefits of transfusion reduction and patient outcome, other positive outcomes such as cost reduction, fewer surgical
cancellations, quality improvement, and marketing opportunities may also be attractive to the CEO, CFO, Board of
Directors and Medical/Nursing leaders. It may also be seen as a patient safety initiative with associated potential for
improvement in patient outcomes and liability reduction.
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Effect of Storage on RBCs: The shelf life of RBCs is determined by a minimum 24-hour post-transfusion
survival of 75% of the transfused red cells. Additional criteria are related to free hemoglobin (<1.0%) and white
blood cell levels (<1 million/unit in leuko-reduced blood). Storage improvement techniques have increased the
shelf-life of blood from 21 to the current 42 days. It has been estimated that 20-40% of all stored RBC units are >28
days old at the time of transfusion, and with supply fluctuations, up to 40% of blood may be within 3 days of
expiration.
RBCs undergo many complex biochemical, environmental, structural and biomechanical changes during storage37.
The shape of the red cell is transformed from a normal biconcave disc to a spiculated and crenated echinocyte, then
to a swollen sphereocyte. There is also a rapid and marked fall in 2 bioactive forms of RBC nitric oxide (Hb-bound
NO, and S-nitrosohemoglobin), as well as their effector response, RBC mediated hypoxic vasodilation37.
Prolonged storage time has been associated with increased morbidity and mortality in a wide variety of clinical
settings, including patients with trauma, sepsis, and critical illness. For cardiac surgery, length of RBC storage has
been correlated with death, renal dysfunction and ICU length of stay38,39,40. It has been estimated that each
additional day of RBC storage increases the risk of pneumonia by 1-6%. Animal studies demonstrated a reduced
ability of stored blood to deliver oxygen to the brain in a hemorrhage resuscitation model41,42,42, and another found
that both aged erythrocytes and the supernatant of aged erythrocytes activate lung coagulation and contribute to
acute lung injury43, suggesting that washing of aged blood may ameliorate some of the adverse effects. However,
Weiskopf et al. found no difference in the ability of fresh or stored blood to restore brain oxygen deficits induced by
anemia in humans, and at least 2 observational studies in cardiac surgical patients have not found an association
between duration of storage and increased morbidity44. Nonetheless, a large clinical report of the effect of RBC
storage in over 6000 cardiac surgery patients found that patients given older blood (>14 days) had significantly
worse composite and individual clinical outcomes, including renal failure, prolonged intubation, sepsis, in-hospital
and 1-year mortality45. Several ongoing clinical trials of transfusion should soon provide more information on how
important age of blood is for clinical outcome.
Guidelines: Several guideline documents contain recommendations relevant to perioperative management of

patients undergoing cardiac surgery. These include guidelines from the STS/SCA, the American Society of
Anesthesiologists, and the European Society for Cardiothoracic Surgeons3,46,47. The degree to which guidelines
influence changes in clinical practice is controversial48. A summary of the STS/SCA guidelines is provided and
select modalities are discussed in more detail below.
Selected summary of STS/SCA Guidelines for Blood Conservation and Transfusion (2007 and 2011)3,10
Indicated (I) Reasonable (IIa) Not unreasonable (IIb) Not indicated/harmful (III)
Preoperative
Preop Hct and platelet D/C aspirin in low risk D/C potent anti-platelet/anti-thrombotic Preop screening of intrinsic
count for risk prediction patients drugs (except unfractionated heparin) coagulation system
Multi-modal, multi- EPO / Iron Preop bleeding time in high-risk patients
disciplinary approach
D/C thienopyridine drugs PAD (up to 2 units)
5-7 days preop (min 3 days)
Intraoperative
Antifibrinolytics Transfusion trigger 6 gm/dl DDAVP for specific platelet dysfunction Transfusion if Hb > 10 gm/dl
Routine red cell-saving OPCAB surgery Trial of therapeutic PEEP Routine DDAVP
Minicircuits Leukoreduced donor blood Centrifugal Pumps High dose Aprotinin
Multi-modal, multi- Reduced/alternatives to Recombinant Factor VIIa for intractable Routine
disciplinary approach blood sampling non-surgical bleeding platelet/plasmapheresis
Modified ultrafiltration TQM program Open venous reservoirs Leukocyte filters
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PCC for warfarin reversal Higher heparin levels for long CPB Prophylactic Plasma
AT III for AT mediated Salvage/centrifugation/ Protamine-titration or empiric low dose Routine ultrafiltration
heparin resistance reinfusion of pump blood regimens
Minimally invasive Intraoperative Platelet Biocompatible/heparin coated circuits Topical bovine hemostatic
procedures (TEVAR) plasmapheresis agents
Platelet/plasma based on Low CPB prime or retrograde autologous Plasma for warfarin reversal
bleeding and/or POC tests priming in absence of bleeding
Topical antifibrinolytics Vacuum assisted venous drainage Dipyridamole
Topical sealants Leukocyte filters
ANH/IAD
Low volume/Microplegia
Postoperative
Multi-modal, multi- Reduced/alternatives to Post-op cell saving Direct re-infusion of shed
disciplinary approach blood sampling blood from chest tubes
TQM program Prophylactic PEEP
Transfusion if Hb > 10 gm/dl
Abbreviations: D/C=discontinue; Hct=Hematocrit; EPO=erythropoeitin; PAD=preoperative autologous donation; DDAVP=desmopressin;
POC=point of care; OPCAB=off pump CABG; TQM=total quality management; ANH=acute normovolemic hemodilution; IAD=intraoperative
autologous donation; MUF=modified ultrafiltration; PEEP=positive end expiratory pressure
Drug related causes of bleeding: Several new oral antiplatelet and anticoagulant medications have recently
been approved49. Administration of dual antiplatelet therapy with aspirin and clopidogrel or oral anticoagulants
within 5 days of cardiac surgery is associated with an increase in perio-operative bleeding. Current guidelines from
the STS/SCA and AHA/ACC recommend discontinuation of such therapy at least 5 days prior to CABG to reduce
bleeding related events3,51. However, in some individuals at high risk of thrombosis (eg recent ACS or stent) urgent
surgery may be required, with or without the opportunity to bridge to alternate therapy. For such individuals, the
risk of bleeding and transfusion can be minimized by applying multiple strategies before and during surgery52.
The optimal timing of discontinuation of new antiplatelet agents depends on the agent and the patient circumstances.
Decisions about the timing of surgery should be determined by clinical factors balancing the risk of bleeding versus
risk of thrombosis. The STS/SCA 2007 guidelines suggest that it is “reasonable to discontinue thienopyridines 5-7
days preoperatively” (Class IIa, Level B)3, and in the 2011 update this “may be as short as 3 days for irreversible
inhibitors of the P2Y12 platelet receptor” (Class I, Level B)10. The recent AHA/ACC CABG guidelines recommend
that for elective CABG, “clopidogrel and ticagrelor should be discontinued for at least 5 days before surgery (Class
I, Level B) and prasugrel for at least 7 days” (Class I Level C). For urgent CABG “it may be reasonable to perform
surgery less than 5 days after clopidogrel or ticagrelor has been discontinued and less than 7 days after prasugrel has
been discontinued” (Class IIb Level C), but “clopidogrel and ticagrelor should be discontinued for at least 24 hours
to reduce major bleeding complications”(Class I, Level B)51.
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Comparison of Antiplatelet Agents

Drug Class Mechanism of Action Metabolism Route of Elimination Permanent Time for adequate
to Active Platelet platelet function
Metabolite Inactivation recovery
Aspirin Salicylate COX Inhibition No Liver – by deacetylation Yes 30% at 48 hours
Clopidogrel Thienopyridine P2Y12 receptor blockade Yes Liver – 2 step process by Yes 40% at 3 days
CytP 3A5/2CD19
Prasugrel Thienopyridine P2Y12 receptor blockade Yes Liver – by CytP 3A4 to Yes 2-3 days
active metabolite
Ticagrelor Cyclopentyltriaz P2Y12 receptor blockade No Liver – active metabolite No 57% at 24 hours
-olopyrimidine
Cangrelor ADP Analogue P2Y12 receptor blockade No Dephosphorylation No Rapid (Min – Hrs)
Cilastazol PDE Inhibitor PDE III Inhibition No Liver - CYP3A4/5 (2C19) No ?2 days
The management of patients coming for surgery with recent exposure to antiplatelet agents presents a clinical
challenge49,53. About 10% of patients with ACS will need CABG during their hospitalization, and approximately 2-
5% will require urgent operation which precludes withholding antiplatelet agents for 3-5 days. There is limited data
to support the use of platelet function testing for timing of operation; patients who have recovered >70% of platelet
function are less likely to bleed. Off-pump or less invasive procedures can be considered. Antifibrinolytics have
been reported to reduce bleeding and transfusion in this situation. Topical hemostatic agents, DDAVP and/or
plasma sequestration may be useful. Platelet transfusions may be indicated although more than usual may be
required. The effectiveness of transfused platelets depends on whether active drug or metabolite is present in the
circulation. Consideration should be given to restarting P2Y12 antiplatelet agents when hemostasis after surgery is
assured in patients with preoperative ACS or with a recent coronary stent.
New Oral Anticoagulants: Because of the problems with Coumadin, several new oral anticoagulant (OAC)
drugs have been developed. These agents are direct reversible inhibitors of either thrombin or factor Xa. They
generally are rapidly absorbed after ingestion, have short half-lives, are unaffected by food or other medications, and
thus can be administered with little need for monitoring of anticoagulant effect. Recommended doses are
standardized, with reductions suggested for patients with renal failure, small BMI or advanced age.
Oral Anticoagulant Mode of RR CVA/STE in AFib Trials Dosing Peak Half % Renal
Agent Action level life (h) Elimination
Apixaban(EliquisTM) Anti-Xa 0.79 (0.66-0.95) 0.45 (0.32-0.62)^ BID 3 hr 8-14 25% renal
Rivaroxaban (Xarelto®) Anti-Xa 0.79 (0.66-0.96) OD 3 hr 7-12 67% renal
Dabigatran (PradaxaTM) DTI 0.91 (0.74-1.11)# 0.66 (0.53-0.82)+ OD or BID 2 hr 9-14 85% renal
DTI-Direct Thrombin Inhibitor; RR-Relative Risk (95% confidence interval); CVA/STE-stroke or systemic thromboembolism; ^-compared to
ASA/clopidogrel; #-110 mg BID; +-150 mg BID
The perioperative management of patients on new OACs can be challenging for several reasons54,55. The two main
clinical concerns with these new agents are that no specific antidotes are yet available and their anticoagulant effect
is not readily quantifiable with routine laboratory testing. The optimal timing of operation will depend on patient
circumstances. For example, the clearance of dabigatran in patients with normal renal function may allow for
operations with low risk of bleeding after 24 hours of last dose56. On the other hand, patients with renal failure
undergoing high risk operations may require more than 5 days for clearance of dabigatran effect. The presence of
drug effect can be ascertained using thrombin time or aPTT – if these are normal, there is little if any drug effect, but
if elevated the degree of elevation is not necessarily directly correlated with magnitude of drug effect. In urgent
situations, charcoal can be administered to inhibit GI absorption of recently ingested drug. Prothrombin Complex
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Concentrates have been shown to reverse the effects of rivaroxaban (and presumably apixaban) in healthy subjects,
but they are not as effective for dabigatran. Activatated PCCs may be preferable. Antifibrinolytics should be
considered to prevent bleeding due to fibrinolysis. Theoretically factor Xa concentrate should help with anti-Xa
agents. Dabigatran may be removed by dialysis, but this may be impractical in the emergency situation.
Recombinant activated factor VIIa may be considered for intractable postoperative bleeding assuming platelets and
coagulation factors are adequate and the risks of bleeding outweigh the risks of thrombosis. Because of the
difficulty in reversing the effect of new OACs, patients would not be restarted on preoperative OACs until the risks
of surgical bleeding complications have abated.
Antifibrinolytic therapy: Antifibrinolytic therapy has become a standard of care for most cardiac operations.
As with any therapy, the benefit and the potential risks of these agents must be assessed. More than 70 randomized
controlled clinical trials (RCTs), systematic reviews and meta-analyses have demonstrated the efficacy of aprotinin,
tranexamic acid and aminocaproic acid compared to placebo in reducing perioperative blood loss. Most RCTs
consist of sample sizes which are too small to properly evaluate safety outcomes such as mortality and major
morbidity. The main safety issues related to antifibrinolytic drugs are hypersensitivity reactions, effects on the
kidney, potential for thrombotic events and effect on mortality57,58,59,60,61.
There continues to be controversy about antifibrinolytic drugs. As a result of the BART data, Bayer and regulatory
authorities temporarily suspended world-wide marketing of Trasylol®, although this has been recently lifted in
Canada and Europe. One reason for the ongoing controversy about antifibrinolytics is that there are few reports
which compare all three antifibrinolytic medications in the same study. In addition, the optimum dosage regimen for
individual antifibrinolytic drugs is not known. All of these agents have been administered as a bolus and/or
infusion, and as either fixed or weight adjusted regimen, thus making inter- and intra-class comparisons sometimes
very difficult. The true estimation of risks and benefits for these agents remains to be determined. For example,
although several papers have suggested a higher mortality with aprotinin, recent observational studies have reported
a higher incidence of seizures in patients receiving high dose tranexamic acid62,63. The mechanism may be related to
GABA or glycine receptors, but these reports do not document long term sequelae from the seizures. Other new
agents are currently under development and clinical investigation.
Recombinant Factor VIIa (rVIIa): Recombinant Factor VIIa (rVIIa) is a safe and effective agent for the
treatment of bleeding episodes in patients with Hemophilia A or B and inhibitors. The mechanism of action of rVIIa
is thought to be increased site specific thrombin generation from activated platelets and/or by tissue factor mediated
activation of coagulation. “Off-label” use of rVIIa has been reported in a wide variety of non-clinical settings.
There are an increasing number of case reports of the use of rVIIa in the cardiac surgical setting, but only a handful
of randomized controlled trials. Two recent large registry reports have documented reduced bleeding and blood
product administration after rVIIa64,65. The safety of this agent has not been firmly established in the perioperative
setting, predominantly related to its thrombotic potential, and a wide variety of adverse thrombotic outcomes have
been reported66,67. An RCT with rVIIa in 172 patients bleeding after cardiac surgery found a significantly reduced
requirement for re-operation or allogeneic blood products and a higher incidence of critical serious adverse events,
including stroke, with rVIIa treatment 68. Two recent systematic reviews have highlighted the increased risk of
arterial thromboses in patients receiving off-label administration of rVIIa69,70. The optimal dose of rVIIa in cardiac
surgery has not been established. The hemophilia dose is 90 ug/kg, whereas doses ranging from 5 to >100ug/kg
have been given in other settings. Many reports in cardiac surgery have used between 20-80 ug/kg with a second
dose repeated within 1-2 hours if necessary. Because of the cost of therapy (~$1000/mg) and the uncertainty
regarding optimal dose, it has been suggested that rVIIa be dosed to the nearest whole vial. rVIIa in cardiac surgery
should only be considered for rescue therapy for intractable non-surgical bleeding2,71,72.
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Other coagulation factors: Prothrombin complex concentrates (PCCs) contain vitamin K-dependent
coagulation factors (II, VII, IX and X; and protein C and S). Several products are available, with some having less
factor VII than others. PCCs are now the agents of choice for rapid reversal of oral anticoagulants; plasma should
not be considered for warfarin reversal unless PCC is not available and/or severe bleeding is present10. The usual
dose of PCC to reverse anticoagulation in an average adult is approximately 1000-1500 IU. In a randomized trial of
cardiac surgical patients, PCC reversed oral anticoagulation safely, more quickly and with reduced bleeding
compared to FFP73.
Fibrinogen concentrates: CPB may lead to degranulation of platelets and consumption of clotting factors
including fibrinogen. A Canadian study has shown that cardiac surgery is the most common indication for
cryoprecipitate transfusion with 0.3-10.1% of cardiac surgery patients receiving cryoprecipitate74. Recent small
preliminary clinical studies have suggested that prophylactic administration of fibrinogen concentrates (~2gm) may
reduce bleeding after CABG surgery, and larger doses (6-8 gm) may treat excessive bleeding after major vascular
procedures75,76,77,78. Larger trials are underway to determine the safety and efficacy of such therapy.
Factor XIII is the final enzyme in the clotting cascade which crosslinks individual fibrin molecules to stabilize the
fibrin mesh. Circulating factor XIII levels are reduced by 1/3-1/2 during and after CPB, and an inverse relationship
between factor XIII levels and postoperative bleeding has been reported for a variety of surgical procedures.
However, a phase II randomized controlled trial of patients undergoing cardiac surgery with CPB found no benefit
of recombinant factor XIII in terms of bleeding or transfusion (ClinicalTrials.gov Identifier: NCT00914589).
Anti-thrombin III (ATIII): Anti-thrombin III is a serine protease inhibitor which combines with heparin,
leading to inactivation of thrombin and Factor Xa. It thus has anticoagulant properties, and is approved for use in
hereditary AT deficiency. Heparin resistance occurs in about 20% of cardiac patients and is related to decreased
ATIII levels. Data from both randomized controlled trials and observational studies demonstrate that administration
of either recombinant or plasma derived ATIII concentrates is effective in management of heparin resistance and
thus reduces exposure of patients to plasma79,80. A few recent retrospective analyses suggest that lower ATIII
concentrations are associated with negative clinical outcomes. However, demonstration of improvement of these
outcomes with administration of AT is currently lacking.
Hemopoetic therapy: Red blood cell production is regulated by erythropoietin, a glycoprotein hormone
produced by the peritubular capillary endothelial cells in the kidney, and dependent on adequate iron for heme
production. Several studies and meta-analyses have shown that administration of recombinant EPO can increase
hemoglobin concentration, reduce allogeneic transfusion, and improve functional capacity and clinical
outcome81,82,83,84. Iron therapy should be considered for patients who are receiving EPO or are iron deficient.
Several EPO doses have been used; generally, a regimen of 40,000 IU (600 IU/kg) SC weekly for a maximum of 4
doses with iron supplementation raises the hemoglobin by about 1 gm/dl and/or reduces transfusion by 1 unit. A
short perioperative course of high dose EPO in OPCAB patients demonstrated a significantly lower transfusion rate
and higher postoperative hemoglobin in the EPO patients85. Even a single dose of EPO administered 1 day
preoperatively combined with iron significantly reduced transfusion in patients undergoing valvular surgery86. The
main concerns about EPO in this setting relate to cost, off-label use, and lack of established safety data87. Adverse
thrombotic outcomes have been reported with EPO therapy, but these seem to occur in cancer patients and when the
hematocrit was maintained >40%.
Preoperative Autologous Donation (PAD) can be considered in some patients undergoing cardiac surgery.
One or two single unit donations can be collected weekly 2-4 weeks preop with iron supplementation (+/- EPO) to
allow hemoglobin to normalize. PAD is contra-indicated in patients with unstable coronary symptoms, stenotic
valvular disease, Hb <13 gm/dl, or bacterial infection. PAD blood can be stored for 35 days. Although it can be
effective, scheduling issues and logistics have limited PAD use in many institutions.
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Summary: Many potential strategies exist for blood conservation in cardiac surgery. There are several notable
examples of successful implementation of blood management programs. In 2001, the province of Ontario embarked
on a program to decrease allogeneic transfusions for surgical procedures by 10-15% over 3 years, with further long
term reductions14,88. One component of this program was the implementation of transfusion co-ordinators to
enhance transfusion practice outside of the Blood Bank by providing a ‘clinical bridge’ between Transfusion Service
and the rest of hospital, and to interact with physicians, nurses and patients to promote blood conservation and
alternatives to allogeneic transfusion. At baseline, there was marked variation between hospitals in the incidence of
transfusion, and after 12 months, most of the hospitals showed a reduction in the proportion of patients transfused.
For CABG surgery, the overall transfusion reduction was approximately 15%. For all procedures, the reduction in
transfusion and associated morbidity, workload, and length of stay resulted in savings of almost $15 million.
Similarly, at Virginia Commonwealth University, implementation of a blood conservation program for cardiac
surgery resulted in net savings of $1.4 million89. Blood conservation can thus be very successful, worthwhile and
rewarding for patients, caregivers and healthcare systems.
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55. Wittkowsky AKNew oral anticoagulants: a practical guide for clinicians. J Thromb Thrombolysis
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DISCLOSURE
Cubist, Novo Nordisk, Hospira, Funded Research; AstraZeneca, Cubist, Medicines Company, Honoraria; Wuark,
Consulting Fees
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Regional Versus General Anesthesia for Vascular Surgery Patients

Peter Rock, M.D., MBA Baltimore, Maryland
Introduction
Vascular surgery patients are at increased risk for complications. These patients may have congestive heart
failure (CHF), a history of cigarette smoking, chronic obstructive pulmonary disease, hypertension, renal failure, and
diabetes (DM). There is an increased incidence of coronary artery disease (CAD) in this population and an increased
risk of myocardial infarction (MI) after vascular surgery. The AHA/ACC guidelines for patients undergoing non-
cardiac surgery categorize vascular surgery as high-risk [1]. Patients who are in jeopardy of developing
perioperative complications would benefit from anesthetic techniques that improve outcomes. Cardiac and
pulmonary complications, graft and deep venous thrombosis, gastrointestinal (GI) and central nervous system
(CNS) function, and mortality are important outcomes to evaluate. This review will address these issues, focusing on
major aortic and lower extremity arterial bypass surgery using general (GA) or regional anesthesia (RA) with either
spinal (SA) or epidural (EA) anesthesia. Since not all aspects of improvement in outcomes have been studied in
vascular surgery patients, it will be necessary to extrapolate to such patients the results of studies performed in other
surgical disciplines. There is conflicting data regarding whether regional analgesia results in superior outcomes
compared to other forms of analgesia. The line between intraoperative anesthesia and postoperative analgesia is
often blurred but the results of analgesic interventions are relevant to perioperative outcomes.
Potential Advantages and Disadvantages of RA and GA

RA does not require airway manipulation or neuromuscular blockade. Volatile agents are not used; there is
less effect on ventilatory control. A hypercoagulable state is seen after surgery. RA, by attenuating the stress
response to surgery, may modify the tendency to clot and decrease the incidence of postoperative venous, arterial,
and graft thrombosis [2, 3]. RA using local anesthetics (LA) and opioids can be administered continuously
postoperatively. RA may permit early ambulation, faster rehabilitation, and a decreased hospital length of stay
(LOS). EA provides better postoperative analgesia compared to intravenous patient-controlled analgesia (PCA) [4].
RA may be more time consuming than GA and is expensive if performed in the OR. Recent studies have
illustrated the risks associated with RA. A prospective study of 103,740 regional anesthetics (40,640 SA; 30,413
EA; 32,687 other) examined the incidence of adverse outcomes. [5]. There were 29 cardiac arrests, most of which
occurred during SA. Neurologic injury was reported in 34 patients. The risk of seizures after injection of LA was
2.2/10,000 and the risk of death was 0.7/10,000. A follow-up study confirmed the previous findings (56 major
complications in approximately 158,083 regional anesthetics) [6]. A recent study of over 1.7 million regional
anesthetics found 127 neurologic complications including permanent neurologic damage in 85 patients [7]. A review
of 8,210 epidural catheters inserted for postoperative pain control revealed a significant incidence of neuraxial injury
[8]. These studies should not discourage the use of RA but illustrate that all anesthetics are associated with
complications. Spinal or epidural hematoma may occur even in patients with normal coagulation function and can
result in devastating neurological consequences. Patients with vascular disease may receive anticoagulants or
antiplatelet agents, which increase the risk of neuraxial bleeding. Other potential drawbacks of RA include: airway
control is assumed; airway secretions cannot be suctioned; and there is no control over ventilation and oxygenation.
But, GA requires airway manipulation and can induce bronchospasm. Inhalational anesthetics attenuate the response
to hypercarbia and hypoxemia, and neuromuscular blockade is often employed.
RA might improve outcomes by attenuating the perioperative stress response; GA does not attenuate the
stress response as well as RA. Elevations in heart rate and blood pressure increase myocardial oxygen demand and
result in myocardial ischemia or infarct in individuals with CAD. Coronary vasoconstriction, as a result of an
increase in circulating catecholamines, decreases coronary blood flow and myocardial oxygen delivery. EA ablates
the catecholamine response to lower extremity vascular surgery and attenuates the catecholamine response to
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surgery above the umbilicus [9]. Postoperative norepinephrine correlates with postoperative hypertension [10].
Impaired fibrinolysis and increases in platelet aggregation after surgery might result in coronary artery thrombosis.
Meta-Analysis and Randomized Clinical Trials (RCTs)

Meta-analyses have suggested the superiority of epidural analgesia over other types of postoperative pain relief,
producing superior pain control and a reduction in the rate of postoperative MI [11]. However, it is possible that
adequate pain relief, regardless of how it is achieved, may reduce the rate of perioperative MI. Older studies
included in meta-analyses have flawed study design. They did not control hemodynamics, temperature, post-
operative care, and analgesic care, between RA and GA groups. Inclusion of such studies in a meta-analysis will
lead to false conclusions. Improvements in clinical practice over time may render the results of a meta-analysis
irrelevant to modern practice. Meta-analyses frequently do not agree with RCTs published on the same topic. One
study concluded if there had been no subsequent RCT the meta-analysis would have led to the adoption of an
ineffective treatment 32% of the time and to the rejection of a useful treatment 33% of the time [12]. New evidence
that changes conclusions of systematic reviews arises frequently within a short time [13]. But, RCTs alter usual
clinical care limiting the ability to generalize the results beyond the conditions of the trial. The MI rate is often lower
in RCTs, where clinical care is controlled, than in studies where perioperative management is not tightly controlled.
Deep Venous Thrombosis (DVT) and Graft Thrombosis

Surgery produces a hypercoagulable state. Increased levels of plasminogen activator inhibitor may result in
impaired fibrinolysis and predispose to arterial or venous thrombosis following surgery [2]. RA may attenuate this
response. Infusing stress hormones to normal subjects does not cause increases in procoagulant proteins and platelet
reactivity or decreases in fibrinolytic proteins [14]. Systemic inflammation and the acute phase response that
accompanies major surgery may lead to synthesis of coagulation proteins and inflammation-related changes in
platelet function. Anesthetic choice might not influence hypercoagulability after surgery.
Few studies in vascular surgery patients address the issue of whether there is an outcome advantage to RA
with respect to DVT. Patients undergoing endovascular abdominal aortic aneurysm surgery have a 6% incidence of
DVT without advantage for RA over GA [15]. An older meta-analysis suggested that RA is associated with a 31%
reduction in the incidence of DVT compared to GA in individuals undergoing hip surgery [16]. Although the
incidence of DVT was decreased, overall mortality was unchanged, and prophylaxis for DVT was not given
routinely or described. There was no standardization of perioperative care, anesthetic regimens or ambulation
protocols, which could have influenced the findings. It is probable that such a large difference in DVT incidence, if
there were a difference at all, would not be found in modern studies employing routine DVT prophylaxis. There are
still conflicting results in the literature regarding the effectiveness of RA over GA in terms of reducing DVT in
orthopedic patients [17, 18]. The overall incidence of DVT and pulmonary embolism is low in orthopedic patients
[19]. A recent Cochrane review suggested RA was superior to GA in reducing the incidence of DVT but noted “this
conclusion is insecure due to possible selection bias in the subgroups in which this outcome was measured” [20].
It has been proposed that a benefit of RA over GA is reduction in the incidence of graft occlusion, perhaps
through its ability to attenuate the hypercoagulable state that accompanies major surgery. Early studies suggested a
decrease in graft occlusion in vascular surgery patients receiving RA [3, 21]. Recent studies have failed to reveal a
benefit to RA with respect to graft occlusion [22, 23]. In one such study, patients (n=315) were randomized to
receive EA, SA, or GA, monitored with a pulmonary artery catheter (PAC), and admitted to an ICU for 48 – 72
hours after surgery [23]. There were no differences between the groups with respect to graft patency. In the “real
world”, it is unlikely that many vascular surgery patients receive a PAC and a three-day ICU stay.
Cardiac Outcomes
In 1987 Yeager published the results of a RCT of EA and “light” GA vs. GA in high risk surgical patients
(n=53) [24]. There was a decreased rate of cardiovascular complications in the EA group. Perioperative care (e.g.
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invasive hemodynamic monitoring) and analgesia were not standardized (analgesia levels differed between groups).
In 1991, Baron reported a RCT in patients (n=173) receiving combined EA and GA vs. GA for abdominal aortic
surgery. There was no difference in cardiovascular morbidity between groups [25]. Tuman reported on the results of
a RCT involving major vascular surgery of the abdominal aorta and lower extremities [3]. Patients (n=80) received
either combined EA and GA or GA alone. Cardiovascular complications were reduced in the EA group. The EA
group had excellent pain control while pain scores were not measured in the control group. Christopherson reported
on a RCT in patients (n=100) receiving either EA or GA for lower extremity bypass grafting surgery [21]. Cardiac
outcomes were similar between the two groups. There was standardization and optimization of patient care and
equal pain control was achieved in both groups. Bode reported a RCT in 423 patients receiving EA, SA, or GA for
peripheral vascular surgery [22]. Cardiovascular morbidity and mortality were not different between groups. The
low mortality rate, 3.1%, means it would have been necessary to study more than 24,000 patients to have sufficient
power to detect a 50% reduction in mortality between groups. Rigg reported the results of a RCT (n=915) in high-
risk patients (DM, renal failure, respiratory insufficiency, CHF, CAD) undergoing high-risk procedures (aortic or
major GI, genitourinary, or gynecologic surgery) and who received combined EA, GA and epidural analgesia or GA
and PCA [26]. There were no differences between groups with respect to cardiovascular events.
Anesthetic Techniques vs. Standardization and Optimization of Perioperative Care

Norris tested the hypothesis that reduction in variation in care and control and optimization of perioperative
pain management and hemodynamics can reduce morbidity and mortality to levels that eliminate the impact of
anesthetic technique. The primary endpoint was hospital LOS. Patients (n = 168) undergoing major aortic surgery
were randomized to one of four groups who received combinations of intraoperative anesthetic type and
postoperative analgesia (thoracic EA/”light” GA/epidural PCA; thoracic EA/”light” GA/iv PCA; sham thoracic
EA/GA/epidural PCA; sham thoracic EA/GA/iv PCA)[27]. Protocols standardized perioperative care. There were no
differences with respect to LOS, death, MI, pneumonia, or pain control. LOS is an “integrated” outcome measure;
an individual that suffered significant morbidity would presumably spend a longer time in the hospital. Perioperative
care rather than a specific anesthetic regimen may be the most important factor in outcome after surgery.
Regional Anesthesia and Analgesia and Postoperative Pulmonary Complications (PPCs)

Because RA does not require the use of neuromuscular blockade, airway instrumentation, or volatile
anesthetics, it might reduce PPCs. It has been difficult to demonstrate the benefits of RA over GA with respect to
reducing PPCs. Use of meta-analysis is problematic as there is no standard definition of a PPC and studies are not
comparable. Meta-analyses suggest that RA, especially epidural local anesthetics, decrease pulmonary infections
(pneumonia) and complications (poorly defined) [28-30]. Older RCTs did not demonstrate a significant
improvement in PPCs as a result of RA although they were not designed with PPCs as a primary outcome [3, 21,
25]. Jayr performed a RCT investigating the impact of analgesia and anesthesia (GA with postoperative parenteral
morphine or GA with postoperative epidural analgesia) on PPCs in patients (n=153) undergoing major surgery [31].
Despite better pain control in the RA group, no benefit could be attributed to RA with respect to LOS or PPCs in
either the group as a whole or in the subgroup of patients with underlying lung disease. In Norris’ study, there were
no differences between anesthetic and analgesic groups with respect to PPCs [27]. PPCs in a RCT conducted by
Fleron were not reduced by regional analgesia in patients undergoing abdominal aortic surgery [32].
Rigg found that respiratory failure (“prolonged” ventilation, PaO2 < 50 mmHg, or PaCO2 > 50 mmHg) was
more common in the control group [26]. This definition of respiratory failure is problematic as few define a PPC as
a mild increase in PaCO2, especially when associated with narcotic analgesia. Postoperative hypoxemia, common
after major abdominal surgery, has not been linked to more significant morbidity (e.g. increased ICU or hospital
LOS) or increased mortality. A recent re-analysis of Rigg’s data found there was a small reduction in duration of
postoperative ventilation (0.3 vs. 0.2 hours) but no difference in the number of patients requiring mechanical
ventilation > 24 hours in any subgroup [33]. The authors concluded there was no evidence that perioperative
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epidural analgesia influences morbidity or mortality after abdominal surgery. A recent systematic review compared
PCA opioid therapy with epidural analgesia for pain control after intra-abdominal surgery in terms of side effects,
patient satisfaction and surgical outcome and found no differences in hospital length of stay or other adverse effects
[34]. Warner has written “although regional techniques may provide excellent analgesia, it is not yet clear that they
consistently improve clinical respiratory outcome” [35]. A recent systematic review concluded that the evidence
regarding the efficacy of regional analgesia and anesthesia in reducing PPCs is “conflicting or insufficient” [36].
Mortality
Yeager’s study reported a decrease in mortality in patients receiving RA but the studies of Tuman, Baron,
Christopherson and Norris did not. The meta-analysis of Rogers found mortality at 30 days post-surgery was
reduced in the RA group [29]. However, that analysis included four trials with a much higher mortality rate than all
the others and which may have influenced the results. Park reported the results of a RCT in patients undergoing
aortic or major GI surgery suggesting that EA resulted in a lower mortality rate than patients receiving GA and
parenteral opioid therapy [37]. There were no protocols implemented and there was superior pain control in the RA
group. Hemodynamic monitoring and management was neither specified nor controlled. Urwin reported the results
of a meta-analysis that demonstrated a difference in 1 month but not 3-, 6-, or 1-year mortality rates and concluded
there were “marginal” advantages for RA compared to GA in patients with hip fracture [18]. Peyton’s re-analysis of
Rigg’s data failed to demonstrate a mortality benefit of anesthetic technique in high risk patients [33]. Wu recently
reported on a nationally random sample of the Medicare database examining the effect of analgesia on outcome in
patients undergoing total hip arthroplasty. Epidural analgesia was not associated with a lower incidence of mortality
[38]. Using similar methodology not confined to patients undergoing hip surgery, Wu found a reduction in death at
seven days after surgery with EA [39]. Liu published a recent meta-analysis that did not demonstrate a reduction in
mortality in patients undergoing CABG as a result of thoracic EA [40].
Wijeysundera used administrative databases to perform a retrospective study of more than 259,000 patients
who underwent elective intermediate or high-risk non-cardiac surgical procedures. EA and epidural analgesia were
associated with a very small decrease in 30-day mortality (0.3% absolute reduction) resulting in a number needed to
treat of 477. They concluded “our study…does not provide compelling evidence that epidural anesthesia improves
postoperative survival” [41]. Recently, Svircevic randomized 654 patients to either thoracic EA (TEA) or usual care
in patients undergoing cardiac surgery. The investigators were unable to demonstrate a benefit of TEA on the
frequency of major complications. Monk reported that duration of deep hypnotic time was an independent predictor
of one-year mortality after surgery but others have not confirmed this finding [42, 43]. Recently, Sessler investigated
the association between blood pressure, deep hypnotic time and anesthetic dose in 24,120 patients undergoing
noncardiac surgery. LOS and mortality was increased in patients having a "triple low" of low blood pressure, low
bispectral index, and low minimum alveolar concentration of volatile anesthesia [44]. In conclusion, there is
conflicting evidence regarding anesthetic technique-related differences in mortality.
Central Nervous System Function, Anesthesia And Surgery

GA, by definition, changes cerebral function while a patient is anesthetized. RA avoids that issue. It has
been proposed that GA may produce long-term alterations in brain function (post-operative cognitive dysfunction,
POCD) although some investigators question whether POCD even occurs [45]. No difference in POCD was
observed in a RCT (n=64; mean age 69) involving knee arthroscopy under RA or GA [46]. A report of 53 men
(mean age 71) undergoing prostate resection receiving GA or EA concluded that the type of anesthesia does not
result in POCD [47]. A RCT involving knee replacement (n=262; median age 69) found that the type of anesthesia
did not affect POCD [48]. The results of an investigation involving 1,218 patients undergoing major surgery found
POCD was present in 26% of patients one week after surgery and in 10% three months after surgery, compared with
3% of controls at the same time points [49]. Risk factors for POCD included age and duration of anesthesia but not
the type of anesthesia. An investigation of POCD (n=508; median age 51) found that risk factors for POCD
included: duration of anesthesia, administration of N20, upper abdominal surgery, heart disease, and interestingly,
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the use of epidural analgesia [50]. Two recent meta-analyses concluded the use of RA does not reduce the incidence
of POCD [51, 52]. Evered studied 678 patients and concluded that POCD is independent of surgical type and
anesthetic [53]. Heyer found the same rate of POCD in patients undergoing carotid endarterectomy under regional
block as those done under GA [54]. There is no evidence of POCD related to the type of anesthetic. However,
emerging evidence suggests that GA may result in long-term CNS changes or damage to the developing brain or in
older patients at risk for Alzheimer’s disease. Ikonomidou, Jevtovic-Todorovic, Xie, and Eckenhoff have variously
reported that GA results in apoptotic neurodegeneration and enhancement of amyloid beta oligomerization, a peptide
associated with Alzheimer’s disease [55-59].
Other Outcomes: GI Function; Cancer Recurrence; Surgical Site infections (SSIs); and
Rehabilitation
Patients that receive EA using local anesthetics (LA) experience faster return of bowel function and meet
discharge criteria sooner than patients receiving parenteral opioids [60, 61]. Systemic absorption of LA could be
responsible for the improvement in bowel function observed after epidural administration of LA [62]. Anesthetic-
related differences in improvement in bowel function may also reflect the effect of opioids on gut motility. Selective
inhibition of gastrointestinal opioid receptors can counteract the effects of systemically administered opioids on the
GI tract while not interfering with pain relief. Their administration speeds recovery of bowel function and shortens
the duration of hospitalization [63]. These antagonists may thus minimize a potential advantage of RA over GA.
Patients undergoing colon surgery who receive EA get out of bed faster, have faster return of bowel function, greater
intake of food, and better exercise tolerance and health related-quality of life than a group receiving PCA at both 3
and 6 weeks after surgery whereas hip surgery patients receiving EA may not have enhanced rehabilitation [64, 65].
There are also intriguing reports suggesting regional anesthesia or analgesia may lessen the risk of cancer
recurrence [66, 67]. Other studies have been unable to confirm these findings [68, 69]. Cummings recently reported
that EA may improve survival in patients with nonmetastatic colorectal cancer undergoing resection but was unable
to find an association between EA and decreased cancer recurrence [70]. Using an administrative database, Chang
investigated whether anesthetic type influences the development of SSIs [71]. In 3,081 patients undergoing total
joint replacement, those receiving GA had a higher risk of SSI compared with RA. A RCT might help further
elucidate the role of anesthetic type on SSIs and also suggests that anesthetic choice may have long-term
consequences deserving of further study. It is not clear whether or how postoperative analgesia affects outcomes that
are important to patients such as quality of life, quality of recovery, and even patient satisfaction. One study
suggested there is no evidence that postoperative analgesia leads to improvements in patient-centered outcomes such
as quality of life and quality of recovery. The authors concluded “modest reductions in pain scores do not
necessarily equate to clinically meaningful improved pain relief for the patient” [72].
Vascular Surgery, Neuraxial Block, and Modification of the Coagulation System

Many vascular surgery patients undergo modification of the coagulation system to prevent thrombus
formation in diseased vessels, or to prevent graft occlusion or embolic events. When patients are on anticoagulants
or receiving anti-platelet agents, RA may be inadvisable because of the risk of neuraxial bleeding. Spinal or epidural
hematoma can occur spontaneously in relation to anticoagulation therapy and can also occur when there has been
vascular trauma related to attempts at neuraxial block [73]. The Society of Regional Anesthesia and Pain
Management has developed recommendations regarding the use of neuraxial techniques in patients receiving
anticoagulation [74]. The increasing use of agents that modify the coagulation system may make future comparisons
of RA vs. GA more difficult; it will be more difficult to achieve true randomization and changes in the coagulation
system may further reduce vascular events resulting in myocardial ischemia.
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The Future
Perioperative beta-blockade (PBB) is thought to improve cardiac outcomes in patients at risk undergoing
major surgery [75, 76]. Questions remain regarding timing of therapy before surgery, target heart rate, duration of
treatment and optimal beta-blocker. A large retrospective study confirmed the benefit of PBB but the recent POISE
study demonstrated an increased rate of stroke and death in patients receiving PBB [77, 78]. These conflicting
results are likely to continue the controversy about indications for and the optimal dose and timing of PBB and result
in more cautious use of beta-blockade in the perioperative time period. Future studies of the ability of RA to
improve outcomes should be performed in the setting of PBB or pharmacologic interventions designed to prevent
DVT. Other outcomes should be examined to demonstrate value and cost-effectiveness of regional analgesia and
RA. Organizational characteristics of ICUs can improve outcomes, lower costs, and reduce length of stay [79-81]. It
will be important to reconcile conflicting results of meta-analyses regarding the role of epidural anesthesia and
analgesia in improving outcomes [82-85]. Efforts to improve outcomes should focus on global perioperative care
rather than on specific anesthetic techniques. It will be important to define the role of RA in improving outcomes in
“real world” settings where optimization of all aspects of perioperative care may not have been achieved.
Conclusions
Evidence in the literature suggests that RA and GA produce equivalent outcomes. Methodological flaws
bias older studies in favor of RA. Carefully conducted RCTs have not demonstrated improvements in cardiac
outcomes, mortality, or LOS with RA for vascular surgery. RA has not been demonstrated to result in superior
pulmonary outcomes, or decrease the incidence of POCD, even in high-risk groups, in carefully performed RCTs.
Demonstration of equivalent outcomes between RA and GA have been performed under the conditions of a tightly
controlled RCT, with protocol-driven management. Optimization and standardization of perioperative care may
result in improvements in outcome independent of the type of anesthetic. RA should be employed carefully in the
setting of perioperative modification of the coagulation system. It is possible that RA may offer advantages in
settings where optimization of care has not been achieved. In the “real world”, the choice of anesthetic may be
crucial. Clinical practice might change, perhaps in favor of RA, if a firm connection is established between GA and
neurotoxicity in humans, if it is conclusively demonstrated that the depth of anesthesia increases mortality after
surgery, or if evidence builds that regional techniques favorably influence cancer treatment. In the meantime, Royse,
in an editorial in A nesthesiology, suggested: “Perhaps it is time to move away from trying to prove that anesthetic
interventions will reduce morbidity or mortality and to focus on tangible benefits to patients or their families.
Epidurals are used primarily to provide excellent analgesia, and any other benefits are a bonus” [86].
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DISCLOSURE
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Management of the Patient With Pulmonary Hypertension and

Right Ventricular Failure
George F. Rich, M.D., Ph.D. Charlottesville, Virginia
Introduction
Pulmonary hypertension (PH) is a risk factor for increased morbidity and mortality in patients requiring
either non-cardiac or cardiac surgery (1). Further, PH may induce right ventricular (RV) failure, which is a predictor
of poor outcome. Managing the patient with PH and RV failure requires an understanding of pulmonary physiology
and how certain factors alter pulmonary vascular resistance (PVR). Therapy primarily consists of intravenous and
inhaled vasodilators to decrease PVR, and inotropic agents to support underlying RV failure resulting from PH.
Pulmonary physiology
The pulmonary circulation is normally a low pressure and resistance circuit. The normal systolic, diastolic,
and mean pulmonary artery pressure (PAP) are 22 mmHg, 10 mmHg, and 15 mmHg, respectively. The PVR is
normally 90 to 120 dynes.sec.cm-5. PH is defined as a mean PAP of greater than 25 mmHg at rest or greater than
30 mmHg with exercise, or a PVR greater than 300 dynes.sec.cm-5. A mean PAP greater than 50 mmHg or a PVR
greater than 600 dynes.sec.cm-5 is considered severe PH. The PVR is important because it represents the afterload
of the RV, and, therefore, affects RV function and cardiac output (CO).
In contrast to the systemic circulation, the pulmonary vessels have relatively thin walls and the vascular
smooth muscle is sparsely distributed in the smaller arterioles. As such, increases in CO distend open vessels and
recruit previously closed vessels resulting in a decrease in PVR. Clinically, this means that increasing CO with
inotropic agents or increasing blood volume will passively decrease PVR. This relationship becomes less
pronounced in disease states of the pulmonary circulation. The endothelium plays an important role in maintaining
low resting pulmonary vascular tone. Normally, endogenous endothelial vasodilators such as nitric oxide (NO) and
prostacyclin (PGI2) predominate although vasoconstrictors (endothelin, thromboxane) may also modulate PVR.
Endothelial dysfunction and alterations of endogenous vasodilators is associated with the development of PH. (2)
Airway pressure and gravity affect the pulmonary circulation. Intra-alveolar vessels are compressed during
inspiration. In contrast, the extra-alveolar vessels’ resistance decreases during inspiration. The contribution of the
two vessels accounts for the U-shaped relationship between lung volume and PVR, which is minimal at functional
residual capacity and increased at high and low lung volumes. Clinically, this is important because extremes in
ventilation that result in hyperinflation or underinflation of the lungs increase PVR. The distribution of blood flow
in the pulmonary circulation is influenced by the relationship between alveolar, pulmonary arterial, and pulmonary
venous pressures. Blood flow increases significantly in the dependent areas of the lung. Ventilation is also greater
in the dependent lung regions although the influence of gravity on ventilation is less than on blood flow. Ventilation
and perfusion are normally well matched; however, in certain diseases lung units are relatively under or over
ventilated and result in ventilation/perfusion mismatching. There are many clinical implications that involve these
relationships. For example, in patients with lung disease primarily in the dependent zones, the blood flow to well
ventilated areas in the upper zones may be decreased if the PAP or CO is decreased, i.e., PH is treated.
Factors affecting PVR
An important aspect of treating PH is understanding how certain factors alter PVR. Oxygenation has a
large influence on PVR, with alveolar hypoxia being a potent vasoconstrictor. Small areas of alveolar hypoxia cause
diversion of blood flow and minimal changes in PVR. In this situation, hypoxic pulmonary vasoconstriction (HPV)
is a protective mechanism that improves ventilation/perfusion matching. This becomes important when treating PH
because all intravenous vasodilators inhibit HPV and may decrease PaO2. Larger areas of hypoxia produce
proportionally greater increases in PVR. Acidosis is also a potent vasoconstrictor, whereas alkalosis vasodilates the
pulmonary circulation. Hypercapnia and hypocapnia most likely alter PVR via their effects on pH, although
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hypercapnia itself may increase PVR. Atelectasis can increase PVR via stimulation of HPV and mechanical
compression; therefore, the lungs should be adequately expanded in patients with PH. Providing adequate
oxygenation and treating acidosis (respiratory or metabolic) represents one of the most important and first line
treatments of PH. Sympathetic stimulation, cold, and catecholamines are also important factors that increase PVR.
Alpha-1 adrenoreceptors and beta-2 adrenoreceptors are the most clinically relevant receptors in the
pulmonary vasculature. Beta-2 agonists decrease PVR, whereas alpha-1 agonists increase PVR. These receptors are
less densely distributed compared to the systemic circulation, so one would expect the effects of agonists to be
decreased. Furthermore, the tone of the pulmonary circulation is normally low, therefore beta-2 stimulation
normally has little effect; however, in the presence of PH beta-2, agonists decrease PVR. Alpha-1 agonists increase
PVR but not to same degree as the systemic vascular resistance (SVR) because there is relatively less vascular
smooth muscle. Beta-2 receptors responsible for vasodilation are on the endothelium; therefore, their effect may be
decreased in the presence of endothelial dysfunction.
Pulmonary hypertension
PH is classified by etiology and pathophysiology. (3) PH most commonly observed in the perioperative
period is caused by cardiac or pulmonary disease. Left ventricular failure, mitral valve disease, and decreased left
ventricular compliance result in elevations in left atrial pressure (LAP). The increase in LAP passively increases the
pulmonary venous pressure, PAP, and PVR. Congenital cardiac diseases that cause left to right shunting result in
chronic increased pulmonary blood flow that eventually leads to an elevated PVR. Respiratory disorders such as
chronic obstructive airway disease lead to PH, at least in part, via hypoxia-induced vasoconstriction. PH may
present as arterial hypertension in which the PAOP is normal (i.e., respiratory diseases) or venous hypertension in
which both the PAP and PAOP are elevated (i.e., mitral valve disease).
PH is a disease of progressive states, and the effectiveness of therapy is dependent on the state. PH may
initially consist of vasoconstriction, which is easily reversible with vasodilator therapy. However, as PH continues,
vasoconstriction results in smooth muscle hypertrophy and narrowing of the vascular lumen. Reversal of smooth
muscle hypertrophy is possible over weeks to months with vasodilator therapy. Further progression of the disease
involves fibrosis and more fixed disease. Therapy at this point becomes difficult, and attempts to decrease PVR
with vasodilators may only result in a decrease in SVR. Endothelial dysfunction may also lead to the loss of
important vasodilating factors. The main focus of acute treatment of PH is reversal of vasoconstriction.
The Right Ventricle
The RV is a thin walled, crescent shaped structure that is suited for volume work, in contrast to the thick
walled LV that is suited for pressure work. Thus, for any given increase in preload a smaller increase in stroke work
would be expected for the RV compared to the LV. While the LV maintains a constant output over a wide range of
afterloads, RV function is more sensitive to changes in PAP. An acute increase in mean PAP above 40 mmHg
results in a decrease in RV ejection fraction, even in the presence of normal RV contractility. In the presence of
decreased RV contractility the RV is even more sensitive to acute increases in afterload. On the other hand, more
gradual changes in PAP may allow time for the RV to hypertrophy and sustain a relatively normal output.
Coronary blood flow to the RV normally occurs throughout systole and diastole because of the continuous
pressure gradient (coronary perfusion pressure, CPP) between the aorta and the RV. The RV blood/oxygen supply
is proportional to the systemic pressure and inversely proportional to the RV pressure. Systemic hypotension (or
attempts to treat PH or systemic hypertension) or increased RV pressure may result in decreased RV CPP. RV
oxygen demand is proportional to the RV pressure, RV volume and heart rate. Hence, increased RV pressure not
only decreases RV oxygen supply but also increases oxygen demand. Therefore, decreasing PAP with the use of
vasodilators to decrease RV pressure is critically important in treating PH and RV failure. At the same time it is
important to avoid decreasing systemic pressure and CPP.
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Right Ventricular Failure

RV failure is most commonly caused by acute or chronic pressure overload. While acute increases in RV
afterload are poorly tolerated, more gradual increases in pressure overload of the RV is sometimes well tolerated for
years before symptoms and signs of RV failure, including an elevated CVP, become evident. In the presence of a
chronic buildup of PH the RV may hypertrophy and be able to generate systemic pressures. Nevertheless, PH
eventually leads to RV dilation, decreased RV ejection fraction/stroke volume, and decreased global cardiac
function. Ischemia and infarction may also contribute to RV failure. Although angina generally occurs because of
LV ischemia, ischemia may also arise from a decrease in RV coronary blood flow or increased RV oxygen demand.
RV ischemia may also result from inadequate myocardial protection during cardiopulmonary bypass (CPB).
Volume overload from tricuspid regurgitation (TR) or atrial septal defects may also contribute to RV failure.
The common symptoms that occur as a result of PH and RV failure are dyspnea, fatigue, reduced exercise
tolerance, syncope, chest pain, and peripheral edema. ECG changes such as right axis deviation and inferior wall ST
segment changes are consistent with RV enlargement or RV ischemia. Signs of PH and RV failure include
tachypnea, tachycardia, and neck vein distension. RV lifts may be palpated and tricuspid regurgitation auscultated.
The CVP, which is normally less than 5 mmHg, may increase to above 20 mmHg in the presence of RV failure.
PH and RV failure can alter LV function. (4) Interdependence between the ventricles occurs in the
presence of increased PVR and RV end-diastolic volume and pressure, such that the intraventricular septum shifts
towards the LV cavity. Consequently, RV failure may decrease LV filling, increase PAOP, and decrease LV output.
RV dilation also may cause an increase in intrapericardial pressure that decreases LV distensibility. Hence, RV
failure may significantly decrease CO from either RV failure itself or by impacting LV function.
Evaluation of PH and RV failure by TEE
The TEE assessment of the RV is not as straightforward as evaluation of the LV; however RV function can
still be evaluated subjectively and objectively. Signs of RV dysfunction include hypokinesis of the RV free wall,
RV dilation or hypertrophy, a change in the normal crescent RV shape to round, and a flattening or bulging of the
interventricular septum from right to left. RV hypertrophy is characterized by RV free wall thickness greater than 5
mm at end-diastole. RV dilation is also defined by an end-diastolic cross-sectional area of greater than 60% of the
LV. TR is also common in patients with PH and RV failure.
Estimates of PA systolic pressure can be made by measuring the TR jet. The continuous wave Doppler
beam is placed across the TR jet and using the Bernoulli equation, the transvalvular pressure gradient is calculated
from the peak velocity TR jet. To estimate the PA systolic pressure this measurement is added to the CVP
Pulmonary Hypertension and/or RV failure: strategies for therapy
Treatment of PH and/or RV failure is based on the understanding of the impact of each on the pulmonary
and systemic circulation. PH increases RV afterload, which may increase RV pressure and volume, while
decreasing RV ejection fraction and stroke volume. This may cause a shift of the intraventricular septum, increase
pericardial pressure and PAOP, and decrease CO. Increased RV volume and pressure may also decrease coronary
blood flow and worsen RV ischemia and RV failure, which will further impact on CO. A decrease in CO may cause
a metabolic acidosis and worsen PH. Treatment of PH may include vasodilators to decrease PVR, inotropic agents
to improve RV function, optimizing ventricular volume, and correction of acid base and/or oxygenation status.
In order to treat PH and RV failure continuous assessment of hemodynamics may be required. Patients
may be best monitored with an arterial line and PA catheter. An ECG for ST analysis of the RV, thermodilution CO
and TEE may be necessary to guide therapy. Patients with chronic PH may already be on medications including
alpha adrenergic antagonist, calcium channel blockers, endothelin receptor blockers, PDE III or V inhibitors, and
prostacyclin. (5) In general, these medications should be continued, while it must be realized that these therapies
modify the effects of inotropic agents and vasodilators that may be added in the perioperative period.
It is important of understand whether the patient has RV failure, PH, or both. Treatment of patients with
PH without RV failure consists primarily of the use of vasodilators. In contrast, patients with RV failure without PH
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may be treated primarily with intotropic agents and possibly diuretics or vasocontrictors. Patients with PH and RV
failure may require both vasodilators and inotropic agents.
-RV, +PH Vasodilator (IV/ inhaled) ± vol

+RV, -PH Inotrope, ± vol/diuretic,
± vasoconstrictor
+RV, +PH Inotrope, vasodilator (IV/ inhaled)
Anesthetics and PH
Anesthetic induction in patients with PH may be challenging. These patients often have high baseline
sympathetic tone and may be catecholamine deprived. As such, these patients may be prone to severe hemodynamic
compromise upon anesthetic induction. Titrated doses of narcotics, etomidate, or ketamine may be appropriate,
with maintenance of systemic pressure the primary goal.
Nitrous oxide and ketamine may increase PVR in patients with PH (6,7), although neither increases PVR in
pediatric patients. It may be prudent to avoid these agents in patients with PH, although ketamine may provide for a
stable induction. Volatile anesthetics are unlikely to have significant effects on PVR, but they depress myocardial
contractility and should be used sparingly in patients with severe RV failure. In patients undergoing extremity
procedures, regional or peripheral blocks may be ideal if preload and afterload can be maintained.
Ventilation strategies and volume loading
Mechanical ventilation may have a significant impact in patients with PH and RV failure. As lung volumes
increase and functional residual capacity decreases with positive pressure ventilation, PVR and RV afterload
increases. This has minimal impact in patient with normal RV function, but in patient with PH and RV failure lung
hyperinflation or excessive positive end-expiratory pressure (PEEP) can drastically decrease CO. Thus, optimal
ventilation strategies may include a low tidal volume and low PEEP, while avoiding hypercapnia.
Volume loading will increase RV output in the absence of PH if RV contractility is normal. Particularly, if
the CVP is below 10 mmHg, increasing preload may increase RV stoke volume. However, if decreased contractility
and PH accompany RV failure then volume loading may be detrimental. In this situation, volume loading may
cause RV dilation and result in a decrease in LV volume and CO. This is particularly true once the CVP reaches
approximately 20 mmHg. The most appropriate action is to assess the effects of volume loading by measuring the
CO and following RV and LV function by TEE. In the presence of RV volume overload, venous vasodilation with
nitroglycerin or diuretic therapy may be beneficial in improving RV function.
Intravenous vasodilators and Inotropic agents
Vasodilator therapy with nitroglycerin or sodium nitroprusside is useful in patients with isolated PH and in
patients with combined PH and RV failure. (8) Nitroglycerin not only decreases PVR but also has the added
advantage over sodium nitroprusside in that it improves coronary blood flow to ischemic myocardium.
Prostaglandin E1 and prostacyclin PGI2 are also potent vasodilators and the ability of these agents to vasodilate the
pulmonary vasculature and improve RV function has been demonstrated in cardiac surgical patients. (9)
All intravenous vasodilators used to treat PH are not selective for the pulmonary circulation and, therefore,
may decrease systemic pressure. Decreasing systemic pressure results in decreased CPP and may worsen RV
ischemia. The degree to which intravenous vasodilators may preferentially vasodilate the pulmonary circulation
depends on the PVR/SVR ratio, i.e., if the PVR is elevated more than the SVR, all intravenous agents may produce
relatively more pulmonary vasodilation than systemic vasodilation. (8) However, the decrease in systemic pressure
secondary to vasodilators may be minimized if RV afterload reduction results in an increase in RV output and CO.
On the other hand, if pulmonary vasodilation does not improve RV function, a decrease in systemic pressure may
not be avoided. Therefore, in determining the potential benefits of intravenous vasodilators, it is important to
evaluate the effects of the vasodilator on RV function and CO.
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↓ AoP
Vasodilator
↑ AoP
↓ PAP ↑ RVSV
↑ CO
Improved acid/base
↓ PVR
The phosphodiesterase (PDE) III inhibitors may be useful in the presence of increased PVR and decreased
RV contractility because they are vasodilators with weak positive inotropic effects. Milrinone has been shown to
cause pulmonary vasodilation in addition to increasing CO. Milrinone, like other vasodilators, is not specific to the
pulmonary circulation and may cause systemic hypotension; however, the PVR may be preferentially decreased in
the presence of high PVR/SVR ratios.(10) PDE III inhibitors are also beneficial in patients with severely decreased
myocardial contractility because the effects of these drugs potentiate the effects of beta adrenergic agonists. PDE III
inhibitors inhibit the breakdown of 3’, 5’cyclic adenosine monophosphate (cAMP). In contrast, beta agonists used
for inotropic support stimulate adenylate cyclase to increase cAMP; hence prevention of breakdown of cAMP by
PDE inhibitors enhances the effects of inotropic agents. Milrinone not only enhances the inotropic effects of
epinephrine and norepinephrine, but causes vasodilation of the pulmonary circulation.
Pulmonary vasodilation has been demonstrated with the PDE V inhibitor sildenafil alone and in
combination with other vasodilators. (11) Sildenafil has been used as an oral premedication to decrease
perioperative PH. The FDA approved non-selective endothelin antagonist Bosentan and the investigative selective
endothelin-A Sitaxsentan also cause pulmonary vasodilation. (5) Both decrease PVR and improve CO. Adenosine
has also been shown to decrease PVR by increasing cAMP.
If the primary etiology for the RV failure is decreased contractility, virtually all beta-1 adrenergic agonists
will be effective therapies. Many studies have demonstrated that epinephrine, norepinephrine, dobutamine,
isoproterenol, and dopamine may be beneficial in managing RV failure secondary to decreased contractility. The
particular agent of choice may depend on the severity of myocardial dysfunction. In the presence of mildly
decreased RV contractility, dopamine or dobutamine may be appropriate. Of the two, dobutamine may be better
than dopamine in treating patients with PH and RV failure because it lacks alpha-1 adrenergic agonist effects and
the subsequent increase in PVR. Isoproterenol may also be used because it has positive inotropic effects and it
vasodilates the pulmonary circulation; however, its usefulness is limited by its profound tachycardic effects. More
severely decreased RV contractility may require treatment with more potent adrenergic agonists such as epinephrine
or norepinephrine. In the presence of systemic hypotension, norepinephrine may be an appropriate choice because it
not only provides inotropic support but it may also increase systemic pressure and RV CPP because of its relatively
potent alpha-1 adrenergic effects in comparison to its beta-2 vasodilating effects. The calcium sensitizer
Levosimendan is an investigational drug in a new class of inotrope that augments myocardial contractility while
decreasing PAP. (12) Pure alpha adrenergic agonists or vasopressin may also be useful in RV failure, because they
increase CPP and thus may reverse RV ischemia. However, these agents may increase PVR.
In an attempt to decrease PVR and increase CO, all inotropic agents can be used in combination with
vasodilators. The precise combination will depend on the degree of inotropic support and vasodilation required. PH
with mild RV failure may be treated with dobutamine, or combinations of dopamine or dobutamine plus
nitroglycerin. In the presence of severe RV dysfunction the more potent inotropic agents epinephrine and
norepinephrine, with or without milrinone, may be required. Milrinone alone may be useful, but the primary utility
of milrinone may be to potentiate the effects epinephrine or norepinephrine while adding pulmonary vasodilation.
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An intraaortic balloon pump may augment CO and subsequently decrease PVR. Right ventricular assist
devices that use a mechanical pump to withdraw blood from the right atrium and return blood to the pulmonary
artery have been demonstrated to support the failing RV.
Inhaled pulmonary vasodilator therapy
The primary inhaled pulmonary vasodilators used clinically are nitric oxide (NO) and prostacyclin (PGI2).
Inhaled vasodilators are selective to the pulmonary circulation, meaning they cause pulmonary vasodilation but not
systemic vasodilation. Inhaled NO acts by diffusing from the alveoli into the pulmonary vascular smooth muscle to
stimulate the production of cGMP which results in vasodilation.(13) NO is prevented from producing downstream
systemic vasodilation because it rapidly combines with hemoglobin. Inhaled PGI2 increases smooth muscle cAMP
to cause pulmonary arterial vasodilation but is hydrolyzed before producing systemic effects. Inhaled vasodilators
also have the potential to increase PaO2 in patients with ventilation/perfusion abnormalities. Since these drugs are
inhaled, vasodilation is primarily limited to areas that are ventilated, and hence, ventilation/perfusion matching is
improved and shunt is decreased. The effect of inhaled vasodilators on oxygenation is in contrast to IV vasodilators,
which vasodilate all lung areas, and potentially worsens oxygenation by inhibiting HPV in poorly ventilated areas.
Inhaled NO and PGI2 have been demonstrated to selectively vasodilate the pulmonary circulation and/or to
improve RV function in pediatric and adult cardiac surgical patients, patients with acute respiratory distress
syndrome, and patients with persistent pulmonary hypertension of the newborn. (13,14) Furthermore, numerous
case reports have demonstrated that inhaled NO may be lifesaving in weaning patients from CPB who have
pulmonary hypertension and RV failure. In patients with RV failure, PH and cardiogenic shock inhaled NO
decreases PAP and PVR while increasing RV stroke volume and CO. (15)
The primary advantage of inhaled vasodilators over intravenous vasodilators is that pulmonary vasodilation
is not accompanied by systemic vasodilation and the resulting decrease in CPP. Therefore, the greatest utility of
inhaled vasodilators is in patients with PH and systemic hypotension or in patients where a decrease in systemic
pressure would critically decrease CPP. In particular, in patients with systemic hypotension inhaled vasodilators
may reverse the pulmonary effects of alpha agonists used to treat of systemic hypotension. Inhaled NO and PGI2
may also be useful in treating patients with PH who are hypoxemic secondary to ventilation/perfusion abnormalities.
Unfortunately, long-term trials with inhaled NO in ARDS patients have shown the positive effects on oxygenation
are temporary and do not improve outcome. (16)
A number of inhaled agents in addition to NO and PGI2 have been demonstrated to be selective
vasodilators.(17) These include PGE1, NO donors, sodium nitroprusside, nitroglycerin, PDE inhibitors specific to
cAMP or cGMP, adenosine, and adrenomedullin. All have been shown to be effective and comparable to NO and
PGI2. Intravenous or inhaled milrinone may potentiate the effects of inhaled PGI2 by the same mechanisms by
which intravenous milrinone potentiate the effects of beta adrenergic agonists. (18). Sildenafil potentiates and
prolongs the effects of inhaled NO. (19). While inhaled NO is delivered as a gas via a specialized delivery system,
PGI2 and the other agents are delivered as simple nebulized drugs.
Most studies indicate that NO and PGI2 are equally effective in decreasing PAP and PVR. (14, 20) Both
cause rapid onset of pulmonary vasodilation that is proportional to the baseline PVR and the degree of
vasoconstriction. Both have dose-dependent effects that may change over the course of the therapy. Both also may
cause rebound PH because their prolonged use may downregulate endogenous vasodilator pathways. NO can result
in methemoglobinemia, although this effect is minimal with low dose NO. NO2 formation in the airway is also a
potential for toxicity but unlikely at low clinical inhaled NO concentrations. Both NO and PGI2 can increase
bleeding because of platelet inhibition, although this is usually not clinically significant. A major difference
between NO and PGI2 is that NO costs significantly more.
There are important differences between the effects of intravenous and inhaled vasodilators that dictate
their clinical utility. Intravenous vasodilators decrease PAP, CVP, PAOP, and systemic pressure. In contrast,
inhaled vasodilators decrease PAP but have minimal effect on LV preload and systemic pressure. In fact, inhaled
vasodilators may increase left ventricular end diastolic pressure in patients with LV dysfunction. (21) This is
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secondary to increased pulmonary blood flow in the absence of vasodilation of the pulmonary venous system. If the
desired effect is to decrease preload or systemic pressure, then intravenous agents may be a more appropriate choice.
If a decrease in PAP without a decrease in systemic pressure is critically important in the treatment of PH and RV
failure, then inhaled agents may be a more appropriate choice.
Inhaled Intravenous
PAP ↓ ↓
PAOP ± ↓
AoP ↔ ↓
CVP ± ↓
References
1. Ramakrishna G, et al: Impact of pulmonary hypertension on the outcomes of noncardiac surgery. J Am
Coll Cardiol. 1691-1699, 2005
2. Hoeper, MM, et al: Update in Pulmonary Hypertension 2005. Am J Respir Crit Care Med Vol 173. 499-
505, 2006
3. Blaise G, et al: Pulmonary arterial hypertension: Pathophysiology and anesthetic approach.
Anesthesiology 99:1415-32, 2003.
4. Bristow MR, et al: The pressure-overloaded right ventricle in pulmonary hypertension. Chest 114:101S-
106S, 1998
5. Sastry, BKS. Pharmacologic treatment for pulmonary arterial hypertension. Current Opinion in Cardiology.
Vol 21(6) 561-568, 2006
6. Schulte-Sasse U, et al: Pulmonary vascular responses to nitrous oxide in patients with normal and high
pulmonary vascular resistance. Anesthesiology 57:9-13, 1982
7. Gooding JM, et al: A physiologic analysis of cardiopulmonary responses to ketamine anesthesia in
noncardiac patients. Anesth Analg 56:813-16, 1977
8. Ziskind Z, et al: The effect of low-dose intravenous nitroglycerin on pulmonary hypertension immediately
after replacement of a stenotic mitral valve. Circulation 72:164-69, 1985
9. D’Ambra MN, et al: Prostaglandin E1-A new therapy for refractory right heart failure and pulmonary
hypertension after mitral valve replacement. J Thorac Cardiovasc Surg 89:567-72, 1985
10. Feneck RO and the European Milrinone Multicentre Trial Group: Intravenous milrinone following cardiac
surgery; II. Influence of patient factors and baseline haemodynamics on therapeutic response. J
Cardiothoracic Vasc Anesth 6:563-567, 1992.
11. Haj, RM, et al: Treatment of pulmonary hypertension with selective pulmonary vasodilators. Current
Opinion in Anesthesiology Vol 19(1) 88-95, 2006.
12. Takaoka S, et al. Current therapies for pulmonary arterial hypertension. Seminars in Cardiothoracic and
Vascular Anesthesia. Vol 11, 137-148, 2007
13. Steudel W, et al: Inhaled nitric oxide: Basic biology and clinical applications. Anesthesiology 91:1090-
121, 1999
14. Walmrath D, et al: Direct comparison of inhaled nitric oxide and aerosolized prostacyclin in acute
respiratory distress syndrome. Am J Respir Crit Care Med 153:991-6, 1996
15. Inglessis I: Hemodynamic effects of inhaled nitric oxide in right ventricular infarction and cardiogenic
shock. J Am Coll Cardiol 44:793- 798, 2004.
16. Griffiths, MJD, et al. Inhaled Nitric Oxide Therapy in Adults. New England Journal of Medicine.
353:2683-95, 2005.
17. Lowson SM: Inhaled alternatives to nitric oxide. Anesthesiology 96:1504-13, 2002.
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18. Haraldsson A: The additive pulmonary vasodilatory effects of inhaled prostacylin and inhaled milrinone in
postcardiac surgical patients with pulmonary hypertension. Anes Analg 93: 1439-1445, 2001.
19. Lepore JJ: Hemodynamic effects of sildenafil in patients with congestive heart failure and pulmonary
hypertension: Combined administration with inhaled nitric oxide. Chest 127:1647-1653, 2005.
20. Haraldsson A: Comparison of inhaled nitric oxide and inhaled aerosolized prostacyclin in the evaluation of
heart transplant candidates with elevated pulmonary vascular resistance. Chest 114, 780-786, 1998.
21. Semigran MJ: Hemodynamic effects of inhaled nitric oxide in heart failure. Am J Coll Cardiol, 24:982-
988, 1994.
DISCLOSURE
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Sepsis: Current Concepts and Perioperative Management

Mark E. Nunnally, M.D., FCCM Chicago, Illinois
Introduction
Sepsis continues to be a high-impact syndrome. In the U.S., about 250,000 people die of sepsis annually. Sepsis
kills more people than breast cancer, prostate cancer and AIDS combined (1). Sepsis is a comorbidity in many
major surgeries, is often responsible for an “emergency” designation. The increased morbidity and mortality of “E”
status patients can be attributed to sepsis physiology.
In an era of powerful antibiotics and a better understanding of how to use them, the primacy of sepsis should
confuse us as clinicians. In simple terms, our patients are dying of the same illness (infection) that other patients did
100 years ago. The details may be different, but sepsis still persists and perseveres. In recognition of this
phenomenon, basic science research, translational clinical trials and guidelines production continue at a fast pace.
Sepsis is a spectrum of disease, requiring aggressive and timely management. The topic for speculative discussion
is the body’s common response to illness. Finally, sepsis is ideal for examining the way clinical care is delivered
and directed at institutional, societal and governmental levels.
The sepsis syndrome: common themes
Sepsis has been defined by a loose set of criteria (2), among which are signs of inflammation. These signs are
linked to known or suspected infection. Another system for describing the syndrome is the PIRO model
(predisposition, infection, response, and organ dysfunction) (3). The criteria for defining and characterizing sepsis
are nonspecific. For example, urosepsis is clinically different from sepsis with influenza, even though many factors
are common to both.
Table: Broad diagnostic criteria for sepsis (Modified from reference 2):
Infection: documented or suspected
General variables: T > 38.3 or < 36°C, HR > 90/min,  RR, encephalopathy, edema or
positive fluid balance, hyperglycemia
Inflammatory variables: WBC > 12,000 or < 4000/mcL, > 10% immature forms,  C-reactive
protein, procalcitonin
Hemodynamic variables: SBP < 90, MAP < 70 mmHg or  > 40 mmHg, SvO2 > 70%, Cardiac
Index > 3.5 L/min
Organ dysfunction variables: hypoxemia, oliguria,  creatinine, coagulopathy, ileus,  platelet

count,  bilirubin
Tissue perfusion variables:  lactate,  capillary refill, mottling
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Central to sepsis is inflammation. Systemic responses to infection range from elevated white blood cell counts to
fever to hyperglycemia to changes in intercellular mediators. Inflammation has been the main focus of sepsis
research for over 40 years. Patients don’t usually die from inflammation, however; they die from organ dysfunction.
Organ dysfunction in sepsis takes many forms and affects every organ system. Renal (e.g., acute kidney injury),
vascular (vasoplegic shock) and respiratory failure (acute lung injury/acute respiratory distress syndrome) are well
recognized sequelae of severe sepsis, but endocrine (hyperglycemia), neurologic (encephalopathy), and
gastrointestinal (ileus) dysfunctions often presage severe sepsis and are signals to intervene before the syndrome
worsens.
Why do patients become septic?
Infection drives the septic response, consistent with the original definition of sepsis. Yet many systemic changes
during the sepsis syndrome are common to noninfectious causes of inflammatory responses. The systemic
inflammatory response syndrome (SIRS) criteria recognize this fact. SIRS criteria describe a sepsis-like syndrome
without a known or suspected infection.
Components of SIRS are conserved across animal species, and in multiple animal models these components protect
an organism from ongoing damage and allow it to heal. The overlap of inflammation, coagulation, metabolism,
immunologic function, neurologic function, and tissue growth is the result of a complicated network of signals and
activities that correct derangements and repair damage. In a case of modern sepsis, these responses can seem
appropriate or inappropriate, although it is not always clear which is the case. With intensive care, patients survive
previously fatal injuries, changing the natural history of the syndrome. Modern critically ill patients are unique and
their illness has progressed to physiology that would never be seen in “the wild.” Many feel that the acute responses
of the sepsis syndrome are adaptive, but that in later phases (i.e., chronic sepsis) dysfunction becomes prominent. It
is in the later phases when many patients die.
Sepsis management: key interventions
The Surviving Sepsis Campaign, first launched in 2002, details the evidence in support of sepsis therapy, translating
the large body of sepsis literature into guidelines (4). Timely diagnosis, antibiotic therapy and goal-directed fluid
resuscitation are key components of sepsis management. Several of the suggestions and recommendations directly
influence management in the operating room. The anesthesia care team contributes to care by managing shock
resuscitation with physiologic goals such as mixed-venous oxygen saturation and lactate clearance; by drawing
blood, urine and sputum cultures to confirm diagnoses; and by facilitating the timely administration of antibiotics
(ideally after cultures are drawn, but as quickly as possible). Central venous and arterial access helps with
resuscitation and management. Support of failing organs is ideally suited to anesthesiologists and should be viewed
as akin to management in the intensive care unit. With surgical sources of sepsis, the locale of the intervention
(intensive care unit versus operating room) should make no difference in the goals of resuscitation and antibiotic
therapy. Facilitating timely surgical intervention, however, can make a major difference in outcomes.
What sort of a difference can these interventions have? Absolute mortality from sepsis decreased more than 6% as
compliance with Surviving Sepsis Campaign recommendation bundles increased (5). Curiously, compliance in one
study increased from 18.4 to 36.1%, suggesting that the recommendations are neither easily nor frequently adopted.
Both evidence and rationale support timely intervention. Anesthesiologists can and should strive to facilitate
cultures, antibiotics and resuscitation for septic and suspected-septic patients in their care.
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An evolving understanding
Any improvements have to be viewed in light of limited progress and continuing mortality. What has been
accomplished in sepsis research in the last 40 years? Goal-directed resuscitation and antibiotics reduce morbidity
and mortality. In fact, indirect evidence suggests that exposure to a septic source over time increases the collateral
physiologic damage and overall organ dysfunction burden. At the same time, the “goals” of resuscitation and timing
of antibiotic therapy remain controversial. One may speculate about whether a fixed goal such as a mixed venous
saturation greater than 60% is as important as attention to other clinical signs in an unstable patient. Aggressive
early antibiotic administration can lead to improper use of antibiotics when a diagnosis of sepsis is unclear, as during
an exacerbation of congestive heart failure.
Investigations document multiple failed therapies. Many of the studies were of inflammatory mediators because of
the theory that the inflammatory response to infection leads to organ dysfunction in sepsis. A long list of failed
therapies, including anti-TNF alpha, ibuprofen, anti-IL-2, branch-chain amino acids and, most famously, drotrecogin
alfa (activated protein C), suggests that not only is a single magic bullet for sepsis unlikely, but that the model for
therapeutic intervention may be wrong. Although inflammation is a key component of sepsis syndromes, immune
suppression, altered endocrine activity and decreased autonomic signaling appear to influence disease progression.
Since the septic patient who dies does so in a state of chronic critical illness after multiorgan failure, a new model of
disease and therapy is necessary. Sepsis patients manifest neuroendocrine exhaustion, immune dysfunction and
energy failure. These findings may provide an opportunity for intervention. In the future, therapies targeting the
central nervous system, hormones, or inflammatory cell apoptosis may improve outcomes more than therapies
targeting inflammation.
An administrative issue
Given the substantial impact that sepsis has on morbidity and mortality, the case has been made for aggressive
management and research investment. The successes of the Surviving Sepsis Campaign argue that recommendation
bundles directed at evidence-based and standardized care make a substantial difference. There is, however, a caveat.
The failures in sepsis management, best documented by the long list of failed anti-inflammatory therapies, suggest
that simple, single solutions will not be common. Controversy continues around resuscitation and antibiotic therapy.
Many adjunctive therapies, such as glucocorticoids, tight glycemic control and pulmonary artery catheter-directed
resuscitation have not fulfilled the promise they had 10 years ago- a warning. Are we too easily tempted to throw
ineffective therapies at a largely insoluble problem? Clinicians who treat disease may be willing to embrace a
therapy just to be able to do something. They want to be optimistic.
At an administrative level, problems like sepsis are an opportunity for regulation, standardization and general
control. Pundits argue eloquently that care variability is the problem and that standardization lets more patients get
better care. Guidelines that are useful tools to help clinicians manage complex problems also restrict their ability to
respond uniquely to unique circumstances. There is a tradeoff. In the case of sepsis, the tradeoff has some benefit
in improving outcomes but should not be taken for granted. The failures in sepsis tell a story about a quest for an
easy solution that sometimes misses the important elements altogether. Re-thinking the problem might reveal elusive
opportunities.
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Conclusions
As anesthesia providers, we must be prepared to deliver the best care to patients with sepsis, participate in the
discussions about its causes and treatments, investigate new ideas, and generate and promote measures that can
improve outcomes. Our unique skills in critical care and resuscitation make us ideally suited to these tasks. At the
same time, we understand as well as any physician the complex nature of medical therapies, the assets and liabilities
of guidelines, and the need to think critically about them during care and consultation. We can continue to care for
septic patients with fluids, vasopressors, inotropes, cultures, monitoring and antibiotic therapy while supporting
organ function. But as clinical experts in neurosciences, anesthesiologists have an opportunity to investigate new
means of treating sepsis. Finally, as experts in safety and guidelines management, anesthesiologists can offer
valuable expertise to future guidelines efforts.
References:
1. NIH Sepsis Fact Sheet. Available from: http://www.nigms.nih.gov/Publications/factsheet_sepsis.htm. Accessed

May 23, 2012
2. Levy MM, Fink MP, Marshall JC, et al. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definition
Conference. Crit Care Med 2003;31(4):1250-6
3. Rubulotta F, Marshall JC, Ramsay G, et al. Predisposition, insult/infection, response, and organ dysfunction: A
new model for staging severe sepsis. Crit Care Med 2009; 37(4):1329-35
4. Dellinger RP, Levy MM, Carlet JM, et al. Surviving Sepsis Campaign: international guidelines for management
of severe sepsis and septic shock. Crit Care Med 2008; 36(1):296-327
5. Levy MM, Dellinger RP, Townsend SR, et al. The Surviving Sepsis Campaign: results of an international
guideline-based performance improvement program targeting severe sepsis. Crit Care Med 2010;38(2):367-74
DISCLOSURE
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Using Evidence in Perioperative Medicine

Brenda G. Fahy, M.D. Gainesville, Florida
INTRODUCTION
EVIDENCE BASED MEDICINE (EBM)
Evidence based medicine (EBM) involves the application of the scientific method to medical practice and clinical
decisions replacing the traditional authority based medical paradigm. A common definition and explanation of
evidence based medicine “…is the conscientious, explicit, and judicious use of current best evidence in making
decisions about the care of individual patients. The practice of EBM means integrating individual clinical expertise
with the best available external clinical evidence from systematic research. Individual clinical expertise is the
proficiency and judgment that individual clinicians acquire through clinical experience and clinical practice.” 50 This
approach involves incorporating the best available scientific literature to substantiate clinical decision making with
the hopes that this will reduce inherent bias that may be present when recent experiences unduly influence
scientifically unsubstantiated care decisions. EBM strives to integrate the physician’s clinical experience (including
cumulative clinical experience, education, and skills), the best scientific evidence for the particular clinical decision,
and patient preferences and values. However, the evidence by itself does NOT determine the clinical decision; EBM
represents one part of the process. The health care provider must examine the risk(s) and benefit(s) of a data based
clinical decision while incorporating individual patient factors. These individual patient factors include personal
experiences, expectations, and values that can impact and at times limit clinical decision making for those unique
circumstances.
What does best evidence entail?

The best evidence is often found when well designed investigational methodology has been used to generate
clinically relevant research. A properly randomized prospective (and ideally blinded) double placebo controlled
clinical trial is a powerful tool to evaluate the effectiveness of one therapy compared to another. However, the
quality and design of the trial can impact the validity and application of the results. For example, a trial with
prohibitively narrow inclusion criteria may not be valid for extrapolation and application to a general population.
Some clinically relevant questions may be more appropriately answered by a carefully designed observation study
than a randomized controlled trial. Certain patient populations, such as the critically ill patients, also may present
logistical and ethical difficulties for research.
What advantages might EBM confer?

Patient encounters generate clinical decision process questions that would be appropriate to apply to EBM. When
studied, only 30% of the physicians’ informational needs for these clinical questions were met during the patient
visit. The majority of questions generated by those physicians were answered by utilizing another colleague.12
Further direct observational study revealed an average of 5 physician generated questions per patient encounter;
52% of these questions could be answered by medical record review or hospital information system query while
25% required review of published information in a textbook or Medline.46 Evidence based medicine removes the
bias of “my experience” care, which can result in therapy that is based on personal experience rather than the best
available evidence. According to studies, American healthcare “gets it right” 54.9% of the time.42
Does EBM application lead to change?

The literature says yes. Using an evidence based cart on hospital rounds led to new therapy or diagnostic tests 25%
of the time and corrected a previous plan 16% of the time.51 EBM requires critical evaluation of the literature so that
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decisions may be based on the strongest applicable evidence. This critical evaluation entails assessing study
validity and design while evaluating the applicability of the final results to this unique patient’s circumstance.
Why is EBM important for perioperative care?

More than thirty million major operations are performed yearly in the United States.5 Despite continued medical
advances in both anesthesia and surgery, and improvements in perioperative care, there still remain variations in
outcome for patients undergoing similar procedures and interventions. Postoperative complications are a major
cause of mortality and excess length of hospital stay and hospital costs.16 Independent of preoperative patient risk,
the occurrence of a complication within the first 30 days of the postoperative period reduced median patient survival
by 61%.33 Many of these complications are potentially preventable.
APPLICATION OF EBM TO PERIOPERATIVE GLUCOSE MANAGEMENT
This handout focuses on one specific globally pertinent perioperative issue - glycemic control. The discussion
reviews current evidence and outlines advantages and limitations of application of evidence based medicine in
perioperative glucose management.
Scope of the problem and implications of hyperglycemia

Approximately 20 million adults (8-10% of the adult population) in the United States have diabetes mellitus.44 Over
90% have type 2 diabetes with deficient insulin production, insulin responsiveness, excessive gluconeogenesis or a
combination of these factors. Diabetes is the 6th most common cause of death in the United States4 with the risk of
death amongst diabetics approximately double that of non-diabetics for the same age.44 Hyperglycemia, even
without the diagnosis of diabetes, is an independent risk factor for sudden cardiac death, myocardial infarction,
cerebral vascular accident, or poor outcome after ICU admission.8, 9, 35, 49 Given the significant morbidity and
mortality11 associated with diabetes and concerns over stress hyperglycemia, various regulatory organizations and
learned societies drafted guidelines on management of perioperative hyperglycemia.3 The following focuses on the
current evidence supporting such recommendations, the need for additional data, particularly regarding the incidence
of intraoperative hypoglycemia, and outlines on-going efforts to address unresolved management issues in
optimizing care of patients with perioperative hyperglycemia.
Hyperglycemia has been shown to impair leukocyte functions,64, 65 resulting in compromised wound healing and
exacerbating other complications (e.g., ischemia). Hyperglycemia also results in increased cytokine levels and
inflammation.34, 56 Particularly noteworthy, is that potent pro-inflammatory signals are generated by an interaction
between advanced glycation end products and various receptor agonists.65 These signals in turn amplify the
expression of the receptor for advanced glycation which can lead to a positive feedback mechanism that potentially
may permit acute inflammation to transition to a chronic state.32
Hospitalized patients and elective surgery patients

Hyperglycemia occurs frequently in hospitalized patients. In a study of 1034 screened hospitalized patients with no
prior history of diabetes, 33% of surgical patients and 38% of medical patients had at least one serum glucose of
greater than 200 mg/dl with two-thirds of these patients having two or more serum glucose levels of greater than 200
mg/dl.40 Hyperglycemia in another study occurs in 38% of hospitalized patients: 26% with a prior history of
diabetes but 12% with no prior history of diabetes.57 Newly discovered hyperglycemia has been linked to adverse
outcome with an 18 fold increase in hospital mortality, longer length of stay, and a higher risk of infection.49
Diabetics are conservatively estimated to represent approximately a quarter of hospitalized patients,10 and are more
likely than non-diabetics to undergo surgery. In diabetic patients undergoing elective surgery, 48 a blood glucose
level > 220 mg/dl resulted in a 5.8 fold increase in nosocomial infections on the first postoperative day compared to
those with lower glucose levels.
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Cardiac surgery patients

Cardiac surgery glucose levels of greater than 200 mg/dl within the first 48 hours postoperatively doubled the risk of
surgical site infections.36 Hyperglycemic events occurred in patients without a prior history of diabetes 47% of the
time in this study. In diabetic patients during cardiac surgery, four consecutive intraoperative glucose levels of
greater than 200 mg/dl worsened hospital outcome.47 Recent studies further examining the impact of long term
glucose control in diabetics revealed in a single academic medical center that diabetics undergoing primary, elective
coronary artery bypass grafting with an elevated hemoglobin A1c had an increased risk of adverse events including
hospital mortality and deep sternal wound infections compared to diabetics with lower hemoglobin A1c reflecting
better long term glucose control.31
In the Portland Diabetic Project, the outcome of 5,510 consecutive diabetic cardiac surgery patients over an 18 year
period revealed that an average glucose of >150 mg/dl for the first three postoperative days was an independent
predictor of mortality, deep sternal wound infection, and increased length of stay.25 Continuous intravenous insulin
infusions were shown to independently reduce the risk of death and deep sternal wound infection. Each deep sternal
wound infection increased care costs and extended hospitalization 16 days.26 Although glucose was controlled
intraoperatively, there was no standardization. Tight glycemic control resulted in no significant higher risk of death
and stroke. In a prospective randomized controlled study,28 patients undergoing cardiac surgery were randomized to
maintain intraoperative glucose with insulin therapy in the range of 80 to 110 mg/dl compared to treatment of
glucose only if >200 mg/dl. Both groups received postoperative insulin infusions. The intensive insulin therapy had
lower glucoses on arrival to the ICU, however, with more deaths and strokes after surgery although this was not
statistically significant. There was no difference in length of ICU or hospital stay between the two groups. A
subsequent systematic review and meta-analysis of perioperative glycemic control in patients undergoing any
surgery showed a trend toward lower mortality with intensive insulin therapy with a higher incidence of
hypoglycemia.29 The authors advocated the collection of additional data.29
Anesthesia and Glucose Homeostasis

The magnitude of surgical trauma in part determines the degree of insulin resistance and thus may impact anesthetic
management. Minimally invasive surgical techniques have less endogenous glucose release and production of
oxidized lipids compared to open procedures.55 Inhaled volatile anesthesia can inhibit insulin secretion and increase
hepatic glucose production37 while regional anesthesia can decrease both intra-and postoperative glucose
production.17, 37, 38 Techniques for perioperative pain management may also have an effect on perioperative glucose
as insulin resistance is decreased in orthopedic patients with perioperative regional anesthesia techniques compared
to patient controlled analgesia 17, 38. Administration of an oral carbohydrate beverage several hours preoperatively
can decrease whole body insulin sensitivity52 and require less inotropic support weaning from cardiopulmonary
bypass.6 Additional benefits may be derived from improved glucose control including in patients who received a
preoperative carbohydrate beverage had a decrease expression of a marker for immunocompetence, Human
Leukocyte Antigen (HLA)-DR compared to controls.43
Intensive Care Unit (ICU) patients

In 2001, Van den Berghe and colleagues performed the first large, major study in a surgical intensive care unit
(SICU) with intensive insulin infusion therapy. This prospective controlled randomized trial enrolled 1548 patients,
all surgical patients, with two-thirds having undergone cardiac surgery. Patients were randomized to receive insulin
for glucose levels above 215 mg/dl versus intensive insulin therapy to maintain glucose between 80 to 110 mg/dl.
All patients on admission received 300 gram of intravenous glucose over a 24 hour period. Overall hospital
mortality rates were 37% lower with tight glucose control with the mortality advantage occurring in patients without
a prior history of diabetes. 59
The Stamford Project used a before and after design for a 14-bed mixed medical/surgical/cardiac ICU. Following
development of an insulin protocol, 800 consecutive patients were followed. Their outcomes were compared to a
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control group of 800 consecutive patients cared for during the period immediately prior to initiation of an insulin
protocol targeting a blood glucose of < 140 mg/dl. 35 Compared to controls, the insulin protocol resulted in
significant improvement in mortality, shorter ICU stay, and better glycemic control.
In a second randomized controlled trial by Van den Berghe in 2006 in 1200 medical ICU (MICU) patients, intensive
insulin infusion therapy to achieve goal glucoses of 80 to 110 mg/dl was compared to the conventional therapy with
goals of 180 to 200 mg/dl.60 Intensive insulin therapy significantly reduced morbidity but not mortality in the MICU
patients who required three or more days in the ICU; but increased mortality in MICU patients who required less
than three days in the ICU. There was a higher incidence of hypoglycemia with the intensive insulin therapy which
raised warnings on potential long term impact41 but was not shown to be associated with mortality.
Due to safety concerns triggered by Van den Berghe’s trials, her group performed a pooled analysis of 2748 patients
enrolled in both randomized controlled trials in the ICU.61 Intensive insulin therapy reduced mortality in these
populations without increasing mortality in patients with short ICU lengths of stay. The incidence of one or more
hypoglycemic episodes was more common during intensive insulin therapy yet death within 24 hours after a
hypoglycemic episode was more frequent in the conventional treatment group. Following a hypoglycemic episode,
there was no increase in delayed mortality or neurological sequelae, although these were not specifically sought data
in the study. When analyzed further there was no survival benefit for BG < 110 mg/dl for patients with a history of
diabetes and there appeared to be a trend toward increased mortality in the diabetic population..
To address the same issue in a nested-case control study62 using a mixed medical-surgical ICU population, 156
consecutive patients with hypoglycemia during intensive insulin therapy were matched with 155 patients at risk for
hypoglycemia. Three patients had possible hypoglycemic induced coma and/or general seizures although there was
no overall risk of increased mortality caused by hypoglycemia. Risk factors that were independent predictors of
hypoglycemic episodes were a decrease in the rate of nutritional supplementation with the same insulin infusion
rate, use of bicarbonate substitution fluids during hemofiltration, preexisting diabetes, sepsis, and inotropic
support.63
A multicenter German trial (VISEP trial)7 was recently halted following enrollment of 537 medical or surgical
patients with severe sepsis comparing conventional versus intensive insulin therapy because of frequent
hypoglycemic episodes associated with intensive insulin therapy (17% with intensive insulin versus 4% with
conventional therapy) mortality. In Europe the Glucontrol trial investigators, examined titration of insulin therapy
to achieve blood glucose levels of 80-110 versus 140-180 mg/dl. It was stopped prematurely15 after inclusion of only
1100 patients of a planned 3500 due to a higher rate of hypoglycemia (< 40 mg/dl) and associated higher mortality
with one episode of hypoglycemia in the tight glucose control (80-110 mg/dl) group. A meta-analysis of 29
randomized controlled trial with over 8,000 patients found no difference in hospital mortality if glucose goals were
≤ 110 mg/dl versus < 150 mg/dl or based on ICU setting (surgical, medical, or combined surgical-medical).
However, there was a significant increase in hypoglycemia with intensive insulin therapy.53
The NICE-SUGAR (Normoglycemia in Intensive Care Evaluation and Survival Using Glucose Algorithm
Regulation) trial conducted by the Australian and New Zealand Intensive Care Society and the Canadian Critical
Care trial group and involving U.S. sites as well enrolled 6104 medical and surgical ICU patients titrating insulin
therapy to achieve blood glucose levels of 80-108 versus 144-180 mg/dl.45 There was a higher 90-day mortality with
intensive insulin therapy compared to controls with no difference in median days in the hospital or ICU, mechanical
ventilation, or renal replacement. A meta-analysis30 included NICE-SUGAR involving 26 trials with 13,000
patients showed no overall effect on 90-day mortality with intensive insulin versus conventional therapy. There was
a pooled relative risk of 6.0 for intensive insulin versus conventional therapy in 14 trials involving over 12,000
patients. When contributing factors were examined there was a benefit of intensive insulin versus conventional
therapy from 5 trials in surgical ICUs with the majority of patients being cardiac surgery patients; no benefit was
observed in medical ICUs or mixed medical-surgical ICUs.
Since the NICE-SUGAR trial, further analyses have raised concerns about the risks of hypoglycemia. In a
retrospective analysis of almost 5,000 ICU patients, 22% had experienced at least one episode of hypoglycemia
(defined as glucose < 81 mg/dl)18 Mortality increased significantly and increased further the lower the glucose the
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hypoglycemic episode. After adjustment for insulin therapy or timing of hypoglycemic episodes, the risk of death
was increased the lower the glucose level with the hypoglycemic episode.
So what does the evidence say?

The optimal target for blood glucose remains unclear and is a key clinical question.23 The evidence is conflicting
with benefits of tight glucose control in certain populations; while other patient populations failed to reap significant
benefits and had significant risks of hypoglycemia. Some trials have been halted because of concerns related to
higher mortality following a hypoglycemic episode(s) associated with achieving target glucoses of 80-110 mg/dl.
Hypoglycemia episodes have associated morbidity including coma and seizures with long-term sequelae including
cognitive dysfunction with more recent data further supporting these concerns and further study is required. In
addition, delineation as to whether the risks of a hypoglycemic episode and whether the definition of symptomatic
hypoglycemia are the same or higher for a newly diagnosed hyperglycemic patient without a history of diabetes
versus long standing diabetes remain to be clarified. Whether the glucose thresholds for treatment and acceptable
ranges should differ for those with preexisting diabetes versus newly diagnosed hyperglycemia has yet to be
answered. The variability of blood glucose concentration19 may be as deleterious as hypoglycemia and is currently
under further investigation. When is the ideal time to begin glucose management? The studies differ on when
glucose management was instituted. In the first randomized control trial in the ICU, therapy was initiated
immediately postoperatively in a SICU population before complications were evident; whereas in the same
institution a subsequent MICU study initiated insulin therapy after there were complications of multiorgan failure.
This latter study failed to show an improvement in outcome but raised safety concerns with hypoglycemia. With the
potential for the hyperglycemic complications including surgical site infections and release of proinflammatory
mediators, early intervention to prevent hyperglycemia would seem reasonable. But, strong evidence is currently
lacking and at the current time there exist no large data base for intraoperative glucose management or
hypoglycemia. Intraoperative hypoglycemia is more worrisome due to lack of the early warning signs. Continuous
monitoring of glucose13 may be a future option to limit these complications but the data is sparse.21 There are
numerous factors that can impact reliability of point-of-care blood glucose measurements22 which must be taken into
account. Circumstances such as anemia or peripheral hypoperfusion due to dehydration or shock may exist in the
intraoperative and perioperative periods and reduce inaccurate glucose measurements. Is there an ideal level of
glucose which might confer benefit and avoid risk? Three large retrospective trials24, 27, 35 have found that glucose
levels below 140 mg/dl compared to higher levels resulted in improved outcomes. Another study16 found poor
intraoperative glucose control (defined as a failure to achieve glucose levels below 144 mg/dl) resulted in
significantly more postoperative morbidity and a higher adjusted odds ratio for severe postoperative morbidity
among those with poor intraoperative glucose control compared to those with intraoperative glucoses below 144
mg/dl. The largest randomized study in the ICUs found glucose levels of 144-180 mg/dl had a lower 90-day
mortality rate than glucose levels of 80-108 mg/dl.45 Questions remain as to the appropriate range(s) of glucose
levels for control. Whether this data can be extrapolated to all patients who become hyperglycemic during the
perioperative period remains unknown. The mortality curve with glucose appears to be a J-shaped curve with
mortality the lowest when glucose is normal for age and highest with hyperglycemia.58 There is also an increased
mortality with hypoglycemia.
Recent recommendations by organizations have recognized the risks of hypoglycemia with the Society of Thoracic
Surgeons published practice guidelines recommending during adult cardiac surgery blood glucose should be
maintained less than 180 mg/dl intraoperatively and at least 24 hours postoperatively.39 However, this guideline does
not adequately address many of the risks of treatment of hyperglycemia including hypoglycemia and limitations of
glucose monitoring techniques.1,14, 20, 22, 54
Recognizing recent concerns, the American Diabetes association is now recommending that a starting threshold for
treatment of glucose in critically ill patients should be 180 mg/dl with glucose maintained 140-180 mg/dl.2 This
guideline recognizes that additional benefits may be achieved at the lower end of the range but cannot recommend
targets <110 mg/dl.
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What is the ideal regime? The ideal method and frequency of glucose monitoring in the perioperative period has not
undergone rigorous study nor has there been identification of the true incidence of intraoperative hypoglycemia.
Tight glucose control also costs resources including personnel costs to monitor glucoses and regulate the insulin
infusion.
SUMMARY
The application of the scientific method to medical practice and clinical decision making to provide improved
outcome in perioperative care can present a significant challenge. The evidence for prevention of
venothromboembolism in the perioperative period has been much more rigorously evaluated in high-risk patient
populations then perioperative glycemic control. Although EBM involves the use of the scientific method to
medical practice and clinical decision making, the “evidence” requires critical evaluation and appropriate
application. Glucose control in the perioperative period includes guidelines that have been developed by reputed
societies but may not be extrapolated to all patients in the perioperative period. In fact, with some of the current
trials failing to show benefit and reporting a risk of hypoglycemic episodes and in one study a higher rate of death
and stroke with intensive insulin therapy, these current recommendations may need further scrutiny and will require
further scientific evaluation. There are many unanswered questions concerning glycemic control. However, first do
no harm and maintaining the safety of surgical patients throughout the perioperative course remains of prime
importance. More data is needed particularly for intraoperative management of glucose and will hopefully be
forthcoming with appropriate interpretation and incorporation into various current protocols and guidelines.
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DISCLOSURE
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Transfusion Therapy: Optimal Use of Blood Products

Stephen Surgenor, M.D. Lebanon, New Hampshire
Introduction
Despite decades of effort, transfusion therapy practice remains suboptimal. This review will examine the
risks and benefits of red blood cell (RBC), platelet, and fresh frozen plasma (FFP) transfusions, as well as strategies
to optimize transfusion practice for each of these components. The American Association of Blood Bankers 2009
Nationwide Blood Collection and Utilization Survey Report describes the current status of blood utilization in the
United States. Key findings include that collection of autologous and directed blood is decreasing and now
represents less than 2 percent of total donation. Second the use of leukocyte reduction continues to increase and
now 80 percent of RBC units are treated. Figure 1 describes the collection and transfusion of blood nationally.
Demand for blood transfusions continues to rise. During 2004, the total number of units transfused was 15 million
units, up 7 percent from 2006.
Figure 1. Allogeneic whole blood and red blood cell collections and transfusions: 1989 – 2008.
Source: American Association of Blood Bankers 2009 Nationwide Blood Collection and Utilization Survey Report.
Variation in Transfusion Practice

Tremendous variation in the indications for and timing of transfusions exists. Large variations in the
indications for and timing of RBC transfusion have been documented for many years among coronary artery bypass
graft (CABG) surgery patients1 2. Importantly, this variation is not explained by patient or surgical variables, but
rather by differences in provider and institutional preferences3. More recently, another observational study
demonstrates that variation continues across institutions in Canada despite new knowledge about the benefits and
risks of RBC transfusions4. Such variation is not limited to just RBC transfusions. Similar observations have been
made for use of platelets and plasma during CABG surgery in Veterans Administration hospitals5. The presence of
significant variation in transfusion rates implies that the best practice has yet to be identified, and that indications for
transfusions are not consistent among providers.
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Guidelines
This variation persists despite the availability of practice guidelines. One of the oldest guidelines for RBC
transfusion is the “10/30” rule which originated from comments made by Adams and Lundy in 19426. Several RBC
transfusion guidelines have been published based on best available evidence by the National Institute of Health
(1988), the American College of Physicians (1992), the Blood Management Practice Guidelines Conference (1995),
as well as the American Society of Anesthesiologists. Most recently, a comprehensive guideline has been developed
by the Society of Cardiovascular Anesthesiologists for the cardiac surgery population7. There has been less activity
to develop guidelines for platelet and plasma therapies; the only one was developed by the College of Americen
Pathologists in 19948. The American Society of Clinical Oncology has developed guidelines for platelet therapy
among the oncology population, which are not easily generalized to either peri-operative or critically ill patients9.
While medical guidelines are believed to be an efficacious method to improve medical care, they have been
relatively ineffective in reducing unwarranted transfusions for several reasons. Specific to RBC transfusion, one
prescribed trigger is not appropriate for all patients and clinical settings, because a consistent physiologic
deterioration in is not observed among all patients at the same hemoglobin level. Second many physicians remain
unaware of available transfusion guidelines.
Today we are better positioned to optimize our use of transfusions than we have been in the past. This is
possible because of a rapid growth in our understanding of not only the risks of anemia, but the risks and benefits of
RBC unit storage and transfusion over the last decade. By understanding the current evidence regarding the
treatment of anemia with RBC transfusion, we can significantly decrease the local, regional, and national variation
currently witnessed for transfusions. Specific to the use of fresh frozen plasma (FFP) and platelets, the risks and
benefits of transfusion are less certain. However, there is growing evidence regarding the risks of transfusing FFP
and platelets that are relevant when making decisions to administer these products.
Red Blood Cell Transfusions

Risks of Anemia
There are numerous reports of severe anemia being well tolerated in healthy subjects. Acute normovolemic
hemodilutional anemia has been safely performed with animal models with dogs and baboons, as well as with
human subjects with and without surgery. Data from patients who decline RBC transfusion for religious reasons
suggests that mortality is more related to substantial blood loss than a low preoperative hematocrit per se.
Importantly this effect was significantly more pronounced among patients with cardiovascular disease10.
Studies from several prospective observational cardiac surgical databases have reported associations of
hemodilutional anemia during cardiopulmonary bypass (CPB) with increased risk of renal failure, stroke, and
mortality during coronary artery bypass graft (CABG) surgery. Plausible explanations for these observations
include direct injury as a result of exposure to hemodilutional anemia or alternatively that these associations a a
marker for another unmeasured process. One such process could be exposure to intra-operative RBC transfusions
administered as treatment for anemia.
A report by the Northern New England Cardiovascular Disease Study Group observed that among patients
managed without intra-operative RBC transfusion, exposure to hemodilutional anemia during CPB was associated
with Low Output Failure (increased need for prolonged inotropes, post-CPB intra-aortic balloon pumps, and return
to CPB after initial separation) (Figure 2)11. These observations support the concept that intraoperative anemia
reduces the oxygen supply available to the tissues to adequately meet demand, leading to ischemic tissue injury and
subsequent adverse outcomes.
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Figure 2. Crude risk of Low Output Failure by quartiles of lowest hematocrit during cardiopulmonary bypass
stratified by RBC transfusion.
Benefits of RBC Transfusion to treat Anemia

The long standing belief for RBC transfusion is that giving back blood will reverse the ill effects of anemia.
We now have three prospective trials comparing liberal and restrictive transfusion strategies among critically ill and
peri-operative patients.
The first prospective trial of RBC transfusion therapy in critically ill patients without active bleeding was
published in 199912. The Canadian Transfusion Requirements in Critical Care, or TRICC trial, evaluated a
restrictive strategy of maintaining hemoglobin between 7 and 9 g/dL versus a liberal strategy of maintaining
hemoglobin between 10 and 12 g/dL. Inclusion criteria included anemic euvolemic patients who were not actively
bleeding. Patients with chronic anemia of following cardiac surgery were excluded, and a large number of patients
with significant coronary artery disease were not enrolled in the study at the discretion of the attending physician.
This study showed that the restrictive strategy was “at least as effective as and possibly superior to a liberal
transfusion strategy.” Furthermore, subgroup analysis showed an association of improved 30 day survival in
patients younger than 55 years old or those with APACHE II scores lower than 20 managed with the restrictive
strategy.
A more recent prospective trial of RBC transfusion during cardiac surgery was completed in Brazil13.
Among 500 patients undergoing cardiac surgery with CPB, a restrictive transfusion strategy of tolerating anemia to a
hematocrit of 24% was just as efficacious as a more liberal goal of maintaining hematocrit above 30%. The rate of
RBC transfusion was 78 percent vs. 47 percent in the liberal versus restrictive groups. These finding are consistent
with the TRICC trial conclusions.
Finally there is a prospective trial of liberal (greater than 10 g/dL) vs. restrictive (less than 8.0 g/dL)
strategies among high risk patients after hip surgery14. Similar to the previously mentioned trials, there was no
outcome benefit, as measured by death or inability to walk without assistance, to patients from a more liberal
approach to transfusion. Nearly 97 percent of patients in the liberal group were transfused withRBCs. In the
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restrictive group, far less blood was administered, and only 40 percent of these patients were exposed to RBC
transfusions.
There is one other randomized trial that provides some evidence regarding the role of RBC transfusion as
part of early goal directed fluid therapy for treatment of sepsis or septic shock. Rivers et al. randomized septic
patients to either standard resuscitation or an explicit goal-directed protocol15. RBC transfusions were indicated in
the goal-directed protocol to maintain central venous oxygen saturation greater than 70 percent, if the hematocrit
was less than 30 percent. Patients in the early goal directed group experienced superior hospital, 28-day, and 60 day
mortality compared to patients managed with standard resuscitation. Because there were multiple interventions used
in this protocol, it is not possible to separate the relative importance of RBC transfusion to the survival benefit.
Risks of RBC Transfusion

During the 1990s, the risks of RBC transfusion seemed to be well characterized. For example, there are
well defined risks of viral transmission for cytomegalovirus, hepatitis C, hepatitis B, HIV and HTLV via
transfusions16. Currently, for these viral risks, sophisticated patient screening, combined with laboratory detection
methods have become quite effective. As a result, the risks for these viral transmissions have decreased
dramatically over time (Figure 3). Transfusion has been estimated to be as safe as anesthetizing ASA I patients17 .
However, screening tests are costly, and contribute to the rising costs of blood therapy. There are emerging
infectious risks that will require attention going forward, including Chagas disease, West Nile virus, Malaria, and
Creutzfeldt-Jakob disease.
1:10
0 HIV
HBC
HCV
1:100
T r a n s m is s io n r is k ,
0
p e r u n it
1:10
000
1:100
000
1:1 000
000
198 198 198 199 199 199 199 199 200 200 200
4 6 8 0 2 4 6 2
Figure 3. Evolution of Viral Risks of Transfusion over
8
Time.
0 4
For current management of the peri-operative or critically ill patient, the risk of viral infections is not
among the major concerns. One issue that is of more consequence for the critically ill patient is the accumulating
evidence that blood transfusion may have profound negative effects on the immune system. Clearly in an
environment like the operating room or the intensive care units, where much of the morbidity and mortality is
directly related to infection, if blood transfusion does in fact increase the risk for infection it is of major concern. In
the late 1970's, it was observed that renal transplant outcome was improved among patients receiving blood
transfusions before the transplant surgery. There have been a large number of observational studies regarding the
association of RBC transfusions with infection, immunosuppression, and mortality.
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Several studies have suggested that exposure to RBC transfusion increases the risk of postoperative
infection. Taylor et al recently observed that patients in a medical-surgical combined ICU experienced nearly a ten
percent increased risk of nosocomial infection with each unit of transfused RBCs18. Chelemer et al made similar
observations among patients undergoing CABG surgery19. There is also observational data that suggest decreased
long-term survival after exposure to RBC transfusion during CABG surgery 20.
Other studies support the concept that transfusions induce immunomodulation in recipients. Fransen et al
observed that intra-operative allogeneic blood transfusions were associated with increased concentrations of
inflammatory mediators as well as increased postoperative morbidity21 . Moore et al. reported the results of a
prospective cohort study of trauma patients22. They found that there was a dose response relationship between early
blood transfusion and later development of multiple organ failure. This was independent of other measures of
shock. The mechanism for these associations remains unclear, but mediation by allogeneic white blood cells is the
most likely etiology. These donor white blood cells may directly impact the recipient’s immune function, or cause
the release of mediators of immunomodulation into the stored RBC unit23.
There are also observational data that suggest an association of RBC transfusions and increased risk of
acute respiratory distress syndrome24. This observation is of interest when considered together with transfusion
related acute lung injury (TRALI). TRALI is a non-specific constellation of dyspnea, hypotension, non-cardiogenic
pulmonary edema, and fever, which has large potential overlap with ARDs, which is defined clinically as dyspnea,
bilateral infiltrates, hypoxemia, and non-cardiogenic edema. Importantly, the mortality rate from TRALI is likely
low, in contrast with ARDs. The predominant hypothesis is that donor anti-leukocyte antibodies react with white
blood cells within the recipient25. A recent analysis of healthy volunteers receiving autologous RBC transfusions
demonstrates consistent impaired gas exchange after transfusion26. This suggests that RBC transfusions have
important immune effects on the respiratory system in the majority of recipients, not just those with obvious TRALI
events. More discussion regarding TRALI can be found in the sections regarding plasma blood products.
The association of decreased long term survival and exposure to red blood cell transfusion after cardiac surgery has
been reported y several investigators27 28. The mechanism for this decreased survivorship is not well understood,
and is likely not explained by infectious events alone. Transfusion exposure may merely be a marker for conditions
that limit survival, such as peri-operative hemorrhage. Alternatively, RBC transfusions may exert a long-lasting
alteration of a recipient’s immune function, thereby impacting long-term survival. The Northern New England
Cardiovascular Disease Study Group recently compared long-term survival for patients who were exposed to
smaller quantities of RBC transfusions (1 or 2 units) to those who were never exposed to RBC transfusion during
their index CABG admission. As a result, this analysis includes patients who were more likely transfused as
treatment for stable peri-operative anemia, thereby reducing the potentially confounding factor of substantial blood
loss or other hemorrhagic complications. Exposure to small doses of RBC transfusions (1 or 2 units) during
admission for cardiac surgery was associated with a 16 percent increased adjusted risk of 5 year mortality in this
regional cohort of cardiac surgical patients. The impact on survival was most pronounced in the first 6 months
following surgery, with an adjusted hazard ratio of 44 percent (Figure 4). This adverse impact on survival after
exposure to RBC transfusion was not explained by differences among patients who received blood nor by
procedural characteristics. This was confirmed using propensity score analysis.
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Figure 4. Adjusted Survival by Red Blood Cell Exposure among 9,079 Cardiac Surgical Patients.
Leukoreduction
Becauase of the concern that donor white blood cells are problematic when administered to the donor
during RBC transfusion, strategies to reduce the presence of these unwanted white blood cells have been considered.
Leukoreduction has been hypothesized to be capable of reducing the previously described morbidity and mortality
related to RBC transfusion. However, meta-analyses of randomized controlled trials on this topic fail to justify
universal application of this therapy beyond previously accepted situations25. It is important to note that this meta-
analysis supported a benefit of leukoreduction in the cardiac surgical population, based on 4 randomized controlled
trials. While some have questioned whether the available data at this point supports the considerable expense
associated with the universal adoption of this change in transfusion practice, leukoreduction has recently been
adapted in Europe and Canada, and is being increasingly adopted in the US29 30.
Storage of RBCs
A final consideration with RBC transfusions is the “Storage Lesion”. This concept considers the
predictable changes to red blood cells during storage31. There are emerging data that question the efficacy of stored
RBCs because of these changes. The goal of administering a RBC transfusion is to increase the hemoglobin
concentration and therefore improve oxygen delivery to the tissues. Normal RBCs have a biconcave shape and are
quite capable of deforming as they pass through capillaries. During storage, RBCs lose their biconcave shape and
become irregular in shape. As a result of these morphologic changes, stored RBCs are less deformable, and more
adherent to endothelium32. Stored RBCs also become depleted of ATP and 2,3-DPG and these changes may
contribute to decreased function. The clinical significance of the storage lesion is not certain.
Platelet Transfusions
A recent review of evidence based indications for platelet and plasma has been completed for the critically
ill patient33. Stored units of platelets are can be collected by two methods. Regardless of collection technique, units
of platelets must be stored at room temperature, kept in constant motion, which results in a short shelf life. They are
stored in a special permeable plastic, as they continue to respire during storage. If respiration were not to occur, the
platelets would become anaerobic, produce lactate which may not be able to be buffered by the small quantity of
plasma in the stored unit, become acidotic and ultimately die.
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Transmission of bacterial infection is a significant risk of platelet therapy, and is several orders of
magnitude more frequent than transmission of viral infections, as mentioned previously34. In addition, the fatality
rate due to bacterial contamination of platelets is several orders of magnitude greater than the transmission rate of
viral infections, such as HIV or hepatitis C. For the peri-operative or critically ill patient, transmission of bacterial
infections via platelet administration is a serious concern.
Potential sources of bacterial contamination of platelet units include the skin of the donor at the time of
collection. Less likely sources are bacteremia of the donor, contamination of the collection bag, or contamination
during processing of the unit. The risk of bacterial transmission is greater with platelet units compared to other
blood products which are stored at cold temperatures. Currently the risk of bacterial contamination is estimated at
1:2000 to 1:3000. Blood banks currently culture stored platelet units to detect units that are contaminated with
bacteria. While this is helpful for reducing the risk of bacterial infection, there are ongoing concerns about both
false positive and false negative results. A recent observational study from the American Red Cross reported a
confirmed positive contamination rate of 1:5,399, from a pool of all positive cultures (crude rate of all positive
cultures was 1:1,641)35. In other words, only 30% of all positive cultures from these aphereis platelet units were
ultimately confirmed positive. This illustrates the limitation of this screening methodology.
Other risks related to platelet transfusions include TRALI, febrile reactions, and transfusion associated
circulatory overload. There are also observational data from CABG surgery patients that describe an association of
platelet transfusion with increased risk of stroke, inotrope use, pulmonary dysfunction, as well as death. These
associations were significant after adjustment for patient and disease characteristics36.
Interpreting these risks of platelet transfusions is challenging, because the data to support a benefit for
platelet transfusion is lacking. What limited data there is derives from the management of non critically ill
hematology and oncology patients who develop thrombocytopenia as a result of chemotherapy. A recent review
regarding platelet therapy summarizes the available literature37. This review suggests generalizing those guidelines
developed for the oncology patients does not make sense. Therefore the decision to use prophylactic transfusions
(i.e, keep the platelet count above a certain threshold) or therapeutic transfusions (i.e., transfuse only for active
bleeding or immediately prior to a procedure) in the operating room or intensive care unit is not currently clear. In
addition what dose of platelets is necessary is not well characterized either.
Fresh Frozen Plasma & Cryoprecipitate
Fresh frozen plasma (FFP) is often administered to patients with elevated prothrombin time (PT) or
activated partial thromboplastin time (PTT). FFP does contain fibrinogen, so this product can also be administered
to patients with a low fibrinogen. Cryoprecipitate is made from FFP, and contains higher concentrations of
fibrinogen, von Willebrand factor, and factor VIII. As such cryoprecipitate is indicated to replete deficiency of
these factors. These indications based on abnormal laboratory coagulation studies are most appropriate prior to an
invasive procedure that is associated with bleeding risks or during an episode of active hemorrhage. These
indications are most often viewed as inappropriate when used to prevent spontaneous bleeding. Also use of FFP as
a volume expander is viewed as inappropriate. Unfortunately, none of these indications are evidence-based.
Furthermore, there is incomplete evidence that first, the correction of abnormal coagulation studies with FFP is
transient in nature (i.e., lasts only 2 to 4 hours), and second that abnormal coagulation studies do not necessarily
predict bleeding risk during procedures32.
While the indications for and benefits of these plasma blood products remain uncertain, some risks related
to their use are more clearly understood. Like all the blood products discussed in this review, use of plasma carries
risks of infection, allergic reactions, hemolysis, and circulatory volume overload. Data from the United Kingdom
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(Serious Hazards of Transfusion) Hemovigilance Systems (SHOT) document that allergic reactions are more
common with plasma units compared to RBC units38. Hemolysis from ABO incompatibility is also possible,
because plasma may contain anti-A and anti-B antibiodies that react within the recipient. The “universal donor” is
AB type plasma. Recent data from the French and the United Kingdom (Serious Hazards of Transfusion)
Hemovigilance Systems document that the risk of transfusion related acute lung injury (TRALI) is also much higher
with “plasma-rich” blood components, such as fresh frozen plasma and platelets, compared to RBC transfusions36.
SHOT data suggests a risk of 1 in 60,000 per unit for plasma transfusion. Interestingly, these data found a strong
association of TRALI and female gender of the donor. It is hypothesized that pregnancy may induce human
leukocyte or human neutrophil antibodies among these female donors. This has led to the preferential use of male
derived plasma for fresh frozen plasma products in some countries.
Massive Transfusion
Observational evidence from Operation Iraqi Freedom and Trauma Centers is informing changes to
Massive Transfusion Protocols at many trauma centers39. One major change has been the suggested ratio of red
blood cell to fresh frozen plasma (FFP) transfusions during resuscitation of the most severely injured and
uncontrollably hemorrhaging trauma patients. An association between red cell to FFP ratios and mortality has led to
the recommendation of administering a ratio o f 1:1 or 1:2 for these patients40. A randomized trial of these ratios is
clearly needed to further investigate whether these observations are indeed valid. Other important considerations
during management of these patients include vigilance for and management of hypothermia, acidosis, and
hypotension.
General Considerations
Currently, there are three predominate risks to consider when deciding to use blood products: 1.
transfusion related acute lung injury (TRALI); 2, bacterial contamination of platelets; and 3. ABO incompatibility.
TRALI and bacterial contamination of platelets have been described above. Administration of an incompatible unit
of blood is not a new problem, but remains a significant risk today. For example, errors with blood specimens and
samples labeled with the wrong patient information are not rare41. ABO incompatibility is most frequently related to
transfusion of RBCs, but can also occur with platelets and plasma products. Sixty percent of the transfusion related
deaths reported to the FDA during 1990-1998 were hemolytic reactions. Every year one to two dozen patients will
die simply from getting the wrong blood in the United States. Of note, transfusion of ABO incompatible blood
products has recently been introduced as a one of the mistakes that will prohibit payment for hospital care of patients
in some states.
In conclusion despite significant advances in the safety of blood therapy, there remain significant risks
related to their use. Variation in the utilization of blood products that are not explained by differences in patient and
disease characteristics suggest that provider behavior is driving at least some of our national use of blood products.
Given the risks to patients that still exist when they are transfused, careful and judicious use of blood products is
appropriate.
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Surgenor DM, Churcill EL, Wallace WH, et al. Determinants of red cell, platelet, plasma and cryoprecipitate
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Surgenor SD, DeFoe GR, Fillinger Likosky DS, et al. Intraoperative red blood cell transfusion during CABG
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Hébert PC, Wells G, Blajchman MA, et al. A multicenter, randomized, controlled clinical trial of transfusion
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13
Hajjar LA, Vincent JL, Galas FR et al. TRACS Randomized Controlled Trial JAMA. 2010;304(14):1559-1567
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Carson JL, Terrin ML, Noveck H. et al. Liberal or Restrictive Transfusion in High-Risk Patients after Hip
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15
Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the treatment of severe sepsis and septic
shock. NEJM 2001; 345:1368-77.
16
Goodnough LT, Brecher ME, Kanter MH, AuBuchon JP: Transfusion medicine: Blood transfusion. N Engl J
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Amalberti R, Auroy Y, Berwick D, Barach P. Five System Barriers to Achieving Ultrasafe Health Care. Ann
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Taylor RW, O’Brien J, Trottier J, et al. Red blood cell transfusions and nosocomial infections in critically ill
patients. Crit Care Med 2006; 34: 2302-8.
19
Chelemer SB, Prato S, Cox PM er al. Asssociation of bacterial infection and RBC transfusion after coronary
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Engoren MC, Habib RH, Zacharias A. Effect of blood transfusion on long term survival after cardiac operation.
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Fransen E, Maessen J, Dentener M, Senden N, Buurman W: Impact of blood transfusions on Inflammatory
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Moore FA, Moore EE, Sauaia A: Blood transfusion: An independent risk factor for postinjury multiple organ
failure. Arch Surg 1997;132:620-625.
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Vamvakas EC. White blood cell containing allogeneic blood transfusion and postoperative infection or mortality:
an updated meta-analysis. Vox Sang 2007; 92: 224-32.
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Gong MN, Thompson BT, Williams P et al. Clinical predictors of and mortality in acute respiratory distress
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Curtis BR, McFarland JG. Mechanisms of transfusion related acute lung injury (TRALI): anti leukocyte
antibodies. Crit Care Med 2006; 34: s118-23.
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Weiskopf RB, Feiner J, Toy P, et al. Fresh and Stored Red Blood Cell Transfusion Equivalently Induce
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Engoren MC, Habib RH, Zacharias A, et al. Effect of blood transfusion on long-term survival after cardiac
operation. Ann Thorac Surg 2002; 74:1180-1186.
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Koch CG, Li L, Duncan AI, et al. Transfusion in coronary artery bypass grafting is associated with reduced long
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Perioperative Indications, Adverse Effects, and Cost Analysis Anesth Analg 2000; 90: 1315-23.
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Tinmouth A, Fergusson D, Yee IC, Hebert PC. Clinical consequences of red cell storage in the critically ill.
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microvasculature. Blood 2004; 104: 2713A.
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Gajic O, Dzik WH, Toy P. Fresh frozen plasma and platelet transfusion for nonbleeding patients in the intesive
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Schrezenneier H, Walther-Wenke G, Muller TH, et al. Bacterial contamination of platelet concentrates: results of
a prospective multicenter study comparing pooled whole blood-derived platelets and apheresis platelets.
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35
Eder AF, Kennedy JM, Dy BA, et al. Bacterial screening of apheresis platelets and the residual risk of septic
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Spiess BD, Royston D, Levy JH, et al. Platelet transfusionduring coronary artery bypass surgery are associated
with seious adverse outcomes. Transfusion 2004; 44: 1143-8.
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Ongjen G, Dzik WH, Toy P. Fresh frozen plasma and platelet transfusion for nonbleeding patients in the
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Maegele M, Lefering R, Paffrath T, Tjardes T, Simanski C, et al. Red Blood Cell to plasma ratios during massive
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Lumadue J, Boyd J, Ness P. Adherence to a strict specimen-labeling policy decreases the incidence of erroneous
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Transfusion 1997; 37: 1169–1172.
DISCLOSURE
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Coagulation Abnormalities Made Easy

Linda L. Liu, M.D. San Francisco, California
Back decades ago, the coagulation cascade was taught in terms of 2 pathways, the intrinsic versus the extrinsic.
Figure 1 shows a very simplified version of the proposed waterfall/ cascade model of the coagulation system.
Unfortunately, as we started to understand more about the coagulation system, it became more and more complex.
Many of the enzymes were found to be cofactors or were precursors to the active form. We also found that the 2
pathways were not completely separate in function. They appeared to be an intertwined system where modulation
of one arm may or may not affect the second arm. The modern view of coagulation is to actually look at the
coagulation system as a series of steps, 1) initiation, 2) amplification, and 3) propagation, as opposed to distinct
pathways, (1) but the old 2 pathway model is still beneficial in terms of helping us understand what abnormal
coagulation tests mean. This chapter will exam some causes of abnormal coagulation in the perioperative period and
discuss agents that are used to modulate the coagulation system.
Figure 1: Waterfall/ Cascade Model of the Coagulation System
Pre-operative causes of abnormal coagulation
Most patients with congenital coagulation abnormalities present in early life and come to surgery with a known
diagnosis. Patients with hemophilia, von Willebrand disease (vWD), and platelet disorders usually need treatment
before, during, and after surgery. For the patient without a diagnosis of a prior coagulation abnormality, the best
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means of detecting a hemorrhagic diathesis is a properly taken history. Some screening pre-operative questions that
may help flush out a bleeding history are:
1) Is there a history of bleeding in the family?
2) Is there a history of bleeding after procedures (such as biopsy, tooth extraction, surgery)?
3) Do you experience recurrent nosebleeds?
4) Do you experience recurrent gum bleeding?
5) Do you experience bruising routinely?
6) And for females, do you have heavy periods (10 pads/d x 4 days)?
Equally important is a detailed history of drug ingestion and herbal remedy use.
Pre-op abnormalities are best classified based on the abnormal laboratory value – platelet count, fibrinogen level,
prothrombin time (PT) or activated partial thromboplastin time (aPTT). PT abnormalities are associated with
deficiencies or inhibitors of FII, FV, FVII, FX, or fibrinogen, which are often associated with liver disease, vitamin
K deficiency, or warfarin effect. Activated PTT abnormalities can be associated with deficiencies or inhibitors of
FII, FV, FVIII, FIX, FX, FXI, FXII or fibrinogen. Diseases often associated with these deficiencies include:
hemophilia A (VIII), hemophilia B (IX), lupus anti-coagulant, and heparin or thrombin inhibitor effect.
An algorithm for further pre-operative work-up for an abnormal PT or aPTT and a positive bleeding history is
shown in figure 2. Patients with a positive bleeding history, but normal PT and aPTT, should be sent for
hematology consultation for more extensive work-up. In this instance, low or dysfunctional platelets, mild
deficiency of von Willebrand factor, vascular disorders, and, rarely, factor XIII deficiency should be considered.
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Figure 2: Algorithm for work-up of an abnormal pre-operative PT or aPTT
Intra-operative causes of abnormal coagulation
There are really only 2 main causes of perioperative bleeding. The first and most common is surgical bleeding,
which will not be discussed here. The second is non-surgical bleeding, or failure of the hemostatic pathways.
Causes for this failure include: massive blood transfusion (leading to thrombocytopenia, low fibrinogen, and
coagulopathy), fibrinolysis (induced by the surgical procedure such as prostatectomy, orthotopic liver transplant, or
exposure to a foreign graft material), disseminated intravascular coagulation (from sepsis, cardiopulmonary bypass,
or transfusion reactions), an undetected pre-existing bleeding disorder or a combination of the above possibilities.
The mainstays of massive blood loss management basically include replacement of red cells, platelets, clotting
factors and fibrinogen. The patient needs to be kept warm and frequent labs are necessary to help guide transfusions
and electrolyte replacements. A basic laboratory profile in the operating room should include hematocrit, platelet
count, PT, aPTT, and fibrinogen level. Antifibrinolytics like tranexamic acid and epsilon-aminocaproic acid can be
given if fibrinogen levels remain low and a mechanism for primary fibrinolysis seems likely. Disseminated
intravascular coagulation (DIC) is difficult to diagnose during surgery since there is no one pathognomonic
laboratory test. Surgical bleeding alone can cause an elevated PT, low fibrinogen levels, and low platelet count.
Distinguishing between primary fibrinolysis and DIC by laboratory values intra-operatively is also very difficult.
The diagnosis may sometimes have to depend on the clinical scenario. D-dimers can be sent, but the results will not
be available quickly. The first goal for treatment of DIC is to correct the primary disorder if possible and then
replace fibrinogen, platelets, and coagulation factors as necessary. In some patients, the correction of the primary
disorder may not be readily possible. Heparin therapy is not universally accepted in the treatment of DIC, and the
decision to use heparin, especially intra-operatively, should be discussed with the surgical team and the
hematologists.
Recombinant factor VIIa (rFVIIa)
One drug that may help during massive hemorrhage is recombinant factor VIIa. A growing number of case reports
suggest that this agent may be effective in various “off-label” indications. It has been used in controlling intractable
bleeding in trauma, obstetrical, and surgical patients where all other efforts to correct the bleeding have failed to
work. Because this drug has seemed to be the magical pill, its use has progressed from rescue therapy to
preventative therapy in surgical situations such as complex cardiac surgery or liver transplantation where heavy
blood loss is expected. When rFVIIa is administered, hemostasis is enhanced because of the additional generation of
thrombin. In the tissue factor dependent or extrinsic system, rFVIIa binds to tissue factor at the site of vessel injury,
causing activation of factor X. In the tissue factor independent or intrinsic system, rFVIIa binds to the surface of the
activated platelet, activating factor X. Both mechanisms result in a “burst” of thrombin and fibrin generation, which
leads to clot formation (Figure 3).
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Figure 3: Mechanism of action of rFVIIa
In a randomized controlled trial conducted in 36 patients undergoing radical prostatectomy, patients were
randomized to placebo, rFVIIa at 20 mcg/kg or 40 mcg/kg. (2) Patients receiving rFVIIa had a mean blood loss that
was statistically significantly lower than the control group. In trauma patients, the use of rFVIIa reduced the need for
massive blood transfusions (defined as > 20 units) from 33% in the control group down to 14% in the treatment
group. (3) While the results for penetrating trauma are just as promising, the results did not reach statistical
significance.
During orthotopic liver transplant (OLT), where there is dilution of coagulation factors and platelets, level 3 or 4
evidence (ie case reports) have been published, but no randomized controlled trials. A few reported studies have
actually been unable to show decreased transfusion requirements with the prophylactic use of rFVIIa in OLT. There
are several reasons why rFVIIa may not work as well during OLT. 1) Recombinant FVIIa has no effect against
heparin or heparin-like substances, which may have been released by the reperfused liver. 2) Recombinant FVIIa
has no direct anti-fibrinolytic effect. Anti-fibrinolytics may be necessary since fibrinolysis may occur after
reperfusion. 3) Because of the fibrinolysis and low fibrinogen levels, rFVIIa may not be as effective. FFP or
cryoprecipitate may still be required since fibrinogen is required for the thrombin burst to produce the fibrin clot.
In all, 2 meta-analyses and 1 Cochrane report have been published. (4-6) Depending on the inclusion criteria, most
included only 7 to 13 trials. Approximately 700 patients have been enrolled in trials involving the prophylactic use
of rFVIIa during OLT, liver resection, prostatectomy, repair of pelvic trauma, and cardiac surgery. Approximately
1200 patients have been enrolled in the therapeutic use of rFVIIa. The underlying etiologies for the use of rFVIIa
have been quite varied, and include stem-cell transplant, dengue fever, trauma, upper GI bleeding, and intracranial
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hemorrhage. If all trials are analyzed together, there is a slight reduction in the number of patients that need PRBC
transfusions with the prophylactic use of rFVIIa. The effect is mostly from the use of high dose rFVIIa (>50
mcg/kg) and not low dose. In the studies that looked at the use of rFVIIa therapeutically, there is no statistically
significant difference between the 2 groups in terms of the number of patients that needed a blood transfusion.
One other end-point of interest other than PRBC transfusions is mortality. The question is: can the use of rFVIIa
improve mortality? With only 14 deaths out of 507 patients, the results give a wide confidence interval that crosses
1, so mortality does not seem to be improved from the meta-analyses.
As the use of rFVIIa increases, there are now more reports of thrombosis. O’Connell et. al. look at the FDA adverse
event database, which is a voluntary reporting system. Pooling all reported cases in which rFVIIa was used in non-
hemophillac patients resulted in 168 cases of thrombosis attributable to the drug. The rate of complication is
uncertain because no one really knows what the denominator is. (7) Patients with procoagulant diseases (cancer,
infections, h/o thromboembolic events, and receiving procoagulant drugs) were usually excluded from the studies,
so the real risk of thromboembolic events may be much higher when we start using the drug more in the general
surgical population or in critically ill patients.
As researchers gain experience with the use of rFVIIa in intracranial hemorrhages, the data show that the drug
decreases the size of the hemorrhage, but increases the incidence of thrombosis to 7%. (8) The study was repeated in
a phase 3 trial. (9) There was decreased growth in the volume of the intracranial hemorrhage, but there was no
significant difference among the groups in terms of mortality. Also, the incidence of severe disability was not
improved in the treatment groups. In the second study, frequency of venous complications were the same in the
groups, but there remained an increase frequency of arterial events, defined as myocardial infarctions and
cerebrovascular accidents, in the rFVIIa group that received the higher dose of 80 mcg/kg.
At this point, the data does not favor the prophylactic use of rFVIIa, but also can’t show definitive harm from its
use. Considering that no RCT has been able to demonstrate a significant benefit in terms of ICU stay, hospital stay
or mortality, the financial burden of this drug needs to be weighed against the cost benefit of transfusing fewer
products. Each clinician will have to weigh the risk of thromboembolic events against the benefit of clotting for the
individual patient. More randomized controlled trials are necessary before a definitive statement can be made about
the safety of rFVIIa.
Post-operative causes of abnormal coagulation
In the post-operative period, usually the deficiency of clotting factors, platelets, and red cells begin to resolve unless
there is ongoing surgical blood loss. Now, the imbalance of procoagulant and anticoagulant agents increases the risk
for prothrombotic complications. Standard of care is to institute thomboembolic prophylaxis in surgical patients
(Figure 4). Heparin is usually the drug that comes to mind, but heparin does have its drawbacks. There is wide
inter-individual variability when administering the drug. It is an indirect thrombin inhibitor and therefore, is
effective on free thrombin only, and has limited inhibition of clot bound thrombin. It requires anti-thrombin as a
cofactor, and it induces platelet activation. The most devastating side effect of heparin is its ability to form a
complex with PF4 (platelet factor 4) that then can generate formation of heparin/PF4 antibodies.
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Figure 4: Site of action of anticoagulants
Direct Thrombin Inhibitors
Direct thrombin inhibitors (DTI), initially isolated from the saliva of Table 1: Direct Thrombin
leeches, have been developed for use as anticoagulants in patients with Inhibitors
HIT. There are now lots of direct thrombin inhibitors on the market that • Hirudin
an anesthesiologist needs to be familiar with (Table 1). Most direct • Lepirudin
thrombin inhibitors are relatively short acting, inhibit free and clot-
• Desirudin
bound thrombin, and are indicated for prophylaxis and treatment of
• Argatroban
patients with HIT. One DTI, melagatran, and its oral formulation,
• Bivalirudin
ximelagatran, were removed from the market due to hepatotoxicity.
The drawback for these drugs is that there are no specific reversal • Ximelagatran/
agents. Dialysis may be somewhat effective, and rFVIIa has shown melagatran
some efficacy in animals and in healthy volunteers ex vivo. (10) • Dabigatran
Argatroban
Argatroban has a 45-minute half-life, and it is cleared by the liver, so no dose adjustments are needed in patients
with low glomerular filtration rate (GFR). It is less immunogenic than lepirudin, but it does increase the
international normalized ratio (INR), which may be a factor when initiating coumadin. Like all direct thrombin
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inhibitors, dose should be titrated to aPTT (1.5-3x normal) or activated clotting time (ACT). The FDA approved
this drug as an anticoagulant for prophylaxis or treatment of thrombosis in patients with HIT and for percutaneous
coronary intervention (PCI) in patients with or at risk for HIT. Two prospective, multi-center trials studied 754
patients with HIT versus 193 historical controls. They found a significant decrease in the primary endpoint of death,
amputation, and new thrombosis (34% vs. 43%). (11, 12) Safety trials for patients with HIT undergoing PCI showed
that argatroban was as safe in terms of procedural success (lack of death, need for emergent CABG, or increased
incidence of Q-wave MI) as historical controls receiving heparin (98.2% vs. 94.3%). There are also a few reports of
the successful use of argatroban in ischemic stroke, hemodialysis, CRRT, and peripheral vascular surgery.
Bivalirudin
Bivalirudin has a 25-minute half-life, and it is 80% cleared by proteolysis and 20% renally cleared. Unlike
argatroban, it needs to be dosed for GFR, and it only causes a slight increase in INR. The dose should be titrated to
aPTT (1.5-3x normal) or ACT. The FDA approved this drug as an anticoagulant for PTCA in patients with unstable
angina (13) and for PCI. Multiple RCTs have studied the use of bivalirudin for PCI versus heparin. (14, 15) Most
show similar ischemic outcomes in both groups with less major bleeding in the bivalirudin group. Other studied
uses of bivalirudin include cardiopulmonary bypass and vascular surgery. Table 2 summarizes a comparison
between the different direct thrombin inhibitors.
Table 2: DTI comparisons

Lepirudin Argatroban Bivalirudin
FDA indications HIT HIT/ PCI PCI
Half-life 1.3 hours 40-50 minutes 25 minutes
Elimination Renal Hepatic Plasma/ Renal
Monitoring INR + INR +++ INR +
Cost $700 $1500 $800
New Oral DTI – Dabigatran
The US FDA recently (October, 2010) approved dabigatran, an oral direct thrombin inhibitor, for the management
of patients with atrial fibrillation. Because of its predictable pharmacokinetics and few drug or food interactions,
dagibatran can be given as a fixed daily dose without the need for coagulation monitoring. The new oral DTIs show
promise in reducing the complexity of current anticoagulants. (16)
Fondaparinux
One new anticoagulant is fondaparinux, a synthetic five saccharide molecule that is functionally and structurally like
heparin. It binds and activates antithrombin, but unlike heparin, it only inhibits FXa and not thrombin. The drug has
not been extensively studied for HIT, but successful use of fondaparinux in patients with HIT has been reported.
One multicenter in vitro study demonstrated a lack of cross-reactivity between fondaparinux and HIT antibodies.
(17) Recently, 2 case reports of thrombocytopenia without thromboembolic complications while receiving
fondaparinux have been described. (18, 19) At this time, the American College of Chest Physicians continues to
recommend the use of direct thrombin inhibitors as the first-line agents in the setting of HIT. (20) Further clinical
trials should be conducted before fondaparinux becomes the therapy of choice for HIT.
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Rivaroxaban
Direct Xa inhibitors are new agents whose activity is directed against the active site of Factor Xa. These agents are
being investigated for use in prophylaxis of DVT, PE, and stroke in patients with atrial fibrillation. Like dabigatran,
these agents also have minimal drug interactions and predictable pharmacokinetics. For the majority of patients,
coagulation monitoring is unnecessary.
Use with Regional Anesthesia
There is not a lot of data on the use of these new anticoagulants with regional anesthesia. The broad clinical
experience with these drugs and neuraxial techniques does not exist. Most recommendations are based exclusively
on the pharmacokinetics. (21)
Drug Reversal
A major disadvantage of the new oral anticoagulants is the lack of a reversal agent in case of serious bleeding. One
study looked at 12 healthy male volunteers in a cross-over study. They received rivaroxaban or dabigatran followed
by a bolus of a prothrombin complex concentrate (PCC). Laboratory values were then followed. It appears that the
PCC was able to reverse the laboratory anticoagulant effect of rivaroxaban but not dabigatran. Of course, it is
unclear whether the chosen laboratory values are good surrogate markers for the actual clinical bleeding potential.
More studies are clearly needed. (22)
Given the lack of data, current recommendations in the face of serious bleeding are to provide support care with
fluid resuscitation, site compression, and transfusion, discontinue the drug, consider activated charcoal for recent
ingestions, and possibly start hemodialysis for dabigatran. (23) There is not enough data to make recommendations
about FFP, PCC, and rFVIIa.
Summary
The modern view of coagulation is of a highly complex system with multiple cofactors and enzymes divided into the
initiation, amplification, and propagation phase of clot formation. The older view of an intrinsic and extrinsic
pathway, although greatly simplified, is still useful because it illustrates what the coagulation tests are measuring.
Analyzing the PT or aPTT can help diagnose the coagulation defect. Bleeding diatheses in the perioperative period
are easier to discuss when we divide the differential into the pre-, intra-, or post-op periods. Several new drugs that
either increase clotting or increase anticoagulation have been introduced, and many more are due on the market. It
is the anesthesiologist’s job to understand their mechanisms of action, how to manipulate the drugs in the
perioperative period, and how the drugs will affect the anesthetic plan.
References
1. Hoffman M, Monroe D: Coagulation 2006: a modern view of hemostasis. Hematol Oncol Clin N Am 21:1-
11, 2007.
2. Friederich P, Henny C, Messelink E, et al.: Effect of recombinant activated factor VII on perioperative
blood loss in patients undergoing retropubic prostatectomy: a double-blind placebo-controlled randomized trial.
Lancet 361:201-5, 2003.
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3. Boffard K, Riou B, Warren B, et al.: Recombinant factor VIIa as adjunctive therapy for bleeding control in
severely injured trauma patients: two parallel randomized placebo-controlled double blind clinical trials. J Trauma
59, 2005.
4. Hsia CC, Chin-Yee IH, McAlister VC: Use of recombinant activated factor VII in patients without
hemophilia: a meta-analysis of randomized control trials. Ann Surg 248:61-8, 2008.
5. Ranucci M, Giuseppe I, Soro G, et al.: Efficacy and safety of recombinant activated factor VII in major
surgical procedures. Arch Surg 143:296-304, 2008.
6. Stanworth SJ, Birchall J, Doree CJ, et al.: Recombinant factor VIIa for the prevention and treatment of
bleeding in patients without haemophilia. Cochrane Database Syst Rev:CD005011, 2007.
7. O'Connell K, Wood J, Wise R, et al.: Thromboembolic adverse events after use of recombinant human
coagulation factor VIIa. JAMA 295:293-8, 2006.
8. Mayer SA, Brun NC, Begtrup K, et al.: Recombinant activated factor VII for acute intracerebral
hemorrhage. N Engl J Med 352:777-85, 2005.
9. Mayer SA, Brun NC, Begtrup K, et al.: Efficacy and safety of recombinant activated factor VII for acute
intracerebral hemorrhage. N Engl J Med 358:2127-37, 2008.
10. Crowther M, Warkentin T: Bleeding risk and the management of bleeding complications in patients
undergoing anticoagulant therapy: focus on new anticoagulant agents. Blood 111: 4871-4879, 2008.
11. Lewis B, Wallis D, Berkowitz S, et al.: Argatroban anticoagulation therapy in patients with heparin-
induced thrombocytopenia. Circulation 103:1838-43, 2001.
12. Lewis B, Wallis D, Leya F, et al.: Argatroban anticoagulant in patients with heparin-induced
thrombocytopenia. Arch Intern Med 163:1849-56, 2003.
13. Weitz J, Buller H: Direct thrombin inhibitors in acute coronary syndromes: Present and Future. Circulation
105:1004-11, 2002.
14. Lincoff, AM, Bittl J, Harrington R, et al.: Bivalirudin and provisional glycoprotein IIb/IIIa blockade
compared with heparin and planned glycoprotein IIb/IIIa blockade during percutaneous coronary intervention.
REPLACE-2 randomized trial. JAMA 289:853-63, 2003.
15. Stone G, Ware J, Bertrand M, et al.: Antithrombotic strategies in patients with acute coronary syndromes
undergoing early invasive management: one-year results from the ACUITY trial. JAMA 298:2497-607, 2007.
16. Lee C, Badhwar G, Ansell J: Oral IIa inhibitors. Hematol Oncol Clin N Am 24:739-753, 2010.
17. Savi P, Chong B, Greinacher A, et al.: Effect of fondaparinux on platelet activation in the presence of
heparin-dependent antibodies: a blinded comparative multicenter study with unfractionated heparin. Blood 105:139-
44, 2005.
18. Rota E, Bazzan M, Fantino G: Fondaparinux-related thrombocytopenia in a previous low-molecular-weight
heparin (LMWH)-induced heparin-induced thrombocytopenia (HIT). Throm Haemost 99:779-81, 2008.
19. Warkentin T, Maurer B, Aster R: Heparin-induced thrombocytopenia associated with fondaparinux. J Engl
J Med 356:2653-5, 2007.
20. Warkentin TE, Greinacher A, Koster A, et al.: Treatment and prevention of heparin-induced
thrombocytopenia: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th
Edition). Chest 133(6 Suppl):340S-380S, 2008.
21. Horlocker T, Wedel D, Rowlingson J et al: Regional anesthesia in the patient receiving antithrombotic or
thrombolytic therapy: American Society of Regional Anesthesia and Pain Medicine Evidence-Based Guidelines
(third edition). Reg Anesth Pain Med 35: 64-101, 2010.
22. Eerenberg ES, Kamphuisen PW, Sijpkens MK et al.: Reversal of rivaroxaban and dabigatran by
prothrombin complex concentrate. Circulation 124: 1573-1579, 2011.
23. Kaatz S, Kouides PA, Garcia DA, et al.: Guidance on the emergent reversal of oral thrombin and factor Xa
inhibitors. Am J Hematol. 87 Suppl 1:S141-5, 2012
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DISCLOSURE
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Respiratory Physiology: Gas Exchange and Respiratory Mechanics
Luca M. Bigatello, M.D. Boston, Massachusets
Respiration provides oxygen (O2) and removes carbon dioxide (CO2) for the body. An extraordinary anatomic
arrangement of functional units (the alveoli) delimited by extra-thin walls (epithelium and endothelium) creates the
interface for gas exchange between air and blood. Repetitive expansion and collapse of the chest wall facilitates
movement of gas in and out of the lungs. This review focuses on the mechanical events that regulate the exchange
of O2 and CO2 between the body and the outside environment.
Gas exchange.
How much O2 gets from the atmosphere to the arterial blood- the alveolar air equation. Oxygen constitutes
approximately 21% of the air. At sea level, air exerts a pressure of 760 mmHg; once inside the airways, it is
saturated by water vapor (47 mmHg) and the partial pressure of O2 in the inspired air (PiO2) can be calculated:
PiO 2 = (760 - 47) mmHg x 0.21 ≈ 150 mmHg
In the alveoli, one volume of O2 is exchanged for 1.2 volumes of CO2 (at a normal respiratory quotient [RQ] of 0.8).
Hence, with a normal PaCO2 of 40 mmHg, the alveolar PO2 (PAO2) will be:
PAO 2 = PiO2 - PaCO2 x 1.2 ≈ 100 mmHg
Past the pulmonary capillaries, the arterial blood receives a small
amount of non- oxygenated blood (e.g., from the bronchial
circulation), and the PaO2 decreases slightly below 100 mmHg.
Causes of hypoxemia. Understanding how oxygen moves from the air
to the arterial blood (Figure 1) provides a convenient framework to
classify the various causes of hypoxemia. From ‘top to bottom’ these
include:
Low PiO2. The most common cause of a low PiO2 is breathing at high
altitude. As a reference, breathing air at 5,300 feet in Denver lowers
the PiO2 from 150 to approximately 120 mmHg, and breathing air at
30,000 feet on the summit of Mount Everest lowers the PiO2 to 40
mmHg. Although rare, causes of low PiO2 at sea level are generally
related to the accidental administration of a hypoxic mixture.
Low PAO2 - hypoventilation. The alveolar air equation explains how
hypoventilation, in addition to hypercarbia, can cause hypoxemia. While a normal PaCO2 and RQ will result in a
PACO2 of 48 mmHg and a PAO2 of 100 mmHg, an increased PaCO2, e.g., 80 mmHg, will decrease the PAO2 to 150
- 80 x 1.2 = 54 mm Hg. This scenario underlies the importance of immediately administering O2 to the patient that
seems to be hypoventilating, as supplemental O2 will rapidly increase PiO2 and offset the effects of a high PaCO2 in
the alveolus. Common causes of hypoventilation include: a) a decrease of the central drive to breathe, as it occurs
with the administration of hypnotics and opiates; b) respiratory muscle weakness, in syndromes such as Guillain-
Barre’ and polineuropathy of critical illness; and c) high resistive or elastic ventilatory loads (see below), as it
occurs in severe asthma and abdominal distention.
Impaired diffusion across the alveolo- capillary membrane is rare. Although this seems to contradict the observation
that the diffusing capacity of carbon monoxide for the lung (DLCO) is a sensitive test to quantify impairment of
lung function, the DLCO is primarily affected by abnormality in ventilation / perfusion ratio rather than of gas
diffusion per se.
Low PaO2. Under normal circumstances, the PaO2 is slightly lower than the PAO2 (see above). Additional increase
in this gradient occurs in physiological conditions such as aging, the sitting and supine positions, and with the
induction of general anesthesia. The decrease of PaO2 under these circumstances is due to the absence or decrease
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of ventilation to variable areas of the lung, which results in shunt and low ventilation / perfusion (V/Q) ratio
respectively. These two phenomena are part of the same physiological continuum, but may have different clinical
implications.
1. Shunt occurs when there is no ventilation at all to alveoli that receive blood flow. Under these circumstances,
the PaO2 is equal to the PvO2. The fraction of total pulmonary blood flow (Qt) that is shunted away from
unventilated alveoli (Qs) can be calculated from the difference in content of O2 between the pulmonary capillary
(CcO2) and the arterial (CaO2) and venous (CvO2) blood, as:
Qs/ Qt = (CcO2 - CaO2) / (CcO2 - CvO2)
where the CcO2 is calculated using the PAO2 as a surrogate for the PO2 in the capillary blood. Clinically, true shunt
occurs in the presence of intracardiac right- to- left flow, and in diverse pulmonary pathology such as atelectasis,
pneumonia, and acute lung injury / acute respiratory distress syndrome (ALI/ARDS). An important feature that
differentiates shunt from a low V/Q ration is that with shunt, increasing the PiO2 through the administration of
supplemental O2 will not correct the hypoxemia. The appropriate intervention to increase PaO2 under these
circumstances is to recruit the collapsed alveoli through, e.g., the application of positive end-expiratory pressure
(PEEP).
2. Low V/Q. A low PaO2 is due more commonly to combinations of low and high V/Q than to shunt (see below).
As V/Q decreases, the arterial blood gas tensions will approach those of the mixed venous gas (Figure 1). Two
corollaries are important. First, although the PaCO2 should also increase towards its venous value, the extent of it is
unpredictable in the spontaneously breathing patient, as a higher PaCO2 will rapidly stimulate alveolar ventilation
and restores normocarbia. Second, coexisting and opposite V/Q abnormalities do not average out but result in
hypoxemia. Figure 2 illustrates this phenomenon. While the O2 content leaving the alveolus with a low V/Q
approximates the content of venous blood (16 and 14 ml O2/100 ml respectively in this example), the O2 content
leaving the alveolus with a high V/Q is barely higher than in the normal alveolus (20 and 19 ml O2/100 ml of blood
respectively). This is due to the shape of the hemoglobin- O2 dissociation curve: once the hemoglobin is fully
saturated, further increase in PaO2 will dissolve in plasma, adding very little to the total content of O2.
Low PvO2. A decreased PO2 in the mixed
Fig. 2 venous blood (PvO2) will feed venous blood
with a lower PO2 through areas of low V/Q
and shunt, further decreasing the PaO2. The
extent of the resulting hypoxemia is difficult
to predict, because it is affected by the
magnitude of the underlying V / Q
abnormality and because a low PvO2 elicits
local vasoconstriction that counteracts the
low V / Q to a certain extent. However, it is
important to think of this as a cause of
hypoxemia in at least two common
circumstances in anesthesia and critical
care. First, during shivering the PvO2 may
decrease significantly and cause hypoxemia,
which is corrected by the administration of
supplemental oxygen. Second, a low PvO2 may result from a low cardiac output and consequent increase in O2
extraction by the periphery; hence, hypotension from low blood flow can cause hypoxemia!
The PaCO2. Carbon dioxide and water are the end- products of aerobic metabolism. Carbon dioxide is stored in
tissues, and transported in blood as carbamino compounds, bicarbonate, and dissolved CO2. The latter determines
the PCO2, and is eliminated as a gas from the lungs. At steady state, the PaCO2 results from the equilibrium
between production of CO2 by cellular metabolism (VCO2) and its elimination by the lungs through alveolar
ventilation (VA):
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PaCO 2 = VCO2 / VA
It is also important to note that the VA is linearly correlated with the PaCO2. In other words, if the PaCO2 rises (see
below) the VA increases nearly instantly and steeply. Albeit with some variability, an increase of the PaCO 2 of 1
mm Hg results in an average increase of VA of 1 - 2 l/min. Of course, we know that many of the drugs that we use
in anesthesia (chiefly hypnotic and opiates) blunt this response.
Causes of hypercarbia.
High CO2 production occurs with fever, shivering, excessive caloric / carbohydrate intake, and, to its maximum
extent, in malignant hyperthermia (MH) and neuroleptic malignant syndrome (NMS). However, except for MH and
NMS, the increase of VCO2 is generally transient, and may or may not cause hypercarbia depending upon the ability
of the respiratory system to increase the VA in response to the hypercarbia. Such response may be limited in the
anesthesia practice by the administration of anesthetics, hypnotics and opiates.
Low CO2 elimination is the most common cause of hypercarbia in anesthesia and critical care practice, and it
includes two main causes: hypoventilation and dead space ventilation.
1. Hypoventilation increases PaCO2 by hindering the elimination of the CO2 produced metabolically. As
discussed earlier, hypoventilation may also causes hypoxemia. Immediate treatment of hypoventilation includes
supplemental O2 and ventilatory support.
2. High V/Q and dead space. Similarly to low V/Q and shunt, high V/Q and dead space are a continuum of the
same phenomenon. As perfusion to an alveolus decreases, the gases dissolved in the venous blood fail to reach the
alveolus; less CO2 is eliminated, the exhaled PCO2 decreases and, at a constant VCO2, the PaCO2 will rise. These
phenomena are at the basis of the measurement of the physiological dead space fraction, which is the fraction of
unperfused (or ‘dead’) ventilatory space (Vd) over the tidal volume (Vt):
Vd/Vt phys = (PaCO2 - PECO2) / PaCO2
This definition of physiological dead space (Vd/Vt phys) includes the anatomical (proximal airways) and the
alveolar dead space (Vd/Vt alv). The Vd/Vt phys is calculated using the mean exhaled CO2 (PECO2), which is
measured as the exhaled PCO2 averaged over several breaths. While the anatomical dead space is for the most part
fixed (approximately 25% of the total ventilation) the Vd/Vt alv is the most useful of these parameters, because it is
close to 0 in normal lungs, and it increases with the inefficiency of ventilation due to disease. The Vd/Vt alv can be
calculated:
Vd/Vt alv = (PaCO2 - PetCO2) / PaCO2
where PetCO2 is the PCO2 at end- expiration, or ‘end- tidal’. When the expiratory flow reaches a plateau, the
PetCO2 is highly representative of the PACO2. A normal PECO2 is approximately 30 mmHg, and a normal PetCO2
is 38 - 40 mmHg (nearly the same as PaCO2).
Respiratory mechanics.
Moving air in and out of the lungs- the law of motion of the respiratory system. When we breathe, we
generate a negative pressure with the respiratory muscles (Pmus) that that causes a flow (V) of gas in the airways
and an increase of volume of the lungs (Vt). Exhalation occurs by passive elastic recoil. This rhythmic movement
is opposed by the impedance of lung and chest wall (the ‘respiratory system’) composed by the resistance to flow
through the airways (Raw) and the elastance (E) or ‘stiffness’ of the respiratory system. When a patient is
mechanically ventilated, the pressure to generate flow is applied from the exterior, generally a positive pressure
from a ventilator (Pvent); when a patient is partially ventilated (e.g., on pressure support ventilation) the pressure
will be a combination of negative (Pmus) and positive (Pvent) pressure. These phenomena describe the law of
motion of the respiratory system:
Paw = Pmus + Pvent = V x Raw = Vt x E
where Paw is the pressure at the airway. This relationship has important corollaries:
1. Ventilation works the same whether spontaneous, mechanical, or a combination of the two.
2. The mechanical characteristics of the respiratory system, i.e., resistance and compliance (C, the reciprocal
value of elastance), are important determinants of the effects of ventilation.
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3. If we set a variable on a ventilator (e.g., Vt) and measure another (e.g., Paw) we can then calculate the third
one, Raw or C.
Bedside measurement of respiratory mechanics. Modern ventilators (included anesthesia ventilators) have the
capability to measure with acceptable precision pressure, flow and volume. A practical way to assess respiratory
mechanics during anesthesia and intensive care includes:
1. Setting the ventilator on volume- limited, constant (‘square- wave’) flow.
2. Verifying that the patient is adequately relaxed and is not taking spontaneous breaths.
3. Performing an end- inspiratory pause (‘inspiratory hold’), which separates the dynamic component of the
Paw (peak inspiratory pressure [PiP]) from the static component or plateau pressure (Pplat) and allows to
calculate Raw and C.
4. Performing an end- expiratory maneuver (rarely available in anesthesia ventilators) to measure the intrinsic
positive end-expiratory pressure (PEEPi).
Figure 3 shows an airway pressure trace obtained as described, with the respective measurements of mechanics-
compliance and resistance:
C = Vt / Pplat –PEEP
Raw = (PiP - Pplat) / V
The volume- limited mode provides the value of Vt; the end- inspiratory pause creates a semi- static condition
(Pplat) that takes away the pressure component due to airway resistance (PiP - Pplat). Normal values of C of the
respiratory system (Crs, sum of C of the lung [Cl] and of the chest wall [Ccw]) is 80 - 100 mls / cm H2O.
The volume- limited mode also provides a convenient
way to calculate Raw by setting the inspiratory flow
rate at 60 l/min (1 l/sec), which will allows to divide the
PiP - Pplat difference by 1. Normal Raw is 1- 3
cmH2O/l/sec.
Finally, it is important to understand the concept of
intrinsic PEEP (PEEPi), or ‘auto- PEEP’. During
normal ventilation (spontaneous and mechanical), at
end- expiration the lung returns to functional residual
capacity (FRC), and the alveolar pressure (estimated by
the Paw) equals atmospheric pressure (‘zero’). When
there is expiratory flow limitation, as in asthma,
emphysema, and upper airway obstruction, the lung
volume may not reach FRC before the next breath. In
these conditions, the lung volume at end- expiration is
larger than FRC, and the alveolar pressure higher than
0. PEEPi has similar effects of externally applied
PEEP: it can increase PaO2 and decrease cardiac output.
However, differently from applied PEEP, the PEEPi has to be overcome by the patient’s effort in order to start each
breath. This wasted effort (wasted because it does not generate any volume) can be taxing on subjects with
borderline respiratory function and contribute to failure. Additional complexities of respiratory mechanics relevant
to our practice include the effect of lung volume and the effect of the chest wall.
Compliance over a range of lung volumes (Figure 4). The bedside measurement of compliance described above is
carried out at the Vt set on the ventilator. Although an acceptable approximation in normal circumstances, in
conditions that decrease (ALI/ARDS) or increase (emphysema) lung volume, the relationship between alveolar
volume and pressure is no longer linear additional measurements at various lung volumes may be of value. A more
comprehensive measurement of compliance includes constructing a semi- static pressure / volume curve by
delivering a series of lung volumes, possibly from FRC to total lung capacity (TLC), with respective measurements
of Pplat. The compliance is the slope of the pressure / volume line. Under normal circumstances, this relationship is
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almost linear, flattening as it nears TLC (25 - 30 cmH2O). In situations characterized by a low lung compliance,
such as ALI/ARDS, the shape of this relationship changes. Here, the curve is not only moved to the right (lower
compliance) but also assumes a sigmoid shape, indicating that at the two extremes of lung volume (near FRC and
near TLC), compliance is much lower. This finding has potential clinical implications:
1. Breathing over the steep part of the line is most
efficient, because it causes the least increase in
pressure for a given volume.
2. Recruiting collapsed alveoli will increase FRC
and reduce the initial flat segment of the curve. This
may be accomplished by a level of PEEP at or above
the flat segment.
3. Setting end- inspiratory pressure below the value
of the high flat segment may avoid lung overdistention
In clinical practice, this kind of measurement is
cumbersome and requires a high degree of expertise.
Nevertheless, the physiological principles behind it are
useful to select the level of PEEP and of Pplat to set
on a ventilator.
The lung, the chest wall, and the transpulmonary
pressure. While we generally use the term
‘compliance’ referring to the compliance of the lungs,
what we are actually measuring with the method
described above is the overall compliance of the
respiratory system (Crs), which includes in equal parts the compliance of the lung (Cl) and of the chest wall (Ccw).
In many cases, changes of CRS are a reasonable estimate of changes of Cl. However, in certain situations, our
measurements of Pplat may not accurately estimate pressures exerted by the lung, and our use of Crs as a surrogate
of Cl may lead to incorrect decisions. To better understand these phenomena, we need to review the concept of
transpulmonary pressure (Ptp):
Ptp = Pplat - Ppl
Where Pplat is the surrogate for alveolar
pressure, and Ppl is the intrapleural pressure.
Since normal Cl and Ccw in humans are equal, if
we apply 10 cmH2O PEEP to the airway of a
normal subject, half of this pressure will be
transmitted across the lung, resulting in a Ppl of 5
cmH2O and a Ptp of 5 cmH2O (Table 1). If the
subject has stiff lungs (e.g., ALI/ARDS) less
PEEP is transmitted, and the Ptp will be higher; if
the subject has a stiff chest wall (e.g.,
laparoscopic surgery) more PEEP will be
transmitted and the Ptp will be lower.
Consider the circumstance of an acutely injured
lung (e.g., ALI/ARDS) that can be damaged by a
high ventilating pressures (‘ventilator- induced
lung injury’), the Pplat. However, the pressure
that hurts the lung is not the Pplat but the Ptp.
Hence, in the ALI/ARDS lung we have to be
concerned when we reach a high Pplat (e.g., 30 cmH2O) because with a stiff lung the Pplat is a good estimate of the
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Ptp. On the contrary, during laparoscopic surgery or during ALI/ARDS with abdominal distention, a high Pplat is
due also to a low Ccw and thus overestimates the Ptp Reducing the VT out of concern of a high Pplat under these
circumstances may lead to alveolar derecruitment and hypoventilation. The most common way to measure Ppl is via
an esophageal balloon (esophageal pressure). Unfortunately, measuring Ppl is imprecise and somewhat
cumbersome, requiring specialized equipment and significant expertise.
Another situation where the pressure measured at the airway may not correctly estimate the pressure in the alveoli
occurs when a patient is adding spontaneous breathing efforts to a set level of mechanical support, typically during
pressure support ventilation.
Here, the VT results from the combination of the pressure applied by the ventilator and the pressure generated by the
patient. Unfortunately, the latter cannot be
measured by the ventilator, and the displayed Paw
is not a reliable surrogate of the Ptp. For
example, a patient generating a VT of 700 mls on
10 cmH2O of pressure support may give the
impression to have an excellent Cl (CRS = 700
mls/10 cmH2O = 70 ml/cmH2O). However, we
do not know how much additional pressure the
patient is generating to get to that 700 mls VT.
An example of this situation is shown in Figure
5, where the proper calculation of the distending
pressure (through the use of an esophageal
balloon) shows that the patient’s compliance was
significantly lower that one would have estimated
just by looking at the set Paw during pressure
support ventilation.
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Suggested reading
1. JB West. Respiratory Physiology- The Essentials. Seventh edition. Lippincott Williams and Wilkins,
Philadelphia, 2005.
2. A Lumb. Nunn’s Applied Respiratory Physiology. Sixth edition. Elsevier, Philadelphia, 2005.
3. AC Guyton, JH Hall. Textbook of Medical Physiology, Eleventh edition. Elsevier, 2006.
4. West, JB. Ventilation- perfusion relationships. Am Rev Respir Dis 1977;116:919-943.
5. Mancini M, Zavala E, Mancebo J, et al. Mechanisms of pulmonary gas exchange improvement during a
protective ventilatory strategy in acute respiratory distress syndrome. Am J Respir Crit Care Med
2001;164:1448-145.
6. Lucangelo U, Blanch L. Dead space. Intensive Care Med 2004;30:576-579.
7. Rossi A., Gottfried SB, Zocchi L, et al. Measurement of static compliance of the total respiratory system in
patients with acute respiratory failure during mechanical ventilation. Am Rev Respir Dis 1985;131:672-677
8. Ninane V, Yernault J-C, De Troyer A. Intrinsic PEEP in patients with chronic obstructive pulmonary disease.
Am Rev Respir Dis 1993;148:1037-1042
9. Lucangelo U, Bernabé F, Blanch L. Respiratory mechanics derived from signals in the ventilator circuit. Respir
Care 2005;50:55-67.
10. Hess DR, Bigatello LM. The chest wall in acute lung injury/acute respiratory distress syndrome. Curr Opin Crit
Care 2008;14:94-102.
11. Hess DR. Ventilator waveforms and the physiology of pressure support ventilation. Respir Care 2005;50:166.
12. Dhand R. Ventilator graphics and respiratory mechanics in the patient with obstructive lung disease. Respir
Care 2005;50:246-261.
13. Bigatello LM, Davignon KR, Stelfox HT. Respiratory mechanics and ventilator waveforms in patients with
acute lung injury. Respir Care 2005; 50:235-244
14. Harris RS, Hess DR, Venegas JG. An objective analysis of the pressure- volume curve in the acute respiratory
distress syndrome. Am J Respir Crit Care Med 2000;161:432-439.
15. Talmor D, Sarge T, Malhotra A, et al. Mechanical ventilation guided by esophageal pressure in acute lung
injury. N Engl J Med 2008;359:2095-2104.
DISCLOSURE
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Protecting the Kidney from Perioperative Injury
Robert N. Sladen, MBChB, FCCM New York, New York
CLINICAL DEFINITIONS AND PATHOGENESIS OF ACUTE KIDNEY INJURY (AKI)

For many years the ability to quantitate renal protection was hampered by the lack of a clear clinical definition of
acute kidney injury (AKI). In 2000 a group of experts (the Acute Dialysis Quality Initiative) met and defined AKI
by five criteria they called RIFLE (Risk, Injury, Failure, Loss, End-stage) 1. The first 3 stages (R,I,F) reflect the
increase in serum creatinine (SCr), decrease in estimated glomerular filtration rate (eGFR) or duration of oliguria
within a 7-day period; the second two (L,E) reflect renal outcome. Subsequently, the group coalesced into the Acute
Kidney Injury Network (AKIN) 2, and simplified the definition into three stages evaluated over 24 hrs, and
acknowledged the adverse implications of even small increases in SCr (Table 1):
2
Table 1: AKIN Criteria for AKI
Stage Serum Creatinine (SCr) Urine Output (UO)

1 Increase by 1.5-2 x baseline, < 0.5 mL/kg/hr x 6 hr
or by > 0.3 mg/dL
2 Increase by 2-3 x baseline < 0.5 mL/kg/hr x 12 hr
3 Increase by 3 x baseline, < 0.3 mL/kg/hr x 24 hr
or by 0.5 mg/dL if SCr > 4 mg/dL or anuria > 12 hr
Limitations of RIFLE and AKIN Criteria

Both the RIFLE and AKIN definitions of AKI identify an increasing severity of insult and show good correlation
with renal outcome. There is actually poor correlation between oliguria alone and AKI unless there is hemodynamic
instability 3, so most studies now use the AKIN SCr criteria only. It may be days before the SCr reaches its peak
postoperative value that reflects the nadir GFR 4, which is unhelpful for real-time diagnosis. A more meaningful
indicator of actual GFR is obtained by a short (< 2 hr), timed creatinine clearance 5. The RIFLE and AKIN criteria
do not address the common postoperative entity of non-oliguric renal failure (NORF) or prerenal oliguria; nor do
they offer any insight into the etiology of AKI.
Renal Biomarkers
More than 50 biomarkers have been studied as indicators of renal injury6. Cystatin C, a cysteine proteinase inhibitor
released by all nucleated cells and completely filtered by the glomerulus, is advocated as a more stable indicator of
GFR than SCr 7. A number of proteins that are released into the urine within hours of ischemia could serve as
biomarkers of acute tubular injury: these include neutrophil-gelatinase associated lipocalin (NGAL) 8, 9, interleukin-
18 (IL-18) 10, and kidney injury molecule-1 (KIM-1) 11. The most promising biomarker to date is liver-type fatty
acid-binding protein (L-FABP), whose urinary concentrations increase earlier and more specifically than NGAL 12.
It is conceivable that a reliable renal biomarker – or panel of biomarkers 13 - for AKI may render the RIFLE and
AKIN criteria obsolete, but we are not there yet. In the interim they do provide surrogate end-points for randomized
controlled trials (RCTs) and allow stratification based upon the severity of injury.
Renal Autoregulation and Urine Output
It is important to note that renal autoregulation maintains RBF and GFR through a broad range of perfusion
pressure, but does not preserve urine flow, which is very pressure dependent14. Blood pressure (BP) invariably
decreases during anesthesia, and urine flow declines accordingly; when BP returns to normal at emergence, so does
urine flow.
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An important endogenous mechanism to preserve GFR in the face of decreased RBF or arterial pressure is
preferential efferent arteriolar constriction induced by local release of norepinephrine (NE), angiotensin II and
arginine vasopressin (AVP). This explains the loss of GFR when a patient under stress is given an angiotensin
converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB).
In patients with chronic hypertension autoregulatory responses are reset, so a higher BP may be required to maintain
RBF and GFR. In certain states, including AKI, sepsis and possibly cardiopulmonary bypass (CPB), renal
autoregulation may be impaired or lost, so RBF becomes much more pressure dependent15.
Perioperative Oliguria and the Prerenal Syndrome

The etiology of oliguria traditionally has been defined as postrenal, prerenal or intrarenal. Postrenal oliguria implies
urinary tract obstruction (renal pelvis, ureters, bladder, urethra or urinary catheter) and typically manifests as anuria
if the obstruction is complete. A postrenal etiology should always be evaluated first.
If postrenal obstruction has been excluded, perioperative oliguria should be interpreted as a prerenal (physiologic)
response to intravascular hypovolemia. The latter may be absolute (acute hemorrhage, severe diarrhea, vomiting,
fluid restriction), or relative (congestive heart failure, sepsis, liver failure).
Hypovolemia and hypotension trigger osmoreceptor, volume receptor and baroreceptor reflexes that include the
sympathoadrenal and renin-angiotensin systems, aldosterone and AVP (formerly called antidiuretic hormone,
ADH). The net effect is avid reabsorption of water and sodium (Na), resulting in oliguria with high urine osmolality
(UOsm) and low urine Na (UNa). When normal renal hemodynamics are restored, the stimulus to the tubules abates
and normal urinary flow resumes. If hypovolemia is severe and/or combined with nephrotoxic insults, frank AKI
may ensue (intrarenal oliguria).
In sepsis and liver failure, circulating endotoxin disrupts the renal circulation and induces a prerenal “vasomotor
nephropathy” characterized by oliguria and Na retention (UNa < 10 mEq/L). It is refractory to fluid replacement
and responds only to treatment of the underlying condition.
In sum, perioperative oliguria is common, but rarely implies AKI 16. It is a sign of intravascular hypovolemia and
should be treated as prerenal until otherwise proven. In contrast, the absence of oliguria does not exclude AKI,
because about 75% is non-oliguric (urine flow rate 15-80 mL/hr) 17, a reflection of incremental smaller insults in a
protected milieu. Until the role of renal biomarkers becomes established, the most reliable early clinical indicator of
AKI and diminished GFR remains a serial decline in measured creatinine clearance.
The Interface between Prerenal Syndrome and AKI
In the classic animal model of ischemic acute tubular necrosis (ATN), the nature of the injury depends on the
duration of infusion of NE into the renal artery. A brief infusion (< 60 min) results in reversible oliguria; the intact
renal tubules avidly conserve Na and water so UNa is low and UOsm high; and oliguria resolves when the NE
infusion stops. This is a typical prerenal syndrome.
A longer infusion (60 – 120 min) results in persistent oliguria and subsequent azotemia after NE is stopped: this is
ATN. The renal tubules lose their ability to conserve salt and water, so urine sodium is high and osmolality low.
When normal renal hemodynamics are restored, GFR remains < 10% of baseline because of tubular obstruction by
necrotic cells in the proximal tubule; loss of glomerular-tubular gradient; and back leak of tubular fluid into the
interstitial tissue 18. The implication of this model is that the physiologic, reversible prerenal syndrome may
deteriorate into frank ATN if the ischemic insult persists long enough. A prerenal (dehydrated) state also sensitizes
the kidney to nephrotoxic insults from non-steroidal anti-inflammatory drugs (NSAIDs), aminoglycoside antibiotics,
radiocontrast dyes and calcineurin inhibitors. Also in this model, administration of “renal protective agents” (saline,
mannitol, vasodilators) prior to NE infusion ameliorates the severity of ATN, akin to the clinical syndrome of non-
oliguric acute renal failure (NORF) 19.
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Nephrotoxic Pathways to AKI

An isolated insult in a normal milieu almost never induces AKI, but risk increases exponentially when multiple
agents are administered in an adverse milieu that may be acute (shock, hypovolemia, CHF) or chronic (advanced
age, diabetes, chronic renal insufficiency) 20. The reasons are explained below.
Nephrotoxic agents directly injure target cells but also cause harm by disrupting renal oxygen balance in the
medullary thick ascending loop of Henle (mTAL). The hypertonic medulla provides renal concentrating ability, but
to do so, RBF must remain very slow (<10% of total RBF) and the tissue PaO2 is accordingly very low (<10
mmHg). The mTAL is at risk when dehydration further compromises available RBF, and/or there is any disruption
to the formation of local nitric oxide or prostacyclin that maintains medullary vasodilation. Nephrotoxic AKI is
usually non-oliguric and SCr increases quite slowly.
A minoglycosides
Aminoglycosides are absorbed into intracellular lysosomes where they inhibit oxidative phosphorylation and ATP
synthesis 21. Their nephrotoxicity is related to sustained high trough serum levels 22, and can be ameliorated by
hydration, monitoring of serum levels and creatinine clearance, and once-daily administration 23.
Non-steroidal A nti-inflammatory Drugs (NSA IDs)

Cyclooxygenase-1 (COX-1) inhibition by NSAIDs (e.g. indomethacin, meclofenamate or ketorolac) impairs
medullary vasodilator prostaglandin synthesis. During stress, this results in decreased RBF and GFR, diuretic
unresponsiveness and hyperkalemia 24.
Calcineurin A ntagonists
Cyclosporine A and tacrolimus induce sympathetic hyperreactivity and renal vasoconstriction. This is counteracted
by calcium channel blockers, which provide renoprotection after cadaveric renal transplantation 25.
Radiocontrast A gents
Hyperosmolar radiocontrast agents induce osmotic diuresis (hypovolemia), RBC crenation (obstructed
microcirculation), and free oxygen radical release (tubular toxicity). The risk of radiocontrast nephropathy (RCN) is
increased by hypovolemia, diabetes, and CHF 26, and may be ameliorated by hydration, low-osmolar radiocontrast
agents, bicarbonate or N-acetylcysteine (see below) 27.
A C LINICAL A PPROACH TO O LIGURIA
Oliguria Algorithm:
1. Assume that oliguria is prerenal 28
2. Evaluate, monitor and treat intravascular volume deficits
3. Maximize renal blood flow by optimizing hemodynamic function
4. Maintain renal perfusion pressure with vasoconstrictor therapy (NE ± AVP)
5. Consider diuretic therapy (see below)
6. Counteract diuretic resistance (see below)
Diuretic Therapy
Therapeutic
Diuretic therapy should be reserved for oliguria that persists despite optimization of intravascular volume,
hemodynamic status and renal perfusion pressure 29. Administration of diuretic agents to “make urine” or relieve
edema in the face of intravascular hypovolemia or hypotension results exacerbates volume depletion and increases
the risk of AKI.
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Prophylactic
Diuretic agents induce renal cortical vasodilation (dopaminergic agents, loop diuretics), prevent tubular obstruction
(osmotic, loop diuretics), suppress reflex vasoconstriction (dopaminergic agents, natriuretic peptides), and decrease
tubular VO2 (dopaminergic agents, loop diuretics) 30. Prophylactic mannitol is commonly used in aortic cross
clamping, CPB, and pigment nephropathy (rhabdomyolysis, intravascular hemolysis, jaundice) 31. However, there is
little evidence that diuretic therapy is more effective in maintaining GFR than fluid volume loading alone 32-34.
Diuretic Resistance
A cute tolerance or the “braking phenomenon” refers to diuretic tachyphylaxis that occurs with hypovolemia, or
when repeated doses contract the ECF and activate Na retention; it is counteracted by fluid repletion 35. Caveat: a
diuretic agent or low dose dopamine is no substitute for rehydration!
Chronic tolerance refers to the situation that arises when long term administration of loop diuretics triggers
compensatory hypertrophy of the distal tubule 36.
Generalized edema refractory to diuretic therapy is encountered in acute and chronic kidney disease (CKD), renal
insufficiency, CHF, cirrhosis and the nephrotic syndrome. The pharmacokinetic handling and pharmacodynamic
effects of diuretics are markedly altered. In uremia, endogenous organic acids compete with loop diuretics for active
transport sites at the proximal tubule 37. Renal clearance of furosemide is inversely proportional to the BUN and
GFR 38. Depleted intravascular volume markedly increases proximal Na reabsorption, restricting Na available for
diuretic action at the mTAL 39.
Strategies for Overcoming Diuretic Resistance 36, 37
1. Restore normal hemodynamics.
2. Administer higher doses of diuretic agent
3. Concomitant administration of human albumin 40
4. Continuous diuretic infusion (furosemide 1-10 mg/hr) 41
5. Dual segment nephron blockade (loop + thiazide) 39
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Combination Diuretic Therapy (Loop + Thiazide)

Loop Diuretic Thiazide Diuretic
furosemide 20-40 mg IV chlorothiazide 125-250 mg IV
bumetanide 1-5 mg IV metolazone 2.5 mg PO bid
torsemide 10 mg IV
ethacrynic acid 25-50 mg IV
P HARMACOLOGIC I NTERVENTIONS TO P REVENT AND R EVERSE AKI
Mannitol
Mannitol is an “inert” sugar that may provide renal prophylaxis by expanding the intravascular volume, which
increases preload, cardiac output and atrial natriuretic peptide (ANP) release. It also induces an osmotic diuresis
that may prevent tubular obstruction; releases intrarenal prostaglandins; and attenuates reperfusion injury by
scavenging of free radicals. For the greatest effect mannitol should be present at the time of the renal insult 42.
Mannitol’s benefit is well established in animal models of AKI but there are few human RCTs that confirm this.
Loop diuretics
Loop diuretics (furosemide, bumetanide, torsemide, ethacrynic acid) inhibit Na reabsorption at the mTAL, and can
attenuate AKI if administered prior to a renal ischemic or nephrotoxic insult 43. However inappropriate diuresis to
“make urine” or relieve anasarca may induce a severe prerenal syndrome and exacerbate nephrotoxic insults. High-
dose (2-10 mg/kg) IV furosemide used to “convert” oliguric to non-oliguric AKI does not alter its outcome 44, 45.
Dopaminergic agonists
Stimulation of DA1 receptors causes renal vasodilation as well as inhibition of active Na transport in the proximal
tubule, leading to natriuresis and diuresis 46. Stimulation of presynaptic DA2 receptors inhibits NE release and
promotes peripheral vasodilation but appears to attenuate the beneficial effects of DA1 effectors on RBF.
Dopamine
Despite the lack of definitive evidence 47, “low dose” dopamine (0.5–3.0 µg/kg/min) has been widely used as a renal
protective agent. However, plasma dopamine levels vary markedly (up to ten-fold) in different individuals 48, and it
is likely that in many cases dopamine benefits the kidney by its beta-adrenergic actions (increased cardiac output,
renal blood flow and perfusion pressure) 49, 50. There is little if any evidence that prophylactic administration of low
dose dopamine has a positive impact on renal outcome 51. The use of low-dose dopamine is often limited by
unpredictable tachycardia, supraventricular and ventricular arrhythmias 52, which likely reflects the inter-individual
variability of plasma dopamine levels.
Fenoldopam
Fenoldopam is a phenol-dopamine analog that is a selective DA1-receptor agonist 53, with relatively rapid onset and
offset and an elimination half-life of 10 min. At infusion rates of 0.03-0.3 µg/kg/min it induces dose-dependent
increases in RBF. In 1998 fenoldopam was approved in the US for the short-term parenteral treatment of
hypertension, but there has been considerable interest in the use of low dose (< 0.05 mcg/kg/min) fenoldopam for
renal protection. A meta-analysis of 16 studies representing 1290 ICU or perioperative patients concluded that
fenoldopam consistently and significantly reduced the risk for AKI, need for dialysis, ICU length of stay and in-
hospital mortality 54. A meta-analysis that focused on cardiac surgery (6 studies, 440 patients) found a significant
benefit on the risk of AKI only, and an increase in the need for vasopressor therapy 55. With regard to nephrotoxic
AKI, a large study of prophylaxis in RCN showed no benefit 56, although a small retrospective one suggested
amelioration of RCN when fenoldopam was directly infused into the renal arteries 57.
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N-Acetylcysteine
N-Acetylcysteine (NAC) is an antioxidant long used as an antidote to acetaminophen toxicity. Initial studies
indicated efficacy in the amelioration of RCN in high-risk patients undergoing contrast radiography 58, with
decreased AKI and mortality in patients undergoing percutaneous coronary intervention 59. However, a recent large
(2308 patients) prospective RCT could not confirm this benefit 60. NAC has not been shown to be effective in
preventing AKI during cardiac surgery with CPB 61.
Sodium Bicarbonate
Through free radical scavenging, alkalinization of the urine (pH > 6.5) with sodium bicarbonate (NaHCO3) or
acetazolamide may theoretically ameliorate renal tubular injury. There are conflicting data on the protective effects
of NaHCO3 versus normal saline for protection against RCN. A large meta-analysis (12 trials, 1854 subjects)
concluded that although hydration with NaHCO3 decreases RCN by SCr criteria, it has no impact on the need for
dialysis or in-hospital mortality 62. In an RCT on 100 patients, a 24-hr infusion of NaHCO3 during high-risk cardiac
surgery decreased the incidence of a >25% rise in postoperative SCr, without any other benefit 63. Clearly, large
RCTs are needed to clarify the risk-benefit ratio of urinary alkalinization on the incidence and outcome of AKI.
Natriuretic Peptides
The natriuretic peptides (22-32 amino acids) oppose the sympathoadrenal, renin-angiotensin, aldosterone, and AVP
systems 64, counteract the vasoconstrictor and anti-natriuretic responses induced by hypovolemia, and induce
vasodilation and natriuresis that protect against hypervolemia and hypertension. Their vasodilator and renal effects
are mediated by cyclic guanosine monophosphate (cGMP), which increases glomerular filtration fraction by afferent
arteriolar vasodilation.
Atrial (A-type) natriuretic peptide (ANP) is synthesized by modified atrial myocytes and released by atrial stretch
and increased CVP 65. Brain (B-type) natriuretic peptide (BNP) is synthesized in the cardiac right and left
ventricles, and is released by ventricular dilation. Assay of BNP (and its precursor, N-terminal-pro-BNP) is used as
an ER diagnostic tool for acute CHF, and BNP levels correlate with outcome in acute myocardial ischemia as well
as heart failure. C-type natriuretic peptide (CNP) is synthesized in the endothelium of the great vessels. Urodilatin
is a renal 22-amino acid peptide that has less vasodilator activity than ANP.
Anaritide
Anaritide is the human recombinant formulation of ANP. Parenteral administration decreases systemic BP by
arterial and venodilation, increases GFR, induces natriuresis, and reverses renovascular hypertension. In animal
models of ischemic66 or nephrotoxic67 ATN anaritide demonstrated great promise as a rescue agent. However a 504
patient RCT showed improved dialysis-free survival in oliguric (urine output < 400 mL/day) patients only, and
outcome was actually worse in patients with non-oliguric ARF17. A follow up study on 222 patients with oliguric
ARF found no difference in renal outcome between anaritide and placebo68. The lack of benefit of anaritide appears
to be related to hypotension induced by its vasodilator effect, and attests to the importance of maintenance of renal
perfusion pressure when renal autoregulation is impaired69.
Nesiritide
Nesiritide is the human recombinant formulation of BNP, approved by the FDA for the parenteral treatment of
patients with advanced decompensated CHF. In these patients it provides preload and afterload reduction, enhances
cardiac function, and also can promote a sustained diuresis with improvement in pulmonary congestion, edema and
anasarca 70. The major adverse effect is dose-related hypotension, which can impair renal function 71. However, in
an RCT of 279 patients with impaired ventricular function (EF <40%) undergoing CPB for coronary
revascularization or mitral valve surgery, patients who received low dose nesiritide had increased urine output, an
attenuated postoperative increase in SCr, and improved survival six months after surgery 72.
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Vasopressor Therapy
Renal autoregulation maintains RBF and GFR over a wide range of renal arterial pressure. In certain situations,
notably ATN itself 69, severe sepsis 15, and possibly during cardiopulmonary bypass 73, autoregulation appears to be
lost or attenuated. Moreover, in these situations systolic BP may fall below the normal autoregulatory limit.
Hypotension results in strikingly decreased RBF, which is restored by normalization of renal perfusion pressure -
even if this is achieved by vasoconstrictor therapy.
Established Acute Renal Failure
In established acute renal failure (stage 3 AKI) there is an almost complete loss of renal autoregulation 69, so that
hypotension during intermittent hemodialysis (HD) provides a repetitive ischemic insult to the kidney that delays or
prevents renal recovery from ATN. In animal models of ischemic ATN, the renal vasculature develops a smooth
muscle injury that renders it relatively unresponsive to the vasoconstrictor effect of NE 74. This suggests that during
intermittent HD, BP should be supported with fluids or even pressor therapy, and that continuous venovenous
hemodialysis (CVVHD), which provides greater hemodynamic stability, should be used in the ICU.
Vasodilatory Shock
In severe sepsis with vasodilatory shock, impaired autoregulation is implicated by the dramatic improvement in
renal function that is observed when BP is normalized by the use of vasopressor therapy. This response has been
observed with infusions of NE 15 and low dose (1-4 u/hr) AVP 75. As well as restoring overall renal perfusion
pressure, AVP preferentially constricts the efferent arteriole, thereby improving glomerular filtration pressure,
filtration fraction and GFR 76.
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DISCLOSURE
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Understanding Clinical Hemodynamics
Micharel F. O’Connor, M.D. FCCM Chicago, Illinois
The physiologic paradigm that clinicians reference in their attempts to explain and understand the biology
of both healthy and critically ill patients has been in evolution for more than 100 years. Interestingly, our
understanding of the clinical circulation has always been thought of as ‘complete’, with creative clinicians invoking
a variety of reasons to explain away apparent discrepancies between commonly used mental models and the realities
of clinical medicine.
The most primitive formulation of the circulation entails simple conservation of matter:
Cardiac Output = Stroke Volume x Heart Rate = Qt = SV x HR
This statement, while obviously always true, offers sapient practitioners little insight into why the
circulation in a particular patient might be unacceptable, and how they might rationally intervene. During the mid-
20th century, a relatively complete paradigm for understanding the role of the venous return in controlling the
cardiac output was refined by Guyton and his co-workers, and has been repetitively validated since it was first
described (refs Jacobsohn, Magder, Guyton, Sylvester). Although not complete, this theory was powerful in the
hands of those who understood it.
The balloon-tipped, flow directed, thermistor equipped pulmonary artery catheter heralded the subsequent
era of the understanding of the clinical circulation. This device, coupled with a deep understanding of the
mechanics of left ventricular function heralded the era in which the circulation and all of its pathology were
understood from the perspective of the left-ventricle – which some now refer to as the LV centered view of the
circulation (Sagawa). For those who trained in that paradigm, preload, afterload, and contractility were the
determinants of cardiac output:
Cardiac Output = CO = MAP-RAP

SVR
(Where MAP = Mean Arterial Pressure, RAP = Right Atrial Pressure and SVR = Systemic Vascular Resistance)
Some patients have a right heart limited circulation, which can be formulated using a very similar equation:
__
CO = PA - LAP
__ PVR
(Where PA = Mean Pulmonary Artery Pressure, LAP = Left Atrial Pressure, and PVR = Pulmonary
Vascular Resistance).
Nevertheless, the LV centered view of the circulation focused on preload, afterload, and contractility, and
was frustrated by a variety of obstacles. The most important was the poor correlation between measured filling
pressures and left ventricular end-diastolic volumes as assessed by echocardiography (refs Kumar,Hofer, Kramer).
Echocardiography has documented that LV compliance is far more dynamic than anyone believed prior to its
widespread clinical use (Coriat). The other, more insidious problem with the LV centered world-view is that
adherents tend to regard RAP almost exclusively as an index of circulatory volume, forgetting that it is the
downstream hydrostatic resistance to venous return in the model of Guyton:
VR = CO = Pms – RAP
RVR
(Where VR = Venous Return, RAP = Right Atrial Pressure, and RVR = Resistance to Venous Return)
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The circulation in any patient at any moment in time is the product of the interaction of the venous circuit
with the heart (the pump). The RAP is a product of that interaction.
All of this has produced the present understanding of clinical hemodynamics, which is predicated on a
synthesis of venous return and cardiac physiology (Sylvester, Jacobsohn). This model can be used to generate a
series of questions that can guide the assessment of a patient in shock.
What is Shock? Shock is globally inadequate perfusion of tissues sufficient to produce both tissue hypoxia and
organ dysfunction. While shock is classically associated with hypotension, there is increasing acceptance of the
contention that hypotension is a relatively ‘late’ indicator of shock, and that clinicians should be more attuned to
organ system dysfunction as evidence of shock.
Signs of Shock:
- altered mentation
- oliguria
- decreased mixed venous or central venous saturation
- hypotension, abnormal heart rate
- lactic acidosis
- peripheral cyanosis (variable)
In both the critical care and trauma literature, the endpoints for resuscitation have also evolved. While
traditional endpoints such as mean arterial pressure and central venous pressure are still regarded as important,
increasing emphasis is being placed on the mixed/central venous oxygen saturation (Ladakis) and lactate levels in
the blood. The combination of inexpensive and readily available serum lactates and increasing appreciation of the
prevalence of hyperchloremic acidosis in the setting of large volume resuscitation has led to the near abandonment
of the base excess/deficit as a guide to the adequacy of resuscitation. Several publications over the past several
years have dampened enthusiasm for the use of central venous oxygenation (Chawla, Sander, Varpula), but it
nevertheless remains a very useful indicator of the adequacy of oxygen delivery.
It is helpful to understand the modern incarnation of the Fick Equation of the relationship between oxygen
consumption, cardiac output, arterial oxygen content, and mixed venous oxygen content. This algebraic
rearrangement emphasizes that the mixed venous saturation is adequate only when the delivery of oxygen to the
peripheral tissues is well matched to their needs:
SvO2 (CvO2) = CaO2 – VO2

Qt
(Where SvO2 is the mixed venous oxygen saturation, CvO2 is the mixed venous oxygen content, CaO2 is the
arterial oxygen content, VO2 is the oxygen consumption, and Qt is the cardiac output)
Importantly, as oxygen delivery to the tissues falls, oxygen extraction rises, and continues until the tissues are no
longer able to extract more oxygen. When this happens, crisis ensues.
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In the above figure, oxygen extraction increases as oxygen delivery decreases. When the tissues reach the limits of their ability
to extract oxygen (the critical extraction ratio ERc), the critical oxygen delivery has been reached (Qo2c), and further decreases
in oxygen delivery will be associated with a decline in oxygen consumption.
Arterial hypoxemia, anemia, hyper-metabolism, and a low cardiac output all lower the mixed venous and central
venous saturation. Increasingly, practitioners are utilizing protocols which include as one of their endpoints a
central venous oxygen saturation above a certain level (Ladakis, Rivers). This strategy of ‘forward defense’ is in
part based on the increasing recognition that hypotension is a relatively late indicator of shock, and that resuscitating
a patient to a marginal blood pressure may leave them with an inadequate physiologic reserve.
__
From Physics : V = I x R Substituting produces: BP – Pra = Qt x SVR
Hypoperfusion (shock) can arise from:

- low cardiac output
- low SVR
- the combination of a low cardiac output and high SVR
We can represent the circulation by superimposing the Starling curve and the venous return curves. Examples of
this are below:
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As demonstrated by the above figure, we can superimpose the Starling curve from above left upon the venous return curve from
the above right and generate a graphical representation of the state of the circulation. The cardiac output is represented by the
Y projection of the intersection of these curves, and the CVP we measure clinically is represented by the X projection of the
intersection of these curves.
Diastolic dysfunction is a generally underappreciated and very important contributor or cause of shock
states.
In animal models of hemorrhagic shock, even small reductions in pleural pressures from reduced levels of
PEEP or reduced respiratory rates can produce dramatic improvements in survival (Herff). This data, coupled with
similar data from animal models of CPR, are generating increased interest in ventilation strategies associated with
the lowest possible airway pressures in patients with shock.
Causes of Diastolic Dysfunction:
Extrinsic Intrinsic Luminal

PEEP, iPEEP Ischemia RV failure/septal shift
tPTX LV H Tumor (e.g. myxoma)
Pericardial fluid Infiltration Clot
Massive ascites Fibrosis
In the above table, those causes listed in italics may be responsive to the infusion of volume. The other causes are minimally
responsive to volume infusion, or not at all.
Bedside Assessment of the patient with shock
The following questions constitute an orderly way to assess the patient with inadequate circulation:
1. Is the Cardiac Output Reduced?

2. Is the heart “too full”?
3. What doesn’t fit?
Is the cardiac output reduced?

No → Vasodilated Shock
Yes → Hypovolemic shock, Cardiogenic Shock, or Obstruction to Venous Return
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The above figure demonstrates the sentinel feature of vasodilated or high cardiac output shock: the wide pulse
pressure. Patients with vasodilated shock almost invariably have a pulse pressure which is greater than half of their
systolic pressure, whereas patients with low cardiac output shock typically have a pulse pressure which is
substantially lower than normal. A patient with a blood pressure of 80/30 almost certainly has vasodilated shock,
whereas a patient with a blood pressure of 80/60 will have one of the causes of low cardiac output. On examination,
patients with vasodilated shock will have brisk capillary refill while patients with low cardiac output shock will have
delayed capillary refill.
Differential Diagnosis of Vasodilated Shock:

- Sepsis, Sepsis, Sepsis
- Systemic Inflammatory Response Syndrome (SIRS) (e.g. pancreatitis)
- Hepatic failure
- Anaphylaxis
- Adrenal insufficiency
- AV fistula
- Others
Is the heart too full?

If the cardiac output is low, the differentiation of hypovolemic and cardiogenic shock is accomplished
through the review of pertinent historical, physical examination, and laboratory data. Historical information is often
compelling in its support for the conclusion that hypovolemia is the cause of an unacceptable circulation.
Causes of Hypovolemia: Supportive of Cardiogenic Shock:

- Hemorrhage - jugular venous distention
- insensible losses - extra heart sounds
- redistribution to extravascular space - pulmonary edema in association with narrow PP
- GI losses - signs or symptoms of myocardial ischemia
- renal losses - new heart murmurs
- vasodilation (venodilation) - cardiomyopathy or myocarditis
Cardiogenic shock is most readily assessed with echocardiography. The differential diagnosis of
cardiogenic shock includes acute LV infarction, acute on chronic LV failure, RV infarction, RV failure from some
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cause of increased pulmonary vascular resistance, and previously undiagnosed valvular lesions such as aortic
stenosis, mitral stenosis, and mitral regurgitation.
Echocardiography has supplanted the Swan-Ganz catheter as the method of choice for assessing the patient
with suspected cardiogenic shock. Reasons for this include increasing recognition that practitioner understanding of
how to utilize data from a Swan-Ganz catheter is generally poor (Iberti), difficulty demonstrating that these catheters
improve outcomes (Sandham), and increasing acceptance that central venous gases correlate well with mixed venous
gases. Perhaps most importantly, echocardiographic studies have documented surprisingly poor correlation between
filling pressures as measured by invasive monitors and left ventricular end-diastolic volume (Osman). Evidence
impeaching the use of central venous pressure measurements continues to accumulate, and is now being
summarized in colorful review articles(Marik).
As a consequence of these insights, experts are increasingly advocating the use of arterial pulse pressure
variation as a guide to administering fluid, with a difference of >10-15% with respiration strongly associated with a
favorable response to fluid administration (Michard, 2005). The two most commonly used metrics are Systolic
Pressure Variation (SPV) and Delta Pulse Pressure (ΔPP). Systolic Pressure Variation is easier to estimate from
conventional monitors, but is slightly inferior to delta Pulse Pressure (also referred to as Pulse Pressure Variation –
PPV). SPV and/or PPV outperform both CVP and Pcwp as predictors of volume responsiveness in septic patients
and cardiac patients, including patients undergoing OPCAB and post-op CABGs (Auler, Hofer, Kramer). Newer
monitors intended for use in either the ICU or the OR incorporate software that facilitates the evaluation of these
parameters. Other technologies, including Stroke Volume Variation (SVV)(Lahner, Machare-Delgado), and the
PICCO derived Intrathoracic Blood Volume Index (ITBV)) are being explored as alternatives to the CVP in
predicting volume responsiveness (Muller), but do not yet match the performance of either PPV or SPV. There is a
growing literature regarding the use of pulse-oximeter derived plethysmography as a less-invasive alternative to
SPV or PPV(e.g. Pizov)
Systolic pressure variation is useful as a guide to the management of the patient in shock in another way:
patients with minimal or no variation in the blood pressure and pulse pressure are very unlikely to respond to
volume administration. The initial efforts to resuscitate such patients should therefore be directed at pharmacologic
or mechanical interventions, which are much more likely to be effective. Because this strategy minimizes the
unnecessary administration of fluid to critically ill patients, it may improve outcomes.
What doesn’t fit?

Most patients with hypovolemic shock, LV shock, and sepsis respond to appropriate therapy. Failure to
respond should raise red flags, and drive an evaluation for obstructive shock. Obstructive shock is shock caused by
an obstruction to venous return. Obstructions to venous return are often insidious. While volume resuscitation and
therapy with vasoactives might produce a transient minor improvement in the circulation, the definitive treatment
consists of relieving the obstruction if this is possible.
Interestingly, as a group, obstructions to venous return produce the kinds of variations in pulse
pressure described above (Magder 2004, 2005). More recent clinical studies have reported that right ventricular
shock can also produce an increase in SPV or PPV that is not responsive to fluid administration (Mahjoud). Hence,
when a patient with significant pulse pressure variation (and a higher CVP) fails to respond to fluid administration,
the sapient practitioner should entertain the possibility of right ventricular shock or an obstruction to venous return
as the explanation. The expeditious evaluation of such patients includes a physical exam with careful attention to
the character of the heart tones, chest wall symmetry and excursion, and abdominal wall tension. In patients with
tense or distended abdominal walls, transducing a bladder pressure is very helpful in completing the evaluation for
abdominal tamponade. In mechanically ventilated patients, the expiratory flow waveform should be evaluated for
auto-PEEP. In most instances, a stat portable chest radiograph, trans-thoracic echocardiogram, and the measurement
of a bladder pressure will be sufficient to complete the evaluation of a patient with refractory shock.
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Causes of Obstructive Shock (Obstructions to Venous Return)

- pericardial effusion
- restrictive pericardium
- tension pneumothorax
- high levels of PEEP or intrinsic PEEP
- massive pleural effusion
- abdominal tamponade
- venous occlusion (clot, air, tumor, pregnancy)
- atrial occlusion (clot, air, tumor)
Reconciliation of Central Venous Pressures and Dynamic Indicators
The following 2x2 table is intended to aid practitioners in their assessment of patients with hypotension:
Studies using strategies similar to this are beginning to be reported in the literature (Benes).
References:
- Magder S: Hemodynamic monitoring in the mechanically ventilated patient. Curr Op Crit Care 2011; 17:36-42
- Machare-Delgado E, Decaro M, Marik PE: Inferior Vena Cava Variation Compared to Pulse Contour Analysis as
Predictors of Fluid Responsiveness: A Prospective Cohort Study Journal of Intensive Care Medicine 26(2) 116-124
- Benes J, Chytra I, Altmann P, et al: Intraoperative fluid optimization using stroke volume variation in high risk
surgical patients: results of prospective randomized study Critical Care 2010, 14:R118
- Pizov R, Eden A, Bystritski D, et al: Arterial and Plethysmographic Waveform Analysis in Anesthetized Patients
with Hypovolemia. Anesthesiology 2010;113:83-91
- Marik PE: Techniques for Assessment of Intravascular Volume in Critically Ill Patient J Intensive Care Med 2009
24: 329-37
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- Mahjoud Y, Pila C, Friggeri A, et al: Assessing fluid responsiveness in critically ill patients: False-positive pulse
pressure variation is detected by Doppler echocardiographic evaluation of the right ventricle Crit Care Med 2009;
37:2570-75
- Marik PE, Cavallazzi R, Vasu T, et al: Dynamic changes in arterial waveform derived variables and fluid
responsiveness in mechanically ventilated patients: A systematic review of the literature. Crit Care Med 2009;
37:2642–2647
- Lahner D, KabonB, Marschalek C, et al: Evaluation of stroke volume variation obtained by arterial pulse contour
analysis to predict fluid responsiveness intraoperatively. Br J Anaesth 2009; 103: 346–51
- Marik PE, Baram M, Vahid B: Does Central Venous Pressure Predict Fluid Responsiveness? A Systematic Review
of the Literature and the Tale of Seven Mares. Chest 2008; 134:172–178
- Muller L, Louart G, Bengler C, et al: The Intrathoracic Blood Volume Index as an Indicator of Fluid
Responsiveness in Critically Ill Patients with Acute Circulatory Failure: A Comparison with Central Venous
Pressure. Anesth Analg 2008;107:607–13
- Herff H, Paal P, von Goedecke A, et al: Influence of ventilation strategies on survival in severe controlled
hemorrhagic shock. Crit Care Med 2008; 36:2613–2620
- Gelman S: Venous Function and Central Venous Pressure. Anesthesiology 2008; 108:735– 48
- Durairaj L, Schmidt GA: Fluid Therapy in Resuscitated Sepsis: Less is More. Chest 2008; 133:252–263
- Buettner M, Schummer W, Huettemann, E et al: Influence of systolic-pressure-variation-guided intraoperative fluid
management on organ function and oxygen transport. British Journal of Anaesthesia 2008;101 (2): 194– 9
- Auler JO, Galas F, Hajjar L, et al: Online Monitoring of Pulse Pressure Variation to Guide Fluid Therapy After
Cardiac Surgery. Anesth Analg 2008;106:1201–6
- Osman D, Ridel C, Ray P, et al: Cardiac filling pressures are not appropriate to predict hemodynamic response to
volume challenge. Crit Care Med 2007; 35:64–68
- Sander M, Spies CD, Foer A, et al: Agreement of central venous saturation and mixed venous saturation in cardiac
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oxygen saturation in septic shock. Intensive Care Med 2006; 32:1336–1343
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DISCLOSURE
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Pulmonary Hypertension and RV Failure
Eric Jacobsohn MB.ChB., MHPE, FRCPC Winnipeg, Manitoba, CANADA
Introduction: Pulmonary hypertension (PH) and the associated RV dysfunction is increasingly being encountered
in the perioperative period. Managing these patients is challenging, but a thorough understanding of the
pathophysiology of PH and the associated RV dysfunction allows the practioner to anticipate, prevent and
successfully manage many of the perioperative risks. The normal systolic, diastolic, and mean pulmonary artery
pressure (PAP) is 25 mmHg, 10 mmHg, and 15 mmHg, respectively; the normal range for pulmonary vascular
resistance (PVR) is 0.9 to 1.4 Wood units (or 90 to 120 dynes · s · cm-5). The PVR is the quotient represented by
PVR = (ΔP)/flow, where ΔP represents the mean PAP (mPAP) minus the left atrial pressure (LAP). This gradient
commonly is referred to as the transpulmonary gradient (TPG). If the TPG is elevated, there is an increase in the
PVR. On the contrary, if the TPG is not elevated, the increase in PAP is caused by an elevated LAP (implicating
elevated LA pressure as a result of cardiac pathology). Flow is the blood flow through the pulmonary circulation i.e.
cardiac output (CO). Thus, PVR = (mPAP - LAP) ÷ CO, or mPAP = LAP + (CO X PVR). Therefore, only 3
physiological factors increase in mPAP: (1) increase in LAP (due to cardiac pathology), (2) an increase in CO
(congenital heart disease [CHD] with left-to right shunt, fluid overload, and hyperdynamic states), and (3) an
increase in PVR (pulmonary parenchymal/airway disease, hypoxia, interstitial lung disease, thromboembolic
disease, and idiopathic pulmonary artery hypertension). Because of pulmonary vascular remodeling, even factors 1
and 2 eventually leads to an increased PVR, and the associated increased mPAP will reflect both an increased LA
pressure as well as increased PVR. For example, a patient with mitral valve stenosis who has an increased mPAP
solely because of an increased LAP (without increased PVR, i.e., “reversible” PH). These patients, mitral valve
replacement is usually uncomplicated and has little risk of RV failure. In comparison, patients with mitral stenosis
and increased mPAP because of increased LAP as well as increased PVR (secondary to pulmonary vascular
remodeling, i.e., “fixed” PH), may have severe RV failure after mitral valve replacement and difficulty in weaning
from CPB. Acute–on-chronic increases in PVR are common the perioperative period, and can lead to acute
decompensation in RV function. These factors include, amongst others, hypoxia, hypercarbia, acidosis, hypothermia
(shivering), increased sympathetic tone (pain, anxiety), and exogenous or endogenous pulmonary vasoconstrictors
such as catecholamines, serotonin, thromboxane, and endothelin. Early recognition and reversal of these causes of
acute deterioration could be lifesaving.
Definition of PH: Normal mPAP at rest is 14± 3 mmHg, with an upper limit of 20 mmHg. The significance of
mPAP between 21-24 mmHg is unclear. The European Society of Cardiology and the European Respiratory Society
define pre-capillary -PH is as persistent increase in mPAP ≥ 25 mmHg at rest as assessed by right heart
catheterization (RHC) in the setting of a normal PCWP of ≤15 mmHg, a PVR of ≤3 Wood units, and normal or
reduced CO. They define post-capillary PH is defined as a persistent increase in mPAP ≥25 mmHg at rest as
assessed by RHC in the setting of an increased PAWP ≥15 mmHg, PVR ≥3 Wood units, and normal or a reduced
CO. The definition of PH according to the American College of Cardiology/American Heart Association 2009
Expert Consensus Document on PH, is a measurement by RHC, of a resting mPAP ≥25 mmHg, a PCWP/LAP ≤15
mmHg, and a PVR ≤3 Wood units.
Classification of PH: PH has undergone several relassifications over the alst 20-years. The most recent
classificaction system is shown in Table 1. It has 5 major categories, which include pulmoanry arterial disease
(PAH), left heart disease, lung disease/hypoxemic states, chronic thrombo-embolic pulmonary hypertension
(CTEPH), and unclear/multifactorial category.
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Table 1
Pathogenesis: PH is a syndrome resulting from a

pathologic increase in PVR, which leads to restricted
flow through the pulmonary arterial circulation and,
ultimately, RV failure. The etiology is often
multifactorial and complex, a schematic of wg hich is
shown in Figure 1. The loss of vascular luminal cross-
section because of vascular remodeling is the main
cause for the increased PVR. Excessive
vasoconstriction may be a significant contributing
factor in about 20% of patients. The pan-vasculopathy
that predominantly affects small resistance pulmonary
arteries and involves intimal hyperplasia, medial
hypertrophy, adventitial proliferation, thrombus in situ,
varying degrees of inflammation, and plexiform
arteriopathy. Mutations in 3 genes in the transforming
growth factor-superfamily receptor pathway, namely,
BMPR-2, activin receptor–like kinase-type 1(ALK-1),
and endoglin, have been implicated in the pathogenesis
of heritable PAH. The markedly reduced penetrance in
families with PAH suggests that some form of “second
hit” is required in addition to the mutation to lead to the
manifestation of clinical disease. Endothelial
dysfunction contributing to PAH involves increased
Figure 1
production of vasoconstrictor and mitogenic compounds such

as endothelin-1, angiotensin-2, serotonin, and thromboxane A2
and a deficient production of vasodilators such as prostacyclin
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and NO. These mechanisms may be partcularly germane to PH assiociated with appeptite suppressant and in cases
of newborm PH associated with SSRI use during pregnancy. Prostacyclin is a potent vasodilator and inhibits platelet
activation, and has antiproliferative properties. In patients with PAH, there is a reduced ratio of thromboxane
A2:prostacyclin, favoring thrombosis, proliferation, and vasoconstriction. Decreased endothelial NO synthase has
been observed in PAH patients. Vasoactive intestinal peptide (VIP) causes vasodilatation and lung VIP levels are
decreased in patients with PAH. Hypoxia causes vasodilatation of systemic vessels and vasoconstriction of the
pulmonary vasculature,in part through the action of endothelin and serotonin. Acute hypoxia further inhibits the
function of voltage-gated KATP channels of the PA smooth muscle, resulting in membrane depolarization, an
increase in cytoplasmic calcium concentration, and vasoconstriction.
Diagnosis and investigation: The most common presenting symptoms are dyspnea on exertion, fatigue, chest
pain, syncope, palpitations, and lowerextremity swelling. Signs of PH and RV failure include tachypnea,
tachycardia, distended neck veins, left parasternal lift, an audible tricuspid regurgitation murmur, ascites, and
lowerextremity edema. The American Heart Association proposes divding the investigation into two sets of tests:
pivotal and contingency tests, and these are shown in Figure 2. An electrocardiogram, chest x-ray, and
echocardiogram may display signs suggestive of PH . An echocardiogram should be considered once PH is
suspected by history, clinical examination, and risk factors. Possible causes of PH that can be excluded or confirmed
by echocardiography are
congenital and acquired valvular
Figure 2
disease, LV systolic and diastolic
dysfunction, large pulmonary
embolus, congenital disease with
shunts. It ia important to rule out
CTEPH as 50% of patients with a
diagnosis of CTEPH have no prior
history of acute pulmonary
embolism. The screening test of
choice to exclude CTEPH is
radionuclide perfusion scanning. A
normal or very low probability
scan essentially excludes CTEPH,
whereas a high probability scan
warrants further evaluation with a
pulmonary angiogram. A spiral
CT scan, although excellent in
excluding an acute PE, is less
sensitive than perfusion scanning
in excluding CTEPH. RHC should
be performed in all cases
diagnosied with PH to confirm the
diagnosis and assess the
hemodynamic profile, inclusing
esponse to an acute vasodilator
therapy. PVR is a more accurate diagnostic criterion to define PH because it reflects the influence of the TPG and
CO and only is elevated if the vascular obstruction occurs within the precapillary pulmonary circulation.
Therapy: Medical therapy: Treatment goals include improvement in symptoms, functional capacity, lowering
mPAP and normalizing CO, slowing the rate of progression of the underlying disease, and improvement in survival.
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Low-level aerobic exercise is encouraged. Avoidance of high altitudes and oxygen supplementation on commercial
aircraft for patients with room air saturations is advised. Oxygen therapy is indicated if oxygen saturation < 90% on
room air. Ideally, pregnancy should be avoided. Routine anticoagulation with coumadin may improve survival.
Digoxin and diuretics are used for RV for failure. Calcium channel blockers are indicated in a small, select group of
patients with idiopathic PAH who show acute vasodilator responsiveness. Prostanoids are the mainstay for many
patients. The 3 prostanoids available for treatment of PAH include intravenous epoprostenol (ie, prostacyclin/PGI2),
subcutaneous treprostinil, and inhlaed iloprost, each with its own adnavatgees and disadvantages. Several studies
have shown improved symptomatology, exercise tolerance, hemodynamics, quality of life, and survival. Although
tachyphylaxis with the need for frequent dose adjustments occurs, the beneficial effects of prostanoids can be
sustained for years, and, as a result, many patients have been removed from heart-lung transplantation lists. The
endothelin antagonists, including drugs such as bosentan and sitaxsentan, are another important class of therapy.
They are increasingly used as first-line oral therapy. The phospdiesterases (PDE) are another important class of
agents. PDE 3 and 5 are enzymes that inactivate cAMP and cGMP, respectively, the principal second messengers of
prostacyclins and NO. PDE inhibitors such as milrinone and sildenafil, act to augment cAMP- and cGMP-mediated
intracellular signaling, leading to vasodilation and decreased PVR. Sildenafil improves exercise capacity, quality of
life, and hemodynamics. Oral sildenafil has been used successfully to manage acute RV dysfunction in heart
transplant recipients,to wean patients from NO, to reduce time on mechanical ventilation, and to prevent the
sequelae of CPB on pulmonary endothelial cell function.85,86 More recently, it has been shown that sildenafil is
absorbed via the sublingual route. Although not yet studied definitively, this may have implications for emergent
perioperative care. The PDE-3 inhibitor, milrinone, acts similarly and can be administered intravenously or by
inhalation. Recent studies have shown symptomatic benefit (without survival benefit) from combination therapies.
The addition of sildenafil to inhaled iloprost or subcutaneous treprostinil is well tolerated and appears effective.
Invasive therapy: Observations have shown that patients with Eisenmenger syndrome (right-to-left shunting through
an atrial or ventricular septal defect) and PAH generally have superior survival rates compared with idiopathic PAH,
mainly because of decompression of a pressure-overloaded RV, improved LV filling, and a resulting increase in CO.
Atrial septostomy is considered as a palliative procedure and/or a bridge to lung/heart-lung transplantation in
patients with intractable RV failure despite maximal medical therapy. The intraatrial shunt causes a decrease in
systemic arterial oxygen saturation that is compensated for by increases in CO and systemic oxygen delivery.
Pulmonary endarterectomy (PEA) is indcated for carefully selected patients with CTEPH. The goal is to remove
enough material to lower PVR and increase CO. Bilateral lung transplantation (and occasional heart-lung
transplanation) is the final option for a minority of patients in whom medical therapy has failed; however, death
rates on waiting lists are high because of a global shortage of donor organs. Although effective medical therapy has
reduced the rate of transplantation in patients with PAH, approximately 4% of lung and combined heart and lung
transplants performed annually worldwide are still for PAH patients. Extracorporeal support is indicated in patients
with PAH are acute RV failure and hypoxemia caused by a massive PE, bridge-to-lung transplant, support after lung
transplant, treatment of severe reperfusion edema after PEA, and for RV failure unresponsive to conventional
medical therapy.Patients with end-stage RV failure because of PAH have done poorly with ventricular assist
devices as tegh increased flow in a compromised pulmonary vascaular bed further increasespulmonar vessel injury,
leaqding to pulmonary hemorrhage, hemoptysis, and death.
Prognosis: Advanced functional class, rapid symptom progression, poor exercise capacity, RV dysfunction, low
CO, elevated brain natriuretic peptide, and an associated diagnosis of scleroderma as re associated with a poor
outcome. The best survival rates are seen in patients with congenital heart disease associated PH. Idiopathic PAH
has a median survival of 2.8 years A recent meta-analysis of 21 trials with 3,140 patients reported improvements in
the exercise capacity and a 43% reduction in mortality.
Perioperative RV failure in patients with PAH: Acute decompensation of patients with PH during the
perioperative period is relatively common, can be lethal, and occurs as a result of acute RV failure. However, it is
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often preventable. Eisenmenger syndrome undergoing a cesarean section have been said to have a perioperative
mortality of up to 70%. It is unlikely however, with todays knowlege and therapy, that this is still the case. Patients
with PAH who require surgery should likely be managed in a centre and by a team experienced with the disease.
Patients with PAH undergoing liver transplantation may have a mortality as high as 80%. The degree of
preoperative RV dysfunction and elevation in PVR, together with the type of surgical procedure, are the major
predictors of perioperative risk. High-risk surgical procedures include those that could cause significant
perioperative systemic inflammatory response; rapid blood loss; high possibility of venous air, CO2, fat, or cement
emboli; loss of lung blood vessels; and (reversible) factors leading to acute increases in PVR (eg, acidosis, hypoxia,
shivering, pain, and anxiety). All attempts must be made to optimize PVR before surgery, including maximizing
medical therapy and preventing conditions that may cause acute deterioration. Patients on chronic intravenous
prostacyclin therapy ideally should continue their therapy throughout the perioperative period because
discontinuation can precipitate an acute pulmonary hypertensive crisis. Changing to inhaled therapy under
controlled conditions may be considered in order to mitigate the potent antiplatelet effect of intravenous
prostacyclin, and potentially allow for neuraxial blockade. In selected patients not on PAH-specific therapies, a
preoperative RHC, vasodilator trial, and PAH-specific therapy may be indicated. Patients with an unacceptable high
risk for perioperative decompensation (even after optimization of medical therapy) should not have surgery or
should be considered for noninvasive alternatives to surgery.
Acute decompensation caused by RV failure frequently is misdiagnosed. Unlike cardiogenic shock from acute LV
failure alone (with systemic hypotension, end-organ hypoperfusion, and relatively normal RA pressures), acute RV
failure causes increases in RA pressure and systemic venous pressure. Acute RV shock therefore has a worse
prognosis than acute LV shock; the reasons for this are shown in Figure 3. As shown, in two hypothetical patients
with similar cardiac outputs, the patient with RV failure has a “double hit” compared to the patient with LV shock
i.e reduced inflow and reduced outflow. This double hit on the vital organs in acute RV failure can rapidly (within
hours) manifest as multiple organ system failure. In addition, the elevated RA pressure may cause hypoxemia in
susceptible patients by causing a right-to-left shunt across a patent foramen ovale. It is important to note that
tricuspid regurgitation (TR) is common in acute and chronic RV failure, and, hence, thermodilution CO
measurements may be misleading. TdCO accuracy depends on the severity of the TR (in severe TR, it
underestimates CO), but there is also a flow dependency of TdCO in TR (in acute TR, there is an underestimation of
Td CO when the CO is high, an overestimation when the CO is low, and a minimal effect when the CO is
midrange). TdCO also may be inaccurate in the presence of anatomic shunts; if there is a left-to-right shunt,
thermodilution will measure pulmonary rather than
Figure 3, 4 systemic blood flow because the cold indicator
will be diluted by shunted blood. If there is a right-to-
left shunt (Eisenmenger), thermodilution will measure
systemic rather than pulmonary blood flow because
some of the cold indicator will pass through the shunt.
However, the PAP measurements still may be useful to
monitor the effect of pulmonary artery vasodilators or
vasopressors. Some of the interventions and drugs that
improve RV function (ie, alpha adrenergic agonists,
phosphodiesterase inhibitors, and calcium sensitizers)
may have potentially deleterious effects on the
systemic vascular resistance (SVR), particularly if the
decrease in SVR is larger than the increase in RV CO.
Similarly, systemic vasopressors used to maintain
systemic blood pressure and RCA perfusion may cause
elevation in PVR.
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The treatment principals of perioperative RV failure (Figure 4) include:
1. Optimize RV rate and rhythm. Sinus rhythm is

optimal filling of a hypertrophied and dilated right
ventricle. Because of the association of RV failure with
TR, higher heart rates may be desirable to reduce end-
diastolic volume. Stroke volume is limited by the
increase in RV afterload, it is best to avoid bradycardia.
If there is significant RV ischemia, excessive
tachycardia may not be tolerated either. A loss of sinus
rhythm may lead to acute hemodynamic
decompensation, and early synchronized cardioversion
should be considered. In cardiac pacing is possible,
atrial or atrial-ventricular sequential pacing leads to
improved RV diastolic filling compared with ventricular
pacing alone. It is crucial to optimize electrolytes and
magnesium, and to consider amiodarone early to control
or prevent atrial fibrillation.
2. Optimize of RV filling. Perioperative CVP monitoring is important; in general, when the CVP is low, the RV
must be “coping” even if the PAP and PVR are elevated (ie, the right ventricle must have been“primed”
[hypertrophied] and exposed to a progressively higher PAP and PVR over time). On the other hand, an elevated
CVP may imply a failing right ventricle with or without TR. The compromised right ventricle will tolerate neither
hypovolemia nor overfilling; therefore, an optimal position has to be determined and maintained on the
compromised failing RV Frank-Starling curve. Because the RV is mainly a “volume chamber,” it is less preload
dependent than the LV; thus, for a given increase in preload, a smaller increase in stroke volume is expected.
However, because it is thin walled, the RV is much more afterload dependent than the LV and the RV CO decreases
significantly with an acute increase in mPAP. Past teachings have often suggested that the RV be filled aggressively
to passively increase pulmonary blood flow and CO. This may hold true with normal PVR (Fontan physiology,
which is not the case in PH) but not in circumstances in which the PVR is high. Excess volume loading will result in
acute RV distention, increased TR, right-to-left shift of the interventricular septum, impairment of LV end-diastolic
filling and pericardial constraint (due to distended RV). These factors all causes a reduced stroke volume, reduced
systemic blood pressure, inadequate RCA perfusion, and an ensuing downward hemodynamic spiral. This is
especially true once the CVP reaches values of 15 to 20 mmHg. It is difficult to determiine optimal RV filling. This
can be assessed with cautious fluid boluses (250 mL of lactated Ringer’s solution) or by an autotransfusion by
elevation of the patient’s legs. Ongoing fluid boluses are indicated if elevation of the legs causes a modest (2-5
mmHg) elevation in CVP and corresponding elevation in PCWP and mean arterial pressure; an elevation of only the
CVP (with minimal/ no change in PCWP or mean arterial pressure) likely indicates RV distention and precludes
further fluid boluses. A relatively underfilled RV is likely the lesser of 2 evils.
3. Maintain RV myocardial performance. This includes maintenance of RV coronary perfusion pressure and RV
inotropic therapy. Normally, RV coronary perfusion occurs during systole and diastole. However, as the PVR and
RV pressure rises, the RCA flow changes to be mainly in diastole (similar to left coronary artery perfusion). RV
subendocardial ischemia, caused by myocardial oxygen supply-demand imbalance, is common in PH. To avoid this,
systemic hypotension, excessive increases in RV pressure, contractility, and heart rate must be avoided. It is
important to immediately increase the systemic blood pressure and, subsequently, RCA perfusion pressure when
acute RV failure is diagnosed. This can be achieved by optimizing the volume status and use of vasopressors (i.e.
norepinephrine and vasopressin). Accumulating clinical experiences as well as animal data suggest that vasopressin
causes less of an increase in RV afterload than does norepinephrine and reduces the dose of norepinephrine required
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to maintain the systemic blood pressure. The choice of type of anesthesitic technque (general versus regional ) and
the type of anesthetic agents is much less improtant than understanding the physiological perturbations induced by
the anesthetic. Anticipating and mitigating the physioological effects will prevent acute decompenstion, allowing
many types of anesthesia for these patients. In this regard, volatile agents, propofol, thiopental, narcotics, ketaime
and etomidate can all be used in the appropriate manner. RV contractilty may have to be enhanced in acutely failing
RV with either beta-adrenoreceptor agonist therapy (e.g. dobutamine), PDE-3 inhibitor (milrinone), or a calcium-
sensitizer (levosimendan). All the classes also reduce PVR. The may be used in combinnation. However, when
given in larger doses, they may also acutely reduce SVR. If the increase in RV CO does not offset the reduction in
SVR, the systemic BP may decrease, and the RCA perfusion will be compromised. This may aggrevate the situation
instead of improving RV function. It is therfore crucial to start these agents at a low- dose to avoid the deletrious
effects on SVR. Dobutaine effects are short-lived and may be easier to titrate than milrinone. The combination of
low-dose dobutaime and low-dose milrinone are synergistic and may optimize cardiac function with less side
effetcs than higher doses of each agent alone. Levosimendan is a cardiac inotrope that binds to troponin C,
sensitizing the cell to calcium, which increasese contractility without increasing intracellular calcium. Epinephrine,
norepinephrine, and dopamine, due to their multi-receptor profiles, are less atractive agents.
4. Maintain the transeptal gradient (TSG) and RV geometry. At normal RV systolic pressure (25 mmHg) and
LV systolic pressure (125 mmHg), there is a large gradient from the left ventricle to the right ventricle (TSG = 100
mmHg), causing the normal interventricular septum to bulge into the RV. This provides a “scaffold” against which
the RV-free wall contracts. Septal function accounts for about 50% of normal RV systolic. Therefore, conditions
that reduce the LV pressure (systemic hypotension) or increase the RV pressure (PH) will reverse the TSG and
severely compromise RV function. These conditions are common in patients with RV dysfunction due to PH, and
the periopetrative period creates many opportunities to aggrevate the TSG changes (e.g. any cause of reduced SVR).
This causes the RV to become more globular (the RV “bulges” into the left ventricle and impairs LV filling). The
missalignment of the oblique arrangement of the RV septal myofibrils (due to dilation and shift) causes RV
dysfunction. In order to maintain the TSG, the PVR needs to be reduced, and the systemic blood pressure needs to
be aggresively maintained.
5. Reduce PV R. Patients on chronic therapy for PH should continue their established treatment during the
perioperative period. Anesthetic agents that increase PVR should be minimized. FRC must be carefully maintained
(Figure 5) and any factors that cause a reduction in FRC must be avoided. In contrast to systemic arteries,
pulmonary vessels constrict with hypoxia (Euler-Liljestrand reflex)
and dilate with hyperoxia. Thus, perioperative hypoxemia,
hypercarbia, atelectasis, pleural effusions, hypothermia, fluid
Figure 5
overload, pain, and anxiety can all cause acute rises in PVR with
resultant RV decompensation. Therefore, perioperative ventilation
strategies of patients with PAH should incorporate high
concentrations of oxygen, low tidal volumes (6 mL/kg of predicted
body weight), a respiratory rate sufficient to achieve mild hypocarbia,
and optimum levels of positive end-expiratory pressure (5-10
cmH2O). Early drainage of pleural effusions and recruitment
maneuvers should be considered.Intravenous air or particulate
material (precipitated drugs) should be avoided because of the
potential for right-to-left embolization through an opened foramen
ovale.
Apart from the previously mentioned physiologic considerations, the PVR be reduced by selective PA vasodilators.
Unfortunately, none of the available intravenous PA vasodilators is selective enough not to cause accompanying
systemic vasodilation, which potentially could lead to reductions in the RV coronary perfusion and RV ischemia.
Hence, we need to use dugs that cause pulmonary artery dilation “selectively”, either by virtue of their specificty for
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PA or by virtue of the method of delivery. Inhaled PA vasodilators cause preferential vasodilation in well-ventilated
lung zones, with improvement in V/Q matching and arterial oxygen saturation. Inhaled agents decrease mPAP, have
little effect on SVR, so TSG is not deletriouasly affected. Commonly used inhaled agents include various
prostanoids (prostacyclin and iloprost), inhaled milrrinoe, and inhaled nitric oxide. The each have the advantages
and limitations, and some of the agents used in combination may have be mechanistically additive. A proposed
algorithm for using sel;ective PA vasodilators is shown Figure 6.
Conclusion: The perioperative management of patients with PH and associated RV dysfunction is complex and
requires a thorough understanding of the PA/RV pathophysiology. Failure to diagnosis RV failure early and institute
the correct therapy will lead to high perioperative morbidity and mortality. The anesthesiologist has to be aware of
the potential treatment strategies including optimizing
physiologic parameters, the use of selective
pulmonary artery vasodilators, and inotropic and
systemic blood pressure support. These patients
should be managed by teams familiar with the disease.
References:
1. Strumpher JS, Jacobsohn E. Pulmonary hypertension and RV failure. Physiology and perioperative management. J Cardiovasc Thorac Anesth
25( 4): 687-704, 2011
2. Farber H, Loscalzo J: Pulmonary arterial hypertension. N Engl J Med 351:655–166, 2004
3. Simonneau G, et al: Updated clinical classification of pulmonary hypertension. J Am Coll Cardiol 54:S43-S53, 2009 (suppl)
4. Galiè N, et al: Guidelines for the diagnosis and treatment of pulmonary hypertension: ESC/ERSGUIDELINES. Eur Heart J 30:2493-2537,
2009
5. McLaughlin V, et al, for the Writing Committee: CCF/AHA 2009 Expert Consensus Document on Pulmonary Hypertension: A Report of the
American College of Cardiology Foundation Task Force on Expert Consensus Documents and the American Heart Association Developed in
Collaboration With the American College of Chest Physicians; American Thoracic Society, Inc.; and the Pulmonary Hypertension Association. J
Am Coll Cardiol53:1573-1619, 2009
6. Benza RL, et al: Predicting survival in pulmonary arterial hypertension. Insights from the Registry to Evaluate Early and Long-Term
Pulmonary Arterial Hypertension Disease Management (REVEAL). Circulation 122:1644 –172, 2010
7. Hoeper MM, et al: Chronic thromboembolic pulmonary hypertension. Circulation 113:2011-2020, 2006
8. Sitbon O, et al: Long-term intravenous epoprostenol infusion in primary pulmonary hypertension: Prognostic factors and survival. J Am Coll
Cardiol 40:780-788, 2002
9. Simonneau G, et al: Continuous subcutaneous infusion of treprostinil, a prostacyclin analogue, in patients with pulmonary arterial
hypertension: A double-blind, randomized, placebo controlled trial. Am J Respir Crit Care Med 165:800-804, 2002
10. Opitz CF, et al: Clinical efficacy and survival with first-line inhaled iloprost therapy in patients with idiopathic pulmonary arterial
hypertension. Eur Heart J 26:1895-1902, 2005
11. Hoeper MM, et al: Long-term treatment of primary pulmonary hypertension with aerosolized iloprost, a prostacyclin analogue. N Engl J Med
342:1866-1870, 2000
12. McLaughlin VV, et al: Survival with first-line bosentan in patients with primary pulmonary hypertension. Eur Respir J 25:244-249, 2005
13. Barst RJ, et al: Sitaxsentan for pulmonary arterial hypertension. Am J Respir Crit Care Med 169:441-447, 2004
14. Lewis GD, et al: Sildenafil improves exercise capacity and quality of life in patients with systolic heart failure and secondary pulmonary
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hypertension. Circulation 116:1555-1562, 2007

15. Hoeper MM, Welte T: Sildenafil citrate therapy for pulmonary arterial hypertension. N Engl J Med 354:1091-1093, 2006
16. De Santo LS, et al: Role of sildenafil in acute post transplant right ventricular dysfunction: Successful experience in 13 consecutive patients.
Transplant Proc 40:2015-2018, 2008
17. Freitas AF, et al: Sublingual sildenafil on pulmonary hypertension in heart failure. Arq Bras Cardiol 92:116-126, 2009
18. Deveci S, et al: Sildenafil in the treatment of erectile dysfunction: Faster onset of action with less dose. Int J Urol 11:989-992, 2004
19. Micheletti A, et al: Role of atrial septostomy in the treatment of children with pulmonary arterial hypertension. Heart 92:969-972, 2006
20. Thistlethwaite PA, et al: Techniques and outcomes of pulmonary endarterectomy surgery. Ann Thorac Cardiovasc Surg 14:274-282, 2008
21. Jamieson SW, et al: Pulmonary endarterectomy: Experience and lessons learned in 1,500 cases. Ann Thorac Surg 76:1457-1464, 2003
22. Orens JB, et al, for the Pulmonary Scientific Council of the International Society for Heart and Lung Transplantation: International guidelines
for the selection of lung transplant candidates: 2006 update—A consensus report from the Pulmonary Scientific Council of the International
Society for Heart and Lung Transplantation. J Heart Lung Transplant 25:745-755, 2006
23. Martin JT, Tautz TJ, Antognini JF: Safety of regional anesthesia in Eisenmenger’s syndrome. Reg Anesth Pain Med 27:509-513,2002
24. Balik M, Pachl J, Hendl J: Effect of the degree of TR on CO measurements by thermodilution. Intensive Care Med 8:1117-1121, 2002
25. Heerdt PM, et al: Flow dependency of error in thermodilution measurement of cardiac output during acute tricuspid regurgitation.
Cardiothorac Vasc Anesth 15:183-187, 2001
26. Kerbaul F, et al: Effects of levosimendan vs. dobutamine on pressure load–induced RV failure. Crit Care Med 34:2814-2819, 2006
27. DeWet CJ, et al: Inhaled prostacyclin is safe, effective, and affordable in patients with pulmonary hypertension, right heart dysfunction, and
refractory hypoxemia after cardiothoracic surgery. J Thorac Cardiovasc Surg 127:1058-1067, 2004
DISCLOSURE
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Mechanical Ventilatory Support:

What Every Anesthesia Provider Should Know
Michael A. Gropper, M.D., PhD. San Francisco, California
Respiratory failure is the leading cause for admission to most intensive care units (ICU’s). Providing mechanical
ventilation is a core competency for every anesthesia provider, whether in the operating room or ICU. Mortality
from respiratory failure continues to fall, in part due to the recognition that the technique of mechanical ventilation
may result in propagation of injury. A number of recent advances have identified superior techniques for the
management of patients with acute respiratory failure and the acute respiratory distress syndrome (ALI/ARDS). In
order for the clinician to develop an understanding of modern mechanical ventilation, this lecture will review new
understanding of the pathophysiology of ventilator associated lung injury (VALI) and new techniques for the
management of patients requiring mechanical ventilation. In addition, new data regarding support of postoperative
respiratory failure is reviewed. New data regarding lung recruitment maneuvers is examined.
Ventilator Associated Lung Injury
Patients with ALI/ARDS usually require mechanical ventilation, yet the process of mechanical ventilation itself can
induce or worsen lung injury.1,2 To understand the rationale behind the various modes of mechanical ventilation, we
must first examine how the interactions between the ventilator and the lung. The mechanisms for VALI are
multifactorial, and include:
1. Volutrauma: Direct injury to alveoli from over-distention of the lung.
2. Barotrauma: Injury resulting from high intra-pulmonary air pressures.
3. Biotrauma: Lung and distant organ injury resulting from the release of inflammatory mediators into the
airspaces and into the systemic circulation.
4. Atelectrauma: Injury to alveoli resulting from the cyclic collapse and opening of atelectatic alveoli.
Volutrauma: Mechanical ventilation with large tidal volumes causes both physiologic and histologic injury to the
lung. This phenomenon can be separated from barotrauma, since when thoracic expansion is prevented, high
inspiratory pressures without lung expansion do not cause injury.3 In patients with ALI/ARDS, the lung
parenchyma tends to be heterogeneous, with atelectasis in dependent areas of the lung, and relative over-expansion
in the non-dependent areas. When a mechanical ventilatory breath is delivered, it will distribute according to
regional compliance. Heterogeneity in compliance may result with large tidal volumes being delivered to normal or
already overdistended lung regions. Limitation of tidal volume can prevent regional overdistention, and was the
basis of the successful ARDSnet trial.4 It is likely that the most important determinant of volutrauma is end-
inspiratory volume, rather than the tidal volume delivered. There is no convincing evidence that volutrauma occurs
in normal lungs until tidal volumes are very large.
Barotrauma: It can be difficult to separate the effects of high inspiratory pressure from those of high tidal volume.
In patients with ALI/ARDS, edema, infiltration of inflammatory cells, and formation of hyaline membranes all
contribute to worsened pulmonary compliance.5 Regardless of the mode of mechanical ventilation used, inspiratory
pressures are increased. Peak inspiratory pressures (PIP’s) are increased from a combination of decreased static and
dynamic lung compliance, and large and small airway secretions. As opposed to PIP, it is likely that the most
important determinant of barotrauma is the inspiratory plateau pressure. It is this pressure that most accurately
reflects end-inspiratory volume, and therefore lung injury. Keeping plateau pressure below 35 cmH2O is a
reasonable target to minimize barotraumas, and has been associated with improved outcomes.
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Biotrauma: Mechanical ventilation, especially with large tidal volumes, results in inflammatory mediator release
into the alveolar space and systemic circulation.6-9 When lung epithelial cells are stretched, they are stimulated to
produce these inflammatory mediators. These mediators have local and systemic effects identical to those seen in
severe sepsis. It is in this manner that patients presenting with primary pulmonary pathology, such as pneumonia,
can progress to multiple organ dysfunction syndrome (MODS). A large number of mediators have been implicated,
including TNFα, IL-1, IL-6, and metalloproteinases.10 There are no specific strategies to prevent biotrauma, other
than targeting prevention of VALI.
Atelectrauma: The cyclic opening and closing of atelectatic alveoli results in the phenomenon of atelectrauma.
ALI/ARDS results in pulmonary edema, and the inflammatory mediators and proteases released into the alveolar
space can disrupt the functioning of surfactant.5 These patients often have pleural effusions, and the combination of
these factors result in significant atelectasis, best appreciated on CT scan.11 When the atelectatic lung is inflated,
there is thought to be transmission of high shear pressures to the delicate alveolar wall. At very low tidal volumes,
lung compliance is low, up to what is termed Pflex, where atelectatic alveoli start to be recruited, and lung
compliance improves. To avoid this region of low lung compliance, and avoid atelectrauma, positive end-expiratory
pressure (PEEP) can be set to a level higher than Pflex. Alternatively, alveolar recruitment maneuvers can be
employed. The efficacy of these maneuvers is discussed in the section on protective mechanical ventilation.
Protective Mechanical Ventilation
Protective mechanical ventilation refers to the practice of setting the mechanical ventilator with the goal of
minimizing lung injury.12 There is no single, agreed upon approach to protective ventilation, yet most strategies
share the basic components of low tidal volumes and permissive hypercapnea. This section will review the rationale
for this practice, along with the major clinical trials demonstrating its efficacy.
Traditionally, patients with ALI/ARDS were mechanically ventilated with large tidal volumes. A 1996 survey by
Carmichael et al found that tidal volumes greater than 10 ml/kg were routinely used.13 Clinicians used these larger
tidal volumes because in general, when tidal volume and therefore mean airway pressure are increased, oxygenation
improves. With recent understanding of the detrimental effects of mechanical ventilation, a number of studies have
been carried out in order to identify the most efficacious (least injurious) method to support patients with
ALI/ARDS. After identification of volutrauma as a probable mediator of VALI, the first study to prospectively test
low tidal volumes was that by Hickling et al, who used low tidal volume and permissive hypercapnea in patients
with ARDS.14 Following this landmark study, a number of prospective clinical trials were performed testing
protective ventilation, culminating in the ARDSnet trial.4
The ARDSnet trial was a randomized, prospective trial comparing traditional tidal volume (12 ml/kg ideal body
weight) to low tidal volume (6 ml/kg IBW). All patients received assist-control ventilation, and were weaned by
protocol. Specific targets were set for all ventilator parameters, including rate, PEEP, FiO2, and management of
acidosis. A total of 861 patients were enrolled, and the trial was halted early by the data safety monitoring board
because of efficacy in the low tidal volume group. The important outcomes in this study included a reduction in
mortality from 40% to 31%, an increase in the number of ventilator-free days, and a decrease in non-pulmonary
organ system failures. There was a considerable amount of controversy regarding this study, focused primarily on
the use of 12 ml/kg in the control group.15 Subsequent investigation fully supported the results of the trial, and at
this time, ventilation of patients with ALI/ARDS should be according to the ARDSnet protocol. This study
contained an important surrogate outcome: patients in the high tidal volume group had significantly improved
oxygenation in the first two study days, yet increased mortality. This finding suggests that biotrauma, with remote
organ injury, is a critical component of the efficacy of protective mechanical ventilation.
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An important component of the ARDSnet trial was the selection of PEEP and FiO2 parameters. As stated
previously, levels of PEEP that exceed Pflex were thought to protect against atelectrauma, and possibly improve
outcomes. Adverse effects of high levels of PEEP include increased risk of barotrauma and decreased venous
return. The ARDSnet group examined the effect of higher levels of PEEP compared to traditional levels of PEEP,
when used in conjunction with 6 ml/kg IBW tidal volume. They were unable to demonstrate additional benefit
when higher levels of PEEP were used, and therefore the same PEEP/FiO2 parameters employed in the ARDSnet
trial are recommended. Similarly, recruitment maneuvers, where the lung is subjected to prolonged periods of
continuous positive airway pressure, have been attempted to try to recruit atelectatic lung. Recruitment maneuvers
in patients with severe ALI/ARDS can be dangerous, as venous return may decrease significantly, causing
hypotension, and alveolar ventilation is decreased, which may result in respiratory acidosis. In general, recruitment
maneuvers have been found to only transiently increase oxygenation, without changing outcome.16 At this time,
routine use of recruitment maneuvers cannot be recommended.
More recently, lung protective mechanical ventilation has been validated in a prospective cohort study. Needham et
al demonstrated an 8% reduction in overall mortality when there was 100% adherence to a lung protective
strategy.27
Prone Mechanical Ventilation
Patients with ALI/ARDS develop dependent atelectasis. Atelectatic areas of the lung cause intrapulmonary shunting
and ventilation/perfusion mismatching, both of which lead to hypoxemia. In addition, dependent atelectasis results
in regional compliance differences, and may contribute to volutrauma in normal lung segments. Computerized
tomography of patients with ARDS clearly shows this relationship.11 If these changes are gravity dependent, then it
is logical to assume that if the patient is turned from the supine to the prone position, that they would dissipate,
resulting in improved gas exchange. Although there are other, theoretical advantages to prone positioning such as
higher functional residual capacity and improved secretion drainage, it is improved oxygenation that has spurred the
enthusiasm for this technique. There are substantial logistical problems to prone positioning, including accidental
extubation, line or chest tube removal, and padding of the facial area. Gattinoni et al performed a multicenter,
prospective, randomized trial in patients with ALI/ARDS comparing supine positioning to placing patients in the
prone position for six or more hours per day for 10 days.17 They studied 304 patients, and did not identify a
difference in mortality. They did find a significant improvement in oxygenation, but as the ARDSnet trial taught us,
this is not a valid outcome parameter in patients with ALI/ARDS. Although there may be specific patients that may
benefit from this technique, routine use of prone positioning is not supported by the data. An alternative to prone
positioning is the use of beds that can provide significant side-to-side rotation. These beds have not been tested in a
randomized, prospective trial.
High Frequency Ventilation
High frequency ventilation (HFV) employs small tidal volumes and a high respiratory rate in an effort to minimize
inspiratory pressures in the injured lung.18 Whereas traditional mechanical ventilation uses respiratory rates from
approximately 2-40 breaths/minute, HFV uses rates up to 100 breaths/minute, and high frequency oscillation (HFO)
uses rates as high as 2,400 breaths/minute. In general, HFV results in increased mean airway pressure without
increasing PIP, but also is less efficacious for CO2 removal than traditional ventilation. This technique is frequently
used in neonatal respiratory failure, but remains controversial.19 The trials that have been conducted in adults,
similar to those trials of prone positioning, have been able to demonstrate improved oxygenation, but not reduced
mortality.20 HFV has recently been reviewed, including its role in lung protection during mechanical ventilation.21
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Dual Control Modes of Mechanical Ventilation
Traditional mechanical ventilation tends to be volume-cycled (synchronized intermittent mandatory ventilation and
assist control ventilation) with the thought that critically ill patients should have guaranteed minute ventilation.
Pressure limited mechanical ventilation may limit inspiratory pressures, but does so at the expense of guaranteed
minute ventilation; a rapid decrease in lung compliance may result in significant alveolar hypoventilation. Dual
control modes of mechanical ventilation try to exploit the advantages of both these methods: limiting inspiratory
pressure while ensuring adequate minute ventilation. A theoretical advantage is improved patient comfort, as the
ventilator can respond instantaneously to increased flow demand. There are a large number of proprietary dual
control modes, depending on the ventilator manufacturer. This fact alone dampens the enthusiasm for this
technique, as a clinician may not be familiar with the modes if multiple ventilators are used in an ICU.
Microprocessor technology now allows a ventilator to change pressure and flow variables both between breaths
(Pressure Regulated Volume Control {PRVC}) and within a breath (Adaptive Support Ventilation).
For example, with PRVC (Siemens), the clinician chooses a minimum respiratory rate, target tidal volume, and
upper pressure limit. The ventilator continuously monitors tidal volume and minute ventilation, and if minute
ventilation falls behind, can increase inspiratory pressures up to the limit in order to “catch up”. None of the dual
control modes have been demonstrated to improve outcomes, including mortality, length of ICU stay, or duration of
mechanical ventilation.
Continuous Positive Airway Pressure for Postoperative Respiratory Failure
Hypoxemia is a common postoperative complication in patients undergoing abdominal surgery, and a portion of
those patients will go on to requiring reintubation.22 Postoperative care of these patients should include lung re-
expansion therapies such as incentive spirometry and intermittent positive pressure breathing (IPPB). A recent
prospective trial examined the efficacy of continuous positive airway pressure (CPAP) in preventing postoperative
hypoxemia and decreasing the incidence of reintubation in patients who had undergone abdominal surgery23.
Squadrone et al compared 6 hours of oxygen therapy by facemask to CPAP at 7 cmH2O in 209 patients. They
measured the need for intubation in the first seven days after surgery. Ten percent of the control group required
intubation, whereas only 1% of the CPAP group required intubation. The event rates for pneumonia, infection, and
sepsis were lower in the CPAP group as well. Criticisms of the study include the large number of patients excluded
(1332 patients were enrolled, but only 209 were randomized), and the fact that the control group received only
supplemental oxygen, without other postoperative respiratory therapy maneuvers. A recent meta-analysis of nine
clinical trials has confirmed the benefit of CPAP in preventing postoperative pulmonary complications.24
Recruitment Maneuvers in ARDS
ARDS is characterized by alveolar flooding and abnormalities in surfactant function. This results in alveolar
collapse, ventilation-perfusion mismatching, and hypoxemia. Use of positive end-expiratory pressure (PEEP) will
recruit collapsed lung units, allowing them to participate in oxygenation and ventilation. One solution to recruiting
collapsed lung is to turn patients prone, whereas another technique is to use high levels of CPAP repeated at regular
intervals. This results in opening of collapsed alveoli, improved oxygenation, and decreased airway pressures.
There is little data, however, that these benefits are more than transient. Gattinoni et al studied the amount of
potentially recruitable lung using CT scanning in patients with ARDS.25 Using airway pressures of 5, 15, and 45
cmH20, they found wide variability in the amount of recruitable lung. They also found that the proportion of
potentially recruitable lung was correlated with the physiologic response to PEEP. This suggests that PEEP should
be chosen based on the potential recruitability of the lung parenchyma.
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How Much PEEP Should We Use?
Although it has been demonstrated that PEEP can improve oxygenation, as can be seen from the literature on prone
mechanical ventilation and recruitment maneuvers that transient improvement in oxygenation doesn’t mean that
patients will show improved outcomes. A recent meta-analysis examined 2299 patients in 3 large trials comparing
lower to higher PEEP levels in patients with ALI and ARDS. Overall, there was no improvement in outcome in the
patients with ALI treated with higher PEEP. However, higher PEEP levels were associated with improved survival
in the subset of patients with ARDS. There were no differences in vasopressor use or in the incidence of
pneumothorax.26
Performance of Newer Generation Anesthesia Ventilators
Earlier models of anesthesia ventilators suffered from poor performance when ventilation demands were high. The
combination of poor lung compliance and high minute ventilation demand require that the ventilator deliver
effective minute ventilation in order to avoid hypercapnea and respiratory acidosis. Maximum ventilatory capacity
can be calculated for a specific ventilator by using the mean inspiratory flow versus airway pressure curves, and the
maximum allowable inspiratory duty cycle (the ratio of inspiratory time to total breathing cycle duration). This
approach permits prediction of ventilator performance for patients with high minute ventilation requirements. With
low lung compliance, inspiratory flow rate falls as airway pressure increases. The clinical implication of this finding
is that alveolar ventilation will fall. Recognition of the limitations of anesthesia ventilators is critical as patients
that are acidotic may not tolerate the respiratory acidosis associated with hypoventilation. In addition, the ventilator
tubing used with ICU ventilators tends to be much less compliant than the tubing used with anesthesia ventilators.
This means that in patients with high airway pressures, a larger fraction of the tidal volume will be “wasted” in
tubing expansion when anesthesia ventilator tubing is used. When a patient with severe respiratory failure requires
mechanical ventilation in the operating room, consider using an ICU ventilator for transport and in the OR if peak
inspiratory pressures are greater than 50 cmH2O and minute ventilation is greater than 15 liters/minute.
References
1. Hudson LD: Progress in understanding ventilator-induced lung injury. Jama 1999; 282: 77-8
2. Pinhu L, Whitehead T, Evans T, Griffiths M: Ventilator-associated lung injury. Lancet 2003; 361: 332-40
3. Dreyfuss D, Soler P, Basset G, Saumon G: High inflation pressure pulmonary edema. Respective effects of
high airway pressure, high tidal volume, and positive end-expiratory pressure. Am Rev Respir Dis 1988;
137: 1159-64
4. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and
the acute respiratory distress syndrome. The Acute Respiratory Distress Syndrome Network. N Engl J Med
2000; 342: 1301-8
5. Ware LB, Matthay MA: The acute respiratory distress syndrome. N Engl J Med 2000; 342: 1334-49
6. Ranieri VM, Suter PM, Tortorella C, De Tullio R, Dayer JM, Brienza A, Bruno F, Slutsky AS: Effect of
mechanical ventilation on inflammatory mediators in patients with acute respiratory distress syndrome: a
randomized controlled trial. Jama 1999; 282: 54-61
7. Ranieri VM, Giunta F, Suter PM, Slutsky AS: Mechanical ventilation as a mediator of multisystem organ
failure in acute respiratory distress syndrome. Jama 2000; 284: 43-4
8. Shimabukuro DW, Sawa T, Gropper MA: Injury and repair in lung and airways. Crit Care Med 2003; 31:
S524-31
9. Tremblay L, Valenza F, Ribeiro SP, Li J, Slutsky AS: Injurious ventilatory strategies increase cytokines
and c-fos m-RNA expression in an isolated rat lung model. J Clin Invest 1997; 99: 944-52
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10. Pittet JF, Mackersie RC, Martin TR, Matthay MA: Biological markers of acute lung injury: prognostic and
pathogenetic significance. Am J Respir Crit Care Med 1997; 155: 1187-205
11. Goodman LR, Fumagalli R, Tagliabue P, Tagliabue M, Ferrario M, Gattinoni L, Pesenti A: Adult
respiratory distress syndrome due to pulmonary and extrapulmonary causes: CT, clinical, and functional
correlations. Radiology 1999; 213: 545-52
12. Moloney ED, Griffiths MJ: Protective ventilation of patients with acute respiratory distress syndrome. Br J
Anaesth 2004; 92: 261-70
13. Carmichael LC, Dorinsky PM, Higgins SB, Bernard GR, Dupont WD, Swindell B, Wheeler AP: Diagnosis
and therapy of acute respiratory distress syndrome in adults: an international survey. J Crit Care 1996; 11:
9-18
14. Hickling KG, Henderson SJ, Jackson R: Low mortality associated with low volume pressure limited
ventilation with permissive hypercapnia in severe adult respiratory distress syndrome. Intensive Care Med
1990; 16: 372-7
15. Eichacker PQ, Gerstenberger EP, Banks SM, Cui X, Natanson C: Meta-analysis of acute lung injury and
acute respiratory distress syndrome trials testing low tidal volumes. Am J Respir Crit Care Med 2002; 166:
1510-4
16. Grasso S, Mascia L, Del Turco M, Malacarne P, Giunta F, Brochard L, Slutsky AS, Marco Ranieri V:
Effects of recruiting maneuvers in patients with acute respiratory distress syndrome ventilated with
protective ventilatory strategy. Anesthesiology 2002; 96: 795-802
17. Gattinoni L, Tognoni G, Pesenti A, Taccone P, Mascheroni D, Labarta V, Malacrida R, Di Giulio P,
Fumagalli R, Pelosi P, Brazzi L, Latini R: Effect of prone positioning on the survival of patients with acute
respiratory failure. N Engl J Med 2001; 345: 568-73
18. Krishnan JA, Brower RG: High-frequency ventilation for acute lung injury and ARDS. Chest 2000; 118:
795-807
19. Courtney SE, Durand DJ, Asselin JM, Eichenwald EC, Stark AR: Pro/con clinical debate: High-frequency
oscillatory ventilation is better than conventional ventilation for premature infants. Crit Care 2003; 7: 423-6
20. Fort P, Farmer C, Westerman J, Johannigman J, Beninati W, Dolan S, Derdak S: High-frequency
oscillatory ventilation for adult respiratory distress syndrome--a pilot study. Crit Care Med 1997; 25: 937-
47
21. Derdak S: High-frequency oscillatory ventilation for adult acute respiratory distress syndrome: a decade of
progress. Crit Care Med 2005; 33: S113-4
22. Thompson JS, Baxter BT, Allison JG, Johnson FE, Lee KK, Park WY: Temporal patterns of postoperative
complications. Arch Surg 2003; 138: 596-602; discussion 602-3
23. Squadrone V, Coha M, Cerutti E, Schellino MM, Biolino P, Occella P, Belloni G, Vilianis G, Fiore G,
Cavallo F, Ranieri VM: Continuous positive airway pressure for treatment of postoperative hypoxemia: a
randomized controlled trial. Jama 2005; 293: 589-95
24. Ferreyra GP, Baussano I, Squadrone V, et al: Continuous Positive Airway Pressure for treatment of
respiratory complications after abdominal surgery. Ann Surg 2008;247:617-626.
25. Gattinoni, L, Cairoini P, Cressoni M, et al: Lung Recruitment in Patients with the Acute Respiratory
Distress Syndrome. NEJM 2006;354:1775-86
26. Briel M, Meade M, Mercat A, et al. Higher vs Lower Positive End-Expiratory Pressure in Patients with
Acute Lung Injury and Acute Respiratory Distress Syndrome. JAMA 2010:303:865-873
27. Needham DM, Colantuoni E, Mendez-Tellez PA, Dinglas VD, Sevransky JE, Dennison Himmelfarb CR,
Desai SV, Shanholtz C, Brower RG, Pronovost PJ. Lung protective mechanical ventilation and two year
survival in patients with acute lung injury: prospective cohort study. BMJ. 2012 Apr 5;344:e2124
DISCLOSURE
Cook Incorporated, Self, Consulting Fees
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Management of the Difficult Airway
Aaron Joffe, D.O. Seattle, Washington
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Delirium and Cognitive Dysfunction in the Perioperative Period

William E. Hurford, M.D. Cincinnati, Ohio
Perioperative cognitive changes are often overlooked until a patient presents with an agitated delirium several days
after surgery. These acute changes in cognitive function, while sometimes dramatic, often are relegated to
“emergence delirium” or “ICU psychosis” and are simply permitted to run their course. Delirium, however, is not a
benign disease. Rather, it is associated with a significant increase in postoperative morbidity, disability, and
death.1,2 Recently attention has focused on a broader set of disorders of postoperative cognitive dysfunction
(POCD), which may represent a spectrum of organ system dysfunction of varying severity, duration, and
reversibility.
Definitions
A gitation, which is simply excessive motor activity, is quite common in the postoperative period. It is a nonspecific
symptom resulting from any type of internal discomfort including pain, anxiety, fear of death, etc. Agitation
resulting from pain or anxiety is relatively easily treated with reassurance and the appropriate use of analgesics and
benzodiazepines. Delirium, however, is more difficult to prevent, diagnose, and treat, and the clinical outcome of
patients with delirium is much different. 3
A nxiety specifically describes an unpleasant alteration of mood and emotions that is not accompanied by cognitive
dysfunction. The patient continues to think and comprehend normally. There appears to be no relationship between
perioperative anxiety and the occurrence of delirium.4,5
Delirium, like anxiety, is characterized by an unpleasant alteration of mood. Unlike anxiety, delirium is an acute
confusional state accompanied by cognitive impairment. Accordingly, delirium has been described as “acute
cognitive dysfunction” or “acute brain failure.” The distinction of cognitive impairment is critical to making the
proper diagnosis and prescribing appropriate therapy. The DSM-IV-TR diagnostic criteria include: 1) a disturbance
of consciousness with reduced ability to focus, sustain, or shift attention; 2) a change in cognition or the
development of a perceptual disturbance that is not better accounted for by a pre-existing or evolving dementia; 3)
development of the disturbance over a short period of time (hours to days) and a fluctuating course over the day.6
Clinical features of delirium are summarized in Table 1. Patients may be hyperactive and agitated, or hypoactive
and lethargic. Hypoactive delirium may be difficult to appreciate, often remains undiagnosed, and may have a
poorer long-term outcome than agitated delirium.1
Table 1. Clinical Features of Delirium

• Prodromal phase
• Fluctuating course with lucid intervals
• Altered arousal and psychomotor abnormalities
• Decreased attentiveness
• Disturbed sleep-wake cycle
• Impaired memory
• Disorganized thinking and speech
• Altered perceptions
• Disorientation
• Dysgraphia
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Etiology and Risk Factors
As many as one to two-thirds of older patients admitted to intensive care units will have an episode of delirium
during their stay. The precise etiology is entirely unclear. Of course, organic causes of an altered mental status
must always be considered and include drug and alcohol withdrawal, Wernicke's encephalopathy, hypertensive
encephalopathy, hypoglycemia, hypoperfusion, hypoxemia, intracranial bleed, meningitis/encephalitis, and side
effects of medications (all designated by the mnemonic WHHHHIMP).7 Some hypothesize that delirium results
from vulnerability on the part of the patient (e.g., cognitive impairment, severe illness, visual impairment, etc.) and
hospital-related insults (e.g., medications and procedures).8 Others suggest that acute brain dysfunction occurs
secondary to a perioperative systemic inflammatory response, similar to other organ failures.6,9-11 Inouye and
Charpentier developed a predictive model for the occurrence of delirium in hospitalized general medical patients
greater than 70 years of age.12 Risk factors included the use of physical restraints, the presence of malnutrition, the
addition of more than three medications over the last 24 hours, the use of a bladder catheter, and the occurrence of
any iatrogenic event. A greater number of factors was associated with an increased incidence of new-onset delirium
(0 factors, 4%; 1 to 2 factors, 20%; > 3 factors 35%).
Subtle pre-existing attentional and cognitive deficits, decreased executive function, and depression are associated
with an increased risk of postoperative delirium.13-19 Other pre-existing factors that have been correlated with the
occurrence of perioperative delirium include: age 70 years or older; self-reported alcohol abuse; poor functional
status; markedly abnormal preoperative serum sodium, potassium, or glucose levels; hypoalbuminemia; surgery for
hip fracture; noncardiac thoracic surgery; and aortic aneurysm surgery.20-25 Overall, vascular surgical patients are
about twice as likely as other elective surgical patients to experience delirium.26 Intraoperative factors include
prolonged operative time, large blood losses, and anemia.6,18,23,27,28 A recent prospective study of 563 cardiac
surgery patients reported a 16% incidence of delirium. Independently associated with delirium were advanced age,
preoperative cognitive impairment, major depression, anemia, atrial fibrillation, prolonged intubation and
postoperative hypoxia.29
Assessment
Many rating scales have been developed to communicate a patient’s level of agitation and/or delirium more easily.
Among them, one of the most common scales, the “Ramsay scale,” simply rates the patient’s degree of arousal from
anxious or agitated (level 1), to deeply sedated (levels 4 and 5), to anesthetized (level 6). 30 Perhaps a more useful
scale for assessment of agitation is the Richmond Agitation-Sedation Scale (Table 2), which rates a patients level of
agitation or sedation on a 10-point scale, ranging from -5 (unarousable to vigorous stimulation) to +4 (physically
combative).31-33
Table 2. The Richmond Agitation-Sedation Scale (RASS) 32,33

Score Term Description
+4 Combative Combative, violent, immediate danger to staff
+3 Very agitated Pulls or removes tubes or catheters; aggressive
+2 Agitated Frequent nonpurposeful movement; dyssynchrony with ventilator
+1 Restless Anxious, but movements not aggressive or vigorous
0 Alert and calm
-1 Drowsy Sustained awakening (>10 sec) with eye contact to voice
-2 Light sedation Briefly awakens (<10 sec) with eye contract to voice
-3 Moderate sedation Movement or eye opening to voice, but no eye contact
-4 Deep sedation No response to voice; responds to physical stimulation
-5 Unarousable No response to voice or physical stimulation
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Delirium in postoperative and ICU patients commonly is assessed using the Confusion Assessment Method
(CAM),34-36 which has been modified for ICU patients (CAM-ICU). The CAM-ICU briefly examines four key
features of delirium: (1) acute onset or fluctuating course; (2) inattention; (3) disorganized thinking; and (4) altered
level of consciousness. Diagnosis of delirium is made if the patient displays the first two features along with either
disorganized thinking or altered level of consciousness. Testing with the CAM-ICU has been highly standardized,
and the assessment is quick, repeatable, and reliable.37,38 A pediatric version of the scale has been recently
validated.39
Therapy
Postoperative delirium usually develops between postoperative days 2 to 7.40 This time-course correlates with the
typical progression of postoperative systemic inflammatory response. One hypothesis for the etiology of delirium is
that the postoperative increase in inflammatory, oxidative, and psychosocial stress stimulates the production of pro-
inflammatory cytokines and the production of delirium-potentiating neurotoxins.6,41,42
Clinically, however, delirium remains a diagnosis of exclusion. Identification and treatment of other causes of acute
brain dysfunction, correction of electrolytes, and avoidance of benzodiazepines and other medications sometimes
can be curative.
Prevention
Evidence for the efficacy of preventative measures for delirium is sparse, but conservative measures, such as prompt
treatment of infections, maintenance of a normal sleep-wake cycle, avoidance of physical restraints, early
mobilization, involvement of family members, and frequent reorientation have been suggested and appear
reasonable on face value (Table 3).6,8,43 The presence of an endotracheal tube, urinary catheter or surgical drains,
urinary retention, and pain are common triggers for acute confusion and agitation, especially in the post-anesthesia
care unit (PACU), and the occurrence of delirium in the PACU appears predictive of continued postoperative
delirium.44 Postoperative pain and increased pain severity have been correlated with the occurrence of delirium. In
a study of hip fracture patients, cognitively intact patients with undertreated pain were nine times more likely to
develop delirium than patients whose pain was adequately treated.45 Elderly patients who received oral opioid
analgesics, compared with intravenous or neuraxial analgesia, had a decreased incidence of delirium. 46
Minimization of tubes and drains and anticipatory treatment of pain are reasonable approaches to reducing the
chance of delirium. A proactive geriatric consultation, or treatment within a specialized hospital program, may
reduce delirium incidence and severity in elderly patients.8,47-51
Table 3. Risk Factors and Interventions for Delirium 8

Risk Factor Example of Intervention
Cognitive impairment Frequent reorientation; provide stimulating activities
Sleep deprivation Noise reduction strategies; schedule adjustments
Immobility Early mobilization; ambulation; active range of motion;
minimize catheters and physical restraints
Visual impairment Provide glasses and adaptive equipment
Hearing impairment Provide hearing aids; special communication techniques
Dehydration Encourage oral intake of fluids
Few studies suggest any efficacy for prophylactic pharmacologic treatment. One study has suggested that
preoperative administration of statins may reduce the risk of postoperative delirium following cardiac surgery,52 but
others have reported that statin use is associated with increased risk.53 The use of ketamine during anesthetic
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induction for cardiac surgery has also been reported to reduce the incidence of postoperative delirium compared to
placebo-treated patients. 54
Most anesthetic agents, with the exception of ketamine, antagonize GABA receptors and can produce confusion and
delirium. Many common perioperative medications can contribute to the occurrence of delirium, including
meperidine55 and anticholinergic medications such as diphenhydramine and atropine. With the exception of
meperidine, neither opioid administration, nor the total dose administered, appears to correlate with the occurrence
of delirium.56 Use of regional anesthetic techniques instead of general anesthesia does not appear to reduce the
incidence of delirium, probably because the variable depth of accompanying sedation.57-59 In a study of elderly
patients receiving a spinal anesthetic for hip fracture repair, a lighter level of propofol sedation (bispectral index >
80 compared with an index of 50) was associated with a 50% reduction in the incidence of delirium.60 A secondary
analysis of 526 elderly patients undergoing hip surgery found no significant harm or benefit from general or regional
anesthesia, or the use of benzodiazepines, narcotics or anticholinergic agents. 61 Postoperatively, there is no evidence
that pain management with neuraxial techniques is superior to management with opioids.62,63
Benzodiazepines
Benzodiazepines are often used for the treatment of anxiety. Their duration of action in critically ill and elderly
patients is unpredictable. While these drugs often are used to treat delirium and withdrawal, no adequately
controlled trials support their use in the treatment of delirium unrelated to alcohol withdrawal.64 Elderly patients
may become further disinhibited with the administration of benzodiazepines. Their use should be minimized in such
patients and may be associated with an increased risk for delirium55,65-67 and prolongation of its duration in elderly
patients.68
Haloperidol
There is insufficient evidence to strongly recommend a particular pharmacologic treatment for delirium, but
haloperidol often is used for this purpose and has been recommended in guidelines of the American Psychiatric
Association (APA).69 Low-dose haloperidol may reduce the severity and duration of delirium, and the length of
hospital stay in delirious elderly patients.70,71 Haloperidol is a butyrophenone with strong dopamine D2 receptor
binding activity, which atypical antipsychotics lack.6 Although it is an alpha-1 adrenergic antagonist, it has few
hypotensive side effects. It has little meaningful effect on ventilation. Extrapyramidal side effects are relatively
uncommon in the critically ill patient, perhaps because of concurrent use of benzodiazepines or beta-blockers.
Prolongation of the Q-T interval and serious ventricular arrhythmias, notably torsade-de-pointes, following
haloperidol administration have been described in a “black box” warning by the Food and Drug Administration
(FDA).72 Monitoring the Q-T interval of the electrocardiogram and correction of serum potassium and magnesium
levels, if necessary, are advisable when high doses of haloperidol are used. APA guidelines suggest that a QTc
interval greater than 450 msec or more than 25% over baseline may warrant discontinuation of the drug.6
Haloperidol also has been associated with neuroleptic malignant syndrome. The drug can decrease the threshold for
seizures and should be used cautiously in patients with delirium tremens. Although not approved by the FDA, the
intravenous route appears preferable in the critically ill patient, since absorption is assured. Side effects may be
reduced with intravenous administration.73
The starting dose for haloperidol is 0.5-1.0 mg, depending on level of agitation, age, and degree of illness. In
general, a starting dose of 2 mg IV is reasonable for mild agitation; 5 mg for moderate; and 10 mg for severe
agitation, with elderly patients receiving approximately one-third of this typical starting dose. Because the onset of
action is about 11 minutes, allow at least 20 minutes between doses (longer in the elderly and critically ill).74 For
continued agitation, double the previous dose. There is no specific upper limit.75 Supplemental anxiolytics and/or
analgesics may be necessary.76 After the patient is calm for 24 hours, reduce the dose by 50% every 24 hours, and
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taper over 3-5 days. Usually only two to three doses per day are necessary since the serum 1/2-life is approximately
14 to 24 hours. Intravenous haloperidol is twice as potent as the oral form.77
Other options
Pharmacologic options that may be useful for treatment of delirium include the atypical antipsychotics olanzapine,
risperidone,78,79 and quetiapine.80-82 Prophylaxis with olanzapine has been reported to reduce the incidence of
delirium, but not its duration or severity, following joint replacement.83 For treatment of delirium, the atypical
antipsychotics appear to have similar efficacy as haloperidol, but additional studies will be necessary before such
drugs can be strongly recommended. Short-term treatment with dexmedetomidine has been demonstrated to be
effective for the treatment of delirium in several prospective studies.84-87 Cholinesterase inhibitors, such as
physostigmine88 have been suggested for treatment, but a recent large study of the cholinesterase inhibitor
rivastigmine did not demonstrate efficacy and the drug was associated with increased mortality.89 Interestingly,
maintaining a body temperature < 36o C during total knee replacement under spinal anesthesia was reported to be
associated with a lower incidence of cognitive dysfunction (delirium was not specifically assessed) following
surgery.90
Outcome
The occurrence of delirium is far from benign, and is associated with an increased risk of death and disability.91-95
In the postoperative period, the occurrence of delirium has been associated with prolonged ICU and hospital length
of stay, greater use of sedatives and physical restraints, increased unintended decannulations and extubations,
increased hospital costs, prolonged cognitive dysfunction, and higher mortality rates.20,96-100 Elderly patients who
experienced delirium during their stay in a surgical ICU were more likely to be discharged to a place other than
home, and have a greater functional decline than nondelirious patients.101,102 While the simple occurrence of
postoperative delirium does not appear to be an independent predictor of mortality, 103 persistence of delirium
appears to be a predictor of increased 1-year mortality.104 One-quarter of delirious elderly patients die within 6
months.105
The Spectrum of Postoperative Cognitive Dysfunction (POCD)
Delirium represents a profound manifestation of cognitive dysfunction. The current definition is binary (yes/no) and
neglects differences in the severity and duration of brain dysfunction. Undoubtedly, there is a spectrum of organ
dysfunction that falls short of a diagnosis of delirium, and can sometimes be diagnosed only by special testing. The
definition of POCD is informal; it refers to any difficulty with memory, cognition, or attention following surgery
and anesthesia. The incidence of POCD appears relatively common following cardiac and non-cardiac surgery,
especially in the elderly. Its occurrence is associated with prolonged hospital stays, decreased likelihood of
returning to the workforce, and increased mortality.106-108 Just as the etiology of delirium is unclear, so is the
etiology of postoperative cognitive dysfunction and its potential relationship to anesthetic exposure. Other
perioperative organ system dysfunctions, such as renal failure, have diverse causes. It is likely that there are
multiple important causes of postoperative cerebral dysfunction. The hypothesis that anesthetic exposure may
exacerbate neurodegenerative diseases such as Alzheimer disease, is receiving intense examination. Current studies,
however, are inadequate to confirm or refute such a relationship. At best, the controversy remains in equipoise: we
don’t have the scientific evidence that any particular anesthetic agent or technique, at clinically relevant doses and
durations, causes or will prevent long-lasting cognitive dysfunction.109,110 In the absence of definitive
recommendations, it seems reasonable to apply those recommendations found useful in reducing the incidence and
severity of delirium, as discussed above, to an empiric effort to minimize the incidence and severity of postoperative
cognitive dysfunction.
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DISCLOSURE
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Evaluating Pain Outcomes
Sean Mackey, M.D., Ph.D. Stanford, California
This refresher course is based on the monograph: A nesthesiology Centric A CLS by Andrea Gabrielli, Michael
F. O’Connor, and Gerald A. Maccioli. It is an approved work product of the ASA’s Committee on Critical
Care, and available at:
http://www.asahq.org/clinical/Anesthesiology-CentricACLS.pdf
The epidemiology of cardiac arrest in the anesthesia world is unique and special. In fact hypoxemic or
dysrhythmic cardiac arrest is rarely observed when sedation, regional or general anesthetics are provided. This
can be attributed to the development of better monitoring, safer medications, adoption of clinical standards and
advances in training. With detailed knowledge of the patient’s medical history, there is an intuitive difference in
a patient’s chance of survival. When cardiac arrest during anesthesia does occur, prompt recognition, and
diagnosis can lead to successful management.
The most recent data of cardiac arrest during anesthesia comes from the Mayo Clinic in Rochester (See Sprung
J, et al. 2002). In this study, cardiac arrest was defined as the requirement for resuscitation with either closed
chest compression or open cardiac message, after the onset of anesthesia in 518,294 patients. Cardiac arrests
after transport to the ICU were not included. The two outcome variables were survival of at least one hour after
initial resuscitation and survival to discharge from the hospital. All probable causes of cardiac arrest were
grouped into three categories: 1) intraoperative hemorrhage, 2) pre-existent cardiac pathology and 3) hypoxia,
both at intubation or extubation. Overall 24 cardiac arrests were determined to be secondary to anesthesia
(0.5/10,000 anesthetics). If one extrapolates this number to the 20 million anesthetics performed annually in the
United States, it translates to at least 1000 patients/year, or about three patients a day going from "sleep" to
cardiac arrest! This number is probably a gross underestimation since the many prestigious academic
institutions in the US and abroad that report their experiences do not necessarily reflect the incidence of this
problem in the “real world,” i.e. outside academic boundaries or abroad.
The impact on favorable outcome of having an anesthesiologist present or immediately available during a
surgical procedure is clear. In a large retrospective review, the adjusted alteration for death and failure to rescue
were greater when care was not directed by a physician anesthesiologist (alteration for death = 1.08, p< 0.04;
alteration for failure to rescue = 1.10, P < 0.01), suggesting that anesthesiologist-directed anesthesia care has a
significant positive effect on the outcome for complications in the OR, and long term mortality (see Silber, et al
2000). Appropriate vigilance and monitoring is often the key to recognition and timely response to such a crisis.
For example, in the late 80s the ASA Closed Claims study reported that 57% of hypoxiarelated deaths could
have probably been avoided simply by improved awareness of life threatening respiratory complications during
anesthesia and the use of pulse oximetry and capnography.
In the perioperative setting, patients typically deteriorate into a pulseless arrest over a period of minutes or
hours, under circumstances wholly dissimilar to other in-hospital or out-of-hospital settings. Consequently,
aggressive measures taken to support patient physiology can avert, avoid, or forestall the need for ACLS.
Additionally, patients in the perioperative period have a different milieu of pathophysiology. For example,
hypovolemia, as a cause of myocardial ischemia, is far more common than transmural infarction from plaque
rupture. Intraoperative myocardial ischemia resulting from an imbalance in O2 delivery and consumption rarely
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evolves to full pump failure or ventricular fibrillation in the operating room. The result is a different spectrum
of dysrhythmias in the operating room than in the ED. The most common cardiac dysrrythmia during general
and neuraxial anesthesia is bradycardia followed by asystole (45%). The other life threatening cardiac rhythms
are severe tachydysrrhythmias including ventricular tachycardia,ventricular fibrillation (14%), and pulseless
electrical activity (7%). Remarkably, in 33% of the cases the heart rhythm is not fully assessed or documented
Chang es in ACLS
Animal models of circulatory crisis and of CPR demonstrate that hyperventilation is almost invariably
associated with worsened survival. Ventilation at 20 breaths a minute is associated with significantly lower
survival than ventilation at 12 breaths/minute. As a whole, these studies emphasize the principle: in a low flow
state the duration of increased intrathoracic pressure is proportional to the ventilation rate and inversely
proportional to blood pressure, coronary and cerebral perfusion. Recent versions of the ACLS guidelines have
recommended lower levels of ventilatory support. This is the rationale driving the development of technologies
to ventilate patients using negative pressure.
Cardio v ersio n: S pecial Considerations

• Immediate cardioversion is indicated for a patient with serious signs & symptoms related to the tachycardia or
if ventricular rate is > 150 bpm (Table 2)
• Always be prepared to externally pace patients who are being cardioverted, as some will convert into a very
bradycardic rhythm.
• Biphasic defibrillators are more effective and utilize less energy than monophasic defibrillators. Thus biphasic
defibrillators have almost completely replaced the monophasic defibrillators discussed in older versions of
ACLS.
Rhythm Energy Sequence Monophasic Energy Sequence Biphasic PSVT 50 J, 100 J, 200 J, 300 J, 360 J 100 j
A Flutter 50 J, 100 J 50 J Atrial Fibrillation 200 J, 300 J, 360 J 50 J, 100 J Over the past two decades, there has
been increased interest in preserving vital organ perfusion during CPR and restoring it as quickly as possible
after there is a return of spontaneous circulation (ROSC). There are multiple animal studies and case series that
have suggested that vasopressin or higher doses of epinephrine may be superior to the standard doses of
epinephrine recommended in ACLS. Larger clinical studies have failed to demonstrate any consistent benefit
to either alternative, but have also not documented worsening of outcome associated with their use. Several of
the algorithms in the work product incorporate vasopressin in addition to epinephrine, as it is the opinion of the
authors that the combination of the two drugs is likely superior to either alone in those clinical settings.
Avoiding ACLS is as important as performing it well. The monograph offers the algorithms below as
reasonable approaches to the management of patients with LV shock and RV shock. Cardiac arrest in
perioperative patients typically occurs as a consequence of either hypoxemia or the progression of a circulatory
process. Avoiding cardiac arrest requires successfully managing acute anemia, hypoxemia, and all contributing
factors to cardiac output: preload, contractility, and afterload. Anesthesiologists are masters of recognizing and
treating hypoxemia. Consequently the focus of the remainder of this document will be on the management of
cardiopulmonary interactions and the circulation in the rapidly decompensating patient. Traditional ACLS is
intended for caregivers summoned to aid a patient who has suddenly collapsed. In the perioperative setting, the
list of causes is substantially larger, and ACLS needs to be managed concurrently with the anesthetic and
operation.
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Co mmo n Causes o f A CLS ev ents in the perio perativ e setting Anesthetic

o Intravenous anesthetic overdose
o Inhalation anesthetic overdose
o Neuraxial block with high level sympathectomy
o Local anesthetic systemic toxicity
o Malignant hyperthermia
o Drug administration errors
Respiratory
o Hypoxemia
o A uto PEEP
o A cute Bronchospasm
Cardiovascular
o V asovagal reflex
o Hypovolemic and/or hemorrhagic shock
o Tension Pneumothorax
o A naphylacticReaction
o Transfusion Reaction
o A cute Electrolyte Imbalance (high K)
o Severe Pulmonary Hypertension
o Increased intraabdominal pressure
o Pacemaker failure
o Prolonged Q-T syndrome
o A cute Coronary Syndrome
o Pulmonary Embolism
o Gas embolism
o Oculocardiac reflexes
o Electroconvulsive therapy
Reco g nizing cardiac arrest in the OR
- EKG with pulseless rhythm (V-tach, V-fib)
- Loss of pulse X 10 seconds
- Loss of end-tidal CO2
- Loss of plethysmograph
B LS /A CLS in the OR – S o me key po ints to remember . . .
- CPR for patients under general anesthesia need not be preceded by “Annie! Annie! Are you okay?”
- Instruct appropriate personnel to start effective CPR.
- Discontinue the anesthetic and surgery
- Call for help, defibrillator
- Bag mask ventilation if ETT not in place followed by immediate
endotracheal intubation if feasible FiO2 = 1.0
- Don't stop CPR unnecessarily! Capnography is a more reliable indicator of ROSC than carotid
or femoral arterial pulse palpation.
- Capnograph to confirm advance airway positioning and effective CPR
- Hand ventilate rate 8 -10, VT to chest rise, TI one second with 100% oxygen – assess for
obstruction, if none, institute mechanical ventilation. If obstruction, suction, fiberoptic bronchoscopy,
consider exchanging the airway. Continue CPR.
- Open all IVs to wide open
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Anaphylaxis
Anaphylaxis is a rare but important cause of circulatory collapse in the perioperative period. While
there is a wide range of minor allergic reactions, hypotension, tachycardia and bronchospasm can be
more easily followed by vasogenic shock when the offending agent is administered as a rapid
intravenous bolus, the most common route of drug administration during anesthesia. The
preponderance of anaphylaxis in perioperative patients is caused by a small number of drugs.
Anaphylactic shock has been identified as a coexisting or major indeterminate factor for dysrhythmic
cardiac arrest during anesthesia occurring in 2.2 to 22.4 per 10,000 anesthetics with 3% to 4% of them
being life threatening.
N euro axial Anesthesia

Cardiac arrest in association with neuraxial (spinal or subarachnoid block) anesthesia remains the most
mysterious cause of morbidity and mortality in the perioperative period. Its existence would be controversial,
except that is has been well documented as an occurrence in younger, otherwise healthy patients undergoing a
variety of clinical procedures. Its pathophysiology remains a mystery. Clinically, the only unifying feature of
this syndrome is the degree of surprise among the caregivers of these patients. Various hypotheses have been
put forward over the years, invoking unrecognized respiratory depression, excessive sedation concurrent with
high block, under appreciation of both the direct and indirect circulatory consequences of a high spinal
anesthetic, and ‘failure to rescue’ with airway management and drugs. Hypoxemia from hypoventilation does
not appear to be the cause, as there are case reports documenting adequate saturation in these patients. Thus
there is a substantial amount of basic science and clinical interest in the effects of high spinal anesthesia on the
sympathetic innervation of the heart and the circulation.
The most recent North American review of the epidemiology of cardiac arrest during neuraxial
anesthesia indicates the prevalence of cardiac arrest at 1.8 per 10,000 patients (neuraxial), with more
arrests occurring in patients with spinal anesthesia versus epidural (2.9 vs. 0.9 per 10,000 ; P = 0.041)
(A nesth A nalg 2005;100:855-
865). In 46% (12/46) of the cases cardiac arrest was associated with recurrent specific surgical events
(cementing of joint components, spermatic cord manipulation, manipulation of a broken femur, and rupture of
amniotic membranes). In 54% (14/26), the anesthetic technique, i.e. subarachnoid block contributed directly to
the arrest. The choice of vasopressors during neuraxial anesthesia is still being debated.
Treatment o f Cardiac A rrest A sso ciated w ith N euraxial Anesthesia

- Discontinue anesthetic or sedation infusion
- Ventilate with 100% Oxygen, intubate trachea
- Begin CPR if patient has significant bradycardia or is pulseless >10sec
- Treat bradycardia with 1mg Atropine
- Treat with at least 1 mg epinephrine IV (up to 0.1mg/kg)
- Consider concurrent treatment with 40 u vasopressin
N.B. – the full monograph covers a variety of other scenarios, which are not
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included in this handout due to space limitations. These include:

o Local Anesthetic Overdose
o Gas embolism
o Tachycardia
o Bradycardia
o Obstretric Patients
D ifferential D iag no sis fo r perio perativ e PEA o r

A sy sto le: 8 H & 8T
Hypoxia Trauma/hypovolemia
Hypovolemia Tension Pneumothorax
Hyper-vagal Thrombosis of Coronary
Hydrogen Ion Tamponade
Hyperkalemia Thrombus in Pulmonary Artery
Malignant Hyperthermia Long QT syndrome
Hypothermia Toxins (anaphylaxis)
Hypoglycemia Pulmonary HTN
REFERENCES
www.asahq.org/clinical/Anesthesiology-CentricACLS.pdf - 2008-02-19
2005 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular
care. Part 4: Adult Basic Life Support. Circulation 2005;112:IV-18-IV-34. Lagasse RS: Anesthesia safety:
Model or myth? A review of the published literature and analysis of current original data. Anesthesiology 2002;
97:1609-1617
Biboulet P, Aubas P, Dubourdieu J, Rubenovitch J, Capdevila X, d'Athis F. Fatal and non-fatal cardiac arrests
related to anesthesia. Can J Anesth 2001; 48:326-332 .
Olsson GL, Hallen B. Cardiac arrest during anaesthesia. A computer-aided study in 250,543 anaesthetics. Acta
Anaesthesiol Scand 1988; 32:653-664
Newland MC, Ellis SJ, Lydiatt CA, et al. Anesthetic-related cardiac arrest and its mortality. A report covering
72,959 anesthetics over 10 years from a US teaching hospital. Anesthesiology 2002;97:108-115
Runciman WB, Morris RW, Watterson LM et al. Crisis management during anaesthesia: Cardiac arrest. Qual
Saf Health Care 2005; 14:e14
Silber JH, Kennedy SK, Even-Shoshan O, et al. Anesthesiologist direction and patient outcomes.
Tinker JH, Dull DL, Caplan RA, Ward RJ, Cheney FW. Role of monitoring devices in prevention of anesthetic
mishaps: a closed claims analysis. Anesthesiology 1989;71:541-546
Sprung J, Warner ME, Contreras MG, et al. Predictors of survival following cardiac arrest in patients
undergoing non-cardiac surgery: a study of 518,294 patients at a tertiary referral center. Anesthesiology 2002;
99:259-269
Kopp SL, Horlocker TT, Warner ME, et al. Cardiac arrest during neuraxial anesthesia: frequency and
predisposing factors with survival. Anesth Analg 2005;100:855-865
Keenan RL, Shaprio JH, Dawson K. Frequency of anesthetic cardiac arrest in infants: effect of pediatric
anesthesiologists. J Clin Anesth 1991;3:433-7
Flick RP, Sprung J, Harrison TE, et al. Perioperative cardiac arrests in children between 1988 and 2005 at a
tertiary referral center: a study of 92,881 patients. Anesthesiology 2007;106:226-37
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DISCLOSURE
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The Mystery of Guideline Non-compliance:

Why don’t Doctors do the Right Thing?
Avery Tung, M.D. Wilmette, Illinois
1. The history of guideline creation

Although the quest for the “best” way to approach specific clinical decisions dates to the beginning of
organized medical care, the drive to standardize physician behavior with respect to management decisions is
relatively recent. The introduction of the Medicare payment system in 1965 allowed large scale analysis of
physician behavior for the first time, and identified geographic variations in care and cost apparently unrelated to
patient characteristics. Further scrutiny uncovered the startling observation that expert recommendations and actual
physician decision-making were often at odds with each other. These observations raised the uncomfortable
possibility that many physicians were not practicing maximally effective medicine. The term “evidence based
medicine” was first coined in 1990 to describe the normative concept that analysis of published research findings
could identify a best approach to patient care, and that once identified, that approach could be spread to all
practitioners to improve outcomes. In 1992, the paper “Evidence-based Medicine: A New A pproach to Teaching
the Practice of Medicine” appeared in JAMA, triggering a massive effort to define, identify, and promulgate best
practice recommendations.
Recent calls for improving health care quality and safety, and reducing variation in healthcare practice,
have provided additional fuel for this effort. Researchers and Policymakers alike are increasingly willing to define
guideline noncompliance as synonymous with poor quality care. Concurrently, efforts by both regulatory and
payment entities to tie certification and reimbursement to guideline-based performance metrics have increased the
pressure to conform. Not unexpectedly, the number of guidelines has exploded, with >10,000 separate guidelines
currently available at the National Guideline Clearinghouse (www.guideline.gov), a nonprofit website run by the
United States Agency for Healthcare Research and Quality.
Anesthesia has historically been in the forefront of specialties willing to establish guidelines for patient
management. The development of patient monitoring guidelines in 1986, explicitly recommending the use of pulse
oximetry and capnography, is one example. Another is NPO status. As of May 31, 2012, the ASA webpage
contains 28 statements, 10 guidelines, and 3 standards. At the guideline clearinghouse, 394 separate guidelines
pertaining to Anesthesia practice are available, including 269 separate guidelines on pain practice alone. Among
these are 11 guidelines created by the ASA committee on guidelines, standards, and practice parameters including
chronic pain, anesthesia for MRI, and brain function monitoring. These guidelines must meet rigorous inclusion
criteria including origination from a specialty association, government, or professional society (not an individual),
and corroboration by a systematic literature search and evidence review
2. We write the guidelines… why don’t we follow them?

One fascinating byproduct of the recent focus on guidelines is the startling observation that physicians
frequently fail to adhere to guideline recommended treatments. This phenomenon is widespread, endemic to all
branches of medicine and all countries, can be documented in the literature since 1980, and is essentially
unexplained. On the surface, such apparent intransigence by otherwise intelligent, caring practitioners seems
inexplicable. Why should physicians choose not to follow recommendations derived from best evidence and
promulgated by national societies? Do they not want to do the right thing?
The increasing importance of clinical guidelines to regulators and insurance companies has even involved
legal and government authorities in the process of guideline creation. Debate over the use of antibiotics for chronic
Lyme disease, for example, has pitted different Infectious Disease societies against each other, involved concerned
patients due to insurance issues, and the Connecticut Attorney General and the United States Institute of Medicine.
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This talk will review the history of guideline development, describe the epidemiology of guideline noncompliance,
review commonly accepted causes (and non-causes) of noncompliance, explore how human cognition and
preferences can affect decision behavior, and describe current and future challenges in guideline creation.
3. But everybody knows why doctors don’t follow guidelines, don’t they?
Perhaps the most interesting aspect of guideline noncompliance is why it exists. Physicians spend years
training in a rigidly hierarchical environment where a premium is placed on answering questions correctly and
deferring decision making to higher authorities. Such a process would be expected to produce a practitioner eager to
adopt clinical practice recommendations. Yet, compliance even with easy to follow guidelines is poor and has
remained so for more than 25 years. On the surface, the reasons for guideline noncompliance seem straightforward.
Inadequate CME, a generally conservative practitioner base, cost and time constraints create environments where
well-meaning physicians are either ignorant of best practice, unwilling to change, or technically unable to deliver
ideal care. An often quoted AHRQ manuscript argued that it can take 20 years for research findings to become part
of clinical practice. But careful analysis of such arguments shows that they fail to adequately explain the extent and
complex nature of guideline noncompliance.
If, for example, a primary cause of guideline noncompliance is the adequacy or concurrency of physician
knowledge, then comparisons between academic and nonacademic hospitals should either show differences in
guideline compliance, patient outcomes, or both. Large scale meta-analyses, however, and single center studies
focusing on patient outcomes have consistently failed to show differences. Some studies even find compliance more
consistently better among nonacademic hospitals.
Similarly, the ‘slow adoption” argument fails to survive close scrutiny. Proponents of this theory argue that
physicians are naturally conservative, that without “nudging” they are unlikely to change practice, and that
guideline compliance must evolve via a gradual influx of younger practitioners trained with the latest techniques.
This argument, however, fails to explain two observations about clinical practice. The first is that clinical practice
frequently changes extremely rapidly in response to new evidence. Acute declines in the use of drug eluting
coronary stents, Avandia, and Aprotinin in response to papers showing adverse effects demonstrate that physicians
are capable of change as rapid as in any other discipline. The rapid shift to robotic laparoscopic prostatectomy is
another example. The slow adoption hypothesis also does not explain failure to comply with longstanding
guidelines. Despite the existence of perioperative beta blockade guidelines for more than 15 years, and studies
including more than 40,000 patients, compliance with beta blockade recommendations remains limited.
4. How SHOULD we make decisions? Utility theory and its limitations

In principle, decisions should be made in a formally reasoned way that maximizes outcomes. The most
widely accepted normative model of logical human decision making, termed “Expected Utility (EU) theory”, is
based on this idea. Under EU theory, decisions are made by identifying all the available options, computing their
probabilities and payoffs, and choosing the one most likely to maximize the interests of the decision maker. For
decisions where the outcomes are uncertain, an “expected value” (probability weighted average of the payoffs for
each outcome) is used to compare choices. Thus, when comparing a gamble that would pay $2 for getting “heads”
on a coinflip and nothing for “tails” (EV = 0.5*$2 + 0.5*0 or $1) with a gamble paying $1 for heads and $0.50 for
tails (EV = 0.5*$1 + 0.5*$0.50 or $0.75), the former choice (larger EV) should prevail. Assumptions of this theory
include a detailed knowledge of the decision-making environment and all possible alternatives, an ability to compute
the potential outcomes and payoffs for each choice, and a well-organized and consistent ordering of preferences for
each payoff.
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4. Clinical decision making; how do we make medical decisions, anyway?

Studies of clinical practice and guideline compliance find the following epidemiologic details:
i. Across all specialties and topics, the overall incidence of guideline noncompliance is 50% overall, but
ranges from 30-80% depending on the guideline
ii. Considerable practice variability exists even when the decision is straightforward and the knowledge base
is extensive
iii. Physicians report higher rates of compliance than are identified by review of actual practice
iv. Failure to adhere to guidelines is sometimes a conscious decision
v. Age and experience correlate inversely with rates of guideline compliance
Taken together, the above observations regarding guideline noncompliance suggest that the roots of guideline
noncompliance do not lie solely in inadequate knowledge or conservatism, but rather in ways in which human
decision making deviate from theoretical models. Among these are:
i. Sources of medical knowledge other than clinical trial results

Because of medicine’s inherent complexity, clinicians reason using two other sources of knowledge besides clinical
trial results. These include physiological relationships (hypoxemia leads to anaerobic metabolism) and experiential
knowledge (observations unexplained by physiological relationships such as an unexplained variability in
Rocuronium effect). It is easy to see how reasoning from multiple sources can lead to guideline noncompliance. A
physician attempting to comply with low tidal volume ventilation targets, for example, may choose to increase tidal
volumes to combat hypoxemia (pathophysiology) or because the patient is less arrhythmic with slightly higher tidal
volumes (experiential). Although physician decision behavior is difficult to research, studies of exceptions to
quality measures suggest that many are appropriate.
ii. V ariation in underlying assumptions

That two physicians may reach different conclusions about the same phenomenon may result from fundamental
differences in underlying assumptions. To see how perspective can affect uncertainty, consider the following
scenario:
A mathematician and a magician come upon a Las V egas street artist entertaining a crowd of tourists. The
artist flips a coin 15 times in a row… and each time it comes up heads. He then asks the crowd to bet whether the
coin will come up heads on the 16th try. The crowd mostly bets “tails”
The mathematician and magician disagree on what will happen on the next flip. The mathematician,
reasoning that a coinflip is a random event, and that each flip is independent, concludes that the likelihood of
another “head” is 50%. The magician, calculating that the historical probability of a fair coin coming up heads 15
times in a row is extremely low (1 in 32,768 or 0.003%), concludes that the coin is not “fair”, and speculates that it
will be more likely to come up heads again (particularly since the crowd is betting “tails”)
Clearly, the appropriate answer may differ in this scenario depending on the underlying statistical behavior
of the coin itself. Abundant evidence suggests that medicine may contain many examples of statistical likelihoods
that change over surprisingly short time periods: the dramatic increase in risk of heparin-induced thrombocytopenia
over the past 15 years is one example.
iii. Cognitive biases

Extensive research into human decision behavior in nonmedical domains reveals that humans have consistent,
demonstrable biases in their decision preferences that can lead them to apparently irrational choices. Two well-
studied examples are preferences for certainty and correlating the likelihood of an event with its memorableness.
These biases can easily be demonstrated by comparing human preferences to ideal decision behavior:
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The first (and most famous) demonstration of a preference for certainty was created by the French economist
Maurice Allais, who demonstrated that given the following choice:
A : Receive $1 million for sure

B: 89% chance of $1 million, 10% chance of $5 million, and 1% chance of nothing
Most would choose the guaranteed $1 million represented by A. But if the choice were reframed to dramatically
lower the certainty of any payoff at all:
A *: 89% chance of nothing, 11% chance of $1 million

B*: 90% chance of nothing, 10% chance of $5 million
Many would choose B*. Note that the difference between the two gambles involves the perceived degree of
certainty. In the first example, both gambles have a baseline 89% chance of $1 million and differ in the remaining
11% (in A, you get a 11 in 11 chance of $1 million, in B you get a 10 in 11 chance of $5 million and a 1 in 11
chance of nothing). In the second, there is an 89% chance of nothing regardless of choice, and the difference is that
A* gives you $1 million for sure and B* gives you a 10 in 11 chance of $5 million. In both, B or B* has the greater
expected value…yet most prefer the certainty represented by A.
That humans correlate the likelihood of an event to its plausibility and memorableness is also easily
demonstrated. Physicians routinely train to “think of horses instead of zebras when you hear hoofbeats”. But the
ability of such seemingly innocent heuristics to cause behavior that deviates from statistical logic is dramatic.
Consider the following (from the Nobel prize winning work of Daniel Kahneman):
Steve is very shy and withdrawn, invariably helpful but with little interest in people or in the world of reality. A
meek and tidy soul, he has a need for order and structure, and a passion for detail.
Is Steve a salesman or librarian?
Or: W hich statement is more likely?
1. Mr. F has had one or more heart attacks

2. Mr. F is over 55 years old, and has had one or more heart attacks
In the first example, the reader’s mental model of a librarian predisposes towards that diagnosis even though
pre-test probability clearly suggests otherwise. In the second, the age clause in statement #2 makes the overall
statement more plausible (and thus intuitively more likely), even though logically statement 1 is more general, and
thus statistically more likely.
Using these and other examples, Kahneman argued that humans generally do not base diagnostic tasks on
calculations of pretest probability, sensitivity, and specificity, but rather on inductively matching the construct to a
library of mental models. This “availability heuristic” then uses closeness of match and plausibility (not
probability), to determine likelihood. So powerful is this intuition that humans will react to descriptive information,
even when explicit statistics are provided:
A group is composed of 70 engineers and 30 lawyers. One member of the group is 30 years old, married, with no
children. He is skilled and motivated, and is likely to be quite successful in his field. He is well liked by his
colleagues. W hat is the likelihood that he is an engineer?
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Although the answer is given in the first sentence, Kahneman found that nearly 50% of volunteers ranging
from college freshmen to sophisticated graduate students provided a figure other than 70%. The tendency to
correlate the likelihood of events to their “memorableness” may also explain the inverse relationship between
age/experience and guideline compliance. Older physicians who have accumulated a lifetime of unusual outcomes
(e.g. a normal stress test followed by a perioperative MI), are more likely than younger ones to consider these
outcomes common, and thus more likely to consider them in clinical decision-making.
iv. Human preferences: Regret, Mitigation, Gender

While human heuristics clearly contribute to diversity in physician behavior, social, emotional and
psychological factors can also play an important role. Regret, for example, clearly can distort actual decision
behavior. Regret-based behavior can be seen in recent recommendations regarding anticoagulation in the presence
of epidural analgesia. According to current literature estimates, the risk of epidural hematoma is 1 in 50,000
(0.002%) whereas the risk of fatal pulmonary embolism may be as high as 0.5%. In light of these numbers, a
decision to reduce the intensity of heparin prophylaxis in favor of epidural hematoma suggests that the epidural
hematoma outcome carries greater potential for regret. Failure to implement other literature-based behaviors such as
eschewing daily Chest X-Rays in the ICU, or deciding the timing of abdominal aortic aneurysm surgery also
represent nonstatistical weighing of decision outcomes. One reason why regret-based decision making may exist in
medicine is that it allows prioritizing of decision outcomes without complete knowledge of likelihoods.
Mitigation, or the prioritizing of social hierarchies ahead of evidence based decision behavior can also
affect clinical decision behavior. This willingness to accede to a single decider may prevent the group from
identifying errors, evolving to best practice, or making consistent decisions. The 1998 Guam airline accident, in
which a Korean 747 crash-landed in the jungle 4 miles short of the runway, is an example. One possible factor in
this crash may have been that the copilot was socioculturally unable to contradict the judgment of the pilot.
Although examples in medicine are less well publicized, many ICU physicians anecdotally administer dopamine and
place pulmonary artery catheters at the request of surgical colleagues even though both therapies unsupported by
evidence. It is likely, particularly in a team environment such as the OR, that team play frequently supersedes
guideline compliant behavior.
The relationship between gender and guideline compliance is also incompletely understood. While the
bulk of existing literature finds that guideline compliance is better among female physicians, studies of more
invasive therapies suggest a more complex relationship. Female physicians are more likely to prescribe
antihypertensives to diabetic patients, but less likely to insert a central line for goal directed therapy in the ER, and
less likely to perform cardiac catheterization 60 days after a myocardial infarction. When interactions between
patient and physician gender are considered, even more variability can be seen.
5. How did humans with such flawed decision behavior not go extinct?
Taken together, these decision factors provide a reasonable answer to the question of why human behavior
deviates from rational models. But conceiving of humans as irrational decision-makers raises as many questions as
it answers. Would not such behavior be devastatingly maladaptive, particularly for a species without strong natural
defenses? Choosing the right place to live or hunt, determining which foods are poisonous, and which animals to
avoid all require consistent, correct decision making to avoid extinction. That humans thrive today implies that the
consequences of heuristic-prone decision making have little clinical impact, that they somehow benefit human
survival, or that conditions inducing poor human decision making rarely occur
In fact, humans have considerable cognitive strengths that facilitate real world performance. These include
an ability to decode poorly quantitatable information (audio, olfactory, or visual perception), a robust situational
memory (remembering the location of one’s office), and an extraordinary ability to recognize items of interest
(faces, situations, voices). These strengths facilitate strategies to solve real world problems where specific
knowledge of payoffs and probability rarely exist. Human “workarounds” for situations with incomplete
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information are also surprisingly good. Consider the following question: Which city has the larger population: San
Antonio or San Diego? Such a question captures much real world complexity. The populations are changing, the
factors governing each population are unknown, and the answer cannot be calculated from information given in the
question. Studies suggest that humans are remarkably good at answering questions such as these, often utilizing
heuristics as simple as “choose the city whose name you recognize”.
Characteristic of these simple heuristics is that they do not demand an exhaustive search of all cues that
discriminate between two objects, do not require that all cues be evaluated, and are geared to a comparative, rather
than absolue choice. In medicine, this recognition heuristic may be particularly effective where a changing disease
spectrum requires that humans detect the unusual. Consider the discovery of HIV infection in the United State.
Over 8 months, physicians at 3 geographically separate hospitals observed 5 cases of unusual pneumonia (only 2 of
which died). This extraordinary diagnostic feat was at least partly due to the human pattern-recognition ability.
6. What’s wrong with the literature?

In part, physician noncompliance with evidence-based guidelines can be explained by weaknesses in the
evidence base itself. While attention to sample size, adequate blinding, statistical rigor and appropriate control
groups is better today than 10 years ago, surprising reversals of recent literature findings have raised concerns about
the validity of basing clinical decisions on the literature alone. In the ICU, recent findings regarding tight glucose
control (that the benefit may be limited only to specific patients), perioperative beta blockade (that many subgroups
may not benefit) and blood transfusions (that hematocrits >30% may have benefit) have all contradicted earlier
findings. In fact, studies of guideline validity find that the median duration of a guideline (before it changes due to
new information) is 5 years, and that 7% of guidelines already have contradictory signals in the literature at the time
they are published.
It is unclear why so many initial results fail to hold up over time. Overall, estimates suggest that as many
as 1 in 3 papers fall victim to subsequent reversals. One possibility is methodological errors such as stopping
clinical trials after interim analyses. Such “early termination” may overestimate treatment effects. Patients may
also change over time, changing the clinical relevance of therapeutic interventions. Finally, difficult-to-identify
aspects of local practice may impair generalizability.
7. Can the quality of literature be assessed? The GRADE and ASA approaches
In response to concerns regarding the accuracy and reproducibility of clinical research findings, proponents
of evidence based guidelines have developed formal systems to assess the validity of recommendations based on
clinical evidence. The most widespread of these is the GRADE system, developed in 2000 by a multinational
consortium of physicians and statisticians. GRADE rates both the quality of the evidence underlying a
recommendation and the strength of the recommendation itself. A recommendation may be a “1B”, signifying a
strong (benefit outweighs risks) recommendation based on moderate quality evidence. GRADE incorporates
explicit criteria for up or downgrading evidence, and explicitly includes an option for preferences and values. As an
example, a randomized trial starts as “high quality” evidence, but size and consistency of effect, explicit or implicit
bias, and/or absence of a dose/response relationship may all downgrade the quality. GRADE argues that, when
complete, a “high quality” finding is unlikely to change with further research, while a “low quality” finding is very
likely to do so.
In contrast, the ASA system combines rigorous statistical analysis of existing evidence with expert opinion,
consultant opinion, and opinions from society members. Resulting recommendations are phrased in terms of
agreement, and opinions of each group (literature, task force members, consultants, and society members) are
broken out separately.
Published criticisms of the GRADE methodology focus on the inconsistency of GRADE recommendations,
the inherent contradiction in divergent quality/strength ratings (what does it mean to have a weak recommendation
based on high quality data?), and the failure to consider the clinical experience of practicing physicians. One critical
issue is that GRADE criteria for high quality data may not identify findings that are clearly true. Dose dependent
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relationships, large, precise clinical effects, and supportive biases are theoretical attributes of a reproducible,
clinically significant research finding and used by GRADE to increase the quality rating for a specific paper. In
reality, multiple examples of research findings meeting these criteria that turn out not to be reproducible (tight
glucose control in the ICU) or simply fraudulent (effects of albumin on systemic inflammation during
cardiopulmonary bypass) exist.
In light of the limitations of systems such as GRADE, the challenge of creating meaningful practice
guidelines is considerable. One approach (ASA) is to explicitly incorporate practitioner input as a “check” against
literature tendencies towards confirmation bias (not publishing what we think cannot be true) and overreaching with
findings that have not stood the test of time. Another is to incorporate a heavy dose of common sense. In recent
ASA guidelines on central line insertion, for example, elements of a sterile “bundle” such as a cap, mask, gown, and
gloves are advocated to minimize line infections even though individual elements of such a bundle do not have
documented efficacy. A third is to harness the potential of large retrospective databases to clarify links between
research findings and real-world outcomes.
Comparative studies examining guideline compliant behavior find mixed results regarding effects on
outcomes. While adherence to guidelines for acute coronary syndrome care seems to improve outcomes, complying
with SCIP measures for surgical infection do not seem to have measurable effects, and following antibiotic
recommendations for hospital pneumonia may actually worsen outcomes. Clearly, more work is required to
optimize the process of guideline creation
8. Decision making: How can we improve?

In the absence of an optimal guideline creation process, how can physicians make better, more consistent
decisions? Existing literature suggests several ways to “fine tune” intuitive decision behavior:
a. Recognize the strengths and weaknesses of intuitive and rational decision making strategies.
Intuitive decision strategies compete best when decisions must be made quickly, large amounts of complex
information must be integrated, in a changing environment, and when visual and recognition information are
required. Rational decision strategies are best where decisions can take time, decision parameters are known (and
static), and both precision and accuracy are important.
b. Seek out feedback wherever possible. Intuitive, experiential decision behavior can be trained.
Considerable evidence suggests that heuristic-driven behavior is extremely difficult to overcome. Because such
behavior is frequently driven by experiential learning, cataloguing information about the outcomes of specific
decisions may reduce the tendency (for example) to equate the most memorable decision outcomes with the most
likely.
c. Recognize the limitations of literature as guides to clinical practice. In addition to limitations in
design and analysis, issues with published research include generalizability, temporal accuracy, and dissimilarities
between literature methods and clinical practice.
d. Acknowledge the potent effect of individual emotional factors such as risk and uncertainty tolerance,
regret, mitigation, and fear of malpractice. Recognize that these factors may differ between individuals and between
specialties, and that they may affect discussions between and among individual physicians.
e. Understand your own preferences for heuristic-based behavior, risk, uncertainty, and regret.
One way to identify asymmetric preferences for gains and losses, for example, is to reframe decisions as losses or
gains and see whether decision preferences change. Below is an adaptation of the risk taking subscale of the
Jackson Personality Index for physicians:
1. I enjoy taking risks

2. I try to avoid situations that have uncertain outcomes
3. Taking risks does not bother me if the gains involved are high
4. I consider security an important element in every aspect of my life
5. People have told me that I seem to enjoy taking changes
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6. I rarely, if ever, take risks when there is another alternative
And here is a scale (Med Care, 1993) to measure ambiguity tolerance:
1. It really disturbs me when I am unable to follow another person’s train of thought.

2. If I am uncertain about the responsibilities involved in a particular task, I get very anxious.
3. Before any important task, I must know how long it will take.
4. I don’t like to work on a problem unless there is a possibility of getting a clear-cut and unambiguous answer.
5. The best part of working on a jigsaw puzzle is putting in that last piece.
6. I am often uncomfortable with people unless I feel that I can understand their behavior.
7. A good task is one in which what is to be done and how it is to be done are always clear.
It is easy to see that different people may respond differently to both of these scales, and that such differences may
alter decision behavior.
9. Summary
Differences between literature guidelines and physician decision behavior occur distressingly frequently.
Most explanations for this lack of physician agreement with literature-based guidelines center on ignorance,
conservatism, or motives other than best patient outcome. All, however, fail to explain why physicians eschew
some strategies while embracing others. Why do anesthesiologists readily agree to tight glucose control, but
stubbornly refuse to embrace perioperative beta blockade? How do studies finding no benefit to pulse oximetry
differ in their clinical impact from similar studies examining brain function monitors?
Decision making studies in nonmedical domains suggest why physicians may not comply with guidelines.
These include reliance on other sources of medical knowledge, effects of cognitive biases, preferences, and
differences in regret and even gender among physicians
Compounding the challenge of creating relevant, evidence based, widely accepted guidelines are
weaknesses in the literature itself. Reproducibility and fraud are two examples by which the literature may mislead
instead of enlightening, potentially harming patients. Assumptions about the characteristics of “real” clinical
findings remain to be validated. Finally, disagreement regarding the degree to which human preferences should be
explicitly considered in practice guidelines may be an under recognized source of guideline noncompliance
10. References
On the origins and causes of guideline noncompliance
1. Wennberg JE et al. Small area variations in health care delivery. Science 1973;117:1102-8
2. Eddy DM Practice policies: where do they come from? JAMA 1990;263(9):1265, 1269
3. Chassin MR et al. How coronary angiography is used. Clinical determinants of appropriateness. JAMA
1987;258:2543-7
4. Moller JT et al. Randomized evaluation of pulse oximetry in 20,802 patients: Perioperative events and
postoperative complications. Anesthesiology. 1993;78:445-53.
5. Translating Research Into Practice (TRIP II) fact sheet, AHRQ publication #01-P017 accessible at:
http://www.ahrq.gov/research/trip2fac.htm
6. McGlynn EA et al. The quality of health care delivered to adults in the United States. NEJM. 2003;348:2635-45.
7. Choudhry NK et al. Systematic review: the relationship between clinical experience and quality of health care.
Ann Intern Med. 2005;142:260-73
8. Papanikolaou PN et al. Patient outcomes with teaching versus nonteaching healthcare: a systematic review. PLoS
Med 2006;3:e341
9. Kolodner DQ et al. Lack of adherence with preoperative beta-blocker recommendations in a multicenter study. J
Gen Int Med 2006;21:596-601
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10. For a discussion of the Lyme Wars see www.lymepolicywonk.org and: Lee DH et al. Analysis of overall level of
evidence behind Infectious Diseases Society of America practice guidelines. Ann Int Med 2011;171:18-22
On reasons for deviation from normative clinical behavior
1. Friedman M, Savage LJ. The Utility Analysis of Choices Involving Risk J Political Economy, 1948; 56:279-304
2. Persell SD et al. Frequency of inappropriate medical exceptions to quality measures. Ann Int Med 2010;152:225-
31
3. Simon HA. A behavioral model of rational choice. Quart J Econ 1955;69:99-118. Also see 1978 Nobel prize
lecture in economics, accessible at www.nobelprize.com
4. Allais, M., Le comportement de l’homme rationnel devant le risque: critique des postulats et axiomes de l’école
Américaine, Econometrica 1953 ;21:503-46
5. Tversky A, Kahneman D. Judgment under uncertainty: heuristics and biases. Science 1974;185:1124-31.
6. Rathmore SS. Sex differences in cardiac catheterization: the role of physician gender. JAMA 2001;286:2849-56
7. Mikkelsen ME et al. Factors associated with nonadherence to early goal drected therapy in the ED. Chest
2010;138:551-8
On human decision strategies
2. Gigerenzer G et al. Reasoning the fast and frugal way. Psych Rev 1996;103:650-69.
3. Dijksterhuis A. Think different: the merits of unconscious thought in preference development and decision
making. J Pers Soc Psychol. 2004;87:586-98.
4. Smith V, Constructivist and ecological rationality in economics. 2002 Nobel Prize Lecture, accessible at:
nobelprize.com, accessed 6/18/09
5. Dale W et al. The effect of specialty and recent experience on perioperative decision making for abdominal aortic
aneurysm repair. JAGS in press 2012
6. Tubbs EP. Risk taking and tolerance for uncertainty: Implications for surgeons
On weaknesses in the literature and challenges inherent in guideline creation
1. Ioannidis JP. Contradicted and initially stronger effects in highly cited clinical research. JAMA. 2005;294:218-28.
2. Montori VM et al. Randomized trials stopped early for benefit: a systematic review. JAMA. 2005;294:2203-9.
3. Shojania KG et al. How quickly do systematic reviews go out of date? A survival analysis. Ann Int Med
2007;147:224-33
4. Eichacker PQ et al. Surviving sepsis-practice guidleines, marketing campaigns, and Eli Lilly. NEJM
2006;355:1640-2
On GRADE and ASA methodologies
1. Guyatt GH et al. GRADE guideline; a new series of articles in the Journal of Clinical Epidemiology. J Clin Epid
2011;64:380-2
2. Kavanagh BP. The GRADE system for rating clinical guidelines. PLoS Med 2009;6:e1000094
3. ASA Task Force: Practice guidelines for central venous access. Anesthesiology 2012;116:539-73
On current outcomes with guideline-based practice
1. Kett DH et al. Implementation of guidelines for management of possible multidrug-resistant pneumonia in
intensive care: an observational, multicentre cohort study. Lancet Infect dis 2011;11:181-9
2. Hawn MT. Surgical site infection prevention: time to move beyond the surgical care improvement program. Ann
Surg 2011;254:494-9
3. Petersen ED et al. Association between hospital process performance and outcomes among patients with acute
coronary syndromes. JAMA 2006;295:1912-20
DISCLOSURE
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Frail, Feeble or Fit? The oldest old – what should we do differently for the
geriatric patient undergoing anesthesia- if anything ?
Sheila Ryan Barnett, M.D. Boston, Massachusetts
Introduction
It is well known that the population is aging. It is estimated that by 2030 the percent of the population over the age
of 65 years will rise to 20%. The oldest old – those over 85 years - actually represent one of the fastest growing
segments of the population and this population is expected to increase to over 20 million in the next 20 years. The
demographic shift in the population in the United States and developed countries in general has significant
ramifications- for health care and socioeconomically. For anesthesiologists, healthcare costs are often estimated
using estimates from surgical volume, however true estimates of cost need to take into account the patient’s medical
services associated with an operation, the hospitalization and the cost to the caretakers and society in general. As
leaders in perioperative care, there are few populations where the impact of our anesthetic care beyond the operating
room is more important than to the elderly individual and our aging population in general.
General Guidelines for treating Geriatric Patients

1. Advanced chronological age is not a contraindication to surgery
2. Clinical presentation of disease may have been atypical, leading to delays and errors in diagnosis
3. Assume inter-individual variability and titrate medications to physiological effect when possible
4. Expect complexity: multiple medications and illnesses: individuals > 65 y have on average 3.5 medical
diseases
5. Diminished organ reserve can be unpredictable and difficulty to measure preoperatively - limitations
may only become apparent during stress
6. A disproportionate increase in perioperative risk may occur without adequate preoperative
optimization for example following emergent procedures
7. Meticulous attention to detail can help avoid minor complications - which in elderly patients can
rapidly escalate into major adverse events
8. Impact of extrinsic factors - smoking, environment, socioeconomic - is difficult to quantify
Surgical Volume
Surgery is common in the older patient; this is not surprising given the steady increase in comorbid conditions
associated with advanced age. Sixty five percent of all visits to general surgeons occur in patients over 65 years, so
it not surprising that many of these patients are subsequently seen in the operating room. It is estimated that almost
50% of adult surgeries are performed in patient over the age of 65 years. In addition, specialty surgery also
continues to expand – in orthopedics there has been marked increase in volume, and similar trends have been
observed in urological and other specialty surgeries.
Morbidity and Mortality

Older patients have higher complication rates and increased morbidity and mortality compared to younger patients,
especially in the oldest age range over 85 years. The highest mortality occurs following emergency surgery;
additional general risk factors for mortality include a low albumin, high ASA classification, limited preoperative
functional status and renal impairment. The development of a complication is one of the most significant predictors
of decreased survival. Hamel et al compared outcomes following non cardiac surgery in patients over 80 years with
a younger population, and found that in patients over 80 years who developed one or more complications the 30 day
mortality was 26 percent vs. 4 percent in patients without a complication. The type of complication mattered and
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mortality rate was highest following a cardiac arrest (88 percent), acute renal failure (52 percent) and MI (48
percent). In this analysis they found that each year over age of 80 was associated with a 5 percent increase in
mortality, thus a 90 year old had a 50 percent higher risk of mortality compared to an 80 years old. In general
studies looking at outcomes in patients over 90 years, mortality following non-cardiac emergency surgery ranges
from 19% to 35%. Of note in a study looking at non hip fracture emergency surgery they found a perioperative
morbidity rate of 62%, and the most common causes were confusion, renal failure and abdominal problems.
In summary, surgery in the very old patient carries a high mortality especially when complications occur. The lack
of tolerance for complications following surgery in older patients reflects an overall lack of physiological reserve in
the aged patient from both age related physiological changes and the impact of comorbid conditions.
Frailty – definitions and impact

Historically preoperative risk has been largely determined through the identification of individual diseases that carry
inherent risk during anesthesia. Congestive heart failure is a good example of a preoperative condition that is
associated with increased morbidity following anesthesia, similarly patients with poor pulmonary function may be at
increased risk of complications following anesthesia and surgery. Most preoperative screening is focused on
specific diseases and there are limited ways to estimate the physiological reserve function in the elderly patient.
Frailty describes a distinct syndrome that is becoming increasingly recognized as an important predictor of survival
and prognosis. Frailty is associated with functional decline, loss of independence and increased mortality. Although
the risk of frailty increases with multiple comorbidities, frailty may also develop in the absence of a major disease.
It is not defined as one single disease entity, instead features of frailty include slow walking speed, sarcopenia,
osteoporosis, malnutrition, immune deficiency and anemia. Frailty is associated with an increased vulnerability
from adverse events such as disability, hospitalization and death.
Makary et al examined the utility of frailty as a preoperative risk marker for adverse events following surgery.
Using a validated 5 point scale they classified patients scheduled for elective surgery into 3 groups: Frail,
intermediately frail, and non frail. The determination of Frailty was based on established criteria: 1. unintentional
weigh loss >10 lbs 2. Weakness measure using a had grip strength 3. Exhaustion with activity 4. Low physical
activity 5. Slowed walking speed measured in 15 secs. Using NSQIP data they looked at rates of surgical
complications, length of stay and discharge to a place other than home within 30 days. They then compared the
utility of the Frailty index with more standard risk indices such as the ASA classification; Lee’s revised cardiac
index and the Eagle score. They found that frail patients had a higher incidence of adverse events, length of
discharge and discharge to institution. The frailty index improved the predictive value of the more standard risk
indices.
Similarly Robinson et al found that frailty in patient undergoing colorectal surgery was associated with significantly
higher costs from discharge to 6 months, and higher degrees of frailty were associated with increased
institutionalization post surgery and 30 day readmission.
In summary, frailty appears to provide a marker of physiological reserve and as such may become an important
preoperative risk factor for older patients. Simple methods to rapidly assess frailty are likely to become increasingly
important as the population ages.
Age related changes predisposing the elderly to poor outcomes

Excess mortality observed in older patients is mostly due to comorbid conditions as opposed to chronologic age per
se, however, some age related deterioration in organ function is observed in all body systems, leading to a reduction
in reserve function. By the age of 80 years an older healthy patient can only increase organ function by about 50%
compared to a healthy 30 year old patient, and in the presence of chronic disease this is further reduced. When
taking care of elderly patients, it is important to consider the underlying age related changes that occur, below is a
brief summary of the key age related changes.
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Cardiovascular system
Age related cardiac changes are amongst the most predictable and important physiological changes that impact
anesthesia administration. Aging is associated with progressive stiffening and decreased compliance in the vessels
and the myocardium. These changes occur secondary to the combined effects of glycosylation and deposition of
free radicals in collagen and connective tissue leading to a gradual loss of elasticity. Ventricular compliance is
further reduced as systolic blood pressure and pulse wave velocity increase, leading to greater impedance to
ventricular outflow and subsequent myocardial hypertrophy. At the same time left ventricular relaxation during
diastole is impaired, leading to a decrease in early diastolic filling. This is known as diastolic dysfunction; it is
estimated that one third of patients with normal preoperative left ventricular function have diastolic dysfunction.
These patients are very susceptible to fluid overload in the perioperative period.
During aging , vagal or parasympathetic tone is decreased and there is an increase in sympathetic nerve activity and
plasma levels of noradrenaline. Alpha receptor activity appears largely preserved, and beta receptors are less
responsive to stimulation with a lesser increase in heart rate and less arterial and venous relaxation with direct
stimulation. The accompanying reduction in baroreflex function and overall vascular stiffening leads to more labile
blood pressure and predisposes elderly patients to orthostatic hypotension. This may be exaggerated during
anesthesia especially in volume depleted patients. The impaired beta receptor responsiveness reduces an older
patients’ ability to respond to an increase in demand through increased heart rate alone and the elderly patient
becomes very reliant on vascular tone and preload.
The incidence of ischemic heart disease increases exponentially with aging and in contrast to younger counterparts,
older patients often present with shortness of breath instead of classic chest pain. This may cause it to be overlooked
preoperatively. Hypertension in the in older individuals and is a leading cause of congestive heart failure.
Congestive heart failure remains one of the most significant risk factors for mortality following anesthesia and
surgery.
Pulmonary System
Risk factors for postoperative pulmonary complications include severe chronic obstructive pulmonary disease,
advanced age and high risk procedures, such as upper abdominal or intrathoracic surgery. Unlike cardiac risk, age
alone remains a significant risk factor for postoperative pulmonary complications. The risk of a postoperative
pulmonary complication is twice as high in patients’ age 60 to 69 years compared to those aged 60 or less, and there
is a 3 fold increase in patients aged 70-79 years.
There are several predictable changes that occur during aging predisposing the older patient to complications; these
include a reduction in respiratory muscle strength, a decrease in chest wall compliance and a decrease in the elastic
recoil.
With aging, chest wall and muscular changes lead to an increase in the work of breathing. The diaphragm becomes
flattened and the chest becomes more barrel shaped; negatively impacting chest wall dynamics. These changes can
lead to diaphragmatic fatigue and a predisposition to respiratory failure in the postoperative period; this may
manifest as difficulty weaning from a ventilator, especially in frail older patients. Pulmonary changes with aging are
similar to those that occur with emphysema and central airways increase in size leading to increased anatomic and
physiologic deadspace. The lack of elastic recoil in smaller airways can result in air trapping with positive pressure
ventilation. Closing capacity is increased, and by mid 60s it exceeds FRC leading to closure of small airways and
increase in shunt fraction, predisposing older patients to hypoxemia.
Central nervous system changes lead to a decrease in hypoxemic and hypercapnic ventilatory drive – this can be as
much as by 50%. This can result in a significant increase in susceptibility to narcotic induced apnea potentially
leading to unexpected hypoxemia and hypercapnia. The susceptibility to hypoxemia is enhanced by the gradual age
related decrease in resting arterial oxygen tension.
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Metabolism and renal function

Changes in body composition, renal function and drug metabolism render the older patient vulnerable from drug
overdoses at ‘usual’ adult doses. There is a decrease in the total body water and an increase in percentage of body
fat, accompanied by a reduction of protein and muscle mass. This can change the distribution of water and fat
soluble medications. For example declines in plasma volume and intracellular water can result in a significant
increase in the initial volume of distribution of a drug like propofol, resulting in an increase in plasma concentration
if the initial dose is not reduced. The change central volume, in addition to a potential delay in redistribution of the
propofol from the central compartment, may explain some of the exaggerated effects seen with propofol boluses in
older patients. In contrast, fat soluble medications, such as some of the opioids, may be deposited in larger fat
stores leading to prolonged and unpredictable recovery.
Glomerular filtration rate and creatinine clearance decline steadily and the degree of baseline impairment may be
underestimated by the serum blood urea nitrogen and creatinine alone. Postoperative renal failure is rare but is
associated with a high mortality rate, accounting for one fifth of postoperative deaths in elderly patients. Although
albumin levels are usually preserved in health, they may be diminished in older patients with chronic disease, and
reduced albumin levels remain a predictor of poor outcome in older patients.
Central Nervous System

In addition to predictable anatomical changes in the central nervous system, there is an increase in dementia,
memory loss and degenerative diseases such as Parkinson’s disease. Anatomical changes include gradual atrophy of
the brain, reduction in gray cells, and widening of the ventricles. The number of neuroreceptors and
neurotransmitters appear to decrease even in the absence of dementia or recognized neurodegenerative diseases.
The most significant declines observed are in acetylcholine and serotonin receptors in the cortex, dopamine
receptors in the neostriata, and dopamine levels in substantia nigra and neostrata. These alterations in
neurotransmitter levels and neuronal circuits leads to pharmacodynamic changes and changes in sensitivity to
certain medications such as midazolam and some of the opioids. Decrease in cholinergic receptor activity may
explain some of the sensitivity elderly patients have when exposed to medication such as scopolamine with high
anticholinergic potency.
Thermoregulation
Older patients are particularly vulnerable from developing hypothermia. Aged patients demonstrate diminished
effectiveness of peripheral vasoconstriction and shivering and have more difficulty maintain body temperature
during surgery and anesthesia. It is known that perioperative hypothermia can lead to significant negative effects
including reduced metabolism of medications, an increased oxygen demand associated with shivering leading to
potential myocardial ischemia, and coagulopathy. These may be poorly tolerated in the older patient with reduced
physiological reserve and comorbid conditions.
Adverse consequences in elderly patients and potential prevention strategies
Postoperative cognitive disorders

Delirium is the one of the most common and dreaded complications occurring postoperatively in the elderly
surgical patient. Delirium is an acute confusional state, usually appearing 1-3 days after surgery; it may persist for
weeks to months in afflicted patients. The etiology is multifactorial including acute medical conditions such as
sepsis, hypoxemia, urinary tract infections, and alcohol withdrawal. Certain medications including meperidine and
medications with anticholinergic effects such as diphenhydramine and scopolamine are associated with delirium.
Pain in the postoperative period may be an important and overlooked cause of delirium. Patients with preexisting
dementia, baseline cognitive difficulties and depression carry a higher risk of developing delirium postoperatively.
Delirium is associated with an increase in morbidity and mortality as well as an increase in the length of stay and
dependent living situations.
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There is no ‘magic bullet’ to treat or prevent delirium in elderly surgical patients. Some of the initiatives that have
been the most successful include the use of structured clinical protocols an specialized geriatric care units focusing
on risk factor modification. Other approaches include avoiding drugs known to precipitate delirium such as the
anticholinergic medication and avoiding meperidine in particular. Other strategies are largely practical including
appropriate treatment of postoperative pain, and careful selection and titration of drugs when sedation is required.
Low dose haloperidol (1.5 mg / per day) has been shown to reduce the length and severity or delirium and may have
some utility in high risk patients.
The initial assessment and treatment of delirium should be directed towards any reversible condition such as pain,
abnormal electrolytes, hypoxia, alcohol withdrawal and infection. Midazolam has been associated with a
paradoxical excitation in elderly patients with delirium and in general is not recommended, similarly long acting
benzodiazepines can accumulate in the older patient and should be avoided. For hip fracture patients, who are at
very high risk from developing delirium, there is some evidence that suggests lighter sedation levels combined with
spinal anesthesia may reduce the incidence of delirium.
In contrast to delirium, post operative cognitive dysfunction (POCD) refers to a specific cognitive disorder
generally recognized in the post operative period and is ultimately diagnosed through neuropsychological testing.
Studies have demonstrated that almost 10% of elderly patients receiving a general anesthesia had some cognitive
dysfunction 3 months after surgery. The etiology of PCOD is unclear at this point in time.
Avoiding Pulmonary complications

As discussed advanced age is associated with a gradual decrease in chest wall compliance and decreased respiratory
muscle strength, so any diminution in strength for example from residual effects of neuromuscular blockade, may
lead to hypoventilation and postoperative pulmonary complications. Long acting neuromuscular blockers such as
pancuronium should be avoided in elderly patients.
Poor pain control may be a factor the contributing to the development of post operative pulmonary complications.
Although the data is limited, it does appear good pain control including epidural analgesia for can be beneficial for
aortic, vascular and thoracic surgery. Finally elderly patients are predisposed to aspiration, and precautions should
be taken to avoid this complication. Patients with swallowing disorders, Parkinson’s and other neurological
syndromes are particularly high risk.
Cardiac risk in the elderly patient

Age is not a consistent independent predictor of perioperative cardiac risk, the role of disease is probably more
relevant as well as functional capacity. However in the event of an acute myocardial infarction, the intraoperative or
perioperative mortality is higher in geriatric vs. younger patients. Thus cardiac care is a very important aspect of
geriatric care. When considering reducing risk in the elderly patient a few important factors are: the use of beta
blockade and statins, the importance of blood pressure control perioperatively and the utility of a preoperative ECG.
In general beta blockers should be continued around surgery and administered perioperatively to high risk
individuals undergoing intermediate or high risk surgery as outlined by the American College of Cardiology
Foundation/American Heart Association guidelines. Indiscriminate and wide spread use of beta blockers is not
recommended.
Perioperative statin use should not be abruptly discontinued in the perioperative period. Statins in the perioperative
period are indicated in patients with high risk indices undergoing intermediate and high risk surgery.
The role of hypertension in attributing risk in the perioperative period is difficult to ascertain. However
observational data suggests that perioperative hypertension and intraoperative hypotension may be associated with
increased risk of myocardial infarction and mortality following surgery.
Age based criteria for patients undergoing low risk surgery is not recommended to guide ordering of preoperative
ECGs. However preoperative ECGs are indicated in patients with cardiac risk factors and active disease under
going at least intermediate surgery.
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Anesthetic administration
Due to age related changes in physiology and comorbidities outlined above, anesthetic administration should be
tapered for the elderly. Older patients represent a heterogeneous group and each anesthetic should be tailored for the
individuals. In general ‘start low, go slow’ remains a valid axiom when taking care of elderly patients – and most
older patients require less anesthesia compared to younger counterparts. For example the MAC of inhalational
agents decreases predictably by 6% every decade after age 20 years. Thus the MAC at age 90 year is reduced by
30% compared to a 40 year old. Similarly, pharmacodynamic changes in elderly patients increase the sensitivity of
the brain to opioids, and as a general rule, opioid doses can be reduced by 50% in older patients. A carefully titrated
anesthetic may have advantages in the older patients especially if medication with known side effects such as
anticholinergic drugs can be avoided.
Dosing in the Elderly

1. Reduce initial dose of opioids by 50%
2. Increase intervals between boluses
3. Minimize medications
4. Monitor vitals signs
5. Consider supplemental oxygen
6. Consider significant comorbidities / complexity
7. Expect a potential longer recovery
Quality measures
In contrast to the standard quality assessment performance measures for surgery (myocardial infarction, surgical site
infection and deep venous thrombosis), process measures looking at multiple aspects of care such as interpersonal
communication, diagnostic and treatment strategies may be more relevant for elderly patients. Examples of areas
that may be included in a ‘geriatric quality index’ are: frailty scores, comorbidity assessment, medication usage and
polypharmacy, documentation of a discussion regarding a patient’s decision making ability and advanced directives,
postoperative management including functional expectations, and discharge planning including a plan for at home
care or post discharge institutionalization. These are some examples, unfortunately there are significant difficulties
in implementing follow up on a large number of both objective and subjective indicators. Despite the difficulties,
measuring quality of care will be especially important given the excess morbidity and mortality observed in this
growing population.
Summary of Challenges of the Geriatric Patient
1. Population is heterogeneous
2. Wide disparity between physiologic and chronological age
3. Advancing age is associated with a steady decline in organ function
4. Preoperative reserve organ function unknown
5. Multiple acute and chronic co-morbidities may co-exist
6. Common conditions may present atypically
7. Emergency procedures are associated with increased mortality and morbidity
8. Patients can have complex medication regimes
9. Potential diminished mental capacity makes history taking difficult
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Conclusion
The elderly represent an heterogeneous and significant portion of the population. As anesthesiologists it will be
important to avoid complications, streamline perioperative care and ensure the highest quality of care for this
vulnerable population. There is no magic bullet for the elderly, instead vigilance , careful titration of medication and
a thorough understanding of the basic physiologic changes and commonly encountered comorbidities is needed.
Recommended Reading
General
• Story D.A. Postoperative mortality and complications. Best Pract & Research Clinical Anesthesiology
2011: 25: 319-327
• Li G, Warner M, Lang BH, Huang L, Sun LS. Epidemiology of anesthesia-related mortality in the United
States, 1999-2005 Anesthesiology. 2009 Apr;110(4):759-65
• Liu, LL; Leung, JM. “Predicting Adverse Postoperative Outcomes in Patients Aged 80 Years or Older.”
Journal of the American Geriatrics Society 48 (2002): 405-412.
• Kheterpal, S; O’Reilly, M; Englesbe, MJ; Rosenberg, AL; Shamks, AM; Zhang,L;Rothman,ED;
Campbell,DA; Tremper, KK. Preoperative and intraoperative predictors of cardiac adverse events after
general, vascular and urological surgery. Anesthesiology 2009; 110-58-66
• Turrentine FE, Wang H, Simpson VB, Jones, RS. Surgical Risk factors, morbidity, and mortality in elderly
patients. J Am Coll Surg 2006: 203: 865-877
• Leung, JM; Dzankic, S. Relative Importance of Preoperative Health Status Versus Intraoperative Factors in
Predicting Postoperative Adverse Outcomes in Surgical Patients. Journal of the American Geriatrics
Society 49 (2001): 1080-1085.
• Hamel, MB; et al. Surgical Outcomes for Patients Aged 80 and Older: Morbidity and Mortality from Major
Noncardiac Surgery. Journal of the American Geriatrics Society 53.3 (2005): 424-429.
• Liu SS, Della Valle AG, Besculides MC, Gaber LK, Memtsoudis SG. Trends in mortality, complications,
and demographics for primary hip arthroplasty in the united states. Int Orthop. 2009;33(3):643-651.
Frailty
• Robinson TN, Wu DS, Stiegman GV, Moss M. Frailty predicts increased hospital and six month healthcare
cost following colorectal surgery in older adults. Am J Surgery 2011; 201: 511-514
• Kanapuru B, Erschler WB. Inflammation, Coagulation and the Pathway to Frailty. Am J Medicine 2009;
122: 605- 613
• Makary MA, Segev DL, Pronovost PJ, et al Frailty as a predictor of surgical outcomes in older patients. J
AM Coll Surg 2010; 210:901-908
• Cook, DJ, Rooke GA. Priorities in Perioperative Geriatrics. Anesth Analg; 2003: 96:1823-1836
General Age Related Changes
• Rooke, GA. “Cardiovascular Aging and Anesthetic Implications.” Journal of Cardiothoracic and Vascular
Anesthesia 17.4 (2003): 512-523.
• Silvey G, Castillo JG, Chikwe J, Flynn B, Filsoufi F. Cardiac Anesthesia and Surgery in Geriatric Patients.
Semin Cardiothorac Vasc Anesth 2008;12:18-28
• Groban, L. “Diastolic Dysfunction in the Older Heart.” Journal of Cardiothoracic and Vascular Anesthesia
19.2 (2005): 228-236.
• Phillip B, Pastor D, Bellows W, Leung JM: The prevalence of preoperative diastolic filling abnormalities in
geriatric surgical patients. Anesth Analg 2003; 97:1214-21
• Sprung J, Gajic O, Warner DO. Review article: Age related alterations in respiratory function - anesthetic
considerations: Can J Anaesth 2006;53:1244-57.
• Schucker DL; Age related changes in liver structure and function: implications for disease? Exper
Gerontol; 2005: 40:650-659
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• Kenney WL, Munce TA. Invited review: aging and human temperature regulation. J Appl Physiol
2003;95:2598-603.
Medications
• Jacobs, JR; et al. “Aging Increases Pharmacodynamic Sensitivity to the Hypnotic Effects of Midazolam.”
Anesthesia and Analgesia 80.1 (1995): 143-148.
• Nickalls, RW; Mapleson, WW. “Age-related Iso-MAC Charts for Isoflurane, Sevoflurane and Desflurane
in Man.” British Journal of Anaesthesia 91.2 (2003): 170-174.
• Gurwitz JH, Field TS, Harrold LR, Rothschild J, Debellis K, Seger AC, Cadoret C, Fish LS, Garber L,
Kelleher M, Bates DW. Incidence and preventability of adverse drug events among older persons in the
ambulatory setting. JAMA. 2003 Mar 5;289(9):1107-16.
Delirium
• Silverstein, JH; Timberger, M; Reich, DL; Uysal, S. “Central Nervous System Dysfunction after
Noncardiac Surgery and Anesthesia in the Elderly.” Anesthesiology 106.3 (2007): 622-628.
• Vaurio LE, Sands LP, Wang Y, Mullen EA, Leung JM, Postoperative Delirium: The Importance of Pain
and Pain Management Anesth Analg 2006;102:1267-1273
• Moller, JT; et al. “Long-term Postoperative Cognitive Dysfunction in the Elderly: ISPOCD1 Study.”
Lancet 351 (1998): 857-861.
• Marcantonio, ER; Flacker, JM; Michaels, M; Resnick, NM. “Delirium is Independently Associated with
Poor Functional Recovery after Hip Fracture.” Journal of the American Geriatrics Society 48.6 (2000):
618-624.
• Inouye SK. Delirium in older persons. N Engl J Med 2006;354:1157-65.
• Monk TG, Weldon BC, Garvan CW, et al. Predictors of cognitive dysfunction after major noncardiac
surgery. Anesthesiology. 2008;108(1):18-30.
• Rudolph JL, Salow MJ, Angelini MC, McGlinchey RE. The anticholinergic risk scale and anticholinergic
adverse effects in older persons. Arch Intern Med. 2008;168(5):508-513.
• Inouye SK, Bogardus ST Jr, Charpentier PA, et al. A multicomponent intervention to prevent delirium in
hospitalized older patients. N Engl J Med. 1999;340(9):669-676.
• Sieber FE, Zakriya KJ, Gottschalk A, et al. Sedation depth during spinal anesthesia and the development of
postoperative delirium in elderly patients undergoing hip fracture repair. Mayo Clin Proc. 2010;85(1):18-
26.
Cardiac and Pulmonary risk
• Lee A. Fleisher, et al: ACC/AHA 2007 Guidelines on Perioperative Cardiovascular Evaluation and Care
for Noncardiac SurgeryA Report of the American College of Cardiology/American Heart Association Task
Force on Practice Guidelines:Circulation. 2007;116:e418-e500.)
• Poldermans D, Hoeks SE, Feringa HH. Pre-operative risk assessment and risk reduction before surgery. J
Am Coll Cardiol. 2008;51(20):1913-1924.
• Liu L, Dzankic S, Leung JM. Preoperative Electrocardiogram Abnormalities Do Not Predict Postoperative
Cardiac Complications in Geriatric Surgical Patients. J Am Geriatr Soc 2002;50:1186-1191
• Fleisher LA, Beckman JA, Brown KA, et al. 2009 ACCF/AHA focused update on perioperative beta
blockade incorporated into the ACC/AHA 2007 guidelines on perioperative cardiovascular evaluation and
care for noncardiac surgery: A report of the american college of cardiology foundation/American heart
association task force on practice guidelines. Circulation. 2009;120(21):e169-276.
• Noordzij PG, Bersma E, Bax JJ, Feringa HH, Schreiner F,Schouten, OKertai MD, Klein J, van Urk H,
Elhendy A, Poldermans D Prognostic value of routine preoperative electrocardiography in patients
undergoing noncardiac surgery. Am J Cardiol (2006 Apr 1) 97(7):1103-6
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• Lawrence VA, Cornell JE,Smetana GW, Strategies to reduce postoperative pulmonary complications
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Quality
• Bentrem DJ, Cohen ME, Hynes DM, Ko CY, Bilimoria KY. Identification of specific quality improvement
opportunities for the elderly undergoing gastrointestinal surgery. Arch Surg. 2009;144(11):1013-1020.
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Surg. 2009;250(2):338-347
DISCLOSURE
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How to Interpret and Use Arterial Blood-Gas Data

Interpretation and Application for the Non-Chemist
Steven J. Barker, Ph.D, M.D. Tucson, Arizona
Introduction The interpretation and application of arterial blood-gas (ABG) data is a task that anesthesiologists
must often perform under difficult circumstances. The time is 3:00 AM; we are fatigued and distracted by multiple
other simultaneous tasks; we need to take action on these ABG results now. In this setting, which bears similarities
to piloting an aircraft on instruments in bad weather, it is useful to have a simple algorithm or “check-list,” both to
ensure consistency and obtain a correct answer within a short time. The purpose of this talk is to develop such an
algorithm and apply it to specific clinical examples, wherein we shall interpret both oxygenation and acid-base
status, and then prescribe appropriate treatment.
Case Example At 3:00 AM, you are presented with an 80 year-old, 60 kg man who has been found unconscious
on the floor at home. He is brought to the operating room for emergency laparotomy, with a presumed diagnosis of
ruptured appendix. His vital signs are BP: 90/60, HR: 120, RR: 26, SpO2: 96%. A pre-operative ABG reveals: pH
= 7.20, PaCO2 = 25, PaO2 = 75, HCO3- = 8. Should you give sodium bicarbonate? How much? What else do you
change?
Oxygenation The first step in evaluating the arterial oxygen tension (PaO2) is to calculate the alveolar oxygen
tension, using the alveolar gas equation:
PAO2 = FIO2(PB – PH2O) – (1/RQ)PaCO2 . [1]
For a normothermic (37oC) patient, breathing room air at sea level:
P AO 2 = 0.21(760 – 47) – (1.25)40
= 99.73 mmHg .
The alveolar PO2 at sea level is roughly 100 mmHg. Next, calculate the RATIO of arterial to alveolar oxygen
tension: PaO2/ PAO2. Do NOT bother with the alveolar-arterial difference, sometimes erroneously referred to as the
“gradient.” The normal value of this difference is a function of the FIO2, whereas the normal or healthy value of the
ratio is roughly 0.85 at any FIO2. Thus a “healthy” PaO2 during normocarbia at sea level is PaO2 ~ 0.85 PAO2 = 85
mmHg.
Now, just for fun, let’s go to the top of Mt. Everest, elevation 29,035 ft, barometric pressure PB = 247 mmHg. Here
is how some humans have actually made it to the summit without supplemental oxygen:
PAO2 = FIO2(PB – PH2O) – (1/RQ)PaCO2
= 0.21(247 – 47) – (1.25)7.5
= 32.6 mmHg
Yes, your PaCO2 on top of Everest is 7.5 mmHg. Talk about hyperventilation!
Furthermore, your predicted PaO2, using the arterial/alveolar ratio of 85%, will be
0.85 X 32.6 = 27.7 mmHg. In laboratory simulations of Everest conditions, this is almost exactly the resulting PaO2
value. If you are wondering why the PaCO2 is so low, try repeating this calculation for normocarbia.
The treatment of hypoxemia is beyond the scope of this lecture, but in general the tools available in the
operating room fall into three categories.
1. Ventilator adjustment: FIO2, PEEP, vent mode (reverse I/E, pressure, HFV, etc.).
2. Drugs: Diuretics, bronchodilators, PDE-5 inhibitors (Cialis is now used for HAPE).
3. Procedures: Chest tube, bronchoscopy, etc.
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Acid-Base Balance At a concentration of 0.00004 mEq/L, hydrogen ion is one of the least plentiful electrolytes
in the extracellular fluid (ECF). Nevertheless, because of its small size and high charge state, H+ is highly reactive
and must be regulated within narrow limits, or we die. The hydrogen ion concentration, denoted [H+], varies
between 0.1 Eq/L (gastric) and 0.000000008 Eq/L (duodenal) within the body. We commonly use a logarithmic
scale to measure it: pH = -log[H+]. The rather wide concentration range above is thus converted to a pH range
between 1.0 and 8.1. An H+ concentration in the ECF that is either too high (low pH: acidemia) or too low (high
pH: alkalemia) will cause a variety of potentially fatal cardiovascular disturbances. These include decreased
myocardial contractility, vasomotor instability, cardiac dysrythmias, and decreased enzyme function. The body uses
several defenses against pH changes, but to understand these we must first review some basics of acid-base
chemistry.
A cids, Bases, Buffers Simply put, and acid is a chemical compound that can give up a free H+ ion in aqueous
solution; a base is a compound that can accept a free H+ ion. This equilibrium is represented as:
HA ↔ H+ + A- , [2]
where HA is and acid, and A- is called the “conjugate base.” A “strong acid” is one that shifts this equilibrium to the
right, producing large amounts of H+. A weak acid shifts the balance to the left, producing less free H+. Similar
definitions apply for strong and weak bases. If an acid is strong, then its conjugate base is by definition weak, and
vice versa. Since excess hydrogen ion (acidemia) is bad for our health, we would generally prefer weak acids to
stronger ones. More on this concept later.
The strength of the acid HA can be quantified by the ratio of concentrations of the two sides of equation 2:
K = [H+][A-]/[HA] [3]
In this and the following equations, square brackets denote concentrations. K is called the “dissociation constant”
and equation 3 is referred to as the “law of mass action.” A large value of K implies a strong acid and weak
conjugate base. Taking the logarithms of both sides of equation 3 and rearranging, we find:
log K = log [H+] + log ([A-]/[HA])
-log [H+] = -log K + log ([A-]/[HA])
pH = pK + log ([A-]/[HA]) [4]
In this last step we have inserted the definitions pH = -log [H+] and pK = -log K, yielding the familiar Henderson-
Hasselbach Equation. This equation is simply a logarithmic form of the law of mass action, or definition of the
dissociation constant.
The most important acid-base equilibrium in the body is that of carbon dioxide and water:
H2O + CO2 ↔ H2CO3 ↔ H+ + HCO3- [5]
The pK of this reaction is 6.1, making carbonic acid a rather weak acid. Henderson-Hasselbach (Eq. 4) for this
reaction becomes:
pH = pK + log {[HCO3-]/[H2CO3]}
pH = 6.1 + log {[HCO3-]/(0.03 PaCO2)} ` [6]
We don’t routinely measure blood carbonic acid concentration, so in the last step we have substituted the empirical
formula: [H2CO3] = 0.03 PaCO2. Equation 6 states a simple and important fact about acid-base physiology: the pH
is determined by the RATIO of the bicarbonate concentration to the PaCO2. We shall see that this is a key feature of
the body’s defenses against pH changes. Inserting normal blood values into Eq. 6:
pH = 6.1 + log {24/(0.03 X 40)} = 7.4 .
It is always reassuring when a new formula gives the correct answer in a known situation.
Body acids, buffers, and defenses Acids are formed in two ways in the human body. Respiratory acid is formed by
the combination of carbon dioxide (product of aerobic metabolism) and water, as shown in Eq. 5. All other acids are
called “metabolic acid.” The latter include lactic acid produced by anaerobic metabolism, as well as sulphuric,
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hydrochloric, and phosphoric acids. We have already noted that carbonic or respiratory acid is a weak acid. In fact,
in the normal ECF equilibrium (Eq. 5) it takes 800,000 molecules of CO2 to produce 800 molecules of H2CO3,
which in turn produce ONE free H+ ion. Insert Acids.jpg This brings us to the body’s first line of defense against
acid “invasion”: a system of “buffers.” A buffer is something that effectively exchanges a strong acid for a weaker
one, as in the following.
H+ + Cl- + NaHCO3 ↔ H2CO3 + NaCl [7]
As this reaction moves to the right, the sodium bicarbonate “trades” the very strong hydrochloric acid (HCl) for the
very weak carbonic acid (H2CO3). A buffer solution thus consists of a weak acid (H2CO3) and a salt of the
conjugate base (NaHCO3), and it uses this combination to trade strong acid for weak acid, thereby reducing the
amount of free H+ released. Bicarbonate, the example we have just considered, is the most important buffer in the
body. Other buffers include proteins, phosphate, and ammonia. Proteins are significant for two reasons: (1) they are
very plentiful in the intracellular milieu (75% of total body buffering power), and (2) they can buffer both metabolic
and respiratory acid, as shown below for the protein hemoglobin (Hb).
HCl + KHb ↔ HHb + KCl [8a]
H2CO3 + KHb ↔ HHb + KHCO3 [8b]
There are two other front-line defenses against pH changes: respiratory and renal control. The lungs, driven by
medullary chemoreceptors, regulate the PaCO2 level. The kidneys, by actively excreting H+ into the urine and
reclaiming Na+ from the urine, effectively ‘pump’ bicarbonate from the urine back into the blood. The kidneys
excrete a normal daily metabolic acid load of 50 mM at a urine pH of 6.0, and healthy kidneys can handle as much
as ten times that amount by reducing the urine pH to 4.5. Looking again at equation 6, the lungs control the
denominator and the kidneys the numerator of the ratio that determines pH.
Evaluation of acid-base balance Given the above background on acids, bases, buffers, and the body’s pH controls,
we are now ready to evaluate and treat the acid-base balance. The first step in this process is a plot of the plasma pH
versus bicarbonate, shown in Figure 1.
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Figure 1. The pH – Bicarbonate Diagram.
Choosing a location on this graph fixes the values of pH and HCO3-, and Eq. 6 (Henderson-Hasselbach) then
determines the corresponding value of PaCO2. The curves labeled 20, 30, 40, etc. are lines of constant PaCO2, called
“isobars.” They are solutions of the Henderson-Hasselbach Equation. The normal acid base status of pH = 7.4,
HCO3- = 24, PaCO2 = 40 corresponds to the center of the graph. Note the straight line passing through the center
with a slight negative slope, labeled “10sl.” This “buffer line” is the path followed by a purely respiratory
disturbance – either hypercarbia or hypocarbia with no metabolic disturbance at all. The slope of the buffer line
represents the body’s chemical buffering power, and its units are called “Slykes,” named after the chemist Van
Slyke. The normal slope is actually nearer to 12, but a value of 10 is easier for the calculations that follow and is
close enough for our purposes.
The two stippled regions along the buffer line, labeled “acute,” are the areas in which an acute, uncompensated,
respiratory disturbance will lie. Take for example an acute respiratory acidosis – the stippled area to the left of the
center of the graph. Referring again to Eq. 6, we see that the body’s compensation for this acute hypercarbia will be
to increase the HCO3- level (the kidneys’ job) to bring the ratio back towards normal, thus correcting the pH. This
“metabolic compensation” may take several days to complete, and it will move us from the “acute” stippled area
upward along the appropriate isobar into the “chronic” stippled area in the upper-left quadrant. Thus a quick exam
of the pH-bicarbonate diagram not only tells us that our patient has a respiratory acidosis, but also evaluates the
metabolic compensation. The same reasoning applies to both acute and compensated respiratory alkalosis, shown in
the lower right quadrant of the diagram.
A pure metabolic acidosis, without compensation, would follow the PaCO2 isobar down into the lower left quadrant
of Figure 1. (Ignore, for now, the arrow in the lower left quadrant. It will be used later.) Metabolic acidosis
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manifests as a decrease in HCO3-, so the body’s compensatory response is to decrease the denominator of the ratio in
Eq. 6, that is, to lower the PaCO2. This compensatory hyperventilation takes us into the stippled area in the lower
left quadrant of Figure 1. Similarly, the respiratory compensation for metabolic alkalosis is hypoventilation, as
indicated by the stippled area of the upper right quadrant. Since hypoventilation will eventually cause hypoxemia,
this compensation is less effective, as indicated by the slopes of the two stippled areas.
Instead of referring the stippled areas of Figure 1, we can also use empirical “rules of thumb” to predict
compensation. Remember that the body’s response to pH imbalance is to restore the ratio of HCO3-/PaCO2 toward
its normal value of 24/40 = 0.6, because this ratio controls the pH (Eq. 6). The following rules are based on clinical
data, and are only approximate predictors.
1. Metabolic compensation for a primary respiratory disturbance.
a. Respiratory acidosis: For every 10 mmHg rise in PaCO2 above 40:
i. Acute: HCO3- increases by 1 mEq/L.
ii. Chronic (compensated): HCO3- increases by 4 mEq/L.
b. Respiratory alkalosis: For every 10 mmHg fall in PaCO2 below 40:
i. Acute: HCO3- decreases by 2 mEq/L.
ii. Chronic (compensated): HCO3- decreases by 3 mEq/L.
2. Respiratory compensation for a primary metabolic disturbance.
a. Metabolic acidosis with maximum compensation:
PaCO2 = 1.5[HCO3-] + 8.
b. Metabolic alkalosis with maximum compensation:
PaCO2 = 0.7[HCO3-] + 20.
One additional tool is required to quantify the metabolic disturbance: “base excess” or BE. The definition of BE is
as follows. “Titrate the pH to 7.40 by varying only PaCO2. BE is the difference between the resulting HCO3- at the
end of this titration and the normal value of 24 mEq/L.” It is easier to understand this definition by using an
example on the pH-bicarbonate diagram, Figure 1. We are given the following arterial blood-gas results: pH = 7.1,
PaCO2 = 32, HCO3- = 10, as indicated by the tail of the arrow in the lower left quadrant. To find BE, we titrate back
to a pH of 7.4 by varying only PaCO2. This titration follows a line parallel to our “buffer line,” shown by the arrow
shaft. Since the slope of this line is -10 Slyke, and the pH changes by 0.3 units (from 7.1 to 7.4), the bicarbonate
will decrease by 3 mEq/L (0.3 times 10), reaching a new value of 7 (10 minus 3) at the head of the arrow. The BE is
thus 7 – 24, or -14. A negative base excess is also called a “base deficit,” so our blood-gas shows a base deficit of
14. You can now calculate BE in your head if you know the pH and the bicarbonate. Should we treat this base
deficit, and if so, how? This is our next topic.
There are many possible causes of metabolic acidosis, but in the operating room it is most often the result of
inadequate oxygen delivery to various organs and tissues. It is the direct result of anaerobic metabolism, and
therefore manifests as a lactic acidosis. The “anion gap,” defined as [Na+] + [K+] – [Cl-] – [HCO3-], is above the
normal range of 8-12. Like most physiological disorders, the ideal prescription is to “treat the underlying cause.” If
the cause of the lactic acidosis is tissue hypoperfusion resulting from hypovolemic shock, correcting the patient’s
volume status may be all that is needed to restore perfusion and rapidly correct the acidemia. On the other hand, a
very low pH (7.1 would fall in that category) will depress cardiac function significantly, and the heart may not be
able to generate sufficient cardiac output to restore organ perfusion while the pH remains so low. This is a judgment
call that we must make on a case-by-case basis. If we decide that the pH must be at least partially corrected before
the heart can do its job, here is how we treat it.
Treatment of acid-base disorders The first step in treating a metabolic acidosis is to determine the “bicarbonate
deficit.” That is, how much bicarbonate would be required to restore the extracellular fluid to its normal value of 24
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mEq/L? This quantity is simply the base deficit times the weight in kg, times the ECF fraction. The ECF comprises
the following fraction of body weight:
ECF fraction = 0.5 (premature neonate)

0.4 (term neonate)
0.3 (2 year-old)
0.25 (older child)
0.2 (adult)
Thus, if the patient above with a BE of -14 is a 70 kg adult, the bicarbonate deficit will be 14 X 70 X 0.2, or 196
mEq.
Treatment of metabolic acidosis with sodium bicarbonate (NaHCO3) is not a risk-free therapy. First, “bicarb” does
not make metabolic acid disappear; it effectively converts it to respiratory acid (see Eq. 7). The additional CO 2
created by this exchange must be removed by increased ventilation. Furthermore, full strength sodium bicarbonate
is a hyperosmolar solution (six times plasma osmolarity) and can thereby cause brain hemorrhage, particularly in
children. Overtreatment can cause alkalemia, which is just as dangerous as acidemia. Insert Biocarbinate Therapy
Dangers.jpg Therefore, the common recommendation is to give about half the amount of total bicarbonate deficit,
increase ventilation to compensate for the additional CO2, and reevaluate in roughly 30 minutes. There are two
approved alternatives to sodium bicarbonate: tris-hydroxy amino-methane (THAM) and “carbi-carb,” which is an
equimolar mixture of sodium bicarbonate and sodium carbonate (Na2CO3). Both can buffer metabolic acid with
little or no increase in CO2, but neither has been shown to have any outcomes advantage over conventional
treatment.
Evaluation/Treatment A lgorithm We conclude by encapsulating the above approach to acid-base evaluation into a
simple four-step algorithm, which we shall apply to our original case example.
Four Step Evaluation of Acid-Base Status: Move to chart or graphic

1. Evaluate the pH: if pH > 7.45, patient has alkalemia; if pH < 7.35, patient has acidemia.
2. Evaluate the PaCO2: if PaCO2 > 45, patient has respiratory acidosis; if PaCO2 < 35, patient has respiratory
alkalosis.
3. Find the base excess BE, using the 10 Slyke approximation: if BE > +2, patient has metabolic alkalosis; if
BE < -2, patient has metabolic acidosis.
4. Evaluate compensation: determine predicted maximum compensation by non-primary variable, using
empirical rules or referring to stippled areas of Figure 1.
Finally, let us use this algorithm to evaluate and treat our original patient, a 60 kg man with a blood gas analysis
showing 7.20/25/75/8 (pH/ PaCO2/PaO2/HCO3-).
1. The patient is acidemic (pH = 7.20).
2. The patient has respiratory alkalosis (PaCO2 = 25).
3. Calculate BE (see Figure 1): titration to pH = 7.4 requires pH to change by 7.4 – 7.2 = 0.2; HCO3- therefore
decreases by 0.2 X 10 = 2; new HCO3- = 8 – 2 = 6; BE = 6 – 24 = -18.
4. Evaluate compensation: Maximum predicted respiratory compensation for this metabolic acidosis is
PaCO2 = 1.5[HCO3-] + 8 = (1.5 X 8) +8 = 20 mmHg. The patient’s actual PaCO2 is 25 mmHg. Given his
physical status, this patient is nearly at maximum compensation.
Treatment: The amount of bicarbonate required to fully correct the patient’s BE of -18 is:
NaHCO3 = 60 kg X 0.2 X 18 mEq/L = 216 mEq.
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A reasonable therapy is to give half this amount, or two ampoules (55 mEq per ampoule), increase mechanical
ventilation, and obtain another ABG measurement in 15-30 minutes.
Conclusions Interpretation of arterial blood-gas data is straightforward, if we follow a prescribed algorithm such
as the one presented in this lecture. The simplest interpretation of PaO2 comes from calculating the ratio of arterial
to alveolar oxygen tension (using the alveolar gas equation) and comparing the result with the normal value of 0.85.
To evaluate the acid-base status, simply follow the four step algorithm, which separates respiratory for metabolic
disturbance and evaluates compensation. The pH-bicarbonate diagram (Figure 1) is an excellent tool for keeping all
of these factors in perspective, and understanding the results of treatment. Finally, if the patient has a severe
metabolic acidosis that may require treatment, calculate the bicarbonate deficit as shown above. I do not
recommend an arbitrary BE threshold for treatment with sodium bicarbonate; that decision should take into account
all aspects of the patient’s clinical status. However, once the decision to treat has been made, it is usually wise to
give about half of the bicarbonate deficit as the initial dose, increase or monitor ventilation, and then reevaluate
acid-base status a short time later. Of course there are exceptions to every rule – that is why you spent all those
years in training. But these guidelines should serve you well as a starting point, and they are simple enough that
even I can follow them at 3:00 AM.
REFERENCES
1. Guyton A, Hall J, Textbook of Medical Physiology, 11th Edition, Saunders, New York, 2005.
2. Nunn J, Applied Respiratory Physiology, 6th Edition; Butterworth-Heinemann, London, 2005.
3. Severinghaus JW, Astrup PB: History of blood gas analysis II. pH and acid-base balance measurements. J Clin
Mon. 1985; 1(4):259-77.
4. Stewart, PA: Modern quantitative acid-base chemistry. Can J Physiol Pharmacol 1983; 61:1444-1461.
5. Adrogué HJ, Madias NE: Management of life-threatening acid-base disorders. N Engl J Med, 1998; 338:26–34,
107–111.
6. Stewart PA: Stewart’s Textbook of Acid-Base, AcidBase.org, 2009.
7. Tremper KK, Barker SJ” Blood Gas Analysis, in “Principles of Critical Care,” Hall JB, Schmidt GA, Wood LD
(ed.); McGraw-Hill, New York, 1992.
DISCLOSURE
Masimo, Inc., Self, Equity Position, Stock Options
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Perioperative Management of the Diabetic Patient
Daniel R. Brown, M.D., Ph.D. Rochester, Minnesota
The term diabetes mellitus describes several syndromes of abnormal carbohydrate metabolism that are characterized
by hyperglycemia. It is associated with a relative or an absolute impairment of insulin secretion, along with varying
degrees of peripheral resistance to the metabolic effects of insulin. Diabetes is the most common endocrinopathy,
occurring in nearly 10% of the general United States population and roughly one third of patients undergoing
cardiac surgery. According to the Centers for Disease Control and Prevention, more than a quarter of those 65 years
or older in the Unites States have diabetes and this number is increasing, largely attributable to changes in lifestyle
and obesity.1 Data showing an association between glycemic control and outcomes in hospitalized patients would
suggest that glycometabolic regulation may have a profound impact on perioperative outcome. This review will
discuss current classification and treatment of diabetes mellitus, the anesthetic implications of diabetes, as well as
the available literature addressing glycemic control and outcomes in a variety of patient populations with
recommendations for perioperative glycemic management.
Classification of Diabetes
Currently, classification of diabetes includes four clinical classes: Type 1 diabetes, Type 2 diabetes, gestational
diabetes and diabetes due to other causes.2 Type 1 diabetes is characterized by destruction of pancreatic β cells,
usually leading to absolute insulin deficiency. While this often is diagnosed during childhood, adults with newly
diagnosed diabetes may have circulating islet cell antibodies and therefore would be considered to have adult-onset
type 1 diabetes. Type 2 diabetes accounts for approximately 90% of all diabetic patients and is characterized by
variable degrees of insulin deficiency and resistance. There is no diagnostic test that is specific for type 2 diabetes.
Although ketoacidosis is not a typical feature of type 2 diabetes, some patients with type 2 diabetes develop diabetic
ketoacidosis under certain circumstances (severe infection or other illness). Genetic defects in insulin action,
diseases of the exocrine pancreas and drugs or chemicals, such as corticosteroids, may also cause diabetes. Finally,
diabetes diagnosed during pregnancy that is clearly not overt diabetes is referred to as gestational diabetes (the most
common medical problem in pregnancy).
Diagnosis
For decades, the diagnosis of diabetes was based on plasma glucose criteria. The American Diabetes Association
(ADA) defines diabetes mellitus as a fasting (8 hours) plasma glucose value > 126 mg/dL (7.0 mmol/L), symptoms
of diabetes (polydipsia, polyuria, unexplained weight loss) with a random plasma glucose value > 200 mg/dL (11.1
mmol/L) or a 2-hr post oral glucose challenge (75 g equivalent anhydrous glucose dissolved in water) glucose value
> 200 mg/dL (11.1 mmol/L). The normal value for fasting plasma glucose is < 100 mg/dL (5.6 mmol/L). In 2010,
the ADA adopted an International Expert Committee recommendation of a hemoglobin A1C of > 6.5% as another
criterion by which to diagnose diabetes.2 The ADA defines fasting plasma glucose between 100-125 mg/dL (5.6-6.9
mmol/L) as ‘impaired’ or pre-diabetes. Approximately one third of adults in the United States have pre-diabetes.
Current thinking suggests that abnormalities in insulin secretion and/or action lie along a continuum and that
patients with impaired fasting glucose levels are at high likelihood to progress to meeting the diagnostic criteria for
diabetes. Recent data support the common clinical observation that patients with increased fasting glucose levels and
body mass indexes are at greater risk for hyperglycemia during times of stress such as the perioperative period.
Outpatient Treatment
A causal association between glycemic control and the development and progression of microvascular complications
(retinopathy, nephropathy, and neuropathy) has been suggested from studies in both type 1 and type 2 diabetic
patients.3,4 The effect of improved glycemic control and macrovascular (peripheral vascular and cardiac)
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complications is less clear. As stated above, glucose management in type 1 diabetic patients relies on
supplementation of insulin. Medical therapy of type 2 diabetes often begins with diet modification and exercise and
oral pharmacotherapy, often starting with metformin. If goal glycemic control is not achieved, alternatives
frequently include combined therapy with other oral agents or the addition of insulin. Types and selected properties
of various treatment options for glycemic control are listed below.
Common Oral Preparations5 (short acting agents typically held the day of surgery, longer acting agents up to 2-3
days prior to surgery; Note: for procedures not expected to be associated with a significant interruption of caloric
intake, many recommend no change to oral diabetic pharmacotherapy).
Biguanides (metformin). Mechanisms not completely understood but improves insulin sensitivity by stimulating
AMP-activated protein kinase and reducing hepatic glucose output. Rarely causes hypoglycemia.
Sulfonylureas (First generation: tolbutamide, acetohexamide, tolazamide, chlorpropamide; Second generation:
glyburide, glipizide, glimepiride). Increased release of endogenous insulin by closure of specific potassium channels
in pancreatic β cells; Variable duration of action, typically less than 24 hours but chlorpropamide up to 72 hours.
Thiazolidinediones (rosiglitazone, pioglitazone). Peroxisome proliferator-activated receptor γ activators that enhance
peripheral insulin sensitivity and reduce hepatic glucose production. Restricted use due to concerns about increased
risk of myocardial infarction.
Meglitinides (repaglinide, nateglinide). Stimulates insulin secretion by binding to ATP-dependent K+ channels in
pancreatic β cells similar to sulfonylureas but have a short duration of action. Most effective preprandially.
Alpha-glucosidase inhibitors (acarbose, miglitol). Decreases GI digestion and absorption of saccharides and thereby
glucose synthesis (no need to hold preoperatively). GI side effects limit use.
DPP-IV inhibitors (sitagliptin, vildagliptin, linagliptin, saxagliptin). Inhibit degradation of blood glucagon-like
peptide 1 (GLP-1) and stimulate insulin secretion in a glucose-dependent manner while inhibiting glucagon
secretion. May cause hypoglycemia when used with insulin or sulfonylureas. Long-term safety unknown. Note:
Injectable forms of GLP-1 receptor agonists (exenatide, exenatide once weekly and liraglutide) are available.
Common Insulin Preparations6 (subcutaneous administration, large variation within and between patients)
Short acting Onset Peak Duration

Regular 30-60 min 2-3 hr 8-10 hr
Lispro/Aspart 5-15 min 30-90 min 4-6 hr
Intermediate acting
NPH/Lente 2-4 hr 4-10 hr 12-20 hr
Glargine 2-4 hr none 20-24 hr
Long acting
Ultralente 6-10 hr 10-16 hr 24-48 hr
Various strategies for diabetic drug management have been described for fasting preoperative patients. No single
method has been shown to be superior. In general, the magnitude and type of drug therapy, anticipated duration of
reduced caloric intake and magnitude of procedural-related stress need to be weighed when determining patient-
specific recommendations. In patients managed with short or intermediate acting insulin, a common
recommendation is to reduce the morning dose of insulin by one half. Implanted insulin pumps may be discontinued
or placed on a constant infusion immediately preoperatively. The most important aspect of preoperative
management of glycemic control is to determine plasma glucose immediately preoperatively with subsequent insulin
or dextrose therapy guided by this result.
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End-organ Dysfunction in Diabetic Patients

Diabetes is a progressive disease that affects many end organs thus coexisting pathologies must be identified and
managed appropriately during the perioperative period for optimal patient outcomes. Unfortunately, up to one third
of patients that are diabetic have yet to be diagnosed. Therefore, an elevated glucose determination in a patient not
diagnosed with diabetes should prompt the clinician to re-evaluate the patient in terms of risk and anesthetic plan.
Major concerns should include:
Cardiovascular Disease. While many metabolic diseases accompany cardiovascular disease, diabetes is the most
common. Diabetics are at increased risk for cardiovascular disease including hypertension, coronary artery disease,
diastolic dysfunction, congestive heart failure, peripheral vascular disease and cerebrovascular disease. Patients may
have clinically “silent” myocardial ischemia or infarction. Current American College of Cardiology/American Heart
Association guidelines for perioperative cardiovascular evaluation list diabetes, along with a history of ischemic
heart disease, compensated or prior heart failure, cerebrovascular disease and renal insufficiency as clinical risk
factors to be considered when determining which patients are candidates for preoperative cardiac testing.7 One area
of debate in earlier literature involved the use of β-adrenergic blockade in diabetic patients. The concern from a
pathophysiologic standpoint is that β-adrenergic antagonists could worsen glucose intolerance; however, multiple
reports have shown no increase in hypoglycemic episodes in diabetic patients receiving such therapy. Furthermore,
available data suggest that diabetic patients have increased cardiovascular benefits compared to nondiabetic patients
receiving β-blockers. It should be stressed that diabetes is not a contraindication to β-adrenergic blocker
administration when such therapy is indicated.
Renal Disease. Renal dysfunction commonly develops in diabetic patients and is the leading cause of renal failure
requiring renal replacement therapy. Angiotensin converting enzyme inhibitors have been shown to decrease
albuminuria and progression of renal dysfunction in diabetic patients and are commonly prescribed. Clinicians need
to consider renal function when selecting medications (avoiding potential nephrotoxic drugs) and dosing renally
cleared drugs.
Other. Peripheral and autonomic neuropathies are common in diabetic patients. Pre-existing neurologic deficits
should be noted prior to procedures. Extra care should be taken when positioning diabetic patients as they may not
notice pressure points due to neuropathy and may be at increased risk for ischemia due to vascular compromise.
Autonomic neuropathy may blunt the compensatory cardiovascular response to hypotension thus predisposing to
hemodynamic lability. Autonomic neuropathy may also cause gastroparesis and predispose diabetic patients to
pulmonary aspiration. In patients with chronic hyperglycemia, non-enzymatic glycosylation of proteins and
abnormal collagen cross-linking may result in decreased joint mobility. Decreased mobility in the
temporomandibular and cervical spine joints may contribute to challenging airway management. Finally, as obesity
and type 2 diabetes often coexist, the myriad of anesthetic implications related to obesity must also be evaluated and
managed.
Acute Glycemic Complications

Hyperglycemia with metabolic alterations and hypoglycemia are serious medical conditions that may have
devastating sequelae. Hyperglycemia may be associated with diabetic ketoacidosis (DKA) and a non-ketotic
hyperosmolar state (NKHS).8 In addition, surgical stress may alter glycometabolic regulation, contributing to
disruption of glucose homeostasis. The response to glucose metabolism during stress and surgery is difficult to
predict but, in general, the perioperative period is associated with relative insulin hyposecretion and increased
resistance. Frequently, factors that precipitate these severe alterations in glucose regulation necessitate surgical
intervention therefore it is important that perioperative care providers understand the pathophysiology and treatment
of these disorders.
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DKA. DKA is a life-threatening complication (reported mortality 5-10%) seen predominantly in type 1 diabetic
patients that results from insulin deficiency and is characterized by hyperglycemia, dehydration, hyperosmolarity
and an increased anion gap secondary to production of ketones. A precipitating event such as infection, surgical
stress, trauma or lack of insulin therapy may be identified. Ketone production frequently results in hyperventilation
with large tidal volumes (Kussmaul breathing), “fruity” breath and nausea and vomiting. Management is focused on
identifying and treating precipitating factors, fluid resuscitation, glycometabolic control and electrolyte replacement.
Fluid deficits are frequently large (> 5 liters) and multifactorial including osmotic diuresis, lack of oral intake,
emesis and insensible losses from sweating and hyperventilation. Dehydration may result in hypotension and pre-
renal stress on an already compromised renal system. Hyperkalemia is frequently present as a result of acidemia-
related extracellular potassium shifts as well as tissue catabolism. With treatment, potassium levels often plummet
and aggressive repletion should be anticipated. Careful monitoring of renal function and urine output must be
maintained as overhydration and potassium supplementation may lead to further patient compromise in the setting of
concomitant renal failure. While a sodium deficit is frequently present, the measured sodium may be falsely low due
to hyperglycemia and hypertriglyceridemia. Corrected sodium concentrations in the hyperglycemic patient may be
estimated by adding 1.5-2.0 mEq/L to the measured sodium value per 100 mg/dL glucose over 100 mg/dL. Other
electrolytes, especially phosphorus and magnesium, are often depleted and should be frequently determined, and
repleted as indicated, during resuscitation. Intravenous insulin as an infusion should be administered with frequent
determination of plasma glucose levels to guide therapy. Intravenous insulin has a rapid onset (minutes) and
duration < 1 hour. Treatment with intravenous insulin is an established practice; however intravenous administration
of regular insulin in the United States is an “off label” use as this mode of delivery is not currently FDA approved. A
dextrose infusion should be started as plasma glucose approaches 200 mg/dL to avoid potential overcorrection of
hyperglycemia. Intravenous insulin should be continued until serum ketones are cleared and the acidemia resolved.
Patients are at risk for cerebral edema, and subsequent intracranial hypertension, during treatment. Careful
monitoring of neurologic status is warranted. Bicarbonate administration is not routine due to concerns of worsening
intracellular acidosis, leftward shift of the oxyhemoglobin dissociation curve and increased hyperosmolarity.
Guidelines for DKA Management

•Routine monitors plus arterial access (for hemodynamic monitoring and frequent blood sampling) and
central venous access (for fluid and electrolyte replacement)
•Aggressive crystalloid replacement (1-3 L in the first hour) starting with 0.9% saline and adjusting free
water content of subsequent fluids based on plasma sodium determinations, with subsequent volume
replacement individualized to patient response
•Intravenous regular insulin infusion titrated by serial plasma glucose determinations adding a dextrose
infusion as glucose values approach 200 mg/dL
•Supplementation of potassium, phosphorus and magnesium as guided by serial plasma determinations
NKHS. Non-ketotic hyperosmolar states occur predominantly in type 2 diabetic patients during periods of stress
such as infection or other illness. Compared to patients with DKA, NKHS patients are typically more dehydrated,
hyperosmolar and hyperglycemic. Neurologic alterations are usually present and may include confusion, coma,
seizures and/or focal neurological deficits. While patients with NKHS lack the acidemia due to ketone production,
severe dehydration may result in significant hypotension leading to lactic acidosis. Thrombotic events may occur
due to hypovolemia, hyperviscosity and hypotension. Fluid resuscitation is the mainstay of treatment. Again, 0.9%
saline is a reasonable choice for initial resuscitation with the subsequent free water composition of fluid guided by
serial sodium determinations. Due to the greater hyperglycemia and hyperosmolarity seen in NKHS patients, they
may be at increased risk for developing cerebral edema. More gradual (>24 hours) correction of hyperglycemia and
hyperosmolarity is recommended along with frequent neurologic evaluations.
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Hypoglycemia. Hypoglycemia is commonly defined in adults as a plasma glucose < 50 mg/dL (2.8 mmol/L).
Altered mental status, progressing to coma and death, along with the physiologic responses to increased
catecholamines are the two major ways by which hypoglycemia is most commonly detected. In the perioperative
environment, and to a greater extent in the setting of general anesthesia, the ability to recognize these signs and
symptoms may be compromised. Clinicians need to have a high index of suspicion for hypoglycemia and frequent
determination of plasma glucose levels should be integral to the care of diabetic patients. Hypoglycemia may
develop due to residual effects of long-acting drugs, overaggressive antidiabetic treatment or decreased caloric
intake. Treatment consists of dextrose administration and correction of the precipitating cause. Since the response to
dextrose administration is quite variable, following an initial bolus (25-50 mL of 50% dextrose in adults), serial
glucose determinations should be performed and a dextrose infusion considered based on the patient’s response.
Glycemic Control in the Critically Ill and During the Perioperative Period
Glycemic control in the critically ill patient is a current topic of debate among anesthesiologists, intensivists and
endocrinologists. Available data support an association between hyperglycemia and increased morbidity and
mortality in many different surgical and medical populations. A retrospective review of adult medical and surgical
inpatients reported worse outcomes in hyperglycemic patients.9 Hyperglycemia was a common finding, present in
38% of patients, and was associated with an 18-fold increase in in-hospital mortality, a longer length of stay, more
subsequent nursing home care and a greater risk of infection. Hyperglycemia in specific disease states has also been
shown to be a marker of poor outcomes. A systematic review of 26 studies in adult stroke patients concluded that
hyperglycemia is associated with increased mortality and greater risk of poor functional recovery in survivors.10 The
same investigators reached similar conclusions when reviewing the association between hyperglycemia and
outcomes in patients with myocardial infarctions.11 Hyperglycemia with myocardial infarction was associated with
increased risk of congestive heart failure and cardiogenic shock in patients without diabetes and in-hospital mortality
in patients with and without diabetes.
Retrospective studies linking hyperglycemia and poor outcomes prompted prospective studies investigating whether
aggressive management of hyperglycemia could improve outcomes in patients with acute illness. The DIGAMI
study followed diabetic patients admitted with acute myocardial infarction and randomly assigned patients to
intensive insulin therapy with intravenous insulin compared to routine antidiabetic therapy.12 Intensive insulin
therapy was shown to be associated with significantly reduced long-term mortality (determined at over 3 years
average length of follow-up). This demonstration that glycemic control could improve long-term patient survival
encouraged investigation in other patient populations. A prospective, randomized trial in critically ill adult patients
comparing intensive intravenous insulin therapy with conventional therapy was conducted by Van den Berghe and
colleagues.13 In this trial, patients were randomized to intensive insulin therapy (goal glucose 80-110 mg/dL) or
conventional therapy (treat for glucose > 215 mg/dL, maintain 180-200 mg/dL). The trial was stopped early due to a
significant reduction in ICU mortality in the intensive insulin therapy group (p < 0.04). In addition to decreased ICU
mortality, significant reductions in in-hospital mortality and bloodstream infections were also observed. It is notable
that in this study, the vast majority of the patients were post-surgical with more than 60% admitted following cardiac
surgery. Other investigators have suggested favorable outcomes in post-cardiac surgery patients with improved
glycemic control. A report of over 3500 diabetic patients undergoing coronary artery bypass grafting showed
improved glycemic control and an absolute and risk-adjusted decrease in mortality of 57% and 50%, respectively,
and decreased infectious complications, following institution of an intravenous insulin management strategy.14
In an effort to address whether findings shown in populations with a preponderance of cardiac disease and surgery
were more broadly applicable, Krinsley reported retrospective data in an adult ICU with a mixed medical and
surgical population showing an association between hyperglycemia and mortality.15 A subsequent study by the same
author reported the effect of instituting an intensive glucose management protocol in critically ill patients in the
same ICU.16 Institution of the protocol significantly improved glycemic control and was associated with decreased
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mortality, organ dysfunction, and length of stay in the ICU. As a follow-up to their earlier study in primarily surgical
patients, Van Den Berghe and colleagues conducted a prospective, randomized trial similar in design to their earlier
trial13 but in critically ill medical patients.17 In this trial, mortality was not reduced in the intention-to-treat analysis
though morbidity was significantly reduced. Mortality was actually increased in those patients with ICU length of
stay less than three days but decreased in those with an ICU length of stay > 3 days. These same investigators
performed an analysis of pooled data set from their two randomized controlled trials.18 Intensive insulin therapy was
associated with reduced mortality and morbidity in the intention-to-treat group and in those whose ICU stay was > 3
days.
More recently, several studies have questioned the benefit of the target glucose values in strict glycemic control
studies. The GLUCONTROL trial randomized a mixed medical/surgical population to maintain blood glucose
between 80-110 and 140-180 mg/dL.19 While the trial was stopped after enrollment of 1100 patients, due to the
incidence of hypoglycemia in the intensive treatment group and thus underpowered, no clinical benefit of tight
glycemic control was observed. The VISEP trial compared fluid resuscitation and glycemic control using a two-by-
two factorial design in septic patients.20 There was no difference in mortality though the rate of severe hypoglycemia
(blood glucose < 40 mg/dL) was significantly higher in the intensive insulin treatment group (17.0 vs. 4.1%). To
date, the NICE-SUGAR study provides the best data comparing target ranges for glycemic control in critically ill
patients.21 This large, international trial investigated 6104 patients randomized to achieve target glucoses of either
81-108 or less than 180 mg/dL. The groups had similar characteristics at baseline. Mortality was significantly
greater in the intensive insulin treatment group (27.5 vs. 24.9%). The treatment effect did not differ significantly
between surgical and medical patients nor were any differences in reported morbidity observed. However, there was
a significant increase in severe hypoglycemia observed in the intensive treatment group (6.8 vs. 0.5%).
There is a growing body of literature which includes intraoperative glycemic control in the study design. A
retrospective study of over 6000 cardiac surgery patients reported high peak serum glucose during cardiopulmonary
bypass to be an independent risk factor for death and morbidity in diabetic, as well as nondiabetic, patients.22 Other
investigators have reported perioperative, including intraoperative, hyperglycemia to be a predictor of adverse
patient outcomes in cardiac surgery,23, 24 carotid endarterectomy,25 and infrainguinal arterial bypass patients.26 A
before-after perioperative, including intraoperative, glucose control protocol study in diabetic cardiac surgery
patients reported a significant reduction in mortality, especially in moderate and high risk patients.27
To date, there are limited prospective data comparing outcomes in patients receiving intensive intraoperative insulin
therapy to conventional intraoperative glucose management. Gandhi and colleagues prospectively randomized 400
cardiac surgery patients to receive intensive or conventional glycemic management intraoperatively followed by
intensive postoperative glycemic management.28 While they were able to achieve a significant difference in mean
intraoperative glucose concentrations, they reported no difference in a composite 30-day endpoint of death or major
morbidity. Interestingly, there were more deaths and strokes in the intensive intraoperative treatment group.
Protocols. It is likely that perioperative practitioners will be asked to obtain tighter glycemic control in their patients
(see below). This is currently best accomplished by intravenous insulin administration. Such care is presently part of
most critical care practices and various protocols for delivery of intravenous insulin in this setting have been
published.13,14,16 An intraoperative insulin protocol has been validated in cardiac surgery patients.28 It is important to
recognize that protocols rely on frequent determinations of plasma glucose to allow for titration of insulin
administration. In addition, since the response to insulin varies from patient to patient and within a patient over time,
protocols should allow for variable insulin administration for a given glucose determination (changing the ‘sliding
scale’). A protocol for treatment of hypoglycemia should also be incorporated into any algorithms for insulin
administration.
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Unanswered questions. If tighter glycemic control is desired, what glucose level should be targeted? Should severe
intensive glycemic control be attempted in all patients? Pathophysiologic reasoning would suggest that avoiding
hyperglycemia would be beneficial though this must be weighed against the risks of hypoglycemia. While multiple
groups have recommended aggressive management of hyperglycemia, more recent data, particularly the NICE-
SUGAR study, have questioned the low recommended targets and associated hypoglycemia. While certain
subpopulations may benefit from stricter glycemic control, it would seem reasonable to avoid perioperative glucose
values over 180 mg/dL by using protocols that minimize hypoglycemia. Hypoglycemia appears to be linked with
adverse outcomes in critically ill patients.29 It is advisable that practitioners validate performance of glucose
protocols in their own institutions as there are significant differences in measured glucose depending on the glucose
monitoring device and technique used.30 Blood glucose variability, not just mean glucose, also appears to affect
morbidity and mortality. In a large cohort of over 7000 critically ill patients, both mean and standard deviation of
blood glucose were shown to be independent predictors of ICU and hospital mortality.31 The optimal balance
between target blood glucose and glucose variability is unknown.32 Other questions remain. Achieving glycemic
control is associated with increased resources in terms of time, testing and treatment. How should this be funded?
For non-diabetic patients found to be hyperglycemic during the perioperative period, how will we ensure that this
information is communicated to primary care providers such that appropriate diabetic testing can occur and, if
indicated, treatment initiated? Recent data would suggest that resources expended in these areas would result in
considerable benefit.33
Policy implications. Despite many questions remaining unanswered, several regulatory and patient advocacy
organizations have listed glycemic control as a marker of quality of care. One prominent example calls for cardiac
surgery patients to have morning blood glucose values on postoperative days 1 and 2 < 200 mg/dL.34 The
appropriateness of the measurement itself, target level and timing of measurement are debatable.
Summary
Diabetes is the most commonly encountered endocrinopathy and is associated with many end-organ sequelae that
impact anesthesia. Acute derangements in glycemic control may be present in patients during the perioperative
period and clinicians need to be aware of the pathophysiology and therapy required for optimal patient care.
Emerging data link poor outcomes with extremes in perioperative glucose values. Available data would favor
maintaining blood glucose values below 180 mg/dL during the perioperative period while reducing blood glucose
variability and avoiding hypoglycemia.
References
1. Available at: http://www.cdc.gov/diabetes/pubs/pdf/ndfs_2011.pdf. Accessed May 31, 2012
2. American Diabetes Association. Standards of medical care in diabetes – 2012. Diabetes Care 2012; 35:
Suppl 1: S11-S63.
3. The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of
diabetes on the development and progression of long-term complications in insulin-dependent diabetes
mellitus. N Engl J Med 1993; 329(14): 977-86.
4. UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or
insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes
(UKPDS 33). Lancet 1998; 352:837-53.
5. Ismail-Beigi, F. Glycemic management of Type 2 diabetes mellitus. N Engl J Med 2012; 366: 1319-27.
6. Hirsch IB. Insulin analogues. N Engl J Med 2005; 352: 174-83.
7. Fleisher LA, et al. ACC/AHA 2007 Guidelines on perioperative cardiovascular evaluation and care for
noncardiac surgery: J Am Coll Cardiol 2007; 50:159-242.
8. Magee MF, Bhatt BA. Management of decompensated diabetes. Crit Care Clin 2001; 17(1): 75-106.
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9. Umpierrez GE, et al. Hyperglycemia: An independent marker of in-hospital mortality in patients with
undiagnosed diabetes. J Clin Endocrinol Metab 2002; 87: 978-82.
10. Capes SE, et al. Stress hyperglycemia and prognosis of stroke in nondiabetic and diabetic patients: a
systematic overview. Stroke 2001; 32: 2426-32.
11. Capes SE, et al. Stress hyperglycaemia and increased risk of death after myocardial infarction in patients
with and without diabetes: a systematic overview. Lancet 2000; 355: 773-8.
12. Malmberg K, et al. Glycometabolic state at admission: Important risk marker of mortality in conventionally
treated patients with diabetes mellitus and acute myocardial infarction. Circulation 1999; 99: 2626-32.
13. Van den Berghe G, et al. Intensive insulin therapy in critically ill patients. N Engl J Med 2001; 345: 1359-
67.
14. Furnary AP, et al. Continuous insulin infusion reduces mortality in patients with diabetes undergoing
coronary artery bypass grafting. J Thorac Cardiovasc Surg 2003; 125(5): 1007-21.
15. Kringsley JS. Association between hyperglycemia and increased hospital mortality in a heterogeneous
population of critically ill patients. Mayo Clin Proc 2003; 78: 1471-8.
16. Kringsley JS. Effect of an intensive glucose management protocol on the mortality of critically ill adult
patients. Mayo Clin Proc 2004; 79(8): 992-1000.
17. Van den Berghe G, et al. Intensive insulin therapy in the medical ICU. N Engl J Med 2006; 354: 449-61.
18. Van den Berghe G, et al. Intensive insulin therapy in mixed medical/surgical intensive care units: Benefit
versus harm. Diabetes 2006; 55: 3151-9.
19. Preiser JC, et al. A prospective randomized multi-centre controlled trial on tight glucose control by
intensive insulin therapy in adult intensive care units: the Glucontrol study. Intensive Care Med 2009; 35:
1738-48.
20. Brunkhorst FM, et al. Intensive insulin therapy and pentastarch resuscitation in severe sepsis. N Engl J Med
2008; 358: 125-39
21. The NICE-SUGAR Study Investigators. Intensive versus conventional glucose control in critically ill
patients. N Engl J Med 2009; 360: 1283-97.
22. Doenst T, et al. Hyperglycemia during cardiopulmonary bypass is an independent risk factor for mortality
in patients undergoing cardiac surgery. J Thorac Cardiovasc Surg 2005; 130: 1144-50.
23. Ouattara A, et al. Poor intraoperative blood glucose control is associated with a worse hospital outcome
after cardiac surgery in diabetic patients. Anesthesiology 2005; 103: 687-94.
24. Gandhi GY, et al. Intraoperative hyperglycemia and perioperative outcomes in cardiac surgery patients.
Mayo Clin Proc 2005; 80: 862-6.
25. McGirt MJ, et al. Hyperglycemia independently increases the risk of perioperative stroke, myocardial
infarction, and death after carotid endarterectomy. Neurosurgery 2006; 58: 1066-73.
26. Malmstedt J, et al. Influence of perioperative blood glucose levels on outcome after infrainguinal bypass
surgery in patients with diabetes. Brit J Surg 2006; 93: 1360-7.
27. D’Allesandro C, et al. Strict glycemic control reduces EuroSCORE expected mortality in diabetic patients
undergoing myocardial revascularization. J Thorac Cardiovasc Surg 2007; 134: 29-37.
28. Ghandi GY, et al. Intensive intraoperative insulin therapy versus conventional glucose management during
cardiac surgery. Ann Intern Med 2007; 146: 233-43.
29. Hermanides J, et al. Hypoglycemia is associated with intensive care unit mortality. Crit Care Med 2010; 38:
1430-34.
30. Kanji S, et al. Reliability of point-of-care testing for glucose measurement in critically ill adults. Crit Care
Med 2005; 33: 2778-85.
31. Egi M, et al. Variability of blood glucose concentration and short-term mortality in critically ill patients.
Anesthesiology 2006; 105: 244-52.
32. Eslami S, et al. Glucose variability measures and their effect on mortality: a systematic review. Intensive
Care Med 2011; 37: 583-93.
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33. DeFronzo RA, et al. Pioglitazone for diabetes prevention in impaired glucose tolerance. N Engl J Med
2011; 364: 1004-15.
34. Available at
http://www.jointcommission.org/specifications_manual_for_national_hospital_inpatient_quality_measures.
aspx:. Accessed June 1, 2012.
DISCLOSURE
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Anesthesia in Satellite Locations

Brenda A. Gentz, M.D. Tucson, Arizona
Introduction
The provision of anesthesia outside the operating room provides a unique set of challenges. The standards
and principles that underlie the care of the patient should not be abandoned in satellite locations. However, patients
who are referred for procedures in satellite locations may present with minimal preoperative information, possess
challenging physical and anesthetic histories, and be scheduled in such a manner as to limit preparation time. The
layout and special requirements of the satellite location can create unexpected barriers and may limit access to the
patient and the availability of the anesthesia equipment. The challenges for the anesthesiologists include an
unfamiliar environment, inadequate anesthesia support and insufficient number of trained personnel, and cramped,
dark quarters and variability of monitoring modalities. In radiation oncology, MRI and occasionally the GI suite
problems with noise and suboptimal positioning of the patient may be an issue.
General Trends for Use of Anesthesia in Satellite Locations

While in most institutions, pediatric patients remain the largest group of patients requiring anesthesia in
remote locations, there appears to be an increasing demand for anesthesia services for adult patients as well. Within
the adult population, there is a need for assistance with vulnerable and critically ill elderly patients, adults with
developmental delay, patients with claustrophobia, and chronic pain disorders. Patients at any age may be
uncooperative or unable to comply with the requirements of a procedure. Hospitals are now requesting and
sometimes paying for additional anesthesia services in remote locations, such as the GI/Endoscopy suites, where it is
thought that anesthesia services may increase the comfort and safety of patients while simultaneously shortening the
duration of recovery and increasing the number of patients who may receive care. Operating room time is at a
premium inside many hospitals, so completing endoscopy and interventional procedures in remote locations
prevents delays in access to diagnostic and interventional procedures.
Complications Related to Remote Locations

In 2009, Metzner et al. completed an ASA Closed Claims Review in which data was taken from the ASA
Closed Claims database of 8496 cases.1 The cases were limited to 1990 or later and excluded all obstetrics, acute
and chronic pain cases. Eighty seven remote location claims and 3287 operating room claims were reviewed.
Patients receiving anesthesia in remote locations were found to be older, have an increased severity of illness and
their procedures more likely to be described as “emergent” when compared to those performed in the operating
room. The predominant anesthetic technique in remote location claims was monitored anesthesia care (MAC) which
was eight times more frequent (50% vs. 6%) than in operating room claims. Twenty-one percent of remote location
claims involved no anesthesia (e.g. emergency endotracheal intubation or resuscitation.) Patients in remote
locations were more likely to receive MAC or no anesthesia.
Inadequate oxygenation/ventilation was the most common respiratory claims event, cited in 21 percent of
claims when care was provided in a remote location, but in only 3 percent of claims when care was provided in the
operating room. Other respiratory events included esophageal intubation, difficult intubation and aspiration of
gastric contents. In 30% of the remote location claims, an absolute or relative overdose of sedative, hypnotic and/or
analgesic drugs led to respiratory depression. More than half of the cases that occurred in the GI suite and 70
percent of the cases that occurred in radiology involved oversedation. 1,2
The ASA Standards for Basic Anesthetic Monitoring state that include that “during all anesthetics, the
patient’s oxygenation, ventilation, circulation and temperature shall be continually evaluated.” 3 The standards
require that to ensure adequate oxygen concentration in the inspired gas and the blood during anesthetics, the
concentration of the oxygen in the patient’s breathing system shall be measured by an oxygen analyzer with a low
oxygen concentration limit alarm in use. For blood oxygenation, a quantitative method of oxygenation, such as a
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pulse oximeter should be employed. To ensure adequate ventilation of the patient during anesthetics, every patient
receiving general anesthesia shall have the adequacy of ventilation continually evaluated. This includes clinical
signs such as chest excursion, observation of the reservoir breathing bag and auscultation of breath sounds.
Continual monitoring for the presence of expired carbon dioxide shall be performed unless invalidated by the nature
of the patient, procedure or equipment.
Despite these recommendations, in the ASA closed claims experience with remote locations, a capnograph
was employed in only a minority of claims associated with oversedation (15%), and no respiratory monitoring was
found in 15% of the cases. 1 In a report of 153 deaths, occurring after upper gastrointestinal endoscopy, 88% of the
patients received intravenous sedation but only 56% had any respiratory monitoring, and then only by pulse
oximeter. 4 During sedation, airway obstruction or hypoventilation may occur that is not detected until hypoxia is
indicated by pulse oximetry. One of the benefits of capnography is the early identification of situations or abnormal
breathing patterns that may result in hypoxia. 5 The use of pulse oximetry and capnography used in conjunction
with one another appears to be much safer than pulse oximetry alone. In 2010, the ASA House of Delegates
approved a change in the monitoring of patients receiving moderate or deep sedation. Effective, July 1, 2011 it will
be recommended that “during moderate or deep sedation the adequacy of ventilation shall be evaluated by continual
observation of qualitative clinical signs and monitoring for the presence of exhaled carbon dioxide unless precluded
or invalidated by the nature of the patient, procedure, or equipment.”6 Fifty four percent of patients receiving care in
remote locations ultimately died compared to 29 percent of patients receiving care in the operating rooms. When
evaluating the care of the patients, it was determined that in 54% of the remote location claims that it was
substandard. This compares to substandard care being cited in 37% of operating room claims. In 32 % of the
remote location claims, care was judged preventable by better monitoring compared to only 8 percent of operating
room claims. Cardiovascular events, equipment failure or malfunction, or medication-related events did not differ in
remote location and operating room claims. 1,2
Safety/Location and Set up

When providing anesthesia in a remote location, medical personnel with adequate training must be
available to respond to any life-threatening emergency. There are times when providing anesthesia in remote
locations that the only personnel available include a technician, a member of the nursing staff and the
anesthesiologist. These individuals should know how to access medical assistance in case of an emergency, know
where the code drugs and emergency equipment and defibrillator are located. Since many of the patients receiving
anesthesia in remote locations are children, it may be appropriate that nurses with specialized pediatric nursing skills
be available. The access to difficult airway equipment has been recommended, but may not always be readily
available. In those cases, a portable difficult airway cart that could be readily transferred to the remote location
might be desirable. Diagnostic or therapeutic equipment that is in use may pose a health risk to the anesthesia team.
In those cases where remote observation of patients is needed, telemetry, clear observation windows, or a remote
camera system may be used. 7
Sedation (MAC) vs. General Anesthesia

Anesthesia in remote locations is unique in that the procedures may be noninvasive and can either have
brief periods of intense stimulation or prolonged periods with minimal stimulation. There are some studies that
cannot be performed adequately or safely if movement is detected and must be completed under general anesthesia.
The age, body hiatus, physical condition of the patient, presence or absence of intravenous access and available
equipment all play important roles in the choice of anesthesia. Anesthetic drugs that may be chosen include
dexmedetomidine, chloral hydrate, midazolam, pentobarbital, propofol, and ketamine or inhalation anesthesia with
either an endotracheal tube or laryngeal mask airway. Propofol has rapidly become one of the most popular drugs
used in remote locations. Propofol infusions can be used with spontaneous ventilation via nasal cannula or LMA.
When muscle relaxation and an endotracheal tube are required, propofol may be used as part of a total intravenous
anesthetic. As noted in the ASA Statement on the Safe Use of Propofol, sedation is a continuum, and the individual
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patient’s response is not always predictable: “Even if moderate sedation is intended, patients receiving propofol
should receive care consistent with that required for deep sedation.8 Opioids may be required in patients who are
unable to lie supine or be positioned for a procedure because of pain.
Airway Issues
Patients who present for anesthesia in remote locations may present emergently with little preoperative
information. A complete history and physical including airway exam must be completed prior to the conduction of
anesthesia. Despite the remote location, the Practice Guidelines for Management of the Difficult Airway should be
followed if a complex airway is detected. Sometimes deciding the most appropriate location to secure the patient’s
airway can be challenging. Procedure or operating rooms closer to trained personnel and intubating equipment may
facilitate the intubation, but require the transfer of the patient on a gurney with sedation to the remote location.
There needs to be at least one additional individual who is immediately available to serve as an assistant in difficult
airway management. If the intubation is to be carried out at the remote location site, one portable storage unit that
contains specialized equipment for difficult airway management should be readily available.9
Temperature Regulation Issues

Unlike operating rooms, temperature control for many off-site locations is not controlled from inside the
procedure room.7 Equipment such as CT or MRI scanners generates a great deal of heat and must be actively
cooled to operate properly. Low ambient temperatures can result in exaggerated rapid decrease in patient
temperature. There are exceptions which may be seen in patients that are at the extremes of age. Two observational
studies report that premature neonates can experience heart rate fluctuations, decreases in oxygen saturation, and
increases in temperature during MRI. 10,11 Skin, rectal and esophageal probes may be used for monitoring
temperatures in remote locations. Infrared ear thermometers may also be used to measure core temperature.12
Caution should be used in remote locations such as MRI, where some types of temperature monitoring devices may
have erroneous readings or result in patient injury.13 MRI-compatible temperature probes are available and should
be used in this setting.
Postoperative hypothermia has been shown to increase perioperative complications including wound
infections, myocardial infarctions and blood transfusion requirements in surgical patients.14,15,16 Mild hypothermia
increases the respiratory rate, which develops to respiratory depression when hypothermia worsens. “Cold diuresis”
can result in an increase in urinary flow from a cold-induced decrease in cellular enzyme activity with decreased
distal tubular reabsorption of sodium and water. Hypothermia also inhibits the enzymatic reactions of the
coagulation cascade, impairing coagulation.17 Acidosis, mild ileus, depressed hepatic function, hyperglycemia,
impaired healing and altered pharmcokinetic and pharmacodynamic properties of anesthetic drugs may occur.18
There are no data to suggest that the effects of hypothermia are any different in remote locations than in the surgical
suite.
Effective methods of warming patients may include air warming blankets, fluid warmers, and radiant
heaters. Compatibility with the remote location equipment must be confirmed prior to using any such device to
avoid injury to personnel or a patient. If the patients cannot be warmed in the remote location, it is possible that
prewarming patients may be helpful.19
Gastroenterology: Endoscopy, Colonoscopy and Endoscopic Retrograde

Cholangiopancreaticography (ERCP)
The role of anesthesiologists in the endoscopy suite has become more prominent as the need for efficient,
but safe anesthesia and analgesia has increased. There are select patient groups that are more likely than others to
require the expertise of an anesthesiologist. Patients who have a history of chronic opioid therapy, tolerance for
benzodiazepines or other enzyme inducing medications, drug addicts, elderly, critically ill, neuropsychiatric
disorder, significant cardio-pulmonary compromise, pregnancy or severe renal or hepatic disease may require a
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higher level of care. The American Society of Gastrointestinal Endoscopy in conjunction with the ASA has
identified patients with increased risk due to airway disease who require consultation.20
Some endoscopic procedures will require deeper levels of sedation to achieve patient comfort and allow the
gastroenterologist to perform the procedure. These procedures include endoscopic retrograde
cholangiopancreaticography, endoscopic ultrasound, and emergency therapeutic procedures. Small changes in
position may have adverse effects during sphincterotomy, insertion of needles for fine needle aspiration, or during
use of electrocautery. 21 The deeper levels of sedation that are required do not go without some risk. It was noted in
the closed claims analysis of anesthesia in remote locations that sedation in the gastrointestinal suite accounted for
more than half of the oversedation claims. Seven of those claims involved ERCP, seven during upper
gastrointestinal endoscopy with the remaining claim involving a patient who received a colonoscopy. 1 The
incidence of cardiopulmonary complication associated with endoscopic procedures ranges from 0.01 to 5.4/thousand
with ERCP having the highest rate of hypoxemia.22 The increase risk with ERCP is in part related to deep sedation,
long duration of the examination, prone position of the patient, mean advanced age, and frequent co morbid
diseases.23 ERCP has been singled out as a procedure in which monitoring of exhaled carbon dioxide should be
considered.24 Because ERCP procedures are also complicated by prone positioning and inability to quickly secure
the airway, these procedures may best be performed under general endotracheal anesthesia if heavy sedation is
required.
Most patients who undergo endoscopic procedures receive some combination of opioid (usually fentanyl),
benzodiazepine (midazolam) or propofol. Benzodiazepines and opioids when given together can blunt the central
response to carbon dioxide, resulting in sedation and significant respiratory depression. When given together,
smaller doses of anesthetic drugs should be used and individually titrated to effect.
When deeper levels of sedation are required, such as during the introduction of the endoscope, propofol may be
employed. Propofol has the benefit of rapid onset and offset of effect, but does not provide analgesia. Patients who
are being sedated with propofol and easily transition to a deeper level than that which was intended. One
investigation found looked at the use of propofol in 202 patients undergoing colonoscopy found that the dosages of
propofol administered were associated with electroencephalography suppression and lack of recall consistent with
general anesthesia.25 Propofol’s vasodilating effects should be considered in the elderly, patients with significant
cardiovascular disease and in patients who have undergoing bowel preparation and may be dehydrated. Ketamine
may be given in conjunction with propofol in patients who require sedation, but cannot tolerate the cardiovascular
effects of propofol alone.21
Hypoxemia during endoscopic procedures has been well documented. Pulse oximetry which will detect
desaturations reliably in the endoscopy suite should routinely be employed. With pulse oximetry there can be a
significant delay in the detection of respiratory depression and airway obstruction which can result in patients
becoming oversedated. Carbon dioxide monitoring (capnography) is a useful adjunct during endoscopy and has
been shown to be a superior monitor when compared to pulse oximetry and visual assessments in the detection of
respiratory depression.26 The benefits of capnography have been touted as providing early recognition of ventilatory
depression, preventing inappropriate administration of additional sedation, and alerting the anesthesiologist that an
airway intervention may be required. 20 A recently reported study that used sidestream capnography through a nasal
cannula sampling device and pulse oximetry reported no episodes of apnea occurring in 300 patients undergoing
upper endoscopy and colonoscopy monitored by both methods.27
Most patients who undergo endoscopies are often ready for discharge from the postoperative care unit in
less than 1 hour. A recovery area specifically dedicated to the postoperative recovery of endoscopy patients is
preferred due to the high turnover rate. Transfer of endoscopy patients to the postsurgical recovery room can be
overwhelming for staff trying to simultaneously treat patient who have undergone more complex surgical
procedures. Like the postsurgical unit, criteria should be in place for hospital discharge. Until the point of
discharge, fall precautions should be kept in place as patients may be more unstable than is realized. 1
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Magnetic Resonance Imaging(MRI)

In 2009, the ASA published the “Practice Advisory on the Anesthetic Care for Magnetic Resonance
Imaging.” 28 There is agreement that the safety, preparation and care of the patients who receive MRIs are a shared
responsibility between the anesthesiologists, radiologists, MRI technologists, and nursing staff. The MRI suite is
considered to be a “hazardous location because of the presence of a strong static magnetic field, high-frequency
electromagnetic (radiofrequency) waves, and a time-varied (pulsed) magnetic field.”28 Additionally, “secondary
dangers include the high-level acoustic noise, systemic and localized heating, and accidental projectiles.”28 The
static and dynamic magnetic fields along with radiofrequency energy emissions may interfere with anesthetic
administration and monitoring capabilities. Patient care may be compromised by noise, a darkened environment
and an obstructed view of the patient. Most of the ASA Closed Claims (70%) from radiology involved anesthesia in
the MRI scanner. Like other remote locations, the majority (four) of the claims were for oversedation. Additional
claims resulted from burns from non-MRI compatible electrodes. 1
Both the anesthetic care providers, ancillary support personnel and patients need to be properly screened.
Anesthetic care providers and ancillary support personnel should not bring ferromagnetic items into the Zone III
(region in which free access by unscreened non-MR personnel or ferromagnetic objects or equipment can result in
serious injury or death) or Zone IV (MRI scanner magnet room) of the MRI. These items include stethoscopes,
pens, watches, wallets, hair clips, name tags, pagers, cell phones, credit cards and batteries.28 Members of the
patient care team should not have spinal cord stimulators or implanted objects. Patients need to be screened for
aneurysm clips, surgical clips, prosthetic heart valves, intravenous infusion pumps, coronary arterial stents, and
implanted dental magnet keepers. There are reports of hemorrhage associated with exposure to iron fillings and
image artifacts, burns, swelling and puffiness occurring with eyeliner tattoos. Increased temperatures have been
documented in patients with deep brain stimulators, neuro- and spinal cord stimulators. Displacement of leads,
pulse generators, or other components of deep brain stimulators and middle ear prostheses may occur. The MRI
scanning may interfere with pacemakers and cardioverter-defibrillators resulting in “pacing artifacts, reed switch
closures, generator movement or displacement, alterations of pacing rate, and temperature increase.”28
Patients with high-risk medical conditions should be identified as part of the preoperative process. The
patients would include those with “neonatal status or prematurity, intensive care or critical care status, impaired
respiratory function, hemodynamic instability with vasoactive infusion requirement and comorbidities such as
obesity and peripheral vascular disease.”28 Neonates and premature infants undergoing MRI may be at particular
risk for fluctuations in heart rate, blood pressure, oxygen saturation levels and temperature changes (both increases
and decreases) when compared with neonates not undergoing MRI.10,11,29 In patients with acute or severe renal
insufficiency, “the anesthesiologist should not administer gadolinium because of the increased risk of nephrogenic
systemic fibrosis.”28
Equipment related risks may result from physiologic and invasive monitoring equipment, intubation,
oxygenation and ventilation equipment, as well as intravenous infusion pumps. There are case reports of infusion
pumps being drawn into the scanner and striking a patient. 30 A death was reported when a non-MRI-compatible
oxygen cylinder was drawn into the magnet. 31 There have been reports of fires or burns have occurred with
beneath or near cardiac electrodes, as well as looping of temperature probes or pulse oximetry cables which have
burns. “Care should be taken in positioning ECG and other monitors to eliminate burns, even with nonferromagnetic
leads.”28 Pulse oximetry probes should be available in multiples sizes.
In general, the equipment and drugs for anesthetic care in the MRI suite should be similar to what is
available in the operating room. The most desirable situation is to have an MRI-safe/conditional anesthesia machine
available. Metals, such as stainless steel, nickel and titanium as well as plastic are all suitable for the MRI
environment. The ASA task force advisory statement indicates that the anesthesiologists should make sure that all
monitors used in zone IV are safe/conditional for the scan.28 A monitor should be available to view vital signs from
zone III when the anesthesia care provider is not in zone IV. If not, then inhalation anesthetics may be administered
from an anesthesia machine inside zone III via an elongated circuit through a wave guide. If total intravenous
anesthesia is used, it should be administered by using either MRI-safe/conditional pumps in Zone IV or traditional
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(MRI-unsafe) pumps in zone III with intravenous tubing passed through a wave guide. Periodic bolus injections
may be given in either zones III or IV. 28
The type of anesthesia required will depend on the study requirements. Motion artifact and the need for
breath-holding may increase the need for general anesthesia. The duration of the procedure, along with patient
positioning may play a role in the practitioner’s decision to use either an LMA or endotracheal tube. While there is
a high success rate in imaging patients who have received sedation or light anesthesia, these anesthesia techniques
may be associated with “respiratory depression, oxygen desaturation, bronchospasm, drowsiness, agitation, and
vomiting.”28 This can result in interruption of the study and the need for emergent intervention. Apnea monitoring
(detection of exhaled carbon dioxide) may decrease risks during both moderate and deep sedation. As previously
noted, the observation of qualitative clinical signs and monitoring for the presence of exhaled carbon dioxide unless
precluded or invalidated by the nature of the patient, procedure, or equipment will be a requirement for moderate
and deep sedation after July 1, 2011.6
If an emergency does occur, a preplanned strategy is advised. The patient should be removed from the
zone IV of the MRI suite to a previously designated “safe” location. A call for help should be initiated.
Cardiopulmonary resuscitation should begin immediately if needed. The safe location should have in place a
defibrillator, vital signs monitor, and a code cart that includes resuscitation drugs, airway equipment, oxygen, and
suction.28 Anesthesiologists should become familiar with projectile emergencies, fire response and “quenching”
which can occur as a result of intentional shutdown of the MRI scanner. When a fire does occur, the ASA Practice
Advisory for the Prevention of and Management of Operating Room Fires should be followed.31 For projectile
emergencies, team members should follow their institutions protocol.
Computed Tomography Suite

The demographics of patients who require sedation or general anesthesia for a CT scan do not differ
significantly from those who need anesthesia for an MRI. Pediatric patients or those patients undergoing biopsies or
percutaneous drainage performed under CT guidance may require the care of an anesthesiologist. The equipment
space issues remain with minimal room for the anesthesia equipment and personnel. Like the MRI, there can be
limited access to the patient. The obvious advantage is that without the strong MRI field, there are few
compatibility problems with equipment. The CT scans tend to be much quicker. Pediatric patients, for example,
may receive sedation which is titrated to effect for short non-invasive scans. Because of the high levels of ionizing
radiation, anesthesia personnel should monitor the patient through a radiation-shielded window and stop the scan
when entering if emergency care must be provided. 33
Radiation Oncology
Radiation therapy is a major part of the treatment plan associated with some malignancies. External beam
radiation is delivered to a very specific target over a period of weeks to affect tumors. Absolute immobility is
needed at the target site when the patients, usually children, are being treated.
Because of the high levels of radiation, the patients are usually isolated and shielded. Remote monitors for EKG,
blood pressure, and pulse oximetry can be used. During some treatments, the anesthesia equipment may need to be
moved. The anesthesia team should be present to check that the anesthesia equipment and computer monitors are
functioning after each move. Like the MRI and CT scanners, the Radiation Oncology rooms can be cool. There is
limited information on the use of warm air blankets in radiation oncology, so their use cannot be recommended.
While the treatments are painless, patients who receive daily therapy sometimes require antiemetics and intravenous
fluid after the procedure is completed.
Transjugular Intrahepatic Portosystemic Shunt

Transjugular intrahepatic portosystemic shunt or “TIPS” procedures involve the creation of an artificial
channel in the liver from the portal vein to a hepatic vein in patients with severe liver disease and elevated portal
vein pressure. TIPS are performed in the interventional radiology suite under fluoroscopic guidance for patients
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who present with recurrent variceal bleeding, refractory ascites or hepatorenal syndrome. A guidewire and
introducer sheath is placed in the jugular vein in the neck to gain access to the patient’s hepatic vein via the vena
cava. The shunt is created by advancing a special needle through the sheath system to connect the hepatic vein to the
portal vein. The channel for the shunt is created by inflating an angioplasty balloon within the liver along the tract
created by the needle. A stent or endograft is deployed to maintain the tract between the higher pressure portal vein
and the lower pressure hepatic vein. Anesthesia challenges include post procedure encephalopathies, cardiac
arrythmias during guidewire placement, and control of respiratory motion during stent deployment, airway
management in the face of rapid GI hemorrhage and potential liver capsule laceration with intraperitoneal
hemorrhage. Anesthetic considerations include careful fluid management, use of medications with limited hepatic
metabolism and potential coagulopathies. 34
Hematology/Oncology: Lumbar Punctures and Bone Marrow Aspiration

Pediatric patients with hematologic disorders (leukemias/lymphomas) must undergo multiple diagnostic
and therapeutic lumbar punctures, bone marrow aspirations and blood draws. These children often have central
venous catheters in place. After the ports are accessed and the heparin withdrawn, the children may be given
incremental boluses of propofol and placed on their side while the procedures are completed. Alternatively, children
may undergo inhalation inductions, followed by placement of an LMA or face mask with spontaneous ventilation.
ASA Standard Monitors should be placed prior to induction in the cooperative patient. In most cases, spontaneous
ventilation can be maintained throughout the procedure. The patients can remain the lateral decubitus position for
recovery with a simple face mask in place. Because of the risk of infection, all ports should be cleaned with a
disinfectant prior to use. Prior to discharge from the postoperative recovery room, the central venous lines should be
reheparinized. If intrathecal chemotherapy is given, an antiemetic, such as ondansetron, may be warranted. While
the anesthesiologist is not usually performing the procedure in this situation, adherence to the “Practice Advisory for
the Prevention, Diagnosis, and Management of Infectious Complications Associated with Neuraxial Techniques”
should be followed. Aseptic techniques should always be used. This includes the removal of jewelry, hand
washing, wearing of caps, masks (covering both mouth and nose and consider changing before each case) and sterile
gloves, use of individual packets of antiseptics for skin preparation, use of chlorhexidine and sterile draping of the
patient. 35
Transportation Issues/Monitoring
Extubation should be completed either in the remote location or in the postsurgical recovery room. The
decision to extubate the patient at the remote location will depend on the patient’s airway complexity and available
personnel. If the patient is extubated at the remote location, emergency drugs, airway equipment, a patient monitor
and oxygen supply should be available during transportation of patients from remote locations should the patient’s
airway be compromised in transit. Portable suction machines should be considered. If electronic medical records
are being used the records should be moved into a “transfer bin” until the patient arrives in the recovery location,
where data collection may resume.
Summary
Anesthesia in remote locations is associated typically with small dark rooms, bulky and sometimes
outdated equipment and personnel that are not always familiar with emergency equipment and procedures. It is the
role of the anesthesiologist to ensure that well-equipped anesthesia machines, standard monitoring
(electrocardiogram, oxygen saturation and non-invasive blood pressure), trained personnel and an anesthetic plan are
in place. Since analysis of closed claims suggests that administration of anesthesia and sedation at remote locations
is associated with a significant risk of adverse effects, it is imperative that the anesthesiologist be particularly
attentive to patients when visual and auditory clues of impending cardio respiratory events may be hindered. 1
There is substantial evidence that the use of continuous monitoring of respiration by capnography is extremely
important in patients receiving both general anesthesia and sedation. Temperature monitoring may be hazardous if
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improper equipment is used in some locations (MRI). In some locations, the requirement of the equipment may
limit the ability to adjust the room temperature. Forced-air warming devices may not be suitable in all locations,
despite the perceived benefits of maintaining normothermia. Transportation of the patients, especially if significant
distance must be traveled to reach the recovery location should consist of an oxygen cylinder, a patient monitor,
emergency drugs and a portable suction device if available. Post anesthesia care for the patient who has undergone
a procedure in a remote location should be similar to that for postsurgical patients. The practicing anesthesiologist
should remain familiar with the ASA practice guidelines, advisories and standards as they relate to anesthesia in
remote locations.
References
1. Metzner, J. Posner KL. Domino KB. The risk and safety of anesthesia at remote locations. The US closed
claims analysis. Cur Opin Anesthesia. 2009; 22:502-508.
2. Metzner, JI. Risks of Anesthesia at Remote Locations. American Society of Anesthesiology Newsletter. 2010;
74, (2): 17 -18.
3. Standards for Basic Anesthetic Monitoring. Park Ridge, IL: American Society of Anesthesiologists; (amended by
ASA House of Delegates October 25, 2005). Available at
www.asahq.org/publicationsAndServices/standards/02.pdf.
4. Thompson AM. Wright DJ. Murray W. et al. Analysis of 153 deaths after upper gastrointestinal endoscopy: room
for improvement. Surg Endosc (2004) 18: 22- 25.
5. Srinivasa, V. Kodali BS. Capnometry in the spontaneously breathing patient. Curr Opin Anaesthsiol
2004;17:517-520.
6. Standards for Basic Anesthetic Monitoring (effective July 1, 2011). Available at http://www.asahq.org/For-
Healthcare-Professionals/Standards-Guidelines-and-Statements.aspx
7. Alspach D. Falleroni M. Monitoring Patients During Procedures Conducted Outside the Operating Room.
International Anesthesiology Clinics 2004; 42(2): 95-111.
8. Statement on Safe Use of Propofol (amended by the ASA House of Delegates on October 21, 2009). Availabe at
www.asahq.org/publicationsAnd Sevices/standards/37.pdf.
9. Practice Guidelines for Management of the Difficult Airway. Anesthesiology 2003; 98 (5): 1269 - 1277.
10. Battin M. Maalouf EF. Counsel S. et al. Physiologic stability of preterm infants during magnetic resonance
imaging. Early Hum Dev 1998; 52:101-110.
11. Taber KH. Hayman LA. Northrup SR et al. Vital sign changes during infant magnetic resonance examinations. J
Magn Reson Imaging 1998; 8: 1252-6.
12. Kamada Y. Miyamoto N. Yamakage M. Tsujiguchi N. Namiki A. Utility of an infrared ear thermometer as an
intraoperative core temperature monitor. Masui 1999;48 (10):1121-5.
13. Hall SC. Stevenson GW. Suresh S. Burn associated with temperature monitoring during magnetic resonance
imaging. Anesthesiology. 1992;76:152.
14. Kurz A. Sessler DI. Lenhardt RA. Study of wound infections and temperature group: perioperative
normothermia to reduce the incidence of surgical wound infections and shorten hospitalization. N Engl J Med.
1996; 334:1209 – 1215.
15. Frank SM. Fleisher LA. Breslow MJ. et al. Perioperative maintenance of normothermia reduces the incidence of
morbid cardiac events. A randomized clinical trial. JAMA. 1997; 277: 1127 – 1134.
16. Schmidt H. Kurz A. Sesser DI, et al. Mild hypothermia increases blood loss and transfusion requirements during
total hip arthroplasty. Lancet 1996; 347:289-292.
17. Hildebrand F. Giannoudis P. van Griensven M. Pathophysiologic changes and effects of hypothermia on
outcome in elective surgery and trauma patients. American Journal of Surgery 2004: 187;363-371.
18. Sessler DI. Complications and Treatment of Mild Hypothermia. Anesthesiology 2001; 95: 531-43.
19. Fossum S. A comparison study on the effects of prewarming patients in the outpatient surgery setting. Journal
of Perianesthesia Nursing 2001;16(3): 187-194.
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20. Vargo, JJ. Waring JP, Faigal DO, et al. American Society for Gastrointestinal Endoscopy. Guidelines for the use
of deep sedation and anesthesia for GI endoscopy. Gastrointest Endosc. 2002;56:613-617.
21. Bryson EO, Sejpal D. Anesthesia in Remote Locations: Radiology and Beyond, International Anesthesiology
Clinics. International Anesthesiology Clinics 2009: 47 (2) 69-80.
22. Christensen M, Matzen P, Schulze S, et al. Complications of ERCP: a prospective study. Gastrointest Endosc.
2004;60:721-23.
23. Fisher L, Fisher A, Thomson A. Cardiopulmonary complications of ERCP in older patients. Gastrointest
Endosc. 2006;63:948-55.
24. Statement on Respiratory Monitoring During Endoscopic Procedures (approved by ASA House of Delegates on
October 21, 2009). Available at www.asahq.org/publicationsAndServices/standards/52pdf.
25. Patterson, SK, Epps JL, Snider CG, et al. Propofol Administration for Endoscopies Associated with BIS Levels
Equivalent to General Anesthesia, Abstract 2007 ASA Mtg, October 13-17, San Francisco, CA.
26. Vargo JJ. Zuccaro G, Dumot JA, et al. Automated graphic assessment of respiratory activity is superior to pulse
oximetry and visual assessment for the detection of early respiratory depression during therapeutic upper endoscopy.
Gastrointest Endosc. 2002;55:826-831.
27. Kulling D. Rothenbuhler R. Inauen W. Safety of Nonanesthetist Sedation with Propofol for Outpatient
Colonoscopy and Esophagogastroduodenoscopy. Endoscopy 2003; 35 (8):679-81.
28. Practice Advisory on Anesthetic Care for Magnetic Resonance Imaging: A Report by the American Society of
Anesthesiologists Task Force on Anesthetic Care for Magnetic Resonance Imaging. Anesthesiology 2009; 110 (3):
459-479.
29. Miller S, Dalal P, Ortwein G, et al. Changes in Body Temperature Following MRI Scanning in Infants: A
Quality Assurance Audit, Abstract 2010 ASA Mtg, October 16-20, San Diego, CA.
30. Wynnychenko TM. Szokol JW. Murphy GS. Infusion pump use in the MRI. Anesth. Analg. 2000;91:249-50.
31. Landrigan C. Preventable Deaths and Injuries during Magnetic Resonance Imaging. N Engl J Med 2001;345
(13): 1000-1001.
32. Practice Advisory for Prevention and Management of Operating Room Fires. Anesthesiology 2008; 108:786-
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33. Henderson KH. Lu JK. Strauss KJ et al. Radiation exposure of anesthesiologists. J. Clin. Anes. 1994;6:37-41.
34. Scher, C. Anesthesia for Transjugular Intrahepatic Portosystemic Shunt. International Anesthesiology Clinics
47; (2): 21-28.
35. Practice Advisory for the Prevention, Diagnosis, and Management of Infectious Complications Associated with
Neuraxial Techniques March 2010, 112 (3): 1 – 16.
DISCLOSURE
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Positioning Problems You Hope to Never Encounter

Mark A. Warner, M.D. Rochester, Minnesota
Perioperative neuropathies, soft tissue injuries, and other positioning-related problems have received increasing
attention from the lay press, plaintiffs’ lawyers, the anesthesiology community, and clinical researchers in recent
years. This lecture will provide an update of current findings and discuss possible mechanisms of injury for these
potentially devastating problems.
A relatively new finding in this field of study is the discovery that a generalized perioperative inflammatory
response is present in a number of patients who have sustained significant prolonged ulnar neuropathy. This is a
surprising, unexpected finding. A 2010 paper by Staff et al describes the remarkably successful treatment of
persistent perioperative ulnar neuropathy with very high doses of steroids (immunomodulation) over several months
after finding generalized microneuritis by sural nerve biopsy in affected patients. Let me repeat that – microneuritis
of the sural nerve located far distant from the symptomatic ulnar nerve. It appears that there might be a diffuse
perioperative inflammatory response throughout the body that contributes to perioperative ulnar neuropathy.
Would a similar mechanism contribute to other perioperative neuropathies? Many perioperative factors have been
associated with acute immunosuppression and subsequent inflammatory responses (e.g., blood transfusions, volatile
anesthetics). It is not clear what role this mechanism might play, if any, in a number of perioperative neuropathies.
There clearly is much more yet to learn. However, the Staff study suggests that there may be factors beyond
anatomic positioning issues that are involved in some proportion of perioperative neuropathies.
Upper Extremity Neuropathies
Ulnar Neuropathy
Ulnar neuropathy is the most common perioperative neuropathy. There are a number of factors that may be
associated with ulnar neuropathy, including direct extrinsic nerve compression (often on the medial aspect of the
elbow), intrinsic nerve compression (associated with prolonged elbow flexion), and inflammation. Key points of
interest:
• Timing of postoperative symptoms: Most develop during the postoperative, not the intraoperative, period.
There are good data that most surgical patients who develop ulnar neuropathy experience their first
symptoms at least 24 hours postoperatively, suggesting that the mechanism of acute injury occurs primarily
outside of the operating room setting. Parenthetically, medical patients also develop ulnar neuropathies
during hospitalization.
• Impact of elbow flexion: The ulnar nerve is the only major peripheral nerve in the body that always passes
on the extensor side of a joint, in this case the elbow. All other major peripheral nerves primarily pass on
the flexion side of joints (e.g., median and femoral nerves). This anatomy difference may play a role in
some perioperative ulnar neuropathies. In general, peripheral nerves begin to lose function and develop
foci of ischemia when they are stretched > 5% of their resting lengths. Elbow flexion, particularly > 90
degrees, stretches the ulnar nerve. Prolonged elbow flexion and stretch of the ulnar nerve can result in
sufficient ischemic areas to cause symptoms in awake and sedated patients and potential long-lasting
damage in all patients.
• A natomy and elbow flexion: Prolonged elbow flexion of > 90 degrees increases intrinsic pressure on the
nerve and may be as important an etiologic factor as prolonged extrinsic pressure. The ulnar nerve passes
behind the medial epicondyle and then runs under the aponeurosis that holds the two muscle bodies of the
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flexor carpi ulnaris together. The proximal edge of this aponeurosis is sufficiently thick, especially in men,
to be separately named the cubital tunnel retinaculum. This retinaculum stretches from the medical
epicondyle to the olecranon. Flexion of the elbow stretches the retinaculum and generates high pressures
intrinsically on the nerve as it passes underneath (fig 1).
• Forearm supination and ulnar neuropathy: Supination of the forearm and hand does not, by itself, reduce
the risk of ulnar neuropathy. The action of forearm supination occurs distal to the elbow. Supination is
typically used when positioning arms on arm boards or at patients’ sides because of the impact it has on
humerus rotation. That is, supination is uncomfortable for most patients, and they will externally rotate
their humerus to increase comfort. It is this external rotation of the humerus that lifts the medical aspect of
the elbow, including the ulnar nerve, from directly resting on the table or armboard surface. This rotation
helps reduce extrinsic pressure on the ulnar nerve.
• Outcomes of ulnar neuropathy: Forty percent of sensory-only ulnar neuropathies resolve within 5 days;
80% resolve within 6 months. Few combined sensory/motor ulnar neuropathies resolve within 5 days; only
20% resolve within 6 months, and most result in permanent motor dysfunction and pain. The motor fibers
in the ulnar nerve are primarily located in its middle. Injury to those fibers likely is associated with a more
significant ischemia or pressure insult to all of the ulnar nerve fibers, and recovery may be prolonged or not
possible.
Brachial Plexopathies
Brachial plexopathies occur most often in patients undergoing sternotomies. The risk for this plexopathy in patients
undergoing sternotomy is particularly high in those with internal mammary artery mobilization. This finding is
presumed to be associated with excessive concentric retraction on the chest wall and potential compression of the
plexus between the clavicle and rib cage or stretch of the plexus. Otherwise, patients in prone and lateral positions
have a higher risk of developing this problem than those in supine positions. Key points of interest:
• Brachial plexus entrapment: There are many problems that can occur to the plexus in prone and laterally-
positioned patients. For example, the brachial plexus can become entrapped between compressed clavicles
and the rib cage. Special attention should be given to altering positions that might exacerbate this potential
problem.
• Prone positioning: In prone positioned patients, it’s prudent to tuck the arms at the side if at all possible;
many patients have somatosensory evoked potential changes when their arms are abducted (e.g., a
“surrender” position).
• A natomy of shoulder abduction: Abduction of a shoulder > 90 degrees places the distal plexus on the
extensor side of the joint and potentially stretches the plexus (fig 2). Therefore, it is best to avoid abduction
> 90 degrees, especially for extended periods.
Median Neuropathies
Median neuropathies primarily occur in men between the ages of 20-40 years of age. These men often have large
biceps and reduced flexibility (think weightlifters). The large biceps and reduced flexibility tend to prevent
complete extension at the elbow. This chronic limitation in range of motion results in shortening of the median
nerve over time. Median neuropathies typically involve motor dysfunction and do not resolve readily. In fact, up to
80% of median neuropathies with motor dysfunction are sustained 2 years after the initial onset. Key points of
interest:
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• Stretch of a nerve: As mentioned in the section on ulnar neuropathy, nerves become ischemic when
stretched more than 5% of their resting length. This amount of stretch tends to kink penetrating arterioles
and exiting venules, both of which decrease perfusion pressure.
• A rm support: When we subsequently anesthetize these men, we may fully extend their arms at the elbow
and place them on arm boards or at the patients’ sides. This full extension of the elbow stretches
chronically contracted median nerves and promotes ischemia, often at the level of the elbow. Thus, it is
important to support the forearm and hand to prevent full extension in men who have large, bulky biceps
and who cannot fully extend their elbows because of a lack of flexibility.
Radial Neuropathies
Radial neuropathies occur more often than median neuropathies. The radial nerve appears to be injured by direct
compression (in contrast to the median nerve being injured primarily by stretch). The important factor appears to be
compression of the nerve in the mid-humerus region where it wraps posteriorly around the bone (fig 3). Radial
neuropathies tend to have a better chance of recovery than ulnar or median neuropathies. Approximately half get
better within 6 months, and 70% appear to resolve completely within 2 years. Key points of interest:
• Surgical retractors: A case series reported several radial neuropathies associated with compression of the
radial nerve by the vertical bars of upper abdominal retractor holders. The arms reportedly were impinged
by these vertical support bars (fig 3.a).
• Lateral positions: The radial nerve may be impinged by overhead arm boards when they protrude into the
mid-humerus soft tissue (fig 3.d).
• A n unsupported arm: Anecdotal reports discuss compression on the nerve in the mid-humeral when the
elbow of a fixated arm (at side or on an arm board) slips, loses support, and the weight of the upper
extremity is supported by the mid-humerus (fig 3.e).
Lower Extremity Neuropathies
Although common peroneal and sciatic neuropathies have the most impact on ambulation, the most common
perioperative neuropathies in the lower extremities involved the obturator and lateral femoral cutaneous nerves.
Key points of interest:
• Impact of hip abduction on the obturator nerve: Hip abduction > 30 degrees results in significant strain on
the obturator nerve. The nerve passes through the pelvis and out the obturator foramen. With hip
abduction, the superior and lateral rim of the foramen serves as a fulcrum (fig 4). The nerve stretches
along its full length and also is compressed at this fulcrum point. Thus, excessive hip abduction should be
avoided whenever possible. With obturator neuropathy, motor dysfunction is common. Thankfully, it is
usually not painful, but it can be crippling. Approximately 50% of patients who have motor dysfunction in
the perioperative period will continue to have it 2 years later.
• Impact of hip flexion on the lateral femoral cutaneous nerve: Prolonged hip flexion > 90 degrees increases
ischemia on fibers of the lateral femoral cutaneous nerve. One-third of this nerve’s fibers pass through the
inguinal ligament as they pass into the thigh (fig 5). Hip flexion > 90 degrees results in lateral
displacement of the anterior superior iliac spine and stretch of the inguinal ligament. The penetrating nerve
fibers are compressed by this stretch and, with time, become ischemic and dysfunctional. The lateral
femoral cutaneous nerve carries only sensory fibers, so there is no motor disability when it is injured.
However, patients with this perioperative neuropathy can have disabling pain and dysthesias of the lateral
thigh. Approximately 40% of these patients have dysesthesias that last for more than one year.
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• Peroneal neuropathies and leg holders: It appears that most peroneal neuropathies are associated with
direct pressure of the lateral leg, just below the knee, where the peroneal nerve wraps around the head of
the fibula. Leg holders, ranging from “candy cane” leg holders to various leg holders or “crutches” that
hold the leg and foot, can impinge on the nerve as it wraps around the head of the fibula. The result can be
devastating, with prolonged foot drop and difficulty ambulating.
Practical Considerations for Perioperative Peripheral Neuropathies
• Use padding to distribute compressive forces. Although there are few studies that demonstrate padding to
impact the frequency or severity of perioperative neuropathies, it makes sense to distribute point pressure.
The use of padding also is found by juries to be positive in medicolegal actions.
• Position joints to avoid excessive stretching, recognizing that stretch of any nerve > 5% of its resting
length over a prolonged period results in varying degrees of ischemia and dysfunction.
• What to do if your patient develops a peripheral neuropathy:
 If the loss is sensory-only, it is reasonable to follow the patient daily for up to 5 days. Many
sensory deficits in the immediate postoperative period will resolve during this time. If the deficit
persists for longer than 5 days, it is likely that the neuropathy will have an extended impact. It is
appropriate at that point to get a family physician, internist, or neurologist involved to provide
long-term care.
 If the loss is motor-only or combined sensory/motor, it would be prudent to get a neurologist
involved early. These patients likely have a significant neuropathy and will need prolonged
postoperative care.
Unique Positioning Problems with Catastrophic Results
• Spinal cord ischemia. This rare event occurs when patients undergoing pelvic procedures (e.g.,
prostatectomy) are placed in a hyperlordotic position, with greater than 15 degrees of hyperflexion at the
L2-L3 interspace. This results in spinal cord ischemia and infarction. It is best detected with magnetic
resonance imaging. Operating room tables made in the U.S. are designed to limit hyperlordosis in supine
patients, even when the table is maximally retroflexed with the kidney-rest elevated. In almost all reported
cases, the table has been maximally retroflexed, the kidney-rest has been elevated, AND towels or blankets
have been placed under the lower back to promote further anterior or forward tilt of the pelvis (to improve
vision of deep pelvic structures). In general, anesthesia providers should not allow placement of materials
under the lower back for this purpose.
• Thoracic outlet obstruction. This rare event occurs when patients with this syndrome are positioned prone
or, less commonly, laterally. In almost all reported cases, the shoulder has been abducted > 90 degrees. In
that position, the vasculature to the upper extremity is either compressed between the clavicle and rib cage
or between the anterior and middle scalene muscle bodies. This entrapment of the vasculature leads to
upper extremity ischemia. When prolonged, the results range from minor disability to severe tissue loss
that requires forequarter amputation. Simple preoperative questions such as “Can you use your arms to
work above your head for more than a minute?” can elicit a history of thoracic outlet obstruction and
reduce the risk of this potentially devastating complication.
• Steep head-down positions. As surgeons gain experience with new technologies (e.g., robotics for pelvic
procedures), they often request steep head-down positions. These positions can be associated with
cephalad shifting of anesthetized patients on operating room tables. Patients often are fixated to these
tables with draw sheets and other retaining devices (e.g., shoulder braces). Cephalad shifting can lead to
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cervical plexopathies from stretch and subclavian vessel obstruction from compression. Although
intracranial pressure also increases, it rarely results in a negative outcome. However, orofacial edema
requires careful airway attention. Recently, there are reports of patients sliding cephaladly off of operating
room tables when they are placed in steep head down positions and not secured to the beds. The resulting
cervical spine and cerebral injuries have been devastating to both patients and providers.
• Steep head-up positions. While many of us think of sitting craniotomies for these positions, the most
common of the steep head-up positions is the “beach chair” position used for many shoulder surgeries.
These positions invoke considerable debate on hemodynamic issues, specifically systemic blood pressure
and cerebral blood pressure. The Anesthesia Patient Safety Foundation held a special workshop on this
issue and published an excellent summary in its Winter 2009-2010 Newsletter. In addition, a number of
severe brachial and cervical plexopathies have been reported. It appears that at least some of these
plexopathies have been associated with nerve stretch or compression when patients who often have their
heads fixated slide laterally or distally during procedures.
• Soft tissue problems. Skin and other soft tissues are particularly vulnerable to sustained pressure, resulting
in ischemia. While there are many examples, several related to prone positions deserve special mention.
Tissues in direct contact with rolls that extend from shoulder girdle across the chest and to the pelvis may
become ischemic with prolonged pressure (fig 6). There are multiple cases of women with large breasts
who developed severe ischemia of one or both breasts when they were pushed in between chest rolls. The
lateral pressure was sufficient to cause necrosis and sloughing. In most of these reported cases, the women
subsequently underwent mastectomies. Similarly, ostomies have developed ischemia from pressure when
they are placed in direct contact with these rolls.
Suggested References
American Society of Anesthesiologists Task Force on the Prevention of Perioperative Neuropathies. Practice
guidelines for the prevention of perioperative neuropathies. Anesthesiology 2000;92:1168-82.
Contreras MG, Warner MA, Charboneau WJ, et al. Anatomy of the ulnar nerve at the elbow: potential relationship
of acute ulnar neuropathy to gender differences. Clin Anat 1998;11:372-8.
Litwiller JP, Wells RE, Halliwill JR, et al. Effect of lithotomy positions on strain of the obturator and lateral
femoral cutaneous nerves. Clin Anat 2004;17:45-9.
Staff NP, Engelstad J, Klein CJ, et al. Post-surgical inflammatory neuropathy. Brain. 2010;133:2866-80.
Warner MA, Warner DO, Matsumoto JY, et al. Ulnar neuropathy in surgical patients. Anesthesiology 1999;90:54-9.
Warner MA. Patient positioning and related injuries. In: Barash PG, et al, editors. Clinical anesthesia. 6th Edition.
Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins; 2009:793-814.
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1a 1b
Figure 1: (a) The ulnar nerve of the right arm passes distally behind the medial epicondyle and underneath the aponeurosis that
holds the two heads of the flexor carpi ulnaris together. The proximal edge of the aponeurosis is
sufficiently thick in 80% of men and 20% of women to be distinct anatomically from the remainder of the tissue. It is commonly
called the cubital tunnel retinaculum. (b) Viewed from behind, the ulnar nerve is intrinsically compressed by the cubital tunnel
retinaculum when the elbow is progressively flexed beyond 90° and the distance between the olecranon and the medial
epicondyle increases.
2a 2b
Figure 2: (a) The neurovascular bundle to the upper extremity passes on the flexion side of the shoulder joint when the arm is at
the side or abducted less than 90°. (b) Abduction of the arm beyond 90° transitions the neurovascular bundle to where it now
lies on the extension side of the shoulder joint. Progressive abduction greater than 90° increases stretch on the nerves at the
shoulder joint.
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Figure 3: The anatomy of the radial nerve is shown in the upper left corner, illustrating how it wraps around the mid-humerus.
Reported mechanisms of perioperative injury include (a) compression by surgical retractor support bar; (b) direct needle trauma
at the wrist; (c) compressive tourniquet effect by a drawsheet at the wrist; (d) impingement by an overhead arm board; (e)
compression in the mid-humerus level as the arm supports much of the weight of the upper extremity.
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3a 3b
Figure 4: (a) The obturator nerve passes through the pelvis and exits out the superior and lateral corner of the obturator foramen
as it continues distally down the inner thigh. (b) Abduction of the hip stretches the obturator nerve and can provoke ischemia,
especially at the exit point of the obturator foramen. The point serves as a fulcrum for the nerve during hip abduction.
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4a 4b
Figure 5: (a) Approximately one-third of the lateral femoral cutaneous nerve fibers penetrate the inguinal ligament as the nerve
passes out of the pelvis and distally into the lateral thigh. (b) Hip flexion, especially when greater than 90°, leads to stretch of the
inguinal ligament as the ilium is displaced laterally. This stretch causes the intra-ligament pressure to increase and compresses
the nerve fibers as they pass through the ligament.
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Figure 6: Soft tissues can be compressed and even become ischemic if there is too much pressure on them for long periods of
time. This figure illustrates how chest rolls may compress the lateral aspects of large breasts or a stoma in prone positioned
patients.
DISCLOSURE
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“Emergency Preparedness and Disaster Management

for Natural Disasters and CBRNE Events”
Michael J Murray M.D. Ph.D. Landstuhl, Germany
OUTLINE:
I Introduction
II Emergency Preparedness
III Disaster Management
IV Mass Casualty Incidents
Natural Disasters
Weather Related
Geologic
Biologic
Terrorism CBRNE
V References
Introduction:
The majority of governments and scientists around the world have been working to decrease the threat from
weapons of mass destruction. For example there are only two known repositories of smallpox in the world. In 2011
the United States destroyed the last of its largest nuclear weapon[1]. In January of 2012 US government completed
its destruction of its chemical stockpile[2]. However as the events of the last few years demonstrate, natural disasters
and terrorists have taken an incredible toll. Hurricane Katrina and Ike, tornadoes throughout the United States in
2011 and 2012, the tsunami and resulting nuclear power plant catastrophe in 2011 underscore how important it is for
anesthesiologists to remain prepared and educated on how they will respond if their hospital or community is faced
with a mass casualty incident [a mass casualty incident has potential to overwhelm the hospital's capability to handle
the number of casualties. A mass casualty event can overwhelm a community’s ability to respond to casualties]. An
incident need not be a major disaster such as a terrorist attack or an influenza epidemic to overwhelm the resources
of a hospital – the Rhode Island nightclub fire of 2003 resulted in 40 burn-patients presenting to the small local
hospital all of whom required major interventions[3].
For the purpose of this refresher course lecture we will focus only on how an individual anesthesiologist would
respond to a mass casualty incident that her or his hospital.
Emergency Preparedness
Family Plan: The first step in in emergency preparedness is to have a family emergency or disaster plan. The three
components of such a plan are 1) develop a plan that takes into account the most likely calamites for which you must
be prepared – a house fire, a tornado in Central United States, a hurricane on the Gulf Coast, or an earthquake on the
West Coast. Meeting places for household members should be identified- one should be immediately outside your
home and the other should be outside your immediate neighborhood. 2) create checklists with which all members of
your household are familiar outlining what each member of the household will do in the event of a disaster. Often
overlooked steps include making adequate preparations for family pets or disabled family members in the event of
evacuation, and maintaining original or copies of important documents in a secure environment e.g. bank safe
deposit box. 3) have periodic drills to ensure familiarity with the plan, and to identify steps of the plan that require
updating as circumstances change.
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Personal Plan:
Long before disaster strikes your community, you should have planned your response for what to do
depending on what disaster strikes. For example if you live in a hurricane zone, the roads may be so clogged with
traffic that they may be impassable, or may well be closed when the hurricane actually strikes, so you should
anticipate arriving at your hospital while roads are still open.
Because during a disaster loss of electricity in the community is common, you should have adequate cash,
fuel in your vehicle, personal hygiene items and food and water that you will bring with you to the hospital. Some
individuals have an emergency medical kit that they keep at home or in their vehicle for use in an emergency
situation. For example during the tornado that struck Joplin Missouri in 2011, because one of the hospitals was
destroyed, paramedics worked out of their ambulances to render aid. A healthcare provider who had such a kit
would be able to render aid to his family members and neighbors if they had been injured. Anticipating
communication needs is also important.
Telephone networks are often overloaded or destroyed during community disasters, as might be the radio
stations. A satellite telephone and a battery-powered radio would be very helpful in such circumstances. Because the
number of potential types of injuries and illnesses with which one might be confronted during a mass casualty event
it is difficult if not impossible for most anesthesiologists to maintain the necessary treatment information. In
advance, as part of your personal plan, and the approach that professional medical societies have adopted is “just-in-
time” training - concise information specific to the patient population being managed at the point of care. This
“training” is Web-based and user-friendly allowing for focused, inexpensive education. Even though in most
situations Internet access would be available, the wise person would download information in advance that could be
used to manage the types of injuries that one could anticipate. For example, in March of 2012 the United States
Department of Defense published Joint Theater Trauma System Clinical Practice Guidelines - Practical Emergency
Information for Critical Trauma Care, Burns, Compartment Syndrome, W ounds, Head and Spine; the 488 page book
is available for download to an e-Reader[4] for a very nominal fee and would prove invaluable if faced with mass
casualties from a high-impact explosive device. Similar information is available from multiple Web sites that could
be stored in advance on your personal digital assistant. For example if you live close to a petroleum refinery or large
petrochemical plant, an industrial catastrophe is likely. Algorithms for the management of patients who have been
involved in a terrorist attack in which CBRNE agents have been used should also be on the device.
Knowing your hospitals plan for managing a disaster is again something that with which you should be
familiar prior to the mass casualty incident; unfortunately fewer than 15 % of anesthesiologists have ever
participated in the biannual drill of its emergency plan.
One factor for which most don’t prepare is the psychological sequelae of a disaster. Depending on severity
and duration of the disaster, maintaining a sleep cycle and adequate nutrition and hydration are vitally important as
is maintaining one’s mental health by what ever means available e.g. talking to a mental health professional, taking
breaks for rest and recuperation.
Disaster Management
There are some basics of disaster management that apply to any mass casualty incident independent of the cause.
Health care workers who do not go to the hospital at which they are employed do so for a number of reasons – they
may have responsibility to evacuate dependents, they may rationalize that the absence (or presence) of one person
will not alter the outcome of a mass casualty incident, or that they have insufficient knowledge of how to recognize
smallpox, know how to manage antibiotics for anthrax, dose atropine for nerve agent injury or treat radiation
syndrome. However in all the scenarios described above the ABCs of managing emergencies are as important as
ever – Airway, Breathing, Circulation etc. Furthermore, anesthesiologists are the most knowledgeable group of
specialists with the requisite the skill-set to manage most if not all of the injuries or illnesses that would manifest in
a mass casualty incident.
However, during a mass casualty incident an anesthesiologist may be asked to provide anesthetic services
in an area other than the operating room or intensive care unit (ICU). One will not know where one will be working
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until reporting to the hospital and the command and control center established to manage the incident. The site of the
command and control center is pre-established and outlined in the hospital’s emergency preparedness plan, but
typically within the hospital’s emergency department or in-close proximity. Other entrances to the hospital are
typically closed during a mass casualty incident for the purposes of maintaining control of the numbers of patients
that might present and to allow for decontamination of patients if necessary avoiding exposure of hospital personnel
to contagious agents or transferrable substances such as nerve agents. The lack of such control and decontamination
of the Tokyo subway sarin attack victims in 1995 resulted in a number of health care workers became ill by
absorbing sarin from patients who had not been properly decontaminated[5]. Not only were they unable to work but
they became patients themselves, increasing the number of patients requiring care and consuming resources.
Triage: If assigned to triage patients the anesthesiologist will be expected to classify patients into 4 groups – those
requiring immediate care, delayed care, first aid, and expectant, the latter those expected not to survive, or, because
of the number of patients arriving, those for whom there are not adequate personnel or resources to adequately
resuscitate without jeopardizing the lives of many more patients who would not receive the care they require and for
whom the prognosis is more favorable. “Expectant” patients are usually transported to an area separate from the ED
where they can be provided comfort care, such a site must be situated such that newly arriving patients are not
exposed to the sight of dying patients. Anesthesiologists may well be assigned to provide such care because of
expertise in managing airways, in establishing intravenous access for the administration of medications, and our
familiarity with the available anxiolytic and analgesic medications. As emotionally difficult as the process might be
of identifying or managing patients not expected to survive is the assessment of patients who may have been injured
or been affected during a disaster but do not appear to require treatment, but who might require delayed care.
Depending on the agent, diagnosis of those requiring therapy:
o Chemical (Nerve) Agents: If only Headache, meiosis, rhinorrhea, & lacrimation after exposure
patients can be decontaminated (see below) and dismissed. Patients with dyspnea, bronchospasm,
or arrhythmias will require treatment with atropine.
o Biologic Agents: Fever, rash, dyspnea, cough
o Radiologic/Nuclear: Nausea within 6 h of exposure; because of the prevalence for those with this
symptom, check leukocyte count, dismiss and have patient return in 48 h for repeat check - if no
change in count no therapy indicated.
o Explosive: If tympanic membranes intact and SpO2 within normal limits other injuries unlikely
Decontamination
In most situations people in contact with chemical agents or radioactive materials are decontaminated by
anyone with proper training - the decontamination is normally performed first and then patients are evaluated and
triaged. The process is usually fairly straightforward; clothes are removed and individuals are washed with copious
amounts of water (the contaminated water and apparel can present quite a challenge!); if individuals have been
exposed to a chemical agent a dilute solution of sodium hypochlorite 0.5% (household bleach) can be used.
However, if the patient presents with life-threatening injury the patient is treated first, and decontaminated
afterwards. Patients with severe chemical agent poisoning may present with acute respiratory failure requiring
emergency tracheal intubation. In this scenario an anesthesiologist would be assigned to the decontamination station.
For obvious reasons the intubation would have to be performed with the anesthesiologist wearing a hazard materials
(HAZMAT) or a biohazard suit with multiple-layered gloves and a gas mask. This is not as easy to perform as one
might suspect – the suits are not insulated and if the decontamination is performed outside the hospital the extremes
of temperature can significantly hinder performance, as does the decreased manual dexterity because of the gloves
and the impairment in vision from the face hoods. Ideally individuals with prior training would manage the airway
intubation but depending on circumstances that may not happen. As many have learned from past experience, it is
best to anticipate the unexpected, and to be flexible if the maximum numbers of patients are to be saved. Preparation
of equipment and drugs before the arrival of contaminated patients decreases the difficulties with manual dexterity
that are encountered while wearing the multiple-layer or rubber gloves. Consider securing the airway with a
laryngeal mask airway, when indicated, rather than with a tracheal tube.
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Emergency Department
The one other place an anesthesiologist might be assigned is the emergency department. While some level I
trauma centers have an anesthesia team assigned to support the emergency department this is not the norm.
Depending on the types of casualties, but especially for casualties from a violent explosion, anesthesiologists might
be assigned to manage the airway and secure central venous access. Anesthesiologists should position themselves at
the head of the bed and assume responsibility for the airway and venous access. For the former it would be ideal to
have 2 or 3 assistants (one providing in-line C-spine stabilization, another individual applying cricoid pressure, and
a third individual administering medications.) Sometimes it is necessary to remind emergency room physicians and
trauma surgeons that “A” (airway) and “B” (breathing) come before “C” (circulation); certainly the primary and
secondary surveys can be conducted during this critical time point but ventilation and oxygenation must be assured
and that is what we as anesthesiologists do best.
Mass Casualty Incidents
Natural Disasters
In the US we are relatively fortunate, but not completely so, in that the effects of the weather (hurricanes,
tornadoes, drought - increasing the number of forest fires) have not been as severe as seen elsewhere in the world
where over one half people are affected annually[6]. However if you experienced first hand hurricane Katrina or Ike,
or the Northfield earthquake of 1994, or developed acute respiratory failure from avian flu, then you know well that
Mother Nature can throw quite a punch, one that the entire planet strives to avoid.
Weather Related
In August 2005, Hurricane Katrina hit New Orleans, flooding much of the city, incapacitating most of its
hospitals. Those hospitals still functioning had to provide care for the “routine” – caesarian sections and
appendectomies, those transferred from other hospitals and those injured by the primary and secondary effects of the
storm. For the anesthesiologists practicing at those hospitals and at outlying hospitals the basics mentioned above
were critical i.e. your family and personal plan, ability to function without electricity, means of communications,
and maintenance of physical and mental health[7].
Geologic
Earthquakes fortunately are not as common as weather-related disasters but still claim almost 5 million victims a
year[8]. Unfortunately because of a lack of building codes most morbidity and mortality occur in third world
countries but not exclusively so as was seen in Northridge CA in 1995. Because many hospitals are destroyed or
non-functional transportation of casualties out of the earthquake zone to healthcare facilities elsewhere is a major
challenge, especially if no triage has been performed. Under these circumstance triage is critical; many can receive
first aid or delayed treatment. The “urgent” patients are those with crush injuries or amputations requiring immediate
care.
Biologic
Diseases such as SARS and influenza are highly contagious and as likely to create as much havoc as would
the use of anthrax by a terrorist. The H1N1 influenza virus fortunately did not become a pandemic but world wide
created considerable morbidity and mortality and placed enormous demands on many institutions. From their
experience with these diseases and because of their airway and ventilator management skills, anesthesiologists will
be at the forefront of providing care for many of these patients, and for those anesthesiologists with critical care
training they will likely be involved in the management of patients who are candidates for ECMO[9].
Terrorism
Chemical
Nerve agents inhibit anticholinesterase resulting in excessive amounts of acetylcholine at cholinergic receptors
leading to copious secretions, meiosis, arrythmias, bronchospasm, flaccid paralysis, seizures and death. The
treatment is the same as for poisoning with an insecticide; atropine is administered to attenuate and block the
muscarinic side effects of the agents.
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If quantities of the pulmonary agents, either chlorine or phosgene are introduced in a closed space sufficient
to displace O2 death results from asphyxia. Individuals who survive often develop acute lung injury or acute
respiratory distress syndrome (ARDS) because of the toxicity of the gases to the lung. The treatment of the resulting
non-cardiac pulmonary edema is symptomatic: mechanical ventilation using small tidal volumes (6-8 mL/kg), peak
airway pressures < 30 cm H2O) and concentrations of inspired oxygen of 50 -60% or less.
Hydrogen cyanide and cyanogen chloride, are considered the two blood agents but because of the
instability of the latter patients exposed to hydrogen cyanide are more likely to be seen. Cyanide inhibits cellular
respiration by interrupting the oxidative electron transfer process in mitochondria. For those who survive, the
treatment is similar to that for an accidental overdose of sodium nitroprusside (intravenous thiosulfate and
supportive care including tracheal intubation, ventilation with 100% oxygen and inotropes and vasopressors to
stabilize the cardiovascular system).
Biologic
Major (Group A) biologic agents used for warfare are:
• Bacillis anthracis (anthrax)
• Variola major (smallpox)
• Yersina pestis (plague)
• Clostridium botulinum (botulism)
• Francisella tularenis (tularemia)
• Viral hemorrhagic fever (Ebola, Lassa, Marburg, Argentine)
Anthrax and smallpox are the two infectious agents most likely to be used as weapons of mass destruction as
small inoculums of either agent are incredibility potent - they are highly infective, very contagious, and in
unprotected individuals, are associated with 50% fatality rates. The U.S. and state governments have prepared to
vaccinate the entire population within 48 hours to prevent the spread of the disease.
Of potentially greater concern is the aerosolized delivery of anthrax spores to large populations. The most
recent data indicate that vaccination and treatment with antibiotics are the best way to provide prophylaxis against
anthrax. Unfortunately, vaccination of the entire population is difficult, and we would need to rely on the use of
antibiotics to control a disease that is highly infectious with a high mortality rate.
Public health care teams in the U.S. are recommended to be vaccinated against small pox, and U.S. military
policy is that all personnel in combat zones must be immunized against anthrax – 6 immunizations over 18 months
and annually thereafter. Ciprofloxacin is an excellent for prophylaxis, but the best prophylaxis is a combination of
immunization and ciprofloxacin.
Radiologic/Nuclear
When it comes to radiation injury events at nuclear power plants the last 30 years have created the most damage,
destruction and long term health problems. Public health officials however, are concerned that terrorists might use a
“dirty” bomb, one with radioactive material wrapped around an improvised explosive device (IED) as Chechen
rebels planned in Moscow in 1995. Injuries from such a device would primarily be from the explosion. However, the
sequelae from the release of radiation in a major population center would be hugely disruptive in terms of 1) the
panic, 2) the amount of radioactive waste produced, 3) lost productivity and health screening of the population and
4) resettling many who are displaced from their homes.
The major challenge to the healthcare system would be screening the entire “exposed” population of
individuals who will demand to be examined. Most individuals will have no exposure and the majority who are
exposed will often be externally radiated only and, depending on the amount of radiation, may require no treatment.
As mentioned previously individuals who have no symptoms after 6 hours are unlikely to require hospitalization.
Symptomatic individuals are hospitalized if possible and have serial WBCs measured. If the WBC remains stable for
48 hours the patient may be dismissed. The US and state governments plan to distribute potassium iodide tablets to
protect the thyroid of all individuals potentially exposed within 24 hours – assuming those who are supposed to
distribute the tablets will do so. Individuals who have symptoms with in minutes or hours of exposure will require
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hospitalization and treatment of the most common sequelae of radiation sickness including bone marrow failure
(infection and coagulopathy), and gastrointestinal bleeding secondary to mucosal damage (and the
thrombocytopenia from the bone marrow failure). Antibiotics, volume resuscitation (pRBCs) and treatment with G-
CSF (granulocyte colony stimulating factor) may be life saving.
A nuclear bomb detonation is very unlikely however there has been significant planning for the management of such
a catastrophe should it occur, and guidelines are in place that are available for the use by health care
professionals[10].
Explosive
As the media reports daily, particularly in Afghanistan, the use of improvised explosive devices is the
terrorist’s favorite weapon. Patients have burns, fractures, lacerations, multiple shrapnel injuries, soft tissue trauma,
and traumatic amputations. As the weapons have become more sophisticated and powerful the extent if injuries has
increased significantly. In 2012 U S military personnel are experiencing more multiple than single traumatic
extremity amputations[11].
Patients with any evidence of burns to the face or airway will require appropriate airway management.
Patients should be intubated, awake if possible, as a significant number of these patients will have mild to moderate
glottic edema at the time of intubation. Those patients with burns must be managed aggressively with respect to
fluid resuscitation. With isolated total body surface injury fluid resuscitation is aggressive. With polytrauma, and no
third degree burns then “damage control resuscitation/surgery” is the norm[12]. Patients’ body temperature is
maintained (operating rooms maintained at > 100 degrees Fahrenheit) and surgery is performed as soon as possible
to stop the bleeding decreasing the need for blood products and the chances of developing a dilutional coagulopathy.
Patients who do develop a coagulopathy appear to benefit from a ratio of pRBCs to fresh frozen plasma to platelets
of 1:1:1[13]. One study has demonstrated that tranexamic acid decreases the need for additional blood products. In
patients with crush injury and markedly elevated creatine phosphokinase, alkalinization of the urine is often tried to
attenuate renal failure from myoglobinurea
Conclusion
It is difficult to anticipate the role anesthesiologists might play in managing patients from natural disasters or
casualties of a terrorist attack. What is clear is that as anesthesiologists, we have the requisite training and
experience to be of vital importance. The process for dealing with such events begins now by familiarizing yourself
with what the possibilities are, becoming involved in your hospital’s disaster plan, participating in semiannual
disaster response training, and remembering most importantly to protect oneself and one’s family. Protecting
oneself includes the use of appropriate protective devices to serve as barriers against radiologic, biologic, and
chemical weapons. The American Society of Anesthesiologists through its Committee on Trauma and Emergency
Preparedness and the Anesthesia Patient Safety Foundation are increasing their efforts to support ongoing
educational programs for anesthesiologists.
References
1. Administration, N.N.S. NNSA A nnounces Dismantlement of Last B53 Nuclear Bomb. 2011; Available
from: http://nnsa.energy.gov/mediaroom/pressreleases/b53dismantle102511.
2. Chemical, B., Radiological and Nuclear Defense Information Analysis Center (CBRNIAC), U.S. A rmy
Chemical Materials A gency Creates a Safer Tomorrow, 2012, Battelle Memorial Institute Washington, DC.
p. 4-7.
3. Dacey, M.J., Tragedy and response- the Rhode Island nightclub fire. N Engl J Med, 2003. 349(21): p.
1990-2.
4. Army, U.S., Joint Theater Trauma System Clinical Practice Guidelines - Practical Emergency Information
for Critical Trauma Care, Burns, Compartment Syndrome, W ounds, Head and Spine (Emergency W ar
Surgery Series), 2012, Progressive Management (March 19, 2012). p. 488.
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5. Okumura, T., et al., Report on 640 victims of the Tokyo subway sarin attack. Ann Emerg Med, 1996.
28(2): p. 129-35.
6. Moszynski, P., Extreme weather affects half a billion people each year. BMJ, 2007. 335(7615): p. 321.
7. Dara, S.I. and J.C. Farmer, Preparedness lessons from modern disasters and wars. Crit Care Clin, 2009.
25(1): p. 47-65, vii.
8. P Hoyois, J.-M.S., R Below, D Guha-Sapir A nnual Disaster Statistical Review: Numbers and Trends, 2007:
Belgium.
9. Hubmayr, R.D. and J.C. Farmer, Should we "rescue" patients with 2009 influenza A (H1N1) and lung
injury from conventional mechanical ventilation? Chest, 2010. 137(4): p. 745-7.
10. Threats, I.P.S.S.f.P.R.t.R.a.N., Planning Guidance for Response to a Nuclear Detonation, H. Security,
Editor 2009: Washington DC.
11. Zoroya, G., IEDs contribute to increase in multiple amputations, in USA Today2012.
12. Holcomb, J.B., et al., Damage control resuscitation: directly addressing the early coagulopathy of trauma. J
Trauma, 2007. 62(2): p. 307-10.
13. Borgman, M.A., et al., The ratio of blood products transfused affects mortality in patients receiving
massive transfusions at a combat support hospital. J Trauma, 2007. 63(4): p. 805-13.
DISCLOSURE
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The Metabolic Syndrome: Tightening the Belt on Perioperative Risk

Judy R. Kersten, M.D. Milwaukee, Wisconsin
Objectives:
1) Describe the metabolic syndrome and how it contributes to increased perioperative risk
2) Identify strategies to decrease risk in patients with the metabolic syndrome presenting for anesthesia and
surgery
Diabetes Mellitus currently afflicts over 17 million people in the United States and the prevalence of this
disease is projected to increase by nearly 200% over the next several decades. Ninety percent of individuals
diagnosed with diabetes have Type 2. disease and 47 million more Americans have the Metabolic Syndrome. The
Metabolic Syndrome is a constellation of risk factors including increased abdominal adiposity, elevated
triglycerides, low HDL cholesterol, hypertension, and increased fasting blood glucose concentration that markedly
increases the risk for developing diabetes and cardiovascular disease. A prominent feature of the Metabolic
Syndrome is the progression of insulin resistance to frank diabetes and the parallel development of endothelial
dysfunction and atherosclerosis that culminate in cardiovascular morbidity and mortality.1 Visceral fat initiates this
deleterious sequence of events through the release of adipokines that increase free fatty acid concentrations. Free
fatty acids induce both insulin resistance and endothelial dysfunction. Stimulation of tumor necrosis factor alpha
(TNFa) also decreases insulin sensitivity and together with increases in C reactive protein (CRP) these mediators
incite vascular inflammation.
Several pharmacological agents may modify cardiovascular risk in individuals with the Metabolic
Syndrome. Thiazolidinediones, or “glitazones”, are a class of insulin sensitizing agents that bind and activate
peroxisome proliferator-activated receptors (PPAR) gamma in adipocytes, vascular smooth muscle and endothelial
cells. Activation of these nuclear receptors alters gene expression, reverses the major defect in insulin resistance,
and attenuates the development of atherosclerotic heart disease by modulating lipid metabolism, decreasing
inflammatory mediators and reducing arterial blood pressure.2 In experimental models of coronary artery occlusion
and reperfusion, PPARγ activators rosiglitazone, ciglitazone and pioglitazone decreased myocardial infarct size and
enhanced recovery of contractile function independently of changes in blood glucose, triglyceride or insulin
concentrations. However, a meta analysis of 42 randomized clinical trials indicated that rosiglitazone increased the
risk of myocardial infarction and death from cardiovascular causes compared to a control group that did not receive
this drug.3 The mechanism for this deleterious effect was not clear, but may have been related to an increased risk
of congestive heart failure and increases in LDL-cholesterol in patients taking this thiazolidinedione. The safety or
benefit of these agents during the perioperative period is unknown.
The biguanide metformin favorably modifies insulin sensitivity and partially reverses abnormalities in lipid
metabolism and inflammatory mediator activation in patients with the Metabolic Syndrome. The mechanism by
which metformin produces these beneficial effects is unclear, but favorable alterations in mitochondrial oxidative
processes and correction of intracellular calcium handling appear to be involved. In the UKPDS 34 clinical trial,4
patients with newly diagnosed type 2 diabetes were randomized to receive metformin, a sulfonylurea, or diet control
alone. Over 10 years of follow-up, patients treated with metformin demonstrated 39 and 42% decreases in MI and
death, respectively, as compared to those treated with diet control. Despite these impressive data, the utility of
metformin to decrease cardiovascular risk acutely in the perioperative setting is unknown. Hypotension and
decreases in renal perfusion during general anesthesia could predispose patients taking metformin to the
development of lactic acidosis. However, in a retrospective analysis of 1284 diabetic patients undergoing cardiac
surgery, metformin-treated patients demonstrated decreases in morbidity compared to untreated patients, and no
differences in lactic acid were observed between groups.5
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Sulfonlyurea drugs effectively decrease hyperglycemia but they do not modulate other components of the
Metabolic Syndrome and they may have deleterious effects on cardioprotective signal transduction.6 Ischemic and
anesthetic preconditioning protects against myocardial ischemic injury in animal models and in humans, and this
process depends on activation of adenosine triphosphate-regulated potassium (KATP) channels. Sulfonylurea drugs
stimulate insulin release by closing KATP channels in the beta cells of the pancreas. They also block myocardial
KATP channels and the beneficial effects of ischemic and anesthetic preconditioning. Although the actions of
sulfonylureas to increase cardiac risk remains a controversial topic, discontinuing sulfonylurea drugs 24-48 hrs
before elective surgery is recommended.
Hyperglycemia is an independent predictor of cardiovascular risk. However, the potential benefit of

aggressive perioperative control of blood glucose concentrations in patients with or without diabetes is controversial.
Poor intraoperative control of blood glucose concentration (4 consecutive measurements exceeding 200mg/dl)
increased the risk of severe morbidity by seven-fold.7 Increased variability of blood glucose concentrations was also
predictive of increased ICU and hospital mortality in critically ill patients.8 Although uncertain, moderate but not
aggressive control of blood glucose concentration in the perioperative period may reduce cardiovascular risk.
Finally, statins are an important class of drugs that decrease cardiovascular morbidity and mortality,
produce favorable actions on lipid metabolism, enhance nitric oxide-mediated pathways, reduce inflammatory
pathways, and produce direct cardioprotective effects. The results of a meta-analysis by Hindler et al highlight the
potential for statin therapy to positively impact cardiovascular risk reduction in patients undergoing cardiac and non-
cardiac surgery.9 Although there remains a small risk of rhabdomyolysis in patients in whom statins are continued
in the perioperative period, mortality rate may be substantially increased in patients in whom statins are
withdrawn.10,11 Thus, patients who are chronically treated with statins should continue to receive these drugs
perioperatively.12
References
1. Hsueh WA, Law R: The central role of fat and effect of peroxisome proliferator-activated receptor-gamma on
progression of insulin resistance and cardiovascular disease. Am J Cardiol 2003; 92:3J-9J
2. Plutzky J: The potential role of peroxisome proliferator-activated receptors on inflammation in type 2 diabetes
mellitus and atherosclerosis. Am J Cardiol 2003; 92:34J-41J
3. Nissen SE, Wolski K: Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular
causes. N Engl J Med 2007; 356:2457-71
4. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2
diabetes (UKPDS 34). UK Prospective Diabetes Study (UKPDS) Group. Lancet 1998; 352:854-65
5. Duncan AI, Koch CG, Xu M, Manlapaz M, Batdorf B, Pitas G, Starr N: Recent metformin ingestion does not
increase in-hospital morbidity or mortality after cardiac surgery. Anesth Analg 2007; 104:42-50
6. Gu W, Pagel PS, Warltier DC, Kersten JR: Modifying cardiovascular risk in diabetes mellitus. Anesthesiology
2003; 98:774-9
7. Ouattara A, Lecomte P, Le Manach Y, Landi M, Jacqueminet S, Platonov I, Bonnet N, Riou B, Coriat P: Poor
intraoperative blood glucose control is associated with a worsened hospital outcome after cardiac surgery in diabetic
patients. Anesthesiology 2005; 103:687-94
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8. Egi M, Bellomo R, Stachowski E, French CJ, Hart G: Variability of blood glucose concentration and short-term
mortality in critically ill patients. Anesthesiology 2006; 105:244-52
9. Hindler K, Shaw AD, Samuels J, Fulton S, Collard CD, Riedel B: Improved postoperative outcomes associated
with preoperative statin therapy. Anesthesiology 2006; 105:1289-90
10. Schouten O, Hoeks SE, Welten GM, Davignon J, Kastelein JJ, Vidakovic R, Feringa HH, Dunkelgrun M, van
Domburg RT, Bax JJ, Poldermans D: Effect of statin withdrawal on frequency of cardiac events after vascular
surgery. Am J Cardiol 2007; 100:316-20
11. Heeschen C, Hamm CW, Laufs U, Snapinn S, Bohm M, White HD: Withdrawal of statins increases event rates
in patients with acute coronary syndromes. Circulation 2002; 105:1446-52
12. Fleisher LA, Beckman JA, Brown KA, Calkins H, Chaikof E, Fleischmann KE, Freeman WK, Froehlich JB,
Kasper EK, Kersten JR, Riegel B, Robb JF, Smith Jr SC, Jacobs AK, Adams CD, Anderson JL, Antman EM, Buller
CE, Creager MA, Ettinger SM, Faxon DP, Fuster V, Halperin JL, Hiratzka LF, Hunt SA, Lytle BW, Nishimura R,
Ornato JP, Page RL, Tarkington LG, Yancy CW. ACC/AHA 2007 guidelines on perioperative cardiovascular
evaluation and care for noncardiac surgery: A report of the American College of Cardiology/American Heart
Association Task Force on Practice Guidelines. J Am Coll Cardiol 2007; 50:e159-e241
DISCLOSURE
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Perioperative Monitoring of Neuromuscular Function: Facts and Fallacies
Aaron F. Kopman, M.D. New York, New York
Lecture Outline and Selected References:
Historical perspective:
• Griffith HR, Johnson GE. The use of curare in general anesthesia. Anesthesiology 1942; 3:412-420
• Cullen SC. Clinical and laboratory observations on the use of curare during inhalation anesthesia.
• Morris LE, Schilling EA, Frederickson EL. The use of tensilon with curare and nitrous oxide anesthesia.
The First Nerve Stimulators and their use:
• Christie TH, Churchill-Davidson HC. The St. Thomas's hospital nerve stimulator in the diagnosis of prolonged
apnea. Lancet 1958; 1:776
• Cohen AD: A simple inexpensive nerve stimulator. Anaesthesia 1963;18:534
• Katz RL: A nerve stimulator for the continuous monitoring of muscle relaxant action. Anesthesiology 1965;
26:832-833
• Churchil-Davidson HC. The d-tubocurarine dilemma.. Anesthesiology 1965; 26:132-133 [Editorial]
• Churchill-Davidson HC. A portable peripheral nerve stimulator. Anesthesiology 1965; 26:224-226
• Evans D, Boyes HW. Experience with a portable peripheral nerve stimulator. Can Anaesth Soc J. 1966; 13:300-
302.
Recent Surveys of How Clinicians Monitor Neuromuscular Blockers:
• Fuchs-Buder T, Hofmockel R, Geldner G, et al. [The use of neuromuscular monitoring in Germany].
Anaesthesist. 2003;52:522-6.
• Grayling M, Sweeney BP. Recovery from neuromuscular blockade: a survey of practice. Anaesthesia. 2007;
62:806-9
• Naguib M, Kopman AF, Lien CA, et al. A survey of current neuromuscular practice in the United States and
Europe. Anesth Analg 2010; 111: 110-119
There is a “Town vs Gown” Disconnect
• Viby-Mogensen J. Postoperative residual curarization and evidence-based anaesthesia. Br J Anaesth 2000;
84:301-303 (Editorial)
• Eriksson LI. Evidence-based practice and neuromuscular monitoring: It's time for routine quantitative
assessment. Anesthesiology 2003; 98:1037-9. (Editorial)
Stimulating a Motor Nerve:
> Definition of supramaximal stimuli and the stimulus response relationship.
• Kopman AF, Lawson D. Milliamperage requirement for supramaximal stimulation of the ulnar nerve with
surface electrodes. Anesthesiology 1984; 61:83-85
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• Mylrea KC, Hameroff SR, Calkins JM, et al. Evaluation of peripheral nerve stimulators and relationship to
possible errors in assessing neuromuscular blockade. Anesthesiology 1984; 60:464-466
• Nepveu M, Donati F, Fortier L: Train-of-Four Stimulation for Adductor Pollicis Neuromuscular Monitoring Can
Be Applied at the Wrist or Over the Hand. Anesth Analg 2005;100:149-154
Choosing a Conventional Peripheral Nerve Stimulator:
> Constant voltage vs constant current devices. Personal recommendations
The train-of-four (TOF) ratio:
• Ali HH, Utting JE, Gray TC. Stimulus frequency in the detection of neuromuscular block in man. Br J Anaesth
1970; 42:967-978
• Ali HH, Utting JE, Gray TC. Quantitative assessment of residual antidepolarizing Block (Part 1). Br J Anaesth
1971; 43:473-477
• Lee C, Katz RL. Fade of neurally evoked compound electromyogram during neuromuscular block by d-
tubocurarine. Anesth Analg 1977; 56:271-275
Clinical Correlates of the train-of-four. How do we define satisfactory neuromuscular recovery?
• Ali HH, Wilson RS, Savarese JJ, Kitz RJ. The effect of d-tubocurarine on indirectly elicited train-of-four muscle
response and respiratory measurements in humans. Br J Anaesth 1975; 47:570-574
• Kopman AF, Yee PS, Neuman GG. Correlation of the train-of-four fade ratio with clinical signs and symptoms
of residual curarization in awake volunteers. Anesthesiology 1997; 86:765-71
• Eriksson LI, Sundman E, Olsson R, et al. Functional assessment of the pharynx at rest and during swallowing in
partially paralyzed humans. Simultaneous videomanometry and mechanomyography of awake human volunteers.
• Eriksson LI, Sato M, Severinghaus JW. Effect of a vecuronium-induced partial neuromuscular block on hypoxic
ventilatory response. Anesthesiology 1993; 78:693-699
• Heier T, Caldwell JE, Feiner JR, et al. Relationship between Normalized Adductor Pollicis Train-of-four Ratio
and Manifestations of Residual Neuromuscular Block: A Study Using Acceleromyography during Near Steady-
state Concentrations of Mivacurium. Anesthesiology 2010; 113:825-32
Clinical Tests of Neuromuscular Recovery:
• Beemer GH, Rozental P. Postoperative neuromuscular function. Anaesth Intens Care 1986; 14:41-45
• Ali HH, Utting JE, Gray TC. Quantitative assessment of residual antidepolarizing Block (Part II). Br J Anaesth
1971; 43:478-485
• Dupuis JY, Martin R, Tétrault JP. Clinical, electrical and mechanical correlations during recovery from
neuromuscular blockade with vecuronium. Canad J Anaesth 1990; 37:192-196
• Sharpe MD, Lam AM, Nicholas FJ, et al. Correlation between integrated evoked EMG and respiratory function
following atracurium administration in unanaesthetized humans. Can J Anaesth 1990; 37:307-312
Subjective Evaluation of the TOF Ratio
• Viby-Mogensen J, Jensen NH, Engbaek J, et al. Tactile and visual evaluation of the response to train-of-four
nerve stimulation. Anesthesiology 1985; 63:440-3
Double-burst stimulation
• Engæk J, Østergaard D, Viby-Mogensen J. Double burst stimulation (DBS): a new pattern of nerve stimulation
to identify residual neuromuscular block. Br J Anaesth 1989; 62:274-278
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• Ueda N, Muteki T, Tsuda H, et al: Is the diagnosis of significant residual neuromuscular blockade improved by
using double burst nerve stimulation? Eur J Anaesthiol 1991; 8:213-218
50 and 100 Hz tetanic Stimuli
• Baurain MJ, et al. Comparison between double-busrt stimulation and 50, 100 Hz tetanic fade during spontaneous
recovery of vecuronium induced neuromuscular blockade. Br J Anaesth 1993; 70, Suppliment 1, A.133
The Train-of-four Count
• Kopman AF. Tactile evaluation of train-of-four count as an indicator of reliability of antagonism from
vecuronium or atracurium-induced neuromuscular blockade. Anesthesiology 1991; 75:588-593
• Lee CM. Train-of-four quantitation of competitive neuromuscular block. Anesth Analg 1975; 54:649-653
The Post-Tetanic Count
• Viby-Mogensen J, Howardy-Hansen P, Chræmmer-Jorgensen B, Ørding H, Engbæk J, Nielsen A. Posttetanic
Count (PTC): a new method of evaluating an intense nondepolarizing block. Anesthesiology 1981; 55:458-461
Limitations of Cholinesterase Inhibitors as Reversal Agents
• Beemer GH, Bjorksten AR, Dawson PJ, et al. Determinants of the reversal time of competitive neuromuscular
block by anticholinesterases. Br J Anaesth 1991; 66:469-475
• Beemer GH, Goonetilleke PH, Bjorksten AR. The maximum depth of an atracurium neuromuscular block
antagonized by edrophonium to effect adequate recovery. Anesthesiology 1995; 82:852-858
Quantitative Monitoring of Neuromuscular block: Mechanomyography (MMG),
Electromyography (EMG), Acceleromyography (AMG), Kinemyography (KMG). Advantages and
Limitations
What muscles should be Monitored: Hazards of using the facial muscles.
• Caffrey RR, Warren ML, Becker KE. Neuromuscular blockade monitoring comparing the orbicularis oculi and
adductor pollicis muscles. Anesthesiology 1986; 65:95-97
• Larsen PB, Gatke MR, Fredensborg BB, et al. Acceleromyography of the orbicularis oculi muscle II: comparing
the orbicularis oculi and adductor pollicis muscles. Acta Anaesthesiol Scand 2002; 46:1131-6
How common is post-operative residual neuromuscular block?
• Viby-Mogensen J, Jorgensen BC, Ørding H. Residual curarization in the recovery room. Anesthesiology 1979;
50:539-541
• Bevan DR, Smith CE, Donati F. Postoperative neuromuscular blockade: a comparison between atracurium,
vecuronium, and pancuronium. Anesthesiology 1988; 69:272-276
• Hayes AH, et al. Postoperative residual block after intermediate-acting neuromuscular blocking drugs.
Anaesthesia 2001; 56:312-318
• Debaene B, et al. Residual Paralysis in the PACU after a Single Intubating Dose of Nondepolarizing Muscle
Relaxant with an Intermediate Duration of Action Anesthesiology 2003; 98:1042-1048
• Yip PC, Hannam JA, Cameron AJ, Campbell D. Incidence of residual neuromuscular blockade in a post-
anaesthetic care unit. Anaesth Intensive Care. 2010; 38:91-5.
Does undetected residual neuromuscular block have clinical consequences?
• Murphy GS, Szokol JW, Marymount JH, Greenberg SB, Avram MJ, VenderJS. Residual Neuromuscular
Blockade and Critical Respiratory Events in the Post-anesthesia Care Unit . Anesth Analg 2008; 107:130-137
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• Sauer M, Stahn A, Soltesz S, Noeldge-Schomburg G, Mencke T. The influence of residual neuromuscular block
on the incidence of critical respiratory events. A randomized, prospective, placebo-controlled trial. Eur J
Anaesthesiol. 2011; 28:842-8
• Butterly A, Bittner EA, George E, Sandberg WS, Eikermann M, Schmidt U. Postoperative residual curarization
from intermediate-acting neuromuscular blocking agents delays recovery room discharge. Br J Anaesth 2010;
105:304-9
• Arbous MS, Meursing A, van Kleef JW, de Lange JJ, Spoormans H, Touw P, Werner FM, Grobbee DE. Impact
of Anesthesia Management Characteristics on Severe Morbidity and Mortality. Anesthesiology 2005; 102:257-
268
• Berg H, Viby-Mogensen J, Roed J, Mortensen CR, Engbaek J, Skovgaard LT, Krintel JJ. Residual
neuromuscular block is a risk factor for postoperative pulmonary complications. Acta Anaesthesiol Scand 1997;
41:1095-1103
Final Issues for Discussion:
> Is objective monitoring of intraoperative neuromuscular function always necessary?
> Is it always mandatory to reverse residual nondepolarizing block?
> Is undetected residual block a frequent occurrence in your hospital?
Other Recent Manuscripts of Particular Relevance
• Plaud B, Debaene B, Donati F, Marty J. Residual Paralysis after emergence from anesthesia. Anesthesiology
2010; 112:1013-22. REVIEW
• Murphy GS, Brull SJ. Residual neuromuscular block: Lessons unlearned Part I: Definitions, incidence, and
adverse physiologic effects of residual neuromuscular block. Anesth Analg. 2010; 111:120-128. REVIEW
• Brull SJ, Murphy GS. Residual neuromuscular block: Lessons unlearned. Part II. Methods to reduce
the risk of residual weakness. Anesth Analg. 2010; 111:129-140 REVIEW
• Kopman AF. Managing neuromuscular block: Where are the guidelines? Anesth Analg 2010; 111:9-10
(Editorial)
• Donati F. Neuromuscular monitoring: What evidence do we need to be convinced. Anesth Analg 2010; 111:6-7
(Editorial)
• Viby-Mogensen J, Claudius C. Evidence-based management of neuromuscular block. Anesth Analg 2010;
111:1-2 (Editorial)
• Miller RD, Ward TA. Monitoring and pharmacologic reversal of a nondepolarizing neuromuscular blockade
should be routine. Anesth Analg 2010; 111:3-5 (Editorial)
• Murphy, GS, Szokol JW, Avram, MJ, et al. Intraoperative Acceleromyography Monitoring Reduces Symptoms
of Muscle Weakness and Improves Quality of Recovery in the Early Postoperative Period. Anesthesiology 2011;
115:946-54
DISCLOSURE
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Renal Anatomy and Physiology

Jerome F. O’Hara Jr., M.D. Cleveland, Ooio

Objectives:
1)Experience an overview of renal anatomy and physiology
2)Understand the effects of mannitol on renal function
3)Differentiate among new surgical TURP techniques and how they impact anesthetic management and patient
outcomes
Renal Anatomy
The kidneys and ureters are located in the retroperitoneal space at the level of the L2 vertebral body. Renal anatomy
is composed of the renal cortex, medulla, and renal pelvis, which drain urine into the ureter. Sympathetic fibers
conduct renal pain sensation to spinal cord segments T10–L1. Preganglionic fibers from T8–L1 provide sympathetic
innervation to the kidney, and the vagus nerve provides parasympathetic innervation. The microscopic functional
unit of the kidney is the nephron, which serves secretory and regulatory functions. Each nephron consists of:
•Glomerulus: the capillary network that filters the blood coming from the afferent arteriole. This blood is then
drained into the efferent arteriole. The glomerular filtration rate (GFR) and ultrafiltrate are determined by changes
in the tone of these two vessels. A molecule can cross from plasma to the tubular fluid only by passing successively
through the fenestrated capillary endothelium, the glomerular basement membrane, and the epithelial slit diaphragm.
Molecular size and charge govern this process..
•Bowman’s capsule: the cup-like sac at the beginning of the renal tubular system; it surrounds the glomerulus of
each nephron and receives ultrafiltrate.
•Proximal convoluted tubule (PCT): a tubule in which most of the ultrafiltrate and solutes are reabsorbed back into
circulation. The systemic transport of almost all substances (glucose, amino acids, phosphate, lactate, etc) is sodium-
coupled. The sodium-potassium-adenosine triphosphatase (Na-K-ATPase) system is the most important protein-
based active transport system. In the proximal convoluted tubule (PCT) about 65% of filtered sodium is actively
reabsorbed, after which water is passively absorbed.
•Loop of Henle: also called the nephron loop. It is composed of thin and thick portions. The thick portion, relatively
impermeable to water, contains very active metabolic cells (mTAL) which, during periods of renal hypoperfusion,
are susceptible to ischemic injury
•Distal convoluted tubule (DCT) and collecting duct: The anti-diuretic hormone (ADH) along with aldosterone
regulate ion exchange and the reabsorption of water back into the circulation.
•Juxtaglomerular apparatus: the microscopic structure which aids in regulating renal blood flow (RBF) and GFR.
When chloride ion delivery to the juxtaglomerular apparatus decreases, renin is released from the macula densa.
Renin activates the formation of angiotensin and angiotensin II. These in turn increase RBF and GFR (by changing
the tone of afferent and efferent arterioles) and release aldosterone.
•Vasa recta: capillaries that originate from the efferent arteriole of juxtamedullary nephrons. They descend deep into
the medulla, parelleling with the loops of Henle, then return in a cortical direction with the loops to join other
peritubular capillaries, which empty into cortical veins. They are the most important structures in the countercurrent
exchange mechanism.
There are two types of nephrons: cortical and juxtamedullary.
Cortical, comprising the majority of the nephrons, are located only in the renal cortex, and have an abundant blood
supply.
Juxtamedullary: their glomerulus and PCT are located in the renal cortex. The loop of Henle descends deep into the
renal medulla. These nephrons maintain the high osmolarity (countercurrent exchange) of the renal medulla and
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promote the kidney’s ability to concentrate the urine. They receive only 5% of total RBF and extract 80% of oxygen
compared to 20% in the cortex; their blood supply is therefore precarious. Because of the ratio of high oxygen
consumption to supply, mTAL cells which are metabolically very active are susceptible to ischemic injury during
renal hypoperfusion.
Renal Physiology
The kidneys play a crucial role in maintaining extracellular volume and composition constant, and in the excretion
of waste substances. They enable large amounts of fluid and solutes to be filtered from the blood, waste products to
be excreted in the form of urine, and necessary substances to be reabsorbed into the circulation. Kidneys receive
about 20% of systemic cardiac output, which means 180 liters per day of glomerular ultrafiltrate. Nearly 100% of
this ultrafiltrate is reabsorbed into systemic circulation, which results in 1 to 2 liters of urine being produced daily.
Filtration
GFR, a measure of glomerular function, is expressed as milliliters of filtrate per minute. GFR stems, on the one
hand, from the glomerular membrane’s facilitation of filtration (i.e. glomerular permeability and surface area) and,
on the other, from the pressure inside the glomerular capillary, which forces fluid through the filter.
GFR depends on the following factors:
•The ultrafiltration constant (Kf) is determined by the surface area and permeability of the glomerular capillaries.
•Glomerular filtration pressure depends on capillary pressure (PGC) and glomerular oncotic pressure (πGC). PGC is
determined mainly by renal artery pressure, but is also influenced by arteriolar tone at points upstream (afferent)
and downstream (efferent) from the glomerulus. When afferent arteriolar tone increases, filtration pressure and GFR
fall. Conversely, an increase in efferent arteriolar tone tends to increase filtration pressure and GFR. The πGC is
directly dependent on plasma oncotic pressure.
Autoregulation of Renal Blood Flow and Glomerular Filtration Rate
In healthy subjects, GFR is preserved by maintaining a constant RBF over the wide range of systemic blood pressure
of MAP 50 to 150 mmHg. However, in hypertensive patients, the range of MAP is higher when RBF is constant.
Renal autoregulation comes about through local feedback signals that modulate glomerular arteriolar tone.
Two mechanisms are believed to enable autoregulation:
•Myogenic mechanism: An increase in arterial pressure causes the afferent arteriolar wall to stretch, then through
reflex to constrict. Conversely, a decrease in arterial pressure causes arteriolar dilatation.
•Tubuloglomerular feedback: It is achieved by the juxtaglomerular apparatus. A decrease in RBF results in a
concomitant decrease in GFR, and signals the afferent arteriole to dilate. Glomerular flow and pressure will then
increase in an attempt to restore GFR to previous levels. A decrease in GFR triggers release of renin, which results
in formation of angiotensin II. In response to angiotensin II efferent arteriolar constriction occurs to increase
glomerular pressure, which in turn increases GFR. Simultaneous afferent arteriolar dilatation and efferent arteriolar
constriction allow glomerular flow and filtration to increase.
Reabsorption of Sodium and Water
The reabsorption of sodium begins almost immediately as ultrafiltrate enters the PCT, where ~65% of sodium is
reabsorbed. Cells of the mTAL are metabolically active as they reabsorb sodium and chloride. Sodium pumps in the
DCT and collecting duct are unique in that they are controlled by aldosterone.
Reabsorption of water is passive and osmotically driven, and tied to sodium and other solute reabsorption occuring
mainly in the PCT. Approximately 20% of the ultrafiltrate flows into the DCT and collecting duct where the
antidiuretic hormone (ADH) secreted by the pituitary gland controls water reabsorption. Production of concentrated
urine depends on the degree of water permeability of the DCT and collecting duct in response to physiologic needs.
When released in large amounts, such as occurs during the physiologic stress response to trauma, surgery, or critical
illness, ADH causes renal cortical vasoconstriction, which in turn induces a shift of RBF to the hypoxia-prone renal
medulla.
Renin-Angiotensin-Aldosterone System
Renin-angiotensin activity plays an important role in regulating RBF and GFR. The release of renin by the macula
densa may be triggered by hypotension, decreased tubular fluid chloride ion concentration, or sympathetic
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stimulation. It enhances the production of angiotensin II, which induces renal efferent arteriolar vasoconstriction
and afferent arteriole vasodilatation. Angiotensin II also promotes the release of ADH from the posterior pituitary,
the reabsorption of sodium, and the release of aldosterone by the adrenal medulla. Aldosterone, in turn, stimulates
the DCT and collecting duct to actively reabsorb sodium (and water); this reabsorption causes intravascular volume
to increase. Stimulation of the sympathetic nervous system may also cause release of aldosterone directly. During
stress the above mechanisms are activated, leading to renal cortical vasoconstriction, a shift in RBF to salt-and-
water–conserving juxtamedullary nephrons, a decrease in GFR, and retention of salt and water.
The sympathetic nervous system responds to stress by releasing epinephrine and norepinephrine, both of which
profoundly affects renal physiology. The action of norepinephrine resembles that of angiotensin II in that it shifts
blood flow from the cortex to the renal medulla and increases reabsorption of sodium and water, resulting in
decreased urine output. Norepinephrine also activates the renin-angiotensin-aldosterone axis as well as the release
of ADH from the pituitary gland. Moderate stimulation of the sympathetic system does not decrease GFR; however,
a more intense stress response may induce a decrease in RBF and GFR by causing afferent arteriolar constriction. If
this extreme condition is not reversed, ischemic damage to the kidney may result, and acute renal failure (ARF) may
manifest clinically. Activation of the renin-angiotensin-aldosterone axis is very important for the preservation of
intravascular volume, and it provides vital organ perfusion during stress.
The posterior pituitary releases ADH in response to an increase in either extracellular sodium concentration or
extracellular osmolality. The arterial baroreceptors are activated when hypovolemia leads to a lowering of blood
pressure, whereas atrial receptors are stimulated by a reduction in atrial filling pressure. Both of these circulatory
reflex systems stimulate release of ADH from the pituitary and cause retention of water by the kidney in an effort to
return the intravascular volume toward normal.
The description above recapitulates several sections of the chapter, “The renal system and anesthesia for urologic
surgery,” by O’Hara JF Jr., Cywinski JB, and Monk TG, in: Barash PG, Cullen BF, and Stoelting R, eds. Clinical
Anesthesia, 5th ed.. Philadelphia: Lippincott Williams & Wilkins, 2006.
Mannitol and Renal Function
Mannitol given at 1.0 gm/kg over 45 minutes in surgical patients demonstrated by transesophageal
echocardiography, a significant but short-duration alteration in left ventricular preload (↑), afterload (↓), and cardiac
output (↑) without concomitant changes in mean arterial pressure or heart rate.
Chatterjee N, Koshy T, Misra S, Suparna B. Changes in left ventricular preload, afterload, and cardiac output in
response to a single dose of mannitol in neurosurgical patients undergoing craniotomy: a transesophageal
echocardiographic study. J Neurosurg Anesthesiol. 2012; 24(1):25-9.PMID: 21959682
The renal effect of mannitol has been attributed to its osmotic action, expansion of extracellular fluid volume,
increased medullary blood flow, and a greater "washout" of solutes and hence diuresis.
Stahl WM. Effect of mannitol on the kidney: changes in intrarenal hemodynamics. N Engl J Med 1965; 272:381-6.
Mannitol as a renal preservation therapy for prophylaxis or treatment of ARF remains controversial. In a recent
study, Redfors and colleagues summarized the effect and current clinical status of the use of mannitol in renal
therapy. It is presented in part below:
Mannitol is a “diuretic agent which has been used in the perioperative setting in the belief that it exerts
renoprotective properties. It is freely filterable in the glomeruli and due to its limited reabsorption it creates an
osmotic force in the tubuli, sufficient to inhibit the reabsorption of fluids and solutes along the nephron. It has been
shown in renal transplant patients, that mannitol given to a hydrated recipient just before renal artery cross-clamp
removal, reduces the incidence of ARF after cadaveric kidney transplantation…. However, several small
randomised controlled trials have found no reduction in the incidence of ARF with mannitol over hydration in a
variety of conditions including cardiac surgery, traumatic rhabdomyolysis and vascular and biliary tract surgery. On
the contrary, it has been suggested that high doses of mannitol may even cause ARF.”
“Most animal studies have shown that mannitol increases RBF by renal vasodilation both during normotensive and
hypotensive conditions. It has been suggested that the mannitol-induced renal vasodilatory response to experimental
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renal ischaemia is mediated directly by increased synthesis of prostacyclin, or indirectly by augmenting plasma
levels of ANP due to plasma volume expansion.”
“Reports on the effects of mannitol on GFR are conflicting. Animal data have shown that mannitol decreases,
increases or has no effect on GFR. In normal volunteers, mannitol does not seem to affect GFR. However,
experimental data have shown that in hypoperfused kidneys, mannitol infusion tends to restore
GFR towards normal levels both when given prior to and after the hypotension has been induced. [Flores and
colleagues, in J Clin Invest 1972; 51:118-126] suggested that mannitol maintains GFR in renal ischaemia primarily
by an osmotic effect to reduce vascular endothelial cell swelling. Another mechanism could be that mannitol
prevents/decreases ischaemia-induced swelling of tubular cells which might obstruct tubular lumen. Mannitol might,
in this situation, open up collapsed tubular segments which will increase tubular flow and restore GFR.”
Redfors B, Swärd K, Sellgren J, Ricksten SE. Effects of mannitol alone and mannitol plus furosemide on renal
oxygen consumption, blood flow and glomerular filtration after cardiac surgery. Intensive Care Med 2009; 35:115-
22.
As previously mentioned, mannitol has the potential to precipitate renal dysfunction. Dickenmann and colleagues
reviewed the topic of osmotic nephrosis. The findings are presented in part below.
“Osmotic nephrosis describes a morphological pattern with vacuolization and swelling of the renal proximal tubular
cells. The term refers to a nonspecific histopathologic finding rather than defining a specific entity. Osmotic
nephrosis can be induced by many different compounds, such as sucrose, hydroxyethyl starch, dextrans, and contrast
media.”
“In the 1960s, studies in rats, rabbits, and dogs showed osmotic nephrosis of the proximal tubules after treatment
with mannitol. The degree of vacuolization was related to the amount of infused mannitol. Furosemide had a
synergistic role in the development of osmotic nephrosis when both agents were used together. Simultaneous
cyclosporine and mannitol infusions in rats led to massive vacuolization of proximal tubular epithelia, but when
each substance was infused alone in the same dose, it did not induce histological changes. This finding, later also
observed in humans, emphasizes the importance of concomitant nephrotoxic factors in the development of osmotic
nephrosis. The infusion rate of mannitol, total applied dose, and resulting osmolal gap (difference between measured
plasma osmolality and calculated plasma osmolality) have an important role in the pathogenesis of osmotic
nephrosis. Such conditions as advanced age and preexisting kidney failure, in which the maximal rate of renal
excretion is decreased, are predisposing factors…. Based on reviewed studies the following conclusions concerning
the risk of mannitol-induced osmotic nephrosis were drawn: (1) acute kidney injury in patients with normal baseline
kidney function usually develops when the total mannitol dose exceeds 1,100 g; (2) in patients with preexisting
kidney disease, much smaller doses (~300 g) can precipitate kidney failure; (3) daily mannitol doses greater than
200 g resulting in an osmolal gap greater than 60 mOsm/kg are likely to cause acute kidney injury; and (4)
preexisting impaired kidney function, comedication with furosemide, and kidney transplantation (including therapy
with cyclosporine) are independent risk factors…. Treatment with hemodialysis in patients with established
mannitol-induced osmotic nephrosis leads to accelerated removal of mannitol from the extracellular space and may
shorten the recovery time from acute kidney injury.”
Dickenmann M, Oettl T, Mihatsch MJ. Osmotic nephrosis: acute kidney injury with accumulation of proximal
tubular lysosomes due to administration of exogenous solutes. Am J Kidney Dis 2008; 51:491-503. Review.
PMID: 18295066 [PubMed – indexed for MEDLINE]
A recent acute kidney injury review evaluating clinical evidence of renal preservation therapies found that mannitol
was “unlikely to be beneficial”.
Kellum JA, Unruh ML, Murugan R. Acute kidney injury. Clin Evid (online) March 28, 2011.
PMID: 21443811 [PubMed – in process], as of May 27, 2011.
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The following is a 2011 description of mannitol indications and description of renal effects. Source:
www.rxlist.com/mannitol_iv-drug.htm Copyright © 2011 by RxList Inc. Accessed May 27, 2011
Mannitol
(mannitol) Injection, Solution
DRUG DESCRIPTION
Mannitol I.V. (Mannitol Injection, USP) is a sterile, nonpyrogenic solution of mannitol in water for injection
available in concentrations of 5%, 10%, 15%, 20% for administration by intravenous infusion only.
Mannitol IV Indications & Dosage
INDICATIONS
Mannitol I.V. (Mannitol Injection, USP) is indicated for the following purposes in adults and pediatric patients.
Therapeutic Use
1.Promotion of diuresis in the prevention or treatment of the oliguric phase of acute renal failure before irreversible
renal failure becomes established
2.Reduction of intracranial pressure and brain mass.
3.Reduction of high intraocular pressure when the pressure cannot be lowered by other means.
4.Promotion of urinary excretion of toxic materials.
Diagnostic Use
Measurement of glomerular filtration rate.
DOSAGE AND ADMINISTRATION
The usual adult dosage ranges from 50 to 200 g in a 24-hour period, but in most instances an adequate response will
be achieved at a dosage of approximately 100 g/24 hours. The rate of administration is usually adjusted to maintain
a urine flow of at least 30 to 50 mL/hr. The total dose should be adjusted according to the clinical response and
adverse events.
Prevention of Acute Renal Failure (Oliguria): When used during cardiovascular or other types of surgery, 50 to 100
g of mannitol may be given.
Treatment of Oliguria: The usual dose to promote diuresis in oliguric patients: Adults, 300 to 400 mg/kg of body
weight (21 to 28 g for a 70 kg patient) or up to 100 g of solution, given as a single dose (often in conjunction with
furosemide); pediatric patients, 0.25 to 2 g/kg body weight over a period of 2 to 6 hours. Doses should not be
repeated in patients with persistent oliguria.
Measurement of Glomerular Filtration Rate (GFR): 100 mL of a 20% solution (20 g) should be diluted with 180 mL
of sodium chloride injection (normal saline) or 200 mL of a 10% solution (20 g) should be diluted with 80 mL of
sodium chloride injection (normal saline). The resulting 280 mL of 7.2% solution is infused at a rate of 20 mL per
minute. The urine is collected by catheter for a specific period of time and analyzed for mannitol excreted in mg per
minute. A blood sample is drawn at the start and at the end of the time period and the concentration of mannitol
determined in mg/mL of plasma. GFR is the number of mL of plasma that must have been filtered to account for the
amount excreted per minute in the urine. Normal clearance rates are approximately 125 mL/minute for men; 116
mL/minute for women.
Mannitol IV Warnings
WARNINGS INCLUDE
1.The obligatory diuretic response following rapid infusion of 25% mannitol may further aggravate pre-existing
hemoconcentration. Excessive loss of water and electrolytes may lead to serious imbalances. Serum sodium and
potassium should be carefully monitored during mannitol administration.
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2.If urine output continues to decline during mannitol infusion, the patient's clinical status should be closely
reviewed and mannitol infusion suspended if necessary. Accumulation of mannitol may result in overexpansion of
the extracellular fluid which may intensify existing or latent congestive heart failure.
3.Excessive loss of water and electrolytes may lead to serious imbalances. With continued administration of
mannitol, loss of water in excess of electrolytes can cause hypernatremia. Electrolyte measurements, including
sodium and potassium are therefore of vital importance in monitoring the infusion of mannitol.
4.Osmotic nephrosis, a reversible vacuolization of the tubules of no known clinical significance, may proceed to
severe irreversible nephrosis, so that the renal function must be closely monitored during mannitol infusion.
Mannitol IV Clinical Pharmacology
CLINICAL PHARMACOLOGY
When administered intravenously mannitol is confined to the extracellular space, only slightly metabolized and
rapidly excreted by the kidney. Approximately 80% of a 100 g dose appears in the urine in 3 hours. The drug is
freely filtered by the glomeruli with less than 10% tubular reabsorption; it is not secreted by tubular cells. Mannitol
induces diuresis by elevating the osmolarity of the glomerular filtrate and thereby hindering tubular reabsorption of
water. Excretion of sodium and chloride is also enhanced.
New Surgical TURP Techniques
Introduction
In males presenting with symptomatic benign prostatic hypertrophy (BPH) the surgeon’s goal is to resect as much
prostatic tissue as possible while preserving the prostatic capsule. Complications occur when surgical resection of
the rich plexus of prostatic veins is opened. This creates a conduit for bleeding and for absorption of bladder
irrigating fluid when under pressure.As a result, bipolar electrode resection and prostate lasers are replacing
monopolar TURP as alternative surgical techniques for BPH resection.
Monopolar TURP
The conventional gold standard for TURP was the monopolar electrode resectoscope. With the monopolar electrode,
layers of prostatic tissue are resected with a cutting current transmitted through a single-limb electrode which exits
the patient by way of a grounding pad. A non-electrolyte bladder-irrigating solution is required to avoid dispersion
of the electrical current as well as tissue damage at the site of prostatic resection. TURP syndrome is a potentially
serious complication which can occur when a nonelectrolyte, hypoosmolar bladder-irrigating solution is used. The
severity of the complication depends on the amount of the intravascular bladder-irrigating solution that is absorbed
via prostatic veins opened during resection.
TURP Complications
Complications caused by TURP include dilutional hyponatremia, glycine toxicity, ammonia toxicity, bacteremia,
anemia, hypothermia, bladder perforation, bleeding, and coagulopathy. Factors related to the volume of irrigating
fluid absorption include the duration of resection and the height of the irrigating solution bag above the patient. The
ideal irrigation fluid for monopolar TURP would be isotonic, nonhemolytic, nontoxic, nonelectrolytic,
nonmetabolized, visually non-distorting, rapidly excreted, and inexpensive. However, since there is no ideal
bladder-irrigating fluid for monopolar TURP surgery, 1.5% glycine is used instead, as the standard solution. A
review of the pathophysiology and management of TURP syndrome in monopolar TURP reported that TURP
syndrome may present clinically as early as 15 minutes after resection begins or up to 24 hours postoperatively, with
intravascular rates reaching 200 ml/min of the bladder-irrigating flud [1].
Bipolar TURP
Bipolar TURP electrode technology incorporates a continuous loop electrode to resect prostatic tissue of BPH. This
surgical tool is designed to contain the inflow and outflow of current via the resectoscope for prostatic tissue
resection. By being completely self-contained within the bipolar unit, the current is prevented from passing through
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the patient. The advantage of this system is that for the bladder-irrigating solution, an electrolyte-containing
solution such as normal saline can be used. Although intravascular absorption of normal saline can occur via
resected prostatic veins opened during prostatic resection, hypoosmolality and hyponatremia associated with TURP
syndrome are prevented. Nevertheless, the risk of volume overload as a consequence of the bladder-irrigating
solution can still occur with the bipolar TURP technique.
In a review of 16 studies conducted over a 10-year period, Issa compared the safety properties of monopolar and
bipolar TURP [2]. He found a statistically significant decrease in overall complication rate, transfusion rate, and
TURP syndrome with bipolar TURP. A randomized outcome study by Chen and colleagues, in which monopolar
and bipolar TURP were compared, found that bipolar TURP was associated with significantly less fluid absorption,
less change in serum sodium and in hemoglobin, and comparable urologic efficacy in prostate symptom scores and
maximum urinary flows [3]. A more recent randomized study also concluded similar benefits in bipolar TURP with
the exception that irrigating fluid absorption was similar to monopolar when ethanol concentrations were measured
[4]. Two meta-analytic studies comparing monopolar and bipolar TURP also reported favorable outcomes in the
bipolar TURP groups [5,6].
Laser TURP
Laser TURP techniques produce a thin coagulation treatment zone (1—7 mm) during prostatic tissue resection
[7].This prevents excessive bleeding and intravascular absorption of bladder-irrigating fluid. In contrast to
monopolar and bipolar TURP techniques, which open prostatic veins, the thin coagulation treatment zone seals
them. As a result, bleeding and absorption of bladder irrigating fluid are minimized. Laser TURP is accordingly
advocated for use in anti-coagulated patients. Laser TURP can, however, require several hours, depending on the
size of the prostatic gland that is to be resected. Initially, sterile water was used as the bladder-irrigating fluid with
laser TURP, without significant hyponatremia occurring [8].Glycine as the bladder irrigating fluid is also acceptable.
Significant absorption of the bladder-irrigating fluid during laser TURP does not normally occur. At present, normal
saline is generally recommended as the bladder irrigating solution during laser TURP. Of interest is our clinical
experience, which suggests that deactivation of an automatic implantable cardioversion device is not routinely
needed during laser TURP.
In their review of the anesthetic implications of newer laser TURP techniques, Hanson and colleagues [9] found that
there was minimal absorption of bladder-irrigating fluid; that the techniques could be performed on anti-coagulated
patients; and that the techniques carried a lower risk of TURP syndrome. These findings placed less emphasis on
regional as the "preferred anesthetic technique". Other studies have suggested that laser TURP is feasible when anti-
coagulation therapy withdrawl was considered a significant patient risk perioperative [10,11].
Geavlete and colleagues [12] reported in a prospective randomized trial that in contrast to monopolar TURP, laser
TURP demonstrated significantly decreased operative times, a shorter catherization period, shorter hospital stay and
fewer complications. A meta-analysis comparing laser and monopolar TURP reported less clot retention and
incidence of TURP syndrome, comparable postoperative bleeding and a higher re-operation rate in the first year
postoperatively [6,12].
Overall mortality from TURP has steadily decreased: by 2.5% (in 1962), 1.3% (in 1974), 0.23% (in 1989), and
0.10% (in 2003) [13]. Smith and Patel published a recent review of the different surgical technigues for TURP and
compared between them safety/complications, advantages/disadvantages, and effectiveness/durability [14].
Conclusion
This session of urology/renal function provided an overview of renal anatomy and physiology. A discussion of the
effects of mannitol on renal function suggest that low-dose mannitol infusion acts as a renal vasodilator whereas
high-dose mannitol can cause ARF. Mannitol-induced ARF responds to hemodialysis therapy. Newer surgical
techniques such as bipolar and laser TURP have been developed to minimize the incidence of TURP syndrome.
These newer techniques are replacing monopolar TURP.
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References
1. Gravenstein D. Transurethral resection of the prostate (TURP) syndrome: a review of the
pathophysiology and management. Anesth Analg. 1997; 84(2):438-46. Review.
2. Issa MM. Technological advances in transurethral resection of the prostate: bipolar
versus monopolar TURP. J Endourol. 2008; 22(8):1587-95.
3. Chen Q, Zhang L, Fan QL, Zhou J, Peng YB, Wang Z. Bipolar transurethral resection in
saline vs traditional monopolar resection of the prostate: results of a randomized trial
with a 2-year follow-up.BJU Int. 2010; 106(9):1339-43.
4.Fagerström T, Nyman CR, Hahn RG. Complications and clinical outcome 18 months after bipolar and monopolar
transurethral resection of the prostate.
J Endourol. 2011 Jun;25(6):1043-9. Epub 2011 May 13.
5.Mamoulakis C, Ubbink DT, de la Rosette JJ. Bipolar versus monopolar transurethral
resection of the prostate: a systematic review and meta-analysis of randomized controlled
trials. Eur Urol. 2009; 56(5):798-809.
6.Burke N. Whelan JP, Goeree L, Hopkins RB, Campbell K, Goeree R, Tarride JE. Systematic review and meta-
analysis of transurethral resection of the prostate versus minimally invasive procedures for the treatment of benign
prostatic obstruction. Urology. 2010; 75(5):1015-22. Review.
7.Wosnitzer MS, Rutman MP. KTP/LBO laser vaporization of the prostate. Urol Clin North Am. 2009; 36(4):471-
83.
8.Malek RS, Kuntzman RS, Barrett DM. High power potassium-titanyl-phosphate laser vaporization prostatectomy.
J Urol. 2000; 163(6):1730-3.
9.Hanson RA, Zornow MH, Conlin MJ, Brambrink AM. Laser resection of the prostate:
implications for anesthesia. Anesth Analg. 2007; 105(2):475-9.
10.Karatas OF, Alkan E, Horasanli K, Luleci H, Sarica K. Photoselective vaporization of the prostate in men with a
history of chronic oral anti-coagulation.
Int Braz J Urol. 2010 Mar-Apr;36(2):190-7.
11.Woo H, Reich O, Bachmann A, Choi B, Collins E, de la Rosete J, et al.: Outcome of greenlight HPS 120-W laser
therapy in specifi c patient populations: those in retention, on anticoagulants and with large prostates (> 80mL). Eur
Urol Suppl 2008; 7: 378-83
12.Geavlete B, Multescu R, Dragutescu M, Jecu M, Georgescu D, Deavelete P. Transurethral resection (TUR) in
saline plasma vaporization of the prostate vs standard TUR of the prostate: ‘the better choice’ in benign prostatic
hyperplasia? BJU Int. 2010; 106(11):1695-9.
13.Reich O, Gratzke C, Bachmann A, Seitz M, Schlenker B, Hermanek P, Lack N, Stief CG.
Morbidity, mortality and early outcome of transurethral resection of the prostate: a prospective multicenter
evaluation of 10,654 patients. Urology Section of the Bavarian Working Group for Quality Assurance. J Urol. 2008;
180(1):246-9.
14.Smith RD, Patel A. Transurethral resection of the prostate revisited and updated. Curr Opin Urol. 2011
Jan;21(1):36-41.
DISCLOSURE
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Hazards of the Anesthesia Workstation

James B. Eisenkraft, M.D. New York, New York
The anesthesia delivery system comprises the anesthesia machine, vaporizers, ventilator, and waste gas
scavenging system. Failure of the delivery system is a rare cause of anesthesia-related injury to, or death of, a patient.
Much more commonly the delivery system is misused, the anesthesia caregiver makes an error, or the delivery system
fails while the user is unaware that a failure has occurred. This lecture will review failures and complications of
anesthesia gas delivery systems from the viewpoint of how they may be detected and thereby harm to the patient
prevented.
PERSPECTIVE
The critical incident (CI) technique was first described by Flanagan in 19541 and was developed to reduce loss
of military pilots and aircrafts during training. It was modified and introduced into anesthesia by Cooper et al.2 who
interviewed staff and resident anesthesiologists in a large metropolitan teaching hospital. They collected and analyzed
1089 descriptions of CI’s during anesthesia.3 A mishap was labeled a CI when it was clearly an occurrence that could
have led, if not discovered or corrected in time, or did lead to an undesirable outcome, ranging from increased length of
hospital stay to death or permanent disability. Other CI study inclusion criteria were: that each incident involve an error
by a member of the anesthesia team or a failure(s) of the anesthetist’s equipment to function properly; it occurred during
patient care; it could be clearly described; and the incident was clearly preventable.3 Of the 1089 CI’s, 70 represented
errors or failures that had contributed in some way to a “substantive negative outcome” (SNO) defined as mortality,
cardiac arrest, canceled operative procedure, or extended stay in the PACU, ICU or in the hospital. While 30% of all
CI’s were related to equipment failures, including breathing circuit disconnections, misconnections, ventilator
malfunctions, and gas flow control errors, only 3 (4.3%) of SNO incidents involved equipment failure, suggesting that
human error was the dominant problem. Although equipment failures rarely cause death, CI’s related to equipment are
common and have prompted improvements in equipment design, construction and in monitoring.
In 1993, the Australian Anaesthesia Patient Safety Foundation published results of the Australian Incident
Monitoring Study (AIMS) that had collected 2000 CI’s.4 Of these, 177 (9%) were due to equipment failure in general
and 107 (60%) involved the anesthesia delivery system.5 Failures included problems due to unidirectional valves,
ventilator malfunctions, gas or electrical supply, circuit integrity, vaporizers, absorbers and pressure regulators.
Concerning the problems with ventilation, it was recommended that critical areas be doubly or triply monitored and that
monitoring equipment be self-activating.6
The role of equipment failures leading to malpractice litigation in the United States has been studied by the
ASA Closed Claims Project (CCP). A 1997 analysis of 3791 claims, 7 of which 76% occurred during the period 1980-
1990, found that gas delivery equipment problems accounted for 72/3791 (2%). Of these 72, 39% were related to
the breathing circuit, 17% to ventilators, 21% to vaporizers, 11% to gas tanks or lines and 7% to the anesthesia machine.
Death or brain damage occurred in 76% of the 72 cases. Initiating events were circuit misconnects, disconnects and gas
delivery system errors. Misuse was judged to have occurred in 75% and equipment failure in only 24%. Anesthesia
caregivers were considered responsible in 70% of use error cases and ancillary staff (e.g., technicians) to have
contributed in 30%. Predominant mechanisms of injury were hypoxemia, excessive airway pressure and anesthetic agent
overdose. Overall, the reviewers deemed 78% of claims to have been preventable by the use or better use of monitoring.
As of May 2012, the Closed Claims Project database included 9536 claims of which 115 were related to
anesthesia gas delivery equipment.8 The most recent gas delivery system claims were for an event in 2005. Thus far,
however, it appears that gas delivery equipment problems are decreasing as a proportion of surgical anesthesia claims.
Anesthesia gas delivery claims represented 4% of surgical anesthesia claims from the l970’s, 3% from the 1980’s, 1%
from the 1990s, and 1% from the period 2000-2010. There were only 39 anesthesia gas delivery system claims from
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1990-2010. These include 4 supplemental oxygen line events, 7 anesthesia machine problems, 13 vaporizer problems, 5
ventilator problems, and 10 breathing circuit problems. The outcomes in anesthesia gas delivery equipment claims from
1990-2010 seem to be less severe than earlier claims. In 1990-2010, 38% of anesthesia gas delivery system claims
resulted in severe injury or death compared to 80% in 1970-1989, p<0.001. Among the 39 claims from 1990-2010 were
10 deaths, 5 permanent brain damage, 6 pneumothorax, and 9 awareness claims. Payments reflect the lower severity of
injury, with a median payment (in 2011 dollars) of $199,000 in the 1990-2010 claims compared with $802,750
(adjusted to 2011 dollars) for earlier gas delivery equipment claims. Thirty-two (82%) of the 39 post-1990 claims
resulted in payment. 8
MONITORING THE ANESTHESIA BREATHING SYSTEM

The anesthesia breathing system (patient circuit) represents the interface between the patient and the anesthesia
delivery system.9 While not all equipment failures are preventable, appropriate monitoring of the patient circuit should
lead to early detection of failures and enable prompt intervention before the patient suffers any harm. Aspects of the
patient circuit that can be routinely monitored include pressure, volume, capnography, respiratory gas composition and,
more recently, gas flows. Used correctly (i.e., appropriate monitors, alarm threshold limits, alarms enabled and
functioning) such monitoring should detect most errors or failures. Each monitoring modality will be briefly considered,
together with its applications and limitations.
Pressure Monitoring.
Many traditional anesthesia breathing systems incorporate an analogue pressure gauge, as well as an electronic pressure
monitoring and alarm system. The pressure gauge, if present, is usually mounted on the CO 2 absorber and may measure
the pressure at that site (Dräger). In the Ohmeda GMS Absorber System, pressure is sensed on the patient side of the
inspiratory unidirectional valve and “piloted” to the pressure gauge and pressure monitoring system. Depending upon
circuit configuration, the pressure monitor may fail to detect certain abnormal pressure situations. Thus monitoring
pressure at the absorber will not detect PEEP produced by a free-standing PEEP-valve that has been placed between the
expiratory limb of the circle system and the expiratory unidirectional valve. Ideally, pressure is monitored at the patient’s
airway. Some newer electronic anesthesia workstations use only electronic monitoring and display of pressures, some on
a virtual analog gauge displayed on the monitor screen.
Low Pressure Alarm. Because breathing system disconnects and misconnects are not uncommon occurrences,
monitoring of breathing system integrity is essential. Circuit low pressure monitors have sometimes been referred to as
“disconnect alarms” but this may be a misnomer because they monitor pressure and the user may infer circuit integrity
only if the monitor is used appropriately. They annunciate an audible and visual alarm within 15 seconds when a
minimum pressure threshold is not exceeded. The pressure threshold should therefore be set by the user to be just less
than the normal peak inspiratory pressure (PIP) so that any slight decrease will trigger the alarm. If the threshold is not
bracketed close to the PIP, a circuit leak or disconnect may go undetected if the low pressure alarm threshold is
exceeded. Thus, a small diameter tracheal tube (e.g., 3.0 mm I.D.) connected to a circle system might be pulled out of
the patient’s airway, leaving the lungs unventilated. Because the 3.00 mm tube has high resistance to gas flow, the
pressure increase in the circuit with each positive pressure inspiration may exceed the low pressure alarm threshold. On
modern anesthesia workstations the circuit pressure waveform is displayed, as are the pressure alarm thresholds, so that
the latter can be suitably adjusted by the user. The most recent workstations offer an “auto-limits” setting automatically
brackets the alarm limits for all monitored parameters in relation to the then existing values.
Modern delivery systems incorporate low pressure alarms that are automatically enabled when the ventilator is
turned on, but there may be still in use some older designs of alarm systems that must be enabled by the user. Because
the low pressure alarm is critical during use of IPPV, the user must be aware of the properties of the monitoring system
on the individual machine that he/she is using. If there is any doubt about whether or not a monitor is interfaced with the
ventilator ON/OFF switch, the alarm can be tested by deliberately creating a disconnect. While modern breathing
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system monitors have a widely adjustable low pressure alarm threshold, older models may provide a choice of only three
settings (e.g., 8, 12 and 26 cm H2O), which may limit the sensitivity to detect slight decreases in breathing system
pressure. Some low pressure monitoring alarm systems offer an optional 60 second delay in the event that a slow
ventilatory rate, e.g., < 4 breaths/min, is set.
Whereas the breathing system low pressure alarm must be enabled (either automatically or manually) in
association with IPPV, the following pressure monitoring modalities are in continuous operation.
Continuing Pressure Alarm. Annunciated when circuit pressure exceeds 10 cm H2O for >15 seconds, it alerts to more
gradual increases in pressure, such as due to a ventilator pressure relief valve malfunction (i.e., valve stuck closed) or a
scavenging system occlusion. In these situations fresh gas continues to enter the breathing system from the machine
flowmeters but is unable to leave. Rate of rise of pressure therefore depends upon the fresh gas flow rate.10
High Pressure Alarm. This alarm is annunciated immediately whenever the high pressure threshold is exceeded. On
modern machines this threshold is adjustable by the user. Some older pressure monitors are not user-adjustable and have
a default setting of +65 cm H2O. This might be too high to detect an otherwise harmful high-pressure condition, e.g.,
total obstruction of the tracheal tube, in which the breathing system pressure fails to exceed +60 cm H 2O. In
contemporary workstations the ventilator incorporates a high pressure relief valve, the opening threshold pressure of
which is set in conjunction with the high pressure alarm limit.
Subatmospheric Pressure Alarm. This annunciates an immediate alarm when pressure is < -10 cm H2O. It should alert
to potential negative pressure barotrauma situations due to suction being applied to the circuit. Negative pressure in the
circuit may be due to spontaneous respiratory efforts by the patient, a malfunctioning waste gas scavenging system, a
side-stream sampling gas analyzer when fresh gas flow into the circuit is too low, a suction catheter passed into the
airway, or suction via the working channel of a fiberscope passed into the airway via a diaphragm.
Volume Monitoring.
In traditional delivery systems monitoring of expired tidal and minute volumes is achieved using a spirometer placed in
the vicinity of the expiratory unidirectional valve. Spirometry is used to monitor ventilation and circuit integrity. A
breathing system disconnect should result in annunciation of the low volume alarm if an appropriate alarm limit for low
volume has been set. Limitations of older spirometers are that the alarm thresholds may not be user-variable. Thus one
older model of machine has a spirometer that has a “Low Volume” alarm threshold fixed at 80 ml. Particularly when a
hanging bellows design of ventilator is used, a circle system disconnection may fail to trigger a low volume alarm
condition because as the weighted bellows descends during exhalation, it may draw a normal tidal volume through the
leak site and through the spirometer, thus satisfying the low volume alarm threshold. A spirometer located by the
expiratory unidirectional valve at the absorber, does not measure the patient’s actual exhaled tidal volume, rather the
volume measured includes both that exhaled by the patient and the gas volume compressed in the breathing system.
While the spirometer low volume alarm is generally more useful in alerting to a low volume/possible disconnect
situation, a high volume alarm feature may also be useful. Unanticipated increases in tidal volume have resulted from
increasing the gas flow into the circuit.11 This may be from the machine flowmeters, by increasing the I:E ratio, or via a
hole in the bellows in a Dräger AV-E ventilator. Thus any gas entering the patient circuit during inspiration has the
potential to be added to the patient’s inspired tidal volume. This may be particularly hazardous to the pediatric patient
for whom a small tidal volume is intended.
Contemporary workstations measure breathing system compliance during the automated preuse checkout, and
use flow sensors located by the inspiratory and/or expiratory unidirectional valves to accurately monitor inspired (VT I)
and expired (VTE) tidal volumes. These data can be used to automatically compensate for small leaks in the breathing
system, and changes in the fresh gas flow, respiratory rate and I:E ratio which otherwise might unintentionally change
set tidal volume. 12
Gas Composition in the Circuit

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Appropriate monitoring of O2, CO2, N2O, N2 and anesthetic agent in the gas mixture at the patient’s airway will
alert to most gas delivery, composition, and agent dosing problems.
Oxygen. This is the most important monitor in the gas delivery system because it is both quantitative and qualitative.
Many anesthesia delivery systems incorporate a galvanic fuel cell oxygen sensor at the inspiratory unidirectional valve.
This analyzer actually senses PO2 (although the display may be in volumes %), is calibrated to 21% using room air and,
unlike other technologies, is not “fooled” by other gases. Most sidestream sampling multigas monitors use a rapid
responding paramagnetic analyzer that can display the oxygen concentration breath-by-breath. On contemporary
workstations the O2 analyzer is automatically enabled whenever the machine is capable of delivering an anesthetic gas
mixture. Causes of inadequate O2 concentration in the circuit include a hypoxic gas being delivered via the pipeline or
tanks, disconnected fresh gas hose during use of a hanging bellows ventilator, O 2 flow control valve turned off, fail-safe
system failure, proportioning system failure, O2 leak in the low pressure system of the machine, and a closed circuit with
inadequate O2 inflow rate.
The O2 analyzer with low concentration alarm appropriately set is an essential safety feature of all anesthesia
delivery systems. A high O2 concentration alarm may also be important in certain situations. Thus during an O2/helium
anesthetic for laser surgery of the airway, if the helium tank were to become depleted or if the O 2 flush is used, a high O2
concentration would be delivered that may lead to a fire.
One likes to assume that it is O2 that flows from O2 wall outlets but this is not always the case. It is important to
recognize that there is no qualitative O2 analyzer between the wall outlet or tanks and the machine oxygen inlet. Only
the gas in the breathing system is analyzed, but not the presumed-to-be O2 gas flowing from an auxiliary O2 flowmeter
on the machine or one connected directly to a wall outlet. In one case two patients died when an auxiliary O2 flowmeter
was connected to a wall N2O outlet.13
Capnography. Capnography is discussed elsewhere in more detail.14 It can provide much information about ventilation
of the patient’s lungs, as well as about anesthesia delivery system function. Failure to ventilate, which might be due to a
circuit disconnect or misconnect, should result in absence of a capnogram and annunciation of an apnea alarm. An
abnormal capnogram may be caused by CO2 rebreathing (e.g., exhausted CO2 absorbent; incompetent inspiratory or
expiratory valves; misconfigured circuit; Bain circuit with inner tube disconnect).
Anesthetic Gases and Nitrogen. Monitoring concentrations of N2O and potent inhaled agent with use of appropriate
high and low concentration alarm settings will alert to most agent dosage problems. Low agent concentration may be
due to the vaporizer being off or empty and could result in patient “awareness.” Excessive agent concentrations may be
due to vaporizer malfunction, tipping, or liquid agent in the circuit. Some analyzers will annunciate an alarm in the
presence of mixed agents (vaporizer contamination; more than one vaporizer on).15 Agent analysis is also reassuring
whenever a new piece of equipment, e.g., a Tec 6 vaporizer (for desflurane), or the Aladin® vaporizing system (on the
GE ADU and Aisys workstations) is being used. Monitoring of N2 concentration is rarely performed but may be useful
in alerting to the presence of an air leak into the breathing system. Some multigas analyzers display the percentage of the
total gas mixture that is not analyzed/identified and this value is termed balance gas. By measuring barometric pressure
(PB), and subtracting from this PN2O, PCO2, PAnesthetic agent (measured by infrared technology) and PO2 (measured
by paramagnetic analysis), the result is the PBalance gas. The PBalance gas/PB x 100 gives the balance gas in volumes
percent. The unmeasured gas is normally nitrogen. If a helium/O2 mixture were being administered, the helium would be
measured as balance gas.
Flows/Sidestream Spirometry
Contemporary anesthesia workstations use flow sensors in the breathing circuit to monitor gas flows, and from
flow and time they calculate volume. This allows display of plots of volume vs. pressure and volume vs. flow so that
changes in these parameters may easily be detected. The various technologies used are described elsewhere.12
Most contemporary multigas analyzers use sidestream sampling of gas from the breathing system. The addition
of a Pitot tube flow sensor to the sidestream sampling adapter makes it possible, with only a small increase in size of the
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adapter, to monitor and set alarm limits for pressure, flow, volume and gas composition, all of which are sensed at the
airway. Such monitoring of multiple aspects of patient ventilation and delivery system function at the patient’s airway
offers many potential advantages over the usual pressure and volume monitoring sites, including the ability to monitor
the patient’s inspired and expired tidal volumes, flow-volume and pressure-volume loops.16 Continuous measurement of
O2 and CO2 concentrations versus inhaled and exhaled volumes makes it possible to monitor CO2 production, O2
consumption, and respiratory exchange ratio (respiratory quotient).
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Alarms
While delivery system failures, use(r) errors and equipment failures cannot always be prevented, appropriate
monitoring should facilitate detection of most such problems and permit intervention before patient harm occurs.
Monitoring/alarm deficiencies include absence (i.e., no monitor); non-function (i.e., monitor present but broken); and
“disabled” (i.e., monitor/alarm not turned on or intentionally turned off) 6 and inappropriate alarm thresholds or volume
settings.
In the AIMS study with respect to ventilation it was concluded that critical areas be doubly or even triply
monitored and that monitoring equipment be self-activating.6 This philosophy might be equally well applied to other
critical variables that are monitored. Alarm setting features are important and easy (“user friendly”) bracketing of
suitable limits is highly desirable, as is annunciation of adequate volume audible (i.e., loud) as well as visual alerts.
Carbon Dioxide Absorbents, Carbon Monoxide, Compound A, Fires and Explosions

Since 1990 there have been several reports of patients who developed increased levels of carboxyhemoglobin in
response to accumulation of CO in the circle system. The CO is generated when desflurane, enflurane and, to a lesser
extent, isoflurane, interact with dry CO2 absorbent, particularly Baralyme®.17 While no case of patient harm has been
reported to date, CO represents a potential hazard of which the anesthesia caregiver should be aware.18 Measures to
decrease this potential hazard include using absorbent that has the standard complement of water, or addition of liquid
water to the top of the absorbent. Fresh gas should be turned off at the end of each case to prevent desiccation of the
absorbent and consideration should be given to replacing the absorbent more frequently, especially if the machine has
been left unused for some time, such as over a weekend.
Another approach is to use a CO2absorbent that does not contain strong bases (Ba(OH)2 and KOH)). 19,20 For
example, Amsorb is a CO2 absorbent that does not contain strong base and does not form CO (or compound A) in vitro.
It also turns purple when desiccated, an additional advantage. While there is currently no analyzer available to monitor
CO in the breathing system, there is now available a pulse oximeter that uses 8 wavelengths of light and displays
COHb%.21
Desiccated Baralyme® acting on sevoflurane can produce absorber temperatures that exceed 400°C,fires, and
explosions.22-26 Animal studies and a bench model demonstrate fires and explosions with sevoflurane.22 and there are
now several reports of fires and explosions in clinical practice with sevoflurane (but none with desflurane or
isoflurane),23-25 in one case causing patient injury. In late 2004 the manufacturer of Baralyme discontinued its
distribution, which may minimize or even eliminate the problems of fire and explosion. The risk of fire and explosion is
considered to be much less with soda lime, although it has been suggested that the absorber temperature be routinely
monitored using a skin probe.26
PREVENTION OF FAILURES AND ADVERSE OUTCOMES

Complications due to the anesthesia delivery system are uncommon but when they occur are usually due to
use(r) error rather than actual equipment failure.27 User education/in-servicing is essential if sophisticated equipment,
such as a new (computerized, electronic) anesthesia workstation, is to be used appropriately. 28 Education of medical and
ancillary (nursing/technical) staff is also important because they may unwittingly contribute to the occurrence of a
complication.29, 30
Studies have shown that anesthesia providers often fail to properly perform the preuse checkout of their
anesthesia delivery system. This may be due to the complexity of previously published checkouts. 31 An updated
approach to the preuse checkout has recently been published on the ASA website (2008 Pre-anesthesia checkout design
guideline: http://www.asahq.org/clinical/fda.htm). Suggested pre-use checkouts for a number of contemporary
workstations are also presented on this website.
The new electronic workstations have preuse checkouts in which many of the checks are automated but some
must be completed by the user. It is essential that the user understand how to perform the tasks that are required. For
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example, the user must correctly assemble and connect the breathing system to the workstation. The automated checkout
is then able to pressurize the system to measure compliance and check for leaks, but not necessarily for correct gas flow
through the components. It may be possible for a breathing system to be incorrectly assembled, be gas tight, yet not
permit any gas to flow to the patient.
Some anesthesia workstations (e.g., Drager Narkomed 6400, Apollo, Fabius GS; Datascope Anestar) use fresh
gas decoupling (FGD) to ensure that changes in fresh gas flow do not affect the desired (“dialed-in”) tidal volume
delivered to the patient’s airway. During the inspiratory phase of IPPV, only gas from the piston chamber (Drager) or
bellows (Anestar) is delivered to the inspiratory limb of the circle system because the decoupling valve closes to divert
fresh gas flow into the reservoir bag. FGD circuits differ from the traditional circle system in design and therefore may
be associated with different problems, including detection of a leak in the breathing system32 and failure of the FG
decoupling valve.33 All indicated and required monitors must be available and used correctly with alarm limits and alarm
volumes set appropriately for the individual patient’s situation. Anesthesia equipment should be regularly serviced by
authorized personnel and the equipment updated as necessary to conform to any existing requirements. A 2004
statement concerning guidelines to determine anesthesia machine obsolescence is available on the ASA website
(http://www.asahq.org/publicationsAndServices/machineobsolescense.pdf).
A pre-use checkout of the delivery system should be developed by each institution to suit local needs and item
#1 on any pre-use checkout should be that a backup means of ventilation should always be immediately available and
functioning. Testing the function of the self-inflating resuscitation bag during the pre-use checkout is essential.
Occasionally, a bag is found to be faulty, either not generating positive pressure when it is squeezed, or not releasing
positive pressure when it is longer being squeezed. Thus in the event of a delivery system failure, the patient’s lungs can
be ventilated with room air (or oxygen if a tank is available) using a self-inflating resuscitation bag. Recent studies
suggest that there is an increased awareness of the importance of the preuse checkout and management of machine-
related critical incidents. 34-37 One national anesthesiology board has even incorporated these into the Objective
Structured Clinical Evaluation (OSCE) component of its Board Examination in Anesthesiology 38
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4. Webb RK et al.: The Australian Incident Monitoring Study: An analysis of 2000 incident reports. Anaesth Int Care
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5. Webb RK et al.: Equipment failure: An analysis of 2000 incident reports. Anaesth Int Care 1993; 21:673-677
6. Russell WJ et al.: Problems with ventilation: an analysis of 2000 incident reports. Anaesth Int Care 1993; 1: 617-620
7. Caplan RA, Vistica MF, Posner KL, Cheney FW: Adverse anesthetic outcomes arising from gas delivery
equipment: a closed claims analysis. Anesthesiology 1997; 87: 741-8
8. Personal communication from Karen L. Posner, ASA Closed Claims Project, May 2012.
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Applications, Ehrenwerth J/Eisenkraft JB, eds. St. Louis, Mosby, 1993
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11. Scheller MS et al.: Influence of fresh gas flow and I:E ratio on tidal volume and PaCO2 in ventilated patients. J
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12. Tham R, Oberle M. How do flow sensors work? APSF Newsletter 2008; 23: 10-14
13. “Surgery mix-up causes 2 deaths.” New Haven Register. January 20, 2002
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14. Good ML, Gravenstein N. Capnography. In: Anesthesia Equipment: Principles and Applications, Ehrenwerth
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15. Eisenkraft JB. Anesthesia Vaporizers. In: Anesthesia Equipment: Principles and Applications, Ehrenwerth
J/Eisenkraft JB, eds. St. Louis, Mosby, 1993
16. Meriläinen P et al.: A novel sensor for routine continuous spirometry of intubated patients. J Clin Monit 1993;
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17. Fang ZX et al.: Carbon monoxide production from degradation of desflurane enflurane, isoflurane, halothane and
sevoflurane by soda lime and Baralyme®. Anesth Analg 1995; 80:1187-93
18. Berry PD, Sessler DI, Larson MD. Severe carbon monoxide poisoning during desflurane anesthesia. Anesthesiology
1999; 90:613-616.
19. Kharasch ED, Powers KM, Artru AA. Comparison of Amsorb, sodalime, and Baralyme
degradation of volatile anesthetics and formation of carbon monoxide and compound A in swine
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20. Olympio MA. Carbon dioxide absorbent desiccation conference convened by APSF. APSF Newsletter 2005; 20:
21. Barker SJ, Curry J, Redford D, Morgan S. Measurement of carboxyhemoglobin and methemoglobin by pulse
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22. Laster M, Roth P, Eger EI, II: Fires from the interaction of anesthetics with desiccated absorbent.
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23. Wu J, Previte JP, Adler E, Myers T, Ball J, Gunter JB: Spontaneous sevoflurane and barium hydroxide lime.
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24. Castro BA, Freedman LA, Craig WL, Lynch C, III: Explosion within an anesthesia machine: Baralyme, high
fresh gas flows and sevoflurane concentration. Anesthesiology 2004; 101: 537-539
25. Fatheree RS, Leighton BL: Acute respiratory distress syndrome after an exothermic Baralyme-sevoflurane reaction.
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27. Eisenkraft JB. A commentary on anesthesia gas delivery equipment and adverse outcomes. Editorial.
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29. Singh S, Loeb RG: Fatal connection: Death caused by direct connection of
oxygen tubing into tracheal tube connector. Anesth Analg 2004; 99: 1164-5
30. Wax DB, Bhagwan S, Beilin Y. Tension pneumothorax and cardiac arrest
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31. FDA Anesthesia apparatus checkout recommendations, 1993. Available on the FDA website:
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32. Sandberg WS, Kaiser S. Novel breathing system architecture: new consequences of old problems. Anesthesiology
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33. Ortega RA, Zambricki ER. Fresh gas decoupling valve failure precludes ventilation in a Draeger Fabius GS
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37. Blasius K, DeMaria S, Neustein SM. Missed steps in the preanesthetic checkout. Anesth Analg 2011; 113: 84-88.
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DISCLOSURE
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Perioperative Management of Patients with Respiratory Disease

David O. Warner, M.D. Rochester, Minneasota
Despite steady advances in care, patients with respiratory disease are still at increased risk for postoperative
pulmonary complications (PPCs) such as atelectasis and pneumonia. Indeed, PPCs may rival cardiovascular
complications in frequency and severity (1). Fortunately, with proper perioperative care, even patients with
crippling respiratory disease can usually be brought safely through surgery.
Respiratory diseases are usually categorized according to how they alter the mechanical properties of the respiratory
system, producing either a limitation of lung expansion (restrictive disease) or a limitation of expiratory airflow
(obstructive disease). Obstructive diseases such as asthma and chronic obstructive pulmonary disease (COPD) are
the most commonly encountered in clinical practice, and this presentation will concentrate upon these patients.
However, many of these principles are also applicable to patients with other forms of respiratory disease.
What causes postoperative pulmonary complications?
Many factors responsible for PPCs are related to disruption of the normal activity of the respiratory muscles (2).
Although we properly think of the diaphragm as of primary importance, many other muscle groups, such as the
intercostal muscles, must work together in a coordinated fashion to maintain proper respiratory function. At high
doses, the activities of all respiratory muscles are depressed by most anesthetics. However, at more moderate depths
of anesthesia, anesthetic drugs have more subtle and complex effects on the timing and distribution of neural drive
to the respiratory muscles. For example, during spontaneous breathing in a patient anesthetized with halothane,
some measures of diaphragm activation are actually increased compared with the awake state. Thus, in many cases
anesthetic effects are best characterized as causing a lack of respiratory muscle coordination, rather than a global
depression of overall activity. As might be expected, this uncoordinated activity reduces efficiency, and
hypoventilation is often the result. In addition, anesthetic-induced changes in the activation of the respiratory
muscles also change the shape of the chest wall that surrounds the lung. Because the shape of the chest wall
determines the shape of the underlying lung, these shape changes affect lung function, decreasing the functional
residual capacity and producing atelectasis in dependent lung regions. These and other effects produce the
ventilation-perfusion inequalities characteristic of anesthesia. Of interest, patients with moderate to severe COPD
actually are less likely to develop dependent lung atelectasis during anesthesia, have relatively normal patterns of
diaphragm motion, and thus often maintain adequate gas exchange during anesthesia (3).
Pulmonary function also may be impaired in the postoperative period, though via different mechanisms.
Postoperative changes are mainly related to surgical trauma, and are most pronounced following thoracic and
abdominal surgery. At least three mechanisms may contribute. First, respiratory muscles disrupted by surgical
transection (e.g., the abdominal muscles) will not function normally in the initial stages of healing. Second, patients
may voluntarily limit motion of respiratory muscles to minimize postoperative pain. Finally, stimulation of visceral
afferent nerves markedly changes the activation of respiratory muscles. For example, removal of the gallbladder
activates vagal afferents, which produces a reflex inhibition of diaphragm activity, presumably to minimize
diaphragm motion and further irritation of these afferents. Of note, laparoscopic techniques may ameliorate the first
two mechanisms, but not the third, and significant decrements in pulmonary function may still be observed after
laparoscopic surgery (e.g., after laparoscopic cholecystectomy) (4).
As a result of these mechanisms, the pattern of respiration following thoracic or abdominal surgery is typically
characterized by an increase in breathing frequency, a decrease in tidal volume, a decrease in functional residual
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capacity and vital capacity, and an abnormal pattern of chest wall motion. These changes may contribute to
continued atelectasis and other alterations in ventilation-perfusion matching that lead to hypoxemia.
Other factors that may contribute to PPCs include 1) reflex stimulation during airway instrumentation or release of
inflammatory mediators by drug administration, which increases airway resistance and limits expiratory gas flow
from the lung; if severe this can produce hyperinflation with risk of barotrauma and gas exchange abnormalities; 2)
impairment of normal mucociliary transport by anesthetic gasses and endotracheal intubation which may delay
clearance of pathogens and promote retained secretions; 3) impairment of lung inflammatory cells function by
prolonged anesthesia and surgery, which could increase susceptibility to postoperative infections; 4) impaired upper
airway reflexes postoperatively, with may increase risk for aspiration, 5) the need for prolonged postoperative
mechanical ventilation, increasing risk for nocosomial infections and; 6) incomplete reversal of neuromuscular
blockade.
In practice, no doubt these factors work together to cause PPCs, especially in patients with respiratory disease. In
general, one can consider anesthesia and surgery as posing additional challenges to a diseased lung with impaired
defenses. For example, a smoker with COPD has impairment of both mucociliary transport and the function of
alveolar macrophages, both of which normally act to defend against lung infection. The additional impairment of
mucociliary transport and alveolar macrophage function caused by anesthesia and surgery further increases
vulnerability to postoperative infection. When combined with atelectasis and impaired coughing caused by
respiratory muscle dysfunction, and the risks associated with prolonged postoperative mechanical ventilatory
support, the stage is set for pneumonia.
How can risk be assessed and the patient prepared?
There are many limitations of studies that examine risk factors for PPCs. However, there are some consistent
patterns. Risk factors for PPCs include the presence of pulmonary disease, longer surgery, emergency surgery, older
age, current cigarette smoking, and site of surgery, with thoracic and abdominal surgery posing the highest risk (2).
A recently published risk index also includes preoperative oxygen saturation, likely as an overall assessment of
cardiopulmonary status (26). Of note, pulmonary function testing per se is not useful in predicting risk. When other
factors are taken into account, observational studies consistently fail to find that any measure of pulmonary function,
such as forced expiratory volume in one second, is an independent predictor of PPCs (5). Thus, routine preoperative
pulmonary function testing is not justified, unless for a surgical indication (e.g., for planning of lung resection
surgery) or as part of an effort to optimize preoperative pulmonary status (see following).
As a general principle, pulmonary function should be optimized preoperatively, although admittedly there is little
evidence available to quantify any such benefit, especially in contemporary practice. The definition of
“optimization” depends on the type of respiratory disease and the individual patient. For example, patients with
asthma should achieve optimal symptom control, as patients with more active symptoms experience more PPCs.
There is no consensus regarding how best to achieve this control, with some advocating routine pretreatment of all
asthmatics with systemic corticosteroids. However, there is currently no firm evidence to support this
recommendation. The preoperative management of asthma also provides an example of the proper role of
pulmonary function testing. Although isolated spirometry or peak flow measurements have little use, serial changes
in these measurements can be very useful to objectively evaluate the status of the disease in an individual patient,
and can be a valuable tool to monitor responses to therapy.
Smoking has special importance as a risk factor for PPCs because it can be modified preoperatively. Unfortunately,
the lung probably requires several months to fully recover from the damage caused by cigarette smoke, and several
weeks of abstinence may be necessary before benefit is observed. Some have suggested that quitting smoking
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shortly before surgery actually increases risk, but analysis of the available evidence does not support this assertion
(6). All smokers should be the targets of interventions specifically designed to help them quit smoking
preoperatively. Interventions should target smokers at the earliest opportunity (e.g., the time of surgical scheduling).
However, those not able to maintain preoperative abstinence should not be ignored as opportune subjects for
interventions at any time in the perioperative period. Sustained abstinence produces tremendous benefits to the
long-term health of the surgical patient (or anyone) who smokes; this consideration alone provides sufficient
justification for concerted efforts to help these patients quit (6).
How should patients be managed intraoperatively?
Although recommended management may vary widely depending on patient and procedure, several general
principles can be stated.
Regional techniques are often recommended for patients with respiratory disease, and may indeed be preferable
when feasible. For example, peripheral nerve blocks may cause minimal changes in pulmonary function. However,
there are several provisos. First, regional techniques may also compromise respiratory function, even when properly
applied. For example, patients with COPD often exhibit expiratory activity in abdominal muscles. Neuroaxial
techniques may abolish this activity and produce dyspnea. Second, sedation used to facilitate regional techniques
may compromise respiratory function. Finally, avoid foolishness in the pursuit of regional techniques. For
example, if neither you nor the surgeon has ever performed an open cholecystectomy using epidural anesthesia, do
not start with the patient afflicted with severe COPD; many case series have shown that even patients with severe
COPD can successfully tolerate general anesthesia.
Laparoscopic techniques may be preferable, again if feasible, but remember that 1) these techniques may reduce but
do not eliminate postoperative pulmonary impairment, and 2) intraoperative interventions such as abdominal
insufflation or one-lung anesthesia may themselves pose challenges in these patients.
Several steps can help prevent bronchospasm in patients with reactive airways. All of these patients should be
pretreated with inhaled ß2-adreneric agonists (e.g., albuterol) or anticholinergic agents (e.g. ipratropium)
preoperatively, especially if endotracheal intubation is planned. If possible, endotracheal intubation should be
avoided by using the laryngeal mask airway or similar. Propofol or ketamine is the induction agent of choice.
Volatile anesthetics should be the maintenance anesthetics of choice because of their excellent bronchodilating
properties, with the exception of desflurane, which because of its irritant properties should be avoided in these
patients (23).
Recent lessons learned from the ventilatory management of critically ill may be of value in patients with respiratory
disease who require general anesthesia. Continued contraction of the diaphragm and other respiratory muscles,
achieved via pressure support ventilation or spontaneous breathing, may optimize V/Q matching. Indeed,
diaphragm function may be particularly well-preserved during anesthesia in patients with COPD, who experience
surprisingly little decrement in gas exchange function during general anesthesia (3). Recruitment maneuvers,
followed by PEEP and limited inspired oxygen concentration, may minimize dependent lung atelectasis and improve
oxygenation. There is now some evidence that “standard” tidal volumes in the 10-12 ml/kg range may cause
subclinical injury even in normal lungs, so lower tidal volumes (6-8 ml/kg) are likely indicated during routine
mechanical ventilation (20, 28). These lower tidal volumes do not increase the extent of atelectasis associated with
anesthesia (21), and may have clinical benefit to outcomes such as reduction in the need for postoperative
mechanical ventilation in some settings (27, 30). Any modest increases in arterial carbon dioxide partial pressure
necessary to achieve this goal are probably not harmful; indeed, intraoperative hypocapnia may slow recovery, and
hypercapnia may increase tissue oxygenation and reduce the rate of wound infection (22).
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Can regional analgesia help prevent postoperative pulmonary complications?
By relieving pain, regional anesthesia can potential ameliorate one of the mechanisms described above that impairs
postoperative respiratory muscle function. The hope is that this will improve chest wall function, increase lung
expansion, and prevent postoperative pulmonary complications. However, there is still considerable controversy
regarding whether regional analgesia improves clinically-relevant postoperative respiratory outcomes.
Epidural analgesia including local anesthetics can acutely change postoperative respiratory function. For example,
segmental epidural blockade with local anesthetics increases tidal volume and vital capacity, and improve indices
interpreted to reflect diaphragm activity after thoracic and upper abdominal surgery. Unfortunately, because epidural
blockade also affects other respiratory muscles, these indices may in fact not reflect diaphragm function. Indeed,
thoracic epidural blockade post thoracotomy in humans does not change the diaphragm electromyogram or
shortening of the muscle, and in fact produces paradoxical lengthening during inspiration in some patients, despite
improving many more global indices of respiratory function such as tidal volume (7). This lack of effect may reflect
the fact that blockade does not affect reflex inhibition of the diaphragm mediated by afferent information carried in
nerves such as the phrenic or vagus. Thus, even from a theoretical point of view, there is reason to question whether
pain relief alone will translate into improved respiratory outcomes.
Three meta-analyses of existing trials conclude that regional anesthetic techniques improve pulmonary outcomes.
The first concluded that epidural local anesthetics decreased the incidence of pulmonary infections and pulmonary
complications overall when compared with systemic opioids (8). The second found that “neuraxial blockade”
decreased the frequency of pneumonia and “respiratory depression” (9), and the third found that epidural analgesia
protects against the development of pneumonia after abdominal and thoracic surgery (28) – although the magnitude
of this effect has been decreasing with time. Unfortunately, there are several problems with these analyses,
including 1) the inclusion of older studies with high rates of PPCs in control groups that do not reflect contemporary
practice, 2) considerable heterogeneity in regional anesthetic techniques (including the drugs used), procedure type,
and definition of PPC, and 3) a dearth of blinded trials, with considerable potential for bias in unblended trials.
Although detailed review of all trials is not possible here, notable recent trials include two large unmasked
multicenter trials with relatively less standardization of care, and two smaller, double-masked single center trials
employing strict protocols for care. Each of the former enrolled approximately 1000 patients, studying epidural
analgesia as the treatment (opioids with or without local anesthetics) beginning before incision, and allowing
substantial variations in practice among patients (10,11). Overall, they found few differences in outcome between
those receiving and not receiving epidural analgesia, with the exceptions that 1) respiratory failure was less frequent
(for some types of surgery), and 2) postoperative pain control was improved by epidural analgesia.
The first masked trial (12) studied 153 patients undergoing abdominal cancer surgery randomized to receive either
continuous epidural bupivacaine and morphine, or subcutaneous morphine infusion via a catheter that simulated
epidural placement. Although the epidural provided better postoperative analgesia, it did not affect the frequency of
prospectively-evaluated PPCs, either in patients with normal or abnormal lungs. Another study (13) randomized
168 patients undergoing abdominal aortic aneurysm repair to receive either thoracic epidural anesthesia combined
with general anesthesia or general anesthesia alone intraoperatively and either intravenous or epidural analgesia
postoperatively (4 treatment groups). A combination of epidural opioids and local anesthetics was used. They
found no differences in outcomes, other than a shortened time to extubation in the epidural group (all patients
received some period of mechanical ventilation postoperatively). Pain scores were equivalent in all groups, perhaps
reflecting the relatively high dose of intraoperative opioids permitted by not planning for immediate extubation.
Hospital length of stay, their primary outcome, was not different (median of 7 days).
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Thus, although benefit has been claimed for regional techniques in relatively small, unblinded, older trials, most of
the more recent clinical trials have shown that although regional techniques can provide excellent analgesia, this
does not necessarily translate to improved respiratory outcomes.
What can be done postoperatively to improve outcomes?
As with intraoperative considerations, management should be tailored to the individual patient and procedure, but
several principles are evident.
Although regional techniques in isolation have not been shown to consistently improve outcomes, they may be a
valuable component of “multimodal” therapy that attempts to maximize analgesia and minimize the use of opioids
(14). Other components may include non-steroidal anti-inflammatory agents, early ambulation, etc. These
techniques may improve outcomes such as hospital length of stay, although there are as of yet few data concerning
their effects specifically on respiratory outcomes.
Maneuvers that increase mean lung volumes seem to be of benefit in preventing PPCs (15) although some have
questioned this benefit (16). There is surprisingly little information regarding the mechanism of benefit; presumably
they act to reduce postoperative atelectasis. Recent studies suggest that inspiratory muscle training preoperatively
may be beneficial in helping to maintain postoperative lung expansion and reducing PPCs (17, 24). Over the years,
different methods have enjoyed popularity, including intermittent positive pressure breathing, simple exhortation to
breathe deeply, incentive spirometry, and others, often accompanied by chest physiotherapy. All appear to be
similarly effective in reducing PPCs after upper abdominal surgery (15). Incentive spirometry is simple,
inexpensive, and provides objective goals for and monitoring of patient performance.
Continuous positive airway pressure (CPAP) is becoming increasingly popular as another method to maintain
increases in mean lung volumes. A recent study demonstrated that CPAP of 7.5 cmH2O dramatically decreases the
frequency of PPCs such as respiratory failure and pneumonia in patients who developed acute hypoxemia after
elective major abdominal surgery (18), and a recent meta-analysis also suggested benefit (29). CPAP can be
somewhat difficult to implement in practice with systems currently available in the US, but these encouraging
results deserve further consideration.
Residual neuromuscular blockade continues to occur in modern practice, and continues to contribute to the risk of
adverse respiratory events – something that can be easily avoided with proper monitoring (25).
Finally, for those patients who require postoperative mechanical ventilatory support, bundles of preventative
measures to prevent ventilator-associated pneumonia may reduce the frequency of this complication.
What’s the “bottom line”?
Most patients with respiratory disease can safely undergo anesthesia and surgery with the application of the basic
principles summarized in the following table. A useful guideline from the American College of Physicians is also
available (19). Although postoperative pulmonary complications still represent a substantial clinical and economic
burden, with proper recognition of those at risk, and a multi-faceted approach to prevention, this burden can be
ameliorated (31).
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Management of Patients with Respiratory Disease – Summary of

Recommendations
PREOPERATIVE
Evaluation and treatment
• Assess general physical status (pulmonary, cardiac, neurologic disease) and treat any reversible
signs/symptoms
• Spirometry used only as guide for treatment.
• CXR only when necessary to evaluate symptoms
• Arterial blood gases as needed to evaluate signs/symptoms
• Cessation of cigarette smoking (as long before surgery as possible, but any time is a good time)
• Treat any reversible component of lung pathology (antibiotics, bronchodilators, steroids)
• Consider postponing elective surgery if improvement of pulmonary function is possible and requires more
time
• Education regarding postoperative deep breathing/incentive spirometry; possibly also CPAP
• Reinforce strategies for postoperative early ambulation (pain management, etc)
A nesthetic/Surgical Planning
• Regional techniques as feasible, but avoid foolishness
• Limit duration of surgery as possible
• Consider use of laparoscopic techniques where feasible
INTRAOPERATIVE
• Consider laryngeal mask airway or similar, especially in those with bronchospasm
• Consider the use of spontaneous breathing when feasible
• Careful and vigilant use of muscle relaxants (to avoid postoperative muscle weakness)
• Consider use of local anesthetics for operative field infiltration
• Maintain adequate hydration to allow mobilization of airway secretions
• Mechanical ventilation: consider recruitment maneuvers (lung expansion followed by PEEP) to achieve
and maintain adequate oxygenation; consider tidal volumes ~4-6 ml/kg
• FIO2 = 80% may balance between avoiding absorption atelectasis and possible benefit of high FIO2 to
postoperative wound infection
• Do not insist upon hypo/normocapnia
POSTOPERATIVE
• Consider regional analgesia for excellent pain control, not necessarily to reduce pulmonary risk
• Maintain tracheal intubation until full reversal of neuromuscular drugs is achieved
• Use multimodal therapy such as non-steroidal antiinflammatory agents, dexmedetomidine, nerve blocks,
etc. to maximize analgesia, encourage early ambulation, and minimize the use of opioids that may depress
ventilation
• Bundles to prevent VAP if prolonged ventilation required
• Consider use of CPAP for postoperative hypoxemia
• Early postoperative respiratory therapy (deep breathing, incentive spirometry)
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References
1. Lawrence VA, Hilsenbeck SG, Mulrow CD, et al: Incidence and hospital stay for cardiac and pulmonary
complications after abdominal surgery. J Gen Intern Med 1995; 10: 671-678
2. Warner DO: Preventing postoperative pulmonary complications: the role of the anesthesiologist. Anesthesiology
2000; 92: 1467-72 – note: portions of the abstract for this presentation were adapted from this reference.
3. Kleinman BS, Frey K, VanDrunen M, et al: Motion of the diaphragm in patients with chronic obstructive
pulmonary disease while spontaneously breathing versus during positive pressure breathing after anesthesia and
neuromuscular blockade. Anesthesiology 2002; 97: 298-305
4. Karayiannakis AJ, Makri GG, Mantzioka A, et al: Postoperative pulmonary function after laparoscopic and open
cholecystectomy. Br J Anaesth 1996; 77: 448-52
5. Lawrence VA, Page CP, Harris GD: Preoperative spirometry before abdominal operations: A critical appraisal of
its predictive value. Arch Intern Med 1989; 149: 280-285
6. Shi Y, Warner DO:. Brief preoperative smoking abstinence: Is there a dilemma? Anesth Analg 2011; 113:1348-
51
7. Fratacci MD, Kimball WR, Wain JC, et al: Diaphragmatic shortening after thoracic surgery in humans. Effects of
mechanical ventilation and thoracic epidural anesthesia. Anesthesiology 1993; 79: 654-65
8. Ballantyne JC, Carr DB, deFerranti S, et al: The comparative effects of postoperative analgesic therapies on
pulmonary outcome: Cumulative meta-analyses of randomized, controlled trials. Anesth Analg 1998; 86: 598-612
9. Rodgers A, Walker N, Schug S, et al: Reduction of postoperative mortality and morbidity with epidural or spinal
anaesthesia: results from overview of randomised trials. Br. Med. J. 2000; 321: 1-12
10. Rigg JR, Jamrozik K, Myles PS, et al: Epidural anaesthesia and analgesia and outcome of major surgery: a
randomised trial. Lancet 2002; 359: 1276-82
11. Park WY, Thompson JS, Lee KK: Effect of epidural anesthesia and analgesia on perioperative outcome: a
randomized, controlled Veterans Affairs cooperative study. Ann Surg 2001; 234: 560-9; discussion 569-71
12. Jayr C, Thomas H, Rey A, et al: Postoperative pulmonary complications. Epidural analgesia using bupivacaine
and opioids versus parenteral opioids. Anesthesiology 1993; 78: 666-76
13. Norris EJ, Beattie C, Perler BA, et al: Double-masked randomized trial comparing alternate combinations of
intraoperative anesthesia and postoperative analgesia in abdominal aortic surgery. Anesthesiology 2001; 95: 1054-
67
14. Kehlet H: Multimodal approach to control postoperative pathophysiology and rehabilitation. Br J Anaesth 1997;
78: 606-17
15. Thomas JA, McIntosh JM: Are incentive spirometry, intermittent positive pressure breathing, and deep breathing
exercises effective in the prevention of postoperative pulmonary complications after upper abdominal surgery? A
systematic overview and meta-analysis. Phys Ther 1994; 74: 3-10
16. Overend TJ, Anderson CM, Lucy SD, et al: The effect of incentive spirometry on postoperative pulmonary
complications: a systematic review. Chest 2001; 120: 971-8
17. Hulzebos EH, Helders PJM, Favie NJ, et al: Preoperative intensive inspiratory muscle training to prevent
postoperative pulmonary complications in high-risk patients undergoing CABG surgery. JAMA 2006; 296:1851-7
18. Squadrone V, Coha M, Cerutti E et al: Continuous positive airway pressure for treatment of postoperative
hypoxemia: a randomized controlled trial. JAMA 2005; 293: 589-95
19. Qaseem A, Snow V, Fitterman N, et al: Risk assessment for and strategies to reduce perioperative pulmonary
complications for patients undergoing noncardiothoracic surgery: a guideline from the American College of
Physicians. Ann Intern Med 2006; 144:575-580.
20. Schultz MJ, Haltsma JJ, Stutsky AS, et al: What tidal volumes should be used in patients without acute lung
injury? Anesthesiology 2007; 106:1226-31
21. Cai H, Gong H, Zhang L, et al: Effect of low tidal volume ventilation on atelectasis in patients during general
anesthesia: a computed tomographic scan. J Clin Anesthesia 2007; 19:125-9.
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22. Fleischmann E, Herbst F, Kugener A, et al: Mild hypercapnia increases subcutaneous and colonic oxygen
tension in patients given 80% inspired oxygen during abdominal surgery. Anesthesiology 2006; 104:944-6
23. Ungen-Sternberg BS, Saudan S, Petak F, et al. Desflurane but not sevoflurane impairs airway and respiratory
tissue mechanics in children with susceptible airways. Anesthesiology 2008; 108:216-24.
24. Dronkers J, Veldman A, Hoberg E, et al. Prevention of pulmonary complications after upper abdominal surgery
by preoperative intensive inspiratory muscle training: a randomized controlled pilot study. Clin Rehab 2008;
22:134-42.
25. Murphy GS, Szokol JW, Marymont JH, et al. Intraoperative acceleromyographic monitoring reduces the risk of
residual neuromuscular blockade and adverse respiratory events in the postanesthesia care unit. Anesthesiology
2008; 109:389-98.
26. Canet J, Gallart L, Gomar C, et al. Prediction of postoperative pulmonary complications in a population-based
surgical cohort. Anesthesiology 2010;113:1338-50
27. Sundar S, Novack V, Jervis K, et al. Influence of low tidal volume ventilation on time to extubation in cardiac
surgical patients. Anesthesiology 2011;114:1102-1110.
28. Popping DM, Elia N, Marret E, et al. Protective effects of epidural analgesia on pulmonary complications after
abdominal and thoracic surgery. Arch Surg 2008;143:990-99.
29. Ferreyra GP, Baussano I, Squadrone V, et al. Continuous positive airway pressure for treatment of respiratory
complications after abdominal surgery. Ann Surg 2008; 247:617-26.
30. Tusman G, Bohm SH, Warner DO, Sprung J. Atelectasis and perioperative pulmonary complications in high-
risk patients. Curr Opin Anesthesiol 2012; 25:1-10.
31. Schander A, Fleischer LA, Barie PS, Bigatello LM, Sladen RN, Watson CB. Clinical and economic burden of
postoperative pulmonary complications: patient safety summit on definition, risk-reducing interventions, and
preventive strategies. Crit Care Med 2011; 39: 2163-72
DISCLOSURE
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Physics in Anesthesiology: Basic Science Review

Jeffrey B. Gross, M.D. Farmington, Connecticut
Why Physics?
a) Understand how our equipment is SUPPOSED to work
b) Understand what might happen if things go WRONG
c) Function as a CONSULTANT in the medical specialty of Anesthesiology
d) Do well on Content Outline Section 1B of the In-Training and Part I American Board of
Anesthesiology Examinations
Pressure
a) Pressure= Force per unit of area
b) Units
• Pounds / in2 (PSI)
- Atmospheric Pressure PATM=14.7 PSI)
• Pascals (nt / m2) (PATM~100 KPa)
• mmHg (7.5 mmHg = 1 KPa)
• cmH2O (1 mmHg = 1.36 cmH2O)
c) Implications
• Even a small pressure exerts a large force if area is large
• A small force can exert a lot of pressure if the area is small
d) Absolute vs. Gauge Pressures
• Gauge pressures: relative to ambient pressure
- Tire pressure, pressure in compressed gas cylinder, blood pressure
• Absolute pressures
- Vapor pressure of anesthetics, H2O
- Blood gases
- Other cases where you need to use gas laws
e) Pressure Gauges
• Bourdon tube (for high pressure gases such as compressed gas cylinders)
- Deformable tube changes shape when filled with pressurized gas causing pointer to move
• Diaphragm (for low pressures such as aneroid blood pressure cuffs--the
kind with a pointer)
- Diaphragm at top of a "pancake" shaped cylinder moves outward
causing pointer to move
f) Pressure Regulators
• Reduces high pressure in compressed gas cylinder to approximately 50
PSIG
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Gas Cylinders
a) E Cylinder (back of machine)
• For ideal gases (air, nitrogen, oxygen)
- Full cylinder pressure = 2000 PSI
- Full cylinder volume = 660 liters
- Volume remaining is proportional to pressure
- 1000 PSI --> 330 L 500 PSI-->165 L
• For pressurized liquids (N2O, CO2, C3H8 [propane--barbecue grill], C3H6 [cyclopropane])
- Pressure depends on vapor pressure of liquid at tank temperature until liquid is “gone” (740
PSI) for N2O at room temperature
- Full cylinder of N2O – 1590 L
- Remaining quantity of gas best determined by weight
• The N2O in a full E cylinder weighs about 3 Kg
- Critical temperature (Tc): gas cannot be liquefied above this temperature regardless of
pressure
• For N2O TC = 36.5o C
b) Some Simple Calculations
• What is the weight of N2O in an E-cylinder?
mole 44 g
1590 L× × = 2900 g = 2.9 kg
24 L mole
• What is the internal volume of an “E” Cylinder?

- Use Boyle's Law: P1V1=P2V2
2000 · V TANK = 14.7 · 660

14.7 · 660
V TANK = = 4.85 L
2000
c) More Simple Calculations

• How many ml of sevoflurane vapor come from 1 ml of sevoflurane liquid?
1.5 g 1 mole 24 L gas
1 ml liquid × × × = 0.18L gas= 180 mL
ml 200 g mole
• If the fresh-gas flow is 2 l/min, how many minutes of 2% sevoflurane anesthesia will 5 ml of
liquid provide?
180 ml gas 1 minute
5 ml liquid × × = 22.5 min
ml liquid 0.02× 2000 mL gas
Adiabatic Compression
a) Rapid compression of gas without giving heat a chance to escape
• Principle of diesel engine (no spark plugs)
b) If there is oil / grease in valve or regulator and tank opened quickly, explosion can occur :-(
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Flows of Liquids and Gases

a) Laminar (streamlined)
η=viscosity of liquid
8× L× η R=radius of tube
Resistance=
π× R4 L=length of tube
• Pressure=Flow x Resistance
b) Turbulent
• Pressure α Density x Flow2
• Transition from laminar to turbulent flow when Reynold's number > 2300
Flowmeters
ρ=density of liquid
ρ× V × D V=velocity of flow
R=
η D=diameter of tube
η=viscosity of liquid
a) Tapered tube with diameter increasing toward the top
b) Bobbin position determined by equilibrium
• Upward force from flowing gas = downward force from gravity
- At low flow rates (laminar flow) upward force depends on
viscosity of gas
- At high flow rates (turbulent flow ) upward force depends on
density of gas
c) Always want O2 flow tube nearest to the common gas outlet
- Minimizes risk of hypoxia if a flow tube is cracked
Fail Safe Valve

a) Cuts off N2O if O2 supply fails
• Does NOT prevent accidental or intentional “dialing in” of a hypoxic gas mixture
b) Testing
• Turn on O2 and N2O flows
• Disconnect wall O2 supply (be sure O2 tank is "off")
• Press O2 flush valve
• Verify that N2O flow ceases when O2 pressure drops to zero
Proportioning Systems
a) Limit N2O flow to 3 times O2 flow
b) Link vs. pressure operated systems
• Link system: mechanically turns down N2O needle valve if O2
flow reduced
- N2O flow will NOT return to initial value if O2 flow
increased
• Pressure system: pneumatically decreases N2O flow if O2 flow
reduced
- N2O flow will return to initial value if O2 flow increased
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Anesthetic Vaporizers
a) Ye Olde Copper Kettle
• Vapor output depends on O2 inflow and vapor pressure of anesthetic
• For sevoflurane, Pv=190 mmHg = 1/4 ATM
- 1/4 of output molecules will be Sevoflurane; 3/4 of output molecules will be O2
- For every 100 ml O2 input, will get 133 ml of total output
• 100 ml O2 (3/4 of total)
• 33 ml sevoflurane (1/4 of total)
- If you use a total gas flow of 3.3 l/min (magic number :-), each 100 ml of O2 through the
vaporizer gives you 1% of sevoflurane concentration
b) Desflurane “Vaporizer”
• Boiling point of desflurane 23.5o C (vapor pressure at room temp nearly atmospheric
• Variable bypass vaporizer not controllable
- Each 100 ml of O2 through vaporizing chamber would give about 900 ml of desflurane output
- Large output swings with changes in temperature
• Alternative: Use a “boiler” and deliver as a gas
- Desflurane output determined by a "needle" valve, just like O2 and N2O
- Uses electronics to make desflurane flow proportional to total gas flow, so a constant
percentage is given regardless of fresh gas flow settings
c) Vaporizers at Altitude
• Recall that MAC is really a partial pressure
- Sevoflurane MAC = 2% x 760 mmHg =15.2 mmHg
• In Tibet PATM = 380 mmHg
• 15.2 / 380 = 4% (MAC of sevoflurane in Tibet)
- Vapor pressure of sevoflurane in Tibet (depends on temperature only) = 190 mmHg (same as
at sea level)
• Since vapor pressure = 1/2 barometric pressure, for every 100 ml of O2 flowing into
vaporizer the output will be 100 ml of sevoflurane plus 100 ml of O2
• This is 3 times as much as at sea level--vaporizer output triples
• Since MAC is only twice as great as at sea level, actually need to turn vaporizer DOWN
to 1.33% in order to get 1 MAC of anesthetic effect
• Desflurane “vaporizer”
- Percentage output unaffected by altitude
- MAC of desflurane in Tibet is 12%
- Need to “dial in” 12% desflurane to get 1 MAC of anesthetic effect
Low pressure leak test
a) Checks for leaks in flowmeters, vaporizers, common gas manifold
b) Check valve just before common gas outlet on many machines
• Allows patient to be ventilated with O2 from flush valve even if there is a leak in low pressure
system--therefore, the fact that the breathing circuit "holds pressure" does not guarantee that there
are no low-pressure leaks
• To check for leaks
- Turn machine fully off (otherwise minimum mandatory O2 flow will look like a leak
- Apply suction bulb to common gas outlet and verify that it remains deflated for at least 5 sec
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Breathing Circuits
a) Open (non-rebreathing)
• Simple face mask or nasal cannula (CO2 diffuses away from the face)
• Bag-Valve-Mask system (Ambu®): uses 3 valves to allow either spontaneous or controlled
ventilation while preventing rebreathing
b) Semi-Open (Mapleson / Bain)
• Most efficient removal of CO2 for a given gas flow when
the "pop off" valve is nearest the source of the ventilatory
power
- Spontaneous ventilation: Mapleson A
- Controlled ventilation: Mapleson D
• However, the "A" system is very inefficient (requires high
gas flows) to prevent rebreathing during controlled
ventilation, while the "D" system is reasonably efficient for
both controlled and spontaneous ventilation, so the "D" is
preferred for most applications.
- Bain circuit is a coaxial Mapleson D
c) Semi Closed Circle System
• Patient gas uptake < fresh gas flow < minute ventilation
• Some rebreathing of exhaled gas (following removal of CO2 by absorber)
d) Closed System
• Gas inflow = Patient Uptake
• If using sidestream agent / CO2 analyzer, must route exhaust back into circuit
• Starting values
- O2: 3-4 ml/kg/min
- Anesthetics: First minute uptake / √time (minutes)
• N2O (80% concentration, 80 kg patient): First minute uptake 1600 ml
• Sevoflurane (2%, 80 kg patient): First minute uptake 50 ml
• Desflurane (6%, 80 kg patient): First minute uptake 100 ml
• Closed System-Adjustments
- Total flow: Adjust N2O and O2 in proportion to keep volume of bag or bellows constant
- FIO2 : Adjust ratio of N2O and O2 to maintain desired FIO2 keeping total flow constant
- Depth of anesthesia: Adjust vaporizer setting to maintain desired depth or inspired
concentration
CO 2 Absorption
a) Granules
• Small enough to have large surface area but large enough to avoid “channeling”
• Typically 4-8 mesh
b) Composition
• Sodalime: NaOH, Ca(OH)2
• Baralyme: KOH, Ca(OH)2, Ba(OH)2
- More likely to react with anesthetics to form CO (desflurane) or compound A (sevoflurane)
c) Moisture
• Necessary for CO2 absorption
• Reduces likelihood of anesthetic breakdown
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d) Absorption Chemistry
• CO2 + H2O-->H2CO3
• H2CO3 + 2 NaOH-->Na2CO3+2H2O + heat
• Na2CO3 + Ca(OH)2 -->CaCO3 +2NaOH
• When the NaOH is gone, acidification causes indicator (ethyl violet) to turn “violet”
e) Zone of maximum absorption feels warm to touch (may be “hot” if malignant hyperthermia)
Pressure Transducer Systems

a) Accuracy with which transducer system reproduces actual intravascular pressure depends on
• Resonant frequency (higher is better)
• Degree of damping (most important if resonant frequency similar to 1/rise-time of waveform)
b) Zeroing Pressure Transducers
• Height of patient relative to transducer must remain constant after zeroing
• At time of zeroing
- Transducer may be at any height relative to patient (need not be at heart level)
- System should be “opened to air” by a stopcock at heart level before zeroing is performed
c) Site of Arterial Pressure Measurement
• Wave reflection causes systolic pressure to be higher and diastolic pressure to be lower when there
is an acute change in vessel diameter (radial / dorsalis pedis)
• This does NOT affect the mean pressure
• Resistance to flow causes a (very slight) decrease in mean pressure as
pressure measurement progresses from aorta to more distal vessels
d) Damping
• Oscillations within the transducer system may exaggerate or attenuate
certain frequency components of the pressure waveform
• Underdamped: Systolic overshoot and diastolic undershoot
• Overdamped: Looks like a “sine wave” with underestimation of
systolic and overestimation of diastolic pressure
• Regardless of damping, electronically determined mean pressures
should be accurate
• “Squeeze and release” flush valve to assess damping
Non-Invasive Blood Pressure Measurement

a) Most “standard cuff” systems use oscillometry
• Pulsations in the cuff pressure monitored as cuff deflates
• Initial pulsations--just above systolic pressure
• Maximal pulsations--mean arterial pressure
• Diastolic pressure by mathematical algorithm
b) Continuous non-invasive monitoring
• Most systems require intermittent calibration with a cuff
Cardiac Output Measurement
a) Fick Principle
• Conservation of mass
• Q=VO2/[CaO2-CvO2]
• Required measurements
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- VO2 (Oxygen uptake--difficult to measure during anesthesia)

- CvO2 (requires PA catheter)
• NICO
- Fick formula applied to CO2 elimination
- Partial rebreathing to estimate mixed venous CO2
- Requires constant ventilatory pattern (controlled ventilation only)
b) Esophageal Doppler Monitor
• Doppler: Change in frequency of sound / ultrasound / light waves when reflected from a moving
object (e.g., RBC)
c
v= f d ·
• 2 f i cos θ
- v=RBC velocity fd= Doppler shift fi=frequency of ultrasound
- θ=angle between ultrasound beam and direction of blood flow
• CO = HR x CSA x VTI
- CO=Cardiac Output CSA=Cross Sectional Area VTI=Velocity-Time Integral
c) Thermodilution
Quantity of Indicator
C.O.= ∞
∫ Δ Temp dt
t= 0
• Quantity of indicator = Volume x (TPATIENT-

TINDICATOR)
• Sources of error
- Quantity of indicator is "dialed in" to the C.O.
computer based on the intended volume and
temperature of injectate
- If volume injected is lower than intended, then
∞
∫ ΔTemp dt will be too low and the Cardiac

t= 0
Output reading will be falsely high

- If the temperature of the indicator is colder than
intended (e.g. using iced rather than room
∞
temperature saline) then ∫ ΔTemp dt will be too high, and the Cardiac Output reading will
t= 0
be falsely low
DISCLOSURE
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Fast-Tracking: Towards a Patient Centered Approach to PACU Bypass

Maged Argalious, M.D., MBA Cleveland, Ohio
I - PACU Discharge and PACU Bypass
Patient recovery from anesthesia has traditionally been divided into three phases 1 :
Early recovery (phase I) : awakening and recovery of vital reflexes

Intermediate recovery (phase II): home readiness
Late recovery: (phase III): full recovery including psychological recovery
Several scoring criteria have been used to assess patients’ early recovery, including the Aldrete scoring system 2 and
its modifications 3, the Mayo modified discharge score 4, and the standardized PACU Bypass/Discharge criteria 5
With the rapid rise in ambulatory surgeries and the introduction of short acting anesthetics, it was recognized that
criteria for early recovery from anesthesia were frequently met in the operating rooms before patients were even
transported to the recovery units (PACU).
Criteria for bypassing (also called fast-tracking) phase I recovery were established to identify patient eligibility for
PACU bypass, including the White and Song fast tracking criteria 6 and the Wake scoring criteria 7 .
These criteria if used by anesthesia team after patient emergence can avoid unnecessary transfer of patients to the
PACU if bypass criteria are met and can:
1- Reduce the “bottlenecks” that occur as a result of routine transfer of patients to phase I recovery areas
2- Reduce PACU nursing staff workload (and the associated high nursing to patient ratio of 1:2)
3- Avoid the delays that occur as a result of transfer of patients from phase I to phase II areas
4- Improve patient satisfaction by reducing the number of postoperative “stations” before patient discharge
5- Reduce the need for PACU recovery for patients undergoing inpatient surgeries with a disposition to
monitored surgical floors.
Table 1 lists a proposed comprehensive PACU Discharge /Bypass scoring system that incorporates heart rate, pain,
PONV, temperature and surgical bleeding with the traditional discharge criteria.
Limitations of PACU discharge and PACU bypass scoring criteria:
1- Various scoring criteria are missing important parameters (temperature, heart rate, shivering…)
2- Scoring criteria can change after disposition, i.e.: a pain free patient may develop sever pain and have
severe nausea /vomiting after rescue narcotics are given)
3- Each institution should assess the impact of PACU bypass on their overall perioperative throughput. To
give an example, while PACU bypass for outpatients to a phase II area may improve throughput, PACU
bypass for inpatients to a phase II area may impede surgical throughput if the phase II area also acts as an
intake unit, especially if patient transfer to the next level of care (surgical floor bed) is delayed.
The Postanesthesia Discharge Scoring (PADS) system is commonly utilized to assess home readiness for
ambulatory patients in same day surgery units and phase II recovery areas.
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Table 1: Proposed Comprehensive PACU Scoring Criteria that can be used for both PACU Phase
I Discharge and Phase I Bypass
A score ≥ 18 is required for PACU discharge/bypass with no category with a score of 0.

A score < 18 requires a physician assessment and sign out
1-Level of consciousness:
2 = Fully awake
1 = Arousable with verbal or tactile stimulation
0 = Unresponsive
2-Physical activity (voluntary or on command) *
2 = Able to move all extremities (excludes extremity with peripheral neuraxial block)
1 = Some weakness in movement of extremities (excludes extremity with peripheral neuraxial block))
0= No movement
3-Blood Pressure
2 = Systolic blood pressure +/- 20 % of preanesthetic level
1 = Systolic blood pressure +/- 21-30% of preanesthetic level
0= Systolic blood pressure +/- 30% of preanesthetic level
4-Heart Rate
2 = 60 to 100 or if outside this range, ≤ 10% change from baseline HR
1 = HR outside the range of 60 to 100 and the change from baseline is > 10% and ≤ 20%
0 = HR outside the range of 60 to 100 and the change from baseline is > 20%
5-Oxygen Saturation
2 = SpO2 ≥ 92% on room air or on supplemental oxygen with IVPCA
1 = SpO2 ≥ 92% on on supplemental oxygen not involving IVPCA
0 = SpO2 <92% on supplemental oxygen
6-Respiration
2= Able to breathe or cough freely
1= Shallow breathing or coughing, maintains airway without support
0= Apnea, dyspnea, tachypnea (RR > 24) or bradypnea (RR <8), or requires airway support
7-Pain
2 = No or mild pain with ot without analgesics
1 = Moderate pain controlled with analgesics
0= Persistent severe pain uncontrolled with analgesics
8-Postoperative nausea /vomiting
2 = No or mild nausea with no active vomiting
1 = Moderate nausea or transient vomiting
0 = Persistent severe nausea or vomiting
9-Temperature (tympanic)
2 = 36.0° C to 38.0° C
1 = 35.5°C – 35.9° C or 38.1°C to 38.3° C
0 = < 35.5° C or > 38.3° C
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10- Bleeding
2 = No active bleeding
1= Minimal oozing or drainage
0 = Active bleeding, blood soaked surgical dressing, or surgical drains filling with blood
* Physical activity criterion in case of central neuraxial anesthesia:

2 = Gross motor movement of all 4 extremities (or return to baseline motor function) with return of sensory level to
L5 (excludes extremity with peripheral neuraxial block)
1 = Two segment regression of central neuraxial anesthesia and return of sensory level to L1
(excludes extremity with peripheral neuraxial block)
0 = < 2 segment regression of central neuraxial anesthesia or sensory level above L1
II Anesthetic Technique and fasttracking
PACU Bypass Protocols

Several studies have reported that the implementation and application of PACU bypass protocols (with
multidisciplinary education) increases PACU bypass success 9, 10, 11.
The lack of uniform PACU Bypass/fasttrack eligibility criteria across studies and the use of different outcomes
measures to compare anesthetic techniques has made interpretation of the results of these trials complex.
In addition to PACU bypass eligibility, other outcomes measures have included mortality, morbidity (pain scores,
PONV), time to discharge, unanticipated hospital admission., hospital re-admission and patient satisfaction.
In a prospective trial involving five surgical centers, the institution of a multidisciplinary educational program,
resulted in a significant increase in overall PACU bypass rate for patients to whom a general anesthetic was
administered , and for those given other anesthetic techniques (monitored anesthesia care, regional or local
anesthetics 9;
During the follow-up period, the average (SD) recovery duration for patients who bypassed the PACU was
significantly shorter compared to that for patients who did not bypass, 84.6 (61.5) versus 175.1 (98.8) min, P <
0.001, with no change in patient outcome. Patients receiving only short-acting anesthetics were 78% more likely (P
< 0.002) to bypass the PACU after adjusting for various surgical procedures.
FastTrack Ineligibility
In a retrospective study of 332 patients, Twersky et al 12 instituted a fast-track protocol for all patients receiving
monitored anesthesia care based on the Modified Aldrete Score and fast-track success rate improved from 23% to
56%, P < 0.001. Risk factors for fast-track ineligibility were significant for patients younger than 60 yr (attributed to
deeper level of intraoperative monitored anesthesia care and therefore a higher incidence of postoperative sedation),
ASA III compared with ASA I patients, and general surgery when compared with ophthalmology and
orthopedics/podiatry.
Although total postoperative time in the fast-track group was, on average, 64 min shorter, there were no differences
in the time spent in phase 2 areas. Therefore, the total time saved was directly related to the mean PACU time in the
fast-track ineligible group.
Propofol vs Desflurane Vs Sevoflurane

In 51 healthy female patients patients scheduled for laparscopic tubal ligation, Coloma et al 13 randomised
maintenance of anesthesia to propofol, sevoflurane or desflurane , in combination with nitrous oxide
in oxygen. The primary maintenance anesthetic was subsequently titrated to maintain a target BIS
value of 60 during the operation.
Patients maintained with sevoflurane or desflurane emerged more rapidly from anesthesia than those
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receiving propofol. A larger percentage of patients in the volatile anesthetic groups was judged to be fast-track
eligible (77% and 94% for Sevoflurane and Desflurane, respectively, compared with 41% for Propofol (P < 0.05).
However, the percentages of patients who actually bypassed the PACU were similar in the three anesthetic groups
The times to home readiness were also similar in all three anesthetic groups. Moreover, the times to home readiness
and actual discharge for the bypassed patients were not significantly shorter than for the nonbypassed group The
overall incidences of side effects were also comparable and patient satisfaction with their quality of recovery was
equally high in all three groups.
Reasons for failure to bypass the PACU included residual sedation, nonspecific factors (e.g., weakness, shivering),
and surgical complications
Desflurane vs Sevoflurane
Fanelli et al 14 randomised 231 ASA Grade I–II patients, undergoing elective laparoscopic cholecystectomy in seven
University teaching hospital to receive a desflurane–remifentanil or sevoflurane–remifentanil anesthetic.
Emergence and postanaesthesia care unit discharge were faster with desflurane–remifentanil than sevoflurane–
remifentanil, but this was not associated with a larger proportion of postanaesthesia care unit bypass, confirming
that no clinically relevant differences are present between the two agents.
General Anesthesia vs Central Neuraxial Anesthesia vs Peripheral Nerve Blocks

In a meta-analysis of randomized controlled trials comparing regional vs general anesthesia for ambulatory
anesthesia 15, both central neuraxial block and peripheral nerve block were associated with
increased induction time, reduced pain scores, and decreased need for postanesthesia care unit analgesics.
However, central neuraxial block was not associated with decreased postanesthesia care unit bypass or time or
reduced nausea despite reduced analgesics, and it was associated with a 35-min increase in total ambulatory surgery
unit time. In contrast, peripheral nerve block was associated with decreased postanesthesia care unit need and
decreased nausea but, again, not with decreased ambulatory surgery unit time. This meta-analysis indicates potential
advantages for regional anesthesia, such as decreased postanesthesia care unit use, nausea, and postoperative pain.
Although these factors have been proposed to reduce ambulatory surgery unit stay, neither central neuraxial block
nor peripheral nerve block were associated with reduced ambulatory surgery unit time. Other factors, such as
unsuitable discharge criteria may have contributed to lack of reduced ambulatory surgery unit time with the use of
peripheral nerve blocks.Table 2 lists a summary of the factors that are likely to increase PACU Bypass Eligibility
Table 2
Factors likely to increase PACU Bypass Eligibility for Patients undergoing elective non-cardiac
surgery
1- Identification and management of preoperative comorbidities

2-Preoperative identification of patients for whom fast tracking is not suitable (fasttrack ineligible)
3- The use of evidence based prophylactic therapies to reduce postoperative morbidity (steroids, serotonin
antagonists, transdermal scopolamine for PONV prophylaxis)
4- Multidisciplinary service specific (e.g.: orthopedic/plastics) pathways/protocols that involve surgeons,
anesthesiologists, acute pain management, pharmacists, nursing and respiratory therapists.
5- Implementation of comprehensive PACU discharge/bypass criteria for GA and regional anesthesia ( see table 1)
6-Continuous education for patients and for the health care team. Preoperative patient education (including
instruction to patients going home with peripheral nerve catheters ) with clear instructions for when and who to
contact helps sets expectations, reduces patient anxiety and increases their satisfaction.
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7-Utilization of anesthetic techniques that optimize surgical conditions while ensuring rapid recovery with minimal
side effects
MAC/GA:
Is endotracheal intubation necessary ?
Is muscle relaxation required ?
Use short acting agents:
Benzodiazepines: Midazolam
Synthetic narcotics: Fentanyl, alfentanil, remifentanil
Anesthetic agents: propofol, sevoflurane, desflurane
Muscke relaxants: Rocuronium, vecuronium, mivacurium, cisatracurium
Central neuraxial anesthesia:
Short acting local anesthetics (mepivacaine, lidocaine, or low dose bupovacaine)
Hypobaric solutions for unilateral anesthesia
Peripheral nerve blocks: surgical anesthesia vs postoperative analgesia
8- Checklist for Fast track eligibility utilized in the operating room by the anesthesia team after patient
emergence.
9- True multimodal approach to acute pain management including: local anesthetic infiltration, peripheral nerve
blocks, acetaminophen, non steroidal agents, low dose ketamine and parenteral and oral narcotics
10- Measurement of outcomes (PACU bypass, time spent in phase II, need for nursing intervention in phase II,
time to home readiness, time to actual discharge, unanticipated hospital admission, hospital readmission,
patient satisfaction, morbidity and mortality)
11- Encourage early ambulation and resumption of normal activities of daily living
IV Impact o continuous centralized monitoring of oxygenation and ventilation on perioperative

workflow
Postoperative opioid induced respiratory depression is reported to occur with a frequency of 0.2 to 0.5%. 16, 17
Preventable deaths and anoxic brain injury from unrecognized opioid related sedation and respiratory depression
remain a serious and growing patient safety concern. Narcotic induced respiratory depression is mediated through
mu receptors . The difference in reported frequencies of postoperative respiratory depression is related to the various
definitions of respiratory depression used, the different patient populations studied and the different types,doses,
dose frequency and routes of administration of narcotics used across studies, with retrospective published reports
reporting a lower frequency than prospectively conducted trials. 18
It is estimated that one-third of code blue arrests in hospitals are from respiratory depression19 ,and that naloxone
administration for opioid induced reversal of respiratory depression is still required in about 0.2-0.7% of patients
receiving postoperative opioids. 20, 21
In most studies, the respiratory effects of opioids are quantified by the observed changes in breathing frequency
(bradypnea) and /or oxygen saturation. Both are considered surrogate indicators of ventilatory drive and provide
only limited information on the effects of a drug on the ventilatory control system (e.g., oxygen saturation is a
measure of gas exchange in the lung rather than a direct indicator of ventilatory efficacy). 17
Direct measures of ventilation such as inspired minute ventilation and arterial carbon dioxide concentration in the
clinical setting and hypercapnic ventilatory drive in the experimental setting , are more accurate measures of
ventilation but are less commonly used because they are more difficult to assess on a continuous basis.
While certain patient populations are more prone to postoperative respiratory depression, including including the
very old, the very young ( premature babies ),the very ill (ASA IV –V), the morbidly obese, patients with sleep
apnea, patients with neuromuscular diseases and patients with renal and liver disease, risk stratification of patients
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according to their comorbidities only predicted about 50% of postoperative arrests or near arrests , highlighting the
fact that it is impossible to predict accurately who will develop postoperative respiratory depression. 22
Recently, approaches to reduce/eliminate the incidence of postoperative opioid induced respiratory depression have
focused on:
Reducing the incidence of postoperative opioid induced respiratory depression:
1- The use of multimodal analgesic regimens to reduce the reliance on narcotic use (peripheral and central
neuraxial blocks, local anesthetic infiltration, acetaminophen, nonsteroidal anti-inflammatory agents, ketamine and
others
Early detection of postoperative opioid induced respiratory depression:
2- Extended monitoring of patients receiving postoperative narcotics by transfer of patients to intensive care units,
intermediate care units (also called step down units) and postoperative monitoring units. 23
3-The implementation of centralized monitoring units on regular surgical nursing floors. These include centralized
pulse oximetry and or endtidal/ subcutaneous capnography monitors.
Compared to patients with traditional monitoring every 2-4 hours on regular nursing floors, patients who were under
continuous postoperative pulse oximetry surveillance with alarms that alerted nurses of abnormal vital signs had
significantly fewer rescues and unanticipated transfers to the intensive care unit, 24 highlighting the potential
beneficial impact of continuous monitoring of oxygenation/ventilation on perioperative workflow
While approaches 1 and 3 can improve the perioperative workflow (earlier achievement of phase II criteria and less
reliance on critical care and intermediate care unit beds which are typically on short supply), the routine transfer of
surgical patients to crtical care units may have a negative impact on perioprative throughput, especially in light of
the finite sumber of critical care unit beds available.
Challenges in implementing continuous monitoring on regular nursing floors include the initial investment capital
required , education of caregivers to the true risk of drug induced respiratory depression, the appropriate monitor to
use (capnography versus pulse oximetry versus respiratory rate), the alarm thresholds that to avoid false positives
(alarm fatigue)while eliminating false negative (missing true events), the creation of rapid response teams that
respond to alarms (nursing, respiratory therapists, physisicans), as well as the appropriate period o monitoring
required
In June 2011, the Anesthesia Patient Safety Foundation convened a multidisciplinary conference on “Essential
Monitoring Strategies to Detect Clinically Significant Drug-Induced Respiratory Depression in the Postoperative
Period.”
The consensus of conference attendees was that continual electronic monitoring should be utilized for inpatients
receiving postoperative opioids.When supplemental oxygen is not being used,pulse oximetry was thought to be the
most reliable and practical monitor currently available. If supplemental oxygen is added (most patients receiving IV
PCA’s), then monitors of ventilation (e.g., capnography) were thought to be necessary to detect hypoventilation.
Improved education of all care providers on the dangers of postoperative opioids, and better assessment of sedation
level were thought to be critical steps in the prevention of postoperative drug-induced respiratory depression. It was
acknowledged that limited resources may result in a staged implementation of continual monitoring strategies with
the highest risk groups being monitored first, but with the goal of monitoring all inpatients receiving postoperative
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opioids. Risk stratification was shown to be insufficient to eradicate postoperative opioid-induced respiratory
depression.
IV Root Causes and Solutions for PACU overflow
Table 3: Summary of Root Causes of PACU Overflow: 26-32
I Large variations in surgical schedule (Lack of level scheduling)

II Lack of PACU/phase II physical space with a reduced PACU/OR bedspace ratio
III The presence of time based versus criteria bases PACU discharge criteria
IV Absence of protocols for PACU bypass/fasttracking
V Reduced PACU staffing levels
Absolute: due to PACU nursing shortage
Relative: High acuity resulting in 1:1 nursing
Mismatch of nursing schedules in relationship to OR schedule
VI High intensive care and surgical nursing floor hospital occupancy (census) resulting in delay in patient
discharge from the PACU and creating a bottle neck in the operating room (OR holds)
VII Logistic challenges :
Lack of a surgical operations unit/team that coordinates bed space availability and patient disposition
Delay in physician orders either for PACU or for the next level of care
Delays in patient transport (porter shortage) from PACU to next level of care
Delays in “turnover” (cleaning) of surgical nursing floor rooms between patients
Delays in hands off communication between PACU nursing and floor nursing
Table 4: Summary of Possible Solutions to PACU Overflow: 26-32
I Operating room schedule optimization through:

- Level scheduling
- Allocation of the right amount of OR time to each service on each day of the week. Optimal allocation of
Operating room time based on historical use by services and then using computer software to minimize the
amount of underutilized time and overutilized time
- Case sequencing to reduce the peak number of patients in the PACU and the risk of a delay in PACU
admission
II Increase in PACU physical space
III Adjusting PACU nurse scheduling each month based on anticipated workloads at each time of day
- Utilize algorithms that use the number of available nursing hours to find the staffing solution with the fewest
number of understaffed days.
- Monitor percentage of workdays with at least one delay in PACU admission to assess progress
IV Adoption and implementation of protocols for PACU bypass/discharge
V Other logistic solutions based on type of constraint

‐ Implementation of a surgical operations team
‐ Implementation of a pull versus push system between the PACU and hospital floors
‐ Hands off communication incomplete until physician orders are completed
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DISCLOSURE
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Anaphylaxis, Allergy, and Adverse Drug Reactions:

Important Considerations for Perioperative Management
Jerrold H Levy, M.D., FAHA Atlanta, Georgia
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Anesthesia For Major Orthopedic Surgery
Andrew D. Rosenberg, M.D. New York, New York
Peripheral Nerve Blocks

Issues currently being considered in regional anesthesia include: 1. Choice of technique: ultrasound (US),
peripheral nerve stimulator (PNS), or paresthesia. 2. The appropriate milliamperage (mA) and nerve response to
accept when performing regional techniques with a PNS (Can we be going too low?); 3. Superficial stimulation as a
guide to nerve location; 4. Choice of regional blocks for procedures below the elbow; 5. Choice of regional blocks
for postoperative pain relief; 6. Whether to perform blocks in anesthetized patients; and 7.Treatment of local
anesthetic systemic toxicity (LAST).
Ultrasound Guided Regional Anesthesia-
The ultrasound approach to performing regional techniques has gained popularity with advocates favoring
the ability to visualize the needle, nerves, and adjacent vascular structures and muscles in real time during
performance of the block. (1-3) When using ultrasound it is important to know the anatomy of the patient, the
terminology involved, and the pitfalls that one can encounter. Reflection of ultrasound waves back to the probe
indicates the characteristic of the substance that is being scanned. Fluid filled vessels and cysts do not reflect the
ultrasound wave, are seen as black objects on the screen and referred to as anechoic structures. Some reflection, as
from nerves and soft tissue are noted as grey structures and are referred to as hypoechoic, and strong reflection of
ultrasound waves from objects such as bones and needles are noted as white structures and referred to as
hyperechoic. The more parallel or less steep of an angle the needle is to the probe as it is advanced, the greater the
reflection of sound waves back to the probe and the better visualization of the needle. As the angle of needle
insertion increases, some sound waves from the needle are not reflected back to the probe and the ultrasound image
is not as hyperechoic. To avoid too steep an insertion angle, the object to be “blocked” should be in the middle of
the screen. If the needle is advanced along the long axis of the ultrasound probe, the block is being performed “in-
plane” and the whole shaft of the needle should be visualized. With this technique, as with all techniques, it is
important to note the needletip, and in the in-plane approach the whole needle, especially the tip should be seen. If
the needle crosses the probe’s long axis, by being advanced perpendicular to it, the technique is called the out of
plane approach. The important needle reflection to be noted is the point at which the reflection starts to be seen as
the needle is advanced as this is the needletip. If the needle is advanced further, a reflection is frequently still noted
as the shaft of the needle will also reflect sound waves, but the exact location of the needletip cannot be verified and
one cannot be certain where the injection is occurring. The ultrasound approach to the infraclavicular area is
performed at a point just medial to the coracoid process. The pulsating axillary artery and surrounding cords of the
brachial plexus can be visualized. Figure A-1 demonstrates the plane that the ultrasound probe cuts and figure A-2
shows the path that the needle takes to the plexus from its insertion point just below the clavicle (from Popovic et al
ref 1). The needle is advanced into the area of the lateral cord, and as local anesthetic is injected, the medication can
be seen to surround the vessel. Additional injections can be made either near the medial or the posterior cords.
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Figure A-1 Figure- A-2
The ultrasound view of the interscalene area (B-1 and B-2) demonstrates the circular trunks of the brachial plexus
as structures with hyperechoic rims and hypoechoic centers surrounded by the anterior and middle scalene muscles.
The carotid and internal jugular can also be noted. If the probe is moved further in a caudad direction, the brachial
plexus divisions can be seen in the supraclavicular area near the subclavian artery. Some physicians have been
performing ultrasound-guided blocks in this area. There is a concern that since the block is being performed near the
lung that a pneumothorax can occur. However, those performing the block in this location believe that the real time
visualization afforded by ultrasound guidance helps prevent against this complication.
Figure B-1 Figure B-2

For lower extremity surgery, lumbar plexus blocks can be used for procedures in the distribution of the
femoral, obturator, and lateral femoral cutaneous nerves. Fractured hip repair, femoral shaft surgery, and other
anterior femur surgery are amenable to this block. Femoral nerve and lateral femoral cutaneous nerve blocks can be
used for femoral neck fractures requiring cannulated pinning. Combined femoral and sciatic nerve blocks are
effective for procedures on the knee or distal to the knee. Postoperative pain relief after knee surgery can be
obtained with a femoral nerve block or a fascia iliaca block. In addition to single injection nerve blocks, catheters
may be used to provide postoperative pain relief by a continuous infusion of local anesthetic.
One block that does not utilize the nerve stimulator technique is the fascia iliaca block.(4) This block is
performed in a location that is between the femoral nerve and the lateral femoral cutaneous nerve so the chance of
nerve damage or inadvertent arterial or venous puncture is diminished. The block is performed in the following
manner. A line is drawn from the anterior superior iliac spine to the pubic tubercle and divided into thirds. A point is
located 2-3 cm (1”) caudad to the junction of the lateral and middle thirds of the line. After a sterile prep, a local
anesthetic wheal is raised at this point. A small entry hole is made in the skin with a sharp sterile needle and then a
blunt-tip spinal needle is advanced at a 45 degree angle to the skin in a cephalad direction. A distinct pop is felt as
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the fascia lata is pierced. As the needle is advanced a more subtle pop is felt as the fascia iliaca is traversed. After
obtaining the second pop, the needle is then advanced another millimeter to be certain that the side port of the blunt
tip needle, the site from which the local anesthetic is injected, is in the correct space. After initial aspiration, local
anesthetic is injected with intermittent aspiration. The local anesthetic then travels medially anesthetizing the
femoral nerve and laterally anesthetizing the lateral femoral cutaneous nerve. (4)
Figure C-1 Figure C-2
Ultrasound can be used to perform a femoral nerve block for perioperative pain relief. The long axis
of the ultrasound probe is placed in the inguinal crease below the inguinal ligament in a plane, which is
approximately perpendicular to the long axis of the femur or leg. The femoral nerve is visualized next to the femoral
artery and vein. Pulsations of the femoral artery help in its identification. Ultrasound also allows visualization of the
fascial planes surrounding the nerve and veins. As the needle is advanced toward the femoral nerve from lateral to
medial a popping sensation can be appreciated. When the needle is next to the nerve local anesthetic is injected and
it surrounds the nerve. (Figure C-1 and Fig C-2, from Popovic et al ref 1)
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The sciatic nerve can be visualized under ultrasound as it courses down the leg and divides in the popliteal area
(Figure D). Sciatic and popliteal US guided blocks, with and without catheters, are becoming popular.
Figure D
The question has been raised as to whether the ultrasound guided technique is safer than paresthesia or nerve
stimulator techniques. An evidence based medicine review of the topic reported that there is no evidence that UGRA
results in less injury than historic controls. (5)
Nerve Stimulation and Paresthesia Techniques

In choosing between PNS or paresthesia techniques, the PNS method is preferred because of its clear
endpoint (a twitch response in the muscle group innervated by the target nerve), its high success rate (frequently >
90%), its ability to minimize paresthesias (and thus theoretically reduce the incidence of traumatic nerve injury
because the needle has come as close to the nerve as possible without actually contacting it), and its proven track
record of a long history with minimal significant complications.(6-12)
When utilizing the nerve stimulator technique, success rate is increased with knowledge of anatomy. Use
proper equipment such as an insulated needle, which localizes the source of the electric current to the tip of the
needle, and a nerve stimulator that has a digital readout in 0.1 mA increments, can be easily adjusted, and provides a
stimulus at a fixed rate. The initial stimulating current should be set low, at 1-1.5mA, depending on the nerve to be
blocked.(13,14) Searching for a twitch response at this level is usually not painful, as it takes less current to
stimulate the motor fibers (A alpha fibers) of a mixed motor and sensory nerve than the sensory or pain fibers (A
delta or C fibers). (6) The initial “search mode” current setting (1.0-1.5 mA) is used to localize the nerves to be
blocked. Once a twitch is obtained the stimulating current can be decreased. During this next phase or the “fine tune
mode” the needle is optimally positioned to obtain a twitch response in the distribution of the nerves to be blocked at
the appropriately low mA needed to produce a successful block. Try to maintain a twitch response as you dial down
the nerve stimulator. If the twitch diminishes on advancing or withdrawing the needle, maximize the twitch response
again by increasing the current or returning the needle to its prior location, change direction if necessary, then
proceed. Injection of local anesthetic should be performed when the best twitch is obtained at the lowest mA
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possible (0.2-0.3 mA range). Two ml of local anesthetic is injected after negative aspiration. Loss of twitch confirms
proximity of the needle to the nerves to be blocked. After this, the remainder of the local anesthetic is injected with
intermittent aspiration. (6,7,12-15)
Some controversy exists about the proper mA to attain prior to injecting local anesthetic. With the use of
insulated needles and close attention to success rates, the mA sought prior to injection of local anesthetic has been
decreased to 0.2-0.3 mA for a number of blocks by some practitioners. Concern has been raised by others that
obtaining "too low" a current can result in nerve damage as the needle may be impaling the nerve and they suggest
levels of 0.5mA as the low point (16,17) There is no strong evidence to demonstrate that a low mA (0.2mA) current
at the time of injection is associated with the needle being intraneuronal. Accepting a twitch response as high as 0.5
mA for infraclavicular, interscalene, or axillary blocks will result in some failed blocks. High success rates without
complications have been obtained at 0.2-0.3 mA in blocks of the upper and lower extremity. (6,7,11,14,19) Higher
currents risk obtaining a twitch response when the needle and nerves to be blocked are on opposite sides of a fascial
plane. To facilitate the PNS technique, patients can receive anxiolysis but blocks should not be performed in adult
patients under general anesthesia as intraneuronal injections and even injection of the cervical spinal cord can occur
without the operator's knowledge.(18) The block should not be performed with the patient asleep and injection
should be stopped if there is unusual resistance or if the patient exhibits significant pain on injection.(18)
Superficial stimulation is a technique in which nerves are located superficially on the skin with a PNS.
(19,20) Superficial mapping facilitates performance of a block since the nerves to be blocked are located prior to
beginning the block, the entry point for the needle is determined before the patient receives a needlestick, the
number of needlesticks to which the patient is subjected is decreased, and the anesthesiologist performing the block
looks more adept. The technique can be performed with the metal component of an ECG electrode.(20) Using an
axillary brachial plexus block as an example, the brachial plexus can be located with superficial stimulation in the
axilla. The metal component of an ECG is connected to the negative lead of the nerve stimulator, and with the
current at approximately 5 mA, twitches of the brachial plexus are sought as proximal in the axilla as possible. Once
an acceptable twitch is obtained, the area is marked and becomes the needle entry location site for performing the
block.
The block should be chosen based upon the site of surgery. An interscalene block is utilized for surgery on
the shoulder down to the mid-shaft of the humerus. If a regional technique is not used for the operative procedure it
can be performed to provide pain relief after the patient is awake in the PACU and is well accepted and appreciated
by both inpatient and ambulatory patients. Infraclavicular nerve blocks are utilized for surgical procedures below the
mid-shaft of the humerus including the elbow, forearm and hand. Axillary blocks can be used for procedures on the
ulnar side of the hand. (13) Intermittent blocks or continuous catheters can be used for postoperative pain relief after
surgery.
The infraclavicular block is a very useful block. When performing the block as described by Raj, the head
is turned away from the side to be blocked and the arm is abducted 90 degrees. An insulated needle is passed at a
45-degree angle from a point 1” below the midpoint of the clavicle, drawn perpendicular to the plane of the clavicle,
to the pulsation of the axillary artery in the axilla (Figures E-1 and E-2). (15) Instead of palpating for the axillary
artery, superficial stimulation can be used to locate the brachial plexus as proximal in the axilla as possible. The
needle is then passed at a 45-degree angle from a point 1” below the clavicle, perpendicular to the clavicle, to the
point determined by superficial stimulation. The endpoint is a twitch in the distribution of the median, ulnar, or
radial nerves (a twitch in the forearm, wrist, or hand) at 0.2-0.4 mA. The advantage of the infraclavicular block is
that at this level the musculocutaneous nerve is still part of the brachial plexus and there is no need for a separate
block of the musculocutaneous nerve in the coracobrachialis muscle. (12,13,15) However, the musculocutaneous
nerve is the most superficial nerve in the brachial plexus at this level (Figure E-2) and it is possible that a twitch
obtained in its distribution, a biceps twitch, may be occurring across a fascial plane or after the nerve has exited
from the sheath. The biceps twitch is not a reliable endpoint to use when performing an infraclavicular nerve block
and other twitches, those in the hand or forearm, which are generated from the median, ulnar, or radial nerve, should
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be used as the endpoint. (10,22). Therefore, use the biceps twitch from musculocutaneous nerve stimulation as an
indication that you are in the correct anatomical region but need to adjust the needle.
Figure E-1 Figure E-2
Although needle direction is away from the lung when performing an infraclavicular nerve block some
prefer to perform the block more laterally. Sims modified the original Raj approach by utilizing an approach that is
slightly more lateral, but care must be taken not to increase the needle angle. (23) While we use either of the two
techniques described above, an even more lateral approach, a vertical approach, in which the needle is advanced at a
90 degree angle in the area of the coracoid process is gaining popularity. (11,24)
Local Anesthetic Systemic Toxicity (LAST)
20% intralipid has been demonstrated to be effective in reversing the cardiotoxic effects of bupivacaine
and other local anesthetics. (25,26) It should be made available for use where local anesthetic is injected in sufficient
doses to cause LAST. Remember to institute ACLS protocols as well with special attention to current
recommendations concerning use of epinephrine and vasopressin. (26,27) Recommended dosing is “initial bolus of
1.5ml/kg IV followed by infusion of 0.25 mL/kg/min continued for 10 min after hemodynamic stability is attained.
Failure to achieve stability should prompt an additional bolus and increase of infusion rate to 0.5ml/kg/min.
Approximately 10mL/kg lipid emulsion for 30min is recommended as an upper limit for initial administration.
(26,27)
Spine Surgery
Current issues in patients undergoing spine surgery include understanding the degree of cervical spine
pathology as it affects endotracheal intubation and neck movement, caring for patients undergoing prolonged
surgical procedures (combined anterior-posterior spinal fusions), use of lung isolation techniques, loss of vision, and
the effect of non-steroidal anti-inflammatory medications (NSAIDS) on bone healing.
Patients presenting for spine surgery or other orthopedic procedures may be suffering from rheumatoid
arthritis (RA), ankylosing spondylitis, and other rheumatologic disorders. Difficulty in intubating patients with RA
can result from temperomandibular joint arthritis, a hypoplastic mandible, an overbite, and effects of RA on the
cervical spine.(12,13) Cervical spine pathology occurs in 80% of patients with RA and may manifest itself in a
number of ways- 1) atlantoaxial subluxation- the anterior arch of C1 and the dens or odontoid move more than 4 mm
apart from each other on flexion and extension 2) subaxial subluxation- greater than a 15% displacement of one
vertebrae on another 3) and superior migration of the odontoid in which collapse of some of the cervical vertebrae
results in displacement of the odontoid into the base of the skull through the foramen magnum. (12,13,28) Patients
with ankylosing spondylitis may present with fused cervical spines fixed in a flexed position. Forced movements can
result in cervical spinal cord damage. An organized approach to the patient with cervical spine disease, whether as a
result of a rheumatologic disorder or other medical conditions, includes proper preoperative evaluation including
range of motion, consideration of x-rays in flexion and extension, and appropriate use of intubation aides such as a
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fiberoptic bronchoscope or other airway assistance device to facilitate intubation.

Major spine surgery in the thorax and lumbar areas may involve anterior, posterior, or combined
procedures in one setting. The anterior component can include thoracic exposure and involve lung isolation
techniques. These procedures can take many hours and result in major blood loss and fluid shifts. Considerations
include controlling blood pressure, monitoring spinal cord function, treating blood loss, and positioning concerns.
Lung isolation techniques for open thoracic or thorascopic procedures can be obtained with a double lumen
tube or a bronchial blocker. One option is to use a Univent® tube, a single lumen tube with the bronchial blocker
attached alongside. The blocker is advanced and inflated at the time of occlusion of the mainstem bronchus and then
the blocker is retracted into the casing, and the tube functions as a single lumen tube. Therefore, you do not have to
change the tube between anterior and posterior portions of the surgery. Additionally the Univent® tube can be left in
place if controlled ventilation is necessary in the postoperative period. A fiberoptic bronchoscope is utilized to
position the bronchial blocker into the mainstem bronchus to be occluded. One drawback is that the external
diameter of the Univent® tube is large since it encompasses both the endotracheal and the separate bronchial
blocker components. It is important to inform the postoperative care team about the type of tube you left in place.
The prone position is associated with alterations in pulmonary function, increases in venous pressure,
pressure and stretch on nerves, and visual loss. Postoperative vision loss (POVL) has become a recent concern (29-
32). A combination of factors including perioperative anemia, hypotension, prolonged surgery and resistance to
blood flow may be causal factors. (29-33) However, the etiology remains unclear. While direct pressure on the eye
can cause problems this does not appear to be the cause for the majority of cases. Ischemic optic neuropathy (ION),
a common diagnosis in postoperative visual loss may result from decreases in ocular perfusion pressure (OPP)
causing decreased blood supply to the optic nerve. Another possible etiology is a compartment syndrome within the
orbit. OPP is a function of mean arterial pressure (MAP) and intraocular pressure (IOP) and can be determined from
the formula OPP=MAP-IOP such that decreases in MAP or increases in IOP will decrease OPP. (26-33) ION may
result from decreased blood flow through the posterior ciliary arteries which are end arteries. The areas receiving
watershed blood supply from these arteries may be compromised resulting in ischemia. Cheng et al. demonstrated an
increase in intraocular pressure over time in the prone position. (31) Prone position, especially if the patient is in a
slight head down tilt, can result in edema and venous engorgement, increasing IOP. Since the etiology of vision loss
was unclear, a postoperative visual loss national database was established to identify risk factors associated with
postoperative visual loss. A report from the registry included 93 cases and pinpoints ION as the most common cause
with blood loss over 1 liter and anesthesia duration over 6 hours being present in 96% of cases. (34) An
accompanying editorial suggested staging long procedures (35). A practice advisory on POVL has recently been
updated. (36). In 2012, an analysis of cases having POVL with matched patients who did not suffer vision loss was
published and noted that male gender, obesity, use of a Wilson frame, longer cases, greater estimated blood loss and
decrease use of colloid were associated with POVL. (37)
Attempts to decrease blood loss during spine surgery include use of antifibrinolytics such as aprotinin as
well as tranexamic acid (TXA) and epsilon aminocaproic acid. (38-40) These medications do tend to decrease blood
loss in orthopedic surgical procedures. Aprotinin is no longer used do to the side effects of renal, cardiac, and
neurologic complications, the increased mortality in some patient populations, warnings circulated by the FDA
about the medication, and that the manufacturer is no longer marketing or supplying the medication. (41) With all
three medications there is a theoretical concern of increased thrombosis.
Non-specific NSAIDS such as ketorolac have been identified as interfering with bone fusion after spine
surgery. Therefore, many surgeons avoid using ketorolac in this setting. (42) Research is being conducted on the
specific COX-2 inhibitors. While studies have been performed on animal models, the recommendation for use of
COX-2 inhibitors in humans where bone fusion is desired needs further clarification. The issue of using these
medications and their effect on bone fusion is now clouded by controversy.
Intraoperative monitoring of spinal cord function may include somatosensory evoked potentials (SSEPs),
motor evoked potentials (MEPs), including transcranial motor evoked potentials, EMGs, or a wake–up test. A
nitrous oxide/oxygen, narcotic technique with an infusion of propofol and muscle relaxant is frequently utilized.
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Dexmetadomidine is also used by some, as is ketamine. Benzodiazepines are avoided and only a low concentration,
a small percent of 1 MAC of inhalation agent is used, if any is used at all, so as to not effect SSEP or TCMEP
monitoring. If EMGs are monitored to assess pedicle screw placement, muscle relaxants need to be discontinued
early enough to allow for proper testing. When transcranial motor evoked potentials (TCMEPs) are employed
muscle relaxant cannot be used as well. Be careful to adequately protect the tongue and endotracheal tube in patients
having TCMEPs performed as there is a strong contraction of the masseter muscles and other muscles of mastication
when the potentials are generated. These contractions can cause lacerations in the tongue and even damage the
endotracheal tube. Alterations in SSEPs and MEPs may take time, as long as half an hour, to occur after distraction
or rotation of the spine. Changes in SSEPs or MEPs may require modifications in the distraction or rotation of the
surgical correction. Be prepared to perform a wake up test if the surgeon requests it.
Since combined anterior-posterior spine procedures can be prolonged, the patient must be carefully
assessed at the end of the procedure. The degree of swelling is an important consideration prior to deciding on
extubation of the patient as significant facial swelling would be an indication to leave the endotracheal tube in place.
Hematocrit, body temperature, pulmonary function, including the effect of the thoracic procedure on respiratory
capability, and reversal of neuromuscular blockade are additional important factors to be considered.
The Beach Chair Position

Shoulder surgery is often performed in the beach chair (BC) position with the pt elevated from 30-90°. In
addition, some surgeons request hypotension. Rare reports of severe neurologic complications including stroke,
ischemic brain injury and vegetative state have occurred.(43,44) A decrease in cerebral perfusion pressure (CPP) is
present in the BC position as compared to supine due to a gradient between the level of the heart and the head. The
location of the BP cuff must be considered when figuring the actual BP at the level of the brain. An adjustment and
decrease of 0.77mm Hg for each cm of height above the level of the BP cuff should be calculated to understand the
perfusion pressure present at the Circle of Willis (COW)-which is roughly at the level of the external auditory
meatus. (43,44) Remember, there is additional brain tissue above the level of the Circle of Willis. Caution should be
used to avoid significant hypotension and decreased CPP when patients are in the BC position. (43,44)
Anticoagulation and the Orthopedic Patient

The Second Consensus Conference on Neuraxial Anesthesia and Anticoagulation (available at the ASRA
website). (45) described the issues of caring for patients with anticoagulation and provided recommendations. Other
anticoagulants or antiplatelet medications should be avoided when LMWH are used, an appropriate length of time
(10 – 12 hours) should elapse after the last dose of LMWH thromboprophylaxis before performing neuraxial
anesthesia, and appropriate timing of the first dose of LMWH in the postoperative period needs to be considered to
decrease the chance of spinal hematoma. (45). Another issue is the use of spinal and regional anesthesia in the
presence of clopidogrel, a potent antiplatelet medication, and how long a patient should have discontinued the
medicine before a neuraxial block is performed.. The recently published guidelines on Regional Anesthesia in the
Patient Receiving Antithrombotic or Thrombolytic therapy (Third Edition) reiterate the 7 day period that has been
suggested in the past but also include the suggestion that “if neuraxial block is indicated between 5 and 7 days of
discontinuation of clopidogrel, normalization of platelet function should be documented.” (46,47) Others suggest
less time and that patients can be off of clopidogrel for 5 days before surgery. As experience grows, it is expected
that these guidelines will be modified and practitioners should make themselves aware of the latest suggestions
when balancing the time a patient is off this medication with the risks of bleeding.
References:
1. Popovic J, Morimoto M, Wambold D, Blanck TJJ, Rosenberg AD. Current Practice of Ultrasound-Assisted
Regional Anesthesia. Pain Practice 2006;6:127-134
2. Sandhu NS, Capan L. Ultrasound guided infraclavicular brachial plexus block BJA 2002;89:254-9
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3. Marhofer P, Greher M, Kapral S. Ultrasound guidance in regional anesthesia. Br J Anaesth 2005 94(1): 7-17
4. Wambold D, Carter C, Rosenberg AD. Pain Practice 2001;1:274-277
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6. De Andres J, Sala-Blanch X. Peripheral nerve stimulation in the practice of brachial plexus anesthesia. A
review. Reg Anes Pain Med 2001;26:478-48
7. Kaiser H, Niesel HC, Klimpel L et al. Prilocaine in lumbosacral plexus block: General efficacy and comparison
of nerve stimulation amplitude. Acta Anes Scand 1992;36:692-697
8. Davies MJ, McGlade DP. One hundred sciatic nerve blocks: Aneasth Intens Care 1993;21:76-78
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limb blockade Anesth Analg 1999;88:847-852
10. Albert DB, Bernstein RL, Rosenberg AD et al. Anesth Analg 78: S3, 1994
11. Wilson JL, Brown DL, Wong GY et al. Infraclavicular brachial plexus block AnesthAnalg 1998;87:870-3
12. Rosenberg AD Anesthesia for major orthopedic surgery. ASA Refresher Courses Chap 15 2004;32:169-178.
13.Bernstein RL, Rosenberg AD. Manual of orthopedic anesthesia and related pain syndromes NY Churchill
Livingstone, 1993
14. Pither CE, Raj P, Ford DJ. The use of the peripheral nerve stimulator. Reg Anes 1985;10:49-58
15.Raj PP, Montgomery SJ, Nettles et al. Infraclavicular brachial plexus block. Anes Analg1973;52:897-902
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stimulation for axillary brachial plexus block. Reg Anes Pain Med 2001;26:100-4
17. Neal JM. How close is close enough? Defining the “paresthesia chad” Reg An Pain Med 2001;26:97-99
18. Benumof JL. Permanent loss of cervical spine cord function associate with interscalene block performed under
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block Anesth Analg 1993;76:914-5
21. Albert DB, Dudarevitch D, Bloom K, Rosenberg AD. Surface Stimulation to Determine Needle Direction and
Angle When Performing an Infraclavicular Brachial Plexus Block. Pain Practice 2006;6:104-106
22. Fitzgibbon DR, Debs AD, Erjavec MK. Selective musculocutaneous nerve block.. Reg Anes 1995;20:239-241
23. Sims JK. Clarification of landmarks for infraclavicular approach. Anes Analg 1977;56:554
24. Jandard C, Gentili ME, Girard F, et al. Infraclavicular block with lateral approach and nerve stimulation: extent
of anesthesia and adverse effects Reg Anesth and Pain Med 2002;27:37-42
25. Rosenblatt MA et al Successful use of a 20% lipid emulsion to resusitate a patient after presumed bupivacaine-
related cardiac arrest. Anesth 2006;105;217-18
26. Weinberg G Treatment of local anesthetic systemic toxicity RAPM 2010;35:188-193
27. ASRA Practice Advisory on Local Anesthetic Toxicity RAPM2010;35(2): 152-161
28. Skues MA, Welchew EA. Anesthesia and rheumatoid arthritis. Anaesthesia 1993;48:989
29. Roth S Perioperative Visual Loss: What do we know, what can we do? BJA 103; BJA/PGA suppl 131-140, 2009
30. Williams EL. Postoperative Blindness. Anes Clin N Am 2002;20:367-384
31. Cheng MA, et al. The effect of prone positioning on IOP in anesthetized patients. Anesth 2001;95:1351-5
32. Lee L, Lam A. Unilateral blindness after prone position lumbar spine surgery. Anesth 2001;95:793-5
33. Roth S, Barach P. Postoperative visual loss: still no answers-yet. Anesthesiology 2001;95:575-7
34. Lee L, Roth S, Posner K et al The ASA Postoperative Visual Loss Registry: Analysis of 93 Spine Surgery
Cases with Postoperative Visual Loss Anesth2006;105:652-659
35. Warner M. Postoperative Visual Loss Experts Data and Practice Anesthesiology 2006 105:641-642
36. Practice Advisory for Perioperative Visual Loss Associated With Spine Surgery Anesth 2012;116:274-85
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38. Neilipovitz DT et al. A Randomized Trial Of TXE to Reduce Blood Transfusion Anes Anal 2001;93;82-87
39. Urban MK et al The Efficacy of Antifibrinolytics in the Reduction of Blood Loss During Complex Adult
Reconstructive Spine Surgery Spine 2001;26;1152-1157
40. ZuffreyP et al. Do Antifibrinolytics Reduce Allogeneic Blood Transfusion in Orthop Surg Anes 2006;105:1034
41. Mangano DT et al. The Risk Associated with Aprotinin in Cardiac Surgery NEJM 2006;354:353-65
42. Glassman SD, Rose SM, Dimar JR, et al. The effect of Postoperative Nonsteroidal Anti-inflammatory Drug
Administration on Spinal Fusion. Spine 1998;23:834-838.
43. Pohl A, Cullen DJ Cerebral Ischemia during shoulder surgery in the upright position: a case series J Clin
Anesth 2005;17:463-469
44. Cullen DJ, Kirby RB. Beach Chair Position May Decrease Cerebral Perfusion Pressure Catastrophic Outcomes
Have Occurred APSF Newsletter 22:2,25 Summer 2007
45. 2nd Consensus Conference on Neuraxial Anesthesia & Anticoagulation2002, R Anes Pain Med 2003;28:172
46. Horlocker TTet al Regional Anesthesia in the Patient Receiving Antithrombotic or Thrombolytic Therapy
(Third Edition) RAPM 2010;35:64-101
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Thrombolytic Therapy (Third Edition) RAPM 2010; 35:102-105
DISCLOSURE
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Strategies for Success in One-lung Anesthesia
Jerome Klafta, M.D. Western Springs, Illinois
Objectives:
1. Explain common and uncommon causes of lung separation failure and present strategies for success
2. Review evidence-based recommendations for management of one-lung ventilation
3. Discuss approaches to lung separation in patients with difficult airways
The big picture

“Success” in the context of one-lung anesthesia means that lung collapse is both complete and well tolerated
by the patient. Although the concept is simple, a number of clinical details frequently make the difference between
success and failure. Lung isolation (= functional lung separation) allows us to ventilate one lung independent of the
other (airtight seal) or to restrict passage of blood or fluids (watertight seal) from one lung to another. One-lung
anesthesia requires not only functional lung separation but also adequate one-lung ventilation (OLV) and
oxygenation. Figure 1 depicts the three clinical endpoints integral to one-lung anesthesia:
• Optimal position of double-lumen tube or

blocker
• Functional lung separation
• Adequate one-lung ventilation and oxygenation
Various overlapping subsets of these conditions can

and do occur. For example, adequate position of the
double-lumen tube (DLT) or bronchial blocker (BB)
does not ensure functional lung separation (condition
A), and adequate OLV can sometimes be achieved
with suboptimal DLT position (condition C). Table
1 lists examples of causes and solutions for each
clinical condition in Figure 1. By identifying the
exact nature of the difficulties, the anesthesiologist
can implement appropriate therapy without wasting
time on maneuvers (DLT repositioning, cuff volume
manipulations, or ventilation changes) that are not
part of the problem.
Table 1: Clinical conditions during one-lung anesthesia

Area Example Situation Typical Solution
A • No airtight cuff seal – lungs not separated • More air in cuff or larger DLT
B • Left DLT in too far occluding LUL orifice • Position DLT optimally
C • Right DLT cuff occluding RUL orifice • Position DLT optimally
• Hypoxemia • 100% oxygen/CPAP/PEEP/TLV
D
• Obstruction of the ventilating lumen of DLT • Consider alternative lung separation technique
E • No Problem!
LUL = left upper lobe; RUL = right upper lobe; TLV = two lung ventilation
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Design characteristics of double lumen tubes and bronchial blockers

Common adult DLT sizes are 35, 37, 39, and 41 French (F). Some manufacturers also provide 26, 28 and 32
F sizes. The particular dimensions and design characteristics vary somewhat between manufacturers (Rusch, Portex,
Sheridan, Mallinckrodt, and Fuji Systems). The resting bronchial cuff volume (defined as the smallest cuff volume
beyond which a 0.5 cc increase results in more than a 10 torr increase in cuff pressure) can differ between sizes (35
F = 3.7 cc; 41 F = 2.0 cc) (1). Inflation of the bronchial cuff beyond its resting volume (or even less than its resting
volume if fitted tightly inside a bronchus) may result in dangerously high intracuff pressures and should be avoided
(1,2).
The Univent tube (www.fujisys.co.jp/en/phycon/phycon.html), an alternative device for providing OLV,

underwent design modifications in 2001. The manufacturer reports that the new Torque Control Blocker (TCB)
Univent has a more flexible shaft that is easier to direct into the target bronchus and a blocker made from a softer
medical grade silicone material that is more compliant. Typical cuff inflation volume is 5-6 cc.
The Arndt endobronchial blocker was the first of several additions to our armamentarium of lung separation
devices (3). This system minimizes some of the traditional difficulties associated with the use of Fogarty
embolectomy catheters as independent BBs and with Univent tubes. A patient’s lungs can be conveniently
ventilated while the blocker is fiberoptically positioned through the Arndt multiport airway adapter. The guidewire
loop that protrudes through the blocker’s tip is used to couple the blocker to the fiberoptic bronchoscope (FOB)
which can be directed fiberoptically to the desired location in the bronchial tree. The blocker’s 1.4 mm lumen can
be used to insufflate oxygen or suction gas from the blocked lung after the wire loop is removed. The smallest
single lumen tube (SLT) for use with this blocker coaxially (≥ 7.5 mm ID) has a corresponding outer diameter that
compares favorably with that of the typical DLTs and Univent tubes used for small adults.
Since its introduction in 1999, Cook Critical Care has made several design modifications. The elliptical cuffs
on the 9 F blocker were discontinued in 2011. A 5 F pediatric blocker has been available since 2001 and can be
used inside SLTs as small as 4.5 mm. A midsize 7 F catheter is also available to permit the use of a larger diameter
FOB or a smaller diameter SLT for coaxial use. “Murphy eye” side holes have been introduced into the distal end
of the 9 F adult catheter to circumvent suctioning difficulty if the end hole abuts the bronchial mucosa, and the
guidewire loop can now be reinserted if needed. Characteristics of available blockers are described in Table 2
below:
Table 2: Arndt Endobronchial Blockers
Average cuff
Size Smallest SLT ID for Length
Cuff shape inflation volume
(F) coaxial use (mm) * (cm)
(cc)
9 7.5 78 Spherical 4–8
7 6.5 65 Spherical 2–6
5 4.5 50 Spherical 0.5 – 2.0

ID = inner diameter * with 3.4 mm FOB (data from Cook Critical Care)
Cook Critical Care introduced the Cohen blocker in 2003. This device is similar to the Arndt blocker except
that its distal tip is directed by way of a proximal control mechanism instead of coupling to a bronchoscope. The
Uniblocker is an independent BB controlled similarly to the one integral to the Univent tube. The use of bronchial
blockers in adults for routine cases (4) and for selective lobar blockade (5) was recently reviewed. The Y-shaped
EZ blocker is the newest BB design (6).
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Size selection of double-lumen tubes

Assuming that the main body of a DLT will fit through the glottic opening and the trachea, an appropriately
sized DLT is the largest tube that will fit in the mainstem bronchus with only a small air leak detectable when the
cuff is deflated (2). The presence of some air leak ensures that the tube is not tightly impacted in the bronchus.
Thus, the goal is to select a DLT with an outer bronchial diameter that is 1-2 mm smaller than the diameter of the
intubated bronchus to allow for the size of the deflated cuff (2). Although some practitioners use 35 F DLTs for all
patients (7), many select 41 F and 39 F DLTs for tall and short men, respectively, and 39 F and 37 or 35 F DLTs for
tall and short women, respectively. However, there is considerable variability in left mainstem diameters and
relatively weak predictive value of gender and height (2,8). Since prediction is imprecise, measurement of the left
mainstem diameter is most reliable. On chest x-ray (CXR), it is discernible only 50-69% of the time (2,9) but it is
reliably identified on chest CT (10). Brodsky et al measured the more readily obtainable tracheal diameter on CXR
at the level of the clavicles and used a previously described mean left bronchial to tracheal width ratio to calculate
the left mainstem diameter (11). However, the confidence limits for this ratio may be too large to be useful
clinically (9). Checking the radiograph to identify unexpectedly large or small bronchi is probably most important.
One critically important assumption is that we clinicians know the dimensions of the differently sized
DLTs. Russell et al independently measured the dimensions of DLTs from 4 manufacturers and found marked
variations even within the same tube size for each manufacturer (12)! See Figure 2. Thus, any effort to predict
appropriate DLT size has this important limitation.
Figure 2 (from ref 12)
While attempting to select an appropriately sized DLT is important, it is equally important clinically to recognize
when a DLT is too large (bronchial lumen will not fit in bronchus or forms an airtight seal with no air in the cuff) or
too small (requires more than 3 cc of air in the bronchial cuff to create a seal) and adjust accordingly.
Right-sided double-lumen tubes

The perceived or real difficulty in achieving adequate OLV with right-sided DLTs is evidenced by the fact
that they are used much less frequently than are left-sided DLTs: 96% of Bronchocath sales are left-sided (Sherri
Cowan, personal communication, 2011). Use of left-sided DLTs is generally encouraged because of the greater
margin of safety in positioning them, but a recent restrospective analysis of 691 cases demonstrated
indistinguishable oxygenation, ventilation, and airway pressure performance betweeen right- and left-sided DLTs
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(13). Moreover, in the hands of infrequent users of DLTs, the 3 aforementioned performance criteria were less
favorable using left-sided tubes (14).
When right- and left-sided DLTs were compared for left-sided thoracic surgery in 40 patients, no right upper
lobes collapsed and the difference in the time to place the tubes was clinically insignificant (3.37 vs. 2.08 min) (14).
Although their routine use in thoracic surgery is controversial (15,16), right-sided DLTs are indicated when a patient
requires a DLT but also has an anatomic abnormality of the left mainstem bronchus such as an exophytic or stenotic
lesion or left tracheobronchial disruption. Regardless of the reasons for use, the right mainstem bronchial length
must be at least 10 mm to accommodate the lateral aspect of the bronchial cuff (17). This length can be determined
bronchoscopically or from a CXR or CT. Attempts to position a right-sided DLT in patients whose right mainstem
bronchi are too short are almost certainly doomed to failure.
Fiberoptic placement and positioning of double-lumen tubes

Precise positioning of a DLT is most reliably achieved with the benefit of a FOB. In comparisons of
fiberoptic positioning of DLTs with conventional methods, over one-third of left DLTs were malpositioned after
blind intubation and the inspection and auscultatory method (18). In a study of 200 patients, the incidence of
malposition (0.5 cm deviation from ideal position) was 39.5% with 14% of them “critical” (19). Critical
malpositions were those in which the left endobronchial limb allowed no clear view of the left upper or lower lobe
bronchus, the right endobroncial limb allowed no clear view of the RUL bronchus, or there was intratracheal
dislocation of more than one-half of the endobronchial cuff. Visually unassisted placement of left DLTs may result
in initial intubation of the wrong bronchus 7-30% of the time (19,20,21,22).
Ovassapian described a reliable and reproducible method of placing left-sided tubes (and right-sided, with
slight modification) on the first attempt (21). This technique involves first inserting the DLT through the glottis
with direct laryngoscopy, rotating it 90° leftward, and advancing it only until the proximal edge of the tracheal cuff
is past the vocal cords. This limited advancement ensures that the tip of the bronchial lumen is supracarinal. After
the tracheal cuff is inflated, ventilation through both lungs is initiated. The FOB is then placed through the
bronchial lumen and advanced until the carina and mainstem bronchi are clearly identified. The posterior
membranous portion of the trachea, the 5 cm left mainstem bronchus, and the characteristic trifurcation of the RUL
bronchus are reliable anatomic landmarks to facilitate directional orientation. The FOB is then advanced into the
left mainstem bronchus to a position just proximal to the left upper and left lower lobe bronchi. After deflation of
the tracheal cuff, the entire DLT is slid over the FOB until its bronchial lumen comes into view beyond the tip of the
FOB. Confirmation of a patent left upper and left lower lobe bronchus ensures that the DLT is not in too far.
Finally, the FOB is passed through the tracheal lumen to check for a carinal or subcarinal position of the bronchial
cuff and ensure patency of the right mainstem bronchus.
When 50 thoracic surgical patients with left-sided DLTs were positioned from supine to lateral, the tubes
tended to move outward by an average of about 1 cm (23). Inflation of the endobronchial cuff before lateral
positioning did not decrease the incidence or the amount of overall distance change. Because of the tendency for
carinal shift and DLT movement upward with lateral positioning, there is an advantage to keeping the bronchial cuff
at least 1 cm inside the left mainstem bronchus before turning laterally. In another study of 61 patients, the
incidence of proximal repositioning was reduced significantly (43% vs. 16%) after turning from supine to lateral
when the left Bronchocath was initially inserted with the proximal edge of its bronchial cuff 5 mm beyond the
tracheal carina (24). Intraoperative use of a rigid neck collar to prevent head and neck movement will minimize but
still not prevent DLT movement while positioning supine to lateral (25). Initially positioning the DLT without a
headrest may minimize this displacement (26).
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Confirming lung separation

Of the techniques described to achieve a minimum occlusive seal (17,27,28), I routinely use the positive
pressure test or bubble test depicted in Figure 3. There are a number of reasons to use a “just seal” technique to
inflate the bronchial cuff of a DLT or bronchial blocker (BB). First, a cuff that is inflated beyond a minimum
occlusive pressure may result in bronchial mucosal ischemia or even rupture (27,29). Second, an over-inflated
bronchial cuff or BB is more likely to herniate over the tracheal carina and interfere with contralateral ventilation.
Third is the ability to immediately and definitively
verify lung separation. That “moment of truth” when
the thoracoscopic port is inserted or the hemithorax is
opened is thoroughly predictable. If lung collapse is
slow or incomplete, documented lung separation
assures the anesthesiologist that manipulation of the
DLT or BB or their cuffs will not improve the
situation. Attention can be focused on other
maneuvers that will improve the surgical exposure:
manual compression, suction, additional time, or
intrahemithoracic CO2 insufflation (30).
Ventilation management
Traditional teaching is that for most patients, tidal volumes during OLV be initiated at 10 cc/kg with a
respiratory rate adjusted to maintain normal pCO2 (18). However, the use of smaller (6 cc/kg) or larger (15 cc/kg)
tidal volumes may be beneficial in some patients (31). In patients with COPD, the development of significant
autoPEEP or dynamic pulmonary hyperinflation is an ever-present risk (32). A growing body of evidence suggests
that lower tidal volumes (5-6 cc/kg) and their associated lower plateau pressures may protect against acute lung
injury during surgery for lung resection (33,34,35,36). A 2006 Pro/Con editorial summarized the “low versus high”
tidal volume debate for OLV (37, 38).
The use of pressure-controlled ventilation (PCV) during OLV results in lower airway pressures compared to
volume-controlled ventilation (VCV) and may improve oxygenation in select patients with preexisting lung
pathology (39,40). PCV with 4 cm H2O PEEP to the dependant lung provides lower airway pressures compared to
VCV with no PEEP (41). Comparisons of desflurane (42) and sevoflurane (43) with isoflurane during OLV
demonstrated that the choice of volatile anesthetic does not significantly influence arterial oxygenation. Sevoflurane
and propofol for maintenance anesthesia also had similar effects of oxygenation during OLV (44). The addition of
dexmedetomidine to desflurane anesthesia did not alter oxygenation (45). Emerging evidence suggests that using
volatile anesthetics compared to propofol decreases the local alveolar inflammatory response to OLV (46).
Predicting which patients are at highest risk for intraoperative hypoxemia during OLV informs our decision
to institute prophylactic nondependent lung CPAP (47) or to even attempt OLV. CPAP is most effectively applied
to a fully inflated lung, since the opening pressure of atelectatic lung units may exceed 20 cm H2O. Factors
associated with the development of desaturation with OLV include poor PaO2 during TLV in the lateral position,
normal preoperative spirometry, right-sided surgery, a significant proportion of ventilation or perfusion to the
operative lung on preoperative ventilation-perfusion testing (47) and supine positioning (48). Applying external
PEEP to the dependent, ventilated lung as the first intervention may benefit some patients (49, 50). A recruitment
maneuver to the ventilated lung at the beginning of OLV also improves oxygenation (51, 52) with only transient
decreases in blood pressure and cardiac index (52). Most recent data suggests recruitment of both lungs before OLV
decreases alveolar dead space and improves oxygenation (53).
The primary mechanism by which the lung fully collapses is absorption atelectasis. This is achieved most
rapidly with an N2O/O2 mixture (FiO2=40%), then 100% O2, and then air/O2 (FiO2=40%) (54,55). Lung collapse
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will be most rapid if lung separation is initiated at end expiration (at FRC), especially when using a BB that has a
small or absent lumen (17). I highly recommend two recent reviews on hypoxemia and OLV (56,57).
Comparison of lung isolation techniques

Campos et al prospectively compared the effectiveness of lung isolation with a left Bronchocath, TCB
Univent tube, and the Arndt endobronchial blocker through a SLT in 64 elective right- and left-sided thoracic
surgical cases (58). There were no statistically significant differences among the 3 groups in frequency of tube
malpositions, number of required bronchoscopies, or overall quality of lung isolation as assessed by the surgeon
(blinded to technique) once lung isolation was achieved. The Arndt blocker took slightly longer to place (3 min, 34
sec) compared to the DLT (2 min, 8 sec) or Univent (2 min, 38 sec) groups, inclusive of time to place the SLT,
although 86- and 46-sec differences are hardly of clinical significance. Complete lung collapse took longer with the
Arndt blocker (26 min, 2 sec) than with the DLT (17 min, 54 sec) or Univent (19 min, 28 sec) and more frequently
required suction assistance.
More recently, Campos et al studied the success with which the occasional thoracic anesthesiologist (< 2
cases per month) correctly placed and positioned these same 3 devices in 66 patients with favorable airways (59).
He found an astonishing overall 38% failure rate with no differences between devices. When successful, placement
times averaged between 6 and 9 minutes regardless of the device used. Their observations suggested that
unfamiliarity with tracheobronchial anatomy and lack of skill in fiberoptic bronchoscopy were most responsible for
the difficulties. An excellent web-based resource for self-assessment and learning of tracheobronchial anatomy is
the Bronchoscopy Quiz and Simulator at www.thoracicanesthesia.com developed by Drs. Kanellakos, Dugas,
and Slinger.
Comparing a left Bronchocath DLT to the Arndt BB for port-access cardiac surgery, more laryngoscopy
attempts (2.3 vs 1.1) and additional time (105 sec) to replace the DLT at the end of the case were trade offs for
slightly better right lung deflation with DLTs (60). Most recently, in comparing three different BBs to left DLTs for
left-sided surgery, all four devices provided equivalent surgical exposure at 10 and 20 minutes after pleural opening
(61). Postoperative hoarseness was prospectively found to be more common with DLTs (44%) than BBs (17%)
(62).
Lung separation and the difficult airway

In the patient with a difficult airway who requires lung separation, the concern for providing lung separation
is subordinate to securing the airway. Several options exist for achieving lung separation once a SLT has been
successfully placed. BBs are especially useful in these situations, particularly when a nasal intubation is required
(63). An algorithm for airway management options is presented in Figure 4.
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A. Upper and lower airway difficulties

Airway difficulties may arise from the upper airway (more common) or the lower airway. Upper
airway anatomic or pathologic features that render conventional rigid laryngoscopy difficult for placement
of SLTs are even more problematic for the placement of DLTs and Univent tubes because of their size and
shape (64). Awake fiberoptic intubation with a SLT or DLT may be the best option in cases of known or
anticipated difficult intubation (20,65,66).
Lower airway difficulties are encountered with anatomical variation or distortion of the tracheal or
bronchial anatomy. Distortion can occur with strictures, extraluminal compression, deviation, or
intraluminal masses. These will influence the selection of the bronchus to be targeted and the choice of a
BB or DLT.
Lower airway difficulties can be detected or predicted by diagnostic bronchoscopy before intubation or by
imaging studies performed preoperatively.
B. Options for lung separation

Double-lumen tubes. The literature on videolaryngoscopy (VL) to facilitate DLT insertion has
blossomed and now contains more comparative trials rather than just case reports or series. One recent
study randomly allocated 60 patients with normal airways to intubation with a Glidescope or Macintosh
direct layngoscope (DL). Although duration of intubation was longer with DL (63 vs 46 sec), the success
of the first intubation attempt (87 vs 100%) was not significantly different (67). Another 2012 study
allocated 170 patients to intubation with a CEL-100 VL or Macintosh DL (this VL has a 30 degree curve
whereas the Glidescope's is 60 degrees). These authors found similar intubation times but a higher first
attempt intubation success (93% vs. 79%) with the CEL-100 (68). Critical analysis of all such studies must
consider both patient characteristics (e.g., average BMIs were all <24) and design features of the particular
VLs.
Oral fiberoptic intubation with a DLT is well described in both awake and asleep patients (66,69,70).
A patient’s mouth opening and oropharyngeal size must be large enough to accommodate a DLT for
orotracheal intubation. Awake placement requires good topical anesthesia, adequate conscious sedation,
and assistance in maintaining soft tissue support. Soaking a DLT in a warm water bath just before
intubation and using sufficient lubrication will minimize its rigidity. Concurrent direct laryngoscopy may
be required to elevate the supraglottic tissues to facilitate passage of a DLT through the glottic opening
after the fiberoptic scope is in the trachea (70). Videolaryngoscopy may add further benefit (71).
Univent tubes. Some anesthesiologists consider a Univent tube easier to place and position than a
DLT (72), particularly in patients with upper airway abnormalities (73). The internal diameter of the
ventilating lumen in a size 8.5 or 9.0 Univent tube will accommodate an adult 5.0 mm bronchoscope (72),
which then precludes the need to change tubes after diagnostic bronchoscopy. Although it is also suitable
for fiberoptic intubation, the Univent tube has several limitations. First, unlike the polyvinyl chloride of the
SLT and DLT, the Univent tube is constructed of a polymeric silicone material that will not soften in a
warm water bath. As such, its curved shape is fixed, and this may be a disadvantage when sliding it over a
bronchoscope. Second, the fixed concavity often makes the leading edge of the tube impinge upon the
vocal cords, impeding its passage into the trachea. A successful nasal intubation with a 7.0 Univent tube
has been described, despite its size and rigidity (74).
Endobronchial blockers. See earlier discussion.
Single-lumen endotracheal tubes. Using a SLT to intubate a mainstem bronchus is another
option for achieving lung separation and is frequently the preferred technique for children who are too
small for DLTs or coaxial BBs (75). Advantages of this approach include its simplicity and the rapidity
with which lung separation can often be achieved, particularly when the right lung must be ventilated.
Blind advancement of a SLT will rarely result in a left mainstem intubation, but rotating an in situ SLT 180
degrees while turning the patient’s head to the right will improve the success rate of left mainstem
intubation to about 92% (76). Fiberoptic guidance of a SLT into the appropriate mainstem bronchus is
probably the easiest and most reliable technique. If significant amounts of blood or secretions preclude
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fiberoptic visualization, using fluoroscopy to visualize and direct the radiopaque bronchoscope is another
option (77).
Disadvantages of the use of a SLT for lung separation include frequent exclusion of RUL ventilation
when a SLT is in the right mainstem bronchus. Left upper lobe ventilation can also be excluded when the
left mainstem bronchus is relatively short (78). Regardless of which lung is ventilated, neither independent
suctioning nor application of CPAP to the nonventilated lung is possible. Lastly, if the nasotracheal route
is used, most SLTs will not be long enough to provide a reliable mainstem intubation.
C. The patient with a tracheostomy

Although the presence of a tracheostomy greatly simplifies airway management for most anesthetics, it
presents an interesting challenge when lung separation is required. As with orotracheal intubation, options
include a DLT (21), Univent tube (79), or BB through the tracheostomy stoma. Depending upon the details
of a patient’s anatomy such as stomal diameter, distance between the skin and the anterior tracheal wall,
and stoma-to-carinal distance, DLTs and Univent tubes may be difficult to place and position precisely and
atraumatically.
Another way to achieve lung separation in a patient with a tracheostomy is using a BB, either
coaxially or alongside a SLT or tracheostomy tube through the stoma (80) or through the mouth (81).
Blind or fiberoptically directed mainstem intubation with a SLT inserted through the stoma is yet another
option, although it has the usual limitations associated with mainstem intubations.
D. Extubation and postoperative intubation

When the decision is made to leave a patient intubated after a procedure involving lung separation,
some special considerations need to be addressed. The possibility of the recurrent need for lung separation
should be
considered a reason to leave a patient intubated. Occasionally, an airway that was not difficult initially may
become difficult after a lengthy procedure involving large fluids shifts that contribute to upper airway or
head and neck edema. An anticipated need for postoperative intubation should therefore inform the
preoperative choice of lung separation technique. If a SLT with a BB was used, then all that needs to be
done at the end of the procedure is to remove the BB. If a Univent was used, then its blocker should be
fully retracted, and the Univent can function as a SLT.
If a DLT was used for lung separation, then the risks and benefits of changing to a SLT must be
carefully weighed. The main advantage to leaving the tube in place is that the hazards associated with a
tube change with a difficult airway are avoided. In this case, one can leave the tube positioned and
ventilate both lungs through both lumens. Alternatively, the tube can be withdrawn to the point at which
the tip of the bronchial lumen is just above the carina, which will position the tracheal cuff below the vocal
cords (82). Increased flow resistance leading to obstructed expiratory flow or increased work of breathing
is probably not clinically significant with 37 F or larger Rusch or Sheridan DLTs (83).
If the DLT is to be changed, it should be done under direct vision if possible. If adequate laryngeal
exposure is not possible with a rigid laryngoscope, an airway exchange catheter (AEC) may be used to
exchange a SLT for a DLT preoperatively or DLT for a SLT postoperatively. Cook Critical Care
manufactures AECs specifically designed for DLT exchanges. These differ from conventional AECs in
that they are longer (100 cm) and have centimeter markings that extend to 50 cm. Eleven and 14 F sizes
will fit inside small and large DLTs, respectively. An extra firm variety colored green became available in
2002 to which a soft tip was added in 2006.
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Keys to success in one-lung anesthesia
•Understand the physical details of DLTs and BBs - select them appropriately
•Use the FOB! – optimize conditions (antisialagogue, suction), learn the tracheobronchial anatomy, and
practice!
•Employ a “just seal” test every time – avoid trouble and identify problems early
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Tusman, et al. Anesth Analg 2004; 98:1604-9 52. Cinnella G, et al. Acta Anaesthesiol Scand 2008;
52:766-75 53. Br J Anaesth 2012; 108:517-524 54. Nunn JF. Nunn’s Applied Respiratory Physiology,
4th ed. Oxford: Butterworth-Heinemann, 1993:496 55. Ko R, et al. Anesth Analg 2009; 108:1092-6
56. Ng A, et al. Br J Anaesth 2011; 106:761-763 57. Losher J. Anesthesiology Clin 2008; 26:241-72
58. Campos JH, et al. Anesth Analg 2003; 96:283-289 59. Campos JH, et al. Anesthesiology 2006;
104:261-266 60. Grocott HP, et al. J Cardiothorac Vasc Anesth 2003; 17:725-727 61. Narayanaswamy
M, et al. Anesth Analg 2009; 1097-101 62. Knoll H, et al. Anesthesiology 2006; 105:471-477 63.
Campos JH. Anesthesiology 2002; 97:1295-1301 64. Wilson RS. Chest Surg Clin N Am 1997; 7:735-751
65. Klafta JM, et al. Probl Anesth. 2001; 13:69-77 66. Patane PS, et al. J Cardiothorac Anesth 1990;
4:229-231 67. Hus H-T, et al. Anaesthesia 2012; 67:411-415 68. Lin W, et al. Anaesthesia 2012;
doi:10.1111/j.1365-2044.2012.07137.x 69. Ovassapian A. J Bronchol 1994; 1:1-8 70. Benumof JL.
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J Cardiothorac Vasc Anesth 1998; 12:131-132 71. Chen A, et al. J Cardiothorac Vasc Anesth 2008;
22:170-2 72. Gayes JM. J Cardiothorac Vasc Anesth 1993; 7:103-107 73. Slinger P. J Cardiothorac
Vasc Anesth 1993; 7:108-112 74. Gozal Y, et al. Anesthesiology 1996; 84:477 75. Hammer GB, et al.
Anesth Analg 1999; 89:1426-1429 76. Kubota H, et al. Anesthesiology. 1987; 67:587-589 77. Klafta
JM, et al. Anesthesiology 1997; 87:1248-1250 78. Lammers CR, et al. Anesth Analg 1997; 85:946-947
79. Andros TG, et al. Anesthesiology 1993; 79:1127-1128 80. Dhamee MS. J Cardiothorac Vasc Anesth
1997; 11:124-125 81. Veit AM, et al. Anesth Analg 1996; 82:1292-1293 82. Cohen E, et al. Curr Opin
Anesthesiol 1999; 12:29-35 83. Slinger PD, et al. J Cardiothorac Vasc Anesth 1998; 12:142-144
DISCLOSURE
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Perioperative Thermoregulation: Meeting the SCIP and PQRI Challenge

Daniel I. Sessler, M.D. Cleveland, Ohio
Homeothermic species require a nearly constant internal body temperature. Significant deviations from "normal"
internal temperature cause metabolic function to deteriorate. Usually, the human thermoregulatory system maintains
core body temperature within 0.2°C of normal, near 37°C. Hypothermia results from exposure to cold, or exposure
combined with drugs or illness that decrease thermoregulatory efficacy. During anesthesia and surgery, exposure to
a cold operating room environment commonly combines with anesthetic-induced inhibition of thermoregulation to
produce hypothermia. Prevention and management of temperature-related complications is expedited by an
understanding of both normal and drug-influenced thermoregulation.
Normal Thermoregulation
Thermoregulation, like many physiological control systems, relies on multiple levels of positive and negative feed-
back to minimize perturbations from the normal status. Temperature is regulated by signals derived from nearly
every type of tissue including the hypothalamus, spinal cord, deep core tissues, and the skin surface. Cold signals
travel to the hypothalamus and other central structures primarily via A-∂ nerve fibers while warm information
travels by unmyelinated C fibers. Most ascending thermal information traverses the spino-thalamic tracts in the
anterior spinal cord. The processing of thermoregulatory information occurs in three phases: afferent thermal
sensing, central regulation, and efferent response.
The hypothalamus regulates temperature by comparing integrated thermal inputs from the skin
surface, neuraxis, and deep tissues with threshold temperatures for heat and cold. When integrated
input exceeds a threshold, the appropriate response is initiated to maintain adequate body temperature. The slope of
response intensity vs. core temperature regression is the gain of that response. The difference between the lowest
warm and highest cold thresholds indicates the thermal sensitivity of the system. The interthreshold range
(temperature range over which no regulatory responses occur) typically is only a few tenths of a °C. Because each
thermoregulatory response has its own threshold and gain, there is an orderly progression of responses and response
intensities are in proportion to need.
How the body determines absolute threshold temperatures is unknown, but the thresholds vary daily in both sexes by
≈1°C (circadian rhythm) and monthly in women by ≈0.5°C. Exercise, food intake, infection, hypo- and hyper-
thyroidism, anesthetic and other drugs (including alcohol, sedatives, and nicotine), and cold- and warm-adaptation
alter threshold temperatures. Central regulation is intact from infancy, but may be impaired in elderly or extremely
ill patients.
The hypothalamus responds to temperatures exceeding the appropriate thresholds via response mechanisms that
increase metabolic heat production or alter environmental heat loss. These responses allow normal individuals to
maintain a core temperature near 37°C despite widely varying environmental temperatures. As thermoregulatory
responses are inhibited (by drugs, etc.), the range of environmental temperatures over which normal core
temperature can be maintained decreases. For example, when shivering is prevented following administration of
muscle relaxants, hypothermia will develop in an environment that previously was well tolerated. When all
thermoregulatory responses are prevented, core temperature will remain normal only in a thermoneutral
environment.
Quantitatively, behavioral regulation (e.g., dressing appropriately, modifying environmental temperature, and
voluntary movement) is the most important effector mechanism.
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Cutaneous vasoconstriction decreases heat loss via convection and radiation from the skin surface. Total digital skin
blood flow is divided into capillary and thermoregulatory arterio-venous shunt components. The arterio-venous
shunts are largely limited anatomically to the fingers, toes, and nose; they are functionally distinct from capillaries
supplying the remainder of the skin. In a thermoneutral environment, shunts are open and capillary flow is nearly
minimal. Shunt vasoconstriction is mediated primarily by release of norepinephrine from presynaptic adrenergic
nerve terminals; vasoconstriction only minimally decreases capillary blood flow.
Nonshivering thermogenesis increases metabolic heat production without producing mechanical work via brown fat
oxidation. Nonshivering thermogenesis increases heat production ≈100% in infants but only slightly in adults.
Vigorous shivering roughly doubles metabolic heat production, although this level of intensity cannot be sustained
long. The net efficiency of shivering thermogenesis is somewhat lower than might be expected because muscle
metabolism increases blood flow to peripheral tissues and consequently, heat loss to the environment. Thus, it is
used only as a last defense against hypothermia (i.e., its activation threshold is a full °C below that for vasocon-
striction and nonshivering thermogenesis).
Sweating is mediated by cholinergic, post-ganglionic sympathetic nerves. Trained athletes can sweat up to
2 liters/hour and lose as much as ten times their resting metabolic rates. Sweating is the only mechanism by which
humans can lose heat in an environment exceeding core body temperature. A ctive vasodilation is mediated by
release of yet-to-be fully characterized mediator (possibly nitric oxide) from sweat glands. Heat stress can increase
capillary blood flow up to 7.5 liters/minute (Table 1).
Table 1. Thermoregulatory System in Humans
Afferent sensing Skin surface
Deep tissues
Spinal cord
Brain, especially hypothalamus
Central control Spinal cord

Hypothalamus
Efferent Defenses Behavioral

Sweating and active pre-capillary vasodilation
Arterio-shunt vasoconstriction
Shivering
Intraoperative Temperature Monitoring

Input to the central thermoregulatory system is derived largely from deep abdominal and thoracic tissues, the spinal
cord, and the brain. Thus, no single tissue temperature can be considered a “gold standard.” Core temperature can be
determined by measuring a single temperature adjacent to the tympanic membrane or in the nasopharynx,
pulmonary artery, or distal esophagus. Carefully obtained oral, axillary, and bladder temperatures approximate core
temperature sufficiently for clinical use except during cardiopulmonary bypass.
Skin temperatures are about 2°C less than core temperature, but the difference between forehead skin and core
temperature varies among individuals and within individuals over time. Forehead skin temperature, with a 2°C
compensation, is thus only a rough estimate of core temperature. Infrared “tympanic” thermometers and “temporal
artery” thermometers are insufficiently accurate for clinical use. Rectal temperatures often seriously lag true core
temperature and should thus be avoided.
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Body temperature measurements usually are not necessary during Monitored Anesthesia Care or minor procedures
performed with regional anesthesia. Major surgery accomplished by epidural or spinal anesthesia can be associated
with considerable hypothermia, and core temperature monitoring is usually appropriate in such cases. Core
temperature alterations immediately following induction of general anesthesia are hard to predict and are influenced
by a variety of factors (see below). Consequently, temperature monitoring often is not helpful during the first
30 minutes of anesthesia and is not required when surgery is completed within this period. In contrast, core
temperature should be monitored at no less than 15-minute intervals during all general anesthetics lasting longer
than 60 minutes.
In intubated patients, an esophageal probe is usually the easiest and most reliable method of
reliably measuring core temperature. During regional anesthesia or when patients are mask ventilated,
axillary, oral, or forehead skin-surface temperatures can be substituted for esophageal or nasopharyngeal
temperatures. Among these, oral temperatures are the most reliable; oral temperatures are also most suitable for
postoperative use (Table 2).
Table 2. Temperature Monitoring

True core Pulmonary artery
Nasopharynx
Distal esophagus
Tympanic membrane (with a thermocouple probe)
Generally adequate Oral

Axillary
Bladder
Often inaccurate Skin surface, including forehead

Infrared aural canal “tympanic”
Infrared temporal artery
Rectal
Thermoregulation During Anesthesia

Typical doses of general anesthesia decrease the activation thresholds for responses to
hypothermia by ≈3°C and increases those defending against hyperthermia by <1°C. Widening the
interthreshold range produces a broad temperature range over which active thermoregulatory responses are absent.
Within this range, patients are poikilothermic and body temperature changes are determined passively by
redistribution of heat within the body and the difference between metabolic heat production and heat loss to the
environment.
Most general anesthetics produce a similar pattern and magnitude of thermoregulatory impairment; this pattern is
illustrated in Figure 1 using propofol. Opioids inhibit thermoregulatory control similarly. In contrast, even very high
plasma concentrations of midazolam have little thermoregulatory effect. The vasoconstriction threshold in infants
anesthetized with halothane or isoflurane differs little from that in adults. Intraoperative vasoconstriction thresholds
are increased by painful stimulation, but decreased by advanced age.
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38 Sweating
Fig. 1. Solid lines show concentration-response regressions;

dotted lines indicate 95% confidence intervals for the thresholds.
Propofol administration linearly, but slightly, increased the 36
sweating threshold. Conversely, propofol markedly decreased Threshold
the vasoconstriction and shivering thresholds. Thermoregulatory (°C) Vasoconstriction
responses are similar in magnitude during administration of 34
other general anesthetics, although volatile anesthetics non-
linearly decrease cold-response thresholds, with a
disproportionately greater effect at high concentrations. (From
32 95% Confidence Interval
Matsukawa T, Kurz A, Sessler DI, Bjorksten AR, Merrifield B,
Cheng C: Propofol linearly reduces the vasoconstriction and
shivering thresholds. Anesthesiology 1995; 82: 1169-1180.) Shivering
30
0 2 4 6 8
[Propofol] (µg/ml)
Perioperative Hypothermia
The typical pattern of intraoperative hypothermia is illustrated in Figure 2: core temperature decreases precipitously
for 1 hour (Redistribution hypothermia), then decreases slowly for 2-3 hours (linear decrease), and finally becomes
constant (plateau phase).
Fig. 2. Hypothermia during the first hour of anesthesia

results largely from a core-to-peripheral redistribution of -1
body heat. Subsequently, core and mean body temperatures ∆Core
decrease when heat loss exceeds heat production. And Temp
finally, a core-temperature plateau results when re- (°C) -2
emergence of thermoregulatory vasoconstriction decreases
cutaneous heat loss and constrains metabolic heat to the
core thermal compartment. -3
0 2 4 6
Elapsed Time (h)
Numerous factors contribute to core hypothermia during the first hour of surgery: (1) patients are undressed in a
cool environment; (2) their skin is prepared for surgery with a cold solution that is allowed to evaporate;
(3) induction of anesthesia decreases metabolic heat production and produces cutaneous vasodilation; (4) cold iv
fluids directly decrease core temperature; and, (5) their lungs are ventilated with dry gasses which increases
respiratory heat loss. Nonetheless, unanesthetized individuals easily tolerate typical operating room temperatures
without becoming hypothermic, and evaporation of skin preparation fluids cannot explain the observed hypothermia.
Furthermore, general anesthesia decreases metabolic heat production only 15-30% and minimally increases
cutaneous heat loss.
Since decreased heat production and increased heat loss are insufficient to explain the initial core hypothermia
following induction of general anesthesia, another mechanism must be invoked. Core temperature poorly represents
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mean body temperature and body heat content because temperature in peripheral tissues (roughly half the body
mass) changes considerably depending on thermoregulatory status, environmental temperature, and duration in a
particular environment. Typically, peripheral tissue temperature (and heat content) is considerably lower than core
temperature. Although anesthetic-induced vasodilation only minimally increases cutaneous heat loss to the
environment, it does allow mixing of heat in the core and peripheral thermal compartments. The result is peripheral
warming at the expense of core temperature (Fig 3). Redistribution hypothermia contributes ≈80% to
observed hypothermia during the first hour of anesthesia and often remains the major cause of
core hypothermia even after three hours of anesthesia. Similar internal redistribution of heat
causes the initial hypothermia during epidural anesthesia.
Fig. 3. The initial hypothermia which develops following

induction of anesthesia results when vasodilation allows
heat in warm core tissues to mix with cooler peripheral
tissues. This warms the periphery at the expense of core
temperature. Although core temperature decreases precipi-
tously, body heat content (and mean body temperature)
remains nearly constant.
The slow, linear decrease in core temperature typically observed during the 2nd-3rd hours of anesthesia likely
results simply from heat loss exceeding metabolic heat production. Heat loss presumably also exceeds production
during the first hour of anesthesia, but usually contributes much less to core hypothermia than redistribution.
When patients are in a relatively warm environment and undergoing small operations, the core temperature plateau
that develops after the 2nd-4th hour of anesthesia may be passive, i.e., without thermoregulation. In contrast, when
patients are sufficiently hypothermic, this plateau is often accompanied by active thermoregulatory vasoconstriction.
Peripheral vasoconstriction decreases cutaneous heat loss and constrains metabolic heat (which is mostly generated
centrally) to the relatively small core thermal compartment, thereby preventing further hypothermia (and sometimes
even increasing core temperature). Heat loss from peripheral tissues not only continues, but these tissues receive less
metabolic heat. Under these circumstances, the core temperature plateau does not represent a true thermal steady
state (heat production equaling heat loss) because body heat content continues to decrease (Table 3).
Table 3. Intraoperative Hypothermia
Initial hour Mostly core-to-peripheral redistribution of body heat
Subsequent 2-4 hours Heat loss exceeding heat production

Radiation
Convection
Core-temperature plateau Passive equilibrium in warm environment

Re-emergence of thermoregulatory vasoconstriction
Typically at a core temperature near 34.5°C
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Consequences of Hypothermia
Temperatures only 2-3°C below normal provide significant protection against cerebral ischemia and hypoxemia in
animals; mild hypothermia may thus be useful during procedures likely to cause ischemia, such as carotid
endarterectomy and neurosurgery. However, it is important to recognize that mild perioperative hypothermia has yet
to be shown to improve outcomes — despite large studies that evaluated cerebral aneurism surgery, brain trauma,
and acute myocardial infarction. Currently, the only two well-documented benefits of therapeutic mild hypothermia
(≈33-34°C) is improved neurologic function after out-of-hospital cardiac arrest and in asphyxiated newborns. And at
least in susceptible swine, mild hypothermia both slows triggering of malignant hyperthermia and reduces severity
of the syndrome once triggered. In contrast mild perioperative hypothermia (i.e., 2°C) causes many
complications including morbid myocardial events, coagulapathy, surgical site infection,
reduced drug metabolism, thermal discomfort, and shivering.
Postoperative myocardial infarction is, perhaps, the most common serious perioperative complication, occuring in
about 5% of moderate- to high-risk patients. Two-thirds of postoperative myocardial infarctions are clinically silent;
however, both silent and clinically apparent postoperative infarctions have the same mortality of about 11%. About
80% occur within two postoperative days. Mild perioperative hypothermia increases the risk of morbid myocardial
events, esepcially infarction. The increase appears to be mediated by autonomic activation, with consequent
tachycardia and hypertension.
Mild hypothermia reduces platelet function and decreases activation of the coagulation cascade. Consistent with
these in vitro data, hypothermia significantly increases blood loss and allogeneic transfusion requirements during
elective primary hip arthroplasty. Blood loss increases roughly 0.5 units for each °C decrease in core temperature.
Just 2°C core hypothermia also significantly increases the incidence of myocardial ischemia in high-risk patients
undergoing peripheral vascular surgery. Myocardial ischemia probably results less from post-anesthetic shivering
than from sympathetic activation, hypertension, and tachycardia.
Mild hypothermia contributes to a common and serious complication of anesthesia and surgery, wound infection, by
directly impairing immune function (especially oxidative killing by neutrophils) and decreasing cutaneous blood
flow which reduces tissue oxygen delivery. Together these effects of mild hypothermia triple the clinical incidence
of surgical wound infections and substantially increase duration of hospitalization in patients undergoing elective
colon resection. Hypothermia-induced protein wasting and decreased collagen synthesis is also likely to impair
wound healing.
Mild hypothermia decreases metabolism of most drugs: for example, the duration of action of vecuronium is more
than doubled at 34.5°C compared with 36.5°C. The effect of hypothermia on metabolism of atracurium and propofol
is somewhat less, but still clinically important. Consistent with decreased drug metabolism and exaggerated drug
effect, mild hypothermia significantly prolongs duration of postoperative recovery (even when temperature is not a
discharge criterion).
Postoperative thermal discomfort per se is not life-threatening; nonetheless, patients who become hypothermic often
remember feeling cold postoperatively as the worst aspect of surgery. Efforts to prevent and treat such unpleasant
sensations deserve the same attention we currently give pain management.
Shivering-like tremor occurs in ≈40% of unwarmed patients recovering from general anesthesia, but is now rare.
Shivering is usually preceded by core hypothermia and peripheral vasoconstriction, indicating that it is
thermoregulatory. Perianesthetic tremor increases oxygen consumption ≈200% and may exacerbate postoperative
pain. Although most of the tremor has electromyographic patterns characterizing normal shivering, some resembles
pathological clonus. The tremor can be treated by skin-surface warming, clonidine (75 µg iv), or meperidine
administration (25 mg iv). Meperidine is more effective than equipotent doses of other opioids, possibly because the
drug is a central alpha-receptor agonist in addition to its primary action at µ-opioid receptors (Table 4).
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Table 4. Consequences of Perioperative Hypothermia

Major Morbid myocardial events
Coagulopathy and increased transfusion requirement
Surgical site infection
Minor Reduced drug metabolism

Prolonged recovery
Shivering, tachycardia, and hypertension
Thermal discomfort
Tremor during epidural anesthesia is normal thermoregulatory shivering triggered by core hypothermia and
preceded by peripheral vasoconstriction (above the level of sympathetic blockade). It can be treated by skin-surface
warming (above the level of blockade), intravenous or epidural meperidine (25 mg) administration, or epidural
sufentanil administration (50 µg).
Prevention and Treatment of Hypothermia

The initial rapid core hypothermia during epidural or general anesthesia is difficult to treat because it results largely
from internal redistribution of heat. However, it can be largely prevented by warming skin and peripheral tissues
before induction to decrease the core-peripheral temperature gradient. Given the large heat capacity of the peripheral
thermal compartment, 30-60 minutes of moderate warming generally is required.
Less than 10% of metabolic heat is lost via respiration, even when patients are ventilated with dry, cool gas. Passive
airway humidification (heat-and-moisture exchangers) can prevent most of this loss and active gas heating and
humidification prevents it all. However, simple thermodynamic calculations indicate that airway heating and
humidification in adults cannot produce clinically significant alterations in body heat content. Technically adequate
clinical studies find that inspired gas conditioning fails to prevent hypothermia in adults. (The clinical impression
that airway heating is effective likely results from artifactual heating of proximal esophageal thermometers.)
Consequently, active airway heating and humidification is rarely indicated. Similarly, heat-and-moisture exchanging
filters contribute little to maintaining normothermia.
Since most heat is lost through the skin (although evaporation from large surgical incisions may contribute
significantly), preventing cutaneous heat loss will minimize the slow, linear decline in core temperature during
surgery. Cutaneous heat loss can be passively decreased by covering skin with cloth or paper surgical drapes,
blankets, plastic bags, etc. A single layer of each insulator reduces heat loss by ≈30%, but efficacy of
different cover types is similar because most insulation is actually provided by a layer of still
air trapped under the cover. Adding additional layers thus does not proportionately increase the benefit:
combining three layers of warmed cotton blankets only reduces heat loss by only 50%. Because cutaneous heat loss
is roughly proportional to surface area, the choice of covering material is far less important than the total surface
area covered.
Active warming can prevent most cutaneous heat loss, and can even reverse the net transfer of heat across skin.
Circulating-water blankets are more effective when placed over (rather than under) patients because little heat is lost
through the 5 cm of foam which pads most operating room tables. Similarly, newer circulating-water wrap-around
garments are quite effective — although expensive. Water temperature should not exceed 40°C to minimize risk of
pressure/heat necrosis, and should be set at even lower temperatures in patients with arterial vascular insufficiency.
Recently developed systems that appear effective include over- or under-body resistive heating, and circulating-
water applied to extremities. Forced-air is by far the best-validated warming approach and seems to
offer the best combination of safety, efficacy, ease of use, and price (Fig. 4).
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0
Bair Hugger ®
Fig. 4. Tympanic membrane temperature decreased uniformly during

the first hour after induction of general anesthesia in each group.
Temperature then increased over the remaining two hours in patients -1 Water Blanket
randomized to forced-air warming (Bair Hugger), but remained nearly ∆T
constant in those lying on a circulating-water blanket set at 40°C. (°C) Control
Patients in the control and heated-humidifier groups continued to
-2
become more hypothermic throughout the operation. The uniform Heated Humidifier
initial hypothermia during the first hour of anesthesia results from
internal redistribution of heat and illustrates the difficulty in treating
this temperature decrease. (From Hynson J, Sessler DI: Intraoperative -3
warming therapies: A comparison of three devices. J Clin Anesth 0 60 120 180
1992; 4: 194-19.) Time (min)
Surgical Care Improvement Project and Physicians Quality Reporting Initiative

The Surgical Care Improvement Project (SCIP) and the Physicians Quality Reporting Initiative (PQRI) are separate
measures. However, they were designed in concert and are harmonized. They each thus have identical requirements.
SCIP is a hospital-based reporting requirement. In contrast, PQRI applies to individuals and is linked to a 2%
Medicare bonus for reporting; presumably, the bonus will soon be provided for meeting the requirements, not just
reporting effort. The ASA strongly supported including thermal management in PQRI because it is
the only measure specific to operating room anesthesia; without it, anesthesiologists would thus
have been excluded from the 2% Medicare bonus. (Full disclosure: I am an ASA delegate to the PQRI
committee.)
The denominator for SCIP and PQRI includes patients who are having a surgical procedures with general or
neuraxial anesthesia lasting at least 60 minutes in which the need for intentional hypothermia is not documented.
Use of cardiopulmonary bypass is considered de facto evidence of intentional hypothermia. Patients having
monitored anesthesia care, peripheral nerve blocks alone, and short procedures are thus excluded. The numerator
includes both a process and (intermediate) outcome component. The outcome component is met when patients have
a documented body temperature ≥36°C within 30 minutes before the end of anesthesia and/or within 15 minutes
thereafter. There is no requirement to use a specific type of thermometer, or to measure temperature at a particular
site. However, accurate thermometers and reliable core-temperature site are most likely to provide higher values.
The process component is met by the use of active over-body warming such as forced-air (Table 5).
Table 5. Surgical Care Improvement Project and Physicians Quality Reporting Initiative
Numerator Body temperature ≥36°C within last 30 minutes of anesthesia
Body temperature ≥36°C within 15 after anesthesia
Use of active over-body warming
Denominator Surgical procedure with general or neuraxial anesthesia

Lasting 60 minutes
Intentional hypothermia not documented
Cardiopulmonary bypass considered intentional
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Recommendations
Body temperature is normally tightly regulated. However, general anesthetics profoundly impair normal
thermoregulatory control with the consequence that unwarmed surgical patients almost inevitably become 1-3°C
hypothermic. Large randomized trials have demonstrated that even mild perioperative hypothermia causes numerous
severe complications including morbid myocardial outcomes, increased blood loss and transfusion requirement,
prolonged recovery and hospitalization, and surgical wound infections. Because thermal disturbances are associated
with severe consequences, the standard-of-care is now to monitor temperature during general anesthesia and to
maintain normothermia unless otherwise specifically indicated. Table 6 lists the most important learning points for
this review.
Table 6. Major Learning Points
Thermoregulation Afferent sensing: skin, deep tissues, spinal cord, and brain
Central regulation: brain, especially the hypothalamus
Behavioral and autonomic defenses; sweating, vasoconstriction, and shivering
Temperature monitoring Core: pulmonary artery, nasopharynx, esophagus, tympanic

General adequate: oral, axillary, bladder
Intraoperative hypothermia Core-to-peripheral redistribution

Heat losss exceeding production
Passive or active core-temperature plateau
Maintaining normothermia Forced-air is good combination of safety, efficacy, and low cost
SCIP and PQRI Numerator: normothermia or active over-body warming

Denominator: surgery >60 minutes with general or neuraxial anesthesia
Suggested Reading
1. Sessler DI: Temperature monitoring and perioperative thermoregulation. Anesthesiology 2008; 109: 318-38
2. Sessler DI: Perioperative heat balance. Anesthesiology 2000; 92: 578-596
3. Sessler DI: Complications and treatment of mild hypothermia. Anesthesiology 2001; 95: 531-543
4. Frank SM, Fleisher LA, Breslow MJ, Higgins MS, Olson KF, Kelly S, Beattie C: Perioperative maintenance of
normothermia reduces the incidence of morbid cardiac events: A randomized clinical trial. JAMA 1997; 277:
1127-1134
5. Rajagopalan S, Mascha E, Na J, Sessler DI: The effects of mild perioperative hypothermia on blood loss and
transfusion requirement: a meta-analysis. Anesthesiology 2008; 108: 71-7
6. Kurz A, Sessler DI, Lenhardt RA, Study of wound infections and temperature group: Perioperative
normothermia to reduce the incidence of surgical-wound infection and shorten hospitalization. N Engl J Med
1996; 334: 1209-1215
DISCLOSURE
Arizant / 3M, Funded Research ; Drager, Funded Research ; Cardinal, Funded Research ; Merck, Funded Research
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Anesthesia and the Patient with Thyroid, Parathyroid, or Adrenal Disease

William R. Furman, M.D. Nashville, Tennesee
Introduction
Management of a patient with adrenal, thyroid, or parathyroid disease is based on an understanding of the
pathophysiology of the specific hormonal system involved. This lecture will discuss current concepts and new
developments in the perioperative care of patients with adrenal cortical insufficiency, hyper- or hypothyroidism,
hyperparathyroidism, or pheochromocytoma.
Adrenal Insufficiency
Normal Hypothalamic-Pituitary-Adrenal (HPA Axis) Function (Fig 1). Adrenal production and secretion of cortisol
is controlled by blood levels of adrenocorticotropic hormone (ACTH). ACTH is secreted by the anterior pituitary
gland which is, in turn, stimulated by hypothalamic corticotropin releasing hormone (CRH) carried directly from the
hypothalamus to the pituitary by a specialized portal venous system. Stress of almost any variety stimulates the
hypothalamus to release CRH, and blood cortisol levels exert a negative feedback influence on the production of
both CRH and ACTH [1].
Figure 1: Normal HPA Axis Function
Cortisol is important because of its effects on the cardiovascular system, especially in the presence of stress. It
maintains vascular tone, endothelial integrity, vascular permeability, the distribution of total body water in the
vascular compartment, and it potentiates the constrictor effects of catecholamines on vascular tone. When cortisol
levels are deficient, systemic vascular resistance and myocardial contractility are decreased [2]. Conversely, patients
with an excess of cortisol have hypertension associated with an increased plasma volume and an increased systemic
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vascular resistance. They also develop left ventricular hypertrophy, and are at risk for coronary ischemia related to
abnormal lipid and glucose metabolism and an increased tendency toward thrombosis [3] (Table 1).
Table 1: Effects of Excess Cortisol
Humoral Structural
Hypertension Left Ventricular Hypertrophy
↑ Plasma Volume Vascular Remodeling
↑ Systemic Vascular Resistance
↓ Diastolic Relaxation
↓ HDL, ↑HDL
Prothrombotic Effects
Most of the symptoms experienced by patients with chronic adrenal insufficiency are non-specific. They include
fatigue, malaise, lethargy, weight loss, anorexia, arthralgias, myalgias, nausea, vomiting, abdominal pain, diarrhea,
and fever. When chronic adrenal insufficiency is due to non-function of the adrenal glands (primary adrenocortical
insufficiency), hyponatremia and hyperkalemia due to concomitant aldosterone deficiency may be seen. These
metabolic abnormalities are less likely when the adrenal insufficiency is due to pituitary or hypothalamic (secondary
or tertiary insufficiency) failure or to HPA Axis suppression by the prior administration of exogenous steroids.
Common etiologies of primary chronic adrenal insufficiency are immunologic (autoantibody), malignant (metastatic
cancer, commonly from lung or breast), or infectious (such as tuberculosis).
Adrenal (“Addisonian”) Crisis. The term acute adrenal failure, or Addisonian crisis, is applied to the condition of
circulatory shock due to cortisol deficiency, usually in the presence of primary adrenal failure. This generally occurs
because of acute stress such as trauma, surgery, or infection in a patient with underlying chronic adrenal
insufficiency. Another etiology is the Waterhouse-Friedricksen Syndrome of bilateral acute adrenal hemorrhage,
usually associated with fulminant sepsis from an endotoxin-producing bacterium such as N. meningitides.
Characteristic physiologic findings are hypovolemic shock with myocardial and vascular unresponsiveness to
catecholamines. Treatment usually requires several liters of isotonic saline plus corticosteroid administration. 100mg
of IV cortisol equivalent every 6-8 hours usually reverses the pathophysiology in the first day of treatment. Tapering
and conversion to an oral agent are usually possible in 1-4 days. The equivalent doses and corresponding relative
potencies of common corticosteroids are commonly expressed using hydrocortisone 100 mg as the standard for
comparison (Table 2). Hydrocortisone is the synthetic form of cortisol. It is worth noting that the commonly-used
dosage of dexamethasone 4 mg, intended for anti-emetic prophylaxis, is approximately equivalent to cortisol 100mg
and has a much longer duration of action.
Table 2: Relative Equivalent Potencies of Common Corticosteroid Drugs
Agent Equivalent Dose Relative Potency Duration (hr)

(mg)
Hydrocortisone 100 1 8-12
Cortisone 125 0.8 8-12
Prednisone; Prednisolone 25 4 12-36
Methylprednisolone 20 5 12-36
Dexamethasone 4 25 >24
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Relative Adrenal Insufficiency or Unresponsiveness

Relative adrenal insufficiency or Critical Illness Related Corticosteroid Insufficiency (CIRCI) is a term that has been
applied in retrospect to clinical situations where 100-300mg per day of IV hydrocortisone eliminates a pre-existing
need for vasopressors. The implication is that the HPA axis may not be abnormal, but the magnitude of the expected
response to stress is reduced. Prior steroid treatment is a potential cause of this condition. Features that have been
described include:
• Unexplained vasopressor-dependent refractory hypotension
• Major discrepancies between the anticipated severity of the disease and the present state of the patient
• High fever without apparent cause (negative blood cultures), or not responding to antibiotics
• Hypoglycemia, hyponatremia, hyperkalemia, neutropenia, eosinophilia
• Prompt resolution with steroid treatment
• Vasopressin can be useful
What steroid management is required for a patient who has received exogenous steroids and may have relative
adrenal insufficiency? Steroid-induced adrenal suppression is highly variable and its duration is unpredictable (days
to perhaps years). The consequences of a short course of steroids are minimal, so anticipatory treatment is generally
safe. Pain, fever, hypovolemia, and surgery all normally cause increases in corticotropin and cortisol that persist for
2 days after surgery. Therefore, in suppressed patients, the recommended approach is 48-72 hours of tapered
replacement beginning with no more than 100-150mg of cortisol equivalent per day [4, 5]. Animal studies have
indicated that higher doses do not offer benefit [6]. The commonly-used dosage of dexamethasone 4mg, intended for
anti-emetic prophylaxis, is approximately equivalent to cortisol 100mg.
Etomidate and Adrenal Function. A single dose of etomidate 0.3mg/kg has been shown to suppress cortisol
production, but while the effect is seen at 4-6 hours, it does not appear to be present at 24 hours [7, 8].
Hyper- and Hypothyroidism

Thyroid hormone production. The thyroid gland is subject to feedback in a manner similar to the adrenal gland.
Thyroid releasing hormone (TRH) is made in the hypothalamus and reaches the anterior pituitary via the long portal
vessels. TRH stimulates pituitary production of thyroid stimulating hormone (TSH), which reaches the thyroid
through the blood stream. TSH stimulates the thyroid to incorporate iodide into thyroglobulin and release thyroid
hormone (~80% as T4 and 20% as the much more potent T3) into the blood stream. T4 is converted to T3 in the
periphery, where it exerts its effects. T3 and T4 exert negative feedback on the production of TRH and TSH [9].
Hyperthyroidism. Overproduction of thyroid hormones results in elevated levels of unbound T3 and T4 and
produces the clinical syndrome known as thyrotoxicosis. The principal manifestations are cardiac (Table 3),
neurologic, and constitutional [10]. Thyroid hormone decreases systemic vascular resistance, increases resting sinus
rate, and increases cardiac sensitivity to catecholamines, resulting in systolic (not diastolic) hypertension and
tachycardia. Atrial fibrillation is common, and may be the presenting sign of hyperthyroidism, as it was for
President George H. W. Bush in 1991. Other signs of marked hyperthyroidism include high-output congestive heart
failure or angina (even in the absence of coronary plaques) and pulmonary hypertension. Tremor, hyperreflexia, and
irritability are common neurologic manifestations. Periodic paralysis, characterized by hypokalemia and proximal
muscle weakness, may also occur. Fever and heat intolerance are common. Gastrointestinal symptoms include
nausea, vomiting, and diarrhea, as well as hepatic dysfunction and jaundice.
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Table 3: Cardiovascular Effects of Hyperthyroidism
Humoral Structural
↓ Systemic Vascular Resistance Left Ventricular Hypertrophy
Sinus Tachycardia, SVT, AFib Cardiomyopathy
↑ Cardiac Contractility Pulmonary Hypertension
Improved Diastolic Relaxation
Coronary Spasm/Coronary Ischemia
↑ Erythropoietin/ ↑ Blood Volume
Systolic Hypertension - Widened Pulse
Pressure
The most common cause of thyrotoxicosis is Graves’ Disease; however it may also be caused by:
• Struma ovarii, which is the presence of thyroid tissue in an ovarian teratoma
• HCG-secreting hydatidiform mole [11]
• The administration of iodinated contrast dye to a susceptible patient
• Amiodarone
Thyroid Storm. All patients with thyrotoxicosis should be considered to be at risk of developing thyroid storm,
which is a life-threatening emergent clinical syndrome that has a ~30% mortality rate despite treatment. Thyroid
storm is characterized by worsening of the signs and symptoms of thyrotoxicosis, including cardiac dysfunction,
hyperglycemia, hypercalcemia, hyperbilirubinemia, altered mental status, seizures, and coma. It may be triggered in
a thyrotoxic patient by any one of several stresses, including:
• Infection
• Stroke
• Trauma, especially to the Thyroid Gland [12]
• Surgery
• Diabetic Ketoacidosis
• Drugs: Pseudoephedrine, Aspirin, Excess Iodine Intake, Contrast Dye, Amiodarone
• Incorrect Anti-Thyroid Drug Discontinuation
Diagnosis of Thyroid Storm. The distinction between thyrotoxicosis and thyroid storm is one of degree. Clinical
scoring systems can be used as a guide. One example (Table 4) assigns points for temperature (up to 30), central
nervous system effects (up to 30), gastrointestinal dysfunction (up to 20), and cardiovascular signs and symptoms
(up to 50). The points are summed, and a total of 45 or above is considered suggestive of thyroid storm, while a
score between 25 and 44 indicates impending storm [10].
Table 4: Example of Scoring System for Thyroid Storm.

System Parameter Scoring Maximum
Thermoregulatory Temperature (°F above 98.9) 5 points for T of 99-99.9° and 30
5 more for every degree higher
up to T ≥104°
Central Nervous Altered Mental Status 10 points for agitation 30
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20 points for delirium

30 points for seizures or coma
Gastrointestinal Nausea, Vomiting, Abdominal Pain 10 points for symptoms 20
Hepatic Disease 20 points for jaundice
Cardiovascular Congestive Heart Failure 5 points for pedal edema 15
5 for bibasilar rales
5 for pulmonary edema
Cardiovascular Rhythm 5 points for heart rate 90-109 35
and 5 more for every 10 bpm
up to HR ≥140 bpm
10 points for atrial fibrillation
45 points = probable thyroid storm; 25-44 points suggests impending thyroid storm
Treatment. The initial approach to treatment for thyrotoxicosis is to reduce thyroid hormone synthesis. Definitive
therapy with either surgery or radioactive iodine may follow after the patient has been made euthyroid[13]. Initial
control is accomplished by administration of propythiouracil (PTU) to inhibit thyroid peroxidase (TPO), the enzyme
that catalyzes the incorporation of iodide into thyroglobulin. At least an hour after giving PTU, large doses of stable
iodide are given. This takes advantage of a paradoxical effect, called the Wolfe-Chaikoff Effect. Rather than
catalyze additional incorporation of iodide into thyroglobulin, as might be expected, large amounts of iodide
suppress gene transcription of TPO, further reducing the gland’s capacity to produce and release hormone. This
benefit is temporary (~1 week), but is useful at the beginning of thyroid suppression.
Treatment of thyroid storm incorporates the above, often at larger doses. In addition to PTU and iodide, it includes
beta adrenergic blockade and corticosteroids. The traditional beta blocker is propranolol, selected because it blocks
peripheral conversion of T4 to T3 in addition to its beneficial cardiovascular effects. Dosages of as much as 120mg
po or 3mg IV every 4 hours have been used. Other beta blockers such as atenolol, metoprolol, and esmolol have
been used and are not contraindicated.
Corticosteroids are recommended to treat the relative adrenal insufficiency that results from accelerated metabolism.
Cortisol levels tend to be in the normal range in thyrotoxic patients, but they ought to be higher to be appropriate to
the level of stress. The recommended approach is tapered replacement beginning with 100mg of cortisol equivalent
every 8 hours.
The general rule regarding surgery in the setting of thyrotoxicosis or thyroid storm is to only undertake that which
cannot be delayed until control of thyroid hormone secretion and effect has been accomplished. It is worth
reiterating that thyrotoxicosis can masquerade as coronary ischemia [14] and present a very difficult dilemma.
Hypothyroidism. The cardiovascular effects of hypothyroidism (Table 5) typically do not pose an impediment to
anesthetic and surgical management. Hypothyroid patients are at increased risk of ischemic heart disease; however
the hypothyroid condition may be protective because it results in a reduced capacity for cardiac work. Thyroid
hormone replacement in hypothyroid patients with coronary artery disease must be undertaken carefully, as it may
provoke ischemia [15].
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Table 5: Cardiovascular Effects of Hypothyroidism
Humoral Structural
↑ Systemic Vascular Resistance Ischemic Heart Disease
Sinus Bradycardia Pericardial Effusion (Rarely Significant in
Volume)
↓ Cardiac Contractility
Diastolic Dysfunction
↓ Response to α and β Adrenergic Agonists
Diastolic Hypertension - Narrowed Pulse
Pressure
Hyperparathyroidism and Hypercalcemia

Serum calcium is regulated by parathyroid hormone (PTH), calcitonin, and the active form of Vitamin D. PTH
stimulates bone resorption, inhibits renal excretion of calcium, and promotes conversion of Vitamin D to its active
form. Calcitonin, which is produced by the medullary cells of the thyroid gland (also called C Cells), antagonizes the
effects of PTH. Vitamin D promotes gut absorption of calcium, phosphate and magnesium, and facilitates the effects
of PTH on bone.
Parathyroid cells have a calcium receptor (“CaR”) on their cell surface that senses ionized calcium levels. In the
presence of an elevated ionized calcium level, the CaR signals a decrease in PTH production. In primary
hyperparathyroidism, a single gland becomes enlarged and its CaR almost always becomes ineffective. As a result,
that gland overproduces PTH, resulting in hypercalcemia. Secondary hypercalcemia is a condition associated with
chronic kidney disease in which chronically low calcium levels lead to down-regulation of the CaR, ultimately and
paradoxically resulting in autonomous excessive PTH production [16]. Typically, this is associated with hyperplasia
of all 4 parathyroid glands.
Calcium has an integral role in neuromuscular function, neurotransmitter signaling, cardiac conduction, energy
metabolism, enzymatic action, hormone secretion, and hemostasis. All of these functions may be disrupted by
hypercalcemia, however patients with mild hypercalcemia commonly have non-specific symptoms. There is,
however, a condition of hypercalcemic crisis, characterized by altered mental status and disturbances of cardiac,
renal, and gastrointestinal function. This condition is most often associated with primary hyperparathyroidism and a
serum calcium >14 mg/dL. The patients are typically dehydrated and the treatment is rehydration followed by
expeditious parathyroidectomy. Correction of the calcium to normal levels prior to surgery is not required [17].
In addition to surgical removal, options for treatment of hypercalcemia include hydration, diuretics to produce a
calciuresis, steroids if the hypercalcemia is related to a non-parathyroid malignant tumor, calcitonin, and cinacalcet.
Cinacalcet is a new calcimimetic agent that stimulates the CaR, resulting in decreased PTH production [18].
Pheochromocytoma
Tumor overproduction of the adrenal medullary hormones dopamine, norepinephrine, and/or epinephrine results in a
hypertension and tachycardia plus heart rate and blood pressure hyper-responsiveness to noxious stimulation. The
cells that produce these hormones are of neural crest origin. When the tumor arises in the adrenal medulla, it is
called a pheochromocytoma; when it arises elsewhere, it is called a paraganglioma. In either case, life-threatening
hypertensive crises are possible, especially during surgery on a previously undiagnosed patient. Pheochromocytoma
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often goes unrecognized because its symptoms (headache, palpitations, sweating) are non-specific and as many as
8% are asymptomatic. Its prevalence in the general population may be as high as 1 in 2000 [19].
Mechanism of hypertension. The conventional theory (unsupported by scientific evidence) is that hypertension
occurs because arteriolar smooth muscle is exposed to norepinephrine, since norepinephrine is the neurotransmitter
for sympathetic nervous system mediated vasoconstriction. According to this theory, exogenous norepinephrine
bathes the synapses directly. But if this were true, the sympathetic nervous system should be suppressed and should
not regulate blood pressure; instead the circulating hormones would do so[20]. This theory has prompted the
practice (also unsupported) of pre-operative alpha adrenergic blockade prior to tumor resection as well as the
mistaken beliefs that blood catecholamine levels correlate with blood pressure level and that hypertension occurs
when the surgeon manipulates the tumor because this squeezes hormones out of the tumor and into the blood stream.
Scientific data suggest contrary interpretations. Catecholamine levels do not correlate with the time or magnitude of
blood pressure levels [21], and in practice two weeks of preoperative non-selective alpha adrenergic blockade with
phenoxybenzamine is usually ineffective at preventing intraoperative hypertension. Published clinical experience
supports an approach in which hypertension, if present, is controlled prior to surgery with any of a variety of agents
[22]. Once the blood pressure is under reasonable control, the procedure is undertaken; however there is no basis to
expect that intraoperative hypertension will not occur.
In theory, the non-specific alpha blocker phenoxybenzamine would not be an agent of choice because it has alpha-2
blocking properties, and blocking the alpha-2 receptor would be expected to raise blood pressure and pulse [23]. It is
also very expensive, as it has no other clinical application. An alpha-1 selective blocker would seem more
appropriate, and all of them cost far less. In fact, calcium channel blockers, ACE inhibitors and receptor blockers,
beta blockers, and alpha-2 agonists have all been used effectively prior to surgery. During surgery, infusions of
vasodilators and esmolol still may be required to treat hypertension and tachycardia. Infusions of magnesium [24]
and the alpha-2 agonist dexmedetomidine [25] may be useful as well.
Why doesn’t receptor blockade work? An alternate theory would be that chronic catecholamine excess amplifies the
sympathetic nervous system’s responses to stress and trauma in general. Hypertension and tachycardia would be
caused by the substantial stress of laryngoscopy (not the induction of anesthesia) and the stress of surgical
manipulations of any kind (not specifically tumor manipulation). This is true in any patient, but the effect appears to
be exaggerated under the influence of chronic catecholamine excess. Such a theory is supported by animal data
showing that the sympathetic nervous system in chronically catecholamine infused rats remains active and
influences blood pressure [26]. The failure of receptor blockade might be explained by the ability of the sympathetic
nervous system to overwhelm the competitive blockade with orders of magnitude greater release of norepinephrine
than normal.
Suggested guidelines for perioperative management prior to pheochromocytoma or paraganglioma removal:

1. Control BP prior to surgery. Use any effective regimen with which you or your colleagues have experience.
2. Aim for 120-160 systolic/65-85 diastolic, and then be prepared to operate. Anesthetic management
recommendations do not appear to be different for the various surgical techniques that have recently been
developed (open vs. laparoscopic; supine, flank, vs. prone position).
3. Cardiomyopathy associated with pheochromocytoma may be uniquely responsive to alpha-adrenergic
blocking agents. Catecholamine cardiomyopathy is an interesting phenomenon whose mechanism is not
fully understood [27-29].
4. No specific agent (volatile or intravenous anesthetic) has been shown to be superior in terms of outcomes.
5. Use what you know best for intraoperative control. For most of us, that’s sodium nitroprusside and esmolol.
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6. It is hard to support the notion that one should use phentolamine if one is not familiar with its use in any
other situation.
7. The common recommendation that antihypertensive therapy should be given for 2 weeks prior to the
operation has not been tested in properly conducted clinical trials, nor has the recommendation to treat until
orthostatic hypotension has developed. These are not evidence-based recommendations, and may be
entirely incorrect.
8. There probably is a limited role for phenoxybenzamine in modern perioperative medicine, although there
are physicians with many years of experience caring for pheochromocytoma patents who continue to use it
rather than the more selective alpha-1 blocking agents or other classes of antihypertensive drug. For the
patient with an unresectable malignant pheochromocytoma, phenoxybenzamine seems valuable because of
its long duration of action. It is, however, quite expensive.
9. If confronted with severe hypertension after induction and you suspect pheochromocytoma in a previously
undiagnosed patient, don’t proceed with surgery unless it is urgent or emergent.
10. But if the surgery is urgent or emergent, see #4 above. Consider using local and regional anesthesia to
supplement your technique.
References
1. Lamberts, S.W., H.A. Bruining, and F.H. de Jong, Corticosteroid therapy in severe illness. N Engl J Med,
1997. 337(18): p. 1285-92.
2. de Herder, W.W. and A.J. van der Lely, A ddisonian crisis and relative adrenal failure. Rev Endocr Metab
Disord, 2003. 4(2): p. 143-7.
3. Deegan, R.J. and W.R. Furman, Cardiovascular Manifestations of Endocrine Dysfunction. J Cardiothorac
Vasc Anesth, 2011.
4. Salem, M., et al., Perioperative glucocorticoid coverage. A reassessment 42 years after emergence of a
problem. Ann Surg, 1994. 219(4): p. 416-25.
5. Purnell, J.Q., et al., A ssociation of 24-hour cortisol production rates, cortisol-binding globulin, and plasma-
free cortisol levels with body composition, leptin levels, and aging in adult men and women. J Clin
Endocrinol Metab, 2004. 89(1): p. 281-7.
6. Udelsman, R., et al., A daptation during surgical stress. A reevaluation of the role of glucocorticoids. J Clin
Invest, 1986. 77(4): p. 1377-81.
7. Schenarts, C.L., J.H. Burton, and R.R. Riker, A drenocortical dysfunction following etomidate induction in
emergency department patients. Acad Emerg Med, 2001. 8(1): p. 1-7.
8. Zed, P.J., et al., Etomidate for rapid sequence intubation in the emergency department: is adrenal
suppression a concern? CJEM, 2006. 8(5): p. 347-50.
9. Pimentel, L. and K.N. Hansen, Thyroid disease in the emergency department: a clinical and laboratory
review. J Emerg Med, 2005. 28(2): p. 201-9.
10. Nayak, B. and K. Burman, Thyrotoxicosis and thyroid storm. Endocrinol Metab Clin North Am, 2006.
35(4): p. 663-86, vii.
11. Chiniwala, N.U., et al., Thyroid storm caused by a partial hydatidiform mole. Thyroid, 2008. 18(4): p. 479-
81.
12. Delikoukos, S. and F. Mantzos, Thyroid storm induced by blunt thyroid gland trauma. Am Surg, 2007.
73(12): p. 1247-9.
13. Ross, D.S., Radioiodine therapy for hyperthyroidism. N Engl J Med, 2011. 364(6): p. 542-50.
14. Lee, S.M., et al., Thyrotoxicosis with coronary spasm that required coronary artery bypass surgery. Intern
Med, 2007. 46(23): p. 1915-8.
15. Toft, A.D., Thyroxine therapy. N Engl J Med, 1994. 331(3): p. 174-80.
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16. Cunningham, J., F. Locatelli, and M. Rodriguez, Secondary hyperparathyroidism: pathogenesis, disease
progression, and therapeutic options. Clin J Am Soc Nephrol, 2011. 6(4): p. 913-21.
17. Cannon, J., J.I. Lew, and C.C. Solorzano, Parathyroidectomy for hypercalcemic crisis: 40 years' experience
and long-term outcomes. Surgery, 2010. 148(4): p. 807-12; discussion 812-3.
18. Duntas, L.H. and N. Stathatos, Cinacalcet as alternative treatment for primary hyperparathyroidism:
achievements and prospects. Endocrine, 2011.
19. McNeil, A.R., et al., Phaeochromocytomas discovered during coronial autopsies in Sydney, Melbourne and
A uckland. Aust N Z J Med, 2000. 30(6): p. 648-52.
20. Bravo, E.L., Pheochromocytoma: an approach to antihypertensive management. Ann N Y Acad Sci, 2002.
970: p. 1-10.
21. Bravo, E.L., et al., Circulating and urinary catecholamines in pheochromocytoma. Diagnostic and
pathophysiologic implications. N Engl J Med, 1979. 301(13): p. 682-6.
22. Ulchaker, J.C., et al., Successful outcomes in pheochromocytoma surgery in the modern era. J Urol, 1999.
161(3): p. 764-7.
23. Bravo, E.L. and R. Tagle, Pheochromocytoma: state-of-the-art and future prospects. Endocr Rev, 2003.
24(4): p. 539-53.
24. James, M.F. and L. Cronje, Pheochromocytoma crisis: the use of magnesium sulfate. Anesth Analg, 2004.
99(3): p. 680-6, table of contents.
25. Wong, A.Y. and C.W. Cheung, Dexmedetomidine for resection of a large phaeochromocytoma with
invasion into the inferior vena cava. Br J Anaesth, 2004. 93(6): p. 873.
26. Johnson, M.D., et al., Paradoxical elevation of sympathetic activity during catecholamine infusion in rats. J
Pharmacol Exp Ther, 1983. 227(1): p. 254-9.
27. Jindal, V., et al., Pheochromocytoma: presenting with regular cyclic blood pressure and inverted Takotsubo
cardiomyopathy. J Clin Hypertens (Greenwich), 2009. 11(2): p. 81-6.
28. Ganguly, A., et al., Rapid cyclic fluctuations of blood pressure associated with an adrenal
pheochromocytoma. Hypertension, 1984. 6(2 Pt 1): p. 281-4.
29. Ahn, J.T., J.U. Hibbard, and J.B. Chapa, A typical presentation of pheochromocytoma as part of multiple
endocrine neoplasia IIa in pregnancy. Obstet Gynecol, 2003. 102(5 Pt 2): p. 1202-5.
DISCLOSURE
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Obstructive Sleep Apnea and Anesthesia–

What an Anesthesiologist Should Know?
Frances Chung, MBBS FRCPC Toronto, Ontario, Canada.
Obstructive sleep apnea (OSA) is a clinical syndrome defined by repetitive partial or complete upper
airway obstruction, characterized by episodes of breathing cessation during sleep lasting 10 or more seconds. The
inherent pharyngeal collapsibility due to depression of pharyngeal muscle regulation during sleep and anesthesia
predisposes to impaired respiration.1 Recurring airway obstruction causes repeated arousals and increased
sympathetic output, cumulating in daytime hypersomnolence, memory loss, executive dysfunction and other
psychological disturbances.2
OSA is the most prevalent of sleep disordered breathing.3 The estimates of mild OSA are in the range of 1 in 4
males and 1 in 10 females in the general population.4 Moderate OSA estimates are in the range of 1 in 9 males and 1
in 20 females.5,6 A significant proportion of OSA patients remain undiagnosed when patients present for surgery.7
About a quarter (24%) of elective surgical patients were found to be at high risk of OSA, of whom 4 out of 5 (81%)
had not been diagnosed with OSA.8 Even in the context of ambulatory surgery, undiagnosed OSA may be frequently
present.9 Furthermore, OSA may be associated with increased risk of postoperative complications. Therefore, OSA
patients can be a potential management challenge and anesthesiologists need to have a thorough understanding of
this disorder.
Classical Diagnosis Criteria for OSA The classical diagnosis of OSA is established by an overnight
polysomnography (PSG). The apnea hypopnea index (AHI) is the number of abnormal respiratory events (complete
cessation or apnea, and partial obstructions or hypopnea) per hour of sleep. These pauses in breathing must last for
10 seconds and are associated with decrease in oxygenation of the blood. There is a lack of conformity as to the
diagnostic criteria for OSA10, 11,12. In 1999, the task force of the American Academy of Sleep Medicine (AASM)
stipulated the minimal clinical diagnostic criteria for OSA as an AHI of 10 plus symptoms of excessive daytime
sleepiness.10 AHI cutoffs have been used to describe the severity of OSA. The AASM defines mild OSA as AHI: 5-
15, moderate OSA as AHI 15-30, and severe OSA as AHI > 30.12
Comorbidities Associated with OSA
OSA has known associations with several comorbidities, including cardiovascular disease (myocardial infarction,
heart failure, arrhythmias, hypertension), cerebrovascular disease, metabolic syndrome, gastro-esophageal reflux
disease, and obesity.13 In bariatric surgery, 7 out of every 10 patients were found to have OSA.14 Certain patient
profiles (male, > 50 years old, neck circumference > 40 cm), endocrine disorders (Cushing’s disease,
hypothyroidism), connective tissue disorders (Marfan’s syndrome), lifestyle habits (alcohol, smoking), and
anatomical abnormalities may predispose to OSA.15 Altered upper airway anatomy (craniofacial abnormalities,
macroglossia, retrognathia) may reduce lumen diameter, increasing the propensity for these episodic airway
obstruction.
Postoperative Complications in Patients with OSA
In the general community, long-standing untreated OSA is an independent risk factor for increased all-cause
mortality.16,17 Two single-center retrospective trials investigated postoperative complications in diagnosed OSA
patients. Gupta et al demonstrated that serious postoperative complications in OSA patients undergoing hip or knee
replacement occurred in 24% vs. 9% in the control group.18 Similarly, Liao and Chung et al found that the incidence
of postoperative complications in the OSA group was 44% vs. 28% in the non-OSA group.19 In another prospective
cohort study, Chung et al demonstrated that the incidence of postoperative complications in 147 OSA patients
compared with those without OSA was 27.4% vs. 12.3%.20 Gali et al found an increased risk of postoperative
complications in 221 high risk OSA patients.21 OSA was also reported to be independently associated with
increased postoperative hypoxemia, intensive care unit transfers and longer hospital stays after non-cardiac
surgery.22 Memtsoudis et al found that sleep apnea patients developed 2X higher risks of pulmonary complications
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after both orthopedic and general surgeries vs. non-OSA patients.23 Flum et al showed that a diagnosis of OSA in
patients undergoing bariatric surgery was an independent risk factor for adverse postoperative outcomes.24
Preoperative Evaluation of the Known OSA Patient (Figure 1)
Both the diagnosis and severity of OSA should be determined in a patient with known OSA through questioning
about OSA symptoms and a review of PSG results. Long-standing OSA may have systemic complications,
including hypoxemia, hypercarbia, polycythemia, and cor pulmonale. The presence of significant comorbidities such
as uncontrolled hypertension, arrhythmias, cerebrovascular disease, heart failure, metabolic syndrome, and morbid
obesity should be determined. Pulmonary arterial hypertension in patients with OSA has been reported to be 15-
20%.25 However, the Evidenced-Based Clinical Practice Guidelines of the American College of Chest Physicians do
not recommend routine evaluation for the presence of pulmonary arterial hypertension in the management of
patients with OSA.26 Intraoperative triggers for elevation in pulmonary arterial hypertension should be avoided in
the OSA patient. In the preoperative clinic, the pulse oximetry may be a simple screening tool for OSA patients with
complications. An oxygen saturation value of < 94% on room air, in the absence of other causes such as COPD,
should be a red flag for severe long-standing OSA.
The OSA patient’s use of and compliance with positive airway pressure (PAP) devices (continuous positive airway
pressure, bilevel positive airway pressures, auto-titrating positive airway pressure) should be assessed. Some of the
patients with known OSA may have to be referred to the sleep medicine physician for reassessment preoperatively –
including those who have had a recent exacerbation of OSA symptoms, or have been non-compliant with PAP
therapy. Due consideration should be given for the re-initiation of preoperative PAP therapy in the non-compliant
OSA patient, although evidence of its efficacy is lacking in this preoperative context and the duration of
preoperative OSA treatment necessary to decrease perioperative risk is unknown.
Patients with moderate and severe OSA who have been on PAP therapy should continue PAP therapy in the
preoperative period.27 The intraoperative anesthesia team should be alerted in advance so that an anesthetic plan can
be formulated. Perioperative OSA risk mitigation strategies and precautions should be undertaken. It is unclear from
the current literature if mild OSA would be a significant disease entity in the perioperative period. Based on expert
opinion, patients with mild OSA would not require preoperative PAP therapy. A published opinion-based algorithm
addressing the preoperative management of the known OSA patient is shown in Figure 1.28
Screening Methods for OSA in the Surgical Setting
The gold standard for diagnosing OSA is by overnight PSG. However, cost, expertise, equipment, and time
constraints make routine PSG screening prohibitive. Therefore, practical screening tools for OSA are needed to filter
out the patients at higher risk of OSA. Several questionnaire-based screening tools have been developed, including
the Epworth Sleepiness Scale,29 the Berlin Questionnaire,30 the ASA checklist,27 the Sleep Apnea Clinical Score,31
and the P-SAP score.32
A concise clinical screening tool was developed for anesthesiologists–the STOP-Bang questionnaire.33 The
STOP-Bang questionnaire is a scoring model based on Yes / No answers to 8 easily administered questions with the
acronym STOP-Bang (Table 1). Patients are considered as at risk of OSA if ≥ 3 items are scored positive on the
STOP-Bang questionnaire. Patients are considered as at high risk of OSA if 5-8 items are scored positive on the
STOP-Bang questionnaire.
OSA screening tools should have a high degree of sensitivity at the expense of lower specificity. The STOP-Bang
questionnaire with a cutoff of 3 has a high level of sensitivity and negative predictive value, especially for patients
with moderate and severe OSA.33 If the patient is scored as a low risk of OSA by the STOP-Bang questionnaire, the
patient is unlikely to have moderate to severe OSA. The corollary is that the STOP-Bang score may be falsely
positive. The STOP-Bang questionnaire has a sensitivity of 93% and 100% at AHI cut-off values of > 15 and > 30
respectively, with the specificity of 43% and 37% respectively.33 A higher score of 5, 6, 7, or 8 is more predictive of
moderate to severe OSA. By using a higher cutoff value of STOP-Bang 5, 6, and 7, the specificity for AHI > 30
(severe OSA) was increased to 74%, 88%, and 95% respectively.34 Depending on the prevalence of OSA, a higher
score of 5- 6 may be more practical. Patients that are identified with a high risk of OSA on STOP-Bang
questionnaire have been shown to be associated with the occurrence of higher postoperative complications.35,36
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Screening questionnaires such as the STOP-Bang can be used preoperatively to categorize OSA severity, triage
patients for diagnostic evaluation or exclude them from harm.37
Preoperative Evaluation of the Suspected OSA Surgical Patient (Figure 1)
Urgent or emergent surgery should not be delayed for the detailed evaluation of suspected OSA. A patient is at risk
of OSA if ≥ 3 items score positive on the STOP-Bang questionnaire. A patient is at high risk of OSA if ≥ 5-6 items
score positive on the STOP-Bang questionnaire. A published opinion-based algorithm addressing the preoperative
management of the suspected OSA patient is shown in Figure 1.28
The anesthesiologist could consider a preoperative referral to the sleep physician and for a PSG if the patient screens
as high risk of OSA with clinical symptoms of OSA, is scheduled for major elective surgery and has significant
comorbidities suggestive of long-standing OSA. These comorbidities include uncontrolled hypertension, heart
failure, arrhythmias, cerebrovascular disease, morbid obesity and metabolic syndrome. A timely and early consult
would be helpful so that the sleep physician can have adequate time to prepare a perioperative management plan,
which may include PAP treatment.27 Major elective surgery may have to be deferred in patients with a high clinical
suspicion of severe OSA with systemic complications. Ultimately, the decision for further preoperative PSG testing
should depend on the clinical judgment and expertise of the attending physician; taking into account the patient-
specific and logistical considerations in its totality.
On the other hand, there may be patients who are at high risk according to the STOP-Bang questionnaire with no
clinical symptoms and significant comorbidities, and are not scheduled to undergo major surgery. Some of these
patients may have had uneventful anesthetics in the past. These “at risk” patients may represent false positives on
screening, or patients with mild OSA. A positive screening test would alert the anesthesiologist so that perioperative
risk mitigation and precautions for possible OSA may be undertaken. If subsequent intraoperative difficult airway38
or postanesthesia care unit (PACU) recurrent respiratory events21 suggest a higher probability of OSA, a PSG and a
sleep physician referral after the surgery may be indicated. Due to the high sensitivity and negative predictive value
of STOP-Bang, the incidence of false negatives will be low. Therefore, patients who are at low risk of OSA (<3 on
STOP-Bang) are unlikely to have OSA. These patients may be managed with routine perioperative care.
Home Sleep Testing and Nocturnal Oximetry
If there is a high index of suspicion for an undiagnosed OSA patient presenting for surgery, home sleep testing may
also be a viable diagnostic alternative to the standard PSG.39 Level 2 portable sleep devices have been shown to be
reliable alternatives in surgical patients.40 In addition, nocturnal oximetry is a sensitive and specific tool to detect
OSA in surgical patients who are STOP-Bang positive.41 There is a strong correlation between oxygen desaturation
index from nocturnal oximetry and apnea hypopnea index from PSG.41 Nocturnal oximetry is 93% sensitive and
75% specific in diagnosing OSA. 41 If PSG is unavailable due to resource constraints, these surrogate investigations
may help to identify the OSA patients, so that preoperative PAP therapy may be considered and appropriate
perioperative precautionary measures may be undertaken.
Perioperative Strategies to Mitigate Risks for the OSA Patient (Table 2)
OSA patients are susceptible to several perioperative risks during the conduct of anesthesia. Strategies or
perioperative precautions that may be undertaken to mitigate these risks and minimize adverse outcomes in OSA
patients are discussed in this section and listed in Table 2.28 Sedative premedication should be avoided.42 Alpha-2
adrenergic agonists such as clonidine and dexmedetomidine may reduce intraoperative anesthetic requirements and
have an opioid-sparing effect.43 Difficulty with tracheal intubation occurs 8X as often in OSA patients vs. non-OSA
patients.44 OSA is also a risk factor for difficult mask ventilation.45 A primary and back-up airway plan should be
formulated in advance, identifying skills and additional equipment necessary to enact the plan.46 A variety of airway
adjuncts (e.g. video laryngoscope, fibreoptic bronchoscope) and skilled anesthesiology assistance should be
available prior to the induction of anesthesia. The entire anesthesia team should be familiar with center-specific
difficult airway algorithms, such as the ASA difficult airway management guidelines.47 Preoxygenation with 100%
oxygen with CPAP at 10 cmH20 for 3-5 min with the patient at 25 degree head-up position is advantageous in
achieving higher end-tidal oxygen concentration.48 Triple airway maneuvers using two-handed mask ventilation
technique may be required to achieve adequate ventilation prior to tracheal intubation. Obese OSA patients may
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require a ramp to be built under the patient from the scapula to the head to allow alignment of the ear and the sternal
notch (head-elevated laryngoscopy position – HELP), thus facilitating laryngoscopy. This may be done by
“stacking” blankets or with specially designed foam devices (Troop Elevation Pillow, Mercury Medical®).
Gastroesophageal reflux disease may be more prevalent in OSA patients due to hypotonia of the lower esophageal
sphincter.49 The use of proton pump inhibitors, antacids, rapid sequence inductions, and cricoid pressure may be
considered to reduce the risk of aspiration. Notably, cricoid pressure may make tracheal intubation and mask
ventilation more difficult, compounding the problem of difficult airways in OSA patients.50 The use of regional
blocks (neuraxial or peripheral nerve blocks) as a sole anesthetic may be beneficial to the OSA patient as it
circumvents the issue of upper airway patency and decreases requirements for opioids in the perioperative period.
Therefore local and regional techniques may be preferred to general anesthesia.27 Presently however, there is no
evidence supporting one anesthetic technique over another. The postoperative use of wound infiltration, nerve block
catheters or epidural catheters with local anesthetics reduces opioid requirements and this may be beneficial.
Patients with OSA are sensitive to the respiratory depressant effects of anesthetic agents including sedatives,
opioids, and inhaled anesthetics. This is because of the propensity of airway collapse, sleep deprivation, and
blunting of the physiological response to hypercarbia and hypoxia. The use of short-acting agents (propofol,
remifentanil, desflurane, sevoflurane), and correspondingly the avoidance or minimization of the use of longer
acting anesthetic drugs, is recommended. Intraoperative triggers for elevation in pulmonary arterial hypertension
such as hypercapnia, hypoxia, hypothermia and acidosis should be avoided. In a recent novel study, intraoperative
administration of intravenous doxapram (a central respiratory stimulant) may be associated with favorable post-
anaesthesia recovery and outcomes in bariatric surgery patients with OSA.51
A multimodal or balanced approach for analgesia is advocated (nonsteroidal anti-inflammatory drugs, COX-2
inhibitors, acetaminophen, tramadol, pregabalin, gabapentin) for the opioid-sparing effect. Notably, postoperative
O2 desaturations were 12-14X more likely to occur in OSA patients receiving postoperative oral or parenteral
opioids vs. those receiving non-opioid analgesic agents.52 Recently, there has been an increasing interest in using
alternative analgesic adjuvants such as corticosteroids (e.g. dexamethasone), ketamine,53 melatonin,54 clonidine and
dexmedetomidine55 to provide improved pain relief.
Postoperatively, tracheal extubation should be performed only after the OSA patient is fully conscious, airway
patency confirmed, and able to follow verbal commands. Muscle relaxants should be fully reversed and this
verified,56 especially in the OSA patient. A non-supine position (semi-upright or lateral) is preferred for
postoperative recovery.57
Patients undergoing surgical procedures under monitored anesthetic care or regional anesthesia with sedation should
have intraoperative capnography available to monitor for ventilation. Based on expert opinion, patients who use
PAP therapy at home should use personal PAP therapy devices during procedures that utilize mild to moderate
sedation and do not involve the face and neck.58 If deep sedation is required, a secure airway is preferable to an
unprotected airway.27
Postoperative Disposition of the Known or Suspected OSA Patient after General Anesthesia
(Figure 2)
Patient, anesthesia, analgesia, and surgery-specific factors influence the requirements for postoperative monitoring
in OSA patients. For example, the patient with severe OSA undergoing major surgery requiring postoperative
opioids would likely require close and continuous postoperative monitoring. In contrast, routine postoperative care
might be appropriate in the patient with suspected OSA undergoing minor elective surgery.
In reality, the final decision of whether the patient requires closer postoperative monitoring is based on the
judgment, expertise and discretion of the attending anesthesiologist. Modeled on similar principles as the ASA 2006
guidelines on OSA management and on recent evidence, the algorithm described in Figure 2 was published to guide
the anesthesiologist in decision-making for the postoperative disposition of the OSA patient.28
After general anesthesia, all patients with known OSA or patients with suspected OSA should be observed in the
PACU with continuous oximetry monitoring for a longer period than a patient without OSA.13 There are currently
no evidenced-based recommendations as to how long OSA patients should be monitored in the PACU. ASA
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guidelines based on expert opinion recommended a 7 hours duration if there was apnea or airway obstruction in the
PACU.27 However, monitoring in the PACU for that length of time may not be feasible in most hospitals.58 We
propose an extended PACU observation of at least 30 to 60 minutes in an unstimulated environment after the patient
has met the modified Aldrete criteria for discharge.28
The observation of recurrent PA CU respiratory events can be used as a reliable second phase indicator to determine
whether the known or suspected OSA patient requires continuous postoperative monitoring. A PACU respiratory
event occurs when a patient has repeated episodes of apnea for ≥ 10 s, bradypnea of < 8 breaths per minute, pain-
sedation mismatch, or desaturations to < 90%.21 PACU nurses play an important role in alerting the health team
regarding which patients will require additional monitoring.
Patients who are at high risk of OSA on the screening questionnaires and encounter recurrent PACU respiratory
events have associated higher postoperative respiratory complications.21,35,36 It may be prudent to monitor these
patients continuously with oximetry, in an area where early medical intervention can occur (Figure 2). This can be
either in a step-down unit, or oximetry with telemetry. These patients may also require commencement of
postoperative PAP therapy. In a similar fashion, Sundar et al published their “sleep trial” protocol – using
desaturation (2 or more episodes), bradypnea (< 8 breaths/min) and obstructive apneic episodes to decide which
suspected OSA patients require PAP therapy.58
There are new monitoring technologies. Monitoring can be continuous and the trend analysis incorporated into the
alarm system. Heart rate, respiratory rate, blood pressure, temperature, end-tidal carbon dioxide, oxygen saturation
and other physiological channels can be monitored continuously and interpreted concurrently with smart algorithms
to optimize sensitivity and minimize false alarms. This technology may have the potential to make surgical wards
safer for our OSA patients and reduce the number of preventable deaths.59,60
Known OSA patients who have been non-compliant with PAP therapy or have severe OSA may have to be fitted
with postoperative PAP therapy and cared for in a monitored environment with continuous oximetry, particularly if
there has been a recurrent PACU respiratory event (Figure 2). Known OSA patients requiring postoperative
parenteral opioids may require continuous oximetry monitoring to detect drug-induced postoperative respiratory
depression.61 Moderate OSA patient requiring oral opioids, and without recurrent PACU respiratory events may be
managed postoperatively on the surgical ward with oximetry monitoring (Figure 2).
OSA patients may have upregulation of central opioid receptors due to recurrent hypoxemia, therefore they are more
sensitive to the respiratory depressive effect of narcotic agents. It may also be expedient to place patients requiring
postoperative parenteral opioids on supplemental oxygen.62 In a recent multi-disciplinary consensus meeting
organized by the Anesthesia Patient Safety Foundation, it was suggested that if supplemental oxygen was used,
monitors of ventilation (e.g. capnography) may be required to detect hypoventilation.61
Multimodal analgesic techniques should be utilized to minimize the postoperative administration of opioids. These
would include local anesthetic wound infiltration, peripheral nerve block catheters or neuraxial catheters running
local anesthetic agents (without opioids), and use of opioid-sparing analgesic agents – such as non-steroidal anti-
inflammatory drugs, COX-2 inhibitors, ketamine, acetaminophen, pregabalin, gabapentin, tramadol,
dexmedetomidine, and dexamethasone.
Known OSA patients previously on PAP therapy should be encouraged to be compliant with PAP therapy
postoperatively. PAP therapy should be ordered in the postoperative period; although high level evidence studies
addressing specifically PAP therapy and postoperative outcomes in OSA patients are lacking. Notably, a recent
retrospective review of 797 patients scheduled for bariatric surgery suggested the possibility that recognition and
appropriate management of OSA (with 93% of the patients receiving perioperative CPAP) may mitigate the risk of
postoperative complications.63
Interestingly, a significant increase in AHI occurred on postoperative night 3, particularly in male patients with
moderate and severe OSA.64 Normalization of sleep architecture and AHI occurs only on the 5th to 7th postoperative
nights.65 This may help to explain the late postoperative complications seen in OSA patients. The necessary level of
monitoring for each individual OSA patient continues to pose a difficult triage decision. To avoid postoperative
complications, it may be best to have the OSA patient received perioperative PAP. Unfortunately, the current
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paucity of high level evidence in the literature does not contribute knowledge to assist the practicing anesthesiologist
with the decision-making process. Further good quality research on the postoperative management of OSA patients
is essential.
OSA Patient and Ambulatory Surgery
Disagreement exists as to whether OSA patients should be discharged for home after surgery. The 2006 ASA
guidelines on OSA highlighted that superficial surgeries or minor orthopedic surgery using local or regional
techniques and lithotripsy may be done on an ambulatory basis.27 In our opinion, patients suspected of OSA or with
mild OSA who have undergone ambulatory surgery, without recurrent PACU respiratory events, and not requiring
higher dose of oral opioids for analgesia, may be discharged home at the discretion of the attending physicians
(Figure 2).28,66 However, severe OSA patients without optimized comorbid conditions are not ideal candidates for
ambulatory surgery.66 The threshold for unanticipated hospital admission should be lowered.
Conversely, retrospective observational studies of OSA patients undergoing bariatric surgery in free-standing
ambulatory surgical centers have demonstrated that postoperative complication rate can be low (<0.5%), and that
these surgeries may be performed on an ambulatory basis or as short-stay surgeries.67,68,69 Judicious patient selection,
preoperative optimization of medical conditions (including PAP therapy for OSA), skilled medical personnel, and
experienced high volume facilities with strict home-care criteria may be the ingredients for successful outcomes in
this high risk population. However, such an approach is still controversial.70
Conclusions
In the perioperative period, OSA is often under-diagnosed. Screening tools such as the STOP-Bang
questionnaire, allows risk stratification of the suspected OSA patients. Individualized and tailored patient care is
required to mitigate the perioperative risks of the known and suspected OSA patient. Practical algorithms based on
the current best evidence and expert opinion may guide anesthesiologists in the perioperative management of these
vulnerable OSA patients. Interdisciplinary collaboration and cross-fertilization of ideas between anesthesiology and
sleep medicine will provide the substrate for further research, with the hope of answering important questions in
OSA management.71
Acknowledgement
The work is written together with Edwin Seet, MBBS MMed, Department of Anesthesia, Alexandra Health Private
Limited, Khoo Teck Puat Hospital, Singapore.
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68. Raeder J: Bariatric procedure as day/short stay surgery: is it possible and reasonable? Curr Opin
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69. Schumann R: Anaesthesia for bariatric surgery. Best Pract Res Clin Anaesthesiol 2011; 25:83-93.
70. Chung F, Hillman D, Lydic R: Sleep medicine and anesthesia – A new horizon for anesthesiologists.
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Table 1: Obstructive Sleep Apnea Screening Tools
STOP-Bang Questionnaire
S Snoring: Do you snore loudly (louder than talking or loud enough to be Yes No
heard through closed doors)?
T Tired: Do you often feel tired, fatigued, or sleepy during daytime? Yes No
O Observed: Has anyone observed you stop breathing during your sleep? Yes No
P Blood Pressure: Do you have or are you being treated for high blood Yes No
pressure?
B BMI: BMI more than 35 kg/m2? Yes No
A Age: Age over 50 years old? Yes No
N Neck circumference: Neck circumference greater than 40 cm? Yes No
G Gender: Male? Yes No
A t risk of OSA : Yes to 3 or more questions for STOP-Bang.

High risk of OSA: Yes to 5 or more questions for STOP-Bang
Adapted from Chung F et al: STOP Questionnaire: A tool to screen patients for obstructive sleep apnea.
Anesthesiology 2008; 108:812-21 and Chung F et al High STOP-Bang score indicates a high probability of
obstructive sleep apnoea. Br J Anaesth 2012; 108: 768-75.
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Table 2: Perioperative Precautions and Risk Mitigation for OSA Patients
Anesthetic Concern Principles of Management
Premedication Avoid sedating premedication.42

Alpha-2 adrenergic agonist (clonidine, dexmedetomidine)43 may
reduce intraoperative anesthetic requirements and have an opioid-
sparing effect.
Possible difficult airway – mask Ramp from scapula to head if patient is obese.
ventilation and tracheal intubation44,45 Adequate preoxygenation.
Consider CPAP preoxygenation.48
Two-handed triple airway maneuvers
American Society of Anesthesiologists Difficult Airway
Algorithm.47
Gastroesophageal reflux disease49 Consider proton pump inhibitors, antacids, rapid sequence
induction with cricoid pressure.
Opioid-related respiratory depression42 Minimize use of opioids for analgesia.
Use of short-acting agents (remifentanil).
Regional and multimodal analgesia (NSAIDs, acetaminophen,
tramadol, ketamine, gabapentin, pregabalin, dexmedetomidine,
clonidine, dexamethasone.)
Carry-over sedation effects from longer- Use of propofol / remifentanil for maintenance of anesthesia.
acting intravenous sedatives and inhaled Use of insoluble potent anesthetic agents (desflurane).
anesthetic agents Use of regional blocks as a sole anesthetic technique.
Excessive sedation in monitored Use of intraoperative capnography for monitoring of respiration.27

anesthetic care
Post-extubation airway obstruction Verification of full reversal of neuromuscular blockade.27

Ensure patient fully conscious and cooperative prior to
extubation.27
Non-supine posture for extubation and recovery.27
Resume use of positive airway pressure device.27
Adapted from Seet E, Chung F. Management of sleep apnea in adults – functional algorithms for the perioperative
period. Can J Anesth 2010; 57: 849-64.
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Screening using STOP-Bang Severity Assessment from
Suspected OSA patient Known OSA patient
questionnaire History or Polysomnography
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t risk of OSA Low risk of OSA Mild OSA Moderate or

≥3 STOP-Bang) ( <3 on STOP-Bang) AHI 5 – 15 Severe OSA
Oximetry ≥ 94% on AHI > 15
room air Oximetry < 94% on
room air
Figure 1:
jor Elective Figure
Surgery & 1 - Preoperative Evaluation of Known or Suspected Obstructive Sleep Apnea Patient in
the Anesthesia Clinic
nificant Comorbidities  Changes in OSA Status
• Recent exacerbation of
Arrhythmias OSA symptoms
Uncontrolled hypertension Non-compliant to PAP
Cerebrovascular disease
Routine perioperative •
therapy‡
Metabolic syndrome management.
• Recently undergone OSA-
Obesity with BMI > 35 kg/m2 No preoperative PAP related surgery
therapy‡ required. • Lost to sleep medicine
follow-up
No Yes
Yes No
e possibility Consider
erate OSA. preoperative referral
rative to sleep medicine Preoperative PAP
ecautions physician, therapy‡.
k mitigation polysomnography, Perioperative OSA
2). and preoperative precautions and risk
PAP therapy‡. mitigation (Table 2).
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Patient monitored in postanesthesia care unit for longer duration
(> 30-60 min after modified Aldrete criteria met)
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Suspected OSA
( ≥3 STOP-Bang)
Known OSA
mpliant with PAP therapy‡,  Recurrent PACU Respiratory Event of oxygen
OSA (AHI > 30), desaturation <90%, bradypnea <8 breaths / min,
erative parenteral opioids,
Figure 2or- Postoperative Management
apneaof≥ the and pain
10 sKnown orsedation mismatch
Suspected Obstructive Sleep Apnea
ent PACU Respiratory Event of oxygen Patient after General Anesthesia
(concurrent high pain and sedation scores) #
ation <90%, bradypnea <8 breaths / min,
10 s and pain sedation mismatch
rent high pain and sedation scores) #
No Yes Yes No
ate OSA (AHI > 16-30),

e postoperative oral
s (> codeine 60 mg q4h, or
lent)
Yes
Consider care in a Consider discharge to

Consider monitored bed† with home if minor surgery
o postoperative continuous oximetry or postoperative care on
nor monitored care and/or postoperative PAP the surgical ward.
on the surgical therapy‡
ward.
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Legend for Figures:
Figure 1: Preoperative Evaluation of Known or Suspected Obstructive Sleep Apnea Patient in

the Preoperative Clinic
‡
Positive Airway Pressure (PAP) therapy – including continuous PAP, bilevel PAP, or auto-titrating PAP.
period Can J Anesth 2010; 57: 849-64.
Figure 2: Postoperative Management of the Known or Suspected Obstructive Sleep Apnea

Patient after General Anesthesia
#
Recurrent Postanesthesia Care Unit (PACU) Respiratory Event.21
‡
Positive Airway Pressure (PAP) therapy – including continuous PAP, bilevel PAP, or auto-titrating PAP.
†
Monitored bed - environment with continuous oximetry and the possibility of early nursing intervention (e.g.
intensive care unit, step-down unit, or remote pulse oximetry with telemetry in surgical ward).
period. Can J Anesth 2010; 57: 849-64.
DISCLOSURE
#
Recurrent PACU Respiratory Event - any event occurring more than once in each 30-min
evaluation period (not necessary to be the same event) [82].
†
Monitored bed - environment with continuous oximetry and the possibility of early nursing
intervention (e.g. step-down unit, general surgical ward near nursing station, or remote pulse
oximetry with telemetry in surgical ward).
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Management of the Patient with Cirrhotic Liver Disease

Randolph H. Steadman, M.D., M.Sc. Los Angeles, California
Definition
Cirrhosis is defined by the presence of hepatic parenchymal necrosis, fibrosis and regeneration, which results in
portal hypertension. Decompensated cirrhosis is associated with ascites, encephalopathy, varices, hepatorenal
syndrome and hepatic synthetic dysfunction. In 2010 chronic liver disease was the twelfth most common cause of
death in the United States.(Murphy 2012)
Causes
The etiology of end stage liver disease (ESLD) includes developmental or genetic defects, metabolic abnormalities,
autoimmune diseases, infectious diseases, neoplasm, alcohol, environmental toxins, and drug toxicity. Chronic viral
infection due to hepatitis C, alcoholic liver disease and nonalcoholic steatohepatitis are the most common causes of
cirrhosis leading to liver transplantation in the U.S.(OPTN 2011) Fourteen million adults in the U.S. meet the
diagnostic criteria for alcohol dependence. Alcohol accounts for 40% of deaths due to chronic liver disease. Three to
four million people in the United States are infected with hepatitis C, and one million have hepatitis B.(CDC 2010)
About 20-30% of these chronically infected individuals develop cirrhosis over a 20-30 year period. Nonalcoholic
fatty liver disease (NAFLD), a consequence of the obesity epidemic, is increasingly recognized as a cause of
cirrhosis. The metabolic causes of cirrhosis include hemochromatosis, Wilson’s disease, alpha-1 antitrypsin
deficiency and cystic fibrosis.
Pre-operative Assessment
Liver disease is common and frequently asymptomatic. History and physical examination may uncover risk factors,
symptoms and/or signs that require further evaluation. Risk factors include a history of blood transfusions, illicit
drug use, sexual promiscuity, excessive alcohol use, jaundice and exposure to hepatotoxic drugs. Symptoms include
pruritus and fatigue. Physical exam findings include icterus, palmar erythema, spider telangiectasias, hepatomegaly,
splenomegaly, ascites, testicular atrophy and/or gynecomastia.
Signs of liver disease should prompt a search for the underlying cause. A combination of serologic testing,
ultrasonography and computed tomography or magnetic resonance imaging will narrow the differential diagnosis
and guide further evaluation. Liver biopsy, the diagnostic gold standard, is necessary on occasion.
Cirrhosis affects nearly every organ system. Cardiac manifestations include a decreased systemic vascular resistance
and increased cardiac output, which result from the production of vasodilators in patients with portal
hypertension.(Moller 2008) Overproduction of vasodilators also accounts for a reduced responsiveness to
sympathetic stimulation.(Schepke 2001) Diastolic dysfunction has been described in cirrhotic patients. This renders
them sensitive to volume changes, making them vulnerable to heart failure and pre-renal insufficiency.
Ascites and hydrothorax can cause hypoxemia and restrictive pulmonary disease. Hepatopulmonary syndrome
(HPS), which results from dilatation of the pulmonary microcirculation, is found in up to a third of patients with
end-stage liver disease. It manifests as hypoxemia, which worsens in the upright position. The hypoxemia associated
with HPS typically responds to supplemental oxygen; however, complications are frequent in patients with severe
disease (room air PaO2 less than 50 mmHg). Portopulmonary hypertension, pulmonary hypertension associated with
cirrhosis, occurs in up to 6% of ESLD patients.(Kawut 2008) Perioperative morality is increased in these patients,
particularly in those with more severe elevations in pulmonary pressure.(Krowka 2004)
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Hepatic encephalopathy is a serious, albeit reversible, complication of cirrhosis that is associated with a sensitivity
to sedatives and a predisposition to pulmonary aspiration. Encephalopathy appears as a result of portal-systemic
shunting, and its onset is generally associated with signs of advanced hepatocellular dysfunction such as ascites,
hypoalbuminemia, and elevations of the prothrombin time. Ammonia elevations due to inadequate hepatic
metabolism are an important contributor to encephalopathy, but other factors are involved. These include gut-
derived neurotoxins, gamma-aminobutyric acid (GABA), GABA receptor agonists, oxidative stress, inflammatory
mediators and abnormal serotonin transmission.(Munoz 2008; Bass 2010)
About one third of patients have esophageal varices at the time the diagnosis of cirrhosis is made, and another 10%
develop varices each year. One third with varices develop bleeding. Prophylactic use of non-selective beta blockers
(propranolol or nadolol) and endoscopic band ligation are useful in preventing gastrointestinal bleeding.(Garcia-
Tsao 2007) Up to 30% of cirrhotics with ascites develop spontaneous bacterial peritonitis (SBP), which has a 25%
in-hospital mortality rate. About 10% of patients with cirrhosis develop hepatorenal syndrome (HRS). Refractory
ascites often precedes the onset of HRS. Treatment of HRS includes midodrine, an alpha-agonist, octreotide and
intravenous albumin.(Gines 2004) HRS is frequently a terminal event unless patients are successfully treated or
transplanted.
Nutritional deficiencies are manifested as muscle wasting, ascites and hypoalbuminemia. Enteral supplementation
improves immunocompetence and prognosis. Electrolyte disturbances, infection, an increased dietary protein load,
or sedatives can precipitate hepatic encephalopathy. The precipitating cause should be sought and treated prior to
elective surgery. Management includes lactulose, which is titrated to 2-3 soft stools per day, and oral antibiotics,
such as neomycin or rifaximin.
Coagulopathy occurs as a result of thrombocytopenia and a prolonged prothrombin time, secondary to splenic
sequestration and decreased hepatic synthesis of clotting factors, respectively. The surgical risk of severe
coagulopathy (INR > 1.5 and platelet count < 50,000/mm3) has not been studied. The decision to treat patients with
fresh frozen plasma, cryoprecipitate and/or platelets should be based upon the presence of intraoperative bleeding or,
in the event of prophylactic transfusions, based upon the risk of potential bleeding (e.g., during craniotomy).
Recombinant factor VII has not been shown to decrease transfusion requirements or to improve outcomes in liver
transplantation; however, it may be valuable in selected patients who cannot tolerate the volumes associated with
plasma transfusions. Maintenance of a low central venous pressure may decrease operative blood loss.(Alkozai
2009)
Risk Assessment
The severity of preoperative liver disease correlates with operative risk. (Friedman 1999) Both the Child-Turcotte-
Pugh (CTP) class and the Model for End-Stage Liver Disease (MELD) score are useful measures of the degree of
underlying liver disease. The CPT score is based on serum bilirubin and albumin levels, prothrombin time, and the
degree of encephalopathy and ascites. Child’s class A patients have a perioperative mortality of 10%, while class B
patients have a 30% perioperative mortality, and class C patients’ mortality is as high as 80%. Emergency surgery is
associated with even higher mortality, and approaches 100% in class C patients. These risk rates are supported by
two large retrospective studies.(Garrison 1984; Mansour 1997) The general consensus is that the perioperative risk
in Child’s class C patients precludes elective surgery.
The MELD score, originally designed to predict mortality after transjugular intrahepatic portosystemic shunt
(TIPSS), is a predictor of ninety-day mortality for patients awaiting liver transplantation. It has been shown to be a
more sensitive indicator of perioperative risk in cirrhotic patients than the CTP score. The MELD score is derived
from a linear regression model that uses three predictor variables: bilirubin, creatinine and INR (International
Normalized Ratio). As opposed to the CTP score, ascites and encephalopathy are excluded from the MELD score,
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making it a more objective, reliable predictor that relies solely on laboratory values. MELD also avoids the arbitrary
categorization of predictors found in the CTP. In cirrhotic patients a 1-point increase in MELD score between the
values of 5 and 20 is associated with a 1% increase in perioperative mortality. Each point increase in MELD over 20
is associated with a 2% increase in mortality.(Northup 2008) American Society of Anesthesiologists Physical Status
category has also been shown to predict risk. Physical Status IV equates to 5 MELD points, or 10% additional
perioperative risk.(Teh 2007)
The Hepatic Effects of Anesthesia and Surgery

Many surgical procedures are accompanied by mild elevations in liver enzymes, regardless of whether general
anesthesia or regional is performed. Usually these changes are insignificant, but in patients with cirrhosis hepatic
function can decompensate further, leading to significant morbidity and mortality. Preoperative efforts to improve
encephalopathy and coagulopathy, elevate albumin levels and reduce ascites (elements of the CTP score) are
recommended, as this approach appears to lower perioperative risk.(D'Albuquerque 1995) Coexisting morbidities,
such as anemia and infection, should be treated prior to surgery. In patients with portal hypertension placement of a
transjugular intrahepatic portosystemic shunt may lower perioperative risk.(Gil 2004)
The perioperative risk depends more on the operative site and the degree of liver impairment than the anesthetic
technique. Upper abdominal surgery (cholecystectomy), when compared to hysterectomy, was associated with liver
enzyme abnormalities, while the anesthetic technique (halothane, enflurane or fentanyl) was not.(Viegas 1979)
Although inhalational anesthetics cause reductions in hepatic blood flow over baseline, the new agents isoflurane,
desflurane and sevoflurane appear similar in this regard, and cause less alteration than older volatile agents. Despite
this the selection of general versus regional anesthesia does not appear to affect surgical outcomes.(Nishiyama 2004)
Hemorrhage, hypotension, positive pressure ventilation and pneumoperitonium can further reduce hepatic blood
flow.
In patients with ESLD the volume of distribution is increased, particularly for neuromuscular blockers. This results
in the need for larger loading doses to achieve the desired clinical effect. Cisatracurium and atracurium are good
choices because their metabolism is unaffected by liver disease. The action of drugs can be prolonged due to
impaired metabolism and reduced levels of albumin. Propofol is a good choice in ESLD patients as its metabolism is
not significantly altered.
Narcotics and sedatives may precipitate or worsen encephalopathy, so dosage must be carefully titrated.
Benzodiazepines that undergo glucuronidation, such as oxazepam and lorazepam, are preferred as their elimination
is unaffected by liver disease.
Acute Liver Failure

Acute liver failure (ALF) is defined as the rapid development of jaundice, coagulopathy and encephalopathy in a
patient without preexisting liver disease. Such patients are critically ill and should not undergo surgery other than
those related to liver transplantation. It is important to establish the etiology of acute liver failure as the prognosis,
and need for liver transplantation, relates to the underlying cause.(Ostapowicz 2002) Transplant-free survival is
highest for patients with ALF due to acetaminophen overdose (roughly two-thirds recover without transplant), but is
less than 25% for ALF due to other causes.
Outcomes for Specific Surgeries

Patients with end stage liver disease frequently require procedures and surgery related to their disease. Biliary tract
obstruction is best managed using percutaneous techniques when possible. Endoscopic sphincterotomy may be
associated with increased rates of bleeding, yet mortality and morbidity is low.(Freeman 1999) The risk of
complications in biliary tract surgery is related to the degree of hepatic synthetic dysfunction as measured by the
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INR; however, the risk of bleeding does not correlate with the INR.(Tripodi 2007) Laparoscopic cholecystectomy is
preferred to open procedures for patients with less severe liver disease; cholecystostomy is preferable in patients
with advanced (Child’s class C) disease. Biliary tract surgery is associated with high infection rates due to the
translocation of bacteria and the absence of bile salts in the gastrointestinal tract, which increases absorption of
endotoxin.
The incidence of hepatocellular carcinoma (HCC) is 1-4% per year in patients with cirrhosis.(El-Serag 2004)
Hepatic resection for HCC carries a high risk in patients with cirrhosis. In patients with MELD scores greater than 9,
perioperative mortality was greater than 25%, while there was no mortality in patients with lower MELD
scores.(Teh 2005)
Patients with Child’s class B and C have high mortality and morbidity rates after cardiac surgery.(Hayashida 2004)
The least invasive option is preferred for the management of coronary artery disease. Bare metal stents may be
preferable to drug eluting stents due to the shorter duration of aspirin and clopidogrel after stent placement.
Summary
Patients with end stage liver disease can have associated abnormalities of nearly every organ system. A thorough
preoperative evaluation with optimization of coexisting problems is important in minimizing perioperative mortality
and morbidity. Patients with high MELD scores (or Child’s class C) should not undergo elective surgery. Non-
elective surgery in patients with severe liver dysfunction is accompanied by a high mortality, and a high risk of liver
failure. Surgery in these patients is best coordinated with a regional liver transplant center to achieve optimal results.
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References
Alkozai, E. M., T. Lisman, et al. (2009). "Bleeding in liver surgery: prevention and treatment." Clin Liver Dis
13(1): 145-154.
Bass, N. M., K. D. Mullen, et al. (2010). "Rifaximin treatment in hepatic encephalopathy." The New England
journal of medicine 362(12): 1071-1081.
CDC. (2010). "Viral Hepatitis Surveillance in the United States, 2010." National Notifiable Disease Surveillance
System, from http://www.cdc.gov/hepatitis/Statistics/2010Surveillance/.
D'Albuquerque, L. A., M. P. de Miranda, et al. (1995). "Laparoscopic cholecystectomy in cirrhotic patients." Surg
Laparosc Endosc 5(4): 272-276.
El-Serag, H. B. (2004). "Hepatocellular carcinoma: recent trends in the United States." Gastroenterology 127(5
Suppl 1): S27-34.
Freeman, M. L., D. B. Nelson, et al. (1999). "Same-day discharge after endoscopic biliary sphincterotomy:
observations from a prospective multicenter complication study. The Multicenter Endoscopic
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Friedman, L. S. (1999). "The risk of surgery in patients with liver disease." Hepatology 29(6): 1617-1623.
Garcia-Tsao, G., A. J. Sanyal, et al. (2007). "Prevention and management of gastroesophageal varices and variceal
hemorrhage in cirrhosis." Hepatology 46(3): 922-938.
Garrison, R. N., H. M. Cryer, et al. (1984). "Clarification of risk factors for abdominal operations in patients with
hepatic cirrhosis." A nn Surg 199(6): 648-655.
Gil, A., F. Martinez-Regueira, et al. (2004). "The role of transjugular intrahepatic portosystemic shunt prior to
abdominal tumoral surgery in cirrhotic patients with portal hypertension." Eur J Surg Oncol 30(1): 46-52.
Gines, P., A. Cardenas, et al. (2004). "Management of cirrhosis and ascites." The New England journal of medicine
350(16): 1646-1654.
Hayashida, N., T. Shoujima, et al. (2004). "Clinical outcome after cardiac operations in patients with cirrhosis." A nn
Thorac Surg 77(2): 500-505.
Kawut, S. M., M. J. Krowka, et al. (2008). "Clinical risk factors for portopulmonary hypertension." Hepatology
48(1): 196-203.
Krowka, M. J., M. S. Mandell, et al. (2004). "Hepatopulmonary syndrome and portopulmonary hypertension: a
report of the multicenter liver transplant database." Liver Transpl 10(2): 174-182.
Mansour, A., W. Watson, et al. (1997). "Abdominal operations in patients with cirrhosis: still a major surgical
challenge." Surgery 122(4): 730-735; discussion 735-736.
Moller, S. and J. H. Henriksen (2008). "Cardiovascular complications of cirrhosis." Gut 57(2): 268-278.
Munoz, S. J. (2008). "Hepatic encephalopathy." The Medical clinics of North A merica 92(4): 795-812, viii.
Murphy, S. L., J. Xu, et al. (2012). "Deaths: Preliminary data for 2010." CDC National V ital Statistics Reports
60(4): 7.
Nishiyama, T., T. Fujimoto, et al. (2004). "A comparison of liver function after hepatectomy in cirrhotic patients
between sevoflurane and isoflurane in anesthesia with nitrous oxide and epidural block." A nesthesia and
A nalgesia 98(4): 990-993.
Northup, P. G. (2008). "Hypercoagulation and thrombophilia in liver disease." Journal of Thrombosis and
Haemostatis 6: 2-9.
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(OPTN) and Scientific Registry of Transplant Recipients (SRTR), from
http://www.srtr.org/annual_reports/2010/flash/03_liver/index.html.
Ostapowicz, G., R. J. Fontana, et al. (2002). "Results of a prospective study of acute liver failure at 17 tertiary care
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Teh, S. H., J. Christein, et al. (2005). "Hepatic resection of hepatocellular carcinoma in patients with cirrhosis:
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DISCLOSURE
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Awake intubation Made Easy!

William H. Rosenblatt, M.D. New Haven, Conneticut
By far the hardest part of performing an awake intubation should be the decision to do it! Once that decision is
made, the mechanics of securing the airway should be routine – familiar to you and comfortable for the patient. A
review of the strategy for deciding upon awake intubation can be found in the notes on “Decision making in airway
management” lecture. Technique of Awake Intubation:
Awake intubation (AI) is one of the most important tools of the airway manager. If you are going to manage
airways, you must be good at AI (one day you’ll need it)! And if you have not performed an awake intubation in
years, you probably are not doing enough of them (Don’t confuse being good with being lucky.) After speaking to
thousands of anesthesiologists, I have come to two conclusions: The typical anesthesia practitioner 1) is insecure
about his or her technique and 2) confuse airway anesthesia with AI technique. The sentinel grounds for these
conclusions are deduced from the single question I have been asked almost every time I speak about airway
management (no matter what the lecture topic): “Dr. Rosenblatt, what local anesthetic do you use?” This question
betrays the misconception most clinicians have about AI: that AI is about producing a “numb” airway. In fact the
topical anesthetic(s) chosen matter little. AI involves a systemic approach to patient preparation – once appreciated,
and a consistent technique developed, AI can become as easy as routine airway management.
AI has 6 distinct elements – in my technique, each element is essential, and rarely do I diverge.
Element Underlying concept/action
Explanation* Patients understand safety
Desiccation Dry the airway
Dilatation Prepare (through) the nose
Topicalization Obtund reflexes
Sedation Maintain patient airway control
Procrastination AI can not be rushed
*substituting the word “Account” those who like pneumonics can recall “ADD a TSP” (Benjamin Sherman, MD)
Explanation: All patients presenting to the operating room for surgery harbor some degree of anxiety. Though we
may be comfortable in the OR, it is a foreign environment for most others, and surgery is most often a daunting
prospect. Patients want the safest experience possible. If you have determined (via the AAA or your own method)
that AI is warranted, you have erred on the side of safety – and the patient will understand this. A clear explanation
to the patient is usually all that is required to gain cooperation. Explaining that they will feel or remember very little
and that they will have some sedation is all that is needed. My typical explanation is always some variant of the
following:
“My job is to make sure that you are breathing during surgery. Your anatomy differs (a lot / a little)
from normal, and I have to make sure I can find your breathing pathway. What I am going to do is to
make your throat numb, just like the dentist does (except I will not use needles unless absolutely
necessary). I will then be looking in your mouth in order to find your breathing pathway. After I make
sure you are comfortable and feeling none of this, I will put the breathing tube in.”
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Desiccation: To desiccate is to “dry.” Before you begin to manipulate the airway below the nasopharynx it must
be dry: 1) saliva is a protective barrier – it will protect the mucosa from your topical agents. 2) saliva dilutes your
topical local anesthetic, and decreases it’s effectiveness. 3) manipulation of the airway produces more secretions –
these secretions are an airway stimulant, causing more cough, laryngospasm, etc. 4) I’m likely to use an indirect
optical device which will be neutralized by secretions. I don’t exclude patients who have had airway radiation and
are already complaining of “dry mouth.” My concern is that any remaining functional salivary tissue will counteract
my efforts. My favorite desiccant is glycopyrolate (0.2 to 0.4 mg). Atropine, clonidine and scopolamine are also
effective. Whatever agent you use, it must be given time to be effective -- at least 15 minutes. I will often give the
agent in the nursing intake area as soon as the patient has changed clothes. If there is no IV in place, I do not hesitate
to use an IM injection. This assures that the agent will have time to be effective. If, by the time the patient reaches
the holding area, they are not complaining of “cotton mouth” I consider giving another 0.2mg.
Dilatation: This is primarily an ellipsis for saying “prepare the nose” which is done in all cases unless medically
contraindicated, regardless of my intent to intubate via the mouth or nose. A vasoconstrictor is used to decongest the
nasal mucosa. This widens the space and reduces the risk of bleeding during manipulation. Oxymetazoline (e.g.,
Afrin, Gensol) is the most effective and long acting agent. Why prepare the nose in all cases? 1) During preparation
of the nose much of the effect occurs in areas of the oropharynx by both cross innervation, and passive leak of local
anesthetic. Nasal preparation can be started before desiccation has been effective. 2) In the case where an oral
intubation is difficult, the nose is prepared for manipulation – too many times I have seen the plan changed from oral
to nasal intubation, and the nose is not prepared. This leads to an ill-fated “rush job.” This is often started in the
intake area.
Topicalization: Except for cases of retrograde intubation, where a cricothyroid puncture is part of the procedure,
I have not used invasive airway blocks for more than 8 years. Though I have no objection to “needle” blocks, I have
not found them necessary. Additionally I use the same topical anesthetic technique in all cases: I don’t discriminate
based on my intent to intubate by a nasal or oral route, or depending on which instrument I plan to use. There are
also topical blocks that I do not employ. Again, its not because I object to them – I just use the techniques which
work best in my routine. I divide the airway into three areas, and use directed blocks for each: Nasal
passage/nasopharynx, base of tongue/posterior oropharyngeal wall, hypopharynx/larynx-trachea. Note, that should
the patient begin coughing during the topical administration, he or she should be assured that the “local anesthetic is
getting to the right place.” I also do not use atomized local anesthetic: Atomization produces significantly higher
blood concentrations of local anesthetic and completely abolishes the cough reflex, which may be useful in case of
deep lung gastric content aspiration.
Nasal passage/nasopharynx: This area is innervated by the anterior ethmoid nerve (anterior 1/3) and nasopalantine
nerve. I take cotton swabs soaking with local anesthetic (4% lidocaine solution or 5% lidocaine ointment) and
advance them slowly into the nasal passage, first up towards the cribiform plate, and then directly posterior until the
boney feel of the sphenoid bone is encountered. Progress is incremental, and I “push to pain” that is, I advance the
swab only until the patient winces or otherwise exhibits discomfort. This may take up to 5 minutes to accomplish. I
will often start this procedure in the nursing intake area. It is complete by the time the patient reaches the holding
area.
Base of tongue/posterior oropharyngeal wall: These are the only two areas in the mouth and pharynx that concern
me. I don’t concern myself with the oral cavity – my dentist regularly performs an aggressive oral exam which I
readily accept unless he accidentally stimulates my gag reflex. The glossopharyngeal nerve is responsible for the
gag. We can access the glossopharyngeal where it travels in the base of the palatoglossal arch – that arch of tissue
which travels from the uvula to the base of the tongue. A new set of lidocaine soaked swabs are inserted along the
tongue until they contact anterior surface of the base of the arch. Some patients will respond to this with a retch.
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This is a good indicator that you are in the correct position. A slight backing off will resolve the gag. A few
moments later the swab can generally be readvanced. The patient can close their mouth on the swabs and hold them
in position for 5 minutes. This, and the following technique are generally accomplished in the holding area.
Hypopharynx/larynx-trachea: Many years ago at an ASA annual meeting I learned an old pulmonologist trick from a
young anesthesiologist: a 10 cc syringe fitted with a large plastic angiocatheter is filled with lidocaine (2%). The
patient extends the tongue maximally, and the anesthesiologist takes an unfolded gauze, wraps the tip of the tongue
and does not allow the patient to retract. After the patient is assured that there is no needle, the catheter is inserted
over the tongue until the distal tip is at the oral-pharyngeal juncture. Slowly lidocaine is “dripped” on to the tongue
base. The procedure may take up to 1-2 minutes, and all 10 cc of lidocaine need not be used: At first the patient will
cough. Once the coughing subsides, yet you can hear the gurgling of the lidocaine deep in the airway, you can let go
of the tongue. Holding the tongue in this manner prevents the patient from swallowing the lidocaine, and encourages
its aspiration. SEE VIDEO 1
If a flexible fiberoptic scope is used for the tracheal intubation, local anesthetic can be injected down the “working
channel.” I prefer a technique described by Dr. A. Ovassapian in the early 1990’s: an epidural catheter is placed via
the working port. Local anesthetic is then administered via the catheter (be sure to cut off a multi-orifice end). This
has several advantages: the image is not obscured by the liquid, the stream can be aimed to an area of need, suction
or oxygen can be administered at the same time. SEE VIDEO 2
The “hardest” airways: I am often called by colleagues to advise on the care of patients who have undergone
extensive upper airway surgery and/or radiation. In these patients, invasive blocks may be difficult or impossible
(altered anatomy). Though these can be “frightening” airways to manage, they are, paradoxically, often the easiest!
1) The patients are usually aware of anesthetist’s problem, and are motivated and willing to cooperate 2) There is
reduced saliva production vis-a-vis prior radiation and surgical manipulation 3) there is often post-surgical
analgesia.
Sedation: Any number of sedative agents can be used: bezodiazpines, opiods, droperidol, haldo, benedryl. There
are three general rules I follow: 1) judicious titration – do not give significant boluses of the drugs. 2) Avoid
polypharmacy – stay with one or two agents. 3) Have reversal agents available. Lastly, don’t confuse deep sedation
with awake intubation. During AI the patient should be able to 1) cooperate with procedures and 2) control their
own airway (including coughing). As of October, 2008, Dexmedetomideine is FDA approved for sedation in the
unintubated for or prior to a surgical procedure. Several authors have demonstrated good cooperative patient
conditions with use of this agent during aware intubation.1
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Procrastination: AI is undertaken when the clinician has decided that it is necessary for the wellbeing of the
patient. As such, the above procedures should be executed in a controlled pace and composed environment.
“Procrastination” is a tongue-in-cheek way of saying, do not hurry to get into the operating room.” The OR is a
highly pressured environment, and it is difficult to allow generous time for antisialogoges and topical anesthetics to
reach their therapeutic effect. Of course, the demands of modern medicine hardly allow such luxury – but we can
achieve this goal through starting our procedures early: Oxemetazoline is applied and glycopyrolate is injected in the
intake area (IM if an IV is not yet available). Topical anesthetics are begun in the holding area and continued with
the patient’s stretcher outside the operating room. The patient does not enter the OR until there is some objective
evidence that a block is being achieved (e.g., the patient tolerates an oral airway.)
1. Abdelmalak B, et al. Dexmedetomidine as sole sedative for awake intubation in management of the critical
airway. J Clin Anesth 2007; 19:370–373
DISCLOSURE
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Awareness and Memory during Anesthesia

Peter S. Sebel, MB,Ph.D.,MBA Atlanta, Georgia
Introduction
The state of general anesthesia implies a lack of consciousness, or awareness. Awareness can occur with or without
conscious recollection of the event. Take, for example, patients who are intubated yet open their eyes to command
at the end of surgery. In terms of responding to command, they are aware. Yet, frequently, they will not remember
having commands in the operating room, nor will they remember extubation. Thus, they are aware without recall.
The challenge for anesthesiologists is to eliminate recall of unpleasant experiences during surgery.
Incidence
The largest prospective study in the United States found an incidence of awareness of 0.13% in nearly 20,000
patients1. These data are in accordance with prospective data from Sweden that found an incidence of awareness of
0.18% in cases where neuromuscular blocking agents were used and 0.1% in the absence of such drugs2.
Since patients will not often spontaneously report the occurrence of awareness with recall, the following set of
questions has been used3 as an instrument to assess the occurrence of awareness in most recent prospective studies:
 What is the last thing you remembered before you went to sleep?
 What is the first thing you remembered when you woke up?
 Can you remember anything between these two periods?
 Did you dream during your operation?
 What was the worst thing about your operation?
Recently, a paper was published suggesting that the incidence of awareness during anesthesia was 0.0068% or 1 per
14,560 patients4. These data were obtained from a retrospective analysis of over 200,000 patients from a continuous
quality improvement database and did not use the questions described above. There is, thus, reason to believe that
this represents an underestimate of the incidence of awareness during anesthesia.
There are limited data on the frequency of adverse events after awareness during anesthesia. Some patients have
fleeting recall and no adverse outcome. In contrast, some patients have pain, anxiety or post-traumatic stress
disorder (PTSD). In Sandin’s study2, when non-paralyzed patients recalled intraoperative events, none of them had
anxiety during the wakefulness or had delayed psychiatric symptoms. In contrast, when neuromuscular blocking
agents were used, 78% of the aware patients had pain, anxiety or PTSD. The psychiatric consequences of an
awareness episode may last for several years5.
Awareness Classification Instrument

One issue in comparing studies on the incidence of awareness is related to variability in reporting cases of
awareness. Mashour and colleagues6 recently proposed the following awareness classification:
Class 0: No Awareness
Class 1: Isolated auditory perception
Class 2: Tactile perceptions (e.g., surgical manipulation or endo tracheal tube)
Class 3: Pain
Class 4: Paralysis (e.g., feeling one cannot move, speak, breathe)
Class 5: Paralysis and pain
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Additionally the designation “D” can be sued to denote patient reports of fear, anxiety, suffocation sense of doom,
impending death etc.
Legal Implications
Cases of awareness represent between 1.9% (ASA Closed Claims Analysis)7 to 12.2% (British data)8 of claims
against anesthesiologists. In the United States, the median payment for such cases is $18,0007, although recently,
there have been several cases in which much larger claims have been settled. The ASA Closed Claims Database7
suggests that the majority of awareness claims occur in women younger than 60 years of age ASA physical class I-II
undergoing elective surgery. It is noteworthy that what are generally considered to be the classic cues for light
anesthesia were absent in most cases: hypertension occurring in 15% of recall cases and tachycardia occurring in
7%.
It is clear that awareness during anesthesia can occur when an apparently adequate anesthetic has been administered.
In order to sustain a case for malpractice against anesthesia personnel, it is necessary to demonstrate that the
anesthetic given deviated from the normal standard of care and that the adverse consequences were a result of that
deviation.
What is it like to be aware?

Patients frequently describe hearing the sounds of the operating room; they describe sensations of paralysis and pain
and felt anxiety and panic, helplessness and powerlessness9. Sixty nine percent of patients had unpleasant sequelae
from this event in terms of PTSD. The anesthetic records from these patients were reviewed in a double-blind
manner using case-matched controls. The authors were unable to reliably distinguish cases of awareness on the
basis of anesthesia records. So, again, the classic cues of light anesthesia were absent in these cases. In this study,
only 35% of patients informed their anesthesiologists about what had happened.
Treatment of the Aware Patient

A substantial number of patients who are aware during general anesthesia develop post traumatic stress disorder
(PTSD). Such a syndrome may develop after a frightening or unpleasant life experience. Characteristic symptoms
include anxiety, irritability, insomnia, repetitive nightmares, depression and a preoccupation with death. There may
be a fear of doctors, hospitals and, particularly, future operations. The patients can relive the unpleasant experience
in their dreams and the symptoms can be severe with a prolonged course.
If an anesthesiologist suspects that a patient may have had awareness (with or without PTSD), it is appropriate to
treat the patient sympathetically and arrange for appropriate follow up with a psychiatrist skilled in the treatment of
PTSD. Many patients become angry and litigious if the physician denies the occurrence of an awareness episode or
belittles the patient.
Can we monitor for awareness during anesthesia?

It is impossible to study, in an ethical manner, the circumstances under which awareness occurs during surgical
stimulation. Most studies on the occurrence of awareness during anesthesia have, therefore, concentrated on the
period prior to skin incision. In order to determine whether a monitor is an effective indicator of awareness, it is
necessary to have some gold standard by which awareness can be measured. The isolated forearm technique (IFT)
comes closest to providing such a standard10. The IFT involves placing a tourniquet to above systolic pressure on
the dominant arm prior to the administration of neuromuscular blocking agents. Then, motor function in the
dominant arm is maintained and the patient can (if aware) respond by moving a finger or squeezing the
investigator’s finger to command. It is generally considered that, if patients can squeeze fingers in response to
command, they are aware. Middle latency auditory evoked potentials have been evaluated as an index of awareness
using the IFT11. However, other workers have suggested that wide inter-patient variability will limit the practical
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usefulness of this technique for assessing intraoperative awareness12. EEG Bispectrum (BIS) has also been assessed
for its relationship to awareness using the IFT. Following induction, patients were allowed to recover consciousness
following a single dose of thiopental or propofol13. Consciousness did not occur in any patient with a BIS value of
less than 58. A BIS value of less than 65 signified a less than 5% probability of return of consciousness within 50
seconds. It should be emphasized that these studies were conducted in the absence of surgical stimulation and we
cannot be certain that these same values will hold true during periods of stimulation.
There are various neuromonitoring devices available on the market for assessing depth of anesthesia. Bispectral
index is the only one of these devices for which substantial data exists about awareness during anesthesia. It has
been suggested that explicit intraoperative recall can occur at a Bispectral index of 4714. However, subsequent
correction of this case report suggested that the BIS was above 70 at the time of explicit awareness15. To date, there
is no convincing evidence that awareness during anesthesia occurs with a Bispectral index of less than 60.
However, there are no large scale prospectively randomized studies to support this. Power analysis suggests that, if
the incidence of awareness is approximately 1 in 1,000 and neuromonitoring reduces the incidence of awareness by
50%, then approximately 41,000 patients would be required in a prospective randomized study to prove this16. In
the absence of such a large-scale prospective randomized study, there is evidence that BIS may be useful in reducing
the incidence of awareness. Ekman and colleagues17 demonstrated a 77% reduction in the incidence of awareness
when BIS-guided anesthesia was used (compared with a historical cohort). A prospective randomized blinded trial
was conducted in 2,500 high-risk patients (where the incidence of awareness was expected to be 1%) and BIS-
guided anesthesia was found to be associated with an 82% reduction in the incidence of awareness18. These results
were confirmed in a recent study which found, in a high risk BIS monitored group, an awareness incidence of 0.2%
vs. an expected incidence of 1%19. They found that guiding anesthetic administration using end tidal gas
concentration produced a similar reduction in awareness19.
ASA Practice Advisory

The American Society of Anesthesiologists issued a practice advisory for intraoperative awareness and brain
function monitoring in October 200520. The advisory states, “Intraoperative monitoring of depth of anesthesia, for
the purpose of minimizing the occurrence of awareness, should rely on multiple modalities, including clinical
techniques (e.g., checking for clinical signs such as purposeful or reflex movement) and conventional monitoring
systems (e.g., electrocardiogram, blood pressure, HR, end-tidal anesthetic analyzer, capnography)…Brain function
monitoring is not routinely indicated for patients undergoing general anesthesia, either to reduce the frequency of
intraoperative awareness or to monitor depth of anesthesia…It is the consensus of the task force that the decision to
use a brain function monitor should be made on a case-by-case basis by the individual practitioner of selected
patients (e.g., light anesthesia)”.
Memory Function
So far, we have been discussing the occurrence of awareness with recall. This is a form of explicit or direct
memory, in that the patient can spontaneously and directly recall the events. There is another form of memory,
implicit memory, which may also function during anesthesia. Implicit memory is characterized by a change in task
performance where the original stimulus cannot be remembered directly. Examples of implicit memory occurring
during anesthesia include: reduced PCA usage when patients have heard tapes (during anesthesia) suggesting that
they will feel more comfortable after surgery; completing word stems with words that they have “been primed with”
during their anesthetic. The characteristic of implicit memory is that the patients cannot remember hearing the
tapes. The circumstances under which implicit memory occurs have been generally unclear21. However, recent data
suggest that the occurrence of implicit memory is directly related to the degree of hypnosis22,23. Indirect memory
does not appear to occur at BIS values between 40 and 6023 whereas at higher BIS values, implicit memory function
can be detected24 and at BIS values greater than 70, some weak evidence of explicit memory can be detected22.
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Prevention of Awareness
The following suggestions may be useful in preventing cases of awareness with recall.
 Inform patients, particularly in circumstances where anesthesia may be deliberately “light” (such as open-heart
surgery, trauma surgery, Cesarean section, etc.), about the potential risk of awareness.
 Avoid complete neuromuscular blockade: Unless necessitated by surgical requirements, always keep at least
one “twitch” in a train-of-four.
 Use adequate concentrations of inhalation or intravenous anesthetic at all times.
o Anesthetic agent monitoring
o Appropriate neuromonitoring
 Remember to re-dose the induction agent during difficult intubations.
 Reverse neuromuscular blockade before discontinuing nitrous oxide.
 Talk to the patients in circumstances where anesthetic delivery is reduced (e.g., acute hypovolemia): When
anesthetic delivery is suspended, speak to the patients and reassure them.
 Consider the use of amnestic agents (especially when anesthesia is “light”).
 Ear plugs: Reducing auditory input to the patient may decrease memory function.
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References
1. Sebel PS, Bowdle TA, Ghoneim MM, Rampil IJ, Padilla RE, Gan TJ, Domino KB: The incidence
of awareness during anesthesia: A multicenter United States study. Anesth Analg 2004; 99: 833-839
2. Sandin RH, Enlund G, Samuelsson P, Lennmarken C: Awareness during anaesthesia: a
prospective case study. Lancet 2000; 355: 707-711
3. Liu WH, Thorp TAS, Graham SG, Aitkenhead AR: Incidence of awareness with recall during
general anaesthesia. Anaesthesia 1991; 46: 435-7
4. Pollard RJ, Coyle JP, Gilbert RL, Bech JE: Intraoperative awareness in a regional medical system:
a review of 3 years' data. Anesthesiology 2007; 106: 269-274
5. Lennmarken C, Bildfors K, Enlund G, Samuelsson P, Sandin R: Victims of awareness. Acta
Anaesth Scand 2002; 46: 229-231
6. Mashour GA, Orser BA, Avidan MS: Intraoperative awareness from Neurobiology to Clinical
Practice. Anesthesiology 2011; 114:1218-1233
7. Domino KB, Posner KL, Caplan RA, Cheney FW: Awareness during anesthesia: A closed claims
analysis. Anesthesiology 1999; 90: 1053-1061
8. Aitkenhead AR: The pattern of litigation against anaesthetists. Br J Anaesth 1994; 73: 10-21
9. Moerman N, Bonke B, Oosting J: Awareness and recall during general anesthesia. Facts and
feelings. Anesthesiology 1993; 79: 454-64
10. Tunstall ME: Detecting wakefulness during general anaesthesia for caesarean section. Br Med J
1977; 1: 1321
11. Thornton C, Barrowcliffe MP, Konieczko KM, Ventham P, Doré CJ, Newton DEF, Jones JG: The
auditory evoked response as an indicator of awareness. Br J Anaesth 1989; 63: 113-115
12. Loveman E, van Hooff JC, Smith DC: The auditory evoked response as an awareness monitor
during anaesthesia. Br J Anaesth 2001; 86: 513-518
13. Flaishon R, Windsor A, Sigl J, Sebel PS: Recovery of consciousness after thiopental or propofol:
Bispectral index and the isolated forearm technique. Anesthesiology 1997; 86: 613-619
14. Mychaskiw GI, Horowitz M, Sachdev V, Heath BJ: Explicit intraoperative recall at a Bispectral
index of 47. Anesth Analg 2001; 92: 808-809
15. Mychaskiw GI, Horowitz M: False negative BIS? Maybe, maybe not! Anesth Analg 2001; 93:
798-799
16. O'Connor MF, Daves SM, Tung A, Cook RI, Thisted R, Apfelbaum J: BIS monitoring to prevent
awareness during general anesthesia. Anesthesiology 2001; 94: 520-522
17. Ekman A, Lindholm ML, Lennmarken C, Sandin R: Reduction in the incidence of awareness
using BIS monitoring. Acta Anaesthesiol Scand 2004; 48: 20-6
18. Myles PS, Leslie K, McNeil J, Forbes A, Chan MT: Bispectral index monitoring to prevent
awareness during anaesthesia: the B-Aware randomised controlled trial. Lancet 2004; 363: 1757-63
19. Avidan MS, Zhang L, Burnside BA, Finkel KJ, Searleman AC, Selvidge JA, Saager L, Turner
MS, Rao S, Bottros M, Hantler C, Jacobsohn E, Evers AS: Anesthesia Awareness and the Bispectral index. N Engl
J Med 2008; 358: 1097-1108
20. Practice advisory for intraoperative awareness and brain function monitoring: A report by the
American Society of Anesthesiologists task force on intraoperative awareness. Anesthesiology 2006; 104: 847-64
21. Ghoneim MM, Block RI: Learning and consciousness during general anesthesia. Anesthesiology
1992; 76: 279-305
22. Lubke GH, Kerssens C, Gershon RY, Sebel PS: Memory formation during general anesthesia for
emergency cesarean sections. Anesthesiology 2000; 92: 1029-34
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23. Kerssens C, Klein J, van der Woerd A, Bonke B: Auditory information processing during
adequate propofol anesthesia monitored by electroencephalogram bispectral index. Anesth Analg 2001; 92: 1210-
1214
24. Lubke GH, Kerssens C, Phaf RH, Sebel PS: Dependence of explicit and implicit memory on
hypnotic state in trauma patients. Anesthesiology 1999; 90: 670-680
DISCLOSURE
An-Alarm, Self, Stock Options
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Coagulation Issues Facing You and Your Patient
Charise Petrovitch, M.D. Washington, District of Columbia
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Hospital System Failures and Hazard Management in the Operating Room
P. Allan Klock, Jr, M.D. Chicago, Illinois
Although we gain experience in our daily practice with hazardous situations such as caring for patients with difficult
airways or compromised cardiac function, it is difficult to become experienced with rarely occurring situations
such as electrical failures or floods in the operating room. Therefore, we need educational activities that show us
how hospital systems work and fail and how we should respond to that failure.
A crisis response template is applied to failures of electrical, oxygen pipeline, and heating, ventilation, and air
conditioning (HVAC) systems and also to hospital floods. A generic crisis response template is presented that can be
applied to a wide range of situations. Anecdotal examples of hospital system failures are given to illustrate the
application of the crisis response template.
The role of the anesthesiologist often involves patient care and managerial or administrative duties. Our function in
both of these roles is integrated into the crisis response template. Improving our understanding of how systems work
and fail should allow us to create a good outcome from a hazardous situation.
GENERIC HAZARDS
Localize Risk
When a hazardous situation arises in a hospital, risks must be localized so resources can be allocated to those areas
most likely to benefit from additional help. This risk localization can be divided into four areas: procedure,
personnel, location, and equipment.
Procedural Risks. A patient on cardiopulmonary bypass or undergoing an endarterectomy with a clamp on the
common carotid artery may be more susceptible to injury from a power failure than a patient undergoing a more
simple procedure, such as a cystoscopy under spinal anesthesia. In the latter case, the surgeon could easily remove
the cystoscope and transport the patient to a safer location.
Personnel Risks. Some staff may be more or less able to perform well under adverse conditions. Resources may
need to be allocated to assist less experienced personnel or those with special needs.
Location Risks. The anesthesiologist delivering anesthesia in the obstetrical suite or remote locations will not have
the support of other operating room personnel when hospital systems fail or hazardous conditions arise. In addition,
they may be isolated if there is a concurrent communications system failure.
Equipment Risks. Certain equipment, especially very new or old equipment, may fail in unexpected ways. For
example, a newly manufactured intensive care unit ventilator ceased to function and was unable to reboot itself after
a transient (less than 1 second) interruption in the power supply to the ventilator was caused by a routine test of a
hospital's backup generator. This ventilator failed without an alarm. An intensive care unit nurse was in the patient's
room at the time and immediately began manual ventilation, protecting the patient from a hypoxic injury.
Preventive Maintenance and Improvements A re Needed but Pose Their Own Risks
Hospital systems require on the fly maintenance and improvements, for which patient care cannot be interrupted.
As the infrastructure of many hospitals continues to age, construction and maintenance have become more visible
and potentially problematic.
An example of such a problem occurs when a construction worker accidentally shuts an oxygen supply valve to an
area supporting patients. Testing a backup generator at another hospital caused a relay within part of the hospital to
become stuck, resulting in a 20 minute interruption of electricity to the critical service outlets in the operating suite.
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Hospital Systems A re Complex

Hospitals are complex structures with convoluted and interrelated systems. At many hospitals, construction workers
install new communication cables in the plenum (the space between the ceiling tiles and the structure of the floor
above) over corridors. Adding to the complexity of the system is the fact that old cable is rarely, if ever, removed
when new cable is put in place. This makes troubleshooting difficult when problems arise. In addition, several
systems have elements in the walls or plenum in the operating room suite. When one system fails, causing a water
leak, for example, it may affect other systems that have components nearby.
CRISIS RESPONSE TEMPLATE

The following template may serve as a guide to direct the thoughts and actions of anesthesiologists and other
operating room staff during an operating room crisis. The template has five elements: (1) coping with local
consequences, (2) establishing the scope of the problem, (3) protecting against side effects of the problem, (4)
addressing administrative issues, and (5) preparing for problem resolution or prolonged failure. The template may be
applied to a wide variety of system failures and crises. The elements gain different levels of importance depending
on the specific circumstances.
Cope with the Local Consequences of the Problem
The goal of coping with local consequences is to counteract the immediate effects of the system failure. For
example, if electricity fails in an operating room, a flashlight or laryngoscope should be used for illumination; if the
ventilator fails, manual ventflation should begin immediately. Anesthesiologists are usually proficient at protecting
their patients from immediate injury. For a detailed description of coping with the local consequences of hospital
system or equipment failure, readers should refer to Crisis Management in Anesthesiologv.1
Establish the Scope of the Problem
After the patient has been protected from imminent peril, the scope of the problem should be established. It is
important to determine what backup systems are available and in operation. How many operating rooms are affected
by the problem and what types of resources are at hand must be determined.
Certainly, if only one operating room has lost its pipeline supply of compressed oxygen, surgery can be continued
there ad infinitum, by repeatedly exchanging oxygen E cylinders at the back of the anesthesia machine. However, if
the entire hospital has no piped oxygen, all the E cylinders will be consumed quickly and all but the most urgent
procedures should be finished as quickly as possible.
Protect Against Side Effects of the Problem
The side effects of the problem must be obviated. These may be difficult to predict, delayed in time, distant in
location, or more serious than the primary problem.
Side Effects May Be Difficult to Predict. For example, if medical vacuum (suction) were to fail, it might not be
obvious that control of the hospital's HVAC system may be affected. In many hospitals, a vacuum control system
communicates between the thermostat and the valve that regulates the flow of steam or hot water through a heat
exchanger for the operating room. Normally, this control system vacuum is completely separate from the medical
vacuum system. However, if the medical vacuum fails, the hospital engineers may link the vacuum lines for the
HVAC control system to the main vacuum line. This will improve the suction for the medical vacuum but possibly
weaken the hospital's HVAC system.
Side Effects May Be Delayed. A small amount of water on the floor of an operating room is not inherently
dangerous. However, the aftermath of even a small flood in the operating room may take weeks to resolve. Many
other systems may need to be interrupted to fix a water leak. In addition, it may be several weeks before a room can
be adequately decontaminated to prevent the growth of mold in the ceiling, walls, or ventilation system. Such mold
growth may pose a serious hazard to immunocompromised patients.
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Side Effects May Occur at a Distant Site. The University of Chicago Medical Center has its call center in Darien,
Illinois, 20 miles away from the hospital. A communication disruption between the hospital and the call center or a
power disruption in Darien would lead to a loss of the ability to page using beepers, overhead page in the hospital,
and to route calls through the hospital switchboard. In addition, the signals for pages for numeric beepers are
transmitted on subcarrier frequencies from local FM transmission towers. A problem with these transmission
systems, which are remote from the hospital, could lead to total or partial failure of the beeper system that can be
dangerous and difficult to detect.
Some Side Effects May Be More Severe than the Primary Problem. Consider a problem with a hospital's fresh water
supply. Bottled sterile water can be used for a surgical scrub and to sterilize instniments. However, when the water
supply is reestablished, it may transiently contain bacterial and mineral impurities that may be more hazardous than
the lack of water itself.
Address Administrative issues (Get the Problem Fixed)
After the patient has been protected from immediate injury, the scope of the problem has been established, and side
effects have been obviated, administrative issues should be addressed and work should begin to get the problem
fixed. It is important to understand who can be helpful. Often, the plant department or hospital engineers should be
called first. Sometimes hospital security needs to be contacted to unlock doors or gain access to areas that require
service. Hospital administrators may need to be involved to allocate the resources required to get the problem fixed
in a timely manner.
Prepare for Prolonged Failure or Problem Resolution
Preparation should be made for prolonged failure or secondary problems that arise as the primary problem is
resolved. Sometimes conditions get worse before they get better. A small water leak in an operating room may lead
to interruption of the communication and electrical supply for an unexpectedly large area during the repair process.
A decision will need to be made regarding how to proceed with the operating room schedule if this occurs. Can
elective cases be delayed? Should only emergent cases be performed? Or should the emergency room be closed,
diverting trauma patients to other hospitals? The answer to these questions will depend on the scope of the problem
and the timing of its resolution.
Application of the Template to Specific Examples
Physicians team about anatomy, physiology, and pathophysiology before they learn about disease treatments and
prevention. This organization of learning also applies to hospital systems. We must understand how they work and
fail before we can learn to respond to and prevent system failures and potential injuries. The relevant "anatomy and
physiology" of hospital systems is presented here before the crisis response template is applied to examples of
electrical, oxygen pipeline, and HVAC failure and floods.
Electrical System Failure
Electrical System Design. Most large institutions, including many hospitals, are connected to the external power grid
in more than one location. This protects against a local failure of the power transmission wires where they are linked
to the hospital. In the event of a failure of the external grid, a backup battery in the hospital should provide power
within one half of a cycle (1/120 of a second). If this battery supply works properly, not even a flicker in the lights
will be noticed. This battery provides alternating current to critical service areas of the hospital. The outlets
supplied by the critical service circuits are red. The battery is also used to crank a starter for the diesel engine, which
will then drive the hospital's generator. This backup power generation will fail if any of its components, such as the
battery, starter, diesel engine, generator, relays, or transmission wires, fail. Problems have been reported with
obtaining an agreement for an adequate supply of diesel fuel for some hospitals.2 In addition, failure of power
transmission relays inside the hospital have resulted in interruption of power to critical service outlets.
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Many localized power failures are caused when a circuit breaker trips. If this occurs, the device most recently
plugged in should be unplugged and the circuit breaker reset. A few points are worth remembering about circuit
breakers in hospitals. First, it may be difficult to tell, by looking at an outlet, where the circuit breaker box is located
that supplies that outlet. It may be worthwhile to contact a hospital engineer for help if a overloaded circuit trips.
Second, many hospitals lock the door covering the circuit breaker panel. Hospital security or the plant department
should be contacted for access. Finally, if it is difficult to determine which circuit is tripped, it is not a good idea to
test every circuit, because service to other patient care areas will be interrupted.
A ctivation of the Line Isolation Monitor A larm. All operating rooms built before 1984 are equipped with an isolated
electrical power system and a line isolation monitor (LIM). Operating rooms built after that date may have isolaged
power or a ground fault circuit breaker interrupter. Under certain circumstances, the LIM may signal its alarm while
an anesthetic is being delivered. Although this does not constitute a hospital system failure, it is important for
anesthesiologists to understand what the LIM protects against, what causes the LIM to signal its alarm, and what
actions to take when that occurs.
The purpose of isolated power and the line isolation monitor. Many anesthesiologists falsely believe that the LIM is
designed to prevent microshock. On the contrary, an LIM may remain silent if conditions exist that would allow up
to 50 times the amount of current required to produce microshock. Isolated power systems and LIMs were
developed during the era of explosive anesthetics. They were installed to minimize the chance of faulty equipment
producing sparks that could cause an explosion.
An isolated transformer converts electricity from a "hot" lead and a grounded lead to a configuration in which
neither of the electrical lines that supply power is grounded. In a nonisolated system, current can pass from the hot
lead to the ground. This can result in a spark or forms of macroshock (e.g., an electrical burn or electrocution) if a
low impedance pathway is produced between the hot wire and the ground. Under normal conditions, an isolated
power system will not allow significant amounts of current to pass from either wire of the circuit to the ground, thus
preventing sparks and macroshock. The LIM measures the ability of the isolated circuit to prevent current flow from
the circuit to the ground. If the isolated circuit becomes degraded (see Response to Line Isolation Monitor Alarm),
then the monitor will signal its alarm.
Most early LIM alarms were set to signal when only 1.7 to 2.0 (mA) would be able to flow between the circuit and
ground. Because many operating rooms were plagued with "nuisance alarms," the total hazard current limit was
increased from 2 to 5 mA in 1978.
The line isolation monitor does not protect against microshock. If a patient has an implanted device that allows
electricity to pass directly into the heart, a high current flux (amps per square centimeter) can occur in the
myocardium. Examples of such devices include temporary pacing wires and electrolyte fluid filled catheters placed
into the heart (such as pulmonary artery or central venous catheters). Microshock results when small amounts of
current pass through these devices, causing ventricular fibrillation. There is no consensus about the minimum
amount of current required to produce ventricular fibrillation, but values of 100 to 200 microamps are usually cited.
Regardless, microshock can occur at a fraction of the current required to make an LIM alarm signal.
The modern advantage of isolated power. Given that flammable anesthetics are no longer used, the one remaining
advantage of an isolated power system is branch circuit protection. If a device with a low impedance connection
between the lead and the ground (a ground fault) is plugged into an isolated circuit, the LIM will produce audible
and visible signals but the circuit will continue to operate as a nonisolated system with one power line grounded,
similar to a circuit outside the operating room. If the operating room did not have an isolated power system,
plugging in the same device might trip the ground-fault circuit breaker interrupter (GFCI), eliminating power to one
or more operating rooms. Thus, an isolated power system with an LIM will alert the staff that there is a problem but
will allow the system to continue operating in a degraded mode, rather than produce an abrupt and complete circuit
failure.
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Recommended response to a line isolation monitor alarm. The LIM alarm will signal when the total possible
leakage current is greater than the threshold value for the monitor; that is, either 2 or 5 mA. This can arise by one of
two circumstances. A faulty device may be plugged in that has a low impedance pathway between the internal
circuitry and the ground (the "faulty device"). Alternatively, several properly functioning devices may each allow a
small amount of leakage current, such that the sum of the leakage current for all the devices on the circuit is greater
than the allowable current limit.
When the LIM alarm signals, the most recently plugged in or turned on device should be removed from the
circuit. If the LIM alarm stops, then the offending device should be impounded, labeled "defective, check for ground
fault," and evaluated by biomedical engineers before it is allowed to be used again. This serves to remove the faulty
device from operation.
If the LIM alarm continues after the most recently plugged in device has been removed, then small amounts of
leakage current from many devices may be causing the problem and additional equipment should be unplugged until
the alarm ceases. An intermittent alarm can be caused by a device that is turning on and off internally, such as the
heating element of a fluid or blanket warmer. If no single offending device can be identified, then the equipment that
has been unplugged can be plugged into a different circuit in the same operating suite. Hospital engineers may need
to be contacted to determine which circuits supply which outlets. It is common for an operating room to have outlets
supplied by several different circuits and more than one isolated power supply.
Application of the Response Template to Electrical Failure.
Cope with local consequences of the problem. If a patient's ventilator fails, manual ventilation should be started
immediately. Obviously, the function of any other life sustaining equipment (e.g., cardiopulmonary bypass machine)
should be checked as soon as possible. The cardiopulmonary bypass machine can be hand cranked to maintain
blood flow. Every anesthesiologist should be familiar with the hand cranking equipment location and procedure.
Many critical devices have internal batteries that should sustain function for at least a few hours.
Simple monitors may be used at this time. The following may be used to monitor a patient in the setting of an
electrical failure: palpating a pulse, checking the patient's color if there is adequate lighting, auscultation with a
precordial stethoscope, and using a manual blood pressure cuff and sphygmomanometer. A battery powered
transport monitor may prove valuable, especially if monitoring the electrocardiograph or an invasive pressure is
critical.
Devices that use a cathode ray tube for display require high currents and usually do not have internal battery backup
systems. Many pulse oximeters and transport monitors use light emitting diodes or liquid crystal displays that
require little current. These devices often have internal batteries that will allow them to function in the event of an
electrical failure.
If the operating room is dark, a decision must be made regarding who holds the flashlight: Should the
anesthesiologist keep it? Should it be given to the surgeon so that surgery can continue? Or should it be given to a
nurse to leave the room to find more flashlights or get help? Pagers have backlighting that provide a small amount
of light. Many smartphones have a screen that is bright enough to provide decent illumination and some phones
have an LED camera flash that can be continuously illuminated to provide a bright light.
Establish the scope of the problem. If only one circuit or one room is without power, the cause must be determined.
Is it possible that a faulty device was plugged in, causing a circuit breaker to trip? If more than one circuit has been
affected, then it is important to establish the scope of the problem. The response to the power failure will be
different if only one operating room or circuit is affected compared with the entire operating room suite or the whole
hospital or city. After investigating the extent of the power failure, it is important to inquire about the expected
duration of the power failure. This may be difficult to determine; however, if the cause can be identified, then it will
be easier to estimate the duration of the failure.
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Protect against side effects of the problem. The immediate effects of an electrical failure are obvious. But other
systems that may be affected by the power failure must be considered. Surgery will become more hazardous as a
result of poor lighting and lack of electrocautery. The heating and ventilation systems may fail. Fluid warmers,
heating lamps, and forced hot air warmers will not work, putting patients at risk for hypothermia. Residual heat may
remain in a blanket or bottle warmer for a long time. This heat may be used to carefully warm fluids, but
overheating the fluids must be avoided. Room temperature blankets and low flow anesthesia may help prevent
hypothermia during a power failure.
Whether the event that caused the electrical failure has caused other systems to fail must be considered. For
example, a fire or explosion in another part of the hospital may lead to failure of the pipeline oxygen supply in
addition to electrical power. The proper functioning of all systems must be confirmed.
Other systems may be affected by the electrical failure. Will patient transportation to and from the intensive care
unit be possible without elevators? Will the central server for your electronic medical record systems continue to
work; will there be enough comuter workstations powered by critical service outlets powered by your hospital’s
generator? Do the pharmacy or nursing stations rely on automated drug dispensing systems (e.g., Pyxis; Pyxis
Corp., San Diego, CA). Will the blood bank be able to cross match and dispense blood products without
electricity?
A ddress administrative issues (Get the problem fixed). The hospital plant department and hospital engineers can be
helpful when internal electrical failures occur. They can tell what backup systems are in place and how long they
can be expected to last. Although it is appropriate to call the plant department first, the engineers may not be able to
fix all internal problems. For example, the University of Chicago Medical Center uses six independent electrical
contractors for its electrical work. It may take a long time before internal electrical problems are properly identified
and repaired. Hospital security may need to be contacted to gain access to areas restricted by identification badge
swipe controls. Finally, hospital administrators may need to become involved to authorize the rental of a large
portable generator or to hire contractors to perform their work in a timely manner.
Prepare for prolonged failure or problem resolution. Preparations must be made for problem resolution or prolonged
failure. It is important to determine how many rooms are affected and how long they will be without power. A
decision must be made regarding the performance of surgical cases. This will largely depend on the scope and
expected duration of the problem. Under the most extreme circumstances, the hospital's emergency room should be
closed and arrangements made for patient transfer. If the backup generator is working properly and only a brief
interruption of the external power supply is expected, then it may make sense to continue with the elective surgical
schedule.
Prevention. Prevention is critical in averting patient injury during a power failure. Every operating room or
anesthetizing location should have a flashlight. Many anesthesiologists may say, "I don't need a flashlight, I have a
laryngoscope." An inexpensive hardware store flashlight will produce significantly more light than a high quality
laryngoscope.
Many critical devices should have their own emergency power source. Backup batteries need to be checked and
maintained routinely (e.g., yearly for anesthesia machine internal batteries). Some batteries may indicate that they
are fully charged even though their capacity to hold a charge is greatly diminished (i.e., the voltage across the
terminals is maintained while the number of joules stored decreases). Thus, batteries in critical devices should
undergo periodic charge-discharge testing and/or replacement according to the manufacturer's recommendations.
Oxygen Failure
Oxygen System Design. A survey of 200 hospitals in 1976 revealed that 31 % of the hospitals reported problems
with their oxygen pipeline supply.3 Although many anesthesiologists may believe they will never experience an
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oxygen pipeline failure, the resulting patient injury can be so severe and rapid that it is important to know what
backup systems are available and how to respond to a system failure.
Oxygen can be supplied to the hospital oxygen pipeline in two ways. The primary method is from a liquid oxygen
tank, which is located outside the building. The second method is through an oxygen tank farm inside the building.
Liquid oxygen flows from the external tanks to evaporator coils, where it is transformed from the liquid phase to the
gas phase and then enters the hospital.
The liquid oxygen supply can be disrupted because the external tanks simply run dry. One hospital had this happen
when the truck dispatcher sent the liquid oxygen truck to the wrong address on three separate occasions. At another
hospital, the delivery truck backed into the liquid oxygen tank, causing the pipes to become disconnected from the
hospital. Liquid nitrogen has been accidentally placed in a liquid oxygen tank leading to episodes of hypoxic injury.4
To protect against these problems with the external liquid oxygen supply, a backup tank farm is located within the
hospital. The tank farm is a collection of H cylinders attached to a manifold. If the pressure in the pipeline decreases
below a specific level, gas will flow from the H cylinder manifold into the oxygen line. The University of Chicago
has 30 H cylinders in its tank farm, which offer approximately a 6 hour supply under conditions of normal use.
Each H cylinder contains 6,900 l oxygen when full. Obviously, if the tank farm starts to be used, this must be
recognized and efforts made to minimize oxygen demand until the problem is corrected.
Application of the Response Template to Oxygen Pipeline Failure.
Cope with local consequences of the problem. The first action to take when the oxygen pipeline fails is to switch to
an E cylinder immediately. If the wrong gas is thought to be delivered through the oxygen pipes, then the oxygen
pipeline must be disconnected from the anesthesia machine or gas will preferentially flow from the pipeline rather
than the E cylinder, because of the pressure setting of the pressure reducing valve in the cylinder yoke. To conserve
oxygen, fresh gas flows should be minimized and manual ventilation used rather than mechanical ventilation if the
machine uses compressed gas to drive the ventilator.
It is important to remember that in many anesthesia machines compressed oxygen drives the bellows for the
anesthesia machine ventilator. If a 3 1 fresh gas flow is used and the patient has a 7 liter per minute (lpm)
ventilation, a full E cylinder will be depleted in 62 minutes (625 l @ 10 lpm = 62.5 minutes). If the same patient
receives a 3 l fresh gas flow with manual ventilation, a full E cylinder will last for 3 hours and 28 minutes (625 l @
3 lpm = 208 minutes). If the patient is manually ventilated with a 0.5 l fresh gas flow, a full E cylinder will last for
more than 20 hours (625 1 @ 0.5 lpm = 1,250 minutes = 20 hours, 50 minutes).
Establish the scope of the problem. The physical plant and hospital administrators should be contacted to determine
the cause of the failure: Is there a problem with the liquid oxygen supply outside the building? Has the supply run
out? When will a truck arrive to refill the tank? Perhaps a construction worker adjacent to the operating room
needed to close the oxygen supply in his area and accidentally shut off the supply to the operating room as well. It is
important to establish the scope of the problem, because the backup resources (E cylinders) will become depleted
more rapidly with a hospital wide supply interruption than with a localized problem.
Protect against side effects of the problem. There are few side effects of oxygen failure as the direct hazard is
potentially lethal enough. It should be remembered that compressed oxygen may drive the anesthesia ventilator. In
planning the conclusion of the anesthetic, it is desirable to have a patient breathing spontaneously. Intensive care
unit ventilators consume oxygen at rates several times the patient's minute ventilation. If the patient can be
extubated, or receive oxygen via a T piece attached to the endotracheal tube, the hospital oxygen supply can be
greatly conserved.
A ddress administrative issues (Get the problem fixed). The plant department should be contacted to determine if
any valves have been closed accidentally, causing the supply interruption. They also may be able to attach new, full
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H cylinders in the oxygen tank farm to increase its capacity. Hospital administrators should be contacted to arrange
for an emergency fill of the liquid oxygen tank if it is empty, or to arrange for the emergency delivery of E and H
oxygen cylinders.
Prepare for prolonged failure or problem resolution. A few special considerations are required after work has been
performed on the oxygen pipeline or an inappropriate gas has been inadvertently flowing into the oxygen pipeline
system. The pipes will need to be purged until 100% oxygen is delivered and measured at each wall outlet.
Prevention. Proper daily performance of the anesthesia machine check will protect against many of the perils that
threaten patient oxygen delivery. In addition, it is wise to have at least one full E cylinder attached to the anesthesia
machine and a second E cylinder with a regulator and a manual resuscitation bag available in each anesthetizing
location.
Heating, Ventilation, and Air Conditioning (HVAC) Failure
Heating, Ventilation, and Air Conditioning System Design. The air that is circulated in most hospitals varies from
30% to 70% recycled air, with the balance being fresh air from outside air intakes. This air mixture is triple filtered
before it is passed over chillers. The chillers are heat exchangers that contain cold water and cool the air to 55° F.
This cold air is blown through the hospital ductwork and passes over a radiator immediately before it enters the area
where it is needed. The radiators are heated by steam or hot water and linked to the thermostat on the wall by the
special "control system" vacuum line. As the setting of the thermostat is adjusted, the amount of vacuum in the
control line is altered, changing the opening of the steam valve. This causes the hissing that can be heard when some
thermostat dials are adjusted.
To have proper HVAC, several elements are necessary: clean fresh and recycled air, fresh water for the chillers,
steam, electricity for the blowers, proper ductwork and plumbing, and a control system vacuum. Any of these
elements may fail, which win produce different failure modes and require appropriate application of the crisis
response template.
Application of the Crisis Response Template to Heating, Ventilation, and Air Conditioning
System Failure
Cope with local consequences of the problem. Failure of the HVAC system usually is not immediately
life threatening. However, it is possible for carbon monoxide poisoning to result from trucks idling near the
hospital's fresh air intake. For this reason, No Idling signs are usually posted by fresh air intakes, and hospital
security should be notified if exhaust fumes are noticed inside the hospital.
Most failures of the HVAC system will challenge patient temperature homeostasis. A forced air blanket (e.g., Bair
Hugger; Augustine Medical, Eden Prairie, MN) blowing warm or ambient air may help to protect patients against
very cold or hot operating room conditions, respectively. In addition, heating lamps, warming blankets, and fluid
warmers should be used if the operating room is unusually cold.
Establish the scope of the problem. Hospital engineers should be informed when a problem with the HVAC system
is possible. It will be helpful to understand the cause of the problem to help guard against side effects of the
problem. Obtaining an estimate of the problem duration will be helpful when plans are made for the rest of the
operating room schedule.
Protect against side effects of the problem. The side effects from HVAC failure will be patient hypo or
hyperthermia and pollution of the operating room environment. If there is no air circulation in the operating room,
escape of anesthetic gasses into the atmosphere should be minimized (e.g., minimize cuff leak). To limit the amount
of smoke in the operating room, surgeons may wish to decease the amount of electrocautery used. If cautery is used,
suction should be applied to evacuate the resulting smoke. Often an element of the HVAC system fails as a result of
another system failure (e.g., lack of steam, water, electricity). After determining the cause of the HVAC failure,
preparations must be made for side effects from the primary system failure.
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Address administrative issues (Get the problem fixed). Often, when the call is made to establish the scope of the
problem, the necessary parties will begin fixing the problem.
Prepare for prolonged failure or problem resolution. Knowledge of the expected duration of the failure will dictate
what measures should be taken to maintain patient temperature homeostasis and reasonable quality of breathing air.
Floods
Hospital W ater Handling Systems. In addition to regular hot and cold running water, hospitals have cooled water
running to and from the chillers and steam or hot water running to and from radiators for the HVAC systems.
Plumbing also includes drainage and sewer lines. Finally, many hospitals have sprinkler systems and dry standpipes
that can be used by firefighters in the event of a fire.
Application of the Crisis Response Template to Floods.
Cope with local consequences of the problem. If a patient is located in a room where water is leaking through the
ceiling, the patient should be relocated as soon as it is safe to do so. If water starts to leak through the ceiling, a large
barrel or garbage can should be brought into the room to catch the overflow when the ceiling tile is pierced or
removed. This will allow the water to drain into a contained space, preventing it from tracking above the ceiling tiles
or over the floor.
Establish the scope of the problem. Water can leak into an operating room from a number of sources. Possible
causes of water entering a basement or a subbasement room include groundwater entry resulting from a sump pump
failure, or sewage backing up because of a clogged pipe or problems with the municipal system. If water is leaking
from the ceiling, possibilities range from something as simple as an overflowing sink on the floor above to a
problem with a pressurized water line, steam pipe, or waste water.
Protect against side effects of the problem. Other critical systems near the leak may be affected. In particular,
electrical and communication lines may fail or need to be interrupted temporarily in the process of repairing the
leak.
A ddress administrative issues (Get the problem fixed). Simply cleaning up the water is not enough. Hospital
engineers and possibly plumbing contractors need to be involved to fix the problem. Hospital security may need to
be contacted to gain access to the rooms above the leak. A spergillus and other molds may grow in the ceiling tiles,
wallboard, and ductwork of an area that has been flooded and not properly decontaminated. If immunocompromised
patients are exposed to spores from these molds, they may experience life-threatening infections. Infection control
personnel should oversee the decontamination and disinfection of the area. Although surgeons may be unhappy
about having an operating room unavailable for a prolonged period of time, they will take the threat of a wound
infection seriously.
Prepare for prolonged failure or problem resolution. Other services may need to be interrupted temporarily during
the repair process. Several weeks may be needed before the hospital infection control officers can certify that an
operating room is fit for use. Hospital administrators should be included in the discussion regarding how long the
surgical schedule will need to be altered.
Summary
Hospitals include complex interrelated systems that may fail in unexpected ways.
Application of the five elements of the crisis response template will help guide actions during system failures and
other hazardous circumstances. The patient should be protected from immediate injury, the scope of the problem
should be established, side effects of the problem should be identified and guarded against, administrative action
should be taken to fix the problem, and then preparations should begin for problem resolution or prolonged failure.
Hospital engineers often will be helpful in establishing the scope of the problem, identifying potential side effects,
and fixing the problem. Working as a team, the operating room staff, physicians, engineers, safety officers, and
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administrators should aim to minimize the effect of these events on patient care and rectify problems as soon as
possible.
References
1. Gaba DM, Fish KJ, Howard SK: Crisis Management in Anesthesiology. New York: Churchill Livingstone, 1994,
pp 195 229
2 . Geyelin M: Hospitals Face Complex Task Preparing for Dec. 31. Wall Street Journal, March 29,1999,B1.
3. Feely TW, Hedley White J: Bulk oxygen and nitrous oxide delivery systems: Designs and dangers.
Anesthesiology 1976; 44:301.
4. Sprague DH, Archer GW: Intraoperative hypoxemia from an erroneously filled liquid oxygen reservoir.
Anesthesiology 1975; 42:360.
DISCLOSURE
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Trauma Anesthesia
Albert J. Varon, M.D., MHPE Miami, Florida
Introduction
Trauma is the leading cause of death among children, adolescents and young adults (ages 1–44) in the United States.
Although few anesthesiologists care exclusively for trauma patients, most anesthesiologists care for trauma patients
at one time or another in their clinical practice. This presentation will provide a concise review of the essential
elements in the care of the severely injured trauma patient including initial evaluation and resuscitation, airway
management, treatment priorities, and fluid, blood component and hemostatic therapy. The presentation will also
identify new trends in trauma and anesthesiology practices that impact the management of these patients.
Initial Evaluation and Management
Active participation of anesthesiologists in the care of the most severely injured patients is essential for improved
outcome and represents an opportunity to highlight the anesthesiologist’s role as a perioperative physician. Early
involvement of the anesthesiologist can provide expert airway and resuscitation management, expedite diagnostic
and operative care, and provide continuity of patient care throughout the perioperative period.
The immediate care required by most severely injured patients is best managed with a multidisciplinary team. As
part of the team, the anesthesiologist contributes to evaluation and resuscitation while gathering information needed
for anesthetic management of surgery or special radiologic procedures.
The Advanced Trauma Life Support (ATLS) course developed by the Committee on Trauma of the American
College of Surgeons helps physicians maximize their resuscitative efforts and avoid missing life-threatening injuries
by using an organized approach in trauma care. Although few anesthesiologists participate in these courses,
familiarity with ATLS guidelines facilitates more effective participation in the trauma resuscitation team and allows
the formulation of airway and perioperative management plans.
The ATLS model consists of four sequential components: a rapid primary survey, resuscitation of vital functions, a
more detailed secondary survey, and initiation of definitive care. Ideally, the anesthesiologist should arrive to the
resuscitation area before patient arrival to verify that essential airway equipment is available and functional.
Primary Survey. The primary survey involves rapid evaluation and stabilization of the functions that are crucial
to survival: Airway maintenance with cervical spine protection, Breathing and ventilation, and Circulation with
hemorrhage control. This is followed by a brief neurologic exam (Disability) and complete removal of the patient’s
clothes to search for injuries (Exposure) while preventing hypothermia (Environment). During this phase, life-
threatening conditions are identified and treated simultaneously.
Resuscitation. Simultaneous resuscitation follows the same ABC sequence. A definitive airway (i.e., tracheal
intubation) should be established if there is airway compromise, impaired ventilation, or any concern about the
patient’s ability to maintain the airway. The airway is secured with continuous protection of the cervical spine. This
is most frequently achieved by rapid sequence tracheal intubation (discussed below). Confirmation of tracheal
intubation by auscultation and capnography is followed by assisted ventilation. Bleeding from external wounds is
usually controlled by direct pressure and circulation restored by volume expansion with warm intravenous (IV)
fluids. A minimum of two large-caliber IV catheters should be inserted, preferable in the upper extremities. At the
time of IV insertion blood can be drawn for type and crossmatch and baseline hematologic tests including pregnancy
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test (when applicable). Monitors used during the primary survey and resuscitation phases include
electrocardiography, blood pressure monitoring, pulse oximetry, and capnography (or CO2 colorimetry) in intubated
patients. Placement of urinary and gastric catheters is also considered part of the resuscitation phase. Essential
laboratory and radiologic examinations (portable AP chest and pelvis) can be performed immediately after the
primary survey but should not delay patient resuscitation.
Ultrasound has become an intrinsic component in the evaluation of trauma patients and has been incorporated into
the ATLS guidelines. The focused assessment with sonography for trauma (FAST) is a useful tool for the quick
detection of intraperitoneal or pericardial fluid after blunt or penetrating injury. More recently, this device has also
been used to rapidly identify the presence or absence of organized cardiac activity in trauma patients presenting with
or progressing to pulseless electrical activity.
Secondary Survey. The secondary survey involves obtaining a history and a more extensive and systematic
(head-to-toe) examination aimed at identifying additional injuries. This information also constitutes the basis for the
preoperative anesthetic evaluation. The mnemonic AMPLE is useful when obtaining the trauma patient’s history. A
stands for known allergies, M for medications currently taken, P is for past illnesses/surgery or pregnancy, L for
timing and contents of last meal, and E stands for events and environment related to the injury. The complete
topographic examination of the patient at this stage should include a neurologic exam and determination of the
Glasgow Coma Scale (GCS) score, if it was not performed during the primary survey. Specialized diagnostic tests to
identify specific injuries may also be conducted during the secondary survey. Tests may include computed
tomography (CT) imaging of the head, cervical spine, chest, abdomen, and pelvis, followed by x-ray examination of
the injured extremities, as indicated by the patient’s injuries. Although establishing the type and severity of injuries
is a surgical task, the anesthesiologist must maintain constant communication with the surgeon to anticipate the
course of action and anesthetic implications. The effects of the measures initiated during the primary survey (airway
patency, ventilation, perfusion) should be frequently reassessed during this and all other phases of management.
Definitive Care. After the completion of the secondary survey, a decision must be made as to the type and
location of subsequent management. Patients that require immediate surgical intervention are taken to the operating
room. Some patients may require surgery to control the adverse consequences of injury before the secondary survey
is completed. In such cases the anesthesiologist plays an important role in the identification of additional injuries.
Patients that require support and monitoring are transferred to the intensive care unit. If definitive care cannot be
provided at a local hospital, the patient should be transferred to a facility that has the resources to care for the
patient.
Airway Management
Airway management of trauma patients may take place in a variety of settings. This may occur in a designated
resuscitation area, emergency department (ED), operating room (OR), intensive care unit (ICU), CT imaging suite,
or in the pre-hospital setting.
Most of the airway tools and algorithms used in the trauma setting are similar to those used in a non-emergency
scenario, with some modifications. One should always be well equipped, be familiar with available devices, and be
able to adapt to rapidly evolving situations. A significant difference is that awakening the severely injured patient
for intubation after a failed asleep intubation or canceling the procedure is rarely, if ever, an option.
Before a patient’s arrival, pre-hospital emergency personnel can convey important information. This includes
mechanism of injury, patient’s age, GCS score, vital signs, and estimated time of arrival, all of which can aid in
preparation and planning. Upon a patient’s arrival, immediate assessment of ventilatory status is essential. A simple
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question such as “What is your name?” can provide a wealth of information. A positive, appropriate verbal response
indicates that the airway is patent, ventilation intact, and circulation is currently adequate for brain perfusion. On the
other hand, an incoherent response or lack thereof will alert the clinician that one or several issues may be present. If
airway or breathing is of concern, the anesthesiologist should immediately prepare to secure the patient’s airway.
Indications for tracheal intubation. ATLS guidelines list the following as indications for securing an airway
in the trauma setting:
• Apnea • Potential airway compromise
• Inability to maintain a patent airway • Glasgow Coma Scale (GCS) score ≤8
• Protection from aspiration • Inability to maintain oxygenation
In addition to the above, tracheal intubation is sometimes performed to prevent a patient from self-harm or to allow
proper medical evaluation; the literature has listed these as “discretionary indications” for tracheal intubation.
Tracheal tube placement should include adequate preoxygenation, rapid-sequence induction (RSI), cricoid pressure
(CP), and in-line cervical spine stabilization (when indicated). Confirmation of correct tracheal tube placement may
occur by several methods including end-tidal carbon dioxide by capnography (or if unavailable, by semi-quantitative
colorimetry), bilateral breath sounds, absence of gastric sounds, bilateral chest expansion, fogging of the tracheal
tube, maintenance of oxygenation by pulse oximetry, direct confirmation by fiberoptic endoscopy, or direct
visualization of lung expansion during emergency thoracotomy. When perfusion is present, capnography is the most
reliable method for confirmation of tracheal tube placement.
Rapid sequence induction (RSI). Securing the airway of a trauma patient can lead to unexpected challenges.
Often patients are combative and uncooperative or their pathology imposes a significant time constraint, all of which
result in a less than an ideal situation. RSI is the most commonly used method for securing a definitive airway in
these patients. The reasons for this preference include the presence of unidentified injuries (e.g., cribriform plate
fracture), hemodynamic instability, unknown or unreliable fasting history, and severe stress and inflammation
leading to delayed gastric emptying and risk of aspiration. RSI has been associated with high intubation success
rates and low complication rates in emergency and trauma intubations.
Pre-oxygenation before induction should take place whenever possible. This may be difficult in situations where a
patient is uncooperative, combative, or has severe facial deformities that impede proper mask seal. When
preoxygenation is inadequate or not possible, bag-valve-mask (BVM) ventilation (while applying cricoid pressure)
should be used through induction to maintain oxygenation. This is especially important in patients with traumatic
brain injury, where maintenance of cerebral perfusion pressure and oxygenation take precedence over the potential
risk of aspiration if BVM ventilation results in stomach insufflation. Therefore, it seems prudent to provide small
positive pressure breaths during RSI to any patient that the clinician believes is at risk of prompt oxygen
desaturation.
Anesthetic agents and neuromuscular blockings drugs for RSI. Every induction agent has advantages
and disadvantages. These may relate to characteristics of the medication itself or how it needs to be dispensed or
handled. All of the commonly used induction drugs have been used in the trauma setting including propofol,
etomidate, midazolam, and ketamine (thiopental is currently not being manufactured in the U.S.). Use of these
agents commonly results in amnesia and intubating conditions within 30–60 seconds. Propofol may cause profound
hypotension in hypovolemic patients and therefore its dose needs to be significantly reduced if used for RSI in these
patients. Etomidate has the advantage of inducing less hemodynamic changes in comparison to other induction
agents. Although some clinicians have challenged the use of etomidate for RSI due to the concern that it can induce
adrenal suppression, it remains the most frequently used agent for RSI outside of the OR. Ketamine may cause
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tachycardia and hypertension from endogenous catecholamine release, which may be advantageous in the trauma
setting. However, concerns of myocardial depression in the catecholamine-depleted patient, increased intracranial
pressure, and increased intraocular pressure may be important considerations when selecting this drug. In the
multiple-trauma patient, who is often in extremis, it is important to recognize that conventional drug doses for
induction of anesthesia need to be reduced since all induction drugs have the potential for causing hypotension and
cardiovascular collapse in this setting. Therefore, when determining which induction agent is most appropriate in a
trauma patient, drug dosage may be more important than the specific medication.
Most neuromuscular blockers (NMB) can be used for rapid sequence intubation if a large enough dose is given. In
clinical practice, the two medications most often used are succinylcholine (depolarizing NMB) and rocuronium
(non-depolarizing NMB). Succinylcholine has withstood the test of time as the most reliable NMB drug for fast and
ideal intubating conditions. Although acute burns and acute paralysis are not contraindications to the use of
succinylcholine, it should not be administered after 24 hours of sustaining such injuries due to the risk of
hyperkalemia. Succinylcholine is also contraindicated if severe hyperkalemia is suspected (e.g., rhabdomyolysis,
renal failure). The recommended dose of succinylcholine for RSI has been cited to be at least 0.6 mg/kg to achieve
ideal intubating conditions within 60 seconds. Common practice includes a range of 1.0–1.5 mg/kg. Increasing the
dose of succinylcholine above 0.6 mg/kg may not provide better intubating conditions, but will provide faster and a
longer lasting muscle relaxant effect. If a muscle relaxant is needed and there is concern about the capability to
ventilate or intubate, one may prefer to use the smallest possible dose that provides adequate relaxation and avoid
long-lasting blockade. However, patients could still be at risk of hypoxemia if there were failure to intubate and
ventilate, regardless of the dose of succinylcholine administered. The availability of a non-depolarizing NMB drug
for RSI is imperative in the trauma setting, since succinylcholine may be contraindicated in certain patients. A
rocuronium dose of 0.9–1.2 mg/kg will provide adequate intubating conditions within 60 seconds of administration.
An alternative plan for securing the airway and ensuring ventilation (including the use of a surgical airway) must be
formulated before proceeding with RSI.
Cricoid pressure. The effectiveness of cricoid pressure (CP) in preventing aspiration continues to be debated.
Some investigators have suggested that CP may displace the esophagus laterally and not compress it because often
the esophagus does not lie directly between the cricoid and the spine. However, magnetic resonance imaging studies
have shown that the lumen of the alimentary tract behind the cricoid cartilage (i.e., the postcricoid hypopharynx) is
compressed regardless of the position of the cartilage relative to the vertebral body. Other investigators have
reported that CP decreases lower esophageal sphincter tone making regurgitation into the esophagus more likely. In
addition, health care personnel frequently apply CP incorrectly by applying pressure to the wrong location (e.g.,
thyroid cartilage) or applying pressure that is too soft or too hard. Controversy also exists as to the ability of CP to
improve or worsen laryngoscopic view, since both effects have been reported in the literature. Despite all of these
concerns, CP continues to be the mainstay for RSI due to its low risk/benefit ratio. CP should be applied throughout
induction and attempts at intubation. However, if necessary, CP should be altered or removed to ease intubation or
insertion of a laryngeal mask airway because securing the airway and providing ventilation are paramount.
Cervical spine immobilization. Prehospital personnel place cervical collars for a variety of reasons including
mechanism of injury, signs of neurologic deficit, or pre-hospital protocol. Hard collars are applied to prevent further
damage of a patient’s cervical spine during transport. Two common reasons for a cervical collar to remain in place
are signs of a cervical injury or inability to clinically “clear the spine.” The latter may occur when a patient is
combative, intoxicated, obtunded, or has distracting injuries. When the airway needs to be secured in a patient with
suspected cervical injury and awake intubation is not possible, manual in-line stabilization (MILS) should be used
during the RSI process. This requires an additional person to hold the cervical spine in place to prevent the person
securing the airway from extending or flexing the cervical spine. After induction, the anterior portion of the cervical
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collar is removed and MILS applied. Cervical collars do not reliably immobilize the neck during intubation and may
significantly limit mouth opening, so the anterior portion should be temporarily removed during laryngoscopy.
The use of MILS has recently come into question. Studies have shown that it may lead to an inferior view causing
the person intubating to apply greater pressure, which may be transferred to surrounding tissues including the
cervical spine. Secondly, an inferior view may lead to a longer time or failure to secure the airway. Although these
are legitimate concerns, MILS is still recommended by ATLS guidelines and is commonly applied in patients with
suspected cervical injury. At this time there is no outcome data suggesting that direct laryngoscopy with MILS is
inferior to any other method, including fiberoptic. Lastly, as was noted for CP, MILS may be reduced if its use
impedes tracheal intubation.
ASA difficult airway algorithm modified for trauma. The American Society of Anesthesiologists’ (ASA)
difficult airway algorithm offers an excellent guideline for the approach to the difficult airway and can easily be
modified for trauma patients (http://www.asahq.org/For-Members/About-ASA/ASA-Committees/Committee-on-
Trauma-and-Emergency-Preparedness.aspx). These modifications are necessary because the urgency and
circumstances of the trauma setting may require deviations from the original algorithm. Trauma patients may be
uncooperative or unstable for awake intubation and therefore may be automatically allocated into the intubation after
induction category. If noninvasive methods to secure the airway are unsuccessful, invasive airway access may be the
only other alternative since awakening the patient or canceling the case is rarely an option. Establishing an
institutional trauma airway protocol that takes into consideration available personnel and resources may enhance the
safety and effectiveness of airway management in trauma patients.
Role of videolaryngoscopy. A variety of videolaryngoscopes are currently available. Their popularity is due to
their increased ability to improve the laryngoscopic view (when compared to the direct approach) and increased
portability. Although videolaryngoscopes have shown to provide better glottic view than other devices, this does not
always translate into an easier intubation. Intubation may still be difficult despite a good view because the tube or
stylette insertion path may not line up with the view obtained by the videolaryngoscope. In addition, the presence of
blood, emesis, or airway injury may disrupt the videolaryngoscopic view. Another potential difficulty is the oral
insertion of fixed-angle videolaryngoscopy devices (e.g., Glidescope) in patients receiving MILS. An observational
study in the ED of a Level 1 trauma center reported that the rates of successful intubation on first attempt were not
significantly different between video and direct laryngoscopy, but videolaryngoscopic intubation required more time
to complete. Therefore, although the advent of videolaryngoscopes continues to expand the armamentarium of the
airway specialist, these devices have not yet replaced direct laryngoscopy in the trauma setting.
Tracheal tube introducers. A new tool in ATLS (although not new for anesthesiologists) is the tracheal tube
introducer, also known as the “gum elastic bougie.” This device has a coude tip that allows the anesthesiologist to
advance the introducer into the trachea despite a limited glottic view, which may be common in the trauma setting
due to MILS or CP. The incorporation of the tracheal tube introducer into ATLS is the result of its success in aiding
to secure a difficult airway in other settings. Many institutions have incorporated algorithms that include a bougie if
a tracheal tube cannot be inserted on the first attempt.
The Aintree intubation catheter (Cook Critical Care, Bloomington, Indiana, USA) may be used as a bridge to
convert a supraglottic airway into a secure airway with a tracheal tube. One of the main characteristics of an Aintree
catheter is its hollow center, which can accommodate a flexible fiberoptic scope or allow oxygen insufflation. This
introducer is shorter than conventional hollow catheters that serve as airway exchange catheters. Due to its shorter
length, it allows a fiberoptic scope to protrude through it and offer visibility beyond the catheter.
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Supraglottic airways. The use of supraglottic devices has greatly increased in the last 25 years and their use has
now been incorporated into ATLS. In the trauma setting, supraglottic airways are most frequently encountered when
patients arrive in the ED. The laryngeal mask airway (LMA), esophageal-tracheal combitube, and the laryngeal tube
airway (LTA) are examples of airway devices commonly used by pre-hospital personnel. Anesthesiologists must
recognize these airways, know their function and capabilities, determine if they provide adequate ventilation, and
have the skill set to safely exchange them for a definitive airway. This may entail removal of the supraglottic airway
followed by tracheal intubation, use of an LMA as a conduit for fiberoptic tracheal intubation, use of an Aintree
catheter to remove the supraglottic airway followed by tracheal intubation over the catheter, or leaving the
supraglottic airway in place to provide ventilation until a surgical airway can be emergently obtained. Although a
detailed discussion of supraglottic airways is beyond the scope of this presentation, an excellent review of this topic
can be found in the references provided.
Fiberoptic endoscopy. The fiberoptic bronchoscope (FOB) is the most versatile of the intubating tools currently
available. With patient cooperation and adequate anesthetic topicalization the airway can be secured in a safe
manner in most cases. This is especially important in patients with suspected cervical spine or airway injury.
Unfortunately, awake intubation can only be performed in a small number of trauma patients. Many times the reason
a patient requires tracheal intubation is the same reason an awake intubation is impractical (e.g., combative,
hemodynamically unstable, soiled oropharynx). Asleep fiberoptic intubations are infrequently performed in the
trauma setting due to the risk of aspiration, except when used as a rescue technique (e.g., through an LMA) or as
part of a rapid tracheal inspection and intubation in patients with penetrating neck injury.
Management priorities in multiple trauma
Setting priorities in the management of patients with multiple injuries is difficult and will depend on the likelihood
that these injuries will impact survival or functional outcome.
Head CT imaging versus emergent laparotomy. In hypotensive patients with a diminished level of
consciousness after blunt trauma it may be challenging to decide whether to proceed with immediate head CT
imaging or urgent laparotomy. Although serious head injury occurs commonly in these patients, the frequency of
urgent laparotomy is greater than emergency craniotomy for intracranial hemorrhage. Although head CT imaging
may precede surgery in injured patients who respond to initial resuscitation, demonstration of a large intraperitoneal
fluid accumulation during initial sonography assessment in combination with unstable vital signs should lead to
immediate laparotomy. Anesthesiologists play a significant role expediting the care and transfer of these patients to
the OR.
Cervical spine clearance. Patients that sustain blunt trauma should be evaluated for cervical spine injury and if
cleared, their cervical collars removed. In alert trauma patients without neurologic deficit or distracting injury who
have no neck pain or motion tenderness radiologic imaging is not necessary. All other patients in whom cervical
spine injury is suspected must have imaging studies. Computed tomography (CT) has replaced plain radiography as
the primary technique for screening suspected cervical spine injury. Controversy persists regarding cervical spine
clearance in the obtunded patient. Options include leaving the cervical collar in place until a clinical exam can be
performed, removing the collar on the basis of CT alone, or obtaining a magnetic resonance imaging (MRI) study. In
the trauma setting, it is often not possible to obtain cervical spine clearance before airway intervention due to the
need for urgent life or limb saving surgical procedures, or due to the inability to clear the spine when a patient’s
altered sensorium or distracting pain interferes with clinical evaluation. In these patients RSI with MILS followed by
direct laryngoscopy and oral intubation appears to be safe.
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Timing of bone fracture fixation. The optimal timing of surgical stabilization of fractures in the patient with
multiple injuries is controversial. Early (<24 h) fixation of long-bone fractures may reduce pulmonary
complications, length of mechanical ventilation, and duration of ICU and hospital stay. However, unstable patients
with multiple injuries or traumatic brain injury (TBI) should be resuscitated and adequately stabilized before
receiving definitive orthopedic care. In such patients debridement and temporary fixation of fractures using external
fixators, followed by definitive fixation (when physiological parameters have stabilized), may increase their chance
for survival. Factors that should be considered when assessing the appropriateness of early fracture fixation include
severity of brain injury, degree of pulmonary dysfunction, presence of hypotension, hypothermia or coagulopathy,
and the patient’s response to initial resuscitation interventions.
Damage control. In the U.S. Navy, the term damage control (DC) is used for the emergency control of situations
that may hazard the sinking of a ship. In the context of trauma the term refers to providing only interventions
necessary to control hemorrhage and contamination and focusing on reestablishing a survivable physiologic status.
This approach consists of a rapid abbreviated laparotomy to stop hemorrhage and peritoneal contamination, and
staged sequential repair. Patients would then undergo continued resuscitation and aggressive correction of the “lethal
triad” of coagulopathy, hypothermia and acidosis in the ICU before returning to the OR for definitive repair. The
damage control strategy has been shown to lead to better than expected survival rates for abdominal trauma.
Based on the DC strategy for abdominal injuries, similar principles have been applied to the management of
multiply injured patients with associated long bone and pelvic fractures (i.e., “damage control orthopedics”) or with
traumatic brain injury (i.e., “damage control neurosurgery”). Damage control orthopedics (see section above)
represents a safer initial approach in unstable patients by significantly decreasing the initial operative exposure and
blood loss. Damage control neurosurgery involves stopping intracranial bleeding, evacuation of intracranial
hematomas, and early surgical debridement to limit wound contamination. Although damage control neurosurgery
may also include decompressive craniectomy, surgical reduction of intracranial pressure has not resulted in better
outcomes in patients with severe TBI.
Damage control resuscitation (DCR) is a concept that has been made popular by the military and is now being
investigated in the civilian trauma setting. DCR differs from current resuscitation approaches by attempting to
couple the surgical control of life-threatening injury with earlier and more aggressive correction of the coagulation
derangements that exacerbate hemorrhage in trauma patients. DCR centers on the application of several principles
including “hypotensive resuscitation,” use of blood products over isotonic fluid for volume replacement, and rapid
and early correction of coagulopathy with component therapy. This resuscitation strategy begins in the prehospital
and ED settings and continues through the OR and ICU until the resuscitation is complete.
Fluid, blood component, and hemostatic therapy
Control of bleeding and fluid resuscitation with crystalloid and blood products is the mainstay of therapy for trauma
patients with hemorrhagic shock. However, aggressive fluid resuscitation before the bleeding is controlled can be
detrimental, as the increased blood pressure and circulating volume may result in clot disruption and reversal of
compensatory vasoconstriction. In addition, the dilution of clotting factors from excessive crystalloid administration
may worsen the coagulopathy often present in severely injured patients. Overly aggressive crystalloid resuscitation
in patients requiring massive transfusion has been associated with a higher risk of acute respiratory distress
syndrome, abdominal compartment syndrome, and multiple organ failure.
Hypotensive resuscitation. Over the past few years an alternative to high-volume fluid resuscitation termed
“hypotensive resuscitation” has been actively investigated in the trauma setting. In contrast to standard fluid
resuscitation, this strategy uses less fluids and blood products during the early treatment of hemorrhagic shock.
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Animal studies indicate that hypotensive resuscitation reduces blood loss and transfusion requirements in both blunt
and penetrating trauma. However, in human studies, decreased blood loss and transfusion requirements have only
been confirmed in penetrating injury. The evidence supporting hypotensive resuscitation in patients with blunt
trauma or traumatic brain injury is limited and the overall long-term outcome of this fluid resuscitation strategy has
not been determined. Concerns about the use of hypotensive resuscitation include the possibility of cardiac arrest (if
small volumes of fluid are insufficient to prevent exsanguination) and late complications from organ damage
sustained during hypotension. Recommendations based on expert opinion and the results of the above studies
suggest titrating fluid to restore consciousness, radial pulse, and a systolic blood pressure of 80–90 mmHg until
definitive surgical control of bleeding can be achieved. Fluid treatment is aimed to a systolic blood pressure of at
least 100 mmHg in patients with hemorrhagic shock and head trauma.
Blood component therapy. Hemorrhage is the most common cause of shock and preventable early death in
trauma patients. Traditional therapy for hemorrhagic shock consists of crystalloid and packed red blood cell (PRBC)
resuscitation with the subsequent use of fresh frozen plasma (FFP) and platelets as indicated by the patient’s
evolving condition and laboratory data. Over the past few years this therapy has being replaced by earlier and more
liberal use of FFP during massive blood transfusion. In many trauma centers the use of a 1:1 ratio of FFP to PRBC
has been implemented based on observational studies that reported a survival advantage associated with the
administration of relatively higher FFP:PRBC ratios. However, the apparent survival advantage associated with high
FFP:PRBC transfusion ratios could be explained by a survival bias. Because component blood products are not
administered evenly and simultaneously in clinical practice, and many deaths occur early, it is possible that the
survival benefit observed among patients receiving a higher FFP:PRBC ratio may merely reflect the fact that they
live long enough to receive the higher ratio of products. Several investigations have reported that the association
between higher FFP:PRBC ratios and improved survival is not statistically significant when adjusted for survival
bias. A recent prospective observational study indicates that a 1:1 FFP:PRBC ratio does not provide any additional
benefit over ratios of 1:2 to 3:4 and that the hemostatic benefits of plasma therapy are limited to patients with
coagulopathy. Without randomized controlled trials controlling for survivor bias, the available evidence supporting
higher FFP:PRBC ratios is inconclusive. Currently, American and European evidence-based guidelines recommend
early intervention with FFP but without a preset FFP:PRBC ratio. The Prospective Randomized Optimum Platelet
and Plasma Ratio (PROPPR) trial is an ongoing large multicenter trial funded by the National Institutes of Health
and U.S. Department of Defense. This study will offer an opportunity to prospectively evaluate the ideal ratio of
blood products for use in trauma.
Massive-transfusion protocols. In addition to providing continued resuscitation and anesthesia care,

anesthesiologists are closely involved with ordering blood products for patients receiving massive transfusion (>10
units PRBC in 24-hour period). Efforts to obtain a continuous and sufficient supply of blood products require
valuable time; communication breakdowns may result in inappropriate or insufficient products for patient
requirements. Several institutions have shown that predefined massive transfusion protocols (MTP) can be
successfully implemented and have a positive impact on patient outcome. The purpose of such protocols is to
provide blood products in an immediate and sustainable manner to patients with hemorrhagic shock. The MTP is
usually initiated by a single phone call to the blood blank by an attending surgeon or anesthesiologist. The blood
bank will provide a continuous supply of blood products (PRBC, FFP, platelets and cryoprecipitate) in a
predetermined sequence, quantity, and ratio until the attending physician calls again to stop. Such protocols require
significant resources and therefore may not be suitable for all institutions. The requirement for uncross-matched
blood during acute resuscitation or the presence of at least 2 out of 4 specific bedside parameters (penetrating
mechanism, ED systolic blood pressure <90 mm Hg, ED heart rate >120 bpm, positive FAST) can help predict the
need for massive transfusion. Although no prospective trial outcome data is available, anesthesiologists and trauma
surgeons have found MTPs to be more efficient than traditional blood bank delivery methods and that they relieve
anesthesia and OR personnel from worrying about the availability of blood supplies while caring for a severely
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injured patient. Sample MTPs can be found on the ASA website at http://www.asahq.org/For-Members/About-
ASA/ASA-Committees/Committee-on-Blood-Management/MTP-for-Hemorrhagic-Shock.aspx
Hemostatic agents. The etiology of the coagulopathy associated with trauma is multifactorial and involves all
components of the hemostatic system. The primary factors responsible for early coagulopathy appear to be tissue
injury and shock with systemic hypoperfusion. As shock progresses and fluid therapy is initiated, hemodilution
exacerbates these hemostatic derangements. After extensive hemodilution, the major antifibrinolytic proteins are
decreased and fibrin clots are more prone to fibrinolysis. Although FFP, platelets, and cryoprecipitate are considered
mainstay hemostatic therapies, there has been an increased interest in the use of other hemostatic agents for
treatment of coagulopathy in massive hemorrhage. These include the use of recombinant activated factor VII and the
antifibrinolytic lysine analogue tranexamic acid. Recombinant activated factor VII (rFVIIa) is thought to act locally
at the site of tissue injury by binding to exposed tissue factor and generating a tight fibrin hemostatic plug through
increased thrombin generation. Several investigations reported that the early administration of rFVIIa decreased red
blood cell use in trauma patients requiring massive transfusion. However, prospective randomized trials reported
that the use of rFVIIa in these patients does not affect mortality compared with placebo. The cost of tranexamic acid
(TXA) is drastically lower than that of rFVIIa. TXA inhibits fibrinolysis by blocking the lysine binding sites on
plasminogen. A prospective randomized placebo-controlled trial (CRASH-2) was conducted in Europe to investigate
the effectiveness of TXA (1 g loading followed by 1 g over 8 h) in 20,211 trauma patients. This multicenter study
demonstrated significant reductions in all-cause mortality and in deaths due to bleeding in the TXA group, compared
to the placebo group. Further analysis by the investigators revealed that the benefit was only seen when TXA was
administered within 3 h of injury and that increase mortality occurred when the drug was given after this period.
More recently, the Military Application of Tranexamic Acid in Trauma and Emergency Resuscitation study
(MATTERs) evaluated the use of TXA in hemorrhagic shock after combat injury. This retrospective analysis of U.S.
and U.K. military trauma registries reported that the unadjusted mortality was lower in the TXA group, despite
being more severely injured. Patients who received massive transfusion benefited the most from the administration
of TXA, with improved survival and less coagulopathy. This inexpensive drug is now being incorporated into
trauma clinical practice guidelines and treatment protocols.
Point-of-care coagulation monitoring. Evidence is accumulating for the use of coagulation testing to identify
traumatic coagulopathy and guide blood component and antifibrinolytic therapy. Conventional coagulation tests
such as PT, PTT, fibrinogen and platelet count involve substantial time delays, provide limited details on clot
formation, and are unable to identify or quantify the degree of platelet dysfunction. In contrast, point-of-care
viscoelastic hemostatic assays such as rapid thromboelastography (TEG) or rotation thromboelastometry (ROTEM)
can rapidly identify and functionally characterize traumatic coagulopathy. These assays measure clot formation and
dissolution and identify coagulopathies secondary to dilution, consumption, deficiencies, and hyperfibrinolysis.
Recent studies in trauma patients have reported on the benefit of using viscoelastic hemostatic assays to identify
coagulopathy, predict need for massive transfusion, and guide therapy. However, further studies are needed to
validate the use of viscoelastic hemostatic assays in the trauma setting.
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the rural setting. J Trauma Acute Care Surg 2012;72:211–5.
38. Magnotti LJ, Zarzaur BL, Fischer PE, et al. Improved survival after hemostatic resuscitation: Does the emperor
have no clothes? J Trauma 2011;70:97–102.
39. Manoach S, Paladino L. Laryngoscopy force, visualization, and intubation failure in acute trauma: Should we
modify the practice of manual in-line stabilization? Anesthesiology 2009;110:6–7.
40. Morrison CA, Carrick MM, Norman MA, et al. Hypotensive resuscitation strategy reduces transfusion
requirements and severe postoperative coagulopathy in trauma patients with hemorrhagic shock: Preliminary
results of a randomized controlled trial. J Trauma 2011;70:652–663.
41. Morrison JJ, Dubose JJ, Rasmussen TE, Midwinter MJ. Military application of tranexamic acid in trauma
emergency resuscitation (MATTERs) Study. Arch Surg. 2012;147:113–9.
42. Muakkassa FF, Marley RA, Workman MC, et al. Hospital outcomes and disposition of trauma patients who are
intubated because of combativeness. J Trauma 2010;68:1305–1309.
43. Naguib M, Samarkandi AH, Abdullah K, et al. Succinylcholine dosage and apnea-induced hemoglobin
desaturation in patients. Anesthesiology 2005;102:35–40.
44. Neal MD, Hoffman MK, Cuschieri J, et al. Crystalloid to packed red blood cell transfusion ratio in the massively
transfused patient: when a little goes a long way. J Trauma Acute Care Surg 2012;72:892–8.
45. Nunez TC, Voskresensky IV, Dossett LA, et al. Early prediction of massive transfusion in trauma: Simple as
ABC (Assessment of blood consumption)? J Trauma 2009;66:346–352.
46. Nunez TC, Young PP, Holcomb JB, Cotton BA. Creation, implementation, and maturation of a massive
transfusion protocol for the exsanguinating trauma patient. J Trauma 2010;68:1498–1505.
47. Pape HC, Tornetta P, Tarkin I, et al. Timing of fracture fixation in multitrauma patients: The role of early total
care and damage control surgery. Am Acad Orthop Surg 2009;17:541–549.
48. Platts TF, Campagne D, Chinnock B, et al. A comparison of Glidescope video laryngoscopy versus direct
laryngoscopy intubation in the emergency department. Acad Emerg Med 2009;16:866–871.
49. Rajasekhar A, Gowing R, Zarychanski R, et al. Survival of trauma patients after massive red blood cell
transfusion using a high or low red blood cell to plasma transfusion ratio. Crit Care Med 2011;39:1507–1513.
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50. Rice MJ, Mancuso AA, Gibbs C, et al. Cricoid pressure results in compression of the postcricoid hypopharynx:
The esophageal position is irrelevant. Anesth Analg 2009;109:1546–52.
51. Rosenfeld JV. Damage control neurosurgery. Injury 2004;35:655–60.
52. Santoni BG, Hindman BJ, Puttlitz CM, et al. Manual in-line stabilization increases pressures applied by the
laryngoscope blade during direct laryngoscopy and orotracheal intubation. Anesthesiology 2009;110:24–31.
53. Scalea TM. Optimal timing of fracture fixation: Have we learned anything in the past 20 years. J Trauma
2008;65:253–260.
54. Schuster KM, Lofthouse R, Moore C, et al. Pulseless electrical activity, focused abdominal sonography for
trauma, and cardiac contractile activity as predictors of survival after trauma. J Trauma 2009;67:1154–1157.
55. Sise MJ, Shackford SR, Sise CB, et al. Early intubation in the management of trauma patients: Indications and
outcomes in 1,000 consecutive patients. J Trauma 2009;66:32–40.
56. Snyder CW, Weinberg JA, McGwin G, et al. The relationship of blood product ratio to mortality: Survival
benefit or survival bias? J Trauma 2009;66:358–364.
57. Stephens, CT, Kahntroff, S, Dutton, RP. The success of emergency endotracheal intubation in trauma patients: a
10-year experience at a major adult trauma referral center. Anesth Analg 2009;109:866 –72.
58. Theusinger OM, Wanner GA, Emmert MY, et al. Hyperfibrinolysis diagnosed by rotational thromboelastometry
(ROTEM) is associated with higher mortality in patients with severe trauma. Anesth Analg. 2011;113:1003-12.
59. Tuttle MS, Smith WR, Williams AE, et al. Safety and efficacy of damage control external fixation versus early
definitive stabilization for femoral shaft fractures in the multiple-injured patient. J Trauma 2009;67:602–605.
60. Varon AJ, Smith CE (editors). Essentials of Trauma Anesthesia. Cambridge, Cambridge University Press, 2012.
61. Warner KJ, Cuschieri J, Jurkovich GJ, et al. Single-dose etomidate for rapid sequence intubation may impact
outcome after severe injury. J Trauma 2009;67:45–50.
DISCLOSURE
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What’s New in Airway Management

Lauren Berkow, M.D. Baltimore, Maryland
Introduction
As patients presenting for anesthesia and surgery continue to become more complex, so has
airway management. In addition, the number of patients requiring anesthesia and airway management
outside the operating room setting continues to increase. New airway devices continue to be introduced into
the market and clinical practice, making airway management decisions even more challenging. Claims
involving airway management, both inside as well as outside the operating room setting, according to the
ASA Closed Claims database, continue to be significant.1,2 This lecture discusses some of the new
evaluation methods and reviews many of the newer airway devices available as well as many of the issues
surrounding airway competency, airway management outside the operating room setting, and the role of
simulation and standardization for airway education and airway management.
1. Airway evaluation
a. Conventional Methods
Routine pre-operative airway examination usually includes an assessment of mouth opening and
dentition, Mallampati classification, measurement of thyromental distance and evaluation of neck
mobility. These methods are quickly and easily performed at the bedside, but unfortunately, their
sensitivity and specificity for accurate prediction of difficulty with airway management is not very
robust.
b. Newer Methods
i. Pre-operative endoscopic airway examination (PEAE)3
Pre-operative endoscopy of the airway can aid in identification of airway pathology that
could potentially alter the choice of airway plan. Conversely, in patients suspected of
airway difficulty, direct observation of airway structures can provide valuable
information. The procedure can be performed in the pre-operative area and requires only
topicalization of the nasal cavity.
ii. Ultrasound assessment of the Airway4
Ultrasonography can also be used to identify airway pathology. It is non-invasive, safe,
portable, and easily repeatable, Ultrasound can also be used to confirm endotracheal tube
placement (or esophageal intubation), identify the cricothyroid membrane, or assist with
percutaneous tracheostomy placement.
2. Predicting the difficult airway
Predicting which patients may be difficult to mask ventilate or intubate can be challenging,
however certain disease processes have been associated with difficult airway management.5 (Table 1)
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Table 1: D isease states associated w ith dif ficult airway management
Co ngeni tal A cquired

Pierre- Ro bin syndrome Morbid obesity
Treacher-Co llins sy ndrome A cromegaly
Goldenhar's sy ndrome Infections involv ing the airw ay (Ludw ig's
ang ina)
Mucopo lysaccharidoses Rheumatoid arthritis
A chondroplasi a Obstructiv e sleep apnea
Microg nathia A nky losing S pondylitis
D own's syndro me Tumors involv ing the airw ay
Trauma ( airw ay, cerv ical spine)
The best predictor of difficulty with airway management is a prior history of difficulty.
3. Predicting difficult mask ventilation
Predicting difficulty with mask ventilation is a very important factor when planning
airway management-the inability to ventilate carries a much higher risk to the patient than the
inability to intubate. Several patient risk factors have been associated with difficult mask
ventilation (Table 2).6 Difficult mask ventilation has also been identified as a risk factor for
difficult intubation.7
Table 2: Risk factors for difficult mask ventilation

Increased Body Mask Index (BMI)
Snoring/Obstructive Sleep Apnea
Presence of Beard
Lack of dentition
Age > 55 years
Mallampati III or higher
Male Gender
Airway masses/tumors
4. Airway management of the obese patient
The prevalence of obesity continues to rise in both the United States and worldwide. Currently,
65% of Americans are classified as overweight, and all states in the U.S. have an obesity rate of 20% or
higher based on 2010 data from the Center for Disease Control.8 The incidence of childhood obesity is also
increasing. The World Health Organization predicts that by 2015 over 0.5 billion people will meet the
criteria for obesity.9
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The current evidence in the literature is equivocal as to whether obesity is a clear risk factor for difficult mask
ventilation or intubation.10,11 Several studies show that with proper “ramp” positioning, airway management of the
obese patient can be successful.12,13There are other studies, however, that do demonstrate an association between
obesity and increased difficulty with airway management.
5. Alternate Airway devices
The ASA Practice Guidelines for management of the Difficult Airway recommend the use of
alternate airway devices when conventional methods fail. The guidelines also recommend that
alternate airway devices be readily available in the operating room setting.14 With the large number of
airway devices now available, it is difficult to become proficient in the use of every device. Individual
providers should choose one or two devices from the variety of classes of devices available to them
and become comfortable with their use in difficult airway management.
The use of the supraglottic airway was added to the current 2003 version of the ASA Difficult
Airway Algorithm as a rescue device in the cannot ventilate-cannot intubate scenario. A variety of
Supraglottic Airway Devices are now available, and many of these devices have been adapted to allow
intubation via the device as well as evacuation of the stomach (Table 3). Two of these devices, the Air-
Q and the i-gel, contain malleable cuffs that do not require insufflation.
Table 3: Supraglottic Airway Devices

Brand Device Offered Allows Designed for Disposable/Reusable Pediatric
decompression of intubation versions sizes
the stomach
LMA Classic LMA No No Yes/Yes Yes
America Proseal LMA Yes No No/Yes Yes
LMA Supreme Yes No Yes/No Yes
FastTrach LMA No Yes Yes/Yes Yes
Ambu AuraStraight No No All disposable Yes
Aura40 No No Yes
AuraFlex No No Yes
Aura-i No No Yes
AuraOnce No No Yes
Smiths Portex LM No No All disposable Yes
Medical Portex Soft Seal No No
Intersurgical i-gel Yes No All disposable Yes
King King LT No No Yes/Yes Yes
King LT-S Yes No
Teleflex Rusch Easy tube Yes No All disposable No
Sure Seal LM No Yes
Mercury Air-Q No No All disposable Yes
Medical
SLIPA SLIPA No No Yes/No No
Flexicare LarySeal LM No No All disposable Yes
Fiberoptic Intubation Devices

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Fiberoptic intubation remains one of the most versatile airway management techniques since it can be
performed via either the oral or nasal route and in both an awake or anesthetized patient. In the awake patient,
adequate airway topicalization is required. Fiberoptic intubation is a necessary skill for any anesthesia provider.
Most fiberoptic scopes allow for suctioning of the airway as well as delivery of lidocaine. Some are battery
operated, and all can be connected to a video system for better viewing as well as recording. A single use, battery
operated fiberoptic scope is also available (Ambu aScope) that can be attached to a portable video monitor.
Videolaryngoscopes (Table 4)
Although videolaryngoscopes are not mentioned in the 2003 version of the ASA difficult airway
algorithm, they now play a major role as an alternative to conventional laryngoscopy. Both reusable and disposable
devices not exist, and all allow more anterior exposure of the larynx compared to conventional laryngoscopy as well
as the ability to display the laryngeal structures on a video screen.
Table 4: Videolaryngoscopes
Brand Disposable? Stylet needed Channel for Battery Pediatric

ETT operated sizes
Glidescope Blades only Yes No No Yes
(Verathon Medical) (Cobalt version)
C-Mac/Video No Yes No No Yes

Macintosh system
(Karl Storz)
Pentax AWS Blades only No Yes Yes Adolescent
(Pentax/Ambu) only
Mcgrath scope Blades only Yes No Yes No
King Vision Scope Blades only Only for Yes Yes No
(King Systems) unchanneled
blade
Airtraq Entire device No Yes Single Yes
use
CoPilot VL (Magaw No No Yes Yes No
Medical)
Bullard No Built into No No Yes
device
Truview (Truphatek) No Yes No Yes Yes
Venner (Venner Blades only No Yes Yes No
Capital)
Clarus Video stylet No No ETT loaded Yes No
(Clarus Systems) directly
onto stylet
RIFL stylet (AI No No ETT loaded Yes No
Medical Devices) directly
onto stylet
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Other Devices:
It is beyond the scope of this lecture to review all the available classes of airway management devices, so
only a short list of additional classes of devices are provided below.
a. Endotracheal tube introducers
i. Frova intubating catheter-available in pediatric and adult sizes
ii. Aintree Intubating Catheter-allows passage of a fiberoptic scope inside the catheter
iii. Cook Airway Exchange catheter-available in a variety of sizes
iv. Sun Med Tracheal Tube introducer-single size
v. Radlyn stylet
b. Lighted intubating stylets
i. Shikani optical stylet
ii. Flexible Airway Scope Tool (FAST)
iii. Levitan stylet
iv. Bonfils retromolar intubation fiberscope
v. Air-Vu Plus fiberoptic stylet
vi. Sensascope semirigid intuboscope
6. Extubation
Extubation, especially in the difficult airway patient, can be just as challenging as

intubation. Recently extubated patients requiring re-intubation pose additional challenges. Often
the airway is edematous, hemodynamic instability may be present, and often the environment in
which the airway must be managed is small. According to the ASA Closed Claims database, 12%
of claims involving airway management are associated with extubation.2
The Difficult Airway Society in the United Kingdom recently published guidelines for
tracheal extubation.15 These guidelines suggest that planning for extubation begin prior to
induction of anesthesia, and propose two algorithms: a “low-risk” and high-risk” pathway. Both
the DAS guidelines as well as other studies support the use of an airway exchange catheter as a
bridge to extubation.15, 16 This technique has several advantages: the catheter can be left in place
for as long as needed, is well tolerated by patients, an provides a conduit for re-intubation.
7. Difficult airway reporting and tracking
Dissemination of difficult airway information among providers and between institutions continues to
be a challenge. Although many institutions and some countries maintain databases of patients identified as
a “difficult airway”, no system currently exists to share this information. In the United States, the Medic
Alert Registry provides a method to collect and disseminate critical information about a variety of medical
conditions including difficult airway but requires a subscription by the patient and encouragement by
medical providers to enroll.17
Alert bracelets are widely used throughout hospitals for allergy alerts and can also be used for difficult
airway alerts, but these bracelets only function in an individual hospital environment.
Electronic patient records also provide an opportunity to document difficult airway information and
disseminate this information to all hospital providers.
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8. Airway challenges outside the Operating Room
Despite the widespread availability of advanced airway devices, airway management continues to be
more challenging outside the operating room environment. Several studies as well as the ASA closed
claims database have demonstrated an increased incidence of complications associated with airway
management outside the operating room setting.18 The Fourth National Audit Project (NAP4) was
published last year (Table 5) and reported that 60% of airway-related adverse events in the ICU resulted in
death or brain damage. 19
Table 5: Fourth Nati onal A udit Pro ject (NA P4) Results
Prospective study of airway-related adverse events over 1 year period of 300 hospitals in UK
61% of airway events in the ICU resulted in death or brain damage
Co mmo n themes:
Almost 50% of cases obese
Large number of events occurred in off hours
Lack of capnography, lack of needed equipment
Lack of experienced personnel, inadequate training
Delayed recognition of high risk patients
Lack of back-up plans for management
9. Role of standardization
Standardization is a common practice in Aviation and Industry to improve efficiency and

decrease errors and has recently been applied to health care and airway management.
Standardization of equipment and procedures as well as standardized training of personnel has
been shown to reduce adverse airway events.20 The ASA also recommends the availability of
consistent airway equipment in the OR setting.
10. Airway Education
As additional airway devices continue to be introduced into practice, continuing education and
practice of these devices is essential for safe airway management. As important as competence in use
of these devices is the ability to create and implement a variety of intubation plans. Specific airway
rotations required during residency training can provide opportunities for exposure to and adequate
experience in a variety of airway techniques. 21,22
Simulation has long been used in Aviation for teamwork training and standardization of practice,
with documented reduction in errors.23 Simulation has recently been introduced into the medical
environment, and is now widely used to teach decision making and teamwork. Simulation provides a
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safe environment in which to teach airway skills, familiarity with new airway devices, as well as
teamwork and communication during complicated airway management scenarios. The additional
advantages of simulation are the opportunity to immediately review and debrief events as well as
simulate rare clinical events.24-28
11. Airway competency-how do we define it?
A current area of controversy is airway competency: how is competency in airway management

defined, and should competency be assessed and documented during residency training? The number of
times an airway procedure must be performed before competency is obtained is currently unknown, and
most likely varies among providers and between airway devices. Formal airway rotations during residency
can help insure that the opportunity exists to obtain competency with a variety of airway techniques and
devices.
Conclusion
Management of the difficult airway, both inside and outside the operating room setting, requires a thorough
airway examination whenever possible to predict difficulty with both ventilation and intubation. Novel airway
evaluation methods such as endoscopy and ultrasound may assist in prediction of difficulty. A variety of airway
devices are available to assist with difficult airway management, and the anesthesia provider should be familiar with
several types of these devices in order to create back-up airway plans. The individual plan will depend on patient
disease, provider expertise, and the airway equipment available for use. Complex airway management outside the
operating room setting continues to be a challenge, and having the correct equipment and training to manage
patients outside the operating room can potentially reduce adverse events.
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References
1.Metzner L, Posner K, Lam MS, Domino KB. Closed claims’ analysis. Best Practice & Research Clinical
2.Domino KB, Posner KL, Caplan RA. Cheney FW. Airway injury during anesthesia-a closed claims analysis.
3.Rosenblatt W, Ianus AI, Sukhupragarn W, Fickenscher A, Sasaki C. Preoperative endoscopic airway examination
(PEAE) provides superior airway information and may reduce the use of unnecessary awake intubation. Anesth
Analg 2011; 112: 602-7.
4.Kristensen MS. Ultrasonography in the management of the airway. Acta Anaesthesiol Scand 2011;55: 1155-1173.
5.Benumof’s Airway Management, 2nd Edition, C. Hagberg, editor, Mosby, 2007.
6. El-Orbany M, Woehlick HJ. Difficult mask ventilation. Anesth Analg 2009;109: 1870-80.
7.Langeron O, Masso E, Huraux C, Guggiari M, Blanchi A, Coriat P, Riou B.. Prediction of difficult mask
ventilation. Anesthesiology 2000;92: 1229-36..
8. Behavioral Risk factor Surveillance System, Center for Disease Control
9. World Health Organization www.who.org
10.Juvin P, Lavaut E, Dupont H, Lefevre P, Demetriou M, Dumolin JL, Desmonts JM. Difficult tracheal intubation
is more common in obese than lean patients. Anesth Analg 2003; 97: 595-600.
11. Lavi R, Segal D, Ziser A. Predicting difficult airways using the intubation difficulty scale: a study comparing
obese and non-obese patients. J Clin Anesth 2009;21: 264-7.
12. Rao SL, Kunselman AR, Schuler HG, DesHarnais S.. Laryngoscopy and tracheal intubation in the head-elevated
position in obese patents: a randomized, controlled, equivalence trial. Anesth Analg 2008;107:1912-8.
13.Cattano D, Melnikov V, Khalil Y, Sridhar S, Hagberg C.. An evaluation of the rapid airway management
positioner in obese patients undergoing gastric bypass or laparoscopic gastric banding surgery. Obes Surg
2010;20:1436-41.
14.American Society of Anesthesiologists Task Force on Difficult Airway management. Practice guidelines for
management of the difficult airway. Anesthesiology 2003; 98:1269-1277.
15. Popat M, Mitchell V, Dravid R, Patel A, Swampillai C, Higgs A. Difficult Airway Society guidelines for the
management of tracheal extubation. Anaesthesia 2012; 67: 318-340.
16.Mort TC. Continuous airway access for the difficult extubation: the efficacy of the airway exchange catheter.
Anesth Analg 2007;107: 1357-62.
17. www.medicalert.org
18.Mort TC. The incidence and risk factors for cardiac arrest during emergency tracheal intubation: a justification
for incorporating the ASA guidelines in the remote location. J Clin Anesth 2004; 16: 508-16.
19.Cook TM et al. Major complications of airway management in the UK: results of the Fourth National Audit
Project of the Royal College of Anaesthetists and the Difficult Airway Society. Part 2: intensive care and emergency
departments. Br J Anaesth 2011; 106: 632-42.
20.Berkow et al. Need for emergency surgical airway reduced by a comprehensive difficult airway program. Anesth
Analg 2009; 109:1860-9.
21.Borovcanin Z, Shapiro JR. Design and implementation of an educational program in advanced airway
management for anesthesiology residents. Anesthesiol Res Pract 2012;epub Feb 28.
22. Baker PA, Weller JM, Greenland KB, Riley RH, Merry AF. Education in airway management. Anaesthesia
2011; 66: Suppl 2101-11.
23. Johnston N. Integrating human factors training into ab initio airline pilot curricula. ICAO J 1993;48: 14-17.
24.Sudikoff SN, Overly FL, Shapiro MJ. High-fidelity medical simulation as a technique to improve pediatric
residents’ emergency airway management and teamwork. Pediatr Emer Care 2009;25: 651-6.
25.Zirkle M, Blum R, Raemer DB, Healy G, Roberson DW. Teaching emergency airway management using
medical simulation: a pilot program. Laryngoscope 2005;115: 495-500.
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26.Volk MS, Ward J, Irias N, Navedo A, Pollart J, Weinstock PH. Using medical simulation to teach crisis resource
management and decision making skills to Otolaryngology housestaff. Otolaryngol Head Neck Surg. 2011
27. Gaba DM, Howard SK, Fish KJ et al. Simulation-based training in anesthesia crisis resource management
(ACRM): a decade of experience. Simul Gaming 2001; 32: 175-93.
28.Capella et al. Teamwork training improves the clinical care of trauma patients. J Surg 2010;67: 439-43.
DISCLOSURE
Masimo Corporation: Speaker board, funded research, Scientific Advisory Board
Ambu Corporation-Consultant, Honoraria
Medtronic Xomed Inc-Consultant, Honoraria
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The Evolution of Our Views of How Anesthetics Act to Produce Anesthesia

Eemond I Eger II, M.D. San Francisco, California
Suggestions as to how anesthetics act arose shortly after the public demonstration (or attempted demonstration) of
anesthesia from administration of nitrous oxide and ether. Most of this discussion of the evolution of our thinking
on anesthetic mechanisms focuses on the workings of inhaled anesthetics, and particularly on their capacity to
reversibly produce immobility in the face of noxious stimulation such as surgery, an immobility mediated by the
central nervous system. We recognize that the anesthetic state also includes the production of amnesia.
Horace Wells failed in his attempt to publically demonstrate the anesthetic effects of nitrous oxide in 1844, but he
had succeeded privately in his dental office. In 1846 he wrote in the Hartford Courant that “…an exhilarating gas,
sufficient to cause a great nervous excitement, would so paralyze the system as to render (it) insensitive to pain….”
Although we may smile at this simplistic explanation, perhaps Wells was on to something. After all, we have many
anecdotes attesting to the loss of pain perception that can attend great excitement as in battle.1 William Morton, who
on 16 Oct 1846 succeeded in his demonstration of the anesthetic properties of diethyl ether, appears to have had no
idea as to what caused anesthesia.
In 1847, Ernst von Bibra and Emil Harless noted that ether could dissolve lipids.2,3 They proposed that anesthetics
extracted fat from brain cells, thereby altering function in some manner that caused anesthesia. Anesthetics dry-
cleaned the brain.
Skip ahead to the 1870s and Claude Bernard, the great French physiologist, who noted that all of life’s forms could
be “anesthetized” (with the caveat that the definition of anesthesia in a plant might be dicey), suggesting to him that
some underlying, unitary mechanism explained anesthesia.4 The notion of a unitary theory was appealing, in no
small part because of its parsimonious nature. Further, Bernard proposed that the mechanism might be reversible
coagulation of nerves, perhaps a protein theory of narcosis.5
At the turn of the century, Meyer6 and Overton7 recognized two difficulties with the Bibra-Harless theory. First,
there was no easy way to explain how the departure of anesthetic from the body would get the brain lipids back to
where they belonged. How could the Bibras-Harless theory explain why the patient woke up so quickly? And there
was the problem that dilute solutions of ether, concentrations sufficient to cause anesthesia, do not dissolve lipids.
Meyer and Overton then turned the Bibra-Harless proposal on its head by suggesting that anesthetics act by
dissolving in lipid rather than by dissolving lipids. In support of this hypothesis, they demonstrated that anesthetic
potency is proportional to anesthetic affinity for a lipid phase relative to an aqueous phase. Their theory can be
expressed in modern terms (changing the relative affinity from water to gas as suggested by Meyer’s son)8 as an
equation: for any anesthetic, MAC (in atmospheres) times the oil/gas partition coefficient of the anesthetic equals a
“constant”. In rats, the constant on average is 1.8 atm for conventional inhaled anesthetics with about a 2-fold range
for a 1,000-fold or greater range of potencies, a remarkable correlation. Of itself, this isn’t a theory, but as Nick
Franks noted (personal communication): “The simplest interpretation of this observation is that whatever
determines the solubility of anesthetics in olive oil, also determines their solubility at their sites of action in the
brain…and that something must be happening to these lipids which causes anesthesia.” Going a step further, the
Meyer-Overton correlation implies that anesthetics might act in the middle of the lipid bilayer.
Some of the giants in the field of mechanisms liked the idea that anesthetics acted by doing something to lipids.9
But others did not. In 1951, TAB Harris argued that there were severe exceptions to the correlation, exceptions that
ruled it out (later, Franks and Lieb said the same thing, as later still so did Koblin and Eger).10 Harris thought that
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anesthetics might act by impeding diffusion through membranes, or, even more likely, by depressing metabolism
[well, after all, Krebs had recently (1937) postulated his cycle]. And lots of evidence indicated that various
anesthetics did decrease metabolism. But then there was the chicken-egg problem: did a decrease in metabolism
cause anesthesia or did anesthesia cause a decrease in metabolism? And, as we were to learn later, some anesthetics
(e.g., nitrous oxide) don’t decrease cerebral metabolism but do cause anesthesia.
In 1961, Pauling11 and Miller12 formulated their hydrate, or clathrate, or iceberg theory of anesthesia. They
suggested that in conjunction with proteins, anesthetics could cause the formation of crystals of water at the surface
of membranes, thereby impairing function and causing anesthesia. They supported their theory by noting that the
partial pressure of anesthetics at 0°C that could form clathrates correlated with their potencies as anesthetics, a
support similar to that used by Meyer and Overton. But there were problems with such support. One was that some
anesthetics did not form clathrates at any pressure that could be generated (i.e., their saturated vapor pressure). And
second, clathrates disintegrated at temperatures slightly greater than 0°C. And third, for those anesthetics that did
form clathrates, there were some that deviated considerably from the line of correlation.13
In 1963, Merkel and Eger, prompted by their mentor John Severinghaus, invented MAC.14 MAC was no theory of
narcosis, but it would help in the testing of theories of narcosis, in defining which might be relevant and where,
anatomically, inhaled anesthetics acted.
The Meyer-Overton “theory” swung back into favor in the 1970s, with several mechanisms proposed that were
prompted by the notion that anesthetics acted in the membrane bilayer. Perhaps anesthetics increased membrane
fluidity,15 thereby destabilizing the structure of proteins embedded in the protein. But then, how did one explain the
finding that increases in temperature increased anesthetic requirement (increased MAC),16 when they also increased
fluidity and thus should have decreased MAC? Or perhaps anesthetics thickened membranes when they dissolved in
the membranes and that was how they worked.17 One of the attractive things about these theories is that they were
testable. When tested they were found wanting. For example, Franks and Lieb didn’t find any thickening – or any
measurable structural changes.18 All these theories collapsed.
Things got worse for the Meyer and Overton correlation. As observed earlier, TAB Harris, and Franks and Lieb had
noted exceptions. So did Koblin et al.19 Koblin found compounds far less potent than their lipophilicity predicted,
and found some compounds that had no potency at all (nonimmobilizers). And then there were alcohols that were
more potent than their lipophilicity predicted.20,21 It was noted, though, that these data might be construed as
suggesting a more complex “Meyer-Overton” correlation, one that asked an anesthetic to have an affinity for both
polar and non-polar components, be amphipathic. Franks had suggested this earlier,18 and Pohorille had added to
the thought.22 If correct, this implied that anesthetics acted at an interface where they could exist partly in a polar
and partly in a non-polar phase.
Then, in the 1980s, Franks and Lieb definitively shifted the focus from lipids to proteins. They pointed out that the
pretty correlation that Meyer and Overton had found also could be found for the action of diverse anesthetics on a
protein, luciferase.23 Adding to their case, they found stereospecific effects of inhaled anesthetics on nerve ion
channels.24 Such findings and the inability to find a defensible lipid theory turned attention to proteins, to actions on
specific channels and receptors. There followed in the next decades an outpouring of reports of effects on such
proteins, most showing an action of inhaled anesthetics that plausibly explained how anesthetics acted – inhibition
of an excitatory channel or enhancement of the response of an inhibitory channel. Adding to the argument for a
specific effect on a protein, Jurd et al. engineered a knockin mouse that was “normally” responsive to GABA but
whose GABAA receptor was not enhanced in its response to GABA by etomidate or propofol. This mouse
responded to pinching the paw after receiving several times the dose of propofol or etomidate that caused
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unresponsiveness in wild-type mice, proving that the GABAA receptor mediated this aspect of etomidate or propofol
anesthesia
But which was the important channel? Were they all important? Or were none of them important? Since inhaled
anesthetics also enhanced the GABAA receptor, shouldn’t the same thing be true for a knockin mouse that didn’t
have enhancement from an inhaled anesthetic – if the GABAA receptor mediated the action of, say, isoflurane? If it
were correct for etomidate and propofol, why not for isoflurane? But it wasn’t; the isoflurane MAC of the
isoflurane knockin mouse did not increase relative to the MAC of the wild-type mouse.25 Indeed, using various tests
of relevance, none of the plausible receptors provided more than slight evidence that they might explain anesthesia
(immobility) by inhaled anesthetics, and most provided no real evidence at all.26 Regarding the knockin mouse test,
it is worth mentioning that GABAA receptors come in many flavors, and etomidate has a different selectivity relative
to isoflurane, so, perhaps the implication of the finding is not quite black and white.
In 1993, Rampil et al.27 and Antognini et al.28 made a major advance. Independently they showed that the spinal
cord, and not the brain, mediated the capacity of inhaled anesthetics to produce immobility in the face of noxious
stimulation. In 2007, Kim et al.29 went one step further, demonstrating that immobility resulted from an action on
the ventral horn of the cord and not on the dorsal horn. And finally, Jinks et al.30,31 provided evidence that the action
in the ventral horn was on central pattern generators and not on motor neurons. So inhaled anesthetics acted on
central pattern generators in the ventral horn of the spinal cord to produce immobility.
But we still did not know how that action might be accomplished. What mediated the effect on a molecular level?
Cantor and Sonner and others have been asking that question with some tentative answers that await further testing.
In 1997, Cantor suggested that an action of inhaled anesthetics at the bilayer surface altered the lateral pressure
profile at the surface.32 By altering this pressure, anesthetics might alter the function of channels embedded in the
bilayer. In 2007, Cantor proposed a different idea, that anesthetics may act on the membrane interface surrounding
an ionophore in a way that mimicked an effect of natural neurotransmitters.33 That year, Milutinovic from Sonner’s
group supplied evidence supporting Cantor’s theory.34
More evidence remains to be gathered regarding the notions presented by Cantor. They are exciting new ideas,
ideas outside the mainstream of thinking regarding anesthetic mechanisms. What is particularly exciting about
Cantor’s notions is that they may also provide radically new insights into how the central nervous system functions.
Acknowledgments: Most of the material in this summary comes from an essay on the title’s topic written by Nick
Franks for an as yet unpublished book on the history of anesthesia, and I thank him for allowing me to use that
material. I also thank him and Jim Sonner for their guidance in the construction of this summary.
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References
1. Beecher HK: Pain in Men Wounded in Battle. Ann Surg 1946; 123: 96-105
2. von Hintzenstern U, Petermann H, Schwarz W: [Early contributions from Erlangen to the theory
and practice of general anesthesia with ether and chloroform. 2. The animal experiments of Ernst von Bibra and
Emil Harless]. Anaesthesist 2001; 50: 869-80
3. von Bibra E, Harless E: Die wirkung des schwefelaethers in chemischen und physiologischen
bezigkung. Erlangen. 1847.
4. Bernard C: Lecons sur les anesthesique et sur l'asphyxsie. Paris: JB Balliere et Fils, 1875.
5. Bancroft WD, Richter GH: Claude Bernard's Theory of Narcosis. Proc Natl Acad Sci U S A 1930;
16: 573-7
6. Meyer HH: Theorie der Alkoholnarkose. Arch Exptl Pathol Pharmakol 1899; 42: 109-18
7. Overton E: Studien über die Narkose, Zugleich ein Beitrag zur allgemeinen Pharmakologie.
Gustav Fischer, Jena 1901, pp 1-195
8. Meyer KH, Gottlieb-Billroth H: Theorie der Narkose durch Inhalationsanästhetika. Z Physiol
Chem 1920; 112: 55-79
9. Henderson VE: The present status of the theories of narcosis. Physiological Reviews 1930; 10:
171-220
10. Harris TAB: The Mode of Action of Anaesthetics. Williams and Wilkins. Baltimore, 1951, pp 1-
768.
11. Pauling L: A molecular theory of anesthesia. Science 1961; 134: 15-21
12. Miller S: Theory of gaseous anesthetics. Proc Natl Acad Sci USA 1961; 47: 1515-24
13. Eger EI, II, Lundgren C, Miller S, Stevens WC: Anesthetic potencies of sulfur hexafluoride,
carbon tetrafluoride, chloroform and Ethrane in dogs: Correlation with the hydrate and lipid theories of anesthetic
action. Anesthesiology 1969; 30: 129-35
14. Merkel G, Eger EI, II: A comparative study of halothane and halopropane anesthesia. Including a
method for determining equipotency. Anesthesiology 1963; 24: 346-57
15. Rosenberg PH, Jansson SE, Gripenberg J: Effects of halothane, thiopental, and lidocaine on
fluidity of synaptic plasma membranes and artificial phospholipid membranes. Anesthesiology 1977; 46: 322-6
16. Eger EI, II, Saidman LJ, Brandstater B: Temperature dependence of halothane and cyclopropane
anesthesia in dogs: Correlation with some theories of anesthetic action. Anesthesiology 1965; 26: 764-70
17. Haydon DA, Hendry BM, Levinson SR, Requena J: The molecular mechanisms of anaesthesia.
Nature 1977; 268: 356-8
18. Franks NP, Lieb WR: Where do general anaesthetics act? Nature 1978; 274: 339-42
19. Koblin DD, Chortkoff BS, Laster MJ, Eger EI, II, Halsey MJ, Ionescu P: Polyhalogenated and
perfluorinated compounds that disobey the Meyer-Overton hypothesis. Anesth Analg 1994; 79: 1043-8
20. Won A, Oh I, Liao M, Sonner JM, Harris RA, Laster MJ, Brosnan R, Trudell JR, Eger EI, 2nd:
The minimum alveolar anesthetic concentration of 2-, 3-, and 4-alcohols and ketones in rats: relevance to anesthetic
mechanisms. Anesth Analg 2006; 102: 1419-26
21. Eger EI, II, Ionescu P, Laster MJ, Fang Z, Gong D, Hudlicky T, Kendig J, Harris A, Trudell J,
Pohorille A: MAC of fluorinated alkanols in rats: Relevance to theories of narcosis. Anesth Analg 1999; 88: 867-76
22. Pohorille A, Cieplak P, Wilson MA: Interactions of anesthetics with the membrane-water
interface. Chem Phys 1996; 204: 337-45
23. Franks NP, Lieb WR: Do general anaesthetics act by competitive binding to specific receptors?
Nature 1984; 310: 599-601
24. Franks NP, Lieb WR: Stereospecific effects of inhalational general anesthetic optical isomers on
nerve ion channels. Science 1991; 254: 427-30
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25. Sonner JM, Werner DF, Elsen FP, Xing Y, Liao M, Harris RA, Harrison NL, Fanselow MS, Eger
EI, 2nd, Homanics GE: Effect of isoflurane and other potent inhaled anesthetics on minimum alveolar concentration,
learning, and the righting reflex in mice engineered to express alpha1 gamma-aminobutyric acid type A receptors
unresponsive to isoflurane. Anesthesiology 2007; 106: 107-13
26. Eger EI, II, Raines DE, Shafer SL, Hemmings HC, Jr, Sonner JM: Is a new paradigm needed to
explain how inhaled anesthetics produce immobility? Anesth Analg 2008; 107: 832-48
27. Rampil IJ, Mason P, Singh H: Anesthetic potency (MAC) is independent of forebrain structures in
the rat. Anesthesiology 1993; 78: 707-12
28. Antognini JF, Schwartz K: Exaggerated anesthetic requirements in the preferentially anesthetized
brain. Anesthesiology 1993; 79: 1244-9
29. Kim J, Yao A, Atherley R, Carstens E, Jinks SL, Antognini JF: Neurons in the ventral spinal cord
are more depressed by isoflurane, halothane, and propofol than are neurons in the dorsal spinal cord. Anesth Analg
2007; 105: 1020-6
30. Jinks SL, Atherley RJ, Dominguez CL, Sigvardt KA, Antognini JF: Isoflurane disrupts central
pattern generator activity and coordination in the lamprey isolated spinal cord. Anesthesiology 2005; 103: 567-75
31. Jinks SL, Bravo M, Hayes SG: Volatile anesthetic effects on midbrain-elicited locomotion suggest
that the locomotor network in the ventral spinal cord is the primary site for immobility. Anesthesiology 2008; 108:
1016-24
32. Cantor RS: The lateral pressure profile in membranes: A physical mechanism of general
anesthesia. Biochemistry 1997; 36: 2339-44
33. Cantor RS: Receptor desensitization by neurotransmitters in membranes: are neurotransmitters the
endogenous anesthetics? Biochemistry 2003; 42: 11891-7
34. Milutinovic PS, Yang L, Cantor RS, Eger EI, 2nd, Sonner JM: Anesthetic-like modulation of a
gamma-aminobutyric acid type A, strychnine-sensitive glycine, and N-methyl-d-aspartate receptors by coreleased
neurotransmitters. Anesth Analg 2007; 105: 386-92
DISCLOSURE
Baxter Healthcare, Self, Consulting Fees
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Patient Blood Management from Blood Product to Patient Centered Care
Aryeh Shander, M.D. Englewood, New Jersey
Evidence has shown that current clinical practice of allogeneic blood transfusion is in dire need of reassessment.
Concerns regarding the safety and efficacy of allogeneic blood transfusions, their impact on patient outcomes, and
the astounding costs and challenges associated with supply reserves of blood products have fueled the quest for
alternative strategies to reduce blood use while meeting the needs of a growing population. Blood has always been
perceived as a “life saver” and as such has become a very emotional topic. The revisiting of transfusion practices
have highlighted the potential risks associated with allogeneic blood and the lack of convincing evidence of its
benefit in non-hemorrhaging and many transfusion dependent patients. The evidence highlighting the association of
allogeneic blood transfusion with worse outcomes – not just the known and relatively rare side effects of
transfusion, but significant and substantial negative impact on mortality, morbidity and length of hospital stay – is
rapidly growing. Most recently, Ferraris and colleagues studied 8,728 cardiac surgeries in 173 U.S. hospitals and
reported that after propensity adjustment, transfusion of 1-2 units of packed blood intraoperatively increased the risk
of composite morbidity, pulmonary complications, systemic sepsis, wound complications, and postoperative length
of stay.1 In another study, Koch and colleagues looked at 16,847 patients undergoing on-pump, coronary artery
bypass grafting (CABG), valve, or combined CABG-valve surgeries, and using propensity-score-matching analysis,
they found out that patients who received red blood cell transfusion had increased risk of respiratory distress (4.8%
vs. 1.5%, p < 0.001), respiratory failure (2.2% vs. 0.39%, p < 0.0001), and acute respiratory distress syndrome
(0.64% vs. 0.21%, p = 0.015), were more likely to need reintubation (5.6% vs. 1.3%, p < 0.0001), and had prolonged
duration of intubation (9.9 hours vs. 7.5 hours, p < 0.0001) compared with patients who were not transfused.2
Reports of negative outcomes of transfusion are not limited to cardiac surgery: Glance et al studied 10,100 patients
undergoing general, vascular or orthopedic surgeries and concluded that intraoperative transfusion was associated
with increased risk of death (Odds Ratio [OR] 1.29, 95% CI 1.03-1.62), pulmonary complications (OR 1.76, 95% CI
1.48-2.09), sepsis (OR 1.43, 95% CI 1.21-1.68), thromboembolic complications (OR 1.77, 95% CI 1.32-2.38) and
wound complications (OR 1.87, 95% CI 1.47-2.37).3 Pedersen et al analyzed data from 28,087 patients undergoing
primary total hip replacement surgery, and reported that transfusion was independently associated with increased
risk of 90-day mortality (OR 2.2, 95% CI 1.2-3.8) and pneumonia (OR 2.1, 95% CI 1.2-3.8).4 Finally, Wu and
colleagues studied 239,286 elderly patients undergoing non-cardiac surgery and showed that after propensity-score
matching, transfusion in patients with hematocrit of 30-36% or surgical blood loss <500 mL was associated with
increased 30-day mortality, while it was associated with lower mortality in patients with preoperative hematocrit
<224% or blood loss >500 mL.5 Based on available evidence, an international multidisciplinary panel has rated
allogeneic red blood cell transfusions to be unlikely or uncertain to improve the clinical outcomes of stable non-
bleeding patients in nearly 90% of the common transfusion scenarios reviewed. Transfusion scenarios that were
deemed appropriate were mostly limited to patients older than 65 years old with hemoglobin of <8 g/dL and pre-
existing comorbidites.6
Burgeoning numbers of studies have indicated that clinical outcomes in patients who are treated without blood or
with a conservative transfusion strategy are often comparable with or better than outcomes of similar patients who
are transfused. While most of these data are from observational studies, a Cochrane systemic review of 17 trials
(including the pivotal TRICC trial) on a total of 3746 patients indicated that restrictive transfusion strategies are
expectedly effective in reducing transfusion rates by 37% (95% Confidence Interval [CI] 26%-46%) and reducing
transfusion volumes by an average of 0.75 units (95% CI 0.2-1.3 units). More importantly, this review shows that
restrictive transfusion strategies do not worsening patient outcomes (including mortality, cardiac events, stroke,
pneumonia and thromboembolism) and are able to reduce infections (Relative Risk 0.76, 95% CI 0.6-0.97) in
hospitalized patients.7 Hence, it is not surprising that newer guidelines from multiple organizations on allogeneic
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blood transfusion are moving towards restrictive rather than a liberal blood transfusion therapy.8-10 Ultimately,
patient outcome has to be the focus rather than the use of blood components and Patient Blood Management (PBM)
is posed to address this need.
Patient blood management is the timely application of evidence-based medical and surgical concepts designed to
maintain hemoglobin concentration, optimize hemostasis and minimize blood loss in an effort to improve patient
outcome. Given the importance of the issue and substantial potentials for improving the quality of care and outcome
of the patients, PBM is being endorsed by various national and international organizations and societies. In the 63rd
World Health Assembly resolution, World Health Organization emphasized the need to implement PBM strategies
and urged member states “to promote the availability of transfusion alternatives including, where appropriate,
autologous transfusion and PBM”.1 Based on this resolution, the Advisory Committee on Blood Safety and
Availability has recently recommended that the U.S. Department of Health and Human Services promulgate national
standards on blood use and management, to establish metrics on PBM, and PBM be integrated into formal medical
education as well as into the electronic health records.2 Similarly, The Joint Commission has developed a number of
PBM Performance Measures. Although not endorsed for use at national level yet, these measures provides useful
tools for evaluating transfusion practices and ways to improve them as institutions.3
Patient blood management focuses on multidisciplinary and multimodality preventive measures to reduce the need
for blood transfusions and ultimately to improve clinical patient outcomes. Strategies associated with PBM can be
applied at every stage of care of surgical and non-surgical patients. Studies have shown that the vast majority of
transfusions in surgical patients can be attributed to one or a combination of the following factors: low preoperative
hemoglobin levels, excessive surgical blood loss, and/or inappropriate transfusion practices.11 For the surgical
patients, patient blood management relies on these key strategies:
• Optimizing hematopoiesis
• Correcting hemostatic abnormalities and minimizing bleeding and blood loss, and
• Harnessing and optimizing physiological “tolerance” of anemia through application of all available
modalities, leaving transfusion as the last resort.12
Although the patient blood management approach is more commonly associated with the peri-operative period,
many strategies are also applicable to non-surgical patient populations, and should be considered in their care.
Clinicians should have a hands-on role in applying PBM strategies to an individual patient’s care, anticipate and be
prepared to address complications; consult with specialists experienced in patient blood management, when possible
utilize evidence-based medicine, and be prepared to modify routine practices (e.g. transfusion triggers) when
appropriate.13
While there are numerous proactive clinical measures that contribute to effective PBM, another key areas of focus
are preventive measures. Planning and preparation as early as possible in the patient care encounter is required to
optimize the patient’s condition (e.g. treatment of anemia, adjustment of the dose of anticoagulant or oral anti-
platelet agents). Patient blood management (PBM) can be more efficient with detailed planning for the procedure,
which can result in better pre-operative management and less blood loss during surgical procedures. For emergent
cases, it is advisable is to plan for rapid control of bleeding, and whenever possible, utilize information from an
advanced patient blood management center. In addition, a hospital-wide patient blood management program
effectively and efficiently collects data and monitors systems for continuous evaluation and improvement to remain
abreast of new and effective developments of this concept.12,13
1
http://apps.who.int/gb/ebwha/pdf_files/WHA63/A63_R12-en.pdf
2
http://hospitals.unitedbloodservices.org/abcnews/ABC_06_10_11.pdf
3
http://www.jointcommission.org/patient_blood_management_performance_measures_project/
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Judicious use of allogeneic blood products, in accordance with current guidelines, was an early consideration of
patient blood management and resulted in improved patient outcome. All transfusion guidelines emphasize that
blood products should be transfused only when clear physiologic need exists, rather than blindly based on arbitrary
hemoglobin or hematocrit “triggers.” The primary goal must always be to treat the patient, rather than achieving a
certain hemoglobin level.12,13 Whenever possible, physiologic indicators of tissue oxygen delivery and ischemia
should be used in guiding transfusion decisions. In many clinical settings, Transfusions occur only because of
missed opportunities for patient blood management.
Pre-operatively, a detailed history, physical examination and list of current medications with special emphasis on
risk factors for anemia and bleeding are critical elements in PBM. Anemia is not only a major risk factor for
transfusion, but it is also an independent predictor of morbidity and mortality. Patients should be monitored for
anemia throughout their course of care, but in particular, before surgery. Management of anemia does not merely
mean correcting the hemoglobin level, but rather treating the underlying cause of anemia with the appropriate use of
hematinic agents before surgery takes place. Untreated anemia should be regarded as a contraindication of elective
surgery.13,14
Intra-operatively, PBM strategies are centered towards minimizing blood loss (e.g. using various systemic and
topical haemostatic agents), auto transfusion techniques (e.g. acute normovolemic hemodilution and cell salvage),
and optimizing physiologic “tolerance” of anemia, (i.e. treating postoperative anemia with the appropriate
medications). Vital signs should be closely monitored and unnecessary hypovolemia and tachycardia should be
avoided.12,14
Patient blood management strategies continue after surgery into the postoperative care unit and beyond. In this
setting, red cell salvage can be performed and any blood lost in drains can be washed, filtered and re-infused if
needed, postoperatively. During the first few hours following surgery, close attention must be given to any ongoing
bleeding. If such postoperative bleeding cannot be promptly controlled, the patient should be returned to the
operating room for re-exploration without any delay. Again, vital signs must be thoughtfully monitored, and cardiac
output and ventilation/oxygenation should be optimized.12-14
The ultimate goal of patient blood management is to carefully evaluate clinical data while evaluating all treatments
for their effect on improving patients’ outcomes. Despite widespread use, allogeneic blood products have not
undergone such scrutiny, and the balance between their established risks and questionable benefits is often masked
by the pursuit to meet and surpass arbitrary laboratory thresholds. The appropriate use of blood components with the
ultimate goal of improving patient outcomes using multimodality approaches remains a challenge. PBM modalities
span every step in the care of patients and include various pharmacologic, anesthetic, and surgical interventions. As
mentioned above, when considering the use of any blood products, the physiologic need and expected benefit, as
well as the potential adverse effect on the outcome of the patients should be considered, rather than arbitrary
threshold values of hemoglobin or hematocrit. Importantly, the attitude of the clinicians toward their patient’s
condition and the role of allogeneic blood components is a central component of patient blood management.
Although the safety and efficacy of various modalities used in patient blood management should be evaluated
individually, clinical data on implementation of PBM is part of routine practice is emerging. A study comparing the
cardiac surgery data from a PBM center with other centers in the same geographical area indicated that transfusion
rate in the PBM center was significantly lower than other centers (10.6% vs. 42.5%), while rates of mortality and
serious complications were significantly lower in the ceter implementing PBM (0.8% vs. 2.5% for mortality and
11.1% vs. 18.7% for complications).15 A systematic review of the literature has confirmed that perioperative anemia
was prevalent in patient undergoing hip or knee surgery (24-44% preoperatively and 51-87% postoperativel) and it
was associated with high transfusion rate as well as unfavorable outcomes. However, implementation of various
PBM modalities (e.g. management of anemia and autologous transfusion) was able to decrease the blood
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transfusions and improved clinical outcomes.16 These and other studies support PBM as a safe and effective concept
in providing better care and improving patients’ outcomes while reducing transfusion of allogeneic blood
components and conserving the much needed resources.
References:
1. Ferraris VA, Davenport DL, Saha SP, Bernard A, Austin PC, Zwischenberger JB. Intraoperative transfusion
of small amounts of blood heralds worse postoperative outcome in patients having noncardiac thoracic
operations. Ann Thorac Surg. 2011 Jun;91(6):1674-80.
2. Koch C, Li L, Figueroa P, Mihaljevic T, Svensson L, Blackstone EH. Transfusion and pulmonary morbidity
after cardiac surgery. Ann Thorac Surg. 2009 Nov;88(5):1410-8.
3. Glance LG, Dick AW, Mukamel DB, Fleming FJ, Zollo RA, Wissler R, Salloum R, Meredith UW, Osler
TM. Association between intraoperative blood transfusion and mortality and morbidity in patients undergoing
noncardiac surgery. Anesthesiology. 2011 Feb;114(2):283-92.
4. Pedersen AB, Mehnert F, Overgaard S, Johnsen SP. Allogeneic blood transfusion and prognosis following
total hip replacement: a population-based follow up study. BMC Musculoskelet Disord. 2009 Dec 29;10:167.
5. Wu WC, Smith TS, Henderson WG, Eaton CB, Poses RM, Uttley G, Mor V, Sharma SC, Vezeridis M, Khuri
SF, Friedmann PD. Operative blood loss, blood transfusion, and 30-day mortality in older patients after major
noncardiac surgery. Ann Surg. 2010 Jul;252(1):11-7.
6. Shander A, Fink A, Javidroozi M, Erhard J, Farmer SL, Corwin H, Goodnough LT, Hofmann A, Isbister J,
Ozawa S, Spahn DR; International Consensus Conference on Transfusion Outcomes Group. Appropriateness of
allogeneic red blood cell transfusion: the international consensus conference on transfusion outcomes. Transfus
Med Rev. 2011 Jul;25(3):232-246.e53.
7. Carless PA, Henry DA, Carson JL, Hebert PP, McClelland B, Ker K. Transfusion thresholds and other
strategies for guiding allogeneic red blood cell transfusion. Cochrane Database Syst Rev. 2010 Oct
6;(10):CD002042. Review. Update in: Cochrane Database Syst Rev. 2012;4:CD002042.
8. Perkins HA, Busch MP. Transfusion-associated infections: 50 years of relentless challenges and remarkable
progress. Transfusion 2010; 50:2080-99.
9. Shander A, Goodnough LT. Why an alternative to blood transfusion? Crit Care Clin 2009; 25:261-77.
10. Shander A, Javidroozi M, Ozawa S, Hare GM. What is really dangerous: anaemia or transfusion? Br J
Anaesth. 2011; 107 Suppl 1:i41-59.
11. Gombotz H, Rehak PH, Shander A, Hofmann A. Blood use in elective surgery: the Austrian benchmark
study. Transfusion. 2007 Aug;47(8):1468-80.
12. Shander A, Javidroozi M, Perelman S, Puzio T, Lobel G. From bloodless surgery to patient blood
management. Mt Sinai J Med. 2012; 79:56-65.
13. Goodnough LT, Shander A. Patient Blood Management. Anesthesiology. 2012 Jun; 116(6): 1367-76.
14. Shander A, Javidroozi M. Strategies to reduce the use of blood products: a US perspective. Curr Opin
Anaesthesiol. 2012; 25:50-8.
15. Moskowitz DM, McCullough JN, Shander A, Klein JJ, Bodian CA, Goldweit RS, Ergin MA. The impact of
blood conservation on outcomes in cardiac surgery: is it safe and effective? Ann Thorac Surg. 2010
Aug;90(2):451-8.
16. Spahn DR. Anemia and patient blood management in hip and knee surgery: a systematic review of the
literature. Anesthesiology. 2010 Aug;113(2):482-95.
DISCLOSURE
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Moderated by Christian Werner, M.D.
Anesthetic Management of Cerebrovascular Disease

Carotid Endarterectomy
Daniel J. Cole, M.D. Phoenix, Arizona
Introduction
There are about 800,000 strokes and 300,000 transient ischemic attacks each year in the United States; and, with an
estimated 144,000 deaths each year, stroke is the third leading cause of death. With six million stroke survivors and
an age-dependent prevalence of asymptomatic carotid artery disease as high as 7.5%,1 carotid artery disease is a
significant anesthetic issue for patients over 50 years of age.
Medical therapy for stroke is directed at prevention by correcting modifiable risk factors, and by utilizing
antiplatelet/anticoagulant/fibrinolytic agents for patients whom have suffered cerebral ischemia of atherothrombotic
origin. A stroke occurs due to occlusive or hemorrhagic conditions. Occlusive cerebrovascular disease can be
thrombotic, embolic, or stenotic in origin. Performing an accurate history and physical examination should identify
nearly all significant neurological symptoms.
Patients with a history of prior stroke or transient ischemic attack have an increased risk of recurrent
perioperative stroke. Major symptoms of carotid artery disease include changes in vision, headache, changes in
speech, or facial and extremity weakness. Signs suggestive of carotid artery disease include a high-pitched bruit at
the origin of the internal carotid artery, increase in size and pulsation of the ipsilateral superficial temporal artery,
and changes in the retinal examination. Confirmation of carotid artery disease is achieved by vascular imaging
which may include ultrasound, MR angiography, or catheter angiography.
Presently, there is insufficient information to regarding the timing of surgery following an ischemic episode.
Data suggests there is a small but real increase in morbidity if surgery is performed shortly after the onset of
symptoms.2-4 Risk may be associated with the presence of a low density lesion on CT scan, vascular territory of the
infarct, brain shift, and level of consciousness.5 One author has suggested that the stroke/death rate may be related
to ASA physical class status if surgery is performed in the first three weeks following a stroke.6
Carotid Artery Revascularization

Carotid endarterectomy (CEA) was introduced in 1954 as treatment for occlusive carotid artery disease. Efficacy
data on CEA was limited until the 1990s. Analysis of three trials7-9 has demonstrated that CEA has a marginal
benefit in symptomatic patients with 50%-69% stenosis of the carotid artery, and was of greatest benefit in patients
with >70% stenosis.10 The ACAS trial demonstrated a marginal benefit for CEA in asymptomatic patients with
>60% stenosis.11
Stenting and angioplasty of the carotid artery (CAS) has been performed for almost two decades. Potential
advantages of this technique include avoiding cranial nerve damage, wound hematoma, and general anesthesia. In
addition, stenting and angioplasty is utilized for patients who present a technical surgical challenge (e.g., post
radiation, restenosis after previous CEA, and surgically inaccessible lesions) or have severe cardiovascular disease.
The anesthetic technique for this procedure involves minimal sedation. This procedure can cause severe bradycardia
and hypotension, and can result in cerebral hyperperfusion. Although the frequency of CAS has been increasing
while CEA has been decreasing, it is unclear whether CAS offers an advantage over CEA (see Table 1). There are
approximately 140,000 carotid artery interventions performed each year. As anesthesiologists are infrequently
involved in the care of CAS, the remainder of this handout will focus on managing the patient for CEA.
Anatomic/Physiologic Considerations
Carotid artery disease is typically the result of atherosclerosis at the bifurcation of the common carotid artery or the
origin of the internal carotid artery. Ischemia is most often embolic in origin but may also have a hemodynamic
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basis.12 There are three phases of the response of various cerebral variables to progressive carotid artery disease (see
Figure 1). During ischemia, collateral flow is a cornerstone of cerebral blood flow (CBF) compensation. The
principal pathways of collateral flow are the Circle of Willis, extracranial anastomotic channels, and leptomeningeal
communications that bridge "watershed" areas between major arteries. During CEA, the risk of ischemia is related
to the dependency of the circulation on the ipsilateral internal carotid artery, and the cerebrovascular reserve of the
contralateral hemisphere.13
Table 1-stroke and death rate following comparative trials of CEA versus CAS.
Stroke/Death (%)
CAVATAS-2001 CEA-9.9 CAS-10.0
SAPPHIRE-2004 CEA-8.4 CAS-5.5
CARESS-2005 CEA-13.6 CAS-10.0
SPACE-2006 CEA-6.3 CAS-6.8
EVA-3S-2006 CEA-6.1 CAS-11.7
ICSS-2010 CEA-4.7 CAS-8.5
CREST-2010* CEA-2.3 CAS-4.4
Figure 1. Relative changes in CBV (cerebral blood volume), CBF, OEF (oxygen extraction fraction), and
CMR (cerebral metabolic rate) in relation to progressive hemodynamic changes in cerebral perfusion.
I II III
300
200
CBV
100
Figure 1. Relative changes in CBV
0
(cerebral blood volume), CBF, and
OEF (oxygen extraction fraction) in
100
relation to progressive hemodynamic
CBF changes in cerebral perfusion (phase
0
I→phase II→phase III.
200
OEF 100
Preoperative Concerns
CEA has an inherent risk of perioperative stroke and cardiovascular events. Approximately ¼ of strokes associated
with CEA occur intraoperatively; and about ⅓ of these stroke are hemodynamic versus embolic in origin.14,15 In
symptomatic patients, there is a 6.5% rate of stroke and death associated with CEA; while the reported stroke and
death rate for patients with asymptomatic disease is 2.3%.14 The risk for stroke following CEA is most strongly
associated with an active neurologic process prior to surgical intervention. Other factors which have been reported
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to increase neurological risk include:

• hemispheric versus retinal transient ischemic attack
• an urgent procedure
• a left sided procedure
• ipsilateral ischemic lesion on computerized tomography
• contralateral carotid occlusion or poor collaterals
• impaired consciousness
• an irregular or ulcerated ipsilateral plaque
In general, carotid artery disease should be considered a manifestation of systemic vascular disease. Medical
complications occur about 10% of the time after CEA and are associated with the following:
• Hypertension (HTN)-the incidence of a neurologic deficit is greater in patients with postoperative HTN, and the
incidence of both postoperative hypotension and HTN is greater in patients who have uncontrolled HTN
preoperatively. In a multicenter study16 diastolic HTN (>110 mmHg) was found to be a predictor of adverse
events. Although it seems reasonable that blood pressure should be controlled before surgery, there is an
absence of prospective data to confirm this logic. A reasonable recommendation would be to delay elective
surgery if the blood pressure is >180/110 mmHg in a patient without anxiety or pain.9
• Cardiac-a cardiac assessment is indicated in patients who present for CEA. An ECG should be routine; and
more advanced tests are often indicated according to national guidelines.
• Diabetes-data indicate that CEA can be performed safely in patients with diabetes.15,17
• Renal insufficiency-patients with renal insufficiency have an overall increased risk for stroke, death, and cardiac
morbidity, associated with CEA.18
Monitoring
Basic Monitoring-this should include basic ASA monitoring and intra-arterial blood pressure monitoring. In
patients with poor ventricular function or myocardial ischemia more advanced monitoring may be considered.
CNS Monitoring-no special cerebral monitor is required in awake patients with regional anesthesia. When general
anesthesia is employed, physiological considerations dictate that it is prudent to monitor the brain during cross-
clamping of the carotid artery, although no difference in stroke rate has been convincingly demonstrated with the
use of a specific monitoring technique.19-22
Electrophysiological Monitoring: The 16-channel EEG remains a sensitive indicator of inadequate cerebral
perfusion. Intraoperative neurologic complications have been shown to correlate well with EEG changes indicative
of ischemia.21,23 Ipsilateral or bilateral attenuation of high frequency amplitude or development of low frequency
activity seen during carotid cross-clamping is indicative of inadequate cerebral perfusion. The computer-processed
EEG24,25 and somatosensory evoked potential (SSEP) have also been found to be useful.
Most studies suggest that SSEPs are useful for monitoring cerebral perfusion during cross-clamping and have
similar or superior sensitivity and specificity to conventional EEG.26-28 Stable anesthesia must be maintained to
minimize the influence of anesthetics on the SSEP amplitude. In general, >50% reduction of amplitude of the
cortical component is considered to be a significant indicator of inadequate cerebral perfusion. In contrast to
conventional EEG, SSEP monitors the cortex as well as the subcortical pathways in the internal capsule, an area not
reflected in the cortical EEG.
Measurement of Stump Pressure: Since one important determinant of CBF is perfusion pressure, it seems
reasonable to assume that the distal arterial pressure in the ipsilateral hemisphere during carotid occlusion would
provide some indication of collateral CBF. Stump pressure involves direct measurement of the retrograde internal
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carotid artery pressure following occlusion of the more proximal common and external carotid arteries. Stump
pressures are neither sensitive nor specific. When stump pressure was compared to EEG monitoring, 6% of patients
demonstrated ischemic EEG changes despite stump pressures in excess of 50 mmHg.29 On balance, extreme values
(<25 mmHg or >60 mmHg) are useful indicators of the state of the cerebral circulation, but not intermediate
values.30,31
Transcranial Doppler (TCD): TCD32-40 has been utilized as a monitoring tool by measuring blood flow velocity in
the middle cerebral artery during CEA. Ischemia is considered severe if mean velocity after clamping is 0-15% of
preclamped value, mild if 16-40% and absent if > 40%.28 TCD has been shown to be beneficial not only for
detection of intraoperative cerebral ischemia,32-35 but also in detecting malfunctioning shunts,36 and identifying high
velocity states associated with hyperperfusion,37-39 as well as emboli detection.40-42 The frequency of emboli has
been positively correlated with postoperative cognitive dysfunction.40,41
Anesthetic Management
No compelling advantage has been demonstrated with any anesthetic regimen, and accordingly, a technique that
optimizes brain perfusion, minimizes myocardial stress, and allows for a rapid recovery is recommended. General
anesthesia is preferred in patients with anatomy/pathology that may make the surgical conditions difficult. One
caveat that is often not appreciated regards nitrous oxide. It is very difficult to place a shunt in the carotid artery, or
to release the carotid artery cross-clamp, without exposing the distal cerebral circulation to air bubbles.
Accordingly, it is recommended that, if used, nitrous oxide be discontinued prior to the above events.
Sevoflurane and desflurane have been shown to result in quicker extubation times and recovery profiles after
CEA, compared to isoflurane, with no significant perioperative difference in cardiac morbidity. Propofol and
narcotics may be associated with better hemodynamic stability than isoflurane, and remifentanil/propofol may have
less evidence of myocardial ischemia than isoflurane/fentanyl.43-45
A regional technique for CEA requires anesthesia of cervical nerves 2-4. Superficial cervical plexus block,
deep cervical plexus block, epidural anesthesia, straight local, and combinations of these techniques have all been
used successfully. Until recently, non-randomized studies suggested that the use of a regional technique may be
associated with reductions (approximately 50%) in the odds of stroke, death, myocardial infarction and pulmonary
complications. However, in 2008, Lewis et al46 published the results of the GALA trial in which 3526 patients were
randomized to undergo their CEA with either general or regional anesthesia. They observed no between groups
difference in the incidence of stroke, myocardial infarction or death.
Modalities of Cerebral Protection

Surgical: a shunt is placed to maintain CBF during cross-clamping. Most often, placement of the shunt is dependent
on the data of a cerebral monitor. A shunt entails the risks of embolization and carotid intimal dissection, and limits
surgical exposure. There is insufficient evidence from randomized controlled trials to support or refute the use of
routine or selective shunting during CEA.47
Physiologic:
1. Hypothermia-much has been studied about the beneficial effect of mild hypothermia on cerebral ischemia.
Although hypothermia has appeal for CEA, the therapeutic sequence of normothermia→hypothermia→
normothermia is not a simple maneuver that one turns on and off. Accordingly, is the concern that if
hypothermia is employed as a cerebral protectant for CEA, many patients may suffer from shivering during
recovery; and a consequent increase in myocardial oxygen consumption which may precipitate myocardial
ischemia. Thus, routine employment of hypothermia is not recommended for patients undergoing CEA.
Conversely, hyperthermia should be avoided.
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2. Hyperglycemia-should be avoided and treated when possible. This is accomplished by eliminating glucose-
containing intravenous solutions, and by treating hyperglycemia with small doses of insulin. If hyperglycemia
is present, a more severe neurologic injury results. This may be due to higher tissue lactate levels.
3. Hypertension-during ischemia, autoregulation is impaired and CBF is dependent on perfusion pressure.
Augmenting arterial blood pressure should open collateral vessels, effecting an increase in flow to the area of
ischemia. Hypertensive therapy has consistently decreased injury in animals; however, the clinical efficacy is
not definitively established. Nevertheless, there is evidence of an ischemic blood pressure threshold in patients
with stroke.48 i.e., above this threshold neurologic symptoms subsided, and below this threshold neurologic
symptoms were manifest. Thus, it is advisable to maintain normal to high arterial pressure in most situations.
4. Hemodilution-using hemodilution to improve CBF is dependent upon the rationale that CBF is inversely related
to hematocrit. Although the optimal hematocrit during cerebral ischemia seems to be about 30%, the clinical
data are not compelling.
5. Carbon Dioxide-normocarbia should be the goal.
A nesthetics:43-45,49-55
1. Barbiturates-as a whole, the evidence does not support the use of barbiturates as a cerebral protectant for
permanent focal ischemia. However, during transient focal ischemia there is evidence to support barbiturate
therapy. One point for barbiturates is just prior to carotid artery cross-clamping; however significant
cardiovascular depression and delayed awakening can occur.
2. Volatile Anesthetics-general anesthesia with isoflurane and sevoflurane is associated with a lower critical CBF
(that at which EEG evidence of ischemia was present) compared to halothane and enflurane.49,50
3. Etomidate-because of its short duration of action, hemodynamic profile, and metabolic properties etomidate has
been used during neurovascular procedures. However, there is evidence in animals that etomidate worsens
ischemic injury while thiopental improves injury.52 Accordingly, etomidate is not recommended for use as a
cerebral protectant.
4. Propofol-although many laboratory models have produced positive results, the amassed database is not as large
as that for barbiturates.
5. Dexmedetomidine-early studies in animals suggest that dexmedetomidine is neuroprotective. Although
controversial, it should be pointed out that in human volunteers dexmedetomidine decreases CBF but does not
increase the incidence of shunt placement during awake CEA.53-55
The Postoperative Period

The objective is a smooth and prompt emergence with optimal systemic and cerebral hemodynamics. Concerns in
the immediate postoperative period include:
1. HTN-may occur as a result of damage or local anesthesia to the carotid sinus or its nerve and is profound in
20% of patients in the immediate recovery period. Patients who have systolic HTN are at greater risk of
developing a neurologic deficit than those patients who remain normotensive. HTN may worsen neurologic
outcome by exacerbating the hyperperfusion syndrome with resultant intracerebral hemorrhage.56
2. Hyperperfusion-is most likely to occur in patients with high grade carotid artery stenosis who develop >100%
increase in CBF after CEA.56,57 Normotension should be maintained in patients at risk for hyperperfusion.
3. Hypotension-after the removal of atheromatous plaques, increased stimulation to baroreceptors may result in
bradycardia and hypotension. Regional anesthesia may be associated with a higher incidence of postoperative
hypotension while general anesthesia is more often associated with postoperative hypertension.
4. Myocardial Infarction-the most frequent cause of morbidity and mortality.
5. Stroke-most often embolic in origin.
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6. Bleeding-airway obstruction has been attributed to neck hematoma that is worsened by hypertension. Soft
tissue swelling with edematous supraglottic mucosal folds compromising the airway also occurs in patients after
CEA.58,59
7. Cranial Nerve Injury-occurs in approximately 10% of patients.13 Damage to the recurrent laryngeal nerve may
compromise protective reflexes as well as cause airway obstruction. Bilateral injuries can result in upper
airway obstruction.
8. Carotid Body Damage-results in reduced ventilatory response to hypoxemia and hypercapnia. Patients
undergoing second-side CEA merit close observation.
9. CNS Dysfunction-there appears to be an association with CEA, per se, and post-operative CNS dysfunction—
without regard to the anesthetic regimen.60
Conclusions
Several multicenter, randomized, trials have validated the efficacy of CEA. Approximately one third of
perioperative strokes are hemodynamic in nature. It is reasonable that tight physiologic management might affect
this subset of patients. Most strokes however, are embolic in nature. Patients who have undergone CEA have
increased risk of a perioperative myocardial event. There is no demonstrable advantage of a specific anesthetic
technique for patients undergoing CEA. Whichever anesthetic technique is employed, it is imperative that CBF is
optimized, there is minimal cardiac stress, and that anesthetic recovery is rapid. During the cross-clamp period, the
risk of ischemia may be decreased by maintaining normal to high perfusion pressure. Additional concerns in the
immediate postoperative period are tight hemodynamic control. The key points when managing a patient for CEA
are summarized in Table 2.
Table 2-key points of anesthetic management of CEA.

Indications • In symptomatic patients, CEA is indicated if stenosis is >70 percent; and for
selected patients if the stenosis is 50-69 percent. In asymptomatic patients, the
indications are controversial.
Preoperative Concerns • Hypertension, coronary artery disease, diabetes mellitus, renal
insufficiency, active neurologic process.
Anesthetic Technique • No proven advantage to a single technique. However, when using a general
anesthetic technique nitrous oxide should be discontinued prior to shunt
placement or reperfusion.
Cerebral Monitoring • Neurologic status in the awake patient and the electroencephalogram may be
close to a "gold" standard. Transcranial Doppler has the advantage of the ability
to detect cerebral emboli.
Postoperative Concerns • Hemodynamic stability, myocardial ischemia, neurologic status,
hyperperfusion syndrome, wound hematoma, cranial nerve dysfunction.
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20. Van Alphen HAM, et al. Acta Neurochir (Wien) 91:95-99, 1988
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36. Gaunt ME, et al. J Vasc Surg 20:104-107, 1994
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38. van der Schaaf IC, et al. Ann Vasc Surg. 19:19-24, 2005
39. Ogasawara K, et al. Am J Neuroradiol. 26:252-7, 2005
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41. Gaunt ME, et al. Br J Surg 81:1435-1439, 1994
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43. Umbrain V, et al. Anaesthesia 55:1052-1057, 2000
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48. Rordorf G, et al. Stroke 28:2133-2138, 1997

49. Messick JM, et al. Anesthesiology 66:344-349, 1987
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51. Allen BT, et al. J Vasc Surg 19:834-843, 1994
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DISCLOSURE
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Anesthetic Management of Cerebrovascular Disease

Surgical Approaches Anesthetic Management During
Operative Aneurysm Clipping
Dr Basil Matta M.D., FRCA, FFICM Cambridge, United Kingdom
Improvements in neurosurgical and neuroanesthetic techniques have reduced the morbidity and mortality
traditionally associated with intracranial hemorrhage. Even patients presenting with significant neurologic deficit
may achieve good outcome provided appropriate therapy is instituted early in their illness. Aggressive coordinated
anesthetic and surgical management achieves the most notable results in those patients with subarachnoid
hemorrhage or traumatic intracranial hematomas. The neuroanaesthetist is pivotal in organising and delivering
preoperative resuscitation and optimisation, intraoperative stabile and optimal hemodynamic conditions, and
postoperative neurointensive care.
Aetiology and Pathophysiology of Subarachnoid Hemorrhage (SAH)

Rupture of cerebral aneurysm accounts for 75-80% of spontaneous subarachnoid haemorrhage, with an incidence of
5-8 cases per 100,000 population per year. It is more common in females over 40 years of age, with peak incidence
at 55 years of age. Other causes of SAH include cerebral arteriovenous malformation (4-5%), traumatic, dural and
spinal ateriovenous malformations, mycotic aneurysms, sickle cell disease, cocaine abuse and some coagulation
disorders. No cause is found in 15-20% of cases.
Despite improvements in anesthetic and surgical care, SAH is associated with high morbidity and mortality. 15% of
patients will die before they reach hospital and 25% of the remaining patients will die in the first 2 weeks. The major
risks for those surviving in hospital are recurrent haemorrhage, development of delayed ischemic neurological
deficits (DIND) caused by vasospasm, and hydrocephalus. If ruptured aneurysms are left untreated 4% re-bleed in
the first 24 hours, 20% within 2 weeks.
Pathophysiology Intracranial Aneurysms

Turbulent flow at arterial junctions causes degenerative changes in the vessel wall which lead to the formation of
aneurysms. Structural vessel wall abnormalities may predispose to aneurysm formation and known risk factors
include atherosclerosis, hypertension, positive family history, co-arctation of the aorta, polycystic kidney disease,
fibromuscular dysplasia and some connective tissue disorders. Most aneurysms are supratentorial and approximately
20% of patients will have more than one aneurysm at presentation.
The majority of aneurysms are small (<12mm diameter) and are described as fusiform or saccular (berry-like), and
less than 2% are classified as giant aneurysms (>24mm). Cerebral aneurysms mainly occur at vascular bifurcations
within the circle of Willis or proximal cerebral artery, 40% anterior cerebral artery, 25% posterior communicating
artery, 25% middle cerebral artery and 10% vertebrobasilar system.
The chance of the aneurysm rupturing is related to previous history of SAH, aneurysm size (>6mm), site and shape
(morphology).
As an aneurysm ruptures for the first time, a number of changes occur rapidly. Intracranial pressure rises and
cerebral perfusion pressure falls. Cerebral vasoconstriction occurs and cerebral blood flow decreases. In the first
instance this may arrest further bleeding, but can worsen cerebral perfusion and lead to cerebral ischemia. The blood
spreads throughout the subarachnoid space irritating the meninges and causing inflammation. Often normal cerebral
pressure autoregulation is lost. Rebleeding can occur but is more likely to cause intraparenchymal (20-40%),
intraventricular (10-20%) or subdural haemorrhage (5%). Mortality and morbidity are related to direct neural
destruction caused by the extravasated blood, cerebral ischemia and sympathetically mediated cardiac dysfunction.
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Anesthetic Management of craniotomy for Vascular Abnormalities

Preoperative Assessment
Timing of Surgery
Definitive aneurysm surgery can be early (1-3 days after SAH) or late (10-14 days after SAH). Although technically
more difficult, early surgery is reduces the incidence of rebleeding with its associated higher morbidity and mortality
and the risk of vasospasm. By removing the blood clot early the risk of developing a delayed ischemic deficit may
also be reduced. If a deficit should occur as a result of vasospasm, induced hypertension can be used safely if the
aneurysm is secured.
A detailed anesthetic history should be taken including previous anesthetics, allergies, past medical history and
medications. Routine investigations must include full blood count, coagulation studies, urea and electrolytes, and
ECG. Further investigations may include chest X-ray, CT head, echocardiography and transcranial Doppler as
appropriate.
Cardiovascular assessment
Although seen in the majority of patients with SAH, ECG changes are more frequent in those with severe neurologic
impairment. The ECG abnormalities occur within 48 hours of the subarachnoid hemorrhage and may last up to six
weeks. Whilst the degree of myocardial dysfunction does not correlate with the SAH-induced ECG changes, the
greatest degree of myocardial dysfunction occurs in those with the worst WFNS grades. Despite ECG changes the
coronary arteries of these patients have been shown to be normal at post mortem. There are areas of subendocardial
ischaemia or localised myocardial necrosis which are thought to arise from an acute increase in sympathetic activity
post SAH. It is postulated this is driven by stimulation of the posterior hypothalamus. It is difficult to assess the
significance of the ECG changes in the arteriopath with SAH and an echocardiogram may be valuable.
The timing of surgery in patients with ECG changes suggestive of myocardial infarction presents a dilemma as the
risk of malignant dysrythmia is high. On balance surgery should be delayed for 72 hours assuming there are no
symptoms of intracranial mass effect and the patients condition is stable. Non-specific, asymptomatic ECG changes
need not delay surgery.
Blood pressure abnormalities are frequent after SAH. Hypertension may be in response to an elevated ICP to
maintain CPP. In this case it should not be treated unless it is severe. That said, systolic blood pressure >160mmHg
increases the risk of aneurysm rupture and rebleeding in the unsecured aneurysm and a compromise is necessary.
Labetalol has little, if any effect on cerebral blood flow and intracranial pressure and is a therefore a good choice of
drug to titrate to effect. Both sodium nitroprusside and hydralazine are vasodilators and may increase CBF. They
should not be used before the dura is opened. Patients with vasospasm will tolerate higher blood pressures.
Hypotension should be avoided and the blood pressure below which neurological deterioration occurs recorded.
These baseline pressures can act as a guide to perioperative blood pressure management.
Respiratory assessment
Respiratory dysfunction (in SAH patients) can occur as a result of neurogenic pulmonary oedema, aspiration of
gastric contents, and decreased level of consciousness or poor ventilatory drive. Neurogenic Pulmonary edema is
usually transient and tends to resolve within 48 hours. The chest should be examined with the above in mind, arterial
blood gas sample interpreted and chest X-ray assessed. It is important to avoid secondary hypoxemia, and patients
with high levels of inspired oxygen requirements and/or dependant on positive end expiratory pressure should have
the operation delayed until their respiratory function improves.
Volume status and blood chemistry

Patients may be intravascularly depleted due to autonomic hyperreactivity, bed rest, negative nitrogen balance,
diuretics and neuroendocrine hormaone imbalance. A central venous pressure line may assist fluid management. A
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hematocrit of 30% is considered optimum as it is associated with improved flow characteristics while maintaining
adequate oxygen delivery. Hyponatraemia is common and can be associated with impaired level of consciousness,
cerebral edema, seizures and vasospasm. It may result from cerebral salt wasting or the syndrome of inappropriate
secretion of antidiuretic hormone. Plasma sodium concentration is low in both (<134mmol/L), but patients with
cerebral salt wasting are hypovolemic and require fluid resuscitation. Patients with SIADH on the other hand require
fluid restriction. A central venous pressure line can assist therapy.
Hyperglycemia is associated with a worse neurological outcome and should be avoided as should hypoglycaemia.
An insulin infusion may be required to ensure normoglycemia in the face of stress-induced hyperglycemia.
Tight glycemic control, once considered desirable in critically ill patients, has been questioned recently in light of
the increased incidence hypoglaycemic episodes in neurologically injured patients. It is probably safer to allow
blood glucose levels to fluctuate around 6 – 7 mmHg in order to reduce the incidence of hypoglaycemia.
Hypomagnesaemia is common (>50% patients) and can be associated with delayed neurological deficit and poor
outcome. The results of the Magnesium and Acetylsalicylic acid in Subarachnoid Hemorrhage (MASH) trial suggest
that giving magnesium may decrease delayed neurological deficit and therefore poor outcome but the results need to
be confirmed in a large randomised controlled trial.
Neurologic assessment
A detailed examination should seek the level of consciousness, presence of focal neurological deficit, evidence of
raised intracranial pressure, cerebral vasospasm, hydrocephalus or intracranial mass effect. Mortality is higher in
patients with SAH and hydrocephalus. If hydrocephalus is present, the ventricles should be drained. This may
improve the neurological status of the patient with an unsecured aneurysm. The CSF should be drained to 15-
20cmH2O to avoid excess ventricular decompression, which may cause the aneurysm to re-rupture. Excessive CSF
drainage can cause CSF hypovolemia. This may cause ‘brain sag’ which may result in considerable postoperative
neurological clinical deterioration. Seizures can occur after SAH and lead to an acute rise in blood pressure and re-
bleeding. Seizures should be controlled if present, but long term use of anti-epileptic drugs has been shown to result
in a worse outcome. Antiepiletic agents should not be given as routine seizure prophylaxis.
Medications
Patients' normal medications should be continued throughout their illness. Nimodipine is usually administred to
prevent cerebral vasospasm. Diuretic may be omitted in those patients considered to be hypovolaemic. Euvolaemia
is important to prevent hypotension on induction of anesthesia. Patient on statins should continue to receive them, as
there is some evidence to suggest that they may reduce the incidence of vasospam and may have a beneficial effect
on outcome.
Anaesthetic Management
Premedication
The use of sedative premedication is controversial as pre- and post-operative neurological assessment may be
difficult. Premedicants may also cause respiratory depression leading to hypercapnia, but anxiety may result in
hypertension and increased CBF, CBV and ICP. Generally, grade III-IV patients rarely require an anxiolytic to
prevent hemodynamic fluctuations associated with anxiety. Midazolam IV can be administered in the anesthetic
room. Midazolam reduces the cerebral metabolic rate and hence CBF and CBV without significantly affecting
cerebral CO2 reactivity or autoregulation. Hypotension must be avoided and the drug should be carefully titrated.
Patients at risk of aspiration should receive standard antacid prophylaxis. Any vasoactive drugs are most likely to be
needed at induction, and may need to be continued throughout the anesthetic.
Monitoring
Routine monitoring will include ECG, pulse oximetry, end-tidal capnography, urinary output and temperature.
Direct blood pressure measurement is established before induction of anesthesia to allow accurate, beat-to-beat
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observation of blood pressure during induction, maintenance and emergence of anesthesia. It will also be useful for
intra-operative blood gas and hemoglobin measurements. Central venous pressure is usually measured in patients
presenting for aneurysm surgery to guide fluid management and allow the administration of vasoactive drugs. These
patients may receive repeated doses of diuretics and/or mannitol. A pulmonary artery flotation catheter or other
method of cardiac output monitoring should be considered in the elderly, those with cardiac disease and in poor
grade SAH patients, especially if hypertension, hypervolemia, hemodilution therapy (triple ‘H’) is contemplated.
A jugular bulb catheter measures jugular venous oxygen saturation and lactate, and reflects whole brain oxygenation
and metabolism. Jugular venous oximetry can be a good global measure of cerebral oxygenation. It can be used to
titrate changes ventilation and blood pressure so that optimal cerebral oxygen delivery is achieved. An
intraparenchymal probe can measure metabolism, pH, temperature and tissue oxygenation in the territory of the
probe.
A cerebral function analysing monitor can be used when burst suppression is required (e.g. prolonged temporary
clipping). Motor evoked potentials (MEPs), somatosensory evoked potentials (SSEPs) and microvascular Doppler
ultrasonography have been used to detect motor impairment from subcortical ischemia and inadequate clip
placement intraoperatively, however, these are not universally used. They are not specific for cerebral ischemia, and
have high false-postitive and false-negative predictive values, that are affected by the anaesthetic. They are also
difficult to site on patients undergoing craniotomy. If used, total intravenous anesthesia inteferes with the evoked
potentials to a lesser degree than inhalational agents.
Induction of anaesthesia
The aims are to titrate the depth of anesthesia and the blood pressure to match the surgical need, control ICP,
minimise cerebral metabolic demands, prevent cerebral ischemia, ensure good operating conditions and allow rapid
awakening. As transmural pressure determines the likelihood of aneurysmal rupture, abrupt increases in arterial
blood pressure or sudden decreases in ICP may cause a rebleed. Although rebleeding is rare during induction of
anaesthesia and tracheal intubation (<0.5% at this institution), it is associated with high mortality and post-operative
morbidity. Aneurysmal rupture is suspected when a sustained rise in blood pressure with or without a bradycardia is
observed on or shortly after induction or tracheal intubation. The surgery may then be deferred for 24-48hr, during
which a detailed assessment of the patient is made.
With the exception of ketamine, any intravenous induction agent can be used. Etomidate is becoming less popular
due to its suppression of the adrenal axis. Propofol and thiopentone are the main anesthetic induction agents used,
with muscle relaxation achieved with vecuronium, rocuronium, atracurium or pancuronium. When rapid control of
the airway is required, suxamethonium can be used but it may result in a transient increase in ICP. This potential
increase in ICP and its possible effect on aneurysmal rupture is balanced against the risk of aspiration, hypoxaemia
and hypercapnia. An alternative is to use rocuronium (0.9mg/kg), and sugammadex for emergency reversal of
muscle relaxation if required.
If a rapid sequence is not required, the patient's lungs are denitrogenated and anesthesia is induced with the
intravenous agent of choice, in combination with a short acting opioid. The agent is titrated to blood pressure and
heart rate. Once the patient is judged ready for intubation (by peripheral nerve stimulator), further aliquots of
induction agent, opioid, labetalol/esmolol, or lidocaine (1-1.5mg/kg) can be used to attenuate the response to
laryngoscopy and intubation. Hyperventilation reduces ICP and may increase transmural pressure leading to
aneurysmal rupture. Futhermore, it can cause cerebral ischemia through vasoconstriction and steal phenomena. The
endotracheal tube is secured, wide bore intravenous access established and the eyes protected. Local anesthesia or
scalp block, or further doses of induction agent or opioid can be used to attenuate the response to head pin insertion.
Lumbar drains may be occasionally be used when a greater degree of brain retraction is anticipated (eg. posterior
circulation or giant aneurysms). Rapid decompression should be prevented as this can increase the risk of
rebleeding. Patients are then transferred into theatre and positioned 15-300 head up to aid venous drainage.
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Maintenance
The ‘best’ anesthetic technique produces a ‘slack’ brain so that retraction pressure is low whilst ensuring maximal
cerebral protection by keeping cerebral metabolic requirements to a minimum. Those agents that maintain cerebral
vasoreactivity to CO2 and autoregulation may reduce fluctuations in CBF, ICP and CPP when blood pressure
changes with varying surgical stimuli.
A combination of a propofol infusion and an opioid is increasingly used to maintain anesthesia during aneurysm
surgery. Propofol allows rapid adjustment of anesthetic depth with more rapid recovery than with thiopentone or
isoflurane. Propofol has no intrinsic vasodilatory effect and therefore does not result in increases in CBF, CBV or
ICP. Furthermore, propofol has been shown not to affect cerebral autoregulation or carbon dioxide reactivity even at
doses high enough to produce EEG isoelectricity. It also reduces the cerebral metabolic rate, with cortical structures
being depressed to a greater extent than subcortical structures, and may be neuroprotective.
Inhalational anesthetic agents have a dual effect on CBF: a reduction consequent on the decrease in cerebral
metabolism and an increase secondary to their direct cerebral vasodilatory effect. The ‘net’ effect of an inhalational
agent on CBF is therefore dependent on the level of cerebral metabolism at the time the agent is introduced38. When
cerebral metabolism is low, as in patients with SAH grades III or IV, the net effect may be vasodilatory with
increases in CBF and ICP on the introduction of the agent. However, in patients with good grade SAH in whom
cerebral metabolism is high, inhalational agents primarily reduce CBF secondary to the reduction in cerebral
metabolism. Therefore, inhalational agents can be safely used in patients with good grade SAH. When there is
uncertainty about the level of cerebral metabolism or when signs of significant cerebral edema are present, total
intravenous anesthesia is the preferred option.
Inhalational agents, with the exception of sevoflurane, impair autoregulation in a dose-dependant manner. Therefore,
isoflurane in concentrations less than 1.0% can be used to supplement intravenous anesthesia. Desflurane increases
ICP and this may be related to its sympathoadrenal effects. Sevoflurane has been shown not to alter cerebral
autoregulation in concentrations up to 1.5 MAC. However, at 1.5 MAC sevoflurane, brain oxygen consumption was
shown to be reduced by 25% and therefore a degree of luxury perfusion may occur. Desflurane may result in a
slightly faster ‘wake up’ than sevoflurane but offers no other advantage.
A number of papers have compared the use of propofol/remifentanil and balanced inhalational anesthesia. Even
though some report more rapid return of cognition with intravenous anaesthesia, others report a greater incidence of
shivering and hypertension in the post-operative period. On balance there was no significant difference between an
intravenous or balanced inhalational technique.
Although Nitrous oxide is cheap and has rapid onset and offset, its use is discouraged due to its effects on ICP and
CBF. Opioids have no direct effects on CBF and metabolism. However, they can affect ICP in patients with low
intracranial compliance (head trauma and tumors), secondary to changes in PaCO2, and systemic hypotension with
concomitant cerebral vasodilatation. The potential increase in ICP reinforces the need to administer boluses of
opiate with caution, taking care to avoid hypotension. Fentanyl, with its medium duration of action and its negligible
cerebral vascular effects is a safe choice. Remifentanil compares favourably with fentanyl in patients undergoing
elective supratentorial surgery and the dose can be rapidly changed according to need. Remifentanil in combination
with 0.5 MAC sevoflurane does not alter cerebral autoregulation in individuals undergoing non-intracranial
neurosurgical procedures.
Brain relaxation
There are times when attention to detail with manipulation of both physiology (PaO2, PaCO2, head up position,
stable hemodynamics) and pharmacology (adequate depth of anesthesia and reduction in cerebral metabolic rate) are
unable to provide enough ‘brain relaxation’ to facilitate surgery and reduce brain retraction. At these times further
measures to reduce ICP or brain swelling may become necessary. These measures include reducing brain bulk with
diuretics, removal of CSF and manipulating CBV.
Mannitol is an osmotic diuretic used to reduce cerebral tissue water. It is usually administered (0.5-1.0g/kg) as a
20% solution and probably acts on all three intracranial compartments. It may reduce brain bulk by osmotic
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dehydration, CBV by improving rheology of red blood cells thus decreasing blood viscosity, and by decreasing CSF
production. The diuretic effect of mannitol depends on an intact blood brain barrier and the generation of an osmotic
gradient across this barrier. As the brain becomes injured, the intact surface area of the blood brain barrier decreases
and so to does the effectiveness of mannitol. In some situations mannitol may follow its own concentration gradient
and enter the brain causing a rebound rise in ICP.
Mannitol’s high osmolarity causes an immediate but transient rise in intravascular volume, CBF, CBV and ICP. If
infused rapidly, a short period of hypotension may occur, quickly followed by an increase in cardiac filling pressures
and cardiac output. This is followed by a reduction in ICP and CBV, which is maximum at 30-60 min. The clinical
effect should be judged by the response of the ICP or the reduction in brain bulk seen, rather than the urine output.
As a diuretic, mannitol can cause derangement of sodium and potassium concentrations and these should be
monitored. Cases of hyperkalemia have been reported. Clearly care must be taken when administering mannitol to
patients with poor cardiac function as they may develop congestive cardiac failure and pulmonary edema. In theory,
mannitol should be given slowly, once the dura is opened to prevent a sudden decrease in ICP and changes to the
transmembrane pressure gradient and brain ‘shrinkage’ (which may tear bridging veins). This is often not the case,
and it is given cautiously at the discretion of the surgeon and anesthetist. Many units aim to maintain hypervolemia
prior to aneurysm clipping to optimize CBF and reduce the effects of perioperative vasospasm.
Mannitol has limited use for repeated doses and an alternative was sought. Hypertonic saline is being used as an
alternative to mannitol to reduce intracranial pressure on the neurocritical care unit, either as a first line agent or
when the osmotic effects of mannitol are exhausted. Its use in theatre as a first line agent has yet to be established.
Furosemide can be given instead (1mg/kg) of, or in addition (0.25-1mg/kg) to mannitol50. Its mechanism of action
on ICP is not clear, but it is not only due to diuresis. If given before mannitol, it may blunt the transient rise in ICP,
and protect those at risk of congestive cardiac failure with an increased intravascular volume. When given in
combination, the diuresis is prolonged, as is the rise in serum osmolarity and therefore the effect on ICP. The
concomitant use of both agents requires close observation of electrolytes, acid-base balance and intra-vascular
volume. Urine output is a poor marker of volume status.
If urgent control of brain volume is required, a short period of moderate hyperventilation (PaCO2 4.0-4.6kPa) can be
used to decrease CBV. Even modest hypocapnia for short periods of time, has been shown to cause an increase in
the ischemic brain volume. The beneficial effect of reducing brain bulk by decreasing CBV has to be weighed
against the risk of cerebral ischemia. It is probably unwise to induce hypocapnia if the SjO2 is less than 50%.
Intravenous anesthesia should be started, and volatile anesthetic agents and nitrous oxide discontinued. In addition a
further bolus of intravenous agent (thiopentone 3mg/kg, propofol 1-2mg/kg) can reduce cerebral metabolism and
therefore CBF and CBV. If brain relaxation is improved, a continuous thiopentone infusion should be considered.
This will delay awakening and is likely to require hemodynamic support and admission to intensive care.
Refractory brain swelling may be due to intracerebral hematoma which may require evacuation.
Deliberate hypotension
Many SAH patients will have impaired autoregulation or cerebral vasospasm and systemic hypotension may lead to
focal or global cerebral ischemia. There are times when the surgeon may still request a short period of hypotension
to facilitate preparation and clipping of the aneurysm or to control bleeding when an aneurysm has ruptured. This is
becoming less common but may not be as detrimental to the patient outcome as previously thought. Careful doses of
intravenous anesthetic agents, opioids or beta-blockers that have a short duration of action can be used.
Temporary Clipping
Temporary clipping of the feeding artery can cause local hypotension and decrease the transmural pressure gradient.
This can be used to facilitate surgery in difficult cases and should be placed after attempts have been made to secure
maximal cerebral protection. A temporary clip occludes the vessels feeding the aneurysm and reduces the transmural
pressure, thus decreasing the risk of rupture. Although the safe length of time for which temporary clipping can be
used before cerebral infarction occurs is unknown, the risk of infarction increases with the duration of clip
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application. Ten minutes has been suggested as a safe duration of time for temporary clip application. Factors that
contribute to new neurological deficit include age >61 years and poor preoperative neurological function. Although
there is no hard evidence to suggest protective therapy is required during temporary clipping, surgeons will often
request the induction of burst suppression, a ~ 20% increase in blood pressure, and mild hypothermia for the
duration of the temporary clipping!
Cerebral Protection
Various cerebroprotective methods have been used including hypothermia, additional doses of intravenous or
inhalational anesthetics, deliberate hyperventilation and drugs such as mannitol, magnesium, phenytoin and calcium
channel blockers. These methods may be used routinely or their use may be guided by changes to the EEG or
evoked potentials. Although the exact mechanism for the neuroprotective action of anesthetics is not fully
understood, barbiturates and propofol may produce their effect by reducing the cerebral metabolic rate. However,
doses of intravenous anesthetic high enough to suppress EEG activity cause marked cardiovascular depression. The
cerebral protective effects of barbiturates may be secondary to their ability to reduce calcium influx, inhibit free
radical formation, potentiate GABA-ergic activity, reduce cerebral edema and inhibit glucose transfer across the
blood-brain barrier.
Isoflurane has been shown to produce ischemic preconditioning when used in low doses prior to the ischemic insult.
The majority of studies so far are animal based and look at either acute MCA occlusion or traumatic brain injury.
The mechanism of neuroprotection is thought to be due to activation of ATP-regulated K channels and protein
kinases after the ischemic event. Sevoflurane and desflurane may also offer the same benefit57. How this can be
related to humans with SAH remains to be shown.
Other pharmacological agents include: erythropoietin, NMDA receptor antagonists and magnesium56. Ketamine, an
NMDA receptor antagonist is traditionally avoided in neurosurgery due to its effects on cerebral blood flow and
ICP. A recent paper in children has suggested that ketamine in a single dose (1-1.5mg/kg) may decrease intracranial
pressure in ventilated children with traumatic brain injury and intracranial hypertension. NMDA receptor
antagonists can prevent neuronal injury by decreasing cellular influx of calcium, and have been shown to be
neuroprotective in animal models of brain injury. The role of ketamine in neuroprotection requires further
evaluation.
In contrast to pharmacological agents which only reduce the active component of cerebral metabolism, hypothermia
reduces both the active and basal components thereby increasing the period of ischemia tolerated. It may also slow
down the pro- and anti-inflammatory cascades initiated by an ischemic insult, and therefore decrease potential
infarct volume. Cerebral metabolism is approximately 15% of normal at 200C. It is now commonly accepted that
hypothermia may be neuroprotective because it affects factors other than cerebral metabolism: cytokines, free
radicals and glutamate. A recent large study found no difference in ICU admission days, hospital length of stay or
rate of death at follow-up between patients with good grade subarachnoid hemorrhage who were cooled but
therapeutic hypothermia is widely used after VF cardiac arrest and increasingly for all cause anoxic brain injury
following cardiac arrest. Cooling is continued for 12-24hrs and the patient is rewarmed at not greater than 10C per
hour. This requires admission to intensive care.
Problems associated with hypothermia include reliability of temperature measurement, the optimal temperature
needed to offer the best benefit:risk ratio and the best method of rewarming the patient safely so that normothermia
is achieved before ‘wake up’. Other problems include delayed awakening, postoperative shivering, coagulation
disorders and aggravation of myocardial disease. To provide safe intensive care, a robust protocol for the use of
hypothermia as a treatment in SAH patients with raised ICP is essential.
Induced Hypertension
This is often employed to improve collateral blood flow during temporary clipping and in patients with areas of
critical perfusion. Adequate volume loading and inotropes such as dopamine are often sufficient for producing the
desired hypertension. However, in patients with abnormal autoregulation, CBF is pressure dependant and increases
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in MAP will increase CBF and may result in blood-brain barrier damage and vasogenic edema. Patients pressure
reactivity index can be assessed and the use of induced hypertension tailored to the individual patient at any given
time. Patients with myocardial disease or unsecured aneurysms are at risk for myocardial ischemia and aneurysm
rupture respectively.
Intraoperative Rupture
If the aneurysm ruptures intraoperatively prognosis is better when the skull and dura are open rather than closed.
Rupture can occur at any point but is more likely if there is an abrupt change in the transmural pressure gradient, for
example a fall in ICP or rise in systemic blood pressure, or with surgical manipulation.
It is important to maintain cerebral oxygenation and perfusion pressure. The lungs should be ventilated with 100%
oxygen. The rate of intravenous fluid infusion should be increased whilst ensuring normovolaemia. Hemorrhagic
shock is uncommon (8%). Cerebral protection can be provided by either thiopentone or propofol induced EEG burst
suppression, and hypothermia (330C) may or may not help63. Temporary occlusion of afferent and efferent blood
vessels may help the surgeon gain control of the rupture. If bleeding persists, a short period of induced hypotension
may be required to facilitate control. Hyperosmolar therapy can be used to treat any resulting brain swelling.
Giant cerebral aneurysms and circulatory arrest

Cerebral aneurysms that are greater than 2.5cm are called giant aneurysms. They lack an anatomical neck and may
have perforating vessels arising from and travelling across the aneurysm wall. They often present with symptoms of
mass lesions such as headaches, visual disturbance and cranial nerve palsies. Although improvements in
microsurgical techniques and neuroanaesthesia have improved outcome, the morbidity and mortality remain higher
than after surgery for smaller aneurysms.
Three main surgical techniques are used: temporary clipping, hypothermic circulatory arrest and arterial bypass
surgery (eg. EC-IC bypass). Interventional radiology may reduce the size of the aneurysm prior to surgery.
Circulatory arrest aids the surgeon. It facilitates visualisation of the aneurysm, a bloodless field and therefore makes
manipulation of the aneurysm and clip placement less challenging. Circulatory arrest also ensures haemorrhage
during dissection and exposure of the aneurysm is minimised. After induction of anaesthesia and with all routine
monitors in place, surface cooling is started. Monitors should include invasive blood pressure, central venous
pressure and EEG to assess burst suppression (or BIS). Other monitors to consider include somatosensory evoked
potentials, brain stem evoked potentials and transoesphageal doppler (to assess ventricular function). Barbiturates
are administered to induce and maintain burst suppression (5mg/Kg bolus followed by 5-10 mg/Kg/h infusion).
Haemodilution to a haematocrit of 30% is achieved by collecting blood and administering cold intravenous saline
containing potassium. After the aneurysm is dissected, femoral artery to vein bypass is established following the
administration of heparin 300 IU/Kg aiming for an ACT between 450-500s. The patient is cooled to 180C. Each 8
degree drop in temperature doubles the tolerable period of circulatory arrest. At 180C, clinical circulatory arrest has
been safely tolerated for 60 minutes. Cardiac fibrillation, which commonly begins at <280C, is stopped by potassium
chloride.
Once the desired temperature is reached and the EEG is isoelectric, circulatory arrest is performed. This should only
be for the duration of the clip application, and not greater than 60 minutes. Once the aneurysm is secured, bypass is
re-established and warming at a rate not exceeding 0.50C/min proceeds with the help of a vasodilator (sodium
nitroprusside). Normal sinus rhythm is established by cardioversion when the heart fibrillates and by the
administration of antiarrhythmic drugs. Bypass is discontinued when the patient’s temperature reaches 360C.
Heparin is reversed with protamine and coagulation factors. Blood is administered as necessary. The bypass is best
coordinated with a cardiac surgeon and cardiac anesthetist.
Postoperative Care
Patients with initial good-grade SAH (Grade I-II) whose surgery is uncomplicated are usually woken up at the end
of the procedure to allow neurologic assessment.
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Once surgery is complete, the anesthetic agents are discontinued and the lungs ventilated with 100% oxygen. Any
residual muscle relaxation is assessed and reversed, the airway suctioned and the patient extubated on regaining full
consciousness. Again the hypertensive response to extubation needs to be obtunded. Boluses of short acting opioids,
liodocaine or propofol can be used. Uncontrolled hypertension at this time can precipitate intracerebral
haemorrhage. If the aneurysm remains unsecured the blood pressure should be kept within 20% of normal. If
hypertension persists despite adequate analgesia, an antihypertensive agent should be given. Esmolol, labetalol and
nifedipine have all been used.
If the patient fails to regain the preoperative neurological state, the usual reasons for this are investigated which
include:
i)Anaesthetic causes (partial neuromuscular blockade, residual narcotic/sedative drugs)
ii)Hypoxia and hypercarbia
iii)Metabolic factors (hyponatraemia, hypoglycaemia)
iv)Postictal state
Those slow to wake up are usually scanned to ensure that there are no new intracranial abnormalities. A CT scan is
performed to exclude hydrocephalus, cerebral oedema, intracranial hemorrhage, hematoma or further subarachnoid
bleed (multiple aneurysms). If the scan is negative, a cerebral angiogram is required to exclude vascular occlusion
(misplaced clip). Vasospasm can also be detected using transcranial Doppler.
Poorer grade patients are generally sedated until they are in the neurocritical care, where decision on extubation will
depend on their preoperative conscious level and ventilatory state.
Although most patients should go to the neurocritical care postoperatively, bed capacity often leads to those patients
presenting with good grade SAH to be transferred to a Neurosurgical ward. All patients are monitored for
neurological complications after surgery such as cerebral vasospasm and delayed ischemic neurological deficit.
Suggested Reading
1. Sacco S, Totaro R, Toni D et al. Incidence, case fatalities and 10-year survival of subarachnoid hemorrhage in a
population-based registry. Eur Neurol 2009;62(3):155-60
2. Warner DS, Laskowitz DT. Changing outcome from aneurysmal subarachnoid haemorrhage. Anesthesiology
2006;104:629-630.
3. Kassnell NF, Torner JC, Haley C et al. The International Study on the Timing of Aneurysm Surgery. Part 1:
Overall management results. J Neurosurg 1990;73:18-36
4. Kassell NF, Peerless SJ, Durward QJ et al. The international Cooperative Study on the timing of aneurysm
surgery. Part II: Surgical results. J Neurosurgery 1990;73:37-47
5. Solenski NJ, Haley EC, Kassell NF et al. Medical complications of aneurysmal subarachnoid hemorrhage: a
report of the multicenter, cooperative aneurysm study. Crit Care Med 1995;23:1007-1017
6. Prakash A, Matta BF. Hyperglycaemia and neurological injury. Curr Opinion Anaesth 2008;21:565-569
7. Lam AM. Cerebral aneurysms:anesthetic considerations. In:Cottrell JE, Smith DS, eds. Anesthesia and
neurosurgery, 4th edition. St Louis, MO:Mosby, 2001;367-96
8. Sturgess J, Matta BF. Brain protection: current and future options. Best Pract Res Clin Anaesthesiol. 2008
Mar;22(1):167-76
9. Marion D, Bullock MR. Current and future role of therapeutic hypothermia. J Neurotrauma. 2009 Mar;26(3):455-
67
10. Todd MT, Hindman BJ, Clarke WR et al for the Intraoperative Hypothermia for Aneurysm Surgery Trial
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(IHAST) Investigators. Mild intraoperative hypothermia during surgery for intracranial aneurysm. NEJM
2005;352:135-145
11. Bernard S. Hypothermia after cardiac arrest: expanding the therapeutic scope. Crit Care Med 2009;37(7
Suppl):S227-33
DISCLOSURE
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Anesthetic Management for Interventional

Neuroradiology/Endovascular Neurosurgery
William L. Young, M.D. San Francisco, California

This review emphasizes perioperative and anesthetic management strategies to prevent complications and minimize
their effects if they occur. We will discuss fundamental management principles of affording protection, which is
predicated on understanding the goals of the therapeutic intervention and anticipating potential problems. A
watershed event in cerebrovascular disease was the ISAT trial, which provided Level 1 evidence that endovascular
coiling furnishes advantages over surgical clipping of intracranial aneurysmsm 1 Interventional Neuroradiology
(INR) or Endovascular Neurosurgery, is rapidly becoming the primary approach for surgical treatment of
cerebrovascular disease of most kinds. Important considerations for the anesthesia team care include: (1)
maintaining immobility during the procedure to facilitate imaging; (2) rapid recovery from anesthesia at the end of
the case to facilitate neurological examination and monitoring, or provide for intermittent evaluation of neurological
function during the procedure; (3) managing anticoagulation; (4) treating and managing sudden unexpected
procedure-specific complications during the procedure, i.e., hemorrhage or vascular occlusion, which may involve
manipulating systemic or regional blood pressures; (5) guiding the medical management of critical care patients
during transport to and from the radiology suites; (6) self-protection issues related to radiation safety.2-4 As part of a
larger picture in the overall management approach to the patient with cerebrovascular disease, there is accelerating
interest and discussion in appropriate management of asymptomatic or unruptured lesions, with a trend towards
more considered patient selection for minimally symptomatic disease.5,6
RADIATION SAFETY
Radiation Safety is a critical part of pre-operative planning.4 It is probably reasonable to assume that the x-ray
machine is always on. There are three sources of radiation in the INR suite: direct radiation from the X-ray tube,
leakage (through the collimators' protective shielding), and scattered (reflected from the patients and the area
surrounding the body part to be imaged). A fundamental knowledge of radiation safety is essential for all staff
members working in an INR suite. The amount of exposure decreases proportionally to the inverse of the square of
the distance from the source of radiation (inverse square law). Digital subtraction angiography (DSA) delivers
considerably more radiation than fluoroscopy. Optimal protection would dictate that all personnel should wear lead
aprons, thyroid shields, and radiation exposure badges. The lead aprons should be periodically evaluated for any
cracks in the lead lining that may allow accidental radiation exposure. Movable lead glass screens may provide
additional protection for the anesthesia team. Clear communication between the INR and anesthesia teams is also
crucial for limiting radiation exposure. With proper precautions the anesthesia team should be exposed to far less
than the annual recommended limit for health care workers. The concept of ALARA (A s Low A s Reasonably
A chievable) is an important concept for minimizing occupational exposure for health care personnel working in
environments with ionizing radiation (see http://www.osha.gov/SLTC/radiation/index.html).
PRE-OPERATIVE PLANNING
For cases managed with an unsecured airway, routine evaluation of the potential ease of laryngoscopy in an
emergent situation should take into account that direct access to the airway may be limited by table or room
logistics. Recent pterional craniotomy can sometimes result in impaired tempomandicular joint mobility. Baseline
blood pressure and cardiovascular reserve should be assessed carefully. This almost axiomatic statement is
particularly important for several reasons. Blood pressure manipulation is commonly required and treatment-related
perturbations should be anticipated. Therefore, a clear sense of “where the patient lives” needs to be established.
One must keep in mind that “autoregulation” as presented in the textbooks is a description of a population;
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individual patients are likely to vary considerably, a concept based on the historical observations that underlie our
modern notions of autoregulatory behavior.7 The lower limit in humans may in fact be higher than the traditional
MAP value of 50 mmHg.8 In those cases where intra-arterial catheters are used, the concordance between blood
pressure cuff and intra-arterial readings needs to be considered; pre-operative blood pressure range is likely to be
known through blood pressure cuff values. Pre-operative calcium channel blockers for prophylaxis for cerebral
ischemia may be used and can affect hemodynamic management, especially in terms of maintaining euvolemia.
These agents or trans-dermal nitroglycerin are sometimes used to lessen the incidence of catheter-induced
vasospasm.
PATIENT PREPARATION
Especially for intravenous (i.v.) sedation cases, careful padding of pressure points and working with the patient to
obtain final comfortable positioning may assist in the patient’s ability to tolerate a long period of lying supine and
motionless, decreasing the requirement for sedation, anxiolysis, and analgesia. The possibility of pregnancy in
female patients and a history of adverse reactions to radiographic contrast agents should be explored. Secure i.v.
access requires adequate extension tubing to allow drug and fluid administration at maximal distance from the image
intensifier during fluoroscopy. Access to intravenous or arterial catheters can be difficult when the patient is draped
and the arms are restrained at the sides; connections should be secure. Infusions of anticoagulant, primary
anesthetics or vasoactive agents should be through proximal ports with minimal dead space. In addition to standard
monitors, capnography sampling via the sampling port of nasal cannula is useful for i.v. sedation cases. A pulse
oximeter probe can be placed on the great toe of the leg that will receive the femoral introducer sheath to provide an
early warning of femoral artery obstruction or distal thromboembolism.
For intracranial procedures and post-operative care, beat-to-beat arterial pressure monitoring and blood sampling is
facilitated by an arterial line. The femoral artery introducer sheath side port can be used, but it is usually removed
immediately after the procedure. In a patient who requires continuous blood pressure monitoring post-operatively or
frequent blood sampling, it is convenient to have a separate radial arterial blood pressure catheter. Using a co-axial
or tri-axial catheter system, arterial pressure at the carotid artery, vertebral artery, and the distal cerebral circulation
can be measured. Pressures in these distal catheters usually underestimate systolic and overestimates diastolic
pressure; however, mean pressures are reliable. Bladder catheters assist in fluid management as well as patient
comfort. A significant volume of heparinized flush solution and radiographic contrast may be used.
CHOICE OF ANESTHETIC TECHNIQUE
Most centers routinely involved use general endotracheal anesthesia (GA) for most therapeutic procedures. Choice
of anesthetic technique varies between centers; there is no unequivocal superior method provided management goals
are met.9
General Anesthesia. A primary reason for employing general anesthesia is to minimize motion artifacts and to
improve the quality of image. Relative normocapnia or modest hypocapnia consistent with the safe conduct of
positive pressure ventilation should be maintained unless intracranial pressure is a concern. The specific choice of
anesthesia may be guided primarily by other cardio- and cerebrovascular considerations. Total intravenous
anesthetic techniques, or combinations of inhalational and intravenous methods, may optimize rapid emergence. To
date, pharmacological protection against ischemic injury during neurosurgical procedures has not been proven. A
theoretical argument could be made for eschewing the use of N2O because of the possibility of introducing air
emboli into the cerebral circulation and reports that it worsens outcome after experimental brain injury.
Intravenous Sedation. The goals of anesthetic choice for intravenous sedation are to: (1) alleviate pain, anxiety,
and discomfort; (2) provide patient immobility; and (3) allow rapid recovery. There may be a discomfort associated
with injection of contrast into the cerebral arteries (burning) and with distention or traction on them (headache). A
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long period of lying can cause significant discomfort. A major benefit of intravenous sedation is to allow continual
assessment of neurological functions during the procedure. A variety of sedation regimens are available, and
specific choices are based on the experience of the practitioner and the goals of anesthetic management. Common to
all intravenous sedation techniques is the potential for upper airway obstruction. Placement of nasopharyngeal
airways may cause troublesome bleeding in anticoagulated patients and is generally avoided. Many patients who
come for INR treatment have compromised collateral cerebral circulation, and may be critically dependent on
adequate collateral perfusion pressure. Dexmedetomidine should be used with care owing to a tendency to cause
relatively low blood pressure in the post-anesthesia recovery period.10
ANTICOAGULATION
Heparin
Careful management of coagulation is required to prevent thromboembolic complications during and after the
procedure. Generally, after a baseline activated clotting time (ACT) is obtained, intravenous heparin (70 units/kg) is
given to a target prolongation of 2 ~ 3 times of baseline. Then heparin can be given continuously or as an
intermittent bolus with hourly monitoring of ACT. Occasionally, a patient may be refractory to attempts to obtain
adequate anticoagulation. Switching from bovine to porcine heparin or vice versa should be considered. If
antithrombin III deficiency is suspected, administration of fresh frozen plasma may be necessary.
Direct Thrombin Inhibitors
Heparin-induced thrombocytopenia (HIT) is a rare, but potentially devastating, prothrombotic syndrome caused by
heparin-dependent antibodies after exposure. Direct thrombin inhibitors may be used in patients with or at risk of
HIT, although they entail their own risks, including a small risk of anaphylaxis. They inhibit thrombin both in the
free form or bound to the clot. Monitoring of action is done by measuring the aPTT, or ACT. Lepirudin is FDA-
approved for anticoagulation in patients with HIT. The half-life of lepirudin is 40 to 120 minutes, and it undergoes
renal elimination. For HIT patients with renal impairment, Argatroban, predominantly metabolized in the liver, may
be preferable. Bivalirudin, a synthetic derivative of lepirudin, has a short half-life of about 25 minutes. Since
bivalirudin is partially renally eliminated, dose adjustments may be needed in patients with renal dysfunction. A
recent report described bivalirudin as a potential alternative during INR procedures to heparin for intravenous
anticoagulation and intra-arterial thrombolysis.11
Antiplatelet Agents
Antiplatelet agents (aspirin, the glycoprotein IIb/IIIa receptor antagonists and the thienopyridine derivatives) are
increasingly being used for cerebrovascular disease management, as well as rescue from thromboembolic
complications.12,13 Activation of the platelet membrane glycoprotein (GP) IIb/IIIa leads to fibrinogen binding and is
a final common pathway for platelet aggregation. Abciximab, eptifibatide and tirofiban are glycoprotein IIb/IIIa
receptor antagonists. The long duration and potent effect of Abciximab also increase the likelihood of major
bleeding. The smaller molecule agents, eptifibatide and tirofiban, are competitive blockers and have a shorter half-
life of about two hours. Thienopyridine derivatives (ticlopidine and clopidogrel) bind to the platelet’s ADP receptors
and permanently alter the receptor; therefore, the duration of action is the life span of the platelet. The addition of
clopidogrel to the antiplatelet regimen is used when stent-assisted coiling is anticipated, and also for management of
unruptured aneurysms.
Reversal of Anticoagulation
At the end of the procedure or in the event of a hemorrhagic complication, heparin may be reversed with protamine.
Since there is no specific antidote for the direct thrombin inhibitors or the antiplatelet agents, the biological half-life
is one of the major considerations in drug choice. Platelet transfusion is a non-specific therapy, should reversal be
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indicated. There is no currently available accurate test to measure platelet function in patients taking the newer
antiplatelet drugs. Desmopressin (DDAVP) has been reported to shorten the prolonged bleeding time of individuals
taking antiplatelet agents such as aspirin and ticlopidine. There are also increasing recent reports on using specific
clotting factors, including recombinant factor VIIa and factor IX complex, to rescue severe life-threatening bleeding,
including intracranial hemorrhage, uncontrolled by standard transfusion therapy. The safety and efficacy of these
coagulation factors remain to be clarified.
THERAPEUTIC BLOOD PRESSURE MANIPULATION
Deliberate Hypertension. During acute arterial occlusion or vasospasm, the only practical way to increase
collateral blood flow may be an augmentation of the collateral perfusion pressure by raising the systemic blood
pressure. The Circle of Willis is a primary collateral pathway in cerebral circulation. However, in as many as 21% of
otherwise normal subjects, the circle may not be complete. There are also secondary collateral channels that bridge
adjacent major vascular territories, most importantly for the long circumferential arteries that supply the hemispheric
convexities. These pathways are known as the pial-to-pial collateral or leptomeningeal pathways. The extent to
which the blood pressure has to be raised depends on the condition of the patient and the nature of the disease.
Typically, during deliberate hypertension the systemic blood pressure is raised by 30-40% above the baseline, in the
absence of some direct outcome measure such as resolution of ischemic symptoms or imaging evidence of improved
perfusion. Phenylephrine is usually the first line agent for deliberate hypertension and is titrated to achieve the
desired level of blood pressure. The risk of causing hemorrhage into the ischemic area must be weighed against the
benefits of improving perfusion, but augmentation of blood pressure in the face of acute cerebral ischemia is
probably protective in most settings.
Deliberate Hypotension. The two primary indications for induced hypotension are: (1) to test cerebrovascular
reserve in patients undergoing carotid occlusion, and (2) to slow flow in a feeding artery of BAVMs before glue
injection. The most important factor in choosing a hypotensive agent is the ability to safely and expeditiously
achieve the desired reduction in blood pressure while maintaining the patient physiologically stable. The choice of
agent should be determined by the experience of the practitioner, the patient's medical condition, and the goals of the
blood pressure reduction in a particular clinical setting. Intravenous adenosine has been used to induce transient
cardiac pause and may be a viable method of partial flow arrest.14
MANAGEMENT OF NEUROLOGICAL AND PROCEDURAL CRISES
A well thought-out plan, coupled with rapid and effective communication between the anesthesia and INR teams, is
critical for good outcomes. The primary responsibility of the anesthesia team is to preserve gas exchange and, if
indicated, secure the airway. Simultaneous with airway management, the first branch in the decision-making
algorithm is for the anesthesiologist to communicate with the INR team and determine whether the problem is
hemorrhagic or occlusive. In the setting of vascular occlusion, the goal is to increase distal perfusion by blood
pressure augmentation with or without direct thrombolysis. If the problem is hemorrhagic, immediate cessation of
heparin and reversal with protamine is indicated. As an emergency reversal dose, 1 mg protamine can be given for
each 100 units of initial heparin dosage that resulted in therapeutic anticoagulation. The ACT can then be used to
fine-tune the final protamine dose. Complications of protamine administration include hypotension, true
analphylaxis and pulmonary hypertension. With the advent of new long-acting direct thrombin inhibitors such as
bivalirudin, new strategies for emergent reversal of anticoagulation will need to be developed.
In an awake patient, bleeding catastrophes are usually heralded by headache, nausea, vomiting and vascular pain
related to the area of perforation. Sudden loss of consciousness is not always due to intracranial hemorrhage.
Seizures, as a result of contrast reaction or transient ischemia and the resulting post-ictal state, can also result in an
obtunded patient. In the anesthetized or comatose patient, the sudden onset of bradycardia and hypertension
(Cushing response) or the endovascular therapist’s diagnosis of extravasation of contrast may be the only clues to a
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developing hemorrhage. Most cases of vascular rupture can be managed in the angiography suite. The INR team can
attempt to seal the rupture site endovascularly and abort the procedure; a ventriculostomy catheter may be placed
emergently in the angiography suite. Patients with suspected rupture will require emergent CT scan, but emergent
craniotomy is usually not indicated.
SPECIFIC PROCEDURES
Intracranial Aneurysm Ablation
The two basic approaches for INR therapy of cerebral aneurysms are obliteration of the aneurysmal sac (preferred),
and occlusion of proximal parent arteries. With the publication of the ISAT trial, coil embolization of intracranial
aneurysms has become a routine first-choice therapy. The anesthesiologist should be prepared for aneurysmal
rupture and acute SAH at all times, either from spontaneous rupture of a leaky sac or direct injury of the aneurysm
wall by the vascular manipulation. There is great interest in the development of stent-assisted coiling methods. The
stent can provide protection of the parent vessel.15 Stent placement requires a greater degree of instrumentation and
manipulation, probably increasing the ever-present intra-procedural risk of parent vessel occlusion,
thromboembolism or vascular rupture. Unruptured patients are treated with anti-platelet agents before and after the
procedure. GA is usually employed, especially in the care of patients with aneurysmal SAH who may have
concomitant increased ICP or decreased intracranial compliance, secondary to the mass of SAH, secondary
parenchymal injury from ischemia or from hydrocephalus. Sedation might be considered for management of
unruptured aneurysms and low grade ruptured aneurysms.16 However, a large fraction of the cases might be
expected to need conversion to GA.
Angioplasty of Cerebral Vasospasm from Aneurysmal SAH
Roughly 1 out of 4 patients with SAH will develop symptomatic vasospasm. Angioplasty, either mechanical
(balloon) or pharmacological (intraarterial vasodilators) may be used as a treatment. Angioplasty is ideally done in
patients who have already had the symptomatic lesion surgically clipped and for patients in the early course of
symptomatic ischemia, in order to prevent hemorrhagic transformation of an ischemia region. A balloon catheter is
guided under fluoroscopy into the spastic segment and inflated to mechanically distend the constricted area. It is also
possible to perform a “pharmacologic” angioplasty by direct intra-arterial infusion. There is the greatest experience
with papaverine, but there are CNS toxic effects.17 Other agents such as calcium channel blockers (nicardipine and
verapamil) are being used.18 Intra-arterial vasodilators may have systemic effects (bradycardia and hypotension).
Patients who come for angioplasty are usually critically ill with a variety of challenging co-morbidities including
neurocardiac injury, volume overload from “triple-H” therapy, hydrocephalus, brain injury from recent craniotomy,
and residual effects of the presenting hemorrhage. Procedural complications included arterial rupture, reperfusion
hemorrhage, thromboembolism, and arterial dissection. Given the combination of technical demands of the
intervention and concerns of patients’ neurological and hemodynamic conditions before and after the treatment,
endovascular treatment for cerebral vasospasm is a high risk procedure. GA is usually employed.
Carotid Test Occlusion and Therapeutic Carotid Occlusion
Large or otherwise unclippable aneurysms may be partly or completely treated by proximal vessel occlusion. In
order to assess the consequences of carotid occlusion in anticipation of surgery, the patient may be scheduled for a
test occlusion in which cerebrovascular reserve is evaluated in several ways. A multimodal combination of
angiographic, clinical, and physiologic tests can be used to arrive at the safest course of action for a given patient’s
clinical circumstances. The judicious use of deliberate hypotension can increase the sensitivity of the test.19 The
most important factor in choosing a hypotensive agent is the ability to safely and expeditiously achieve the desired
reduction in blood pressure while maintaining the patient physiologically stable. The choice of agent should be
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determined by the experience of the practitioner, the patient's medical condition, and the goals of the blood pressure
reduction in a particular clinical setting.
Brain Arteriovenous Malformations (BAVMs)
Also called cerebral or pial AVMs, these are typically large, complex lesions made up of a tangle of abnormal
vessels (called the nidus) frequently containing several discrete fistulae served by multiple feeding arteries and
draining veins. The goal of the therapeutic embolization is to obliterate as many of the fistulae and their respective
feeding arteries as possible. BAVM embolization is usually an adjunct for surgery or radiotherapy. The
cyanoacrylate glues offer relatively “permanent” closure of abnormal vessels. Passage of glue into a draining vein
can result in acute hemorrhage; in smaller patients, pulmonary embolism of glue can be symptomatic. For these
reasons, deliberate hypotension may increase safety of glue delivery. There is no compelling reason to choose any
particular method to achieve the hypotension. The flow through the fistula is a pressure-dependent phenomenon.
Although less durable, polyvinyl alcohol microsphere embolization is also commonly used. If surgery is planned
within days after PVA embolization, the rate of recanalization is low. A major drawback to NBCA is that it is
adhesive, with the potential to inadvertently glue the catheter to the injected polymer and passage of the glue into the
draining veins, predisposing to rupture. Onyx™ is a new, non-adhesive liquid embolic agent consisting of ethylene-
vinyl alcohol copolymer and tantulum powder in a dimethyl sulfoxide (DMSO) solvent, and may theoretically
decrease overall complication rates,20,21 although aggressive therapy may have intrinsic risks. The agent, or its
vehicle DMSO, may have unusual adverse effects;22 DMSO can cause a garlic-like taste and odor on the breath and
skin that may last several hours.
Dural Arteriovenous Fistulae (DAVF)
DAVF are considered acquired lesions resulting from trauma and/or venous stenosis or occlusion (often dural sinus),
opening of potential AV shunts, and subsequent recanalization. Symptoms are variable according to which sinus is
involved. When pial veins are pressurized, there is a high risk for intracranial hemorrhage. Dural AVMs are fed by
extracranial arteries, and usually by multiple vessels. Accordingly, multi-staged embolization may be necessary.
Another consequence of increased intracranial venous pressure is a net decrease in cerebral perfusion pressure.
Therefore, presence of venous hypertension should be factored into management of systemic arterial pressure.
Angioplasty and Stenting for Atherosclerotic Lesion
Angioplasty and stenting for atherosclerosis for treatment of atherosclerotic disease involving the cervical and
intracranial arteries continue to supplant open surgical management.23,24 Risk of distal thromboembolism is a major
issue in this procedure. Catheter systems that employ some kind of trapping system distal to the angioplasty balloon
are being developed. There are multiple ongoing trials to compare the utility of stenting compared to carotid
endarterctomy for extracranial carotid disease. Preparation for anesthetic management may include placement of
transcutaneous pacing leads, in case of severe bradycardia or asystole from carotid body stimulation during
angioplasty. Intravenous atropine or glycopyrrolate may be also used in an attempt to mitigate against bradycardia,
which almost invariably occurs to some degree with inflation of the balloon. This powerful chronotropic response
may be difficult or impossible to prevent or control by conventional means. Adverse effects of increasing
myocardial oxygen demand need to be considered in anti-bradycardia interventions. Potential complications include
vessel occlusion, perforation, dissection, spasm, thrombo-emboli, occlusion of adjacent vessels, transient ischemic
episodes, and stroke. Angioplasty and stent placement for cerebral artery stenosis have been successfully performed
under GA or sedation with local anesthesia.25 However, in certain specific lesions, such as basilar artery stenosis,
GA is preferred to provide airway control when vascular occlusion from balloon inflation can cause loss of
consciousness and apnea. In published studies of intracranial angioplasty and stenting in the awake patients,
alterations of intervention techniques secondary to intolerance of procedures have been described, although the
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analyses did not reveal how many of the intra-procedure complications occurred in lesions in posterior cerebral
circulation.26,27
Thrombolysis of Acute Thromboembolic Stroke
In acute occlusive stroke, it is possible to recanalize the occluded vessel by superselective intra-arterial thrombolytic
therapy. Thrombolytic agents can be delivered in high concentration by a microcatheter navigated close to the clot.
Neurological deficits may be reversed without additional risk of secondary hemorrhage if treatment is completed
within 4-6 hours from the onset of carotid territory ischemia and 24 hours in vertebrobasilar territory. One of the
impediments in development in this area has been the fear of increasing the risk of hemorrhagic transformation of
the acute infarction patient. Despite an increased frequency of early symptomatic hemorrhagic complications,
treatment with intra-arterial pro-urokinase within six hours of the onset of acute ischemic stroke with MCA
occlusion significantly improved clinical outcome at 90 days.28 Details of anesthetic management are reviewed
elsewhere.29 A newer and promising approach is use of mechanical retrieval devices to physically remove the
offending thromboembolic material from the intracranial vessel, as reviewed by Smith et al.30,31 Retrieval devices
are efficacious in terms of recanalizing occluded vessels, but whether outcome is also affected is less clear.
There has been extensive recent debate on choice of anesthetic techniques in INR procedures.32,33 The results of
Abou-Chebl et al. study, a multi-center cohort of 980 patients, suggest the use of GA was associated with poorer
neurological outcome at 90 days and higher mortality. 32 This conclusion, however, did not take account of various
peri-procedure variables, including the patients’ baseline co-morbidities and severity of the stroke, or any anesthesia
and hemodynamic parameters. The more recently published retrospective review of the charts of 129 patients by
Davis et al. made a significant step further to include patients’ baseline characteristics, as well as the time-to-
treatment, peri-procedure blood pressure and glucose measurements into their analyses.33 Their findings suggest
hypotension might be contributing to the worse neurological outcome associated with GA.
POST-OPERATIVE MANAGEMENT
Endovascular surgery patients should pass the immediate post-operative period in a setting to monitor for signs of
hemodynamic instability or neurologic deterioration. Control of blood pressure may be necessary during transport
and post-operative recovery. Complicated cases may go first to CT or some other kind of tomographic imaging;
critical care management may need to be extended during transport and imaging.
Restoration of normal perfusion pressure to a chronically hypotensive or ischemic vascular bed (note that
hypotension and ischemia are not synonymous) is empirically associated with intracranial hemorrhage or brain
swelling. This may be the case after angioplasty and stenting, and obliteration of arteriovenous shunts (AVM or
DAVF). Similar to carotid endarterectomy, there is about a 5% risk after carotid angioplasty,34 and probably less
after AVM or DAVF obliteration.35 Although the etiology of this syndrome is unknown, it has been associated with
cerebral hyperperfusion, and it appears to be related to poor post-operative blood pressure control. A commonly
discussed theory holds that abrupt restoration of perfusion pressure overwhelms autoregulatory capacity, which
leads to hemorrhage or swelling, but this is far from clear.36 However, fastidious attention to preventing
hypertension is warranted.
In contrast, those patients who have inadequate perfusion (by stenosis, occlusion of a primary conductance vessel, or
marginal collateral perfusion) require judicious maintenance or augmentation of systemic arterial pressure. Careful
interdisciplinary communication is necessary among various teams who will provide post-operative care for optimal
outcomes.
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1. Molyneux AJ, Kerr RS, Birks J, Ramzi N, Yarnold J, Sneade M, Rischmiller J. Risk of recurrent
subarachnoid haemorrhage, death, or dependence and standardised mortality ratios after clipping or coiling
of an intracranial aneurysm in the International Subarachnoid Aneurysm Trial (ISAT): long-term follow-
up. Lancet Neurol. 2009 May;8(5):427-433.
2. Young WL, Pile-Spellman J. Anesthetic considerations for interventional neuroradiology. Anesthesiology.
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3. Young WL, Pile-Spellman J, Hacein-Bey L, Joshi S. Invasive neuroradiologic procedures for
cerebrovascular abnormalities: anesthetic considerations. Anesthesiol Clin North America.
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4. Anastasian ZH, Strozyk D, Meyers PM, Wang S, Berman MF. Radiation exposure of the anesthesiologist
in the neurointerventional suite. Anesthesiology. 2011 Mar;114(3):512-520.
5. Stapf C, Mohr JP, Choi JH, Hartmann A, Mast H. Invasive treatment of unruptured brain arteriovenous
malformations is experimental therapy. Curr Opin Neurol. 2006 Feb;19(1):63-68.
6. Wiebers DO, Whisnant JP, Huston J, 3rd, Meissner I, Brown RD, Jr., Piepgras DG, Forbes GS, Thielen K,
Nichols D, O'Fallon WM, Peacock J, Jaeger L, Kassell NF, Kongable-Beckman GL, Torner JC.
Unruptured intracranial aneurysms: natural history, clinical outcome, and risks of surgical and
endovascular treatment. Lancet. 2003 Jul 12;362(9378):103-110.
7. Drummond JC. The lower limit of autoregulation: time to revise our thinking? Anesthesiology.
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8. Patel PM, Drummond JC. Cerebral physiology and the effects of anesthetic drugs (Chapter 13). In: Miller
RD, Eriksson LI, Fleisher LA, Wiener-Kronish JP, Young WL, editors. Miller's Anesthesia. 7th ed. Vol 1,
Section II. New York: Churchill Livingstone; 2010. p. 305-339.
9. McDonagh DL, Olson DM, Kalia JS, Gupta R, Abou-Chebl A, Zaidat OO. Anesthesia and sedation
practices among neurointerventionalists during acute ischemic stroke endovascular yherapy. Front Neurol.
2010;1:118.
10. Arain SR, Ebert TJ. The efficacy, side effects, and recovery characteristics of dexmedetomidine versus
propofol when used for intraoperative sedation. Anesth Analg. 2002 Aug;95(2):461-466.
11. Harrigan MR, Levy EI, Bendok BR, Hopkins LN. Bivalirudin for endovascular intervention in acute
ischemic stroke: case report. Neurosurgery. 2004 Jan;54(1):218-222; discussion 222-213.
12. Hashimoto T, Gupta DK, Young WL. Interventional neuroradiology--anesthetic considerations.
Anesthesiol Clin North America. 2002 Jun;20(2):347-359, vi.
13. Fiorella D, Albuquerque FC, Han P, McDougall CG. Strategies for the management of intraprocedural
thromboembolic complications with abciximab (ReoPro). Neurosurgery. 2004 May;54(5):1089-1097;
discussion 1097-1088.
14. Hashimoto T, Young WL, Aagaard BD, Joshi S, Ostapkovich ND, Pile-Spellman J. Adenosine-induced
ventricular asystole to induce transient profound systemic hypotension in patients undergoing endovascular
therapy. Dose-response characteristics. Anesthesiology. 2000;93(4):998-1001.
15. Wong GK, Kwan MC, Ng RY, Yu SC, Poon WS. Flow diverters for treatment of intracranial aneurysms:
current status and ongoing clinical trials. J Clin Neurosci. 2011 Jun;18(6):737-740.
16. Ogilvy CS, Yang X, Jamil OA, Hauck EF, Hopkins LN, Siddiqui AH, Levy EI. Neurointerventional
procedures for unruptured intracranial aneurysms under procedural sedation and local anesthesia: a large-
volume, single-center experience. J Neurosurg Anesthesiol. 2011 Jan;114(1):120-128.
17. Smith WS, Dowd CF, Johnston SC, Ko NU, DeArmond SJ, Dillon WP, Setty D, Lawton MT, Young WL,
Higashida RT, Halbach VV. Neurotoxicity of intra-arterial papaverine preserved with chlorobutanol used
for the treatment of cerebral vasospasm after aneurysmal subarachnoid hemorrhage. Stroke. 2004
Nov;35(11):2518-2522.
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18. Feng L, Fitzsimmons BF, Young WL, Berman MF, Lin E, Aagaard BD, Duong H, Pile-Spellman J.
Intraarterially administered verapamil as adjunct therapy for cerebral vasospasm: safety and 2-year
experience. AJNR Am J Neuroradiol. 2002 Sep;23(8):1284-1290.
19. Marshall RS, Lazar RM, Pile-Spellman J, Young WL, Duong DH, Joshi S, Ostapkovich ND. Recovery of
brain function during induced cerebral hypoperfusion. Brain. 2001 Jun;124(Pt 6):1208-1217.
20. van Rooij WJ, Sluzewski M, Beute GN. Brain AVM embolization with onyx. AJNR Am J Neuroradiol.
2007 Jan;28(1):172-177.
21. Linfante I, Wakhloo AK. Brain aneurysms and arteriovenous malformations: advancements and emerging
treatments in endovascular embolization. Stroke. 2007 Apr;38(4):1411-1417.
22. Murugesan C, Saravanan S, Rajkumar J, Prasad J, Banakal S, Muralidhar K. Severe pulmonary oedema
following therapeutic embolization with Onyx for cerebral arteriovenous malformation. Neuroradiology.
2008 May;50(5):439-442.
23. Higashida RT, Meyers PM, Connors JJ, 3rd, Sacks D, Strother CM, Barr JD, Wojak JC, Duckwiler GR.
Intracranial angioplasty & stenting for cerebral atherosclerosis: a position statement of the American
Society of Interventional and Therapeutic Neuroradiology, Society of Interventional Radiology, and the
American Society of Neuroradiology. AJNR Am J Neuroradiol. 2005 Oct;26(9):2323-2327.
24. Goodney PP, Schermerhorn ML, Powell RJ. Current status of carotid artery stenting. J Vasc Surg. 2006
Feb;43(2):406-411.
25. Schumacher HC, Meyers PM, Higashida RT, Derdeyn CP, Lavine SD, Nesbit GM, Sacks D, Rasmussen P,
Wechsler LR. Reporting standards for angioplasty and stent-assisted angioplasty for intracranial
atherosclerosis. Stroke. 2009 May;40(5):e348-365.
26. Abou-Chebl A, Krieger DW, Bajzer CT, Yadav JS. Intracranial angioplasty and stenting in the awake
patient. J Neuroimaging. 2006 Jul;16(3):216-223.
27. Chamczuk AJ, Ogilvy CS, Snyder KV, Ohta H, Siddiqui AH, Hopkins LN, Levy EI. Elective stenting for
intracranial stenosis under conscious sedation. Neurosurgery. 2010 Nov;67(5):1189-1193; discussion
1194.
28. Furlan A, Higashida R, Wechsler L, Gent M, Rowley H, Kase C, Pessin M, Ahuja A, Callahan F, Clark
WM, Silver F, Rivera F. Intra-arterial prourokinase for acute ischemic stroke. The PROACT II study: a
randomized controlled trial. Prolyse in acute cerebral thromboembolism. JAMA. 1999;282(21):2003-2011.
29. Lee CZ, Litt L, Hashimoto T, Young WL. Physiologic monitoring and anesthesia considerations in acute
ischemic stroke. J Vasc Interv Radiol. 2004 Jan;15(1 Pt 2):S13-19.
30. Smith WS. Safety of mechanical thrombectomy and intravenous tissue plasminogen activator in acute
ischemic stroke. Results of the multi Mechanical Embolus Removal in Cerebral Ischemia (MERCI) trial,
part I. AJNR Am J Neuroradiol. 2006 Jun-Jul;27(6):1177-1182.
31. Smith WS, Sung G, Starkman S, Saver JL, Kidwell CS, Gobin YP, Lutsep HL, Nesbit GM, Grobelny T,
Rymer MM, Silverman IE, Higashida RT, Budzik RF, Marks MP. Safety and efficacy of mechanical
embolectomy in acute ischemic stroke: results of the MERCI trial. Stroke. 2005 Jul;36(7):1432-1438.
32. Abou-Chebl A, Lin R, Hussain MS, Jovin TG, Levy EI, Liebeskind DS, Yoo AJ, Hsu DP, Rymer MM,
Tayal AH, Zaidat OO, Natarajan SK, Nogueira RG, Nanda A, Tian M, Hao Q, Kalia JS, Nguyen TN, Chen
M, Gupta R. Conscious sedation versus general anesthesia during endovascular therapy for acute anterior
circulation stroke: preliminary results from a retrospective, multicenter study. Stroke. 2010
Jun;41(6):1175-1179.
33. Davis MJ, Menon BK, Baghirzada LB, Campos-Herrera CR, Goyal M, Hill MD, Archer DP. Anesthetic
management and outcome in patients during endovascular therapy for acute stroke. Anesthesiology. 2012
Feb;116(2):396-405.
34. Meyers PM, Higashida RT, Phatouros CC, Malek AM, Lempert TE, Dowd CF, Halbach VV. Cerebral
hyperperfusion syndrome after percutaneous transluminal stenting of the craniocervical arteries
Neurosurgery. 2000;47(2):335-343; discussion 343-335.
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35. Young WL, Kader A, Ornstein E, Baker KZ, Ostapkovich ND, Pile-Spellman J, Fogarty-Mack P, Stein
BM. Cerebral hyperemia after arteriovenous malformation resection is related to "breakthrough"
complications but not to feeding artery pressure. Columbia University AVM Study Project. Neurosurgery.
1996;38(6):1085-1093; discussion 1093-1085.
36. Young WL, Pile-Spellman J, Prohovnik I, Kader A, Stein BM, Columbia University AVM Study Project.
Evidence for adaptive autoregulatory displacement in hypotensive cortical territories adjacent to
arteriovenous malformations. Neurosurgery. 1994;34(4):601-610; discussion 610-611.
DISCLOSURE
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Supratentorial Tumors: Evolving Management and Techniques

Audrée A. Bendo, M.D. Brooklyn, New York
Alex Bekker, M.D., Ph.D. Newark, New Jersey
Introduction
Anesthetic management of supratentorial tumors is evolving as we develop a greater understanding of
neurophysiology and new techniques to guide tumor resection. Traditionally, neuroanesthetic care focused on
intracranial hypertension and therapeutic modalities to reduce intracranial volume. Through more sophisticated
preoperative work-up and diagnosis of the disease, tumor location and size, we have learned to individualize therapy
and anesthetic management of these patients.
This lecture will discuss three different management techniques—traditional craniotomy under general anesthesia,
neuronavigation/computer-assisted surgery and awake craniotomy. A rational approach to anesthetic management
and control of intracranial hypertension will be described, and the impact that new techniques have on patient care
and outcome will be reviewed.
Pathophysiology
Supratentorial tumors (meningiomas, gliomas and metastatic lesions) change intracranial dynamics predictably.
Initially, when the lesion is small and slowly expanding, volume-spatial compensation occurs by compression of the
CSF compartment and nearby cerebral veins, which prevents increases in intracranial pressure (ICP). As the lesion
grows, compensatory mechanisms become exhausted, and any further increase in tumor mass will cause
progressively greater increases in ICP. The intracranial compartment can compensate, up to a point, and patients
may exhibit minimal neurologic dysfunction despite the presence of a large mass, elevated ICP, and shifts in the
position of brain structures. Significant changes in ICP can occur if the tumor enlarges and develops a central area
of hemorrhagic necrotic tissue and/or a wide border of brain edema (non-autoregulating). With such compromised
intracranial compliance, small increases in arterial pressure can produce large increases in cerebral blood flow
(CBF), which can markedly increase intracranial volume and ICP with its attendant complications.
Significant increases in ICP result in two major deleterious effects on the brain – cerebral ischemia and herniation.
The cerebral perfusion pressure (CPP) is determined by the mean arterial pressure (MAP) minus the ICP. If ICP
increases to a greater extent than MAP, CPP is reduced. If ICP rises sufficiently, the brain becomes ischemic. The
second important effect of increased ICP is its ability to induce brain herniation. The herniation could be across the
meninges, down the spinal canal, or through a craniotomy. Herniation can rapidly lead to neurologic deterioration
and death. Those elements that can increase cerebral blood volume, such as hypertension, hypercarbia and hypoxia
are treatable and should be avoided perioperatively.
The goal of neuroanesthetic care for patients with intracranial hypertension is to maximize therapeutic modalities
that reduce intracranial volume. Various maneuvers and pharmacologic agents can be used to reduce brain bulk
(Table 1).1, 2 The application of these methods selectively, or together when necessary, is often accompanied by
marked clinical improvement.
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Table 1. Methods to Control Intracranial Hypertension.2
Diuretics:
Osmotic: 20 % Mannitol (0.25-1 g/kg iv) or 3 % Hypertonic saline3;
Furosemide: (0.5-1 mg/kg iv alone or 0.15-0.3 mg/kg iv) in combination with mannitol.
Corticosteroids:
Dexamethasone4: effective for localized cerebral edema surrounding tumors; requires 12-36 hours.
Adequate ventilation: Pa02 > 100 mm Hg, PaC02 33-35 mm Hg; hyperventilation on demand5.
Maintain hemodynamics (MAP, CVP, PCWP, HR):
Target normotension and maintain cerebral perfusion pressure (CPP = MAP – ICP) to avoid cerebral ischemia6.
Fluid therapy: Target normovolemia before anesthetic induction to prevent hypotension. Use glucose – free
isoosmolar crystalloid solutions to prevent increases in brain water content (from hypoosmolality) and ischemic
damage (from hyperglycemia).
Position to improve cerebral venous return: neutral, head-up position7.
Drug-induced cerebral vasoconstriction: e.g., thiopental, propofol.
Temperature control: Avoid hyperthermia perioperatively.
Cerebral spinal fluid damage – to acutely reduce brain tension.
Preoperative Evaluation
The initial approach to the neurosurgical patient is similar to that of all other patients. However, there is additional
information that must be obtained prior to craniotomy. This includes:
1. a complete baseline neurologic evaluation with special attention paid to the patient’s level of consciousness,
magnitude of intracranial hypertension, extent of neurologic deficits, and seizure history;
2. review of all neurodiagnostic studies with the neurosurgeon; and
3. discussion preoperatively, with the neurosurgeon, of the planned operative intervention [patient position,
surgical approach (tumor size, proximal structures, vascular involvement, radical excision), tumor type
(working diagnosis)].
Anesthetic Management: Special Considerations

Whether the patient is anesthetized, awake or sedated, anesthesia for craniotomy must be conducted with
emphasis on:
- hemodynamic stability and maintenance of CPP;
- avoidance of agents and techniques that increase ICP;
- producing a slack brain that facilities surgical dissection; and
- planning for smooth emergence and rapid awakening for early neurologic assessment and follow-up.
I. Craniotomy Under General Anesthesia

Induction. Before laryngoscopy and intubation of the trachea, the patient is smoothly and deeply anesthetized
with agents that reduce ICP. In the presence of elevated ICP, propofol is commonly used to induce anesthesia;
however, alternative agents such as thiopental or midazolam may be administered depending on the patient’s
medical condition and surgical plans.
A typical induction sequence might include the following:

Preoxygenation, then the intravenous administration of propofol (1.25 – 2.5 mg/kg) is followed by an opioid
(fentanyl 3-5 mcg/kg) and muscle relaxant. If no airway difficulties are anticipated, a nondepolarizing muscle
relaxant is administered while controlled hyperventilation with 100% oxygen is instituted. In patients who have
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been vomiting because of elevated ICP, cricoid pressure is applied during mask ventilation. To deepen the
anesthetic, fentanyl is administered in 50-mcg increments to a total dose of 10 mcg/kg, depending on the blood
pressure response. Lidocaine (1.5 mg/kg) is also administered intravenously 90 seconds before intubation to
suppress laryngeal reflexes. When the peripheral muscle twitch response disappears, an additional 20-30 mg bolus
of propofol may be administered, and endotracheal intubation is performed as rapidly and smoothly as possible. An
esmolol infusion or bolus may also be used to reduce the heart rate and blood pressure response to laryngoscopy and
intubation. After induction of anesthesia, ventilation of the lung is controlled mechanically. Arterial blood gases
are measured after intubation to establish the arterial end-tidal C02 gradient.
Routine institution of hyperventilation is no longer recommended in neurosurgical patients because of the risk of
cerebral ischemia in some conditions. Although not evidence-based in brain tumor patients, current
recommendations are to adjust PaC02 between 33-35 mm Hg when using volatile agents or when significant
intracranial hypertension exists. In other words, surgical conditions should define the PaC02 for each patient.
Maintenance. Since anesthetics affect the intracranial environment, there continues to be controversy over the
best choice of anesthetics for neurosurgical patients, i.e., intravenous or volatile-based anesthetics. In practice, the
anesthetics most frequently administered to neurosurgical patients are either propofol-fentanyl or isoflurane-
fentanyl.10 There have been no large clinical outcome studies conducted comparing anesthetic techniques in patients
undergoing craniotomy. Our choice of anesthetics has been based primarily on information derived from
experimental and clinical studies of cerebral hemodynamics (CBF, CMR02) and ICP.
Volatile anesthetics (isoflurane, sevoflurane and desflurane) have been shown to increase CBF (direct
vasodilation), reduce CMR02, increase ICP and impair autoregulation.1,2,11,12,13,14 Nitrous oxide (N 20) alone is
known cerebrostimulant (↑ CBF, ↑ CMR02 and ↑ ICP).2 For the normal brain, these effects can be controlled by
hypocapnia or intravenous anesthetics. Volatile anesthetics add to the increases in CBF obtained with N20.12,13
Recommendations: Volatile anesthetics should be used only for cases without elevated ICP or brain bulk
problems; use with early moderate hyperventilation; use less than 1 MAC and avoid combination with N20.
Intravenous anesthetics (thiopental, propofol and midazolam) show a dose-related decrease in CBF,
CMR02 and ICP and intact autoregulation.2,10,19,20 Propofol – Questions have been raised regarding the risk of
cerebral hypoperfusion with propofol anesthesia.21,22 Studies have demonstrated a reduction of CBF larger than a
reduction in CMR02 with propofol, suggesting a direct cerebral vasoconstricting activity and a decrease of the
CBF/CMR ratio.21,22 Dexmedetomidine (DEX) has been studied in patients undergoing intracranial tumor
surgery.24,25,26 When compared to propofol, one study reports lower analgesic requirements, better hemodynamic
stability, but longer extubation time with DEX.24 Opioids (fentanyl and remifentanil) cause either a minor
reduction or no effect on CBF and CMR02. Remifentanil, a rapidly metabolized opioid, allows a more rapid
postoperative neurologic assessment of the patient.2 Recommendations: Intravenous anesthetics should be used
for patients at risk for elevated ICP/brain bulk problems. In addition, total intravenous anesthesia is the technique of
choice when intraoperative neuromonitoring is required. Consider using a continuous infusion of propofol (50-150
mcg/kg/min) or thiopental (2-3 mg/kg/h), fentanyl (0.016-0.03 mcg/kg/min) or remifentanil (0.125-0.2 mcg/kg/min)
with midazolam and a nondepolarizing muscle relaxant.
Emergence. In the usual craniotomy for excision of a supratentorial tumor, the conduct of the anesthetic is aimed
at awakening and extubating the patient at the end of the procedure to permit early assessment of surgical results and
postoperative neurologic follow-up. The risks and benefits of an early versus delayed recovery in neurosurgical
patients have been reviewed1 Factors other than anesthetics that may delay awakening include: large intracranial
tumor, preoperative decreased level of consciousness, surgical complications (seizures, cerebral edema, hematoma,
pneumocephalus, vessel occlusion/ischemia), metabolic or electrolyte disturbances, and residual hypothermia.
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Emergence from anesthesia should be as smooth as possible, avoiding straining or bucking on the endotracheal tube,
arterial hypertension and elevated ICP. To avoid bucking during emergence, muscle relaxants are not reversed until
the head dressing is applied. Intravenous lidocaine (1.5 mg/kg) can be administered 90 seconds before suctioning
and extubation to minimize cough, straining, and hypertension. Antihypertensive agents such as labetalol and
esmolol are also administered during emergence to control systemic hypertension.27 It has been shown that many
patients who develop postoperative hematomas have had episodes of hypertension during emergence or early
recovery.28
II. Neuronavigation / Computer – Assisted Surgery

Neuronavigation allows precise anatomic mapping and orientation of tumors before the operation and throughout
the procedure.29,30,31 Image-guided surgery can be performed with an MRI in the operating room or in a “twin
operating theater” close by the conventional operating room. A study comparing the impact of neuronavigation on
patients undergoing glioblastoma surgery found that absolute and relative residual tumor volumes were significantly
lower with neuronavigation.32 Further, radical tumor resection was associated with a highly significant
prolongation in survival. In another study, image-guided resection of meningiomas was associated with less
complications and shorter hospital stays when compared to conventional surgery.33 Anesthetic management
concerns regarding intraoperative MRI have been discussed in several articles.35,36,37 Along with concerns of
administering anesthesia in a remote location and using MRI compatible anesthesia equipment, neuroanesthetic
principles must also be applied when caring for these patients.
III. Awake Craniotomy

Awake craniotomy represents an important option for resection of tumors which are located in close proximity to a
functionally important areas of the cortex (e.g. speech, motor) The main reason for performing surgery on awake
patient is a need for intraoperative testing of neurological function (functional cortical mapping) 38,39
Potential Advantages of Awake Craniotomy:

- Opportunity for brain mapping allows maximal tumor resection, minimizing postoperative neurologic deficits due
to retraction, edema, and/or resection of eloquent tissue.40,41
- Avoidance of general anesthesia and need for more intensive monitoring intraoperatively and postoperatively38, 42
- Low complication rate and reduction in resource utilization (shorter intensive care time and total hospital
stay).38,42,43
Awake Craniotomy: Challenges

- Requirement for providing analgesia and sedation during periods of intense surgical stimulation and having the
patient awake and cooperative during functional testing.
- Uncontrolled pain during head-holder placement, skin incision, craniotomy, and dura opening may lead to
hemodynamic instability, emotional distress, and loss of patient’s cooperation.
- Excessive sedation may result in hypoventilation and hypoxemia, both hazardous to the patient with intracranial
lesion. Uncooperative, oversedated or agitated patient may require urgent induction of general anesthesia. Either
controlled ventilation or endotracheal intubation is exceedingly difficult in a patient positioned laterally under
surgical drapes while the head holder fixes the head.
- Relatively high incidence of seizures that may be caused by the cortical stimulation.
Preoperative Evaluation and Preparation:

The preoperative visit to the patient scheduled for awake craniotomy is of paramount importance irrespective of the
chosen technique, especially in pediatric patients.
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The objectives of the preoperative visit are to:

- identify a motivated patient with good psychological profile and establish a relationship of confidence and trust;
- inform the patient about the procedure and what to expect (e.g., detailed verbal description, video tape);
(It should be emphasized that a patient would be deeply sedated for the most painful episodes which,
usually, occur during the initial and final parts of the operation.)
- inform and reassure the patient that the anesthesiologist will be at bedside throughout the procedure and will
administer analgesics and sedative, if required.
O.R. equipment and staff must be prepared in advance.
Intraoperative Management. Various intraoperative management strategies have been proposed. Adequate
analgesia and sedation are needed for head frame application, skin incision, craniotomy, and opening of the dura.
During brain mapping and tumor resection, the patient should be fully awake and cooperative to enable continuous
neurologic assessment. Several different anesthetic protocols have been recommended for awake craniotomy.44 The
current trend is to use controlled ventilation with LMA airway protection for the initial part of the procedure and
awaken the patient for functional testing. This approach became popular with the introduction of short acting,
titratable drugs, and, more recently, monitors of depth of sedation (i.e. BIS).
Many sedation techniques have been described for awake craniotomy. Several reports have endorsed the use of
propofol for sedation during awake craniotomy45. The rapid onset and a fast redistribution offer flexibility and ease
of titration. In addition, the use of propofol reduced the incidence seizures and nausea/vomiting. Oversedation and
respiratory depression are ever-present concern. Skucas and Artru have reported SpO2 of 91% -95% in16.9 percent
and SpO2 < 90% in 1.5% of 332 patients who were sedated with propofol without other sedatives46. Obesity was a
consistent risk factor requiring a secure airway. Other complications included hypotension (56.3%), tachycardia
(14.2%), seizures (3%), and patient movement (1.5%). Asleep-awake-asleep technique without airway devices was
used in that series of cases.
A combination of propofol and remifentanil has been successfully used for the awake brain lesion resection 47,48.
Remifentanil’s context-sensitive half-life is less than 5 minutes and independent of infusion duration. These
characteristics allow a rapid modulation of analgesia and sedation that is required during the course of the surgery.
The adverse effects of remifentanil, however, are similar to those of all fentanyl congeners and include respiratory
depression, oversedation, and nausea. A retrospective chart review of 98 procedures revealed high incidence of
respiratory depression49. The authors report PaCO2 of 50 (36-69) mm Hg and at least one 30-s epoch of apnea in 69
patients. In addition, 8 patients experienced nausea, 3 had intraoperative seizures, and 7 were unable to tolerate
awake state (include disoriented patients).
Dexmedetomidine (DEX), a highly specific alpha-2 adrenoreceptor agonist, has been recommended for use during
awake craniotomy.50,51,52 It does not suppress ventilation. The sedation produced by alpha-2 adrenoreceptor
agonists, unlike that by traditional sedatives such as benzodiazepines and propofol, does not depend primarily on
activation of the gamma-amino butyric acid (GABA) system. Furthermore, the primary site of alpha-2 agonist
sedative action does not appear to be the cerebral cortex, as would be the case with GABA-mimetic drugs. Perhaps
because of a non-cortical site of action, alpha-2 agonists appear to engender a different type of sedation when
compared to GABA-mimetic drugs. DEX produces an unusually cooperative form of sedation, where patients easily
transition from sleep to wakefulness and task performance when aroused, and then back to sleep when not
stimulated. Furthermore, disinhibition, cited as a common problem for propofol and the benzodiazepines, has not
been described for DEX. It is possible that given DEX appears to exert its sedative action at the LC, a brain
wakefulness and anxiety center, cognitive compromise and accompanying disinihibition is less prominent. This
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theory is consistent with healthy volunteer data indicating that cognitive integrity is well preserved in patients
receiving DEX.
Regional scalp blockade supplemented with field blocks are commonly used to reduce pain associated with the bone
flap removal and dura opening. Techniques for regional analgesia is well described and include blockade of the
greater and lesser occipital, auriculotemporal nerve, supraorbital, and zygomaticotemporal nerves53. Bupivacaine
0.5% with epinephrine 1:200,000, 2.5 cc is usually injected at each site. In addition, approximately 40 cc of
bupivacaine 0.33% with epinephrine 1:200,000 is injected along the incision line prior to commencing surgery. The
regional block is done at least 1 hr prior to skin incision to allow maximal diffusion of anesthetic agent and reduces
local anesthetic toxicity.
All awake procedures with sedation run the risk of respiratory depression and poor patient cooperation.
Complications such as seizures, increased ICP, hypertension, nausea and vomiting can occur.46,49,50 Therefore, most
anesthetic protocols include prophylaxis with antihypertensives, anticonvulsants and antiemetics.
Summary
There are several challenges to anesthetizing patients with intracranial mass lesions. Patients with large tumors and
mass effect will continue to require intensive monitoring and aggressive methods to lower ICP. Other patients with
small tumors may require standard monitoring and minimal techniques to lower ICP. As we develop facility with
awake craniotomy, intraoperative MRI and other technological advances, we must continue to balance the needs of
the patient (e.g., maintaining cerebral homeostasis and cardiorespiratory status) with those of the surgeon (e.g.,
unusual position, brain exposure without retraction, intraoperative neurologic assessment, early emergence for
neurologic examination). Appropriate selection of anesthetics and monitoring with meticulous general management
of the patient’s respiration, circulation, fluid replacement and positioning are all essential to improving outcome.
References and Suggested Reading
1. Bruder R, Ravassin PA. Supratentorial Masses: Anesthetic Considerations. In Cottrell JE and Young WL (eds):
Cottrell and Young’s Neuroanesthesia, 5th ed, Mosby Elsevier, Philadelphia, 2010 pp. 184-202.
2. Bendo AA, Kass IS, Hartung J, Cottrell JE. Anesthesia for Neurosurgery. In Barash PG, et al (eds). Clinical
Anesthesia, 5th ed., Lippincott Williams & Wilkins, Philadelphia, 2006, pp 746-89.
3. Wu CT, Chen LC, Kuo CP, et al. A comparison of 3% hypertonic saline and mannitol for brain relaxation
during elective supratentorial brain tumor surgery. Anesth Analg 2010; 110 (3): 903-7
4. Lukins, MB and Manninen PH. Hyperglycemia in patients administered dexamethasone for craniotomy. Anesth
Analg 100: 1129-33, 2005.
5. Gelb AW, Craen RA, Rao, GSU, et al. Does Hyperventilation improve operating condition during supratentorial
craniotomy? A multicenter randomized crossover trial. Anesth Analg 2008; 106:585-94.
6. Moore LE, Sharifpour M. Shanks A, et al. CPP below 60 mm Hg is common in the intraoperative setting. J.
Neurosurgl Anesthesiol 2012; 24: 58-62.
7. Tankisi A, Cold GE. Optimal reverse trendelenberg position in patients undergoing craniotomy for cerebral
tumors. J Neurosurg 2007; 106:239-44.
8. Rasmussen M, Bundgaard H, Cold GE. Craniotomy for supratentorial tumors: Risk factors for brain swelling
after opening the dura mater. J Neurosurg 2004; 101: 621-6.
9. Tolani KA, Bendo AA. Prevention and treatment of Homeostatic Disorders after Central Neurosurgical
Procedures. Best Practice and Research Clinical Anesthesiology 2007; 21:539-56.
10. Petersen KD, Landsfeldt U, Emil Cold, G, et al. Intracranial pressure and cerebral hemodynamic in patients
with cerebral tumors: A randomized prospective study of patients subjected to craniotomy in propofol-fentanyl,
isoflurane-fentanyl, or sevoflurane-fentanyl anesthesia. Anesthesiology 98(2):329-36, 2003.
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11. Kaye A, Kucera IJ, Heavner J, et al. The comparative effects of desflurane and isoflurane on lumbar
cerebrospinal fluid pressure in patients undergoing craniotomy for supratentorial tumors. Anesth Analg
98:1127-32, 2004.
12. Kaisti KK, Långsjö JW, Aalto S, et al. Effects of sevoflurane, propofol and adjunct nitrous oxide in regional
cerebral blood flow, oxygen consumption, and blood volume in humans. Anesthesiology 99:603-13, 2003.
13. Holström A, Åkeson J. Desflurane increases intracranial pressure more and sevoflurane less than isoflurane in
pigs subjected to intracranial hypertension. J Neurosurg Anesthesiol 16(2):136-43, 2004.
14. Strebel S, Lam AM, Matta B, et al. Dynamic and static cerebral autoregulation during isoflurane, desflurane
and propofol anesthesia. Anesthesiology 83:66-76, 1995.
15. Magni G, La Rosa I, Melillo G, et al. A comparison between sevoflurane and desflurane anesthesia in patients
undergoing craniotomy for supratentorial intracranial surgery. Anesth Analg 2009; 109: 567-71.
16. Myles PS, Leslie K, Chan MTV, et al. Avoidance of nitrous oxide for patients undergoing major surgery. A
randomized controlled trail. Anesthesiology 2007; 107:221-31.
17. Leslie K, Myles PS, Chan MTV, et a;. Nitrous oxide and long-term morbidity and mortality in the Enigma
trial. Anesth Analg 2011; 112:387-93.
18. Beattie WS, Badner NH. The Enigma of Enigma-I. Anesth Analg 2011; 112:255-7.
19. Larsen B, Seitz A, Larsen R. Recovery of cognitive function after remifentanil-propofol anesthesia: A
comparison with desflurane and sevoflurane anesthesia. Anesth Analg 2000; 90: 168-74.
20. Cenic A, Craen RA, Lee T-Y, et al. Cerebral blood volume and blood flow responses t hyperventilation in
brain tumors during isoflurane or propofol anesthesia. Anesth Analg 2002; 94:661-6.
21. Jansen GFA, van Praagh BH, Kadaria MB, Odoom JA.. Jugular bulb oxygen saturation during propofol and
isoflurane/nitrous oxide anesthesia in patients undergoing brain tumor surgery. Anesth Analg 1999; 89:358:63.
22. Kawano Y, Kawaguchi M, Horiuchi T, et al. Jugular bulb oxygen saturation under propofol or
sevoflurane/nitrous oxide anesthesia during deliberate mild hypothermia in neurosurgical patients. J Neurosurg
Anesthesiol 2004; 16:6-10.
23. Drummond JC, Dao AV, Roth DM, et al. Effect of dexmedetomidine on cerebral blood flow velocity, cerebral
metabolic rate and carbon dioxide response in normal humans. Anesthesiology 2008; 108:225-32.
24. Gunes Y, Gunduz M, Ozcengiz D, et al. Dexmedetomidine-remifentanil or propofol-remifentanil anesthesia for
patients undergoing intracranial surgery. Neurosurg Q 2005; 15(2):122-6.
25. Tanskanen PE, Kyttä JV, Randell TT, Aantaa RE: Dexmedetomidine as an anaesthetic adjuvant in patients
undergoing intracranial tumour surgery: A double-blind, randomized and placebo-controlled study. Br J
Anaesth 2006; 97:658-65.
26. Ilhan O, Koruk S, Serin G. et al. Dexmedetomidine in supratentorial craniotomy. Eurasian J Med 2010; 42:61-5.
27. Grillo P, Bruder N, Auquier D, et al. Esmolol blunts the cerebral blood flow velocity increase during emergence
from anesthesia in neurosurgical patients. Anesth Analg 2003; 96: 1145-9.
28. Basali A, Mascha EJ, Kalfas I, et al: Relation between perioperative hypertension and intracranial hemorrhage
after craniotomy. Anesthesiology 2000; 93:48-54.
29. Keles GE. Intracranial neuronavigation with intraoperative magnetic resonance imaging. Curr Opin Neurol
2004; 17:497-500.
30. Tuominen J, Yrjana SK, Katisko JP, et al: Intraoperative imaging in a comprehensive neuronavigation
environment for minimally invasive brain tumor. Acta Neurochir Suppl 2003; 85:S115-20.
31. Bernstein M, Al-Anazi AR, Kucharczyk W, et al: Brain tumor surgery with the Toronto-open magnetic
resonance imaging system: Preliminary results for 36 patients and analysis of advantages, disadvantages, and
future prospects. Neurosrugery 2000; 46:900-9.
32. Wirtz CR, Knauth M, Staubert A, et al: Clinicl evaluation and follow-up results for intraoperative magnetic
resonance imaging in neurosurgery. Neurosurgery 2000; 46:1112-20.
33. Paleologos TS, Wadley JP, Kitchen ND, et al: Clinical utility and cost-effectiveness of interactive image-
guided craniotomy: Clinical comparison between conventional and image-guided meningioma surgery.
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Neurosurgery 2000; 47:40-7.

34. Pinsker MO, Nabavi A, Mehdorn HM. Neuronavigation and resection of lesions located in eloquent brain areas
under local anesthesia and neuropsychological-neurophysiologic monitoring, 2007; 50:281-4.
35. Manninen PH, Kucharczyk W: A new frontier: Magnetic resonance imaging-operating room. J Neurosurg
Anesth 2000; 12(2):141-8.
36. Archer DP, McTaggart Cowan RA, Falkenstein RJ, Sutherland GR: Intraoperative mobile magnetic resonance
imaging for craniotomy lengthens the procedures but does not increase morbidity. Can J Anesth 2002; 49:420-6.
37. Schmitz B, Nimsky C, Wendel G, et al: Anesthesia during high-field intraoperative magnetic resonance
imaging experience with 80 consecutive cases. J Neurosurg Anesth 2003; 15:255-62.
38. Bilotta F, Rosa G. “Anesthesia” for awake neurosurgery. Curr Opin Anaesthesiol 2009; 22:560-5.
39. Bulsara KR, Johnson J, Villavicencio AT. Improvements in brain tumor surgery: the modern history of awake
craniotomies. Neurosurg Focus 2005; 18:1-3.
40. Meyer FB, Bates LM, Goerss SJ, et al. Awake craniotomy for aggressive resection of primary gliomas located
in eloquent brain. Mayo Clin Proc 2001; 76:677-87.
41. Vitaz TW, Marx W, Victor JD, et al. Comparison of conscious sedation and general anesthesia for motor
mapping and resection of tumors located near motor cortex. Neurosurg Focus 2003; 15:1-5.
42. Manninen PH, Tan TK. Postoperative nausea and vomiting after craniotomy for tumor surgery: A comparison
between awake craniotomy and general anesthesia. J Clin Anesth 2002; 14:279-83.
43. Blanshard HJ, Chung F, Manninen PH, et al. Awake craniotomy for removal of intracranial tumor:
Considerations for early discharge. Anesth Analg 92:89-94, 2001.
44. Dinsmore J. Anesthesia for elective neurosurgery. Br J Aneaesth 2007; 99:68-74.
45. Herrick I, Craen R, Gelb A, et al. Propofol sedation during awake craniotomy for seizures. Anesth Analg 1997;
84, 1280-4.
46. Skucas A, Artru A. Anesthetic complications of awake craniotomy for epilepsy surgery. Anesth Analg 2006;
102:882-7.
47. Berkestadt H, Perel A, Hadami M, et al. Monitored anesthesia care using remifentanil and propofol for awake
craniotomy. J Neurosurg Anesth 2001; 13:246-9.
48. Sarang A, Dinsmore J: Anaesthesia for awake craniotomy – evolution of a technique that facilitates awake
neurological testing. Br J Anaesth 2003; 90:161-5.
49. Keifer J, Dentchev D, Little K et al. Retrospective analysis of a remifentanil/propofol general anesthetic for
craniotomy before awake functional brain mapping. Anesth Analg 2005; 101:502-8.
50. Bekker A, Kaufman B, Samir S, et al. The use of dexmedetomidine foe awake craniotomy. Anesth Analg 2001;
92:1251-3.
51. Ard J, Bekker A, Doyle W. Dexmedetomidine in awake craniotomy: a technical note. Surg Neurol 2005;
63:114-7..
52. Mack PF, Perrine K, Kobylarz E, et al. Dexmedetomidine and neurocognitive testing in awake craniotomy. J
Neurosurg Anesth 2004; 16(1):20-5.
53. Pinosky M, Fishman R, Reeves S, et al. The effect of bupivacaine skull block on the hemodynamic response to
craniotomy. Anesth Analg 1996; 83:1256-61.
DISCLOSURE
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Impacting Traumatic Brain Injury Outcomes in Adults: Role of the

Anesthesiologist
Martin Smith, MBBS London,United Kingdom
Approximately 1.7 million people sustain a traumatic brain injury (TBI) in the United States every year, resulting in
around 275,000 hospitalizations and 52,000 deaths.1 TBI is a contributing factor in almost one-third of all trauma-
related deaths. The overall mortality of severe TBI is around 23% and more than 60% of survivors have residual
deficits, including cognitive impairment and behavioral problems, which affect their functional status and quality of
life. The total annual costs of TBI in the USA are estimated at more than $80 billion.
The epidemiology of TBI in high-income countries is changing as the reduction in high-velocity impacts because of
improvements in road safety is offset by an increase in fall-related injuries in an aging population.
Pathophysiology
Head injury is a heterogeneous diagnosis, encompassing a wide range of pathologies including diffuse axonal injury,
focal contusions and space occupying hematomas. If the initial (primary) injury is not immediately fatal, it is usually
exacerbated by secondary injury that develops over the subsequent minutes, hours and days. The distinction between
primary and secondary injury is relatively artificial since the pathophysiological changes are a continuum. The
primary injury activates an auto-destructive cascade of ionic, metabolic, immunological and inflammatory changes
that result in further neuronal damage or death and also render the brain more susceptible to systemic insults.2
Although the pathophysiology of TBI is multifactorial and complex, two components are of key importance -
reduction in substrate delivery below critical thresholds and the inability of brain cells to utilize delivered oxygen
and glucose because of metabolic failure. The end point of both is cerebral hypoxia/ischemia and the burden of
hypoxia/ischemia is directly related to outcome. Management is therefore directed towards preventing, minimizing
or treatment secondary ischemic insults.
Resuscitation and acute management

Resuscitation and early management is a crucial stage at which mortality and morbidity after TBI can be influenced.
In particular, the prevention or immediate correction of hypoxemia and hypotension, and rapid diagnosis and
evacuation of an expanding intracranial haematoma and treatment of raised intracranial pressure (ICP), are key
determinants of outcome.3
Consensus guidelines for the management of TBI are available and the most comprehensive, from the Brain Trauma
Foundation, have recently been revised.4 Optimization of systemic and intracranial physiological variables offers
effective neuroprotection and is associated with improved outcome after TBI. Simple things are important and the ‘6
Ns’ should guide treatment in the early management phase:
• normotension
• normovolaemia
• normoxia
• normocapnea
• normoglycemia
• normothermia
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Perioperative management
The perioperative period is of particular importance in the management of TBI. Despite interventions to correct
systemic physiological disturbances, such as hypotension, hypoxemia, hypo- and hypercarbia, and hypo- and
hyperglycemia, in the emergency department or neurointensive care unit, it is not uncommon for one or more of
these factors to persist as the patient is transferred for emergent surgery. The perioperative period is therefore an
opportunity to pursue ongoing resuscitation and to correct risk factors for secondary brain injury.
Patients may be exposed to additional secondary insults during surgery. These include intraoperative hypotension,
arterial blood gas abnormalities, hyperglycemia, blood loss, large fluid shifts and the systemic and cerebral effects of
anesthetic agents.5 There is no specific evidence to guide intraoperative management of TBI and the general
principles are therefore based on those applied in the intensive care unit.6 The major goals of anesthesia
management are to maintain cerebral perfusion and oxygenation to minimize the risk of cerebral ischemia and
secondary brain injury. Meticulous control of systemic physiological variables also offers effective intraoperative
neuroprotection after TBI.7
Monitoring
Cardiovascular variables should be continuously monitored throughout the perioperative period. Regular arterial
blood gas analysis should also be undertaken and continuous end-tidal carbon dioxide monitoring is essential to
minimize the intraoperative risk of excessive hyperventilation. Patients with severe TBI presenting for emergent
craniotomy will frequently have ICP monitors in place and such monitoring should be continued into the
postoperative period.8 ICP monitoring is also recommended during non-neurosurgical interventions after TBI,
particularly if large blood loss or fluid shifts are anticipated. Multimodal intracranial monitoring is frequently used
to identify impending brain ischemia and guide management on the neurointensive care unit9 but intraoperative
applications are less well defined.10
Blood pressure control

Hypertension is common in the presence of an expanding intracranial mass lesion because of the associated
sympathetic response. However, hypotension often ensues on dural opening as the sympathetic drive is suddenly
reduced.11 Other risk factors for the development of intraoperative hypotension include multiple lesions on CT scan,
subdural hematoma and duration (but not type) of anesthesia.12 The incidence of intraoperative hypotension has
previously been reported to lay between 30% and 45% 11;13;14 but a recent study suggests that it might be much
higher. A recent single center study identified intraoperative hypotension (defined as systolic BP < 90 mmHg
irrespective of duration) in 65% of patients during craniotomy for TBI.12 The average number of episodes of
hypotension per patient was five but some patients experienced as many as 40 episodes of low blood pressure. This
high burden of intraoperative hypotension is likely to represent a substantial risk to the injured brain because a
single episode of hypotension during resuscitation after TBI is associated with an approximate doubling of mortality
and a parallel increase in poor outcome in survivors.15 Intraoperative hypotension is associated with a higher
mortality14 and, since even short periods of hypotension are detrimental, meticulous control of intraoperative blood
pressure is crucial.
Euvolemia is the primary cardiovascular goal and intravascular volume should be maintained with isotonic
crystalloids and colloids, although there are no clear data supporting the use of one over the other. 0.9% saline is a
justified choice but the complications of infusion of large volumes of isotonic saline are well known. Although 4%
albumin is associated with increased mortality in patients with TBI,16 synthetic colloids do not worsen outcome.17
Glucose containing solutions should be avoided and blood loss replaced with blood products as appropriate.
Hypertonic saline has multiple beneficial actions on the injured brain. These include vasoregulatory, immunological
and neurochemical effects as well as the well-known osmotic action.18 There has been interest in the use of
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hypertonic saline solutions (with or without colloid added) for fluid resuscitation after TBI but a recent meta-
analysis reported no outcome benefit over isotonic crystalloids.19
A vasoactive agent is required if adequate blood pressure cannot be achieved with fluid resuscitation alone, although
there is currently no reliable evidence to support the use of one vasopressor over another.20 Some centers
preferentially use phenylephrine 5 but norepinephrine has a predictable and consistent effect on systemic blood
pressure and cerebral hemodynamics and is considered by many to be the agent of choice.21
Ventilation
Ventilation and inspired oxygen fraction should be adjusted to maintain PaO2 > 95 mmHg (13.0 kPa) if possible but at
least > 60 mmHg (8.0 kPa), and PaCO2 33.5-37.5 mmHg (4.5-5.0 kPa).4;6 Hyperventilation (PaCO2 < 25 mmHg) was
once the cornerstone of ICP control after TBI but it can precipitate or worsen regional cerebral ischemia because of
critical reductions in cerebral blood flow (CBF).22 Its routine use is now discouraged. Modest hyperventilation
(PaCO2 28-33.5 mmHg, 4.0 - 4.5 kPa) is indicated in selected cases but should be undertaken in conjunction with
cerebral monitoring that can identify impending ischemia. Acute hyperventilation is probably relatively safe for
short term use in threatened or actual brain herniation.
Glycemic control
Hyperglycaemia is common after TBI and related to the severity of injury, reflecting a normal response to stress. It
is associated with early mortality and poor functional outcome in survivors.23 Approximately 50% of patients
present with blood glucose >200 mg/dl (11.1 mmol/l) and levels greater than this in the first 24 h after admission
are associated with higher mortality24 and worse functional outcome in survivors.25 Hyperglycemia is also a
common finding during emergent craniotomy for TBI and associated with a higher rate of in-hospital mortality.26
Independent risk factors for the development of intraoperative hyperglycemia include more severe head injury, age
greater than 65 years, preoperative hyperglycemia and the presence of subdural hematoma. Furthermore, the stress
of general anesthesia and surgery brings an additional risk for the development of hyperglycemia.27
Blood glucose is a potentially modifiable risk factor and therefore a target for treatment during the perioperative
period. ‘Tight’ glycemic control with intensive insulin therapy has gained popularity in intensive care but may result
in cerebral hypoglycaemia and a higher prevalence of brain energy crises and higher mortality in some patients after
TBI.28 Insulin therapy also risks systemic hypoglycemia, although this was not observed in a recent intraoperative
study.26 There is no evidence to guide intraoperative glycemic control but it is recommended that systemic glucose
levels should be maintained between 110-180 mg/dl (6-10 mmol/l) and that hypoglycaemia and large swings in
blood glucose concentration should be avoided.29
Temperature
Both high and low admission brain temperature is associated with increased mortality after TBI, and increased brain
temperature with worsened neurological outcome in survivors.30 Pyrexia should therefore be avoided. Anti-pyretic
medication and cooling to normothermia are standard interventions on the neurointensive care unit but no
adequately powered randomized trial has confirmed their benefits and there are no data to support intraoperative
applications. Therapeutic hypothermia and controlled normothermia have recently been reviewed31 and clinical
studies of efficacy are on-going.
Anesthetic agents
Volatile agents reduce cerebral metabolic rate but at higher concentrations cause cerebral vasodilatation, increased
CBF and intracranial hypertension.32 However, these effects are minimal at concentrations less than 1 MAC.
Volatile agents also impair carbon dioxide reactivity. Sevoflurane has the most favorable profile in all these respects
and is preferred.32 Nitrous oxide should be avoided because it stimulates cerebral metabolism, resulting in
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vasodilation and increased CBF.33 Propofol reduces cerebral metabolic rate, CBF and ICP up to doses sufficient to
cause EEG suppression,34 and cerebral autoregulation is preserved. Total intravenous anesthesia (TIVA) using
propofol, usually in combination with an ultra-short acting opioid, is often a good choice, although there are some
data suggesting that propofol is associated with higher oxygen extraction than equipotent doses of sevoflurane.33;35
No studies have demonstrated an outcome advantage of one technique - inhalation anesthesia or TIVA – over the
other.36
Summary
The brain is at high risk of secondary injury during the perioperative period. Optimization of systemic physiological
variables offers effective neuroprotection and the anesthesiologist plays a key role in the management of these
complex patients.
References
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2. Maas AI, Dearden M, Servadei F, Stocchetti N, Unterberg A. Current recommendations for neurotrauma. Curr
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3. Moppett IK: Traumatic brain injury: assessment, resuscitation and early management. Br J Anaesth 2007; 99:
18-31
4. The Brain Trauma Foundation. The American Association of Neurological Surgeons. The Joint Section on
Neurotrauma and Critical Care. J Neurotrauma 2007; 24: S1-S106
5. Sookplung P, Siriussawakul A, Malakouti A, Sharma D, Wang J, Souter MJ, Chesnut RM, Vavilala MS.
Vasopressor use and effect on blood pressure after severe adult traumatic brain injury. Neurocrit Care 2011; 15:
46-54
6. Helmy A, Vizcaychipi M, Gupta AK. Traumatic brain injury: intensive care management. Br J Anaesth 2007;
99: 32-42
7. Klein KU, Engelhard K. Perioperative neuroprotection. Best Pract Res Clin Anaesthesiol 2010; 24: 535-49
8. Smith M. Monitoring intracranial pressure in traumatic brain injury. Anesth Analg 2008; 106: 240-8
9. Tisdall MM, Smith M. Multimodal monitoring in traumatic brain injury: current status and future directions. Br
J Anaesth 2007; 99: 61-7
10. Smith M. Perioperative uses of transcranial perfusion monitoring. Anesthesiol Clin 2007; 25: 557 – 77
11. Kinoshita K, Kushi H, Sakurai A, Utagawa A, Saito T, Moriya T, Hayashi N. Risk factors for intraoperative
hypotension in traumatic intracranial hematoma. Resuscitation 2004; 60: 151-5
12. Sharma D, Brown MJ, Curry P, Noda S, Chesnut RM, Vavilala MS. Prevalence and Risk Factors for
Intraoperative Hypotension During Craniotomy for Traumatic Brain Injury. J Neurosurg Anesthesiol 2012;
Aptil 11: Epub ahead of print
13. Kawaguchi M, Sakamoto T, Ohnishi H, Karasawa J, Furuya H. Preoperative predictors of reduction in arterial
blood pressure following dural opening during surgical evacuation of acute subdural hematoma. J Neurosurg
Anesthesiol 1996; 8: 117-22
14. Pietropaoli JA, Rogers FB, Shackford SR, Wald SL, Schmoker JD, Zhuang J. The deleterious effects of
intraoperative hypotension on outcome in patients with severe head injuries. J Trauma 1992; 33: 403-7
15. Chesnut RM, Marshall LF, Klauber MR, Blunt BA, Baldwin N, Eisenberg HM, Jane JA, Marmarou A, Foulkes
MA. The role of secondary brain injury in determining outcome from severe head injury. J Trauma 1993; 34:
216-22
16. Myburgh J, Cooper DJ, Finfer S, Bellomo R, Norton R, Bishop N, Kai LS, Vallance S. Saline or albumin for
fluid resuscitation in patients with traumatic brain injury. N Engl J Med 2007; 357: 874-84
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17. Sekhon MS, Dhingra VK, Sekhon IS, Henderson WR, McLean N, Griesdale DE. The safety of synthetic colloid
in critically ill patients with severe traumatic brain injuries. J Crit Care 2011; 26: 357-62
18. White H, Cook D, Venkatesh B. The use of hypertonic saline for treating intracranial hypertension after
traumatic brain injury. Anesth Analg 2006; 102: 1836-46
19. Tan PG, Cincotta M, Clavisi O, Bragge P, Wasiak J, Pattuwage L, Gruen RL. Review article: prehospital fluid
management in traumatic brain injury. Emerg Med Australas 2011; 23: 665-76
20. Curry P, Viernes D, Sharma D. Perioperative management of traumatic brain injury. Int J Crit Illn Inj Sci 2011;
1: 27-35
21. Steiner LA, Johnston AJ, Czosnyka M, Chatfield DA, Salvador R, Coles JP, Gupta AK, Pickard JD, Menon
DK. Direct comparison of cerebrovascular effects of norepinephrine and dopamine in head-injured patients. Crit
Care Med. 2004; 32: 1049-54
22. Coles JP, Fryer TD, Coleman MR, Smielewski P, Gupta AK, Minhas PS, Aigbirhio F, Chatfield DA, Williams
GB, Boniface S, Carpenter TA, Clark JC, Pickard JD, Menon DK. Hyperventilation following head injury:
effect on ischemic burden and cerebral oxidative metabolism. Crit Care Med 2007; 35: 568-78
23. Lam AM, Winn HR, Cullen BF, Sundling N. Hyperglycemia and neurological outcome in patients with head
injury. J Neurosurg 1991; 75: 545-51
24. Laird AM, Miller PR, Kilgo PD, Meredith JW, Chang MC. Relationship of early hyperglycemia to mortality in
trauma patients. J Trauma 2004; 56: 1058-62
25. Young B, Ott L, Dempsey R, Haack D, Tibbs P. Relationship between admission hyperglycemia and neurologic
outcome of severely brain-injured patients. AnnSurg 1989; 210: 466-72
26. Pecha T, Sharma D, Hoffman NG, Sookplung P, Curry P, Vavilala MS. Hyperglycemia during craniotomy for
adult traumatic brain injury. Anesth Analg 2011; 113: 336-42
27. Bower WF, Lee PY, Kong AP, Jiang JY, Underwood MJ, Chan JC, van Hasselt CA. Peri-operative
hyperglycemia: a consideration for general surgery? Am J Surg 2010; 199: 240-8
28. Oddo M, Schmidt JM, Carrera E, Badjatia N, Connolly ES, Presciutti M, Ostapkovich ND, Levine JM, Le RP,
Mayer SA. Impact of tight glycemic control on cerebral glucose metabolism after severe brain injury: a
microdialysis study. Crit Care Med 2008; 36: 3233-8
29. Bilotta F, Giovannini F, Caramia R, Rosa G. Glycemia management in neurocritical care patients: a review. J
Neurosurg Anesthesiol 2009; 21: 2-9
30. Greer DM, Funk SE, Reaven NL, Ouzounelli M, Uman GC. Impact of fever on outcome in patients with stroke
and neurologic injury: a comprehensive meta-analysis. Stroke 2008; 39: 3029-35
31. Polderman KH. Induced hypothermia and fever control for prevention and treatment of neurological injuries.
Lancet 2008; 371: 1955-69
32. Engelhard K, Werner C. Inhalational or intravenous anesthetics for craniotomies? Pro inhalational. Curr Opin
Anaesthesiol 2006; 19: 504-8
33. Kaisti KK, Langsjo JW, Aalto S, Oikonen V, Sipila H, Teras M, Hinkka S, Metsahonkala L, Scheinin H.
Effects of sevoflurane, propofol, and adjunct nitrous oxide on regional cerebral blood flow, oxygen
consumption, and blood volume in humans. Anesthesiology 2003; 99: 603-13
34. Turner BK, Wakim JH, Secrest J, Zachary R.Neuroprotective effects of thiopental, propofol, and etomidate.
AANA J 2005; 73: 297-302
35. Kawano Y, Kawaguchi M, Inoue S, Horiuchi T, Sakamoto T, Yoshitani K, Furuya H, Sakaki T. Jugular bulb
oxygen saturation under propofol or sevoflurane/nitrous oxide anesthesia during deliberate mild hypothermia in
neurosurgical patients. J Neurosurg Anesthesiol 2004; 16: 6-10
36. Grathwohl KW, Black IH, Spinella PC, Sweeney J, Robalino J, Helminiak J, Grimes J, Gullick R, Wade CE.
Total intravenous anesthesia including ketamine versus volatile gas anesthesia for combat-related operative
traumatic brain injury. Anesthesiology 2008; 109: 44-53
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DISCLOSURE
Codman, Johnson and Johnson Company, Self, Honoraria
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Impacting Pediatric Traumatic Brain Injury Outcomes:

Role of the Anesthesiologist
Monica S. Vavilala, M.D. Seattle, Washington
Introduction
Neurotrauma primarily includes TBI and spinal cord injury (SCI). TBI is the leading cause of death and disability in
children over 1 year of age. Approximately 1/2 of children with cervical spine injury have concomitant TBI and the
presence of TBI increases the risk of spine injury. After TBI, mortality is lower in children compared to adults
(10.4% vs. 2.5%), but certain factors such as young age, poor pre-hosptial care and poor rehabilitation as well as
hypoxia, hypotension predict worse outcomes. Since secondary insults can progressively worsen outcome, basic life
support algorithms (such as Pediatric Advanced Life Support (PALS) and Advanced Trauma Life Support (ATLS)
and principles of ATLS, including primary and secondary surveys, should be immediately applied. The spine cannot
be “cleared” by radiographic examination alone; a child with normal cervical spine radiographs should be
maintained with cervical spine immobilization until he/she can be thoroughly examined. In children, cervical spine
fractures can occur without neurological deficit and neurological deficit can occur without fracture. Neurological
deficit without fracture has been termed SCIWORA (spinal cord injury without radiological abnormalities). Most
children have an MRI. Blunt abdominal trauma and long bone fractures may occur with TBI/SCI and can be major
sources of blood loss. Craniotomies for the evacuation of either epidural or subdural hematomas are at high risk for
massive blood loss and VAE. Infants with inflicted trauma often present with a myriad of chronic and acute subdural
hematomas (Duhaime et al., 1998). Most inflicted injuries involving death involve TBI (iTBI). Children with iTBI
commonly present with altered consciousness, coma, seizures, vomiting or irritability and either injuries out of
proportion to history or developmental milestone and or incomplete histories. Types of injuries include subdural
hematoma, subarachnoid hemorrhage, skull fractures or diffuse axonal injury with or without cerebral edema.
Outcome is poor after iTBI. Recently, the Brain Trauma Foundation Guidelines on the Acute Care of Infants and
Children with Severe TBI were published (Ped Crit Care Med 2012).
Cerebral Hemodynamics after TBI

Cerebral Metabolic Rate (CMR), Blood Flow (CBF), A utoregulation and CO2 Reactivity.
During the first 6–12 hours after TBI, the brain may suffer poor perfusion and cerebral ischemia. This may be
followed by hyperemia and ICP. Finally, vasospasm may occur in 0-19% of TBI and poor perfusion may occur
(White et al., 2001; Mandera et al., 2002). Compared to children without TBI, children with TBI have lower VMCA
and cerebral hypoperfusion (CBF < 25ml/100g/min) is associated with cerebral ischemia and poor outcome
(Adelson et al., 1997; Skippen et al, 1997). However, following TBI, CBF and CMRO2 may not be matched,
resulting in either cerebral ischemia or hyperemia. As noted before, there are age-related changes in VMCA, CBF,
and CMRglu. (Kennedy and Sokoloff, 1957; Bode, 1988; Vink et al., 1988; Ogawa et al., 1987). One study of 30
children showed CO2 vasoreactivity changes < 2% to be associated with poor outcome (Adelson et al., 1997).
Cerebral autoregulation is impaired more often following severe (42%) compared to mild (17%) pediatric TBI
(Vavilala et al., 2004; Bouma et al., 1998; Stoyka and Schutz, 1975; Vavilala et al., 2007) and autoregulation may
be more impaired in children with inflicted TBI (Vavilala et al., 2007). Hemispheric differences in cerebral
autoregulation are common (40%) after focal TBI (Vavilala et al., 2008). If cerebral autoregulation is impaired,
lower blood pressure may passively result in diminished CPP and. Autoregulation is not a static condition and may
deteriorate in patients with initially intact autoregulatory capacity. Empirically increasing MAP to prevent cerebral
ischemia in the presence of unilaterally impaired cerebral autoregulation in the presence of hyperemia could result in
cerebral hemorrhage (Mandera et al., 2002; Bruce et al., 1981; Aldrich 1992). Impaired cerebral autoregulation has
been associated with poor outcome after pediatric TBI (Vavilala et al., 2007; Vavilala et al., 2006).
Cerebral Perfusion Pressure
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In 2003, the Pediatric Guidelines recommended that CPP < 40 mmHg be avoided after severe TBI to prevent
cerebral hypoperfusion leading to cerebral ischemia (Adelson et al., 2003). However, while not well understood,
there is likely an age dependent CPP threshold, with older children with TBI requiring higher CPP (Chambers et al.,
2005). Furthermore, there may be variability (low and high) in CBFV despite CPP > 40 mm Hg (Philip et al., 2009).
These data suggest that empiric CPP management may not have predictable effects on CBF. However, today either
systolic blood pressure (SBP) or CPP, are clinically used surrogates of estimating cerebral perfusion. The presence
of the Cushing’s reflex and autonomic dysfunction might be the only indicators of increased ICP. While SBP < 5th
percentile defines hypotension, in the absence of ICP monitoring and suspected increased ICP, supranormal systolic
blood pressure may be needed to maintain CPP. At a minimum, MAP should not be allowed to decrease below
values normal for age by using vasopressors. Intravenous phenylephrine infusion is often used to maintain CPP >
50mmHg.
Intracranial Pressure (ICP) and Intracranial Pressure Monitoring (ICPm)

The management of increased ICP in children is similar to adults. The indications for ICP monitoring (ICPm) and
treatment threshold for increased ICP are given in the 2003 Pediatric Guidelines (Adelson et al., 2003). The use of
ICPm in infants and children with severe TBI with a Glasgow Coma Scale (GCS) < 8 is variable but supported by
several clinical several clinical studies (Adelson et al., 2003). Symptoms of increased ICP (> 20mmHg) are
nonspecific in children and intermittent apnea may be its first sign in infancy (Sharples et al., 1995). Intracranial
pressure measurements from ventricular catheters and fiberoptic intraparenychymal transducer have a good
correlation (Gambardella et al., 1993). Ventricular catheters also provide a conduit to withdraw cerebrospinal fluid.
Intracranial hypertension can be initially managed through elevation of the head, neuromuscular blockade, and
hyperosmolar therapy. Mannitol can be given at a dose of 0.25 to 1.0 g/kg intravenously. All diuretics will interfere
with the ability to utilize urine output as a guide to intravascular volume status. Hypertonic saline (3% NaCl)
decreases ICP and increases CPP (Khanna et al., 2000). High-dose barbiturate therapy can be titrated to produce a
burst suppression pattern on the EEG which results in a reduction in cerebral metabolic rate. Refractory ICP can be
treated with thiopental infusions, but volume loading and intotropic support may be needed to counter myocardial
depression and hypotension (Adelson et al., 2003). If these maneuvers fail to control elevated ICP, decompressive
craniectomy should be considered. Careful monitoring of blood gasses, minute ventilation, and end-tidal carbon
dioxide tensions are recommended. Current guidelines recommend maintaining normocapnia (PaCO2 35mmHg-
40mmHg) except in the presence of impending herniation.
Anesthetic Management
The anesthetic approach to the traumatized child are based on the principles as outlined in the 2003 Pediatric
Guidelines for managing children with severe TBI and on ATLS Guidelines and as previously described. Children
with a GCS score < 9 require tracheal intubation for airway protection, and management of increased ICP. The
most common approach to tracheal intubation remains direct laryngoscopy and oral intubation with cricoid pressure
after induction of anesthesia, ventilation with 100% oxygen, under in-line stabilization, without traction. Naso-
tracheal intubations are contraindicated in patients with basilar skull fractures. If increases in ICP occur despite
hyperosmolar therapy during surgery, changing from < 1 MAC volatile anesthesia to TIVA may be considered.
Invasive arterial blood pressure monitoring should be used to guide blood pressure management and for hourly
sampling of blood gases, glucose and coagulation. Central access should be attempted by experienced personnel;
intraosseous lines are second line options if immediate vascular access is required. Muscle relaxants should be used
in unstable patients and opioids should be used sparingly in TBI if tracheal extubation is planned for the end of the
case. For SCI) when neuromonitoring (including motor evoked potentials) is used, TIVA should be used to
maintain anesthesia. Patients are currently maintained normothermic unless refractory ICP is present.
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Indications for Surgery

The major goal of surgery for TBI is to optimize the recovery of viable brain. Most operations deal with the removal
of mass lesions for the purpose of preventing herniation, intracranial hypertension, or alterations in CBF. In general,
unless small and deemed likely venous, epidural hematomas should be evacuated in comatose patients. Subdural
hematomas that are associated with herniation, are greater than 10 mm thick, or produce a midline shift of > 5 mm
should be removed. Indications on intraparenchymal mass lesions include progressive neurological deterioration
referable to the lesion, signs of mass effect on CT, or refractory intracranial hypertension. Penetrating injury may
often be managed with local débridement and watertight closure if not extensive and if there is minimal intracranial
mass effect (as defined above). Patients with severe brain swelling as manifest by cisternal compression or midline
shift on CT or intracranial hypertension by monitor are potential candidates for decompressive craniectomy. The
relatively increased frequency of diffuse swelling in the pediatric population makes children more frequently
candidates for such treatment. Generous decompressive craniectomy with duraplasty should be considered when
intracranial hypertension reaches or approaches medical refractoriness in salvageable patients where the ICP
elevation and its effects are felt to be the major threat to recovery. Unilateral craniectomy is appropriate for
lateralized swelling; bifrontal decompression is selected for diffuse disease. In general, surgical removal of mass
lesions in comatose patients should be performed as early as safely feasible. As this often involves incompletely
resuscitated patients, close collaboration between surgery and anesthesia is critical. Bidirectional communication
should be maintained regarding issues such as the stage of the procedure, anticipated and ongoing blood loss,
systemic stability, and unanticipated events so that the procedure can be altered or even terminated if necessary.
Induced Hypothermia
Head cooling and mild hypothermia has been demonstrated to be protective in asphyxiated neonates (Wyatt et al.,
2007). However, induced hypothermia in adult traumatic brain injury has mixed results (Clifton et al., 2001).
Recently, Adelson and colleagues demonstrated in a Phase II Trial that induced hypothermia can be a safe
therapeutic option in children with TBI (Adelson et al., 2005). An international multicenter trial of induced
hypothermia in pediatric patients reported that hypothermia did not improve the neurologic outcome and may
increase mortality (Hutchison et al., 2008). Interestingly, the International Hypothermia in Aneurysm Surgery Trial
(IHAST), failed to demonstrate any advantage of hypothermia over normothermia intraoperatively during surgical
clipping of intracranial aneurysms (Todd et al., 2005).
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References
Adelson PD, Clyde B, Kochanek PM, Wisniewski SR, Marion DW, Yonas H. Cerebrovascular response in infants
and young children following severe traumatic brain injury: a preliminary report. Pediatr Neurosurg. 1997
Apr;26(4):200-7.
Adelson PD, Bratton SL, Carney NA, Chesnut RM, du Coudray HE, Goldstein B, Kochanek PM, Miller HC,
Partington MD, Selden NR, Warden CR, Wright DW; American Association for Surgery of Trauma; Child
Neurology Society; International Society for Pediatric Neurosurgery; International Trauma Anesthesia and Critical
Care Society; Society of Critical Care Medicine; World Federation of Pediatric Intensive and Critical Care Societies.
Guidelines for the acute medical management of severe traumatic brain injury in infants, children, and adolescents.
Chapter 8. Cerebral perfusion pressure. Pediatr Crit Care Med. 2003 Jul;4(3 Suppl):S31-3.
Adelson PD, Ragheb J, Kanev P, Brockmeyer D, Beers SR, Brown SD, Cassidy LD, Chang Y, Levin H. Phase II
clinical trial of moderate hypothermia after severe traumatic brain injury in children. Neurosurgery 2005 56:740-54.
Aldrich EF, Eisenberg HM, Saydjari C, Luerssen TG, Foulkes MA, Jane JA, Marshall LF, Marmarou A, Young HF.
Diffuse brain swelling in severely head-injured children. A report from the NIH Traumatic Coma Data Bank. J
Neurosurg. 1992 Mar;76(3):450-4.
Bode H. and Wais U. Age dependence of flow velocities in basal cerebral arteries.Arch Dis Child. 1988
Jun;63(6):606-11.
Bouma GJ, Muizelaar JP, Fatouros P. Pathogenesis of traumatic brain swelling: role of cerebral blood volume. Acta
Neurochir Suppl. 1998;71:272-5.
Bruce DA, Alavi A, Bilaniuk L, Dolinskas C, Obrist W, Uzzell B. Diffuse cerebral swelling following head injuries in
children: the syndrome of "malignant brain edema". J Neurosurg. 1981 Feb;54(2):170-8.
Chambers IR, Jones PA, Lo TY, Forsyth RJ, Fulton B, Andrews PJ, Mendelow AD, Minns RA. J Neurol
Neurosurg
Psychiatry. 2006 Feb;77(2):234-40. Epub 2005 Aug 15.
Clifton GL, Miller ER, Choi SC, Levin HS, McCauley S, Smith KR, Jr., Muizelaar JP, Wagner FC, Jr., Marion DW,
Luerssen TG, Chesnut RM, Schwartz M: Lack of effect of induction of hypothermia after acute brain injury. N Engl
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Duhaime AC, Christian CW, Rorke LB, Zimmerman RA. Nonaccidental head injury in infants--the "shaken-baby
syndrome". N Engl J Med. 1998 Jun 18;338(25):1822-9.
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external ventricular device with the fiberoptic system. Childs Nerv Syst. 1993 9:470-3.
Hutchison JS, Ward RE, Lacroix J, Hebert PC, Barnes MA, Bohn DJ, Dirks PB, Doucette S, Fergusson D,
Gottesman R, Joffe AR, Kirpalani HM, Meyer PG, Morris KP, Moher D, Singh RN, Skippen PW. Hypothermia
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ultrasonography in children after head injury. Childs Nerv Syst. 2002 Apr;18(3-4):124-8. Epub 2002 Mar 20.
Philip S, Chaiwat O, Udomphorn Y, Moore A, Zimmerman JJ, Armstead W, Vavilala MS. Variation in cerebral
blood flow velocity with cerebral perfusion pressure >40 mm Hg in 42 children with severe traumatic brain injury. Crit
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Sharples PM, Stuart AG, Matthews DS, et al. Cerebral blood flow and metabolism in children with severe head
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DISCLOSURE
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Postoperative Cognitive Dysfunction

Sulpicio Soriano, M.D.-Moderator
Gregory Crosby, M.D. Boston, Massachusetts
Adrian W. Gelb, MBChB, DA, FRCPC San Francisco, California
Pratik Pandharipande, M.D. Nashville, Tennesee
Cardiac surgery, and especially cardiopulmonary bypass (CPB), has been the poster child for postoperative
cognitive morbidity. Over the past 10-15 years, however, it has become increasingly clear that disruption or decline
in cognitive function is also fairly widespread among elderly non-cardiac surgical patients. The reasons are a matter
of considerable controversy and this brief overview will recap current perspectives on the problem.
Delirium
Delirium, or acute brain dysfunction, is by far the most common cause of perioperative cognitive morbidity in
elders. In fact, it may be the most common of all perioperative complications in older patients; the incidence is 15-
55%, with orthopedic (hip fracture), major peripheral vascular, and cardiac surgery patients and at greatest risk.1-3
Prevalence approaches 100% among those requiring an ICU stay.4. Delirium is not just an annoyance. It is
associated with prolonged hospital stay and expense, greater likelihood of discharge to a nursing home or other post
acute-care facility, and higher 1-year mortality, with a hazard ratio of death in cardiac surgery patients not unlike
that of postoperative stroke.1,5,6 It is also associated with prolonged decline in cognitive performance and may even
be a marker for subsequent development of dementia.7,8
Delirium is a clinical diagnosis; it is defined by an acute and fluctuating course and inattention along with either
disorganized thinking and/or altered level of consciousness. Because it is so common and costly, hospitals are
increasingly focused on identifying and managing delirium. Non-psychiatrists typically use the CAM (Confusion
Assessment Method), a simple and well-validated bedside test, to diagnose delirium. However, delirium is under-
diagnosed because the symptoms fluctuate, patients may simply appear sedated (hypoactive delirium), and its
seriousness is underappreciated so caregivers may not look closely.1,9
The neurobiological mechanisms of delirium are not known but the vulnerability and predisposing factors are well
characterized. A leading hypothesis is that cognitive reserve and susceptibility to delirium are inversely
proportional, such that a lesser insult is required to trigger acute brain dysfunction in a cognitively or medically
fragile person.1,10 Given differences between the young and old brain, this would explain why elders are at higher
risk. Age and co-morbid diseases are major vulnerability factors, and there may be genetic component as well;
important predisposing factors include hypoxia, alcohol abuse, anemia, metabolic disturbances, and pre-existing
emotional or mental disability (i.e. depression, executive dysfunction, dementia).10-13 Infection is also a notorious
precipitator of delirium.1,14 This suggests that surgery, which produces an acute inflammatory response both
peripherally and within the CSF,14 may trigger delirium. Indeed, delirium is more common after ‘big’, invasive
procedures like cardiac surgery than minor ones but a causal relationship between cytokines and delirium remains
speculative. Likewise, while it is tempting to implicate intraoperative microemboli in the pathogenesis of
postoperative delirium, the data are inconclusive.15
Drugs and drug interactions are a major factor, a point of considerable relevance to the OR and ICU. Drugs with
anticholinergic activity, of which there are many besides atropine and scopolamine, are perhaps the most classic
delirium promoting agents but many other drugs (including ketamine and benzodiazepines) do so as well.16
Curiously, the mode of anesthesia (spinal, epidural, general) seems to have little bearing, perhaps because use of
sedatives and depth of hypnosis / anesthesia are not controlled.17 This is important for two reasons: there appears to
be a relationship between deep sedation and delirium risk18,19 and procedural “sedation” often ends up being general
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anesthesia.20 The agent used may also make a difference. During prolonged sedation of patients in the ICU, the risk
of delirium, or delirium plus ‘coma-free’ days, length of ICU stay, and 30 d mortality are all lower if
dexmedetomidine is used instead of a benzodiazepine,21,22 observations that are changing the way ICU patients are
sedated.23 As far as postoperative pain management goes, most, but not all, studies indicate the effectiveness of pain
control is more important than the specific agents or route of analgesia used.24-26 Pain itself is a cause of delirium so
the main point is that analgesics should not be withheld in elderly post-surgical patients for fear of inducing
delirium.
What can be done about perioperative delirium? First, identify the patient at high-risk and try to prevent it. Consider
obtaining a geriatric consultation since a simple, low-tech, geriatrician-directed perioperative re-orientation program
markedly reduces the incidence of delirium, particularly in high risk patients.27 Prophylactic administration of low-
dose haloperidol should be considered in high risk cases, as it has been shown to decrease the duration and severity
of delirium after hip surgery, albeit without reducing prevalence.28 Recent data suggest preoperative use of a statin
decreases the risk of perioperative delirium by 46% after cardiac surgery but a large retrospective study found the
opposite in non-cardiac surgery, so the role of these drugs remains controversial.29-31 During and after surgery, be
especially meticulous about minimizing or avoiding delirium-inducing agents (e.g. anticholinergics,
benzodiazepines) and managing potential precipitating factors (e.g. oxygenation, anemia). This is not always easy
since many drugs have anticholinergic effects, so use drugs sparingly. Recognize also that delirium is often an early
sign of serious underlying disease in the elderly.1 Because many factors contributing to delirium are not modifiable
(e.g. age of patient, type of surgery), it is particularly important to identify and manage remediable causes such as
hypoxemia, infection / sepsis, and pain. Maintaining a lighter plane of anesthesia might be useful but this remains
controversial.18,19,32 Lastly, when prevention fails, pharmacological intervention for symptom management may be
appropriate. There is no evidence benzodiazepines are effective and, as mentioned above, may actually make
matters worse. Haloperidol is the agent of choice but its efficacy is largely unproven.33 It should be used sparingly
and in low doses (0.5-1 mg iv initially) because of heightened sensitivity in advanced age, risk of QTc prolongation,
and oropharyngeal dysphagia.
Postoperative Cognitive Dysfunction (POCD)

Many elderly patients experience cognitive dysfunction weeks to months after surgery.34,35 This POCD is manifest
mainly as subtle deficits in memory and/or executive function that, unlike delirium, are diagnosed by performance
on a battery of neuropsychological tests rather than by clinical criteria. POCD is present after non-cardiac surgery in
30-40% of patients in the 1st postoperative week regardless of age but 3 months later it is 2-3 times more common in
aged patients (10-13%) than younger adult surgical controls or age-matched non-hospitalized controls (4-6%).36-38
Persons with POCD leave the workforce prematurely and, if they have POCD at both hospital discharge and 3
months postoperatively, are nearly 5-times more likely to be dead 1 year later.36,39 Thus, prolonged postoperative
cognitive impairment is real, common, and associated with poor functional outcomes and higher 1-year mortality.
The key question, of course, is what causes it? The short answer is that no one is certain but the problem is almost
certainly multifactorial. Advanced age clearly plays a role but it is not known whether this reflects loss of brain
reserve, prevalence of comorbid diseases (especially cerebrovascular disease), lack of neurotrophic factors, poor
reparative ability, etc. Although it is reasonable to speculate that poor baseline cognitive performance might identify
patients at greatest risk for POCD, most trials have excluded such people in part because poor baseline performance
makes decline difficult to detect.40 Genetic susceptibility may be a factor; a recent study found a strong association
between the Apo E4 alle, a major susceptibility gene for Alzheimer’s disease and other types of cognitive decline,
and POCD following inhalation but not intravenous anesthesia but previous work does not confirm greater
vulnerability.41-43 Similarly, physiologic changes seem to contribute minimally or not at all to POCD. Investigation
of perioperative hypotension (defined as MAP 45-55 mmHg or < 60% of baseline for ≥ 30 min) and/or hypoxia
(SpO2 ≤ 80 for > 2 min) during non-cardiac surgery, for example, has found little evidence of an association with
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POCD.17,38 Even the abnormal physiology of CPB does not explain late POCD, as comparison of on-pump and off-
pump CABG reveal similar cognitive (and neurologic) outcomes.44-46
This means we need to look elsewhere. Surgery itself is a good place to start, as surgery induces inflammation and
inflammation can impair cognition. Consistent with this hypothesis, the incidence of POCD is higher after major
inpatient than minor outpatient procedures, suggesting the magnitude of the surgical insult and inflammatory
response play a role.40 Recent work in young animals shows that a surgical procedure disrupts the blood brain
barrier, increases migration of macrophages into the brain, and produces transient neuroinflammation and learning
impairment that is reversed by a cytokine antagonist or a nicotinic acetylcholine receptor agonist.47-49 Unexpectedly,
however, isoflurane anesthesia alone also produces an inflammatory response in the brain.50 So, the
neuroinflammation hypothesis is viable and may be as relevant for explaining anesthetic-induced cognitive
impairment as it is for understanding surgically-induced cognitive deficits.
Could general anesthesia be the problem? Surely, among all the things that happen in the perioperative period,
general anesthesia has the most obvious effect on the brain (i.e. coma). The data, however, are inconsistent. Several
studies have found general anesthesia without surgery in old rodents induces prolonged changes in gene and protein
expression and learning impairment that lasts days to weeks, implying either that the neurobiological machinery of
memory is altered in an enduring way or that damage occurs.51-54 In addition, there is evidence that some volatile
anesthetics promote processes implicated in the neuropathogenesis of Alzheimer’s disease55 including promoting
formation and/or reducing clearance of Aβ, increasing Aβ aggregation and oligomer formation, augmenting its
neurotoxic qualities, and hyper-phosphorylating the microtubule protein tau (which also occurs with
hypothermia).54,56,57-62 What this means clinically is unclear. Thus far, clinical studies reveal no difference in the risk
of prolonged POCD between regional and general anesthesia63 and retrospective epidemiological studies report no
link between general anesthesia (plus surgery) and the development or progression of Alzheimer’s disease.64,65
However, the studies are either underpowered or challenged on methodological grounds and should be interpreted
cautiously.66 The fact that hospitalization for non-critical illness increases the risk of incident dementia67 makes it
reasonable to worry that the same might be true for surgical illness, although it could also point to the importance of
patient factors.
Indeed, what about the patient? Could it be they come to the OR with a cognitive deficit and we don’t know it?
Absolutely! About 20% of patients coming for elective total hip surgery meet criteria for MCI (mild cognitive
impairment) and the incidence of cognitive impairment is probably twice that in patients having CABG surgery.68-70
These patients go undetected, however, because we don’t ordinarily perform a preoperative cognitive
assessment.70,71 In addition, some studies indicate the type of surgery or anesthesia does not matter as far as POCD
is concerned.72 Furthermore, when one examines the cognitive trajectory of patients with coronary artery disease
who do or do not have CABG surgery, it turns out that over 5 years both groups decline but do so at the same
rate.73,74 Therefore, the likelihood of experiencing cognitive impairment postoperatively may be determined more by
preoperative cognitive status and comorbid conditions such as extent of cerebrovascular disease than the details of
the surgery or anesthesia.
So, while we know a little about what it isn’t (e.g. cardiolpulmonary bypass), we have no definitive answer for what
causes perioperative cognitive morbidity. Patient, medication, and surgical factors are likely to interact in a way still
poorly understood. What is clear is that like a “weak heart”, having a “bad brain” puts seniors at high risk for serious
cognitive morbidity perioperatively—which is at least as debilitating and ominous as problems we worry about in
other organ systems (e.g. low cardiac ejection fraction). Whatever the cause, the brain appears to take a ‘hit’ that
manifests as volume loss in cortical gray matter and the hippocampus that lasts for several months.75 With this in
mind, there is good reason for anesthesiologists and surgeons to be informed about the issue, as many of our elderly
patients and their families are justifiably interested.
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Postoperative CNS Dysfunction: Stroke

Adrian W. Gelb, MBChB, DA, FRCPC San Francisco, California
Stroke is an uncommon but potentially catastrophic complication in the perioperative period. A stroke is defined as a
focal or global neurological deficit of vascular origin lasting more than 24 hours. A transient ischemic attack (TIA)
lasts less than 24 hours and most less than a few hours. Because of the brevity we know nothing about the incidence
of TIA after surgery. The frequency of stroke varies among surgical procedures: 0.08 - 0.7% after general surgery,
0.8 – 3% after peripheral vascular surgery, 2 – 5% after head and neck surgery, and 1.5 – 10% after cardiac surgery.
Important risk factors include age, previous stroke, vascular disease, hypercoagulable states, and atrial fibrillation.
Fewer than 10% of strokes are apparent in the PACU. The majority manifests in a bimodal fashion, either in the first
24 hours or spread over the next days to weeks. Thus only a small percentage actually occurs intraoperatively. The
etiology is not always clear because most of the current literature uses administrative databases to derive the
incidence and the pathology is frequently not known or not documented. The vast majority when documented are
embolic or thrombotic. The role of hypotension is hard to determine, as even watershed infarcts, the hallmark of
hemodynamic strokes, are now believed to have an important embolic component. Hypotension is likely causative in
some but is probably more often a compounding factor when it occurs. This applies to both intraoperative and
postoperative strokes i.e. an embolic stroke associated with hypotension has a worse outcome. In a large stroke
study, not an intraoperative study, every 10mmHg reduction in blood pressure below 150mmHg increased mortality
by 18%.
The mortality from perioperative stroke ranges from 25 – 80%; the latter in patients with a previous stroke. The
mortality from a stroke not associated with surgery is 10%. Delay in diagnosis is a likely contributing factor. Nurses
are usually the first to detect neurological dysfunction but clinical neurological assessment is not a routine part of
general surgical care. A further delay ensues between nursing informing the surgical team and the latter obtaining a
neurological consultation. To address this, a growing number of hospitals have implemented a “code stroke”
whereby nurses can get an immediate neurology assessment. Another important contributing factor is the fact that
stroke is associated with a systemic inflammatory response and the greater the response, the greater the mortality.
Surgery is also associated with a profound systemic inflammatory response and this presumably has a synergistic
interaction with the similar response in stroke leading to a greater mortality.
There is no standard definition of hypotension in the anesthesia literature. Depending on the definition used, the
incidence ranges from 5 to 99% of patients. This makes it difficult to determine the contribution of blood pressure to
perioperative stroke and also the blood pressure threshold for treatment. Using the population lower limit of
autoregulation is not recommended. The population average is approximately 70-80mmHg, which is much higher
than shown in many current textbooks. Further the range is from 40 to 110mmHg making it impossible in any given
patient to know their lower limit. A retrospective study by Bijker et al found a small but statistically significant
relationship between a 30% reduction in mean blood pressure, but not systolic, from baseline and perioperative
stroke. Using this threshold seems a reasonable approach.
A CT scan is the fastest way to confirm the diagnosis when perioperative stroke is suspected. The patient should be
started on aspirin and moved to an ICU or intensive monitoring area. Many stroke patients die from cardiac
arrhythmias so continuous monitoring and appropriate treatment are important. Most patients in the immediate
postoperative period will not be candidates for intravenous thrombolysis with tPa. However they may be suitable for
intracranial intra-arterial tPa if within 6 hours of the stroke and this should be discussed with the surgeon, stroke
neurologist and interventional radiologist.
Further Reading:
Bateman BT, Schumacher HC, Wang S, Shaefi S, Berman MF. Perioperative acute ischemic stroke in noncardiac
and nonvascular surgery: Incidence, risk factors, and outcomes. A nesthesiology. 2009; 110: 231–238.
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Bijker JB, Gelb AW. The Role of Hypotension in Perioperative Stroke. Canadian J Anesthesia 2012; in press.
Bijker JB, van Klei WA, Kappen TH, van Wolfswinkel L, Moons KGM, Kalkman CJ. Incidence of intraoperative
hypotension as a function of the chosen definition: Literature definitions applied to a retrospective cohort using
automated data collection. A nesthesiology. 2007; 107: 213–220.
Bijker JB, Persoon S, Peelen LM, Moons KGM, Kalkman CJ, Kappelle LJ, van Klei WA. Intraoperative
hypotension and perioperative ischemic stroke after general surgery: a nested case-control study. A nesthesiology.
2012; 116: 658–664.
Bijker JB, van Klei WA, Vergouwe Y, Eleveld DJ, van Wolfswinkel L, Moons KGM, Kalkman CJ. Intraoperative
hypotension and 1-year mortality after noncardiac surgery. A nesthesiology. 2009; 111: 1217–1226.
Bucerius J, Gummert JF, Borger MA, Walther T, Doll N, Onnasch JF, Metz S, Falk V, Mohr FW. Stroke after
cardiac surgery: a risk factor analysis of 16,184 consecutive adult patients. A nn. Thorac. Surg. 2003; 75: 472–478.
Cao L, Li Q, Bi Q, Yu Q-J. Risk Factors For Recurrent Stroke After Coronary Artery Bypass Grafting. Journal of
Cardiothoracic Surgery. 2011; 6: 157.
Didier TJ, Giles M, Mashour GA, Shanks AM, Adelman EE, Gelb AW, Moore LE. Management of perioperative
stroke in noncardiac nonvascular patients. In: A476. Washington D.C.: ASA Annual Meeting; 2012.
Klöhr S, Roth R, Hofmann T, Rossaint R, Heesen M. Definitions of hypotension after spinal anaesthesia for
caesarean section: literature search and application to parturients. A cta A naesthesiol Scand. 2010; 54: 909–921.
Lam AM, Baldwin G. Blood pressure and adverse perioperative neurologic outcomes: an uncomfortable position.
Anesth Analg. 2012; 114:1156
Larsen FS, Olsen KS, Hansen BA, Paulson OB, Knudsen GM. Transcranial Doppler is valid for determination of the
lower limit of cerebral blood flow autoregulation. Stroke. 1994; 25:1985-8
Leonardi-Bee J, Bath PM, Phillips SJ, Sandercock PA; IST Collaborative Group. Blood pressure and clinical outcomes
in the International Stroke Trial. Stroke. 2002; 33:1315-20
Limburg M, Wijdicks EF, Li H. Ischemic stroke after surgical procedures: Clinical features, neuroimaging, and risk
factors. Neurology. 1998; 50: 895–901.
Mashour GA, Shanks AM, Kheterpal S. Perioperative stroke and associated mortality after noncardiac,
nonneurologic surgery. A nesthesiology. 2011; 114: 1289–1296.
Momjian-Mayor I, Baron J-C. The pathophysiology of watershed infarction in internal carotid artery disease: review
of cerebral perfusion studies. Stroke. 2005; 36: 567–577.
Ng JLW, Chan MTV, Gelb AW. Perioperative stroke in non-cardiac, non-neurosurgical surgery. A nesthesiology.
2011; 115: 879–890.
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Selim M. Perioperative stroke. N Engl J Med. 2007; 356: 706–713.
Sposato LA, Suárez A, Jáuregui A, Riccio PM, Altounian M, Andreoli MG, Rodriguez AI, Ressia JF, Bressan GJ,
Klein FR, Raffaelli H, Bozovich GE. Intraoperative hypotension, new onset atrial fibrillation, and adverse outcome
after carotid endarterectomy. J. Neurol. Sci. 2011; 309: 5–8.
Szeder V, Torbey MT. Prevention and treatment of perioperative stroke. Neurologist. 2008; 14: 30–36.
DISCLOSURE
These speaker have indicated that they have no significant financial relationship with the manufacturer of a
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The Current State of the Art in Intra-operative Neuroprotection

Piyush Patel, M.D.-Moderator San Diego, California
John C Drummond, M.D., FRCPC San Diego, California
Bradley J. Hindman, M.D. Iowa City, Iowa
David Warner, M.D. Durham, North Carolina
Why Have Neuroprotective Drugs Failed in Clinical Trials?
Piyush Patel, M.D. San Diego, California
The past three decades have witnessed a dramatic expansion of our understanding of the pathophysiology of cerebral
ischemia. Cellular signaling cascades that are initiated by ischemia, and which lead to brain injury, have been
delineated. Energy failure, ionic fluxes and dysregulation, glutamate excitotoxicity, oxidative stress, peri-infarct
depolarization and inflammation all contribute to injury (Kunz). The extent of damage to neurons, glia, blood brain
barrier and the neurovascular unit have been well characterized. This detailed knowledge of the pathophysiology is
the foundation upon which the concept of neuroprotection is based. Pre-clinical studies have documented the
efficacy of a variety of pharmacologic agents targeting multiple aspects of ischemic pathophysiology. This success
in the laboratory has generated enthusiasm about the possibility of reducing injury in patients with stroke. However,
despite intensive investigative effort, agents with demonstrated efficacy in reducing cerebral injury in pre-clinical
studies have not found success in clinical trials (Table 1). A variety of factors contribute to this incongruity between
excellent neuroprotection in the laboratory and lack of efficacy in humans; the present discussion is focused on a
brief review of these factors.
Table 1: Neuroprotective agents that did not demonstrate efficacy in Phase III trials
Glutamate antagonists Selfotel

Eliprodil
Aptiganel
Gavestinel
YM872
Calcium channel blockers Nimodipine
Anti-inflammatory drugs Enlimomab
LeukArrest
Antioxidants Tirilazad
NSY-059
GABA agonist Clomethiazole
Opioid antagonist Nalmefene
Growth factors bFGF
Other Lubeluzole
Citicoline
Adequacy of pre-clinical testing
Based on a high degree of efficacy in the laboratory, NMDA receptor antagonists were some of the first drugs to be
evaluated in patients with stroke. Unfortunately, large-scale clinical trials did not confirm NMDAR antagonist
neuroprotection (Hoyte). A post hoc examination of the pre-clinical data indicated that there was a significant
amount of variability in the conduct of laboratory studies. A lack of physiologic homeostasis, varying models of
ischemia, permanent versus transient ischemia, timing of the evaluation of efficacy, as well as dose and duration of
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therapy confounded interpretation. In addition, studies were often underpowered, were not randomized and blinding
of the observers was not assured (Donnan). To obviate these concerns, a consortium of academic and industry
scientists developed a set of recommendations for the conduct of preclinical stroke drug development (Table 2).
Adherence to these recommendations should improve the quality of the preclinical data upon which clinical trial
agents are selected.
Table 2: STAIR (Stroke Therapy Academic Industry Roundtable) Recommendations

1. Evalaute efficacy of candidate drug in models of permanent and transient focal ischemia
2. Employ rodent and gyrencephalic species
3. Develop dose response relationships
4. Maintain physiologic homeostasis
5. Randomization and blinding should be performed
6. Outcome measures should include histopathologic and functional assessments
7. Evaluation of drug in both genders
8. Replication of results in several laboratories, including both academic and industry laboratories
9. Publication of all data, both positive and negative
NXY-059, a spin trap agent that can reduce free radical mediated injury, underwent extensive preclinical evaluation
and many of the STAIR recommendations were followed. These included development of a therapeutic window,
dose-response relationships, duration of treatment, time of initiation of treatment with respect to stroke onset,
pharmacokinetic profile and histologic and functional outcomes. Importantly, efficacy was demonstrated in
subhuman primates. In a pilot SAINT I trial (Lees), modest efficacy was demonstrated. In the larger SAINT II trial
(Shuaib), no difference between treated and control subjects was found. Moreover, reduction in the complications of
tPA administration was also not observed.
The failure of NXY-059 in humans has prompted an increase in the recommended rigor in preclinical studies (Table
3). Based on these revised criteria, NXY-059 received on a modest score, and this questions whether preclinical
testing of NSY-059 was sufficient to warrant clinical trials (Donnan). Clearly, an improvement in the quality of
preclinical investigation is needed.
Table 3: Score for experiments using animal models of stroke (Donnan)

1. Publication after peer review
2. Statement of control of temperature
3. Random allocation to treatment or control groups
4. Blinded induction of ischemia
5. Blinded assessment of outcome
6. Anesthetic without neuroprotective efficacy
7. Appropriate animal model (age, diabetic, hypertensive)
8. Sample size calculation, power analysis
9. Compliance with animal welfare regulations
10. Statement of potential conflict of interests
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Matching of Preclinical Studies to Clinical Trials
There is considerable discrepancy in the variables that define efficacy in the laboratory and their application in
clinical trials. A better matching of preclinical studies with clinical trials might improve the conduct of trials
(Gladstone, Savitz):
1) The therapeutic window in animal studies is relatively short (usually 3h) whereas the time of entry of
patients in clinical trials is much longer. It is possible that the administration of a candidate neuroprotective agent
within a shorter time after stroke onset might demonstrate efficacy.
2) In laboratory settings, protection is defined by a reduction in cerebral injury; reduction in infarction occurs
primarily within the ischemic penumbra. In clinical trials, there is a wide variability in the nature of stroke. For
example, patients with lacunar strokes in the thalamus or internal capsule may have significant deficits but the
penumbra would be limited. Efficacy of neuroprotective agents would therefore be limited. Restricting trials to those
patients who have cortical strokes and who have salvageable penumbra (defined by a perfusion and diffusion
mismatch on MRI) can increase homogeneity of patients.
3) Experimental studies are, appropriately, primarily conducted in rodents. Rodent brains are lissencephalic
and have a greater proportion of grey to white matter. The human brain has proportionately more white matter.
Conduct of preclinical studies in gyrencephalic species (subhuman primates) might better predict efficacy in the
clinical setting.
4) Evaluation of efficacy of drugs in reducing cerebral injury is evaluated histologically in the laboratory and
by behavioral evaluation in the clinic. Behavioral evaluation of rodents is relatively crude and consists primarily of
motor function. To improve the quality of preclinical studies, detailed motor, sensory and cognitive function should
be performed
5) The time of evaluation of injury is short in experimental subjects whereas in patients, evaluation is often
performed 30 to 90 days after the stroke. Protection that is apparent within a short time after the initiating stroke
might not be apparent months later. The duration of evaluation should be increased in preclinical studies.
6) Experimental studies are performed in young and healthy animals. By contrast, patients who sustain strokes
are generally elderly and have a number of co-morbid conditions that impact the extent of injury and the ability of
the brain to recover from the ischemic insult. Performance of laboratory studies in hypertensive, aged and diabetic
animals might be better able to define the neuroprotective efficacy of a candidate drug.
7) Thrombolysis is a first line treatment in patients with stroke. Administration of candidate neuroprotective
drugs is likely to occur in patients who have already received thrombolytic agents. To date, however, the potential
interaction of neuroprotective drugs with thrombolytics has not been investigated in detail. The possibility of a
significant interaction, either positive or negative, has to be better defined.
8) Although thrombolysis has shown to be efficacious when administered with 3h after the onset of stroke,
reperfusion of the brain is heterogeneous and seldom complete. By contract, in the most commonly used model of
filament occlusion of the MCA in experimental studies, reperfusion is prompt and almost complete. This is then
followed by a delayed period of hypoperfusion. It has been proposed that prompt reperfusion in this model increases
the probability that a given candidate might have neuroprotective efficacy, a probability that may not be matched in
other models of focal ischemia or in patients (Hossmann). The relevance of the filament model of MCA occlusion to
human stroke is currently a subject of much debate.
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Targeting multiple cascades simultaneously to effect neuroprotection
The pathophysiology of cerebral ischemia is complex and variety of pathways has been implicated in brain damage.
A single agent with multimodal effects that simultaneously modulates several of these pathways might provide
neuroprotection. To date, such an agent has not yet been identified. The alternate is to administer a “cocktail” of
drugs, the components of which can target specific pathways. With this approach, agents that target excitotoxicity
might be used early in the management while anti-inflammatory agents can be added later. During the recovery
phases, agents that accelerate neuronal restoration might improve clinical outcome. Although the logic behind this
approach is appealing, there are a number of obstacles. First, the evolution of injury occurs over time and it is not
clear when a neuroprotective agent that targets a specific pathway should be introduced and for how long the
treatment should continue. Moreover, there is regional heterogeneity within the stroke region such that pathways
that are operative in one region of the ischemic brain may not be operative in other ischemic brain regions. Finally,
many putative neuroprotective agents have a Janus effect in that they can provide neuroprotection in certain
circumstances but can exacerbate injury or prevent recovery in other circumstances. For example, NMDA receptor
antagonists reduce injury when administered for a short time after stroke in experimental subjects. However,
prolonged administration of NMDA antagonists increases functional deficits because NMDA receptor activity is
important in neuronal growth (Adeleye). Similarly, TNFa antagonism is effective early after brain injury but
prolonged TNFa suppression reduces recovery (Scherbel). These opposing effects of neuroprotective agents make
difficult the timing and duration of treatment.
Summary
There has been a considerable advance in our understanding of the molecular mechanisms that underlie ischemic
cerebral injury. A reduction in injury has been clearly and repeatedly demonstrated by agents that target specific
aspects of the complex molecular cascade initiated by ischemia in preclinical studies. This efficacy has not been
demonstrated in clinical trials. This lack of translation can be traced to inadequate preclinical testing and drug
selection, improper matching of preclinical models to clinical trials and improper patient selection. Given multiple
failures, a key question is whether neuroprotection against stroke is possible. The improvement in outcomes in
patients with cardiac arrest and in neonates with hypoxic ischemic injury when subjected to mild hypothermia
indicates that protection and salvage of injured brain is certainly possible. This offers the hope that it may well be
possible to protect the brain against stroke.
References
Kunz A, Dirnagl U, Mergenthaler P. Best Prac Res Clin Anaes 2010;24:495-509.

Hoyte L, Barber PA, Buchan AM, Hill MD. Curr Mol Med 2004;4:131-6.
Donnan GA. Stroke 2008;39:242-248.
Lees KR, Zivin JA, Ashwood T et al. NEJM 2006;354:588-600.
Shuaib A, Lees LK, Grotta J et al. Stroke 2007;38:471.
Gladstone DJ, Black SE, Hakin AM. Stroke 2002;33:2123-2136
Savitz SI, Fisher M. Ann Neurol 2007;61:396-402
Hossmann KA. JCBFM 2012;32:1310-1316.
Adeleye A, Shohami E, Nachman D et al. Eur J Pharmacol. 2010 Mar 10;629(1-3):25-30.
Scherbel U, Raghupathi R, Nakamura M et al. Proc Natl Acad Sci U S A. 1999 Jul 20;96(15):8721-6.
DISCLOSURE
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Intraoperative Neuroprotection - Doing what really matters
John C Drummond, M.D., FRCPC San Diego, California
Pharmacologic Neuroprotection. The notion that anesthetics are other pharmacologic agents provide
“protection” can be reasonably characterized as an unsubstantiated fantasy. While the concept of the
“Pharmacologic Neuroprotective silver bullet” has great appeal, that gun is firing blanks. Administering propofol
and sometimes other drugs, often to achieve burst suppression of the EEG is au courant. The practice is unlikely to
have any measureable patient benefit. However, as long as the practice does not have adverse effects on
hemodynamics (see below), it is unlikely to be harmful. The exception is etomidate, which may actually be
deleterious in the setting of focal ischemia.
Temperature. While the pre-clinical literature, makes us believe in hypothermia as a protective strategy,
prospective trials in traumatic brain injury and intracranial aneurysm clipping have failed to confirm its efficacy in
those contexts. It is only following cardiac arrest that it is relevant today. Many of those of us who once routinely
induced mild hypothermia for aneurysm surgery, continue to allow temperatures to “drift” downward. But, it is hard
to advocate the continued use of active cooling. Assiduous prevention of hyperthermia should, however, be the
norm.
Glucose Management. Because of pre-clinical demonstrations of poorer neurologic outcomes after a variety of
standardized neurologic insults when plasma glucose (PG) is elevated, more aggressive control of PG prior to
neurosurgical interventions has been often proposed. The recent clinical enthusiasm for “tight” glucose control has
added some momentum to that phenomenon. But . . . . temper your enthusiasm with some caution. First, there is
very little convincing proof in human investigation that anything other than very high PGs actually aggravate
outcome. Secondly, and more importantly, the injured brain is more vulnerable to hypoglycemia than the normal
brain. Hyperglycolysis (with increased glucose demand) is common in cerebral injury states. As a result the injured
brain becomes “hypoglycemic” at higher PGs than does the normal brain. If insulin therapy is undertaken in the
neurologically injured, a PG target should probably not be less than 140 mg/dl and PG monitoring should performed
assiduously.
Blood Pressure Management. It’s not very glamorous. Giving a wonder drug makes a clinician feel more
sophisticated. But assuring the perfusion of the nervous system is both fundamental and critical. The principals that
deserve emphasis are:
1) The lower limit of adult CBF autoregulation is a higher value than you may have been taught. It is on average
70-75 (not 50) mmmHg.
2) The injured brain (or spinal cord) has low resting blood flow and impaired autoregulation. And is therefore more
vulnerable to hypotension.
3) Much of the CNS’s tolerance to hypotension is a function of collateral pathways, but there is considerable
heterogeneity in the extent of collateral pathways and therefore vulnerability to hypotension.
The Lower Limit of CBF A utoregulation. Diagrams that appear in standard texts have frequently depicted the lower
limit of human cerebral blood flow autoregulation (LLA) as being a mean arterial pressure (MAP) of 50 mmHg.
While this number may in fact be a reasonable representation of the LLA in several animal species, it is unlikely to
be an accurate value in adult humans. The first rendering of a CBF autoregulation curve was probably that drawn by
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Lassen (JAP 39:183-238, 1959). His diagram depicted an LLA that might be easily interpreted to be 50 mmHg. On
close inspection, however, the inflection point is probably at 60 mmHg. However, the inflection point on that hand-
drawn curve (where ever it is) is anchored by only two CBF values, both of which were obtained in pregnant
females at term in whom blood pressure was lowered using cerebral vasodilating drugs and in whom base line
pressures were probably well below the population average for normal adult humans. Furthermore, numerous
subsequent investigations (Morris, Surg Forum 4: 140-3, 1953; see Drummond, Anesthesiology 86; 1431-2, 1997
for additional references) suggest that the LLA in non-anesthetized adult humans is nothing less than 70 mmHg.
However, it should be acknowledged that the “rules” might be different during general anesthesia for at least two
reasons. The first is the frequent inclusion of vasodilating substances in anesthetic recipes. Vasodilators might serve
to shift the autoregulation curve in a leftward direction. The second resides in the observation that sympathectomy in
both experimental animals and humans during hypotension increases CBF. This suggests that the normal autonomic
response to hypotension includes some vasoconstriction of large extracranial and perhaps intracranial vessels
thereby producing effective right shifting of the autoregulation curve. If a general anesthetic were to effectively
prevent that autonomic response, it is possible that some resultant left shifting of the curve might occur. The reality,
however, is that there has been exceptionally little systematic study of adult human cerebral autoregulation during
anesthesia. The only context in which extensive study has occurred is during cardiopulmonary bypass. The most
recent investigation suggested the LLA is in fact about 65 mmHg (Joshi, Anesth Analg 2012;114:503–10).
However, it seems inappropriate to extrapolate those observations (hemodilution, non-pulsatile flow) to all other
anesthetic circumstances. In fact, it further seems likely that what pertains to any one anesthetic circumstance, e.g.,
spontaneous ventilation during anesthesia with a volatile agent, might not be relevant in another, e.g. a TIVA
anesthetic with remifentanil and propofol. We know very little about the LLA during general anesthesia in humans
and conservative assumptions should be made in the absence of more detailed knowledge.
The Physiologic CBF reserve. Many clinicians may well respond to the preceding discussion of the LLA with their
own observation that numerous patients in the span of their experience have tolerated MAPs in the 40s, 50s and 60s,
i.e., well below the proposed LLA of 70 mmHg. That is inevitably true. Patients tolerate blood pressures below the
LLA because there is a substantial CNS blood flow reserve. CNS flow can fall by approximately 40% of baseline
values before symptoms of ischemia begin to occur. That reserve is, in essence, a physiologic buffer that protects
patients in the event of hypotension. However, it is important that clinicians recognize the situations in which that
buffer may not be present, often because it has been encroached upon by some preexisting pathologic process. The
most common situations in which the buffer is likely to have been attenuated occur in circumstances in which CNS
tissue is under increased pressure. This may occur in the circumstances of increased ICP, increased ocular pressure
or when CNS tissue is under extrinsic pressure, e.g., compressed under retractors or by a bulging disc. The
significance of these situations is that the principal determinant of flow to the tissue is “perfusion pressure” rather
than “blood pressure”. Cerebral perfusion pressure (CPP) equals MAP minus local tissue pressure. Among the most
commonly overlooked situations in which tissue pressure is increased (and CPP is therefore less for a given value of
MAP) is in the circumstances of spinal stenosis, in particular cervical spinal stenosis. In that group of patients, the
normally wide latitudes for intraoperative blood pressure that anesthesiologists commonly allow should be tightly
restricted. It is our approach at UCSD to maintain MAPs during anesthesia in these patients (at least until the
decompression is complete) very close to normal waking levels. The agent we use most commonly to achieve this is
phenylephrine. This introduces another common misconception, which is addressed in the next paragraph.
A lpha1 A gonists and Cerebral V asoconstriction. It is often asserted that the various alpha1 agonists are significant
CNS vasocontrictors. While that may be so in canines, it is not true in humans. See "Miller's Anesthesia", 6th Ed.,
Ch. 21, p 818 for references. (The references were regrettably omitted in the corresponding section in the 7th edition
– Ch. 13, p 311.) In human investigations done many years ago, alpha one agonists were infused directly into the
cerebral circulation in concentrations sufficient to produce substantial increases in systemic arterial pressures; and
no changes in CBF were observed. The concern that phenylephirine is a CNS vasoconstrictor has too often restricted
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its use in situations where there was a pressing need to augment cerebral perfusion pressure. Clinicians should “get it
out of their heads”. Phenylephrine is NOT a significant CNS vasoconstrictor in the doses that we commonly
employ. When blood pressure support is warranted in patients who have sustained SAH or TBI or when CNS
structures are under compression (spinal stenosis, retractor pressure), after assuring appropriate volume status and
depth of anesthesia, phenylephrine given by infusion is a reasonable choice!
The Effect of Hydrostatic Gradients on CPP. In patients who undergo anesthesia in horizontal positions (supine,
prone, lateral), it is standard to measure blood pressure with cuffs or transducers at the level of the heart. When
positions are used that result in a vertical height difference between the height of the heart and the head, a pressure
differential between the two that is equivalent to the weight of a column of blood of that height can be expected to
occur. That gradient will be equal to approximately 2 mmHg for each one inch of height difference. The standard
teaching in neuroanesthesia has long been that blood pressure should be transduced at (or an arithmetic correction
imposed to correct to) the level of the external auditory meatus (EAM). Clinicians who are unfamiliar with the use
of the sitting position have occasionally failed to make this correction in transducer height, or have raised it only to
the level of the heart with sometimes severe adverse consequences for the perfusion of the brain and/or the cervical
spinal cord. This issue has been popularized recently in the context of injuries occurring in the so called “beach-
chair position”. A minority have disputed this notion, arguing that siphon-like mechanism maintains CBF in spite of
reductions in CPP calculated in the manner above (Hicks and Munis. Am J Physiol Regul Integr Comp Physiol.,
289(2): R629-32, 2005). Unless and until there is wider proof of that concept, conventional hydrostatic gradient
concepts should apply, and arterial tranducers should be raised to the level of the EAM or arithmetic corrects should
be applied to cuff pressures in order to “think” in terms of BP at the EAM.
Collateral blood supply to the CNS. Brain: Diagrams of the circle of Willis (CW) suggest considerable
collateralization to the brain. However, the CW is complete in only 42-52% of neurologically normal adults.
Approximately 25% of adults have some combination of bilaterally hypoplastic or absent PComs and/or P1
segments, i.e., no functional communication between the carotid and vertebro-basilar distributions. Absent or
hypoplastic ACom or A1 segments occur at an incidence of 3-6. Combinations of anterior and posterior CW
anomalies resulting in functional isolation of one carotid distribution from the remainder of the are observed in 7-8%
of healthy subjects (see Drummond et al., Anesth Analg 102: 896-9, 2006).
Spinal cord: The collateral input to the anterior spinal artery system is very variable and, in some individuals,
relatively limited. The cadaver dissections of Dommisse et al. revealed that the number of segmental medullary
vessels supplying the ASA varied between two and 17 (J Bone Joint Surg Br 1974;56:225-35). The arteria
radicularis magna (ARM) (AKA: artery of Adamkiewicz) most commonly arises from the aorta between T8 and L1
and enters the spinal canal via an intervertebral foramen on the left side. The ARM typically makes a “hairpin turn”
in the caudad direction and delivers blood to the spinal cord below its level of access. The blood supply to the spinal
cord above the level of entry of the ARM is typically provided by blood flowing in a caudal direction from more
cephalad regions of the cord. The anterior spinal artery is typically of very small caliber immediately cephalad to
the entry point of the ARM (and is sometimes discontinuous (Lazorthes. J Neurosurg 1971;35:253-62.).
Accordingly, there is relatively little potential for collateral flow from the ASA cephalad to the ARM’s entry point
to the lumbo-sacral enlargement to which the latter commonly supplies blood. Furthermore, the ARM is functionally
an end artery in some patients. There may be collateral supply to that distribution via vessels of low aortic or
internal iliac origin that travel along the roots of the cauda equina to reach the conus medullaris. But those vessels
are present in as few as 40 percent of adults(Domisse. J Bone Joint Surg Br 1974;56:225-35) and are thought, when
present, only to become important collateral pathways when gradually progressive vascular disease has limited flow
to the ASA via other vessels(Shine. Anesthesiology 2008;108:580-7; Lazorthes. J Neurosurg 1971;35:253-62.).
DISCLOSURE
Hospira, Self, Honoraria
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Intraoperative Neuroprotection— Lessons from IHAST
Bradley J. Hindman, M.D. Iowa City, Iowa
IHAST Study Design and Protocol

The Intraoperative Hypothermia for Aneurysm Surgery Trial (IHAST) was a multi-center (n=30),
prospective, randomized, controlled, partially-blinded trial designed to determine whether mild intraoperative
systemic hypothermia (33°C) would result in improved neurological outcome in patients undergoing surgery to treat
acutely ruptured intracranial aneurysms as compared with intraoperative normothermia.1 Major inclusion criteria
included a preoperative World Federation of Neurological Surgeons (WFNS) class of I, II, or III, and not being
tracheally intubated at the time of enrollment. Information regarding the characteristics of the ruptured aneurysm
(location, angiographic diameter) and its immediate effects (amount of subarachnoid blood [Fisher Scale], WFNS
class, and NIH Stroke Scale were recorded before surgery.
After induction of anesthesia, patients were randomized to one of two groups: 1) hypothermia (n=499,
target esophageal temperature 33.0°C) or 2) normothermia (n=501, target esophageal temperature 36.5°C), achieved
with surface cooling/warming techniques. Knowledge of intraoperative temperature was limited to each patient’s
anesthesiologist; surgeons were not informed of patient temperature. Intraoperative surgical management consisted
primarily of clipping the ruptured aneurysm. The decision to utilize temporary cerebral occlusion was at the
discretion of the neurosurgeon and was defined as the temporary occlusion of any major intracranial vessel for ≥1
minute. Rewarming of hypothermic patients began after the last aneurysm had been secured and was largely
complete by two hours after surgery.
All data collection, pre- and post-operative management decisions, and outcome assessments were made by
individuals who had no knowledge of intraoperative temperature assignment. Pre- and post-operative management
was not standardized, but all aspects of treatment and patient condition were prospectively documented daily for
either 14 days or until discharge (if discharge occurred before 14 days). Quantitative neurologic examinations using
the NIH Stroke Scale were performed at 24 and 72 hours after surgery and at discharge. Final neurological outcome
assessments were made approximately 3 months after surgery by certified examiners. The primary outcome
measure was the 5-point modified Glasgow Outcome Score (GOS): 1 = good recovery, 2 = moderate disability, 3 =
severe disability, 4 = vegetative state, 5 =death. Secondary outcomes included the Rankin scale, NIH Stroke Scale,
Barthel’s Activities of Daily Living Index, and a neuropsychological assessment.2 IHAST was powered to detect a
difference in the projected incidence of good 3-month outcome (GOS=1) of 75% in the hypothermia group and 65%
in the normothermia group (α=0.05, 1-β=0.90).
IHAST Study Rationale

Patients undergoing surgery for acutely ruptured cerebral aneurysms were selected as the study population
because prior studies had shown new postoperative neurologic deficits were relatively common, observed in
approximately 20-30% of patients in the first 24-48 hours after surgery.3-5 Similarly, approximately 35% of
aneurysmal SAH patients who had a good preoperative clinical grade had less than good outcome (i.e., GOS>1) 3-6
months after surgery. These acute deficits and long-term disabilities were generally thought to be related to
intraoperative events such as brain retraction, temporary and permanent vessel occlusion, hypotension, and
aneurysmal hemorrhage. A high baseline frequency of an unwanted outcome (e.g. neurologic injury), decreases the
number of study patients necessary to demonstrate the effect of a protective intervention. For example, if the
baseline incidence of an unwanted outcome is 50%, an intervention that decreases the incidence by 25% (i.e., from
50% to 38%) requires 494 study subjects (α=0.05, 1-β=0.80). In contrast, if the baseline incidence of an unwanted
outcome is 25%, an intervention that decreases incidence by 25% (i.e., from 25% to 17%), requires 1,372 study
subjects. That new postoperative neurologic deficits in cerebral aneurysm surgery patients appeared to originate in
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the intraoperative period allowed for application of a protective intervention (hypothermia) before and/or during the
period of highest risk.
Mild systemic hypothermia (33oC) was selected as the protective intervention because, in the late 1980’s
and early -90’s, animal experiments demonstrated mild-to-moderate hypothermia decreased neurologic injury
following a variety of ischemic insults.6-8 In fact, mild hypothermia appeared to decrease injury in virtually all
models of temporary ischemic insults. In particular, in rat temporary focal ischemia models, hypothermia (32-33ºC)
markedly decreased infarct volumes.9-11 These latter models were especially compelling because they are highly
analogous to temporary vascular occlusion (“temporary clipping”) as often used during cerebral aneurysm surgery.
Mild hypothermia was attractive as an intraoperative neuroprotective intervention because the physiology and
adverse effects of hypothermia were already fairly well known and, in anesthetized patients, mild hypothermia could
be relatively rapidly induced and reversed during surgery.
A small pilot trial of systemic hypothermia in cerebral aneurysm surgery patients with acute SAH (n=52)
showed that clinical outcomes appeared to be more favorable 24 hours after surgery and this apparent benefit
remained 3 months after surgery.12
Table 1. IHAST Pilot Trial Data12
Outcome Hypothermia Normothermia
(33.7, n=24) (36.7, n=27)
24 hour neurologic deterioration 5, 21% 10, 37%
3-Month Glasgow Outcome Score
1: Good 17, 71% 16, 57%
2: Moderate disability 3, 13% 6, 21%
3: Severe disability 2, 8% 3, 11%
4: Vegetative 0, 0% 0, 0%
5: Death 2, 8% 3, 11%
Thus, it was with highly consistent and supportive clinical, experimental, and pilot data, that IHAST trial began
patient enrollment in March, 2000; completing enrollment and follow-up of 1,000 patients three years later. At the
time, all indications were that IHAST would establish that intraoperative neuroprotection could be achieved with
mild systemic hypothermia. It did not; see Table 2.
Table 2. IHAST Primary Outcome Data1
Primary Outcome Hypothermia Normothermia
3-Month Glasgow Outcome Score (33.3±0.8, n=499) (36.7±0.5, n=501)
1: Good 66% 63%
2: Moderate disability 21% 22%
3: Severe disability 7% 9%
4: Vegetative 0% 0%
5: Death 6% 6%
Why didn’t hypothermia “work” as expected? What lessons can be learned from a clinical trial that seemed almost
“guaranteed” to have a positive result that didn’t?
Lesson #1— Beware of studies with small numbers

IHAST pilot data was wholly consistent with expectations and hypotheses of the time but, because of the
small sample size, it was not statistically significant. In small studies, different outcomes in a very few patients can
provide a very different qualitative impression of the result. As shown in Table 3, if there had been just one less
hypothermia patient with a GOS=1, and one more normothermia patients with a GOS=1, the incidence of good
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outcomes would have been practically equivalent between the two groups. Most likely, the apparent treatment
effect of hypothermia would have been considered too small to study—IHAST might not have happened. In fact,
the incidences of GOS=1 in the hypothetically revised pilot data (Table 3) are almost an exact match to what was
observed in the subsequent main IHAST trial (Table 2). This is probably not a coincidence.
Table 3. Hypothetical Revision of IHAST Pilot Data12
Outcome Hypothermia Normothermia
(33.7, n=24) (36.7, n=27)
3-Month Glasgow Outcome Score
1: Good—Original data 17, 71% 16, 57%
1: Good—Hypothetical revision 17-1=16, 66% 16+1=17, 61%
The lesson is clear. Small pilot studies— even when randomized— are not reliable. Small studies are highly
susceptible to sampling error, with the outcomes of a very few patients having a large effect on the apparent result.
Pilot trials can give you the wrong, or at least a misleading, answer. This is not to suggest that pilot studies are not
essential, only that clinical practice should not be changed prior to, or in the absence of the larger, definitive trial.
Lesson #2— Translation of animals studies to the operating room is not guaranteed
As discussed above, a central concept on which IHAST was based was that SAH patients undergoing
aneurysm surgery would have a high incidence of new postoperative neurologic deterioration. This was, in fact,
observed to be the case. In IHAST, 426 patients (43%) were found to have signs of neurologic deterioration 24
hours after surgery.13 Most of the patients with deterioration had a new focal motor worsening (65%) and/or ≥4
point worsening of on their NIH stroke scale exam (60%) and/or ≥2 point worsening in the Glasgow coma scale
(51%). In only a few patients (12%) was delayed ischemic neurologic deficit (DIND) (symptomatic “vasospasm”)
considered to contribute to neurologic deterioration 24 hours after surgery. As shown in Table 4, new postoperative
neurologic deterioration was associated with a significantly decreased incidence of good 3-month outcome (GOS=1)
and significantly greater incidence of death.
Table 4. IHAST 24 Hour Neurological Status and Final Outcome13
24 Hour Neurologic Status 3-Month GOS=1 Mortality
No Neurologic Deterioration (n=574) 77% 1%
Neurologic Deterioration (n=426) 46% 13%
A multivariate model determined that four preoperative and five intraoperative factors were independently
associated with 24 hour neurologic deterioration: 1) patient age, 2) increasing Fisher grade; 3) preoperative
ventriculostomy; 4) timing of surgery (days 4-6 after SAH worse); 5) increasing pre-induction blood pressure, 6)
difficulty of aneurysm exposure, 7) use of deliberate hypotension during surgery, 8) intraoperative blood loss, and 9)
temporary clip time >20 minutes.13 These factors substantiate the notion that some patients present to the operating
room with less tolerance for any unfavorable intraoperative events, and that events during surgery that compromise
cerebral perfusion contribute to less favorable outcomes. Based on the experimental literature, hypothermia would
have seemed likely to increase tolerance to ischemic events during surgery. However, it did not. As shown in Table
5, mild systemic hypothermia did not affect the incidence of 24 hour neurologic deterioration; P=0.22. Thus, in the
entire IHAST population, there was no short-term (24 hour) evidence of intraoperative neurologic protection with
hypothermia.
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Table 5. IHAST 24 Hour Neurologic Status

24 Hour Neurologic Status Hypothermia Normothermia
(33.3±0.8, n=499) (36.7±0.5, n=501)
No Neurologic Deterioration (n=574) 59% 55%
Neurologic Deterioration (n=426) 41% 45%
Lesson 2a—Animal models of disease/injury may not represent clinical disease. Because there were not
models in which animals spontaneously developed aneurysmal subarachnoid hemorrhage, the findings from
“substitute” models were extrapolated to the intraoperative setting—forebrain ischemia models for temporary global
hypoperfusion and/or retraction, and temporary focal ischemia models for temporary clipping. While numerous
animal studies showed that intra-ischemic hypothermia (32-33°C) was neuroprotective with temporary middle
cerebral artery (MCA) occlusion,14 two fundamental differences between animal models and the clinical situation
must be appreciated. First, in animal temporary occlusion models, 1-3 hours of MCA occlusion are necessary to
result in infarction whereas, in humans, only 20 minutes appears to be sufficient. Thus, animals appear to have
much greater ischemic tolerance than humans. Second, in animal temporary occlusion models, with few exceptions,
outcomes have been determined only 1-4 days after the insult. The long-term protective value of isolated intra-
ischemic hypothermia (with no post-ischemic hypothermia) in the setting of temporary focal ischemia is not well
established.
In IHAST, 441 patients underwent temporary clipping.15 As shown in Table 6, the percentage of patients
who did not have neurologic deterioration at 24 hours after surgery did not differ between hypothermic and
normothermic patients. Although temporary clip durations greater than 20 minutes were associated with less
favorable outcome, hypothermia did not change this.
Table 6. Percentage of IHAST Temporary Clip patients with No 24 h Neurologic Deterioration15
No 24 hour Neurologic Deterioration
Temporary Clip Hypothermia Normothermia
Duration (n=208) (n=233)
≤10 min (n=279) 59% 55%
11-19 min (n=104) 65% 54%
≥20 min (n=58) 37% 35%
All durations 54% 56%
Similarly, there were no differences between hypothermic and normothermic temporary clip patients in 3-month
GOS scores and neuropsychologic scores. The use of supplemental pharmacologic drugs (thiopental) also did not
affect the outcomes of patients undergoing temporary clipping.15 The lesson is that patients, in comparison to
animals, appear to be much more sensitive to ischemic insults and, as a result, are much less able to favorably
respond to a protective intervention.
Lesson 2b-An intervention applicable in the laboratory may not be applicable in the operating room.
Because of a large surface to volume ratio, hypothermia is readily induced and reversed in small animals using
surface methods. Also, in the laboratory, in contrast to the operating room, the onset of the ischemia insult can be
delayed until the target hypothermic temperature is achieved. In IHAST patients randomized to hypothermia
(n=499) the goal was to achieve an esophageal temperature of 33.0°C by clipping of the first aneurysm (acceptable
range of 32.5-33.5°C). However, surgery was not to be delayed so as to achieve target temperature. In fact, the
IHAST hypothermic temperature goal was not reached in many patients: 309 (62%) had a temperature >33.0°C,
126 (25%) had a temperature >33.5°C, and 70 (14%) had a temperature >34.0°C. Subgroup analysis limited to
hypothermic patients who were in the target range did not find evidence of hypothermic protection.1 Nevertheless,
the lesson is that even “simple” interventions will often be imperfectly applied in the clinical setting—a dose of
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protective agent may be incompletely administered, given late, or even missed. For this reason, it is essential to
monitor for protocol (intervention) compliance, to assure that effective levels of the intervention are actually being
achieved. IHAST utilized an independent Protocol Monitor to confirm that intraoperative temperatures recorded on
anesthesia records matched values on case report forms. Furthermore the Protocol Monitor was empowered to
contact participating centers if protocol compliance issues were identified and, when necessary, to take action. This
resulted in two IHAST centers being dropped (patient data were retained) and three centers being temporarily
restricted from enrollment while local investigators underwent retraining.
The “take home” lesson is that any neuroprotective intervention that is applied to the operating room must
be very robust—the treatment effect in animals must be very large in order to have a decent chance of having any
demonstrable effect in humans, and to overcome the frequent reality of imperfect clinical application.
Lesson #3— Randomized controlled trials: Essential to randomize but difficult to perfectly
control
The fact is that, in clinical trials, almost nothing is truly controlled. The only thing that is controlled is the
intervention. That is why randomization is so important and why randomization must be delayed until the last
possible moment. The goal of randomization is to attempt to have patient risk factors and uncontrolled patient
management decisions—factors that will likely affect outcome—to be equally distributed between the treatment
groups. Patient management decisions that are based on knowledge of the intervention have the potential confound
the results of the trial. In IHAST, the randomization envelope was opened after induction of anesthesia, such that
the selection of anesthetic agents and monitors had largely already taken place. In fact, in IHAST, hypothermic and
normothermic patients did not differ in a single anesthesia-related variable—agents, monitors, pressors, etc.; see
Table 7.
However, the intervention itself, may lead to changes in other factors that have the potential affect outcome
and, potentially, confound the results of the trial. As shown in Table 7, patients randomized to hypothermia had
greater intraoperative blood glucose than normothermic patients.
Table 7. IHAST Intraoperative Variables
Variable Hypothermia Normothermia
(33.3±0.8, n=499) (36.7±0.5, n=501)
Nitrous Oxide Use 38% 37%
Intraoperative glucose (mg/dL)* 138±37 127±31
*P<0.001
While a few secondary outcome measures appeared to be unfavorably associated with increased blood
glucose (3-month NIH stroke scale and neuropsychologic status), fortuitously, the primary outcome measure—the 3-
month Glasgow Outcome Score, was not.16 Nevertheless, the effect of hypothermia to increase blood glucose had
the potential to affect the outcome of the trial, potentially negating any neuroprotection afforded by hypothermia had
it been present.
In a “controlled” clinical trial, how much do you try to control beyond the intervention itself? If IHAST
protocols had included control of intraoperative glucose, it would have no longer been a trial of a single
intervention—hypothermia, but rather two interventions—hypothermia and glucose control. This assumes, of
course, that one knows what the secondary effects of the intervention are, and that they can be controlled. The
lesson is that the intraoperative neuroprotective intervention may have side-effects that decrease, negate, or even
overwhelm the neurologic benefits of the intervention. It is essential to know these side-effects and decide which, if
any, you plan to try to control.
Lesson #4— Clinical events/complications may mask or overwhelm the benefit of the
intervention
In contrast to animal models, patients often have coexisting medical conditions and have postoperative
complications that can affect neurologic outcome. While laboratory and clinical studies indicate that hypothermia
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appears to provide a level of neurologic protection, hyperthermia appears to be detrimental. Notably, in IHAST, 410
patients (41%) had at least one episode of fever, defined as a core temperature ≥38.5°C.17 In almost all patients
(97%), fever occurred postoperatively (median onset postoperative day 3). Fever occurred equally frequently in
patients randomized to intraoperative hypothermia (43%) and normothermia (39%); P=0.28. As shown in Table 8,
the occurrence of fever was associated with decreased good 3-month outcome (GOS=1). Notably, in the absence of
fever, the rate of good outcome in the hypothermia and normothermia groups—75% and 65%, respectively—was
exactly what was projected for IHAST.
Table 8. IHAST 3-Month Good Outcome (GOS=1) and Fever17
Good 3-Month Outcome (GOS=1)
Hypothermia Normothermia
(33.3±0.8, n=499) (36.7±0.5, n=501)
No Fever (n=590) 75% 65%
Fever (n=410) 54% 58%
Fifty-one percent (51%) of patients with fever had a documented infection, and infection was also
associated with less favorable outcomes.17 Infections occurred equally frequently in the hypothermic and
normothermic patients, except for a slightly greater rate of bacteremia in hypothermic patients.1 Nevertheless, even
after controlling for infection, fever remained independently associated with less favorable outcome for most
outcome measures.17 Thirty-two percent (32%) of patients with fever had delayed ischemic neurologic deficits
(DIND), and DIND was also associated with less favorable outcomes; see Table 9. DIND occurred equally
frequently in the hypothermic and normothermic patients (22%).1 Nevertheless, even after controlling for DIND,
fever remained independently associated with less favorable outcome for some outcome measures.17
Table 9. IHAST 3-Month Good Outcome (GOS=1) and Delayed Ischemic Neurologic Deficit13
Good 3-Month Outcome (GOS=1)
No 24 hour Neurologic 24 Hour Neurologic
Deterioration (n=574) Deterioration (n=426)
No DIND (n=781) 79% 50%
DIND (n=219) 69% 37%
Given these observations, it is not entirely clear that fever independently results in less favorable outcome or,
instead, may often be a marker of complications such as infection and/or DIND that are the primary injurious events.
Nevertheless, it is clear that events after the operation can significantly affect neurologic outcome and can
potentially overwhelm or mask any neurologic benefits provided by an intraoperative neuroprotective intervention.
The lesson is that intraoperative neuroprotection may in fact, be possible. However, other common clinical
events and complications may mask or overwhelm intraoperative neuroprotection such that it cannot be detected
against the background of secondary neurologic injury occurring in the course of clinical care. As discussed above,
the next intraoperative neuroprotective intervention to be tested in a large clinical trial will need to be very robust. It
will need to have a very large effect size to overcome: 1) the inherent sensitivity of the human brain to ischemia, 2)
the variability of application of any intervention in the clinical environment, and 3) the multitude of uncontrolled
factors that can also affect neurologic outcomes clinical medicine.
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References
1. Todd MM, Hindman BJ, Clarke WR, Torner JC, IHAST Investigators: Mild intraoperative hypothermia
during surgery for intracranial aneurysm. N Engl J Med 2005; 352:135-45.
2. Anderson SW, Todd MM, Hindman BJ, Clarke WR, Torner JC, Tranel D, Yoo B, Weeks J, Manzel KW,
Samra S, IHAST Investigators: Effects of intraoperative hypothermia on neuropsychological outcomes
after intracranial aneurysm surgery. Ann Neurol 2006; 60:518-27.
3. Manninen PH, Lam AH, Nantau WE: Monitoring of somatosensory evoked potentials during temporary
arterial occlusion in cerebral aneurysm surgery. J Neurosurg Anesthesiol 1990; 2:97-104 .
4. Proust F, Hannequin D, Langlois O, Freger P, Creissard P: Causes of morbidity and mortality after
ruptured aneurysm surgery in a series of 230 patients. The importance of control angiography. Stroke 1995;
26:1553-7.
5. Le Roux PD, Elliott JP, Newell DW, Grady MS, Winn HR: The incidence of surgical complications is
similar in good and poor grade patients undergoing repair of ruptured anterior circulation aneurysms: A
retrospective review of 355 patients. Neurosurgery 1996; 38:887-95.
6. Busto R, Dietrich WD, Globus MYT, Valdes I, Scheinberg P, Ginsberg MD: Small differences in
intraischemic brain temperature critically determine the extent of ischemic neuronal injury. J Cerebral
Blood Flow Metab 1987; 7:729-38.
7. Minamisawa H, Nordstrom C-H, Smith M-L, Siesjö BK: The influence of mild body and brain
hypothermia on ischemic brain damage. J Cerebral Blood Flow Metab 1990; 10:365-74.
8. Clifton GL, Jiang JY, Lyeth BG, Jenkins LW, Hamm RJ, Hayes RL: Marked protection by moderate
hypothermia after experimental traumatic brain injury. J Cerebral Blood Flow Metab 1991; 11:114-21.
9. Ridenour TR, Warner DS, Todd MM, McAllister AC: Mild hypothermia reduces infarct size resulting from
temporary but not permanent focal ischemia in rats. Stroke 1992; 23:733-8.
10. Goto Y, Kassell NF, Hiramatsu K, Soleau SW, Lee KS: Effects of intraischemic hypothermia on cerebral
damage in a model of reversible focal ischemia. Neurosurgery 1993; 32:980-5.
11. Karibe H, Chen J, Zarow GJ, Graham SH, Weinstein PR: Delayed induction of mild hypothermia to
reduce infarct volume after temporary middle cerebral artery occlusion in rats. J Neurosurg 1994; 80:112-9.
12. Hindman BJ, Todd MM, Gelb AW, Loftus CM, Craen RA, Schubert A, Mahla ME, Torner JC: Mild
hypothermia as a protective therapy during intracranial aneurysm surgery: a randomized prospective pilot
trial. Neurosurgery 1999; 44:23-32.
13. Mahaney KB, Todd MM, Bayman EO, Torner JC, IHAST Investigators: Acute postoperative neurological
deterioration associated with surgery for ruptured intracranial aneurysm: incidence, predictors, and
outcomes. J Neurosurg 2012; published online March 9, 2012; DOI: 10.3171/2012.1.JNS111277.
14. van der Worp HB, Sena ES, Donnan GA, Howells DW, Macleod MR: Hypothermia in animal models of
acute ischaemic stroke: a systematic review and meta-analysis.. Brain 2007; 130:3063-74.
15. Hindman BJ, Bayman EO, Pfisterer WK, Torner JC, Todd MM, IHAST Investigators: No association
between intraoperative hypothermia or supplemental protective drug and neurologic outcomes in patients
undergoing temporary clipping during cerebral aneurysm surgery. Findings from the Intraoperative
Hypothermia for Aneurysm Surgery Trial. Anesthesiology 2010; 112:86-101..
16. Pasternak JJ, McGregor DG, Schroeder DR, Lanier WL, Shi Q, Hindman BJ, Clarke WR, Torner JC,
Weeks JB, Todd MM, IHAST Investigators: Hyperglycemia in patients undergoing cerebral aneurysm
surgery: its association with long-term gross neurologic and neuropsychologic function. Mayo Clin Proc
2008; 83:406-17.
17. Todd MM, Hindman BJ, Clarke WR, Torner JC, Weeks JB, Bayman EO, Shi Q, Spofford CM, IHAST
Investigators. Perioperative fever and outcome in surgical patients with aneurysmal subarachnoid
hemorrhage. Neurosurgery 2009; 64:897-908.
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DISCLOSURE
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Preventing CNS Complications During Anesthesia and Surgery
James E. Cottrell, M.D. Brooklyn, New York
The assumption that anesthesia has no serious, long-term, adverse CNS consequences may be true for most patients between six
months and sixty years of age. However, for patients younger than 6 months or older than 60 years, that assumption is under
challenge from a growing body of evidence. Fetuses and newborns appear to be at risk because systems that would enable them
to fully recover from the effects of more than 2 hours of anesthesia are still in development. In distinction, the elderly appear to
be at risk because systems that once enabled them to fully recover have ever-diminishing capacity. Even for those between the
age of 6 months and 60 years, full recovery may require replacing apoptosed neurons and pruning overabundant dendritic spines
… perhaps leaving patients not quite the same person that they were before they were anesthetized.
THE YOUNG BRAIN
After 28 weeks of gestation, fetal neurons develop an acute ability to die from boredom.1 Given estimates of 40-50 billion
neurons at birth,2 and evidence that at least one fetal proto-neuron, and more likely two, undergo apoptosis for each neuron that
survives,3 a midpoint estimate is that the human brain averages about 8,000 apoptotic neuronal deaths per second during the last
11 weeks in utero. Those cellular suicides are selective, leaving the core material and sculpting the primary architecture for
subsequent CNS development.4
The trigger for that avalanche of apoptosis is a lack of synaptic feedback. Apoptosis appears to be the default program of
many excitable cell types, with cell-typical activity promoting proteins like anti-apoptotic Bcl-2’s that prevent the default
program from running its course. Put differently, the old saying “Use it or lose it” is not only for the old … synaptic activity may
be as crucial to the survival of late-term fetal neurons as are O2, ATP and CBF. So what happens to fetal neurons that would be
receiving and sending signals were it not for the presence of anesthesia?
In laboratory animals
One of the first animal models to test the effect of anesthesia on fetuses was developed by Chalon et al in 1981. He exposed
pregnant mice to halothane and found that their offspring, and the offspring of those offspring, learned significantly more slowly
than the first and second generation of control mice.5 Chalon’s findings for first generation offspring were recently substantiated
and extended for in utero exposure to isoflurane in rats6 and Hogan has found first generation epigenetic effects of fetal exposure
to nitrous oxide that may extend to those offsprings’ offspring.7 Recent studies notwithstanding, early laboratory reports
indicating a potential problem did not receive the attention that they deserved until 2003 when Jevtovic-Todorovic and colleagues
published “Early exposure to common anesthetic agents causes widespread neurodegeneration in the developing rat brain and
persistent learning deficits” — a title that says it all.8 Many subsequent studies have confirmed and augmented those findings for
desflurane, isoflurane, sevoflurane, propofol, nitrous oxide and ketamine in rodents.
Neonatal apoptosis subsequent to a clinically relevant depth and duration of general anesthesia also occurs in mammals with
periods of rapid synaptogenesis more analogous to humans, including pigs9, 10 and a non-human primate.11-14 Potentially relevant
for burn victims, twenty-four hours of “a light surgical plane” of ketamine anesthesia also causes long term cognitive deficits in
Rhesus macaque neonates.15 Apoptosis notwithstanding, Stratmann and colleagues found that exposing 7-day-old rats to four
hours of isoflurane induced a decrease in neurogenesis that contributed to a permanent deficit in hippocampal-dependent learning
and memory.16 Neurogenesis, of course, requires neural stem cells, and Culley et al have presented evidence that 1 MAC
isoflurane reduces the production of neural stem cells by 20% in vitro twenty four hours after exposure.17 Decreased
neurogenesis and decreased neural stem cell proliferation notwithstanding, using 16-day-old rats, Briner and coauthors found that
sevoflurane, desflurane, isoflurane18 and propofol19 rapidly increase dendritic spine density, which “could interfere with
physiologic patterns of synaptogenesis and thus might impair appropriate circuit assembly in the developing cerebral cortex.”
In humans
Since 1945, investigators have observed an association between impaired neuro-cognitive-behavioral development and post-natal
exposure to surgery and anesthesia prior to 3 or 4 years of age,20-38 with Levy20 having found a statistically significant association
between near-term emotional sequelae and younger age at anesthetic exposure (p<0.0004, data not statistically analyzed in
original article). However, Bartels and colleagues’ investigation of monozygous twins addressed the hypothesis that children
who need to undergo surgery and anesthesia at an early age are inherently predisposed to impaired neuro-cognitive-behavioral
development. They studied 110 pairs of identical twins, one of whom had been anesthetized prior to age 3 with the other having
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not been anesthetized prior to age three. They found, in a pair-by-pair analysis, that the anesthesia-exposed twins had virtually
the same score as their non-exposed twin on a national measure of educational achievement administered near age twelve.39
Unfortunately, the Bartels study is not known to have included children who were anesthetized prior to six months of age. That
shortcoming, together with Kalkman and colleagues finding of a trend toward a greater detrimental effect of anesthesia on neuro-
cognitive development with decreasing age at administration,34 see also 29 suggests that if there is a period of extraordinary
vulnerability in humans, it is similar to that found at analogous developmental stages in non-humans — in utero to six months
post partum.
Bartels et als’ methodology was also not able to provide an estimate of duration of anesthetic exposure. If duration of
anesthesia is as important in human fetuses and neonates as it is in nonhumans,9 then a 30-60 minute exposure may not be
sufficient to affect long term learning capacity, even in the high-vulnerability age group. Accordingly, Hansen and colleagues
finding of no substantive impairment in children “exposed to a single, brief anesthetic procedure in infancy” leaves the question
open for two or more hours of exposure.40 The same concerns apply to a recent report from Dimaggio and coauthors.41 They
looked for developmental effects in children exposed to anesthesia and surgery prior to 3 years of age and replicated Bartels et
als’ finding for twins on a smaller but more refined subsample. Nevertheless, only 6 or 7 of the 304 anesthesia-exposed children
included in Dimaggio and coauthors’ epidemiological investigation were less than 6 months old at age of exposure, with the vast
majority having been anesthetized for short procedures. Accordingly, they concluded “that a meaningful proportion of the
association measured in the overall analysis … may not be causally attributable to surgery/anesthesia” — a conclusion that I
agree with in reference to children exposed to anesthesia for less than 2 hours after they are 6 months old.
In distinction, a recent examination of children under 1 year of age (average age 101 days) exposed to anesthesia for
procedures that lasted up to about 3.75 hours found an association with decreased academic performance after correcting for
related CNS complications. Block and colleagues analyzed achievement test scores of 7-17 year old children who received
general anesthesia during infancy for procedures that are not independently associated with cognitive impairments: inguinal
hernia repair/orchiopexy, pyloromyotomy and circumcision. After excluding children with any of 14 pre-specified CNS
problems or medical conditions associated with learning disabilities, they found that a substantial proportion of children without
such risk factors scored below the 5th percentile of the normative population (p<0.01), with increased duration of anesthesia
associating with reduced performance.37
To date, perhaps the most intriguing evidence for anesthesia-induced neurodevelopmental deficits comes from a
retrospective dose-response study of 96 infants who underwent staged reconstructive surgery for hypoplastic left heart syndrome.
Initial surgery with cardio-pulmonary bypass was performed at less than two months of age. All subsequent surgical
interventions as well as ICU stays, up to neurodevelopment assessment at age 4 years, were included in a cumulative anesthetic
exposure analysis. “Total exposure to VAA [volatile anesthetic agents] and fentanyl from birth to testing was calculated from an
anesthetic database and intensive ICU flowsheets. Exposure to halothane, isoflurane, sevoflurane and/or desflurane was
calculated, converted to age-adjusted minimum alveolar concentration-hours (MAC-hrs) and summed to yield total VAA
exposure … Of 537 total anesthetic exposures, 478 had VAA, with total VAA exposure ranging from 0.9-35.3 MAC-hrs (median
7.54). There were 337 intraoperative fentanyl exposures. Cumulative intraoperative and ICU fentanyl dosage ranged from 118.59
to 3998.28 µg/kg (median 309.87). After adjustment for patient and operative confounders (including stage 1 length of stay and
number of cardiac operations), increasing VAA exposure was associated with worse full-scale IQ, total language, executive
function, memory, reading and math skills (all p< 0.05). Increasing fentanyl exposure predicted worse full scale IQ, total
language, processing speed, memory, fine motor skills and math skills (all p< 0.05)."38
Findings for fetuses may be stronger than those for post-natal humans. In 1986 Hollenbeck and coauthors reported
decreased cognitive capacity in four-year-olds whose mothers had been anesthetized while they were in utero.42 Several
subsequent studies found analogous associations between pre-natal exposure to anesthetics and developmental problems
including autism,43 hydrocephalus,44 diminished general intelligence,45 impaired spatial ability,46 small head size and mental
retardation.47
Ongoing Trials
With an anticipated completion date of December, 2016 and a projected sample size of 660 children, the ‘GAS’ study will test for
a difference in preschool IQ between children who received sevoflurane or neuraxial bupivacaine for inguinal hernia repair when
they were 26-60 weeks old.48 A recent laboratory experiment does not support the GAS study because although it found
substantially reduced neuronal apoptosis in post-natal rats that received spinal injection of bupivacaine compared to rats
anesthetized with isoflurane, the spinal analgesia did not last long enough (40 to 60 minutes) to be expected to trigger apoptosis,
while the apoptosis-inducing sevoflurane exposure lasted for 6 hours.49 A large retrospective study by Flick and coauthors found
no difference in frequency of learning disabilities between: 1) a group of children whose mothers (16%) received inhaled
anesthesia or did not receive inhaled analgesia for vaginal delivery (84%), versus; 2) a group of children delivered vaginally
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whose mothers received neuraxial block with only 3.1% also receiving inhaled anesthesia.50 That study did not test for an
developmental differences between the children whose mothers received inhaled analgesia without neuraxial block versus the
children whose mothers received neuraxial block without receiving inhaled anesthesia (the GAS study question), but even if
those relevant sub-samples are large enough to withstand such an analysis, one worries that fetal anesthetic exposure during birth
in the Flick study was, and during hernia repair in the GAS study, are too brief to test the anesthesia-development question (per
Hansen et al40 and Dimaggio et al41). It may also be the case that the sample size of the GAS study will be effectively diminished
because too high a proportion of participants will be too old at their age of exposure (per Bartels et al39 and Dimaggio et al41).
The other major prospective study scheduled for completion in 2016, the Infant Anesthesia Exposure and Neuro-Outcome
study (formerly ‘PANDA’) is shooting for 1000 participants to compare “Global and Domain-specific Neurocognitive Function”
between children exposed to general anesthesia prior to 3 years of age during hernia repair versus siblings of nearly the same age
(within 3 years) who were not exposed to general anesthesia prior to age three. Unfortunately, like the GAS study48 and the
Hansen study,40 this investigation will test for an effect of exposures that are probably too brief to have an effect in a study
population that may be substantially comprised of children who are also too old to be sufficiently susceptible.51
So where do we stand?
The data in laboratory rodents are conclusive: clinically relevant doses and durations of anesthesia during the period of rapid
synaptogenesis cause neuronal apoptosis, other neuronal derangements, and long term learning deficits. The same has been
established in pigs and a non-human primate with regard to apoptosis. In distinction, the effect of anesthesia in human neonates
remains a concern that is confounded by genetics, by age at anesthetic exposure, by the effects of surgery independent of
anesthesia, and by the duration of anesthesia exposure. Data from human fetuses may be a cause for even more concern because
they associate anesthesia with adverse outcomes that are probably less confounded by genetics (the mother’s genetic
predispositions would be the primary association with a need for surgery, but half of her fetus’ genes are not derived from her),
by age at exposure (second and third trimester have now been implicated as high risk periods in rodents, perhaps translating back
to late-first-trimester in humans), and by the effects of surgery independent of anesthesia (although the fetus and mother are
equally anesthetized, the effects of surgery on the mother are likely to be diminished in the fetus).
What might be done?

Olney and his group have proposed that anesthetic drug effects on fetal and neonatal gamma-aminobutyric acid and N-methyl-D-
aspartic acid receptors cause translocation of the Bcl-2–associated protein to mitochondrial membranes, leading to an apoptotic
cascade.52 Perhaps this problem can be alleviated by anesthetic choice in pregnant females. Maze and his group have presented
evidence that “xenon mitigates isoflurane-induced neuronal apoptosis in the developing rodent brain,”53 as does
dexmedetomidine,54 and xenon is currently in clinical trials for perinatal hypoxic-ischemic brain injury.55 Analogously, Laing
and coauthors found that sevoflurane causes less apoptosis than isoflurane, but this difference was not manifest in behavioral
tests.56 cf. 57, 58 Several adjunct pharmaceuticals have also shown promise. L-carnitine, an l-lysine derivative that transports long-
chain fatty acids into mitochondria, appears to have a beneficial effect in N2O/isoflurane-damaged neonatal rats59 and lithium
reduces damage from ketamine and propofol in neonatal mice.60 Patel’s lab has shown that inhibition of p75 neurotrophin
receptors attenuates both isoflurane61, 62 and propofol63 neurotoxicity in mice. Using the early post-natal rat model, Yon and
coauthors found that melatonin reduced anesthetic-induced damage in the most vulnerable brain regions: “Melatonin-induced
neuroprotection was mediated, at least in part, via inhibition of the mitochondria-dependent apoptotic pathway since melatonin
caused an up-regulation of the anti-apoptotic protein, bcl-XL, reduction in anesthesia-induced cytochrome C release into the
cytoplasm and a decrease in anesthesia-induced activation of caspase-3 [precursor of apoptosis].”64 More recently, Jevtovic-
Todorovic’s lab found that both EUK-134, a synthetic reactive oxygen species scavenger, and R(+) pramepexole, a synthetic
aminobenzothiazol derivative that restores mitochondrial integrity, “completely prevented general anesthesia-induced cognitive
impairment” in rats that had been exposed to 6 hours of midazolam/isoflurane/N2O anesthesia on post-natal day 7.65 cf. 66 It
would be a perfect circle if the investigator who did so much to bring this problem to the world’s attention also headed the team
that found its solution.
Prevention of perinatal anesthesia-induced neurotoxicity notwithstanding, Stratmann’s lab has produced evidence that
delayed environmental enrichment can mitigate sevoflurane-induced memory impairment in rats.67 Unfortunately, as put by
Davidson, “it is difficult to see how we could practically further enrich the environment for the average [human] infant in the 21st
century”68 because, as put by Stratmann, “we already live in a vastly enriched environment, compared with lab rats.” An
alternative perspective is that sevoflurane is among the less toxic anesthetic agents56, 58 and environmental deprivation (the usual
state of lab rat housing) exacerbates toxic effects.
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Have the data already changed clinical practice?

How would you answer the following question?
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A 27-year-old female presents with an operable, slow-growing, benign, mildly symptomatic brain tumor. Her neurosurgeon has
scheduled the case and estimates an operation time of 4.5 hours. She is 25 weeks pregnant. Would you:
A. Use state-of-the-art equipment, procedures and drugs to proceed with the case?
B. Discuss evidence that has emerged or gained renewed recognition since 2003 that 4.5 hours of anesthesia may cause
neurodegeneration and persistent learning deficits in the developing brain with the neurosurgeon and leave the decision in his/her
hands?
C. Discuss the above evidence with the neurosurgeon and the parents and leave the decision in their hands?
D. Discuss the above evidence with the neurosurgeon and the parents and, barring development of substantive symptoms, advise
postponing surgery until after the patient has given birth or undergone a caesarian section?
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Our guess is that prior to Jevtovic-Todorovic and coauthors’ 2003 shot-heard-round-the-anesthesia-world,8 most of us
were on the A train. In the absence of survey data, our best guess is that most of us would now opt for B, C or D.
THE OLDER BRAIN
The older brain has less cognitive reserve — less resilience to neurological challenges. Oxidative phosphorylation does not work
as well. We have acquired genetic mutations that can alter outcomes. Genetic alleles that were silent when we were young
manifest themselves (have phenotypic effects) as we age. And then there is free radical build-up with reduced levels of
scavengers like vitamin C, melatonin and vitamin E. All of these dreary realities probably contribute to Kline and coauthors’
finding that “Elderly subjects after surgery experienced an increased rate of brain atrophy … a time associated with enhanced risk
for postoperative cognitive dysfunction … subjects with mild cognitive impairment suffered greater subsequent cognitive
effects.”69
POCD After Non-Cardiac Surgery

In 1955 P.D. Bedford published "Adverse cerebral effects of anaesthesia on old people."70 He reviewed 1,193 (presumably non-
cardiac) patients over 50 years old who had received general anesthesia. Mental deterioration in 10% of patients appeared to be
long-term or permanent — a figure that concurs with subsequent findings. Bedford concluded that cognitive decline is related to
anesthetic agents and hypotension. He recommended that “Operations on elderly people should be confined to unequivocally
necessary cases” and that “postoperative medication should not be a routine matter.” The next major study to report POCD skips
ahead 43 years to 1998 — the first International Study of Postoperative Cognitive Dysfunction (ISPOCD).71 In non-cardiac
patients more than 59 years old, the incidence of cognitive dysfunction 1 week after surgery was 22% higher than in age-matched
controls and 7% higher 3 months after surgery (p<0.004 for both) with 10% of patients (91/910) evidencing POCD (identical to
Bedford’s finding at a longer postoperative interval). Increasing age, duration of anesthesia, lesser education, a second operation,
postoperative infection, and respiratory complications were risk factors for early postoperative cognitive dysfunction. However,
under a circumstance of significantly reduced statistical power due to a 22% loss of follow-up at 3 months, among the risk factors
that were significant in the early postoperative period, only age remained statistically significant.
Monk and colleagues found that 12.7% of elderly (>59 y o) non-cardiac patients had POCD three months after surgery72 —
again, within a narrow confidence interval around Bedford’s 1955 report. Corroborating earlier work,73 this study also found a
substantial relationship between POCD and death within one year of surgery.see also 74, 75 Independent risk factors for sustained
POCD included greater age, less education, POCD at hospital discharge and a history of stroke without residual damage.
Consistent with many investigations, more education may indicate greater pre-surgical cognitive reserve, just as prior stroke may
indicate pre-surgical reduction of cognitive reserve.75, 76 Notably, Monk’s ‘08 study did not find duration of anesthesia to be a
risk factor. However, the risk of a false negative conclusion is high, because the sample size of elderly patients at the 3-month
measurement was even smaller (308 with 39 POCD patients72) than in the International Study of POCD (901 with 91 POCD
patients71). The longest follow-up study of POCD patients (median = 8.5 years) was published by the ISPOCD group in 2009:
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"Cognitive dysfunction after noncardiac surgery was associated with increased mortality, risk of leaving the labor market
prematurely, and dependency on social transfer.77
POCD After Cardiac Surgery

Most of us have heard friends or relatives say something like “since he had open-heart surgery, he’s not the same … he can’t
think as well, he’s not as happy.” The New York Times brought attention to this problem with an article entitled “Saving the
Heart Can Sometimes Mean Losing Your Memory.”78 In that article, Juhar explained the basics of extracorporeal circulation and
discussed reasons for memory loss, focusing on a patient who had gone back to work and found that he had difficulty with his job
… a patient who could not perform functions that he had performed for many years. That article raised a great deal of concern,
setting the stage for a paper published a year later in the New England Journal of Medicine by Newman and colleagues.79 see also 80
They found POCD in 53% of Coronary Artery Bypass Graft (CABG) patients at discharge and in 36% of patients six weeks later.
That proportion went down to 24% six months after surgery, but came back up to 42% five years after surgery — a pattern of
early improvement followed by subsequent decline that was predicted by POCD at discharge.see also 81
Aggravating Factors
The factors that cause decline in cognitive capacity among non-CABG patients also affect CABG patients. However, some of
those risk factors, like duration of exposure to anesthetics, may be masked by damage done to CABG patients from increased
liability to cerebral emboli, cerebral ischemia during re-perfusion, and over-warming after bypass.82
Does off-pump versus on-pump make a neurocognitive difference? Several major studies have failed to detect a
neurocognitive advantage to off-pump83, 84 and although Shroyer et al failed to find a statistically significant difference across
their composite test battery, they did find a significant difference on one important test in favor of off-pump, suggesting the
possibility of a false negative conclusion.83 cf. 85 More recently, Puskas and colleagues found that “After a mean of 7.5 years of
follow-up, patients undergoing off-pump coronary artery bypass performed better than those undergoing cardiopulmonary
bypass in several neuropsychological domains.”84 Less direct evidence came from a study of over 16,000 patients in whom a
greater incidence of delirium occurred after on-pump cardiopulmonary bypass, with duration of surgery (and so anesthesia) as a
significant risk factor.86 Although these patients were not followed up for POCD, Girard and coauthors found that in
“mechanically ventilated medical intensive care unit patients, duration of delirium (which is potentially modifiable) was
independently associated with long-term [12 month] cognitive impairment87 and Morandi et al found that “delirium duration in
the intensive care unit was associated with white matter disruption at both discharge and 3 months. Similarly, white matter
disruption was associated with worse cognitive scores up to 12 months later.”88 Clearly, a relationship between depression,
sedation, delirium, poor neurological outcome and POCD should not be discounted,89-94 such that off-pump patients may be at
lesser risk for POCD. Unfortunately, in a recent study that had the potential to address this issue, some surgeons took the liberty
of performing off-pump surgery on 102 patients who had been randomly assigned to on-pump surgery because they had
calcification of the aorta. In an intention-to-treat analysis, those patients’ results were then analyzed as if they had on-pump
surgery. These very non-random protocol violations notwithstanding, the authors expressed surprise that off-pump surgery had
not evidenced “a beneficial effect on stroke”!95 Dr. Hartung and I have argued that intention-to-treat analysis should always be
accompanied by on-treatment analysis.96
Inflammation caused by surgical trauma may also aggravate POCD and is associated with the pathogenesis of Alzheimers’
Disease (AD) in a mouse model.97 We know about the up-regulation of IL-1, and this in turn can affect anesthetic receptors.98
The ensuing cascade of events ultimately affects the anesthetic gamma-aminobutyric acid and N-methyl-D-aspartic acid receptors
and increases production of beta amyloid … and we know that beta amyloid, even in non-demented patients, associates with
cognitive problems if there is enough of it. Genetic predispositions are another aggravating factor. For example, Matthew and
coauthors have shown the contribution of P-selectin and C-reactive protein alleles in modulating susceptibility to cognitive
decline caused by inflammation after cardiac surgery,99 and Cai et al found an association between APOE4 and early POCD in
elderly patients undergoing inhalation anesthesia.100
Are anesthetics aggravating factors? If so, are some more toxic than others? Le Freche and coauthors were able to link an
increase in phosphorylated tau, a marker for AD, to diminished memory in sevoflurane-exposed adult mice.101 Dong et al found
that just 2 hours of clinical anesthesia with isoflurane generates caspase-3 in adult mice,102 and Eckenhoff’s group has found that
a presenilin-1 mutation associated with familial AD renders PC12 cells more vulnerable to isoflurane cytotoxicity, but not to
sevoflurane or desflurane cytotoxicity,103 while Xie’s group found that isoflurane induces more caspase-3 activation and A-beta
oligomerization in AD transgenic neonatal mice than does propofol.104 Xie’s group also found greater cognitive decline in
patients 1 week after surgery who received spinal anesthesia with desflurane versus spinal anesthesia with isoflurane or spinal
anesthesia alone.105
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Jevtovic-Todorovic and Carter reported that old rat brains are equally (nitrous oxide) or more sensitive (ketamine w/ and
w/o nitrous) to anesthetic neurotoxicity than infant rat brains,106 and Culley and coauthors found that spatial memory is impaired
for 2 weeks after 2 hours of 1.2% isoflurane with 70% nitrous oxide in aged rats.107 What about nitrous oxide alone? Culley et al
found that aged rats exposed to 70% nitrous oxide for 4 hours took more time to complete a maze and made fewer correct choices
before making their first error compared to control rats over the following two weeks.108 In a separate group of rats, they found
that the same nitrous oxide exposure profoundly, but transiently, reduced the activity of cortical methionine synthase — an
enzyme that is implicated in dementia and may be related to accumulation of homocysteine (a cytotoxic amino acid normally
remethylated to methionine, an essential amino acid, by methionine synthase).108 Examining autopsy brain tissue, Crary and
coauthors found that PKMzeta, an atypical protein kinase C isoform, accumulates in the neurofibrillary tangles of Alzheimer’s
patients, but not control patients.109 One wonders whether anesthetics might increase this tangling in both AD and non-AD
patients. My lab is currently investigating the effect of anesthetic preconditioning on PKMzeta in transgenic AD mice.
Deeper vs. Lighter & Regional vs. General Anesthesia

A study by Schubert’s group looked at lighter anesthesia (bispectral index 50) versus deeper anesthesia (bispectral index 39) and
found that deeper levels of anesthesia were associated with better cognitive function 4-6 weeks post-operatively.110 That finding
was replicated in adult mice111, 112 and then again in humans.113 This unexpected result may account for the frequently observed
lack of difference in POCD, or the weakness of the difference in POCD, between patients who receive general anesthesia and
patients who receive regional anesthesia with sedation.1114, 115 Ancelin found that “Adding sedation to peridural anaesthesia led
to a decline in verbal secondary memory”116 and Sieber et al found that lighter sedation during spine surgery led to less
delirium.117 Again, there are empirical and neuropathological reasons to suspect a link between delirium, deep sedation, poor
neurological outcome, and POCD.86-94 Examining results from 980 patients who underwent intra-arterial therapy for acute
ischemic stroke under conscious (light) sedation versus (light) general anesthesia, Abou-Chebl and colleagues found poorer
neurological outcome and higher mortality in the GA patients.118 If the association between POCD and deep sedation had been
discovered before the association between POCD and general anesthesia, perhaps we would have come more readily to the
hypothesis that lighter anesthesia110-113 and deeper sedation116-117 occupy an equivalent middle-ground (approximately BIS 45-
55) when it comes to increasing the risk of POCD relative to both lighter sedation (approximately BIS 60 and above) and deeper
anesthesia (approximately BIS 35-45).119
Anesthesia and Neurodegenerative Diseases

Do anesthetics affect neurodegenerative diseases? Hydrophobic cavities keep sticky proteins from becoming irreversibly glued
together. Unfortunately, molecules of inhalational anesthetics can fill those cavities and reduce the amount of energy required to
maintain protein assembly.120 This anesthesia-facilitated disinhibition of protein binding helps monomers aggregate into
oligomers, and if those monomers are amyloid β (Aβ), the resulting oligomerization can lead to protofibrils that are small enough
to diffuse into neurons and large enough to be neurotoxic. Amyloid β oligomers appear to contribute to the neurodegeneration
characterized by Alzheimer in the early 20th Century. Thirteen million Americans are projected to have Alzheimer’s Disease
(AD) by the middle of the 21st Century. Many of them will need to be anesthetized, and many of them will have been
anesthetized before they became demented.
The role of inhalational anesthetics in the above scenario has been verified in vitro by a decade of work from Eckenhoff and
coauthors,121 now supported in vivo by mouse models.102,122 In addition to the Aβ-anesthesia connection, Xie's group has utilized
human neuroglioma cell cultures to add anesthesia-induced apoptosis as a factor contributing to AD102, 123-124 and they have
found that isoflurane, but not desflurane, degrades mitochondrial function and impairs learning and memory in mice.125 Do the
rodent and cell culture findings apply to humans? Eckenhoff’s group reported that the total-tau/amyloid-β(1-42) ratio in CSF, the
only biomarker validated for use in the diagnosis of AD by the Alzheimer’s Disease Neuroimaging Initiative (ADNI), elevates
during surgery and anesthesia in healthy patients and rises above ADNI’s threshold for mild cognitive impairment within 48
hours.126 In an article entitled “Coronary artery bypass surgery provokes Alzheimer’s disease-like changes in the cerebrospinal
fluid,” Palotas and colleagues found an increased tau/amyloid-β ratio in patients 6 months after surgery.127
Results from retrospective studies remain inconclusive, but are unsettling. Examining records of 9,170 veterans, Lee et al
compared the risk of developing AD within 5-6 years of cardiac surgery (CABG) under inhalational anesthesia versus the risk of
developing AD within 5-6 years of percutaneous transluminal coronary angioplasty, the latter seldom requiring general
anesthesia.128 After adjustment for age, length of hospital stay, co-morbidity and number of procedures, the CABG patients
developed AD at nearly twice the rate of percutaneous transluminal coronary angioplasty patients (hazard ratio 1.71, p<0.04).
Yes, CABG patients faced more predisposing factors than percutaneous transluminal coronary angioplasty patients, including
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embolic ischemia, but given in vitro evidence supporting mechanisms for a causal link between anesthesia and AD, it would be
reckless to dismiss prolonged inhalational anesthesia as an independent contributing factor to Lee and coauthors’ finding.
Bohnen and coauthors performed a case-controlled retrospective study of 252 AD patients.129 Unfortunately, 199 of the 252
controls (non-AD patients) had prior exposure to general anesthesia, which greatly dilutes their statistical power to evidence an
effect of anesthesia relative to AD patients. Nevertheless, Bohnen et al found non-statistically significant effects in the direction
of a link between AD and general anesthesia on each of three independent variables: cumulative exposure to anesthesia,
exposure to six or more episodes of general anesthesia (OR = 1.44) and cumulative exposure to 600 minutes or more of general
anesthesia (OR = 1.63). Gasparini and coauthors also performed a retrospective case-controlled study of AD patients. In their
study the controls were Parkinson’s disease patients and patients with other neurological diseases130 — but a link between general
anesthesia and other neurological diseases has been hypothesized,120 such that lack of a difference in anesthetic exposure between
AD patients and patients with Parkinson’s or other neurological diseases does not imply a lack of a deleterious effect of
anesthetic exposure.
Although a connection between anesthetics and AD has received more attention than a possible relationship between
anesthesia and Parkinson’s or Huntington’s disease, two investigations suggest that further research is warranted. Peretz and
coauthors have found evidence that supports an elevated risk of Parkinson’s disease among anesthesiologists as compared to
internists131 and Wang et al have found in vitro laboratory evidence that isoflurane may exacerbate Huntington’s disease.132
So there is evidence that anesthetics are a particular problem for older patients, but before we make recommendations more
firm than Bedford’s admonition from 1953 that “Operations on elderly people should be confined to unequivocally necessary
cases”70 … we need to know more about genetic profiles in order to know which older patients are most at risk.
Potential Alleviating Factors

How might we reduce the risk of POCD in older patients? Are some anesthetics less deleterious than others? Crosby’s group has
presented data indicating that “In aged rats, propofol anesthesia is devoid of the persistent memory effects observed with other
general anesthetic agents in this model. Thus, it appears that general anesthesia-induced memory impairment may be a function
of the agent rather than the anesthetic state itself.”133 Complementary in vitro work by Wei and Xie also suggests that sevoflurane and
desflurane are less potent triggers of apoptosis than isoflurane.134 In a hippocampal slice model, desflurane was more protective
than propofol135 and in a rat cardiopulmonary bypass model, isoflurane with 60% Xenon has been shown to prevent the
decrement in neurocognitive function caused by bypass under isoflurane alone.136 The protective potential of xenon is being
evaluated in humans by Maze’s group and preliminary results are encouraging.137
One of my department’s laboratories has investigated the effects of lidocaine during global ischemia in rats, finding that
neuron death in the hippocampus is substantially reduced in animals that have received clinically relevant doses of lidocaine.
Function was also better retained after global ischemia in animals that received lidocaine.138, 139 Looking at CABG patients,
Wang and coauthors found that lidocaine (1.5 mg/kg bolus followed by a 4 mg/min infusion during operation and 4 mg/kg in the
priming solution of cardiopulmonary bypass) reduced POCD measured 9 days after surgery.140 Looking at a larger number of
CABG patients, Mitchell and colleagues also found reduced POCD in patients that received lidocaine — from 75% to 40% at 10
days (p<0.025), from 75% to 46% at 10 weeks (p<0.05) and then from 48% to 28% at 6 months (ns).141 cf. 142 Most recently,
Newman's group at Duke reported a significant reduction in POCD at 6 weeks and 1 year among non-diabetic cardiac patients.
This effect was most pronounced in non-diabetic patients who received less than 43 mg/kg lidocaine (total dose), while lidocaine
appears to have had a deleterious effect in diabetic patients and in patients who received higher total doses.143
What about erythropoietin, melatonin, cholinesterase inhibitors, memantine, insulin, statins, dantrolene and exercise?
Lauretani and colleagues found that EPO levels are lower in 60-to-98-year-olds with impaired peripheral nerve function and/or
clinical diagnosis of polyneuropathy.144 Haljan et al found a trend toward improved neurocognitive recovery with erythropoietin
use in CABG patients,145 and in post-hoc analyses Tseng et all found EPO to be protective in SAH patients who are younger,
non-septic, and on statin therapy.146 Hakim and coauthors found that risperidone reduces delirium after on-pump cardiac surgery
in elderly patients, which may auger well for POCD.147 Cheng and colleagues’ review of the beneficial effects of melatonin in
experimental models of AD is encouraging148 and a clinical study by Furio et al found that melatonin improved cognitive
function in elderly outpatients who suffered from mild cognitive impairment.149 More recent studies indicate that cholinesterase
inhibitors,150 memantine,150-152 and insulin therapy,153 improve cognitive function, or delay clinical worsening, in AD patients
and dantroline has been shown to reduce memory deficits and amyloid plaque in AD mice.154 The jury has looked hard for
evidence that statin therapy prevents or ameliorates AD, but a definitive verdict is still pending.155, 156 In distinction, a
retrospective review of 12,689 patients by Flint and colleagues found that “Statin use during ischemic stroke hospitalization is
strongly associated with improved poststroke survival”157 and “discharge disposition,”158 even for patients without prior statin
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use. Pharmacological approaches notwithstanding, unless crenezumab fulfills its promise,159 perhaps age-appropriate exercise
remains the best all-round regimen for both prevention and cure of POCD.160-163
Preconditioning
Although fetuses and the elderly are particularly sensitive to ischemia, hypo-perfusion and hypoxia, “Nietzsche’s Toxicology:
whatever doesn’t kill you might make you stronger”164 could lead to improved clinical management of patients with fragile
brains.
In 1964 Dahl and Balfour published evidence of “prolonged anoxic survival due to anoxia pre-exposure.”165 This
phenomenon was eventually replicated in a model of cerebral ischemia,166 and induction of endogenous proteins of repair and the
genes that code for them are now well documented. Our laboratory has added sevoflurane as a potential preconditioner,167 and
Maze's group reported that in comparison to sevoflurane, 168 nitrous oxide and hypoxia,169 xenon preconditions in a manner that
"might mimic the intrinsic mechanism of ischemic preconditioning most closely." But if a limited dose of anesthesia triggers the
same protective mechanisms as a limited bout of hypoxia, how much anesthesia can we give before what would have been a
protective effect becomes a deleterious effect on balance?137
Clinically acceptable means of accomplishing cerebral preconditioning are being sought. Volatile anesthetics
notwithstanding, pharmacological cerebral preconditioning may be eclipsed by mechanical Remote Ischemic Preconditioning
(RIPC). Several clinical studies have demonstrated that three 5-minute inflations of a blood pressure cuff to 200 mmHg around a
patient's upper arm, followed by 5-minute intervals of reperfusion, improves outcome after cardiovascular procedures170-173 and
evidence from laboratory investigations indicates that the same technique initiated prior to neurosurgery may improve
outcome.174-177 Clinical studies of RIPC in neurosurgical patients are underway or have recently been completed,178 and a
published study by Hu and colleagues has reported reduced biochemical markers of neuronal ischemia and improved rate of
recovery after cervical decompression in patients who received RIPC.179
Neurogenesis
The old adage that neurogenesis is only for the young was shown to be wrong for rodents in 1965,180 is known to be wrong for
non-human primates,181 and is almost certainly wrong for humans.182 This raises the possibility that negative effects of surgery
and anesthesia on the elderly, as well as the very young, can be compensated by therapies that strengthen the neurogenic
response. Results in rats encourage the conclusion that "neural precursors resident in the brain initiate a compensatory response
that results in the production of new neurons. Moreover, administration of growth factors can enhance this compensatory
response … [and] we may eventually be able to manipulate these precursors to improve recovery of function."183, 184 In addition
to ischemic preconditioning,185 granulocyte-colony stimulating factor186 and erythropoietin187, 188 appear to be such manipulators,
and neurogenesis may be the mechanism of electroconvulsive therapy in patients with depression.189, 190
Unfortunately, however, as noted above, Culley and colleagues have presented evidence that 1 MAC isoflurane reduces the
production of neural stem cells by 20% in vitro 24 hours after exposure.17 Noting that “a 15-20% decrease in neurogenesis in
vivo … is sufficient to impair hippocampal-dependent memory in rodents,191 and even more striking, recall of remote spatial
memory in adult animals depends on recruiting as few as 1-4% newly born neurons into hippocampal circuits192 … even a
transient adverse effect of isoflurane on self-renewal of NSCs [neural stem cells] might have far-reaching consequences for brain
development and function across the life-span.” If so, this raises concern about the effect of all anesthetics on NSC proliferation
“at critical periods of brain development as well as in adulthood.”17
CONCLUSION
Reports of possible adverse cognitive effects of anesthetics on young patients appeared in our literature during the 1940’s, on
elderly patients in the 1950’s, and on fetuses in the 1980’s ... so these problems and some of their potential solutions are not new,
but our awareness of them has experienced a renaissance over the past decade. Fortunately, the vast majority of anesthetics
delivered to infants last less than 1.5 hours or are administered to children that are more than 6 months old. For that majority, I
agree that the “evidence is most consistent with the premise that ‘anesthesia per se,’ given to an otherwise healthy child who
needs only a ‘routine’ surgical procedure, is not neurotoxic”193 … or is not toxic enough to cause a currently measurable adverse
effect. However, for children less than 6 months old, fetuses of any age (given Hogan’s recent finding7) and patients over 60,
until and unless we are able to classify substantive anesthetic neurotoxicity as a rare complication, the conservative first-do-no-
harm approach should: 1) count anesthesia on the cost side of the cost/benefit equation when making decisions about whether and
when to proceed with surgery; 2) avoid nitrous oxide, isoflurane and ketamine because multiple laboratory studies indicate that
they are particularly toxic; 3) limit the duration of continuous anesthesia to less than 2 hours whenever possible; and 4) consider
the possibility that deep sedation may trigger as much neuronal apoptosis as light anesthesia.
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At the very least, newfound concerns generated by available data should inspire a great deal of translational research. If that
research is funded, our guess is that we will soon have anesthetic, sedative and adjuvant drugs ranked according to their
deleterious effects … and cerebral preconditioning with augmentation of endogenous processes of regeneration will deliver brain
protection and recovery to the very young, the old, and everyone in between … before the younger among us are too far gone to
benefit!
References: (Most references are given as PubMed ID number … just put the number in the PubMed search box.)
1
8786390 29215725 312773370 46474175 57197490 621307768 7Hogan K. ASA 2011 Abstract BOS01
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press 14Brambrink et al, 2012, Abstract, ASA 2012 1521241795 1619293705 1721666433 1820124985 1921701379
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36
22305025 37Block et al, 2012, Anesthesiology, in press. 38Diaz et al, 2012, IARS Abstract S-400. 3919456216
40
21368654 4121415431 423792096 431709436 447977913 457474220 469803015 4710852187 48(google)
NCT00756600 4921555934 5020736436 51(google) NCT00881764 5215277906 5317413912 5419352168
55
(google) NCT00934700 5620460994 5721293251 5821956042 5918201836 6019293695 6119293698 6221169791
63
22198221 6416289675 6522198380 6621909020 6722354242 6822258021 6922293721 7013243706 719525362
72
18156878 7315616043 7420418692 7519910621 7616894104 7719225398 78Jauhar, New Y ork Times, September
19, 2000 (Science, p.1) 7911172175 8022256807 8116645936 8211823666 8319890125 8421334013 8516387994
86
14752413 8720473145 8822584766 8917234824 9019414723 9121474660 9221372278 9321386669 9420838332
95
22449296 9615840989 9720711073 9816402109 9917498578 10022108393 10122343471 10219433662
103
18227305 10422069482 10522075020 10615718054 10715502036 10817578961 10916691113 11016931673
111
18710841 11220885290 11321252704 11415138912 11516803914 11611282816 11720042557 11820395617
119
22238041 12019820235 12117346857 12216564662 12317287498 12418326038 12522368036 12621857497
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21504113 12816131734 1298126336 13012111615 13116078210 13221059370 13318806029 13419199872
135
19236906 13612606913 13716508392 13815099683 13921777661 14012401580 14110320260 14219231397
143
19164788 14418439654 14519556536 14619929191 14722436797 14816412260 14917910609 15022541366
151
22513699 15222397651 15321911655 15422516463 15521482915 15622473869 15722020026 15822614435 159New
York Times, A new attack on Alzheimer’s. May 20, 2012 16016177036 16122267788 162Reynolds, New York
Times, Exercising to fire up the body’s trash furnaces. February 7, 2012 16321971406 16412951822 16514205366
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+preconditioning 17919996767 1805861717 18117405451 18221519376 18315271491 18419860727 18517434685
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DISCLOSURE
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Perioperative Management of Patients Undergoing Spine Surgery

Susan Black, M.D. Birmingham, Alabama
Management of patients undergoing spine surgery varies with location and type of the planned surgical procedure.
Understanding of the patient’s spine disease, planned procedure, and other co morbidities are crucial to providing
optimal perioperative care.
Airway Management
Patients with cervical spine pathology require special consideration for airway management. Patients with cervical
spine disease have a higher incidence of difficult intubation, in particular those with rheumatoid disease, cervical
fractures or tumors, disease involving the upper cervical spine, and with internal or external fixation.1
Endotracheal intubation in the presence of cervical spine disease may be associated with risk of neurologic injury.
In patients with a recognized unstable cervical spine, intubation is not associated with an increased risk of
neurologic deterioration compared to those not requiring intubation (1-2%).2 In patients with unrecognized cervical
3
spine instability, risk of neurologic deterioration with intubation is approximately 10%. Studies have attempted to
2,4-7
identify optimal techniques for intubation in patients at risk for cervical spine injury. During airway maneuvers,
the greatest motion of the cervical spine has been shown to occur at the atlanto-occipital junction followed by the
junction of the first two cervical vertebrae.8 In evaluation of stabilization maneuvers, manual in line stabilization
has been shown to eliminate motion indicative of cervical instability during direct laryngoscopy in severe cervical
spine injury, while axial traction may increase motion and hard collars have no impact on motion and increase
intubation difficulty.6,8 In the presence of a recognized unstable cervical spine a variety of intubation techniques in
experienced hands have consistently been shown to be safe with no single best technique identified.2 Results of
studies of cervical motion and intubation characteristics of different intubation tools suggest potential advantages
with fiberoptic bronchoscopy, indirect laryngoscopes, video laryngoscopes and use of intubation guides for
decreasing cervical spine motion during intubation.2-9 Use of the laryngeal mask airway (LMA) and intubating
LMA have generated considerable interest. Potential benefits of the LMA include less motion of the cervical spine
and higher success rate when used emergently by physicians with limited airway experience. Potential
disadvantages include increased risk of aspiration and the impact of flexion of the cervical spine.7,10 Both awake
intubation and intubation after induction of general anesthesia have been used safely.2 Advantages of awake
intubation include maintenance of normal muscle tone and the ability to perform a neurologic examination following
intubation. Intubation after induction of general anesthesia also has advantages including the ability to secure the
airway with limited neck movement in the patient who is unable to cooperate. In planning airway management of
patients undergoing cervical spine surgery awareness of the risk of spinal cord injury with intubation, recognition of
the increased risk of encountering a difficult airway, and attention to minimizing motion of the cervical spine are
more important to success than choice of a particular technique.
Cervical Spine Procedures

Positioning the patient with cervical spine disease may be associated with risk of neurologic injury and in some
situations may be done with neurologic monitoring, either of the awake patient or with electrophysiologic
monitoring. Patients undergoing surgical decompression for cervical stenosis with myelopathy are at higher risk for
postoperative neurologic deterioration. It is a common practice to maintain very strict control of blood pressure
intraoperatively utilizing direct arterial pressure monitoring and attempting to maintain systemic perfusion pressure
at or very near awake levels. While this has not been studied in a prospective fashion, it is believed by many
neurosurgeons and neuroanesthesiologists to be important in minimizing risk for new neurologic injury in this
patient population.11
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Certain patient groups may also have risk of postoperative airway problems – the difficult extubation patient.
Patients undergoing multiple level anterior cervical spine procedures may be at risk for postoperative neck and
airway edema causing airway compromise with airway complications occurring in up to 6%, requiring reintubation
in approximately 2%, and leading to mortality in 0.3%. Identified risk factors are operative time > 10 hours,
requirement for > 4 units transfusion, obesity, reoperations, and operations of 4 or more cervical spine levels or
involving C2.12
Thoracic Spine Procedures

Thoracic spine procedures present particular challenges in surgical management when the pathology is anterior or
lateral. Numerous lateral and anteriolateral surgical approaches have been developed to allow adequate surgical
access with acceptable neurologic injury rates. These approaches, including thoracotomy, thoracoscopy, and lateral
extracavitary approaches are associated with more severe postoperative pain and often require techniques to deflate
the lung on the operative side. Double lumen endotracheal tubes and bronchial blockers have been used
successfully. On occasion, the surgical goals can be accomplished by simply decreasing tidal volume, either via jet
ventilation or traditional ventilation with temporary decrease of tidal volume, during critical points in the procedure.
Thoracic spine procedures are often associated with large intraoperative blood loss, particularly when treating
scoliosis, traumatic fractures, and tumors. Endoscopic approaches to the spine have been used with increasing
frequency over the last decade. Thoracoscopic approaches are beneficial primarily in patients with lateral or anterior
pathology, resulting in decreased postoperative pain, lower blood loss, fewer pulmonary complications, and
decreased ICU utilization than open approaches. Thoracoscopy requires utilization of one lung ventilation, which is
not required for all open approaches.13
Lumbar Spine Procedures

Procedures on the lumbar spine vary in complexity from simple discectomy to complex multi-level reconstructive
procedures. Anesthetic management also may vary greatly with a recent resurgence in use of regional anesthesia for
some lumbar spine procedures, primarily discectomy. Studies suggest that spinal anesthesia may be associated with
decreased blood loss, early postoperative pain, incidence of nausea and vomiting, and incidence of deep venous
thrombosis.14 Additional use of epidural clonidine may further decrease postoperative pain.15 Of note, most authors
who utilize this technique avoid patients with severe spinal stenosis. Use of spinal anesthesia in patients with severe
spinal stenosis not undergoing spine surgery has been reported to be associated with increased risk for new
neurologic deficits.16
Endoscopy is utilized in lumbar spine disease in posterior approaches for discectomy as well as anterior approaches
for instrumentation. Benefits demonstrated in some clinical scenarios include shortened hospital stay, decreased
postoperative pain, and shortened disability duration with similar long term results.17 Vertebroplasty and
kyphoplasty, done percutaneously with fluoroscopic guidance are being used increasing to treat painful osteoporotic
fractures of the thoracic and lumbar spine. It has a high success rate, but may be associated with pulmonary
embolism (in up to 4% of patients) or pericarditis caused by intravenous administration of the cement material.
These complications may manifest during or several hours after the procedure.18,19
Lumbar decompressive surgery for spinal stenosis is being performed increasingly in the very elderly (over 75 to 80
years of age). Recent long term studies suggest that these patients who present with on average 3 to 4 comorbid
conditions have significant improvement in symptoms and quality of life, with low perioperative morbidity and
hospital stays of 2 to 4 days on average.20,21 Interestingly, obesity was related to increased incidence of major
complications, while increasing age was related to incidence of minor complications.22
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Transfusion Management
While many surgical procedures of the spine are not associated with large blood loss, procedures involving
significant bone work at multiple levels, particularly in the thoracic and lumbar regions, may be associated with
large intraoperative blood loss and a high incidence of transfusion. During lumbar spine surgery a number of factors
have been found to predict requirement for transfusion including age greater than 50, preoperative hemoglobin level
(less than 12 gm/dl) fusion of more than 2 levels, and transpedicular osteotomy.23 Strategies to reduce transfusion of
homologous blood products include attempts at reduction of intraoperative blood loss (induced hypotension,
alteration of operative position, changes in surgical techniques, and administration of antifibrinolytic agents) and
reduction of transfusion of homologous products (preoperative recombinant human erythropoietin, intraoperative
and/or postoperative blood salvage, preoperative autologous donation, and perioperative hemodilution and
apheresis). Each of these techniques have demonstrated efficacy in some clinical scenarios. Of note a recent large
retrospective review (>1000 patients) of transfusion practice during spine surgery comparing early practice (1980-
1985) to more recent practice (1995-2000) revealed older patients with more co-morbidities undergoing longer
procedures in the recent practice group. Over time allogenic transfusion decreased, preoperative donation and
intraoperative salvage increased. Of particular interest was the observation that in the late practice group
postoperative hemoglobin values were significantly lower in an admittedly higher risk group of patients with no
increased risk of complications.24
Several techniques to decrease intraoperative blood loss have been investigated. Induced hypotension is applied
most commonly to multiple level thoracic or lumbar spine procedures in healthy patients without neurologic deficits.
Efficacy in decreasing blood loss and transfusion has not been consistently demonstrated.25 Operative positions
which prevent abdominal compression (such as the Jackson table) have been reported to result in less blood loss and
lower incidence of transfusion as compared to positions in which some degree of abdominal compression may occur
(prone on bolsters or Wilson frame).26 Antifibrinolytic agents, tranexamic acid and aminocaproic acid, have been
shown in many studies to decrease intraoperative and total perioperative blood loss with some studies demonstrating
a decrease in transfusion of blood products and others revealing no difference in transfusion requirements. Use of
these agents has not been associated with complications related to hypercoagulation.23,25,27 In a small series,
recombinant activated factor VII was shown to be effective at decreasing intraoperative blood loss and transfusion in
patients undergoing multiple level spinal fusion procedures when given after loss of 10% of estimated blood
volume.28 However this practice has not been studied in a large population.
Numerous approaches to decrease requirement for homologous blood transfusion have also been investigated.
Epoetin alfa administration preoperatively has been shown to decrease requirement for homologous transfusion in
combination with preoperative autologous donation by increasing the number of units that could be collected, and
without preoperative autologous donation in procedures associated with lower intraoperative blood loss.29 In
patients undergoing procedures with likely high intraoperative blood loss such as correction of neuromuscular
scoliosis, erythropoietin was not effective at decreasing transfusion requirements when used alone.30 In one
prospective study, use of erythropoietin was associated with a higher incidence of deep venous thrombosis when
pharmacologic antithrombotic prophylaxis was not used, but no increase in symptomatic thromboembolic
complications. This lead the authors to recommend consideration of pharmacologic antithrombotic prophylaxis
when erythropoietin was to be used.31 Preoperative donation of autologous blood, immediate preoperative
hemodilution and collection of autologous blood, and perioperative blood salvage have all been utilized in spine
surgery to decrease requirement for intraoperative homologous transfusion. Each has been shown to be similarly
effective used alone to decrease requirement for transfusion of homologous blood products during major spine
procedures. However, in most circumstances combination of more than one of these techniques does not further
decrease requirement for homologous blood products compared to use of a single technique.26,29,32-34 In addition,
numerous recent studies have pointed out the high rate of wasting of autologous units collected prior to spine
surgery with wasting of at least one unit in up to 50% of patients undergoing scoliosis correction.35
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Table 1: Efficacy of Maneuvers for Decreasing Blood Loss and Transfusion

Decrease Estimated Blood Loss Decrease Transfusion
Antifibrinolytics 9-58% 31-80%
Positioning with abdomen free 60-65%
Recombinant Factor VII 56-84% 41-82%
Preoperative autologous donation 52-71% (↓ homologous transfusion)
Hemodilution 39-62% (↓ homologous transfusion)
Cell Salvage 0-45% (↓ homologous transfusion)
Erythropoietin 20-83%
A recent meta analysis reviewing available maneuvers to decrease transfusion found that there was good evidence to
support the use of antifibrinolytic agents, while there was little of no evidence to support recombinant factor VII,
induced hypotension, staging of long procedures, normovolemic hemodilution, or intraoperative cell salvage.
Erythropoietin use and preoperative autologous donation were not evaluated by these authors.36
Neurologic Monitoring and Injury Prevention

Neurologic monitoring may be utilized in a number of spine procedures. To monitor integrity of the spinal cord
somatosensory evoked potentials (SSEP) are the modality with the longest history of intraoperative use with more
recent introduction of transcranial motor evoked potentials (TcMEP). The wake up test is an adjunct technique.
Electromyography (EMG) may be utilized to monitor nerve root function. SSEP monitoring during scoliosis repair
is considered an indicated technique by the Scoliosis Research Society and is felt to result in a lower risk of
intraoperative neurologic injury.37 Neurologic monitoring of other spine procedures in patients felt to be at high risk
for neurologic injury is felt by some to decrease risk of neurologic injury, but is not utilized consistently in all
centers. In a survey reported in 2007, 40-60% of centers reported using neurologic monitoring during cervical spine
surgery, 55-70% for thoracic spine surgery and only 11-26% for lumbar spine procedures.38 SSEP and TcMEP
monitoring are utilized in patients felt to be at risk for spinal cord injury either from surgical trauma, operative
position, or impairment of blood supply. EMG is utilized when it is felt that nerve roots may be at risk during the
procedure, most commonly with lumbar stabilization procedures. Conclusions from a recent literature review were
that there is good evidence that neurologic monitoring effectively detects intraoperative neurologic injury, but little
evidence that use of monitoring decreases the risk of developing a new neurologic deficit. The authors recommend
consideration of intraoperative neurologic monitoring during spine surgery.39 SSEP monitoring places some
limitation on anesthetic management, most notably limiting the dose of volatile agents and benzodiazepines.
Likewise TcMEP monitoring impacts anesthetic management. Most commonly intravenous techniques are utilized
(propofol and/or narcotic infusion with nitrous, benzodiazepines, ketamine, or lose dose volatile agents). With use
of multi-pulse stimulators and determination of optimal stimulating parameters for each patient, reliability and
success of TcMEP monitoring has greatly increased so that monitoring is gaining more widespread acceptance.40,41
EMG requires avoidance of muscle relaxants.
Table 2: Rate of Neurologic Injury, Sensitivity, Specificity, and Positive and Negative Predictive Value
Outcome SSEP TcMEP EMG Multimodal
Rate new neurologic deficit 0.09-28.5 0.8-3.2 3.2 4.9-28.5
Sensitivity 0-100 81-100 46 70-100
Specificity 27-100 81-100 73 53-100
Positive predictive value 15-100 17-96 3 5.2-100
Negative predictive value 95-100 97-100 97 96-100
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Postoperative Pain Management

Thoracic and lumbar spine procedures may be associated with significant postoperative pain. Postoperative epidural
analgesia has been shown to be more effective compared to intravenous patient controlled analgesia (PCA) for
anterior as well as posterior approaches in both children and adults. The catheter is usually placed by the surgeon in
the operative field. It is not associated with increased incidence or delayed diagnosis of neurologic injury if the
dosing regimen is planned to allow early neurologic assessment. Benefits include earlier return of bowel function,
earlier mobilization, shorter hospital stay, improved pain control at rest and with movement, less nausea and
vomiting, and less puritis.42,43 Wound catheters with infiltration of local anesthetic have also been effective in pain
relief and to decrease the incidence of chronic dysesthesias.44 Epidural infusions of clonidine alone have been
shown to have significant benefits in terms of pain control, lower required doses of systemic narcotics.45 Other
techniques including pre and post operative oral controlled release narcotics, preoperative methadone (0.2 mg/kg),
perioperative oral pregabalin (150 mg preop and 12 hours post op), and local anesthetic wound infiltration have been
shown to improve pain management and decrease systemic narcotic side effects.46-50 In patients requiring chronic
narcotics preoperatively, intraoperative ketamine (0.5 µg/kg on induction, 10 µg/kg/min infusion) has been shown
to effectively decrease pain scores and narcotic use in both the early and late postoperative period.50
Outpatient Spine Surgery

Increasingly, spine procedures are being performed as outpatient procedures. Not only are lumbar procedures
commonly outpatient procedures, but in addition cervical spine procedures are being considered as outpatient
procedures. Available literature suggests this can be done successfully provided careful patient and procedure
selection is carried out. Patients undergoing outpatient spine surgery tend to be relatively healthy, without
myelopathic symptoms, younger than the inpatient spine surgery population, undergoing shorter procedures, and
live nearby with a caregiver available. Unplanned admission or readmission is uncommon (2-5%), with no reported
complications specifically related to the outpatient status. The most common causes of admission are dural tear,
anesthetic complications, poor pain control, new neurologic symptoms, and urinary retention. In centers with
successful outpatient spine surgery practices, common exclusion criteria for outpatient procedures include
significant co-morbidities, difficult airway, living a long distance away or living alone, and procedures finishing late
in the day. In general postoperative stay is at least 4 to 6 hours. The majority of complications after spine surgery
will have occurred by this time. With careful perioperative planning, outpatient spine surgery can be performed
safely offering our patients the benefits associated with outpatient procedures including lower cost and lower risk for
hospital associated complications.51-54
Postoperative Vision Loss

Postoperative vision loss is a rare complication of spine surgery occurring in 0 – 0.1% of cases.55-59 While
awareness of this complication has increased over the last decade, the incidence nationally appears to be
decreasing.59 Postoperative vision loss is most often due to posterior ischemic optic neuropathy (PION), less
commonly anterior ischemic optic neuropathy (AION), and rarely due to other reported causes of postoperative
vision loss; central retinal artery or vein occlusion and occipital lobe infracts. Reported risk factors for
postoperative ION include patient factors such as risk factors for atherosclerotic disease and intraoperative factors.
While occasional cases of vision loss due to positioning errors with pressure on the eye are reported, this rarely
appears to be a factor. Intraoperative hypotension and anemia are the most consistent observations in patients
developing postoperative ION. However, in the majority of spine cases the level and duration of hypotension and
anemia are not different from values reported in patients who undergo similar procedures without developing vision
loss.56-57 Cases of ION after procedures without any perioperative hypotension or anemia have occurred. The
prone position is associated with significant increases in intraocular pressure and potentially, retrobulbar pressure.
Some have postulated that acute venous congestion and a compartment-like syndrome develops in the retrobulbar
space predisposing these patients to ischemic of the optic nerve. Both head dependent positioning and vigorous
fluid resuscitation could contribute to this phenomenon.60 In procedures with high blood loss, avoidance of
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administration of large volumes of fluid requires either earlier transfusion or reliance on vasopressors. Use of
vasopressors while supporting blood pressure at a higher level might also cause vasoconstriction of the optic nerve
blood supply. Whether fluid therapy or vasopressors is the ideal approach has not been determined. Long operative
duration, high intraoperative blood loss, fluid resuscitation, and periorbital edema have been reported to be
associated with increased risk for ION.56 Because most patients undergoing even long prone spine surgery with
large intraoperative blood loss do not develop ION, other as yet unidentified risk factors are felt to exist such are
variations in optic nerve blood flow and autoregulation. It has also been suggested that changes in transfusion
practice over the last decade to lower hematocrit values as triggers for transfusion may have led to an increased
incidence in postoperative ION. In a recent case control study the Postoperative Visual Loss Study Group
investigated factors reported to be with PION.61 Results are shown in Table 3.
Table 3: Proposed Risk Factors Postoperative ION

Risk factors associated ION Risk factors not associated with ION
Male sex Age
Obesity Comorbid conditions (diabetes, hypertension, smoking)
Use of Wilson frame Number levels
Anesthetic duration Head positioning device
Estimated blood loss Hypotension
Lower colloid use (as % of nonblood infusions) Lowest HCT
Vasopressor use
Total volume, total nonblood volume replacement
Because neither the mechanisms nor definitive risk factors have been identified, methods to prevent this
complication are unknown. In fact, the patient profile for those suffering this complication after spine surgery is
males aged 45 to 55 with risk factors for vascular disease present in only about 50%. The recommendations from
the ASA Practice Advisory are shown in Table 4.62
Table 4: ASA Practice Advisory for Perioperative Visual Loss Associated with Spine Surgery
There is a subset of patients who undergo spine procedures while they are positioned prone and receiving general
anesthesia that has an increased risk for development of perioperative visual loss. This subset includes patients who
are anticipated preoperatively to undergo procedures that are prolonged, have substantial blood loss, or both (high-
risk patients).
Consider informing high-risk patients that there is a small, unpredictable risk of perioperative visual loss.
The use of deliberate hypotensive techniques during spine surgery has not been shown to be associated with the
development of perioperative visual loss.
Colloids should be used along with crystalloids to maintain intravascular volume in patients who have substantial
blood loss.
At this time, there is no apparent transfusion threshold that would eliminate the risk of perioperative visual loss
related to anemia.
High-risk patients should be positioned so that their heads are level with or higher than the heart when possible. In
addition, their heads should be maintained in a neutral forward position (e.g., without significant neck flexion,
extension, lateral flexion, or rotation) when possible.
Consideration should be given to the use of staged spine procedures in high-risk patients.
Postoperative surgical site infections (SSI) after spine surgery cause significant increases in morbidity, hospital
length of stay and health care cost. SSI’s occur at rate of 0.7 to 4.0 per 100 cases. A number of risk factors have
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been identified, many of which are not amenable to perioperative intervention and are reflections of the patients
disease or co-mordid conditions. These include ASA physical classification, prior spine surgery, operative duration,
obesity, and age. However a number of factors can be modified and are under the purview of the anesthesiologist.
These include perioperative glucose management, temperature control, and administered FiO2. A recent case
control study revealed elevated postoperative glucose and administration of FiO2 below 50% as predictors of
increased risk of postoperative infection after spine surgery, with a low FiO2 carrying an adjusted odds ratio of 12.63
Patients undergoing spine surgery present diverse challenges to the anesthesiologist. Optimal management depends
on the anesthesiologist understanding the pathologic process and the risk and needs of the operative procedure.
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26. Nuttall GA, Horlocker TT, Santrach PJ, Oliver WC, Dekutoski MB, Bryant S: Predictors of blood
transfusions in spinal instrumentation and fusion surgery. Spine 25(5):596-601, 2000
27. Shapiro F, Zurakowski D, Sethna NF: Tranexamic acid diminishes intraoperative blood loss and
transfusion in spinal fusions for Duchene muscular dystrophy scoliosis. Spine 32:2278-2283, 2007
28. Sachs B, Delacy D, Green J, Graham S, Ramsay J, Kreisler N, Kruse P, Khutoryansky N, Hu SS:
Recombinant activated factor VII in spinal surgery. Spine 32:2285-2293, 2007
29. Shapiro GS, Boachie-Adjei O, Dhawlikar SH: The use of epoetin alfa in complex spine surgery. Spine
27:2067-2071, 2002
30. Vitlae MG, Privitera DM, Matsumoto H, Gomez JA, Waters LM, Hyman JE, Roye DP: Efficacy of
preoperative erythropoietin administration in pediatric neuromuscular scoliosis. Spine 32:2662-2667, 2007
31. Stowell CP, Jones SC, Enny C, Langhooff W, Leitz G: An Open-label, randomized, parallel-group study
of perioperative epoetin alfa versus standard of care for blood conservation in major elective spine surgery. Spine
34:2479-2485, 2009.
32. Blais RE, Hadjipavlou AG, Shulman G: Efficacy of autotransfusion in spine surgery: comparison of
autotransfusion alone and with hemodilution and apheresis. Spine 21(23):2795-2800, 1996
33. Cavallieri S, Riou B, Roche S, Ducart A, Roy-Camille R, Viars P: Intraoperative autologous transfusion in
emergency surgery for spine trauma. J of Trauma 36(5):639-643,1994
34. Cha CW, Deible C, Muzzonigro T, Lopez-Plaza I, Vogt M, Kang JD: Allogeneic transfusion requirements
after autologous donations in posterior lumbar surgeries. Spine 27:99-104, 2002
35. Bess RS, Lenke LG, Bridwell KH, Steger-May K, Hensley M: Wasting of preoperatively donated
autologous blood in surgical treatment of adolescent idiopathic scoliosis. Soine 31:2375-2380
36. Elgafy H, Bransford RJ, McGuire RA, Dettori JR, Fischer D: Blood loss in major spine surgery: are there
effective measures to decrease massive hemorrhage in major spine fusion surgery?
Spine 20;35(9 Suppl):S47-56, 2010.
37. Nuwer MR, Dawson EG, Carlson LG, Kanim LE, Sherman JE: Somatosensory evoked potential spinal
cord monitoring reduces neurologic deficits after scoliosis surgery: results of a large multicenter survey.
Electroencephalography Clin Neurophysiology 96:6-11, 1995
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38. Magit DP, Hilibrand AS, Kirk J, Rechtine G, Albert TJ, Vaccaro AR, Simpson AK, Grauer JN:
Questionnaire study of neuromonitoring availability and usage for spine surgery. J Spinal Disord Tech 20:282-289,
2007.
39. Fehlings MG, Brodke DS, Norvell DC, Dettori JR: The evidence for intraoperative neurophysiological
monitoring in spine surgery. Does it make a difference: Spine 37:S37-S46, 2010
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anesthesia. J Neurosurg Anesthesiol 17:13-19, 2005.
41. Scheufler KA, Reinacher PC, Blumrich W, et al. The modifying effects of stimulation pattern and propofol
plasma concentration on motor-evoked potentials. Anesth Analg 100:440-447, 2005.
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98;956-965, 2004.
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intravenous opioids versus epidural analgesia on recover after surgery for idiopathic scoliosis. Spine 25:2355-2357,
2000
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randomized placebo-controlled trial. Anesth Analg 108: 631-4, 2009.
46. Blumenthal S, Min K, Marquardt M, Borgeat A: Postoperative intravenous morphine consumption, pain
scores, and side effects with perioperative oral controlled-release oxycodone after lumbar discectomy. Anesth
Analg 105:233-237, 2007
47. Ersayli DT, Gurbert A, Bekar A, Uckunkaya N, Bilgin H: Effects of perioperatively administered
bupivacaine and bupivacaine
-methylprednisolone on pain after lumbar discectomy. Spine 31:2221-2226, 2006
48. Gottschalk A, Durieux ME, Nermergut EC: Intraoperative methadone improves postoperative pain
control in patients undergoing complex spine surgery. Anesth Analg 112:218-223, 2011
49. Kim JC, Choi YS, Kim KN, Shim JK, Lee JY, Kwak YL: Effective dose of peri-operative oral pregablin
as an adjunct to multimodal analgesic regimen in lumbar spinal fusion surgery. Spine 36:428-433, 2011
50. Loftus RW, Yeager MP, Clark JA, Brown JR, Abdu WA, Sengupta DK, Beach ML: Intraoperative
ketamine reduces periperative opiate consumption in opiate-dependent patients with chronic pain undergoing back
surgery. Anesthesiology 113:639-646, 2010
51. Trahan J, Abramova MV, Richter EO, Steck JC: Feasibility of anterior cervical discectomy and fusion as
an outpatient procedure. World Neurosurg 75(1):145-8, 2011.
52. Wohns R: Safety and cost-effectiveness of outpatient cervical disc arthroplasty: Surg Neurol Int13;1:77,
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53. Walid MS, Robinson JS 3rd, Robinson ER, Brannick BB, Ajjan M, Robinson JS Jr: Comparison of
outpatient and inpatient spine surgery patients with regards to obesity, comorbidities and readmission for infection.
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54. Purzner T, Purzner J, Massicotte EM, Bernstein M: Outpatient brain tumor surgery and spinal
decompression: a prospective study of 1003 patients. Neurosurgery. 69(1):119-26, 2011.
55. Stevens WR, Glazer PA, Kelley SD, Lietman TM, Bradford DS: Ophthalmic complications after spine
surgery. Spine 22:1319-1324, 1997
56. Myers MA, Hamilton SR, Bogosian AJ, Smith CH, Wagner TA: Visual loss as a complication of spine
surgery. A review of 37 cases. Spine 22:1329, 1997
57. Cheng MA, Sigurdson W, Tempelhoff R, Lauryssen C: Visual loss after spine surgery: a survey.
Neurosurgery 46(3):625-631, 2000.
58. Lee LL, Newman NJ, Wagner TA, Dettoir JR, Dettori NJ: Perioperatie Ischemic Optic Neuropathy. Spine
35:S105-S116, 2010
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59. Shen Y, Drumm M, Roth S: The prevalence of periperative visual loss in the United States: A 10-year
study from 1996-2005 of spinal, orthopedic, cardiac, and general surgery. Anesth Analg 109:1534-1545, 2009
60. Cheng MA, Todorov A, Tempelhoff R,et al: The effect of prone positioning on intraocular pressure in
anesthetized patients. Anesthesiology 95:1351-1355, 2001.
61. The Postoperative Visual Loss Study Group: Risk factors associated with ischemic optic neuropathy after
spinal fusion surgery. Anesthesiology 116:15-24, 2012.
62. Practice Advisory for Perioperative Visual Loss Associated with Spine Surgery. Anesthesiology 104:1319
–28, 2006
63. Maragakis LL, Cosgrove SE, Martinez EA, Tucker MG, Cohen DB, Perl TM: Intraoperative fraction of
inspired oxygen is a modifiable risk factor for surgical site infection after spinal surgery. Anesthesiology 110:556 –
62, 2009.
DISCLOSURE
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Neonatal Resuscitation
Valerie Arkoosh, M.D., MPH Philadelphia, Pennsylvania
Following birth, numerous physiologic changes must rapidly transpire in order for the fetus to successfully
make the transition to a neonate. Despite the complexity of this process, on average ten percent of newborns require
some assistance to begin breathing and only one percent of newborns require full resuscitation in the delivery room.1
This percentage rises quickly, however, among newborns who weigh less than 1500 grams. Given the relative rarity
of the need for full resuscitation, it is optimal for all delivery room personnel to frequently review the neonatal
adaptations to extrauterine life, make provision for resuscitation, understand the predictors of need for resuscitation
and know how to respond appropriately.
Neonatal Adaptations to Extrauterine Life 2,3 The placenta is the organ for gas exchange in the fetus. A
substantial right-to-left shunt exists. The shunt persists due to high pulmonary vascular resistance (PVR) coupled
with low systemic vascular resistance (SVR). Ninety percent of right ventricular output shunts across the ductus
arteriosus. Forty percent of cardiac output flows to the low resistance placenta. During vaginal delivery,
compression of the infant thorax expels fluid from the mouth and upper airways. With crying, the lungs fill with air,
surfactant is released and oxygenation increased. In animal models, the presence of increased oxygen tension and
increased blood flow stimulate endothelial cells in the pulmonary vasculature to release nitric oxide ultimately
resulting in pulmonary vasodilatation.4 These changes significantly decrease PVR. Simultaneously, clamping of the
umbilical cord removes the low resistance placental bed from the circulation, increasing SVR. Within minutes after
birth the right-to-left shunt across the foramen ovale and ductus arteriosus is substantially reduced. Transient
hypoxemia or acidosis is well tolerated by a normal newborn and prompt resuscitation usually prevents any
permanent physiologic alteration. Prolonged neonatal hypoxemia or acidosis impedes the transition from fetal to
neonatal physiology. The fetus/neonate initially responds to hypoxemia by redistributing blood flow to the heart,
brain and adrenal glands. Tissue oxygen extraction increases to the maximum extent possible. Eventually, as
additional oxygen extraction is unattainable, myocardial contractility and cardiac output decrease. Hypoxemia and
acidosis promote patency of the ductus arteriosus, counteracting the normal neonatal increase in pulmonary artery
blood flow. Blood flowing through a patent ductus arteriosus is not oxygenated, contributing to increasing
hypoxemia. Spontaneous ventilatory drive is reduced by both indirect central nervous system depression and direct
diaphragmatic depression. The net result of these physiological responses is a neonate with persistent pulmonary
hypertension and little or no ventilatory drive. Ideally, prompt resuscitation prevents these physiologic perturbations.
Preparation for
Table 1. Equipment & Medications for Neonatal Resuscitation Resuscitation Preparation
Suction Equipment Bag & Mask Equipment
for neonatal resuscitation is an
Bulb syringe Neonatal resuscitation bag with pressure relief valve
Mechanical suction Face masks - newborn & premature sizes ongoing activity on all labor
Suction catheters 5F - 10F Oral airways and delivery units. A number of
Meconium Aspirator Oxygen with flowmeter & tubing tasks including acquisition and
Intubation Equipment Medications maintenance of the proper
Laryngoscope Epinephrine 1:10,000 equipment, identification,
Straight blades #0 and #1 Naloxone hydrochloride 0.4 mg/mL or 1.0 mg/mL
Extra bulbs & batteries Volume expander education and training of
Endotracheal tubes 2.5 - 4.0 mm Sodium bicarbonate 4.2% (5 mEq/10 mL responding personnel and
Stylet Dextrose 10% development of contingency
Scissors & gloves Sterile water & Normal saline plans for additional personnel if
Miscellaneous needed must be constantly
Radiant warmer Umbilical artery catheterization tray
Stethoscope Umbilical tape monitored for completeness.
ECG Umbilical catheters 3.5F, 5F Equipment and medications
Adhesive tape Three-way stopcocks should be organized together in
Syringes & needles Feeding tube, 5F one location in the delivery
Alcohol sponges
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room, checked frequently for proper functioning and expiration date, and replenished immediately after use (Table
1).1
At least one person skilled in newborn resuscitation should attend every delivery. Additional personnel should be
available when a high-risk delivery is anticipated. The importance of trained personnel following protocol driven
maneuvers is critical. The need for anesthesia personal to participate in neonatal resuscitation is likely to increase as
pediatric residents spend more time in primary care training and less in neonatology. A recent survey of the
proficiency of third year pediatric residents at performing neonatal endotracheal intubation (n=131 observed
intubation attempts) found that intubation was successful on the first or second attempt by only 62% of these
residents.5 The technical competency of pediatricians at performing neonatal endotracheal intubation should be
assessed on an individual basis and not assumed to be present by the anesthesia team.
In determining need for personnel trained in neonatal resuscitation, anesthesiologists in the United States can refer to
Guideline VII of the American Society of Anesthesiology, Guidelines for Regional Anesthesia in Obstetrics. The
guideline states: "Qualified personnel, other than the anesthesiologist attending the mother, should be immediately
available to assume responsibility for resuscitation of the newborn. The primary responsibility of the
anesthesiologist is to provide care to the mother. If the anesthesiologist is also requested to provide brief assistance
in the care of the newborn, the benefit to the child must be compared to the risk to the mother."
Assessment of Risk By using ante- and intrapartum fetal assessment, the need for neonatal resuscitation can
be predicted in about 80% of cases. Antepartum assessment includes evaluation for major fetal anomalies and
identification of maternal factors that may influence fetal well being (Table 2).1,2 Intrapartum events often predict
the need for neonatal resuscitation (Table 3).1,6 Assessment must continue throughout labor as the clinical situation
can change rapidly. Intrapartum evaluation includes fetal heart rate monitoring with, when indicated, fetal scalp
stimulation or fetal scalp blood sampling for pH determination. Intrapartum fetal heart rate (FHR) monitoring is the
first line of fetal assessment.7 FHR monitoring is most reliable in confirming fetal well-being and is more than 90%
accurate in predicting a 5 minute Apgar score greater than 7.8,9 In predicting fetal compromise, however, FHR
monitoring has a false positive rate of at least 35-50%.9,10 Even though an abnormal fetal heart rate trace may not
correlate well with a poor long-term prognosis, the presence of an abnormal tracing is highly correlated with the
need for neonatal resuscitation in the delivery room.6 Additionally, it is important to remember that even in the
presence of a reassuring fetal heart rate trace nearly 50% of babies born by cesarean delivery will require some
active form of resuscitation.6 Fetal pulse oximetry has been tested as a method of intrapartum fetal assessment.
Consensus from several large human trials is that normal fetal oxygen saturation is between 35% and 65% and that
metabolic acidosis develops after the fetal oxygen saturation is less than 30% for 10 to 15 minutes.11-13 One
Table 2. Maternal & Fetal Factors Associated with Need for Resuscitation randomized study of 1010
Maternal diabetes Post-term gestation patients found a >50%
Pregnancy-induced hypertension Pre-term gestation reduction in the number of
Chronic hypertension Multiple gestation
Previous Rh sensitization Size-dates discrepancy cesarean deliveries
Previous stillbirth Polyhydramnios performed for nonreassuring
Bleeding in the second or third trimester Oligohydramnios fetal status when fetal pulse
Maternal infection Maternal drug therapy including oximetry data was used
Lack of prenatal care Reserpine, lithium carbonate
Maternal substance abuse Magnesium, adrenergic-blockers compared with FHR
Known fetal anomalies monitoring alone but, no
Table 3. Intrapartum Events Associated with Need for Resuscitation difference in the overall
Cesarean delivery General anesthesia cesarean delivery rate or
Abnormal fetal presentation Uterine tetany
Premature labor Meconium-stained amniotic fluid
neonatal outcome between
Rupture of membranes > 24 hours Prolapsed cord the two groups.14 A larger
Chorioamnionitis Abruptio placentae randomized trial of 5341
Precipitous labor Uterine rupture nulliparous women found no
Prolonged labor > 24 hours Difficult instrumental delivery
Prolonged second stage > 3-4 hours Maternal systemic narcotics within 4 hours
difference in the cesarean
Nonreassuring fetal heart rate patterns of delivery
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delivery rate when clinicians had access to fetal pulse oximetry data and no difference in neonatal outcome between
the two groups.15 Thus, there is no evidence to support the clinical use of fetal pulse oximetry.16
In the presence of a non-reassuring fetal heart rate trace, the practitioner may wish confirmatory studies of
fetal well-being or lack thereof. Digital stimulation of the fetal scalp will result in fetal heart rate accelerations in a
healthy, non-acidotic fetus. Fetal scalp pH determination can confirm or exclude fetal acidosis. A pH of less than 7.2
is considered abnormal and if confirmed by a second measurement may indicate the need for delivery. Predictors
specifically of the need for endotracheal intubation include administration of general anesthesia to the mother and
low infant weight.17,18 In growth-restricted infants, factors predicting low uterine artery pH and/or 5 minute Apgar
score <7 include: preeclampsia, fetal distress, breech delivery, forceps use, older maternal age, need for
amnioinfusion, general anesthesia and nalbuphine use during labor.18
Response: Intrapartum Intrapartum resuscitation is attempted once fetal compromise is identified. Maternal
factors that may impair oxygen delivery to the fetus must be identified and corrected if possible. Considerations
include maternal hypotension or decreased cardiac output secondary to aorto-caval compression, sympathectomy,
hemorrhage or cardiac disease. Disease states that may interfere with maternal oxygenation such as asthma,
pneumonia, or pulmonary edema should be considered and if present, treated appropriately. Attention must also be
directed to the uterus where hyperstimulation, tetany, placental abruption or uterine rupture may interfere with blood
flow to the fetus. Stopping an oxytocin infusion or administering a tocolytic agent will reduce uterine tone and
potentially allow the fetus the opportunity to recover. Emergent delivery will be required if placental abruption or
uterine rupture are severe. Umbilical cord prolapse should always be considered if fetal heart rate changes are
sudden, severe and prolonged. Oligohydramnios is a risk factor for umbilical cord compression and variable
decelerations. Obstetricians may administer a saline amnioinfusion to try to alleviate cord compression.19 Saline
amnioinfusion is performed by infusing warm saline into the uterus via an intrauterine pressure catheter. Saline
amnioinfusion, once frequently utilized in cases of thick meconium in an attempt to dilute the meconium, has been
shown to have no impact on the severity of meconium aspiration syndrome.20
At Birth The American Heart Association/American Academy of Pediatrics recommends the neonatal resuscitation
protocol that follows. Updated protocol recommendations were released in late 2010.21 The first 30 seconds of
neonatal resuscitation should include an assessment of the overall condition of the neonate and steps to minimize
heat loss (Figure 1). Depressed, asphyxiated infants often have an unstable thermal regulatory system. Cold stress
leads to hypoxemia, hypercarbia and metabolic acidosis, all of which will promote persistence of the fetal
circulation and hinder resuscitation. Within the first 20 seconds of birth, the newborn should be dried, placed under a
radiant warmer and evaluated for an open airway.
Management of Meconium: A major shift in thinking has occurred over the last decade concerning the management
of meconium. In the presence of meconium, routine intrapartum oropharyngeal and nasopharyngeal suctioning is no
longer recommended.21,22 Additionally, routine endotracheal intubation and suctioning are no longer recommended.
Even for depressed infants born through meconium stained fluid, the available evidence does not support or refute
routine tracheal suctioning.21,23-25
Following the first steps of stabilization, further resuscitative efforts should be guided by auscultation of
the heart rate.21 Heart rate is the primary vital sign by which to judge the need for and efficacy of resuscitation. For
babies requiring resuscitation or respiratory support pulse oximetry should be used in conjunction with auscultation
of the heart rate. Color has been removed as an indicator of oxygenation or efficacy of resuscitation. If the neonate is
gasping or apneic and/or has a heart rate <100 bpm, begin positive-pressure ventilation (PPV) at a rate of 40-60
breaths per minute. Peak inspiratory pressures of 30 to 40 cmH2O or higher may necessary for initial lung expansion
but should quickly be reduced.26 Ventilation that is adequate should promptly restore the heart rate to >100 bpm.
The majority of infants requiring any resuscitation will respond to these first two steps. Indications for endotracheal
intubation include ineffective bag and mask ventilation, anticipated need for prolonged mechanical ventilation, or as
a last resort route for administration of medicine.1 With prolonged bag and mask ventilation, a nasal or oro-gastric
tube should be inserted to decompress the stomach.
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Figure 1. Use of Oxygen The scientific basis for

the use of 100% oxygen to resuscitate
newborns has never been established.
Evidence is growing from both human
Birth Time Line clinical trials and animal models that
resuscitation with oxygen may not be
-Term gestation? Yes
Routine care
-Provide warmth optimal for all neonates.27-36 Exposure to
-Breathing or crying?
-Good muscle tone?
-Assure open airway
-Dry
high concentrations of oxygen during
30 seconds
-Ongoing evaluation resuscitation appears to promote the
No
formation of excessive levels of reactive
oxygen intermediates in neonatal tissue,
-Provide warmth
-Position, clear airway prn producing injury.34 A recent meta-
No
-Dry, stimulate, reposition analysis including randomized or
pseudo-randomized trials of neonatal
resuscitation with room air (n=881)
-HR below 100,
gasping, or apnea?
No Labored breathing or versus 100% oxygen (n=856) found the
persistent cyanosis?
following: overall neonatal mortality was
Yes 8.0 versus 13.0% in the 21 and 100%
30 seconds
Yes
-Consider SPO
2
groups, respectively (OR 0.57, 95% CI
-Provide positive-pressure monitoring 0.42-0.78); neonatal mortality in term
ventilation -Consider CPAP
- Consider SPO monitoring
2
infants was 5.9 versus 9.8% in the 21 and
100% groups, respectively (OR 0.59 95%
No
CI 0.40-0.87); for infants with a 1 minute
HR < 100?
Apgar score less than 1, there was no
Yes
difference between groups; Apgar score
-Ensure adequate ventilation
-Consider ET intubation Post-resuscitation
at 5 minutes and heart rate at 90 seconds
care were significantly higher in the room air
HR < 60? No group; time to first spontaneous breath
Yes was significantly shorter in the room air
Chest compressions group.33 Study of premature infants
suggests that initiating resuscitation with
HR < 60? less than 100% oxygen confers benefit in
Yes this patient population, as well.37 Data is
IV Epinephrine
accumulating from normal newborns not
requiring resuscitation that normal
neonatal oxygen saturations are quite low
during the first minute of age, ranging
from 43% to 77%. At 3, 5, and 10
minutes after birth, preductal mean
values were 82%, 89% and 94%, respectively.38,39 This data must be balanced with concerns about tissue damage
from prolonged asphyxia. The current guidelines reflect these concerns and recommend beginning resuscitation with
room air in term infants. If there is no increase in heart rate or SaO2 use of a higher concentration of oxygen should
be considered.21 For infants <32 weeks gestation resuscitation should begin with either 30% or 90% oxygen then
titrated to oxygen saturation. There is insufficient evidence to define a strategy for infants between 32 and 37 weeks
gestation.
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Chest compressions are indicated for a heart rate < 60 bpm despite adequate ventilation with supplemental
oxygen for 30 seconds.21 Neonatal cardiac arrest is generally secondary to respiratory failure producing hypoxemia
and tissue acidosis. The result of these metabolic changes is bradycardia, decreased cardiac contractility and
eventually cardiac arrest. Cardiac auscultation with a stethoscope should be used for the most accurate assessment of
the neonatal heart rate.40 Chest compressions should be instituted at a rate of 90 compressions per minute. The
recommended ratio between chest compressions and ventilations is 3:1, producing 90 compressions and 30
ventilations each minute. In practice, this equals thirty, 2-second cycles/minute. A 2 second cycle consists of 3 chest
compressions in 1.5 seconds,
Table 4. Medications for Neonatal Resuscitation
Medication Concentration Dosage / Route Rate leaving 1/2 second for
Epinephrine 1:10,000 0.01 – 0.03 mg/kg Give rapidly ventilation. Compressions
(0.1 – 0.3 mL/kg) Flush catheter/ET tube should be delivered by the
IV preferred with saline
ET dose up to 0.1 mg/kg
two thumb encircling hands
Volume expanders* Normal saline 10 mL/kg Give over 5 - 10 minutes technique and continue until
O negative blood IV (umbilical vein) the spontaneous heart rate is
Naloxone 0.4 mg/mL 0.1 mg/kg Give rapidly greater than 60 bpm.21
hydrochloride* IV
Sodium Bicarbonate* 0.5 mEq/mL 2 mEq/kg Give slowly, over at
Medications are
(4.2% solution) (4 mL/kg) least 2 minutes indicated if, after adequate
IV (umbilical vein) Give only if neonate is ventilation with 100%
effectively ventilated oxygen and chest
*Rarely indicated; see text. ET = endotracheal, IV = intravenous
compressions for 30 seconds,
heart rate remains below 60 beats per minute. Medications, doses and routes of administration are given in Table 4.
Epinephrine is the vasopressor of choice and can be repeated every 3 to 5 minutes until the heart rate is greater
than 60 beats per minute. Intravenous administration of epinephrine is strongly preferred due to lack of evidence of
efficacy for the recommended dose given endotracheally.1,21,41 While working to obtain IV access, epinephrine up to
0.1 mg/kg can be given via the endotracheal tube but the safety and efficacy of this practice has not been evaluated
in neonates.21 Epinephrine is not indicated before adequate ventilation has been established because it will increase
myocardial oxygen consumption. In the absence of adequate oxygen, this will likely lead to myocardial damage.
Establish the airway first. The use of blood volume expanders is rarely indicated and may be detrimental.42,43
Their use should be restricted to situations in which there is evidence of acute blood loss, such as feto-maternal
hemorrhage, accompanied by lack of response to resuscitative efforts.21,42,43 Volume expansion should occur over 5
to 10 minutes. Rapid expansion has been associated with intracranial hemorrhage. Naloxone hydrochloride is
not recommended as part of the initial resuscitative efforts; ventilation and heart rate must first be restored. The
preferred route is IV or IM. Keep in mind that no study has examined the efficacy of the recommended dose in
newborns. Naloxone should not be given to a neonate born of a narcotic addicted mother as this can precipitate acute
withdrawal and seizures in the neonate.44 The use of sodium bicarbonate is not recommended during the initial
neonatal resuscitation. Sodium bicarbonate should be given only if ventilation is adequate (or respiratory acidosis
will replace metabolic acidosis) and metabolic acidosis is documented or presumed, or all other measures have been
unsuccessful.26,45 Recent data from a small randomized trial suggests that sodium bicarbonate administered to
neonates still requiring positive pressure ventilation at 5 minutes of age had no impact on morbidity or mortality.46
Apgar Score (Table 5) Although 1 and 5 minute Apgar scores are recorded as one way of assessing neonatal
response to resuscitation, the practitioner should not wait for the 1 minute score to begin resuscitation. If the 5
minute score is less than 7, additional scores should be obtained every 5 minutes until 20 minutes have passed or
until 2 successive scores are greater than or equal to 7.47 In a study of stillborn infants, 66.6% were resuscitated and
left the delivery room alive.48 Of these, 39% survived beyond the neonatal period. Survival is unlikely if the Apgar
score is 0 at ≥ 10 minutes of age.48 Current guidelines now suggest that after 10 minutes of continuous and adequate
resuscitative efforts, discontinuation of resuscitation may be justified if there is no heart rate.21 A recent
retrospective cohort analysis of 151,891 live-born singleton infants without malformations found that an Apgar
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score between 0 and 3 at 5 minutes was a better predictor of neonatal mortality than the umbilical-artery blood pH
value.49
Laryngeal Mask Airway (LMA) The size-1 LMA has been used successfully to resuscitate newborns of both normal
Table 5. APGAR Score and low birth
Sign 0 1 2 weight requiring
Heart Rate Absent < 100 bpm > 100 bpm PPV at birth.50-54
Respiratory Effort Absent Slow, irregular Crying
The size-1 LMA
Muscle Tone Flaccid Some flexion of extremities Active motion
Reflex Irritabililty No response Grimace Vigorous cry
can be life-saving
Color Blue, pale Blue extremities Completely pink in neonates with
Pierre-Robin
Syndrome or other
conditions associated with a hypoplastic mandible in whom both bag and mask ventilation and endotracheal
intubation have failed.55,56 The LMA should be considered when face mask ventilation is unsuccessful and tracheal
intubation is unsuccessful. The LMA may also be considered as an alternative to a face mask for ventilation of
newborns weighing >2000g or at ≥34 weeks gestation.21
End-tidal CO2 Detection Both infrared absorption and pediatric size colorimetric disposable devices are readily
available for the detection of expired carbon dioxide. Clinical trials have shown that both devices are reliable and
significantly more rapid than clinical exam in both confirming endotracheal intubation and detecting esophageal
intubation.57,58 End-tidal CO2 confirmation is the recommended technique to confirm intubation in neonates with
spontaneous circulation.21
Neonatal Hypoglycemia Approximately 10% of healthy term neonates have transient hypoglycemia. Other neonates
at risk include those born of diabetic mothers or mothers who received a large amount of intravenous dextrose
during labor. If a dextrose strip glucose level is <40 to 45 mg/dl, the neonate should be treated either with oral
feedings (2-3 cc/kg D10% in water) or by intravenous infusion (8 mg/kg/min) with the goal of restoring glucose to
the normal range.
References
1. American Heart Association, American Academy of Pediatrics. 2005 American Heart Association (AHA)
Guidelines for Cardiopulmonary Resuscitation (CPR) and Emergency Cardiovascular Care (ECC) of Pediatric and
Neonatal Patients: Neonatal Resuscitation Guidelines. Pediatrics 2006;117:e1029-38.
2. Wimmer JE. Neonatal resuscitation. Pediatrics in Review 1994;15:255-65.
3. Ostheimer GW. Anaesthetists' role in neonatal resuscitation and care of the newborn. Can J Anaesth
1993;40:R50-R6.
4. Lakshminrusimha S, Steinhorn RH. Pulmonary vascular biology during neonatal transition. Clin Perinatol
1999;26:601-19.
5. Falck AJ, Escobedo MB, Baillargeon JG, Villard LG, Gunkel JH. Proficiency of pediatric residents in
performing neonatal endotracheal intubation. Pediatrics 2003;112:1242-7.
6. Posen R, Friedlich P, Chan L, Miller D. Relationship between fetal monitoring and resuscitative needs:
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7. Guay J. Fetal monitoring and neonatal resuscitation: what the anaesthetist should know. Can J Anaesth
1991;38:R83-R8.
8. Krebs HB, Petres RE, Dunn LJ, Jordan HVF, Segreti A. Intrapartum fetal heart rate monitoring I.
Classification and prognosis of fetal heart rate patterns. Am J Obstet Gynecol 1979;133:762-72.
9. Schifrin BS, Dame L. Fetal heart rate patterns. Prediction of Apgar score. JAMA 1972;219:1322-5.
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10. Tejani N, Mann LI, Bhakthavathsalan A. Correlation of fetal heart rate patterns and fetal pH with neonatal
outcome. Obstet Gynecol 1976;48:460-3.
11. Kuhnert M, Seelbach-Gobel B, Butterwegge M. Predictive agreement between the fetal arterial oxygen
saturation and fetal scalp pH: results of the German multicenter study. Am J Obstet Gynecol 1998;178:330-50.
12. Seelbach-Gobel B, Huepel M, Kuhnert M, Butterwegge M. The prediction of fetal acidosis by means of
intrapartum fetal pulse oximetry. Am J Obstet Gynecol 1999;180:73-81.
13. Carbonne B, Langer B, Goffinet F, et al. Multicenter study on the clinical value of fetal pulse oximetry. II.
Compared predictive values of pulse oximetry and fetal blood analysis. The French study group on fetal pulse
oximetry. Am J Obstet Gynecol 1997;177:593-8.
14. Garite TJ, Dildy GA, McNamara H, et al. A multicenter controlled trial of fetal pulse oximetry in the
intrapartum management of nonreassuring fetal heart rate patterns. American Journal of Obstetrics and Gynecology
2000;183:1049-58.
15. Bloom SL, Spong CY, Thom E, et al. Fetal pulse oximetry and cesarean delivery. New England Journal of
Medicine 2006;355:2195-202.
16. Greene MF. Obstetricians still await a deus ex machina. New England Journal of Medicine 2006;355:2247-
8.
17. Parsons SJ, Sonneveld S, Nolan T. Is a paediatrician needed at all caesarean sections? J Paediatr Child
Health 1998;34:241-4.
18. Levy BT, Dawson JD, Toth PP, Bowdler N. Predictors of neonatal resuscitation, low Apgar scores, and
umbilical artery pH among growth-restricted neonates. Obstet Gynecol 1998;91:909-16.
19. Sivan E, Seidman DS, Barkai G, Atlas M, Dulitzky M, Mashiach S. The role of amnioinfusion in current
obstetric care. Obstet Gynecol Surv 1992;47:80-7.
20. Fraser WD, Hofmeyr J, Lede R, et al. Amnioinfusion for the Prevention of the Meconium Aspiration
Syndrome. N Engl J Med 2005;353:909-17.
21. Perlman JM, Wyllie J, Kattwinkel J, et al. Neonatal Resuscitation: 2010 International Consensus on
Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations.
Circulation 2010;122[suppl 2]:S516-S38.
22. Vain NE, Szyld EG, Prudent LM, Wiswell TE, Aguilar AM, Vivas NI. Oropharyngeal and nasopharyngeal
suctioning of meconium-stained neonates before delivery of their shoulders: multicentre, randomized controlled
trial. Lancet 2004;364:597-602.
23. Wiswell TE, Gannon CM, Jacob J, et al. Delivery room management of the apparently vigorous meconium-
stained neonate: results of the multicenter, international collaborative trial. Pediatrics 2000;105:1-7.
24. Halliday HL. Endotracheal intubation at birth for preventing morbidity and mortality in vigorous,
meconium-stained infants born at term. The Cochrane Database of Systematic Reviews 2000;2.
25. Liu WF, Harrington T. Delivery room risk factors for meconium aspiration syndrome. Am J Perinatol
2002;19:367-77.
26. Leuthner SR, Jansen RD, Hageman JR. Cardiopulmonary resuscitation of the newborn. Pediatr Clin N Am
1994;41:893-907.
27. Ramji S, Ahuja S, Thirupuram S, Rootwelt T, Rooth G, Saugstad OD. Resuscitation of asphyxic newborn
infants with room air or 100% oxygen. Pediatr Res 1993;34:809-12.
28. Saugstad OD, Rootwelt T, Aalen O. Resuscitation of asphyxiated newborn infants with room air or oxygen:
An international controlled trial: The Resair 2 Study. Pediatrics 1998;102:E1.
29. Vento M, Asensi M, Sastre J, Garcia-Sala F, Pallardo FV, Vina J. Resuscitation with room air instead of
100% oxygen prevents oxidative stress in moderately asphyxiated term neonates. Pediatrics 2001;107:642-7.
30. Saugstad OD, Ramji S, Irani SF, et al. Resuscitation of newborn infants with 21% or 100% oxygen:
Follow-up at 18 to 24 months. Pediatrics 2003;112.
31. Ramji S, Rasaily R, Mishra PK, et al. Resuscitation of asphyxiated newborns with room air or 100%
oxygen at birth: a multicentric clinical trial. Indian Pediatrics 2003;40:510-7.
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32. Saugstad OD. The role of oxygen in neonatal resuscitation. Clin Perinatol 2004;31:431-3.
33. Saugstad OD, Ramji S, Vento M. Resuscitation of depressed newborn infants with ambient air or pure
oxygen: a meta analysis. Biol Neonate 2004;87:27-34.
34. Kutzsche S, Ilves P, Kirkeby OJ, Saugstad OD. Hydrogen peroxide production in leukocytes during
cerebral hypoxia and reoxygenation with 100% or 21% oxygen in newborn piglets. Pediatric Research 2001;49:834-
42.
35. Rabi Y, Rabi D, Yee W. Room air resuscitation of the depressed newborn: A systematic review and meta-
analysis. Resuscitation 2007;72:353-63.
36. Higgins RD, Bancalari E, Willinger M, Raju TNK. Executive summary of the workshop on oxygen in
neonatal therapies: Controversies and opportunities for research. Pediatrics 2007;119:790-6.
37. Stola A, Schulman J, Perlman J. Initiating delivery room stabilization/resuscitation in very low birth weight
(VLBW) infants with an FiO2 less than 100% is feasible. Journal of Perinatology 2009;29:548-52.
38. Rao R, Ramji S. Pulse oximetry in asphyxiated newborns in the delivery room. Indian Pediatrics
2001;38:762-6.
39. Kamlin C, O'Donnell C, Davis P, Morley C. Oxygen saturation in healthy infants immediately after birth. J
Pediatr 2006;148:585-9.
40. Owen CJ, Wyllie JP. Determination of heart rate in the baby at birth. Resuscitation 2004;60:213-7.
41. Barber CA, Wyckoff MH. Use and efficacy of endotracheal versus intravenous epinephrine during neonatal
cardiopulmonary resuscitation in the delivery room. Pediatrics 2006;118:1028-34.
42. Saugstad OD. Practical aspects of resuscitating asphyxiated newborn infants. Eur J Pediatr 1998;157:S11-
S5.
43. Roberton NRC. Use of albumin in neonatal resuscitation. Eur J Pediatr 1997;156:428-31.
44. Ginsberg HG, Goldsmith JP. Controversies in neonatal resuscitation. Clin Perinatol 1998;25:1-15.
45. Hein HA. The use of sodium bicarbonate in neonatal resuscitation: Help or harm? (letter). Pediatrics
1993;91:496-7.
46. Lokesh L, Kumar P, Murki S, Narang A. A randomized controlled trial of sodium bicarbonate in neonatal
resuscitation-effect on immediate outcome. Resuscitation 2004;60:219-23.
47. Jain L, Vidyasagar D. Controversies in neonatal resuscitation. Pediatric Annals 1995;24:540-5.
48. Jain L, Ferre C, Vidyasagar D, Nath S, Sheftel D. Cardiopulmonary resuscitation of apparently stillborn
infants: Survival and long-term outcome. J Pediatr 1991;118:778-82.
49. Casey BM, McIntire DD, Leveno KJ. The continuing value of the Apgar score for the assessment of
newborn infants. N Engl J Med 2001;344:467-71.
50. Brimacombe J. The laryngeal mask airway for neonatal resuscitation (letter). Pediatrics 1994;93:874.
51. Paterson SJ, Byrne PJ, Molesky MG, Seal RF, Finucane BT. Neonatal resuscitation using the laryngeal
mask airway. Anesthesiology 1994;80:1248-53.
52. Gandini D, Brimacombe JR. Neonatal resuscitation with the laryngeal mask airway in normal and low birth
weight infants. Anesthesia and Analgesia 1999;89:642-3.
53. Trevisanuto D, Micaglio M, Pitton M, Magarotto M, Piva D, Zanardo V. Laryngeal mask airway: is the
management of neonates requiring positive pressure ventilation at birth changing? Resuscitation 2004;62:151-7.
54. Zanardo V, Weiner G, Micaglio M, Doglioni N, Buzzacchero R, Trevisanuto D. Delivery room
resuscitation of near-term infants: Role of the laryngeal mask airway. Resuscitation 2010;81:327-30.
55. Baraka A. Laryngeal mask airway for resuscitation of a newborn with Pierre-Robin Syndrome (letter).
56. Denny NM, Desilva KD, Webber PA. Laryngeal mask airway for emergency tracheostomy in a neonate.
Anaesthesia 1990;45:895-0.
57. Repetto JE, Donohue PK, Baker SF, Kelly L, Nogee LM. Use of capnography in the delivery room for
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58. Aziz HF, Martin JB, Moore JJ. The pediatric disposable end-tidal carbon dioxide detector role in
endotracheal intubation in newborns. Journal of Perinatology 1999;19:110-3.
DISCLOSURE
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Neuraxial Labor Analgesia and Pregnancy Outcome: Fact and Fiction
Cynthia A. Wong, M.D. Chicago, Illinois
Objectives: To describe the effects, if any, of neuraxial labor analgesia on the progress of labor, rate of cesarean
delivery, and need for instrumental delivery.
Labor is a complex physiologic process. The mechanisms responsible for the progress of labor are not well
understood.1 The effects of analgesia on the progress and outcome of labor are of concern to anesthesiologists,
obstetricians, and parturients. This lecture will review the available data on the effects of neuraxial analgesia on the
progress of labor and mode of delivery.
Cesarean Delivery
Factors associated with risk of cesarean delivery: Multiple studies have attempted to identify factors associated with
cesarean delivery. These factors include maternal age and body habitus, maternal obstetric complications (e.g.,
diabetes, preeclampsia), fetal weight, obstetric practitioner and type of maternal insurance, parity, induction of labor,
and premature rupture of membranes. Additionally, observational studies suggest that epidural analgesia,
particularly epidural analgesia in early labor,2,3 is associated with an increased risk of cesarean delivery. Association,
however, does not necessarily mean cause and effect.
Randomized controlled trials: Our understanding of the nature of the association between neuraxial labor analgesia
and mode of delivery is limited by the difficulty in performing controlled trials in which parturients are randomized
to receive neuraxial analgesia vs. placebo. It is not ethical to assign women to placebo (no analgesia). Therefore,
randomized controlled trials have compared labor outcomes in parturients assigned to receive neuraxial vs. systemic
opioid analgesia. Because neuraxial analgesia is markedly superior to all other forms of analgesia, it is not possible
to blind these studies. The cross-over rate may be high.4 Other factors which influence the outcome of labor are
difficult to control. Nonetheless, in the twopast decades there have been a number of randomized controlled trials
comparing neuraxial (mostly epidural) to systemic labor analgesia (mostly IM or IV meperidine).
Systematic reviews (meta-analyses) have all reached similar conclusions: epidural analgesia compared to systemic
opioid analgesia does not cause an increased incidence of cesarean delivery (Fig. 1).5,6 The most recent systematic
review included data from over 8417 parturients from 27 randomized controlled trials.6 The incidence of cesarean
delivery did not differ between patients who received epidural compared to systemic opioid analgesia (relative risk
1.10, 95% CI 0.97 to 1.25). Investigators from Parkland Hospital in Texas, USA published a meta-analysis of 5
randomized trials comparing neuraxial to systemic meperidine analgesia conducted at their institution between 1993
and 2000 in over 2,700 nulliparas.5 The incidence of cesarean delivery was not different between groups (OR 1.04,
95% CI 0.81 to 1.34).
Impact studies: A number of studies have compared the cesarean delivery rate immediately before, and shortly after,
the introduction of epidural analgesia in a single institution. For example, epidural analgesia was introduced into a
tertiary military hospital in 1993.7 The rate of epidural labor analgesia increased from 1% to 84% in a one-year
period. The rates of cesarean delivery immediately before and after the introduction of epidural analgesia were the
same (adjusted relative risk 0.8, 95% CI 0.6 to 1.2), as was the rate of instrumental vaginal delivery. Segal
performed a meta-analysis using data from 9 impact studies (n = 37,753).8 The rate of cesarean delivery and
operative vaginal delivery did not differ between periods of low and high epidural analgesia rate.
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Dose-response effect: If neuraxial analgesia adversely affects the outcome of labor, one would expect to observe a
dose-response effect, i.e., more dense analgesia should be associated with a higher cesarean delivery rate. Several
large randomized controlled trials compared traditional epidural analgesia with 0.25% bupivacaine to epidural or
combined spinal-epidural (CSE) techniques resulting in less dense analgesia (low-dose bupivacaine/fentanyl).9,10
These studies found no difference in the rate of cesarean delivery between the traditional epidural and low-dose
techniques.
Given that the totality of these studies suggests that neuraxial labor analgesia does not increase the risk of cesarean
delivery, why do women who choose neuraxial analgesia more often have cesarean deliveries compared to those
who do not? Studies have shown that women who have more pain during labor are at increased risk for cesarean
delivery. Women who required ≥ 3 manual epidural boluses during continuous low-dose epidural bupivacaine-
fentanyl labor analgesia were at increased risk for cesarean delivery compared to women who received ≤ 2 boluses
(odd ratio 2.6, 95% CI 2.0 to 3.4).11 The minimum local anesthetic concentration (MLAC, concentration required to
produce satisfactory epidural labor analgesia for 50% of parturients) of bupivacaine required to initiate epidural
analgesia was lower for women who went on to deliver vaginally compared to the MLAC for those who delivered
by cesarean (0.085% vs. 0.106%).12 A secondary analysis of data obtained from women who were randomized to
receive patient controlled intravenous analgesia (PCIA) with meperidine found that women who gave themselves
meperidine ≥ 50 mg/h had a 20% cesarean delivery rate compared to 2% for women who gave themselves
meperidine < 50 mg/h (P < 0.001).13 These data suggest that pain, and the subsequent request for epidural analgesia,
is a marker for risk of cesarean delivery. Dysfunctional labor, large fetuses, and malpositioned fetuses may increase
labor pain and are associated with risk for cesarean delivery.
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Figure 1. Meta-analysis: Neuraxial vs. systematic opioid analgesia, effect on rate of cesarean delivery.6
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Timing of neuraxial analgesia in labor

Multiple observational studies have found that early labor initiation of epidural analgesia is associated with a higher risk
of cesarean delivery.2,14 In randomized controlled trials, however, early initiation of neuraxial compared to systemic
opioid analgesia, followed by later labor initiation of epidural analgesia, has not been shown to result in a increased risk
of cesarean delivery. Chestnut found no difference in cesarean delivery rate between nulliparas randomized to early
epidural analgesia (cervical dilation between 3 and 5 cm) compared to late epidural analgesia (cervical dilation ≥ 5 cm,
nalbuphine in early labor).15,16 Wong et al. randomized 750 nulliparas in spontaneous labor who requested labor
analgesia at cervical dilation < 4 cm to receive early initiation of neuraxial analgesia (combined spinal-epidural [CSE]
analgesia) or early systemic hydromorphone analgesia followed by epidural analgesia at 4 cm dilation.17 The median
cervical dilation at the time of initiation of neuraxial analgesia was 2 cm in the early group and 4 cm in the late group.
There was no difference in the cesarean delivery rate between groups (early 17.8%, late 20.7%; 95% CI of the difference
-9.0 to 3.0%; P=0.31). A study of both induced and spontaneously laboring nulliparas (N=449) randomized to early
epidural analgesia (mean cervical dilation 2.4 cm), compared to early meperidine followed by late epidural analgesia
(mean cervical dilation 4.6 cm) found no difference in the rate of cesarean delivery (13% vs. 11%, P=0.77).18 A
randomized controlled trial of 806 nulliparas with induced labor randomized to receive early CSE vs. systemic
hydromorphone analgesia found there was no difference in the cesarean delivery rate (early 32.7%, late 31.5%; 95% CI
of difference, -3% to 6%: P=0.65).19 Finally, a randomized controlled trial of over 12,000 nulliparas in China found no
difference in the rate of cesarean delivery in women randomized to early labor (cervical dilation ≥ 1 cm, < 4 cm)
epidural vs. systemic opioid analgesia.20 A 2011 meta-analysis which included 6 studies (15,399 nulliparous women)
found no difference in the rate of cesarean delivery between the early and late groups (pooled risk ratio 1.02; 95% CI
0.96 to 1.08) (Fig. 2).21
Figure 2. Meta-analysis early vs. later labor initiation of neuraxial labor analgesia, effect on rate of cesarean delivery.21
Taken together, these studies suggest that the request for analgesia early in labor is a marker for some other risk
factor for cesarean delivery (see discussion of labor pain above) and that early labor initiation of neuraxial analgesia
does not increase the risk of cesarean delivery. In a Committee Opinion from June 2006, the American College of
Obstetricians and Gynecologists (ACOG) stated that that they “previously recommended that practitioners delay
initiation of epidural analgesia in nulliparous women until cervical dilation reached 4-5 cm. However, more recent
studies have shown that epidural analgesia does not increase the risks of cesarean delivery… The fear of
unnecessary cesarean delivery should not influence the method of pain relief that women can choose during labor.”22
Instrumental vaginal deliveries

Multiple randomized controlled trials comparing epidural to systemic opioid analgesia have also assessed the rate of
instrumental vaginal delivery (forceps or vacuum) as a secondary outcome variable. Most systematic reviews have
concluded that epidural analgesia is associated with an increased risk of instrumental vaginal delivery compared to
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systemic opioid analgesia (Table 1).5,6 In contrast, the systematic review of impact studies by Segal found no
increase in instrumental vaginal delivery rate after the institutional initiation of neuraxial labor analgesia.8
Table 1. Meta-analyses: Rate of instrumental vaginal delivery, epidural compared to systemic opioid analgesia
Study N Included Study Outcome 95% CI
Designs
Sharma5 2,703 RCT Odds ratio: 1.86 1.43 – 2.40
Anin-Somuah6 7935 RCT Risk ratio: 1.42 1.28 – 1.57
Segal8 28,443 Impact Percent change: 0.76 -1.2 – 2.8
Although study results are inconsistent, the weight of evidence suggests there may be a dose-response effect in
terms of risk of instrumental vaginal delivery. A multi-center study in over 1000 nulliparas found that the rate of
instrumental vaginal delivery was higher in women who received traditional epidural analgesia with bupivacaine
0.25% compared to women who received low-concentration bupivacaine techniques (bupivacaine 0.1% and
fentanyl) (37% vs. 29%).9 Similarly, in another study, women randomized to receive CSE analgesia (maintained
with bupivacaine 0.0625% plus fentanyl) had a lower rate of instrumental vaginal delivery (31%) compared to
women who received epidural analgesia initiated with bupivacaine 0.25% and maintained with bupivacaine 0.125%
with fentanyl (40%).10 Olofsson et al. demonstrated a lower risk of instrumental vaginal delivery in women
randomized to “low-dose” epidural bupivacaine 0.125% with sufentanil compared to “high-dose” epidural
bupivacaine 0.25% with epinephrine.23 In contrast, Collis et al. found no difference in mode of delivery in women
randomized to receive low-dose vs. high-dose neuraxial analgesia.24 It is possible that these inconsistent results can
be explained by the absolute differences in bupivacaine dose and motor blockade. For example, there may be a
clinically significant difference in outcome between bupivacaine 0.25% and 0.125%, but not between 0.125% and
0.0625%.
Several investigators have randomized women with first stage epidural analgesia to continue to receive epidural
analgesia vs. epidural saline during the second stage of labor.25-28 A meta-analysis concluded that 1) there is
insufficient evidence to support the hypothesis that discontinuing epidural analgesia during the second stage of labor
reduces the rate of instrumental vaginal delivery, but that a larger study was needed, and 2) there is evidence that
this practice increases the rate of inadequate pain relief in the 2nd stage of labor.29
The current evidence suggests that effective second stage neuraxial analgesia may cause an increased risk of
instrumental vaginal delivery.30 The effect of neuraxial analgesia on the outcome of the second stage of labor may
be influenced by the density of neuraxial analgesia. High concentrations of epidural local anesthesia may cause
maternal motor blockade, causing relaxation of pelvic and pelvic floor musculature, which in turn may interfere with
fetal rotation during descent. Abdominal muscle relaxation may decrease the effectiveness of maternal expulsive
efforts. The risk of motor blockade and instrumental vaginal delivery may be minimized by using low-dose
neuraxial techniques, but this may be associated with less effective analgesia and requires that anesthesiologists
tailor the density of analgesia to the needs of individual parturients. The specific techniques used to maintain
epidural analgesia (e.g., manual bolus, continuous infusion, patient-controlled epidural analgesia), as well as the
concentration of local anesthetic, may influence the density of neuraxial blockade.
Duration of the first stage of labor

The data as to whether neuraxial analgesia adversely effects the duration of the first stage of labor are conflicting.
The results of meta-analyses of randomized studies comparing epidural to systemic analgesia differ, depending in
which studies are included in the analysis. The most recent meta-analysis included duration of labor data from 11
studies and 2981 patients.6 The mean difference in the duration of the first stage of labor was not significantly
different between epidural and systemic opioid analgesia (mean difference 19 min, 95% CI -13 to 50 min. However,
the heterogeneity among trials was significant (I2 86%, P < 0.0001) and the 95% CI of the mean difference is quite
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wide. In contrast, in the meta-analysis of the five Parkland Hospital studies (N=2703), the first stage of labor
duration was significantly longer in the epidural group (8.1 ± 5 h vs. 7.5 ± 5 h (P=0.01).5 Finally, most study
protocols did not dictate regular cervical examinations, therefore, the diagnosis of complete cervical dilation may
have been made later in women with effective neuraxial analgesia compared to women with systemic opioid
analgesia, thus artificially prolonging the calculation of the duration of the first stage of labor.
It is unclear whether specific neuraxial techniques differ in their effects on the progress of labor. Tsen found a faster
rate of cervical dilation in nulliparas randomized to CSE compared to epidural analgesia.31 In contrast, Norris found
no difference in the duration of the first stage of labor between these two types of neuraxial analgesia.32 This area
requires further study. The early compared to late initiation of neuraxial analgesia was associated was a significantly
faster first stage of labor in two large studies (one CSE17 and one epidural analgesia18).
In summary, it is unclear whether neuraxial analgesia prolongs the first stage of labor. Differences may be due to
management of labor (e.g., active management of labor) and fluid management protocols or the timing of the
diagnosis of the end of the 1st stage. If neuraxial analgesia does prolong labor, it appears to do so to a minor degree.
There is no evidence that this has an adverse effect on the mother or fetus/neonate.
Duration of the second stage of labor

The bulk of evidence suggests that neuraxial analgesia causes a longer second stage of labor (Table 2).5,6
Table 2. Meta-analyses of RCTs: Duration of second stage

Study N Duration 2nd stage (min) P
Epidural Systemic
6
Anim-Somuah 4233 Mean difference: 14 min (95% CI 7 – 21) < 0.001
Sharma5 2,703 60 ± 56 47 ± 57 < 0.001
Several studies have sought to determine whether immediate or delayed pushing for women with epidural analgesia
during the second stage of labor effects labor duration and outcome. Data are conflicting. A meta-analysis that
included 9 randomized controlled trials and approximately 3000 women concluded that delayed pushing did not
change the rate of instrumental vaginal delivery (RR 0.92, 95% CI 0.84 to 1.01) or second stage cesarean delivery,
but did result in a decreased incidence of rotational or mid-pelvic instrumental deliveries (RR 0.69, 95% CI 0.55 to
0.87).33 The total duration of the second stage was longer with delayed pushing, but there were no differences in
neonatal outcomes.
Conclusions
• Neuraxial analgesia does not increase the risk of cesarean delivery.
• Effective neuraxial analgesia may increase the risk of instrumental vaginal delivery, but this may be
dependent on the density of neuroblockade. More dense neuroblockade is associated with a higher rate of
instrumental vaginal delivery than less dense neuroblockade.
• It is unclear whether neuraxial analgesia prolongs the duration of the first stage of labor, but if it does it is
only by a small amount.
• Neuraxial analgesia prolongs the duration of the second stage of labor.
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20. Wang F, Shen X, Guo X, Peng Y, Gu X. Epidural analgesia in the latent phase of labor and the risk of
cesarean delivery: a five-year randomized controlled trial. Anesthesiology 2009;111:871-80.
21. Wassen MM, Zuijlen J, Roumen FJ, Smits LJ, Marcus MA, Nijhuis JG. Early versus late epidural analgesia
and risk of instrumental delivery in nulliparous women: a systematic review. BJOG 2011;118:655-61.
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22. American College of Obstetricians and Gynecologists Committee Opinion No. 339, June 2006. Analgesia
and cesarean delivery rates. Obstet Gynecol 2006;107:1487.
23. Olofsson C, Ekblom A, Ekman-Ordeberg G, Irestedt L. Obstetric outcome following epidural analgesia
with bupivacaine-adrenaline 0.25% or bupivacaine 0.125% with sufentanil--a prospective randomized
controlled study in 1000 parturients. Acta Anaesthesiol Scand 1998;42:284-92.
24. Collis RE, Davies DW, Aveling W. Randomised comparison of combined spinal-epidural and standard
epidural analgesia in labour. Lancet 1995;345:1413-6.
25. Johnsrud ML, Dale PO, Lovland B. Benefits of continuous infusion epidural analgesia throughout vaginal
delivery. Acta Obstet Gynecol Scand 1988;67:355-8.
26. Chestnut DH, Bates JN, Choi WW. Continuous infusion epidural analgesia with lidocaine: efficacy and
influence during the second stage of labor. Obstet Gynecol 1987;69:323-7.
27. Chestnut DH, Laszewski LJ, Pollack KL, Bates JN, Manago NK, Choi WW. Continuous epidural infusion
of 0.0625% bupivacaine-0.0002% fentanyl during the second stage of labor. Anesthesiology 1990;72:613-
8.
28. Luxman D, Wolman I, Niv D, Cohen JR, Lottan M, Pauzner D, Groutz A, David MP. Effect of second-
stage 0.25% epidural bupivacaine on the outcome of labor. Gynecol Obstet Invest 1996;42:167-70.
29. Torvaldsen S, Roberts CL, Bell JC, Raynes-Greenow CH. Discontinuation of epidural analgesia late in
labour for reducing the adverse delivery outcomes associated with epidural analgesia. Cochrane Database
Syst Rev 2004:CD004457.
30. Chestnut DH. Epidural anesthesia and instrumental vaginal delivery. Anesthesiology 1991;74:805-8.
31. Tsen LC, Thue B, Datta S, Segal S. Is combined spinal-epidural analgesia associated with more rapid
cervical dilation in nulliparous patients when compared with conventional epidural analgesia?
32. Norris MC, Fogel ST, Conway-Long C. Combined spinal-epidural versus epidural labor analgesia.
33. Roberts CL, Torvaldsen S, Cameron CA, Olive E. Delayed versus early pushing in women with epidural
analgesia: a systematic review and meta-analysis. BJOG 2004;111:1333-40.
DISCLOSURE
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Anesthetic Management of the Preeclamptic Patient
Joy L. Hawkins, M.D. Aurora, Colorado
Introduction
Hypertensive disorders of pregnancy are responsible for 15% of maternal deaths after a live birth in the U.S. (1)
Death usually results from cerebrovascular accident. Preeclampsia occurs in 6-8% of pregnancies; 75% of cases are
mild and 25% are classified as severe. Anesthesiologists will be involved when these high risk parturients deliver,
and we should consider ourselves an important part of the team caring for critically ill obstetric patients. The most
recent triennial report on maternal mortality in the United Kingdom found that the anesthetic management (or its
lack) contributed in 8 of 19 deaths due to preeclampsia or eclampsia.(2)
Definitions
The American College of Obstetricians and Gynecologists (ACOG) has a classification system for hypertensive
diseases of pregnancy.(3) They clarify terminology and provide an estimate of risk for the mother and fetus.
• Preeclampsia / Eclampsia presents after 20 weeks gestation with hypertension > 140/90, proteinuria, and a
spectrum of multi-organ system dysfunction such as thrombocytopenia. HELLP syndrome is a subset of
severe preeclampsia defined by hemolysis (H), elevated liver enzymes (EL) and low platelets (LP).
• Chronic hypertension is unrelated to pregnancy and presents before 20 weeks gestation (or before
conception).
• Preeclampsia superimposed on chronic hypertension presents with new onset thrombocytopenia or
proteinuria. This diagnosis carries substantial risk for the mother and fetus.
• Transient or gestational hypertension is hypertension in late pregnancy without other evidence of
preeclampsia that completely resolves postpartum. There is minimal or no increased risk to the mother or
her fetus.
• The terms “PIH” or “pregnancy-induced hypertension” are no longer used.
Etiology and Pathogenesis
Despite decades of research, the etiology of preeclampsia remains unknown. Theories include a placental origin,
immunologic origin, and genetic predisposition. No theory has withstood the test of time, and no preventive
measure has proven useful. Preventive measures that have been tested include supplementation with magnesium,
zinc, fish oil, anti-oxidant vitamins (C and E) and calcium, protein or salt restriction, antihypertensive medications
in women with chronic hypertension, heparin or LMWH treatment, and exercise.(4) None have reduced the
incidence of preeclampsia. Low-dose aspirin therapy has led to a small decrease in preeclampsia and fetal/neonatal
deaths in some studies, and may be used in high-risk pregnancies. In contrast, the risk factors for developing
preeclampsia are well known: nulliparity, extremes of age (< 18 and > 35), a family or personal history of
preeclampsia, barrier contraception, donor egg or sperm, African-American race, obesity, multiple gestation (twins,
triplets), thrombophilias, and vascular diseases such as diabetes, collagen vascular disorders, and chronic
hypertension.
The pathophysiology of preeclampsia develops in early and late stages. The early stage involves abnormal
placentation. The spiral arteries fail to become the dilated, flaccid vessels seen in normal pregnancies, and may even
show signs of atherosis. Placental perfusion is reduced and leads to release of vasoactive substances. Later, the
disease is a maternal systemic disorder with increased vascular sensitivity to any pressor agent, activation of the
coagulation cascade, microthrombi and intravascular fluid loss. Vasospasm, hemoconcentration, and ischemic
changes in the placenta, kidney, liver and brain are seen.
Prediction and Diagnostic Tools
A gene encoding a protein (sFlt1) is overactive in preeclamptic placentas. sFlt1 is known to thwart blood vessel
growth; i.e., it is anti-angiogenic. There is growing evidence that the measurement of antiangiogenic proteins
soluble Flt1 and soluble endoglin can predict preeclampsia months before its clinical onset. They are secreted by the
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placenta and increase in the maternal circulation weeks before the onset of preeclampsia, producing systemic
endothelial dysfunction such as hypertension, proteinuria and other manifestations of preeclampsia. A systematic
review of the literature on use of elevated sFlt-1 and reduced placental growth factor (PlGF – a pro-angiogenic
protein) to predict preeclampsia concluded that third-trimester increases in sFlt-1 combined with decreases in
placental growth factor levels are associated with severe preeclampsia. A comparison of soluble sFlt-1 and soluble
endoglin levels in gestational hypertension, chronic hypertension, preeclampsia and normal pregnancies
demonstrated a high sensitivity and specificity in differentiating women with preeclampsia from those with other
hypertensive diseases during pregnancy.(5) In the future, levels of these proteins may be used as a screening test for
early diagnosis of preeclampsia. A pilot study of 5 very preterm pre-eclamptic women used apheresis treatments to
remove elevated circulating sFlt-1, trying to prolong the pregnancy.(6) Besides lowering circulating sFlt-1 levels,
the treatment reduced proteinuria and stabilized blood pressure without adverse effects on mother and with evidence
of interim fetal growth.
Controversial Areas in the Clinical Management of the Patient with Preeclampsia

• When and by what route should delivery occur, especially when preeclampsia develops at an early
gestational age?
• When is invasive monitoring needed for maternal management?
• What are the benefits and risks of various anti-hypertensives?
• How should we manage an eclamptic seizure?
• Why administer magnesium sulfate rather than other anti-seizure medications?
• How should we manage fluid intake?
• Platelet counts – how low can we go during neuraxial anesthetic management?
• Is spinal anesthesia for cesarean delivery safe and appropriate in severe preeclampsia?
• Should α-agonists replace ephedrine as our first-line pressor to treat hypotension?
Current Obstetric Management Strategies
The only cure for preeclampsia is delivery, but the benefit to the mother must be weighed against the risks of
prematurity to the fetus. Women with gestational hypertension or mild preeclampsia may be managed expectantly
at home with frequent maternal monitoring and fetal surveillance. Patients with severe preeclampsia must be
admitted to L&D for maternal and fetal assessment and development of a delivery plan. Those with a favorable
cervical exam may undergo induction, but elective cesarean delivery may be preferable in very early gestation if the
cervical exam is unfavorable.
Maternal assessment must define the extent of end-organ involvement. Systems evaluated should include:
hematologic (↓ platelets, hemolysis), hepatic (epigastric pain, ↑ LFT), neurologic (headache, visual changes), renal
(oliguria, proteinuria, ↑ creatinine), pulmonary (pulmonary edema), and placental (growth restricted fetus,
oligohydramnios, abnormal umbilical artery Doppler studies). Fetal evaluation will include a non-stress test,
ultrasound for amniotic fluid volume, fetal growth percentile and estimate of gestational age, and a biophysical
profile. Based on these results, a decision for immediate delivery or in-hospital expectant management will be
made. If the pregnancy is < 34 weeks, the obstetrician may delay delivery for 48 hours to administer steroids for
fetal lung maturity, but this requires daily maternal and fetal monitoring, magnesium sulfate infusion, and anti-
hypertensive drugs as needed for systolic BP > 160 or diastolic BP > 110 mmHg.(7) Delivery is required for
worsening maternal or fetal condition. Patients who are not candidates for expectant management include women
with eclampsia, pulmonary edema, DIC, renal insufficiency, abruption, abnormal fetal testing, HELLP syndrome, or
persistent symptoms of severe preeclampsia.
HELLP syndrome is a variant of severe preeclampsia. Administration of high-dose glucocorticoids
(dexamethasone 10 mg BID for example) has been reported to improve maternal and fetal outcome, but without
large multicenter trials to define the limits of benefit and any maternal or fetal risk. A review of the literature on
glucocorticoids for HELLP syndrome (including a management algorithm) concludes that the bulk of evidence to
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date is positive - improved platelet count, reduced stroke and death, and less hepatorenal morbidity. The authors
conclude that glucocorticoids should be considered during treatment of HELLP syndrome.(8)
Management of Hypertension and Use of Invasive Monitoring
The goal of anti-hypertensive therapy is prevention of maternal morbidity from pulmonary edema or cerebral
hemorrhage by decreasing systolic blood pressure < 160 mmHg and diastolic < 110 mmHg. At the same time,
treatment should not impair uteroplacental perfusion or cause fetal compromise. Systolic hypertension may be more
important than diastolic for preventing stroke related to severe preeclampsia.(9) A review found that 93% of the
strokes in their series were hemorrhagic, 54% of women died, and almost all who lived had severe permanent
disability. All had systolic pressure >155 mmHg while only 12% had diastolic pressure >110.
Use of invasive monitoring is rarely necessary in obstetric patients. To quote, “Critically ill obstetric
patients differ from those usually encountered in medical-surgical intensive care units. They are likely to be
younger, to have fewer major organ systems involved, to have fewer chronic illnesses, and to recover fully with
supportive care.”(Chest 1992) However, arterial lines are low risk and can be useful when blood pressures are
consistently > 160/110 mmHg and when vasodilator infusions are used. They may also be helpful for patients with
coagulopathy who need frequent blood draws, and when the patient is obese or has marked edema making
venipuncture difficult. If pulmonary edema develops, the arterial line can be used to monitor arterial blood gases.
Pulse waveform analysis (e.g., LiDCOplus™) can be used for hemodynamic monitoring as it correlates well with
thermodilution measurements from a pulmonary catheter.(10) In contrast, central venous monitoring is higher risk
and has not been shown to affect outcome. A CVP or PA catheter may be useful if there is cardiac failure or
pulmonary edema, a large A-a oxygen gradient, or oliguria despite fluid administration and afterload reduction.
Consider your nursing resources on L&D before initiating invasive monitoring however. Can the L&D nursing staff
manage a CVP or pulmonary artery catheter on L&D, or will ICU admission be necessary?
The ACOG Committee Opinion entitled “Emergent Therapy for Acute-Onset, Severe Hypertension with
Preeclampsia or Eclampsia” defines a hypertensive emergency as lasting 15 minutes or longer with systolic pressure
> 160 mmHg or diastolic pressure > 110 mmHg.(11) Previous work has shown hypertension is the most important
predictor of cerebral hemorrhage or infarction and can result in maternal death. Intravenous labetalol or hydralazine
are considered first-line treatments, and the document includes order sets for both. Importantly for
anesthesiologists, the document states that if these two medications fail to control her blood pressure, “emergent
consultation with an anesthesiologist, maternal-fetal medicine subspecialist, or critical-care specialist to discuss
second-line intervention is recommended.”
Many agents are effective and safe to use as anti-hypertensives:
1. Magnesium sulfate has no substantial long-term effect on blood pressure, but has other benefits. It
attenuates the vascular response to pressor substances (either endogenous or exogenous) and dilates
vascular beds by increasing prostacyclin release from endothelial cells, decreasing plasma renin activity,
and decreasing ACE levels.
2. Hydralazine 5-20 mg is a popular choice in obstetrics because it is an arteriolar vasodilator that increases
uterine and renal blood flow. However it has an unpredictable onset and duration, causes reflex
tachycardia and occasional ventricular arrhythmias. It has also been reported to cause neonatal hypotension
by crossing the placenta.
3. Labetalol decreases systemic vascular resistance without maternal tachycardia and while preserving
placental blood flow. It does not cause sympathetic blockade in the neonate. It can be transitioned to an
oral form after delivery. However its dosing and duration may be quite variable.
4. Nitroprusside has a fast onset, short duration, and preserves uterine blood flow. However there is reflex
tachycardia and the potential for cyanide toxicity. It causes cerebral vasodilation and potential hypoxia
from decreased hypoxic pulmonary vasoconstriction. Finally, it is inconvenient to use and requires an
arterial line, as does nitroglycerin.
5. Calcium channel blockers such as nifedipine and nimodipine cause a rapid smooth fall in blood pressure
while increasing renal perfusion and urine output. Although there has been concern about combining
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magnesium and nifedipine therapies, a study found that in women receiving magnesium sulfate therapy,
there was no increase in muscle weakness over magnesium alone and there was less hypotension with
nifedipine than with other anti-hypertensives.(12) Nimodipine reverses cerebral vasospasm as measured by
trans-cranial Doppler and is well-tolerated by mother and fetus. However, calcium channel blockers cause
uterine relaxation, making induction of labor more difficult and potentially causing atony and hemorrhage
after delivery.
Prevention and Management of Seizures / Eclampsia
Eclampsia has a maternal mortality rate of ~ 4% and a perinatal mortality rate of up to 30%. Seizures occur
antepartum in 50% of patients, intrapartum in 25% and postpartum in 25%. Why do we use magnesium to prevent
eclampsia versus other anti-seizure medications? In large randomized clinical trials, magnesium has been proven
superior to placebo (58% lower risk of seizures), phenytoin (no seizures in the magnesium group versus ~1% in the
phenytoin group), diazepam (52% lower risk of recurrent convulsions), and nimodipine (risk of eclampsia was 3.2
times higher in the nimodipine group). No drug is superior at preventing eclampsia.(13,14)
Magnesium therapy can cause maternal morbidity and unpleasant side effects however. It has tocolytic
properties that prolong labor and increase bleeding at delivery. It decreases fetal heart rate variability, depresses
maternal and neonatal neuromuscular function, and can cause maternal respiratory depression and cardiac toxicity at
high blood levels. Clearance is reduced with renal insufficiency, and signs of toxicity are only partially reversed
with calcium.
Since major complications of preeclampsia primarily occur in the 25% of patients with the severe form of
the disease, should mild preeclampsia even be treated with magnesium? What is the risk/benefit ratio for the
mother? A decision analytic model of magnesium therapy or no magnesium therapy found that 400 women with
mild preeclampsia need to be treated to prevent one seizure. The number needed to treat to prevent a seizure (NNT)
fell to 129 in severe preeclampsia, and the NNT fell to only 36 in severely preeclamptic women who had symptoms
such as headache, visual disturbances or epigastric pain.(15) Not all women with mild preeclampsia will need to
receive magnesium sulfate therapy.
When an eclamptic seizure occurs, the following steps should be taken:
• Administer high flow supplemental oxygen by mask and place a pulse oximeter.
• Turn her full left or right lateral decubitus and have suction immediately available.
• Give a small dose of propofol or benzodiazepine to terminate the seizure if available. Avoid poly-
pharmacy and long-lasting medications so that a neurologic exam can be done as soon as possible.
• Administer an additional 2 gram magnesium sulfate bolus.
• Monitor the fetus if possible, but realize that heart rate abnormalities are common during a seizure and
usually resolve soon after the seizure is terminated. Do not intervene to deliver immediately unless
abruption or cord prolapse has occurred.
• Consider CT or MRI imaging to rule out a cerebral hemorrhage if seizures are recurrent or focal, if
seizures occur despite therapeutic and repeated magnesium dosing, or if there is decreasing level of
consciousness when not post-ictal.
• Although eclampsia is an indication for delivery, it is not an indication for cesarean delivery. Consider
whether induction is feasible or whether labor is already progressing.
Anesthetic Management During Labor and Delivery
When the decision has been made to proceed to delivery, the anesthesiologist must have plans for three potential
scenarios in mind: 1) labor followed by a spontaneous or instrumented vaginal delivery, 2) trial of labor followed
by an urgent or emergent cesarean for fetal or maternal reasons, and 3) planned cesarean for the patient who is not a
candidate to labor. All plans must take into account whether neuraxial techniques are appropriate based on platelet
count or other measures of coagulopathy.
The advantages of neuraxial analgesia for labor are numerous. It provides the best quality of pain relief,
attenuates hypertensive responses to pain, reduces circulating catecholamines, and does not require fluid preload
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when dilute local anesthetic + opioid solutions are used. Two studies have compared the use of intravenous patient-
controlled opioids (IV PCA) to epidural analgesia for women with severe preeclampsia. In the first, 738 women
were randomized to IV PCA or epidural, and cesarean delivery rates were similar.(16) Neonates in the IV PCA
group required more naloxone (12% versus 1%), but women in the epidural group had a longer second stage of
labor, more forceps deliveries and required ephedrine more often (11% versus 0%). Not surprisingly, epidural pain
relief was superior.(16) Results were similar in the second study.(17) They found was no difference in cesarean
delivery rates, neonates were more likely to receive naloxone in the opioid group (54% versus 9%), and epidural
patients had significantly better pain relief but required more ephedrine (9% versus 0%). Perhaps most importantly,
there were no differences in preeclampsia-related complications.(17) ACOG makes a strong statement in their
Practice Bulletin Diagnosis and Management of Preeclampsia and Eclampsia: “With improved techniques over the
past two decades, regional anesthesia has become the preferred technique for women with severe preeclampsia and
eclampsia – both for labor and delivery. A secondary analysis of women with severe preeclampsia in the NICHD
trial of low-dose aspirin reported that epidural anesthesia was not associated with an increased rate of cesarean
delivery, pulmonary edema or renal failure.”(18)
Fluid management has been a controversial subject between obstetricians who want to restrict fluids and
anesthesiologists who want to administer fluids, however the obstetric view is probably correct. The vasculature in
preeclamptic patients has been described as contracted and porous due to endothelial damage but not underfilled. In
addition to endothelial damage, the colloid osmotic pressure is low in pregnancy, and even lower in preeclamptic
patients with proteinuria. Crystalloids and colloids readily leak out, increasing the risk of postpartum pulmonary
edema. Typical obstetric management is to “run dry” at 80-100 ml per hour total fluid intake including magnesium
and oxytocin infusions. Anesthetic fluid management should complement theirs, using conservative preload for
surgical regional anesthesia and no preload for labor analgesia. Many studies including a systematic review have
shown little if any benefit of preloading in preventing hypotension during obstetric regional anesthesia (19)
Despite years of concern and study, there is still no test of platelet function and no specific platelet count
that predicts bleeding into the neuraxis after regional anesthetic techniques. For patients with preeclampsia, many
anesthesiologists are comfortable with platelet counts as low as 75,000 provided the count is stable and not falling,
and that there are no signs of clinical bleeding at venipuncture sites, gums, etc. Thromboelastography (TEG) can
add information if the test is available, but there is still no cut-off value for any TEG variable that predicts
complications. Since pregnancy is a thrombophilic state, parturients have tremendous reserve before becoming
coagulopathic. A review of 1.7 million spinal or epidural blocks found that complications were more common after
epidural than spinal anesthetics, and that obstetric patients were less likely than surgical patients to have an injury
(1:25,000 obstetric patients versus 1:3600 after surgical epidurals in females).(20) There were 2 obstetric patients in
their series that developed a neuraxial hematoma, for an incidence of 1:200,000. One occurred after a spinal and the
other after epidural catheter removal; both patients had HELLP syndrome. This low incidence is reassuring, but
balance the risk-benefit ratio for each case and each patient.
Factors that might support using a regional technique even with borderline labs would include a worrisome
airway exam, the prospect of a lengthy induction of labor, and the rarity of an epidural hematoma. Factors that
would support avoidance of regional anesthesia and use of IV opioids or general anesthesia would be clinical signs
of bleeding, a rapidly worsening platelet count, the need for an urgent cesarean and a good airway. If you feel that a
neuraxial anesthetic is not appropriate, remember that anesthesiologists are consultants in pain management. Our
obstetric colleagues may appreciate help with an IV regimen for the patient’s labor analgesia. For example, fentanyl
can be used in an IV PCA as follows: give an IV bolus loading dose of 2-3 µg/kg to initiate analgesia. Set the PCA
pump for a 50 µg incremental bolus, 10 minute lockout interval and no basal rate. As labor progresses and titration
is needed, decrease the lockout from 10 to 5 minutes, then increase the bolus dose from 50 to 75 µg.(21)
The choices for cesarean anesthesia are epidural, spinal (or combined spinal-epidural) and general. In the
past, spinal anesthesia was avoided because of concerns that hypotension would be more severe and less treatable
than that seen after sympathectomy from an epidural anesthetic. However, a comparison of women with severe
preeclampsia to healthy women, all having a cesarean delivery with spinal anesthesia, found that preeclamptic
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women actually had less hypotension (17% versus 53%) despite receiving less fluid preload and (by chance) a larger
dose of bupivacaine in their spinal.(22) A randomized comparison of spinal or epidural anesthesia for cesarean
delivery in women with severe preeclampsia found that although hypotension was more frequent after spinal and
required slightly more ephedrine, the duration of hypotension was short and neonatal outcomes were similar in both
groups.(23) A small study of “stable” eclamptic patients described their cesarean deliveries under spinal anesthesia
without intraoperative complications such as excessive hypotension or additional seizures.(24)
Regardless of the choice of neuraxial technique (spinal or epidural), pressors must be immediately available
to treat even mild hypotension since these fetuses may not tolerate any decrease in uteroplacental perfusion.
Clinical studies in humans have consistently shown that use of α-agonists such as phenylephrine produce better
umbilical pH values in the newborn than use of ephedrine.(25) A study randomizing women with severe
preeclampsia to spinal or general anesthesia for cesarean delivery for non-reassuring fetal heart tones found that
spinal anesthesia was associated with more acidotic fetal pH values and higher base deficits.(26) Maternal
hemodynamics were similar between groups, but the patients receiving spinal anesthesia received more ephedrine
(14 mg versus 3 mg) than those in the general anesthesia group. Phenylephrine was not used. Did the use of
ephedrine worsen fetal acidosis? If maternal heart rate is above 70, choose phenylephrine as the first-line pressor
agent.
If general anesthesia is chosen, the areas of concern are attenuating hypertensive responses during
laryngoscopy and intubation, managing a difficult edematous airway, and treating complications related to
magnesium therapy such as uterine atony and maternal weakness. A number of adjuncts to rapid sequence induction
have been described and used successfully to control hypertension associated with laryngoscopy, e.g. esmolol,
labetalol, lidocaine, remifentanil and nitroglycerin. Include at least one as part of a rapid sequence induction, or
have them immediately available to treat hypertension if it occurs. Airway management may be difficult. Use of
the laryngeal mask airway (LMA) has been described in the setting of HELLP syndrome when there was inability to
intubate or ventilate.(27) Postoperatively, this patient was even ventilated for 8 hours in the ICU using the LMA.
Magnesium therapy has anesthetic interactions. Magnesium is a uterine relaxant and additional oxytocics
such as Cytotec® or Hemabate® should be available to treat uterine atony after delivery in addition to the oxytocin
infusion. Magnesium also causes skeletal muscle weakness. If the mother exhibits muscle weakness prior to
induction (i.e., can she do a 5-second head lift before her anesthetic?), it may be best to discontinue the magnesium
sulfate infusion during the case and let her magnesium level decrease. Non-depolarizing muscle relaxants should be
avoided. If she cannot meet criteria for safe extubation at the end of the cesarean, she may require a brief period of
mechanical ventilation until she is strong enough to protect her airway.
Postpartum issues will require intense monitoring on L&D. The mother may need both acute and long term
blood pressure control with anti-hypertensives. Fluid mobilization will begin to occur during the first 24 hours
postpartum, and this is when she is most at risk for pulmonary edema. Monitor urine output, lung fields and pulse
oximetry. Thrombocytopenia may not resolve for several days. If she has an epidural catheter in place, decide
when removal is appropriate based on her platelet count and coagulation studies. About a third of eclamptic seizures
occur postpartum. A review of 89 cases of eclampsia found that 33% of seizures occurred postpartum and 79% of
those presented > 48 hours postpartum.(28) Most did not have an antepartum diagnosis of preeclampsia, but most
did have prodromal symptoms such as headache and visual changes.(26) If the anesthesia team is called to evaluate
a headache, be vigilant and consider late-presenting preeclampsia in your differential diagnosis.
Prognosis After the Diagnosis of Preeclampsia
Does development of preeclampsia provide a marker for maternal disease risks later in life? A growing literature
indicates that pregnancy is a form of “stress test” that may predict later health issues in the mother. For example,
post-menopausal women who had preeclampsia decades earlier were 57% more likely to have coronary calcification
on CT.(29) A 22-year follow-up of formerly preeclamptic women versus controls found hypertension present in
55% of the formerly preeclamptic women and only 7% of the controls.(30) These studies all recommend better long
term follow-up of preeclamptic women; the implications of this disease do not end at delivery.
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In Conclusion:
• Be conservative with your fluid preload before neuraxial procedures.
• Normalize low blood pressure with phenylephrine in preference to ephedrine.
• The goal for management of hypertension is to keep maternal pressure close to her baseline to sustain
uteroplacental perfusion, but < 160 mmHg systolic to prevent maternal cerebrovascular
complications.
• Use platelet count trends and your clinical judgment. There is no absolute platelet count or TEG
value to use as a cut-off for use of neuraxial anesthetic techniques.
• Spinal anesthesia for cesarean delivery is safe. Limit fluid preload and treat hypotension
aggressively with α-agonist medications.
• Participate as part of the L&D team when caring for high risk obstetric patients.
References
1. Obstet Gynecol 2010;116:1302
2. BJOG 2011;118:105
3. Am J Obstet Gynecol 2000;183:S1-23
4. Lancet 2005;365:785
5. NEJM 2006;355:992
6. Circulation 2011;124:940
7. Am J Obstet Gynecol 2011;205:191
10. Br J Anesth 2011;106:77
13. Lancet 2002;359:1877
14. NEJM 2003;348:304
19. Anesth Analg 2011;113:677
20. Anesthesiology 2004;101:950
21. Clin Obstet Gynecol 2003;46:616
22. Anesth Analg 2003;97:867
23. Anesth Analg 2005;101:862
24. J Clin Anesth 2011;23:202
25. Br J Anesth 2004;92:459
27. Anesth Analg 2004:98:1467
29. Hypertension 2007;49:1
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DISCLOSURE
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Hail Caesar: Anesthesia for Cesarean Delivery

Lawrence C. Tsen, M.D. Boston, Massachusetts
Cesarean delivery predates the Roman Emperor Julius Cesar (100 BC), who was most likely not born in this
manner. Associated with high maternal mortality until the turn of the 20th century, cesarean delivery now accounts
for approximately one third of all births in developed countries;1 this increase has resulted from improvements in
surgical and anesthetic techniques, diminished use of forceps for extractions, fewer breech and multiple gestation
vaginal deliveries, and greater use of repeat cesarean deliveries. The provision of anesthesia for this method of
delivery is multifaceted, which in turn represents a number of opportunities to influence maternal and fetal care and
outcomes.
PREVENTION OF CESAREAN DELIVERY

The relationship between neuraxial analgesia and the progress and outcome of labor deserves a separate discussion,
however, recent evidence confirms that neuraxial (particularly CSE) analgesia techniques result in shorter, more
comfortable labor compared to systemic techniques without increasing the cesarean delivery rate.2 Anesthetic
participation can also reduce the incidence of cesarean deliveries [e.g. improving forcep/vacuum analgesia,
increasing the success of multiple gestation vaginal births, reducing fetal head entrapment with intravenous
nitroglycerin, and improving external cephalic version (ECV) success].
The use of ECV for term breech pregnancies (3-5% prevalence) can decrease maternal and fetal morbidity and costs
associated with a breech or operative delivery. Neuraxial techniques improve ECV success by relaxing the
abdominal wall muscles, improving patient comfort, and allowing a more concerted attempt. Even in the setting of a
previously failed ECV attempt without analgesia, spinal anesthesia (lidocaine 45 mg with fentanyl 10 µg) combined
with uterine tocolysis (nitroglycerin 50 µg iv, wait 50 sec) has been associated with a high success rate (83%).3
Whether utilized for primary or failed ECV attempts, a CSE technique with a short duration spinal anesthetic may be
optimal: the short spinal allows for a timely discharge in the event of a successful version, and if success merits a
trial of labor, or failure results in an operative delivery, the epidural catheter allows for the extension of either
analgesia or anesthesia.3
ANESTHESIA FOR CESAREAN DELIVERY

The updated Practice Guidelines for Obstetrical Anesthesia from the ASA Task Force on Obstetrical Anesthesia
observe that neuraxial techniques (spinal, epidural, CSE) are associated with improved maternal and fetal outcomes
when compared to general anesthesia (GA), particularly in the presence of high body mass index and airway issues.4
However, specific anesthetic management should be chosen on a case-by-case assessment of patient, medical,
anesthetic, and obstetric issues.5
Is there a Preferred Anesthetic Technique?

Complications related to anesthesia still represent the sixth leading cause of peripartum maternal mortality in the
United States.6 Not surprisingly, these deaths most commonly result from failures in oxygenation and ventilation,
however, these episodes are currently being witnessed more frequently during extubation and postoperative
recovery, rather than with intubation.6, 7
The estimated case-fatality risk ratio for GA versus neuraxial anesthesia has undergone a significant reduction from
16.7 in 1985-1990 to a non-significant risk ratio of 1.7 in 1991-2002.8 This change most likely represents two
trends: 1) a reduction in GA use, coupled with improved attention9 and more successful manipulation (e.g. alternate
airway devices) of the maternal airway, and 2) a growing acceptance of neuraxial technique use in parturients with
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significant comorbidities (e.g. obesity, severe preeclampsia, hematologic and cardiac disease). A review of
anesthetics used for cesarean deliveries performed at the Brigham & Women’s Hospital from 1990-1995 indicated a
GA rate of 3.5-7.2%;10 further rate reductions to less than 1% annually occurred between 2000-2005.5 This low GA
rate reflected advanced planning and communication with patients, obstetricians and nursing colleagues about
patient characteristics and co-morbid conditions including those associated with a potentially difficult airway or
prolonged neuraxial technique attempts; early patient assessment and “prophylactic” epidural catheter placements,
even if not utilized for labor analgesia, have been associated with improved outcomes.4
The combined spinal epidural (CSE) technique may offer the most flexibility in terms of reducing the initial drug
dose (allowing for potentially less hypotension and faster recovery), as well as prolonging the blockade should
operative complications or postoperative pain management issues occur.
Should Newer Local Anesthetics be used?

Potentially reduced recovery times and toxicity profiles have fostered an interest in the newer local anesthetics,
ropivacaine and levobupivacaine. Although established to be safe and acceptable for elective cesarean deliveries,11,
12
these two local anesthetics may not be significantly less cardiotoxic than bupivacaine when adjusted for potency.
Moreover, because the toxicity of ropivacaine and bupivacaine does not appear to be enhanced in pregnancy,13
cardiac toxicity should only occur with unintentional large intravascular doses. With the common and more
forgiving use of chloroprocaine 3% and lidocaine 2% for conversion of epidural labor analgesia to cesarean
anesthesia, coupled with proper drug administration practices (e.g. attention to incremental dosing practices, total
dose guidelines, and toxicity symptoms), toxic intravascular levels should be a rare.
Should Lower Doses of Bupivacaine be used?

The dose of local anesthetics has been reduced as a method to potentially obtain less hypotension, faster motor
recovery and discharge times, and improved maternal satisfaction. Such dose reductions may be achieved by using
spinal versus epidural anesthesia, as well as less total local anesthetic; with these changes, reductions in time, costs,
charges, and complications have been realized.14 When spinal bupivacaine in intermediate to low doses (3-9 mg) are
used, the need for supplemental medications can be significant (up to 40%), and thus a catheter based technique
(CSE) should be used.
Intrathecal Bupivacaine Dose (hyperbaric) Motor Recovery to T10 (min) Notes

15 mg15 162.1 ± 33.8 7/12 cervical level
12 mg22 140 ± 16.5 3/16 cervical level
7.5-8.0 mg + 25 mg epidurally16 146 ± 43.9 CSE
6.6 mg + 3.3µg sufenta 17 110 ± 27 plain; 92 ± 24 hyperbaric CSE
Epidural catheters placed for labor and used subsequently for surgery have a low failure rate following a traditional
epidural versus CSE technique (6% (n = 133) vs. 4% (n = 183), respectively).18
Can Hypotension be prevented?
Neuraxial-induced hypotension, when severe and sustained, can impair uterine and intervillous blood flow and result
in fetal hypoxia, acidosis, and neonatal depression.20 Left uterine displacement and treatment or prophylaxis with
vasopressors have reduced the incidence of hypotension with variable success.21 Preloading with crystalloid has
limited effects on mitigating hypotension, even with large doses (30 mL/kg); more effective is preloading with
colloids, or simultaneously giving rapid crystalloid or colloids coincident (co-loading) with the spinal technique.
Hypotension may also be reduced with the use of smaller spinal local anesthetic doses.22 Prophylaxis and treatment
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of maternal hypotension with phenylephrine, versus in combination with ephedrine or ephedrine alone,23 is more
effective in improving maternal hemodynamics and fetal acid-base values; this is particularly true when an infusion
target of 100% baseline value is used.24
What Adjuvant Medications should be used?

Adjuvant medications express a number of benefits, including the ability to reduce the dose and side effects of local
anesthetics. Neostigmine and clonidine are two novel agents undergoing clinical investigation. In women
undergoing elective cesarean delivery, neostigmine in spinal doses up to 100 µg significantly reduced post-operative
pain with no effect on fetal heart rate or Apgar scores.27 However, in spinal doses as little as 6.25 µg, a high
incidence of side effects including prolonged motor blockade, nausea, and vomiting have been observed.28 As a
consequence, the spinal route will most likely be abandoned; however, some promise has been noted with the
epidural route.29
Clonidine, in spinal and epidural doses varying from 15-50 µg and 50-120 µg, respectively, can prolong analgesia
and decrease shivering; however, mild hypotension and sedation are not infrequent side effects.30 Currently
clonidine has only one specific neuraxial indication (intractable cancer pain), and a “black box” FDA warning that
“epidural clonidine is not recommended for obstetrical, postpartum, and perioperative pain management”. Further
research will most likely advance the clinical use of this drug in the postcesarean delivery setting.
Preservative free morphine sulfate can provide 17-27 h of post-cesarean analgesia. Palmer et al. evaluated the dose
responses to intrathecal31 and epidural32 morphine following cesarean delivery. Intrathecally, a comparison of 0.0,
0.025, 0.05, 0.1, 0.2, 0.3, 0.4, and 0.5 mg doses observed that 0.1mg produced analgesia comparable to doses as high
as 0.5mg. The incidence of pruritus, but not nausea and vomiting, appeared dose related. In the epidural space, a
comparison of 1.25, 2.5, 3.75, and 5 mg doses observed that the quality of post-cesarean analgesia did not improve
beyond 3.75 mg. Pruritus, nausea and vomiting did not appear dose related. Extended-release epidural morphine
(Depodur) can provide analgesia for 48 hrs with 10 and 15 mg doses; however, caution should be applied to dosing
the epidural catheter with local anesthetic immediately after the Depodur dose, and even up to 1 hour before, as the
maximum plasma concentrations of morphine will be higher.33
Does a Perfect Cocktail Exist?
The most recent evidence would suggest the following combinations are optimal:
Medication Spinal Epidural

Local Anesthetic Bupivacaine 9-12 mg Lidocaine 2% + Bicarb 8.4% (10 mL/1 mL ratio)
Fentanyl 15-35 µg34 50-100 µg
Morphine 0.1 mg 3.75 mg
ASSOCIATED ANESTHETIC CONCERNS DURING CESAREAN DELIVERY
Antibiotic Use and Timing
Postpartum infection is 5 to 20-fold greater in those patients delivering by cesarean versus vaginal routes and
remains within the top five causes of pregnancy-related mortality.35 The traditional practice of administering
antibiotics after infant delivery and umbilical cord clamping originated to prevent fetal exposure to antibiotics.
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However, recent studies of antibiotic use prior to cesarean skin incision have observed significantly fewer maternal
infections with no differences in the frequency of neonatal sepsis work-ups or proven sepsis cases.35 The recent joint
publication from the American College of Obstetricians and Gynecologists and the American Academy of Pediatrics
acknowledges these findings, however, does not explicitly recommend pre-incision antibiotic prophylaxis or
extended spectrum antibiotic coverage.36 Regardless, the implementation of pre-incisional antibiotic coverage
appears to be increasing, unifying the obstetric practice with other operative settings.
Oxytocin and Uterotonic Agent Use
The administration of oxytocin is associated with significant maternal, fetal, and neonatal adverse events, including
maternal death. The current guidelines for the administration of oxytocin during cesarean delivery are diverse,
empiric, and vague, with nonevidence-based doses of 20-40 IU being advocated. However, adequate uterine
contractions during elective cesarean deliveries in non-laboring women require only small loading doses of oxytocin
(ED 90 = 0.35 IU);37 a similarly low loading dose (ED 90 = 2.99 IU) is required in laboring women.38
Consequently, a lower oxytocin, evidence-based protocol has been advocated:
Oxytocin Protocol for Cesarean Delivery: “Rule of Threes”39

3 IU Oxytocin IV Loading Dose (administered by rapid infusion, rather than a bolus, no faster than 15 seconds40)
3 Minute Assessment Intervals. If inadequate uterine tone, give 3 IU Oxytocin IV rescue dose.
3 Total Doses of Oxytocin (Initial Load + 2 Rescue Doses)
3 IU Oxytocin IV Maintenance Dose (3 IU/L at 100 mL/h) up to 8 hrs.
3 Pharmacologic Options (e.g. ergonovine, carboprost and misoprostol) if inadequate uterine tone persists
Intra- and Post- partum Hemorrhage
Hemorrhage occurring during or following cesarean delivery is an increasing complication that is associated with
significant maternal morbidity and mortality. The identification of risk factors associated with uterine atony
requiring blood transfusion is of value,41 to allow preventative and therapeutic measures to be considered, including
the use of intrauterine balloons, pro-coagulation and antifibrinolytic agents, and interventional radiology and blood
bank/hematology consultations.42
Predictors of PPH Odds Ratio P

Retained Placenta 4.1 (3.1-5.5) < 0.001
Antepartum Hemorrhage 3.8 (3.0-4.8) < 0.001
Multiple Gestation 2.8 (2.2-3.6) < 0.001
Chorioamnionitis 2.5 (1.9-3.3) < 0.001
Hypertensive Diseases of Pregnancy 2.5 (2.1-2.8) < 0.001
Polyhydramnios 2.5 (1.9-3.1) 0.01
Age < 20 1.8 (1.5-2.2) < 0.001
Age > 40 1.7 (1.3-2.2) < 0.001
Cesarean with Labor 1.7 (1.5-2.0) < 0.001
Cesarean without Labor 1.3 (1.1-1.5) 0.002
Vaginal Delivery, Age 20-34 Reference
Post-operative Bliss
Pain, pruritis, nausea/vomiting, and postoperative shivering are the postoperative elements that concern patients.
Pain is optimally handled with neuraxial morphine administered intra-operatively, which provides good analgesia of
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long duration. With breakthrough pain, analgesia can be augmented with a non-steroidal agent; Wilder-Smith et
al.43 observed that the combination of an opioid and NSAID was more effective for post-cesarean analgesia and
preventing sensitization, than the two drugs given individually. Torodol has been listed as being compatible with
breast-feeding by the American Academy of Pediatrics, and has been demonstrated to be effective for post-cesarean
analgesia.44
Although pruritus following neuraxial blockade has a number of postulated mechanisms and treatments,45 a direct
antagonist or partial antagonist, such as nalbuphine 4 mg IV, appears to have a greater effect than some other
modalities. Nausea and emesis following cesarean delivery can be difficult to treat; recently cyclizine 50 mg IV has
been observed to be superior to dexamethasone 8mg IV following intrathecal morphine for cesarean delivery.46
Finally, postoperative shivering can have a number of causes and treatments. Intravenous meperidine 25 mg,
clonidine 150 µg, doxapram 100 mg, ketanserin 10 mg, or alfentanil 250 µg have all been demonstrated to be
effective, although meperidine appears to be the most consistently effective.47
CONCLUSION
The rapidly changing field of obstetrical anesthesia has placed more emphasis on certain techniques and dosing
regimens. By reflecting on and adopting many of these advances, more parturients (and anesthesiologists) will have
a favorable experience before, during, and after a cesarean delivery.
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12. Bader AM, Tsen LC, Camann WR, Nephew E, Datta S. Clinical effects and maternal and fetal plasma
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13. Santos AC, DeArmas PI. Systemic toxicity of levobupivacaine, bupivacaine, and ropivacaine during
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15. De Simone CA, Leighton BL, Norris MC. Spinal anesthesia for cesarean delivery. A comparison of two
doses of hyperbaric bupivacaine. Regional anesthesia 1995;20:90-4.
16. Choi DH, Kim JA, Chung IS. Comparison of combined spinal epidural anesthesia and epidural anesthesia
for cesarean section. Acta anaesthesiologica Scandinavica 2000;44:214-9.
17. Vercauteren MP, Coppejans HC, Hoffmann VL, Saldien V, Adriaensen HA. Small-dose hyperbaric versus
plain bupivacaine during spinal anesthesia for cesarean section. Anesthesia and analgesia 1998;86:989-93.
18. Norris MC. Are combined spinal-epidural catheters reliable? International journal of obstetric anesthesia
2000;9:3-6.
19. Davies SJ, Paech MJ, Welch H, Evans SF, Pavy TJ. Maternal experience during epidural or combined
spinal-epidural anesthesia for cesarean section: a prospective, randomized trial. Anesthesia and analgesia
1997;85:607-13.
20. Corke BC, Datta S, Ostheimer GW, Weiss JB, Alper MH. Spinal anaesthesia for Caesarean section. The
influence of hypotension on neonatal outcome. Anaesthesia 1982;37:658-62.
21. Ngan Kee WD. Prevention of maternal hypotension after regional anaesthesia for caesarean section.
Current opinion in anaesthesiology 2010;23:304-9.
22. Langesaeter E, Rosseland LA, Stubhaug A. Continuous invasive blood pressure and cardiac output
monitoring during cesarean delivery: a randomized, double-blind comparison of low-dose versus high-dose spinal
anesthesia with intravenous phenylephrine or placebo infusion. Anesthesiology 2008;109:856-63.
23. Ngan Kee WD, Lee A, Khaw KS, Ng FF, Karmakar MK, Gin T. A randomized double-blinded comparison
of phenylephrine and ephedrine infusion combinations to maintain blood pressure during spinal anesthesia for
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2008;107:1295-302.
24. Ngan Kee WD, Khaw KS. Low-dose spinal anesthesia with low-dose phenylephrine infusions for cesarean
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25. Tsen LC, Boosalis P, Segal S, Datta S, Bader AM. Hemodynamic effects of simultaneous administration of
intravenous ephedrine and spinal anesthesia for cesarean delivery. Journal of clinical anesthesia 2000;12:378-82.
26. Sarvela PJ, Halonen PM, Korttila KT. Comparison of 9 mg of intrathecal plain and hyperbaric bupivacaine
both with fentanyl for cesarean delivery. Anesthesia and analgesia 1999;89:1257-62.
27. Krukowski JA, Hood DD, Eisenach JC, Mallak KA, Parker RL. Intrathecal neostigmine for post-cesarean
section analgesia: dose response. Anesthesia and analgesia 1997;84:1269-75.
28. Liu SS, Hodgson PS, Moore JM, Trautman WJ, Burkhead DL. Dose-response effects of spinal neostigmine
added to bupivacaine spinal anesthesia in volunteers. Anesthesiology 1999;90:710-7.
29. Eisenach JC. Epidural neostigmine: will it replace lipid soluble opioids for postoperative and labor
analgesia? Anesthesia and analgesia 2009;109:293-5.
30. D'Angelo R. Should we administer epidural or spinal clonidine during labor? Regional anesthesia and pain
medicine 2000;25:3-4.
31. Palmer CM, Emerson S, Volgoropolous D, Alves D. Dose-response relationship of intrathecal morphine for
postcesarean analgesia. Anesthesiology 1999;90:437-44.
32. Palmer CM, Nogami WM, Van Maren G, Alves DM. Postcesarean epidural morphine: a dose-response
study. Anesthesia and analgesia 2000;90:887-91.
33. Atkinson RL, Drover DR, Clavijo CF, Carvalho B. Prior epidural lidocaine alters the pharmacokinetics of
extended-release epidural morphine (DepoDur) after cesarean delivery. Anesthesia and analgesia 2011;113:251-8.
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34. Dahl JB, Jeppesen IS, Jorgensen H, Wetterslev J, Moiniche S. Intraoperative and postoperative analgesic
efficacy and adverse effects of intrathecal opioids in patients undergoing cesarean section with spinal anesthesia: a
qualitative and quantitative systematic review of randomized controlled trials. Anesthesiology 1999;91:1919-27.
35. Tita AT, Rouse DJ, Blackwell S, Saade GR, Spong CY, Andrews WW. Emerging concepts in antibiotic
prophylaxis for cesarean delivery: a systematic review. Obstetrics and gynecology 2009;113:675-82.
36. Gynecologists AAoPaACoOa. Guidelines for Perinatal Care. 2007;6.
37. Carvalho JC, Balki M, Kingdom J, Windrim R. Oxytocin requirements at elective cesarean delivery: a
dose-finding study. Obstet Gynecol 2004;104:1005-10.
38. Balki M, Ronayne M, Davies S, et al. Minimum oxytocin dose requirement after cesarean delivery for
labor arrest. Obstet Gynecol 2006;107:45-50.
39. Tsen LC, Balki M. Oxytocin Protocols during Cesarean Delivery: Time to Acknowledge the Risk/Benefit
Ratio? International journal of obstetric anesthesia 2011;20 In Press.
40. Butwick AJ, Coleman L, Cohen SE, Riley ET, Carvalho B. Minimum effective bolus dose of oxytocin
during elective Caesarean delivery. Br J Anaesth 2010;104:338-43.
41. Bateman BT, Berman MF, Riley LE, Leffert LR. The epidemiology of postpartum hemorrhage in a large,
nationwide sample of deliveries. Anesthesia and analgesia 2010;110:1368-73.
42. Kodali BS. Bloodless trilogy? Anesthesia, obstetrics and interventional radiology for cesarean delivery.
International journal of obstetric anesthesia 2010;19:131-2.
43. Wilder-Smith CH, Hill L, Dyer RA, Torr G, Coetzee E. Postoperative sensitization and pain after cesarean
delivery and the effects of single im doses of tramadol and diclofenac alone and in combination. Anesthesia and
analgesia 2003;97:526-33, table of contents.
44. Lowder JL, Shackelford DP, Holbert D, Beste TM. A randomized, controlled trial to compare ketorolac
tromethamine versus placebo after cesarean section to reduce pain and narcotic usage. American journal of
obstetrics and gynecology 2003;189:1559-62; discussion 62.
45. Szarvas S, Harmon D, Murphy D. Neuraxial opioid-induced pruritus: a review. Journal of clinical
anesthesia 2003;15:234-9.
46. Nortcliffe SA, Shah J, Buggy DJ. Prevention of postoperative nausea and vomiting after spinal morphine
for Caesarean section: comparison of cyclizine, dexamethasone and placebo. British journal of anaesthesia
2003;90:665-70.
47. Sessler DI. Treatment: meperidine, clonidine, doxapram, ketanserin, or alfentanil abolishes short-term
postoperative shivering. Canadian journal of anaesthesia 2003;50:635-7.
DISCLOSURE
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Anesthetic Management of the Morbidly Obese Parturient

Brenda A. Bucklin, M.D. Aurora, Colorado
Recent reports from 2009-10 suggest that obesity rates in the U.S. have plateaued.1 Although rates have increased in
Mexican American and non-Hispanic black women, the overall rate of obesity among women has remained stable at
35.8%. In 2009, the Institute of Medicine released a new range for weight gain during pregnancy that limits the gain
to 11 to 25 pounds when the BMI is greater than 30 kg/m2 and 15 to 25 pounds when the BMI is between 25 and
29.9 kg/m2.2 The costs associated with the care of an obese parturient have been shown to increase in direct
proportion with the body mass index (BMI).3 These women require more prenatal tests, ultrasonographic
examinations, medications, and prenatal visits compared to women of normal weight.4
MORBID OBESITY AND PREGNANCY

Obstetric and neonatal risk Morbid obesity increases the risk for instrumented and cesarean delivery (CS),5
with the risk of CS increasing linearly with increasing BMI. Failure to progress, abnormal labor, nonreassuring fetal
status, abnormal presentation, shoulder dystocia, and birth trauma are more common. Cesarean deliveries are more
often complicated by longer operative times, increased operative blood loss and postpartum hemorrhage,
postoperative endometritis, wound infection, as well as increased length of hospital stay. Babies of obese women
have increased risk of congenital anomalies, prematurity, stillbirth, neonatal intensive care unit admissions, and
neonatal death in complicated cases.6
Comorbid conditions Coexisting disease(s) often complicate(s) obstetric and anesthetic management of these
women. They are at increased risk for hypertensive disorders (e.g., preeclampsia, chronic hypertension),5 respiratory
disorders (e.g., asthma, sleep apnea), cerebrovascular disease, diabetes mellitus,5 nonalcoholic fatty liver disease as
well as thromboembolic disease. The risk of ischemic heart disease is also increased in parturients with obesity,
hypertension, diabetes.7 All of these conditions can complicate obstetric management and lead to greater maternal,
neonatal, surgical, and anesthetic risk.
Maternal morbidity and mortality Obesity and CS have been identified as independent risk factors for
maternal mortality.5 More importantly, obesity is an important risk factor for anesthetic-related maternal mortality.8
Although there has been longstanding concern about risk of maternal mortality and general anesthesia for CS, there
are emerging concerns about complications occurring during the administration of neuraxial anesthesia as well as
during the postoperative period in the obese. A review by the Doctors Company of 22 anesthesiology claims that
were filed after maternal arrests on labor and delivery wards between 1998 and 2006 again revealed morbid obesity
as a significant risk factor for maternal arrest.9 Outcomes of the 22 patients were poor with only 1 patient leaving the
hospital neurologically intact. Of the others, 10 of 22 patients died and 11 had anoxic brain damage. Thirteen of the
arrests were related to respiratory arrest following spinal (5 for CS) or labor epidural (8 with unintended
subarachnoid placement) placement. Of these cases, morbid obesity was documented in 3 out of the 8 labor epidural
cases and in1 out of 5 CS. Resuscitation of the mother was delayed in 7 of the epidural cases because of a lack of
airway equipment in the labor room or a delay in transfer of the patient to the operating room (OR).
A state review of 855 maternal deaths in Michigan between 1985 and 2003 revealed 8 of these deaths were
anesthesia-related and 7 were anesthesia-contributing.10 Of the anesthesia-related deaths, 6 of the patients were
obese. None of the deaths occurred during induction of anesthesia, however hypoventilation and airway
obstruction occurred during emergence or recovery. More than half of the deaths resulted from lapses in
postoperative monitoring and inadequate supervision by an anesthesiologist.
In the most recent triennial report of maternal deaths in the United Kingdom (UK) between 2006-2008, obesity
contributed to 261 maternal deaths.11 There were 18 Direct or Indirect maternal deaths in which perioperative
anesthetic management contributed. Obesity contributed to 9 of the 18 deaths. The authors caution that “many of the
avoidable factors identified remain the same as in previous reports and more research is needed to identify methods,
tools and training to reduce substandard care by health professionals.”11
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Compared to other developed countries, maternal morbidity and mortality are increased in the U.S. Preeclampsia,
pulmonary emboli, amniotic fluid embolus, hemorrhage, and cardiac disease have been associated with increased
rates of maternal mortality.12 A recent report by the Centers for Disease Control and Prevention determined that
~50% of maternal deaths were preventable.13 There has been increasing interest in near miss maternal morbidity and
mortality. A near-miss occurs when a pregnant or recently postpartum woman survives a life-threatening event,
either by chance or because of high-quality medical care.14 Although obesity was not independently associated with
near-miss morbidity/mortality, Mhyre et. al15 identified the most common comorbidities in the 2003-06 Nationwide
Inpatient Sample that were associated with near-miss morbidity/mortality: hypertensive disorders of pregnancy
(34.7%); previous cesarean delivery (15.7%); diabetes mellitus (10.5%); preexisting hypertension (10.2%); and
multiple gestation (9.8%). The authors concluded that women with preexisting conditions or antenatal obstetric
complications suffer a majority of cases of near-miss morbidity/mortality. “Antepartum multidisciplinary
coordination and careful delivery planning and implementation can improve outcomes for these high-risk patients.”
Although American College of Obstetricians and Gynecologists (ACOG) recommends anesthesiology consultation
for obese women who are pregnant or planning a pregnancy,16 a recent survey of obstetric providers suggests that
the anesthetic implications of obesity may not be a routine part of prenatal care for obese pregnant women.17
OBESITY AND PHYSIOLOGIC CHANGES OF PREGNANCY:

Implications for preoperative assessment and anesthetic planning
Both pregnancy and obesity lead to physiologic changes in multiple organ systems that can lead to profound
functional impairment, decreased physiologic reserve, as well as obstetric and anesthetic complications.
Airway The airway undergoes important changes during pregnancy and the effects of obesity are additive.
Obesity and pregnancy each increase the risk of difficult intubation. The incidence of failed tracheal intubation is
estimated to be 1 in 280 in the obstetric population compared to 1 in 2230 in the general surgical population.18
Similarly, a 6-year review of obstetric cases of failed intubation in the UK revealed 36 cases of failed intubation
occurring in 8,970 obstetric general anesthetics (incidence 1:249).19 The average BMI of these patients was 33. A
careful airway examination should be completed immediately prior to any anesthetic procedure because this exam is
known to change during labor. In a recent evaluation of airway changes during labor, there was a significant
increase in airway class from prelabor to postlabor.20 Thirty-eight of 61 parturients developed a class 3 or 4 airway
that was independent of duration of labor or fluid administration.
The airway exam should include assessment of neck circumference, Mallampati score, mouth opening, dentition,
thyromental distance, neck mobility and the ability to sublux the lower teeth beyond the upper teeth. Pregnancy
increases mucosal edema of the nasopharynx, oropharynx, and larynx but preeclampsia, upper respiratory tract
infections, stridor, and voice changes are all indicators of airway edema. Difficult laryngoscopy and failed
intubation in obstetric patients have been associated with large breasts, increased anteroposterior diameter of the
chest, airway edema and reduced chin-to-chest distance.21 The importance of proper airway positioning
prior to CS cannot be overemphasized.
Respiratory The respiratory system is challenged in pregnancy but even more so when the parturient is obese.
Pulmonary mechanics, lung volumes, functional residual capacity (FRC), oxygenation, and ventilation are altered in
these individuals. Chest wall compliance decreases because of increased weight of excess adipose tissue.
Respiratory work and oxygen consumption are increased.
In these patients, oxygen consumption increases in direct proportion to excess adipose tissue. Although pulmonary
diffusion is normal in these individuals, excess abdominal weight and decreased chest wall compliance lead to
airway collapse in dependent portions of the lungs. Consequently, supine and Trendelenburg positioning can lead to
deterioration of lung volumes and further reductions in FRC. Functional residual capacity may fall below closing
capacity promoting small airway collapse, atelectasis, ventilation perfusion mismatch, and hypoxia, especially with
supine and Trendelenburg positioning.22 Although evaluation of the real FRC may be very difficult, it is often
helpful to measure the oxygen saturation in the sitting and supine positions to indicate the degree of pulmonary
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reserve. The physiologic demands of pregnancy and obesity as well as reduced FRC reduce the period of time
available for direct laryngoscopy and intubation before hypoxemia ensues.
Although the prevalence of obstructive sleep apnea (OSA) in pregnancy is unknown, OSA in the morbidly obese
parturient is more likely. In many cases, this disorder may be undiagnosed.23 Diagnosis during pregnancy may be
difficult because sleep disturbance and daytime fatigue are common during pregnancy, especially near term.
Obstructive sleep apnea should be suspected in women with BMI > 35, neck circumference > 16 inches,
frequent/loud snoring, periods of apnea during sleep, frequent arousals during sleep, or profound daytime
somnolence. Prompt diagnosis by polysomnography and treatment with continuous positive airway pressure may be
beneficial to reduce postoperative respiratory complications. Obesity hypoventilation syndrome (Pickwickian
Syndrome) can also occur in individuals with OSA. These patients are at risk for increased cardiac output,
pulmonary hypertension, cardiomegaly, polycythemia, and right heart failure. Patients at risk should be referred to
cardiology for further evaluation.
Cardiac Hypertension, ischemic heart disease, dilated cardiomyopathy, heart failure, and pulmonary hypertension
can complicate the care of these patients. Obesity and pregnancy are associated with increases in circulating blood
volume, pulmonary blood volume, stroke volume, and cardiac output. These cardiovascular changes contribute to
worsening of the baseline comorbid condition. The excess weight of the uterus and abdominal wall can compress the
vena cava, causing decreased cardiac preload, reflex tachycardia, and decreased cardiac output. Two cases of cardiac
arrest have been reported after supine positioning in nonobstetric morbidly obese patients.24 A change to the supine
position likely contributed to the circulatory changes resulting in these arrests.
A careful preoperative history, physical exam, 12-lead ECG, and chest x-ray may be helpful for screening for
cardiac disease in these patients. Cardiology consultation should be obtained in women with a BMI > 35 who have a
preexisting medical condition (e.g., hypertension) prior to labor and delivery.16
Gastrointestinal Frequency of gastroesophageal reflux is strongly correlated with increasing BMI.25 Although
hiatal hernia is more common in obese individuals compared to the non-obese, it is unknown whether the effects of
obesity are additive with pregnancy in reducing lower esophageal sphincter tone. However, it is likely that
pregnancy and obesity increase the risk for regurgitation and aspiration of gastric contents.
Endocrine Diabetes mellitus and gestational diabetes are frequent endocrine disorders in morbidly obese
parturients. Diabetes and obesity increase the risk for fetal macrosomia and obstetric complications. Women with
gestational diabetes will generally not require insulin during labor, whereas women with Type 1 or 2 diabetes will
require careful monitoring and adjustment of insulin.
Coagulation Hypercoagulability results in venous thromoboembolism and is a leading cause of maternal
mortality.
ANALGESIA FOR ANTICIPATED VAGINAL DELIVERY

Neuraxial analgesia is the preferred analgesic technique in morbidly obese parturients. Parenteral opioid and
inhalation techniques can be used but often at the expense of maternal drowsiness, airway obstruction, and
hypoxemia. Epidural techniques provide excellent pain relief with the benefits of reducing oxygen consumption and
attenuating increases in cardiac output. Because these patients are at risk for CS, a labor epidural catheter can be
easily converted to a surgical catheter in the event of urgent CS in order to avoid the risks of general anesthesia.
Early catheter placement is imperative since successful placement of neuraxial catheters can be time-consuming and
technically more challenging. The ASA Practice Guidelines for Obstetric Anesthesia state that “Early insertion of a
spinal or epidural catheter for obstetric or anesthetic indications (e.g., anticipated difficult airway or obesity should
be considered to reduce the need for general anesthesia if an emergent procedure becomes necessary. In these cases,
the insertion of a spinal or epidural catheter may precede the onset of labor or a patient’s request for labor
analgesia.”26 Critical evaluation of neuraxial catheters is imperative to ensure that the epidural catheter can be used
emergently for CS. The block should be bilateral and almost perfect. Every provider should ask the question, “Can I
use this epidural for cesarean delivery?” Multiple studies have demonstrated that obese patients require more
attempts, catheter replacements, have a higher risk of failures, and more inadvertent subarachnoid catheter
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placements compared to nonobese parturients.27-29 Any epidural catheter that is questionable should be promptly
replaced. Hood and Dewan27 demonstrated a high rate of success when catheters were carefully evaluated and
replaced early. In their series, only 1 of 55 patients required conversion to general anesthesia because of inadequate
epidural anesthesia.
Preparation Preparation should include placement of adequate intravenous access early in labor. Central venous
access may be necessary if peripheral access is unobtainable or inadequate. Blood pressure (BP) monitoring may be
particularly problematic in these patients. Use of an appropriately sized cuff is imperative to ensure accurate BP
measurements. If the BP cuff is too small, the BP reading will be overestimated. The forearm can be used if the
upper arm is too large or cylindrical in shape. In some cases, an arterial line will be necessary to accurately
determine the BP as well as obtain arterial blood gases in patients with respiratory compromise.
Positioning An important step in successful catheter placement is positioning. The sitting position is
recommended to assist with identification of the midline. The patient’s back should be parallel to the edge of the bed
to prevent lateral needle deviation away from the midline. If spinal processes cannot be appreciated with deep
palpation, a line can be drawn from the cervical vertebral spinal process to the uppermost portion of the gluteal cleft.
This line marks the midline of the patient over the vertebral column. Prepuncture ultrasonography may be useful to
facilitate epidural placement in obese parturients.30 When iliac crests are difficult to appreciate, the skin indentation
from the fetal heart rate monitor belt can be used as a guide. This belt usually rests on the iliac crests over the
Tuffier line. By drawing a perpendicular line from the cervical spinal processes down to this line, the intersection
point is a reasonable spinal or epidural needle insertion guide.
Identification of the epidural space Identification of the epidural space is often problematic, especially when
bony landmarks are nonpalpable, there is limited back flexion,31 and there are false loses of resistance due to fat
deposition. It is also difficult to predict the depth to the epidural space but, the depth often positively correlates with
BMI.32 A recent study evaluated the effects of ethnicity and body mass index on the distance from skin to epidural
space in parturients and determined both body mass index and ethnicity significantly influenced the distance from
skin to lumbar epidural space in parturients.33 In the study, distance to the epidural space was significantly greater in
Black/British Black and White parturients compared with their Asian and Chinese counterparts. A long 25-gauge
needle can be used for infiltration of local anesthetic as well as to identify spinal processes. To determine whether
needle placement is midline or lateral, the patient is often helpful in directing the needle to the midline. Failure of
midline placement increases the depth to the epidural space and chance of catheter malposition.34 In most cases,
standard neuraxial needles (9-10 cm) are usually of sufficient length.35 However, longer needles (16 cm) are
sometimes needed in extremely obese parturients. These needles can cause serious injury so they should only be
used when a standard needle is inadequate.
Combined spinal-epidural (CSE) Combined spinal-epidural labor analgesia is one alternative to
conventional epidural analgesia, however there is concern that the technique is more complicated than either spinal
or epidural alone and the epidural catheter is “unproven” during the duration of spinal analgesia. Although CSE
catheters fail at similar rates compared with conventional epidural catheters,36 delayed recognition of a non-
functional epidural catheter is a disadvantage of this technique. However, even if the patient does not receive a
“spinal dose” during CSE placement, the return of CSF in the spinal needle is confirmation of midline needle
placement. This increases the likelihood of a bilateral block.
Dosing and infusions Epidural analgesia for labor should ideally provide pain relief with minimal motor
blockade.26 This is most often accomplished with dilute local anesthetic and opioid solutions. However, these
opioid-laden solutions can mask a malpositioned epidural catheter because opioid administration by any route
produces pain relief. Therefore, practitioners will often initiate the block with only local anesthetic to document a
bilateral block before adding opioid to the epidural solution.
Catheter dislodgement Catheter dislodgment is another potential problem. Before the epidural catheter is
secured, the patient should assume an upright sitting position then a lateral position.37 Because the ligamentum
flavum has a mild grip on the epidural catheter, repositioning allows the epidural catheter to be pulled into the
subcutaneous fat, sometimes by several centimeters. My practice is to insert the catheter 5 cm into the epidural space
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while the patient is in the sitting position. Before taping, the patient moves to a lateral position. The catheter is
subsequently taped in place without adjusting the catheter.
Inadvertent dural puncture In cases of inadvertent dural puncture, catheters may be threaded into the
subarachnoid space for continuous spinal analgesia. Although there have been suggestions that obesity reduces the
risk for postdural puncture headache, routine use of spinal catheters is not recommended because accidental
administration of an epidural dose of local anesthetic through the spinal catheter increases the risk of a high spinal,
respiratory compromise, and loss of the airway in a labor room. When inadvertent dural puncture has occurred, these
catheters can be used during labor with administration of more concentrated local anesthetics for CS. However,
higher levels of spinal anesthesia may result from reduced CSF volume.38 Large buttocks may also increase
cephalad spread.
ANESTHESIA FOR CESAREAN DELIVERY

Several studies have demonstrated a significant relationship between increasing maternal BMI and CS. A meta-
analysis of these studies suggests an odds ratio of 2.05 for CS in obese women compared to those with normal
BMI.39 Although the use of general anesthesia for CS has decreased in the last two decades and deaths attributed to
anesthesia have decreased,40 morbidly obese women undergoing scheduled CS have greater overall anesthesia
complications, more complicated placement of neuraxial anesthesia, and more frequent requirements for general
anesthesia than lower-weight women.41 Obesity and CS remain independent risk factors for maternal morbidity and
mortality.5 Goals of anesthetic management include:
• Aspiration prophylaxis
• Neuraxial anesthesia unless contraindicated
• Preparation (personnel, equipment, monitoring, positioning)
• Careful evaluation and management of the airway and ventilation
• Reduction of cardiovascular stress
• Management of hypotension
• Judicious use of neuraxial, oral, or intravenous opioids
• Careful postoperative monitoring
Operating room considerations Weight limits of standard OR tables range from 130 to 160 kg. However,
some newer tables will support up to 360 kg. It may also be necessary to extend the width of the table with side
extensions. If extensions are unavailable, it may be possible to improvise with arm boards placed along the sides of
the OR table. Adequate padding should be used to prevent pressure-related injuries. If the maternal weight exceeds
the capacity of the OR table, the surgery should be performed on a hospital bed. Transport gurneys should be of
similar size limits. Patients must be properly secured so that left uterine displacement can be achieved. If patient-
moving assistance devices are unavailable, additional personnel are required to prevent lifting injuries.
Surgical considerations A panniculus in a morbidly obese patient may weigh more than 70 kg. Therefore it is
an important surgical consideration with respect to the surgical approach. In such cases, the panniculus must be
retracted in order to permit exposure of the surgical field. The panniculus can either be retracted caudad to permit a
vertical incision above, retracted cephalad to permit a transverse incision, or retracted vertically. Many techniques
(retention sutures or towel clamps attached to IV poles, an assistant to retract the panniculus during the surgery,
suspender-type taping to the shoulders, securing the panniculus to the anesthesia screen, suspending the panniculus
from hooks in the ceiling) are used to achieve exposure. However, cephalad retraction of the panniculus can cause
hypotension, respiratory distress, nonreassuring fetal heart tones, and even fetal death.42 During retraction, the force
exerted on the upper abdomen and chest can causes compression of the inferior vena cava as well as decreased
respiratory compliance. The increased pressure can decrease venous return resulting in a profound decrease in
cardiac output and arterial BP. Increasing pressure on the chest may exacerbate an already compromised respiratory
state. Regardless of the surgical approach, the uterus must be displaced adequately, but carefully, to avoid aortocaval
compression.
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Positioning for airway management Careful positioning is imperative in the care of these patients regardless
of the primary anesthetic technique. A study investigating the effects of position on laryngoscopic view in 60
morbidly obese non-pregnant patients determined that the ‘ramped’ position or head elevated laryngoscopy position
43
(HELP) clearly improved the laryngeal view when compared with the standard ‘sniff’ position. The ‘ramped’
position can be achieved by arranging blankets, or one of the commercially available pillow devices, underneath the
patient’s upper body and head until horizontal alignment is achieved between the external auditory meatus and the
sternal notch. This positioning allows easy access to the airway and facilitates placement of a laryngoscope (short-
handled), if general anesthesia becomes necessary. However, some operating room tables are equipped with a head
section capable of angulation. By tilting this section downwards and then flexing the table forwards, the ramped
position can be created with the use of only one pillow to produce the exact degree of angulation desired.44 Since
neuraxial anesthesia has been associated with a significant decrease in spirometric parameters45 a 30-degree head-up
position may improve respiratory mechanics and oxygenation. Uterine displacement is also necessary to avoid
aortocaval compression by either the uterus or the panniculus.
Anesthetic plan Spinal (single-injection or continuous), epidural, CSE, and general anesthesia are all acceptable
techniques for CS but the choice of technique is dependent upon the clinical situation. Skills of the surgical and
anesthesia team, anticipated operative time, and communication26 are imperative for making a decision about
anesthetic choice.
Spinal anesthesia Spinal anesthesia is the most common type of anesthesia utilized for CS because of its quick
onset, reliability, and dense surgical anesthesia. However, there are concerns about technical difficulties,
exaggerated spread of local anesthetic, hemodynamic compromise, and an inability to prolong the block. Spinal
anesthesia is reasonable if the airway exam is normal, there is no cardiorespiratory disease, and the surgery is
expected to be less than 90 minutes. It is often easier to identify the epidural space with a large gauge stiff epidural
needle compared to a smaller flexible spinal needle so that the epidural needle acts as an introducer.
In a large series of obese patients undergoing non-obstetric surgery who had received spinal anesthesia, more than
one-third developed hypotension.46 Three of the patients also experienced cardiac arrest. Although decreased
cerebral spinal fluid volume has been confirmed in obese patients by magnetic resonance imaging,38 the median
dose of bupivacaine for successful anesthesia in morbidly obese parturients undergoing CS was 9.8 mg using a
randomized dose response of spinal bupivacaine with fentanyl and morphine.47 These study findings were similar to
a previous study in nonobese parturients. In order to avoid a high block when hyperbaric bupivacaine is used, a ramp
can be placed under the patient’s chest to elevate the cervical and thoracic spines to avoid the Trendelenburg
position induced by large buttocks. Regardless, spinal anesthesia should be performed with caution because of the
consequences of extensive blockade, prolonged surgery and the hazards of intraoperative induction of general
anesthesia. Continuous spinal anesthesia may offer the benefits of a single-injection spinal (i.e., reliability,
density).48
Epidural anesthesia Epidural anesthesia offers several advantages over single-injection spinal anesthesia
including titratable dosing of local anesthetics, ability to prolong the block, decreased risk of excessive motor block,
more controllable hemodynamic changes, and utilization for postoperative analgesia. However, a multicenter
prospective observational study found that epidural anesthesia failed more often than spinal or CSE techniques.49
Increased maternal BMI was significantly related to failure of neuraxial techniques. Hodgkinson and Hussain50
demonstrated that the height of an epidural block for a given volume of local anesthetic is proportional to BMI and
maternal weight but not height. Incremental dosing of local anesthetics reduces risk of hypotension and high block.
Combined spinal-epidural anesthesia CSE offers advantages in cases where the surgical duration is unclear
by providing rapid onset and dense blockade with the flexibility of prolonging the anesthetic. However, one
potential disadvantage is an untested epidural catheter.
General anesthesia should be avoided unless absolutely necessary. Hood and Dewan27 found that one-third of
morbidly obese parturients were difficult to intubate versus none in the nonobese control group. The anatomic
changes produced by both pregnancy and obesity increase risk for difficult intubation, rapid desaturation, and
hypoxia during periods of apnea. The urgency of the obstetric situation must be weighed against the risk of general
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anesthesia. If general anesthesia is necessary, additional experienced personnel and difficult airway equipment must
be available. In all cases, proper positioning of the neck, shoulders, and chest is imperative and
the key to successful intubation. In some cases, an awake fiberoptic intubation may be the safest option but it
poses its own problems. Nasal intubation should be avoided due to mucosal engorgement and risk of hemorrhage.
Hypertension and catecholamine release can adversely affect uterine blood flow.51 Fiberoptic intubation can be
difficult and time-consuming. However, a recent study of patients with anticipated difficult randomized to either
awake fiberoptic (BMI 31 [14-57]) vs. awake video laryngoscopic (BMI 29 [18-47]) tracheal intubation determined
that there was no difference of performance between the two techniques,52 suggesting that videolaryngoscopy may
be useful as the primary device or first alternative for securing the trachea, even when awake intubation is being
considered.53 If the patient’s airway appears normal, a rapid sequence intubation in a ramped position can be
performed following denitrogenation. Denitrogenation can be accomplished with 3 minutes of tidal breathing or 4
maximal breaths with 100% oxygen.54
Lean body weight is optimal for dosing most drugs used in anesthesia including opioids and induction agents.55
Lean body weight is defined as 20-30% more than ideal body weight. Succinylcholine is the muscle relaxant of
choice. The dose of succinylcholine (1.0-1.5 mg/kg up to a maximum of 200 mg) is based on total body weight.56
Verification of proper endotracheal intubation can only be accomplished by capnography. If intubation is
unsuccessful, a failed intubation drill should be instituted immediately.57 The goal of failed intubation management
is to ensure maternal oxygenation despite concerns of fetal well-being or aspiration. Mask ventilation may require
several people, one to continue cricoid pressure, a second to institute jaw-thrust, and the third to squeeze the bag and
monitor the patient. Repeated attempts and additional succinylcholine are detrimental but a laryngeal mask airway
can be lifesaving.58
In morbidly obese parturients, there are further reductions in FRC due to supine positioning, use of volatile
anesthetics, muscle relaxants, and retraction of the panniculus.59 This leads to early closure of small airways and
hypoxemia. Increased tidal volumes, high-inspired oxygen concentrations, reverse Trendelenburg positioning, and
positive end-expiratory pressure60 have been used to maintain oxygenation and ventilation. However, use of positive
end-expiratory pressure can worsen cardiac output and oxygen delivery to the fetus. Although isoflurane,
sevoflurane, and desflurane can be used in standard concentrations, desflurane provides a faster recovery.61 Titration
of additional muscle relaxant may be needed besides an intubating dose of succinylcholine. Although the induction
of anesthesia was previously reported to be the most critical time during anesthetic administration in parturients,
more recent reports suggest that emergence, extubation, and recovery are the most critical
periods of anesthetic care in the obese parturient. 10 The morbidly obese parturient should only be
extubated when she is awake with adequate reversal of muscle relaxant. A head-up position should also be used
instead of supine positioning.
POST-OPERATIVE CARE
Morbid obesity increases the risk for postoperative complications, including: hypoxemia, atelectasis, deep venous
thrombosis, pulmonary embolus, pneumonia, pulmonary edema, postoperative endometritis, wound infection, and
dehiscence. Goals of effective postoperative care should be aimed at enhancing pulmonary function and preventing
venous thrombosis. Early ambulation, thromoboprophylaxis, chest physiotherapy, and effective postoperative pain
control are essential in preventing complications in these patients.
Effective postcesarean analgesia is important to hasten recovery. Opioids can be administered either neuraxially or
parenterally but epidural morphine administration in the morbidly obese has been shown to result in earlier
ambulation, fewer pulmonary complications, and shorter hospital stay compared to parenteral morphine
administration.62 Multimodal analgesic techniques (e.g., nonsteroidal anti-inflammatory agents) should be used to
decrease total opioid requirements.63
Because obesity and postoperative respiratory complications have been identified as significant risk factors for
anesthesia-related mortality,10 respiratory monitoring must be vigilant. A recent survey suggests that the level of
care provided for postanesthesia recovery from CS in North American academic institutions may not meet the
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guidelines established by the American Society of PeriAnesthesia Nurses. In addition, obstructive sleep apnea is
common and often undiagnosed in this patient population. The American Society of Anesthesiologists has published
recommendations for the care of these patients although they are not pregnancy-specific.63 Included in the guidelines
are recommendations for postoperative monitoring:
• Regional anesthetic techniques should be considered to reduce or eliminate the requirements for systemic
opioids in patients with OSA.
• If neuraxial anesthesia is planned, the benefits and risks of using an opioid or opioid-local anesthetic
mixture as compared to local anesthetic alone must be considered.
• If patient-controlled systemic opioids are used, continuous background infusions should be avoided or used
with extreme caution.
• Nonsteroidal anti-inflammatory agents and other modalities should be considered to reduce opioid
requirements.
• Supplemental oxygen should be administered continuously to all patients who are at increased
perioperative risk from OSA until they are able to maintain their baseline oxygen saturation while breathing
room air.
• Hospitalized patients at increased risk of respiratory compromise from OSA should be monitored with
continuous pulse oximetry after discharge from the recovery room.
CONCLUSION
A complete understanding of the physiology, pathophysiology, comorbidies and their implications for analgesia and
anesthesia in morbidly obese parturients should lead to improved safety and anesthetic care. Communication
between the anesthesiologist, obstetrician, nursing staff, and patient is imperative in caring for these patients. The
mother’s life should not be endangered to save a compromised fetus!64
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51. Shnider SM, Wright RG, Levinson G, et al. Uterine blood flow and plasma norepinephrine changes during maternal
stress in the pregnant ewe. Anesthesiology 1979;50:524-527.
52. Rosenstock CV, Thogersen B, et al. Awake Fiberoptic or Awake Video Laryngoscopic Tracheal Intubation in Patients
with Anticipated Difficult Airway Management: A Randomized Clinical Trial. Anesthesiology 2012;116:1210-1216.
53. Moore AR, Schricker T, Court O. Awake videolaryngoscopy-assisted tracheal intubation of the morbidly obese.
Anaesthesia 2012;67:232-235.
54. Norris MC, Dewan DM. Preoxygenation for cesarean section: a comparison of two techniques. Anesthesiology
1985;62:827-829.
55. Ingrande J, Lemmens HJ. Dose adjustment of anaesthetics in the morbidly obese. British journal of anaesthesia
2010;105:i16-23.
56. Lemmens HJ, Brodsky JB. The dose of succinylcholine in morbid obesity. Anesthesia and analgesia 2006;102:438-
442.
57. Practice guidelines for management of the difficult airway: an updated report by the American Society of
Anesthesiologists Task Force on Management of the Difficult Airway. Anesthesiology 2003;98:1269-1277.
58. Rahman K, Jenkins JG. Failed tracheal intubation in obstetrics: no more frequent but still managed badly. Anaesthesia
2005;60:168-171.
59. Vaughan RW, Wise L. Intraoperative arterial oxygenation in obese patients. Ann Surg 1976;184:35-42.
60. Pelosi P, Ravagnan I, Giurati G, et al. Positive end-expiratory pressure improves respiratory function in obese but not
in normal subjects during anesthesia and paralysis. Anesthesiology 1999;91:1221-1231.
61. Strum EM, Szenohradszki J, Kaufman WA, et al. Emergence and recovery characteristics of desflurane versus
sevoflurane in morbidly obese adult surgical patients: a prospective, randomized study. Anesth analg 2004;99:1848-1853.
62. Rawal N, Sjostrand U, et al. Comparison of intramuscular and epidural morphine for postoperative analgesia in the
grossly obese: influence on postoperative ambulation and pulmonary function. Anesth analg 1984;63:583-592.
63. Practice guidelines for the perioperative management of patients with obstructive sleep apnea: a report by the ASA
Task Force on Perioperative Management of patients with obstructive sleep apnea. Anesthesiology 2006;104:1081-1093.
64. Saravanakumar K, Rao SG, Cooper GM. Obesity and obstetric anaesthesia. Anaesthesia. 2006;61:36-48.
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DISCLOSURE
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Postpartum Hemorrhage
Jill Mhyre, M.D. Ann Arbor, Michigan
The learner will: 1) Identify women at risk for major postpartum hemorrhage; 2) List options available to control
and mitigate the consequences of obstetric hemorrhage; 3) Discuss how contemporary transfusion practices apply in
the obstetric setting; and 4) Draw from published guidelines and protocols to inform both individual clinical practice
and systems solutions to prepare for these emergencies.
Definition
Hemorrhage is most commonly defined by estimated blood loss (EBL) ≥500 mL for vaginal delivery and ≥1000
mL for cesarean delivery.1 However, blood loss estimation is notoriously inaccurate, bleeding may be concealed
within the uterus, the drapes, or in the retroperitoneal space, and the physiologic impact of hemorrhage depends on
the mother’s initial blood volume, hematocrit, and the speed of blood loss.2 Enhanced strategies to evaluate blood
loss in real time are described below.
Etiology
Primary postpartum hemorrhage develops within 24 hours of delivery and is due to uterine atony, retained
placenta, genital tract trauma, placenta accreta, increta and percreta, uterine inversion, or coagulopathy.
Coagulopathy may be inherited or result from a range of disorders in pregnancy, with amniotic fluid embolism being
the most severe.3 Secondary postpartum hemorrhage is relatively infrequent, develops over 24 hours after delivery,
and is ascribed to subinvolution of the placental site, retained products of conception, infection, or inherited
coagulation defects.
Epidemiology
Maternal hemorrhage complicates approximately 3% of all deliveries. While the incidence of antepartum
hemorrhage appears to be relatively stable, postpartum hemorrhage (PPH) is increasing in developed countries
around the globe.4-7 In the U.S., between 1994 and 2006, rates of PPH increased 30%, and the proportion of all U.S.
deliveries complicated by a blood transfusion increased 90% (from 2.4 to 4.6 per 1,000 deliveries) between 1998
and 2005.7 These rising rates are almost entirely attributable to increases in abnormal placentation (placenta accreta,
placenta previa) and postpartum uterine atony. Hemorrhage-related morbidities include anemia, disseminated
intravascular coagulopathy (DIC), respiratory failure, renal failure, secondary surgical procedures, fertility loss, and
delayed postpartum functional recovery. Hemorrhage is the leading indication for intensive care unit admission in
obstetric patients.8
Peripartum hysterectomy increased 15% in the U.S. between 1994 and 2007 up to a rate of 0.83 per 1,000
deliveries (1 in 1200).9 Placenta accreta with or without placenta previa leads to approximately half of all peripartum
hysterectomies, and rates have increased in conjunction with the burgeoning population of pregnant women with
previous cesarean delivery.9 Hysterectomy attributed to uterine atony more than doubled, and currently accounts for
one-third of all peripartum hysterectomies.9 Infection and inflammatory findings in the placenta and uterus (e.g.,
chorioamnionitis, vasculitis, funisitis, endometritis, and cervicitis) are associated with hysterectomies performed for
intractable uterine atony, as opposed to other indications (e.g., suspected accreta, lacerations, leiomyomas), (45%
compared with 19%, P=.03).10
The shift towards cesarean birth, from 21% of all births in 1997 to 32.3% in 2009,11 underlies the increasing
rates of abnormal placentation, uterine atony, and PPH. Other factors contribute to the increasing risk of uterine
atony including: 1) increasing population rates of obesity, multiple gestation, and advanced maternal age; 2)
increasing rates of induction of labor12; and 3) increasing use of oxytocin for induction and/or augmentation of
labor. Prolonged exposure to oxytocin infusions down-regulate oxytocin receptors in the lower uterine segment,13
and increase risk of PPH attributed to both uterine atony14 and retained placenta.15
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Historically, hemorrhage was the leading cause of maternal death in the United States, but is now tied with 7
other conditions, each contributing 10-13% of all deaths (i.e., hypertensive disorders of pregnancy, infection,
thrombotic pulmonary embolism, cardiomyopathy, cardiovascular conditions, and non-cardiovascular medical
conditions).16 Over the past ~20 years, the hemorrhage-related maternal mortality ratio fell 30% from 2.6 to 1.8 per
100,000 live births, (comparing 1987-1990 with 1998-2005).16
While hemorrhage is no longer the leading cause of maternal death, it remains among the most preventable.17 In
California, between 2002 and 2003, hemorrhage accounted for just 10% of pregnancy-related deaths, but in 70% of
these cases improved clinical care had a good or strong chance to alter the fatal outcome.2 This rate of potential
preventability was higher than any other condition, and established hemorrhage as a top priority for the California
Maternal Quality Care Collaborative (CMQCC). Consequently, CMQCC developed the Obstetric Hemorrhage
Toolkit and deployed a statewide campaign “to improve California hospital capabilities and resources for
responding to obstetric hemorrhage by increasing the use of protocols and drills and by improving availability of and
training in standard and state-of-the-art medical, surgical and blood replacement options.”2
Anticipated Hemorrhage
Even with the physiologic anemia of pregnancy, a hematocrit less than 32% should be treated to reduce the risk
of peripartum blood transfusion (e.g., oral or intravenous iron, erythropoietin for select cases). In addition, three
groups need special antenatal preparation: 1) women with abnormal placentation; 2) those with inherited coagulation
disorders; and 3) those who refuse blood products. This section also discusses a risk-stratified algorithm to guide
blood product preparation.
Abnormal Placentation
With normal placentation, the chorionic villi grow into the uterine decidua and extravillous trophoblasts invade
uterine spiral arteries to establish the placental blood supply. At term, approximately 200 spiral arteries feed the
intervillous space, bathing the chorionic villi in 500-800 mL/min of maternal blood. Residual decidua forms the
basal plate, which then cleaves at delivery, creating the normal plane of placental separation, and the placenta is
delivered with the intravillous space intact. With placenta accreta, the decidua basalis (i.e., the decidual basal plate)
is absent, and the placenta adheres to a floor of uterine myometrium. With placenta increta, chorionic villi invade
into the myometrium, and with percreta, the placenta penetrates the uterine serosa, and may even grow into other
pelvic structures, most commonly the bladder. Estimated intrapartum blood loss has been reported as >2L in 66%,
>5L in 15%, and >10L in 6.5% of these cases.18
Prior cesarean delivery, other uterine surgery, placenta previa, and maternal age ≥35 years are important risk
factors for placenta accreta. The incidence of a morbidly adherent placenta increases from 0.03% among primary
cesarean deliveries, to 0.2%, 0.3%, 0.6%, 2.1%, 2.3% and 6.7% after one, two, three, four, five and six or more prior
cesarean deliveries, respectively.19 With placenta previa, the corresponding risks of a morbidly adherent placenta are
3%, 11%, 40%, 61%, and 67% with zero, one, two three, and four or more prior Cesarean deliveries, respectively.19
Given the rising incidence and prevalence of cesarean birth, placenta accreta has increased from 0.8 per 1000
deliveries in the 1980s to 3 per 1000 deliveries in the past decade.20
Antenatal recognition and controlled surgical delivery improve outcomes.21-23 Recent evidence suggests that
maternal morbidity is reduced when women with placenta accreta deliver in tertiary care centers with a multi-
disciplinary care team.24,25 The Society of Maternal-Fetal-Medicine recommends that “women with a suspected
placenta accreta should be scheduled for delivery in an institution with appropriate surgical facilities and a blood
bank that can facilitate transfusion of large amounts of various blood products.”20 Nevertheless, placenta accreta
remains the leading indication for unplanned peripartum hysterectomy,26 likely as a consequence of the limitations
of diagnostic accuracy.
Ultrasonography to locate the placenta and evaluate for markers of placenta accreta is recommended for every
woman who has undergone prior uterine surgery, or found to have a low-lying placenta on the routine first or second
trimester ultrasound.20 Magnetic resonance imaging (MRI) may help to confirm the diagnosis when ultrasound is
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inconclusive, and define the extent of invasion into surrounding organs in the case of placenta percreta.20 Women
with a diagnosis of abnormal placentation based on ultrasonography are more likely to require blood transfusion and
peripartum hysterectomy, and require more units of blood products transfused, when compared with women without
definitive ultrasound findings.27,28
In cases of extensive accreta, optimal surgical management is directed towards delivering the neonate, then
closing the uterus with the placenta left in situ, followed by planned peripartum hysterectomy. When the area of
accreta is small, a trial of spontaneous placental separation may be attempted followed by deep myometrial sutures,
a uterine compression suture (e.g., B-Lynch), and/or intrauterine balloon tamponade (e.g., with a Bakri balloon). For
placenta percreta, depending on the extent of placental invasion into surrounding organs, multidisciplinary surgical
management may require gynecologic oncologists, general surgeons, urologists, interventional radiologists, and/or
vascular surgeons. For women who desire fertility preservation, uterine conservation techniques include
prophylactic uterine and hypogastric artery balloon catheters, stepwise uterine devascularization, pelvic vessel
ligation or embolization, uterine compression sutures, and/or postpartum methotrexate to facilitate placental
involution.29
Optimal management by the anesthesiologist ensures sufficient intravenous access and blood products to
respond to massive hemorrhage, hemodynamic and hemostatic monitoring capability (e.g., central venous and
peripheral arterial access), compression stockings to prevent venous thromboembolism, padding and positioning to
prevent nerve compression injury, warming devices to ensure normothermia, standard preoperative antibiotic
prophylaxis in the hour prior to surgical incision and repeated if surgery is prolonged (i.e., ≥3 hours) or if heavy
bleeding occurs.20 Given inaccuracy of models to predict total blood loss in these cases, the total number of
recommended blood products to prepare depends on institutional capacity to maintain ongoing supply in the face of
massive hemorrhage (Table 1).28,30 Aggressive uterotonic administration, cell-saver auto-transfusion, massive
transfusion management, and electrolyte and hemostatic measurement and management are discussed below.
Combined spinal epidural (or standard epidural) anesthesia allows the mother to be awake for the delivery, and
may be extended for prolonged surgery. On the other hand, general anesthesia is preferred for cases with massive
transfusion in the event of airway edema, fluid overload with pulmonary edema, or transfusion associated lung
injury (TRALI). The decision about the primary anesthetic technique will weigh the magnitude of anticipated blood
loss, the extent of the operative plan, the availability of additional anesthesia staff to assist with an unplanned
conversion to general anesthesia, and the anticipated risk of a difficult airway.
Prophylactic embolization catheters may be inserted preoperatively into the anterior internal iliac or uterine
arteries to facilitate balloon inflation or embolization immediately following delivery of the infant.31,32 Success rates
vary based on institutional experience; cesarean delivery in the interventional radiology suite may improve efficacy
of intra-arterial occlusion by avoiding catheter dislodgement.33 While these catheters may be indicated for women
who desire fertility preservation, and in women with extensive or unrespectable placenta percreta, routine use is not
recommended by the Society for Maternal-FetalMedicine due to potential complications including insertion site
hematoma, abscess, tissue infection and necrosis.20 Epidural anesthesia should be initiated prior to femoral sheath
insertion, to facilitate optimal positioning for both procedures and patient comfort.
Inherited Coagulation Disorders
Von Willebrand disease, hemophilia A and B, and factor XI deficiency account for approximately 90% of
inherited bleeding disorders.34-36 Inherited platelet disorders (e.g., Bernard Soulier Syndrome, Glanzmann
thrombasthenia) are rare. Given the clinical heterogeneity within each diagnosis, consultation with a hematologist
and blood bank personnel will help to clarify optimal management for each patient. Sixteen percent of women who
have von Willebrand disease will experience PPH within 24 hours of delivery, and 29% will experience delayed
postpartum bleeding.37 A familial history of inherited coagulopathy, postpartum or perioperative hemorrhage,
significant menorrhagia, gingivorrhagia or epistaxis may help to identify patients at increased risk for disordered
hemostasis with delivery.35,37
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Jehovah’s Witnesses and other women who refuse blood products

Antepartum consultation should review a comprehensive list of blood products, alternatives, and blood
conservation strategies to determine acceptability of each intervention for the patient.2 Antepartum iron and
erythropoietin are often acceptable ways to optimize hematocrit prior to delivery, aiming for a goal of 35-40%, and
may be continued postpartum in the event of significant blood loss.38,39 Neuraxial anesthesia with a catheter-based
technique may be preferred for operative anesthesia because an awake patient may change her mind in the face of
impending death.
In the event of hemorrhage, permissive hypotension with a mean arterial blood pressure of 50 mmHg may help
limit blood loss following delivery of the fetus.38 Volume replacement with crystalloid or colloid can decrease
viscosity of the blood and improve peripheral perfusion while maintaining oxygen delivery (by increasing oxygen
extraction in the periphery), and minimizing cardiac work. However, excessive fluid resuscitation can contribute to
dilutional coagulopathy and decreased oncotic pressure. Cell-saver autotransfusion is discussed below, and a
continuous circuit technique is often acceptable for patients who would otherwise refuse blood products.39,40 In the
event of massive blood loss and profound anemia (hgb ≤4 g/dL) prolonged postoperative sedation, intubation,
thermoregulation, and paralysis may be required to limit oxygen consumption while erythropoietin and iron are used
to restore the patient’s red cell mass. Erythropoietin requires 48-72 hours for a significant reticulocyte response in
peripheral blood, and 10-14 days to increase hemoglobin levels. Laboratory testing should be minimized using
pediatric tubes and finger-stick testing where possible.38
Risk stratified blood product preparation
Patients usually receive a type and screen as part of routine prenatal care to determine blood type, the
requirement for RhoGAM®, and the presence of minor antibodies. This result in combination with antepartum risk
factors can help determine the optimal blood tests that should be submitted at the time of admission to the labor and
delivery unit. Risk-stratified blood testing has been shown to reduce excess cost associated with testing for low risk
women, and is also thought to focus attention and resources on high risk patients, and to reduce inconsistences in
transfusion ordering.2,41 Nevertheless, specific algorithms vary among centers, and are largely based on expert
opinion supported by limited empirical data. Recommendations in Table 1 synthesize algorithms from the
CMQCC,2,3 Stanford University,41 Northwestern University (Cynthia Wong e-mail communication, October 2011),
and risk factors reported elsewhere in the literature.39
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Table 1. Blood product preparation based on the level of risk for blood transfusion
Risk level AND Conditions
Recommendations
Low risk (~1/4000)42 • Elective CD with no prior uterine surgery
A clotted sample can be sent to the • Admitted for labor with fewer than 5 prior VB
blood bank at the time of admission
• No known bleeding disorder
for delivery
• No history of PPH
Risk < 5% • 2nd through 4th elective CD
• More than four prior VB
Either a type & screen or clot only,
depending on institutional resources • Multiple gestation
• Prior PPH
• Uterine fibroids
• Fetal macrosomia
• Maternal obesity
• Unplanned CD in labor without additional risk factors
Risk 5 - 10% • Antenatal observation for placenta previa without active bleeding
• Chorioamnionitis
At least a type & screen
• Elective CD with prior myomectomy or fundal surgery
• Trial of labor after any uterine surgery
• A history of RhoGAM® therapy‡
Risk > 10% • Severe anemia (antepartum Hct <25%)
• Mild anemia (Hct<30%) in the presence of other risk factors
Type and crossmatch
≥2 units PRBC • Thrombocytopenia (platelets <100k)
• Active bleeding on admission
• Coagulation disorder including HELLP
• Higher order CD (≥5)
• Positive antibodies on type and screen
• CD for patients who have: placenta previa, intrauterine fetal
demise, placental abruption, uterine rupture, chorioamnionitis
Highest risk • A planned cesarean hysterectomy
Type and crossmatch † • Suspected: placenta accreta, placenta increta, placenta percreta
• 4-20 units PRBC
• 4-20 units FFP
• 4-20 platelets
CD = cesarean delivery; FFP = fresh frozen plasma; Hct = hematocrit; PPH = post partum hemorrhage; PRBC =
packed red blood cells; VB = vaginal births;
†The exact number of units determined by a patient-specific assessment of risk for massive blood loss, and
institutional resources to rapidly procure additional blood products.28,30
‡Extra time is needed to discriminate between anti-D antibiodies due to RhoGAM® and any additional antibodies
that could interfere with a type and crossmatch.43
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Unanticipated Postpartum Hemorrhage

System Factors
Clear multidisciplinary guidelines and regular skills training (multidisciplinary drills) reduce the incidence of
massive PPH,44-46 and are recommended for all units by the Centre for Maternal and Child Enquiries in the United
Kingdom.17 Simulation-based training for obstetric hemorrhage encounters can reveal specific management deficits,
and thereby facilitate targeted quality improvement and staff education.47
Accumulating evidence suggests that treatment delays substantially increase risk for severe obstetric
hemorrhage and hemorrhage-related maternal death.17,48,49 Calling for the obstetrician within 10 minutes, the
anesthesiologist within 10 minutes, administering oxytocin within 10 minutes, and exploring the uterus within 20
minutes each decrease the likelihood of severe obstetric hemorrhage from uterine atony following vaginal delivery.49
Neuraxial labor analgesia reduces the risk-adjusted odds of severe atonic hemorrhage following vaginal delivery by
half, likely by facilitating rapid manual exploration and surgical repair.49 Prompt placement of uterine compression
sutures within 1 hour of delivery decreases risk for peripartum hysterectomy.50
Bundling personnel, equipment, and drug resources ensures rapid and reliable delivery to the bedside. For
example, group paging systems can simultaneously request an entire Obstetric Medical Emergency Team including
an attending obstetrician, critical care physician, anesthesiologist, respiratory therapist, and several nurses.51
Likewise, an obstetric hemorrhage cart can be used to store essential equipment, including a laminated copy of the
institutional hemorrhage protocol, important phone numbers, equipment for lines, fluid resuscitation and serial
laboratory tests, and surgical equipment including a hysterectomy tray.52 Lastly, an obstetric hemorrhage drug pack
containing fentanyl, oxytocin, methylergonovine, misoprostol, and carboprost allows for efficient retrieval in the
event of an emergency. (Manuel A. Vallejo, Jr., e-mail communication, May 2011)
The CMQCC Staged Approach
The CMQCC describes four stages of PPH, based on estimated blood loss, vital sign stability, need for
blood products, and interventions.
Stage O
Stage O begins with all deliveries, and focuses on ongoing risk assessment and active management of the third
stage of labor. This includes prophylactic oxytocin administration with delivery, vigorous fundal massage lasting at
least 15 seconds, and controlled cord traction to deliver the placenta.53
Oxytocin is the preferred first line uterotonic, because it is clearly shown to decrease blood loss of the third
stage of labor,53,54 and decreases need for additional uterotonics.54 Rapid intravenous infusion of oxytocin may cause
peripheral vasodilation, hypotension, flushing, nausea, chest pain, myocardial ischemia, and in the face of
substantial hemorrhage, cardiovascular collapse.55,56 Phenylephrine may be used to counteract the hemodynamic
effects of oxytocin.57 As little as 0.35 IU is needed to initiate acceptable uterine tone in 90% of elective cesarean
delivery patients.58,59 Three IU is effective to establish uterine tone in 90% of women undergoing cesarean in labor.60
One of the cardinal recommendations from the CMQCC is to establish the standard of structured assessments of
blood loss, vital signs, fundal height, and uterine tone following all deliveries, and to define specific triggers for
action to limit the risk for denial and delay. Accurate blood loss estimation is improved by the use of calibrated
drapes and formal staff training in blood loss estimation.2,61,62 Blood contained in absorbing materials (e.g., pads,
sponges) can be quantified by weight, subtracting the dry weight of each item, assuming 1 gm weight = 1 mL
blood.2 Immediately following delivery, the team should routinely tabulate fluid volume in suction canisters,
calibrated drapes, and absorbing materials; any subsequent volume can be assumed to be blood, not amniotic fluid.
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Because hemorrhage is so often concealed or underestimated, monitoring protocols with clear triggers for
escalating care are essential.2,17 A Modified Obstetric Early Warning Scoring (MEOWS) system adapted from that
published in the Saving Mothers’ Lives report is presented here.63 Additional signs and symptoms of severe obstetric
hemorrhage include narrow pulse pressure, pallor or mottled appearance, cold and clammy extremities, oliguria
(<0.5mL/kg/hr), anxiety, restlessness, confusion, palpitations, dizziness, diaphoresis, and dyspnea or air hunger.
Modified Early Obstetric Warning Scores

Contact a physician for early intervention if the patient scores ≥2 at any time.
Score 2 1 0 1 2
Pulse ≤40 41-50 51-100 101-120 or >120 or
10-20% >20% increase
increase
SBP ≤85 or 85-100 101-150 151-160 >160
>20% decrease
DBP <45 45-80 81-100 >100
SpO2 <90% 90-94% 95-100%
RR ≤10 11-20 21-30 >30
Temp ≤35.0 35.1-35.9 36.0-37.9 ≥38.0
CNS Normal Responds to Responds only to pain or
voice unresponsive
Stage 1: EBL>500 vaginal delivery, >1000 cesarean delivery, brisk gush or boggy uterus, or multiple clots
AND vital signs stable. At this point, both the anesthesiologist and the obstetrician should be requested to the
bedside. Monitoring intensity of both vital signs and EBL should increase. The patient likely requires additional
venous access, colloid or crystalloid resuscitation, active warming, a request to the blood bank to crossmatch at least
2 units packed red blood cells (PRBC), and analgesia for initial obstetric interventions to investigate and control the
source of bleeding. The initial diagnostic evaluation should address the five Ts: (1) Tone—uterine atony; (2)
Trauma—lacerations or genital tract trauma; (3) Tissue—retained placenta; (4) Thrombin—abnormalities of
coagulation; and (5) Turned inside out—uterine inversion.
Once oxytocin is infusing (500 mL/hr of 10-40 units/liter), administering a second uterotonic agent is more
effective than increasing the oxytocin infusion rate. Second line options include: 1) methergine 200 mcg if the
patient is not hypertensive, repeated every 2 hours; 2) carboprost 250 mcg IM every 15-20 minutes up to 8 total
doses (avoided in women with asthma); and 3) misoprostol 800-1000 mcg buccally, rectally, or vaginally.
Stage 2: Continued bleeding OR vital sign instability (change>20% from baseline of HR, SBP/DBP, or
HR>110, BP<85/45, SpO2<95%, RR>20, narrow pulse pressure) OR symptomatic (coldness or clamminess,
pale appearance, anxiety, restless, dizzy, short of breath, hunger for air, confusion) AND <1500 mL
cumulative blood loss. With Stage 2, it becomes very important to mobilize a full team, including: the charge nurse,
the blood bank, a second obstetrician, a second anesthesiologist, interventional radiologist if appropriate, the nursing
supervisor, and additional staff to communicate with the blood bank and to provide family support.
The patient should be moved to an operating room, large bore venous access secured, and a full panel of
laboratory values sent, most importantly Type and Cross, hematocrit, platelets, PT, and fibrinogen. Fibrinogen <2
g/L is an early predictor of the severity of subsequent PPH.64-66 Ongoing uterotonics, thermoregulation, antibiotic
coverage, and venous thromboembolism prophylaxis should be addressed. Decisions about transfusion, requesting
additional blood products, activating a massive transfusion protocol, converting to general anesthesia, initiating cell
salvage, and establishing invasive hemodynamic monitoring depend on the ongoing state of the patient, the rate of
blood loss, and the degree to which obstetricians are effective in controlling the source of bleeding.
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Following manual exploration and repair of lacerations, stepwise escalation of surgical therapy includes D&C,
intrauterine balloon (e.g., Bakri balloon), uterine compression suture (e.g., B-Lynch, O’Leary, multiple squares),
selective embolization, peripartum hysterectomy, and abdominal packing. Uterine inversion requires anesthesia and
uterine relaxation to facilitate manual replacement.
Stage 3: EBL>1500, >2 u PRBC given, vital sign instability, evidence of coagulopathy, or ongoing bleeding.
Stage 3 qualifies as major obstetric hemorrhage. In the event of unanticipated massive hemorrhage, an interosseous
needle may be rapidly inserted in the proximal humerus and used to initiate fluid resuscitation while additional
intravenous access is established.67 Temporizing maneuvers include leg elevation, manual compression of the aorta
at the umbilicus, and non-pneumatic anti-shock garments.68 Permissive hypotension (MAP 50 mmHg) may help to
limit bleeding, but is not well studied in the postpartum patient.38
While a hemoglobin transfusion threshold of 7 g/dL is generally appropriate, laboratory results are
inaccurate in the face of ongoing hemorrhage, and transfusion should proceed empirically without waiting for
laboratory results. Failure to maintain adequate hematocrit during acute obstetric hemorrhage has been associated
with end organ dysfunction.69 Retrospective analyses suggest that hemostatic resuscitation with low transfusion
ratios (FFP: PRBC and Platelet: PRBC ratios of 1:1 to 1:2) may increase survival in massively transfused trauma
victims.70 However, this evidence base suffers from survival bias. Furthermore, plasma and platelets are pro-
inflammatory, and may actually increase risk of TRALI and other morbidity among survivors.71-73 Regardless, the
full panel of laboratory values (i.e., hematocrit, platelets, ionized Ca, K, PT, fibrinogen, ABG) should be sent every
30-60 minutes to establish trends. Serial coagulation tests are more helpful than single time point measurements in
assessing for development of coagulopathy.5 Additional FFP may be needed to maintain the PT ≤1.5 times normal,
platelets to maintain the platelet count over 50 x 109/L, and cryoprecipitate or fibrinogen concentrate 4 g to maintain
the fibrinogen over 2 g/L.64-66 Central laboratory turn-around time within 20 minutes is possible.74 Point-of-care
viscoelastic monitors are an alternate strategy to facilitate goal directed therapy.75,76
Massive transfusion protocols can be established to treat life-threatening obstetric hemorrhage. At Stanford
University, upon activation of the massive transfusion protocol, the blood bank provides a standard pack to initiate
resuscitation (e.g., 6 units O negative blood, 4 units FFP, 1 apheresis platelet unit [5-pack]).77,78 Subsequent matched
blood products are continuously prepared to maintain blood product availability, and the protocol is automatically
discontinued once additional blood products have not been requested for at least one hour.
Adjunctive agents: Cell salvage—Over 400 published cases of obstetric patients have described auto-transfusion
with blood salvaged and processed from the surgical field. The technique is gaining acceptance as newer machines
in combination with leukocyte reduction filters have demonstrated effective clearance of fetal squamous cells,
phospholipid lamellar bodies, plasma heparin, cytokines, and other coagulopathic mediators. Cell-salvaged blood
does contain up to 2% fetal red blood cells; Rhesus-negative women require dose-adjusted RhoGAM®
administration. Emergency cell salvage may be most appropriate in institutions where cell saver devices are
routinely used, and dedicated technicians are available to set up the equipment.79
The anti-fibrinolytic agent tranexamic acid (1 g over 10 minutes Q 4-8 hr) improved survival in an
international randomized controlled trial of trauma patients with significant hemorrhage.80 Although fibrinolysis
may be less important in the pathophysiology of PPH, the WHO recommends tranexamic acid when PPH continues
despite standard uterotonic agents.81 A large trial in postpartum hemorrhage patients is currently ongoing.82
Registries of recombinant factor VIIa report an overall 80% success rate to control hemorrhage when other
interventions have failed, with reported doses ≤90 mcg/kg.83 Temperature, acidosis, calcium, platelets and
fibrinogen should be first optimized for maximal hemostatic effect. For women with refractory hemorrhage in the
setting of amniotic fluid embolism, recombinant factor VIIa has been associated with a high rate of devastating
thrombotic complications.84
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Lyophylized fibrinogen concentrate 2-4 g has been reported to be helpful in obstetric patients.85 Although
derived from human serum, fibrinogen concentrate is pasteurized, available in a standard concentration, and may be
reconstituted and administered rapidly in a low volume.86 The optimal amount of FFP to administer with fibrinogen
concentrate is unknown.
References
1. Obstet Gynecol 2006; 108:1039-48.
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DISCLOSURE
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Neurologic Complications in Neuraxial Obstetric Anesthesia

David J. Wlody, M.D. Brooklyn, New York
Neuraxial anesthesia in obstetric patients is very infrequently associated with significant neurologic sequelae, with
one recent study suggesting an incidence of less than 1 in 29,000 anesthetics (1). Nevertheless, a thorough
knowledge of neurologic deficits seen in pregnancy is of critical importance. First, such knowledge may allow us to
modify our practice in a way that can minimize the likelihood of neurologic injury. Second, familiarity with
common neurologic deficits that are unrelated to anesthesia, the so-called obstetric nerve palsies, will enable us to
both eliminate anesthesia as an etiology for a given patient’s deficit, as well as provide guidance as to the expected
course of the deficit, in particular the likelihood of full and rapid recovery.
Infectious Complications-Meningitis
When appropriate aseptic precautions are utilized, the risk of bacterial meningitis after neuraxial anesthesia is quite
low. Breaks in sterile technique are certainly more common than we realize, but the presence of normal host
defenses and the integrity of the intact dura serve to minimize infection of the subarachnoid space.
Nevertheless, the potential for meningitis to develop in this setting must never be underestimated, and every effort
should be made to minimize the risk of this complication. Although the use of spinal anesthesia in patients with
chorioamnionitis and low grade fever is acceptable, subarachnoid block in the presence of documented or suspected
bacteremia is controversial, as animal studies have shown that lumbar puncture in the setting of bacteremia leads to
meningitis (2). It appears, though, that the prior initiation of antibiotic therapy eliminates the risk of meningitis in
this setting. Multiple use bottles of skin disinfectants should be avoided, as they can become colonized with bacteria
after opening (3). There is increasing recognition that chlorhexidine-alcohol prep solutions have improved and
persistent antibacterial activity compared to povidone-iodine solutions, and as such are increasingly used in this
setting.
At a minimum, a mask and cap must be worn by the physician performing a block; in patients who are
immunosuppressed, the use of a sterile gown is recommended. Many practitioners also require that anyone present
in the labor room during epidural placement, including family members, should wear masks. When drugs for spinal
or epidural administration are drawn from ampules that are not on a sterile tray, a bacterial filter needle should be
used. Finally, there have been an increased number of reports of meningitis after the combined spinal epidural
technique (4), presumably due to the presence of a route of entry (the epidural catheter) in close proximity to a dural
puncture; the placement of a bacterial filter on the epidural catheter should be considered, especially when
prolonged catheter use, e.g. postoperative pain management, is anticipated.
Rapid recognition of meningitis is essential to insure a good outcome. The incubation period for
meningitis has been reported to be approximately 40 hours after the original anesthetic procedure (5). The presence
of fever, headache, photophobia, altered sensorium, stiff neck and positive Kernig’s sign should lead to the
immediate initiation of diagnostic studies, including lumbar puncture and head CT or MRI. Appropriate antibiotics
should be initiated based on the clinical history, pending the identification of a specific organism and determination
of its antibiotic sensitivity.
Infectious Complications-Epidural abscess

Bacterial colonization of indwelling epidural catheters is surprisingly common, yet the incidence of epidural abscess
after regional anesthesia is quite low. The great majority of epidural abscesses do not occur in patients who have
undergone anesthetic procedures, but rather in those who have a remote focus of infection that spreads
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hematogenously to the epidural space. Nevertheless, epidural abscess has been reported after regional anesthesia,
and it is important to be able to rapidly recognize this complication if full recovery is to occur.
Unlike the rapid development of CNS symptoms seen in anesthesia-related meningitis, the primary manifestation of
epidural abscess is the delayed development of spinal cord compression symptoms. These symptoms typically
follow an incubation period of up to one week, and initially consist of severe lower back pain accompanied by fever
and leukocytosis, followed by radiating segmental pain, and finally by loss of lower extremity motor and sensory
function. Once these late symptoms develop, a rapid intervention is essential; if spinal cord decompression is
delayed for more than eight hours, full recovery of neurologic function is highly unlikely. The
gradual onset of low back pain after regional anesthesia, especially if accompanied by neurologic signs of spinal
cord compression, should lead to immediate MRI or CT scan of the lumbar spine, and expeditious neurosurgical
consultation. Antibiotic treatment has been used as the sole treatment of epidural abscess in patients without
progression of neurologic deficit, but in the great majority of cases decompressive laminectomy will be an essential
adjunct to appropriate antibiotic therapy.
Epidural hematoma
The presentation of an epidural hematoma resembles that of an epidural abscess, except the time frame is
considerably shorter; symptoms may develop within 12 hours of the initial neuraxial procedure. This can pose a
diagnostic dilemma; unlike epidural abscess, in which motor weakness can develop many days after resolution of
the block, an epidural hematoma can develop during the time period in which motor and sensory blockade might be
expected to persist after an uncomplicated regional anesthetic. Recurrence of motor block after partial
recovery, or prolonged block in patients at risk for an epidural hematoma, should serve as a red
flag to initiate diagnostic studies to rule out possible spinal cord compression.
A detailed discussion of the many coagulation disturbances that predispose to the development of an epidural
hematoma in the parturient are beyond the scope of this review, but a few principles can be established. First, in
patients with pre-eclampsia, a recent platelet count is essential. While it has traditionally been suggested that a
platelet count of 100,000 should be considered the absolute minimum requirement for neuraxial anesthesia, more
recent consensus suggests that a platelet count of 75,000 or even lower may be acceptable if there is no clinical
evidence of bleeding. Furthermore, the recent rate of decline may be as important as the absolute platelet count; a
platelet count that has remained stable in the 75-90,000 range is probably acceptable. The decision to perform a
regional anesthetic in a patient with thrombocytopenia must be made on a case-by-case basis, with a careful
consideration of the risk-benefit ratio, e.g. risk of airway disaster during general anesthesia vs. the risk of neuraxial
hematoma in a morbidly obese patient with a difficult airway. In the setting of thrombocytopenia, prothrombin time
(PT) and partial thromboplastin tine (PTT) should be obtained. Conversely, a normal platelet count essentially
precludes an abnormal PT and PTT, and these tests would not provide much additional useful information regarding
risk of neuraxial hematoma formation.
The major risk factor for epidural hematoma after neuraxial anesthesia is therapeutic anticoagulation. Patients
receiving low dose aspirin do not appear to be at significantly increased risk of epidural hematoma. Likewise,
patients receiving subcutaneous unfractionated heparin for thromboprophylaxis are not at increased risk. However,
patients who are receiving therapeutic doses of coumadin should have a documented normal PT before receiving a
regional anesthetic. In patients receiving low molecular weight heparin (LMWH), regional anesthetic techniques
should be avoided for at least 12 and, with high dose therapy, at least 24 hours after the last dose of LMWH (6).
Neural injury
Although rare, permanent neurologic injury has resulted from the spinal or epidural injection of incorrect drugs. The
causes for such errors are numerous, including “look-alike” drug ampules, incorrect labeling of syringes, and the
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accidental attachment of intravenous lines to epidural catheters. Clearly, such errors can never be eliminated, but
appropriate vigilance should minimize their occurrence. Ampules should be identified by their labeling, and not
color; hospital pharmacies should be notified if a potentially neurotoxic agent has labeling similar to commonly used
local anesthetics.
Direct needle trauma to the spinal cord or nerve roots can occur. The spinal cord ends at the L2-3 interspace, and
injection should not occur at this interspace or above. However, it should be noted that identifying a spinal
interspace by physical examination alone can be unreliable. The sequelae of a single puncture of a nerve root or
even the spinal cord may be minimal, with a nerve deficit that resolves over a period of days to months. However,
whenever needle placement is accompanied by significant pain, the needle must be removed. Injection of local
anesthetic into the cord or a nerve root is much more likely to produce a permanent neurologic deficit than insertion
of the needle alone. Pain upon needle placement cannot be ignored.
Spinal headache
The risk of headache after dural puncture has been recognized since 1899, when August Bier first described the use
of subarachnoid local anesthetics. After submitting himself to a spinal anesthetic, he remained bedridden for nine
days, although his assistant forced himself to work the next day despite his own headache. Unfortunately, we see a
similar pattern today, with new mothers either forcing themselves to care for their infants despite severe headache,
or remaining bedridden (or hospitalized) for prolonged periods.
The diagnosis of post-dural puncture headache (PDPH) is usually straightforward. In the setting of a previous
neuraxial anesthetic, a headache that is markedly improved by the supine position and worsened by the sitting or
upright position should be assumed to represent PDPH, whether or not a dural puncture was recognized at the time
of the procedure. The headache is usually frontal or occipital; pain may also be referred to the neck or the upper
back. Patients occasionally complain of diplopia or auditory disturbances. They may also complain of nausea,
vomiting, and photophobia; the similarity of these symptoms to those of bacterial meningitis is obviously
worrisome.
The pathophysiology of PDPH remains controversial, with two commonly proposed mechanisms. The first suggests
that continued leakage of CSF via a dural puncture leads to decreased intracranial CSF pressure, allowing the brain
to sag within the cranial vault and place traction on the pain-sensitive meninges. When patients assume the supine
position, the flow of CSF into the intracranial compartment alleviates this traction and reduces the pain. The second
theory is that the headache is due to reflex vasodilatation secondary to intracranial hypotension. This is supported
by the similar symptoms of PDPH and migraine headache, as well as MRI findings consistent with compensatory
venodilatation in patients with PDPH. Treatments based on each of these purported mechanisms have been utilized.
There are a number of risk factors for PDPH, some of which cannot be modified in a given patient. PDPH is more
likely in patients 20-40 years of age, in women compared to men, and in pregnant women compared to non-pregnant
age-matched controls. On the other hand, the incidence of PDPH is significantly decreased in obese patients.
The major modifiable risk factors for PDPH are the size and shape of the needle used to make the dural puncture. It
is difficult to compare the absolute incidence of headache with a given needle size across multiple studies, but there
is undoubtedly a decreased incidence of headache as needle size decreases from 17 gauge (50-60%) to 27 gauge
(0.5-1%). For a given needle size, the incidence of headache is considerably lower when a pencil point needle
(Whitacre, Sprotte, Gertie Marx) is used compared to a cutting edge needle (Quincke); for a 25 gauge needle, the
incidence of headache is 8.5% for a Quincke needle compared to 3% with a Whitacre needle (7). The reasons for
this difference are unclear, but it has been suggested that pencil-point needles produce a hole that heals more rapidly
than that produced by a cutting needle. There are other factors that influence the incidence of headache (orientation
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of the needle bevel, use of combined spinal-epidural anesthesia, paramedian approach) but these are considerably
less important than needle size and shape.
In patients who develop PDPH, the initial treatment is symptomatic, consisting of bed rest, oral analgesics, and
avoidance of dehydration. Forced intravenous hydration is not beneficial, as the production of CSF is not increased
by overhydration. None of these measures alters the disease process; they only provide symptomatic relief.
The supposition that PDPH is related to cerebral vasodilatation has encouraged the use of multiple cerebral
vasoconstrictors to treat the disorder. 500 mg intravenous caffeine benzoate has been shown to lead to permanent
resolution of symptoms in 70% of patients with PDPH (8). Intravenous preparations of caffeine are difficult to find,
and oral caffeine has been proposed as a substitute. Oral caffeine 300 mg has been shown to relieve symptoms, but
only temporarily; the eventual need for more aggressive therapy is unchanged compared to controls. Theophylline
and sumatriptan have been utilized in a small number of studies; the lack of a consistent response to these drugs
argues against their routine use.
When conservative treatment fails, the next step is usually an autologous epidural blood patch (EBP). This consists
of the epidural placement of 15-25 ml of the patient’s own blood, aseptically obtained, in close proximity to the
initial puncture site. This frequently leads to immediate relief, due to compression of the dural sac and subsequent
translocation of CSF from the lumbar region to the intracranial compartment. There is a more prolonged effect as
well, presumably due to the formation of a clot over the dural puncture, preventing further leak of spinal fluid. It is
difficult to make a specific recommendation about the optimal time for performing an EBP, but in the presence of a
severe disabling headache and in the absence of contraindications (maternal fever, localized infection), it is common
to perform the procedure 36-48 hours after the initial dural puncture.
Unfortunately, despite continuing enthusiasm for EBP, the success rate defined as complete, persistent pain relief
may be as low as 60-75% (9). Success rates appear to be improved when larger volumes of blood are used, and
when the patient is encouraged to lay supine for a longer interval (i.e. 2 hours) after completion of the EBP. Failure
to provide relief with an initial EBP, or recurrence of headache after an initially successful EBP, should lead to a
search for other possible causes of headache. If the presumptive diagnosis remains PDPH, a second EBP can be
performed. Fortunately, the great majority of headaches will resolve spontaneously, although this may be a
prolonged, difficult process for a new mother.
Catheter and needle related complications

On occasion, small spinal needle fragments or portions of epidural catheters break off and remain within a patient.
As distressing as this development may appear, these devices are biologically inert, and do not typically produce an
inflammatory response. In most cases, surgical exploration is neither simple nor even necessary, is often
unsuccessful, and therefore, in the absence of symptoms, these fragments can be left alone. A radiograph should be
obtained in order to demonstrate the location of the retained object, and the patient must be notified of this
occurrence and alerted of the need to report any future neurologic symptoms. Otherwise, no specific follow up
should be necessary.
Back pain
Early retrospective patient surveys suggested that the administration of epidural analgesia for labor contributed to
the development of persistent postpartum back pain. The problems with these studies are twofold; first, there is an
unknown degree of recall bias, that is, an increased likelihood that patients with back pain will complete and return a
survey instrument. Second, there is selection bias, in that patients who self-selected epidural analgesia might have
conditions that predispose to the development of persistent back pain. In more recent prospective studies, the
incidence of back pain in patients receiving epidural analgesia was increased only on the first postpartum day (10).
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Persistent back pain was unrelated to the use of epidural anesthesia; the strongest predictor of chronic back pain is a
history of antepartum back pain.
Obstetric nerve palsies

Not every neurologic deficit seen after regional anesthesia is a result of the regional anesthetic; some of these may
be due to pregnancy or childbirth itself. It is important to be able to identify the common obstetric nerve palsies,
both for medicolegal reasons, as well as to be able to provide a more accurate prognosis for recovery. Here follows
a description of the causes, anatomic considerations, and pattern of deficit seen with the common obstetric nerve
palsies (11).
Lumbosacral trunk injury-Anatomically, this injury is caused by compression of the lumbosacral trunk (consisting
of fibers derived from the L4 and L5 roots) by the fetal head at the sacral ala. Patients present with weakness of
ankle dorsiflexion and eversion (foot drop), and decreased sensation along the lateral aspect of the lower leg and the
dorsum of the foot. These findings are almost always seen on the side opposite the fetal occiput. Risk factors
include prolonged labor, a large fetus, and a flattened, wide posterior pelvis with pronounced sacroiliac joints. It
classically (but not exclusively) presents after mid-forceps rotation. Like the other obstetric nerve palsies, recovery
can be expected over a period of weeks to several months.
Common peroneal nerve palsy-This nerve injury occurs secondary to compression of the nerve against the fibular
head, usually due to poorly positioned stirrups when patients are placed in the lithotomy position. The presentation
is similar to lumbosacral trunk injury, but the area of decreased sensation is limited to the dorsum of the foot.
Meralgia paresthetica-Perhaps the most common of the obstetric nerve palsies, this injury is secondary to
compression of the lateral femoral cutaneous nerve under the inguinal ligament. There is a unique pattern of
decreased sensation in the superior portion of the anterolateral thigh. The major risk factor is prolonged
hyperflexion of the hips, as in the lithotomy position or when a McRobert’s maneuver is performed.
Femoral nerve palsy-The femoral nerve can be compressed within the pelvis by the fetal head or by retraction
during pelvic surgery. It can also be compressed more peripherally under the inguinal ligament due to exaggerated
hip flexion. This lesion presents with quadriceps weakness, perhaps most noticeable during stair climbing. There is
commonly a loss of sensation in a strip extending to the ankle.
Obturator nerve palsy-The rarest of the obstetric nerve palsies, caused by compression of the nerve within the
obturator canal. It is associated with diminished sensation on the upper inner thigh, and weakness of hip adduction
and rotation.
Evaluation of neurologic deficit after regional anesthesia
The most important step in evaluating a post-anesthetic neurologic deficit is to rule out a rapidly expanding mass
lesion, such as an epidural hematoma or epidural abscess. As cannot be overemphasized, the prognosis for recovery
decreases dramatically if compression is delayed for more than eight hours; urgent radiologic investigation should
not be delayed if there is any suggestion of spinal cord compression.
With a non-progressive deficit, investigation can occur at a more leisurely pace. History and physical examination
alone may be sufficient to make the diagnosis of an obstetric nerve palsy. The use of both routine lumbosacral films
and more advanced imaging techniques can be helpful in delineating the anatomic location of an injury.
Electromyography (EMG) can be helpful in defining both the anatomic and temporal location of a lesion, as
denervation potentials do not develop until two weeks after a nerve injury; the presence of such potentials soon after
a regional anesthetic suggests that the injury preceded the anesthetic.
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Local anesthetic neurotoxicity: 2-chloroprocaine

The ester local anesthetic 2-chloroprocaine (2-CP) is unique in its combination of extremely rapid onset, short
duration, and minimal systemic toxicity. However, it has been reported to produce significant neural toxicity when
large volumes are accidentally injected into the subarachnoid space. A widely accepted study suggested that the
cause of neural injury was a combination of low pH and the antioxidant sodium metabisulfite, and not 2-CP itself.
(12) As a result, 2-CP was reformulated in a less acidic solution without sodium metabisulfite. The newer
preparation utilized EDTA as an anti-oxidant. This preparation, unfortunately, was associated with a number of case
reports of severe back pain after injections of large volumes of the drug, presumably due to chelation of calcium and
subsequent tetanic contraction of paraspinous muscles. This led to another reformulation of the drug, which
currently does not contain any preservative or antioxidant. However, more recent work suggests that the role of
bisulfite has been overstated (13), and that 2-CP in fact does have intrinsic neurotoxicity. It thus remains critically
important that an epidural catheter should be demonstrated to be within the epidural space before large doses of
local anesthetics are injected.
Lidocaine and transient neurologic symptoms

The use of lidocaine for spinal anesthesia has been associated with the postoperative development of bilateral aching
pain in the buttocks, radiating into the sacral dermatomes of the legs, unassociated with any other motor or sensory
disturbances. It has been estimated to have an incidence of as high as 20%, and is seen more commonly in patients
who underwent procedures in the lithotomy position. Fortunately, it seems to be much less common in obstetric
patients, with an estimated incidence of no greater than 3% (14). Symptoms typically resolve within one week.
Despite the low incidence of this syndrome, however, some have recommended that the use of lidocaine be
abandoned in obstetric patients (15). When lidocaine is used, it should be diluted with an equal volume of CSF or
preservative free saline. The association of TNS with surgery performed in the lithotomy position suggests that its
use be avoided in cervical cerclage. (16)
References
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3. Birnbach DJ, Stein DJ et al. Povidone iodine and skin disinfection before initiation of epidural anesthesia.
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5. Bromage PR. Neurologic complications of labor, delivery, and regional anesthesia. In: Chestnut DH, ed.
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needles. Reg Anesth 1993; 18:166-9.
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cohort study. BMJ 1995; 311:1336-9.
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12. Gissen A, Datta S, Lambert D: The chloroprocaine controversy: II. Is chloroprocaine neurotoxic? Reg Anesth
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13. Taniguchi M, Bollen AW, Drasner K.‡ Sodium Bisulfite: Scapegoat for Chloroprocaine Neurotoxicity?
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symptoms? Anesth Analg 2001; 92:401-4.
15. Schneider MC, Birnbach DJ. Editorial: Lidocaine neurotoxicity in the obstetric patient: is the water safe?
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DISCLOSURE
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Post Dural Puncture Headache: How to Keep It the Patient's Headache

Robert R. Gaiser, M.D. Mount Laurel, New Jersey
The Problem
Headache remains a major problem to both the obstetrician and the obstetric anesthesiologist. Headache is
one of the most common symptoms encountered in the postpartum period. In a study of 95 postpartum parturients
with a headache lasting greater than 24 hours, 47% were due to tension/migraines, 24% to preclampsia, and 16%
were PDPHA.(1) When examining obstetric anesthesia claims from the Closed Claims Study, the proportion of
claims has not changed from the period before 1990 to the period 1990-2003(2) The third most common reason for
a claim was headache (14% of obstetric claims). Headache was more common than maternal death, back pain, and
maternal brain damage. Headache remains a problem even after the patient is discharged. Hayes, et al, reviewed the
records of those parturients who contacted the department after discharge. Of the 98 parturients who contacted after
discharge, 43 complained of headache (44%). Of these, only 4 were felt to be due to PDPHA (all received CSE).
Seven of the 43 patients received radiologic investigations; all were normal.(3) Academic anesthesiologists disclose
to patients that headache is the greatest risk of neuraxial anesthesia with an incidence of 1:100.(4)
Symptoms
The International Headache Society has defined a PDPHA as a bilateral headache that develops within 7
days after lumbar puncture and disappears within 14 days after the lumbar puncture. The headache worsens within
15 minutes of assuming the upright position and disappears or improves within 30 minutes of resuming the
recumbent position.(5). These symptoms are helpful in distinguishing from migraine headaches. PDPHA usually
occurs in the frontal, occipital, or both areas, but also may involve the neck and upper shoulders. Although it
generally occurs within 48 hours of the dural puncture, it can occur later than 3 days in 25% of the cases.(6) In
regard to duration, the largest study is by Vandam and Dripps.(7) They followed 8,460 patients who received
10,098 spinal anesthetics. The needles used were Quincke gauges 16 to 24. They reported that 72% of the
headaches resolved within 7 days and 87% by six months. The persistence of headache beyond 6 months has been
documented and has been successfully treated by epidural blood patch.(8) Duration of the headache is directly
related to the gauge of the needle causing the dural puncture.
Other symptoms include nausea, vomiting, neck stiffness, visual disturbances, and hearing alteration.
Visual disturbances (blurred vision or double vision) are due to dysfunction of the extraoccular muscles from
transient paralysis of the cranial nerves (CN) of the eyes (CN III, IV, and VI) due to traction from downward
displacement of the cranial contents.(19) CN VI is the most frequently affected because of its long intracranial
course. Hearing (CN VIII) is also affected. Fog performed audiograms preoperatively and 2 days postoperatively in
28 patients given spinal anesthesia.(10) In 14 patients, a 22-gauge Quincke needle was used and a 26-gauge
Quincke needle was used in the other 14 patients. Hearing alteration of 10 decibels or more was observed in 13/14
patients in the 22-g group and 4/14 patients in the 26-g group. The alteration tended to occur in the low-frequency
range. Alterations in hearing are variable and depend upon the patency of the adult cochlear aqueduct. If the
aqueduct is open, loss of CSF leads to an endolymphatic hydrops which affects the hair cells of the inner ear.(11)
Incidence
The incidence of accidental dural puncture (ADP) with an epidural needle is 1.5% but the incidence of
headache in the parturient depends upon the type of delivery.(12) The incidence of ADP in patients with prior
history of spine surgery is 2.7%.(13) The incidence of headache with a 16-gauge epidural needle is 88% and is 64%
with an 18-gauge Tuohy needle.(14) See Table
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Etiology
In the central nervous system, there is approximately 150 cc CSF. Of this CSF, 75 cc is located
supraspinally and 75 cc spinally. The production rate of CSF is approximately 0.35 ml/min.(15) It is believed that
PDPHA is due to leakage of CSF though the dural tear. Kunkle showed that in volunteers, removal of 10% of CSF
through a lumbar needle reliably produced a headache that was relieved by replacement with an equal volume
saline.(16) An extradural collection of CSF has been seen on MRI in a patient with a PDPHA.(17)
If the rate of leakage exceeds production, low CSF pressure results in a loss of the cushion effect provided
within the cranium. The decrease in CSF volume results in sagging of the brain in the cranial vault, pulling on the
falx cerebri, cerebral blood vessels and tentorium. In seven patients with positional headache, downward descent of
the brain was seen in five patients.(18) Another hypothesis is cerebral venous dilation. Loss of CSF causes a
decrease in CSF pressure without a decrease in intravenous pressure. The pressure difference causes these veins to
dilate. Paradoxical postural headache is felt to be due to this response, only exaggerated, resulting in the headache
being worse with standing and relieved by the supine position.(19) There is another component to PDPHA. A total
of 3730 epidural blocks were performed in 2955 patients.(20) The identification of the epidural space was by loss-
of-resistance to either saline or air using a total of 1-5 ml of either substance. In all patients with evident or
suspected ADP, a CT scan was immediately obtained. Although ADP occurred to a similar extent in both groups
(2.6% for air and 2.7% for saline), the incidence of headache was different, 66.7% for air and 9.8% for saline. In the
air group, supraspinal intrathecal air bubbles were found on CT examination in 78% of those with a PDPHA. Air
can enter the subarachnoid space with “nicking” the dura. The headache from intrathecal air was more rapid in
onset and has a shorter duration than a PDPHA. The entry of air into the intrathecal space when using LORA after a
previous dural puncture has been reported.(21) A meta-analysis comparing loss-of-resistance with air to saline
demonstrated no difference in adverse outcome when used for the obstetric patient.(22) If the provider chooses the
preferred medium (air vs saline), there is less attempts, fewer paresthesias, and fewer ADPs.(23) Furthermore, being
awake for 24 hours does not increase the number of attempts or success rate of epidural catheter placement in
parturients.(24)
Risk Factors
Not all patients who have dural puncture develop a PDPHA. The frequency of PDPHA is inversely
associated with age.(25) A meta-analysis comparing men vs women (excluding obstetric patients) demonstrated that
the odds of developing a PDPHA were significantly lower for men than women (odds ratio 0.55).(26) Men have a
larger cerebellar hemisphere resulting in a gender difference in the craniospinal junction.(27)
The greatest influence on the incidence of PDPHA is technique and choice of needle. Technique is
important for the Quincke needle, ensuring the direction of the bevel is parallel to the longitudinal axis of the dural
cylinder. The dura mater is a laminated structure built up from well-defined layers oriented concentrically with no
predominant direction to the fibers.(28) The cells of the arachnoid mater are oriented parallel to the long axis of the
spinal cord and parallel insertion my result in less disruption.(29) For epidural needles, bevel orientation is not as
important. Leakage from puncture with a 18-gauge Tuohy needle is similar whether the puncture is parallel or
transverse.(30) The thickness of the lumbar dura mater varies. The hole created when the needle penetrated a
thinner part of the dura mater resulted in a larger hole and greater leakage than when punctured in a thicker part.
For needle type, size of needle and needle design are important. Smaller needles have a lower incidence of
PDPHA, especially with the Quincke needle. Kang showed the incidence of PDPHA was 9.6% with the 26-gauge
needle and 1.5% with the 27-gauge.(31) Gauge is not as important for the pencil point needle. I feel that some of
the headaches from the pencil point needle are due to advancing the local infiltration needle too far. Absalom
described a case of cord injury when the local infiltration needle was inserted to the hub.(32) Another example
would be the occurrence of a PDPHA following acupuncture for the treatment of back pain.(33) For needle design,
the pencil point needles have a low incidence of PDPHA. Comparing 676 PS I or II patients undergoing spinal
anesthesia with either a 27-gauge Quincke or 27-gauge Whitacre needle, the incidences of PDPH in the Quincke and
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Whitacre groups were 2.7% and 0.37%, respectively.(34) The Practice Guidelines for Obstetric Anesthesia
recommend the use of the pencil-point needles to reduce the frequency of PDPHA.(35)
Another factor affecting the incidence of PDPHA after accidental dural puncture is management of the
second stage. In 33 patients with accidental dural puncture, 23 engaged in active pushing and 10 went to cesarean
section before pushing. 17/23 patients developed a headache in the pushing group and 1/10 in the nonpushing
group.(36) Active bearing down causes a marked increase in cerebrospinal fluid pressure and possibly leads to
greater CSF loss, accounting for the higher incidence in parturients.
A patient with a previous PDPHA is at risk for subsequent PDPHA. In 258 patients who received a repeat
spinal anesthetic, 42 had a previous PDPHA. Of these, 19% developed PDPHA again as compared to an incidence
of 6.9% in those who did not have a previous PDPHA.(37)
Prevention
Various maneuvers are used to prevent PDPHA and the majority are poorly supported by the literature. A
survey of practicing anesthesiologists in the United States revealed that the majority of hospitals do NOT have
written protocols for the management of unintended dural puncture.(38) Many recommend bed rest to prevent a
PDPHA. A systematic examination of recumbence showed no benefit.(39)
Following dural puncture during attempted epidural analgesia, a subarachnoid (SA) catheter may be passed.
Norris and Leighton failed to note any difference in the incidence or severity of PDPHA with a SA catheter.(40) In
this study, the catheter was pulled at the end of delivery. Ayad studied 115 parturients who had accidental dural
puncture.(41) The patients were randomized into one of three groups: resite the epidural catheter, SA catheter with
removal after delivery, and SA catheter with removal 24 hours after delivery. The incidence of PDPHA was 91.1%
in the resite group, 51.4% in the immediate group, and 6.2% in the delayed group. This data suggest the placement
of a SA catheter after the occurrence of a wet tap and leaving it in for 24 hours may be helpful. Extreme care should
be used when a SA catheter is left in place for 24 hours. A case report discussed a patient who had the catheter
adapter dislodge, resulting in a CSF leak while another presented a patient who developed meningitis.(42,43) The
use of SA catheters is increasing. No randomized study has demonstrated the effectiveness of intrathecal catheters.
An audit of a ten year experience failed to demonstrate a benefit to the intrathecal catheter.(44) In the US survey,
50% of practicing anesthesiologists would remove the intrathecal catheter after delivery.(37)
A randomized study compared 3 mg of preservative free morphine injected epidurally at delivery and 24
hours later in 50 parturients who had dural puncture. As compared to saline, there was a lower incidence of
headache (12% vs 48%) and a lower need for EBP (0 vs 6). There was also a higher incidence of pruritus in the
epidural morphine group.(45) Consyntropin 1.0 mg has been shown to decrease the incidence of PDPHA following
accidental dural puncture and to decrease the need for EBP.(46) The concerns with the study were the lack of
postulated reason for effectiveness as well as the lack of definition for PDPHA and for need for EBP.
Treatment
The treatment of PDPHA ranges from conservative to invasive. Conservative measures include bed rest,
analgesics, intravenous hydration, and other medications. Caffeine is commonly recommended for PDPHA because
of its ability to increase cerebral vascular resistance, decrease cerebral blood flow, and decrease cerebral blood
volume. The original study examining intravenous caffeine was published in 1978. The authors studied 1932
patients undergoing spinal anesthesia with a 22-gauge Quincke needle.(47) 41 patients developed PDPHA and were
randomized to either intravenous saline or intravenous caffeine benzoate 500 mg. Caffeine had an overall
effectiveness of 85%. To achieve this effectiveness, 2 patients required a repeat dose. There has been no study
examining its effectiveness for accidental dural puncture with an epidural needle. A review concluded that there is
no valid pharmacological rationale for caffeine as a treatment for PDPHA.(48)
It is thought that epidural saline increases pressure in the area and decreases the outflow of CSF. In 15
patients who had a PDPHA following dural puncture with a 25-gauge needle, 30 ml of saline administered
epidurally provided relief in 9/15 patients. No patient who had a PDPHA following dural puncture with a 17-gauge
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needle had relief.(49) Epidural saline provides temporary relief that disappears once the saline is absorbed.
In 1960, Gormley reasoned that blood could serve as the sealing material. In his report of 7 cases (one of
which was himself), 2-3 ml of blood injected into the lumbar epidural space at the same level as the dural puncture
was effective.(50) Crawford recommended up to 20 ml of blood, stopping if the patient complains of back or leg
pain. Using this method, he reported 97/98 had complete success.(51) Some practitioners recommend injecting
blood until the patient develops symptoms but a case report of hematoma in one patient and arachnoiditis in another
patient raises a concern with this practice.(52) A recent study upheld Crawford’s recommendation of 20 cc for an
EBP.(53) The postulated mechanism for its effectiveness is compression of the thecal space and elevating the
subarachnoid pressure. Maintenance of the therapeutic effect is attributed to clot preventing further CSF leak.(54)
Blood in the epidural space will spread between 7 and 14 spinal segments. The mean spread of blood is six
segments upward and three segments downward.(55) MRIs performed in two patients after 20 ml of blood being
injected into the lumbar epidural space revealed blood in the upper cervical region.(56) MRI shows the blood patch
as a large extradural collection mainly in the posterior space, with spread to the anterior epidural space as well as out
the intervertebral foramina and into the paravertebral space.(57) Complications of the EBP include back pain
(occurs during the first 48 hours in 35% of patients and persists in 16% of patients with a mean duration of 27
days)(58) and bradycardia(59). A previous EBP is not a contraindication to epidural anesthesia although EBP may
cause scarring in the space and ineffective anesthesia.(60,61) An EBP is contraindicated if the patient is febrile.
During an epidural blood patch, it is possible to inject the blood subarachnoid.(62) The literature concerning this
complication is scant. Subarachnoid injection may result in meningitis, arachnoiditis, or paresthesias. To give an
idea of the effectiveness of EBP, the number needed to treat to result in success is 1.(63) In the first randomized
trial of EBP, 42 patients with PDPHA following lumbar puncture with a 22-gauge Quincke needle were randomized
to conservative treatment or EBP. (64) EBP reduced the severity of PDPHA and resulted in quicker resolution. In
the literature, there are 5 patients who developed cerebral venous thrombosis after EBP. Pregnancy is associated
with a hypercoagulable state and it is unclear if this association of cerebral venous thrombosis with EBP is valid.(65)
The timing of the EBP is debated. Loeser noted a 71% failure rate if the epidural blood patch was done
within 24 hours of dural puncture as compared to a 4% failure rate if done greater than 24 hours. Subsequent studies
have also noted this finding.(66) The largest series consists of 504 patients. 75% achieved complete relief, 18%
incomplete relief, and 7% no relief.(67) Performing the EBP within 3 days was a risk factor for failure (odds ratio
2.63). Vilming et al questioned when should an EBP be done.(68) According to these authors, an EBP should be
performed after an initial observation period of 24 hours if the patient is symptomatic. This delay increases the
success rate while reducing the suffering of the patients. The optimal time to place an epidural blood patch is >24
hours after development of the PDPHA. This 24 hour delay is supported by a survey of Nordic countries.(69)
Given the improved outcome if the EBP is delayed, one would have to question the prophylactic EBP. A
prophylactic blood patch involves the injection of blood through the epidural catheter before the development of a
headache. 64 parturients with accidental dural puncture with a 17-gauge epidural needle were randomized either to
blood patch through a catheter or to sham blood patch (blood drawn but not injected).(70) There was no difference
between groups in the incidence of PDPHA or in the need for therapeutic blood patch. A Cochrane review did not
recommend prophylactic epidural blood patch and determined that therapeutic EBP to be beneficial.(71)
Conclusion
PDPHA continues to be a problem following neuraxial anesthesia. It is due to a decrease in CSF volume
and is not easily prevented. It is easily treated with an EBP. An EBP performed within the first 24 hours of PDPHA
may decrease its effectiveness.
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29. Richman JM, et al. Bevel direction and PPHA: a meta-analysis. The Neurologist 2006;12:224-228.
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31. Kang SB, et al. Comparison of 26- and 27-G needles for spinal anesthesia for ambulatory surgery patients.
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33. Horng HC, et al. Postdural puncture headache following acupuncture. J Anesthesia 2011;25:788-9.
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35. Practice Guidelines for Obstetric Anesthesia: An Updated Report by the American Society of
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41. Ayad S, et al. Subarachnoid catheter placement after wet tap for analgesia in labor: Influence on the risk of
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placed after accidental dural puncture. Reg Anesth Pain med 2005;30:591.
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44. Van de Velde M, , et al. Ten years of experience with accidental dural puncture and post-dural puncture
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45. Al-metwalli RR. Epidural morphine injections for prevention of post dural puncture headache.
46. Hakim SM. Cosyntropin for prophylaxis against postdural puncture headache after accidental dural
puncture. Anesthesiology 2010;113:413-20.
47. Sechzer PH, Abel L. Post-spinal anesthesia headache treated with caffeine. Evaluation with demand
method. Part 1. Current Therapeutic Research 1978;24:307-12.
48. Halker RB, Demaerschalk BM, et al. Caffeine for the prevention and treatment of postdural puncture
headache: Debunking the myth. The Neurologist 2007; 13: 323-7.
49. Bart AJ, Wheeler AS. Comparison of epidural saline placement and epidural blood placement in the
treatment of post-lumbar puncture headache. Anesthesiology 1978;48:221-3.
50. Gormley JB. Treatment of postspinal headache. Anesthesiology 1960;21:565-6.
51. Taivainen T, et al. Efficacy of epidural blood patch for postdural puncture headache. Acta Anaesthiol
Scand 1993;37:702-5.
52. Riley CA, et al. Complications following large-volume epidural blood patches for postdural puncture
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53. Paech MJ. The volume of blood for epidural blood patch in obstetrics: a randomized, blinded clinical trial.
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54. Rosenberg PH, Heavner JE. In vitro study of the effect of epidural blood patch on leakage through a dural
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55. Szeinfeld M, et al. Epidural blood patch: Evaluation of the volume and spread of blood injected into the
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56. Beards SC, et al. Magnetic resonance imaging of extradural blood patches: appearances from 30 min to 18
h. Br J Anaesth 1993;71:182-8.
57. Su CS, et al. Clinical features, neuroimaging and treatment of spontaneous intracranial hypotension and
magnetic resonance imaging evidence of blind epidural blood patch. European Neurology 2009;61:301-7
58. Abouleish E, et al. Long-term follow-up of epidural blood patch. Anesth Analg 1975;54:459-63.
59. Andrews PJD, et al. Transient bradycardia associated with extradural blood patch after inadvertent dural
puncture in parturients. Br J Anaesth 1992;69:401-3.
60. Hebl JR, Horlocker TT, Chantigian RC. Epidural anesthesia and analgesia are not impaired after dural
puncture with or without epidural blood patch. Anesth Analg 1999;89:390-4.
61. Collier CB. Blood patches may cause scarring in the epidural space: two case reports. Int J Obstet Anesth
2011;20:347-51.
62. Kalina P, et al. Intrathecal injection of epidural blood patch: a case report and review of the literature.
Emergency Radiology 2004;11:56-59.
63. Bussiere M, Wiebe S. The numbers needed to treat for neurological disorders. Can J Neurol Sciences
2005;32:440-9.
64. van Kooten F, et al. Epidural blood patch in post dural puncture headache: A randomized, observe-blind,
controlled clinical trial. J Neurol Neurosurg Psychiatry 2008;79:553-8.
65. Kueper M, Goericke SL, Kastrup O. Cerebral venous thrombosis after epidural blood patch: Coincidence
or causal relation? A case report and review of the literature. Cephalalgia 2008;28:769-773.
66. Loeser EA, et al. Time vs. success rate for epidural blood patch. Anesthesiology 1978;49:147-8.
67. Safa-Tisseront V, et al. Effectiveness of epidural blood patch in the management of post-dural puncture
headache. Anesthesiology 2001;95:334-9.
68. Vilming ST, et al. When should an epidural blood patch be performed in postlumbar puncture headache?
A theoretical approach based on a cohort of 79 patients. Cephalalgia 2005;25:523-7.
69. Darvish B, et al. Management of accidental dural puncture and post-dural puncture headache after labour:
a Nordic survey. Acta Anaesthesiol Scand 2011;55:46-53.
70. Scavone BM, et al. Efficacy of a prophylactic EBP in preventing post dural puncture headache in
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Incidence of PDPHA
Needle Type Gauge Incidence of PDPHA
Quincke 16 18%
Quincke 19 10%
Quincke 20 16%
Quincke 22 10%
Quincke 24 6%
Quincke 25 6%
Quincke 26 6%
Quincke 27 1.5%
Pencil Point 22 1.6%
Pencil Point 24 2%
Pencil Point 25 1.1%
Tuohy 16 88%
Tuohy 18 64%
Data is extrapolated from several various studies
DISCLOSURE
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Malpractice or Miscommunication? Lessons Learned to Improve Patient Safety

on the Labor and Delivery Suite.
David J. Birnbach, M.D. MPH Miami, Flordia
INTRODUCTION
Perceptions regarding the quality of healthcare in the US changed dramatically following the publication of Institute
of Medicine report titled “To Err is Human: Building a Safer Health Care System” in 1999 (1). Prior to that
publication, many patients and physicians did not realize that our healthcare system was often causing preventable
morbidity and mortality. We now know that many patients in the US die each year due to medical errors. A number
of changes have been advocated to improve patient safety, including mandating minimum nurse-to-patient ratios (2),
reducing working hours of resident physicians (3), and advances to the science of simulation and teamwork training
(4,5). This talk will review medical errors with an emphasis on the role of the anesthesiologist and also highlight
several modalities that can be used by labor and delivery personnel to reduce risk to patients, especially as relates to
errors caused by suboptimal communication.
PATIENT SAFETY IN OBSTETRICS
There has been a recent renewed interest in changing health care culture, so as to build safer systems, including
appropriate physical work environment, developing redundancies in safety procedures, having the ability to allow
health care workers to “painlessly” report their mistakes (including near misses) and to provide mechanisms to learn
from those experiences. Unfortunately, none of these systems will achieve the ultimate goal of patient safety
without the support from physicians as well as hospital leadership and administrators. Anesthesiologists may play a
vital role in this change in culture.
A recent American College of Obstetricians and Gynecologists (ACOG) Committee Opinion states that promoting
safety requires that all those in the healthcare environment recognize that the potential for errors exists and that
teamwork and communication are the basis for fostering change and preventing errors (6). The Committee
recommended the following seven objectives for safety:
1. Develop a commitment to encourage a culture of patient safety.

2. Implement recommended safe medication practices including improving legibility of handwriting and
avoiding use of non-standard abbreviations.
3. Reduce the likelihood of surgical errors.
4. Improve communication.
5. Identify and resolve system problems.
6. Establish a partnership with patients.
7. Make safety a priority in every aspect of practice.
An updated version of ACOG’s Optimal Goals for Anesthesia Care in Obstetrics also recommends good
interpersonal relations between obstetricians and anesthesiologists (7).
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MEDICAL ERRORS
The Institute of Medicine (IOM) has defined medical error as a “failure of a planned action to be completed as
intended, or the use of a wrong plan to achieve an aim.” Communication problems are consistently identified as a
leading cause of medical errors in obstetrics (8) and the Joint Commission reports that lack of effective
communication is often the primary reason for sentinel events (9).
Traditional medical and nursing education has relied on the treatment of real patients in actual clinical settings.
There is a belief now that the current availability of medical simulations and the knowledge gained from the science
of team training may improve patient outcomes, and there is a paradigm shift occurring in many universities and
training programs. Many medical and nursing schools have purchased simulators and are increasingly using them in
undergraduate and graduate education.
TEAMS and TEAMWORK
Healthcare can be considered a team activity. Teams take care of hospitalized patients. Furthermore, healthcare
teams operate in an environment characterized by acute stress, heavy workload, and high stakes for decision and
action errors (10). Individuals have limited capabilities. When the limitations are combined with organizational and
environmental complexity, human error becomes virtually inevitable (11). The labor and delivery suite is a
particularly complex and stressful environment. In fact, the labor and delivery suite requires intense, error-free
vigilance with effective communication and teamwork between many different clinical disciplines who while
working together, have probably never trained together. The group includes obstetricians, midwives, labor nurses,
operating room staff, anesthesiologists, and pediatricians (12).
What is teamwork? It can be defined as a “set of interrelated behaviors, actions, cognitions and attitudes that
facilitate the required task work that must be completed.” (13) Lack of teamwork has been identified as leading
sources of adverse events in medicine. Team behavior and coordination, particularly communication or team
information sharing, are critical for optimizing team performance (14). Baker and colleagues have stated that to
work together effectively, team members must possess specific knowledge, skills and attitudes (KSAs) such as the
skill in monitoring each other’s performance, knowledge of their own and teammate’s task responsibilities, and a
positive disposition toward working in a team (15). These authors have described characteristics of effective teams,
which include team leadership, mutual performance monitoring, backup behavior, adaptability, shared mental
models, communication, team/collective orientation, and mutual trust. Moreover, effective team performance in
complex environments requires that team members hold a shared understanding of the task, their equipment, and
their teammates (16). Salas and colleagues (17) have defined the characteristics of effective teams, as highlighted in
Table 1.
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Table 1
Characteristics of Effective Teams
Knowledge/Skills/Attitudes Characteristic of Team
Leadership Roles clear but not overly rigid

Team members believe leaders care about them
Backup Behavior Members compensate for each other

Provide feedback to each other
Mutual Performance Monitoring Members understand each other’s roles
Communication Adaptability Members communicate often, anticipate each other
Mutual trust Trust each other’s intentions
There is a clear difference between the leadership of individuals versus team leadership. One who is leading
independent individuals will diagnose a problem, generate possible solutions, and implement the most appropriate
solution. Team leadership, conversely, does not usually involve handing down solutions to individual team
members, but rather defining team goals, setting expectations, coordinating activities, organizing team resources,
and guiding the team toward their goals (18).
Team leaders can improve team performance in many ways, such as by promoting coordination and cooperation.
These individuals must not only be technically competent, but they must also be competent in leadership skills (19).
But when do anesthesiologists and other physicians learn to be competent team leaders? If not taught to
undergraduate medical students, are these skills taught in residency programs? Unfortunately, the answer is all too
often a resounding “no”. Many of the tasks necessary can and must be learned during residency training. Simulation
therefore plays a key role in this education and may thus reduce errors (20). Team leadership training has been
developed to successfully train specific team leader behaviors. The implementation of these programs has been
shown to increase team performance (13). The Joint Commission has recommended a risk-reduction strategy for
decreasing perinatal death or injury. This strategy includes the implementation of team training and mock
emergency drills for shoulder dystocia, emergency cesarean delivery, and maternal hemorrhage (21).
The IOM has also recommended that team training and implementation of team behaviors could improve patient
safety (22). In a recent editorial, Murray and Enarson stated that “when a crisis complicates patient care, teamwork
among healthcare professionals is frequently strained, resulting in more frequent as well as more serious failures in
managing critical events.” (23) Team training promotes the acquisition of adaptive behaviors, shared cognitions and
relevant attitudes and is an instructional strategy that ideally combines practice-based delivery methods with realistic
events guided by medical teamwork competencies (i.e., the behaviors, cognitions, and/or attitudes).
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TEAM TRAINING
Patient safety is “predicated on trust, open communication, and effective interdisciplinary teamwork.” (24) It is
often the interactions of healthcare workers that produce effective or ineffective performance (25). But where do
medical students, residents, attending physicians, nursing students, nurses, and midwives learn to work as team
members?
Thomas and colleagues conducted a qualitative assessment of teamwork and suggested that factors which influence
the ability to work together could be divided into 3 categories: (1) provider characteristics (personal attributes,
reputation, expertise); (2) workplace factors (staffing, work organization, work environment); and (3) group
influences (communication, relationships, and team) (26). These categories can be addressed, at least in part, by
working together in teams in a simulated environment and evaluating teamwork and human performance. Lyndon
has suggested that the application of human performance-based theory has demonstrated that “communication
patterns, team function, workload, and coping mechanisms affect both individual and group ability to identify
evolving problems and make appropriate management decisions in complex decision-making situations” (27).
Why is teamwork training important for Labor and Delivery personnel? As previously described, communication
problems are consistently identified as a leading cause of medical error. Many of these communication issues can be
addressed during team training. The recent Confidential Enquiry in Maternal Deaths in the UK has emphasized that
“emergency drills for maternal resuscitation should be regularly practiced in clinical areas in all maternity units”
(28). We know from research that when trainees have an opportunity to practice relevant competencies in a
structured scenario and get diagnostic feedback on their individual and collective performance, it works. A recent
review of a comprehensive obstetrics patient safety program which included labor and delivery team training
reported a decrease in number of sentinel events as well as a decrease in compensation payments (29).
SIMULATION-BASED TRAINING IN L&D

Do “drills” work? According to the Agency for Healthcare Research and Quality (AHRQ), “drills that are carefully
planned can decrease medical errors by addressing unintended events that may result in injury to a patient arising
from unintentional actions, mistakes in judgment, or inadequate plans of action”
http://www.qualityindicators.ahrq.gov). It has been suggested that simulation can be used as an educational tool to
assist in transfer of knowledge, practicing diagnostic skills, surgical skills training, emergency drill training, and
human factors and team training (30). Chopra and colleagues have reported that training with high fidelity
simulation improves the speed with which anesthesiologists respond to emergencies and the quality of their care
(31).
Simulation of L&D events can range from high fidelity human simulators (often located off site) to low tech
simulations and drills, that can often be done in the L&D suite (32). L&D events that are commonly addressed
include maternal hemorrhage (antepartum as well as postpartum), failed intubation, failed neuraxial block, seizure,
cardiac arrest, anaphylaxis, cord prolapse, and shoulder dystocia.
Obstetricians, anesthesiologists, pediatricians, labor nurses, midwives, and OR staff all work together as part of a
system and when an error occurs, it is usually associated with the system. Therefore, optimal simulation exercises
involve all these key players and evaluate not only their behaviors and communication skills, but also problems
within the system in which they work. Simulation allows the re-creation of a labor and delivery room or operating
room, where reality-based scenarios can be recreated allowing anesthesiologists, obstetricians, midwives, nurses,
and pediatricians to practice their roles and communication skills.
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Both high tech and low tech approaches to simulation have been utilized for training Labor and Delivery staff.
Simulation centers often use high fidelity simulation with interactive computerized mannequins in a realistic
environment. The mannequin is quite realistic and has pulses, O2 saturation, heart and breath sounds, ventilatory
movements and electrocardiogram tracing. All vital signs can be adjusted via computer control, as can the ability to
intubate or ventilate. Not all simulation exercises and drills for obstetrics need to be performed in high fidelity
simulators and some authors have advocated classroom training as superior (33). The inability to arrange for staff of
several disciplines to be off the L&D floor simultaneously often precludes the use of high tech simulation and may
make on-site exercises advantageous (34).
Some authors believe that classroom training may be advantageous and it has been suggested that high fidelity
simulation is too expensive (35). Gaba, however, has countered by stating that simulation need not be cost-
prohibitive and that it provides the required “real-life” experience necessary for training of complex real-life
scenarios (36). Morgan et al have reported on an obstetric model that allowed a more realistic participation of real
surgeons (rather than actors playing the role of surgeons) in a simulated scenario (37).
There are several available options for teaching teamwork and crisis intervention in obstetrics. Multi-disciplinary
obstetric simulated emergency scenarios (MOSES) was first reported by the St. Bartholomew Hospital Group in
2002. (38) Obstetricians, anesthesiologists and midwives participated in team training on a high fidelity simulator.
MedTeams was developed by the US Armed Forces and Dynamics Research Corporation. Originally described in
Emergency Departments (39, 40) it has now been used for labor and delivery teams (12). AHRQ and the
Department of Defense have teamed to build a teamwork system termed Team Stepps to improve communication
and teamwork skills among health care professionals (41). This program has also become a popular tool for
obstetrics team training. A recent review on the use of simulation as part of a comprehensive patient safety program
concluded that following simulation-based training, “the evidence is overwhelming that, with practice, obstetricians
improve their technical and communication skills” (42).The same is no doubt true for anesthesiologists and labor
nurses, as well as for multi-disciplinary teams.
Conclusions
The data in support of the use of medical simulation and team training in Labor and Delivery is very encouraging.
These modalities improve teamwork and communication and allow recognition of potential areas of weakness.
Despite a somewhat yet unproven track record for objective findings of improved patient safety, many authors
similarly believe that team training is essential in the healthcare arena (43, 44).
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system. Washington DC. National Academy Press, 2000.
2. Aiken LH, Clarke SP, Slonae DM et al. Hospital nurse staffing and patient mortality, nurse burnout and job
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3. Landrigan CP, Rothschild JM, Cronin JW et al. Effect of reducing interns’ work hours on serious medical
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4. Gaba DM. Anaesthesiology as a model for patient safety in health care. BMJ 2000;320:785-88.
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6. ACOG Committee Opinion Number 286. INnt J Gynaecol Obstet 2004;86:121-3.
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8. Simpson KR, Knox GE. Adverse perinatal outcomes. Recognizing, understanding & preventing common
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9. Joint Commission. Root cause of sentinel events, all categories: 1995-2004
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10. Salas E, Rosen MA, King H. Managing teams managing crises: principles of teamwork to improve patient
safety in the Emergency Room and beyond. Theoretical issues in Ergonomics Science 2007;8:381-94.
11. Wilson KA, Burke CS, {riest HA, Salas E. Promoting simulation-based training through high reliability
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12. Nielsen PE, Goldman MB, Mann S et al. Effects of teamwork training on adverse outcomes and process of
care in labor and delivery. A randomized controlled trial. Obstet Gynecol 2007;109:48-55.
13. Salas E, Guthrie JW, Wilson-Donnelly KA, Priest HA, Burke CS. Modeling team performance: The basic
ingredients and research needs. Chapter 7. Organizational Simulation. Rouse WB ed. Wiley and Sons, NJ,
2005.
14. Blum RH, Raemer DB, Carroll JS, Dufresne RL, Cooper JB. A method for measuring the simulation-based
team training for improving communication skills. Anesth Analg 2005;100:1375-80
15. Baker DP, Day R, Salas E. Teamwork as an essential component of high reliability organizations. Health
Service Res 2006;4;1576-98.
16. Salas E, Rosen MA, Burke CS, Nicholson D, Howse WR. Markers for enhancing team cognition in
complex environments: the power of team performance diagnosis. Aviation Space Environ Med
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17. Salas E, Sims DE, Klein C. Cooperation and teamwork at work. In Encyclopedia of Applied Psychology.
Vol1. Edited by Spielberger CD. P499-505. San Diego: Academic press. 2004
18. Salas E, Wilson-Donnelly KA, Sims, DE, et al. Teamwork training for patient safety: Best practices and
guiding principles. From: Teamwork Training for Patient Safety. Chapter 44.
19. Salas E, Rosen MA, King H. Managing .teams managing crises: principles of teamwork to improve patient
safety in the Emergency Room and beyond. Theoretical Issues in Ergonomics Science. 2007;8;381-94.
20. Birnbach DJ, Salas E. Can medical simulation and team training reduce errors in labor and delivery.
Anesthesiology Clinics 2008;26:159-168.
21. Joint Commission on Accreditation of Healthcare Organizations. JCAHO Sentinel Event Alert #30, 2004.
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21st century. Washington, D.C., National Academy Press, 2001.
23. Murray D, Enarson C. Communication and teamwork: essential to learn but difficult to measure.
24. Simpson KR, James DC, Knox GE. Nurse-physician communication during labor and birth: implications
for patient safety. JOGNN 2006;35:547-56.
25. Rosen MA, Salas E, Wilson KA, King HB, Salisbury M, Augenstein JS, Robinson DW, Birnbach DJ.
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Measuring team performance in simulation-based training: adopting best practices for healthcare. Sim
Healthcare 2008;3:33-41.
26. Thomas EJ, Sherwood GD, Mulhollem JL, Sexton BJ, Helmreich RL. Working together in the neonatal
intensive care unit: provider perspectives. J Perinatol 2004;24:552-59.
27. Lyndon L. Communication and teamwork in patient care: how much can we learn from aviation? JOGNN
2006;35:538-46.
28. RCOG. Why Mothers Die 2000-2002, the Confidential Enquiries into Maternal Deaths in the United
Kingdom. London, RCOG Press 2004, pp96-101.
29. Grunebaum A, Chervenak F, Skupski D. Effect of a comprehensive obstetric patient safety program on
compensation payments and sentinel events. Am J Obstet Gynecol. 2011;204(2):97-105.
30. Johannson H, Ayida G, Sadleer C. Faking it? Simulation in the training of obstetricians and gynecologists.
Current Opin Obstet Gynecol 2005;17:55-61.
31. Chopra V, Gesnik BJ, DeJong J, et al. Does training on an anaesthetic simulator lead to improvement in
performance? Br J Anaesth 1994;73:293-7.
32. Sorensen SS. Emergency drills in obstetrics: reducing risk or perinatal death or permanent injury. JONAS
Healthc Law Ethics Regul 2007:9;9-16.
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34. Sorensen SS. Emergency drills in obstetrics: reducing risk of perinatal death or permanent injury. JONAS
Healthc Law Ethics Regul 2007:9;9-16.
35. Kurrek MM, Devitt JH. The cost for construction and operation of a simulation centre. Can J Anaesth
1997;44:1191-5.
36. Gaba DM. Two examples of how to evaluate the impact of new approaches to teaching. Anesthesiology
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37. Morgan PJ, Pittini R, Regehr G, Marrs C, Haley MF. Evaluating teamwork in a simulated obstetric
environment. Anesthesiol 2007;106:907-15.
38. Davis C, Gregg A, Thornley D. Initial feedback on MOSES (multidisciplinary obstetric simulated
emergency scenarios): a course on team training, human behaviour and “fire drills.” Anesthesiol
2002;96:A
39. Morey JC, Simon R, Jay GD, et al. Error reduction and performance improvement in the emergency
department through formal teamwork training: evaluation results of the MedTeams Project. Health Serv
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40. Simon R, Salisbury M, Wagner G. MedTeams: teamwork advances emergency department effectiveness
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41. http://teamstepps.ahrq.gov/index.htm
42. Argani CH, Eichelberger M, Deering S, Satin AJ. The case for simulation as part of a comprehensive
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of health-care professionals. J Am Coll Surg 2004;199:843-8.
DISCLOSURE
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Thrombocytopenia and Low Molecular Weight Heparin in the Parturient:

Implications for Neuraxial Anesthesia
Yaakov Beilin, M.D. New York, New York
Introduction
Neuraxial analgesia is routinely administered to the parturient. A devastating, albeit rare, complication of
neuraxial anesthesia is spinal or epidural hematoma, and primarily occurs in patients with disorders of hemostasis.
A parturient with a clinically active coagulation disorder, or someone with a history of easy bruising and/or
bleeding, is considered to have an absolute contraindication to regional anesthesia. However, many areas of
controversy exist. The concern most anesthesiologists have regarding thrombocytopenia is determining the lowest
platelet count at which it is still safe to perform a neuraxial anesthetic technique. In addition, an increasing number
of women are receiving anticoagulant medications during pregnancy and low molecular weight heparin (LMWH) is
a commonly used agent. During this lecture I will review the role of platelets in the coagulation process, the most
common disorders in pregnancy that lead to thrombocytopenia, the laboratory tests available to assess platelet
function and provide practical recommendations as to the anesthetic management of the parturient with
thrombocytopenia and one who is taking LMWH.
Thrombocytopenia and neuraxial anesthesia

Platelet counts generally decrease by approximately 20% during a normal pregnancy. This decrease is
usually not clinically significant and does not generally impact on the decision to place an epidural anesthetic.
However, approximately 7% of all parturients will present with a platelet count < 150,000·mm-3, and 0.5-1% will
present with a platelet count < 100,000·mm-3.1
An epidural or spinal hematoma can be a catastrophic complication and can lead to permanent paralysis. In
1988, Cousins and Bromage recommended that one should not place an epidural catheter if the platelet count is less
than 100,000·mm-3.2 Recently, their recommendation has been challenged, primarily because thrombocytopenia
occurs frequently during pregnancy1 and neuraxial anesthesia is safer than general anesthesia for the parturient.3 An
absolute platelet count below which a neuraxial anesthetic is considered unsafe would lead to more frequent use of
general anesthesia, which is far riskier in the parturient.
Hawkins et al.3 reviewed pregnancy-related deaths in the United States between 1985 and 1990 and found
that the anesthesia-related maternal mortality rate was 32.3 deaths per million in parturients who had general
anesthesia for cesarean delivery, but only 1.9 deaths per million in women who had regional anesthesia. There is an
increasing trend to use regional anesthesia in the parturient, so an absolute conservative cut-off for a sufficient
platelet count is not prudent. Failure to provide neuraxial anesthesia during labor and delivery based solely on a low
platelet count commits the patient, at a minimum, to a painful labor. Furthermore, if the woman later requires a
cesarean delivery, perhaps emergently, the anesthesiologist may then be forced to administer an anesthetic under
less than optimal conditions.
Coagulation
Clotting can be thought of as occurring in two phases, primary and secondary hemostasis. Primary
hemostasis refers to the creation of the initial platelet plug and secondary hemostasis refers to the creation of the
stable fibrin clot. Platelets play an important role in both processes. Generally, blood vessels prevent platelet
adhesion by releasing a potent vasodilator, prostacyclin. After vessel wall injury, prostacyclin levels decrease
allowing platelets to adhere to the vessel wall. This adhesion leads to activation and degranulation of platelets with
release of adenosine 5-diphosphate (ADP), serotonin and thromboxane, which then leads to platelet aggregation.
Further aggregation leads to formation of a platelet plug. This plug is unstable and requires fibrin deposition to
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make it more stable, which occurs by activation of the intrinsic and/or extrinsic coagulation system. Platelets
provide the phospholipid membrane on which the coagulation cascade occurs.
Platelet abnormalities can be qualitative or quantitative and are the most common hematologic disorders
during pregnancy. Most cases (99%) of thrombocytopenia during pregnancy are related to one of three causes:
gestational thrombocytopenia (74%), hypertensive disorders such as preeclampsia (21%), and immune
thrombocytopenic disorders of pregnancy such as idiopathic thrombocytopenic purpura (ITP) (4%).4 When
evaluating the parturient with thrombocytopenia, there are two specific issues to consider. The first concern is
whether the disorder is static or dynamic. If the disorder is static, as occurs during gestational thrombocytopenia or
ITP, the platelet count is usually stable. If the disorder is dynamic, as occurs during preeclampsia, the platelet count
may rapidly change and it is important to obtain serial platelet counts. The second issue is whether platelet function
is normal or abnormal. Platelet function is typically normal in gestational thrombocytopenia and ITP, and may be
abnormal in preeclampsia.
The parturient with thrombocytopenia is difficult to evaluate with standard laboratory tests because both
platelet quantity and quality must be assessed. Tests of platelet function have been criticized for being difficult to
perform, for lacking reproducibility and being of questionable clinical relevance. The ideal test should be easy to
perform, inexpensive, would not require specialized equipment and the results could be reproduced and correlated
with outcome. Bedside tests of coagulation include the bleeding time, thromboelastography (Haemoscope
Corporation, Skokie, IL), and the Platelet Function Analyzer, PFA-100 (Dade Behring, Newark, DE).
The bleeding time is a simple bedside test that evaluates both the quality and quantity of the platelets. A
small skin nick is made with a template on the volar surface of the forearm and the time until the blood clots is
calculated. A bleeding time of less than 10 minutes is considered normal. Anesthesiologists formerly used the
bleeding time to assess the safety of epidural or spinal placement. If the results of the bleeding time were normal,
they would proceed with neuraxial anesthesia, and if the results were abnormal, they would not. However, the
bleeding time is no longer recommended to determine the safety of epidural catheter placement because bleeding at
the test site does not necessarily reflect the risk of bleeding at other sites,5,6 and there is also wide observer
variation.7 O’Kelly et al.7 asked twelve observers to assess the bleeding time on five separate volunteers and the
reliability of the measurements obtained was poor. Although no longer recommended, a survey by Beilin et al.8 in
1996 found that 48% of anesthesiologists in academic practice and 76% in private practice still used the bleeding
time to assist them in deciding whether to place a neuraxial anesthetic in the parturient with thrombocytopenia.
The thromboelastogram (TEG) measures all phases of coagulation and fibrinolysis by using less than 1 mL
of a whole blood sample to measure the elasticity of clotting blood. Blood is placed in a cylindrical cup that
oscillates. A pin is then suspended in the blood by a torsion wire and is monitored for motion. The torque of the
rotating cup only affects the pin after fibrin-platelet bonding has linked the cup and pin together. The strength of the
developing clot affects the magnitude of the pin motion such that strong clots move the pin directly in phase with the
cup, and weak clots do not. The resulting profile is a measure of the time taken for the first fibrin strand to form,
and the kinetics, strength, and breakdown of the clot (Figure). The maximum amplitude (MA) has been found to
correlate best with platelet function.
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Orlikowski et al.9 measured platelet counts, TEG parameters and bleeding time in healthy pregnant women
and in those with preeclampsia. They found that the MA remained normal (53 mm) until the platelet count
decreased to less than 54,000·mm-3 (95% confidence limit 40-75,000·mm-3). Based on their study, they suggested
that a platelet count of 75,000·mm-3 should be associated with adequate hemostasis. However, there is no clinical
evidence that a normal MA correlates with safe epidural analgesia.
The PFA-100 is an intriguing test because it is specific to platelet function, the primary disorder in
preeclampsia. The machine simulates the in-vivo hemostatic mechanism of platelet function by accelerating citrated
whole blood through a small, 150 micrometer, aperture cut into a collagen membrane. The collagen membrane is
coated with one of two platelet activators, epinephrine or ADP. The collagen membrane cartridges are named for
the platelet activator that coats them, CEPI or CADP, respectively. The time taken for the aperture to close is called
the closure time (CT). This machine is commonly used by hematologists as a screening tool for patients who
present with unknown coagulopathies and is especially sensitive for the detection of Von Willebrand disease.10
Some have found a correlation between an increasing CT and decreasing platelet count,11 however, this has not been
confirmed in all studies.12
The overall risk of epidural or spinal hematoma following neuraxial anesthesia is in the range of 1:150,000-
220,000.13 Vandermeulen et al.13 reviewed the literature and found 61 cases of anesthesia-related spinal hematoma.
Most (68%) occurred in patients with coagulopathies, and 75% of all cases had an epidural rather than a spinal
anesthetic. Of those who received an epidural anesthetic, 88% had an epidural catheter inserted and almost 50% of
those patients developed an epidural hematoma following catheter removal.
This author is aware of ten reports in the literature of neuraxial (spinal or epidural) hematoma occurring in
parturients and only one in a woman with preeclampsia with thrombocytopenia.14-23 This woman had an epidural
anesthetic with 13 mL of bupivacaine 0.5% for uneventful cesarean delivery, but had a seizure in the recovery room
one hour after the procedure. It was noted that her legs did not move and a CT scan revealed an epidural collection
of fluid. A laminectomy was performed six hours after epidural catheter placement at which time four mL of blood
were drained. The patient recovered 72 hours later. Whether the four mL of epidural blood was sufficient to cause
her symptoms is unknown; it is possible that the symptoms were related to residual local anesthetic effects.23
The origin of the recommendation to not place an epidural catheter if the platelet count is < 100,000·mm-3
may be related to a study demonstrating that the results of the bleeding time are not prolonged until the platelet
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count falls below 100,000·mm-3.24 However, we are now aware that the bleeding time test is not reliable. The
safety of initiating an epidural anesthetic when the platelet count is < 100,000·mm-3 is supported by the results of
three retrospective studies.1,25,26 In the largest study, Beilin et al.1 reviewed the medical records of 15,919
consecutive parturients during a three-year period. They found 80 women who presented with a platelet count <
100,000·mm-3, and thirty of these women received an epidural anesthetic without sequelae. None of these 30
women had a decreasing platelet count at the time of epidural catheter placement and none had clinical evidence of
bleeding. Five women were denied an epidural anesthetic because of decreasing platelet counts and two because of
clinical evidence of bruising. There is also one case report of a woman who safely received an epidural anesthetic
without prior knowledge of a platelet count of 2,000·mm-3.27
Most authors do not define a minimum platelet count below which it is unsafe to perform an epidural
anesthetic. Indeed, each patient must be individualized and the responsible anesthesiologist must weigh the risks
versus the benefits. Based on the results of the survey by Beilin et al.8, most anesthesiologists (66% of those in
academic practice and 55% of those in private practice) will perform an epidural anesthetic when the platelet count
is between 80,000 and 100,000·mm-3. Below 80,000·mm-3, most were unwilling to place an epidural catheter.
Practical recommendations
A routine platelet count is not necessary in the otherwise healthy parturient and should be drawn based on
patient history, physical examination and clinical signs.28 If the platelet count is found to be low it is important to
confirm this finding since automated counters can be unreliable, especially at lower platelet counts. A manual count
should be undertaken as it is not uncommon to find the platelets are clumping and the count is really greater than
calculated.29 The patient history and physical examination are key components when deciding whether to proceed
with a regional anesthetic in the parturient with thrombocytopenia. Consultation with a hematologist, preferably
prior to labor, can also help with assessing the etiology of thrombocytopenia and determining whether the platelets
are functioning adequately. If there is any history of easy bruising, or the patient has evidence of petechiae or
ecchymosis, regional anesthesia should not be offered. If the patient has no bleeding history, then our general
practice is to obtain at least one additional platelet count as close in time to epidural catheter placement as possible
to ensure that it is not decreasing further. This is especially important for disease processes that are dynamic, such
as preeclampsia. We do not obtain any bed-side tests of platelet function nor do we have any absolute platelet count
cut-off. A patient with a stable platelet count of 50,000·mm-3, as seen in ITP, is probably at lower risk than one with
a platelet count of 75,000·mm-3 that is rapidly decreasing, as seen in preeclampsia. In general this author will place
an epidural catheter in a woman with a stable platelet count of approximately 75,000 mm-3 and some are
comfortable with lower platelet counts especially in women with ITP.30 There is no absolute cut-off and the risks of
epidural placement versus general anesthesia has to be individualized and informed consent must be obtained.
If the decision is made to proceed with neuraxial anesthesia, a subarachnoid block using a small gauge
spinal needle may be preferable to epidural anesthesia. This is not always possible, especially for women in labor
who will require repeated doses of local anesthetic. If possible, the newer flexible soft-tip epidural catheters should
be utilized as they are associated with a smaller incidence of inadvertent placement into a blood vessel.31 The
epidural catheter should be placed in the midline and analgesia produced with the lowest concentration of local
anesthetics, so as to preserve motor function. The patient should be examined periodically to assess the extent of the
motor block, and these examinations should continue until after the anesthetic has worn off and the catheter has been
removed. In this way, if the patient develops a motor block out of proportion to what one would expect, or if the
anesthetic has a prolonged duration of action, the patient can be immediately assessed with magnetic resonance
imaging (MRI) for the development of an epidural hematoma. Immediate evaluation is necessary because if the
patient has an epidural hematoma, an emergent laminectomy and decompression must be performed as soon as
possible, preferably within 8 hours, hours to preserve neurologic function.13 If the patient has an epidural catheter in
situ and develops a coagulopathy, the catheter should be removed only after the coagulation status is corrected.13
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Low molecular weight heparin

The release of low molecular weight heparin (LMWH) for general clinical use occurred first in Europe in
1987, and then in the United States in 1993. From May 1993 to February 1998, there were over 40 reports of spinal
or epidural hematoma in conjunction with LMWH use in the U.S.32 Emergency laminectomy was performed in 28
patients, and 16 of these patients suffered permanent paraplegia. The American experience contrasted sharply with
the 1992 European data where Bergqvist et al.33 showed a greater margin of safety with LMWH. They reviewed
forty-four controlled studies involving LMWH and epidural analgesia and were not able to find any reported case of
spinal hematoma among 10,000 cases. Furthermore, they estimated that LMWH has been used in conjunction with
spinal/epidural anesthesia in almost one million patients and there is only one case report of an epidural hematoma.34
These discrepancies prompted a reevaluation of the risks, benefits and uses of LMWH in conjunction with neuraxial
anesthesia.
Standard, unfractionated heparin (UH) is a mixture of linear polysaccharide chains, with a molecular
weight that ranges from 5,000 to 30,000 daltons. Heparin acts as an anticoagulant by binding to antithrombin III
and potentiates the inhibition of factors IIa (thrombin), IXa, Xa, XIa and XIIa. A specific pentasaccharide sequence
on the heparin chain has a high-affinity binding site for antithrombin III, but only about 30% of the heparin
molecule has this sequence. In order to catalyze inhibition of factor Xa, only the pentasaccharide binding sequence
is necessary. But to catalyze inhibition of factor IIa, a heparin molecule must contain both this high-affinity
pentasaccharide sequence and an additional chain of at least thirteen sugars.35 UH is highly sulfated and negatively
charged; as a result, it has a great affinity for plasma proteins and vascular matrix proteins, and has less than a 30%
bioavailability.
LMWH is produced by chemical or enzymatic depolymerization of standard heparin, which produces
shorter polysaccharide chains of 13 to 22 sugars and a molecular weight of 4,000 to 6,000 daltons.36 LMWH has the
same anti-Xa activity as standard heparin with less anti-IIa (thrombin) activity. The concentration of LMWH is
referred to in international standards and expressed as anti-Xa units per millimeter. The reduced molecular size
leads to lower binding to plasma and endothelial cell proteins. This results in greater than 90% bioavailability after
subcutaneous injection, a longer plasma half-life (4-6 hrs versus 0.5-1 hrs for standard heparin) and a predictable
and reproducible dose response.37 Laboratory monitoring is not required. The peak LMWH anti-Xa activity occurs
3-4 hours after subcutaneous injection, and at 12-hour anti-Xa levels are approximately 50% of peak levels. LMWH
excretion is accomplished almost solely by the kidneys. Protamine sulfate is able to neutralize 100% of anti-IIa
activity but only 60-70% of anti-Xa activity, and therefore is not effective at neutralizing LMWH effects.
Pregnancy induces a hypercoagulable state. Although the incidence of thromboembolic complications is
rare, they are a major cause of maternal morbidity. Some parturients require anticoagulant medication during the
antepartum period, for example those with disorders of hemostasis or mechanical heart prostheses, or those at high
risk for venous thromboembolism. Additionally, anticoagulant medication is used in women with a history of fetal
loss related to thrombophilia and hypercoagulable syndromes, such as antithrombin III deficiency, antiphosholipid
syndrome and protein C or S deficiency. Warfarin causes abnormal fetal development and congenital
malformations during the first trimester, such as nasal hypoplasia and skeletal dysplasias, and increases the risk of
maternal and fetal hemorrhage when given during the peripartum period. Unfractionated heparin and LMWH do not
cross the placenta and are not teratogenic. LMWH has gained widespread use in pregnancy, and has certain
advantages over unfractionated heparin. Both UH and LMWH have similar hemorrhagic complication rates and
antithrombotic efficacy; however, LMWH, unlike UH, does not require laboratory monitoring. Also, there is less
risk of serious complications with LMWH, such as heparin-induced thrombocytopenia and osteoporosis.38
The release of LMWH for general use in the United States in May 1993 sparked a new challenge for
anesthesiologists. Previously, a spinal or epidural hematoma was a rather rare occurrence, reportedly less than 1 in
150,000-220,000.13 Enoxaparin, the first LMWH to be approved by the United States Food and Drug
Administration (FDA), had been used for many years in Europe. However, the approved dosing schedule of
enoxaparin was 30 mg (3000 U) every 12 hours in the U.S. as opposed to 40 mg (4000U) once daily in Europe.
Within one year of its introduction in the U.S., two cases of epidural hematoma were voluntarily reported through
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the Med Watch system. The warning section of the drug label was revised, a letter from the manufacturer and from
the FDA Health Advisory was issued to practitioners to alert them to the risk of spinal hematoma in patients
undergoing neuraxial anesthesia while receiving LMWH.39
The actual risk of spinal or epidural hematoma in patients receiving LMWH while undergoing neuraxial
anesthesia is difficult to estimate. The reported incidences of spinal or epidural hematoma in patients receiving
LMWH may be as great as 1 in 3,000 for continuous epidural anesthesia and 1 in 40,000 for spinal anesthesia.40 Of
the 40 cases of spinal or epidural hematoma associated with LMWH in conjunction with neuraxial anesthesia, two
patients received epidural steroid injections, six underwent spinal anesthesia, of which one was continuous spinal
anesthesia, 23 had continuous epidural anesthesia, six were unspecified techniques, and two had general anesthesia
after attempted or failed neuraxial anesthesia. Some of these patients had other risk factors for the development of
spinal or epidural hematoma, such as difficult needle placement or administration of antiplatelet or anticoagulant
medication. None of these patients was pregnant.
Neuraxial anesthesia can be safely administered to the patient receiving LMWH if certain guidelines and
precautions are met. The American Society of Regional Anesthesia (ASRA) formed a consensus committee on
neuraxial anesthesia in association with anticoagulation on May 2-3, 1998. The committee reconvened for a second
consensus conference in 2002 and a third meeting in 2009 with the findings published in 2010.41 The findings are
summarized in the Table, but of note neuraxial anesthesia should be delayed by either 12 or 24 hours from the last
injection of LMWH depending on whether the patient is receiving low or high dose LMWH.
Conclusions
In summary, the parturient with coagulation defects, whether related to thrombocytopenia or to
anticoagulation therapy, presents a unique challenge to the anesthesiologist. The risk of spinal or epidural
hematoma in these patients has not been fully quantified, but is nevertheless a factor that one must consider on a
case-by-case basis in determining whether a neuraxial anesthetic is appropriate for the parturient. Following the
guidelines set forth in this lecture should help reduce the risk of spinal or epidural hematoma, without sacrificing the
quality of care provided to our patients.
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Table
Summary of the Recommendations of the consensus conference convened by the American

Society of Regional Anesthesia and Pain Medicine regarding anticoagulants and neuraxial
anesthesia and analgesia 41
1. The decision to perform a neuraxial block when a patient is receiving LMWH must be made on an
individual basis by weighing the risk of spinal hematoma with the benefits of regional anesthesia for a
specific patient.
2. Monitoring of the anti-Xa level is not recommended, because it is not predictive of the risk of bleeding.
3. Concomitant medications known to potentiate bleeding, such as antiplatelet agents or oral anticoagulants,
create an additional risk for the development of spinal hematoma.
4. If blood is seen during needle or catheter placement, the first dose of LMWH should be delayed for 24
hours.
5. If a patient is receiving LMWH preoperatively, neuraxial anesthesia should occur at least 10-12 hours after
the last LMWH dose. Patients receiving high doses of LMWH, such as enoxaparin 1 mg/kg twice a day, or
enoxaparin 1.5 mg/kg daily will require waiting 24 hours.
6. The first dose of LMWH after surgery depends on the dosing schedule
a. Twice–daily dosing: The first dose of LMWH should be given no sooner than 24 hours
postoperatively. Indwelling catheters should be removed prior to initiation of LMWH, and the
first dose may be given two hours after catheter removal.
b. Single-daily dosing: The first dose of LMWH should be given 6-8 hours postoperatively. The 2nd
dose should be given no sooner than 24 hours after the 1st dose. Indwelling catheters may be
maintained but should be removed 10-12 hours after the last dose of LMWH. Subsequent dosing
should occur two hours after catheter removal.
References:
1. Beilin Y, Zahn J, Comerford M. Safe epidural analgesia in thirty parturients with platelet counts between 69,000
and 98,000 mm-3. Anesth Analg 1997;85:385-388.
2. Cousins MJ, Bromage PR. Epidural neural blockade. In: Cousins MJ, Bridenbaugh PO, eds. Neural Blockade in
Clinical Anesthesia and Management of Pain, 2nd ed. Philadelphia: J.B. Lippincott Company, 1988:335-336.
3. Hawkins JL, Koonin LM, Palmer SK, et al. Anesthesia-related deaths during obstetric delivery in the United
States, 1979-1990. Anesthesiology 1997;86:277-284.
4. Burrows RF, Kelton JG. Fetal thrombocytopenia and its relation to maternal thrombocytopenia. N Engl J Med
1993;329):1463-6.
5. Channing Rodgers RP, Levin J. A critical reappraisal of the bleeding time. Semin Thromb Hemost 1990;16:1-10.
6. Lind SE. The bleeding time does not predict surgical bleeding. Blood 1991;77:2547-2552.
7. O'Kelly SW, Lawes EG, Luntley JB. Bleeding time: Is it a useful clinical tool? Br J Anaesth 1992;68:313-315.
8. Beilin Y, Bodian CA, Haddad EM, et al. Practice patterns of anesthesiologists regarding situations in obstetric
anesthesia where clinical management is controversial. Anesth Analg 1996;83:735-741.
9. Orlikowski CE, Rocke DA, Murray WB, et al. Thrombelastography changes in pre-eclampsia and eclampsia. Br J
Anaesth 1996;77:157-161.
10. Favaloro EJ, Kershaw G, Bukuya M, et al. Laboratory diagnosis of von Willebrand disorder (vWD) and
monitoring of DDAVP therapy: efficacy of the PFA-100 and vWF:CBA as combined diagnostic strategies.
Haemophilia 2001;7:180-189.
11. Davies JR, Fernando R, Hallworth SP. Hemostatic function in healthy pregnant and preeclamptic women: an
assessment using the platelet function analyzer (PFA-100) and thromboelastograph. Anesth Analg 2007;104:416-20.
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12. Beilin Y, Arnold I, Hossain S. Evaluation of the platelet function analyzer (PFA-100®) vs. the
thromboelastogram (TEG) in the parturient. Int J Obstet Anesth 2005;15:7-12.
13. Vandermeulen EP, Van Aken H, Vermylen J. Anticoagulants and spinal-epidural anesthesia. Anesth Analg
1994;79:1165-1177.
14. Ballin NC. Paraplegia following epidural analgesia. Anaesthesia 1981;36:952-953.
15. Crawford JS. Some maternal complications of epidural analgesia for labour. Anaesthesia 1985;40:1219-1225.
16. Newman B. Postnatal paraparesis following epidural analgesia and forceps delivery. Anaesthesia 1983;38:350-1.
17. Scott DB, Hibbard BM. Serious non-fatal complications associated with extradural block in obstetric practice. Br
J Anaesth 1990;64:537-41.
18. Jaeger M, Rickels E, Schmidt A, et al. Lumbar ependymoma presenting with paraplegia following attempted
spinal anaesthesia. Br J Anaesth 2002;88:438-40.
19. Roscoe MW, Barrington TW. Acute spinal subdural hematoma. A case report and review of literature. Spine
1984;9:672-5.
20. Esler MD, Durbridge J, Kirby S. Epidural haematoma after dural puncture in a parturient with
neurofibromatosis. Br J Anaesth 2001;87:932-4.
21. Lao TT, Halpern SH, MacDonald D, et al. Spinal subdural haematoma in a parturient after attempted epidural
anaesthesia. Can J Anaesth 1993;40:340-5.
22. Yarnell RW, D'Alton ME. Epidural hematoma complicating cholestasis of pregnancy. Curr Opin Obstet Gynecol
1996;8:239-42.
23. Yuen TS, Kua JS, Tan IK. Spinal haematoma following epidural anaesthesia in a patient with eclampsia.
24. Harker LA, Slichter SJ. The bleeding time as a screening test for evaluation of platelet function. N Engl J Med
1972;287:155-9.
25. Rasmus KT, Rottman RL, Kotelko DM, et al. Unrecognized thrombocytopenia and regional anesthesia in
parturients: a retrospective review. Obstet Gynecol 1989;73:943-6.
26. Rolbin SH, Abbott D, Musclow E, et al. Epidural anesthesia in pregnant patients with low platelet counts. Obstet
Gynecol 1988;71:918-208.
27. Hew-Wing P, Rolbin SH, Hew E, et al. Epidural anaesthesia and thrombocytopenia. Anaesthesia 1989;44:775-7.
28. Practice Guidelines for Obstetric Anesthesia: An Updated Report by the American Society of Anesthesiologists
Task Force on Obstetric Anesthesia. Anesthesiology 2007; 106:843–63
29. Solanki DL, Blackburn BC. Spurious thrombocytopenia during pregnancy. Obstet Gynecol. 1985;65:14S-17S.
30. Douglas MJ. Platelets, the parturient and regional anesthesia. Int J Obstet Anesth 10:113-120,2001.
31. Banwell BR, Morley-Forster P, Krause R. Decreased incidence of complications in parturients with the arrow
(FlexTip Plus) epidural catheter. Can J Anaesth 1998;45:370-2.
32. Wysowski DK, Talarico L, Bacsanyi J, et al. Spinal and epidural hematoma and low-molecular-weight heparin.
N Engl J Med 1998;338:1774-5.
33. Bergqvist D, Lindblad B, Matzch T. Low molecular weight heparin for thromboprophylaxis and epidural/spinal
anaesthesia-is there a risk? Acta Anaesthesiol Scand 1992;36:605-9.
34. Tryba M. Hemostatic requirements for the performance of regional anesthesia. Workshop on hemostatic
problems in regional anesthesia. Reg Anaesth 1989;12:127-31.
35. Horlocker TT, Heit JA. Low molecular weight heparin: biochemistry, pharmacology, perioperative prophylaxis
regimens, and guidelines for regional anesthetic management. Anesth Analg 1997;85:874-5.
36. Cosmi B, Hirsh J. Low molecular weight heparins. Curr Opin Cardiol 1994;9:612-8.
37. Heit JA. Low-molecular-weight heparin: biochemistry, pharmacology, and concurrent drug precautions. Reg
Anesth Pain Med 1998;23:135-9.
38. Bazzan M, Donvito V. Low-molecular-weight heparin during pregnancy. Thromb Res 2001;101:175-86.
39. Horlocker TT. Low molecular weight heparin and neuraxial anesthesia. Thromb Res 2001;101:141-54.
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40. Schroeder DR. Statistics: detecting a rare adverse drug reaction using spontaneous reports. Reg Anesth Pain
Med. 1998;23:183-189.
41. Horlocker TT, Wedel DJ, Rowlingson JC, Enneking FK, Kopp SL, Benzon HT, Brown DL, Heit JA, Mulroy
MF, Rosenquist RW, Tryba M, Yuan CS. . Regional Anesthesia in the Patient Receiving Antithrombotic or
Thrombolytic Therapy. American Society of Regional Anesthesia and Pain Medicine Evidence-Based Guidelines
(Third Edition). Reg Anesth Pain Med 2010;35:64-101.
DISCLOSURE
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Anesthetic Effects on the Fetus and Newborn
B. Scott Segal, M.D. Boston, Massachusetts
Obstetric anesthesia is remarkably safe. Modern regional anesthetic techniques are now much safer than such
anachronistic techniques as paracervical block or twilight sleep (parenteral morphine and scopolamine). Indeed, it
can be argued that the field is “six sigma” at least with respect to maternal mortality, which is approximately 1.3 per
million live births (1). Obstetric anesthesiologists have enjoyed such success in reducing maternal and neonatal
mortality and morbidity over the preceding few decades that we may have developed a sense of well-deserved
confidence which unfortunately may border on arrogance, that obstetric anesthetic interventions cause no adverse
effects whatsoever on the baby. Nonetheless, there are several areas of ongoing concern regarding the effects of
anesthetics on the fetus and newborn. This lecture will review the state of our current understanding of these effects
and highlight the areas of uncertainty for future research.
Effects on the early developing fetus: teratogenicity of anesthetics

It is estimated that 1-2% of all pregnant women will undergo nonobstetric surgery during gestation (2,3), resulting in
some 75,000 developing fetuses being exposed to anesthetic drugs. Fortunately, no anesthetics or commonly used
adjunctive drugs are known to be teratogens. Unfortunately, studies of human teratogenicity are virtually
nonexistent due to ethical concerns, and evidence regarding anesthetics comes from either studies in other species or
from epidemiologic surveys. The former can be confounded by species differences, uncontrolled hemodynamics
and respiratory status, and from artificially long exposures to anesthetics. The latter are complicated by
uncontrolled variables, most notably the disease process requiring surgery itself. Nonetheless, the news is generally
good, though two agents are worthy of special attention.
Nitrous oxide, which can inhibit methonine synthase in DNA synthesis and methylation reactions, was implicated as
a teratogen in animal studies in the 1970’s and 1980’s. Twenty-four hours of exposure to 75% nitrous oxide on Day
8 or 9 of a 21 day gestation led to significant increases in skeletal abnormalities and fetal resorption in rats (4).
However, folate supplementation, which should bypass methionine synthase inhibition, does not block these effects,
while addition of halothane does (5). This suggests that the mechanism may not be enzyme inhibition but perhaps
changes in uterine blood flow (N2O can reduce UBF, halothane is a vasodilator that may counteract this effect).
More importantly, human epidemiologic studies do not show an important association between N2O exposure in
utero and birth defects. Mazze (whose lab performed many of the rat studies) studied 5405 operations in 720,000
pregnancies recorded in a Swedish birth registry. Surgery during pregnancy was not associated with any difference
in stillbirth or congenital abnormalities, though it was with low birthweight and death within one week of delivery.
54% of mothers received general anesthesia, 98% of whom received nitrous oxide (6). Similarly, a case-control
study of all 2565 mothers in Manitoba, Canada who underwent surgery during pregnancy found no difference in
congenital abnormalities but a small increase in early pregnancy loss which was not attributable to anesthetic
technique (7).
Benzodiazepines were once feared to be associated with cleft left and palate, based on poor epidemiologic studies of
chronic use/abuse and some but not all animal or cell-culture models. More recent data contradicts these earlier
flawed investigations, and benzodiazepines are likely safe, particularly in the small doses used in anesthesia (8). A
large systematic review of cohort and case-control studies demonstrated no increased risk of major malformations or
cleft lip/palate in cohort studies but a small increase in risk in case-control studies. However, the latter were
frequently confounded by chronic and multiple medication use; psychiatric diagnoses, epilepsy, and other medical
conditions associated with birth defects; and small sample size (9).
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Inhalation anesthetics, induction agents, opioids, and neuromuscular blocking drugs are all considered free of
teratogenic effect (3). Of course, a newborn exposed in utero to most anesthetics immediately prior to delivery may
be transiently depressed and require respiratory support for a brief period.
A recent wrinkle in this story is the growth of assisted reproductive technologies (ART; IVF and other associated
procedures), now numbering over 150,000 cycles per year in the U.S. Epidemiological evidence (10) suggests
major birth defects are more common in babies born from IVF pregnancies compared to a controlled cohort of
natural pregnancies or products of intrauterine insemination alone (OR 1.3). More recent evidence from a case-
control study in 10 states pointed to specific defects increased in IVF pregnancies. After excluding diabetic mothers
(who are at higher risk for birth defects) and controlling for age, study center, parity, family income and prematurity,
four defects were increased: septal heart defects (OR 2.1), cleft lip/palate (OR 2.4), esophageal atresia (OR 4.5),
and anorectal atresia (OR 3.7) (11). Most recently, a large epidemiologic survey of over 300,000 births in South
Australia found an association between all assisted reproductive procedures and birth defects (OR 1.47), including
increased risks of cardiovascular, musculoskeletal, urogenital, and gastrointestinal defects and cerebral palsy (12).
After adjusting for multiple confounders, the OR was reduced to 1.28. Importantly, the OR for IVF, as opposed to
other ART, were 1.26 (95% CI, 1.07 to 1.48) and 1.07 (95% CI, 0.90 to 1.26), or not significant after correcting for
confounders. The ORs were higher for intracytoplasmic sperm injection (ICSI). Birth defects were also more
common, however, in women with spontaneous conceptions but a history of infertility, suggesting that parental
factors may explain much of the unadjusted association. It remains to be determined whether infertility or
underlying conditions causing infertility, or the IVF treatment itself, is responsible for the increases. Because the
oocytes retrieved for fertilization are exposed to anesthetics at the time of harvest, it will be an important research
question to determine whether this exposure contributes to subsequent malformations.
In concluding our discussion of teratogenicity, it is reassuring to note the lack of any clear association between
common anesthetic agents and adjuncts and congenital malformations. However, it is prudent to use any drug in
pregnancy thoughtfully and conservatively, for example, reserving benzodiazepines for truly anxious patients.
Effects on the fetal brain: behavioral teratogenicity

Unlike the other major organs and structures of the fetus, which form in the first few weeks of gestation, the brain
continues to develop throughout gestation and after birth (2). Enduring change in behavior without obvious
structural abnormalities has been termed behavioral teratogenicity. For over ten years, it has been clear that
compounds that interact with NMDA (N-methyl D-aspartate) and GABAA (gamma aminobutyric acid) receptors can
trigger programmed cell death, or apoptosis, in developing brain (13). Although apoptosis is a normal part of
embryogenesis, some animal experiments have also demonstrated functional or behavioral abnormalities
accompanying the increase in cell death, such as impaired maze learning. These changes may persist at least into
young adult life (14). Because many anesthetic agents are NMDA antagonists or potentiators of GABA
transmission, it is conceivable that anesthetic exposure during brain development could lead to neurodegeneration.
Jevtovic-Todorovic et al. (14) exposed neonatal rats to 6 hr of midazolam, N2O and isoflurane anesthesia at 7 d of
age (which corresponds to the peak of synaptogenesis in the rat, a period likely to span many weeks from
midgestation to the postnatal period in humans). The authors used doses that produce a surgical plane of anesthesia
in the rat, which were substantially larger than those commonly employed in humans. They observed significant
increases in staining for apoptosis throughout the brain and evidence of impaired synaptic function in the
hippocampus, important for memory formation. Studies in animals allowed to mature into young adulthood showed
impaired learning in various maze tests, compared to air and vehicle treated controls. No intraoperative blood gas
abnormalities, or other gross alterations in body or sensory or motor function were observed.
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Subsequent investigations by these and other laboratories have demonstrated similar results with other anesthetics,
including ketamine and propofol, in both anesthetic and even subanesthetic doses (13,15,16). In addition, similar
results have been obtained in other species, including those in which synaptogenesis occurs in utero (16). There is
even some preliminary data in non-human primates that GABA-mimetic agents can induce apoptosis in developing
brain (15,17,18) and that early exposure to ketamine in rhesus monkeys can cause long term cognitive impairment in
juveniles and young adults (19). In addition, other mechanisms of neuronal injury have been demonstrated,
including inhibited neurogenesis and altered dendritic connections between neurons (20).
Despite these tantalizing and frightening results, there remains substantial controversy regarding the degree of risk
anesthetics pose to humans undergoing general anesthesia, or fetuses exposed in utero to maternal anesthesia. As
with all non-human animal studies, extrapolation is difficult. The arguments posed by skeptics include (15,21,22):
• Large doses and prolonged exposures are commonly employed
• No surgical stimulation accompanies the anesthetics
• Hemodynamics, respiratory status, and glucose have not been uniformly observed or controlled
• Neuroplasticity implies regeneration of neurons lost to apoptosis is likely
• Some effects are only observed when exposure occurs on certain developmental days and not others
• Most behavioral consequences have only been observed in rats
• Human experience with neonatal anesthesia spans decades and does not demonstrate significant
neurotoxicity
• Some anesthetics, such as xenon, are NMDA antagonists but cause no toxicity or are even protective
In response to some of these criticisms, Jevtovic-Todorovic studied guinea pigs exposed to a similar anesthetic
(isoflurane-nitrous oxide-midazolam) for 4 hr in utero. This species is larger, has a longer gestation, and features
predominantly antenatal brain development. Compared to animals exposed only to induction of anesthesia and
mechanical ventilation during fentanyl anesthesia, or to untreated animals, the animals exposed to the triple drug
cocktail demonstrated increased apoptosis and neuronal cell loss throughout the brain. Respiratory, cardiovascular,
and glycemic homeostasis was demonstrated (16). Other laboratories have similarly found in utero exposure to
isoflurane alone at late second trimester in rats led to behavioral and learning abnormalities in young adults (23).
The field is currently in hot pursuit of data applicable to humans. Recently, Wilder et al. (24) searched the records
of 593 children who underwent general anesthesia before age 4, compared to nearly 5000 who did not, all of whom
lived in the same region of Minnesota and received care in one of two health care facilities for many years. They
recorded the prevalence of learning disabilities, defined by scores on standardized IQ, reading, writing, or math
achievement tests. Exposure to a single anesthetic was not associated with any difference in learning disabilities,
but exposure to two or three or more was associated with an increase in disabilities (hazard ratio 1.6-2.6). Although
the study controlled for a number of known risk factors for learning disability, the authors noted that it is not
possible to distinguish between the effects of anesthesia and surgery, the stress response to illness and operation, or
the underlying disease process. Similarly, DiMaggio compared 383 children who underwent hernia repair under
general anesthesia to 5050 who did not, matched for age, sex, and complicating birth-related conditions such as low
birth weight. They found an increased risk of behavioral or developmental disorders in the anesthetic-exposed
cohort with a hazard ratio of 2.3 (25). The same group found a dose-response effect of exposure to general
anesthesia at less than 3 years of age in a case control study, with a relative risk of behavioral or developmental
disorders increasing from 1.1 to 2.9 to 4.0 for 1, 2, and 3 or more anesthetics (26). However, in matched sibling
pairs, exposure was not linked to an increased risk, raising the possibility that the effect is not definitively causal.
Similarly, Bartels et al. (27) studied monozygotic twin pairs in which one was exposed and the other unexposed to
anesthesia before age 3. Children exposed to anesthesia had a lower test scores at age 12 overall than those who
were unexposed, but exposed twins did not differ from their unexposed twin siblings. Most recently, a large Danish
cohort study found no difference in 9th grade test scores in children who underwent hernia repair in infancy vs. those
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who did not. However, a larger fraction of anesthetic-exposed children were never tested, possibly implying
significant developmental delay was more common (28).
There is limited data on in utero exposure in humans. Sprung et al. examined the effect of anesthetic type in 497
women undergoing cesarean delivery and found no difference in the incidence of learning disabilities in children
exposed to general anesthesia compared to those delivered vaginally (29). Children delivered by cesarean under
maternal regional anesthesia had a significantly lower incidence of learning disabilities (hazard ratio = 0.64 for
comparison of CD under regional anesthesia compared to vaginal delivery). In a follow-up investigation, the same
group found no difference in learning disabilities in children delivered vaginally with or without maternal neuraxial
labor analgesia (HR 1.05; 95% CI, 0.85-1.31; P = 0.63) (30).
Hopefully, a better understanding of the mechanism of toxicity in the coming years will also point to strategies to
block the harmful effects. Encouraging results have recently been reported in vitro and in rodent models with
dexmedetomidine. This drug partially blocked isoflurane-induced apoptosis and cognitive deficits in a dose-
dependent fashion by an alpha2-adrenergic mechanism (31,32). While laboratory and larger clinical investigations
proceed, it is prudent to assume that general anesthetics are potentially toxic to the developing fetal brain, and their
use in obstetric anesthesia should continue to be a rare event reserved for emergencies.
Effects in the peripartum period: epidural analgesia and maternal fever

Women receiving labor epidural analgesia experience a greater incidence of clinical fever. Two decades ago,
observational studies demonstrated a gradual rise in temperature in women receiving epidurals compared to those
receiving no analgesia or systemic opioids alone (33,34). Although originally ascribed to altered thermoregulation,
it is now evident that this represents an artifact from averaging afebrile women’s temperatures and those developing
clinical fever (35,36). Substantial evidence suggests that true clinical fever develops more often in women with
epidurals than in those without them. The data comes from retrospective observations (which attempt to statistically
control for confounding factors such as longer labors, prolonged rupture of membranes, and number of cervical
examinations), sentinel event studies (in which epidural analgesia suddenly becomes available to a population), and
randomized, controlled trials (37-39). Once dismissed as a physiological curiosity or artifact of selection bias, this
phenomenon can no longer be ignored.
The mechanism of epidural-associated fever remains unclear. Earlier, investigators noting the very slow gradual rise
in temperature on average, hypothesized that thermoregulation might be altered in laboring women with epidurals.
For example, by inhibiting sweating and hyperventilation, the block might impair heat dissipation. Other
investigators suggested that opioids given to women without epidurals might be suppressing temperature elevation,
rather than epidurals causing it. There is some evidence from nonlaboring volunteers to support each of these
mechanisms. However, the observation that “epidural fever” is actually clinical fever in some women averaged with
normal temperature in others leads to a search for an explanation of more frequent overt fever in some women with
epidural analgesia. Some evidence suggests placental inflammation (chorioamnionitis) is more common in febrile
women with epidural analgesia (40). Importantly, in a nonrandomized comparison, bacterial infection in the
placenta was not found to be associated with epidural analgesia, though inflammation was (41). It is less clear,
however, how this could explain a higher incidence of fever in women randomly selected to receive epidural
analgesia (37). Possibly, the presence of an epidural alters obstetrical management in ways that might increase the
chance of chorioamnionitis (e.g., more cervical exams, earlier rupture of membranes).
Epidural-associated fever may have significant effects on the fetus and newborn. One of the earliest recognized
effects was an indirect one, namely, an influence on the practice of neonatologists. Lieberman (38) demonstrated
that babies born to mothers with epidurals underwent evaluation for sepsis four times more often than babies born to
mothers electing natural childbirth or systemic opioids. Actual sepsis was vanishingly rare and did not differ
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between epidural and no-epidural groups. This phenomenon may be a function of neonatology practice style,
however, because other institutions have reported different results (40). Other adverse effects related to intrapartum
maternal fever include increased need for bag-mask ventilation and increased incidence of otherwise unexplained
neonatal seizures (42).
A far more worrisome possibility is that maternal fever may cause neonatal brain injury. Over fifty years ago, an
association between cerebral palsy and maternal fever was first noted, but the observation was not investigated
further until recently. Substantial epidemiologic evidence now confirms a 4-9 fold increase in the risk of otherwise
unexplained cerebral palsy in term and near-term infants exposed to maternal fever or clinical or pathologically
diagnosed chorioamnionitis (43,44). Other neonatal brain injuries have likewise been associated with maternal
fever, including neonatal encephalopathy (which often has devastating lifelong neurological consequences for the
infant) (45). Even babies not manifesting these profound impairments may nonetheless experience neurological
injury. Dammann found cognitive deficits at age 9, as measured by the Kaufman Assessment Battery for Children,
were four times as common in children whose mothers had fever at the time of delivery compared to controls (46).
The link between maternal fever and neurologic injury in the newborn is most likely inflammation. In experimental
pregnant animal preparations, bacterial intrauterine infection causes white matter lesions in the fetuses. Yoon (47)
injected E. coli or saline into the cervix of pregnant rabbits. 36% of infected dams delivered fetuses with white
matter lesions (6% of all fetuses of infected mothers had such lesions), compared to 0% in the saline control group.
Similarly, Rodts-Palenik (48) demonstrated white matter lesions and enlarged cerbral ventricles in pups of infected
pregnant rats more frequently than in saline-treated rats. Importantly, these lesions were not seen if the mothers
were treated with the anti-inflammatory interleukin IL-10. Although such experiments do not definitively
demonstrate that maternal intrapartum fever causes neonatal brain injury via fetal inflammation in humans, Yoon
(49) has documented increased IL-6 and IL-8 (pro-inflammatory cytokines) in amniotic fluid in a cohort of
pregnancies resulting in babies with cerebral palsy, compared to controls with normal brain development.
Many questions remain. First, it is far from clear how epidural analgesia is associated with maternal fever. If
thermoregulatory mechanisms (increased heat production and/or impaired heat dissipation) are not primarily
responsible, then a link between epidural blockade and maternal inflammation must be found. It is difficult to
speculate how a light regional blockade could cause chorioamnionitis, unless it alters obstetrical practice, as noted
above. If the block itself causes inflammation, the mechanism would be unique and startling. Second, it is not clear
yet whether fever itself can cause injury, or whether inflammation causes both fever and inflammation. Many
women with epidurals and fever do not appear to be clinically infected. However, the animal models of intrauterine
infection are quite suggestive. Moreover, high dose methylprednisolone (but not acetaminophen) given to laboring
women with epidurals blocks the febrile response (50). Unfortunately, this treatment also leads to a substantial
increase in asymptomatic bacteremia in the exposed babies, making it untenable as a clinical strategy. Third, it is
not known whether epidural-associated fever is specifically associated with brain injury (as opposed to
chorioamnionitis). Fourth, it is unknown whether epidural-associated fever can be safely blocked. Trials of n-
acetylcysteine and other anti-inflammatory strategies are ongoing. These questions will likely be the subject of
intense investigation in the near future.
Effects on the postpartum period: epidural analgesia and breastfeeding

There has long been controversy regarding the effect of labor epidural analgesia on breastfeeding in the postpartum
period. A review article in the breastfeeding literature in 1997 concluded that epidural analgesia was likely a cause
of reduced breastfeeding success, perhaps due to transient depression of the neurologic and adaptive capacity score
(NACS) (51). The NACS has largely been discredited, and even in 1997 the differences observed were small,
probably irreproducible, and likely confounded by such factors as obstetrical interventions, mode of delivery,
systemic medications, and demographics of mothers selecting epidural analgesia (52). Similar confounders likely
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were strong influences in anecdotal or observational studies suggesting epidural analgesia interfered with
breastfeeding. Nonetheless, the idea was persistent in the lactation and lay birthing communities. In 2006, an
apparently damning report appeared in an online lactation journal, suggesting that intrapartum epidural analgesia
was strongly negatively correlated with breastfeeding success (53). The study was plagued with fatal
methodological flaws, the greatest of which were that delivery mode was uncontrolled, and that all women self-
reporting their analgesic choice as “epidural” also received parenteral meperidine and possibly nitrous oxide (54).
The authors did acknowledge that the effect of epidural analgesia might not be causal. The worldwide popular press
seized on this investigation as a definitive indictment of epidural analgesia.
Is there better information on the effect of labor analgesia on breastfeeding? The best data would be results from
RCTs in which women were randomized to epidural vs. alternative analgesia. This has been accomplished more
than a dozen times in the last 15 years, but none of these investigations has examined breastfeeding success (37).
Nonetheless, potentially confounded retrospective studies continue to appear and claim an association between
epidural analgesia and less breastfeeding success in the immediate postpartum period (55). Conversely, several
large carefully performed retrospective studies do not show any adverse effect of epidural analgesia (56-59). Two
recent studies examined effects of variations in epidural technique on breastfeeding success. In a large multicenter
comparison of conventional, low-dose, and combined spinal epidural approaches, no difference was found among
the techniques. Furthermore, no difference was found between any technique and a non-randomized matched
control group not receiving neuraxial analgesia (60). Conversely, a huge single-center RCT comparing latent phase
to active phase initiation of epidural analgesia observed an 8-hour difference in the exposure to epidural
medications. A small but statistically significant difference in breastfeeding at 6 weeks, a secondary outcome
measure, was observed (latent, 70% vs. active, 78%). Importantly, it appears that systemic opioids, or larger doses
of epidural fentanyl, can interfere with early breastfeeding success (61,62). Nearly all investigators agree that
emotional and professional lactation support is the most important factor predicting long-term breastfeeding success.
Conclusions
Anesthesia for expecting mothers has never been safer and is likely to have few adverse effects on the developing
fetus. In particular, epidural analgesia is still probably the safest form of pain relief for laboring women and their
babies. However, there is reason for some concern and definitely strong justification for aggressive research. The
effects of anesthetics, both general and regional, on the developing fetal brain must be elucidated and if necessary,
effective protective strategies developed, as a high priority.
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DISCLOSURE
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State of the Art Labor Analgesia

Kenneth E Nelson, M.D. Winston-Salem, North Carolina
Introduction
The options for providing labor analgesia have undergone continuous change over the past few decades,
culminating in the current state of the art. Although the available number of topics, issues, and controversies in
labor analgesia are nearly unlimited, the current discussion will be limited to the following three topics:
Maintenance of Labor Analgesia, Controversies, and Techniques.
Maintenance of Labor Analgesia
PCEA/PIEB
Once a catheter has been placed into the epidural space, several options exist to maintain analgesia. The
first methods to be employed was intermittent bolusing on patient request. Once the effect of the initial dose of local
anesthetic began to subside, contraction pain would return and the patient would request more medication, at which
time the anesthesiologist would provide analgesia using another bolus dose of local anesthetic. The obvious
disadvantage to this technique is the relatively large amount of manpower required, and other disadvantages include
non-continuous pain relief, and an intermittent increase in side effects such as hypotension and motor block. The
natural progression in management was to employ infusions to maintain analgesia, but early infusion pumps were
relatively primitive and sometimes unreliable, and data were lacking to guide infusion rates1. A large volume of
research was eventually published to help rectify this problem, and it was during this time that the next step in the
evolution of maintenance of labor analgesia occurred: patient controlled epidural analgesia (PCEA)2. By this time, a
large amount of experience had accumulated with the use of intravenous PCA, and the same principles were then
applied to PCEA. However, it was soon discovered that there are some important differences between opioid-based
IVPCA for acute postoperative pain and local anesthetic-based PCEA for labor analgesia. Perhaps most
importantly, a basal infusion was found to be very effective with PCEA3. Studies continued, however, and further
information has emerged over the past 2 decades suggesting that even more effective methods can be employed,
such as intermittent bolusing at programmed intervals4. Pumps are currently being developed in order to exploit this
advantage. The next step might be computerized pumps with a feedback loop that can continuously adjust basal
infusion rates based on average patient requirements, allowing for automatic changes in infusion rates to match the
changing analgesic needs during the course of labor.
Intravenous Opioids
There are several acceptable opioids that can be used to provide labor analgesia. Partial agonists such as
butorphanol have a ceiling effect for respiratory depression, thus making them an attractive choice in laboring
women due to a theoretically lower risk of maternal side effects and neonatal depression5. However, the analgesic
effect is likewise limited, and analgesic efficacy has been reported to range from moderate to non-existent. A
commonly used dose of butorphanol is 1mg IV every hour as needed, held when delivery is imminent.
Other opioids without ceiling effect have also been used, and one of the most commonly studied is
meperidine. However, as with all intravenous opioids for labor analgesia, the reported efficacy is variable and often
disappointing. One report even concluded that intravenous opioids for labor analgesia are “unethical and medically
incorrect”6, but the vast majority of studies report at least a moderate effect7. Potential drug interactions with
meperidine have contributed to its decline in popularity, including serotonin syndrome in patients taking MAOIs or
SSRIs. Another potential problem with meperidine is accumulation of the metabolite norrmeperidine, which has
been reported to cause convulsions, yet should only be an issue with chronic administration.
Fentanyl is another commonly used intravenous opioid for labor analgesia, and it has been extensively
studied for this use. It rarely causes allergic reaction, and is relatively free of drug interactions, but has no ceiling
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effect for respiratory depression, so must be used with caution on the labor ward. It can have a cumulative effect,
and therefore neonatal respiratory depression is an important concern8. Dosage recommendations will be discussed
during the lecture.
Remifentanil is a newer opioid analgesic with a rapid onset and short duration of action. Its unique
pharmacodynamic profile created early enthusiasm for its use in labor analgesia. However, even with the rapid
onset, it is nearly impossible to deliver remifentanil in such a way that the analgesic effect mirrors the time course of
the contraction. In spite of this shortcoming, there are several reports of its successful use in labor analgesia,
including a comparison with fentanyl, which concluded that either one provides moderate analgesia, with
remifentanil causing more maternal oxygen desaturation, and fentanyl causing more neonatal depression8. Dosage
recommendations will be discussed during the lecture.
Neuraxial Adjuvants
Although epidural labor analgesia relies primarily on local anesthetic agents (and likely will continue to do
so in the foreseeable future), there are a variety of adjuncts that have proven to be effective in reducing the amount
of local anesthetic required. The common goal of using adjunctive agents is to reduce the amount of local anesthetic
required, thereby reducing side effects such as motor block, hypotension, and toxicity. The list of spinal adjuvants
which have been studied is extremely long, and this discussion will be limited to four: morphine, fentanyl, clonidine,
and neostigmine.
Morphine is a very commonly used adjuvant for postoperative analgesia, and less so for labor analgesia. It
is one of the few spinal adjuvants that has FDA approval. Although several reports of its use for labor analgesia
have shown promising results, its long duration of action means that a longer period of monitoring for respiratory
depression is required9. Morphine is also likely to increase the incidence of side effects such as nausea and
pruritus10.
Fentanyl is a very commonly used adjuvant for labor analgesia, because it reduces the amount of local
anesthetic required to produce labor analgesia, thereby reducing side effects such as motor block. The most
common side effect is pruritus, and clinically significant respiratory depression is very rare when 20mcg or less is
used.
Clonidine is an alpha-2 agonist which has been shown to be effective in a variety of pain states when used
neuraxially. Early studies showed promise as an adjunct in labor analgesia11, but side effects such as maternal
sedation, hypotension, and bradycardia resulted in a black box warning against its use in this setting12.
Neostigmine is an inhibitor of the enzyme acetylcholinesterase, and therefore causes acetylcholine to
remain for a longer period of time in the synapse, thus prolonging its action. Acetylcholine is known to be an
important neurotransmitter in the descending inhibitory pathway initiated by opioid receptor activity in the midbrain,
and it is this pathway by which it is believed that neostigmine exerts its analgesic effect. Although intrathecal
neostigmine is effective as an analgesic adjunct to local anesthetics, the nausea that it causes is prohibitive to routine
use13. However, when used in the epidural space, it is equally effective as fentanyl, yet does not increase the
incidence of nausea14. It is currently being used only as an investigational drug, but shows promise in replacing
lipid soluble opioids as an epidural adjunct to local anesthetic, which would eliminate opioid side effects, and the
need to account for a controlled substance on the labor and delivery ward.
Controversies
Air vs Saline for Loss of Resistance

Either air or saline can be safely used to test for loss of resistance when accessing the epidural space.
Recent debates on the subject have brought to light the list of reasons to avoid air, whereas no such list exists for the
argument against saline. The proponents of air correctly argue that the efficacy and overall incidence of clinically
significant morbidities have not been shown to differ between the two techniques, yet case reports and clinical
experience have amassed a list of reasons to avoid air. Incomplete analgesia due to air pockets in the epidural space
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has been reported in pediatric patients15. For the same to occur in obstetrics, it would presumably require large
volumes of air, but this is still a potential risk that is avoided by using saline. Venous air embolism16 and
pneumocephalus17 are more likely to occur with the use of air, and although a small amount of intravenous air is
rarely a problem, pneumocephalus is the presumed reason that using air for loss of resistance is more likely to cause
headache than when using saline. Finally, nerve root compression18 and subcutaneous emphysema19 have been
suggested as additional potential complications. One argument against saline that is now antiquated, but deserves
mention, is the theoretical possibility of confusing saline for CSF when performing a CSE. In a recent study
comparing air to saline for LOR during the CSE technique, no difference was seen in failure rates, and there were no
cases of saline being confused for CSF20. This scientific report concurs with what should be expected under these
circumstances, where saline injected into the epidural space distributes amongst the tissues such as fat and blood
vessels, and is then not available to subsequently aspirate through a spinal needle.
Accidental Dural Puncture: What Next?

The risk of accidental dural puncture (ADP) can be minimized, but not completely eliminated, with an
overall risk of approximately 1 in 200. Once an ADP occurs, there are two basic management choices that can be
made: 1) resite the epidural, or 2) thread a spinal catheter. When choosing a spinal catheter, potential complications
to keep in mind include infectious risk21, spinal cord trauma22, neurotoxicity23, and inappropriate injection through
the catheter24. When choosing to resite an epidural, potential complications to consider include inferior analgesia25
(compared to a spinal catheter), increased headache risk26 (also compared to the spinal catheter), and the risk of
unexpected high block27. The data are mixed on whether the use of a spinal catheter after wet tap can reduce the
incidence of PDPH, but no study has demonstrated an increase in headache risk. The SCORE (Serious
Complications Obstetrics REpository) Project has demonstrated that one of the highest risk scenarios for developing
high spinal is when an epidural that is resited after a wet tap is being dosed for surgery.
Techniques
Combined Spinal Epidural (CSE)

A discussion on state of the art labor analgesia would not be complete without a look at the techniques
involved. Combined spinal epidural analgesia was developed as a way of combining the attributes of both
techniques, i.e. the reliability and fast onset of the spinal combined with the duration and versatility of the epidural.
Although the CSE technique is well established, its role in labor analgesia is still in the process of being defined.
For instance, the use of CSE for patients at high risk for Cesarean delivery remains controversial to some, due to the
“untested” nature of the catheter immediately after placement. This theoretical concern has not been borne out in
studies, but the thought of a STAT Cesarean delivery in an obese parturient with an untested catheter is enough to
dissuade the most conservative anesthesiologist.
Dural puncture epidural

A recent addition to the obstetric anesthesiologist’s toolbox is the “dural puncture epidural”28. This
technique seeks to improve the quality and reliability of epidural analgesia by making a small dural puncture during
epidural placement, but without the introduction of spinal medication. Then, the catheter can be fully tested for
efficacy, while small amounts of the epidural drug passes through the dural puncture to improve efficacy. While
still not in widespread use, this technique has been thoroughly investigated and appears to improve analgesia
without increasing side effects.
Ultrasound guided neuraxial block

Advancing technology has made its way onto the labor ward in the form of ultrasound guided epidural
placement29. Popular for many years in the arena of peripheral nerve blocks, the use of ultrasound has recently seen
a flurry of activity in the obstetric anesthesia literature.
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Beyond the use of hand held ultrasonography, the use of ultrasonic waves emanating from the tip of the
needle has proven successful in animal models, and is expected to reach clinical trials in the future. The hope is that
some day, our current “blind” approach to the epidural space through loss of resistance will be replaced with
technologically advanced techniques that will allow identification of the tissue planes and epidural space with real-
time visualization.
References
1. Glover DJ. Continuous epidural analgesia in the obstetric patient: a feasibility study using a mechanical
infusion pump. Anaesthesia. 1977 May;32(5):499-503.
2. Gambling DR, Yu P, Cole C, McMorland GH, Palmer L. A comparative study of patient controlled
epidural analgesia (PCEA) and continuous infusion epidural analgesia (CIEA) during labour. Can J
Anaesth. 1988 May;35(3 ( Pt 1)):249-54.
3. Halpern S. Recent advances in patient-controlled epidural analgesia for labour. Curr Opin Anaesthesiol.
2005 Jun;18(3):247-51.
4. Wong CA, Ratliff JT, Sullivan JT, Scavone BM, Toledo P, McCarthy RJ. A randomized comparison of
programmed intermittent epidural bolus with continuous epidural infusion for labor analgesia. Anesth
Analg. 2006 Mar;102(3):904-9.
5. Atkinson BD, Truitt LJ, Rayburn WF, Turnbull GL, Christensen HD, Wlodaver A. Double-blind
comparison of intravenous butorphanol (Stadol) and fentanyl (Sublimaze) for analgesia during labor. Am J
Obstet Gynecol. 1994 Oct;171(4):993-8.
6. Olofsson C, Ekblom A, Ekman-Ordeberg G, Hjelm A, Irestedt L. Lack of analgesic effect of systemically
administered morphine or pethidine on labour pain. Br J Obstet Gynaecol. 1996 Oct;103(10):968-72.
7. Nelson KE, Eisenach JC. Intravenous butorphanol, meperidine, and their combination relieve pain and
distress in women in labor. Anesthesiology. 2005 May;102(5):1008-13.
8. Marwah R, Hassan S, Carvalho JC, Balki M. Remifentanil versus fentanyl for intravenous patient-
controlled labour analgesia: an observational study Can J Anaesth. 2012 Mar;59(3):246-54.
9. Carvalho B. Respiratory depression after neuraxial opioids in the obstetric setting Anesth Analg. 2008
Sep;107(3):956-61.
10. Vasudevan A, Snowman CE, Sundar S, Sarge TW, Hess PE. Intrathecal morphine reduces breakthrough
pain during labour epidural analgesia. Br J Anaesth. 2007 Feb;98(2):241-5.
11. Chiari A, Lorber C, Eisenach JC, Wildling E, Krenn C, Zavrsky A, Kainz C, Germann P, Klimscha W.
Analgesic and hemodynamic effects of intrathecal clonidine as the sole analgesic agent during first stage of
labor: a dose-response study. Anesthesiology. 1999 Aug;91(2):388-96.
12. Missant C, Teunkens A, Vandermeersch E, Van de Velde M. Intrathecal clonidine prolongs labour
analgesia but worsens fetal outcome: a pilot study. Can J Anaesth. 2004 Aug-Sep;51(7):696-701.
13. Nelson KE, D'Angelo R, Foss ML, Meister GC, Hood DD, Eisenach JC. Intrathecal neostigmine and
sufentanil for early labor analgesia. Anesthesiology. 1999 Nov;91(5):1293-8.
14. Ross VH, Pan PH, Owen MD, Seid MH, Harris L, Clyne B, Voltaire M, Eisenach JC. Neostigmine
decreases bupivacaine use by patient-controlled epidural analgesia during labor: a randomized controlled
study. Anesth Analg. 2009 Aug;109(2):524-31.
15. Dalens B, Bazin JE, Haberer JP. Epidural bubbles as a cause of incomplete analgesia during epidural
anesthesia. Anesth Analg. 1987 Jul;66(7):679-83.
16. Naulty JS, Ostheimer GW, Datta S, Knapp R, Weiss JB. Incidence of venous air embolism during epidural
catheter insertion Anesthesiology. 1982 Nov;57(5):410-2.
17. Nafiu OO, Urquhart JC. Pneumocephalus with headache complicating labour epidural analgesia: should we
still be using air? Int J Obstet Anesth. 2006 Jul;15(3):237-9.
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18. Overdiek N, Grisales DA, Gravenstein D, Bosek V, Nishman R, Modell JH. Subdural air collection: a
likely source of radicular pain after lumbar epidural. J Clin Anesth. 2001 Aug;13(5):392-7.
19. Viel EJ, de La Coussaye JE, Bruelle P, Saïssi G, Bassoul BP, Eledjam JJ. Epidural anesthesia: a pitfall due
to the technique of the loss of resistance to air. Reg Anesth. 1991 Mar-Apr;16(2):117-9.
20. Grondin LS, Nelson K, Ross V, Aponte O, Lee S, Pan PH. Success of spinal and epidural labor analgesia:
comparison of loss of resistance technique using air versus saline in combined spinal-epidural labor
analgesia technique. Anesthesiology. 2009 Jul;111(1):165-72.
21. Scott DB, Hibbard BM. Serious non-fatal complications associated with extradural block in obstetric
practice. Br J Anaesth. 1990 May;64(5):537-41.
22. Broadbent CR, Maxwell WB, Ferrie R, Wilson DJ, Gawne-Cain M, Russell R. Ability of anaesthetists to
identify a marked lumbar interspace. Anaesthesia. 2000 Nov;55(11):1122-6.
23. Rigler ML, Drasner K, Krejcie TC, Yelich SJ, Scholnick FT, DeFontes J, Bohner D. Cauda equina
syndrome after continuous spinal anesthesia. Anesth Analg. 1991 Mar;72(3):275-81.
24. Mappes A, Schaer HM. Accidental injection of ether into the epidural space Anaesthesia. 1991
Feb;46(2):124-5.
25. Arkoosh VA, Palmer CM, Yun EM, Sharma SK, Bates JN, Wissler RN, Buxbaum JL, Nogami WM,
Gracely EJ. A randomized, double-masked, multicenter comparison of the safety of continuous intrathecal
labor analgesia using a 28-gauge catheter versus continuous epidural labor analgesia Anesthesiology. 2008
Feb;108(2):286-98.
26. Ayad S, Demian Y, Narouze SN, Tetzlaff JE. Subarachnoid catheter placement after wet tap for analgesia
in labor: influence on the risk of headache in obstetric patients. Reg Anesth Pain Med. 2003 Nov-
Dec;28(6):512-5.
27. Leach A, Smith GB. Subarachnoid spread of epidural local anaesthetic following dural puncture.
Anaesthesia. 1988 Aug;43(8):671-4.
28. Cappiello E, O'Rourke N, Segal S, Tsen LC. A randomized trial of dural puncture epidural technique
compared with the standard epidural technique for labor analgesia. Anesth Analg. 2008 Nov;107(5):
1646-51.
29. Fanning N, Arzola C, Balki M, Carvalho JC. Lumbar dural sac dimensions determined by ultrasound helps
predict sensory block extent during combined spinal-epidural analgesia for labor. Reg Anesth Pain Med.
2012 May-Jun;37(3):283-8.
DISCLOSURE
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Fast-tracking Pediatric Ambulatory Anesthesia:

Challenges and Controversies
Linda J. Mason, M.D. Loma Linda, California
The Upper Respiratory Tract Infection Dilemma

Most anesthesiologists agree that the presence of an acute purulent upper respiratory tract infection (URI),
fever or any symptomatology of a lower respiratory infection would be sufficient grounds to postpone an elective
surgical procedure. However, the child with a nonpurulent active or recent URI (within 4 weeks) nearly always
presents a conundrum even for the most experienced anesthesiologists.
It has been documented that 20-30% of all children have a runny nose a significant part of the year. In the
preanesthetic evaluation we must rely on history, physical, and occasionally laboratory data to decide whether to
proceed with the anesthetic. A differential diagnosis of a child with a runny nose should include:
Noninfectious causes
Allergic Rhinitis: Seasonal, perennial
Vasomotor Rhinitis: Emotional (crying), temperature
Infectious Causes
Viral infections
Nasopharyngitis (common cold)
Flu syndrome (upper and lower respiratory tract)
Laryngotracheal bronchitis (infectious croup)
Viral exanthems
Measles
Chicken pox
Acute bacterial infections
Acute epiglottitis
Meningitis
Streptococal tonsillitis
Previous studies have shown that children with a URI, particularly those less than 1 year of age, have an
increased risk of respiratory related adverse events intraoperatively and postoperatively.1,2 Also symptomatic infants
with a URI have decreased time to desaturation during apnea.2 Endotracheal intubation (ETT) has been shown to be
a major risk factor for hypoxemia, bronchospasm and atelectasis in children with a URI.1-3 Temporary airway
hyperactivity is known to exist for 6 weeks after a viral infection.4
One recent study looked at 2051 children of which 22.3% had symptoms of URI on the day of surgery,
45.8% had a “cold” in the preceding 6 weeks and 30% were asymptomatic controls.5 Forty of the 2051 children did
not proceed to anesthesia and surgery on the basis of the preanesthetic consult. The nonanesthetized children were
more likely to have runny nose, cough, wheezing, malaise and fever and were said to have a cold by the parents.
There is some bias in this study first because the policy in this hospital is to reschedule elective cases with a URI if
they are under 12 months of age and require intubation and the second bias is the use of anesthesiologists to record
adverse events occurring during anesthesia rather than an independent observer who was blinded to the patients
perioperative condition.
Significant patient predictors were parental confirmation of the child’s URI symptoms, presence of nasal
secretions, history of snoring, passive smoke exposure and sputum production. As far as anesthetic risk factors,
choice of airway management was identified as an independent risk factor for postoperative adverse events,
specifically the risk was higher with ETT than with LMA or face mask use respectively.
Thiopental for induction was associated with the highest probability of an adverse event followed by
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halothane and sevoflurane with propofol having the lowest probability. Propofol depresses laryngeal reflexes and
may decrease airway responsiveness by relaxation of bronchial smooth muscle.6,7 The administration of
neostigmine was the final predictor. Children who had muscle relaxants reversed had a lower probability of an
adverse event than those who did not. Residual neuromuscular blockade may have subtle effects on outcomes and
atropine administration with neostigmine may have the beneficial effect of decreasing secretions.
In conclusion, this study suggests children whose parents say they have a cold, who are snorers, passive
smokers, have nasal congestion or a productive cough have a higher risk of anesthetic complications. Intubation
increases the risk of complications and with LMA or face mask use the probability is decreased. Propofol is the
safest intravenous induction agent and muscle relaxants should always be reversed. It is prudent to cancel non-
urgent surgery if the patient wheezes, is febrile, is suffering malaise or if the child is very young (<1 year of age).
In a prospective study with 1078 patients comprising roughly equal thirds having active URI symptoms,
recent URI symptoms within the previous 4 weeks, or no URI symptoms, respiratory adverse events were most
prevalent in the active URI group.8 There was also a significantly higher incidence of desaturation in both the active
(15.7%) and recent (14.7%) URI groups versus the non-URI group. There was no statistically significant difference
in the incidence of bronchospasm or laryngospasm between groups. In this study only nine of 407 patients (2.2%)
with an active URI confirmed by the parent required succinylcholine for management of laryngospasm, and only
three children – one with a recent URI and two with active URIs – required unanticipated admission to hospital.
By employing logistic regression8 in 1078 children with active, recent or no URI symptoms, patient risk
factors associated with adverse outcomes included copious secretions (P=0.0001), ex-premature infants (P=0.007),
nasal congestion (P=0.014), parental smoking (P=0.018), and reactive airway disease (P=0.028). ASA status did not
correlate with adverse outcomes.
The specific role age plays in the presence of URI has not been elaborated in all studies, but this study6
showed that infants less than 6 months old with active URIs had a higher incidence of bronchospasm (20.8% versus
4.7%, P=0.08) than older children. This same study also showed that children under 2 years old had a higher
incidence of oxygen desaturation than older children (21.5% versus 12.5%, P=0.023).
Anesthetic risk factors identified ETT in children under 5 years of age as an independent risk factor for
postoperative respiratory adverse events (P=0.0002).8 Of note, duration of anesthesia and awake versus deep
extubation were not identified as risk factors. Children with active URIs had the lowest incidence of problems when
induced and maintained with sevoflurane. There was a high incidence of adverse respiratory events in children
undergoing airway surgery eg. tonsillectomy and adenoidectomy, direct laryngoscopy and bronchoscopy in all 3
groups.
The conclusions of this study were children with active and recent URI’s (within 4 weeks) are at increased
risk for adverse respiratory events particularly if they have a history of reactive airway disease, require surgery
involving the airway, have a history of prematurity, are exposed to environmental tobacco smoke, have nasal
congestion or copious secretions or require placement of an endotracheal tube.
Schreiner found URIs a predictor of increased risk of laryngospasm9 while by Tait and Knight’s definition it
was not.10,11 Risk of laryngospasm has been found to be 10 fold higher in children exposed to tobacco smoke.12
Children with a URI within 30 days prior to surgery had a 2.3 fold higher risk of laryngospasm.13 Comparison of
ETT with laryngeal mask airway (LMA) use in children with a URI showed a significant lower incidence of mild
bronchospasm, major desaturation events (oxygen saturation < 90%) and overall respiratory events with LMA use.14
The incidence of laryngospasm was equal.
A study in 831 children (27% of whom presented with a recent URI within the last 2 weeks before
anesthesia) demonstrated that LMA use in children with a recent URI was associated with a higher incidence of
laryngospasm, cough and oxygen desaturation compared with healthy children. However, if anesthesiologists allow
a 2 week interval after a URI, the use of an LMA was confirmed to be a safe technique.15
In 20 children age 1-6 undergoing elective surgery with tracheal intubation those with either a respiratory
tract infection in the past 2 weeks before surgery or asthma had an increase in airway resistance with desflurane as
opposed to sevoflurane or propofol, questioning the use of desflurane in children with airway susceptibility.16
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In afebrile ASA I or II children having either a URI within 6 weeks or an active URI disease undergoing
noncavitary, nonairway surgery for less than 3 hours, pretreatment with bronchodilators prior to anesthesia (either
inhaled ipratropium or albuterol) showed no decrease in adverse airway events.17 A more recent article showed
preoperative salbutamol in children with a recent URI (<2 weeks) decreased the incidence of laryngospasm,
bronchospasm, oxygen desaturation (<95%) and severe coughing with LMA or endotracheal tube use.18
In a risk assessment study, URI was associated with an increased risk for perioperative respiratory adverse
events only when symptoms were present or less than 2 weeks before the procedure.19 However, in another study
assessing risk factors for adverse events in children with colds emerging from anesthesia a correlation with
respiratory adverse events occurred if peak URI symptoms have occurred within the preceding 4 weeks.20
There is risk to anesthesia even in children without URIs. The child with a URI has an increased risk for
laryngospasm, bronchospasm, desaturation and postintubation croup especially if someone in the home smokes. Not
all children with a URI should be anesthetized but careful consideration should be given to severity of presenting
symptoms, a patients respiratory history, need for endotracheal intubation, choice of anesthetic agent and the
anesthesiologists overall comfort with anesthetizing children with URIs.
We must wait 4-6 weeks to decrease these risks as compared to the normal child. We can tailor our
anesthetic to decrease these risks (propofol, LMA or face mask instead of ETT) but they cannot be reduced to zero.
Good judgment, common sense, clinical experience and informed consent of parents must be used when deciding
whether to cancel or proceed and discussions should be documented in the chart.
Obstructive Sleep Apnea

Sleep apnea is a sleep-related breathing disorder in children characterized by a periodic cessation of air
exchange, with apnea episodes lasting >10 seconds and an apnea/hypopnea index (AHI) – total number of
obstructive episodes per hour of sleep >5.21 Air flow cessation is confirmed by auscultation or oxygen desaturation
<92%. Types of sleep apnea include central (absent gas flow, lack of respiratory effort), obstructive (absent gas
flow, upper airway obstruction and paradoxical movement of rib cage and abdominal muscles) and mixed (due to
both CNS defect and obstructive problems). Diagnosis is made by clinical assessment (a history of snoring and
restless sleep), nocturnal pulse oximetry or polysomnography studies (PSG).
Obstructive sleep apnea syndrome (OSAS) is manifest by episodes that disturb sleep and ventilation. These
episodes occur more frequently during REM sleep and increase in frequency as more time is spent in REM sleep
periods as the night progresses. OSAS occurs in children of all ages (about 2% of all children) but more commonly
in children 3-7 years of age. It occurs equally among boys and girls but the prevalence may be higher in African
American individuals.22 Childhood obesity is increasing in modern societies and OSAS is increased in children with
obesity. Signs of OSAS are sleep disturbances (including daytime sleepiness), failure to thrive from poor intake due
to tonsillar hypertrophy, speech disorders, and decreased size (decreased growth hormone release during disturbed
REM sleep). This syndrome can cause significant cardiac, pulmonary and CNS impairment due to chronic oxygen
desaturation. In children with OSAS and morbid obesity the incidence of hypertension and diabetes are seen at
much higher rates. Therefore it is important that prior to surgery that the cardiovascular status be evaluated in this
group of children. Although right ventricular dysfunction is classic, biventricular hypertrophy can develop. It is
more likely to be seen in patients with severe OSAS but has been reported in patients with only mild OSAS.23
Pulmonary vasoconstriction can increase pulmonary vascular resistance with resultant decrease in cardiac output due
to cor pulmonale. Relief of the tonsillar/adenoidal obstruction can reverse many of these problems and prevent
progression of others (pulmonary hypertension and cor pulmonale). Cardiac evaluation is recommended for any
child with signs of right ventricular dysfunction, systemic hypertension or multiple episodes of desaturation below
70%. Electrocardiogram and chest radiograph are not sensitive tools; echocardiography is recommended.24
Patients that are at high risk for postoperative upper airway obstruction after tonsillectomy and/or
adenoidectomy for OSAS include age < 2 yr, craniofacial anomalies, failure to thrive, hypotonia, morbid obesity,
previous upper airway trauma, cor pulmonale, a polysomnogram with a respiratory distress index (RDI) > 40 or O 2
saturation nadir <70% or patients undergoing an additional uvulopalato pharyngoplasty (UPPP).25 If upper airway
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obstruction occurs postoperatively in these patients, nasal CPAP/BIPAP should be considered as a therapeutic
intervention.25
The American Academy of Pediatrics Clinical Practice Guidelines22 give the following recommendations for
inpatient monitoring in patients at high risk for postoperative complications that have OSAS and are undergoing
adenotonsillectomy. These include:
Age younger than 3 years

Severe OSAS on polysomnography
Cardiac complications of OSAS (eg right ventricular hypertrophy)
Recent respiratory infection
Craniofacial disorders
Neuromuscular disorders
Cerebral palsy
Down syndrome
Failure to thrive
Obesity
Prematurity
Sickle cell disease
Central hypoventilation syndromes Genetic/metabolic/storage disease
Chronic lung disease
As far as outpatient surgery for adenotonsillectomy in patients with OSAS, children age 1-18 years without
underlying medical conditions, neuromuscular disease or craniofacial abnormalities with mild sleep apnea (<15
obstructive events per hour) will have improvement of their airway obstruction documented by polysomnography
the night of surgery and do not need to be monitored intensively. In these patients a smaller number of obstructive
events and fewer severe oxygen desaturations occurred on the operative night.26 Based on this and other studies it is
possible to consider discharge to home for children age 3-12 years if they meet these criteria. However, in children
with severe obstructive sleep apnea (AHI >16.4 events/hr, SaO2 <85%) obstructive events occurred more frequently
on the first night after adenotonsillectomy suggesting overnight monitoring with pulse oximetry is indicated.27
OSAS patients with preoperative nocturnal oximetry oxygen saturation of 80% or less had an increase from
20% of postoperative respiratory complications to 50%. Usually these children were younger (<2 years) and had an
associated medical condition.28 Sixty percent of OSAS patients requiring urgent adenotonsillectomy had
postoperative respiratory complications. Risk factors for respiratory complications were again an associated
medical condition and preoperative nocturnal oxygen saturation nadir less than 80%. Atropine administration at
induction decreased the risk of postoperative respiratory complications. There was an 11.1% incidence of
reintubation and a 9.3% incidence of postoperative pneumonia in this urgent adenotonsillectomy group.29
Children with severe OSAS who had adenotonsillectomy in the morning were less likely to have
postoperative desaturation than those who were operated in the afternoon.30 The shortened time interval between
postoperative morphine dosing and bedtime may contribute to the incidence of postoperative desaturation because of
an exaggerated respiratory depressive response to opioids which has been reported in children with severe OSAS.31
There is a strong possibility that the combination of opioids and sleep promote desaturation in these patients.
Children with OSAS in general may have a diminished ventilatory response to CO2 rebreathing compared
with normal children.32 Therefore drugs known to cause ventilatory depression (sedative hypnotics, anxiolytics,
narcotics and inhaled agents) must be used judiciously in these patients as they may be more sensitive to their
effects. Preoperative administration of midazolam 0.5 mg/kg in 70 children undergoing adenotonsillectomy for
OSAS (diagnosed as severe in 40% of subjects by polysomnography) resulted in 2 children having respiratory
events; one had a self limited desaturation event before surgery and one had a postoperative obstruction with
desaturation requiring a nasal airway.33 Patients with OSAS can receive sedatives but require monitoring.
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During inhalational induction of anesthesia, children with OSAS are at a high risk for airway obstruction due
to relaxation of the genioglossus muscle. Positioning in an upright or lateral position, use of jaw thrust maneuver,
delivery of positive pressure by face mask and placement of an oral airway may aid in relieving the obstruction.34,35
Once anesthesia is induced and intravenous access is established, a single dose of IV propofol 1.5-2 mg/kg (lean
body weight) may facilitate tracheal intubation.36
Children with OSAS usually need pain medication after surgery yet chronic hypoxemia renders them more
susceptible to the respiratory depressant effects of opioids.37,38 Younger aged patients or those with preoperative
nocturnal oxygen saturation less than 85% had reduced morphine requirement possibly due to up-regulation of
central opioid receptors consequent to recurrent hypoxemia.39 Children whose minimum nocturnal saturation was
less than 85% required one half of the dose of opioids for similar pain scores after T & A surgery compared with
children whose minimal saturation was 85% or greater.40
One technique for opioid administration is that after tracheal intubation and spontaneous ventilation is
restored, small incremental aliquots of IV morphine (10-20 ug/kg) or fentanyl (0.2-0.5 ug/kg) can be administered.
If apnea occurs after the first aliquot of opioid, the child may be considered opioid sensitive. If they continue to
breathe additional increments up to the standard total dose of 50-100 ug/kg of morphine can be administerd.36 Drugs
for pain management to decrease opioid use include ketamine 0.1 mg/kg41 IV, or peritonsillar infiltration of
ketamine 0.5 to 1 mg/kg given 3 minutes before surgery42, dexamethasone 0.0625-1 mg/kg (maximum 25 mg) with
an average dose of 0.5 mg/kg and IV acetaminophen 15 mg/kg (maximum 75 mg/kg/d, children 2-12 years).43-45
Concern over dexamethasone use in tonsillectomy patients in respect to postoperative bleeding was raised in
an article that compared three doses of dexamethasone 0.05 mg/kg, 0.15 mg/kg and 0.5 mg/kg. The primary
objective was a decrease in nausea and vomiting and the secondary objective was postoperative analgesia.
Regardless of the dose, children who received dexamethasone needed less rescue analgesia and antiemetics,
however the larger dose 0.5 mg/kg was associated with the highest decrease in postoperative nausea and vomiting
(PONV). Of concern was that both the 0.5 mg/kg dose and the 0.05 mg/kg dose of dexamethasone were associated
with a higher incidence of postoperative bleeding. The problem with this study was the lack of standardization of
surgeon, surgical technique and use of nonsteroidal antinflammatory drugs. This study has too many flaws to
change the practice of giving dexamethasone to tonsillectomy patients and needs to be repeated with bleeding as a
primary outcome in relation to dexamethasone use.46 In a more recent retrospective review of 2788 children age 2-
18 undergoing tonsillectomy were given either 0.5 mg/kg or 1.0 mg/kg of dexamethasone. The study was adjusted
for age, sex, primary diagnosis (sleep related disorder and infectious tonsillitis) and surgical technique, either
extracapsular electrosurgical tonsillectomy, extracapsular radiofrequency ablation tonsillectomy or intracapsular
microdebrider tonsillotomy. Perioperative dexamethasone administration was not associated with a dose dependent
elevation of postoperative hemorrhage.47 A recent Cochrane review of 19 randomized placebo controlled, double
blinded studies conclude that children receiving a single intraoperative dose of dexamethasone (dose range 0.15-0.5
mg/kg) were half as likely to vomit in the first 24 hours and had less pain than the placebo group.48
A recent report of adenotonsillectomy for children who demonstrated recurrent episodes of profound
hypoxemia (<80% saturation) during the perioperative sleep study demonstrated that a decrease in major medical
respiratory interventions by >50% was accomplished by administration of dexamethasone 0.3 mg/kg (maximum 10
mg) and the titration of morphine 0.02 mg/kg.49
Nonsteroidal anti-inflammatory drugs (NSAIDS) have been avoided in post-tonsillectomy patients because of
reports of association postoperative bleeding. However, a systematic review did not find an increased risk of
reoperation for bleeding and found less vomiting when NSAIDS were part of an analgesic regimen.50 The use of
NSAIDS after attainment of hemostasis is reasonable.51
Emergence delirium may be decreased with a single IV bolus dose of dexmedetomidine 0.5 ug/kg given 5
minutes before the end of surgery thus providing a smoother transition to the post anesthesia care unit.52 A
prospective study of 122 patients, age 2-10 years undergoing tonsillectomy with sevoflurane anesthesia received IV
dexmedetomidine 2 ug/kg over 10 min followed by 0.7 ug/kg/hr and were compared to a group receiving IV
fentanyl 1 ug/kg. The dexmedetomidine group needed less rescue analgesics with fentanyl, had a lower heart rate
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and systolic blood pressure and also required less morphine in their postoperative period. Severe emergence
agitation on arrival to PACU was lower and the duration was shorter in the dexmedetomidine subjects.53
After completion of the procedure patients should be awake and be able to maintain their upper airway
patency. Deep extubation is not recommended in patients with severe OSAS or those with comorbidities because
they are at risk of persistent OSAS after surgery. Before extubation a nasal airway can be placed in patients with
severe sleep apnea. The lateral decubitus or prone position can help relieve airway obstruction after extubation.
Postoperative intensive care unit admission is reserved for very severe OSAS, very young children, morbid
obesity (BMI >40) and those with comorbidities that cannot be managed in a regular unit.54 Asthma is also
associated with an increased risk of respiratory complications after adenotonsillectomy and these children may need
a higher level of monitoring postoperatively.55 Patients with mild to moderate obstructive disease (AHI <10) and no
comorbidities can usually be discharged home the same day if they are greater than 3 years of age.
However, there have been fatalities reported in children with OSAS given oral codeine for pain management
at home. These children may be part of a group of extensive or ultra rapid metabolizers that have a greater
production of potent morphine from its parent drug codeine. The genetic pattern occurs in 1-10% of individuals of
European descent but up to 30% of North African descendants and must be considered with codeine use.56
Although the respiratory distress index improves in children with severe sleep apnea and in obese children
with OSAS after adenotonsillectomy, OSAS may not resolve in the majority of these children. In addition, enlarged
lingual tonsils were found to contribute to persistent OSAS after adenotonsillectomy in children and was found to be
more prevalent in patients with Down syndrome.57 It is important to realize that these children may have increased
anesthetic risk and need special care if they return for other surgeries.
What is the Youngest Age Appropriate for Outpatient Surgery?
Apnea Risk
There is little specific evidence of the risk of apnea in full term infants. There are facilities that feel
comfortable performing outpatient surgeries if the infant is born at greater than 37 weeks gestational age. However,
other ambulatory centers prefer to wait until the infant is 2-4 weeks of age to ensure decreased physiologic jaundice,
decreased pulmonary vascular resistance and to give time for the ductus arteriosus to close. As far as sudden infant
death syndrome (SIDS) there is no evidence anesthesia increases the risk.58 However, if the patient has a sibling
with a history of SIDS or if the mother has abused drugs in her pregnancy the risk increases many fold. The infants
whose histories suggest a high risk for SIDS should be monitored closely for a longer perioperative period.
In the premature infant apnea is more likely to occur as well as other airway complications such as
atelectasis, aspiration pneumonia, stridor and coughing with desaturation in infants undergoing inguinal
herniorrhaphy.59 The best evidence based data is found in Cote’s60 combined analysis of 255 preterm infants
undergoing inguinal herniorrhaphy under general anesthesia. Apnea was defined as >15 seconds without
bradycardia or <15 seconds when accompanied by bradycardia. Apnea was strongly and inversely related to both
gestational age (GA) and post conceptual age (PCA), continuing apnea at home and anemia (<10 gm/dl). In the
nonanemic infant with a GA of 32 weeks and a PCA of 56 weeks or with a GA of 35 weeks and a PCA of 54 weeks,
the probability of apnea was less than 1%.
Caffeine has been shown to decrease the risk of apnea in preterm infants undergoing general anesthesia. In
32 preterm infants (37-44 weeks post-conceptual age) who received IV caffeine 10 mg/kg or placebo – the caffeine
group had no postoperative bradycardia, prolonged apnea, periodic breathing or postoperative oxygen saturation
<90% while 81% of the patients in the control group had prolonged apnea at 4-6 hours postoperatively.61 A
systematic review supported the evidence that caffeine administration reduces apnea risk.62
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Anesthetic Technique
Spinal anesthesia alone has been shown to have a lower incidence of postoperative apnea and bradycardia in
former premature infants when compared to spinal plus sedation or general anesthesia.63 Also a decreased incidence
of oxygen desaturation and bradycardia has been seen.64 Central apnea was not reduced – so obstructive apnea may
play a role with sedation or general anesthesia.65 Spinal anesthesia may be indicated in high risk infants. A
Cochrane review that was based on evaluating all the previous trials (which actually included only 108 patients)
stated there is not enough evidence to show whether or not spinal anesthesia improves outcomes for a preterm baby
having surgery for inguinal hernia and that a large well designed randomized control trial is needed.66 Still the
chance for cardiopulmonary events are increased in these infants and the same postoperative monitoring as for
general anesthesia is indicated.67,68
Patients less than 60 weeks post conceptual age for hernia repair had shorter times to extubation with no
postoperative apnea after thiopental or halothane induction with desflurane maintenance than either halothane or
sevoflurane for the entire anesthetic.69 Avoidance of opioids where possible, using regional anesthetic techniques
and nonopioid systemic analgesics such as acetaminophen and nonsteroidal anti-inflammatory agents may decrease
the risk of apnea.
Recommendations
The recommendation for outpatient surgery in infants born before 37 weeks may be 50-52 weeks PCA as
long as there is no anemia, on going apnea or coexisting disease, if a risk of apnea in 5% of the patients is accepted.
However, looking at the evidence based literature to decrease the risk of apnea to <1%, patients should be greater
than 54 weeks PCA without anemia, ongoing apnea or other significant medical problems. Recent
recommendations are that infants with a PCA of less than 46 weeks should be admitted for continuous monitoring
for at least 12 h postoperatively. In infants with a PCA between 46 and 60 weeks with a history of apnea at home,
chronic lung disease, neurological disease or anemia, 12 h of respiratory monitoring is recommended. The
otherwise healthy infant in this PCA group should be monitored for 6 h postoperatively.70 Postoperative monitoring
recommendations should include oxygen saturation, heart rate and impedance pneumography and that the infants are
apnea free before discharge.
Caffeine or spinal anesthesia may decrease the risk of apnea but patients should not be discharged if they are
not eligible for anesthesia on an outpatient basis by the previously stated criteria. Full term infants are acceptable
for outpatient procedures provided that they are otherwise healthy and the procedure is not likely to result in
significant physiologic changes or postoperative pain requiring opioid medication and the anesthetic is uneventful.
Even in term infants some facilities will not allow outpatient surgery until they are 44-46 weeks post conceptual age
or may require longer observation if younger e.g. 4 hours.
References
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2. Cohen MM, Cameron CB. Should you cancel the operation when a child has an upper respiratory tract infection? Anesth
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3. Rolf N, Cote CJ. Frequency and severity of desaturation events during general anesthesia in children with and without
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4. Aquilina AT, Hall WJ, Douglas RG Jr., Utell MJ. Airway reactivity in subjects with viral upper respiratory tract
infections: the effects of exercise and cold air. Am Rev Respir Dis 1980;122:3-10.
5. Parnis SJ, Barker DS, Van der Walt JH. Clinical predictors of anaesthetic complications in children with respiratory tract
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7. Cheng EY, Mazzeo AJ, Bosnjak ZJ, et al. Direct relaxant effects of intravenous anesthetics on airway smooth muscle.
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8. Tait AR, Malviya S, Voepel-Lewis T, et al. Risk factors for perioperative adverse respiratory events in children with
upper respiratory tract infections. Anesthesiology 2001;95:299-306.
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respiratory tract infection? Anesthesiology 1996;85:475-80.
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11. Tait AR, Knight PR. Intraoperative respiratory complications in patients with upper respiratory tract infections. Can J
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13. Flick RP, Wilder RT, Pieper SF, et al. Risk factors for laryngospasm in children during general anesthesia. Pediatric
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14. Tait AR, Pandit UA, Voepel-Lewis T, et al. Use of the laryngeal mask airway in children with upper respiratory tract
infections: A comparison with endotracheal intubation. Anesth Analg 1998;86:706-11.
15. von Ungern-Sternberg BS, Boda K, Schwab C, et al. Laryngeal mask airway is associated with an increased incidence of
adverse respiratory events in children with recent upper respiratory tract infections. Anesthesiology 2007;107:714-9.
16. von Ungern-Sternberg BS, Saudan S, Petak F, et al. Desflurane but not sevoflurane impairs airway and respiratory tissue
mechanics in children with susceptible airways. Anesthesiology 2008;108:216-24.
17. Elwood T, Morris W, Martin LD, et al. Bronchodilator premedication does not decrease respiratory adverse events in
pediatric general anesthesia. Can J Anesth 2003;50:277-84.
18. von Ungern-Sternberg BS, Habre W, Erb TO, Heaney M. Salbutamol premedication in children with a recent respiratory
tract infection. Pediatric Anesthesia 2009;19:1064-9.
19. von Ungern-Sternberg BS, Boda K, Chambers NA, et al. Risk assessment for respiratory complications in paediatric
anaesthesia: a prospective cohort study. Lancet 2010;376:773-83.
20. Homer JR, Elwood T, Peterson DO, Rampersad S. Risk factors for adverse events in children with colds emerging from
anesthesia: alogistic regression. Pediatric Anesthesia 2007;17:154-61.
21. Warwick JP, Mason DG. Obstructive sleep apnoea syndrome in children. Anaesthesia 1998;53:571-9.
22. Clinical practice guideline: diagnosis and management of childhood obstructive sleep apnea syndrome. Section on
pediatric pulmonology, subcommittee on obstructive sleep apnea syndrome. American Academy of Pediatrics. Pediatrics
2002;109:704-12.
23. Amin RS, Kimball TR, Bean JA, et al. Left ventricular hypertrophy and abnormal ventricular geometry in children and
adolescents with obstructive sleep apnea. Am J Respir Crit Care Med 2002;165:1395-9.
24. Schwengel DA, Sterni LM, Tunkel DE, Heitmiller ES. Perioperative Management of Children with Obstructive Sleep
Apnea. Anesth Analg 2009;109:60-75.
25. Rosen GM, Muckle RP, Mahowald MW, et al. Postoperative respiratory compromise in children with obstructive sleep
apnea syndrome: can it be anticipated? Pediatrics 1994;93:784-8.
26. Helfaer MA, McColley SA, Pyzik PL, et al. Polysomnography after adenotonsillectomy in mild pediatric obstructive
sleep apnea. Crit Care Med 1996;24:1323-7.
27. Nixon GM, Kermack AS, McGregor CD, et al. Sleep and breathing on the first night after adenotonsillectomy for
obstructive sleep apnea. Pediatr Pulmonol 2005;39:332-8.
28. Wilson K, Lakheeram I, Morielli A, et al. Can assessment for obstructive sleep apnea help predict
postadenotonsillectomy respiratory complications? Anesthesiology 2002;96:313-22.
29. Brown KA, Morin I, Hickey C, et al. Urgent adenotonsillectomy: an analysis of risk factors associated with postoperative
respiratory morbidity. Anesthesiology 2003;99:586-95.
30. Koomson A, Morin I, Brouillette R, Brown KA. Children with severe OSAS who have adenotonsillectomy in the
morning are less likely to have postoperative desaturation than those operated in the afternoon.
Can J Anesth 2004;51:62-7.
31. Waters KA, McBrien F, Stewart P, et al. Effects of OSA, inhalational anesthesia, and fentanyl on the airway and
ventilation of children. J Appl Physiol 2002;92:1987-94.
32. Strauss SG, Lynn AM, Bratton SL, Nespeca MK. Ventilatory response to CO2 in children with obstructive sleep apnea
from adenotonsillar hypertrophy. Anesth Analg 1999;89:328-32.
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33. Francis A, Eltaki K, Bash T, et al. The safety of preoperative sedation in children with sleep-disordered breathing. Int J
Pediatr Otorhinolaryngol 2006;70:1517-21.
34. Arai YC, Fukunaga K, Hirata S, Fujimoto S. The effects of chin life and jaw thrust while in the lateral position on stridor
score in anesthetized children with adenotonsillar hypertrophy. Anesth Analg 2004;99:1638-41.
35. Clarke MB, Forster P, Cook TM. Airway management for tonsillectomy: a national survey of UK practice. Br J Anaesth
2007;99:425-8.
36. Lerman J. A disquisition on sleep-disordered breathing in children. Pediatric Anesthesia 2009;19 (Suppl 1):100-8.
37. Moss IR, Belisle M, Laferriere A. Long-term hypoxia in developing rat attenuates respiratory responses to subsequent
acute hypoxia. Pediatr Res 2006;59:525-30.
38. Moss IR, Brown KA, Laferriere A. Recurrent hypoxia in rats during development increases subsequent respiratory
sensitivity to fentanyl. Anesthesiology 2006;105:715-8.
39. Brown KA, Laferriere A, Moss IR. Recurrent hypoxemia in young children with obstructive sleep apnea is associated
with reduced opioid requirement for analgesia. Anesthesiology 2004;100:806-10.
40. Brown KA, Laferriere A, Lakheeram I, Moss IR. Recurrent hypoxemia in children is associated with increased analgesic
sensitivity to opiates. Anesthesiology 2006;105:665-9.
41. Elhakim M, Khalafallah Z, El-Fattah HA, et al. Ketamine reduces swallowing-evoked pain after paediatric tonsillectomy.
Acta Anaesthesiol Scand 2003;47:604-9.
42. Honarmand A, Safavi MR, Jamshidi M. The preventative analgesic effect of preincisional peritonsillar infiltration of two
low doses of ketamine for postoperative pain relief in children following adenotonsillectomy. A randomized, double-
blind, placebo-controlled study. Paediatr Anaesth 2008;18:508-14.
43. Pappas AL, Sukhani R, Hotaling AJ, et al. The effect of preoperative dexamethasone on the immediate and delayed
postoperative morbidity in children undergoing adenotonsillectomy. Anesth Analg 1998;87:57-61.
44. Elhakim M, Ali NM, Rashed I, et al. Dexamethasone reduces postoperative vomiting and pain after pediatric
tonsillectomy. Can J Anaesth 2003;50:392-7.
45. Uysal HY, Takmaz SA, Yaman F, et al. The efficacy of intravenous paracetamol versus tramadol for postoperative
analgesia after adenotonsillectomy in children. J Clin Anesth 2011;23:53-7.
46. Czarnetzki C, Elia N, Lysakowski C, et al. Dexamethasone and the risk of nausea and vomiting and postoperative
bleeding after tonsillectomy: A randomized trial. JAMA 2008;300:2621-30.
47. Brigger MT, Cunningham MJ, Hartnick CJ. Dexamethasone administration and postoperative bleeding risk in children
undergoing tonsillectomy. Arch Otolaryngol Head Neck Surg 2010;136:766-72.
48. Steward DL, Grisel J, Meinzen-Derr J. Steroids for improving recovery following tonsillectomy in children. Cochrane
Database Syst Rev 2011(8):CD003997. Evidence-based recommendations for the use of dexamethasone in pediatric
adeontonsillectomy.
49. Raghavendran S, Bagry H, Detheux G, et al. An anesthetic management protocol to decrease respiratory complications
after adenotonsillectomy in children with severe sleep apnea. Anesth Analg 2010;110:1093- 101.
50. Cardwell M, Siviter G, Smith A. Non-steroidal anti-inflammatory drugs and perioperative bleeding in paediatric
tonsillectomy. Cochrane Database Syst Rev 2005;CD003591.
51. Dsida R, Cote CJ. Nonsteroidal anti-inflammatory drugs and hemorrhage following tonsillectomy: do we have the data?
Anesthesiology 2004;100:749-51; author reply 751-2.
52. Guler G, Akin A, Tosun Z, et al. Single-dose dexmedetomidine reduces agitation and provides smooth extubation after
pediatric adenotonsillectomy. Paediatr Anaesth 2005;15:762-6.
53. Patel A, Davidson M, Tran MCJ, et al. Dexmedetomidine infusion for analgesia and prevention of emergence agitation
in children with obstructive sleep apnea syndrome undergoing tonsillectomy and adenoidectomy. Anesth Analg
2010;111:1004-10.
54. Leong AC, Davis JP. Morbidity after adenotonsillectomy for paediatric obstructive sleep apnoea syndrome: waking up to
a pragmatic approach. J Laryngol Otol 2007;121:809-17.
55. Kalra M, Buncher R, Amin RS. Asthma as a risk factor for respiratory complications after adenotonsillectomy in
children with obstructive breathing during sleep. Ann Allergy Asthma Immunol 2005;94:549-52.
56. Kelly LE, Rieder M, van den Anker J, et al. More codeine fatalities after tonsillectomy in North American children.
Pediatrics 2012;129:e1343-7.
57. Fricke BL, Donnelly LF, Shott SR, et al. Comparison of lingual tonsil size as depicted on MR imaging between children
with obstructive sleep apnea despite previous tonsillectomy and adenoidectomy and normal controls. Pediatr Radiol
2006;36:518-23.
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58. Steward DJ. Is there risk of general anesthesia triggering SIDS? Possibly not! Anesthesiology 1985;63:326-7.
59. Steward DJ. Preterm infants are more prone to complications following minor surgery than are term infants.
60. Cote CJ, Zaslavsky A, Downes JJ, et al. Postoperative apnea in former preterm infants after inguinal herniorrhaphy.
61. Welborn LG, Hannallah RS, Fink R, et al. High-dose caffeine suppresses postoperative apnea in former preterm infants.
62. Henderson-Smart DJ, Steer P. Prophylactic caffeine to prevent postoperative apnea following general anesthesia in
preterm infants. Cochrane Database Syst Rev 2001;4:CD000048.
63. Welborn LG, Rice LJ, Hannallah RS, et al. Postoperative apnea in former preterm infants. Prospective comparison of
spinal and general anesthesia. Anesthesiology 1990;72:838-42.
64. Somri M, Gaitin L, Vaida S, et al. Postoperative outcome in high-risk infants undergoing herniorrhaphy: Comparison
between spinal and general anesthesia. Anaesthesia 1998;53:762-6.
65. Krane EJ, Haberkern CM, Jacobson LE. Postoperative apnea, bradycardia, and oxygen desaturation in formerly
premature infants: Prospective comparison of spinal and general anesthesia. Anesth Analg 195;80:7-13.
66. Craven PD, Badawi N, Henderson-Smart DJ, O’Brien M. Regional (spinal, epidural, caudal) versus general anaesthesia
in preterm infants undergoing inguinal herniorrhaphy in early infancy (Review). Cochrane Database of Systemic
Reviews 2003, Issue 3. Art. No.: CD003669. DOI: 10.1002/14651858. CD003669.
67. Frumiento C, Abajian JC, Vane DW. Spinal anesthesia for preterm infants undergoing inguinal hernia repair. Arch Surg
2000;135:445-51.
68. Shenkman Z, Hopperstein D, Litmanowitz I, et al. Spinal anesthesia in 62 premature, former-premature or young infants:
Technical aspects and pitfalls. Can J Anaesth 2002;49:262-9.
69. O’Brien K, Robinson DN, Morton NS. Induction and emergence in infants less than 60 weeks post conceptual age:
Comparison of thiopental, halothane, sevoflurane and desflurane. Br J Anaesth 1998;80:456-9.
70. Walther-Larsen S, Rasmussen LS. The former preterm infant and risk of post-operative apnoea: recommendations for
management. Acta Anaesthesiol Scand 2006;50:888-93.
DISCLOSURE
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Common Pediatric Emergencies

Randall P. Flick, M.D. Rochester, Minneasota
Introduction
The practice of pediatric anesthesia is highly variable and as a consequence the type of emergency that may be
encountered in the community hospital will differ from that which may be routinely encountered in a children’s
hospital. This lecture is intended to provide guidance to the generalist practicing in a non-pediatric hospital and will
be presented as case based discussions. Each of the cases describe a situation that may be encountered in any acute
care hospital and include some of the following. Those that have been presented in previous years have been
updated with new information and insight. In order to ensure that the lecture contains new information
for repeat attendees I will abbreviate some areas of the discussion so that scenarios can be added
that will cover common urgent or emergent condition that may be encountered in daily practice.
These may include; laryngospasm, sudden cardiac arrest, post –obstructive pulmonary edema,
vomiting and aspiration, malignant hyperthermia or others.
1. The toddler with a suspected aero-esophageal foreign body

2. The school age child with a bleeding tonsil
3. An infant with fever and severe stridor
4. A young child with massive trauma presenting to the emergency department.
5. The neonate with pyloric stenosis
Each of these cases could be encountered in any practice. I have tried to include cases involving children of a
variety of ages. However young children are emphasized as they pose the greatest challenge in the community
setting given that emergencies in this age group are less common and less familiar to the generalist.
Case #1
The toddler with a suspected foreign body is one of the most common cases that one encounters on-call in a
children’s hospital. Suffocation related to aspiration is among the most common causes of death among children
under the age of five years. These cases are extremely challenging as they usually involve a toddler who is very
anxious uncooperative and who may have some degree of airway compromise. Although most of cases involve a
coin lodged in the esophagus some may actually involve the airway and others may involve a foreign body that is
not radio-opaque and cannot be easily localized. The first task for the team caring for a child that is suspected of
aspirating or swallowing a foreign body is differentiating aspirated foreign bodies from those that are swallowed. In
the case of the typical coin this is relatively easily and simply requires a plain radiograph of the chest and neck with
inclusion of the abdomen to ensure that a coin that has passed into the stomach is not missed. Coins that are seen on
face in an antero-posterior view are virtually by definition esophageal whereas those seen on edge in that view must
be suspected of being lodged in the airway. In both cases the child may have stridor as esophageal foreign bodies
rapidly produced edema of the esophageal wall which in turn encroaches on the membranous trachea causing a
narrowing of the subglottic airway and resulting stridor.
Removal of tracheal foreign bodies represents an enormous challenge requiring close teamwork between the
procedural team and the anesthesiologist.1,2 Controversy exists as to the proper induction technique (mask versus
intravenous), whether ventilation should be controlled or spontaneous and whether rigid or flexible bronchoscopy is
most appropriate. In the case of esophageal coins the technique used for removal remains controversial as in some
institutions these children are managed in the radiology suite using a foley catheter to remove the coin under
intravenous sedation. I will discuss both the approach to the esophageal and airway foreign bodies in this lecture
including my thoughts on the various areas of controversy.3,4
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Case #2
The case of a child with a bleeding tonsil is a classic problem in the care of children. Tonsillectomy is the second
most common procedure performed under anesthesia in children after myringotomy and in about 1% of cases there
will be bleeding in the postoperative period. A recent study has suggested that the use of steroids may increase the
risk of bleeding in the perioperative period.5 A finding not confirmed in other studies.6 Most of these bleeding
episodes will occur in the first 24 hours although a significant number will occur 5 to 7 days after the procedure and
are related to the sloughing of the eschar. Although most cases of bleeding after tonsillectomy are relatively minor
and do not present a major challenge those associated with younger children and or those with significant bleeding
represent one of the most challenging cases encountered in any setting. As in the case of the airway foreign body,
close cooperation with the surgical team is an imperative in the safe management of these children. In this lecture
we will discuss risk factors for bleeding, the evaluation of the child with the bleeding tonsil as well as the approach
to ensuring that intravascular volume is sufficient and the airway is secured.7,8
Case #3
Since before the middle of the last decade children have been vaccinated against Haemophilus influenza B and as a
consequence the frequency of epiglottitis has declined dramatically. However, these cases still do occur although
rarely. More common are the children that present with severe viral croup or the more serious disorder, bacterial
tracheitis. Bacterial tracheitis has replaced epiglottitis as the most common infectious airway emergency in children
occurring slightly more commonly than sever viral croup.9-11 Typically caused by Staph or Strep, the presentation of
bacterial tracheitis is dramatic and often emergent airway management is lifesaving. The approach to the young
child with bacterial tracheitis and severe viral croup are similar to the approach most of us learned for epiglottitis.
As with epiglottitis, the management of tracheitis requires close cooperation between the surgical team and the
anesthesiologist. Important differences exist between the treatments of the various causes of acute infectious airway
obstruction in children. These will be discussed in this section.
Case #4
Trauma, usually blunt force associated with motor vehicle crashes, is by far the most common cause of death in all
ages of children (except neonates) making it important for all anesthesiologists to be familiar with some of the basic
principles of initial management of these kids. The evaluation and care of the traumatized child is an enormous
topic and cannot be adequately covered in this refresher course lecture. Therefore, in this section I intend to focus
only on the initial management primarily of the airway as this is the role that most community anesthesiologists are
likely to assume in this setting. Anesthesiologists responding to the emergency department must be alert to the
frequent errors that occur in the field management of the pediatric airway as well as the difficulty and common
complications associated with vascular access in the young child. Important differences in the pediatric airway,
cervical spine response to hemorrhage will be emphasized as will common pitfalls that one is likely to encounter in
the chaotic environment of the emergency department. 12,13
Case #5
Care of the neonate presents obvious challenges especially for those who only occasionally care for infants. The
most common “call case” among neonates is most probably pyloric stenosis. Pyloric stenosis results from
hypertrophy of the muscle surrounding the gastric outlet and presents classically in first born males with a history of
projectile vomiting in an otherwise vigorous neonate that continues to have an interest in feeding. Hypovolemia as
well as electrolyte abnormalities including hypochloremia, hypokalemia and metabolic alkalosis are frequently
encountered. Although most texts continue to admonish the anesthesia practitioner not to be convinced by an
impatient surgeon to take these babies to the operating room until they have had several hours of intravenous
rehydration (usually overnight) those cases that are diagnosed early can be safely taken to the operating room for
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pyloromyotomy as soon as the electrolytes have been confirmed to be normal and the child has received a modest
amount of isotonic fluid. The need for prolonged rehydration and electrolyte correction and other aspects of the
care of the neonate with pyloric stenosis remain controversial.14 15,16 Perioperative management will be outlined
including advice for those uncomfortable with the care of neonates who may wish to limit their groups practice to
older children.
Each of the cases outlined above have potential pitfalls and controversies that could easily occupy more than the
time allotted for this refresher course lecture. I will therefore cover as much of the material as time allows and
provide the audience with an opportunity to help choose the cases that are of the greatest interest.
1. Litman RS: Anaesthesia for bronchial foreign body removal: what really matters? Eur J Anaesthesiol
2010; 27: 928-9
2. Fidkowski CW, Zheng H, Firth PG: The anesthetic considerations of tracheobronchial foreign bodies
in children: a literature review of 12,979 cases. Anesth Analg 2010; 111: 1016-25
3. Waltzman ML: Management of esophageal coins. Curr Opin Pediatr 2006; 18: 571-4
4. Soprano JV, Mandl KD: Four strategies for the management of esophageal coins in children. Pediatrics
2000; 105: e5
5. Beutner D, Koll C: Dexamethasone and postoperative bleeding after tonsillectomy in children. JAMA
2009; 301: 1764; author reply 1765-6
6. Brigger MT, Cunningham MJ, Hartnick CJ: Dexamethasone administration and postoperative bleeding
risk in children undergoing tonsillectomy. Archives of Otolaryngology -- Head & Neck Surgery 2010;
136: 766-72
7. Fields RG, Gencorelli FJ, Litman RS: Anesthetic management of the pediatric bleeding tonsil. Paediatr
Anaesth 2010; 20: 982-6
8. Czarnetzki C, Elia N, Lysakowski C, Dumont L, Landis BN, Giger R, Dulguerov P, Desmeules J,
Tramer MR: Dexamethasone and risk of nausea and vomiting and postoperative bleeding after
tonsillectomy in children: a randomized trial. JAMA 2008; 300: 2621-30
9. Graf J, Stein F: Tracheitis in pediatric patients. Semin Pediatr Infect Dis 2006; 17: 11-3
10. Sendi K, Crysdale WS, Yoo J: Tracheitis: outcome of 1,700 cases presenting to the emergency
department during two years. J Otolaryngol 1992; 21: 20-4
11. Hopkins A, Lahiri T, Salerno R, Heath B: Changing epidemiology of life-threatening upper airway
infections: the reemergence of bacterial tracheitis. Pediatrics 2006; 118: 1418-21
12. Bankole S, Asuncion A, Ross S, Aghai Z, Nollah L, Echols H, Da-Silva S: First responder
performance in pediatric trauma: A comparison with an adult cohort. Pediatr Crit Care Med 2010
13. Ehrlich PF, Seidman PS, Atallah O, Haque A, Helmkamp J: Endotracheal intubations in rural pediatric
trauma patients. J Pediatr Surg 2004; 39: 1376-80
14. Cook-Sather SD, Tulloch HV, Cnaan A, Nicolson SC, Cubina ML, Gallagher PR, Schreiner MS: A
comparison of awake versus paralyzed tracheal intubation for infants with pyloric stenosis. Anesth
Analg 1998; 86: 945-51
15. Willschke H, Machata AM, Rebhandl W, Benkoe T, Kettner SC, Brenner L, Marhofer P: Management
of hypertrophic pylorus stenosis with ultrasound guided single shot epidural anaesthesia--a
retrospective analysis of 20 cases. Paediatr Anaesth 2011; 21: 110-5
16. Allan C: Determinants of good outcome in pyloric stenosis. J Paediatr Child Health 2006; 42: 86-8
DISCLOSURE
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Current Controversies in Pediatric Anesthesia
Jerrold Lerman, M.D. Buffalo & Rochester, New York
OBJECTIVES:
The purpose of this lecture is to bring to your attention important controversies in the practice of anesthesia
for children. None of us practice anesthesia as we did 10, 20 or 30 years ago in training and thus our practices are
continually evolving based on new concepts and new strategies. In some instances, the literature appears rather
confusing and even contradictory. Thus, it is important to review and dissect the literature to ensure we are not
misled by weak evidence and modify our practices to the detriment of our patients. Accordingly, we will explore
eight subjects, focusing on the most credible and novel evidence to improve the quality of care for children.
• Apoptosis
• Laryngospasm
• Tracheal tubes
• Perioperative fluid management
• Hypotonia
• MH
• OSA & PONV
• Emergence delirium
APOPTOSIS:
Both anesthesiologists and lay persons have been inundated with information regarding the association
between anesthesia and brain damage in infants. Most recently in the New England Journal of Medicine, a
perspective paper highlighted select studies that potentially incriminate anesthetics in the genesis of apoptosis while
overlooking dissenting studies.1 Moreover, the authors reiterated a conclusion espoused by the Anesthetic and Life
Support Advisory committee at the FDA from 2007 that read: “there was insufficient evidence to change the
practice of pediatric anesthesia other than to forego elective procedures in children less than 3 years of age.” I view
this as a staggering misrepresentation of the current anesthetic literature and a failure to consider all of the literature
that fortunately has been completely ignored by all those with common sense.
What are the incriminating data? Studies in neonatal rodents and primates identified a plethora of NMDA
receptor antagonists and GABAA-ergic agonists that are used in anesthesia in the pathogenesis of apoptosis.2-4
However, several medications (including lithium) have been shown to protect against apoptosis.5,6 Until recently,
none of these studies included a surgical stimulus or systemic inflammatory response. In a single study, the effects
of anesthesia were studied together with inflammation and determined to increase the severity of apoptosis.7 Most
recently, memory loss after general anesthesia in rats was substantively attenuated when the rats were stimulated in
an exercise program.8 These data suggest that compensatory mechanisms (used in humans routinely) such as
stimulation may enable the brain to offset the defects reported in newborn animals.
In humans, several retrospective studies have suggested that neurocognitive dysfunction occurs after
multiple anesthetics in young children.9 However, in a twin study from Denmark, there was no evidence of a
difference in intelligence testing between identical twins who were discordant for anesthesia.10 Currently, in stark
contrast to the perspective published by the FDA in the NEJM, I inform parents that there is no evidence that
anesthetics that are given during or after surgical procedures in infants and children are harmful.
LARYNGOSPASM:
Laryngospasm occurs in almost 2% of infants and children (twice the incidence reported in adults).
Epidemiologically, the incidence decreases (~8% per year) with increasing age, and more than 50% of cases
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occurring in children <5 years of age.11 Additional factors associated with laryngospasm include a recent upper
respiratory tract infection in the preceding two weeks (two-fold increase), smoking in the home, surgical factors
(airway and urgent surgeries) and anesthetic factors (including ASA physical status, airway anomalies, light levels
of anesthesia, foreign substances in the airway, use of airway irritants and inexperienced operators).11,12
Pathophysiologic mechanisms of laryngospasm involve an afferent nociceptive stimulus, brain stem integration and
efferent neural pathways that result in closure of the glottis aperture (true and false vocal cords) through adduction
of the supraglottic muscles around the vocal folds. This is recognized as a protective reflex that likely has its origins
in the diving reflex in mammals.
The airway is most commonly lost during or immediately after induction of anesthesia or after extubation
of the trachea. Loss of a patent upper airway when spontaneously breathing through a mask often results from upper
airway obstruction, which may be relieved by manually adjusting the facemask on the face. Application of a proper
jaw thrust13 (rather than inserting an oral airway) will be demonstrated using a video (as described below). If the
jaw thrust does not establish an airway, the reservoir bag is not moving and the capnogram is flat, then
laryngospasm may be present. To prevent the development of laryngospasm or to stop it from progressing, we
require a specific skill set to recognize it and institute appropriate treatment. This has recently been summarized in a
review that includes a management algorithm.11,14 A properly fitting facemask is essential. The mask must seal
around the nose, cheeks and mouth to allow the delivery of CPAP. An unsealed mask leads to a dilution of the
anesthetic (preventing our ability to deepen the level of anesthesia or to administer 100% oxygen as needed) and
prevents the administration of positive pressure. The most expeditious means to deepening the level of anesthesia is
to administer intravenous propofol. The dimensions of the upper airway decrease as anesthesia is induced. The
dimensions may be further compromised by the presence of large tonsils and adenoids. If the airway becomes
obstructed (as evidenced by suprasternal and supraclavicular retractions, chest wall in-drawing and extreme
diaphragmatic excursions), inspiratory noises (crowing) due to a partially closed glottis are often heard. With
complete airway closure (ie., severe laryngospasm), the noisy airway suddenly becomes silent. To remedy this
rapidly deteriorating situation, a tight-fitting facemask should be held to the face with 100% oxygen flowing at an
appropriate rate. The pop-off valve should be closed to pressurize the breathing circuit to maintain 5-20 cm H2O
pressure during the full respiratory cycle. These maneuvers tent open the upper airway, and prevent the false-vocal
cords from being drawn into the glottis and triggering laryngospasm. If chest wall movement continues with a
questionable respiratory effort, it remains possible to break the laryngospasm. I rarely (if ever) use oral airways in
children. I prefer to apply the “jaw thrust” maneuver to the condyles (ie., not to the angle of the mandible) of the
mandible by applying digital pressure behind the pine while pulling towards the frontal hairline.13 This maneuver
translocates the mandible anteriorly as well as rotates the temperomandibular joint (TMJ) thereby pulling the tongue
and other tissues off the posterior pharyngeal wall. When applied correctly to the anesthetized child, this maneuver
actually opens the mouth. The TMJ does not dislocate because of ligaments within the joint, but rather subluxes. No
fingers other than the single digit applied to each condyle need touch the mandible. This maneuver is also extremely
painful and tends to wake the child up at the end of surgery, causing him/her to breathe deeply and move. This
maneuver will be demonstrated with videos during the lecture. Whatever you do, DO NOT ATTEMPT TO FORCE
GAS into the “lungs” against a closed glottis because the gas takes the path of least resistance and inflates the
stomach, increasing the risk of regurgitation. If the child is able to pull some air through the vocal cords (ie., there
are faint but audible noises from gases passing through the vocal cords), then attempt to augment the respiratory
efforts in synchrony with the child’s efforts. If the laryngospasm does not abate, atropine 20 µg/kg and propofol 1-2
mg/kg IV should be administered.11,15,16 Sooner rather than later, is my philosophy for administering atropine and
propofol.11 At this point, the pulmonary system is tenuous, but the cardiovascular system remains stable. It is crucial
to prevent more than one organ system from failing to decrease the risk of an adverse neurologic outcome. If the
lungs cannot be manually ventilated after these maneuvers, then either complete airway closure (laryngospasm) has
occurred or the airway is obstructed for another reason (ie., foreign body). It is prudent not to wait until hypoxia
relaxes the vocal cords to establish an airway.11 Rather, it is key to intervene before the saturation is too low or
bradycardia occurs by administering intravenous atropine and succinylcholine to prevent a cardiac arrest.
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Remember, the tone and numerical display of the pulse oximeter generally underestimates the true oxygen saturation
when the saturation is decreasing rapidly. Underestimating the saturation hastens intervention by the
anesthesiologist. If complete laryngospasm occurs, then it is important to administer atropine (20 µg/kg) promptly
followed by succinylcholine, 0.5-1.0 mg/kg intravenously or 3-4 mg/kg intramuscularly, if no intravenous access is
available.17 Again, do not wait for bradycardia to occur to administer these medications.
TRACHEAL TUBES:
Tracheal tubes in infants and children have traditionally been uncuffed out of concern for upper airway
obstruction in the recovery room and ICUs after extubation. With the introduction of the MicroCuff® tube and
several publications in which cuffed tubes were well tolerated in children, practice has begun to shift to the routine
use of cuffed tracheal tubes in infants and children in the operating room. The external diameter of cuffed tracheal
tubes is approximately 0.5 mm larger than uncuffed tubes because of the cuff. When this adjustment was considered,
the cuffed tube size formula was ID (mm) = 3 (or 3.5) + age (years)/4 for children >1 year of age.18
Studies have enumerated the advantages of cuffed tubes over uncuffed tubes in children including a
reduced number of re-intubations, a smaller leak around the tracheal tube, greater ease and consistency of
ventilation, reduced cost of anesthetics, and a reduced risk (theoretically) of aspiration.19,20 If a cuffed tracheal tube
is used, the cuff is inflated to provide a leak between 20 and 30 cm H2O peak inflation pressure and/or the cuff
pressure should be monitored. It should be noted that these tubes are packaged with ~0.5 ml of air in the cuff. The
cuff should be completely deflated before intubation and only the minimum amount of air should be used to inflate
the cuff to achieve a sufficient seal. The advantages of the MicroCuff® tube include a cuff that is closer to the tip of
the tube, a reduced cuff sealing pressure (potentially reducing injury to the mucosa of the trachea), and less gas and
fluid leakage around the cuff. Nitrous oxide readily diffuses into the cuff, which may increase the cuff pressure
unless it is filled with saline. Since the MicroCuff® tube seals the airway at a reduced pressure compared with
uncuffed tubes, the time interval until the pressure within the cuff becomes excessive during nitrous oxide
administration is greater with the MicroCuff® tube than it is with traditional cuffed tubes.21 Cuffed tracheal tubes
have been shown to reduce the cost of inhalational anesthetics by reducing the fresh gas flow compared with
uncuffed tubes which in terms of the MicroCuff® tube, may offset the nearly five-fold greater cost compared with
uncuffed tubes.22
Molded preformed tracheal tubes are especially useful for head and neck surgery to ensure an unkinked
tube while the anesthesia breathing circuit remains in tact. There is substantial variability in the length of the tubes
from the curvature to the tip for oral and nasal RAE tubes among manufacturers of the tubes, particularly for cuffed
tubes. In children, the length of a nasal tube is 1 cm longer than the oral tube and the oral tube is 10 cm plus the age
in years ≥2 years (eg., 12 cm at 2 years for an oral tube). Caution should be exercised in selecting the correct tube
because of the discrepant lengths from the preformed bend to the mid-trachea as in the case of the nasotracheal RAE
tubes. Failure to appreciate these differences in the length of the tubes may make it difficult to rest the tube on the
forehead after it is positioned or worse, the tube impacts on the carina or passes endobronchially.
PERIOPERATIVE FLUID MANAGEMENT:

Traditional maintenance fluid therapy for children who are ill or fasting before surgery has been a
hyponatremic solution with glucose. Many different formulations of intravenous solutions have been used for this
purpose over the years including 2/3 dextrose and 1/3 saline, and D5/0.2N/S. In the operating room, practice has
shifted (at least in North America) from these solutions to the use of balanced salt solutions. However, outside the
operating room, these hyponatremic solutions continue to be used. Over the years however, evidence has
accumulated that these solutions could cause very serious harm including death if infused in hospitalized children
for any period.23,24 Reports of severe hyponatremia and hyperglycemia that resulted in cerebral edema, seizures,
regurgitation and aspiration appeared leading to anoxic brain damage, neurologic injury and death in up to 50% of
the cases.25
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The mechanisms underlying these complications are not far-fetched: 1. a source of free water, and 2.
release of antidiuretic hormone (in response to dehydration, stress, pain and certain medications (including opioids)).
ADH causes distal renal tubular reabsorption of water to maintain fluid homeostasis. In some circumstances
however, ADH secretion occurs in the absence of dehydration resulting in excess water retention that may induce
hyponatremia that causes cerebral edema, seizures, regurgitation and aspiration. In the UK and other parts of the
world, hypotonic, hyponatremic, glucose-containing solutions continue to be administered to susceptible children.26-
28
With the secretion of ADH an unknown variable in children, the safe solution for intravenous use was deemed to
be an isotonic salt solution throughout and after surgery.25
In some situations, a second or supplemental solution should be infused to prevent hypoglycemia.
Neonates, particularly those born premature, have inadequate glucose and calcium body stores. In the early
postnatal period, these infants are at risk for hypoglycemia and hypocalcemia. Furthermore, their immature kidneys
are incapable of regulating sodium concentration if challenged with a sodium load. Accordingly, many of these
infants receive a D10% solution with calcium as their maintenance solution until they no longer require them. When
these infants present for surgery, these solutions should always be continued to preclude reactive hypoglycemia.
Similarly, children who receive D10 or D20 in TPN should continue these solutions for the same reasons, although
some decrease their infusion rates during surgery. Whether the infusion rates of these concentrated glucose solutions
should be decreased during anesthesia to account for the stress response has not been clarified. If any concern exists
regarding the serum glucose concentration, a glucose measurement should be performed.
Several groups of infants and children may benefit from the addition of small quantities of glucose (ie., 1-
2% dextrose concentration) in their balanced salt solution for maintenance.29 The purpose is to prevent those
children who may not be capable of maintaining an adequate glucose concentration when stressed, from becoming
hypoglycemic. These include infants < 6 months of age, those afflicted with chronic diseases, those with
malnutrition and those taking oral hypoglycemics.
Fifty years ago, Holliday and Segar developed the 4-2-1 rule for the hourly rate for maintenance fluid
therapy.30 The rule states that 4 ml/kg IV solution be given for the first 10 kg, 2 ml/kg for the second 10 kg and 1
ml/kg for every kg thereafter. The authors recommended infusing this volume hourly for maintenance. In addition,
third space losses (1 ml/kg/h for minimal surgery up to 10-15 ml/kg/h for open abdomen or thoracic surgery) should
be replaced with a balanced salt solution. The deficit volume, a contentious volume to replace, has also been the
focus for replacement. When fasting intervals were prolonged, this was a large issue. But as the fasting intervals
have been abbreviated (currently 2h clear fluids is the rule, but is often not the practice), the importance of replacing
the deficit has diminished. In situations where the child has fasted for an extended period of time, many still
consider replacing half of the deficit in the first hour with a balanced salt solution and the remainder in the second
hour should be considered.
Recently however, Holliday and Segar revised their strategy for fluid resuscitation in infants and
children.31,32 They did so because the 4-2-1 rule was never intended for balanced salt solutions and they failed to
appreciate the impact of SIADH in the perioperative period. As a result, they revised their recommendation to give
20-40 ml/kg intravenously of an isotonic salt solution to restore euvolemia in most infants and children (with a few
exceptions) administered over 2-4 hours in the perioperative period, followed by half the daily maintenance rate of
an isotonic solution during the postoperative period (ie., 2-1-0.5 ml/kg rather than 4-2-1 ml/kg). Lactated Ringer’s
solution may be preferable to Normal Saline as the latter increases the risk of a non-anion gap acidosis.33 Not only
does this new fluid management strategy provide for early fluid resuscitation (and decreasing ADH release), but
balanced salt solutions minimize the risk of free-water overload. However, simply substituting iso-osmolar for
hypo-osmolar solutions without restoring euvolemia does not prevent hyponatremia as ADH will continue to be
released.34 Postoperatively, this revised fluid management strategy reduces the risk of hyponatremia (from SIADH),
a problem that is being reported increasingly, particularly postoperatively in children who are fasted.35
Unrecognized perioperative hyponatremia may be avoided by mandating that the electrolytes are analyzed daily in
any child who receives an IV solution for >24h.35 Furthermore, establishing euvolemia reduces postoperative nausea
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and vomiting.36 Rather than focus on the fluid administration for every 10 kilograms, the volume of isotonic fluid
administration during and after surgery should aim to restore normovolemia or produce mild hypervolemia.
Exceptions to this revised fluid practice include children with renal or cardiac insufficiency as well as
neonates who may not tolerate the hypervolemia (without developing a patent ductus arteriosus). In the latter case,
controlled infusions of intravenous fluids with calibrated pumps are recommended. Prolonged administration of
large volumes of isotonic solutions may, in some instances, may lead to hypernatremia, which is an equally serious
problem. Hence, judicious use of reduced volumes of maintenance solutions is indicated.
MYOPATHY:
The child who presents with an undiagnosed myopathy is often a challenge for the anesthetic team. In the
absence of a definitive diagnosis, identifying the characteristics of each myopathy, the risks of anesthesia and the
ideal or preferred anesthetic is often problematic for those not commonly managing these children. The spectrum of
myopathies is exceedingly variable, the symptoms non-specific and the signs obscure. The infant with hypotonia or
a “floppy” appearance, may be at risk for acute rhabdomyolysis, hyperkalemia and cardiac arrest.37 Alternately, the
adolescent with a chronic myopathy is more likely to have a cardiomyopathy and less of a skeletal myopathy,
requiring a more patient induction.
The treatment of acute rhabdomyolysis requires discontinuing the offending anesthetic, hyperventilation,
hydration, alkalinize the urine, induce a diuresis (to prevent myoglobinuria), treatment of hyperkalemia with calcium
IV and beta agonists until the urine returns from Coca-Cola colored to clear and yellow. This may require several
hours of treatment.
The approach to the child with an undiagnosed myopathy is to elicit a history and family history of the
myopathy, as well as the outcomes of previous anesthetics (complications including cardiac arrests and ICU
admissions).37 The age of onset of the symptoms is often a clue to the diagnosis. The progression of the disease as
the child has aged, physical examination looking for evidence of pseudohypertrophy of the calf muscles or
contractures, laboratory investigations including blood tests (CK levels, lactate levels, electrolytes), echocardiogram
and electrocardiogram, and chest Xray all assist in establishing the current severity of the disease and extra-oorgan
involvement.37 It may be necessary to contact the primary physician to learn further about the child.
The key considerations include establishing the risks of MH in the child, of developing rhabdomyolysis and
of a decompensating cardiomyopathy in the perioperative period.37,38 Today, MH is often diagnosed from a family
history and much more rarely, from a reaction de novo. Only two myopathies, which are rare, are associated with
MH: central core disease and King Denborough syndrome.37,38 Many myopathies ranging from Wernig-Hoffman in
infants to Duchenne’s muscular dystrophy in school-age children predispose to rhabdomyolysis in the presence of
inhalational anesthetics and/or succinylcholine. However once reaching adolescence, children with Duchenne’s
more likely present with cardiorespiratory deterioration rather than myopathic reactions. As a result, we often
provide intravenous anesthesia for these children with propofol. Some suggest that the anesthetic workstation
(AWS) should be flushed as in MH for these children but there is no data that establish the concentration of
inhalational anesthetics that triggers rhabdomyolysis in these children.
The third large diagnosis is that of mitochondrial myopathies.37-39 This heterogeneous group of disorders is
characterized by defects in the mitochondrial respiratory chain, with defects resulting from gene mutations in either
the mitochondrial or the nuclear (more common in children) DNA. The variability in the presentation of these
myopathies results from variability in expression of the mutations in various organs at different stages of
development. Possible organ involvement ranges from the central nervous system to the abdomen and skeletal
musculature. Curiously, in the absence of any clear link, many have recommended the avoidance of propofol (some
proscribing it completely) in children with these disorders on the basis that propofol infusion syndrome, a disorder
predicated on a systemic inflammatory response, interferes with the mitochondrial respiratory chain on several
levels. However, incriminating any anesthetic in triggering an untoward reaction in a child with a mitochondrial
myopathy is without basis. I usually use a propofol infusion for maintenance in these children, although I have used
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an inhalational anesthetic as well. Nitrous oxide, opioids, benzodiazepines and alpha2 agonists all appear to be safe
for use in these children.
MALIGNANT HYPERTHERMIA:
There have been several developments in the management of children with MH that warrant our attention.
First, when preparing contaminated AWSs for MHS patients, we now recognize that there is no single flush period
that reliably removes inhalational anesthetics to <10 ppm from all AWSs. For GE Ohmeda machines, a 25 minute
flush is required and for Drager machines, ≥100 minutes may be required.38,40,41 Variability in these times depends
on whether the ventilator is running and which parts of the AWS are replaced. I agree with the MHAUS guideline to
use charcoal filters to protect patients from inhalational anesthetics,42 particularly since we cannot verify that the
AWS has <10 ppm inhalational anesthetic present. Curiously, despite the variability in flushing contaminated
AWSs, no reactions have been reported after a machine was flushed. Whether the anesthetic concentration must be
< 10ppm remains to be established.
Second, it is now well-established that only two myopathies are associated with MH: central core disease
and King Denborough myopathy.38 Third, two new rapid dissolving formulations of dantrolene have been
developed, although the dose per ampoule has not changed (we do need 100 mg/ampoule formulations). Ryanodex
dissolves about 20-30 times more rapidly than dantrolene. Fourth, reports indicate that the skin temperature may not
yield abnormal temperatures if an MH reaction occurs and could lead to delays in treatment.43 We caution against
using skin temperature in MH patients.
OSA & PONV:

Although T&A surgery is one of the most common surgeries performed in children, it has become one of
the more complex pathophysiologies to understand in pediatric anesthesia for several reasons. Two of these reasons
are new frontiers in T&A surgery hold great interest for the practicing pediatric anesthesiologist: OSA & PONV.
Obstructive sleep apnea is the most severe form of sleep-disordered breathing, which may complicate T&A
surgery as well as any other surgery for which a child is scheduled. In the absence of a sleep study, clinical criteria
do not reliably predict the presence of OSA in children. However, it is crucial to recognize those children with
manifestations of OSA including morning somnolence, nocturnal enuresis, weight gain or loss, poor eating habits,
poor school performance, inability to concentrate/focus, attention deficit disorder and behavioral problems.44
Snoring is an insensitive metric for diagnosing OSA, most children presenting for T&A surgery have a snoring
history. Gozal proposed that we consider OSA as two distinct entities: type 1 and type 2 (analogous to the two types
of diabetes).45 1 refers to OSA without obesity and Type 2 refers to OSA with obesity. With the latter type, there is
evidence that type 2 also involves a systemic inflammatory response.
Caution must be exercised when administering opioids to children whose nocturnal saturation nadir is
<85%; these children may express an exaggerated response to a usual dose of opioids administered at any time
including after T&A surgery.44,46 Intermittent nocturnal hypoxia as does chronic hypoxia, up-regulates several genes
including hypoxia-inducing factor, c-FOS and c-JUN.44 These genes ultimately code from mu opioid receptors
resulting in an increase in receptors and therefore an exaggerated response to a standard dose of opioids. The
precise mechanism that leads to the increased opioid sensitivity remains unclear, although proliferation of the µ1
receptors may be involved. If true, we may find that hypoxia up-regulates the opioid receptor mu 1 (OPRM1), the
gene responsible for coding for the mu-1 receptor.47 Using the observations from one of the first reports of apnea in
response to a small dose of fentanyl in children with OSA,48 I routinely evaluate the respiratory responses (in terms
of apnea) to a small dose of an IV opioid (usually 20 µg/kg morphine) while the child breathes spontaneously during
tonsillectomy. If the child becomes apneic, the child may require no additional opioids or minimal incremental doses
to achieve a pain-free state. The PACU nurses and surgeon should be advised of the child’s sensitivity to reduce the
postoperative dose of the opioids. Alternatively, it may be preferable to avoid opioids in these children (substituting
ketamine or tramadol) or use regional blocks/local anesthesia. Lastly, the severity of OSA improves after T&A
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surgery in most children, although as many as one-third of those with severe OSA do not improve their sleep studies
by 6 months post-surgery and require further investigation and therapy.49
Emergence Delirium:
Emergence delirium (ED) is an unpredictable behavior that occurs during the arousal phase from anesthesia
primarily in preschool age children (and in the elderly). This is not a new disorder, re-emerging with the
introduction of every new (and more rapid acting than the previous) anesthetic in the past 50 years. The behavior
begins in the PACU and lasts for up to approximately 20 minutes once the child recovered from anesthesia. The
characteristics of ED include inconsolability, and failure to focus or fixate on known and familiar
faces/people/objects, irritability, non-purposeful movement and restless. Several scales have been used to measure
ED, although none were validated until the introduction of the Pediatric Anesthesia Emergence Delirium (PAED)
scale.50 With this scale we have finally had a validated metric to determine who has and does not have delirium.
Nonetheless, we have not proven that the PAED scale is sufficiently robust to detect ED distinct from pain.
The incidence of ED in the preschool age population is as great as 40%.51 Initially, this disorder was
associated with the use of sevoflurane, but subsequent evidence has shown that ED occurs with the entire class of
ether anesthetics, that is desflurane and isoflurane anesthesia.52 It occurs much less commonly after propofol. It is
associated with neither rapid recovery nor the absence of parents.
Differentiating ED from pain has been a dilemma since a number of studies of ED evaluated behaviors
after surgery that was potentially painful. Until a study of ED was conducted in the MRI suite, it was not possible to
completely establish the incidence of ED after anesthesia.53 That study showed that the incidence of ED after
sevoflurane for MRI in children, 30%, was substantively greater than that after halothane, 0%.
Strategies to prevent ED have included midazolam and 5-HT3 receptor antagonists, but these were
ineffective.54 In contrast, propofol (a continuous infusion or a bolus at the end of surgery were effective, not a bolus
at induction), ketamine, fentanyl (by intra-nasal not intraoperative IV route), alpha2 receptor antagonists, and
preoperative analgesics were all found to be effective to varying degrees in a meta-analysis on ED in children.54
A great deal of work is needed to further refine and define ED in children.55 Whether this problem warrants
further investigation and heralds additional behavioral problems, remains to be established.
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27. Cunliffe M, Potter F. Four and a fifth all that. Br J Anaesth 2006:97;274-7
28. Stewart P. New maintenance fluid guidelines for children: is 0.9% sodium chloride with 5% glucose a good
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29. Paut O, Lacroix F. Recent developments in the perioperative fluid management for the paediatric patient. Curr
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31. Holliday MA, Friedman AL, Segar WE, et al. Acute hospital-induced hyponatremia in children: a physiologic
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33. Zunini GS, Rando KAE, Cox RG. Fluid replacement in craniofacial pediatric surgery: normal saline or
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36. Goodarzi M, Matar MM, Shafa M, et al. A prospective randomized blinded study of the effect of intravenous
fluid therapy on postoperative nausea and vomiting in children undergoing strabismus surgery. Ped Anesth
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37. Veyckemans F. Can inhalation agents be used in the presence of a child with myopathy? Curr Opin Anaesth
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38. Lerman J. Perioperative management of the paediatric patient with coexisting neuromuscular disease. Br J
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39. van Adel BA, Tarnopolsky MA. Metabolic myopathies: update 2009. J Clin Neuro Dis 2009:10;97-121
40. Kim TW, Nemergut ME. Preparation of modern anesthesia workstation for malignant hyperthermia-susceptible
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43. Larach MG, Gronert GA, Allen GC, et al. Clinical presentation, treatment, and complications of malignant
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45. Dayyat E, Kheirandish-Gozal L, Gozal D. Childhood obstructive sleep apnea: one or two distinct disease
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analgesic sensitivity to opiates. Anesthesiology 2006:105;665-9
47. Wu WD, Want Y, Fang YM, et al. Polymorphism of the µ-opioid receptor gene (OPRM1 118A>G) affects
fentanyl-induced analgesia during anesthesia and recovery. Mol Diagn Ther 2009:13;331-7
48. Waters KA, McBrien F, Stewart P, et al. Effects of OSA, inhalational anesthesia, and fentanyl on the airway
and ventilation of children. J Appl Physiol 2002:92;1987-94
49. Mitchell RB, Kelly J. Outcome of adenotonsillectomy for obstructive sleep apnea in obese and normal-weight
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51. Aono J, Ueda W, Mamiya K, et al. Greater incidence of delirium during recovery from sevoflurane anesthesia
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53. Cravero J, Surgenor S, Whalen K. Emergence agitation in paediatric patients after sevoflurane anaesthesia and
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DISCLOSURE
Abbott Canada, Self, Honoraria
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Preoperative Evaluation, Premedication, and Induction of

Anesthesia in Infants and Children
Zeev Kain, M.D., MBA Irvine, California
Anxiety in children undergoing invasive medical procedures and anesthesia and surgery is characterized by
feelings of tension, apprehension, and nervousness. Some children verbalize their fears explicitly, whereas others
express their anxiety only by behavioral changes. Children may appear scared or agitated, breathe deeply,
tremble, stop talking or playing, and start to cry. These behaviors may give children some sense of control in the
situation and thereby diminish the damaging effects of a sense of helplessness.
Risk Factors
Identifying risk factors for anxiety prior to undergoing invasive medical procedures is important because
the routine use of pharmacologic and behavioral interventions is associated with both advantages and
disadvantages. Routine administration of sedative premedication, for example, may increase indirect pharmacy
costs, the need for nursing staff, and appropriately monitored bed space. Delayed discharge in children
undergoing extremely short outpatient sedation procedures may also occur. Similarly, behavioral
preparation programs administered preoperatively are associated with increased hospital operational costs.
Likewise, anxious children can utilize hospital resources that would be reduced with appropriate pharmacologic
preparation. Variation in children's behavioral response has its orgin in at least four domains:
• Age and developmental maturity
• Previous experience with medical procedures and illness
• Individual capacity for affect regulation and trait anxiety (baseline anxiety)
• Parental state (situational) and trait (baseline) anxiety
Children between the ages of 1 and 5 years are at greatest risk for developing extreme anxiety and distress.
This is not surprising,
because separation anxiety often does not peak until 1 year of age, and children older than the age of 5 years
can more easily cope with new and unpredictable situations. A history of prior stressful medical encounters,
such as in the pediatrician's office, the dentist's office, with previous surgery, or with previous hospitalization,
affects how a child reacts to new medical encounters. These
are each important risk factors for anxiety prior to undergoing invasive medical procedure or anesthesia. Children
who are shy and inhibited, as identified by temperament tests, are also at increased risk for developing anxiety and
distress before the procedure. In addition, children who lack good social adaptive abilities are likewise at risk.
Parental characteristics also have a strong influence on a child's behavior during the experience. Children of
parents who are more anxious, children of parents who use avoidance coping mechanisms, and children of
separated or divorced parents all appear to be at high risk for developing anxiety. Because children of anxious
parents are more likely to experience high levels of anxiety, it is important to identify the predictors of increased
parental anxiety prior to the child undergoing invasive medical procedures. Parent gender (mothers are more
anxious than fathers, the child age (< one year), children with repeated hospital admissions, and child
temperament are all predictors of increased parental anxiety. Identification of children and parents who are at
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the greatest risk for anxiety and distress allows for appropriate intervention for this "at-risk" population.
Interventions
Parental Presence during Invasive Medical Procedures

It is well established that most parents and children prefer to remain together during procedures such as
immunization, bone marrow aspiration, and dental treatment. Several survey studies have also indicated that most
parents prefer to be present during induction of anesthesia regardless of the child's age or previous surgical
experience. This is even the case for those parents who have had previous experience with pharmacologic
interventions. Indeed, parents of children undergoing repeated surgery were likely to request parental presence
regardless of their experience with prior parental presence or premedication of their child with midazolam. That
is, even if children were calm after midazolam during their first surgery, parents still preferred to be present
during induction of anesthesia during the second surgery.
Potential benefits from parental presence include minimizing the need for premedication and avoiding the
screaming and struggling of the child that may result on separation from the parents. Whether parental presence
decreases child anxiety or impacts the long-term behavior following the procedure remains controversial. Common
objections to parental presence include concern about disruption, compromising sterility, crowded treatment
rooms, and a possible adverse reaction of the parent. For some children, their behavioral response to stress may
be more negative when a parent is present than when the parent is absent. Despite objections, the prevalence of
parental presence is becoming more common in the United States. The experimental evidence to date does not
clearly support the routine use of parental presence. Although early studies suggested reduced anxiety and
increased cooperation if parents were present during induction of anesthesia, later investigations indicate that
routine parental presence may not always be beneficial. The match between parent and child anxiety level also
appears to be important. Calm children with anxious parents do more poorly when compared with calm children
with calm parents or anxious children with either calm or anxious parents.
When interpreting the results of these studies, however, several factors should be considered. First, the
design of a randomized controlled study, while considered a gold standard in research, may not reflect
clinical practice. That is, although a randomized controlled study is applicable to centers that offer parental for
all parents, it may not be applicable to centers in which each request for
parental presence is considered individually based on personality characteristics of each child and parent.
Such centers may have different results with parental presence than were demonstrated in experimental studies.
Second, allowing parental presence without adequate preparation of the parent may be counterproductive. Some
parent behaviors, such as criticism, excessive reassurance, and commands, are associated with greater distress.
Given the drawbacks just discussed, interests in this area have begun to shift toward an emphasis on what parents
actually do during induction of anesthesia. The development of a new tool for assessing child and adult behavior
in the perioperative setting (The Perioperative Child-Adult Medical Procedure Interaction Scale [P-CAMPIS]) has
been developed to facilitate such research. Preliminary validation of this measure indicates that parental behavior
affects the child's anxiety during induction in a similar manner as it impacts a child's distress during
immunizations.
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Healthcare Provider Intervention
In addition to behavioral interventions targeting children and their parents, a promising new line of research
supports the use of behavioral interventions targeting healthcare providers. Specifically, an empirically-derived
intervention titled Provider-Tailored Intervention for Perioperative Stress (P-TIPS) was shown to be successful in
changing healthcare provider behaviors in the perioperative setting and represents a new clinical avenue for
decreasing anxiety in children undergoing invasive medical procedures. The development of P-TIPS was based
upon research documenting that adult behaviors {parents and healthcare providers) impact children's distress
during invasive medical procedures, including surgery. Specifically, the use of distraction, non-procedural talk, and
humor are conceptualized as "coping promoting" behaviors and have been shown to decrease children's distress.
Conversely, adults' use of reassurance, apology, empathy, and criticism, or allowing the child too much control
over the medical procedure is conceptualized as "distress promoting" behaviors and lead to increased distress
in children. With P-TIPS, a new behavior that impacted child distress also emerged: medical reinterpretation
(i.e., reconceptualizing medical experiences and equipment as non- threatening) and was found to increase child
coping when used with medical experiences that were in the child's immediate environment, but increase distress
when used in reference to objects outside of the immediate environment.
Preliminary investigation revealed that P-TIPS was successful at both increasing desired behaviors (coping
promoting) and
decreasing undesired (distress promoting) behaviors among healthcare providers. Both resident and attending
anesthesiologists were included in this study and evidenced behavior change as did OR nurses, who were
charged with not only changing their own behaviors, but impacting parent behavior in the perioperative
setting as well. In fact, nurses demonstrated appropriate behavior change and in tum, parents demonstrated
increases in desired and decreases in undesired behaviors. Included in this study were both attending and resident
anesthesiologists and, as previously predicted, there were differences in the effectiveness of the training
between the two groups. Resident anesthesiologists demonstrated greater increases in rates of desired behaviors;
whereas, attending anesthesiologists demonstrated greater decreases in rates of undesired behaviors. Attending
anesthesiologists, having more experience than their resident counterparts, generally displayed higher rates of
baseline desired behaviors, which likely contributed to the lower gains in this area. However, in consideration of
anesthesiologists' rates of undesired behaviors, attending physician's greater years of experience may also allow
for the incorporation of some undesired behaviors into their usual manner of interaction with patients and parents.
Residents' amenability to the training intervention represents a potential key population to shape and educate
in order to change the clinical practice of pediatric anesthesiology. Nurses represent medical specialists who can
have a tremendous amount of influence over children's experience in the perioperative environment. Nurses'
behaviors were highly malleable to the training; they demonstrated the largest changes in their behaviors. Not
only were nurses effective in integrating information from the training into their own behavioral repertoires, they
were also able to effectively convey this knowledge to the parents. In tum, parents in the intervention
condition demonstrated higher rates of desired behaviors, and lower rates of undesired behaviors; this is a strong
indicator of the effectiveness of utilizing nurses as trainers for parents in the clinical setting.
Pharmacologic Interventions
Discussion on specific agents is beyond the scope of this lecture. The primary goals of administering a
premedication to children are to facilitate an anxiety-free separation from their parents and a smooth, stress-free
invasive medical procedure. When pharmacologic interventions are directly compared with behavioral
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interventions, children receiving a sedative are less anxious and more compliant than those who are accompanied
by a parent. Interestingly, parental anxiety is also decreased when the child receives a premedication. Examining
both sedative premedication and parental presence revealed that a combination of parental presence and sedative
premedication was more effective than medication alone for reducing child and parent anxiety and improving
parent satisfaction. However, parental presence offered no additional anxiolysis for children who received a
sedative preoperatively. Nonetheless, parents who accompanied their sedated children into the operating rooms
were themselves significantly less anxious and more satisfied both with the separation process and with the
overall anesthetic, nursing, and surgical care provided. In conclusion, although sedative premedications are
effective for treatment of preoperative anxiety, they should not be used routinely in all children undergoing
surgery. Their use should be directed to children who are at a significant risk for the development of preoperative
anxiety. Variables such as age, duration of surgery, and potential recovery delays should also be considered.
However, it is important to not withhold premedication if that premedication would likely be of benefit to a
selected child. For example, a child undergoing a very brief procedure who is very anxious would likely benefit
from a premedication regardless of the negative effects on recovery and discharge.
References
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will benefit most from parental presence during induction of anesthesia. Anesth Analg 2006;102:81-84.
Cassady FJ, Kain ZN. Preoperative preparation for parents of pediatric surgery patients. Curr
Anesthe Rep 2000;1:67-71. McCann ME, Kain ZN. The management of preoperative anxiety in
children: an update. Anesth Analg 2001;93(1):98-105.
Kain ZN, Caldwell-Andrews AA, Mayes LC, et al. Family-centered preparation for surgery improves
perioperative outcomes in children: a randomized controlled trial. Anesthesiology 2007;106(1):65-74.
Shaw EG, Routh DK. Effect of mother presence on children's reaction to aversive procedures. J Pediatr
Psychol 1982;7(1):33-42.
Dahlquist LM, Gil KM, Armstrong FD, DeLawyer DD, Green P, Wouri D. Preparing children for medical
examinations: The importance of previous medical experience. Health Psychol1986:249-259.
Miller SM. Monitoring versus blunting styles of coping with cancer influence the information patients want
and need about their disease. Implications for cancer screening and management. Cancer 1995;76(2):167-177.
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with an Empirically Based Intervention. Anesthesiology 2011;115(1):18-27.
Uman LS, Chambers CT, McGrath PJ, Kisely S. A Systematic Review of Randomized Controlled Trials
Examining Psychological Interventions for Needle-related Procedural Pain and Distress in Children and
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M, Steele R, eds. Handbook ofPediatric Psychology, 4th ed. New York: Guilford Press; 2009:171-188.
DISCLOSURE
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Anesthesia For the Patient With Congenital Heart Disease

For Noncardiac Surgery
Dean B. Andropoulos, M.D., M.H.C.M. Houston, Texas
October 2012
Introduction
Congenital heart disease (CHD) is present in 9 per 1000 live births in the United States, making it the most common
congenital defect requiring invasive treatment in the first year of life. With the current mortality for all congenital
cardiac operations less than 5%, an increasing number of these patients survive, and it is currently estimated that
there are between 650,000 and 1.3 million adults and children in the U.S. living with congenital heart disease. Of
these, approximately 55% have simple lesions, 30% have moderately complex lesions, and 15% have complex
lesions. The learning objectives of this lecture are: 1) Understand the pathophysiology of common congenital heart
diseases and its impact on anesthetic management for non-cardiac surgery; 2) Understand the most common non-
cardiac surgical procedures in patients with congenital heart disease; 3) Understand the updated SBE prophylaxis
guidelines from the American Heart Association.
Basic Approach to Congenital Cardiac Lesions
One practical approach to assessing patients with CHD is to ask the following questions: 1. Is the patient cyanotic,
with either obligatory right-to-left intracardiac shunting, or mixing lesions? And if cyanotic, does the patient have a
functional single ventricle? If acyanotic is this a left-to-right shunting lesion, or an obstructive lesion? 2. Has the
patient undergone corrective or palliative surgery, and if so, what is the resulting anatomy and residual defects? 3.
What is the patient’s current status: well compensated with no limitations, moderately well compensated with few
limitations, or poorly compensated with significant limitations? 4. What is the proposed procedure and what
anticipated effects will the procedure and anesthetic management have on the patient’s pathophysiology? 5. Does
this patient need infective endocarditis prophylaxis?
Pathophysiology of Common Cardiac Lesions
The common complex and moderately complex cardiac lesions include: Tetralogy of fallot (incidence 9-14% of
CHD), transposition of the great arteries (10-11%), atrioventricular septal defects (4-10%), coarctation of the aorta
(8-11%), hypoplastic left heart syndrome (4-8%), and ventricular septal defects (VSD)(10-20%). All of these
lesions, with the exception of transposition of the great arteries, have a wide range of anatomical abnormality
ranging from relatively mild, to severe, which must be assessed and which have great influence on the patient’s
symptomatology and anesthetic considerations.
Tetralogy of Fallot
Tetralogy of fallot (TOF) consists of 1) large subaortic VSD, 2) right ventricular outflow tract obstruction/
pulmonary stenosis, 3) right ventricular hypertrophy, 4) right sided aortic arch (present in 25% of patients). In the
unrepaired TOF patient, pathophysiology depends on the degree of right ventricular outflow tract (RVOT)
obstruction. With significant RVOT obstruction, infundibular spasm constricts the RVOT, limiting blood flow into
the pulmonary artery, forcing blood right to left across the VSD and resulting in significant arterial desaturation, or
“Tet spells.” These spells are incited by catecholamine release due to pain, stress, light anesthesia, and emotional
upset in the infant. Many of these patients receive oral propranolol to prevent these spells. Treatment involves
intravascular volume administration to increase RV stroke volume, increasing sedation or anesthesia, avoidance of
exogenous catecholamines, increasing FiO2, and increasing systemic vascular resistance to force blood left-to-right
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across the VSD and out the RVOT, increasing pulmonary blood flow and thus oxygenation. Surgical treatment of
TOF with pulmonary atresia or significant pulmonary stenosis with spells involves either placing a systemic to
pulmonary artery shunt in early infancy followed by a complete anatomic repair at 6-12 months, or complete repair
in early infancy. Patients without cyanotic spells are normally repaired at 6-12 months. It is important to note that
repaired TOF patients often have residual defects, usually involving varying degrees of pulmonary insufficiency, or
residual RVOT obstruction. Assessment of these patients with periodic echocardiography or cardiac MRI is
important, and planning the anesthetic should involve review of these data. Teenage or adult TOF patients may have
RV dilation and are prone to ventricular arrhythmias.
D-Transposition of the Great Arteries
In this lesion the great arteries fail to rotate and the aorta and coronary arteries arise from the right ventricle, and the
pulmonary artery from the left ventricle. D- refers to dextro- meaning the aorta is rightward and anterior to the
pulmonary artery. About 85% of these patients have an intact ventricular septum and 15% have a VSD. Since the
systemic venous blood is recirculated to the RV and the aorta and is not oxygenated by this pathway, adequate
arterial saturation depends on mixing between right and left sides of the heart, either at the VSD level, atrial septal
defect level, or patent ductus arteriosus. For this reason, neonates with significant desaturation undergo a balloon
atrial septostomy, which creates a much larger communication at the atrial level and normally increases oxygen
saturation to the 80-90% range. Standard surgical treatment since the mid-1980’s has been the arterial switch
operation, which includes translocation of the coronary arteries and leaves the normal physiology. The vast majority
of infants do very well and have little if any residual defect, and thus can be treated as a well-compensated,
corrected CHD patient. Residual problems might include coronary artery ischemia due to anatomic problems with
the re-implanted coronary arteries, or regurgitation or stenosis in the neo-artic root. Older patients with D-TGA
repaired before the mid-1980’s most often had the Mustard or Senning operations, which both re-routed the blood
flow at the atrial level, leaving the aorta arising from the RV and pulmonary artery from the LV. These patients are
now adults, and most have significant problems including systemic ventricle failure, as the RV is inadequate as a
systemic pump; and frequent significant atrial arrhythmias from the atrial suture lines. These patients require
thorough preoperative evaluation by a cardiologist addressing ventricular function and arrhythmias.
Atrioventricular Septal Defects
Atrioventricular septal defects (AVSD) are classified as partial, intermediate or transitional, and complete. AVSD
are also known as atrioventricular canals (AVC), and derive from a deficiency or absence of the endocardial cushion
during cardiac development. Partial AVC consist of a primum atrial septal defect, no VSD, and separate
atriventricular valves with a cleft mitral valve. These defects have pathophysiology similar to that of a large atrial
septal defect (ASD), and thus are rarely symptomatic in infancy, and are usually repaired at age 2-4 years. Residual
mitral stenosis or regurgitation may be encountered. Intermediate or transitional AVC has a primum ASD, common
single atrioventricular valve, often with regurgitation, and a small or absent VSD component. These patients are also
usually not symptomatic in infancy and are repaired at 2-4 years of age, and also may have residual mitral valve
disease. Complete AVC have both a large primum ASD, and VSD component and common atrioventricular valve.
These patients have very large left-to-right shunts in infancy, and develop congestive heart failure that necessitates
repair before 6 months of age. Residual mitral or tricuspid valve regurgitation may be problematic for these patients.
The majority of CAVC patients also have Trisomy 21, and these patients develop severe pulmonary hypertension
earlier than patients with CAVC and normal chromosomes. If these patients are not repaired in the first several years
of life, the high pressure and flow in their pulmonary arteries may result in significant muscular development in
smaller and more distal pulmonary arteries, and then produce severe pulmonary hypertension, that is equal to or
even higher than systemic pressures. This results in right-to-left shunting, increasing cyanosis, and eventually results
in Eisenmenger’s Syndrome, which denotes irreversible, fixed pulmonary hypertension. These patients are at high
risk for anesthesia for any procedure. With early repair of CAVC that is offered to all patients, this syndrome is seen
much less frequently over the past two decades.
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Coarctation of the Aorta
Coarctation is a narrowing of the aorta most commonly in the juxtaductal area, or opposite the insertion of the
ligamentum arteriosum near the left subclavian artery. As with nearly all congenital defects, there is a wide range of
anatomy and patients may present as neonates in cardiovascular collapse when their patent ductus arteriosus closes
if they have a very tight coarctation, or may not present until later in childhood with milder forms of coarctation.
Later presentation is usually with hypertension in the right upper extremity; patients may also have a soft systolic
murmur, or continuous murmur over the back due to development of extensive arterial collaterals which form to
increase blood flow to areas below the coarctation. Repair is normally done as soon as the coarctation is diagnosed,
usually via left thorocotomy by direct end-to-end anastomosis after resection of the coarctation segment. Residual
coarctation may occur and is usually treated with balloon angioplasty and stenting in the cardiac catheterization
laboratory. Patients may have residual hypertension, and adults with late treatment of coarctation often have severe
coarctation, early coronary artery disease, and are prone to cerebral vascular accidents. Most repaired patients,
however, have essentially normal cardiac function when presenting for non-cardiac procedures.
Hypoplastic Left Heart Syndrome
This syndrome (HLHS) has varying degrees of underdevelopment of the left ventricle, and has either significant
stenosis, or atresia of both the aortic and mitral valves, resulting in very limited or no flow through the left ventricle
and aortic valve. At birth systemic blood flow is dependent on a patent ductus arteriosus (maintained by
prostaglandin E1 infusion) to supply blood flow to the lower body, and to augment blood flow to the brain and
coronary arteries in a retrograde manner. Since the mid 1980’s these patients have survived in increasing numbers,
and now there are teenagers and even young adults with HLHS presenting for anesthesia for non-cardiac procedures.
The initial surgical palliation involves reconstruction of the aorta by using the native pulmonary valve, native aorta,
and augmenting the repair with a cryopreserved homograft patch to create a neo-aorta to provide systemic blood
flow, which arises from the single right ventricle. An atrial septectomy must be performed to allow unimpeded flow
of blood from left atrium to right atrium to bypass the hypoplastic left heart. And, since the pulmonary valve has
been used to construct the neo-aorta, a new source of pulmonary blood flow is provided, either a small 3-4 mm
systemic to pulmonary artery shunt, or a larger right ventricle to pulmonary artery shunt. In either case, the single
systemic RV in parallel with the pulmonary circulation, bridged by a shunt, is inherently unstable, and
hemodynamic stability depends on balancing pulmonary to systemic flow ratio to approximately 1:1. Excessive
pulmonary vasodilation with high FiO2, or low PaCO2 will steal flow from the systemic and coronary circulations,
often resulting in myocardial ischemia and a vicious cycle ending in cardiac arrest. These patients are most
precarious after the neonatal Stage I Norwood palliation, and unfortunately often need non-cardiac procedures such
as fundoplication and gastrostomy tube, during this period. These patients must be managed carefully during non-
cardiac procedures, and should be cared for in an intensive care setting after most procedures.
The second stage of the palliation sequence for HLHS is a bidirectional cavopulmonary connection done at 2-6
months of age, where the systemic-pulmonary, or RV-pulmonary shunt is replaced by direct anastomosis of the
superior vena cava to the right pulmonary artery. This greatly stabilizes the circulation by unloading the systemic
single ventricle by diverting SVC flow directly to the lungs, resulting in much improved myocardial function.
Although the balance of pulmonary to systemic flow is still a consideration at this stage, and hyperventilation will
result in hypocarbia, decreased cerebral blood flow and thus decreased SVC and PA flow which results in arterial
desaturation, it is after the bidirectional cavopulmonary connection that elective non-cardiac procedures should be
performed. These may include procedures such as cleft lip and palate repair, craniosynostosis repair, or other
common procedures.
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The third stage of HLHS palliation is the Fontan operation, whereby the inferior vena cava blood is routed to the
pulmonary arteries, bypassing the right ventricle to form a total cavopulmonary connection, either intracardiac
(lateral tunnel Fontan), or by an extracardiac conduit. This is normally performed at 18 months-4 years of age and
results in a patient with a completely unloaded systemic single right ventricle, and no pumping chamber for the right
side of the heart. Instead, blood flow into the thorax and out through the pulmonary arteries depends on the small
transpulmonary pressure gradient from the vena cavae into the pulmonary arteries, across the lungs, and into the
pulmonary veins. This flow is augmented by normal breathing and its negative thoracic pressure augmenting the
transpulmonary pressure gradient. After the Fontan operation, signs and symptoms of right sided cardiac failure may
occur, such as pleural effusions, ascites, and lower extremity edema. Although after the Fontan the patient may no
longer be cyanotic, because of the high right sided pressures a 3-5 mm fenestration is often created in the Fontan
tunnel, to lower right sided pressures. Systemic cardiac output is augmented at the expense of a small amount of
right to left shunting, producing patients with varying degrees of desaturation. It is important to determine if the
patient has a fenestration when presenting for an anesthetic. After the Fontan operation, patients may be intolerant
of excessive positive pressure ventilation as commonly perfomed during general endotracheal anesthesia, because it
reduces the transpulmonary pressure gradient and thus flow into the Fontan circuit, resulting in low cardiac output.
In addition, hypovolemia from prolonged fasting, third space loss, or blood loss is not well tolerated. These patients
merit careful evaluation and planning for anesthesia, and should be monitored postoperatively in an intensive care
setting after major interventions.
Other forms of single ventricle such as tricuspid atresia have been treated with the Fontan operation since the
1970’s. These patients are often adults with the older Fontan configurations, such as a direct atriopulmonary
connection between the right atrial appendage and the pulmonary artery. These patients often have severe refractory
atrial arrhythmias and signs of significant right heart failure. Before anesthesia these patients need careful
evaluation, and many undergo Fontan conversion to a more hemodynamically favorable arrangement, or heart
transplant.
Ventricular Septal Defects
VSDs are the most common single isolated defect, and are a component of many more complicated defects as well.
In isolation, VSDs range from tiny asymptomatic muscular VSDs seen at birth that close spontaneously, to large or
multiple “Swiss cheese” defects in the ventricular septum that produce severe symptoms and signs of congestive
heart failure in early infancy. The degree of left to right shunting depends on the size of the defect, and the relative
ratios of pulmonary to systemic pressure and resistance and the compliance of right and left ventricles. Neonates and
infants with large unrepaired defects may have significant cardiomegaly and myocardial dysfunction, and in addition
if intubated and hyperventilated with high FiO2 may deteriorate further from increased pulmonary blood flow, steal
from the systemic blood flow, and further increases in end-diastolic volume. Patients with large defects who are
unrepaired can progress to Eisenmenger Syndrome. Patients with smaller defects are much more hemodynamically
stable, and patients with repaired VSDs and no residual defects most of ten have normal myocardial function and
can be treated as corrected well compensated patients for non-cardiac procedures.
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Common Simple Lesions
Atrial Septal Defect
This common lesion may be essentially asymptomatic and not diagnosed until adulthood in some patients. The three
major types are: 1. primum ASD which is low in the atrial septum and usually associated with atrioventricular canal
and repaired in the first five years of life; 2. secundum ASD in the center of the atrial septum, often closed in the
cardiac catheterization laboratory with ASD closure devices; 3. sinus venosus ASD, high in the atrial septum near
the superior vena cava and most often associated with partial anomalous pulmonary venous return. The latter two
types of ASD may be undiagnosed until adulthood; pulmonary vascular disease usually will not develop until the 4th
or 5th decade or later. These patients may come to medical attention because of transient ischemic attacks or strokes
due to right to left movement of platelet fibrin thrombi during valsalva maneuver. If unrepaired, besides assessment
for cardiac symptoms, meticulous attention needs to be paid to avoid introduction of air via intravenous infusion, or
during the surgical procedure itself.
Patent Ductus Arteriosus
A small patent ductus arteriosus (PDA) is usually asymptomatic, and may not warrant treatment. Larger PDA
produce significant left to right shunting, and are closed, often in the cardiac catheterization laboratory with PDA
closure devices. Large PDA are often components for more complex cardiac lesions and are addressed during
surgery. If isolated and not suitable for catheterization laboratory closure, they are closed via left thoracotomy, and
the patient is treated as a well compensated simple cardiac patient for future anesthetics. If a PDA is large, and not
closed in childhood, pulmonary vascular disease and even Eisenmenger Syndrome can develop, and these patients
are approached with great caution.
A thorough history and physical examination, focusing on cardiac signs and symptoms, previous surgical and
catheterization procedures, and available data such as recent echocardiograms, is important for all patients with
CHD presenting for non-cardiac procedures. Cardiac rhythm status is important to determine, especially in older
patients with residual defects or in single ventricle patients. Common medications in the CHD population include
ACE inhibitors for single ventricle patients, or those with significant CHF or mitral regurgitation; beta blockers for
TOF patients or those with atrial arrhythmias such as paroxysmal supraventricular tachycardia; amiodarone for
patients with significant atrial or ventricular arrhythmias; and diuretics for patients with CHF. Digoxin is rarely used
in the modern era because of its lack of effectiveness in either the adult or pediatric population. Endothelin
antagonists, phosphodiesterase-5 inhibitors, or prostaglandin analogs are used in pulmonary hypertensive patients.
Many patients with CHD are taking aspirin or other antiplatelet therapies to decrease risk of thrombus formation in
shunts or conduits. Finally, some patients are taking coumadin for mechanical cardiac valves, which will merit
careful planning of perioperative anticoagulation regimens. Many patients, particularly adults with CHD will have
implanted transvenous or epicardial pacemakers or automated defibrillators, and it is critical to understand the
patient’s underlying cardiac rhythm, the reason for placement of the device, and the current modes and settings of
the device.
Echocardiography is the mainstay of diagnostic testing in the CHD population, and the latest echocardiography
results should be reviewed. If there is any history of cardiac rhythm abnormality a recent ECG or Holter
examination should be reviewed. Cardiac catheterization is most often performed for interventional procedures, but
valuable diagnostic data is also available from this modality. Cardiac MRI has assumed an increasingly important
role to assess anatomy, function, and progression of pathophysiology, and results should be reviewed.
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A frequent question in the preanesthetic evaluation of the CHD patient for non-cardiac procedures is whether the
patient should be evaluated by their cardiologist prior to the procedure. In general, if the patient has a simple or
moderately complex lesion that has been completely corrected and is well compensated and so is followed by their
cardiologist on an infrequent basis, a standard preanesthetic visit without a cardiology consultation is appropriate. A
patient with a moderately complex lesion who is not well compensated, any cyanotic or single ventricle patient or
patient with a complex lesion needs a recent cardiology evaluation that usually includes at least an echocardiogram,
within no more than 3-6 months before the surgery. If the patient’s condition has changed significantly since the last
evaluation, they should be seen again by the cardiologist.
In general, all cardiac medications should be continued through the perioperative period for most types of surgeries.
Low dose ASA use is not a contraindication for most simple, superficial surgeries, but if the surgery is major,
including intracranial, a discussion with the patient’s cardiologist and surgeon should take place and ASA is usually
stopped 7-10 days preoperatively. Standard NPO orders apply to the CHD population including clear liquids up to 2
hours before anesthesia, breast milk up to 4 hours before, and infant formula, milk, or solids up to 6 hours before. It
is critically important that patients with cyanotic lesions, shunt-dependent patients, and those with outflow tract
obstruction are not left NPO for long periods of time. Hypovolemia can be a critical problem for these patients,
especially with induction of anesthesia and institution of positive pressure ventilation. These patients should be
scheduled early in the day, and if there are delays should be fed clear liquids until 2 hours before induction.
Conduct of Anesthetic
The setting for the non-cardiac procedure for the well compensated patient with a simple or moderately complex
lesion can be in a normal well equipped and staffed community hospital setting. However, with less well
compensated patients and complex and single ventricle patients, the procedures should be done in centers with
expertise in CHD, and necessary backup support in case these patients deteriorate. In general, the more complex
patients can have outpatient surgery, but admission to the hospital must be readily available. For complex patients
having major surgery, postopertative care in an ICU is essential and must be planned in advance.
Standard monitors including ECG, non-invasive blood pressure, pulse oximetry, and capnography are essential for
all procedures, including diagnostic imaging procedures, where end-tidal CO2 can be monitored via a nasal cannula
for sedation procedures. The decision to institute more invasive monitoring such as invasive arterial pressure, central
venous pressure, continuous central venous oxygen saturation monitoring, or cerebral/somatic near-infrared
spectroscopy for brain and tissue oxygenation, is anesthesiologist-dependent to a large extent and depends on the
assessment of the potential for hemodynamic and respiratory instability due to the patient’s pathophysiology and the
invasiveness of the planned procedure. Patients with significant baseline myocardial dysfunction, pulmonary
hypertension, or cyanosis often benefit from preoperative intravenous access if possible.
Any anesthetic and sedation technique may be used in CHD patients, with careful attention to the particular
pathophysiology of the patient and the desired hemodynamic goals. Premedication, often with oral midazolam, is
well tolerated. Since halothane is no longer available, inhalation induction with sevoflurane is appropriate and well
tolerated for many CHD patients. Propofol may be used for induction and maintenance in CHD patients, with
careful attention to veno- and vasodilation produced by this agent. Ketamine, either IM or IV, is a very useful agent
for many of these patients, preserving myocardial function and providing sedation and analgesia. Etomidate has little
effect on myocardial contractility and hemodynamics, and is an excellent agent for the patient with impaired
myocardial function. Dexmedetomidine is increasingly used for sedation in patients with CHD, and is usually well
tolerated if the patient can withstand the bradycardia, and hypotension that sometimes results from the use of this
agent. Any opioid can be used, and single shot caudal and nerve block techniques can also be used, even with low
dose ASA use. Major neuraxial techniques, i.e. lumbar/thoracic epidural and spinal are best avoided with ASA use.
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Airway management may range from sedation with spontaneous respiration, to mask or LMA general anesthesia, to
endotracheal anesthesia, again being mindful of the effects of hyper- or hypocarbia, and postive pressure ventilation
for the individual patient. With endotracheal anesthesia, the decision to extubate at the end of the procedure of
course must take into account the severity of the underlying pathophysiology, and the magnitude of the surgical
procedure. In single ventricle infants undergoing major abdominal procedures, for example, it is very often prudent
to ventilate the patient in the early postoperative period.
Pacemakers and defibrillators must be interrogated before the procedure, and a discussion held with the patient’s
cardiologist as to the underlying cardiac rhythm and reason for placing the device. In general, the pacemaker should
be converted to asynchronous mode just before the surgery, to avoid electrocautery interference inhibition of the
pacemaker in demand mode. The defibrillator function must also be turned off, and external defibrillator capability
immediately available. The device settings are restored as soon as possible after the completion of the procedure.
Common Non-Cardiac Procedures
Although CHD patients may undergo any surgical or diagnostic procedure, there are several common procedures
that merit discussion. Young CHD patients often present for dental restorations and extractions under general
anesthesia, due to the need for excellent dental hygiene to prevent infective endocarditis. A thorough preoperative
evaluation is essential, and these procedures must be performed in the hospital setting with adequate expertise and
backup in case of decompensation. Laparoscopic procedures such as fundoplication and gastrostomy tube, and
cholescystectomy, are performed in CHD patients, but careful attention must be paid to the effects of CO2
insufflation on PaCO2, and increased intra-abdominal pressure. The combination of acute hypercarbia and decreased
venous return is not well tolerated by single ventricle infants and patients with a Fontan circulation, and careful
monitoring, or consideration for an open procedure are important. Scoliosis surgery is often done in patients with
CHD, and must be very carefully planned, especially in patients with the Fontan circulation, who do not tolerate
hypovolemia and hypotension. Careful monitoring, blood and volume replacement, and careful consideration of
anesthetic technique in light of the need for spinal cord monitoring must be performed for these complicated
patients. Craniofacial surgery, especially cleft lip and palate, and craniosynostosis repair, are done in the CHD
population, with careful consideration for prevention of air embolus, and monitoring and replacing blood loss. As
noted above, in single ventricle infants, elective surgery is best performed after the cavopulmonary connection,
which yields a much more stable circulation to withstand the stresses of major surgery. Diagnostic imaging
procedures, especially MRI, are commonly performed in the CHD population, and either sedation or general
anesthesia techniques can be used, again with careful attention to the hemodynamic and respiratory goals of each
individual patient.
Infective Endocarditis Prophylaxis
The American Heart Association significantly changed its guidelines for prevention of infective endocarditis (IE) in
2007, resulting in a narrowing of the indications for administering IE prophylaxis. This has resulted in confusion for
patients, parents, surgeons, and even cardiologists, and it is important to understand the new indications, which were
based on an extensive review of the data and discussions among a large panel of experts. The patient must have
BOTH a cardiac indication, and a surgical/procedural indication. The major cardiac indications are: 1. prosthetic
cardiac valve or material; 2. previous IE; 3. congenital heart disease, but ONLY a) unrepaired cyanotic CHD
including palliative shunts and conduits; b) completely repaired CHD with prosthetic material or device during the
first 6 months after the procedure; c) repaired CHD with residual defects at or near the site of a prosthetic patch or
device; 4. cardiac transplant recipients who develop valvulopathy. The surgical/procedural indications are 1. all
dental procedures that involve manipulation or the gingival tissue or perforation of the oral mucosa; 2. respiratory
tract procedures or procedures on infected skin, or musculoskeletal tissue. IE prophylaxis is not recommended for
simple gastrointestinal or genitourinary procedures where the mucosa is not incised, i.e. simple endoscopy and
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cystoureteroscopy, but is recommended for surgery where mucosa is incised. For dental prophylaxis, a single dose
of ampicillin 30-60 minutes before the procedure, or as soon as IV access is obtained, is the recommended regimen,
with clindamycin, cefozolin, or ceftriaxone acceptable for penicillin allergic patients.
Summary
The large and growing population of patients who are living with CHD requires anesthesia care for the same types
of non-cardiac surgeries and other procedures as the non-CHD population, and anesthesiologists will increasingly
care for these patients in a variety of settings. Knowledge of the pathophysiology of the common CHD lesions, as
well as careful preoperative assessment and preparation, and communication with the patient’s cardiologist and
surgeon, are essential to provide optimal care in the best setting for these patients.
Bibilography
1. Baum VC, Barton DM, Gutgesell HP. Influence of congenital heart disease on mortality after noncardiac surgery
in hospitalized children. Pediatrics 2000; 105: 332-5.
2. Ramamoorthy C, Haberkern CM, Bhananker SM, et al. Anesthesia-related cardiac arrest in children with heart
disease: data from the Pediatric Perioperative Cardiac Arrest (POCA) registry. Anesth Analg. 2010;110:1376-82.
3. Diaz LK, Andropoulos DB. New developments in pediatric cardiac anesthesia. Anesthesiol Clin North America.
2005;23:655-76.
4. Diaz LK, Hall S. Anesthesia for non-cardiac surgery and magnetic resonance imaging. In, Andropoulos DB,
Stayer SA, Russell IA (eds.) Anesthesia for Congenital Heart Disease. Blackwell-Futura Publishing, Malden MA,
2005, pp. 427-52.
5. Dorfman AL, Odegard KC, Powell AJ, et al. Risk factors for adverse events during cardiovascular magnetic
resonance in congenital heart disease. J Cardiovasc Magn Reson. 2007;9:793-8.
6. Friesen RH, Williams GD. Anesthetic management of children with pulmonary arterial hypertension. Paediatr
Anaesth. 2008 Mar;18(3):208-16.
7. Williams GD, Maan H, Ramamoorthy C, et al. Perioperative complications in children with pulmonary
hypertension undergoing general anesthesia with ketamine. Paediatr Anaesth. 2010;20:28-37.
8. Hedequist DJ, Emans JB, Hall JE. Operative treatment of scoliosis in patients with a Fontan circulation. Spine.
2006 Jan 15;31:202-5.
9. Hennein HA, Mendeloff EN, Cilley RE et al. Predictors of postoperative outcome after general surgical
procedures in patients with congenital heart disease. J Pediatr Surg 1994;29: 866-70.
10. Kipps AK, Ramamoorthy C, Rosenthal DN, et al. Children with cardiomyopathy: complications after noncardiac
procedures with general anesthesia. Paediatr Anaesth. 2007;17:775-81.
11. Roger VL, Go AS, Lloyd-Jones DM,et al. Heart disease and stroke statistics--2012 update: a report from the
American Heart Association. Circulation. 2012;125:188-97.
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12. Pérez-Caballero C, Sobrino E, Vázquez JL, et al.Complication of surgery for scoliosis in children with surgically
corrected congenital cardiac malformations. Cardiol Young. 2009 ;19:272-7.
13. American Society of Anesthesiologists. Practice advisory for the perioperative management of patients with
cardiac implantable electronic devices: pacemakers and implantable cardioverter-defibrillators: an updated report by
the american society of anesthesiologists task force on perioperative management of patients with cardiac
implantable electronic devices. Anesthesiology. 2011;114:247-61.
14. Slater B, Rangel S, Ramamoorthy C, et al. Outcomes after laparoscopic surgery in neonates with hypoplastic
heart left heart syndrome. J Pediatr Surg. 2007;42:1118-21.
15. Stayer SA, Andropoulos DB, Russell IA. Anesthetic management of the adult patient with congenital heart
disease. Anesthesiol Clin North America. 2003;21:653-73.
16. Warner MA, Lunn RJ, O’Leary PW et al. Outcomes of noncardiac surgical procedures in children and adults
with congenital heart disease. Mayo Clin Proc 1998; 73: 728-34.
17. Warnes CA, Williams RG, Bashore TM, et al. ACC/AHA 2008 guidelines for the management of adults with
congenital heart disease: a report of the American College of Cardiology/American Heart Association Task Force on
Practice Guidelines. J Am Coll Cardiol. 2008;52:e1-121.
18. Wilson W, Taubert KA, Gewitz M, et al. Prevention of infective endocarditis: guidelines from the American
Heart Association. Circulation. 2007;116:1736-54.
19. Shukla AC, Almodovar MC. Anesthesia considerations for children with pulmonary hypertension. Pediatr Crit
Care Med. 2010 Mar;11(2 Suppl):S70-3.
20. van der Griend BF, Lister NA, McKenzie IM, et al. Postoperative mortality in children after 101,885 anesthetics
at a tertiary pediatric hospital. Anesth Analg. 2011;112:1440-7.
21. Galante D. Intraoperative management of pulmonary arterial hypertension in infants and children--corrected and
republished article. Curr Opin Anaesthesiol. 2011;24:468-71.
22. Seal R. Adult congenital heart disease. Paediatr Anaesth. 2011;21:615-22.
DISCLOSURE
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Practical Pediatric Regional Anesthesia
Santhanam Suresh, M.D. Chicago, Illinois
Introduction: Regional anesthesia is experiencing resurgence in pediatric anesthesia. The use of ultrasound
guidance has increased the variety of blocks that can be performed in infants, children and adolescents. The
increased safety of performing blocks with US guidance has allowed the practitioner to attempt to perform more
difficult blocks compared to previously described using landmark techniques.1-3 The use of ultrasound guidance can
also allow minimal use of local anesthetic solutions thereby decreasing the risk of toxicity. In this lecture, a variety
of regional anesthesia techniques will be described that you can use in your everyday practice. Central neuraxial as
well as peripheral nerve blocks will be described with clinical techniques as well as images for reference while
performing these blocks.
Equipment: As the field of regional anesthesia is exploding, the use of ultrasound imaging is undergoing constant
improvement. Several ultrasound imaging machines with the capability of offering a variety of applications
including echocardiography have entered the market with greater emphasis on user-friendliness and portability.
This may be of greater importance in the pediatric population since most of these blocks are performed in the
operating room under general anesthesia. In children, it may be easier to perform regional anesthesia with deep
sedation or under general anesthesia.5 US probes commonly used in children include a high frequency hockey stick
probe and a linear 25 mm high frequency probe. Since most of the neurovascular structures are located superficially
in children, visualization of neural structures is easier with a high frequency probe. The physics and equipment
descriptions can be found in textbooks on US guided regional anesthesia. US guidance can be used for central
neuraxial blocks as well as for peripheral nerve blocks. A brief description of each of these blocks will be provided
at this refresher course. In general, the use of curvilinear probes is limited to the use in older children and obese
individuals.
Central neuraxial blocks:

Epidural Analgesia:
Ultrasound imaging seems promising for use either pre-procedurally (prior to puncture) or during block performance
(US aided), although the latter may be most suitable in infants. The largely cartilaginous posterior vertebral column
of neonates and infants enables good US beam penetration to view the spinal structures and can in some cases
enable a view of the needle tip trajectory.
Techniques
Sonoanatomy:
A moderate-high frequency probe (hockey stick, 13-6 frequency probe) is utilized using a paramedian longitudinal
view. The ‘window’ between the two spinous processes will allow the operator to visualize the anterior complex
(anterior duramater, and the posterior longitudinal ligament), the posterior duramater and the ligamentum flavum.
Our preference is to visualize the neuraxis using a paramedian approach. In a paramedian longitudinal view at the
thoracic spine, the spinous processes are represented by slanted hyperechoic lines beneath the homogeneous-
appearing paravertebral muscle mass. Dorsal shadowing will be apparent deep to the spinous processes and other
posterior vertebral elements. The highly hyperechogenic ligamentum flavum and dura mater are captured lying in
the alternate ‘windows’, and the underlying spinal cord appears largely hypoechoic with an outer bright covering of
the pia and a central line of hyperechogenicity (median sulcus).2 In the first report of US imaging in central
blockade, Chawathe et al. performed a pilot study in 12 patients (1 day old to 13 months) to evaluate the possibility
of detecting catheters, and verifying their placement, within the epidural space after placement (within 24 hours) via
the direct lumbar route.6 The important point from this paper is that US imaging (specifically using the midline
approach) of static structures such as catheters can be performed, yet only reliably in very young patients where
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much of the posterior bony elements of the spinal column may exist as cartilage, thus allowing good US beam
penetration. An optimal angle of probe alignment needs to be evaluated in children and surrogate markers for
viewing needle and catheters may be necessary to facilitate a dynamic technique. Willschke et al placed epidural
catheters under real-time US guidance using the paramedian longitudinal imaging plane in 35 neonates.7 Needle tip
entry and the injection of local anesthetic solution within the epidural space were used to confirm epidural
placement; these parameters could be viewed in all neonates. Epidural catheters could only be identified via
surrogacy through tissue movement (i.e., anterior movement of the duramater) and fluid injection
.
Epidural Analgesia:
- US-guided technique does not preclude continuous testing for loss of resistance.
- The limitation of the technique is that the needle shaft and tip may be hard to localize with the
tangential relationship of the needle (midline) and the probe (paramedian longitudinal).
- An assistant (2nd set of hands) is required during catheter placement in order to perform the imaging
real-time for US aided catheter placement. It is important to use saline for LOR to facilitate US
imaging.
Caudal Needle Placement

Caudal blocks, including both single-shot caudal and lumbar or thoracic epidural catheters advanced from the caudal
epidural space (thus avoiding the spinal cord), is a commonly practiced regional anesthesia technique in children.
Although this technique is practiced with the identification of landmarks, there is a small, but not insignificant
chance for failure.
Sonoanatomy: Ultrasound imaging at the midline using both transverse and longitudinal alignment of the probe
should be performed prior to needle placement in order to appreciate the patient’s anatomy and to identify the
sacrococcygeal ligament, dural sac and cauda equina. A linear high-frequency small footprint or hockey stick probe
is a suitable choice, although a larger footprint may be used when viewing the longitudinal axis to allow an adequate
field of view. Placing the probe initially in a transverse plane at the coccyx and scanning in a cephalad direction can
help with landmark identification particularly during training in sonoanatomy. This view allows a good delineation
of the sacral hiatus; the sacral cornua are viewed laterally (as “humps”) and the sacral hiatus is located between an
upper hyperechoic line representing the sacrococcygeal membrane/ligament and an inferior hyperechoic line
representing the dorsum of the pelvic surface (base) of the sacrum. Placing the probe longitudinally between the
sacral cornua will capture the dorsal surface of the sacrum, the dorsal aspect of the pelvic surface of the sacrum and
the sacrococcygeal ligament. The sacrococcygeal ligament covers the sacral base beyond the end of the dorsum of
the sacrum. It appears as a relatively thick linear hyperechoic band, sloping caudally. The sacral hiatus is identified
as a hypoechoic space located between the dorsum of the sacrum and the dorsal side of the pelvic surface of the
sacrum. In older patients where the structures may be ossified at the midline, the paramedian longitudinal view may
be necessary since it will allow the US beam to penetrate the spaces on either side of the spinous processes. This
paramedian view would allow appreciation of the ventral movement of the duramater during fluid injection, but
would not allow a real-time view of the needle along its axis.
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Technique: During or after skin puncture with the needle, both transverse and longitudinal sonographic planes can
be used for confirming caudal epidural needle placement. Roberts at al. published a prospective observational study
of 60 children, in which they determined whether a saline test bolus could be reliably imaged with US in order to
confirm cannula placement in the caudal epidural space.8 While transverse imaging was performed in the pre-
puncture scan to help visualize the neuraxial structures (there was no mention of measurements or skin markings),
longitudinal imaging (approximately 1 cm above the cannula insertion site) was used during the saline test bolus of
0.2-0.3 ml kg-1 to view the anterior displacement of the posterior duramater. The longitudinal plane may allow a
view of the long axis of the needle as it penetrates the sacrococcygeal ligament. This technique may be particularly
beneficial to allow adjustments in needle angle to ensure adequate length of advancement and depth of penetration
without intraosseous placement. The optimal angle for needle insertion during caudal block has been evaluated
using US, since many of the previous recommendations include multiple angles, necessitating needle manipulations,
including a steep initial angle, which may increase the incidence of bony puncture. When introducing a catheter into
the caudal space to reach the lumbar or thoracic spine, similar technique to the above is used for cannula placement
Caudal Needle Placement
- Initially use a transverse plane of imaging to identify the sacral hiatus located between the cornua; the
sacral hiatus is located between an upper hyperechoic line representing the sacrococcygeal
membrane/ligament and an inferior hyperechoic line representing the dorsum of the pelvic surface
(base) of the sacrum.
- Rotate the probe to the longitudinal plane (a paramedian plane may be required in older children) to
capture the sacrococcygeal membrane, a relatively thick linear hyperechoic band, sloping caudally.
- Insert the needle under either plane of view, although a longitudinal view may allow for optimal
viewing along the needle. A transverse view can be used after needle placement within the epidural
space, in order to view the spread of local anesthetic (as dilation of the caudal space and localized
turbulence).
and the catheter is viewed during advancement using US imaging at the level of the spine above the sacrum. The
above section describing intervertebral epidural catheter placement can be referred to for imaging techniques when
viewing the spinal column.
Head & Neck Blocks: Head and neck blocks are often performed in infants and children for managing pain in
the postoperative period. Although these blocks are simple and easy to use, the prevalence of their use has been
lower than expected due to inexperience as well as the need for education of surgeons regarding their use. Two
common blocks that we use in our practice are the infraorbital nerve blocks and the superficial cervical plexus block.
Infraorbital nerve blocks: The infraorbital nerve is the terminal branch of the trigeminal nerve (V1). This nerve, as
it exits the maxillary foramen supplies the sensory innervation to the upper lips, the maxillary sinus area and parts of
the nasal septum. We have used it successfully for infants undergoing cleft lip repair as well as in sinus surgery.9
Technique: The upper lip is everted, using a 27-G needle, it is advanced towards the infraorbital foramen, and after
careful aspiration 1 mL of 0.25% bupivacaine is injected. The area is gently massaged to allow easy spread of the
local anesthetic solution.
Adverse effects: The upper lip remains numb after the block and some children may find it distressing. In addition,
a small hematoma can develop at the site of injection.
Superficial cervical plexus block: The superficial cervical plexus is derived of the cervical nerve roots and supply
the pain fibers for the neck, the pinna and the mastoid area. The superficial cervical plexus wraps around the belly
of the sternocleidomastoid to supply the anterior neck as well as the mastoid area with its branches, the great
auricular, the lesser occipital, the transverse cervical and the supraclavicular.
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Technique: Using a sterile technique, the sternocleidomastoid is identified at the level of the cricoid cartilage(C6), a
27- g needle is inserted along the posterior border of the sternocleidomastoid, after careful aspiration, 2 mL of
0.25% bupivacaine is injected to provide pain relief. We have used this technique for children undergoing mastoid
surgery repair as well as for cochlear implants.10
Adverse effects: Serious adverse effects can be seen from injection into a blood vessel but with superficial injection,
there is little chance for major problems.
Upper Extremity Blocks

The most common approach to the brachial plexus in infants and children is the axillary approach and the
supraclavicular approach. With the advent of US guidance, the interscalene approach has resurfaced as a viable
technique for placement of a catheter.
Interscalene Block
Sonoanatomy: A small footprint hockey stick probe will allow optimal recognition of the superficial structures in
this region for infants and small children. In a transverse oblique plane at the level of the cricoid cartilage and at the
posterolateral aspect of the sternocleidomastoid muscle, the superficially-located sternocleidomastoid muscle
appears triangular in shape and overlies the internal jugular vein and common carotid artery. In small infants, the
US probe footprint is wide enough to capture the great vessels along the brachial plexus in the same image screen.
Lateral to the vessels and deep to the sternocleidomastoid muscle lies the anterior scalene muscle, and more
posterolaterally, the middle and posterior scalene muscle (the latter two often appearing as a single mass). The
hyperechoic (bright)-appearing tissue forming a lining around the muscles is presumably the fibrous tissue of the
interscalene sheath. Brachial plexus trunks and/or roots in this sagittal oblique section are usually visualized as three
(or more) round or oval-shaped hypoechoic (grey or dark) structures, lying between the scalenus anterior and medius
muscles.11 Continuous interscalene blockade was performed for a 10-year old girl in the Philippines during a plastic
surgery medical mission with an intravenous catheter.12 Without the availability of perineural catheters as well as
stimulating needles, a 22 gauge angiocatheter was used for the block, utilizing an in-plane alignment to the posterior
edge of the probe using the US equipment from the obstetric suite. This case demonstrates the ubiquitous nature of
US equipment in most medical centers across the globe.
Supraclavicular Block
Sonoanatomy: The probe is placed along the upper border of the clavicle. The carotid and the internal jugular vein
are recognized. The probe is moved laterally while looking for the pulsation of the subclavian artery. The
supraclavicular brachial plexus is located lateral to the artery and appears hyperechoic mixed with hypoechoic
shadows in a grape like fashion surrounding the artery.
Technique: The supraclavicular block is performed using a high frequency hockey stick or linear probe. The
subclavian artery to identified, inferior to it is the dome of the pleura and lateral and inferior to it is the 1st rib. The
plexus can be accessed using an in-plane approach from laterally. Nerve stimulation can be used in conjunction
with US guidance for this block.
Clinical Pearls - Supraclavicular block

Place a linear probe superior to the clavicle scanning lateral to the great vessels
Notice the 1st rib and the subclavian artery
The supraclavicular plexus is seen surrounding the subclavian artery as a ‘bunch of grapes’
Using an in-plane approach, place the needle below the plexus, injection of 0.3mL/kg of local
anesthesia will produce adequate analgesia.
Stay away from using a medially positioned needle due to close proximity to the pleura.
Comment: When performing a supraclavicular block there is a greater risk of pneumothorax as the cupola of the
lung lies just medial to the first rib, not far from the plexus; the distance of the plexus from the lung being especially
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short in children. It is critical to ensure that clear visibility of the needle shaft and tip is obtained by aligning the
needle in-plane to the ultrasound probe at all times. Single injection techniques are generally sufficient; however
multiple injections of local anesthetic can be performed if needed with the needle redirected to ensure sufficient
circumferential spread around the plexus. However, care should be taken to avoid intravascular injection of the
surrounding vessels (including the transverse colli artery located cephalad to the plexus). Auscultation of the lungs
should be performed before and after performance of the block as well as prior to discharge to detect clinical signs
of pneumothorax. A simple method to recognize the viability of the radial median and ulnar nerve can be performed
by a ‘thumbs up sign’ radial nerve; flexion of PIP (median nerve) and scissoring of the fingers (ulnar nerve) prior to
performance of the block to recognize prior injury.13
Axillary Block
Sonoanatomy: With the probe placed perpendicular to the anterior axillary fold, short-axis view of the
neurovascular bundle can be obtained; the biceps brachii and coracobrachialis muscles are seen laterally; the triceps
brachii muscle is medial and deep to the biceps brachii muscle. The anechoic and circular pulsating axillary artery
lies centrally, adjacent to both the biceps brachii and coracobrachialis muscles, and is surrounded by the nerves. The
median nerve is typically located superficial and between the artery and biceps brachii muscle, the ulnar nerve is
commonly located medial and superficial to the artery, and the radial nerve often lies deep to the artery at the
midline. At this level, the musculocutaneous nerve is located between the biceps brachii and coracobrachialis
muscles.
Technique: The terminal nerves are visualized in an axial plane, the probe is placed in the axillary fold. A needle is
placed in an in-plane approach to access the median, radial and ulnar nerves individually. Local anesthetic solution
is placed to surround the plexus in its entirety to provide an adequate blockade. We feel that the use of ultrasound
may allow reduction in dosing for the block although further studies are required to prove the pharmacodynamic
ability of US guidance with lower volumes for axillary blocks in children.
Comment: Multiple injections and needle redirections are commonly required to ensure circumferential spread of the
local anesthetic around each of the individual nerves. Since there is an abundance of vessels in this region, complete
avoidance of vessel puncture can be a challenge even when utilizing ultrasound imaging. It is important to
understand that the plexus remains very close to the surface and hence the needle should be directed cautiously
while this block is attempted. Smaller doses can be used to provide an adequate blockade of this plexus in infants
and children.
Axillary Block
Place a hockey stick probe or a linear small footprint probe in the axilla as proximal as possible.
The needle is directed from superior to inferior using an in-plane approach.
The structures are superficial and hence are located fairly superficial and can be easily identified.
Color Doppler can be used to recognize the vascular structures.
Local anesthetic solution is injected to surround the cords.
Lower Extremity Block

Femoral Nerve Block
Sonoanatomy: Similar to using conventional technique, arterial pulsations of the femoral artery is the key landmark
when using US guidance for femoral nerve blockade. With the probe placed at the level of and parallel to the
inguinal crease, the nerve appears lateral to the large, circular and anechoic femoral artery (color Doppler may be
used to identify the femoral artery and vein). The nerve often appears triangular in shape and may be variable in
size. The fascia lata (most superficial) and iliaca (immediately adjacent to the nerve and in fact separating the nerve
from the artery) are seen superficial to the femoral nerve and often appear as bright and longitudinally angled
echogenic signals.14
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Technique: A linear high frequency US probe is placed at the level of the inguinal crease and using an in-plane
approach, the femoral nerve is accessed from the lateral aspect. Once the needle enters the fascia iliaca
compartment, local anesthetic solution is injected to envelope the nerve entirely. If a nerve stimulator is used
adjunctly, quadriceps contraction is elucidated. Although one cannot be sure about intraneural injection while using
US guidance, it may be prudent to place the needle in the fascia iliaca compartment and not place it directly into the
neural plexus.
Femoral Nerve Block

Place a linear probe along the inguinal/femoral crease.
Place a needle in an in-plane approach.
The local anesthetic is injected to surround the nerve.
The needle has to be placed inside the fascia iliaca compartment and the local anesthetic is seen
surrounding the nerve bundle.
Lateral Femoral Cutaneous Block:

Sonoanatomy: The lateral femoral cutaneous nerve is located at the lateral aspect of the insertion of the Sartorius
and medial to the tensor fascia lata. The nerve is located between the fascia lata and the fascia iliaca. This supplies
the lateral aspect of the thigh and can be used for providing analgesia for surgery to the lateral aspect of the thigh
including muscle biopsies15 and for percutaneous hip pinning.
Technique: A finger is placed to identify the ridge between the tensor fascia lata and the Sartorius. A linear probe
is placed straddling the tendinous ridge. The fascia between the tensor fascia lata and the Sartorius houses the
lateral femoral cutaneous nerve. After sterile preparation, a 22-G needle is inserted through the fascia lata, after
aspiration, 5 to 10mL of local anesthetic solution is injected.
Complications: Rare, bruise at the site of injection.
Sciatic Nerve Block:
Sonoanatomy: The sciatic nerve block is commonly used in children for providing analgesia for lower extremity
surgery. We use it in combination with a femoral nerve block for providing analgesia for knee surgery. The sciatic
nerve is usually scanned at the level of the popliteal crease. The biceps femoris tendon is identified. The popliteal
artery is identified with the popliteal vein on top of the artery. Immediately above that is the tibial nerve. On
scanning further laterally, the common peroneal nerve can be located.
Technique: In the supine or prone position, the popliteal fossa crease is identified; a linear US probe is placed at the
level of the popliteal crease. The popliteal artery is identified; the popliteal vein deeper to it and deep to that
structure is the tibial nerve. The US probe is moved laterally to visualize the common peroneal nerve. The probe is
advanced cephalad to where the common peroneal and tibial nerves coalesce to form the single sciatic nerve. A
needle is placed in an in-plane orientation; the sciatic nerve can be stimulated if a stimulating needle is used to elicit
inversion or eversion of the foot.
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Sciatic Nerve Block at the Popliteal Fossa

Place a linear probe in the popliteal fossa at the crease at the knee.
Look for the popliteal artery.
The popliteal vein is noted above the artery.
The tibial nerve is often located in close proximity to the popliteal artery.
The common peroneal nerve is located lateral to the tibial nerve.
A linear probe is gently moved cephalad until the two branches confluence; the nerve will diverge from
the vessels.
Using an in-plane approach, a needle is placed in close proximity to the sciatic nerve and local
anesthetic solution is injected to surround the nerve.
Blockade of the Anterior Trunk

Among many blocks performed at the anterior trunk, Ilioinguinal/iliohypogastric nerve blockade is one of the most
commonly performed blocks for surgery in the inguinal region and may be one of the most common peripheral
nerve blocks in children. (Pediatric Regional Anesthesia Network PRAN, personal communication Dr. Suresh)
Various other nerve blocks are also becoming popular to provide analgesia for procedures in the umbilical or
epigastric regions. Ultrasonography can be particularly beneficial for truncal blocks in children due to the close
anatomical relations between the nerves and various critical abdominal structures.
Ilioinguinal/Iliohypogastric Nerve Block

Sonoanatomy: A linear high frequency probe is placed immediately medial to the superior aspect of the anterior
superior iliac spine (ASIS) to capture a short-axis view of the ilioinguinal nerve sandwiched between the internal
oblique abdominal and transverse abdominal muscles. The ASIS appears hypoechoic (due to dorsal shadowing
beyond the highly-reflective periosteum) and nodular-shaped at the lateral edge of the screen. The lateral abdominal
muscles will appear with multiple hyperechoic dots within a hypoechoic background. The nerve can be identified as
an elliptical-oval shaped structure with a hyperechoic film surrounding a hypoechoic core.16,17
Technique: A hockey stick probe will be suitable for many infants and younger children, since the nerves are closely
situated beneath the skin (8 mm on average) and medial (7 mm on average) to the ASIS. The probe is placed with
the direction pointed towards the umbilicus. A needle is inserted in an in-plane approach to place in between the
internal oblique and the transversus abdominis muscle. Local anesthetic solution is injected to hydro-dissect
between the two layers thereby providing a blockade of the L1 nerve root. We use a volume of 0.1mL/kg with a
total maximum volume of 5mL for this blockade.
Ilioinguinal Nerve Block

Place a linear probe or a hockey stick probe along the ASIS with the probe oriented towards the
umbilicus.
The three layers of the abdominal wall muscles can be recognized.
The ilioinguinal nerve and iliohypogastric nerves are seen as 2 hypoechoic structures between the
internal oblique and transversus abdominis muscles.
Using an in-plane approach, a 27-Gauge needle is advanced and placed between the internal oblique
abdominal and the transversus abdominis muscle.
After aspiration, 0.1mL/kg of local anesthetic solution is injected.
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Rectus Sheath Block

Sonoanatomy: The rectus sheath is located between the rectus abdominis muscle and the posterior rectus sheath. A
small footprint probe will be suitable for viewing unilateral anatomy. The anterior and posterior aspects of the
rectus sheath and the enclosed rectus abdominis muscle are visualized. The sheath appears hyperechoic with
multiple linear layers, lying on the anterior and posterior aspects of the rectus muscle.
Technique: A linear high frequency probe is placed on the abdominal wall lateral to the umbilicus. Using an in-
plane approach and coming in from laterally, a needle is inserted posterior to the rectus abdominis muscle but
anterior to the posterior rectus sheath. Superior displacement of the rectus abdominis muscle is seen with injection
of the local anesthetic solution. This block can be used for umbilical hernia repairs as well as most midline
abdominal surgeries involving the T10 distribution.
Rectus Sheath Block

A linear high frequency probe or a hockey stick probe is placed at the level of the umbilicus.
The rectus abdominis muscle is identified along with the anterior and posterior rectus sheaths.
Using an in-plane technique, a 27-gauge needle is advanced until it penetrates the space between the
rectus abdominis and the posterior rectus sheath.
0.1mL/kg of local anesthetic solution is injected into the potential space between the posterior rectus
sheath and the rectus abdominis muscle.
Hydro-dissection can be used to find the exact plane since the space is small and may need exact
localization.
Transversus Abdominis Plane (TAP) Block

Sonoanatomy: The layers of the abdominal wall can be easily distinguished using ultrasonography. The thoraco-
lumbar nerve roots (T10 to L1) provide the sensory supply to the abdominal wall. The nerves run in a plane
between the internal oblique and transversus abdominis muscle, hence referred to as the transversus abdominis plane
or TAP. A linear probe placed along the lateral aspect of the abdomen can distinguish the various layers of the
abdomen including from superficially, fascia/fat, external oblique, internal oblique and the transversus abdominis
muscle. A blockade at this level can provide analgesia for anterior abdominal wall surgery. This may be especially
useful in infants and children who may have underlying coagulopathy, spinal dysraphism or as a rescue block
following a failed neuraxial blockade. The block has been demonstrated to be effective for abdominal surgery in the
adult population.19
Technique: A simple step by step approach to this block has been recently described.20 A linear high frequency
probe or a hockey stick probe is used for the procedure. Recognize the various layers of the abdomen. A needle is
inserted in the in-plane technique to enter the plane between the transverses abdominis and the internal oblique.
Local anesthetic solution (0.2mL/kg) is injected. The downward movement of the transverses abdominis signifies
correct placement of the needle in the TAP plane.
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Transversus Abdominis Plane Block

A high frequency linear probe or a hockey stick probe is placed lateral to the umbilicus.
Sliding the probe laterally, the three muscle layers of the abdominal wall are recognized (external and
internal oblique abdominal and transverse abdominal).
In the mid-axillary line, using an in-plane approach, place a needle between the internal oblique and the
transverse abdominal muscles.
As local anesthetic is injected, the plane is seen to expand with posterior movement of the transversus
abdominis muscle.
Conclusion: US guidance for peripheral and central neuraxial blocks are becoming the mainstay of regional
anesthesia in children. As equipment improves and becomes more cost-effective, the use of US guidance may
become the norm rather than the exception. Multiple hands-on workshops offered by the ASA, ASRA and SPA
may shed greater insight into some of the common techniques. The steep learning curve for US guidance can be
offset by offering it as routine curriculum for training residents and fellows in anesthesia training programs. A
block-rotation (as offered by the fellowship program at the Ann & Robert H Lurie Children’s Hospital of Chicago)
can improve and reinforce the use of regional anesthesia in infants, children and adults. Ongoing data is being
collected prospectively by the Pediatric Regional Anesthesia Network (PRAN), a consortium of Children’s hospitals
in North America. As more data is collected, we will be able to provide a more meaningful insight into adverse
effects, dosing and pharmacodynamics of regional anesthesia in infants, children and adolescents.
1. Frigon C, Mai R, Valois-Gomez T, Desparmet J: Bowel hematoma following an iliohypogastric-

ilioinguinal nerve block. Paediatr Anaesth 2006; 16: 993-6
2. Tsui B, Suresh S: Ultrasound imaging for regional anesthesia in infants, children, and adolescents: a review
of current literature and its application in the practice of extremity and trunk blocks. Anesthesiology; 112:
473-92
3. Tsui BC, Suresh S: Ultrasound Imaging for Regional Anesthesia in Infants, Children, and Adolescents: A
Review of Current Literature and Its Application in the Practice of Extremity and Trunk Blocks.
Anesthesiology; 112: 473-492.
4. Willschke H, Bosenberg A, Marhofer P, Johnston S, Kettner S, Eichenberger U, Wanzel O, Kapral S:
Ultrasonographic-guided ilioinguinal/iliohypogastric nerve block in pediatric anesthesia: what is the
optimal volume? Anesth Analg 2006; 102: 1680-4
5. Bernards CM, Hadzic A, Suresh S, Neal JM: Regional anesthesia in anesthetized or heavily sedated
patients. Reg Anesth Pain Med 2008; 33: 449-60
6. Chawathe MS, Jones RM, Gildersleve CD, Harrison SK, Morris SJ, Eickmann C: Detection of epidural
catheters with ultrasound in children. Paediatr Anaesth 2003; 13: 681-4
7. Willschke H, Bosenberg A, Marhofer P, Willschke J, Schwindt J, Weintraud M, Kapral S, Kettner S:
Epidural catheter placement in neonates: sonoanatomy and feasibility of ultrasonographic guidance in term
and preterm neonates. Reg Anesth Pain Med 2007; 32: 34-40
8. Roberts SA, Guruswamy V, Galvez I: Caudal injectate can be reliably imaged using portable ultrasound--a
preliminary study. Paediatr Anaesth 2005; 15: 948-52
9. Simion C, Corcoran J, Iyer A, Suresh S: Postoperative pain control for primary cleft lip repair in infants: is
there an advantage in performing peripheral nerve blocks? Paediatr Anaesth 2008; 18: 1060-5
10. Suresh S, Barcelona SL, Young NM, Seligman I, Heffner CL, Cote CJ: Postoperative pain relief in children
undergoing tympanomastoid surgery: is a regional block better than opioids? Anesth.Analg. 2002; 94: 859-
62, table
11. Fredrickson MJ, Ball CM, Dalgleish AJ, Stewart AW, Short TG: A prospective randomized comparison of
ultrasound and neurostimulation as needle end points for interscalene catheter placement. Anesth Analg
2009; 108: 1695-700
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12. Mariano ER, Ilfeld BM, Cheng GS, Nicodemus HF, Suresh S: Feasibility of ultrasound-guided peripheral
erve block catheters for pain control on pediatric medical missions in developing countries. Paediatr
naesth 2008; 18: 598-601
13. Suresh S, Sarwark JP, Bhalla T, Janicki J: Performing US-guided nerve blocks in the postanesthesia care
unit (PACU) for upper extremity fractures: is this feasible in children? Paediatr Anaesth 2009; 19: 1238-40
14. Oberndorfer U, Marhofer P, Bosenberg A, Willschke H, Felfernig M, Weintraud M, Kapral S, Kettner SC:
Ultrasonographic guidance for sciatic and femoral nerve blocks in children. Br J Anaesth 2007; 98: 797-
801
15. Maccani RM, Wedel DJ, Melton A, Gronert GA: Femoral and lateral femoral cutaneous nerve block for
muscle biopsies in children. Paediatr Anaesth 1995; 5: 223-227
16. Willschke H, Marhofer P, Bosenberg A, Johnston S, Wanzel O, Cox SG, Sitzwohl C, Kapral S:
Ultrasonography for ilioinguinal/iliohypogastric nerve blocks in children. Br J Anaesth 2005; 95: 226-30
17. Jagannathan N, Sohn L, Sawardekar A, Ambrosy A, Hagerty J, Chin A, Barsness K, Suresh S: Unilateral
groin surgery in children: will the addition of an ultrasound-guided ilioinguinal nerve block enhance the
duration of analgesia of a single-shot caudal block? Paediatr Anaesth 2009; 19: 892-8
18. de Jose Maria B, Gotzens V, Mabrok M: Ultrasound-guided umbilical nerve block in children: a brief
description of a new approach. Paediatr Anaesth 2007; 17: 44-50
19. McDonnell JG, O'Donnell B, Curley G, Heffernan A, Power C, Laffey JG: The analgesic efficacy of
transversus abdominis plane block after abdominal surgery: a prospective randomized controlled trial.
Anesth Analg 2007; 104: 193-7
20. Suresh S, Chan VW: Ultrasound guided transversus abdominis plane block in infants, children and
adolescents: a simple procedural guidance for their performance. Paediatr Anaesth 2009; 19: 296-9
Figure-6 Ilioinguinal N Block Figure-7 TAP block
DISCLOSURE
BK Medical, Other Material Support; AAOS, Consulting Fees
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Anesthetizing the Neonate for Surgical Emergencies:

Avoiding Common Errors
Lynne G. Maxwell, M.D. Philadelphia, Pennsylvania
Surgery for repair of congenital anomalies as well as for acquired conditions is common in the newborn period
(birth to 28 days of age). The newborn requires anesthesia for surgical procedures for the same reasons that older
infants and children do: to maintain physiologic homeostasis, prevent pain, stress responses and their sequelae.
Although neonates were formerly suspected of having blunted, immature responses to pain, it is now clear that
premature and full term newborns have the neuroanatomic and physiologic pathways from periphery to cortex
required for nociception. In fact, by the 24th week of gestation, painful stimuli can be associated with physiologic,
hormonal, and metabolic markers of the stress response.1, 2 Indeed, the stress response may be greater in preterm
infants because of immaturity of descending inhibitory pathways. These responses, if not mitigated by anesthesia
and analgesia, have been associated with increased postoperative circulatory, respiratory and metabolic
abnormalities and morbidity, as well as evidence of alteration of neurobehavioral response to pain later in life.3
Therefore, newborns, no matter how small, require anesthesia and analgesia for surgery and postoperative pain.
Because anesthesia-related morbidity and mortality are higher in infants 4, 5, perioperative administration of
anesthesia and analgesia must be modified to take into consideration the unique features of physiology,
pharmacology, and anatomy present in the newborn period.6 This review will discuss the management of some of
the most common problems that are seen in anesthesia practice with a focus on avoiding adverse outcomes.
Anatomy/Physiology/Pharmacology Review
Airway: One of the areas of greatest anatomic difference between the newborn and older infants and children is in
the airway. Unlike the adult larynx that is at the level of C4-5, the neonatal larynx is at the level of the second and
third cervical vertebrae and is more anterior as well. The relatively large occiput in the neonate results in a natural
sniffing position. Excess neck extension may interfere with good visualization of the more cephalad larynx. The
epiglottis is omega-shaped and lies at 45°, obscuring the view of the vocal cords if not elevated using an
appropriately sized straight laryngoscope blade. The neonatal larynx is narrowest at the level of the cricoid, rather
than the vocal cords. Care should be taken to choose an endotracheal tube which passes the subglottis easily and has
a leak with less than 20-25 cm H2O airway pressure. Depth recommendation is only a guide. ETT tip position above
the carina should be confirmed by bilateral auscultation.
Guide to equipment for intubation in pre- and full term neonates

Weight (kg) Blade (Miller) Tube diameter (mm) Depth mark at lip (cm)
<1 0 2.5 6-7
1-2 0 2.5 - 3.0 7-8
2-3 0 or 1 3.0 8-9
>3 1 3.0 – 3.5 9
Respiratory: Newborns are obligate nose breathers. Respiratory mechanics are similar to the older patient (TV= 7-
10 mL/kg VC= 50-70 mL/kg, FRC= 20 mL/kg; but minute ventilation (respiratory rate) is 3-4 times the adult value
primarily because oxygen consumption is so much greater. Thus, MV:FRC ratio is 4-5:1 in newborns vs.: 1–1.5:1 in
adults (shorter time constant). This results in more rapid desaturation during apnea. The neonate responds to hypoxia
paradoxically: i.e., with apnea instead of hyperpnea. This immaturity of brainstem respiratory control mechanisms
and increased sensitivity to the respiratory depressant effects of anesthetics, sedatives and analgesics, combined with
increased work of breathing and easy fatigability of the diaphragm, increases the risk of life-threatening apnea or
hypoventilation during spontaneous ventilation in the operating room and following surgery.
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Cardiovascular: The immediate neonatal period involves the transition of the circulation from the fetal pattern to
the adult. During fetal life, the pulmonary circulation is marked by low flow and high resistance. In the fetus, the
foramen ovale and ductus arteriosus allow systemic circulation (i.e., R to L shunt). When the umbilical cord is
clamped the systemic resistance rises after elimination of the placental circuit via the ductus venosus, and the
pulmonary vascular resistance falls as the infant takes its first breaths. Anything that increases pulmonary vascular
resistance (pain, hypothermia, hypoxemia, hypercarbia, acidosis, nitrous oxide, high pulmonary inflating pressures)
can result in return of the fetal circulatory pattern with reopening of the foramen ovale (ASD) and ductus (PDA),
This can lead to life threatening hypoxia and right heart failure. Blood pressure is related to cardiac output and
systemic vascular resistance (SVR). In newborns, SVR is relatively fixed because of immature autonomic control of
blood pressure with large arteries in a relatively dilated state. When newborns are hypovolemic, SVR cannot
increase to compensate. The neonatal ventricle is relatively stiff with a fixed stroke volume, because it has 50% of
the contractile tissue present in adult ventricles and increased Type I collagen.7 Maintenance of blood pressure is
related to maintenance of cardiac output via heart rate (CO = HR x SV, normal HR > 120bpm). Because of these
factors, volume replacement (preload) and preservation of heart rate are essential to maintenance of blood pressure
in newborns.
Neurologic: Immaturity of the brain and its blood vessels (immature autoregulation) increases the risk of
intraventricular hemorrhage (IVH) in the neonatal period, especially in infants born at less than 32 weeks gestational
age.8 The first 72 hours of life (the time when many neonatal surgeries occur) is the time of highest risk for IVH.
Factors which increase the risk of IVH include hypoxia, hypercarbia, fluctuations in blood pressure or venous
pressure (increased intrathoracic pressure), low or high hemoglobin, and pain.9 Questions have been raised about the
vulnerability of the developing neonatal brain to injury due to anesthetic and/or analgesic agents such as isoflurane,
nitrous oxide, ketamine and midazolam.10,11 Despite epidemiological studies which raise some concerns,12 at this
time there is no evidence that human neonates are at risk for such brain injury.13,14 Be prepared for parents who may
have questions about neurodevelopmental risks of anesthesia because of media coverage of these studies. Concern
has also been raised about the potential for pulmonary and neurologic injury from oxidative stress induced by
prolonged exposure to high oxygen concentrations. Optimal intraoperative FiO2, PaO2 and SpO2 are yet to be
determined.15
Pharmacology: The pharmacokinetic differences in neonates are primarily related to body fluid composition and
renal and hepatic function. Differences in pharmacodynamics are related to differences in the central nervous system
and neuromuscular junction. These differences impact choices and doses of medications in the perioperative period.
Pharmacokinetics:Body water (BW) comprises 90-105% of the newborn’s weight (pre-term/full term), of which
the extracellular fluid (ECF) represents 50% vs. 60% BW vs. 33% in adults. Preterm and term neonates have a
greater percentage of body water and blood volume than older infants and adults:
Age-related Changes in Body Fluid Composition

Parameter Premature (<37 weeks) Full term >37 weeks) Infant/Child
Total body water (% body wt) 90-100 70-85 60
Extracellular fluid (% body wt) 40-60 40 20
Intracellular fluid (% body wt) 40 40 40
Blood volume (mL/kg) 90-105 80-95 60-70
This combined with lower serum protein results in an increased volume of distribution for water-soluble drugs.
Organ system function is immature at birth, most notably kidney and liver. Immature tubular function results in
decreased clearance of some drugs, especially morphine and its active metabolite M6G.16 Maturation of kidney
function occurs over the first 3 months of life. Immature liver function results in decreased biotransformation of
many drugs (e.g. opioids/local anesthetics) by the cytochrome P450, glucuronidation, and other enzyme systems.
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Other factors affecting drug metabolism include cardiac function, protein binding, and factors affecting liver and
kidney blood flow, (e.g., high intra-abdominal pressure).
Pharmacodynamics
Opioids: The immaturity of the blood-brain barrier results in higher CSF opioid levels in newborns.17 Immaturity
of brainstem respiratory control mechanisms result in greater respiratory depression in newborns at similar CSF
levels,18predisposing to postoperative apnea when opioids are used. Monitoring and capability for ventilatory
support/control (CPAP, ETT/ventilator) must be available. Indeed, the desire for early extubation with less risk of
apnea has led to increasing use of remifentanil in newborn anesthesia, especially in infants with minimal
postoperative pain, 19 or those in whom postoperative analgesia is provided by regional techniques. Remifentanil is
metabolized by plasma esterases, not by biotransformation in the liver; half-life is the same in patients of all ages.
Muscle relaxants: Although the increased body water and associated increased volume of distribution results in
lower concentrations of non-depolarizing muscle relaxants at the neuromuscular junction, neonatal receptors are
more sensitive so there is no difference in initial dosage; 2nd doses on the other hand may last longer than expected.
The larger volume of distribution has a greater impact on the effect of succinylcholine; newborns require higher
doses (2 mg/kg) than older infants (1 mg/kg).20
Local anesthetics: The use of bupivacaine, the drug most commonly used for caudal epidural anesthesia, is
associated with higher blood levels in neonates, due to immature liver metabolism. Blood levels continue to rise
after 48 hrs of continuous infusion.21 As bupivacaine is 95% protein bound, there is greater risk of toxicity due to
low albumin and α1-acid glycoprotein levels in the newborn’s blood.22 Ropivacaine may reach steady state blood
levels, but concentration of free drug is similarly elevated, and caution is advised.23 Alternatively, lidocaine may be
used for epidural infusion (0.3% at 0.5mL/kg/hr). Lidocaine is not as highly protein bound as bupivacaine; blood
levels are easily determined and can be used to guide infusion rate adjustment.24 Chloroprocaine, an amino ester, is
metabolized by plasma esterases, and might be used with greater safety in newborns.25
Inhalation agents: Neonates have a higher rate of uptake of inhalational anesthetic agents due to their high
cardiac output and increased minute ventilation. Because of differences in solubility and blood proteins, they attain a
higher FA/FI ratio than adults. Further, MAC is lower in neonates than in older infants. Sevoflurane has less effect
on infant hemodynamics, especially heart rate, compared to halothane, but has not been systematically studied in
neonates.26
Induction agents: With the unavailability of thiopental in the United States, propofol has become the most
common intravenous induction agent in patients of all ages. Study of the pharmacokinetics of an intravenous bolus
of propofol (3 mg/kg) in a small number of preterm and term neonates suggests significantly lower clearance than in
toddlers27 while the use of doses as low as 1mg/kg resulted in significant hypotension in very low birth weight
(<1500gm) infants.28 Well-controlled studies in the anesthesia setting have not been reported.
Postoperative apnea: Risk of post-anesthetic apnea (PAA) should be considered in all patients born prematurely
(<37 weeks gestation) regardless of the anesthetic technique. This risk persists until 60 weeks postconceptual age
(PCA). Though rare, PAA has been reported in full term infants < 44 weeks PCA even in the absence of opioid
administration. More common in full term infants is periodic breathing, which may be especially pronounced during
emergence from anesthesia. Although all preterm and ex-preterm infants are at risk for PAA, factors which increase
risk include younger gestational and PCA, prior history of apnea events, hemoglobin < 10 gm/dL.29 Other factors
include hypothermia, hypoglycemia, hypoxia, sepsis, and hypocalcemia, which occur with greater frequency in
neonates who undergo emergency surgery. As discussed previously, these children are at risk whenever opioids are
administered. Spinal anesthesia in the absence of any other anesthetics/sedatives/analgesics may decrease the risk of
postoperative apnea, and is reserved for elective inguinal herniorrhaphy in the former premature infant, although
some centers successfully employ it for a wider age range of patients and surgical procedures.30
Intraoperative management
Thermoregulation is of utmost concern in the operative management of neonates. Neonates easily become
hypothermic in the operating room (and during transport) due to their high body surface area to weight ratio, thin
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skin, decreased body fat, and inability to shiver. Anesthetics impair non-shivering thermogenesis from brown fat,
which is the newborn’s only mechanism to maintain body heat. The consequences of hypothermia include
pulmonary hypertension, delayed drug metabolism, hypoxia, and apnea. Heat is lost by evaporation, radiation,
conduction, and convection. Strategies to maintain body temperature include increasing the temperature in the
operating room to 80°F to prevent loss by radiation, using forced air warming, plastic drapes and overhead radiant
warmers. Additional modalities include heated airway humidification and intravenous fluid warmers.
Monitoring: Optimal monitoring includes precordial stethoscope, pulse oximetry, capnography, NIBP, ECG and
temperature (esophageal or rectal). The pulse oximeter should be placed on the right hand or ear (preductal). A
second post-ductal oximeter probe may be placed for back up, or when right to left shunting is anticipated. An intra-
arterial catheter (IAC) is useful in critically ill neonates who are at risk for large intraoperative blood and/or fluid
losses, due either to coagulopathy or resection of large masses (e.g. NEC, sacrococcygeal teratoma). An IAC allows
for continuous monitoring of blood pressure and periodic assessment of blood gases, glucose, electrolytes including
ionized calcium, hemoglobin, and base deficit. Central venous catheters (3 Fr) (CVP) are usually placed in the right
internal jugular vein and are very useful for both monitoring and as a secure IV access, particularly in procedures
with anticipated large blood or fluid loss. Decrease in the arterial blood pressure wave form and CVP with
inspiratory positive pressure (pulsus paradoxus) is a sensitive indicator of hypovolemia. Patients undergoing non-
abdominal surgery may have umbilical arterial and/or venous catheters.
Fluids, electrolytes and glucose management
The immature kidney has diminished ability to handle a solute load. Newborns are born with excess sodium and
require none in the first 72 hours of life. Therefore, maintenance fluid consists of hypotonic glucose solutions (D5 or
D10 in either water or 0.2NS). For replacement of insensible and small volume blood loss, isotonic fluid should be
administered separately. To prevent excessive fluid (and glucose) administration it is wise to deliver both
maintenance fluids (4 mL/kg/hr) and operative (insensible and blood loss) fluid replacement (3-10 mL/kg/hr) with
infusion pumps. Although total parenteral nutrition solutions containing high concentrations of glucose should not
be stopped abruptly due to the possibility of rebound hypoglycemia, perioperative hyperglycemia can occur easily
when high glucose containing fluids are given in combination with operative stress. Hyperglycemia (glucose >175
mg/dL) has been associated with increased morbidity in premature infants with necrotizing enterocolitis31 and may
worsen the outcome of IVH. During neonatal surgery, glucose administration should continue, but blood glucose
measurement should be performed at frequent intervals to avoid both hyper- and hypoglycemia in all but the
shortest, most minor neonatal cases (hernia repair, pyloromyotomy). Hypoglycemia is defined as blood glucose
below 45mg/dL during the 1st 3 days of life, 75 mg/dL thereafter. Hypoglycemia is more common in infants born to
diabetic mothers, those that are small for gestational age and infants that have required neonatal resuscitation.
Blood and colloid administration
Small amounts of blood loss may be replaced with isotonic electrolyte solutions as newborns are born with high
hematocrit (sometimes > 50%). However, because the oxygen affinity of fetal hemoglobin (HbF) is higher than
hemoglobin A, oxygen delivery is reduced at any given hematocrit. In emergency surgical situations with large
blood and/or fluid losses, hematocrit should be maintained > 35. Administration of large amounts of electrolyte
solutions may cause increased lung water, especially in preterm neonates. This may result in worsening of
oxygenation and ventilatory status and may lead to the need for postoperative ventilation. Administration of albumin
has not been shown to improve outcomes in medically hypotensive neonates when compared to isotonic saline.32
Excessive blood replacement should be avoided, as high hematocrit (> 60) causes increased blood viscosity and risk
of thrombotic stroke and IVH in preterm infants. Blood administered to newborns should be irradiated (risk of graft
vs. host disease) and screened for CMV. It should be relatively fresh, or washed to decrease the risk of
hyperkalemia. Three mL/kg of packed red blood cells will raise the hemoglobin by 1g/100ml. Rapid administration
of blood may cause ionized hypocalcemia; calcium gluconate (10 mg/kg) should be available for administration.
Ventilation: are special circuits or NICU ventilators needed?
Although the use of open or semi-open circuits such as the Mapleson has long been advocated for small infants in
textbooks of pediatric anesthesia, such recommendations have their origin in an era when spontaneous ventilation
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was much more common, which necessitated using a circuit of the lowest possible resistance to breathing. Modern
anesthetic management of neonates almost always utilizes controlled ventilation, with the exception of some patients
with tracheoesophageal fistula (see below). Improved anesthesia ventilator technology allows safe and effective
ventilation in neonates with a wide range of pulmonary compliance. Studies utilizing an infant lung model have
shown that anesthesia ventilators with a circle breathing system compare favorably with respect to ventilatory
parameters with semi-open circuits such as the Bain, as well as comparing favorably with NICU ventilators in
settings of low lung compliance.33 Pressure-limited ventilation is probably the best choice for most neonates, but
vigilance is required in settings of low or changing pulmonary compliance, with careful attention to ventilatory
parameters, such as respiratory rate, expired tidal volume, peak inspiratory pressure, I:E ratio, and end-tidal carbon
dioxide.34 Some preterm infants with very poor lung compliance may benefit from use of a NICU ventilator in OR.
Extubation
Immediate postoperative extubation in the neonate requires that the patient be awake with full strength (hip flexion,
arms lifting), have a low likelihood of airway obstruction (normal airway anatomy), normal temperature, blood
pressure and volume status, and regular respiratory pattern with adequate minute ventilation.
Commonly performed surgical procedures: Patients born with one anomaly, particularly of midline
structures, frequently have associated anomalies. Before proceeding to surgery in these patients, it is wise to get a
cardiac evaluation (echocardiogram) looking for congenital heart disease.
Abdominal surgery: Despite having no feeding since birth, most newborn abdominal surgical emergencies are
“full stomachs” and require volume loading (10-20 mL/kg LR) and preoxygenation (1 min) prior to induction. An
orogastric tube should be placed, suctioned and removed to decompress the stomach prior to induction. After
administration of atropine (0.15mg), airway control is either via a rapid sequence intubation (propofol 2-3 mg/kg,
and either succinylcholine 2 mg/kg or rocuronium 1 mg/kg) or awake intubation. My preference is a rapid sequence;
your preference may be different based on your experience and technical skills and any anatomic condition in which
difficult intubation is a consideration. Patients who are hemodynamically stable and not septic may have a caudal
catheter placed after intubation if extubation is desired and anticipated.
Intestinal atresia/bowel obstruction: Duodenal atresia/annular pancreas usually presents with bilious
vomiting. Duodenal atresia may be associated with trisomy 21, in which case congenital heart disease may be
present. The infant should be examined for signs of dehydration associated with vomiting and electrolytes should be
checked. Central line placement is not necessary for anesthetic management but may be placed for postoperative
intravenous nutrition. Jejeunal or ileal atresia presents later than duodenal atresia with bilious vomiting and/or signs
of abdominal distention/ileus.
Malrotation/midgut volvulus: This condition is a true surgical emergency as the bowel may be ischemic due to
interruption of blood flow. The entire small bowel may become necrotic and/or perforation may occur with
associated sepsis and coagulopathy. Careful but rapid physical and laboratory assessment with fluid resuscitation of
20 mL/kg of isotonic crystalloid should be performed prior to rapid sequence induction. An arterial catheter may be
advisable as hypotension may occur and frequent laboratory assessment may be necessary. Blood, FFP, and platelets
should be available. Fluid resuscitation, albumin or FFP, and dopamine or low dose epinephrine infusion may be
necessary. Derotating the bowel may cause vasoactive mediator release which may cause acidosis and hypotension.
Caudal catheter should not be placed in the setting of possible sepsis and coagulopathy. Most patients will require
postoperative ventilatory support. A central venous line provides reliable venous access, measurement of CVP and a
route for postoperative parenteral nutrition, which may be necessary in these cases.
Omphalocele/gastroschisis: Defects of the abdominal wall look alike but are different. Omphalocele is a
midline defect and 80% of patients have other anomalies. Gastroschisis is a defect adjacent to the midline and is not
associated with non-intestinal anomalies, but there is a 10% incidence of intestinal atresia. Both require large fluid
resuscitation before, during and after surgery. Although small defects can be closed without difficulty, large ones
can be difficult to close primarily and can result in increased intra-abdominal pressure and compromised organ
blood flow (kidney and gut) and ventilation. Therefore, in recent years, surgeons have used a staged approach to
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closure, first putting the bowel in a silo with a spring ring which slips inside the fascia under the edges of the
abdominal defect.
Management: These patients are treated as full stomachs (see above). Anesthetic maintenance can include
fentanyl in addition to inhalational agent as the increased intra-abdominal pressure and diaphragmatic elevation
reduces respiratory compliance and makes extubation inadvisable. Primary closure should be abandoned if
measurement of intra-gastric or -vesical pressure is > 20 cm H20, if peak airway pressure increases, and if central
venous pressure increases by more than 4 cm H20.35 A pulse oximeter probe should be placed on the foot in addition
to the hand as too tight abdominal wall closure can result in loss of the pulse oximeter wave form. If a caudal
catheter is placed, increased abdominal pressure can result in decreased metabolism of amide local anesthetics.
There is large insensible fluid loss from the large area of irritated bowel exposed. Administration of isotonic fluid 10
mL/kg/hr or more is often required to maintain blood pressure. Colloid such as albumin may be required; sometimes
dopamine infusion may be necessary. Maintenance of temperature may be a problem due to exposed bowel. Usual
warming methods as well as warmed irrigation fluids should be employed.
Necrotizing enterocolitis (NEC): NEC is a condition which primarily affects preterm infants (< 1500 gm). It
occurs as a result of bowel ischemia and may be caused by hypotension due to poor cardiac output, hypertonic
formulas, and/or infection. So-called “medical NEC” may present with feeding intolerance and abdominal distention
with small air bubbles in the bowel wall on abdominal x-ray. This condition may resolve with cessation of enteral
feeding and antibiotic administration. Frequently the condition progresses to severe abdominal distention with
sepsis, hypotension and coagulopathy. These infants are critically ill and usually come to the operating room
intubated and on inotropic support (usually dopamine 5-20 mcg/kg/min). They require careful fluid management
(usually > 70 mL/kg) and may benefit from central venous line placement. An opioid (fentanyl)-relaxant anesthetic
affords hemodynamic stability. Sometimes NEC is initially managed in the NICU with percutaneous placement of a
right lower quadrant abdominal drain in a critically ill intubated neonate (facilitated by IV analgesia).36 After sepsis,
coagulopathy, and hypovolemia are stabilized, the patient may later present to the OR for resection of a stenosis of
the bowel at the area of previous ischemia.
Congenital diaphragmatic hernia (CDH)

CDH is a defect of the diaphragm, most commonly on the left (foramen of Bochdalek), which is commonly
diagnosed by prenatal ultrasound and presents at birth with respiratory distress due to hypoplasia of the lung because
of the presence of bowel in the chest. With large defects, the infant has severe respiratory distress at birth with
hypoxia and pulmonary hypertension. The chest may appear distended and the abdomen scaphoid. Chest x-ray
reveals air-filled viscera in the chest. The severity of the condition is primarily due to the pulmonary hypoplasia;
surgery to reduce the abdominal viscera into the abdomen will not necessarily result in improvement in ventilation.
Although in the past, these patients were frequently rushed to the OR, it is now recognized that stabilization with
sedation/analgesia and careful ventilatory management is necessary before operation is considered.37 Management
may include surfactant, high frequency oscillation,38 inhaled NO, sildenafil, and possibly ECMO.39,40 Although
maintenance of a pCO2 of < 40 mm Hg may result in a lower PVR, this may be achieved at the cost of excessive
peak inspiratory pressures, which may increase the risk of barotrauma which may lead to parenchymal lung damage
and pneumothorax. Permissive hypercapnia may be employed. The use of ECMO has been shown to double survival
in the infants at highest risk of mortality (80% or greater), but overall, CDH infants placed on ECMO have a lower
survival rate than those not placed on ECMO (52.9 vs. 77.3%).41 Infants placed on ECMO may, of course, be sicker
and have more hypoplastic lung than infants not placed on ECMO; their increased mortality may be due to their
underlying lung hypoplasia. Operation to reduce the viscera into the abdomen (through a subcostal or thoracic
incision or increasingly thoracoscopically) is commonly performed in the NICU, to avoid disruption of ventilation in
these very fragile patients who are prone to increasing pulmonary artery pressures and deterioration of oxygenation.
The viscera are reduced into the abdomen and the diaphragm closed, usually primarily, although some large defects
require the use of a Gore-Tex® patch. Optimal reduction of the viscera is facilitated by intermittent suction via
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naso- or oro-gastric tube. Hypotension during reduction may be due to compromise of venous return caused by
kinking of liver blood vessels. Minimal pulmonary vascular resistance (PVR), and therefore optimal oxygenation, is
achieved by careful attention to temperature control, analgesia (high dose fentanyl), and careful ventilation. High
ventilatory pressures should be avoided to minimize the risk of pneumothorax of the non-operative lung. Sometimes
surgery is performed on ECMO with analgesics and blood/fluids administered into the ECMO circuit. While
surgical bleeding complications in infants having surgery while on ECMO have been decreased by use of an
antifibrinolytic agent such as tranexamic acid,42 their use is not common and fewer bleeding complications occur if
surgery occurs after pulmonary hypertension improves and the infant has been weaned from ECMO. CDH survivors
have a high incidence of neurodevelopmental problems (20-67%).43
Thoracic surgery: Tracheoesophageal fistula/esophageal atresia. TEF is characterized as type A-E, with
type C being the most common. It is most commonly diagnosed in the delivery room when a suction catheter cannot
be passed from the mouth into the stomach due to the esophageal atresia. 20-30% of infants with TEF are premature
and there is a high incidence of congenital heart disease and other anomalies. All infants with TEF should have an
echocardiogram. CXR should be performed. The side of the aortic arch should be identified, as the surgical incision
should be made on the opposite side. Surgery may be delayed until the workup is completed. Infants have pooling of
secretions in the esophageal pouch and should be kept in a semi-upright position with a drainage catheter in the
pouch on low suction. Failure to do so can result in aspiration of secretions. Gastric contents can also enter the lungs
through the fistula. Patient should have IV access prior to induction and receive atropine 0.15mg. The pouch should
be aspirated and inhalation induction performed with avoidance of positive pressure ventilation to prevent gastric
distention. The infant is intubated deep without muscle relaxant. A Magill tube (no Murphy eye) should be used.
With gentle PPV the location of the fistula is identified by listening over the lungs and the stomach. Many surgeons
perform a rigid bronchoscopy after induction to locate the fistula. The tube is taped at a location below the fistula
but above the carina. If the fistula is at the carina, the tube may be advanced into the bronchus of the lung on the
non-operative side. If ventilation can be accomplished without gastric inflation, the patient may receive muscle
relaxant. A caudal catheter can be advanced (tip at T5-T7) to supplement the general anesthetic (iso-, des-, or
sevoflurane/air/oxygen) and provide excellent postoperative analgesia without the use of opioids and to facilitate
extubation. Infants < 2000g may require postoperative mechanical ventilation. There is debate but little evidence
whether the risk of reintubation is greater in these infants than the risk of continued intubation with respect to trauma
at the site of the fistula. Infants <2000g may have delayed repair of esophageal atresia after placement of a
gastrostomy tube at the time of fistula repair to allow time for growth of the infant and the esophageal segments.
Pyloric Stenosis: Despite being a congenital defect, pyloric stenosis usually does not present until 2-4 weeks of
age. Infants have repeated projectile non-bilious vomiting with resultant hypochloremic dehydration. Surgery is now
done at younger age, as the diagnosis is made earlier with the use of ultrasound. Prior to surgery, measurement of
electrolytes and correction of hypovolemia and alkalosis should be accomplished by administration of 10- 20 mL/kg
isotonic fluid, with the goal being to lower the serum HCO3 to <30 mEq/L. Maintenance fluid of D5 0.45NS at 4
mL/kg/hr should be administered concomitantly. Although alkalosis is usually associated with hypokalemia, 36% of
patients with PS present with hyperkalemia.44 If there is no gastric tube present, one should be placed orally and
suctioned (after administration of 0.15 mg atropine) with the infant turned from side to side to empty the stomach as
fully as possible prior to rapid sequence induction, performed as described above with placement of a 3.5 ETT, or
the size which yields a leak of 15-25 cm H2O. An inhalation agent is usual for maintenance of anesthesia, although
use of remifentanil has been reported with good outcomes.19 These patients have minimal discomfort
postoperatively after wound infiltration with local anesthetic, rectal acetaminophen (30 mg/kg), and ketorolac.
Opioids are not required, especially for laparoscopic procedures. Postoperative apnea has been reported in this
population of full term infants, which may be related to delayed correction of CSF alkalosis, even when opioids
have been avoided. Therefore postoperative oximetry and cardiorespiratory monitoring is essential. Although not
widely adopted, spinal anesthesia for open pyloromyotomy has been reported to be safe and associated with reduced
operating room time.30, 45
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Inguinal Hernia: Repair of inguinal hernia is frequent in the neonatal period, especially in ex-preterm infants.
Because of a high risk of incarceration in these infants, repair is frequently performed electively prior to discharge
from the NICU, at postconceptual ages < 60 weeks. Some infants may present after hospital discharge with
incarcerated inguinal hernia. Some of these infants may have residual chronic lung disease (CLD) with reactive
airways and parenchymal damage. Careful evaluation of respiratory status, including oxygen saturation, medications
and CXR is essential. Infants of this PCA may be anemic (hemoglobin 8-9), which has been shown to increase the
risk of postoperative apnea.29 When hernia repair is elective, inhalation or IV (if present) induction may be
performed, with subsequent placement of IV if necessary and endotracheal intubation. Former premature infants
who had been intubated and ventilated in the neonatal period are at risk for subglottic narrowing due to granuloma
or stenosis which may be asymptomatic. Smaller tubes (2.5-3.0) should be available and placed as indicated to allow
a safe leak pressure. Patients with incarcerated hernia require rapid sequence induction after orogastric suction. In
infants with CLD, care should be taken to ensure adequate depth of anesthesia for intubation as severe
bronchospasm with desaturation may occur. Care should be taken to avoid placement of the ETT near the carina.
Bronchospasm may also occur on emergence and may be ameliorated by intraoperative administration of albuterol
through the ETT. Maintenance with inhalation agent and caudal bolus administration of bupivacaine 0.25% with
epinephrine 1:200,000 (1 mL/kg) obviates the need for opioids, but does not eliminate the risk of apnea. In a large
series, the use of spinal anesthesia alone for elective repair of inguinal hernia in ex-premature infants has been
shown to virtually eliminate the incidence of apnea.30 It is my group’s policy to admit these children for 24 hours
following surgery to a monitored bed regardless of the anesthetic technique, although they usually do not require
ICU admission.46 Additionally, some of my colleagues administer caffeine citrate10 mg/kg slowly IV at the start of
surgery to minimize the risk of post-anesthetic apnea.47
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16. Lynn AM, Slattery JT. Morphine pharmacokinetics in early infancy. Anesthesiology 1987; 66:136-9.
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18. Hertzka RE, Gauntlett IS, Fisher DM et al. Fentanyl-induced ventilatory depression: effects of age.
19. Davis PJ, Galinkin J, McGowan FX et al. A randomized multicenter study of remifentanil compared with
halothane in neonates and infants undergoing pyloromyotomy. I. Emergence and recovery profiles. Anesth
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20. Meakin G, McKiernan EP, Morris P, Baker RD. Dose response curves for suxamethonium in neonates, infants
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21. Larsson BA, Lonnqvist PA, Olsson GL. Plasma concentrations of bupivacaine in neonates after continuous
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22. Lerman J, Strong HA, LeDez KM et al. Effects of age on the serum concentration of alpha-1 acid glycoprotein
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23. Bosenberg AT, Thomas J, Cronje L et al. Pharmacokinetics and efficacy of ropivacaine for continuous epidural
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24. Kost-Byerly S, Jackson EV, Yaster M et al., Perioperative anesthetic and analgesic management of newborn
bladder exstrophy repair. J Pediatr Urol 2008; 4:280-5.
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infants. J Clin Anesth 1993; 5:129-33.
26. Wodey E, Pladys P, Copin C et al. Comparative hemodynamic depression of sevoflurane versus halothane in
infants: an echocardiographic study. Anesthesiology 1997; 87:795-800.
27. Allegaert K, deHoon J, Verbesselt R et al., Maturational pharmacokinetics of a single intravenous bolus of
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28. Welzing L, Kribs A, Eifinger F et al. Propofol as an induction agent for endotracheal intubation can cause
significant arterial hypotension in preterm neonates. Ped Anesth 2010; 20:605-611.
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herniorrhaphy: A combined analysis. Anesthesiology 1995; 82:809-22.
30. Williams RK, Adams DC, Aladjem EV et al. The safety and efficacy of spinal anesthesia for surgery in infants:
the Vermont Infant Spinal Registry. Anesth Analg 2006; 102:67-71.
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in neonates with necrotizing enterocolitis. J Pediatr Surg 2004; 39:898-901.
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34. Habre W. Neonatal ventilation. Best Practice Res Clin Anaesth 2010; 24: 353-64.
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defects using intraoperative measurements. J Ped Surg 1989; 24:1217-20.
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37. Weber TR, Kountzman B, Dillon PA, Silen ML. Improved survival in congenital diaphragmatic hernia with
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38. Bouchut JC, Dubois R, Moussa M et al. High frequency oscillatory ventilation during repair of neonatal
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39. Okawada M, Okazaki T, Yamataka A, et al. Efficacy of protocolized management for congenital diaphragmatic
hernia. a review of 100 cases. Pediatr Surg Int 2006; 22:925-30.
40. Noori S, Friedlich P, Wong P et al., Cardiovascular effects of sildenafil in neonates and infants with congenital
diaphragmatic hernia and pulmonary hypertension. Neonatology 2007; 91:92-100.
41. The Congenital Diaphragmatic Hernia Study Group. Does extracorporeal membrane oxygenation improve
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42. van der Staak FH, de Haan AF, Geven WB et al., Surgical repair of congenital diaphragmatic hernia during
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43. Rothenbach P, Lange P, Powell D. The use of extracorporeal membrane oxygenation in infants with congenital
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DISCLOSURE
Cubist, Self Funded Research
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A Child with a Difficult Airway
Samuel H. Wald, M.D. Los Angeles, California
Differences between the pediatric and the adult airway
Infants and children are in the process of rapid developmental changes that must be a strong consideration when
caring for a pediatric patient with a difficult airway. Though smaller in size, the metabolic demands are relatively
increase which accentuates losses of oxygen through consumption and in the cases of respiratory compromise
hastens the effects of apnea. Oxygen consumption is inversely related to age as required by the metabolic demand
of growth. Apnea under this circumstance requires much more rapid restoration of oxygenation and ventilation to
avoid the complications of hypoxia.
Anatomical Differences
The head and occiput of infants and young children is disproportionately large relative to the size of the torso.
Therefore, the usual placement of a cushion under the head may or not be necessary to aid in the alignment of the
axes of the mouth, pharynx and glottic opening and also applies to the use of a small shoulder roll. Exact
positioning needs to be carefully individualized for each patient. The larynx is a more superior structure at the level
of the third or fourth cervical vertebrae rather than the inferior location in adults at the sixth cervical vertebral level.
During laryngoscopy, this superior position of the glottis will make the airway appear to be more “anterior” from the
oral vantage point making it more of a challenge to align the oral, pharyngeal and laryngeal axes, especially in a
child with a difficult airway.1 The epiglottis is also larger relative to the size of the glottic opening and may obstruct
the view of the vocal cords and passage of an endotracheal tube. The tongue is bigger relative to the size of the
oropharynx requiring proper approach with a laryngoscope. However, the small mouth opening especially in infants
may limit the use of airway devices with large profiles that may be helpful in adults. For example, the reusable of
the Glidescope (Verathon, WA, USA) has a large size relative to a standard larygoscope that is not a limitation for
larger patients.
Physiologic Differences of the Respiratory System
The size of the FRC of infants and children is directly related to age, weight and height.2 The smaller FRC is due to
the fact that the chest wall is not fully formed into bone from cartilage and that the lung is less compliant until the
age of five to eight years. Functional Residual Capacity (FRC) is determined by the balance of the tendency of the
chest wall to expand and the lungs to collapse at the end of passive exhalation. Until this time, the connective tissue,
elastin is still maturing in the lung. Additionally, the work of breathing is greater as the box-shaped chest of infants
is characterized by the ribs at right angles to the vertebral bodies, so that the effects of respiratory distress and/or
respiratory depression from anesthetic agents may be exacerbated. Another important consideration is that the great
majority of pediatric patients have not reached an emotional/behavioral stage where they can be compliant or
cooperative with the health care practitioner. Depending also on age and co-morbidities such as developmental
delay, the pharmacodynamics of anesthetic agents may be unpredictable, exaggerated or may have paradoxical
effects.
Lastly, the American Society of Anesthesiologists Difficult Airway Algorithm may require some
modification for use in pediatric patients especially infants.3 Patients with craniofacial anomalies may not tolerate
the supine position and may require induction of anesthesia and airway management in the elevated, lateral or even
prone position. The techniques available for surgical rescue of the unanticipated airway may be limited when
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compared to adults. For instance, there are case reports of trans-tracheal jet ventilation in this age group4, but as of
the writing of this document, none reported emergently. Additionally, in a study of the trachea in infant cadavers it
was found that the neonatal cricothyroid membrane is too narrow to accommodate even a 2.0 mm I.D endotracheal
tube.5
General Approach to Airway Management
A pre-induction estimation of the difficulty of mask ventilation may be a guide that anesthetization of the
airway should be used along with sedated intubation versus intubation following the induction of general anesthesia.
For infants and children, there is less literature on the predictability of a difficult airway other than the known
syndromes or an obviously small mouth or airway obstruction. There are few studies in infants and in children (one
predicting the airway in Goldenhar/hemifacial microsomia), but no consistent guidelines specifically for pediatric
patients.8,14 In a prospective study of over one-thousand children aged 6-18 years, increased neck circumference was
evaluated or a possible effect on difficult laryngoscopy. High neck circumference was prevalent in almost one-
quarter of the children and was correlated with obesity and adverse respiratory events for non-cardiac surgery.
However, there was no association with difficult laryngoscopy found. Airway evaluation of the airway in infants
and children may be limited by the fact that these patients are often uncooperative.
Sedated Intubation
For a plan of sedated intubation with a patient spontaneously breathing, topicalization is entirely possible,
even in neonates, and will aid in sedated intubation possibly allowing for less intravenous anesthetic medications. If
topicalization of the airway is desired, a number of approaches have been described, such as nebulization,
atomization and regional anesthesia of the airway.15 Consideration in limiting the amount of local anesthetic to avoid
toxicity in small patients. If a fiberoptic scope is to be used, sizes 2.8 mm O.D. and above will have a side-port in
most circumstances for use in the installation of oxygen and to spray additional local anesthetic on the vocal cords
and in the trachea once those structures are visualized. Unfortunately, the 2.5 mm O.D. and smaller scopes do not
have side ports due to the size limitation. Both the 2.8 mm O.D. and 2.5 mm O.D. will fit through a 3.0 mm I.D.
endotracheal tube, but it will be necessary to remove the endotracheal tube connector for the circuit before placing
the tube onto the scope.
A number of medications for use in children have been described in the literature including propofol,
opioids, benzodiazepines, ketamine and dexmedetomidine.16,17,18
Intubation under General Anesthesia
If a general anesthetic with an inhalation induction with an agent such as sevoflurane has been selected for
the predicted difficult airway19 and spontaneous ventilation is maintained, a nasopharyngeal device (endotracheal
tube20 or standard nasopharyngeal airway with an endotracheal tube connector [FIGURE]) may be placed and
attached to the anesthesia circuit. Inhalation anesthesia can continue along with oxygen as can monitoring of carbon
dioxide from the hypopharynx while a definitive airway is established though the other nostril or orally. The
advantage is the maintenance of anesthetic depth and oxygenation and continuous monitoring for apnea as opposed
to intermittent mask ventilation between intubation attempts.
In one case series of eleven infants neonates weighing 2-3 kilograms an 8 French airway exchange was
used in patients with severe narrowing of the trachea. The device was used for assisted and manual ventilation as a
bridge to a definitive airway during laryngotracheal reconstruction.
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The unpredicted difficult airway in pediatric patients is especially challenging for the reasons outlined
earlier due to the decreased reserve in oxygen in the scenario of difficult mask and difficult intubation. A review of
100 pediatric tracheotomies placed between 2004 and 2007 in a single institution found that a Laryngeal mask
Airway (LMA) was a useful airway adjunct. Six of the patients were emergency tracheostomies, five of which
could not be intubated and all of these were managed with an LMA or a facemask while the tracheostomy was
established.21
Pediatric Airway Devices
Beyond the use of the standard direct laryngoscope or a fiberoptic scope, a number of supraglottic and intubation
devices are now available specifically designed for use in infants and children. There have been two recent reviews
of the equipment available at this time in 2009 and 2010 that would be recommended reading for those who care for
infants and children.22,23The options are continually being expanded and many are available in both pediatric and
adult sizes. One recommendation that might be useful is to get familiarized with the larger sizes before attempting
the smaller versions depending on the scope of one’s practice.
Currently, there are several devices that are designed specifically for use in children. Two of these, the Storz
Videolarygoscope (Karl StorzTuttlingen, Germany) and the Truview Infant EVO2 (Truphatek, Netanya, Israel)
utilize blades for laryngocopy similar to a standard laryngoscope. The Storz scope offers the advantage of a view by
both direct laryngoscopy and a videoscopic one and has been used in difficult airway rescue. The Truview provides
a side-channel for the administration of oxygen during videoscopy. In a series of sixty neonatal intubations
comparing the Truview to standard laryngoscopy in neonates, this device allowed for a shorter time for
laryngoscopy and an improved Cormack and Lehane grade.
The Glidescope (Verathon, Bothell, WA, USA) now has a re-designed option, the AVL Preterm/Small Child in a
smaller profile which has both a disposable and reusable blade options. For the small endotracheal tubes less than
6.0 mm I.D. there is no rigid stylet available. A published suggested solution is to curve the endotracheal tube with
a standard pediatric stylet as the same shape as the blade of the device.
The Airtraq (Prodol Meditec, Bizkaia, Spain) also a videoscopic-only device is a single use blade with a side
channel guide for the endotrcheal tube. It does require a minimum mouth opening of 12.5 mm for both pediatric
sizes (www.airtraq.com) and may require a slight rightward redirection of the device as the channel in on the right
side.
The device with the smallest profile is the Shikani Optical Stylet (Clarus Medical, Minneapolis, MN, USU) that is
beneficial with a limited mouth opening. It is a rigid style with video capability and can be used with down to a 2.5
mm I.D endotracheal tube.
When intubation is not possible due to the inability to have a view of the glottis by direct laryngoscopy or by video
laryngoscopy a supra-glottic device may be used as a conduit for an endotracheal tube. Another device called the
AirQ ILA (Mercury Medical, Clearwater, FL, USA) may offer some advantages over the LMA for this purpose and
has been used in patients with a difficult airway for intubation and for blind intubation with airway hemorrhage in
pediatric patients. The AirQ ILA has a removable circuit adapter that allows for passage and removal of a cuffed
endotracheal tube and is shorter than an LMA that makes removal of the device over the endotracheal tube easier
and a stabilizing rod is also available to facilitate the removal.
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Extubation
Extubation of pediatric patients with a known difficult airway may also be fraught with the peril of airway
obstruction. A number of reports have been published using various devices in innovative ways as an exchange
catheter in preparation for a potential re-intubation (non-FDA approved) such as ureteral stent guidewire and a
guidewire sheath adapted to the size needs of a pediatric patient.24,25 Also conversion from oral intubation to nasal
intubation in children has also been described. 26 Lastly, in a review of 20 intubated children, an airway exchange
catheter was a successful bridge to extubation or re-intubation.27 Re-intubation was accomplished using the airway
exchange catheter as a guide to re-pass the endotracheal tube.
References
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when used for intraoperative sedation, Anesth Analg 2002;95:461-466.
Bahk J, Sung J, Jang I, A comparison of ketamine and lidocaine spray with propofol for insertion of laryngeal mask
airway in children: a double-blinded randomized trial, Anesth Analg 2002;95:1586-1589.
Fayoux P, Marciniak B, Engelhardt T, Airway exchange catheters use in the airway management of neonates and
infants undergoing surgical treatment of laryngeal stenosis, Pediatr Crit Care Med. 2009 Sep;10(5):558-61.
Fiadjoe J, Stricker P, Pediatric Difficult Airway Management: Current Devices and Techniques, Anesthesiology
Clinics 2009;27:185-195.
Holm-Knudsen R, The difficult pediatric airway-a review of new devices for indirect laryngoscopy in children
younger than two years of age, Paediatr Anesth. 2011;21: 98–103.
Holm-Knudsen R, Eriksen K, Rasmussen LS, Using a nasopharyngeal airway during fiberoptic intubation in small
children with a difficult airway, Pediatric Anesthesia 2005;15:839–845.
Iravani M, Wald, SH, Dexmedetomidine and ketamine for fiberoptic intubation in a child with severe mandibular
hypoplasia, Journal of Clinical Anesthesia 2008;20:455-457.
Jagannathan N, Roth AG, Sohn LE, Pak TY, Amin S, Suresh S, The new air-Q intubating airway for tracheal
intubation in children with anticipated difficult airway: a case series, Paediatr Anesth. 2009.
Jagannathan N, Wong DT, Successful tracheal intubation through an intubating laryngeal airway in pediatric
patients with airway hemorrhage, J Emerg Med 2011 Oct;41(4):369-73.
Kandasamy R, Sivalingam P, Use of sevoflurane in difficult airways, Acta Anaesthesiol Scand 2000;44:627-629.
Liu HP, Xue FS, Guo XL, Liao X, Orotracheal to nasotracheal intubation exchange in pediatric patients with a
difficult airway, Pediatric Anesthesia 2010;20:377-378.
Liu HP, Xue FS, Liu JH Yuan YJ, Guo XL, Liao X, Facilitating tracheal intubation in pediatric patients with the
Airtraq optical laryngoscope, Can J Anesth. 2011 Mar;58(3):338-9.
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Mirghassemi A, Soltani AE, Abtahi M, Evaluation of laryngoscopic views and related factors in a pediatric
population, Pediatric Anesthesia, 2011;21:663-667.
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Nargozian C, The airway in patients with craniofacial abnormalities, Pediatric Anesthesia 2004;14:53-59.
Nargozian C, Ririe DR, Bennun RD, Mulliken JB, Hemifacial microsomia: anatomical prediction of difficult
intubation, Paediatr Anaesth. 1999;9: 393–398.
Navsa N, Tossel G, Boon JM, Dimensions of the neonatal cricothyroid membrane-how feasible is a surgical
cricothyroidotomy?, Pediatric Anesthesia 2005;15:402-406.
Olomu PN, Szmuk P, When viewing isn’t enough - a simple method for intubation using the pediatric Glidescope
Cobalt video laryngoscope blade, Br J Anaes January 26, 2011 (online publication).
Ravussin P, Bayer-Berger M, Monnier P, Savary M, Freeman J, Percutaneous transtracheal ventilation for laser
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DISCLOSURE
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Sedation/Analgesia Outside the Operating Room for Diagnostic and Therapeutic

Procedures in Infants and Children
Richard F. Kaplan, M.D. Washington, District of Columbia
SCOPE:
Sedation and analgesia in pediatric patients for procedures outside the operating room including offices and free
standing medical facilities continues to increase as healthcare is being pushed to be more cost effective and
“efficient”. It is the fastest growing part of pediatric anesthesiology services. Sedation for procedures at the
Children’s National Medical Center (CNMC) in Washington, DC continues to grow at a rate of 10% per year and
occurs in the Emergency Department (fractures, lacerations - 1500/yr); diagnostic imaging area (CT scan, MRI,
barium studies - 4000/yr); GI (endoscopy - 1200/yr); Pulmonary (bronchoscopy - 100/yr); Cardiology
(echocardiography, catheterization 750/yr); Burn Unit (dressing change); and in other areas (chest tube removal,
bone marrow aspirations, etc.).(1) These procedures require various depths of sedation in multiple locations. Some
procedures by their very nature (i.e. upper esophagoscopy, bronchoscopy) are associated with loss of airway reflexes
and are at increased risk for complications. The upsurge in demand as well as apparent safety of drugs such as
Propofol, Ketamine and Dexmedetomidine has propelled non-anesthesiologists (emergency room physicians,
intensivists, pediatricians, gastroenterologists, RN’s) to provide “anesthesia services”. Recent CMS standards(2,3)
require ALL “anesthesia services” (i.e. general, regional, MAC, deep sedation, analgesia, moderate and minimal
sedation) to fall under the direction and responsibility of the same physician who directs and is responsible for
operating room anesthesia. Thus it is clear and appropriate that anesthesiology with its expertise in safety,
monitoring and use of anesthetic drugs continue to take the lead in sedation/anesthesia outside of the operating
room.
THE CONTINUUM OF SEDATION/ANESTHESIA:

The Joint Commission regulations(2,3) contain recommendations made by the ASA.(4) The ASA's efforts in
developing guidelines for sedation led to updated CMS language in 2009. The amended standards include language
pertaining to the definition of the continuum of sedation/anesthesia. The definition of the four levels of sedation and
anesthesia are:
ASA & Joint Commission Continuum of Sedation
Minimal Moderate Deep

General
Sedation Sed/Analg Sedation/
Anesthesia
“Anxiolysis” Analgesia
• Responds • Responds • Responds • No response/

normally to purposefully to purposefully to Reflex
verbal verbal commands/ repeated or withdrawal
commands light touch painful stimuli
• airway maintained • ? airway maintained
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Minimal sedation (anxiolysis). A drug-induced state during which patients respond normally to verbal commands.
Although cognitive function and coordination may be impaired, ventilatory and cardiovascular functions are
unaffected. In the author's opinion this level of sedation is rarely adequate for completion of diagnostic/therapeutic
procedures in children.
Moderate sedation/analgesia. A drug-induced depression of consciousness during which patients respond

purposefully to verbal commands, either alone or accompanied by light tactile stimulation. No interventions are
required to maintain a patent airway and spontaneous ventilation is adequate. CV function is usually maintained.
This level of sedation was referred to as “conscious sedation” in the past.
Deep sedation/analgesia. A drug-induced depression of consciousness during which patients cannot be easily
aroused but respond purposefully following repeated or painful stimulation. Reflex withdrawal is not considered a
purposeful response. The ability to independently maintain ventilatory function may be impaired. Patients may
require assistance in maintaining a patent airway. Ventilation may be inadequate. CV function is usually maintained.
General Anesthesia. A drug-induced loss of consciousness during which patients are not arousable, even by painful
stimulation. The ability to independently maintain ventilatory function is often impaired. Patients often require
assistance in maintaining a patent airway and positive pressure ventilation may be required because of depressed
spontaneous ventilation or drug-induced depression of neuromuscular function. CV function may be impaired.
MAC. Monitored anesthesia care is anesthesia care that includes monitoring by a qualified anesthesia provider.
Deep sedation/analgesia is included under “MAC”.(3)
The line between “sedation” and “analgesia” as well as provider qualifications can be easily blurred. CMS(2)
specifies that “hospitals must establish policies and procedures that address whether specific clinical situations
involve anesthesia versus analgesia. In addition, hospitals must also specify the qualifications for each category of
practitioner who administers analgesia and their supervision requirements.”
The above terms were not specifically designed for children. Many pediatric patients are developmentally delayed or
too young to understand verbal commands. Procedures performed in children younger than 6 yrs often require deep
levels of sedation to gain control of their behavior. There is also a tendency to misinterpret any response to
stimulation as a purposeful one. Thus the patient may be misclassified as moderately sedated when they are truly
deeply sedated or misclassified as deeply sedated when they are truly under anesthesia depending on the
interpretation of a purposeful response. Clear examples of the stages of sedation for different age groups are very
helpful in clarifying any misconceptions. There is also the assumption in these definitions that there is a consistent
correlation between different levels of sedation and the ability to maintain a patent airway. This correlation has not
been carefully studied in children especially when different drugs are used for sedation (e.g. propofol, fentanyl,
dexmedetomidine).
Other organizations use other classifications of sedation. The term “procedural sedation” is a term used by the
American College of Emergency Physicians. “Procedural sedation” is defined as the use of agents that allows the
patient to tolerate procedures while maintaining cardio-respiratory function (5). This term has been misunderstood
and therefore misused to include any form of sedation/anesthesia when used for any procedure whether or not
cardio-respiratory function is preserved. It is not clear where “procedural sedation” lies in the ASA continuum of
anesthesia/sedation. Some patients who are given general anesthesia with potent inhalational anesthetics may also
“maintain cardio-respiratory function”. The line between deep sedation, procedural sedation and general anesthesia
becomes dangerously blurred by various nonuniform definitions of “sedation”.
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GUIDELINES / JOINT COMMISSION STANDARDS / CONTROVERSY / WORK TO BE DONE:
Recent changes in CMS interpretive guidelines (IG’s)(2,3) has stirred fierce debate among anesthesia and non-
anesthesia providers of deep sedation. The CMS guidelines reaffirm “anesthesia” to include general anesthesia,
regional anesthesia, deep sedation/analgesia and MAC. CMS limits the ability to administer “anesthesia” to:
qualified anesthesiologists, non-anesthesiologists MD/DO’s, certified registered nurse anesthetists, anesthesiologist
assistants, dentists, oral surgeons and podiatrists who are qualified to administer anesthesia under state law.
In an effort to guarantee hospital wide uniform standard of care CMS states(2,3): “anesthesia services throughout the
hospital (including all departments in all campuses…) must be organized into one anesthesia service”. “Anesthesia
services must be under the direction of one individual…” Thus it is clear that the Division of Anesthesiology has
oversight responsibility for defining privileges and quality performance of ALL practitioners involved in sedation
(i.e. emergency room, intensive care, gastroenterologists and nurses). In an effort to help anesthesiology
departments create consistent guidelines the ASA in 2010 has created recommendations on deep sedation guidelines
for non-anesthesiologists.(6) This is a change from the previous position(7) of 2006 which stated “privileges to
administer deep sedation should be granted only to practitioners who are qualified to administer general anesthesia
or to appropriately supervised anesthesia professionals”.
The 2010 statement is not meant to be an ASA endorsement of non-anesthesiologists providing deep sedation but
rather a guide to members who will be called upon by hospital administrators to provide input into the privileging
process. The new statement details: licensure, education and training, performance evaluations and performance
improvement. Highlights of formal training include: specific formal training in deep sedation (part of an ACGME
residency/fellowship or separate ACGME CME program), knowledge based test, methods to obtain informed
consent, skills in history taking and physical exam, assessment of risk of aspiration, knowledge of pharmacology of
sedative/analgesia and reversal agents, adequacy of oxygenation and ventilation function, airway rescue and
physiologic monitoring, documentation as well as ACLS (or PALS). Clinical experience with at lease 35 patients or
simulations is required. A quality assurance system must have oversight by the director of anesthesia services. In
addition, special education and training is required for pediatric deep sedation. The details are not defined. Specific
educational opportunities within the ASA are being actively reviewed.
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ETCO2 monitoring. ETCO2 monitoring is a mainstay of general anesthesia practices. In October 2010 the Standards
and Practice Committee amended its guidelines for ETCO2 to be effective July 1, 2011.(8) Under ventilation it states:
“during moderate or deep sedation the adequacy of ventilation shall be evaluated by continual observation of
qualitative clinical signs and monitoring for the presence of exhaled carbon dioxide unless precluded or invalidated
by the nature of the patient, procedure, or equipment.” Since the Joint Commission frequently follows ASA
recommendations all divisions supplying moderate and deep sedation should prepare for compliance. An informal
pool of pediatric institutions shows that not all places are prepared for this requirement.
The CMS deep sedation regulations and ASA guidelines for granting privileges have met stiff opposition. This is
particularly true from emergency medicine physicians.(9) They take umbrage with “anesthesiologists unilaterally
regulate the deep sedation practice of all specialties”, “dictate the scope of practice” and “exclusively
regulate…deep sedation practice”. They point to studies and clinical practice guidelines for the safe E.D. use of
Ketamine(10) and Propofol(11) as proof of safety. The question of E.D. physician qualifications are partially answered
in the frequently asked questions (FAQ’s) of the 2011 CMS manual system.(3) It states that “these practitioners” are
uniquely qualified to provide all levels of analgesia/sedation and anesthesia (moderate to deep to general). The
ASA’s response(12) notes that FAQ’s are not CMS policy and emphasizes that the “skill set of the clinical staff must
be taken into consideration in developing the policies”. Letters from the ASA for ACEP(13) have clarified some of
the issues of anesthesiology oversight of E.D. sedation. Clearly, much discussion is needed to further clarify and
resolve these new guidelines and resolutions.
Our Children's Hospital anesthesiology division leads oversight and compliance with ALL sedation requirements.
Our department's credentialing process includes:
1) An on-line intranet course on sedation. The course is mandatory for sedation practitioners and is given to all
faculty, residents and RN's. It is required every 2 years. The course describes personnel, regulations, drugs
(including reversal drugs) and techniques. A post-course quiz is required (> 80% correct). The intranet course
is being updated to include training on our new sedation electronic record as well as simulation training using
computerized game therapy (“AVITARS”).
2) BLS certification is required for practitioners of moderate sedation. BLS training should provide basic airway
support and thus allow RESCUE from deep sedation.
3) PALS certification is required for practitioners of deep sedation. PALS training should provide airway and
cardiovascular support training and thus allow RESCUE from general anesthesia.
4) Intranet course attendance, post-course quiz score and BLS/PALS certification are tracked by the medical staff
office and is a requirement for hospital privileges in sedation.
5) Each direct supervisor must attest to the competence of individuals providing sedation.
RISKS OF SEDATION:
There are numerous case reports and clinical studies attempting to document and quantitate the risks of sedation.
The Food and Drug Administration has collected over 150(14) severe adverse drug reactions using a self-reporting
system.
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CONCLUSIONS FROM THE FDA AND OTHER STUDIES:
• ALL sedatives and narcotics have caused problems even in “recommended doses”.
• ALL areas using sedation have reported adverse events.
• Children 1-5 yr of age are at most risk. Most had no severe underlying disease.
• Respiratory depression and obstruction are the most frequent causes of adverse events.
• Adverse events involved - multiple drugs, drug errors or overdose, inadequate evaluation, inadequate
monitoring, inadequate practitioner skills, and premature discharge.
A now classic article(15) emphasizes the above results and brings to light complications both inside and outside of the
hospital setting. It emphasizes the need for uniform, specialty-independent guidelines for monitoring children
during sedation both inside and outside of the hospital setting. A group of over 26 institutions has been created to
carefully review pediatric sedation techniques and complications. This “Pediatric Sedation Research Consortium”
has now received data on over 150,000 sedation encounters. The initial data (16) showed differences in complication
rates based on types of providers and location with sedation provided by an anesthesiologist having the lowest
complication rate.
Recent data(17) reviews over 130,000 pediatric procedural sedation cases. Comparisons are made between different
providers and major adverse events (death, cardiac arrest, emergency anesthesia consult, aspiration, unplanned
admission, and increase in care). Major complication rates were: anesthesiologists (7.6/10,000), emergency
medicine (7.8/10,000), intensivists (9.6/10,000), pediatricians (12.4/10,000) and other (pediatric resident, fellow,
radiologist, surgeon, dentist, advanced practice nurse, CRNA or registered nurse) (10.2/10,000). There was no
difference in severe complications in any group. This study is a major step in carefully analyzing data. Limitations
of interpretation and conclusions are recognized by the authors and include lack of comparison of the different levels
of sedation used, painful vs. non-painful procedures, selection bias of patients with anticipated complicated patients
referred to anesthesiologists rather then the sedation service (i.e. data not collected). The use of propofol was
“adjusted” (without giving details) and found not to influence speciality complication rate. Although other
investigators have found an increase in complications due to age < 1 yr and ASA physical status > 2 the present
study found no increased risk due to age, physical status, NPO status or emergent procedures. The limitations noted
above and conflicting results compared to other studies require careful review.
SEDATION/ANESTHESIA DRUGS AND NEURODEVELOPMENT:

Additional issues which have recently surfaced also need resolution and national guidelines. The recent information
regarding the effects of anesthesia on apoptosis in animals and learning disabilities in young children(18) need to be
addressed. In March 2011, the FDA convened its second meeting on neurotoxicity of anesthetic agents and brain
maturation in humans.(19) NMDA antagonists and GABA agonists were both associated with neuroapoptosis.
NMDA antagonists and GABA agonists include most anesthetic/sedation agents (ketamine, isoflurane, sevoflurane,
propofol, benzodiazepines, chloral hydrate, barbiturates, and nitrous oxide). Multiple studies in animals and humans
have implicated a potential for learning deficits from these agents when used in children < 3 yrs of age.(19) Future
studies to determine age risk, drugs, doses and duration in humans are underway to resolve these questions. In
particular, the FDA and IARS have forged a partnership (Smart Tots – Strategies for Mitigating Anesthesia Related
Neurotoxicity in Tots) to encourage studies. No changes in practice in the use of these drugs are required at this
time. The 3rd PANDA (Pediatric Anesthesia and Neurodevelopment Assessment) symposium recently reviewed
available animal and human studies on neuroapoptosis and learning disabilities. No new clinical recommendations
were advised with the exception of possibly delaying elective procedures until they are past the most critical age of
neurodevelopment (3 years) and grouping essential procedures using one anesthetic. Of all sedatives drugs
presently available dexmedetomidine appears to have unusual properties. Dexmedetomidine prevents cortical
apoptosis in vitro and in vivo in the developing rat brain.(20) Dexmedetomidine is a selective high affinity alpha2
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agonist which has recently been used for various sedation procedures (0.5-1 microgram/kg over 10 minutes followed
by 1 microgram/kg/hr). It provides sedation and some analgesia with minimal respiratory depression.( 21,22) Low heart
rate may be associated with this technique. It should be used with caution in patients taking digoxin.(23) Studies
have shown the drug to be effective for sedation with minimal respiratory effects and acceptable cardiovascular
parameters.(24)
Anesthetic Drug Shortages. There has been a recent surge in anesthetic drug shortages. The list of drug shortages
can be found on the American Society of Health System Pharmacists (www.asahq.org/shortages). The list includes
etomidate, fentanyl, ketamine and sufentanil. Chloral hydrate is no longer available as of April 2012. Chloral
hydrate is frequently used for BAER studies and is a mainstay for many nonpainful procedures in children < 3 yrs.
Oral alternatives (oral midazolam) may interfere with certain EEG studies and are not ideal. Chloral hydrate may be
bought in crystallin form and compounded by individual hospital pharmacies.
Propofol and Mitochondrial Diseases: Propofol has gained widespread acceptance and is regarded in some circles
as the automatic sedative of choice for all procedures in children. Mitochondrial diseases raise concern regarding
the use of propofol. Mitochondrial disorders have an incidence of one in 4000. Mitochondrial diseases affect ATP
production and present as clinical disorders of skeletal muscle, brain and heart. The clinician is frequently presented
with patients (i.e. developmental delay, muscle weakness, epilepsy) for procedures such as MRI, CT and muscle
biopsy who may be at risk for mitochondrial disease.( 25,26,27) Some children with these disorders have developed
progression of their disease after sedation and anesthesia. Propofol has several negative effects on mitochondrial
ATP production which include: 1) inhibition of enzyme activity of electron transport complex 1; 2) inhibition of
carnitine palmitoyl transferase; and 3) inhibition of β-oxidation. These depressant mitochondrial effects may
account for propofol infusion syndrome occurring in these susceptible patients. Propofol infusion syndrome is
characterized by severe lactic acidosis, rhabdomyolysis and lipidemia which can lead to cardiovascular collapse(28)
The suggested dose and duration to avoid propofol infusion syndrome in healthy patients is > 4 mg/kg/h over 48
hours. The syndrome may occur with smaller doses and duration in children with underlying mitochondrial
disorders (200 mcg/k/min over 150 min in a 7 y.o.).(29) The best management of these children is still under
discussion with no proven clinical advantage of inhalation anesthesia vs. propofol TIVA(30)
Propofol and the Non-Anesthesiologist:

There is presently a desire for clinicians other than anesthesiologists (i.e. intensivists, pulmonologists, emergency
medicine, gastroenterologists, RN’s etc.) to use propofol for sedation in pediatric patients.(31) An ASA statement on
sedation with propofol(32) states that “propofol is a anesthetic drug, and the ASA believes that the involvement of a
anesthesiologist in the care of every patient undergoing anesthesia is optimal.” Other providers, however, do
administer this drug. Anesthesiologists, as leaders of sedation need to take all these factors into consideration so
that policies are created to assure that all patients receive safe care." Our Children's Hospital has strict regulations
on the use of propofol by non-anesthesiologists. The reasons include: 1) propofol causes significant decreases(33)
and changes(34) in airway dimensions in children in sedation doses; 2) propofol can unpredictably cause loss of
airway reflexes even in sedative doses in children; and 3) the most recent PDR does not recommend the use of
propofol for sedation of pediatric patients in the ICU. It must be appreciated, however that many drugs presently
used in children are not recommended for such use in the PDR and that propofol (although not approved for
pediatric sedation) may be the drug of choice for sedation in some circumstances. Therefore, until further studies on
safety are published our Children's Hospital recommends that propofol sedation be considered deep sedation/general
anesthesia. Its use by non-anesthesiologists should be restricted to short procedures in intubated patients in intensive
care unit patients and administered by qualified and credentialed intensive care faculty. Monitors, equipment and
personnel skilled in airway resuscitation and deep sedation must be immediately available.
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MRI – Anesthesiology Supervised Deep Sedation Service:

There is a growing need to provide deep sedation for children needing MRIs. An anesthesiology supervised deep
sedation service is efficient, provides deep sedation with agents that allow smooth and rapid induction and
emergence and is uniquely qualified to “rescue” from general anesthesia. Further, if general anesthesia is required
then rescheduling is not necessary. RNs involved in deep sedation receive extensive training in identifying the
difficult airway, identifying airway obstruction, resolving airway obstruction, PALS, starting IV’s and receive
additional training in the pharmacology and use of agents used for deep sedation.
Anesthesia is induced immediately outside of the MRI room using propofol (1-2 mg/kg) or sevoflurane (if an IV is
not initially placed). The child is then stabilized, nasal cannulae (with CO2 sampling) applied and a propofol
infusion is started and titrated to a level of deep sedation (100 – 250 mcg/kg/min). Deep sedation is verified when
the child moves appropriately to a painful stimulus (lifts arms towards a painful stimulus at the shoulder in an
attempt to remove the stimulus).
Once stable and deeply sedated, the child is transported to the MRI room where the RN stays with the child. Vital
signs, SaO2, ETCO2 and level of sedation are monitored and recorded q 5 min. Adjustments in propofol
administration if necessary are made by the anesthesiologist. The anesthesiologist is immediately outside the magnet
preparing another child for sedation in the second MRI scanner. After the scan is complete the child is recovered in
the MRI recovery area and is discharged within 1 hour after completion of the study. This technique is efficient,
quick, safe, easy and allows one anesthesiologist to supervise the care of over 4000 deeply sedated children for
MRIs per year using 3 MRI scanning machines.
REFERENCES:
1. Kaplan RF, Cravero JP, Yaster M, Coté C. Sedation for diagnostic and therapeutic procedures outside the
operating room. In “A Practice of Anesthesia for Infants and Children”. Coté Lerman, Todres, 2009, pp1023-
49.
2. CMS manual system. Pub 100-07 state operational provide certification. Subject: Revised Appendix A,
Interpretive Guideline for Hospitals, January 2011.
3. CMS manual system. Pub 100-07 state operational provide certification. Transmittal 59. “Clarification of
Anesthesia Services”. May 21, 2010.
4. Practice Guidelines for Sedation and Analgesia by non-Anesthesiologists (Amended October 17, 2001)
Anesthesiology 96, 1004-7,2002
5. Mace SE, et al. Clinical policy: evidence-based approach to pharmacologic agents used in pediatric sedation
and analgesia in the emergency department. Journal of Pediatric Surgery. 39(10):1472-84, 2004 Oct.
6. Granting privileges for deep sedation to non-anesthesiologist sedation practitioners (ASA House of Delegates,
Oct 2010)
7. Statement on granting privileges to non-anesthesiologist practitioners for personally administering deep
sedation or supervising deep sedation by individuals who are not anesthesia providers. (ASA House of
Delegates, Oct 18, 2006)
8. Standards for Basic Anesthetic Monitoring (Approved by the ASA House of Delegates, amended October 20,
2010, effective July 1, 2011).
9. Green S, Kraus B. Who owns deep sedation? Annals of Emerg Med 2001; 57(5):105, pp470-474.
10. Green S, et al. Clinical practice guidelines for emergency department ketamine dissociative sedation: 2011
update. Annals of Emerg Med 2011; 57(5):449-61.
11. Mallory M, et al. Emergency Physician – Administered propofol sedation: A report on 25,433 sedations from
the pediatric sedation consortium. Annals of Emerg Med 2011;57(5):462-468.
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12. Statement by American Society of Anesthesiologists on granting deep sedation to non-anesthesiologists

sedation practitioners. Letter to S. Schneider, MD from M. Warner, MD, President, ASA, January 2011.
13. www.asahq.org/for-members/advocacy/federal-legislative-and-regulatory-activities/interpretive-guidelines
14. Report of Anesthesia and Life Support Advisory Committee, 3/94 FDA, Rockville, Maryland.
15. Coté CJ, Notterman DA, Karl HW, Weinberg JA, McCloskey C. Adverse sedation events in pediatrics:
analysis of medications used for sedation. Pediatrics 106:633-44, 2000.
16. Cravero JP, et al. The incidence and nature of adverse events during pediatric sedation/anesthesia with propofol
for procedures outside the operating room: A report from the pediatric sedation research consortium. Anesth
Analg 2009; 108(3):795-804.
17. Couloures KG, Beach M, Cravero J, et al. Pediatrics 127(5):May 2011, pp1154-1160.
18. Rappaport R, et al. Defining safe use of anesthesia in children. NEJM, March 9, 2011.
19. Durieux M, Davis P. The safety of key inhaled and intravenous drugs in pediatrics (SafeKids): An Update.
Anesth Analg 2010; 110(5):1265-6.
20. Sanders RD, et al. Dexmedetomidine provides cortical neuroprotection: impact on anesthetic-induced neuro
apoptosis in the rate developing brain. Acta Anaesthesiol Scand 2010; 54(6):710-6.
21. Tobias, JD, Berkenbosch JW, Initial experience with dexmedetomidine in paediatric aged patients. Paediatric
Anaesthesia, 2002. 12(2):p 171-5.
22. Tobias, JD, Berkenbosch JW, Russo P, Additional experience with dexmedetomidine in pediatric patients
(Review). Southern Medical Journal, 2003. 96(9): p. 871-5.
23. Berkenbosch JW, Tobias, JD. Development of bradycardia during sedation with dexmedetomidine in an infant
concurrently receiving digoxin. Pediatr Crit Care Med 2003 Apr;4(2):203-5.
24. Mason KP, et al. High dose dexmedetomidine as the sole sedative for pediatric MRI. Paediatr Anaesth
2008;18(5):403-11.
25. Morgan PG, Hoppel CL, Sedensky. Mitochondrial defects and anesthetic toxicity. Anesthesiology
2002;96(5):1268-70.
26. Schwartz D, Ragunathan K. Anesthesia and mitochondrial disorders. Paediatr Anaesth 2009;19(1):60-1.
27. Driesen JJ. Neuromuscular and mitochondrial disorders: What is relevant to the anesthesiologist? Current
Opinion in Anesthesiology 2008;21:350-5.
28. Faraq E, et al. Metabolic acidosis due to propofol infusion. Anesthesiology 2005;102:697-8.
29. Kill C, et al. Lacticacidosis after short-term infusion of propofol for anaesthesia in a child with osteogenesis
imperfecta. Paed Anaesth 2003;13:823-6.
30. Driesen J, et al. Anesthesia-related morbidity and mortality after surgery for muscle biopsy in children with
mitochondrial defects. Ped Anesth 2007;17:16-21.
31. Green SM, Krauss B. Barriers to propofol use in emergency medicine. Ann Emerg Med, Feb 21, 2008.
32. Phillip BK. Sedation with Propofol: A new ASA statement. ASA Newsletter. Feb 20:5, Vol 69, No 2, 2005,
p29-30.
33. Evans RG, Crawford MW, Noseworthy M, Shi-Joon Y: MRI examination of airway geometry during propofol
anesthesia in children. Anesthesiology 2001;A1277.
34. Litman RS, Weissend EE, Shrier DA, Denhams: “Morphologic changes in the upper airway of children during
awakening from propofol administrations". Anesthesiology 2002; 96(3):607-11.
DISCLOSURE
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Pediatric Advanced Cardiac Life Support in the Perioperative Setting:

2012 Update
Jayant K. Deshpande, M.D., M.P.H. Little Rock, Arkanas
This refresher course will provide the anesthesiologist a) a summary of the most recent
American Heart Association guidelines for pediatric life support and b) a discussion on
management of perioperative cardiac arrest resulting from selected causes.
Capsule of the Current AHA Guidelines for Pediatric Resuscitation

Pediatric B asic Life S upport
• CHAN GE IN CPR S EQU EN CE (C- A- B replaces A- B-C) : Start with chest compressions
instead of rescue breaths. Start CPR with 30 compressions (one rescuer) or 15 compressions with
two providers, instead of with two rescue breaths.
• Chest compressio n depth: Appropriate depth for chest compressions is at least 1/3 of the
anterior-posterior chest diameter, or approximately 1½ inches (4 cm) for infants; 2 inches (5 cm) for
children.
• N o need to “Loo k, Listen, and Feel f or B reathing”: just open the airw ay.
• Pulse check de- emphasized: In the unresponsive infant or child who is not breathing or only
gasping, if a pulse is not apparent, chest compressions should be initiated. Time is wasted (almost 10
seconds) trying to find pulse.
• D efibrillation and use of the A ED in inf ants: For infants, use a manual defibrillator instead
of an AED. If manual defibrillator is not available, use AED with a pediatric dose attenuator. If
neither is available, use AED without the pediatric dose attenuator.
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Pediatric A dvanced Life S upport

• Monito r exhaled CO2: In addition to clinical assessment, use exhaled CO2 detection
(colorimetry or capnography) to confirm tracheal tube position for patients with a perfusing rhythm
in all settings and during interhospital/intrahospital transport. Continuous monitoring, when
available, can be beneficial during CPR to gauge effectiveness of chest compressions.
• D efibrillation energ y doses: Initial dose is 2-4 J/kg. For refractory VF, dose may be increased
start with 4 J/kg (biphasic) up to but not to exceed 10 J/kg (maximum dose 360 J monophasic).
• Limit supplemental oxy gen to minimum levels needed after resuscitation:
Oxyhemoglobin saturation (SpO2) should be monitored following return of circulation. Titrate the
FiO2 to maintain an SpO2 ≥ 94%.
• Resuscitation of infants and children with congenital heart disease: The guidelines
include resuscitation measures for cardiac arrest in infants and children with single-ventricle
anatomy, Fontan or hemi-Fontan / bidirectional Glenn physiology, and pulmonary hypertension.
• Medications during cardiac arrest and sho ck: The routine use of calcium during pediatric
cardiopulmonary arrest is not recommended. Calcium may be used to treat documented
hypocalcemia, calcium channel blocker overdose, hypermagnesemia, or hyperkalemia. In septic
shock, etomidate is not recommended.
• Post-cardiac arrest care: Therapeutic hypothermia (32°C-34°C) may provide benefit for
adolescents who remain comatose after resuscitation following sudden witnessed out-of-hospital VF
cardiac arrest. Therapeutic hypothermia may also be beneficial for patients remaining comatose
after resuscitation from cardiac arrest.
• A rapid respo nse sy stem in the inpatient setting may beneficial to reduce rates of cardiac and
respiratory arrest and in-hospital mortality.
• Evaluation of sudden cardiac death victims: Past medical and family history, as well as
review of previous ECGs may point to the cause of sudden, unexplained cardiac death in a child or
young adult. When possible, tissue from the patient should be analyzed for the presence of
channelopathy.
(adapted from Go oden CK. S PA New s, S ociety for Pediatric A nesthesia, 2 4(1 ),
S pring 20 11 and Kleinman et al Circulation October 2 010 )
Perioperative cardiac arrest progressively has become less of a concern over the past two decades. Yet when it
occurs is a traumatic event for the anesthesiologist and perioperative care team. Knowledge of the epidemiology of
pediatric cardiac arrest and of current resuscitation techniques may further reduce the associated morbidity and
mortality. Recent studies of pediatric cardiac arrest (Flick et al 2007;Bhananker et al 2008) indicate that the
principal causes of perioperative arrest have remained fairly consistent throughout the years. In decreasing order
these are cardiovascular, respiratory, medication, equipment, combination of events and other miscellaneous causes.
Intraoperative arrests often are related to the cardiovascular system while respiratory events are more likely to cause
postoperative arrests. Higher ASA physical status and emergency procedures have the highest association with
perioperative cardiac arrest in children.
Epidemiology
Cardiac arrest in infants and children who are in-hospital or in the perioperative setting may occur from various
causes. Causes include Respiratory failure, Sepsis, Drug toxicity or overdose, Metabolic disturbances and
Dysrhythmias. Perioperative cardiac arrest may occur because of cardiovascular reasons; respiratory obstruction or
failure; medication overdose or adverse reactions; equipment failure or malfunction; a combination of events.
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The causes of cardiac arrest are different for the different phases of care. In the presurgical setting, cardiovascular,
respiratory and medication related events are equally likely as the underlying cause of cardiac arrest.
Intraoperatively, the precipitating cause most likely is a cardiovascular event. Post-operatively, respiratory causes
account of the majority of cases, followed by cardiovascular events. The anesthesiologist must be cognizant of the
common causes in the different phases of surgical experience in order to properly treat the patient in a timely
manner. (Bhananker et al 2007)
The American Heart Association (AHA) Committee on Pediatric Resuscitation completed an exhaustive process of
evidence review and expert consensus development to revise and update the guidelines for resuscitation of children.
This process culminated in the dissemination of the new AHA guidelines in November 2010 and significant
modification of the AHA Pediatric Advanced Life Support (PALS) course.
Cardiorespiratory arrest in infants and children is an infrequent phenomenon as compared to adults. In the majority
of cases the etiology is respiratory distress and failure which can lead to cardiac arrest if not treated and reversed in a
timely manner. Primary cardiac events leading to arrest are rare in infants and children, whereas in adults cardiac
arrest may be the primary event resulting from dysrhythmias, which can quickly deteriorate to a non-perfusing state.
Out-of-hospital arrests have a poor prognosis, with less than 9% survival to hospital discharge. For in-hospital
arrest, CPR is successful in restoring spontaneous circulation in over 60% of patients. However, the rate of survival
to discharge decreases rapidly to approximately 15% or less.
Respiratory Failure
Successful cardiorespiratory resuscitation of infants and children begins with early recognition and reversal of
respiratory distress or shock.
Respiratory distress may be characterized by tachypnea, increased respiratory effort, nasal flaring, intercostal,
subcostal or substernal retractions, and stridor or grunting. Lethargy in a child with respiratory distress is a bad sign
indicating impending respiratory failure and requires immediate treatment. Other signs include inadequate or low
respiratory rate, decreased unilateral or bilateral breath sounds and pallor or cyanosis. Untreated, the patient will
suffer respiratory failure – defined as inadequate ventilation and possibly respiratory arrest.
Shock
Shock is defined as blood flow and oxygen delivery that is inadequate to meet metabolic demands. During the early
stage of compensated shock, tachycardia and peripheral vasoconstriction may sustain systemic blood pressure and
vital organ perfusion at marginally adequate levels. When the body’s ability to compensate is exceeded,
decompensated shock leads to rapid deterioration reflected as systemic hypotension and weak central pulses.
Because the normal values for vital signs vary with age, signs of compensated or decompensated shock may be easy
to miss. Bradycardic shock or arrest in infants and children is characterized by a heart rate significantly lower than
expected (usually under 100) in the presence of other signs of circulatory failure.
Airway
Airway problems are a leading cause of respiratory distress and failure in children. Young infants are obligate nose
breathers who may develop significant distress which may be relieved by suctioning of the nostrils. The infant
anatomy may contribute to airway obstruction because of the relatively large tongue, rostrally placed larynx (“more
anterior”) and large occiput. Proper positioning of the head and neck or placement of an oral airway may relieve an
apparent airway obstruction. Airway adjuncts including laryngeal mask airway and endotracheal intubation should
be used as appropriate.
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Oxygen
Standard recommendations for resuscitation include the use of 100% oxygen. This recommendation is classified as
Indeterminate because of the possible adverse effects of 100% inspired oxygen. These effects include increased
cerebrovascular resistance, oxidative stress on lung, cardiac and other tissues, and atelectasis. Once the patient has
been resuscitated, the FiO2 should be decreased to a level sufficient to maintain adequate systemic oxygen levels.
Ventilation
Manual ventilation during resuscitation often results in significant overventilation. Overexpansion of infant lungs
may result in barotrauma and even pneumothorax, and impede proper venous return and affect cardiac output.
Hypocapnia may exacerbate brain hypoperfusion. Therefore, care should be used to provide ventilation that is
adequate to inflate the lungs while avoiding overdistention.
Cuffed Versus Uncuffed Tubes

Both cuffed and uncuffed tracheal tubes are acceptable for infants and children.If cuffed tracheal tubes are used,
avoid excessive cuff pressures. Appropriately sized endotracheal tubes should be used and care should be taken to
minimize glottic and subglottic trauma. Tube size can be approximated as (age in years/4) + 4 for uncuffed tubes
and (age in years/4) + 3 for cuffed tubes. Even in emergency situations, tube placement should be confirmed by
chest auscultation and by detection of exhaled CO2.
Vascular Access
PALS guidelines emphasize the need for timely vascular access. If peripheral access is not obtained within 90
seconds, intraosseous (I/O) needle placement is advised. All resuscitation carts and operating rooms should have
access to I/O needles. Experienced providers may be able to place a central line for more secure access, but the
procedure may impede the ability to perform adequate chest compressions during cardiac arrest. In the absence of
IV or I/O access, most emergency medications may be administered via the endotracheal route but will require
higher doses than with the IV or I/O route.
Cardiac Arrest
Pulseless arrest requires both ventilatory support and effective chest compressions. The likelihood of effective
resuscitation and return of spontaneous circulation improves with starting timely and adequate chest compressions.
The goal is to achieve longer periods of diastolic pressure sufficient to perfuse the coronaries. Therefore, the
pediatric recommendations are similar to those for adults. For single rescuer, 2 breaths are given after each 30
compressions. The two rescuer method involves a ratio of 15 compressions to 2 manual ventilations. Compressions
should be of sufficient depth (1/3 to 1/2 of the anterior-posterior chest diameter) and allow full recoil of the chest.
The compression rate for all ages is 100/minute. Chest compression often is inadequately performed (Niles et al
2012).
Fluids and Medications

Dosing of fluids and medications in children is based on the child’s weight. Patients in hospital should have a
recently measured weight and pre-calculated doses of emergency medications available at the bedside. If the child’s
weight is unknown, length-based tape measures with pre-calculated doses have been validated and are commercially
available.
Isotonic crystalloid solutions should be used for resuscitation. Glucose containing solutions are not recommended
for routine use. Because infants are at high risk for developing hypoglycemia, blood glucose should be measured
early during the resuscitation.
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Resuscitation medications for children are similar to those used in adults. When indicated in pulseless cardiac
arrest, the “standard dose” of epinephrine IV is 0.01 mg/Kg. The higher dose may in fact have significant adverse
effects including worse outcomes, such as hypertension, ventricular ectopy, myocardial necrosis and prolonged
myocardial dysfunction.
Defibrillators in Pediatric Resuscitation

Because most pediatric arrests are a result of respiratory events, the most common dysrhythmias in children are
asystole and bradycardia with a wider QRS complex. Sudden cardiac arrest in children may result from ventricular
fibrillation (VF) or pulseless electrical activity (PEA). For children with VF, defibrillation may be a life-saving
intervention with the chance of survival approaching 20%. Out-of-hospital pediatric arrests are associated with 5-
15% incidence of VF. For these children, especially those with witnessed sudden cardiac arrest, defibrillation has
resulted in rapid resuscitation and functional survival. Because of the significant benefit of automated external
defibrillators (AED’s), many communities have instituted Public Access Defibrillator (PAD) programs.
Supraventricular tachycardia (SVT) and ventricular tachycardia (VT) in children may be associated with a pulseless
state or pulses may be present. For the pulseless patient, treatment should be instituted according to the cardiac
arrest guidelines. If pulses are present, treatment should include oxygen and airway support and assessment of the
underlying cardiac rhythm. Narrow QRS complexes likely represent supraventricular tachycardia which may be
treated progressively with vagal stimulation, intravenous adenosine, and electrocardioversion. Amiodarone or
procainamide may be needed if the SVT is unresponsive to other treatments or the rhythm relapses. These
medications prolong the QT interval and therefore should be used with caution. Wide complex tachycardia may
represent SVT with aberrant conduction or VT. This rhythm may respond to electrocardioversion but often requires
amiodarone or procainamide as well.
Torsade de Pointes
This is a polymorphic form of VT in children which may be congenital in origin or occur because of toxicity of
certain antiarrhythmics, antidepressants, or drug interactions. Intravenous magnesium sulfate is the treatment of
choice for torsade of any etiology. The initial dose of magnesium is 25 - 50 mg/Kg IV.
Miscellaneous
Cardiorespiratory arrest in children may occur as a result of toxic ingestion. A focused history and rapid diagnostic
tests may indicate the specific causative toxin or medication. Treatment of the systemic effects depends on the
ingested drug or toxin. Tricyclic antidepressants, β-blockers, calcium channel blockers, methamphetamine and
cocaine pose additional challenges.
Post-Resuscitation Neuroprotection
Preservation of brain function and prevention of secondary brain injury is an important goal of resuscitation.
Hyperventilation and hypocapnea should be avoided as there is no demonstrated benefit. Severe hypocapnea may
cause cerebral ischemia and myocardial dysfunction. Maintaining a normal body temperature is a foundational
practice in pediatric anesthesia. However, hyperthermia can have deleterious effects on brain recovery. Rapid
rewarming of a child during and after resuscitation is not necessary as it may result in hyperthermia. In patients who
remain comatose, therapeutic hypothermia (32oC-34oC) may improve brain recovery.
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Family Presence During Resuscitation

Patient families may have a strong desire to be present during resuscitation. Although not practical in the operating
room, it may be possible to have family members present in the emergency department or hospital bedside during
the resuscitation. For children with chronic conditions, family members may be able to provide useful information
about the child’s history and clinical conditions. The healthcare team is encouraged to consider allowing families to
be present during resuscitation and to have a team member assigned to support the family.
Cardiac Arrest in the Perioperative Setting

Several special circumstances related to anesthetic management and surgery warrant mention. These will be
discussed in more detail during the Refresher Course. Anesthetic agent related effects include overdose of
Intravenous or Inhalation anesthetic. A high neuraxial block may result in near-total sympathectomy. Unsuspected
malignant hyperthermia or drug administration errors may result in circulatory compromise. Hypoxemia, auto
PEEP, or acute bronchospasm may go undetected or untreated. Cardiovascular effects of interventions under
anesthesia may result cardiac arrest or circulatory compromise. Infants and young children with high
parasympathetic tone may experience severe bradycardia induced by Vasovagal reflex. Other conditions that can
result in arrest include hypovolemic and/or hemorrhagic shock, tension pneumothorax, anaphylactic reaction,
transfusion reaction, acute electrolyte imbalance (high K) – particularly after succinylcholine administration, severe
pulmonary hypertension, increased intraabdominal pressure (e.g., laparoscopy) and known or unrecognized
prolonged q-t syndrome, pulmonary embolism, gas embolism.
Anaphylaxis
Common causes include IV contrast agents, latex, beta lactam antibiotics, non-depolarizing neuromuscular blockers.
The management of the patient with anaphylaxis consists of measures to interrupt the reaction and support the
patient. Surgery should be interrupted when feasible and the patient should be immediately supported with IV fluid
and vasopressors. It is imperative to remember that the Epinephrine administered to patients with anaphylaxis is
intended to interrupt the reaction, and not support the circulation. Thus it should always be given and at the full
recommended dose (0.01 mg/kg, or approximately 1mg in most adults).
Complications of Central Venous Access

Pneumothorax is a well described and relatively rare complication of central line placement in perioperative
patients. Most practitioners astutely suspect this complication in patients who become unstable after undergoing
central venous cannulation. More recent analysis from the closed-claims database suggests that both hemo-
pneumothorax and tamponade may be important and sometimes unrecognized fatal complications of patients who
undergo attempts at central venous cannulation. In those instances where a patient deteriorates following central line
placement, echocardiography should be considered in addition to chest radiography.
Local Anesthetics
Risk of local anesthetic toxicity is difficult to predict. In general, local anesthetics depress the heart in a dose
dependent fashion. Of the local anesthetics in widespread clinical use, bupivacaine is the most potent myocardial
depressant and most often associated with cardiac arrest. Most children receive local anesthetic blocks while they
are under general anesthesia. Therefore, clinical symptoms that may presage cardiac arrest in this setting are usually
masked. Signs of local anesthetic toxicity include PVCs, wide QRS complex EKG which can subsequently
deteriorate into EMD/PEA or asystole (bupivicaine), bradycardia or atrioventricular block (lidocaine and
etidocaine). Treatment includes stopping the administration of local anesthetic, CPR as indicated (pulseless for >10
sec), Epinephrine 10 mcg/Kg, tracheal intubation and ventilation with 100% oxygen. Intralipid (20%) 1.5ml/Kg IV
load, then 0.25ml/Kg/hr IV may be lifesaving. Sodium Bicarbonate should be used to maintain a pH >7.25. Other
treatment may include H1 and H2 blockers, transcutaneous or intravenous pacemakers for all bradycardic rhythms.
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Continue CPR for at least 60 minutes, as very good neurologic recovery has been reported in patients after very
prolonged cardiac arrests from local anesthetic overdoses.
Summary
The guidelines for pediatric advanced life support emphasize early recognition and treatment respiratory failure and
shock. In cases where IV placement is difficult rapid placement of an intraosseous needle is recommended for
venous access. Vagal maneuvers are a first line intervention for SVT with progressive advancement to adenosine
and cardioversion, if the patient fails to improve. Amiodarone is recommended as the first-line treatementfor most
dysrhythmias, especially VT. Epinephrine remains a crucial medication in resuscitation. The standard dose of 0.01
mg/Kg is recommended; while the high-dose (0.1 mg/Kg) may actually cause harm. AED’s are recommended to
treat children >1 year of age; their effectiveness in infants <1 year of age is unclear. Chest compressions during
CPR should be “hard and fast” maintaining a ratio of 15 compressions to 2 manual ventilations. Therapeutic
hypothermia may be neuroprotective. Family presence during resuscitation should be considered.
Table 2. Summary of Selected Doses in Pediatric Resuscitation

Dosage Comment
Adenosine 0.1 – 0.2 mg/Kg SVT
Amiodarone 5 mg/Kg VT or SVT
(up to 3 doses)
Epinephrine 0.01 mg/Kg Pulseless or Bradycardic

Arrest
Magnesium 25 – 50 mg/Kg Torsade de Pointes
Cardioversion 0.5 – 1 joule/Kg SVT
Defibrillation 2 joules/Kg Ventricular fibrillation
(max 4 joules/Kg)
AED (Automatic External Adult dose > 8 yoa Sudden Collapse

Defibrillation)
Pediatric attenuator Pulseness
< 8 yoa
VT/VF
See Circulation October 2010 for detailed guidelines and precautions.
Recommended Reading:
Aufderheide T, Lurie KG: Death by hyperventilation: a common and life-threatening problem during
cardiopulmonary resuscitation. Crit Care Med 2004; 32[Suppl]:S345-351.
Berg RA, Otto CW, Kern KB et al: A randomized, blinded trial of high-dose epinephrine versus standard-dose
epinephrine in a swine model of pediatric asphyxial cardiac arrest. Crit Care Med 1996, 24:1695-1700.
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Bhananker SM, Ramamoorthy C, Geiduschek JM, Posner et al: Anesthesia-related cardiac arrest in children: update
from the pediatric perioperative cardiac arrest registry. Anesth Analg 2007;105:344 –50.
Boudreaux ED, Francis JL, Loyacano T: Family presence during invasive procedures and resuscitations in the
emergency department: a critical review and suggestions for future research. Ann Em Med 2002; 40:193-205.
Davis PG, Tan A, O’Donnell CPF et al: Resuscitation of newborn infants with 100% oxygen or air: a systematic
review and meta-analysis. Lancet 2004; 364:1329-1333.
Flick RP, Sprung J, Harrison TE, et al: Perioperative cardiac arrests in children between 1988 and 2005 at a tertiary
referral center. Anesthesiology 2007; 106:226–37.
Gabrielli A, O’Connor MF, Macchioli GA. Anesthesia Advanced Circulatory Life Support. American Society of
Anesthesiology Committee on Critical Care Medicine and American Society of Critical Care Anesthesiology.
February 2008. Downloaded May 2010 from <http://asahq.org/clinical/Anesthesiology-CentricACLS.pdf>.
Gooden CK. 2010 Update: American Heart Association guidelines for pediatric resuscitation. SPA News, Society
for Pediatric Anesthesia, 24(1), Spring 2011.
Hazinski MF, Nolan JP, Billi JE, Böttiger BW, Bossaert L, de Caen AR, Deakin CD, Drajer S, Eigel B, Hickey RW,
Jacobs I, Kleinman ME, Kloeck W, Koster RW, Lim SH, Mancini ME, Montgomery WH, Morley PT, Morrison LJ,
Nadkarni VM, O'Connor RE, Okada K, Perlman JM, Sayre MR, Shuster M, Soar J, Sunde K, Travers AH, Wyllie J,
Zideman D. Part 1: Executive summary: 2010 International Consensus on Cardiopulmonary Resuscitation and
Emergency Cardiovascular Care Science With Treatment Recommendations. Circulation. 2010;122(16 Suppl
2):S250-75.
Kleinman ME, de Caen AR, Chameides L, Atkins DL, Berg RA, Berg MD, Bhanji F, Biarent D, Bingham R,
Coovadia AH, Hazinski MF, Hickey RW, Nadkarni VM, Reis AG, Rodriguez-Nunez A, Tibballs J, Zaritsky AL,
Zideman D; Pediatric Basic and Advanced Life Support Chapter Collaborators. Part 10: Pediatric basic and
advanced life support: 2010 International Consensus on Cardiopulmonary Resuscitation and Emergency
Cardiovascular Care Science With Treatment Recommendations. Circulation. 2010;122(16 Suppl 2):S466-515.
Perondi M, Reis A, Paiva E, et al: A comparison of high-dose and standard-dose epinephrine in children with
cardiac arrest. N Engl J Med 2004; 350:1722-1730.
Niles DE, Nishisaki A, Sutton RM, et al: Comparison of relative and actual compression depths during cardiac arrest
in children, adolescents and young adults. Resuscitation 2012; 83:320-326.
Ramamoorthy C, Haberkern CM, Bhananker SM, Domino KB, Posner KL, Campos JS, Morray JP. Anesthesia-
Related Cardiac Arrest in Children with Heart Disease: Data from the Pediatric Perioperative Cardiac Arrest
(POCA) Registry. Anesth Analg 2010; 110:1376-1382.
Reis AG, Nadkarni V, Perondi MB, et al: A prospective investigation into the epidemiology of in-hospital pediatric
cardiopulmonary resuscitation using the internation Utstein reporting style. Pediatrics 2002, 109:200-209.
Spittler KL: Family presence during CPR and invasive procedures. Pulmonary Reviews.Com 2006; 11(3). accessed
07/06/08 at [http://www.pulmonaryreviews.com/mar06/family.html].
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Young KD, Gausche-Hill M, MCClung CD et al: A prospective population-based study of the epidemiology and
outcome of out-of-hospital pediatric cardiopulmonary arrest. Pediatrics 2004;114:157-164.
DISCLOSURE
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Using Information Systems to Manage Departmental Staff, Hospital

Administration, and Payers
David L. Reich, M.D New York, New York
There are many commercial products that are marketed as anesthesia information management systems (AIMS) in
the United States (US) and worldwide. Despite incentives to adopt electronic health records and their various
benefits, there was low penetration into the U.S. market in a recent years (<10% of academic anesthesia practices in
2007). Adoption by smaller anesthesia practices is likely much lower. When surveyed as to why an AIMS had not
been adopted, commonly cited reasons were cost, perceived medicolegal risk, and inertia.1
With meaningful use incentives stemming from the ARRA funds, many institutions are now purchasing enterprise
electronic medical records (EMR) with an anesthesia/perioperative module. Thus, it is likely that many
anesthesiology departments have recently implemented or will be implementing AIMS in the near future. A detailed
summary of the process of choosing and implementing an AIMS was the subject of a recent multi-center publication
by Muravchik et al.2 There is a major opportunity to use the data from AIMS and perioperative information systems
to manage many aspects of anesthesia and hospital practice. This Refresher Course outline will review the literature
on management applications of AIMS and also provide detail regarding the utility of specific analytical reports that
are created from AIMS and related information systems data. A partial list of the regular reports that support
departmental and other hospital departmental functions at the author’s institution is detailed in Table 1.
Table 1. AIMS-Based and Associated Scheduling System Reports

1. Financial
a. Automatic anesthesia billing
i. OR billing records creation
ii. Missing data report
iii. Updates monitoring and reporting
iv. Pain and ICU billing
v. Real-time notification of missing data elements
vi. Reports for administrative assistant to follow up
b. Faculty compensation program
i. Web display and emails
ii. Resident bonus pay
2. Administrative
a. ACGME report automatic generation
b. EPIC interface
c. Tracking system
i. OR Control Desk
ii. Family Waiting Room
iii. Assessment Area
iv. PACU
v. Bed assignment unit
vi. Cardiac White Board
vii. Events Notification: Surgeons, Anesthesia attendings, and residents
d. Scheduling system
e. Daily assignments
f. Night and weekend calls
g. Time off
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h. Web displays and reports

i. Personnel system
3. Quality
a. Return to OR
b. Anastomotic leak
c. Surgical operation log
d. PACU statistics and pain level upon discharge
e. Second operations in same hospitalization
f. 48 hour post-anesthesia mortality
g. Postop complications (standard CMS list)
h. Central Line Associated Blood Stream Infection (CLABS) prevention program compliance
i. Central line education report
j. OR utilization reports
k. Fairness of assignment report (Anesthesia Atttendings)
MANAGING THE DEPARTMENT
Improving Clinical Documentation

Several investigators have assessed the impact of an AIMS on the quality of clinical documentation. One study
comparing AIMS-produced records to completely manual records showed that AIMS records required less
practitioner time (both absolute time and percentage of case time), recorded more vital signs and clinical notes, had
a similar number of artifacts, and fewer illegible entries.3 Another study concluded that missing or erroneous data
occurred more frequently in handwritten records, especially during the first 15 minutes and last 10 minutes of a case,
when greater attention to patient care is typically required which detracts from attention to documentation.4
Accuracy of physiologic (i.e., vital sign) data was also found to be more accurate (or at least more variable) in AIMS
records compared with manual records.5 AIMS records are still imperfect. Additional studies have shown that
information may be incomplete even in an AIMS record secondary to a dependence on free text remarks an inability
to automatically present entries in logical sequences consistent with workflow, and because practitioners
deliberately smooth variability and extreme values in automatically acquired physiologic data in AIMS records.6,7
Overall, the improvement realized after AIMS implementation is supported by several surveys that showed that the
majority of users, both in OR and obstetric settings, were satisfied with their AIMS and would not want to return to
a completely manual system.8,9,10,11
Enhancing Performance Improvement and Patient Safety

In addition to providing better documentation of clinical care, AIMS have the potential to improve quality of care.
Several studies using simple reminders in an AIMS showed that this intervention could significantly improve
compliance with prophylactic antibiotic administration timing.12 ,13 ,14 Another group used a computer-generated
reminder to enhance rates of re-dosing of antibiotics.15 In addition to the contemporaneous reminders, data from
AIMS may be extracted and analyzed to generate daily reminders for US Physician Quality Reporting Initiative
reports and communication with practitioners encouraging them to improve their performance.
Another use of an AIMS is to provide decision support, such as for determining completeness of the anesthesia
record. In one study, an AIMS-based algorithm that alerted the clinician if a patient had multiple risk factors for
post-operative nausea/vomiting nearly doubled the use of antiemetic prophylaxis for these high-risk patients.16
Using an AIMS to screen for intraoperative markers of complications may also be helpful in identifying cases for
quality assurance reviews. Electronic screening yielded many more cases of interest than voluntary reporting by
clinicians.17,18 Overall, the evidence in the literature is just emerging, but the trend towards pay-for-performance
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and other quality measurement efforts will provide further impetus to foster systems that help health care
practitioners adhere to guidelines proven to enhance patient safety.
Technologies in common use in other industries are also beginning to be used in healthcare and integrated into
AIMS. Use of barcodes on medication labels in conjunction with a special scanning device may decrease
medication errors and improve documentation.19,20,21 Barcodes and radiofrequency identification tags can also be
used to verify patient identity, locate patients and vital equipment, and ensure blood product compatibility.
Other areas of potential improvement with AIMS include: 1) the capacity to retrieve records of prior anesthesia
encounters to identify previous problems; 2) an improvement of summary documentation for transfer of care (i.e.,
handoffs); 3) guidance during emergencies (e.g., malignant hyperthermia or cardiac arrest); 4) laboratory data
interfaces that report and record pertinent lab values when they become available; 5) alerts to worrisome trends in
physiologic values beyond the simple limit alarms built into monitors; and 6) the ability to monitor cases remotely
by accessing live AIMS records from a remote workstation or personal digital assistant (PDA).
The possibility that an AIMS could actually jeopardize patient safety has been considered. With clinicians free of
the need to record vital signs manually, there is potential for inattention to the vital signs that are both measured and
recorded automatically. This issue was addressed in two studies that concluded that the use of an AIMS did not
decrease vigilance.22,23
Enhancing Professional Billing Metrics and Clinical Productivity

Use of an AIMS creates opportunities to improve the economics of practice. In addition to recording the clinical
documentation that is needed to support billing, the AIMS can function as a point-of-care charge capture system as
well. A complete AIMS record can contain all of the necessary patient information, procedure, time, and special
technique information that, in combination with other patient insurance information, can be used to create a bill of
service by a billing provider. Using an AIMS to drive billing can eliminate the need for paper billing vouchers and
can reduce charge lag, clerical and processing costs, lost bills, days in accounts receivable, and practitioner
paperwork burden.24 Using automatic electronic mail and PDA alerts to practitioners about deficiencies in the
AIMS record, so that they can be expeditiously corrected, has also led to improved billing metrics.25
AIMS can also increase revenue by helping to identify potentially reimbursable items. One study showed that
screening AIMS records for presence of vital signs from an invasive monitor but without supporting documentation
of placement of that monitor (necessary for billing) identified a significant source of missed revenue that could be
corrected.26 Another study showed that use of an AIMS-based pre-operative evaluation system by hospital coders
resulted in additional abstracted diagnoses that increased hospital revenue under the diagnosis-related-group (DRG)
system.27
Not only does an AIMS allow for documenting anesthesia care, but it has potential applications for monitoring and
incentivizing practitioner activities. One report demonstrated a role for using an AIMS as the basis of a
productivity-based compensation system for faculty and house staff in an academic anesthesia practice.28 Another
study found that an AIMS-based cost-analysis was helpful in implementation of practice guidelines regarding
anesthetic drug usage, and could lead to significant cost savings.29 Also reported is the use of an AIMS to help
identify practitioners who may be diverting controlled substances.30
Good communication with anesthesia providers is a key to realizing productivity gains with an AIMS. Table 2
demonstrates an excerpt from a weekly report to an anesthesia provider. Note that one case did not have a
postoperative note documented within 48 hours and was subjected to a 10% case points penalty. Figure 1
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demonstrates the marked effect of the postoperative note points penalty in achieving extremely high compliance
with postoperative note documentation guidelines.
Table 2. Example of a Daily Faculty Productivity Report with Penalty for Late Postoperative Note
PostOp
Case Concurrency Call Completeness
Start Time End Time Points Adjustment Final Points
Number Adjustment Related Adjustment
for Lateness
Cardiac 1 N/A 450
Worked
N/A 450
Pre-Call
1 9:28 10:34 195 0.97 1 1 190
2 20:00 23:24 310 N/A after 1800 1 1 310
3 9:00 10:43 255 0.97 1 1 248
4 17:45 18:00 27 0.97 1 1 27
4 18:00 21:28 378 N/A after 1800 1 1 378
5 11:10 15:25 420 0.97 1 1 409
6 15:50 18:00 206 0.97 0.9 1 181
6 18:00 20:15 214 N/A after 1800 0.9 1 193
Total 2836
Figure 1. Hours between End-Anesthesia Time and Postoperative Note Entry
Postop Note Latency

140
Mean Hours
120
100
80
60
40
20
0
Jan‐09
Mar‐09
May‐09
Nov‐09
Mar‐10
Nov‐11
Mar‐12
Jul‐09
Sep‐09
Jan‐10
Jul‐10
Sep‐10
Jan‐11
Mar‐11
May‐11
Jul‐11
Sep‐11
Jan‐12
Nov‐10
May‐10
May‐12
Conducting Clinical Research

Continued use of an AIMS leads to accumulation of large amounts of clinical data that can be used for research
purposes. These data can mined (extracted) and used to generate hypotheses prior to planning prospective studies,
to study rare events, or questions that cannot be ethically or practically studied prospectively. There is also
opportunity to combine the electronic records created by AIMS from multiple centers, allowing multicenter
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retrospective analyses. Such efforts are hindered, however, by the lack of standardization of structure and
terminology in electronic medical records. Multiple efforts are underway to create such standards.31 For
prospective studies, an AIMS can be configured to collect necessary data elements, and an AIMS-based pre-
operative evaluation can be used to screen patients for inclusion in research protocols.
The AIMS data structure can also be modified to include additional variables of interest that will facilitate future
studies. Since the standards for controlled anesthesia terminologies have only begun to be incorporated by the
AIMS vendors, there is very limited exchange of clinical data among AIMS in different institutions, though it can be
still be accomplished with manual mapping of variables between each system.32
Whenever possible, data should be acquired from anesthesia practitioners in a structured format. Although it is
easier for practitioners to enter the operation performed as a free text field rather than choosing from a long list of
current procedural terminology (CPT) or international classification of diseases (ICD)-10 codes, the quality
improvement and research tasks will be much simpler with the database-generated list. Free text fields are very
difficult to search, and the variability of spacing, abbreviations, and misspellings greatly complicates the task,
compared with the ease of searching across ranges of numerical codes.33 For US practice, surgical CPT codes are
preferable to anesthesia CPT codes for many reasons, but mainly because it is possible map one or more surgical
CPT codes to a single anesthesia code using the American Society of Anesthesiologists (ASA) Crosswalk Program
(ASA, Chicago, IL), but the reverse is not possible.
External Databases
One of the greatest challenges in AIMS-based research is the merging of data from separate databases. In the
process of conducting evidence-based patient safety research, it is inevitable that hospital, surgical, and
governmental databases will be used at some point for collecting demographics, process and outcome variables that
are not present in the anesthesiology database. For example, length of hospital stay and co-morbid conditions
leading to prolonged hospital stays are data that are not routinely found in the anesthesiology database. In the
reconciliation of databases, it is often critical to use multiple identifiers for patients, including medical record
numbers, hospital account numbers that are specific to each hospital encounter, dates of surgery, etc. This is
necessary in order to positively identify the data (e.g., a postoperative infection) that coincides with the hospital
encounter of interest (e.g., an abdominal surgical operation).
MANAGING THE HOSPITAL
Dexter et al34 implemented an automatic method to estimate the times remaining in OR cases. Instant message
dialogs appearing on AIMS workstations were used to elicit estimates of times remaining from anesthesia providers,
with acknowledgment occurring on average within 1.2 min. For cases taking nearly as long as or longer than
scheduled, each 1 min progression of OR time reduced the median time remaining in a case by <1 min. Based upon
historical surgeon performance, they demonstrated more accurate automated calculation of times remaining for
every case occurring at a 29 OR hospital. Table 3 below is an example of a PACU length-of-stay analysis.
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Table 3. Post-Anesthesia Care Unit Length of Stay Data by Type of Anesthetic

General MAC Spinal Non-Spinal Regional
Number of Patients 1266 553 84 87
5th Percentile (min) 40 30 76 47
Mean ± SD (min) 135±89 205±2025 209±148 113±63
MAC = monitored anesthesia care
The lecture will demonstrate how many of the reports detailed in Table 1 are used to manage hospital administrative,
operational and quality needs.
MANAGING THE PAYERS
Although an AIMS is not required to manage a billing operation and payers, the author’s institution noted a decrease
of 6-7 days in charge lag that was associated with a switchover to electronic billing voucher creation for OR
anesthesia.24 Vigilant review of charge lag metrics are an excellent surrogate for “front-end” problems in the billing
operation for the various anesthesia departmental business lines.
Figure X. Excerpt of Charge Lag Metrics Monthly Report

Location Data Nov-11 Dec-11 Jan-12 Feb-12 Mar-12 Apr-12
OR Avg Lag 10 10 10 9 9 9
SESM% 67% 75% 75% 71% 72% 66%
Claims 4413 4259 4057 4486 4852 4039
SESM Current 79% 86% 75% 78% 80% 71%
Mode 8 8 8 8 8 9
Amb Suite Avg Lag 10 10 14 9 8 10
SESM% 71% 74% 76% 70% 76% 60%
Claims 141 108 123 149 144 128
SESM Current 83% 77% 71% 76% 81% 63%
Mode 8 8 8 8 8 9
Acute Pain Avg Lag 28 31 29 22 18 19
SESM% 22% 13% 47% 55% 42% 38%
Claims 1107 991 793 667 587 760
SESM Current 0% 0% 0% 0% 0% 0%
Mode 21 20 16 16 23 15
SESM = Same entry, same month
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Figure 2 demonstrates an analysis of accounts receivable that is particularly useful for managed care organizations.
Even with a contracts management module, underpayments require appeal and resubmission. The effect of a special
project are evident in the oldest service dates payments that were received in March and April of 2012.
Figure 2. One Managed Care Payer’s Performance by Date of Service
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Conclusion
The extensive functionality of AIMS and custom add-on systems in many of the “early adopter” centers developed
over many years. Such systems are likely to be implemented more rapidly in the future by others. This process most
often begins with the deployment of a standard commercial AIMS software package, which is then extensively
configured to meet the individual departmental needs. Significant additional programming resources and initiative
are needed for a full exploitation of the potential of an AIMS. Control of extensive perioperative information
resources is an intangible but real return on investment.
References
1. Egger Halbeis CB, Epstein RH, Macario A, Pearl RG, Grunwald Z. Adoption of anesthesia information
management systems by academic departments in the United States. Anesth Analg. 2008 Oct;107(4):1323-9.
2. Muravchick S, Caldwell JE, Epstein RH, Galati M, Levy WJ, O'Reilly M, Plagenhoef JS, Rehman M, Reich DL,
Vigoda MM. Anesthesia information management system implementation: a practical guide. Anesth Analg. 2008
Nov;107(5):1598-608.
3. Edsall DW, Deshane P, Giles C, Dick D, Sloan B, Farrow J. Computerized patient anesthesia records: less time
and better quality than manually produced anesthesia records. J Clin Anesth. 1993;5:275-83.
4. Lerou JG, Dirksen R, van Daele M, Nijhuis GM, Crul JF. Automated charting of physiological variables in
anesthesia: a quantitative comparison of automated versus handwritten anesthesia records. J Clin Monit 1988;4:
37-47.
5. Reich DL, Wood RK Jr, Mattar R, Krol M, Adams DC, Hossain S, Bodian CA.Arterial blood pressure and heart
rate discrepancies between handwritten and computerized anesthesia records. Anesth Analg. 2000;91:612-6.
6. Driscoll WD, Columbia MA, Peterfreund RA. An observational study of anesthesia record completeness using an
anesthesia information management system. Anesth Analg. 2007;104:1454-61.
7. Wax DB, Beilin Y, Hossain S, Lin HM, Reich DL. Manual editing of automatically recorded data in an
anesthesia information management system. Anesthesiology. 2008;109:811-5.
8. Eden A, Grach M, Goldik Z, Shnaider I, Lazarovici H, Barnett-Griness O, Perel A, Pizov R. The implementation
of an anesthesia information management system. Eur J Anaesthesiol. 2006;23:882-9.
9. Coleman RL, Stanley T 3rd, Gilbert WC, Sanderson IC, Moyer GA, Sibert KS, Reves JG. The implementation
and acceptance of an intra-operative anesthesia information management system. J Clin Monit. 1997;13:121-8.
10. Quinzio L, Junger A, Gottwald B, Benson M, Hartmann B, Jost A, Banzhaf A, Hempelmann G. User acceptance
of an anaesthesia information management system. Eur J Anaesthesiol. 2003;20:967-72.
11. Beilin Y, Wax D, Torrillo T, Mungall D, Guinn N, Henriquez J, Reich DL. A survey of anesthesiologists' and
nurses' attitudes toward the implementation of an Anesthesia Information Management System on a labor and
delivery floor. Int J Obstet Anesth 2009;18:22-7.
12. O'Reilly M, Talsma A, VanRiper S, Kheterpal S, Burney R. An anesthesia information system designed to
provide physician-specific feedback improves timely administration of prophylactic antibiotics. Anesth Analg.
2006;103:908-12.
13. Wax DB, Beilin Y, Levin M, Chadha N, Krol M, Reich DL. The effect of an interactive visual reminder in an
anesthesia information management system on timeliness of prophylactic antibiotic administration. Anesth Analg.
2007;104:1462-6.
14. St Jacques P, Sanders N, Patel N, Talbot TR, Deshpande JK, Higgins M. Improving timely surgical antibiotic
prophylaxis redosing administration using computerized record prompts. Surg Infect (Larchmt). 2005;6:215-21.
15. Zanetti G, Flanagan HL Jr, Cohn LH, Giardina R, Platt R. Improvement of intraoperative antibiotic prophylaxis
in prolonged cardiac surgery by automated alerts in the operating room. Infect Control Hosp Epidemiol. 2003;24:
13-6.
16. Kooij FO, Klok T, Hollmann MW, Kal JE. Decision support increases guideline adherence for prescribing
postoperative nausea and vomiting prophylaxis. Anesth Analg 2008;106:893-8.
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17. Sanborn KV, Castro J, Kuroda M, Thys DM. Detection of intraoperative incidents by electronic scanning of
computerized anesthesia records. Comparison with voluntary reporting. Anesthesiology. 1996;85:977-87.
18. Benson M, Junger A, Fuchs C, Quinzio L, Böttger S, Jost A, Uphus D, Hempelmann G. Using an anesthesia
information management system to prove a deficit in voluntary reporting of adverse events in a quality assurance
program. J Clin Monit Comput 2000;16:211-7.
19. Merry AF, Webster CS, Mathew DJ. A new, safety-oriented, integrated drug administration and automated
anesthesia record system. Anesth Analg 2001;93:385-90.
20. Webster CS, Merry AF, Gander PH, Mann NK. A prospective, randomised clinical evaluation of a new safety-
orientated injectable drug administration system in comparison with conventional methods. Anaesthesia.
2004;59:80-7.
21. Nolen AL, Rodes WD 2nd. Bar-code medication administration system for anesthetics: effects on documentation
and billing. Am J Health Syst Pharm 2008;65:655-9.
22. Allard J, Dzwonczyk R, Yablok D, Block FE Jr, McDonald JS. Effect of automatic record keeping on vigilance
and record keeping time. Br J Anaesth 1995;74:619-26.
23. Loeb RG. Manual record keeping is not necessary for anesthesia vigilance. J Clin Monit 1995;11:5-8.
24. Reich DL, Kahn RA, Wax D, Palvia T, Galati M, Krol M. Development of a module for point-of-care charge
capture and submission using an anesthesia information management system. Anesthesiology. 2006;105:179-86.
25. Spring SF, Sandberg WS, Anupama S, Walsh JL, Driscoll WD, Raines DE. Automated documentation error
detection and notification improves anesthesia billing performance. Anesthesiology 2007;106:157-63.
26. Kheterpal S, Gupta R, Blum JM, Tremper KK, O'Reilly M, Kazanjian PE. Electronic reminders improve
procedure documentation compliance and professional fee reimbursement. Anesth Analg 2007;104:592-7.
27. Gibby GL, Paulus DA, Sirota DJ, Treloar RW, Jackson KI, Gravenstein JS, van der Aa JJ. Computerized pre-
anesthetic evaluation results in additional abstracted comorbidity diagnoses. J Clin Monit 1997;13:35-41.
28. Reich DL, Galati M, Krol M, Bodian CA, Kahn RA. A mission-based productivity compensation model for an
academic anesthesiology department. Anesth Analg 2008;107:1981-8.
29. Lubarsky DA, Sanderson IC, Gilbert WC, King KP, Ginsberg B, Dear GL, Coleman RL, Pafford TD, Reves JG.
Using an anesthesia information management system as a cost containment tool. Description and validation.
30. Epstein RH, Gratch DM, Grunwald Z. Development of a scheduled drug diversion surveillance system based on
an analysis of atypical drug transactions. Anesth Analg 2007;105:1053-60.
31. Warner MA, Monk TG. The impact of lack of standardized definitions on the specialty. Anesthesiology.
2007;107:198-9.
32. Monk TG, Sanderson I. The development of an anesthesia lexicon. Seminars in Anesthesia Perioperative
Medicine and Pain. 2004;23:93–8.
33. Levin MA, Krol M, Doshi AM, Reich DL. Extraction and mapping of drug names from free text to a
standardized nomenclature. AMIA Annu Symp Proc 2007;11:438-42.
34. Dexter F, Epstein RH, Lee JD, Ledolter J. Automatic updating of times remaining in surgical cases using
Bayesian analysis of historical case duration data and "instant messaging" updates from anesthesia providers. Anesth
Analg 2009;108:929-40.
DISCLOSURE
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Ethical Dilemmas Coming Your Way: A Trio of Turmoil
Jeffrey S. Jacobs, M.D. Cleveland Clinic Florida
Bioethics vignettes classically involve end-of-life, consent, and Jehovah’s Witness challenges, but
there are many other situations that affect the practicing anesthesiologist. Some of these topics involve
clinical practice, some deal with professional relationships, and others revolve around national and political
issues. The unique feature of these is their removal from the usual doctor-patient interaction. The goal of
is to outline three of these unusual bioethical issues and help formulate a strategy for addressing them.
Organ Donation after Cardiac Death

The first of these relates to the operating room management of a specific patient: the one
undergoing end-of-life organ donation. However, this is not the customary brain-dead patient, where the
anesthetic management is clearly outlined. Rather, this is the anesthetic management of the donor who is
not brain-dead, but who wishes to be first removed from life-support, and then donate organs. This type of
organ donation would help rectify the enormous imbalance between the need for organ donors and the
supply. In fact, there are currently over 110,000 United States citizens awaiting an organ transplant1. In
order to increase the availability of potential organs, the concept of donation after cardiac death (DCD) was
resurrected. It has been estimated that DCD may increase the pool of available organs between 20-50%2.
While there are many synonyms for this practice, including non-beating heart donation, and asystolic
donation, among others, they all refer to organ donation after the heart stops.
Difference
The main differentiator between DCD and brain-dead organ donation is that with the latter, the
donor is already dead. Brain death is synonymous with death in the eyes of medicine and the law.
Therefore, the anesthesiologist provides not analgesia or amnesia, but circulatory support so the organs
continue to receive oxygen until they are harvested. In the DCD patient, the decision is first made to
withdraw care from a patient who has no chance of meaningful survival. Examples of this might include
someone in a persistent vegetative state from a brain injury or someone with progressive neurologic disease
leading to ventilator dependency. When care is withdrawn from a patient with these conditions, typically
circulation slowly decreases until the heart ultimately stops. Once the heart stops, the organs begin to die.
Thus, unlike the brain-dead donor, the surgeons need to scramble to procure the organs.
Ethical Considerations
In the DCD patient, the primary responsibility is to ensure that the donor has decided to have care
withdrawn prior to and separate from the decision to become an organ donor. In other words (and very
loudly), the decision when to withdraw care and how to withdraw care should have no bearing on whether
the patient will become an organ donor. The comfort of the donor takes precedent over the donation
process. In some circumstances after care is withdrawn, the patient will not die, but instead become
hypotensive for several hours. While this might result in the organs becoming unsuitable for transplant, so
be it.
DCD satisfies patient autonomy. Patients have the right to make end-of-life decisions, donate
organs, forgo life-sustaining therapy, and make unencumbered choices about their bodies. Surrogates can
make these choices on behalf of the patient, if necessary. The practice of DCD is beneficent for the donor.
Withdrawal of care preserves patient dignity, and subsequent donation is an act of kindness by the donor.
Additionally, this act might ease the donor’s family and loved ones’ grief. Sustaining life in a patient in a
persistent vegetative state could be viewed as harming that patient, and therefore withdrawal of care could
be seen as an avoidance of maleficence.
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When does death occur in these patients? A lack of circulation (as opposed to a lack of cardiac
electrical activity) is used as the definition. The recommendation is that at least two minutes, but no more
than five minutes of circulatory silence is required to declare death.
Mechanistic Considerations
Where should the withdrawal of care occur? If organ donation was not planned, in most
circumstances, this would take place in the intensive care unit (ICU) (with or without the patient’s loved
ones). Because organ death begins with the cessation of circulation, withdrawal in the ICU could lead to
the lack of organ viability or could lead to chaos as the patient is then rushed to the operating room. Of
course, if care is withdrawn in the operating room, would that necessitate the patient being without family
members? A system should be developed to invite family presence in the operating room, with the
understanding that they will leave as soon as their loved one is pronounced dead.
Pre-Transplant Medications/Interventions
To evaluate potential organs for donation and prepare them for harvesting, pre-death interventions
are sometimes necessary. This might include the administration of heparin, vasodilators, and/or
antioxidants, cannulation of large vessels, and sometime NG tubes and bronchoscopy (for lung donors). In
general, the consensus is that the administration of medications is ethical, but insertion of catheters or
procedures should receive consent from the health care surrogate.
ASA Committee on Ethics Statement 3

(1) The donor’s care and decisions are paramount
(2) The decision for withdraw of ICU treatments must be made before and separate from any decision
to donate organs
(3) In order to avoid the appearance of conflict of interest, the physician caring for the donor should
not be involved in any of the organ recipient procedures, and that physician should be the
declarant of time of death
Other considerations include defining the criteria for death by circulatory arrest (2 minutes, 5 minutes, etc.)
and the development of a plan for determining how long the potential donor should remain in the operating
room if death does not occur. Finally, there must be no pressure to hasten death by the caregivers to
facilitate harvesting.
Should Anesthesiologists Be Involved?

Arguments for:
(1) Anesthesiologists are involved in operating room policy, and organ harvesting occurs in the
operating room
(2) Anesthesiologists are able to handle end of life issues
(3) Anesthesiologists make the transition from the ICU to the OR a seamless process
Arguments against:
(1) DCD does not require anesthesia – the patient is dead without circulation
(2) Withdraw of care can be performed by any physician in the operating room
(3) Gives the impression that the donor needs anesthesia (is somehow still alive)
(4) Last minute transfer of patient care is complex
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Recommendations
(1) The decision to withdraw care should precede and be independent of the decision to become an
organ donor.
(2) Transplant surgeons and transplant staff should have no role in the withdrawal of care.
(3) Anesthesiologists who will participate in the transplant anesthetic should not be involved in the
withdraw of care
(4) If, by chance, a donor is in the same ICU as a potential recipient, the medical teams caring for the
two patients should be different4.
(5) Recognition that prolonged periods of hypotension (without death) may damage potential
transplantable organs, but that possibility needs to be respected.
(6) No organs can be procured until death is pronounced. Skin can be prepped if the patient is
unconscious.
(7) Unless the anesthesiologist has been caring for the patient in the ICU, there is no need for an
operating room anesthesiologist to be involved during the DCD harvesting process. This is best
left to an intensivist.
Physician Involvement in State Ordered Executions (Lethal Injection)

History
In 1977, Oklahoma was the first state to adopt lethal injection as a means of execution, and the
first execution using lethal injection took place in Texas in 1982. The method was developed by the State’s
Medical Examiner, and it was called the Chapman Protocol5.” It was approved by an Oklahoma
anesthesiologist and then adopted by the Oklahoma legislature. Currently, 34 states plus the United States
government and military have a death penalty, and all but one utilizes lethal injection as the method.
Protocol
The protocol that has been most commonly utilized is the three drug method: sodium thiopental,
pancuronium, and potassium administered intravenously and in sequence. The drugs are administered to
the condemnedand using EKG monitoring, pronounced dead after asystole occurs. It has been the
exception to have a physician involved with the execution process.
Recent History
In 2005, an article published in Lancet6 suggested that some of the executed may not have been
asleep when the pancuronium and potassium were taking effect. This landmark article awoke the skeletons
in the nation’s closet regarding the lethal injection process. Based on this article, many death row defense
attorneys claimed that lethal injection was a form of cruel and unusual punishment, which is specifically
banned by the United State Constitution. As a result, various judges ruled that either executions should
occur with the barbiturate alone, or the entire process would need to be supervised by someone with
training in general anesthesia (anesthesiologist). A Missouri District Court ruled that “a board certified
anesthesiologist shall be responsible for the mixing of all drugs which are used in the lethal injection
process.” Further, the court ruled that “pancuronium and potassium…will not be administered until the
anesthesiologist certifies that the inmate has achieved sufficient anesthetic depth…” No anesthesiologist
volunteered, and the judge reversed the ruling. Medical societies countered that physician participation in
the execution process violated medical ethics, while state medical boards threatened license revocation for
participation. In North Carolina, the state legislature passed a law banning the board of medicine from
disciplining a participating physician. To help circumvent this, the Department of Corrections used a
Bispectral Index Monitor (BIS) during one execution. Aspect Medical requested this not be done again7.
Thus, the judicial and legislative branches of government were squarely at odds with the executive branch
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leading to stalemates. In the past two years, two states (Ohio and Washington) have moved to a one-drug
protocol.
Recently, the Italian government forbade the exportation of sodium thiopental to the United State
because it is used for lethal injections. Because this was the only manufacturer of the medication, this
compounded the induction agent shortage. Some states have set up sharing plans with other states to make
the execution drugs more readily available, while other states have changed from thiopental to
phenobarbital for lethal injections.
Case Reports
In 2006 a Florida inmate was being executed by lethal injection. The process took 34 minutes
from the initiation of medication administration to being pronounced dead. At least twice during the
process, the condemned asked “what’s happening?” He had agonal respiratory efforts for 24 minutes.
After this event, Governor Jeb Bush suspended executions and formed a Commission8 that identified at
least two dozen deficiencies in the execution process.
In one Ohio execution in 2006, it took 22 minutes to start an IV. Four minutes after the injection,
the condemned sat up and said, “It’s not working.” Another 30 minutes elapsed until another vein was
secured and the execution was successful9 (Figure 1). In unpublished data (because execution logs are not
public records), there are at least 36 other documented “botched” lethal injections including six in
California where evidence suggested that the condemned were breathing or conscious when the
pancuronium and potassium were administered.
Ethical Analysis – Should Physicians Participate in the Lethal Injection Process?

Yes
(1) Historical Perspective – physicians have been involved with executions for centuries, and
their involvement might make for a more humane execution process
(2) Civic Duty – as members of society, physicians possess unique skills which should be used
under the laws of their country, when needed, to assist in carrying our rules and maintaining
order
(3) Humane – physicians can argue that the lethal injection process is barbaric and inhumane, and
by assisting, they are acting in a beneficent manner
(4) Not Abandoning the Dying – physicians are trained not to abandon the dying patient. Inmates
with a death sentence are no different that someone with terminal cancer, except that the exact
time of death is known.
(5) Physician is not the Executioner - The Governor signs the death warrant, not the physician.
(6) Does not Violate the AMA’s Code of Ethics – “…should preserve life when there is hope of
doing so.” There is no hope of preserving life in a patient about to undergo lethal injection.
(7) Do Similar Things Already – Physicians already perform termination of pregnancy, withhold
and withdraw care from the terminally ill, and in some states, provide euthanasia services.
This is no different.
No
(1) No existing doctor-patient relationship – therefore, not acting as a physician
(2) Violates Nonmaleficence – this is the ultimate malfeasant act
(3) Violates Distributive Justice – It is well-known that minority prisoners and those who commit
murder against Caucasians are more likely to receive the death penalty. By participating, a
physician is implicitly accepting the unbalanced distribution of death penalty administration.
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(4) Condemned by the International Medical Community – The World Medical Association is
opposed to participation. The United States, with the exception of Russia and some of the
former Soviet states, stands alone as the only “developed’ nation with a death penalty.
(5) Ethical-Legal Dilemma – There is no consensus as to how to punish physicians who breach
their “ethical guidelines” but remain within the law.
(6) Physician Becomes a Handmaiden of the State – The participating physician would not be
acting as a doctor, but instead as a “tool.”
(7) Capital Punishment should be a Lesson – Some believe that capital punishment should not be
painless, and that if it is not painless, it would act more as a deterrent.
(8) Violates the Hippocratic Oath to “do no harm.”
Studies and Data

Nearly 50% of polled physicians believe that some involvement in the lethal injection process was
appropriate, although not necessarily injecting10. In a follow up study, Farber queried the level of
involvement physicians would be willing to undertake11. Eight of the ten options in his study are
specifically banned by the AMA, but despite that, 20-30% of those surveyed would participate in most
aspects of the process, with nearly 20% willing to administer the lethal injection itself. In an interview of
four physicians who helped with lethal injections12, Gawande found that none were death penalty zealots,
the role “crept up on them,” and all had valid ethical reasons for doing it.
While the trend has been for medical associations to discourage and possibly ban participation,
there are others who have recently taken an opposite side of this argument. Waisel14 recently opined that
“organized medicine has an obligation to permit physician participation in legal executions,” and Nelson
and Ashby “…believe that the most that can be fairly said [about this issue] is that physician participation
neither fully advances the ethical ideals of medicine nor is strictly anathema to them.”15
Statements
Despite the rationale for assisting, the AMA’s Code of Medical Ethics states that “…a
physician…should not be a participant in legally authorized executions15.” The American Society of
Anesthesiologists affirms this statement, and states that “the ASA strongly discourages participation by
anesthesiologists in executions.”
Conclusion
There is no clear answer with this issue. World medical associations are against participation by
physicians, perhaps because they are against the death penalty in general. American medical societies
forbid it. The government not only allows physician participation, but sometimes demands it. Many
physicians think participation is reasonable. The ethical arguments support both sides. To help solve this
puzzle, recommendations are: (1) language in state laws that require physician participation should be
removed, (2) the condemned should be involved in the decision to involve a physician, (3) the role of
awareness monitors during the process should be reconsidered, (4) the practice of lethal injections and the
role of the death penalty should be continuously reevaluated in our criminal justice system.
Protecting the Patient from Incompetence
How many times has an anesthesiologist heard the question, “my surgeon is good, right,” coming from a
preoperative patient? What happens if the answer is “no?” This section will explore the issues that
surround the answer to this question.
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Importance
In this era of health care reform, one of the missing pieces of the puzzle from the physician’s
perspective is tort reform: i.e.: medical malpractice reform. In fact, the American Medical Association
produced a white paper regarding the topic16. One of the sticking points with tort reform is the claim by
personal injury attorneys that the public needs to be protected from bad doctors. The claim is that
physicians do a poor job of “policing” themselves. Just as important is the idea of patient protection from
these subpar physicians. It is indisputable that anesthesiologists have led all other medical specialties in the
category of patient safety initiatives. There is no reason that safety stops with technology, physiology, and
pharmacology.
Epidemiology
Is there a problem with self-policing in the house of medicine? In 1998, more the 4500 medical
malpractice cases were filed against physicians in Texas17. Seven hundred fifty resulted in payments. Of
the closed claims, only 121 were investigated by the state board of medicine. Of those cases investigated
only three resulted in discipline (Figure 2). Over a 5 year period in Texas, there were 18 medical license
revocations, but none due to medical errors. In Minnesota over a 20 year period, of the 35,000 doctors with
five or more malpractice claims against them, only 13% were disciplined by the state18. In Florida over a
12 year period, of the 23 doctors with TEN or more judgments against them, only 12 were disciplined by
the State19. In the August 10, 2011 edition of the LA Times, the lack of physician discipline was a lead
story20.
According to the National Practitioner Data Bank, 5% of the doctors account for more than ½ of
all malpractice payouts. Furthermore, there is no interstate mandatory data sharing. In other words, one
physician could practice terribly in one state, lose his license, move to another state and start all over.
Additionally, nearly ½ of doctors have witnessed a serious medical error but have not reported it21. It’s
possible the attorneys have a valid point (Figure 3).
Ethical Discussion
Considering the above information, is there an ethical obligation to protect patients from bad
physicians? According to the AMA, the answer is yes. Code E-9.031 addresses the requirement to report
impaired, incompetent, or unethical colleagues22.The principle of beneficence dictates that in order to do
what’s in the patient’s best interestan incompetent physician should be reported. At a minimum, a patient
should be protected from a physician who is working above his/her skill level. To protect society from a
dangerous physician, the principle of utility is invoked. Whose happiness and safety is more important: the
incompetent physician’s or society’s? The principle of nonmaleficence dictates that a physician must not
do harm to patient. Undoubtedly, there is compelling ethical evidence to support protecting patients from
an incompetent physician.
One of the finest examples of protecting patients on ethical grounds came from the Manitoba
Pediatric Cardiac Surgery Inquest23. The anesthesia group of the only hospital providing pediatric cardiac
surgery in the Province of Manitoba, Canada recognized that the new (and only) heart surgeon was taking
much longer on most operations than the norm, making more intraoperative errors, and his patients were
suffering significant morbidity and mortality. The cardiac group went to the chief of their anesthesia group
and ultimately to the hospital’s chief with this information and with their refusal to provide services to this
surgeon. A moratorium was placed on the program, and an inquest was held reviewing all of his cases. His
care was deemed substandard, and he was mentored with a contraction of his privileges. When his bad
outcomes continued, he was fired. This group of anesthesiologists had nothing to financially gain from
this, and quite possible stood to suffer a significant financial loss, yet they opted for patient protection.
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Barriers
Despite the undeniable ethical justification for protecting patients, it is rarely done. Why does this
not happen with more frequency? Some quote the Golden Rule: do unto others…Many believe that
something bad will eventually happen to every provider including themselves, and therefore they would
want the benefit of the doubt. Others plead ignorance stating that they weren’t present or don’t have all of
the facts. Many claim that the outcome to the patient will not change, and therefore why go through all of
those unpleasant steps for nothing. Some are afraid they might become a target as a whistleblower and this
could cause career suicide. Courageous anesthetist Stephen Bolsin from England spent five years battling
the unsatisfactory performance of the pediatric heart surgeons at the Bristol Royal Infirmary. Despite two
surgeons and the chief executive being found guilty of serious professional misconduct, Dr. Bolsin moved
to Australia after being ostracized by the local medical community. Since that time, the United Kingdom
passed a new law protecting whistleblowers24. While these are all theoretical reasons, there are safeguards
in place to protect physicians who take the high road. More importantly, there are legal precedents that
protect reporting physicians.
Legal Discussion
From the institutional point of view, it is a breach of duty for a hospital to permit a physician on its
staff that the hospital knows or should know is negligent. Additionally, a credentialing body must
truthfully respond to inquiries about a practitioner. In KadlecMedicalCenter v. Lakeview Anesthesia
Associates25, the group of anesthesiologists lost a lawsuit when they failed to fully answer a credentialing
inquiry by a new hospital. The group had terminated a prior anesthesiologist for failing to respond to his
pager and diversion of a controlled substance, but when questioned about his competence, they only
responded that he was a former employer and could not supply the other information due to a “large
volume of requests.” This anesthesiologist’s intraoperative impairment resulted in brain damage to a
patient under his care.
When protecting patients, are anesthesiologists protected from litigious surgeons? In one of the
earliest legal cases addressing this topic, Locksley v. Anesthesiologists of Cedar Rapids26, a group of
anesthesiologists refused to continue providing anesthetics for a specific neurosurgeon. His operations
included wrong-sided procedures, clipping incorrect vessels, and multiple bad outcomes. Despite peer-
review by two other hospitals finding him “not medically incompetent,” the group refused to work with
him. The neurosurgeon sued the group for “putting him out of business,” but the Supreme Court of Iowa
found in the anesthesiologists favor.
In one landmark case, Mansmith v. Hameeduddin27, a primary care physician referred a patient
with chronic back pain and a herniated disc to a spine surgeon. The spine surgeon operated on the wrong
level. The patient returned with continued symptoms, and despite noticing the discrepancy about the MRI
findings and the operative report, did not inform the patient, but instead sent the patient to a pain specialist.
After a lumbar epidural steroid injection, the patient developed sepsis from an abscess, and ultimately died.
The primary care physician lost the suit for failing to notify the patient of the wrong-site surgery and failing
to protect the patient from further harm.
State Boards
The purpose of state medical boards is to ensure the quality of licensed practitioners to the public.
One of their rules is often the demand that physicians police themselves and their colleagues. In Florida,
the Board of Medicine requires that “…failure to report to the Department of Health any person who the
licensee knows is in violation of this chapter [Ground for Disciplinary Action]… 28” can result in
disciplinary action. In other words, if a licensed physician observes another licensed physician committing
malpractice and fails to report him/her, the observer can be punished. While this sounds ideal, over a 14-
year period, only four doctors were punished under this rule, and this infraction was always grouped with
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more serious charges. No physician has ever been sanctioned solely for this. Most states have rules similar
to Florida’s with similar experiences.
How to Report
Before reporting someone, it is crucial to discriminate between medical incompetence and a bad
outcome. If true medical ineptitude exists, reporting should be factual, objective, and unemotional. There
are many options of where to report, and the dynamics of each practitioner’s institution should be taken
into account when deciding. Possibilities include reporting to the chief of anesthesia, administration, or the
credentialing department. If there is a hostile environment, anonymous reporting to the State Medical
Board is another option. There is always the possibility of retribution, but the law usually prevails. In
perhaps the most egregious example of this, WinklerCountyTexas v. Anne Mitchell29, a nurse reported a
physician to the State Medical Board for falling below the standard of care in many instances. In the past,
the physician had successfully treated both the county sheriff and the local district attorney (DA), and in a
cruel twist, the DA charged the nurse with misuse of official information. Unsurprisingly, the nurse was
acquitted.
The goal of reporting incompetence should never involve personal retribution, business-related
issues, or “getting rid” of someone. The objective should be to protect future patients from someone who is
potentially dangerous. Ideally, with remediation, refresher courses, and further education, the incompetent
physician can be reinstated to full practice. If not, a limitation of privileges is another viable and
reasonable option. A license revocation should be the last resort.
Summary
There are compelling ethical reasons to protect patients from medical incompetence. Additionally,
there is case law that suggests this act is required. Furthermore, there are closed cases that adjudicate on
the side of protecting those who protect patients. The role of the anesthesiologist is not just limited to
protecting a patient during an operation or procedure, but sometimes extends to guarding future patients
before they even get through the door.
Selected References
1. www.unos.org., accessed April 18, 2011
2. Herdman et al. “The Institute of Medicine’s Report on Non-Heart-Beating Organ
Transplantation.” Kennedy Inst Ethics J 1998; 89-90.
3. Palmer, Susan. Chair, Committee on Ethics. ASA Newsletter, 2006.
4. National Recommendations for Donation after Cardiocirculatory Death in Canada, CMAJ , 2006.
5. “So Long as They Die: Lethal Injections in the United States,” Human Rights Watch, 2006, 18(1).
I. Development of Lethal Injection Protocols.
6. Koniaris LG, et al. “Inadequate Anaesthesia in Lethal Injection for Execution,” Lancet 2005; 365:
1412-14.
7. “Aspect Medical Systems Comments on Perspective Article in June 15, 2006 New England
Journal of Medicine,” June 15, 2006.
8. The Governor’s Commission on Administration of Lethal Injection, 2007.
9. “Execution of Joseph Clark Fails to go Smoothly,” Copley News Service, May 2, 2006.
10. Farber N, et al. “Physicians’ Attitudes about Involvement in Lethal Injections for Capital
Punishment.” Arch Intern Med 2000; 160:2912-16.
11. Farber N, et al. “Physicians’ Willingness to Participate in the Process of Lethal Injection for
Capital Punishment.” Ann Intern Med 2001; 135(10): 884-8.
12. Gawande A. “When Law and Ethics Collide: Why Physicians Participate in Lethal Injections.” N
Engl J Med 354;12:1221-9, March 23, 2006.
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13. Waisel, D. “Physician Participation in Capital Punishment,” Mayo Clinic Proceedings 82, no. 9
(2007):1073-80.
14. Nelson L and Ashby B. “Rethinking the Ethics of Physician Participation in Lethal Injection,”
Hastings Center Report, May-June 2011: 28-37.
15. AMA Code of Medical Ethics, 2.06, July, 1980.
16. http://www.ama-assn.org/ama/pub/advocacy/current-topics-advocacy/practice-
management/medical-liability-reform.shtml
17. Swanson DJ. “Patient’s Deaths Haven’t Moved State Board to Act,” The Dallas Morning News,
7/28/02
18. Minnesota Medical Malpractice Lawyers, www.minnesotamedicalmalpractice.com/Facts.htm
19. Florida’s Real Medical Malpractice Problem: Bad Doctors and Insurance Companies, Not the
Legal System. Public Citizen: Congress Watch, Sept. 2002
20. “California Medical Board Fail to Discipline 710 Troubled Doctors,” LA Times, August 10, 2011.
21. Campbell EG et al. “Professionalism in medicine: results of a national survey of physicians.”
Annals of Internal Medicine, Dec. 4, 2007. Vol. 147:11, pp. 795-802
22. http://www.ama-assn.org/ama/pub/physician-resources/medical-ethics/code-medical-
ethics/opinion9031.page
23. Manitoba Pediatric Cardiac Surgery Inquest. http://pediatriccardiacinquest.mb.ca/
24. Dyer Clare. “UK Introduces far Reaching Law to Protect Whistleblowers.” Brit Med J, 319
(7201): 7. July 3, 1999.
25. Kadlec Medical Center v Lakeview Anesthesia Associates. US Court of Appeals, 5th Circuit, No.
06-30745.
26. Locksley v. Anesthesiologists of Cedar Rapids. Supreme Court of Iowa, April 20, 1983.
27. Mansmith v. Hameeduddin. Illinois Court of Appeals, No. 1-04-1243.
28. Florida Board of Medicine Rules.
https://www.flrules.org/gateway/ChapterHome.asp?Chapter=64B8-9
29. Winkler County Texas v. Anne Mitchell, Winkler County, Texas
DISCLOSURE
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Anesthesia Practice Trends:

What is Changing? What Does it Mean?
Robert E. Johnstone, M.D. Morgantown, West Virgina
Overview
Socioeconomic, generational and political forces are changing the organization of anesthesia practice. The changes
include a movement from full-time clinicians practicing primarily within individual hospital departments of
anesthesiology, employed by a corporation they formed that bills patients for anesthetics they administer, and
compensates them on a basis they have set up with their corporate partners. The movement is towards flexible work
arrangements for clinicians; multiple employers; integration of anesthesia care within multi-institutional and multi-
specialty systems; compensation mechanisms that include quality and other performance measurements; and fewer,
larger, more dominant, evolving hospitals within markets. Individual anesthesiologists often find these changes
surprising, disruptive, and threatening. Understanding the drivers of these changes and what is valued in new
practice arrangements facilitates adapting to them. Individual anesthesiologists can find much benefit and personal
satisfaction among the choices of newer practice arrangements.
Trend: Demand for anesthesia services is increasing, with more anesthetics administered outside
traditional surgical suites
The demand for anesthesia services is increasing as more surgery is being done per year, anesthesia is needed for
more procedures outside the surgical suite, and anesthesiologists assume broader roles within institutions.
Anesthesia demand for endoscopic procedures has remained high, while cosmetic surgeries, largely office-based, are
recovering from the economic recession. The American Society of Plastic Surgeons reports 13.8 million cosmetic
procedures in 2011, of which 1.6 million were cosmetic surgeries. Anesthesiologists are increasingly involved in
office-based surgeries and procedures. Groups generally cannot provide anesthetics outside surgical suites with the
same efficiencies that they can within surgical suites, further increasing the demand for anesthesia practitioners.
A recent search of gaswork.com, the largest internet listing of open positions for anesthesia practitioners, showed
679 positions for anesthesiologists and 573 for nurse anesthetists.
Rand Corporation in a 2010 study predicted a shortage of 4,479 anesthesiologists and a surplus of 7,970 nurse
anesthetists in 2020. 1
Trend: Percentage of mid-level anesthesia providers is increasing

The membership of the American Society of Anesthesiologists is 47,000, while the membership of the American
Association of Nurse Anesthetists is 40,000. Estimates of the number of anesthesiologists and nurse anesthetists
currently practicing are 40,000 each. Approximately 1600 residents in anesthesiology and 2500 nurses in anesthesia
training programs finish each year and enter practice. The membership of the American Academy of
Anesthesiologists Assistants is approximately 1000, with approximately 200 per year expected to finish training for
the next few years. Although anesthesiologists currently constitute 50 percent of anesthesia practitioners, this
percentage seems likely to decline towards 40 percent over the next decade as more mid-level providers than
anesthesiologists enter practice. This change will facilitate the practice of anesthesiology in team or medical-
direction modes.
Trend: More anesthesiologists are working less than full-time

A 2011 survey of physicians performed by Cejka and the American Medical Group Association identified 22
percent of male physicians and 44 percent of female physicians as working less than full-time, up from 7 and 29
holders.
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percent in a similar 2005 survey.2 The survey authors related this to two of the fastest growing demographics – men
near the end of their careers and women at the beginning or middle. The desire of these groups and others for part-
time work, combined with the strong market for anesthesiologists, has led groups recruiting new members to
become more flexible in work arrangements.
Anesthesiology practice is more complex and demanding than ever before, and many physicians feel “burned out”
with full-time practice. 3
Locum tenens is an increasingly popular mode of practice, with national companies that specialize in locums
placements facilitating entry into this practice mode. Three in four healthcare organizations used temporary
physicians during the last year, and a survey by Staff Care, a locums staffing company, found 41 percent of
healthcare organizations currently looking for temporary physicians.
Trend: Hospital employment of anesthesiologists is increasing

Hospitals are acquiring primary and specialty practices and employing physicians to position themselves better
under various emerging payment scenarios, especially those that favor integration of care. Hospitals that employ
anesthesiologists may be able to control costs and improve quality better than through contracting with independent
groups, thus positioning themselves to compete for greater market shares and profits.4 Large dominant hospital
systems have more power to negotiate high payment rates.5 Hospitals are merging at an increasing rate to achieve
better bargaining positions. A consulting firm valued the top 10 hospital mergers in 2011 at $5.6 billion, up from
$3.8 billion in 2010.6
Many anesthesiologists find employment with large institutions more secure than with small contracted groups. For
anesthesiologists, who are already hospital-based, direct employment may represent less of a culture change than for
other specialties. Those accepting hospital employment can generally expect a shift from a guaranteed salary to
incentive-based compensation linked to productivity and clinical behavior, with base compensation that is lower
than their previous earnings but incentives that can increase it to that level or higher.4 Employment of
anesthesiologists is a logical extension for hospitals from contracted group subsidization that has reached a point
where employment would not cost much more. Subsidization of groups had reached 80 percent of hospitals by
2007,7 and grown to $109,000 per faculty member by 2008.8 Many arrangements for hospitals to support and direct
anesthesiology groups are possible, and may succeed.9
A recent Price Waterhouse Institute survey reported 46 percent of physicians are interested in hospital employment.6
Ultimately hospitals or ambulatory surgery centers that gain sufficient market clout can pressure anesthesiologists to
accept employment in entities with which they contract for services and then pay the anesthesiologists less than the
revenue they generate. Some of these arrangements are abusive and may be illegal. Under a “company arrangement”
for ambulatory surgery centers anesthesiologists are forced to share a portion of their professional fees with the
owners of the ASC in order to obtain access to their patients.10
Trend: Healthcare reform is changing the organization and priorities of anesthesia practices
Healthcare reform legislation has led to the increasing roll-out of federal regulations. Physicians have many
requirements under these regulations, e.g. the adoption and use of electronic health records, prescribing of
medications electronically, upgrading of payment claims and refund systems, and reporting of practice quality
information. The frequency and diversity of these regulations makes implementing them difficult, while the rewards
and penalties associated with them makes failing to implement them costly. Federal regulations are thus a driver of
practice consolidation to achieve adequate size, expertise and capital to implement new regulations.
holders.
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High healthcare costs are driving reform, and spurring payment innovation. In 1950, health expenditures accounted
for only 4.6 percent of United States gross domestic product, while in 2009, they accounted for more than 17
percent.11 A perceived cause of the high costs is lack of coordination among healthcare providers with waste of
resources. Innovation is thus focused on new models that improve coordination and efficiency, such as accountable
care organizations and bundled payment programs. The American Society of Anesthesiologists has endorsed a
perioperative or Surgical HomeTM model where anesthesiologists coordinate and manage surgical patients to reduce
complications and improve efficiencies and cost-effectiveness of perioperative care.12 A nascent trend is thus for
anesthesiologists and practices to assume more responsibility throughout the perioperative process.
Another result of the increasingly difficult economic and political situation for healthcare is that the number of
hospitals in the United States is decreasing. This means fewer competing institutions in some markets, and is another
driver for larger groups. The hospitals closing or being acquired by mergers are frequently critical access hospitals,
those with 25 in-patient beds or fewer. Some of these hospitals are staffed only by nurse anesthetists, and after
closure their patients are cared for in larger institutions where anesthesiologists direct care.
Trend: New technology is leading to more specialization and increasing compensation for
subspecialists
Ultrasound guidance of nerve blocks, catheter placements for continuous pain therapy, echocardiographic imaging
of cardiac function, and real-time use of digital information for decision support are examples of desired skills for
anesthesiologists. Recruitment and retention of anesthesiologists with these skills has increased the value of younger
and fellowship-trained physicians. Many practices pay bonuses for these skills and have reduced or eliminated the
traditional increase in incomes for practice longevity.
Trend: Anesthesia practices are growing in size, and expanding nationally

More than fifteen anesthesia practices in the United States exceed 500 clinicians or work in three or more states. 13
Three national anesthesia practices are publicly traded companies, seeking acquisition and growth opportunities.
Anesthesiologists joining these national practices generally express satisfaction with them.
Trend: Business skills are increasingly valued in anesthesiology practices

Payers are focusing on costs and quality, requiring practices to justify their payments. Practices that lead in these
areas have a market advantage. This requires a multitude of skills in practice leaders, including strategic analysis,
budgeting, managing, communicating and technology use. These skills are learned in business and management
courses, and practices seek members who have them in addition to anesthesiology knowledge.
Anesthesiologists with MBA degrees are increasingly common. The ASA offers a Certificate of Business
Administration course that approximately 100 anesthesiologists per year attend. Attendance at the ASA Practice
Management Conference is increasing annually, with more than 800 present in 2011.
References
1. Kumar K. An Analysis of the Labor Markets for Anesthesiology. RAND Corporation. 2010
2. Elliott SE. Demographics driving more flexible schedules. Amer Med News 2012 (Apr 9)
3. Singleton MA. Part-time work: Advantage to everyone. ASA Newsletter 2007; 71(4):13-4
4. Kocher R, Sahni NR. Hospitals’ race to employ physicians – The logic behind a money-losing
proposition. N Engl J Med 2011; 364:1790-3
5. Berenson RA, Ginsburg PB, Christianson JB, Yee T. The growing power of some providers to win
steep payment increases from insurers suggests policy remedies may be needed. Hlth Affs 2012;
31(5):973-81
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6. Five core concepts for healthcare providers this year. Becker’s Hospital Review 2012; 2012(2):7
7. Bierstein K. Anesthesiology practice costs, revenues and production survey data. ASA Newsletter
2007; 71(4):32-3
8. Kheterpal S, Tremper K, Shanks A, Morris M. Seventh and eighth year follow-up on workforce and
finances of the United States anesthesiology training programs: 2007 and 2008. Anesth Analg 2009;
109:897-9
9. Hill LL, Evers AS. Hospital support for anesthesiology departments: Aligning incentives and
improving productivity. Acad Med 2012; 87:348-55
10. DeMuro PR, Lauer KA, Huston BE. Profiting from anesthesia services: An analysis of emerging
compensation arrangements between ambulatory surgery centers and anesthesiologists. CCH Hlth Care
Compl Ltr 2010 (Mar 23):4-7
11. Fuchs VR. Major trends in the US health economy since 1950. N Engl J Med 2012; 366: 973-7
12. Warner MA. The Surgical Home TM. ASA Newsletter 2012; 76(5):30-2
13. Maccioli G, Johnstone RE. Very large and multistate anesthesiology practices. ASA Newsletter 2010;
74(5): 12-4
DISCLOSURE
Anesthesiology News, Self, Honoraria
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Chemical Dependency and Anesthesiology
John Tetzlaff, M.D. Cleveland, Ohio
The discovery of anesthesia and addiction to the drugs used to provide anesthesia have a common origin. Cocaine
had a social use profile before its incidental discovery as a topical anesthetic. Experiments with injection of cocaine
to anesthetize plexus and peripheral nerves led to addiction of early 20th century master surgeons, such as Halsted,
who performed the experiments. (1) Early experimentation with ether, nitrous oxide and chloroform also caused
psychological and even physical addiction. It is not surprising, therefore, that addiction to anesthetic drugs and
anesthesiology remain linked and that addiction remains the most prevalent, serious occupational health risk
associated with anesthesia. Because of the morbidity, much is known.
Scope of the Problem

Although addiction to anesthetic drugs has become a prominent issue for anesthesiology in the United States, this
issue is neither new nor restricted to the USA. In an early report, Bruce(2) reported on the mortality and causes of
death of anesthesiologists, noting lower death rates in most categories, except suicide, which was three times the rate
for other physicians (1947-66). Lew (3) reported similar data (1954-76), with lower overall age-adjusted mortality,
except for 6.2% suicide (2 times normal) and 6.9% “accidental”. Although the suicide rate is higher in general for
physicians (4), suicide in anesthesia providers is highly associated with addiction. (5) Ward (6) surveyed residency and
nurse anesthesia programs for 10 years prior to 1982. With a 74% response rate, the incidence of addiction was 1%
per year of giving anesthesia for the first five years. Gravenstein (7) reported the same 1% addiction rate with an
alarming mortality of 7 providers out of 44 reported. The issue is also not restricted to the United States. Berry(8)
survey 304 departments of anesthesia in the United Kingdom and Ireland and found cases in this interval (1990-99)
in 39% of departments reporting (71.7% response rate) and drew the remarkable conclusion that one anesthesia
provider per month in the United Kingdom was disabled by addiction. Weeks reported a comparably high incidence
for Australia and New Zealand (51). The risk is not limited to physician anesthesiologists, with comparable or higher
rates in CRNAs, with as high as 10% risk for a full career. (9)
Even though the issues are now well known and education/prevention steps are widely in use, the incidence has not
seemed to change. Booth(10) surveyed 133 programs in 1997, achieved a 93% response rate, and reported 1.6%
addiction rate in residents and 1.0% in faculty, despite 47% of respondents reporting increased education and steps
to prevent diversion of controlled drugs. Collins(11) surveyed 176 programs (M.D. and D.O.), achieving a 66%
response rate, with 80% of responding programs reporting at least one incident in the interval (1991-2001) with 19%
reporting mortality. If anything, the mortality may actually be increasing, by comparison of the Collins (11) data for
the 1990’s with the 10% mortality reported by Spiegelman. (12)
Speculation about the Cause

While there will never be absolute proof, there is a consensus that a variety of issues combine to create a high risk of
addiction. These include exposure to the drugs, familiarity with their pharmacology, access, stress and the uniquely
addictive properties of anesthetic drugs. Prior addictive and high risk behaviors seem to be highly associated.
Chemical experimentation in medial students has been reported (13) be 30-50%, and several reports have suggested
that prior illicit drug use may motivate (consciously or unconsciously) the individual to choose anesthesia. (11, 14) In
a large series, high risk behavior was found to be highly predictive of addiction. (15)
Occupational exposure seems to be a clear association. As previously mentioned, early experiments to create safe
anesthesia techniques (nitrous oxide, ether, chloroform, cocaine) created victims of addiction in the investigators.
The high incidence identified is even more remarkable when the early presentation of addiction is considered. In
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both physicians and CRNA, the incidence of addiction is highest during the first 5 years of giving anesthesia. (6, 16, 17,
18, 52)
There is other suggestive evidence that the risk is giving anesthesia. Oral surgery residents in some
maxillofacial residency programs receive extensive training (often from anesthesiologists) in giving anesthesia, and
they report the same incidence of addiction proportionate to time in anesthesia with the same drug profile. (17) The
converse is equally true- physicians who do not practice anesthesia (internists) have a lower rate of addiction and
suicide compared to an age and gender matched cohort of anesthesiologists (53).
Simply experiencing clinical anesthesia alone is too simple of an explanation for the risk of addiction. Gold has
presented a provocative hypothesis that aerosol contact with fentanyl during opening of fentanyl ampoules(1) or from
exhaled breath of patients(72) or contact with fentanyl or propofol from working surfaces within the operating room
(77)
may cause neurochemical changes in the brain that predispose some providers to become addicted (73). They
confirmed this hypothesis by detecting fentanyl and propofol in the air in several locations within active operating
rooms (78). The ASA Committee on Occupational Health has responded with the observation that exposure to
fentanyl as a cause is preliminary data that should be further evaluated, citing a variety of methodological issues. (57)
The neurochemistry of addiction is becoming well understood, with chemical changes in the reward centers leading
to exaggerated need for drug acquisition, and exaggerated reward from experience with the drug.89 Another possible
explanation is a lower density of dopamine receptors in reward centers, resulting in less reward from natural
reinforcers. 91, 92 A molecular mechanism for the sensitization has been suggested by Kovacic, who reports that
addictive substances have in common the ability to create reactive oxygen species (ROS) that result in electron
transfer that activates brain reward centers (80). Further work has established that metabolites of propofol and
fentanyl create these ROS messengers (81).
Other elements of anesthesia practice that contribute to addiction are less objective but undisputed. The anesthesia
provider is unique in organized medicine in providing “start-to-finish” administration of controlled substances.
Even the most junior resident will obtain-fentanyl, draw it up, decide to inject, observe the effect, chart the
intervention and handle the accounting of waste, often without any observed assistance. No other resident routinely
has this experience or possesses these skills. New anesthesia providers also rapidly learn the clinical pharmacology
of these substances by observation, reading and trial and error. This creates both the skill for self-medication, and
the more ominous skill to achieve painless suicide. Self-medication may be an occupational hazard of the operating
room related to stress and lack of positive reinforcement. New anesthesia providers get a disproportionate level of
the work, their skill level is lower and as a result, their efficiency is low. And the operating room is rough on
newcomers. These factors, combined with some natural curiosity about the drugs being used, create an unfortunate
propensity for anesthesia newcomers to self-mediate. They know how, what to use, and the fallacy in the highly
educated provider is that they can control the experience. Unfortunately, this initiates a cascade of use and addiction
that accelerates at a very rapid rate. Gold (1) reports a case where a single experiment with intranasal accelerated to
injection of 30mL/day of sufentanil within 30 days. In the context of high stress, reduced self-esteem and
availability of synthetic opioid, Ward (18) states that control is gone after the first self-medication even though the
individual doesn’t know it. Farley (19) identifies other unique element of anesthesia practice, including a “chemical
solution” to solving problems, and the isolated nature of anesthesia practice. Moleskin (20) further speculates that
routine use of controlled substances minimizes the importance of tight accounting, desensitizing the individual to its
relevance.
Other features may be triggering events for the subset of providers. Prior experience with substance abuse or high
risk behavior has been previously identified. A prior history of psychiatric illness (contributory or coincident) can
be contributory in the addicted anesthesia provider. (15, 16, 21) Personality disorders (74) and primary psychiatric
diagnoses (75) are commonly found in addicted physicians, and self-medication may represent a response to these
symptoms. (76) Depression is known to be associated with suicide, and although complicated, may be linked to self-
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medication and addiction (82). There is strong evidence for a genetic susceptibility to addictive behavior, especially
the transition from abuse to dependency.88
Drugs Involved in Addiction for Anesthesiologists

From the substance abuse literature, the progression of substance (ETOH to marijuana to cocaine) is a common
observation. Addiction within anesthesiology does not follow this pattern. Although the incidence of addiction to
drugs used in anesthesia is alarmingly high, the incidence of abuse of illicit drugs (alcoholism, THC, cocaine) is
low. Addiction within anesthesia has always focused on anesthetic drugs. Prior to 1980, the drugs involved were
meperidine, diazepam, and barbiturates.(22.23) After 1980, addiction has been heavily concentrated in the fentanyl
family (6,10,17,19) Although parenteral fentanyl is the rule, severe addiction to oral fentanyl has been reported,
although the victim was a nursing supervisor who lacked some of the parenteral administration skills.(24) Although
rapid metabolism would seem to make parenteral remifentanil abuse seem unlikely, intranasal self-administration
has been reported as the entry point to a fentanyl addiction (79). Midazolam(17) and ketamine(25) have been reported in
addiction cases, as has nitrous oxide(54) and potent inhalation agents, such as enflurane.(26) In a survey of academic
departments, 22% reported at least one incident with an inhaled agent with less than half of the individuals involved
entering rehabilitation, less than 30% return to practice, and a 26% mortality rate.(64) Propofol is the newest player
on the scene with one case report(27) involving injection to unconsciousness up to 15 times per day. In a survey of
academic anesthesiology programs from 1995-2005, Wischmeyer reported 18% of programs had a propofol abuse
incident with 28% of the cases detected by death.(71) Repeated, prior exposure to propofol may be causative, with
experience of the euphoria leading to intense craving and psychological dependence. 94, 95, 96
The addiction potential with anesthetic drugs has been reviewed. Propofol has been tested in volunteers and found
to have properties associated with addiction,(27) although the pharmacokinetics predict a difficult abuse pattern,
requiring either pump infusion or frequent, intermittent injection. The addictive potential for other uncommon
substance has been predicted based on the side effect profile, (28) including local anesthetics (dysphoria), cocaine
(euphoria, stimulation), anticholinergics (psychotomimetic), antihistamines (sedation) and ephedrine (stimulant).
Ketamine has an obvious role in those with prior psychotropic drug use, such as LCD, or PCP. (25, 29)
Detection
Unfortunately, self-reporting of serious addiction is uncommon. Direct observation of abuse and audits that confirm
suspicion are the most common means of detection. Unfortunately, suicide, accidental death and coma combined
are more common than self reporting.(19) Suicide during evaluation of possible addiction is a serious issue.(30)
Intervention must be conducted carefully, with the goal of getting the suspected addict into a safe treatment facility,
using progressively increasing motivators like reporting, termination, and as a last resort, police involvement. In
one case, the cause of death was determined to be propofol by hair analysis where blood and urine toxicology were
negative.(31) In cases where suspicion is high and urine toxicology is repeatedly negative, hair analysis has
detected addiction to fentanyl, sufentanil, and alfentanil (55). Detection of drugs with brief half-lives such as
ketamine, midazolam and propofol are difficult or impossible in routine toxicology(27,32) and may require either
observed abuse and rapid “for cause” screening, or hair analysis.(33,55) The fentanyl family is especially difficult to
detect because of the brief plasma half-life and non-detection of metabolites.(24,34) A computer profile of drug use to
detect outliers might be a better approach.(35) Epstein has prospectively applied this computer profile, and
demonstrated that it detects diversion months before clinical detection, although its sensitivity needs to be refined
before it becomes a first line tool, due to false positives. 87 Another electronic approach, using run charts comparing
individual use against time to identify upward trends in individuals, also shows promise.90 A promising opportunity
for detection of propofol abuse is a urine assay for detection of the glucuronide metabolites of propofol, present in
the urine for up to 3 days after exposure.
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Re-entry
Addiction is a disease as well as a federally protected disability, as long as the addict remains in treatment. (67)
Treatment only succeeds when evaluation reveals addiction and the victim is able to fully acknowledge their
addiction. This is rarely (if ever) successful without in-patient treatment, graded re-entry with a contract, handling
of addictive substances by other providers, and random testing, including periodic hair samples.
Even with the risk, a simple majority of providers will want to re-enter anesthesia. The outcome, however, is not
always promising. In general physicians have a better outcome in rehabilitation from addiction than non-physicians
(36)
even from opioid (prescription) abuse. (60) The California Physician Diversion Program’s data suggests that this
also applies to addiction involving anesthesiologists, although their definition of recovery may be very generous.(37)
Some other data is in agreement,(38) however there is also evidence that re-entry is both ineffective and risky.
Collins reports a 40% failure rate with re-entry of residents and 9% mortality. Re-entry for student nurse
anesthetists has the same poor prognosis.(39) Merk reports 34% successful re-entry for residents with 13 having the
first presentation of relapse as death.(40) Bryson(58) reported a graded re-entry of residents involving work in a
simulation center for the first 12-15 months prior to re-entry. The value of this approach has been challenged (59) in
light of the 60% relapse rate they report, and there remains a serious doubt that re-entry is ever the right choice for a
resident (67). The failure rate, the cost to the department with attempted re-entry, and the mortality rate led Berge (68),
in an editorial in Anesthesiology, to advocate “one strike and you’re out”, a universal prohibition to re-entry.
Oreskovich (69) and others responded to this strong position with circumstances where this would be excessive and
highlighted the role of the highly effective state Physician Health Committees (PHC). It may be that the resident
failure rate is related to the less universal role of PHC in the re-entry of residents.
Hedberg (41) has attempted to quantify the process by defining criteria that predict success and failure with re-entry.
He has divided anesthesia providers in rehabilitation into three categories based on specific criteria, with category
two needing delay and re-evaluation after one to two years and category three being individuals who should never
practice anesthesia. Domino reports greatly increased risk of relapse when there is a coexisting psychiatric disorder,
family history of substance abuse, or in those addicted to opioid, with the increase even greater if more than one of
these risk factors is present(56). Re-entry may actually oppose the process of recovery by re-exposing the addict to
the visual, olfactory or physical cues to the emotions that triggered self-medication, and also may explain why
delayed re-entry is required (65). If re-entry is attempted, the focus should be on prevention of relapse (84). There is
even risk of relapse from subsequent required medical care, if exposure to triggering substances (opioids, propofol)
is required for medical or surgical care. 93
Prevention
There is universal agreement that mandatory education about the risk of substance abuse, stress and fatigue
management should be a part of all anesthesia training programs at the entry point and regularly thereafter. There is
also general agreement that this education process should continue beyond residency, although this is less
universally applied. Despite evidence that the majority of training programs have increased their education
programs, Booth (10) reports no change in the incidence of substance abuse. Previous reports of inadequate education
(42)
have created the education but not decreased the risk. Increased effort to prevent the diversion of controlled
substances has also been instituted in a majority of programs (10, 43) including locked boxes, dispensing machines,
video surveillance and satellite pharmacies. Some effect has been observed, including reduced controlled substance
discrepancy. (20) Electronic data analysis can reveal average user profiles, and provide detection via outliers. (20, 35)
The subject of random drug testing is controversial (83). The almost infinite number of ways to tamper with urine
toxicology screening must be considered.(70, 86) Although a promising avenue in the future, detection of anesthesia
drugs in oral fluid is not possible at this time (85). In responses to the survey of Booth, (10) a majority of chairs favored
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random testing, although only two programs outside the military have instituted such a program. Fitzsimons (61)
presents the first five years of one of these programs designed to prevent addiction which includes a random testing
element, and reports no addicted providers detected. The Department of Transportation (DOT) has had a random
screening program for almost two decades for commercial drivers, railroad and airline pilots. Industry has followed,
with more than 90% of companies with more than 5000 employees having some kind of testing. (44) Random testing
programs have been shown to reduce positives (45) and save health care dollars. Mike Scott, previous council to the
ASA, has written a review of random testing, (46) in which he identifies the AMA endorsement of “for cause” testing
and discusses the unresolved legal issues with random testing. Although random testing is prohibited in 12 states,
there are exceptions for industry involved in safety. Concerns by the AMA are expressed in an editorial which
discusses privacy, handling of false positives, confidential records and the approaches to randomization.(47) DOT
rules have created the need for the role of a Medical Review Officer, a physician with specific training to handle the
initially positive screen.(48) All recovering physicians are subject to random screening during recovery and any
failure or absence requires action.(49) Collins (11) data reveals a slightly higher rate of pre-employment screening
(16%) and pre-employment toxicology screening. Based on the kind of data in Men’s Health(50) ( “the Junkie in the
OR”) and two recent cases that made headline news in the press on the East Coast, the lay public may begin to
demand random screening. It is clear that detection during residency training is a responsibility of the residency
program.(62) Failure to report provider impairment may incur legal liability for the anesthesia department, the
hospital or anesthesia groups who know.(63) Regardless of the legal risk, protocols for handling of impairment and
substance abuse should be present in every department.(66)
Conclusion
Substance abuse is the most serious occupational safety hazard for anesthesiology. Causing devastating
consequences to the career, morbidity, personal stress and death, it is a high attractive target for prevention. The
nature of anesthesia (working alone, production pressure, isolation) and the handling of highly addictive drugs are
contributors. Up to 1% per year of residents may become addicted. The mortality rate of relapse may approach 9%.
Prevention by education, tight control of controlled substance use, profiling for outliers and possibly random urine
toxicology may be needed to arrest this serious hazard of providing anesthesia.
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treatment. Harv Rev Psychiatr 2008;16:181-94.
61. Fitzsimons MG, Baker KH, Lowenstein E, Zapol WM. Random drug testing to reduce the incidence of
addiction in anesthesia residency: preliminary results from one program> Anesth Analg 2008;107:630-5.
62. Aach RD, Girard DE, Humphrey H, McCue JD, Reuben DB, Smith JW, Wallenstein L, Ginsburg J.
Alcohol and other substance abuse and impairment among physicians in residency training. Ann Int Med
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63. Liang BA. To tell the truth: potential liability for concealing physician impairment. J Clin Anesth
2007;19:638-41.
64. Wilson JE, Kiselanova N, Stevens Q, Lutz R, Mandler T, Tran ZV, Wischmeyer PE. A survey of
inhalational anaesthetic abuse in anesthesia programmes. Anaesthesia 2008;63:616-20.
65. Wilson H. Environmental cues and relapse: an old idea that is new for reentry of recovering anesthesia
professionals. Mayo Clin Proc 2009;84:1040.
66. Berge KH, Seppala MD, Schipper AM. Chemical dependency and the physician, Mayo Clin Proc
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67. Bryson EO, Silverstein JH. Addiction and substance abuse in anesthesiology. Anesthesiology
2008;109:905-17.
68. Berge KH, Seppala MD, Lanier WL. The anesthesiology community’s approach to opioid and anesthetic-
abusing personnel: time to change course. Anesthesiology 2008;109:762-4.
69. Oreskovich MR, Caldeiro RM. Anesthesiologists recovering from chemical dependency: can they safely
return to the operating room? Mayo Clin Proc 2009;84:576-80.
70. Jaffee WB, Trucco E, Levy S, Weiss RD. Is this urine really negative? A systematic review of tampering
methods in urine drug screening and testing. J Substance Abuse Treatment 2007;33:33-42.
71. Wischmeyer PE, Johnson BR, Wilson JE. A survey of propofol abuse in academic anesthesia programs.
Anesth Analg 2007;105:1066-71.
72. Gold MS, Meljer RJ, Dennis DM, Morey TE, Bajpain LK, Pomm R, Frost-Pineda K. Fentanyl abuse and
dependence: further evidence for the second hand exposure hypothesis. J Addict Dis 2006;25:15-21.
73. Mohar AR, Yao WD, Caron MG. Genetic and genomic approaches to reward and addiction.
Neuropharmacology 2004;47:101-10.
74. Nance EP, Davis CW, Gaspart JP. Axis II co-morbidity in substance abusers. Am J Psychaitr
1991;148:118-20.
75. Udel MM. Chemical abuse/dependence: physician’s occupational hazard. J Med Assn GA 1984;73:775-8.
76. Markov A, Kosten TR, Koob GF. Neurobiological similarities in depression and drug dependence: a self
medication hypothesis. Neuropharmacology 1998;18:135-74.
77. Merlo LJ, Goldberger BA, Kolodner D, Fitzgerald K, Gold MS. Fentanyl and propofol exposure in the
operating room: Sensitization hypotheses and further data. J Addict Dis 2008;27:67-76.
78. McAuliffe PF, Gold MS, Bajpain L, Merves ML, Frost-Pineda K, Pomm RM, Goldberger BA, Melker RJ,
Cendan JC. Second-hand exposuere to aerosolized intravenous anesthetics propofol and fentanyl may cause
sensitization and subsequent opiate addiction among anesthesiologists and surgeons. Medical Hypotheses
2006;66:874-82.
79. Levine AI, Bryson EO. Intranasal self-administration of remifentanil as the foray into opioid abuse by an
anesthesia resident. Anesth Analg 2010;110:524-5.
80. Kovacic P. Unifying mechanism for addiction and toxicity of abused drugs with application to dopamine
and glutamate mediators: electron transfer and reactive oxygen species. Medical Hypothesis 2005;65:90-6.
81. Kovacic P. Unifying electron transfer mechanism for addiction involvement by the anesthetic propofol.
Med Hypotheses 2010;74:206.
82. Rose GL, Brown RE. The impaired anesthesiologist: not just about drugs and alcohol anymore. J Clin
Anesth 2010;22:379-84
83. Donohoe M. Urine trouble: Practical, legal, and ethical issues surrounding mandated drug testing of
physicians.
84. Carcini AJ, Christo PJ. Physician impairment: is recovery feasible? Pain Physician 2009;12:487-91.
85. Pil K, Verstraete A. Current developments in drug testing in oral fluids. Ther Drug Monit 2008;30:196-202.
86. Dasgupta A. The effects of adulterants and selected ingested compounds on drug-of-abuse testing in urine.
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87. Epstein RH, Gratch DM, McNulty S, Grunwald Z. Validation of a system to detect scheduled drug
diversion by anesthesia care providers. Anesth Analg 2011;113:160-4.
88. Hiroi N, Agatsuma S. Genetic susceptibility to substance dependence. Mol Psychiatry 2005;10:336-44.
89. koob GF, Volkow ND. Neurocircuitry of addiction. Neuropsychopharacology 2010;35:217-38.
90. Chisholm AB, Harrison MJ. Opioid abuse amongst anaesthetists: a system to detect personal usage.
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91. Volkow ND, Fowler JS, Wang GJ. The addicted human brain: insights from imaging studies. J Clin
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92. Volkow ND, Fowler JS, Wang GJ. The addicted human brain viewed in light of imaging studies: brain
circuits and treatment strategies. Neuropharmacology 2004;47:3-13.
93. Hamza H, Bryson EO. Exposure of anesthesia providers in recovery from substance abuse to potential
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94. Welliver M. Propofol alert. Gastrointestinal Nursing 2011;34:398-99.
95. Koopmann A, von der Goltz C, Hermann D, Keifer F. Propofol addiction initiated by anesthetic use. Am J
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97. Bryson EO, Hamza H. The drug seeking anesthesia care provider. Int Anesth Clinics 2011;49:157-71.
DISCLOSURE
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Safety and Human Factors in the Operating Room

Keith J Ruskin, M.D. New Haven, Conneticut
Introduction
Effective decision-making, risk management, and teamwork are essential components of patient safety.
Anesthesiologists were among the first to adopt human factors, industrial engineering, and operations research as
part of clinical practice, but other specialties soon followed. A recent editorial highlighted the growing body of
human factors articles in the medical literature (over 140 papers on crisis resource management [CRM]),
demonstrating the growing level of interest in this topic.1 Research in the fields of safety and human factors
continues to evolve, and current interests include the early detection of error-producing situations and the design of
error-resistant systems.2 Using these well developed tools for risk assessment, judgment, and decision making may
help to make the operating room a safer place.
Safety
The operating room is a complex environment in which critical events can happen without warning.
Anesthesiologists are frequently required to make decisions quickly, with incomplete information, in an
environment that is intolerant of errors. At any time, one or more factors, including patient illness, the surgical
procedure, or equipment malfunction, may combine to cause a life threatening condition. For example, rolling a
surgical microscope over the anesthesia gas machine’s evacuation hose can cause barotrauma and a tension
pneumothorax within minutes. Although accidents and “near misses” in the operating room are relatively
uncommon on an individual scale, thousands of adverse events occur throughout the United States annually.
Effective decision-making, risk assessment, and risk management are therefore essential components of patient
safety.
Deviations from safe practice can be divided into errors, which are unintended, and violations, which are
deliberate. Errors can be caused by unfamiliarity with a given task, external pressures such as production pressure,
or systemic problems such as a poor human-system interface or fatigue due to extended work hours. Errors can
occur as a result of improperly formed plans (mistakes) or while implementing plans (slips of action or lapses of
attention). Violations in the operating room are usually the result an attempt to achieve a goal that is incompatible
with safe practice. Although it is tempting to dismiss violations as the actions of “someone else,” even the most
dedicated physician may deviate from safe practice for a seemingly plausible reason. Skipping a few tasks on the
anesthesia machine checkout in order to get a case started on time, for example, might please the hospital
administration but increases the risk of an equipment malfunction at a critical point in the procedure. Violations may
be caused by inadequate supervision, workplace conflicts, poor morale, a perceived lack of concern by supervisors,
and the lack of an institutional safety culture.
Systemic failures, or latent errors, may go undetected for months or years. Latent errors can be caused by
failures in equipment design and maintenance, staffing shortages or inappropriate staffing, communication failure,
and lack of training. Improperly developed procedures (for example, a poorly developed time out that does not
specifically address the laterality of the surgery) may ultimately result in an adverse event. Latent errors may be the
result of conflicting institutional, surgical, and anesthetic goals. This may be due to improper planning and
organization, or from simply not having an anesthesiologist on the appropriate hospital committee. For example, the
nursing staff or surgeon may pressure the anesthesiologist to bring the patient into the operating room on time,
which prevents the anesthesiologist from verifying that the necessary patient workup has been completed.
Production pressure and fatigue are examples of systemic problems that affect patient safety. In one study,
647 California anesthesiologists were asked how production pressure affected their practice. Nearly all reported that
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there was an overt pressure to proceed with cases, while 49% admitted to making errors as a direct result of
production pressure. Errors included inadequate monitoring, elective surgery without an appropriate patient workup,
and surgery despite contraindications.3 Fatigue plays a role in both violations and errors. Simply being tired
predisposes to mistakes. In one study, surgical residents were asked to perform both cognitive and motor tests using
a laparoscopic surgical simulator. Residents who had been on call the night before had a significant decline in motor
skills and made a significant number of cognitive errors. EEG monitoring revealed objective evidence of a
significant decline in performance.6 Working overnight has been associated with a significant increase in the risk of
percutaneous needle injuries. Fatigue and lapses in concentration were the two most commonly cited risk factors.4
Physicians who have gone 24 hours without sleep experienced degradation in judgment that is equivalent to that of a
person with a blood alcohol concentration of 0.1%; this meets the legal definition of impaired driving in many
states. In one study of 1554 emergency medicine residents, 76 residents reported a total of 96 motor vehicle
accidents while 553 residents reported 1446 near collisions on the road. Nearly 80% of accidents and near misses
occurred after the residents had worked the night shift.5 Another study from this group suggests that eliminating
extended-duration work shifts (defined as greater than 24 hours) may significantly reduce the risk of medical errors.6
Human Factors in Clinical Practice

Over the past 20 years, there has been an increased emphasis in implementing human factors and systems-
oriented approaches to organizational safety in health care. Relatively simple interventions can produce significant
improvements in patient safety. For example, a “time-out” procedure assures that all personnel agree on the surgical
procedure and operative site and that everyone is aware of the critical components of the procedure.
Recommendations for improving safety in the operating room include minimizing the number of handoffs during the
procedure so that information is not lost during transfers of care.7 Effective communication is critical to
perioperative safety; steps include team training, making the electronic health record available in the operating
room, and using video cameras to improve situational awareness.7 Standardizing procedures and minimizing the
variety of drugs and equipment where possible help to create an environment that is resistant to error by limiting the
number of choices that a provider must make. Forcing functions (which prevent personnel from taking an action
without conscious consideration), automation, and checklists and double-check systems all help to reduce the
number of errors made in the operating room.
High Reliability Organizations (HROs) have an exceedingly low rate of accidents or incidents despite
accomplishing technically challenging tasks with a high level of intrinsic hazard. Classic examples of HROs include
aircraft carrier flight operations and nuclear power plants. HROs maintain safe operation because of systems that are
designed to maximize a climate of safety.8 Shared values of safety begin with senior management and are
transmitted throughout the workforce. There is ongoing monitoring of performance with frequent, candid
communication among all workers. Instead of being hidden, errors are viewed as an indication of a potential
weakness of the entire system. Failures are reported and extensively discussed, enabling new processes to be
developed that make the entire system more resistant to failure. Although there is no simple recipe for creating an
HRO within the healthcare environment, Christiansen et al have identified several key processes: HROs use failures
as a way to gain insight into the weaknesses of the entire system. They do not simplify or explain away a failure.
They try to understand how all components of the operation fit together and can interact to cause problems. HROs
are resilient; processes are designed to recover from unexpected failures. Lastly, decisions about how to deal with
failures (or potential failures) are made by personnel with expertise in that specific aspect of the operation.8
Becoming an HRO is not the product of a single decision, but rather a coordinated effort that involves a significant
change in organizational culture that must be embraced by everyone from senior management to individual staff.
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Anonymous or confidential reporting of critical incidents can detect latent failures that impact safety. The
Aviation Safety Reporting System, managed by the National Aeronautics and Space Administration, is an
anonymous reporting system used by pilots, air traffic controllers, and mechanics to describe near misses. Reports
are studied for common characteristics and this information and specific recommendations for improvement are
shared with all stakeholders. Each month, NASA publishes an on-line newsletter in which selected reports are
published along with a brief discussion that places the report into context and recommends simple steps to prevent
future occurrences. The Anesthesia Quality Institute was created several years ago to create a National Clinical
Outcomes Registry in order to track anesthesia outcomes nationwide. The data collected will be used for
benchmarking, quality improvement, research, and eventually maintenance of certification. AQI also developed a
near miss registry called the Anesthesia Information Reporting System (www.aqiairs.org) that allows either
anonymous or confidential reporting of near misses in the operating room. In order to protect contributors from legal
action, AQI is now classified as a Patient Safety Organization. This gives information submitted to AIRS the same
legal protections as that discussed at quality improvement conferences. Like the ASRS, cases submitted to the
database will be studied and reported, most likely in a recurring feature in the ASA Newsletter.
Anesthesia Decision Making

Crisis Resource Management is a series of techniques for managing critical events in the operating room
that was developed by Gaba et al over 20 years ago.9 It is based on Crew Resource Management techniques
originally developed by the airlines, and stresses management and use of collective resources that are readily
available. Operating room resources include personnel, equipment, and cognitive aids such as the medical record,
handbooks, and online references. A well-formulated anesthetic plan as well as generalized plans for critical events
can help to guide initial management of a problem. Checklists may be used to increase certainty that critical steps
are not missed. Team training is essential to improve communication and the ability to work together when things
are not going well. Whenever possible, the team leader should delegate tasks in order to avoid becoming fixated on a
single component of patient management. Lastly, it is important to use all available information. Even though the
team leader is ultimately responsible for making decisions, other people in the room often have critical information.
It is important to solicit this information whenever possible.
Vigilance is the motto of the American Society of Anesthesiologists, and anticipating critical events before
they occur will make successful resolution more likely. Situational awareness can be defined as maintaining
awareness of the entire environment while attending to a single problem.10 It can also defined as knowing where you
are, where you are going, and everything that is going on around you. In the operating room, this means being aware
of the surgeons’ actions and the most likely complications of the procedure at that moment, the nurses’ actions, the
equipment’s status and function, and, most importantly, the patient’s condition. Situational awareness is a skill that
can be taught. Carbo et al reported a “Code Blue” simulation in which the providers became so focused on the
“patient’s” tachycardia that the airway was neglected. The debriefing from this simulation stressed the importance of
a shared mental model that would allow team members to divide tasks and more efficiently coordinate their
actions.10
Although anesthesiologists are told early in their training to maintain vigilance, few if any receive formal
training on how to maintain rapidly evaluate a situation and make the best decision. Human factors specialists
working with the Federal Aviation Administration have developed a series of practical decision-making and risk
management tools for pilots. These models are essentially thought process checklists, and can be applied to many
elements of clinical practice. One such model is called 3P, for “Perceive, Process, Perform.” The 3P model is a
structured, efficient, and systematic way to identify hazards, assess risk, and implement risk controls that are
effective. Using this model, one first perceives that there has been a change in the patient’s course. He or she then
processes the information to create a strategy to eliminate or mitigate the hazard. The last step is to perform the
actions necessary to solve the problem. At that point, one returns to the Perceive step to determine whether the
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intervention worked. By constantly following these steps, an anesthesiologist can detect a problem, take the steps to
solve it, and then, most importantly, determine whether the solution actually fixed the problem. [Federal Aviation
Administration. System Safety Course Developers’ Guide.
http://www.faa.gov/training_testing/training/fits/training/flight_instructor/media/Volume2.pdf Accessed 11 July 2012.]
The ability to constantly evaluate and manage risk is critical to patient safety, but anesthesiologists receive
little training in risk assessment. Risk can be defined as the exposure to the possibility of loss, injury, or other
adverse circumstance. (Oxford English Dictionary) This definition can be further expanded to include the
probability and severity that an injury will occur because of an exposure to a given hazard. Risk management is a
formal method of evaluating the probability that a given hazard will occur and then formulating a strategy for
minimizing the exposure, decreasing the possibility or severity of an adverse outcome, or making a decision to avoid
the hazard altogether.11
Communication is critical to safe patient care. Unfortunately, the traditional medical hierarchy creates an
environment in which lower ranking members of the team (e.g., junior residents and medical students) are reluctant
to speak when they see a problem. In one case series, for example, medical students who were in a position to
prevent medical errors sometimes hesitated to identify the hazard to operating room personnel. Mistakes seen by
medical students and missed by residents or attending staff included contamination of a sterile field, medication
errors, and a failure to implement respiratory precautions in a patient with a presumed diagnosis of tuberculosis. In
some of these cases, the medical student who observed the error was afraid to speak up for fear of retribution.12
Reports such as these underscore the importance of listening carefully to all members of the team and creating an
environment where team members will call attention to problems.
A variety of tools are used to improve team communication. One such model is SBAR, which stands for
“Situation, Background, Assessment, Recommendation.” Using this paradigm, a provider can briefly state the
situation (“The patient is hypotensive and tachycardic.”), background (“The surgical blood loss is greater than
anticipated.”), assessment (“I believe that the patient is hypovolemic.”), and recommendation (“We should
administer additional fluids and check a hematocrit.”). Although the effectiveness of this technique has not been
studied in the operating room, it has been shown to improve the effectiveness of communication on a busy pediatric
service that included a general ward, a labor and delivery suite, and a pediatric intensive care unit.13 United Airlines
developed a “critical language” program called “CUS,” which stands for “I am concerned.” “I am uncomfortable.”
“This is a safety issue!” These phrases are used to point out threats that present an immediate hazard instead of using
indirect language that may not emphasize the importance of a serious problem. The use of critical language allows
all members of the team to express concern about a safety issue in a manner that is understood by everyone.14
Simulation
Simulation training, which is now a part of the Maintenance of Certification program, is of particular
benefit to personnel who work in an operating room. The operating room is a dynamic, complex environment staffed
by a large, interdisciplinary team with varying levels of training whose members may not work together frequently.
Simulation has been shown to improve interactions between team members and facilitate exchange of information.15
Although high-fidelity mannequin simulators can be used to recreate critical events, it is also possible for team
members to improve their interaction skills using role-playing either in an operating room or around a table. This
technique has been used to teach assertive communication and also to plan complex surgery. The most critical part
of simulator training is the debriefing process after the simulation is complete. During this process, which is
essential to the learning process, team members discuss what happened openly and honestly.
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Conclusions
Effective decision-making, risk management, and teamwork are essential components of patient safety.
Errors can be caused by unfamiliarity with a given task, misperception of risk, latent errors, and systemic problems
such as production pressure and fatigue. Fortunately, accidents and “near misses” in the operating room are
relatively uncommon, and adopting techniques that improve risk assessment, judgment, and decision-making will
make our patients safer.
References
1. Gaba DM: Crisis resource management and teamwork training in anaesthesia. Br J Anaesth 2010; 105: 3-6
2. Kontogiannis T: A systems perspective of managing error recovery and tactical re-planning of operating teams in
safety critical domains. J Safety Res 2011; 42: 73-85
3. Gaba DM, Howard SK, Jump B: Production pressure in the work environment. California anesthesiologists'
attitudes and experiences. Anesthesiology 1994; 81: 488-500
4. Kahol K, Smith M, Brandenberger J, Ashby A, Ferrara JJ: Impact of fatigue on neurophysiologic measures of
surgical residents. J Am Coll Surg 2011; 213: 29-34; discussion 34-6
5. Ayas NT, Barger LK, Cade BE, Hashimoto DM, Rosner B, Cronin JW, Speizer FE, Czeisler CA: Extended work
duration and the risk of self-reported percutaneous injuries in interns. JAMA 2006; 296: 1055-62
6. Barger LK, Ayas NT, Cade BE, Cronin JW, Rosner B, Speizer FE, Czeisler CA: Impact of extended-duration
shifts on medical errors, adverse events, and attentional failures. PLoS Med 2006; 3: e487
7. Schimpff SC: Improving operating room and perioperative safety: background and specific recommendations.
Surg Innov 2007; 14: 127-35
8. Christianson MK, Sutcliffe KM, Miller MA, Iwashyna TJ: Becoming a high reliability organization. Crit Care
2011; 15: 314
9. Howard SK, Gaba DM, Fish KJ, Yang G, Sarnquist FH: Anesthesia crisis resource management training:
teaching anesthesiologists to handle critical incidents. Aviat Space Environ Med 1992; 63: 763-70
10. Carbo AR, Tess AV, Roy C, Weingart SN: Developing a high-performance team training framework for internal
medicine residents: the ABC'S of teamwork. J Patient Saf 2011; 7: 72-6
11. Haimes YY: Systems-Based Guiding Principles for Risk Modeling, Planning, Assessment, Management, and
Communication. Risk Anal 2012
12. Seiden SC, Galvan C, Lamm R: Role of medical students in preventing patient harm and enhancing patient
safety. Qual Saf Health Care 2006; 15: 272-6
13. Beckett CD, Kipnis G: Collaborative communication: integrating SBAR to improve quality/patient safety
outcomes. J Healthc Qual 2009; 31: 19-28
14. Leonard M, Graham S, Bonacum D: The human factor: the critical importance of effective teamwork and
communication in providing safe care. Qual Saf Health Care 2004; 13 Suppl 1: i85-90
15. Moorthy K, Munz Y, Adams S, Pandey V, Darzi A: A human factors analysis of technical and team skills among
surgical trainees during procedural simulations in a simulated operating theatre. Ann Surg 2005; 242: 631-9
DISCLOSURE
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How to Avoid Recruiting the Problem Employee

(and What to Do Once You Have One)
Catherine M. Kuhn, M.D. Durham, North Carolina
Introduction and Pre-Recruitment Considerations
The goal for any anesthesiology practice, academic or private, should be to add partners and employees who
improve the function and value of the group. Hiring an underperforming employee immediately decreases the
productivity of the organization. Managers quickly realize that they spend most of their time dealing with their
underperforming employees, at a cost to their groups. The best employees require relatively little effort from
managers once established in the group. This seems obvious--how is it, then, that nearly every organization at some
point fails to hire the best person for its needs?
All physicians are products of standardized education processes, with rigid timelines and criteria for application for
training positions. Residency and fellowship programs across the country spend enormous amounts of time and
money trying to recruit the best students into their training programs, and have the advantage of standardized, online
applications, defined recruitment cycles and primary source verification through the Electronic Residency
Application System (ERAS) and the National Resident Matching Program (NRMP). Every academic
anesthesiology department has infrastructure and resources dedicated to the process of recruiting trainees into their
programs. Despite this, not all medical students succeed in their training programs, and both trainees and their
programs are often surprised that the outcome was not predicted during the recruitment process. The application
and interview process as it exists for undergraduate and graduate medical education is imperfect. (1,2)
Is there any evidence that recruitment for the next level of employment, i.e., anesthesiology faculty appointments or
positions in a private practice, offers better success? There is no standardized process for that recruitment and even
state licensure and hospital accreditation practices vary considerably. Adding to the problem, people looking for
faculty or attending jobs are often hopeful to find a stable position for the long term, often with compelling reasons
to do so. The stakes are much higher for a successful job search, and for the employer, the stakes are equally high.
Despite this, departments vary tremendously in the resources allocated to the recruitment and retention of physicians
and other employees.
Organizational Self-Assessment
Before considering the quality or suitability of candidates for a practice, it is important to take some time to define
what “success” means for a particular group. What are the essential characteristics all employees require to uphold
the core values of the practice? What character traits and behaviors are essential? A clear definition of the purpose
for hiring new employees should be articulated. Are there particular clinical needs? Does the group need
subspecialty expertise or generalists? Is the group engaged in new business practices that require partners with
management experience? Does the group employ an anesthesia care team model or provide solo anesthesia care? Is
there a preference for hiring into a partnership track or an employee track? For academic groups, is there a specific
research or educational requirement that needs to be met? These considerations may help refine the criteria used
during the recruitment process. The recruitment process should be developed to optimize the likelihood of hiring
the type of physician who will most likely advance the goals of the group. Finding candidates whose career goals
are aligned with those of the group minimizes the likelihood of disappointment for either party. Similarly, the
available resources of the group should be considered when considering a successful hire. For example, a group that
has limited pediatric case volume may not be able to accommodate the desires of a newly-minted graduate of a
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pediatric fellowship who wants to practice as much pediatric anesthesia as possible, while still allowing
opportunities for other group members to maintain their pediatric anesthesia skills.
Another useful exercise is to consider the history of the hires in the group, and consider the attributes of the most
successful, as well as those who struggled. Although every individual is different, there may be some hints about
the type of physician who thrives in the environment of the group, and targeting those types of candidates may prove
useful.
It is important to predict the short- and long-term needs of a group when making hiring decisions. Some candidates
may be unable to commit to an indefinite term of employment due to spousal careers or other considerations. It is
important to consider the structure that will work best for a particular group, so that honest discussions are held
during the interviews. If hiring this person meets an important practice goal, how will the group manage after the
short-term hire leaves the group? Can the recruit enhance the practice quickly and train a replacement? Conversely,
filling a position with a less desirable candidate simply to accommodate burdensome short-term clinical needs
deprives the group of the possibility of hiring a more attractive candidate for the long term, so decisions about hiring
must balance the current demands on the group with its future desires for growth and accomplishment.
Application Materials
An application can provide useful information about candidates and if reviewed carefully, can be used by employers
to identify potential problems. Many employers discover too late, after being faced with a problem employee,
whether a physician or other staff member, that there were predictors of problems in the application materials and
application process.
Cover letters: Although viewed as a less important part of the application, review of the cover letter can glean some
information about the candidates’ previous experience and plans for the future. This can provide pre-interview
insight into the alignment of the applicant’s interests with opportunities available within the enterprise. Measures of
creativity and the candidate’s ability to communicate in writing are also addressed. The care with which a candidate
puts together his or her application and documentation (e.g., spelling, typographical errors) may be relevant for a
detail-oriented specialty such as anesthesiology. Promptness of responses and interaction with department staff
prior to interviews are also worthy of attention.
Letters of Recommendation: Many letters of recommendation are unhelpful in providing meaningful information
about a candidate’s performance. Particularly with difficult employees, former employers may be hesitant to
commit negative information in writing. Instead, a bland report of facts about employment dates and other similar
demographic information is provided. There are, however some important considerations about letters of
recommendation. The names of the letter writers should be correlated against the list of referees the candidate
provided. Discrepancies should be explained; was the candidate “shopping” for the best letter possible? Letters
from family members, friends or former students are less objective and valid. Were the letters provided by the
candidate, or were they mailed directly from the source? Do the letters address cognitive, technical and
interpersonal attributes, or one area exclusively? In reviewing letters, what isn’t said is at times more important than
what is said (3). Any letter that seems cautionary or incomplete should be followed up with a phone call to the
referee. Indeed, prior to offering a position to a candidate, it is advisable to contact all letter writers, to validate their
information and provide an opportunity for the letter writer to add additional useful information which might not
have been included in the letter. Every recommendation letter can be turned into a reference check. One important
question to ask is whether the candidate is eligible to be rehired by the group (4).
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Standardized Test Scores: (United States Medical Licensing Examination (USMLE), Comprehensive Osteopathic
Medical Licensing Examination (COMLEX), Intraining Examinations). After successful completion of American
residency training, it is likely that applicants have passed all steps of the USMLE or COMLEX, as this is a
requirement for entrance into the American Board of Anesthesiology’s examination system. All states require
passage of Steps 1, 2 and 3 of the USMLE for licensure. A candidate who is not a part of the American board
examination process may have comparable examination scores from another country. Although a group may rely on
the fact that a physician has completed his or her residency program successfully, and therefore may discount
examination scores, the examination history and scores may provide useful information, particularly if the candidate
is newly graduated from a training program and is not yet board certified (5). It is assumed that achieving diplomate
status with the American Board of Anesthesiology is a desired goal for all members of a practice, especially as
licensure and credentialing requirements have become more strict. Of note, the American Board of Anesthesiology
currently limits the use of the term “board eligible” to candidates who are active in the examination process, whereas
in the past anyone who completed a residency program could identify themselves as board-eligible. Board
eligibility implies that the candidate has unrestricted medical licensure and has met other important qualifying
characteristics.
Employment History: When reviewing applications, particular attention should be paid to information about gaps in
training, gaps in employment and negative administrative action. A single gap may be easily explained, but a
pattern of frequent job changes, and numerous gaps in employment should generate concern. A candidate with
medical licenses in many more states than s/he has practiced in may have had issues with licensure, and this should
be pursued and explained.
It is also important to consider the trajectory of the applicant’s career thus far. Simply stated, trajectory refers to the
rate and progress of accomplishment in a career. Is the candidate on a pathway that shows growth and
improvement, stasis, or backsliding? Is s/he considering your practice because of new opportunities or because of
problems with the former group? What unmet needs could be achieved in your group?
Honorary society selection: It is generally believed that Alpha Omega Alpha (AOA) selection is indicative of higher
achievement in medical school. Although it would seem that AOA selection should predict future success in
residency and beyond, this has not been a universal finding in all specialties. This may relate to the criteria used to
determine AOA eligibility, which at times are largely focused on cognitive accomplishments (6, 7, and 8).
Recently, many schools have formed chapters of the Gold Humanism Honor Society (GHHS) (9). Students are
selected by their peers and faculty for membership based on humanistic traits such as altruism, professionalism, and
interpersonal skills. The intent of the Arnold P. Gold Foundation in establishing these societies is to honor and
celebrate the non-cognitive aspects of medical practice. Whether selection to GHHS will predict success in
residency training, much less eventual practice, remains to be seen. The importance of selection to honorary
medical societies generally indicates that the candidate was a high achiever in medical school or residency, but may
not predict success as a faculty member or member of an anesthesiology practice. Again, careful consideration of
the core values of the practice and focus on the likelihood that the candidate possesses these values is most critical in
making good hiring decisions.
The Interview
As illustrated above, traditional residency application materials are not sufficient to use as the sole source of
information about candidates for residency programs (7, 8). A number of studies have suggested that the residency
interview is a more effective mechanism for discovering candidates who are best suited for training in a specialty
(10, 11). It could be extrapolated that the same consideration would be important for permanent employment
decisions. The interview process is time-consuming and expensive for both candidates and groups. At its worst, an
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interview is reduced to an opportunity for candidates to meet prospective colleagues, as well as to see their work
environment. At its best, the interview experience can be structured in a way to provide both candidates and the
group with more useful information about the job and mutual suitability. Is there a way to use the interview and
related activities more productively?
Most interviews include a combination of opportunities for potential recruits to meet physicians in the group, to tour
the facilities where they would work, and to learn incremental information about the clinical practice, finances,
business arrangements and potential salaries enjoyed by group members. Often social activities such as dinners
with business partners and spouses are arranged as well. Structured, formal interviews have been shown in other
settings to be useful in distinguishing the attributes of candidates (11). However, they are rarely used for medical
job interviews. In most settings, interviews are either semi-structured, or unstructured, and the combined
information gathered by the interviewers is often incomplete, or duplicative.
However, the practical reality is that most employers use, and will continue to use, semi-structured interviews.
Semi-structured interviews can be more reliable if attention is paid to the way they are conducted. Consideration
should be given to including non-departmental members in the interview process at some point, to emphasize that
team work and relationships are important. It is ideal if some subset of the organization interviews most if not all of
the candidates being considered for a position. This gives the group a better sense of the range of the applicants and
will lead to more careful discrimination of who might be the best candidate (4). Second, asking each interviewer to
use consistent questions for each applicant will also provide some additional perspective for comparison. This can
be facilitated by drafting some sample topics for each interviewer to cover, and will potentially reduce redundancy
in the questions for the candidate. Lastly, in business and other industries, the use of behavior-based, or Behavior-
Descriptive Interviewing (BDI) has been shown to improve the selection process (11, 12, and 13). The premise of
BDI is that past behavior is the best predictor of future behavior. Traditional BDI questions include a main question,
followed by probing questions to elaborate upon the described behavior and help gather more information about
non-cognitive competencies. A grading scale can be applied to the answers received. Conducting an entire
interview with behavior-based questions may be laborious, and would require a large investment in training the
interviewers. However, utilizing one or two behavior based questions, even without a formal grading scale, if
applied consistently to all candidates, can be quite illustrative. Some typical questions used by the author for
residency applications, and the attribute of interest are listed below:
• Give me an example of a time when you went above and beyond expectations to help a friend. (altruism)
• Tell me about a situation where you disagreed with the suggestion of your supervising resident. (conflict
resolution)
• Tell me about the hardest thing you’ve ever accomplished (work ethic)
• Give me an example of a time when you exceeded your own expectations (ambition)
These questions can easily be modified to reflect important elements of success within an academic department or
private practice, for example:
• Give me an example of your most frustrating day at work. (adaptability)

• Tell me about a time when you and your surgical colleague really disagreed over a patient’s management.
(conflict resolution)
• How would you handle a colleague who makes inappropriate comments to the nursing staff?
(professionalism)
As one gains experience using these questions, differences in candidates become apparent. Additionally, candidates
do not typically expect these questions, and are less likely to have a prepared answer ready. This allows some
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opportunity to see how well a candidate thinks on his or her feet, and is a better test of communication than the
standard questions about why a candidate is interested in your practice, their strengths and weaknesses, etc. These
traditional questions typically yield only predictable answers which provide very little useful information upon
which to distinguish candidates, unless further probing questions are employed. It is important to not settle for the
candidate’s assurance that they possess admirable traits; instead, interviewers should ask for evidence from the
candidate’s experience that this is the case. In the internet era, problems with plagiarism in application materials
have been found, and BDI or modifications can be used to validate the information included in a job application.
(15) Although the tone of a formal interview can be friendly and include some social elements, savvy interviewers
should be looking for reasons not to hire a candidate. Once these concerns are raised, they should be considered
carefully and discussed with the candidate. Good candidates will not be put off by a challenging but fair interview
and recruitment process. Such a process demonstrates that the organization values the job highly and places
emphasis on hiring the right person for it (4). It also sets the tone for the values and work culture in the department.
Another important suggestion for interviewers is to refrain from dominating the conversation. Often well-
intentioned interviewers spend so much time providing a candidate with information about the practice, community,
school systems, etc., that the candidate is not given much opportunity to speak. This deprives the interviewer from
getting a better sense of the character of the candidate. Allowing the candidate time to speak can provide insight
into whether he or she is a problem identifier or solver, an optimist or a pessimist, etc.
The Problem Employee
Despite all caution and efforts, anesthesiology groups will inevitably recruit an employee who presents problems in
the work place. This is one of the most challenging tasks for department leaders, and can require an enormous
amount of time, effort and hard work to diagnose the problem, and then implement a plan to help the employee.
The first aspect of dealing with a problem employee is identifying exactly what the problem is. This is more easily
identified when performance standards and policies are clearly defined, agreed upon by the group members, and
communicated clearly to the entire group. Having standards established makes it easier to determine when an
employee’s behavior is problematic. “Problem” employees can manifest in many ways, but can be categorized in
one of three domains. However, it is important to realize that it is rare for a struggling employee to have problems
limited to one domain. Typically even if one domain predominates, there is impact in the other domains.
The Employee with a Cognitive Problem: Cognitive problems are less likely than affective problems, but still
manifest themselves, even at the level of practicing physicians. An anesthesiologist may have poor learning and
studying habits, or may even have learning disabilities for which they have compensated quite well. A graduated
resident who is a memorizer may finally reach his or her limits as the volume of material to learn increases, and may
fail to pass the ABA examination (16). Other group members may not have the initiative to prioritize continuing
education. This can be problematic for some groups or institutions which require board certification or maintenance
of certification for credentialing, and will be an increasing potential issue as one-time certification is replaced by
Maintenance of Certification in Anesthesiology. Additionally, physicians who have not developed a system for
continued learning will become outdated in their practice and this can pose a problem for the smooth functioning of
the group.
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The Employee with an Affective Problem: This is probably the most common problem encountered by leaders of
medical groups and can be the most difficult to solve. Affective problems tend to lead to more problematic
outcomes with medical boards and other organizations (18, 19). Examples of problems in this domain include:
• Work ethic
• Compliance with requirements: e.g. HIPAA, supervision
• Compassion
• Respect for others
• Fairness
• Impairment
o Substance abuse
o Medical illness
o Psychiatric illness
o Disruptive behavior
The Employee with a Psychomotor Problem: This type of problem is less common in anesthesiology, but does
occur. There can be some overlap between Affective and Psychomotor problems. Some examples include problems
with:
• Stamina
• Eye-hand coordination
• Technical skills
• Pace of practice
Diagnosing the type of problem is the first important part of finding a solution. Once a plausible sense of the
problem is identified, it is then appropriate to meet with the employee to try to establish a plan of action for
improvement. The goal is to try to help the individual achieve success. Leaders of departments must define what
resources they are willing to commit to helping individuals who are struggling, and weigh this against the expense
and time of recruiting another employee. At a certain point, a decision to terminate the employment might be
reached, particularly if resources are not available to remediate the problem.
Affective problems seem to be the major category of issues program departmental leaders deal with. The effective
management of these problems can be difficult, as physicians are often uncomfortable giving a colleague feedback
about affective problems, and frequently there is little objective information to support the concerns. The key to
approaching affective issues is to describe them in behavioral terms. For example, an anesthesiologist who is
termed “lazy”, “disinterested”, “difficult”, etc. will almost certainly set up a defensive posture, making further
dialogue about the problem difficult. If however, using “lazy” as an example, the problem is described by the
doctor’s arrival time each day, versus the expected standard, the message is less emotional and can’t be argued about
as easily. Describing the problem in behavioral terms with nouns and verbs rather than adverbs also makes it easier
to define the expected outcomes to help the individual achieve the goal more readily (16, 17).
Meetings to address these issues should be carefully planned. The goal is to help the employee accept the problem,
and be willing to engage in the solution. For some individuals, the transition from resident to attending level
responsibility is difficult, but even experienced but new-to-the-practice employees may need specific guidance and
instruction to help them adjust to the practice setting. In short, the idea is to help the individual understand the
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consequences of the undesired behavior. In the setting of a potentially permanent job, the specter of unemployment
can motivate some individuals quite well.
The expense in time and effort of hiring a good employee is tremendous. Good departments will create an
environment that assists new employees with the transition to the practice. Establishing a trial period of
employment, which includes careful scrutiny of the new employee, feedback and opinions from other members of
the group, surgeons/obstetricians, other consultants, nursing staff and departmental staff may help. This can include
formal 360 degree assessments, observation of clinical practice, and monitoring of compliance with departmental
policies. A similar, but perhaps less intense model should be applied to all department members, as problems may
develop long after an initial provisional employment period.
Each state and institution has policies regarding due process and appeals of negative administrative employment
decisions. Good employment contracts also specify the expectations and rights of the employee, and if a decision
has been made to terminate an employee, it is important to consult with all entities including legal counsel about the
appropriate process and procedures. The importance of keeping appropriate documentation to support any adverse
decision cannot be overemphasized.
In summary, even the most careful application and interview process cannot guarantee that a problem employee will
never be hired. Additionally, group members can change over time in their capabilities, adaptability and reactions to
a stressful work environment. Thoughtful leadership includes the development of a highly selective hiring process,
creation of a supportive environment for the transition of new employees into the organization, and appropriate
feedback about performance. Implementation of these strategies should increase the likelihood of success for the
employee and the group.
References:
1. Ferguson E, James D, and Madeley L. Factors associated with success in medical school: systematic review of
the literature. BMJ (324) 952-7, 2002.
2. Ferguson E, Sanders A, O’Hehir F et al. Predictive validity of personal statements and the role of the five-
factor model of personality in relation to medical training. J Occ Org Psychol (73) 321-44, 2000.
3. Lurie SJ, Lambert DR, Grady-Weliky TA. Relationship between dean’s letter rankings and later evaluations by
residency program directors. Tch Learn Med (19) 251-6, 2007.
4. www.pbpexecutivesummaries.com Accessed June 10, 2010.
5. Wenghofer E, Klass D, Abrahamowicz M et al. Doctor scores on national qualifying examinations predict
quality of care in future practice. Med Educ (43) 1166-73, 2009.
6. Crane JT and Ferraro CM. Selection criteria for emergency medicine residency applicants. Acad Emerg Med
(7) 54-60, 2000.
7. Fine PL, and Hayward RA. Do the criteria of resident selection committees predict residents’ performances?
Acad Med (70) 834-838, 1995.
8. Brown E, Rosinski EF, and Altman DF. Comparing medical school graduates who perform poorly in residency
with graduates who perform well. Acad Med (68) 806-808, 1993.
9. http://www.humanism-in-medicine.org/ accessed 6/10/2010.
10. Brothers TE and Wetherholt S. Importance of the faculty interview during the resident application process. J
Surg Educ (64) 378-385, 2007.
11. Altmaier EM, Smith WL, O’Halloran CM et al. The predictive utility of behavior-based interviewing compared
with traditional interviewing in the selection of radiology residents. Invest. Radiol (27) 385-389, 1992.
12. Easdown LJ, Castro PL, Shinkle EP et al. The behavioral interview, a method to evaluate ACGME
competencies in resident selection: A pilot study. JEPM (7) 1-10, 2005.
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13. Prager JD, Myer CM, Hayes KM et al. Improving methods of resident selection. Laryngoscope (120) 2391-
2398, 2010.
14. Wood PS, Smith WL, Altmaier EM et al. A prospective study of cognitive and noncognitive selection criteria
as predictors of resident performance. Invest Radiol (25) 855-9, 1990.
15. Segal S, Gelfand BJ,, Hurwitz S et al. Plagiarism in residency application essays. Ann Int Med (153) 112-120,
2010.
16. Willenkin RL. Helping residents with cognitive learning problems. Int Anes Clinics (46) 41-54, 2008.
17. Willenkin RL. Helping residents with affective learning problems. Int Anes. Clinics (46) 55-66, 2008.
18. Papadakis MA, Teherani A, Banach MA et al. Disciplinary action by medical boards and prior behavior in
medical school. NEJM (353) 2673-82, 2005.
19. Papadakis MA, Arnold GK, Blank LL et al. Performance during internal medicine residency training and
subsequent disciplinary action by state licensing boards. Ann Intern Med (148) 869-76, 2008.
Suggested Additional Readings:
Baker JD, Bailey MK, Brahen NH et al. Selection of anesthesiology residents. Acad Med (68) 161-163, 1993.
Leichner P, Eusebio-Torres E, and Harper D. The validity of reference letters in predicting resident performance. J
Med Educ (56) 1019-1021, 1981.
Wagoner NE, and Suriano JR. Recommendations for changing the residency selection process based on a survey of
program directors. Acad Med (67) 459-465, 1992.
Wagoner NE, Suriano JR, and Stoner JA. Factors used by program directors to select residents. J Med Educ (61)
10-21, 1986.
Powis DA, Neame RLB, Bristow Tet al. The objective structured interview for medical student selection. Br Med J
(296) 765-768, 1988.
Friedman RB. Fantasy Land. N Engl J Med (308) 651-653, 1991.
Young TA. Teaching medical students to lie. The disturbing contradiction: medical ideals and the resident-
selection process. Can Med Assoc J (156) 219-222, 1997.
Metro DG, Talarico JF, Patel RM et al. The resident application process and its correlation to future performance as
a resident. Anesth Analg (100) 502-5, 2005.
Berner ES, Brooks CM, Erdmann JB. Use of USMLE to select residents. Acad Med (6) 753-5, 1993.
DISCLOSURE
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Compensation for Services-

When the Revenues Don’t Support the Expectations
Asa C. Lockhart, M.D., M.B.A Tyler, Texas
COMPENSATION FOR SERVICES

Developing a Strategy for Success
Stable anesthesia groups have a good payor mix, efficiently run operating rooms, an equitable compensation model,
and a sound internal professional and business infrastructure. While severe problems can overwhelm a group with a
strong infrastructure, relatively minor issues can engulf a group that has not invested in strategic and business
planning. If any of the above elements are missing or diminished, the initial warning signs of retention and
recruiting instability brought on by below-market compensation and lack of patient access to surgical services can
quickly erode a practice. These confounding factors justify compensation for service (CFS) arrangements between
anesthesia groups and hospitals, but the days of merely asking hospital administrators to stabilize an anesthesia
group by giving them an unsubstantiated “stipend” are gone. Therefore, reframe the negotiation process from a
simple request for money into a concept that more accurately reflects the driving force—compensation for the
desired level of anesthesia services requested by the hospital not supported by the revenue generated from clinical
activities due to poor operating room efficiency, surgeon practice patterns, utilization, and/or payor mix. If your
group determines that a CFS is required, you must develop a strategy for a successful negotiation.
You cannot manage what you cannot measure. In order to have a winning strategy, one must define the stakeholders
and their expectations, evaluate the data, convert the data to information, the information to knowledge, and develop
a fact-based story. The internal and external stakeholders include patients, surgeons, anesthesiologists,
proceduralists, obstetricians, perioperative staff members, and hospital administrators. A benefit, either real or
perceived, must exist to motivate the various stakeholders who require, utilize, or provide anesthesia services to take
action. Each stakeholder group has its own goals and deliverables that may or may not conflict, and which other
stakeholders may or may not understand. Most anesthesia groups want to maximize efficiency while most surgeons,
proceduralists, obstetricians, and administrators want to maximize access and market share. As stated above, patient
access to surgical services is the basic justification for a CFS agreement. If there is a threat to access due to
anesthesia recruitment and retention deficiencies, there will be a greater sense of urgency from multiple stakeholders
for a successful CFS negotiation. It is also important to evaluate the practice patterns and customer service
philosophies of all of the anesthesiologists and their employees to determine if there will be pushback from external
stakeholders if the hospital agrees to a fair-market value CFS agreement.
When preparing a strategy for a contract negotiation that requires a CFS, it is important to include the following
steps: (1) identify the appropriate staffing utilizing a staffing grid (SG), (2) evaluate operational and practice
performance against national benchmarks, (3) quantify the OR utilization metrics, and (4) embrace strategic
planning concepts. The goal is to develop a logical sequence of events that results in a story of why the group cannot
provide the desired level of access of anesthesia services with its native revenue stream.
Staffing
The OR is an inherently interdependent environment and demands a four-way conversation to develop an optimal
staffing configuration. Surgeons/proceduralists, anesthesiologists, hospital administrative, and OR nursing
representatives should develop the SG in conference so that there are no misunderstandings of the coverage
expectations; two-way conversations may not reflect the needs of the missing stakeholders resulting in a patchwork
or inadequate plan. This process permits the adjudication of conflicts in real time. The ability to perform a surgical
procedure requires a functional and synchronized unit—a surgeon/proceduralist/obstetrician, patient,
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anesthesiologist/anesthetist, nursing staff, and an operating room—otherwise someone is wasting resources. The
proceduralists and obstetricians are included since out-of-OR (OOOR) sites are the fastest growing service lines
requiring anesthesia, and these services are often not represented on the OR Committee. All sites requiring
anesthesia must be included in the Staffing Grid to determine the number of anesthesiologist and anesthetist FTEs
that are required. There should be a consensus among all stakeholders that the grid is a “just-say-yes” grid. If the
hours are on the grid, anesthesia services will be available and reflected in the budget. It should specify the hours
per day, number of days per week, and personnel configuration for each potential location. Additionally, there must
be appropriate administrative, vacation, and day-after-call (DAC) allowances. All potential anesthetizing locations
should reflect either dedicated, cross (or best efforts) coverage, flip rooms, and closed rooms. Best efforts coverage
is coverage that is not included in the budget or guaranteed contractually but may be provided with slack capacity or
DAC personnel. A flip location is a second dedicated clean room that would permit a rapid turnover for a surgeon,
but would not duplicate anesthesia personnel; duplicated personnel would require two locations on the staffing grid.
A closed location is a room: (1) that lacks the necessary equipment and is not functionally available at anytime, or
(2) one closed for a defined period (hours or days) with no assigned personnel. (See Figure 1)
Evaluate the Data

In preparation for CFS negotiations, it is important to see where your group fits in the local and national
marketplace. Remember that you are not asking for an undefined amount of money, you are developing a strategy
with concrete data to present to the hospital administration. For operational trending purposes, three years or two
years plus year-to-date (YTD) performance data will provide staffing, collection, business cost, and productivity
metrics. The basic benchmark data utilized in this process are charges, contractual adjustments/allowances/refunds,
revenue, cases, full-rate or undiscounted conversion factor (CF), and physician/anesthetist full time equivalents
(FTEs). Adjustments include contractual allowances and refunds. The contractual allowances represent the
difference between the full charge and the allowable charge (i.e., Medicare or managed care). Charges should be at
the full-undiscounted rate or they may later understate the relative performance of the group relative to benchmarks.
The question of what represents an FTE varies greatly by group. For fractional FTEs, they may represent a relative
percentage of days worked, hours worked, or relative percentage of compensation compared to full time personnel.
The Medical Group Management Association (MGMA) represents business managers for all specialties, and the
Anesthesia Administrators Assembly (AAA) represents anesthesia and pain management practices. The MGMA
produces a number of publications, including those formulated by AAA, that are useful in benchmarking your
practice. Other organizations produce salary surveys, but most of their surveys do not make a distinction between
the salary of a new hire and a partner, and some of their sample sizes are not statistically significant relative to the
number of anesthesia personnel in represented in a survey that may have over 1,000 responses for all physicians and
physician extenders. Executive search firms produce some of the surveys and tend to have lower numbers; this is
not surprising given their population, which occasionally makes them a popular resource during negotiations even
though they may not reflect the true market value for services rendered.
There is statistically significant compensation survey data for the country as a whole as well as well as geographic
sections in the annual MGMA Compensation and Productivity Survey. The geographic sections are Eastern,
Midwest, Southern, and Western. On the disc version only, there are minor regions as well. They are Northeast,
North Atlantic, Mid-Atlantic, CA-AK-HI, Eastern Midwest, Lower Midwest, Northwest, Rocky Mountain,
Southeast, and Upper Midwest. Since the relevant markets often extend beyond the minor regions, most clients use
either the geographic sections or national data points. Although not present in the printed 2009 survey, the data
previously permitted the calculation of demographic and multi-specialty differentials. The compensation categories
are anesthesiologists, pediatric anesthesiologists, pain medicine, and anesthetists. Since anesthesiologists
historically average 44 weeks of productivity per year, this translates into eight weeks of vacation and CME. By
calculating an adjustment/vacation modifier if the group takes a different time than benchmark, neither the group nor
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the hospital are penalized for the variation. Most groups fall between a 6- and 10-week range. Most anesthetists are
around six weeks with a much smaller variation. By factoring in these variables, the calculation will reflect similar
practice comparables. Trending and confounding factor explanations build an even more compelling story.
Data to Information – Information to Knowledge

Tabulate the basic and derived data and convert it to information with the derivation of other key performance
indicator (KPI) metrics. The derived data provides the basis for the calculations that yield information but in and of
themselves do not provide a context for the determination of fair-market value (FMV). These include the average
charge per case, the average revenue per case, the average units per case, cases per FTE, FTEs per 1000 cases,
average charges per physician, compensation to gross charges ratio, average or aggregate conversion factor, and
total group units generated, and per FTE average. However, from an administrative viewpoint, the most important
KPI metrics are the net collection percentage (NCP), bad debt percentage based on total charges or revenues, benefit
costs, units per physician FTE, and billing and administrative costs.
Additionally, to demonstrate the billing and revenue-cycle management efficiency, evaluate the accounts receivable
(A/R). With the A/R, it may be necessary to evaluate it with adjustments for accounts that are greater than 180 days
since many practices roll those accounts into bad debt or suspended accounts (e.g., auto accident where the account
may not be adjudicated for several years). It is also important to know whether accounts have been re-aged; the
desired methodology is not to re-age the accounts. One can better evaluate A/R performance based on date of
service or date of posting as opposed to date of payment. Date of insurance payment is important in evaluating
prompt pay from the insurance company. However, except for the group inserting language into their contracts and
enforcing the provision, practice managers have little control over this metric. The calculation of an aggregate or
average conversion factor (CF) demonstrates the group’s economic potential and may be useful in evaluating the
billing performance. Another major determinant for a viable practice is the public payor mix (i.e., Medicare,
Medicaid, Worker’s Comp, and Tri-Care). Due to the disproportionate impact of Medicare and Medicaid relative to
other specialties and facilities, the public payor mix is a key factor in an anesthesia group’s economic potential
making the aggregate CF benchmark determination an important part of the story. This will allow the
administration to appreciate the performance trends of the practice. As one compares the practice information to
benchmarks, there is a transformation from information to knowledge. With benchmarks in anesthesia, it is
important to know when to use “All Respondents” data and when to use “mode of practice” data. If the mode of
practice is material to the metric, use the “By Staffing Model” section; otherwise, use the “All Respondents” section
data since it will have a higher number of responses. Full charges and revenue per unit, A/R, and payor mix are
examples that are appropriate for “All Respondents” metrics. The productivity per FTE will vary significantly
between practice modes such as personally provided, anesthetist-to-physician ratio of <1:1, and anesthetist-to-
physician ratio of >1:1. Avoid using the “All Respondents” data for productivity related metrics since it does not
accurately portray any of the specific practice modes, and the billing/administrative overhead is very practice mode
sensitive (See Figure 2). Having calculated the above data, benchmarking against national databases will build your
story.
The development of a budget summary sheet based on projected revenues and expenses will display the financial
impact of the group-facility relationship. Unless a substantial change is expected, the previous year’s revenues are
the basis for the following year’s revenue projection; as one passes midyear, year-to-date (YTD) calculations may be
used. However, one must be careful to avoid extrapolating data points that do or do not include unusual or onetime
events (e.g., lump sum adjudication from previous year accounts or lump sum professional liability premiums and/or
retirement contributions paid at the end of the year). The expenses will be the number of anesthesiologists and
anesthetists required multiplied by the salary and benefit costs, billing and administrative costs, and other
professional overhead (OPOH). The OPOH represents professional overhead that is not discretionary, which
includes FICA, Medicare tax, various unemployment taxes, professional liability insurance, dues and subscriptions,
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CME allowances, business and occupational taxes, and miscellaneous items. Other than CME, these costs are
essential professional overhead categories that are non-negotiable and mandatory. The net income of revenue less
expenses may justify a CFS if it is negative and the hospital is requesting a level of coverage not supported by the
net income.
Once there is a validation of sound business practices, assess whether the practice is above, at, or below market
since a CFS can only be justified if a practice is materially below market. Two common methods for determining
CFS are net income guarantees pegged to a commonly accepted benchmark such as the MGMA Compensation
Survey and guaranteed units per location per day that result in a targeted income. As stated above, these levels will
vary with acuity, geographic location (Eastern, Southern, Midwest, and Western), number of vacation/CME weeks,
and demographic category. Anesthesia departments within multi-specialty clinics require further adjustments. One
basis for selecting the appropriate compensation survey percentile (25th, 50th, 75th, and 90th) is the relative practice
acuity, but it may also reflect local/regional competitors to avoid defections in a retention-based strategy. Some
consultants will use an average of several performance metrics. These metrics may include information such as call
frequency and acuity that are material considerations, but they may not carry equal weight with potential recruits.
This method may skew the FMV if one of the metrics is unusually low where one is only averaging a handful of
numbers. The FMV must ultimately reflect the percentage of the workforce that is able to meet the clinical
expectations and willing to make the lifestyle sacrifice required by the position.
Utilization
The nationally accepted utilization benchmarks are 70% without turnover time and 80% with turnover time.
Suboptimal utilization of operating rooms can be attributed to a silo culture, pre-admission testing (PAT) strategies,
block posting policies without discipline, high cancellation rates, and physician referral patterns. By far, the major
opportunity for stabilization is block posting—if there are consequences for poor citizenship. An anesthesia group
cannot sustain itself if the surgeons and proceduralists operating patterns leave large blocks of time in the daily
schedule and then insist on adding patients to the evening schedule. Even though it is clear that utilization is the key
to a self-sufficient anesthesia group, many administrators are not willing to eat the political fire by telling the
surgeons they must be more efficient, which may be a legitimate strategic consideration to retain market share in
very competitive markets. That business decision is another reason for a CFS agreement. In the post-health system
reform world, these considerations will become even more significant.
Strategic Planning
The cornerstones of strategic planning are a S-W-O-T Analysis and Business Plan that includes an Action Plan. A
S-W-O-T analysis identifies the group’s internal Strengths and Weaknesses and external Opportunities and Threats.
The planning process is most successful when utilizing a survey instrument that is enhanced through group
discussion after the results have been tabulated. Running a medical practice like a business is not only helpful
internally, it strengthens the group’s position with the hospital if there is a “partnership” element to the negotiations.
Deliverables might include improved on-time starts, group discipline, and champions for improved utilization and
perioperative redesign. The focus is to determine what issues enhance or diminish utility. The goal is to develop a
“win-win” scenario where both organizations reinforce their relative strategic plans in a mutually beneficial
relationship on a functionally unified balance sheet.
Develop and Execute Your Story

Your success will depend upon your ability to convert information into knowledge in an impactful, organized
manner. Additionally, it is crucial that a decision-making committee and negotiating team be empowered to affect
change in order to assess the achievable goals and implement them to the benefit of the anesthesia group and/or
various stakeholders. Mere discussion and vetting of the issues does not achieve the goal of correcting the
underlying factors that led to the stated difficulties. There must be an alignment of incentives with a clear
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understanding that CFS is not the same as Pay for Performance (P4P), nor is it an annuity. It is essential that the
practice data be in the same format as the benchmark (i.e., the number of time units per hour) and presented in a
tabular, trended format to optimize the visual impact. Benchmark the KPI against the Medical Group Management
Association (MGMA) Anesthesia Cost Survey results, published every other year, to assess the relative efficiency
and productivity of your organization. As noted earlier, one must be cautious in using the generic MGMA Cost
Survey that is produced annually and cannot be used for data points impacted by mode of practice.
Since failure to implement the required changes is the most common reason for a failed result, adequate time and
resources should be devoted to this aspect of the process. Once a consensus is reached, the formal implementation
phase should begin immediately. Although the appropriate plan will give the stakeholders a sense of well-being, it
is the implementation, and not the plan itself, that ultimately solves the problems and meets expectations.
Persistence is the key!
While the numbers tell the story, they tend to be arcane and confusing to hospital administrators and their
consultants if they the lack anesthesia experience. The goal is to develop an easy to follow story utilizing a logical
sequence of information that explains outliers and anticipates potential flashpoints. For instance, assigning revenue
and expenses to a responsibility center such as OB may explain why OB places undue pressure on a group since
fully staffed in-house OB coverage may easily consume 40% of the gross revenues of a small anesthesia practice.
Another example would be a primary-care physician hospital board member who would have to be educated in
advance regarding anesthesiologist and anesthetist salaries since primary care salaries tend to be unfairly low and
could result in a disruptive or subversive position in closed-door facility board of director meetings.
Anesthesiologist salaries do not surprise them, but many are justifiably incensed that a nurse out earns them!
Depending on the level of trust and market knowledge of the key stakeholders, it is important not to create a
perception that this exercise is only to guarantee high levels of income to the anesthesiologists. There is a higher
chance of success if framed in the context of stabilizing the anesthesia platform when it is requested to provide a
level of service that is not supported by the revenue stream generated. Recruitment, retention, and stability are the
desired goals.
Your presentation/story should flow in a logical and believable manner that demonstrates an alignment of incentives
between the group, hospital, and community as well as providing the desired level of access. Assess the political
timing before scheduling your first hospital meeting to make sure that this is the right moment in time to raise the
question. It must pass the “smell test” internally before being presented externally. If the objective assessment is
that there is not a satisfactory answer to these issues/questions, then the negotiation is not ready for prime time.
New Options and Current Trends

In the survey realm, the 2010 MGMA Compensation and Productivity Survey in the electronic format added the
Health and Human Services (HHS) Regions One through Ten as another option in addition to the previously
mentioned Major and Minor Regions as well as state specific data on 26 states. Although there is much crossover
with the Minor Regions, they are somewhat different. Some may feel that the existing options are not representative
of their practice setting. Depending on the scope of the data request and the content of their data repository, MGMA
may be able to run a custom report for your project for a region of the state or several adjoining states if there were
not enough respondents from your particular state.
In the past, coverage alone may have provided justification for a CFS. However, as the levels have grown both in
magnitude and prevalence, facilities are questioning what they are getting for their money. They seek to align the
incentives between the group, facility, and other stakeholders such as surgeons, hospital staff, and patients on
quality, performance, OR utilization, and/or other local issues.
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Quality metrics often focus on Physician Quality Reporting Initiatives (PQRI) and Surgical Care Improvement
Program (SCIP) measures such as timely antibiotic administration, prevention of catheter-related bloodstream
infections, and normothermia. Local issues drive other requested metrics such as acceptable patient and/or surgeon
satisfaction scores, medication management (e.g., charge capture and controlled substance documentation), and
clinical adverse events. Jerry Stonemetz, MD, who is the National Medical Director, Anesthesia Services, Clinical
and Physician Services Group for HCA, advocates putting some portion of the CFS at risk with assignment of
weighted values to each metric with a sliding scale allocation depending upon the level of performance (e.g., 20%
potential on timely antibiotic administration with 100% payment for >95% compliance, 75% payment for 91-95%
compliance, 50% for 80-90% compliance, and zero for <80%).
Common performance metrics include assessment of on-time first-case-of-the-day (FCD) starts, timely pre-op
assessments, acute pain blocks, case delays, cancellation rates, turn-over-time (TOT), PACU sign-outs, and other
throughput process steps. The key point for a fair and meaningful assessment is the degree to which anesthesia has
control over the activity. Global metrics should be avoided since they may fail to meet expectations through no fault
of anesthesia. With FCD, it is fair to set a time certain where anesthesia is expected to be dressed and ready to work
(e.g., arrive by 0645 for 0715 in-room cases) and receive credit for an on-time arrival. However, if a patient enters
the room at 0735 due to a delayed surgeon arrival, patient site-marking, or missing lab results/instruments,
anesthesia should not be penalized since these delays would be beyond their control.
While an emergency room or primary care physician may have control over their productivity per unit of time, an
anesthesiologist’s productivity is more likely to be related to the requested number of simultaneous sites. The
conundrum is access versus efficiency, which are diametrically opposed. However, the group may be able to
position itself in a favorable light by providing accurate utilization numbers and suggestions on how the schedule
might be reasonably adjusted. Many productivity metrics are particularly risky since some of the more popular
facility options are beyond the control of their anesthesia department (e.g., units or cases per anesthesiologist). On
the other hand, groups do have control over many elements that drive their financial efficiency performance so long
as they are reasonably adjusted for payer mix as discussed earlier in the section on benchmarks such as net
collection percentage or overhead. One must remember to use the appropriate benchmark for any metric driven by
mode of practice (e.g., units or cases per anesthesiologist).
Local issues vary greatly. They are often related to problems with citizenship and professionalism. It may reflect
past or present conflicts and general attitudes of individual members or the group culture as a whole such as dress, or
personal interactions with surgeons, patients, and/or staff. The failure to discipline unruly members is one of the
most common, if not leading, factors for a group to lose a contract for non-economic reasons. This facet tends to be
very fact specific with much emotion and passion that at times may defy logic in relative terms.
Health system reform has impacted CFS arrangements in several ways. Hospitals on average will face a $2.5
million Medicare cut in the new payment paradigms. This does not include other potential cuts in revenue due to
excess readmissions and an expanding list of “never” event penalties. Accountable care organizations (ACO) and
bundled payments give hospitals a sense of empowerment since they are better positioned with capital to fund new
initiatives. Closely related is the push towards physician employment—the ultimate CFS!
Showtime
Lastly, it is important to determine the group’s organizational BATNA or best alternative to no (or negotiated)
agreement. The BATNA determines when to walk away from the negotiation, and group members must be
intellectually honest in determining what they are willing to accept or not accept. One should never walk out of the
room unless they are willing to stay out until the other party blinks. Be cautious in asking the consultant what they
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would do; they are not the one who has to relocate if things do not work out to the group’s preference! If the
hospital administration senses a weakness in the group’s resolve, they will make the most of it since that is their
fiduciary responsibility to their organization. Our economic system is built on a price-quantity combination between
two willing parties—nothing mandates that both, or either, are happy with the outcome! The best plan in the world
is worthless unless implemented. Once the strategic analysis indicates that the presentation is ready for primetime,
execute it!
Conclusion
Determine the critical success and critical failure factors, objectively assess your reasonable needs, assets, and
liabilities, and then synchronize your requests with the institutional objectives as well as your mutual key
stakeholders. The result should be a fair-market value proposition that truly benefits the community by providing a
stable and sustainable anesthesia platform. Persistence is the key!
903-521-6728
aclhart@aol.com
Sources
MGMA Compensation and Productivity Survey – published annually
MGMA Cost Survey for Anesthesia and Pain Management Practices – published every other year
MGMA Cost Survey – published annually
Jerry Stonemetz, MD, National Medical Director, Anesthesia Services, Clinical and Physician Services Group for
HCA– Personal communication
holders.
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Figure 1
STAFFING GRID EXAMPLE
Reprinted with permission from Golden Caduceus Consultants. © 2011.
Figure 2
EXAMPLES OF DATA POINTS FROM COST SURVEY for ANESTHESIA and PAIN
MANAGEMENT PRACTICES: 2011 Report based on 2010 Data
Data: Median
holders.
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Note that per physician data points vary by mode of practice while those that are independent of mode of practice
have less variation.
Data used with permission from the MGMA-ACMPE, 104 Inverness Terrace East, Englewood, Colorado 80112.
877.ASK.MGMA. www.mgma.com. Copyright 2011.
DISCLOSURE
Golden Caduceus Consultants, Ownership
holders.
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The Expert Pathway: What You Can Do to Improve Your Performance

Keith Baker, M.D., Ph.D Boston, Massachusettes
The Expert Pathway is an approach to professional development aimed at improving teaching, learning and
performance in the domain of medicine. The approach is derived from the study of actual experts from a variety of
different domains. Results from cognitive science are also applied as they relate to performance improvement. The
ultimate goal is not simply to become competent (i.e. sufficient or adequate but not exceptional) rather the goal of
the expert pathway is to reach towards expert performance. Performance in the domain of medicine has a great
many contributing factors. These include motivation, environment, native ability or talent, employed strategies,
self-regulation, costs and goal orientation. The expert pathway focuses on aspects of performance that are under an
individual’s control such as employing selected strategies and persisting in the face of a setback.
Is there a need for improved performance in the domain of medicine?

The literature documents the nearly inescapable conclusion that significant performance improvement is needed in
the domain of medicine. For example, the Rand Corporation demonstrated that Americans receive recommended
care only about 55% of the time1. An example from anesthesia showed that even when anesthesiologists design
their own post-operative nausea and vomiting (PONV) guidelines they only follow them about half of the time2.
Theses authors then showed that these same anesthesiologists delivered much higher PONV guideline-based
performance when they received decision support. The fact that performance improved substantially means that this
was an achievable goal and not an impossible feat. These two representative examples demonstrate that there is
significant room for performance improvement in health care.
A learning orientation is foundational to attaining expert performance.

All expert performers use setbacks, challenges and difficulties as opportunities for growth and improvement. All
individuals face occasional challenges. For example, an individual may make a drug error or be unable to
accomplish a technical task such as securing an airway. Recently, ongoing professional performance evaluations
(OPPE) have been introduced and act as challenges or threats to many individuals. The response to any hurdle or
challenge is fundamentally based on an individual’s achievement goal orientation3. When facing a challenge the
goal can be to master the challenge and learn how to meet the competency demands of the challenge – this is termed
a learning goal orientation, or simply a learning orientation. Individuals with a learning orientation strive for
development or growth in competence. Broadly speaking, an individual with a learning orientation will respond to a
challenge or setback by altering their strategy, increasing persistence or adding additional time and effort until they
succeed. Such individuals enjoy and want to learn from challenges and their basic definition of success is
improvement and learning. A learning orientation is sometimes called a mastery orientation, a task-involved goal or
a theory of incrementalism. Alternatively, the goal can be to validate the individual’s ability and perform well in the
eyes of others – this is termed a performance goal orientation, or simply a performance orientation. Individuals who
hold a performance orientation seek to validate their own ability, gain favorable judgment of their attributes and
avoid negative judgments at all costs. Individuals with a performance orientation respond to a challenge or setback
by avoiding challenging situations, assuming they can’t succeed with the challenge, dropping expectations or
lowering persistence or effort on the task. The underlying premise for those who have a performance orientation is
that their success and failure is due to their inherent ability (or lack thereof) for the challenge that confronts them.
For example, if a person holds a performance orientation and they come across a difficult task or one that requires a
great deal of effort, they might conclude that they do not have an inherent ability to succeed at the task. In turn, they
would be likely to disengage from the task. Individuals with a performance orientation are particularly concerned
about how they compare to others. A performance orientation is sometimes referred to as an entity theory, ego goal
or an ability-focused theory. Importantly, learning and performance orientations are either essentially independent
or at most only slightly related tendencies or traits4. This means that within a single person there can be any
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combination of these two achievement goal orientations. Numerous studies have shown that when individuals are
not facing a challenge, threat, or setback then both of these achievement goal orientations are equally efficacious in
advancing one’s performance. Thus, when things are going well, achievement goal orientation is unimportant.
However, when an individual is confronted with a challenge, setback or failure, a learning orientation is reliably
more effective in overcoming the challenge3, 5-6. In contrast, studies indicate that a strong performance orientation
results in maladaptive and dysfunctional responses to a challenge, threat or setback. An example of the different
consequences of holding a learning orientation as compared to a performance orientation can be seen in how
residents respond to feedback on their performance7. Residents who primarily hold a learning orientation find
benefits in feedback and do not see costs or threats with feedback. Residents who primarily hold a performance
orientation believe there is a high cost to feedback and that feedback is a threat. This means that individuals are
much more likely to accept feedback, a necessary component of performance improvement, if they hold a learning
orientation. Individuals who are strongly performance oriented are more likely to act defensively when negative
feedback is delivered8. Fortunately numerous studies have demonstrated that people can, at least acutely, become
more learning orientated8. In summary, a learning orientation is essential for overcoming challenges, setbacks and
failures and serves as the foundation for achieving expert performance.
How do experts differ from other proficient individuals?

An expert can be defined as the one who can reliably outperform others who have significant experience in the same
domain. For example, an airway expert would be defined as somebody who can more reliably secure the airway as
compared to others with say, 10 years of experience. Essentially the expert is the individual who can outperform
others who are already performing at a highly proficient level. The primary strategy used by nearly all experts is the
process of deliberate practice9. Deliberate practice was initially described as the activity that distinguished elite
musicians from other world class musicians10. Deliberate practice is a specific activity with the single goal of
improving performance by identifying and overcoming weaknesses. It is highly structured, purposeful and requires
a significant degree of effort. Performance is monitored and feedback is delivered to enhance performance.
Deliberate practice leads to improved performance, requires a learning orientation, is not inherently enjoyable or
fun, usually generates costs, typically cannot be sustained for more than a few hours at a time and does not have
immediate rewards. This description of deliberate practice characterizes the practice patterns of almost all elite
performers across a wide variety of domains. As a proof of concept, deliberate practice was used by an otherwise
average college student named S.F. to memorize series of random digits. S.F. initially displayed average memory
performance on this task but through the process of deliberate practice he was able to attain savant-level memory
performance for random digits11. Elite performers from a variety of domains reliably engage in more deliberate
practice than their lower performing counterparts. Specifically, better violinists, pianists10, spellers12 and chess13
players engage in more deliberate practice.
More recently, deliberate practice has been applied to resident physicians performing ACLS14. When residents
performed their typical duties and engaged in the usual repeated episodes of hospital-based ACLS their measured
performance did not improve. In contrast, when they engaged in the deliberate practice of ACLS they distinctly
improved their ACLS performance to well above a control group of peers. During the deliberate practice of ACLS
skills they identified weaknesses, received feedback on performance gaps and were required to repeat the skill until
the performance improved and reached accepted levels. This example demonstrates how the practice of medicine
does not necessarily lead to enhanced performance. Instead, deliberate practice enhanced performance. A much
older example of deliberate practice was published by Cormack and Lehane when they first described their
laryngoscopic views of the larynx15. They proposed a new method to practice intubating the difficult grade 3 view
of the larynx. As obstetric anesthesiologists they were quite aware of the morbidity and mortality associated with
general anesthesia in the parturient. They also realized that grade 1 views of the larynx were common and easy to
intubate whereas grade 3 views were infrequent and difficult to intubate. Thus there were very few opportunities to
practice intubating the difficult grade 3 view. As a solution, they proposed purposely degrading the grade 1 views to
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iatrogenically create a grade 3 view. This allowed them to create plenty of grade 3 views for practice. They then
practiced these difficult airways to enhance their skills for when they encountered a true grade 3 view of the larynx.
This example demonstrates a learning orientation as well as deliberate practice. The deliberate practice component
relates to identifying weaknesses, namely, intubating the grade 3 view and then designing practice opportunities to
help master what is difficult or challenging, namely, intubating the non-visualizeable larynx. Such an approach
requires a learning orientation since the process of learning to intubate the iatrogenically created grade 3 view is
likely to result in a challenge and even failure, at least initially. The learning orientation allows the practitioner to
persist and change strategy until they attain competence with the difficult or challenging situation.
Isn’t experience enough to become an expert?

Experience typically results in an experienced non-expert. Without the active application of deliberate practice,
experience results in stable long-term mediocrity. The finding that experience does not lead to expertise was nicely
demonstrated in a longitudinal study of residents learning epidural placement16. Over time residents were able to
demonstrate increasing success in performing correct epidural placement. However, their adherence to sterile
technique did not improve whatsoever as the number of epidurals increased. This study demonstrated that without
active attention to improving sterile technique it will not spontaneously improve just because experience increases
over time.
Automaticity is a double-edged sword.

When a new activity is initially being learned the person needs to spend significant amounts of attention and effort
on the new task. This places a significant cognitive load on the person making it very difficult or even impossible to
attend to other concurrent activities. As the task becomes better learned, execution requires fewer and fewer
cognitive resources. In time, the task can be accomplished almost automatically as which point it requires few
cognitive resources for completion. Once a task can be completed with a high degree of automaticity then, by
definition, it is not being attended to in a conscious way17. For example, with experience most people do not have to
think about how to tie their shoes or use a fork since these actions are occurring automatically. Unfortunately,
automaticity is a double-edged sword. Automaticity allows the task to be accomplished easily and with little
attention. However, precisely because the action requires little or no conscious attention it renders the task
unavailable for purposeful improvement. Thus, the upside to automaticity is that it frees cognitive resources for use
on other tasks, the downside is static task performance.
Becoming an expert or simply elevating one’s performance level is a personal choice.

Currently there are no requirements for healthcare providers to attain expert levels of performance. Competence is
the requirement and it is a low bar. The great majority of practitioners attain competency which assures a minimum
level of performance. However, unless an individual chooses to develop their performance level well beyond basic
competence they are very likely to become an experienced non-expert. Thus it falls to the individual to decide if
they want to reinvest the time and effort which becomes available through the process of automaticity back into the
transformational process of improving performance. As mentioned above, when individuals become fluent in their
daily practice, much of their behavior and decision-making can be carried out at a fairly automatic level. Once an
individual’s practice becomes fairly automatic or routine, it frees up cognitive resources for the individual to do with
as they wish. Most people use this available resource to fluently and easily get through the day. Few people,
including physicians, choose to reinvest this cognitive resource back into performance improvement via deliberate
practice18. Attainment of advanced levels of performance requires the reinvestment of the available cognitive
resources back into performance improvement via deliberate practice.
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Can we improve performance by paying individuals?

Apparently many people think so based on the ever increasing number of pay-for-performance programs that are
arising in medicine. However, the real answer appears to be no. The use of pay-for-performance metrics did not
result in improved performance even when such pay-for-performance programs were in place for years19. In
addition, studies have reliably demonstrated that paying individuals for engaging in inherently interesting activities
causes a paradoxical decrease in interest and in motivation for these interesting activities20-21. Thus, money can act
as a demotivator and, so far, paying for performance has not been associated with improved outcomes in the domain
of medicine.
Performance is limited by a number of obstacles.

Expert performance requires deliberate practice but it also requires the management of numerous obstacles that
thwart efforts at attaining better performance. Performance obstacles can take a variety of forms and include
cognitive biases, motivated reasoning, anxiety, acute or chronic stress, limited working memory capacity, high
cognitive load, choking, multi-tasking and self-regulatory failure. Managing all of these obstacles is essential to
attaining expert performance but only a few will be discussed here.
Higher levels of performance can be attained by managing obstacles to performance.

Better diagnosis can be attained through managing cognitive biases22. The ‘availability bias’ refers to the strong
tendency of physicians to diagnosis a patient with an ailment that comes easily to mind. For example, if a physician
recently saw a patient with a pulmonary embolism, then subsequent patients would be more likely to be diagnosed
with a pulmonary embolism even if it is not necessarily the diagnosis. This bias was recently documented in a
randomized controlled trial22 where the availability bias was easily demonstrated with internal medicine residents.
The availability bias was then corrected by engaging in the process of reflective reasoning. Reflective reasoning
requires the diagnostician to name a diagnosis and then list features of the case that do not fit with that diagnosis.
The diagnostician then assumes that the working diagnosis is wrong, generates a second diagnoses and repeats the
process. After they can’t come up with any more diagnoses, a single diagnosis is chosen. This approach yields a
superior diagnostic performance and circumvents the availability bias. Reflective reasoning encompasses many
features of deliberate practice: it is designed to improve performance, focuses on a weakness, is effortful, costly of
time and effort and is not inherently enjoyable.
Enhanced ACLS performance was recently demonstrated when individuals were required to purposefully train under
anxiety-provoking conditions. Such anxiety-provoking conditions resulted in better long-term ACLS performance.
This approach to training also has aspects of deliberate practice since it is more difficult, focuses on a weakness, is
distinctly unpleasant and results in better performance23.
Mastery learning also results in significant gains in performance by changing the general structure of learning from a
time-based experience to an outcome-based process. Most medical training is based on a time-limited training. For
example anesthesia residency is three years in duration. In contrast, mastery learning allows the length of training to
vary in order to reach a preset outcome or mastery level for a given task. The amount of time that it takes to attain
this preset level of performance is what determines the duration of training. This changes the priority away from
time itself and to actual performance instead. When a mastery learning approach was applied to central line
placement by trainees it resulted in a significant and persistent improvement in central line performance24.
The Expert Pathway is not a final destination; rather it is a process which results in ever
increasing levels of performance.
In short, the goal is to become better irrespective of the current level of performance. Such an approach requires the
individual to never be entirely satisfied with their current level of performance25. It is this dissatisfaction that causes
the individual to reinvest their time and cognitive resources back into improving their performance which then
moves them beyond their current level and towards to a higher level of performance. Currently there is no shortcut
for becoming an expert. Instead, it requires a number of foundational activities such as adopting a learning
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orientation and application of deliberate practice as a normal part of one’s professional development. Additionally,
individuals must manage the many obstacles that tend to derail most individuals from attaining higher levels of
performance. For example, if an individual is highly performance oriented and minimally learning oriented, this
would derail achievement because a performance orientation will cause the individual to be defensive with feedback
that is needed for enhancing performance. For individuals who have made the choice to improve their performance,
the active application of deliberate practice coupled with a learning orientation will result in enhanced performance.
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24. Barsuk JH, Cohen ER, McGaghie WC, Wayne DB. Long-term retention of central venous catheter insertion
skills after simulation-based mastery learning. Acad Med. Oct 2010;85(10 Suppl):S9-12.
25. Guest CB, Regehr G, Tiberius RG. The life long challenge of expertise. Med Educ. Jan 2001;35(1):78-81.
DISCLOSURE
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Cognitive Errors In Anesthesiology:

Making Mistakes Even When We "Know" Better
Marjorie Podraza Stiegler, M.D. Chapel Hill, North Carolina
"I never make stupid mistakes. Only very, very clever ones." ~John Peel
Introduction
What does it feel like to be wrong? How can we know when are making a mistake? We cannot, of course, because
being wrong feels exactly like being right. We are oblivious to our errors at the time that we commit them. There is
only the experience of realizing that we have been wrong. This idea of error-blindness, put forth by Kathryn Schulz,
is summarized by her as: "we can be wrong, or we can know it, but we can't do both at the same time."[1]
Naturally, erroneous thinking can be due to lack of information. However, this course focuses on cognitive errors -
mistakes rooted in faulty subconscious thought processes. They are distinct from knowledge gaps because the
thinker possesses adequate information and understanding of the subject matter to arrive at the correct conclusion.
Simply put, cognitive errors are mistakes that are made despite "knowing better."
Why are cognitive errors important?
In the early 1990s, medical errors were exposed for the enormous problem that they are. Few physicians need a
reminder that medical errors have been estimated to account for up to 98,000 deaths annually in the United States at
a cost to the US healthcare system of $24 billion per year.[2] According to Brennan et al[3], 1.5 jumbo jets would
need to crash every day for an equivalent death rate, making "medical errors" the fifth leading cause of death in the
United States (ahead of motor vehicle accidents, diabetes, kidney disease, breast cancer, and influenza).
While it is easy to agree that medical errors must be reduced, significant challenges remain regarding error
reporting, management, and prevention. Recent studies suggest that cognitive errors, a subset of medical errors
involving faulty thought processes and subconscious biases, are important contributors to missed diagnoses and
patient injury.[4] Indeed, according to Groopman, "technical errors account for only a small fraction of incorrect
diagnoses and treatments. Most errors are mistakes in thinking." He goes on to say that these thinking mistakes are
caused in part by subconscious processes, such as biases we may not even recognize, and certainly not admit.[5]In
the 1990s, early pioneers of the "crisis resource management" paradigms at Harvard and Stanford introduced this
topic by including fixation error, or "tunnel-vision", in their curricula. This is indeed a cognitive error, and likely a
very common one. Today, the psychology of decision-making is becoming ever more appreciated, as more vast
descriptions of a variety of cognitive errors have now been described in safety culture industries and many medical
specialties including anesthesiology[6]
"Be not ashamed of mistakes and thus make them crimes." ~Confucius
Historically, there has been a notion that making a mistake is shameful, diminishing a person's worth and
undermining their expertise. However, fallibility is not equivalent to stupidity.[1] In fact, Pulitzer winner Hallinan,
an expert on human perception pitfalls, asserts that the same qualities that make us efficient (rapid pattern
recognition in lieu of detail scrutiny, for example) also make us error prone; thus the mechanisms by which we
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perceive, process, and remember actually set us up to make mistakes. As well, he asserts, humans have significant
capacity for self-deception and/or delusion. We are prone to bias, and are poorly calibrated, meaning that our
perception of our performance rarely approximates our actual performance. We tend to hold fast to old strategies
that work poorly in new situations, and rely upon memories that are much less accurate than we realize.[7]
Any reader now thinking, "This subject may be interesting, but it doesn't actually apply to me," is in fact committing
a cognitive error right now! Study after study consistently shows that people, including doctors, tend to
overestimate their capabilities and remain very certain of decisions even in the face of irrefutable evidence to the
contrary.[8-10] We attribute favorable personal characteristics (talent, intelligence, dexterity) to our successes, yet
blame circumstances for our failures.[8] Whether or not we are personally prepared to be open to our own fallibility
factors prominently in our potential abilities to avoid and manage these kinds of thought process errors.
What exactly are cognitive errors?
Cognitive errors are thought process traps that are ubiquitous human experiences, usually linked to failed biases or
heuristics. It is worth repeated that they are distinct from knowledge gaps. It is noteworthy that heuristics and
biases are frequently useful in clinical medicine; they allow experts to arrive at decisions quickly and (usually)
accurately. However, cognitive error arises when these subconscious processes and mental shortcuts are relied upon
too heavily, or under the wrong circumstances.
Because cognitive errors are rooted in subconscious processes, we are often unaware of their influence. According
to Kida, humans believe strongly in anecdotes, demonstrating a powerful preference for stories over statistics and a
tendency to ignore the concepts of chance and coincidence. The human brain subconsciously reshapes and
enhances memories as time goes by, and then we rely on these faulty memories to shape future decisions. People
seek to confirm what they already believe and gloss over contradictory evidence. We tend to oversimplify or
misinterpret complex situations. While there is a plethora of science and documentation of evidence to these points,
we humans continue to repeat the same errors of thinking.[11]
"Experience is that marvelous thing that enables you to recognize a mistake when you make it again."
~ Franklin P. Jones
How do cognitive errors manifest in anesthesiology?
Experts rely heavily on cognitive shortcuts and intuitive processes, especially when making high-stakes decisions
under time pressure; this thinking environment may be particularly prone to cognitive error. [10, 12]In
anesthesiology, it is easy to describe examples of particular cognitive errors that may arise in routine practice and
during emergency situations.
The following is a brief introduction to just a few specific examples (which may be known by other synonymous
terms). By way of an acknowledgement, it is true that the mere provision of a vignette example may bias the
reader's interpretation of the error. Please consider these illustrations to be just that, and focus on the thought
process problem being described, rather than the medical situation in which it is depicted. Refrain from judging the
error as careless or stupid, and keep an open mind to the fallibility of human nature, even among experts.
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Premature Closure
"No problem can withstand the assault of sustained thinking." ~Voltaire
Premature closure describes the cognitive error of accepting the first plausible diagnosis before it has been fully
verified. For example, if a patient is hypotensive after induction, the tendency may be to attribute this to the effect of
deep anesthesia without adequate stimulation, and not investigate further. (A different physician may select
anaphylaxis just as readily, or myocardial infarction, etc – and not consider other key items on the differential
diagnosis). The error lies not in the nature of the preliminary diagnosis, but in the premature cessation of
investigation. Putting premature closure in the context of useful heuristics is important, for patients often do have a
decrease in blood pressure after induction, particularly in the period prior to surgical stimulation. This experience
shapes the expert mind to expect this result, and does not require an exhaustive differential diagnosis at every
occurrence. Playing the odds, this premature conclusion will be correct a good percentage of the time. It becomes a
cognitive error on the more rare occasions when these shortcuts lead us astray.
Feedback Bias
"The greatest of faults is to be conscious of none" ~Thomas Carlyle
Feedback bias is another cognitive error that may be particularly pertinent to anesthesiology. This describes the
process that occurs when significant time elapses between actions and consequences, or outcome data is never
reported back to the practitioner. When important information does not return to the decision maker, it is impossible
to shape future decisions based upon that information. As such, the absence of feedback is subconsciously noted as
positive feedback.
Confirmation Bias
"I will look at any additional evidence to confirm the opinion to which I have already come"
--Lord Molson
Believing is seeing: confirmation bias is an error characterized by seeking confirming evidence to support a
diagnosis while discounting disconfirming evidence, despite the latter often being more definitive. Sometimes this
will manifest by "cherry-picking", or trying to force data to fit a desired or suspected diagnosis. A simple example in
anesthesiology might be the repeating of blood pressure measurements, changing cuff sizes and locations, in an
effort to get a reassuring reading, instead of recognizing the hypotension as real. The same could be said for nearly
any monitoring device or interpretation of labs or other studies.
Availability Bias
"Nothing fixes a thing so intensely in the memory as the wish to forget it." ~Michel de Montaigne
Availability bias is an error in diagnosis due to an emotionally memorable past experience. These are the
experiences by which physicians sometimes say they've "been burned", and these memories make the diagnosis
readily available at the forefront of the mind. When this error occurs, the physician may subconsciously ignore
important differences between the current presentation and that prior experience.
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Omission Bias
"The man who makes no mistakes does not usually make anything." ~Edward Phelps
Omission Bias is the tendency toward inaction rather than action, out of fear of failure or being wrong. In the
operating room environment, "group think" can contribute heavily towards this, especially if others do not agree
with the proposed diagnosis or treatment. Consider the case of a suspected pneumothorax, yet the surgeons are
adamant that none could exist and they resist placing a chest tube. Psychologically, it may be difficult to override
this and perform needle decompression. This may be especially likely when a significant authority gradient is
perceived (as with a less experienced anesthesiologists and very senior surgeon) or is real (as may be the case with a
surgeon directly supervising a nurse anesthetist, without an anesthesiologist).
Other cognitive errors include:
Commission Bias
"You will do foolish things, but do them with enthusiasm." ~ Sidonie-Gabrielle Colette
This describes the tendency towards action rather than inaction, even when those actions are un-indicated or founded
on desperation.
Sunk Costs
"Insanity is doing the same thing over and over again and expecting different results." ~ Albert Einstein
Sunk costs describes the phenomenon during which the more effort and commitment invested towards a plan, the
harder it may become psychologically to abandon or revise that plan, because it has been established as the "right"
plan. Continued unsuccessful perseveration may result in patient harm.
Fixation
"If you can see the light at the end of the tunnel, you are looking the wrong way.” ~ Barry Commoner
"He who has a one-track mind, his train of thought often becomes derailed” ~ Arthur Blank
Fixation is focusing on one feature or problem exclusively, at the expense of comprehensive situation awareness.
This may lead to misdiagnosis of a single problem by failing to understand all of its facets, or missing concurrent
diagnoses by focusing on just one.
Framing Effect/Unpacking Principle

"An error does not become truth by reason of multiplied propagation" ~ Gandhi
These describe the mistake of allowing early presenting features to unduly influence decisions. This may be related
to the way a patient history is presented by others, or to our own filters as we review information. Related to this
concept is that of the "Sticky Diagnosis," in which an erroneous diagnosis is recorded in the chart (Latex allergy, for
example) and is never removed despite its discovery by many subsequent caregivers.
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Overconfidence/Denial
"Thinking you know when in fact you don't is a fatal mistake” ~ Bertrand Russell
The labels "Overconfidence" and "Denial" need no explanation, but it may be puzzling as to why these are so
heavily represented in adverse outcome anecdotes, cases resulting is legal action or quality committee reviews, and
autopsy studies.[10]
What can be done to prevent cognitive errors?
Cognitive errors are considerably less tangible than procedural or factual errors. They are described as "low-
visibility", rarely witnessed or recorded, usually with low awareness on the part of the thinker, not conducive to
root-cause analysis, yet potentially highly preventable. [13]
Before we can do anything to prevent errors, we need to understand why we make them.
Reducing cognitive errors depends upon a few distinct but related factors: self-awareness, metacognition, and
cognitive de-biasing.
Increased self-awareness is imperative. Studies of unconscious mental influences demonstrate that increased self-
awareness leads to better management of these cognitive distortions. 7 How can we increase our self-awareness
about our own errors? Although error-blindness presents an inherent challenge, one strategy is the systematic and
deliberate reflection upon one's thoughts, forecasts, and predictions to reveal inherent biases. [1] A self-guided
"debriefing" at the conclusion of each case or each day is one way to accomplish this, though it requires routinely
challenging one's own decisions and rationale with a good deal of skepticism.
Second, because no single strategy of decision making is appropriate for every situation, selection of thought
strategy must be deliberate, and less automatic. Our brains are pluralist: we can carefully analyze and reason
through options, and we can make intuitive "gut instinct" decisions. A crucial step towards avoiding error is
figuring out which brain system is best for a given circumstance. Should we trust our intuitions or calculate the
probabilities? Have we considered the true base-rate, or are we allowing anecdotes to inflate or deflate the
prevalence of a particular problem? We must be thinking about how we think, and considering the specific
environment in which we are thinking. [14]This process is called metacognition.
Third, we must employ de-biasing strategies in our metacognitive practice, which have been shown to reduce the
impact of subconscious tendencies on decision making. Some strategies are as simple as active contrarianism, and
others as challenging as truly cultivating an open mind and mental flexibility.[15] Basic features of metacognitive
practice include recognition of limitations of memory, ability to mentally "step back" and appreciate a broader
perspective, good capacity for self-critique and harnessing overconfidence, and the ability to select specific
strategies for best decision making. Engage in deliberate self checks, asking: "Am I using the best decision-making
strategy right now?" and "Am I relying too heavily on pattern-recognition or bias?" Routinely force yourself to be
less certain, and treat predictions as provisional works-in-progress at all times. [1]
The prior behaviors can be considered "generic" strategies, as they may be ubiquitously useful practices. Still to be
developed in our specialty are context-specific strategies. As an example borrowed from radiology, "systemic
deconstruction" is a specific strategy used to combat confirmation bias. The radiologist reads every chest film in
the exact same systematic way, reporting on all structures and findings, whether positive or negative, regardless of
the study indication or clinical question asked. Further work is needed in anesthesiology to develop these situation-
specific strategies to manage cognitive errors in pitfall-prone contexts.
"An expert is a man who has made all the mistakes which can be made in a very narrow field."
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~Niels Bohr
1. Schulz, K., Being Wrong: Adventures in the Margin of Error.2010, New York, NY: Harper Collins
Publishers.
2. Kohn, L.T., J. Corrigan, and M.S. Donaldson, To err is human : building a safer health system2000,
Washington, D.C.: National Academy Press. xxi, 287 p.
3. Brennan TA, L.L., Laird NM, Hebert L, Localio AR, Lawthers AG, et al. , Incidence of adverse events and
negligence in hospitalized patients. . N Engl J Med, 1991(324): p. 370-376.
4. Croskerry, P., Achieving quality in clinical decision making: cognitive strategies and detection of bias.
Acad Emerg Med, 2002. 9(11): p. 1184-204.
5. Groopman, J., How Doctors Think2007, New York, NY: Houghton Mifflin.
6. Stiegler, M.P., et al., Cognitive errors detected in anaesthesiology: a literature review and pilot study. Br J
Anaesth, 2012. 108(2): p. 229-35.
7. Hallinan, J., Why We Make Mistakes: How We Look Without Seeing, Forget Things in Seconds, and Are All
Pretty Sure We Are Way Above Average2009, New York, NY: Random House.
8. Fine, C., A mind of its own: how your brain distorts and deceives. . 1st ed ed2006, New York, NY: W.W.
Norton & Company.
9. Tavris C, A.E., Mistakes Were Made (But Not By Me): Why We Justify Foolish Beliefs, Bad Decisions, and
Hurtful Acts. 2007, Orlando, FL: Houghton Mifflin Harcourt.
10. Berner, E.S. and M.L. Graber, Overconfidence as a cause of diagnostic error in medicine. American
Journal of Medicine, 2008. 121(5): p. 2-23.
11. Kida, T., Don't Believe Everything You Think: The 6 Basic Mistakes We Make in Thinking2006, Amherst,
NY: Promethius Books.
12. Graber, M.L., N. Franklin, and R. Gordon, Diagnostic error in internal medicine. Arch Intern Med, 2005.
165(13): p. 1493-9.
13. Croskerry, P., Cognitive forcing strategies in clinical decisionmaking. Ann Emerg Med, 2003. 41(1): p.
110-20.
14. Lehrer, J., How We Decide2009, New York, NY: Houghton Mifflin Harcourt.
15. Shore, Z., Blunder: Why Smart People Make Bad Decisions. 2009, New York, NY: Bloomsbury USA.
DISCLOSURE
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Anesthesiologists and the Environment: Can We Save Lives and Do No Harm?

Jodi Sherman, M.D. New Haven, Conneticut
Despite vast successes in modern medicine, industrialized health care unintentionally contributes to environmental
factors that threaten human health and planetary ecosystems. In the United States, health care consumes 8% of
energy production, and produces 18% of the gross national product1. In England, the National Health Service
(NHS) produces 25% of the public sector greenhouse gases. 60% of these emissions come from procurement, and
more than half of this derives from pharmaceuticals and medical devices2. Operating rooms typically account for
30% of overall hospital waste3. The world population is projected to increase to 9 billion by 2050, yet presently we
are already consuming more resources than the planet can sustain. If the current trajectory of modern medicine is
left unmitigated, the costs of “business as usual” will contribute to the worsening of public health and increase the
demand for health services.
The World Health Organization names climate change the defining issue for health systems in the 21st
century, and has called upon physicians to use their authority to lead mitigation4. The United Nations Framework
Convention on Climate Change recognizes six disease categories linked to climate change: cardiovascular disease,
obesity from chemical exposure, asthma and respiratory disease, infectious disease, compromised food security,
malnutrition, increased weather disturbances, saltwater inland, and threat to blood supply through changing vectors
for blood borne illnesses5. It behooves physicians to make every effort possible to limit behaviors that contribute to
the generation and release of greenhouse gases and pollution, and to encourage others to do so. Anesthesiologists
can do better without compromising patient safety, through understanding the connectivity and contribution of
modern practice to public and ecological harm, by employing lesser footprint practices whenever clinical choices
exist, by taking on hospital leadership roles to transform delivery systems and education, and through innovation6.
Life Cycle Assessment (LCA): “cradle-to-grave” environmental and human health impacts
For anesthesiologists to begin to factor environmental impacts into clinical decision-making, environmental impacts
require quantification. Life cycle assessment (LCA) is an internationally accepted scientific method (ISO 14000) of
such quantification. LCA illuminates particular processes or substances that contribute significantly to impacts, and
enables comparison of related products along environmental dimensions7. LCA begins with an inventory (Life Cycle
Inventory, or LCI) of all the inputs at each ‘life’ stage, including 1) raw material extraction, 2) refining and
manufacturing, 3) packaging and transportation, 4) use, reuse and maintenance, 5) recycling and 6) waste disposal.
Several LCA impact categories exist, including CO2 emissions, human health (e.g., carcinogenesis, respiratory
disease), and ecosystem disruption (e.g. eutrification or promotion of algae growth). Comparisons between items
may indicate relative advantages for one outcome (e.g., CO2 emissions), which may be contrary to other outcomes
(e.g., water use), and prioritization of risks and benefits must be considered.
Life cycle assessment applications range from basic materials (e.g., chemicals), to familiar products (e.g.,
coca cola bottles), to complex technological processes (e.g. automobiles), to entire infrastructures and sectors of the
economy8. LCA applications to health care so far have included hemodialysis practices9 and non-surgical
management approaches to acute myocardial infarction management10. LCA applications to anesthetic drugs and
devices are also appearing, and can already aid clinicians in decision-making11-14, though much more LCAs are
needed.
Inhaled anesthetics, greenhouse gases and ozone depletion

Inhaled anesthetics are themselves potent greenhouse gases (GHGs). These inspired drugs undergo very little in
vivo metabolism, and are exhaled virtually unconsumed and unchanged into anesthesia machines or indoor
atmosphere. Exhaled agents are “scavenged” by anesthesia machines and then vented directly into the atmosphere
as medical waste gases. All exhaled anesthetic gases remain for a long time in the troposphere—the lowest layer of
the atmosphere in which the greenhouse effect occurs-- sevoflurane 1.1 years, isoflurane 3.2 years, desflurane 14
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years, and nitrous oxide 114 years. Global Warming Potential (GWP) is determined by the atmospheric lifetime of a
gas, combined with its infrared absorption property or ability to trap heat. A given device or activity can be
quantified by GWP with carbon dioxide as the reference point of 1. GWPs enable comparisons on a kilogram per
kilogram basis over a given time period. A GWP 100-year (GWP100) time frame is commonly reported in the
international community. GWP100 for anesthetic gases include: sevoflurane 130, isoflurane 510, desflurane 2540,
nitrous oxide 29815. Because of the shorter lifetimes of the volatile agents, and because of the current critical
“tipping point” in human history with anthropogenic contributions to planetary warming, the 20-year time frame is
considered my many scientists to be even more meaningful. GWP20 for anesthetic gases include: sevoflurane 440,
isoflurane 1800, desflurane 6810, nitrous oxide 28915. All of these agents are potent greenhouse gases, and
desflurane stands out with the highest global warming potential, followed by isoflurane, sevoflurane and nitrous
oxide.
In addition to global warming potentials, differences exist in drug potency and fresh gas flow rates. When
an hourly amount of each anesthetic, necessary for 1 minimum alveolar concentration (MAC) at appropriate gas
flows, is weighted by the GWP— the clinical impact of these anesthetics can then be compared16. Taking into
account global warming potentials (atmospheric lifetimes and infrared absorption properties), drug potency, and
fresh gas flow rates, the GHG impact of desflurane is several fold higher than isoflurane and sevoflurane. Because
of its low potency and therefore high concentration requirements, and because of its long atmospheric lifetime, the
GHG impact of nitrous oxide rivals that of desflurane11, 15, 16.
Beyond the direct greenhouse gas effects of inhaled agents, life cycle assessment has been applied to look
at the overall impacts of all of the inputs including manufacturing, transportation and use, as well as disposal of
these drugs. LCA further permits conversion and comparison of impacts of inhaled and non-inhaled agents such as
propofol. LCA demonstrates that desflurane accounts for the largest life cycle GHG impact among the common
anesthetics by several fold: 15 times that of isoflurane and 20 times that of sevoflurane on a per MAC-hour basis
when administered in an O2/air. Nitrous oxide GHG impacts are comparable to desflurane, and utilizing it as a
carrier dramatically worsens all of the drug profiles. Because all of the inhaled drugs are potent GHGs in and of
themselves, the uncontrolled emissions of waste anesthetic gases dominate life cycle assessment impacts compared
to other life cycle phases. By comparison, the total life cycle GHG effects of propofol are quite small, nearly 4
orders of magnitude lower than those of desflurane or nitrous oxide. Unlike the inhaled drugs, the GHG impacts of
propofol primarily stem from the electricity requirements for pump delivery systems and not from drug production
or direct release to the environment11.
One estimate commonly cited for the total worldwide contribution of inhaled anesthetics to global warming
is 0.01%17. This number is likely considerably underestimated. Only one U.S. institution’s anesthetic practices
where used to base this extrapolation, and this institution uses comparatively little desflurane. Further still, this one
estimate does not account for dental, veterinary and laboratory medicine. It also fails to account for the combined
inputs of other life cycle phases such as worldwide manufacturing and transportation. This number undoubtedly
underestimates the total worldwide contribution of inhaled anesthetics, which in reality may be closer to 0.1% or
higher. Regardless, experts do consider this contribution a significant target for mitigation.
Separate from greenhouse gas effects, nitrous oxide, and to a lesser extent halothane, are directly
destructive to the ozone layer. The ozone layer exists in the stratospheric layer of the atmosphere and serves to
protect the Earth and its inhabitants from ultraviolet radiation. National Oceanic and Atmospheric Administration
scientists declared nitrous oxide emissions the single most important threat to the ozone layer. Anthropogenic N2O
emissions currently represent the largest contribution to ozone-depleting gas emissions18. While most N2O
emissions come from fertilizer use in industrial agriculture, where alternatives exist it appears prudent to reconsider
its medical use.
Gas capturing and gas destruction technologies do exist. Anesthetic capturing systems can reclaim volatile
drugs, and prevent their release into the environment. Further, there is potential for reprocessing captured gases for
reuse. The Dynamic Gas Scavenging System designed at Vanderbilt University is a cryogenic condensing system,
built or retrofitted into the OR exhaust systems. It is activated only when the patient exhales, as opposed to standard
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continuous scavenging systems, and thereby saves considerable energy use19. DeltasorbTM is an alternative
technology consisting of a canister that snaps into existing scavenging circuits and adsorbs volatile anesthetic
drugs20. The Food and Drug Administration is presently considering approval for reprocessed volatile drugs, which
could also find applications in laboratory and veterinary medicine. Technologies on the near horizon include
photochemical air purification. This approach can destroy all waste anesthetic gases. The advantage of the
destruction technology is that it also handles nitrous oxide whereas the capturing systems do not. Reprocessing a
captured agent as opposed to destroying it and manufacturing anew may or may not have a better environmental
profile, and life cycle assessment is required to discern this.
All inhaled anesthetics are potent greenhouse gases, and additionally nitrous oxide is damaging to the
ozone layer. Inhaled anesthetics should be used thoughtfully. Conscious effort should be made to minimize fresh
gas flows21. Research suggests that desflurane and nitrous oxide should only be restricted to cases where they could
reduce morbidity and mortality over other drugs. Nitrous oxide should not be used simply to spare volatile
anesthetics, or routinely applied in healthy obstetric deliveries without physiologic indication. Gas capturing systems
are already in use, and widespread implementation should be given serious consideration. When appropriate, IV
anesthesia and regional anesthesia techniques may provide the most environmentally sound approach to anesthesia.
Industrial chemicals in manufacturing

Every day, the United States produces or imports 42 billion pounds of chemicals. The health care sector is the single
largest purchaser of chemicals, representing 106.1 billion dollars annually3. Pharmaceutical and industrial pollutants
have become widespread in air, water, soil, food chains, and are also found in humans. Unlike pharmaceuticals,
current regulation of industrial chemicals is covered under Toxic Substance Control Act of 1976 (TSCA) that does
not require safety testing in humans prior to introduction into the marketplace. The Center for Disease Control
(CDC) only recently provides an ongoing assessment of the exposure of the U.S. population to environmental
chemicals through the use of biomonitoring. Of the 84,000 industrial chemicals in the marketplace, only 300 are
currently measured in humans22. Of those measured, hundreds of pollutants can routinely be found in any human
being. Contamination by synthetic chemicals has been observed in amniotic fluid23 and humans as early as birth,
with an average of 200 industrial chemicals identified in the umbilical cord blood of babies born in the United
States24. Many of these substances are known carcinogens, teratogens, neurodevelopmental toxicants, and endocrine
disruptors25-26. Waste reduction and device reuse can lessen the contribution of manufacturing and waste disposal to
environmental pollution, and should be a priority in health care.
Pharmaceutical waste
The majority of all medications that patients take are secreted in the urine, either unchanged or as metabolites.
Medications are often adapted to resist biodegradation and can therefore remain in the environment for a long time.
Municipal wastewater treatment currently does not handle drugs, and pharmaceuticals leach into the environment.
Many medications have been found in drinking water, which is a warning sign that current handling is inadequate.
While these quantities typically are not of therapeutic levels, small quantities and unknown synergies may result in
human disease and developmental disorders as well as ecosystem disruption27-29.
There is currently no information available to health care providers or consumers that adequately compares or
standardizes environmental harm of pharmaceuticals. The environmental department of Stockholm County
Council30 initiated an environmental hazard assessment in 2003, aimed at reducing pharmaceutical residues in the
ground, water, and air. A hazard ‘‘PBT’’ Index for substances emerged that newly includes persistence (P) and
bioaccumulation (B), in addition to traditional consideration for toxicity (T). The index rates pharmaceuticals on a 0
to 9 point scale based equally on these 3 factors. When choices exist, the PBT index can aid clinicians to give
priority to pharmaceuticals that are least harmful to the environment. In 2012, the National Health Service
launched the Greenhouse Gas Protocol Product Life Cycle Accounting and Reporting Standard project, to
encompass the Pharmaceutical and Medical Device Sector31. The NHS project will not only aid clinicians but
importantly will direct industry towards environmentally safer practices and innovation.
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In addition to selecting and developing low-impact pharmaceuticals, it is critical to reduce pharmaceutical

waste. The use of prepackaged drug syringes is gaining in popularity. When anesthesiologists draw up drugs, they
may directly introduce contamination; thus, unused drugs must be discarded in a matter of hours. Prepackaged
syringes, however, are prepared in sterile conditions, and expiration times are comparable with unopened vials,
offering ecologic and economic advantage. Prepackaged syringes are widely available for purchase or can be
prepared in hospital pharmacies.
Problems with plastics

The trend toward disposable devices is epidemic in modern healthcare. In 2007, the US generated almost 14 million
tons of plastics in the Municipal Solid Waste (MSW) stream just as containers and packaging alone. Plastic is
highly resistant to degradation, and can last hundreds of years in the environment. Incinerated plastic produces
many harmful chemicals such as heavy metals, air pollutants, and carcinogens. In 1996, the US EPA declared
medical waste incineration the number one source of dioxin contamination in the atmosphere. This declaration lead
to a Memorandum of Understanding between the US EPA and the American Hospitals Association (ASA) resulting
in the closure of the majority of medical incinerators from 5000 in 1995 to less than 100 in 2008. The majority of
medical waste is now treated and sent to landfills, though hazardous waste is still incinerated making it a prime
target for waste reduction strategies3.
Polyvinyl chloride (PVC) is the most commonly used polymer in plastic hospital devices. The plasticizer di-
ethyl-hexyl phthalate (DEHP) is routinely added to impart flexibility to PVC-based products, and many medical
devices such as IV bags and tubing, and LMAs and ETTs contain up to 40% DEHP by weight. DEHP is lipid
soluble and leaches out of PVC, and urinary metabolites are measurable. The EPA classifies DEHP as a probably
carcinogen, and as a possible endocrine disrupter32-33.
The FDA conducted a safety assessment and subsequently issued an advisory in 2002 recommending steps be
taken to reduce the risk of exposure to DEHP in certain populations. There is enough evidence of reproductive and
developmental toxicant effects from DEHP for the US FDA to recommend alternatives for patients deemed at high
risk, namely infants, toddlers, and pregnant and lactating women. Furthermore, the AMA urges hospitals and health
systems to reduce their use of PVC products, especially those containing DEHP34. There are currently no
recommendations for reduction of DEHP-containing products specific to anesthesia or the operating rooms, and they
are used pervasively.
Solid waste stream diversion: reusing, reprocessing, and recycling

Criteria for the selection and purchase of medical devices typically include safety for patients and
staff, efficacy and ease of use, and purchase and handling costs. On the basis of such criteria, single-use disposable
(SUD) medical devices are increasingly supplanting reusable devices in the U.S. and elsewhere12. Purchase and
maintenance costs for disposable devices are typically perceived to be less than for reusables, yet in reality costs are
typically spread across multiple cost centers making comprehensive assessment challenging. Further, when the
ecological footprint is extended to include manufacturing, materials, labor, and energy and water use on the front
end and disposal labor, energy, landfill costs, and environmental and human health impact on the back end, the
economic and environmental costs may more often be in favor of reusable equipment. Indirect costs to society from
the environmental impacts attributable to the entire life cycle of a device are not yet routinely accounted for, though
models do exist. Comprehensive analysis can be performed using life cycle assessment, and LCA should be
included in purchasing processes and device selection criteria12,14.
Particular concern for infection prevention has led to the proliferation of disposable (one-time use)
equipment options. Laryngeal mask airways (LMAs) provide a good anesthesia example. Although reusable LMAs
can be adequately cleaned and have not been noted to transmit disease35, studies have shown that a biofilm remains
after cleaning which is concerning to some. Further, the purchase of disposable LMAs is believed less expensive
particularly when reusables are accidentally disposed of prematurely. A recent LCA comparing reusable and
disposable laryngeal mask airways (LMAs) found that at Yale-New Haven Medical Center, reusable LMAs were
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environmentally preferable to disposable LMAs if at least 10 uses were achieved. Reusables were actually cheaper
if the manufacturer recommended lifetime of 40 uses could be achieved ($8 per use for reusable vs. $9.60 per
disposable). Certain practices would further reduce the environmental impacts of reusable LMAs, such as simply
autoclaving full loads of devices as opposed to partial loads. For both environmental and economic considerations,
management and operating procedures should be put in place to ensure that reusable LMAs are not discarded
prematurely12. These benefits must be weighed against concerns regarding transmission of infection, though routine
use of disposables appears unwarranted.
Another option that can lower environmental impact of disposable items is the reprocessing of single-use
items. Many equipment items that are sold as ‘‘single use,’’ are designated as such only by the manufacturer, and
not the Food and Drug Administration (FDA). This includes many surgical instruments, and anesthesia items such
as pulse oximeters, blood pressure cuffs, and sequential compression devices. Several companies now reprocess
these used equipment items (Renu, Ascent, and Nellcor for example). Equipment is collected, cleaned, tested to
insure performance mandated by the FDA36, then resterilized and packaged. Unlike new items that are sample batch
tested, every reprocessed device is tested, and device failure rate is no different between them37. In addition to waste
stream diversion, reprocessed items may be sold back to hospitals with as much as a 40% discount. Surgical
equipment such as laparoscopic trochars are routinely reprocessed, and anesthesia equipment such as pulse oximeter
probes, blood pressure cuffs, and laryngoscope blades can be as well. Reprocessing reduces environmental impacts
and provides considerable cost savings on disposal and purchasing38.
Recycling is now making its way into the ORs. Without doubt, reuse is preferable. Where this is not
possible, e.g., with packaging, significant cost and environmental savings can be achieved through diversion from
waste streams. OR recycling may be achieved through collecting items during case setup, where more than one
third of OR waste is generated. Doing so prior to bringing patients into the OR eliminates concern for infectious
contamination. Single source waste stream recycling is gaining in popularity, making collection simply by
eliminating the need to separate types of recyclables39-40.
Environmental impact and anesthesia practice

The ecological footprint of healthcare is enormous. Noble concern and care for the individual patient often neglects
the impact of such dedicated practice on community and planetary health. The specific ecological footprint of
perioperative practice is one of the largest in all of healthcare, representing more than a third of hospital waste
streams. Many strategies are available for reduction of waste and pollution from operating rooms and perioperative
areas. These include environmentally preferable purchasing (EPP), shifting back to reusable devices, reprocessing
equipment, recycling materials, avoiding DEPH-laden plastics, donating equipment to programs such as
REMEDY41, and energy efficient OR re-design42. Additionally, clinicians can select least-impact drugs, use pre-
packaged syringes, minimize lowest fresh gas flows, chose least impact volatile agents, and use IV anesthesia and
regional anesthesia where safe and feasible. Some of these more basic strategies may be in place already, with
education and awareness limiting factors of implementation.
Environmental impact assessments of every single anesthetic device and drug are long over due.
Anesthesiologists must consider the ecologic impact of manufacturing and waste disposal when devising and
implementing an anesthetic plan. Given the current safety profile of agents and devices, anesthetic plans should be
guided by concern for their ecological repercussions. The future of the field of anesthesia, and all of healthcare, lies
in innovation and incorporation of sustainability into practice.
References:
1.Chung JW, Meltzer DO. Estimate of the carbon footprint of the US health care sector. JAMA 2009;302:1970–2
2.U.K. Sustainable Development Commission. NHS Eng Carbon Footprinting Report 2009
3.Ecological Responsibility in Anesthesia Practice, Sherman J and Ryan S, I'nat Anest Clinics, Vol. 48, No. 3, 139–
151 r 2010, Lippincott Williams & Wilkins
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4.World Health Organization. Protecting Health from Climate Change, 2009:

http://whqlibdoc.who.int/publications/2009/9789241598880_eng.pdf
5.IPCC, 2007: Climate Change 2007: Impacts, Adaptation, and Vulnerability, http:// www.ipcc-wg2.org/index.html.
Contribution of Working Group II to the Fourth Assessment Report of the Intergovernmental Panel on Climate
Change, http:// www.eia.doe.gov/
6.Ryan S, Sherman J. Sustainable Anesthsia. Anesth Analg 2012;114: 921-3
7.Finnveden G, Hauschild MZ, Ekvall T, Guinee J, Heijungs R, Hellweg S, Koehler A, Pennington D, Suh S.
Recent developments in life cycle assessment. J Environ Manage 2009;91:1–21
8.Hendrickson C, Lave L, Matthews H. Environmental Life Cycle Assessment of Goods and Services: An Input-
Output Approach. Resources for the Future Press, Washingon, DC, 2006
9.Connor A, Lillywhite R, Cooke MW. The carbon footprints of home and in-center maintenance hemodialysis in
the United Kingdom. Hemodialysis International 2011;15:39–51
10.Zander A, Niggebrugge A, Pencheon D, Lyratzopoulos G, Changes in travel-related carbon emissions associated
with modernization of services for patients with acute myocardial infarction: a case study. J Public Health 2011
Jun;33(2):272-9
11.Sherman J, Le C, Lamers V, Eckelman M. Life cycle greenhouse gas emissions of anesthetic drugs. Anesth
Analg 2012;114: 1086-90
12.Eckelman M, Mosher M, Gonzalez A, Sherman J. Comparative life cycle assessment of disposable and reusable
laryngeal mask airways. Anesth Analg 2012;114: 1067-72
13.McGain F, McAlister S, McGavin A, Story D. A life cycle assessment of reusable and single-use central venous
catheter insertion kits. Anesth Analg 2012;114: 1073-80
14.McGain F, Story D, Kayak E, Kashima Y, McAlister S. Workplace Sustainability: The “cradle to grave” view of
what we do. Anesth Analg 2012;114: 1134-39
15.Sulbaek Andersen MP, Nielsen OJ, Karpichev B, Wallington TJ,vSander SP, Atmospheric Chemistry of
Isoflurane, Desflurane,and Sevoflurane: Kinetics and mechanisms of reactions with chlorine atoms and OH radicals
and global warming potentials. J Phys Chem A. 2012 Jun 21;116(24):5806-20
16.Global Warming Potential of Inhaled Anesthetics: Application to Clinical Use, Ryan S, Nielson C, et al., A & A
July 2010 vol. 111 no. 1 92-98
17.Sulbaek Andersen MP, Nielsen OJ, Wallington TJ, Karpichev B, Sander SP. Assessing the impact on global
climate from general anesthetic gases. Anesth Analg 2012;114: 1081-5
18. Nitrous Oxide (N2O): The Dominant Ozone-Depleting Substance Emitted in the 21st Century, Ravishankara A,
et al., Science 326, 123 (2009); DOI: 10. 1126/science. 1176985
19.Barwise JA, Lancaster LJ, Michaels D, Pope JE, Berry JM. An initial evaluation of a novel anesthetic scavenging
interface. Anesth Analg 2011;113:1064–7
20.www.bluezone.ca/
21.Feldman JM. Managing fresh gas flow to reduce environmental contamination. Anesth Analg 2012;114:
1093–101
22.http://www.cdc.gov/biomonitoring/
23.Jensen, MS, B Nørgaard-Pedersen, G Toft, DM Hougaard, JP Bonde, A Cohen, AM Thulstrup, R Ivell, R
Anand-Ivell, CH Lindh and BAG Jönsson. 2012. Phthalates and perfluorooctanesulfonic acid in human amniotic
fluid: temporal trends and timing of amniocentesis in pregnancy. Environ Health Perspect. 2012 Jun;120(6):897-903
24.Pollution in People Cord Blood Contaminants in Minority Newborns, 2009, http://www.ewg.org/files/2009-
Minority-Cord-Blood-Report.pdf
25. Collaborative on Health and the Environment, Consensus Statement,
http://www.healthandenvironment.org/about/consensus
26.Center for Disease Control and Prevention, National Report on Human Exposure to Environmental Chemicals,
Fourth Report, 2009, http://www.cdc.gov/exposurereport/
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27.European Community Regulation on chemicals and their safe use (EC 1907/2006),
http://ec.europa.eu/environment/chemicals/reach/reach_intro.htm
28.Stackelberg P, Furlong ET, Meyer MT, et al. Persistence of pharmaceutical compounds and other organic
wastewater contaminants in a conventional drinking-water-treatment plant. Science Total Environ. 2004;329:99–113
29.Jean J, Perrodin Y, Pivot C, Trepo D, Perraud M, Droguet J, Tissot-Guerraz F, Locher F, Identification and
prioritization of bioaccumulable pharmaceutical substances discharged in hospital effluents. Journal of
Environmental Management 103 (2012) 113-21
30.Janusinfo, Stockholms lans landsting, http://www.janusinfo.se/v/About-theenviron ment- and-
pharmaceuticals//?id = 9930
31. GHG Protocol Product Life Cycle Accounting and Reporting Standard: Sector Guidance for Pharmaceutical and
Medical Device Products, National Health Service Sustainability Development Unit, Consultation Draft June 2012
32.Bis(2–ethylhexyl) phthalate (DEHP), Hazard Summary-Created in April 1992; Revised in January 2000, US
Evironmental Protection Agency, http://www.epa.gov/ ttn/atw/hlthef/ethphth. html
33. Safety Assessment of di-(2-ethylhexyl)-phthalate (DEHP) Released from PVC Medical Devises,
hhtp:/www.fda.gov/cdrh/safety/dehp.html
34.AMA Policy H-135.945 36. Chu LF, Mathur P, Trudell JR. Contamination problems with reuse of laryngeal
mask airways and laryngoscopes. Saudi J Anesth. 2008;2:58–61
35.Rutala, WA Ph.D., Weber, David, M.D., Healthcare Infection Control Practices Advisory Committee (HICPAC).
CDC Guideline for Disinfection and Sterilization in Healthcare Facilities, 2008
36.FDA-cleared Sterilants and High Level Disinfectants with General Claims for Processing Reusable Medical and
Dental Devices-March 2009
http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/ReprocessingofSingle-
UseDevices/UCM133514
37.Government Accountability Office (GAO). Report to the Committee on Oversight and Government Reform,
House of Representatives. Reprocessed Single-Use Medical Devices: FDA Oversight Has Increased, and Available
Information Does Not Indicate That Use Presents an Elevated Health Risk. Jan. 31, 2008.
38.Kwakye G, Pronovost PJ, Makary M, Commentary: a call to go green in health care by reprocessing medical
equipment. Acad Med. 2010 Mar;85(3):398-400.
39. ‘‘Greening Hospitals’’ an Analysis of Pollution Prevention in America’s Top Hospitals, Health Care Without
Harm, Environmental Working Group, Campaign for Environmentally Responsible Care,
http://www.ewg.org/files/greening.pdf
40.Green Guide for Healthcare: www.gghc.org
41.http://remedyinc.org/default.aspin
42.Leadership in Energy and Environmental Design (LEED) program of the US Green Buildings Council,
www.usgbc.org
DISCLOSURE
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Occupational Hazards and Health for Anesthesiologists

Jonathan D. Katz, M.D. New Haven, Conneticut
INTRODUCTION
Employment in the health care industry can be hazardous to one’s health. According to the U.S. Bureau of
Labor, health care is second only to manufacturing in the number of occupational illnesses and injuries sustained by
their workers.1 Anesthesia personnel are at risk of acquiring a number of occupational illnesses and injuries that are
endemic to the high intensity environment of the operating room. Workplace hazards include exposure to waste
anesthetic gases, ionizing radiation, and to infectious agents. Anesthesia care providers are vulnerable to injury from
accidents, fires, or explosions. Additionally, anesthesia personnel are susceptible to emotional and psychological
disorders such as burnout and substance abuse engendered at least in part by the high stress and other demands
inherent in their work.
In the following discussion we will consider the sources of many of these injuries and practical means of
avoidance. We will also discuss the growing awareness of the importance of preventative strategies that encourage
wellness among our colleagues.
PHYSICAL HAZARDS
Accidents: Injuries as a result of accidents are the most common of the physical hazards in the operating room.
However, few of these injuries are reported and much of the information on accidents in the operating room comes
from anecdotes or incident reports.
Needle stick injury is the most frequent accident suffered by anesthesiologists. The majority of needle stick
injuries occur during use, but many occur during recapping and disposal. Needle stick injuries are preventable and
potentially lethal.
Waste Anesthetic Gases: Potential health hazards from waste anesthetic gases have been a concern since
the introduction of inhalation anesthetics into clinical practice. Extensive investigation has failed to identify any link
between the level of exposure to trace gases that anesthesiologists receive in a modern, scavenged operating room
and adverse health effects.2 Effective scavenging of waste gases is essential as demonstrated by reports of reduced
fertility and elevated spontaneous abortion among female dental assistants and veterinarians working in
unscavenged operating rooms.
Ionizing Radiation: A growing concern within modern operating suites is exposure of personnel to radiation as
a result of the increasing number and complexity of procedures requiring x-ray imaging. Anesthesia personnel are at
risk of exposure from both direct and indirect sources of ionizing radiation.
The biologic consequences of radiation exposure vary depending on age, gender, and specific organ site of
exposure. The deterministic effects of radiation cause cell death and organ injury and are cumulative in a dose
related fashion. Common examples of deterministic injuries include skin damage, infertility, and certain types of
cataracts. Stochastic effects of radiation are those that result in DNA injury and the development of cancer. There is
no known threshold below which the risk of developing these consequences completely disappears. And there is
frequently a long latency period before the clinical presentation of an induced neoplasm.
The Occupational and Safety Heath Administration (OSHA) has set an annual limit for workers with
potential exposure to ionizing radiation of 5 Rems and a life time limit of (N-18) x 5 Rems (where N is the age in
years). Early studies found the exposure to radiation among anesthesia personnel to be safely below these limits.
However, more recent studies, conducted subsequent to the increased utilization of ionizing radiation in operating
rooms and many other anesthetizing locations, such as cardiac catheterization labs, have revealed a trend towards
increased exposure among anesthesia personnel. In one study, the mean radiation exposure for members of a
department of anesthesiology doubled in the six months after a new electrophysiology service was introduced 3
Anesthesiologists in this study increased their average exposure to almost 500 mRem on an annualized basis. A
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similar study reported a significant level of exposure to anesthesiologists during endoscopic retrograde
cholangiopancreatography (ERCP) and cardiac catheterization 4In both of these studies, exposure remained well
below the annual limit set of 500 mRem. However, it must be appreciated that many of the diseases associated with
radiation exposure exhibit a direct dose response relationship—making as low as reasonably practical (ALARP) the
safest practice. Preventative strategies for anesthesiologists to limit their radiation exposure include decreasing the
exposure time, distancing oneself from the source of the radiation, and using maximal shielding from both primary
and scattered sources of radiation.
A second form of radiation with potential health hazards comes from chronic exposure to low-frequency
electromagnetic fields such as those emitted by MRI equipment. It is often necessary for the anesthesia care
provider to remain in close proximity to the patient, and thus the magnet during MRI studies. Data are not yet
available to determine the safety of long-term exposure to high-intensity magnetic fields. Therefore, until such time
that safety thresholds have been determined for this type of exposure, anesthesiologists should obey the general
admonition regarding all radiation exposure-as low as reasonably practical.
Infectious Agents: The risk to anesthesia personnel of acquiring infections in their workplace continues to
increase because of the growing number of antimicrobial resistant bacteria, and the frequent appearance in operating
rooms of immune-compromised patients who might serve as vectors for resistant and opportunistic organisms.
Additionally, diseases that were once thought to be noninfectious, such as peptic ulcer disease (Heliobacter pylori),
invasive cervical cancer (human papillomavirus), Kaposi’s sarcoma (human herpesvirus type 8) and certain
lymphomas (Epstein-Barr virus) are now understood to be long-term consequences of infection, making
occupational health precautions even more important.
Immunity against some viral pathogens, such as hepatitis B, can be obtained through vaccination.
Transmission of other blood-borne pathogens, such as hepatitis and human immunodeficiency virus (HIV) can be
prevented by rigorously applying “Standard Precautions” as detailed by the Centers for Disease Control and
Prevention (CDC). These precautions include the appropriate use of hand washing, personal protective equipment
(PPE), and respiratory hygiene/cough etiquette. The selection of specific barriers or PPE can be as basic as wearing
gloves for some patient contacts, or as complicated as employing advanced personal protection gear, such as gown,
mask, and face shield or respirator for many invasive procedures.
In addition to CDC guidelines, OSHA has developed standards designed to protect employees from
occupational exposure to blood-borne pathogens. Among other requirements, these standards require that an
employer encourage strategies to reduce blood exposures, furnish appropriate PPE, and provide an annual
educational program focused upon employees’ risk of blood-borne infection. In addition, the institution’s employee
health service is required to maintain protocols for workers exposed to contagious diseases such as Tuberculosis,
HIV or hepatitis.
Case reports of occupationally acquired infection have appeared for virtually every communicable disease.
Pathogens of special concern for anesthesiologists include: influenza types A B and C, human respiratory syncytial
virus, SARS-associated coronavirus, norovirus, c. difficile , herpes simplex viruses, Epstein-Barr virus , rubella,
rubeola, hepatitis virus A B and C, human immunodeficiency virus, methicillin resistant staphylococcus aureus, and
tuberculosis.
In the event of an exposure to a pathogenic microorganism, the incident should be reported to the employee
health service. There are extensive post- exposure treatment protocols for many of the pathogens that should be
initiated immediately after exposure to many of these pathogens. Detailed recommendations for post- exposure
prophylaxis in the event of exposure to HIV can be obtained from the National Clinicians' Post-Exposure
Prophylaxis Hotline (PEPline) at 888-448-4911.
Work Hours, Night Call, and Fatigue: Inadequate sleep resulting from any number of factors, including
obstructive sleep apnea or disruptive work schedules, can have deleterious effects upon work practices and
contribute to illness. Workers who are sleep deprived suffer a decrement in performance and are at greater risk of
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committing workplace errors and to suffer work related injuries. The impairments associated with sleep deprivation
bear a striking similarity to those seen with alcohol intoxication.
The contribution of sleep loss and fatigue to accidents has been documented in many well-publicized
industrial catastrophes, including those that occurred at Chernobyl, Three Mile Island, Exxon-Valdez, and the
Challenger space shuttle disaster.
The changes imposed by fatigue have the potential to adversely impact an anesthesiologist’s ability to
conduct a safe anesthetic. Important fatigue related changes include: impairment of mood, alertness, short term
memory and cognition, prolonged reaction time, diminished, compromised clinical decision making, and reduced
attention, vigilance and performance. In one study, 58% of New Zealand anesthesiologists reported that they had
exceeded their self-defined limit for safe continuous administration of anesthetic and 86% reported that that they had
committed a fatigue-related error.5 Similar reports of fatigue-related complications have appeared in the surgical
literature where as many as 16% of preventable adverse surgical events have been attributed to surgeon fatigue. 6
However, others disagree and cite reports in which there was no evidence that suboptimal clinical management or
poor outcomes occurred to patients managed by sleep deprived clinicians.7
Medicine remains significantly behind other industries in regulating work hours. The Accreditation Council
for Graduate Medical Education (ACGME) established the first set of standards to limit resident duty hours in 2000,
which were revised in 2011. However, these restrictions on duty hours apply only to trainees and work hours in
medical practice remain largely unregulated.
An unintended consequence of the restrictions on trainee’s duty hours has been a shift of work from
residents to faculty. Practicing anesthesiologists continue to work long hours. Attending anesthesiologists and nurse
anesthetists still commonly work 10- to 12-hour workdays and 24 hour on-call shifts. Gravenstein et al reported that
the average anesthesiologist’s work week was 56 hours and that 74% of the respondents had worked without a break
for longer periods than they personally thought was safe.8
Noise: Noise levels in a modern operating room frequently exceed established limits for safe noise exposure and
pose a potential health hazard. Ventilators, suction equipment, music, and conversation produce background noise
at a level of 75 to 90 dB. Sporadic noises caused by surgical equipment and alarms can elevate these noise levels to
greater than 100 dB with peak levels in excess of 120 dB. These are the noise levels produced on a busy freeway or
by a rock and roll band.
Excessive levels of noise can diminish an anesthesiologist’s mental efficiency, short-term memory, and
ability to multitask. Noise also interferes with the ability to hear crucial verbal communications and equipment
alarms. There are also health ramifications of long-term exposure to excessive noise. Chronic exposure has been
associated with elevated levels of endogenous catecholamines and heightened levels of stress, increased irritability,
and elevated blood pressure.
Ultimately, exposure to excessive noise levels will result in hearing loss. Although no direct connection has
been established with noise levels in operating rooms, it is interesting to note that more than 50% of
anesthesiologists have a substantial hearing deficit and 7% have deficits that potentially interfere with their ability to
hear operating room alarms.9
Music is the one form of background noise that provides a number of beneficial effects. Music has proven
advantageous as a supplement to sedation and analgesia for surgical patients. Self-selected background music can
contribute to reducing autonomic responses and improving performance of operating room personnel. The beneficial
effects are lost when a third party chooses the music. The selection of music, and the volume at which it is played,
should be by mutual agreement of all parties present in the operating room.
Impairment and Disability: Impairment and disability can result from physical, mental, emotional, sensory or
developmental etiologies. The onset can be sudden, as occurs with injury or acute illness, or more gradual, as is the
case with many chronic diseases. Many cases of physician impairment are the result of substance abuse.
Unwillingness or inability to keep up with current literature and techniques can be considered a form of impairment.
Depression is often the presenting syndrome among impaired physicians. Unfortunately, many of the
personality traits that serve as risk factors for depression are the same as those found, perhaps to a lesser degree, in
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the most successful physicians, such as self-sacrifice, achievement orientation, and intellectualization of emotions.
Observations of alcoholic physicians offer examples of the potential association between emotional disturbance and
achievement orientation. In one study, researchers found better first-year grades and higher scores on Part I
National Board of Medical Examiners among those students identified as alcohol abusers. 10 Similarly, more than
one half of alcoholic physicians had graduated in the upper one third of their medical school class, and only 5%
were in the lower one third of their class.11
It can be very challenging to appropriately respond to all of the problems created by and an impaired or
unsafe colleague. Management protocols for dealing with the impaired physician are covered in a series of articles
by Canavan. 12
EMOTIONAL HAZARDS
Stress: Chronic occupational stress can contribute to poor mental and physical health, industrial accidents and
injury. Mild, brief, and controllable episodes of occupational stress are unavoidable and can serve as an impetus to
personal achievement. On the other hand, extreme degrees of chronic stress are harmful and can contribute to mood
and sleep disturbances, and gastrointestinal, musculoskeletal and cardiovascular disease. Stress-related outcomes in
the workplace include physical injuries, absenteeism, decreased productivity and increased disability.
The work environment of an anesthesiologist contains many of the features of a classically defined stressful
workplace. The background of chronic, low-level stress is frequently punctuated by intermittent episodes of extreme
stress. Many of the clinical demands are externally paced and unpredictable in timing or urgency. Habituation to the
ever changing demands is difficult. Finally, failure to meet the demands imposed by the workplace can result in
serious consequences.
Certain specific stressors are commonly reported by anesthesiologists. These include the unpredictability of
the work, the need for sustained vigilance during long intervals, production pressure, concern about litigation,
difficult interpersonal relations, and economic uncertainties.
To many who work in the operating room, interpersonal relationships and conflict are the greatest source of
workplace stress. Conflict can easily occur where overlapping areas of professional responsibility exist, as routinely
occurs in the operating room, where surgeon and anesthesiologist simultaneously share patient responsibility. Recent
work has focused upon applying the principles of Crisis Resource Management, first developed in the aerospace
industry, to improve communication and team work in the operating room. 13
Catastrophic intraoperative incidents, bad patient outcomes and the accompanying threat of litigation are
frequent sources of stress to anesthesiologists. Many anesthesiologists experience long lasting emotional
disturbances after being involved in a catastrophic incident in the operating room that resulted in patient injury or
death. In a recent survey, 84% of anesthesiologists admitted to being involved in a serious or fatal incident and
greater than 70% reported that they experience lingering guilt, anxiety or a sense of personal responsibility for the
patient's injury or death.14 Approximately 20% never completely recovered from the episode.
Burnout: Burnout is characterized by physical and emotional exhaustion, poor judgment, cynicism, guilt, feelings
of ineffectiveness, and a sense of depersonalization. Unfortunately, many of the attributes desired in health care
providers, such as idealism, perfectionism, and a heightened sense of responsibility, can also make these individuals
more vulnerable to feelings of inadequacy if their high standards are unmet.
Commonly cited causes of burnout among anesthesiologists are production pressure, excessive regulation,
long hours of work, lack of control of one’s schedule, decreasing reimbursement, a rapidly expanding base of
medical knowledge and difficulty balancing personal and professional lives.
Physicians suffering from burnout are prone to medical errors and malpractice lawsuits. Burnout has also
been shown to be a contributor to various illnesses, including cardiovascular disease and substance abuse.
Significant degrees of burnout have been identified among anesthesiologists. Greater than 50% of
American academic chairs meet the criteria for high or moderate degrees of burnout. 15
Substance abuse: Substance abuse occurs when an individual repeatedly abuses a drug despite significant adverse
consequences. The addicted individual continues to use the substance in spite of the need for larger amounts of the
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substance, unsuccessful attempts to control its use, the necessity of spending greater amounts of time seeking the
substance, and symptoms of withdrawal.
The prevalence of alcoholism and substance abuse is approximately equal for physicians and the general
population. However, physicians are less likely to abuse tobacco or illicit drugs and more likely to self-medicate
with prescription drugs.
Many studies have reported a disproportionately high prevalence of substance abuse among
anesthesiologists as compared to other physicians. Additionally, these reports demonstrate that anesthesiologists are
more likely than other physicians to become addicted to potent intravenous drugs such as opioids or propofol that
are potentially lethal. As a result, many authorities now consider substance abuse to be the number one occupational
hazard of anesthesiology.
One particularly troubling aspect of this problem is the persistently high incidence of substance abuse
among anesthesiology residents. In one of the most cited studies, anesthesiology residents constituted 33.7% of the
resident population of the treatment group in the Medical Association of Georgia Disabled Doctors’ Program,
despite representing only 4.6% of the overall resident population. 16 The incidence of substance abuse within
anesthesiology training programs continues to run close to 2% despite increased emphasis on substance abuse
educational programs and more stringent accounting of controlled substances.17
Addiction is a chronic progressive disease that, if untreated, is frequently fatal. Alexander et al calculated a
relative risk of 2.79 for drug related deaths among anesthesiologists compared to a matched cohort of internists.18
Re-entry into clinical practice after rehabilitation is a particularly vulnerable period, with drug-related death rates as
high as 20% among anesthesiology residents who were re- enrolled after treatment for chemical dependency . 19
There is an ongoing debate about the ultimate career path of the anesthesiologist in recovery. Reports have
ranged from very pessimistic to more optimistic regarding the ability of recovering anesthesiologists to successfully
return to practice. An early study reported only a 34% success rate for reentry for residents who had used
parenteral
opioids. Included among the 52 failures were 14 cases of suicide or lethal overdose .19 More recent data
found that 76% of anesthesiologists who had completed rehabilitation in a state run physician health program
remained in practice at 5 year follow up. There was no difference between anesthesiologists and non-
anesthesiologists with regard to rates of relapse, mortality or disciplinary action. 20Guidelines from physician
treatment centers may be helpful to assist in the decisions surrounding re-entry.
THE AGING ANESTHESIOLIOGIST

Important physiologic changes can impact an older anesthesiologist’s ability to administer a safe anesthetic.
Commonly observed physiological changes include impairments in hearing, vision, short term memory, and
problem-solving abilities. Intellectual quickness, learning, and reaction time all slow. These changes have the
potential to limit the older anesthesiologist’s ability to rapidly process information, assimilate and apply new
knowledge, make complex decisions and initiate a proper response.
Age related changes in the cardiovascular and musculoskeletal systems can make it more difficult for older
anesthesiologists to sustain the long, demanding work shifts common in anesthetic practice. Older individuals are
particularly sensitive to disturbances of the sleep–wake cycle and are less well suited to night time work. Night call
has been identified as the most stressful aspect of practice and most frequently cited impetus toward retirement
among older anesthesiologists.21
On the other hand, normal aging also contributes advantages, such as wisdom, judgment, and the
experience acquired by a lifelong practice of the specialty. There is a strong positive correlation between experience
and performance of many tasks required for administration of a safe anesthetic.
Anesthesiology is often regarded as a young person’s profession. Anesthesiologists tend to retire at a
younger age than many other physicians. The decision to retire from anesthesiology is frequently precipitated by
concerns about deteriorating clinical skills and the growing burdens of night call.
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MORTALITY AMONG ANESTHESIOLOGISTS

A number of studies have examined mortality among anesthesiologists and arrived at different conclusions
regarding the average life expectancy. The most recent study found that the average age at death among
anesthesiologists was 78 years, the same as the national average for all Americans. 22
Inconsistent findings have also been reported about the most common causes of death among
anesthesiologists. Earlier work found an increased incidence of certain types of cancer. More recent reports have
failed to find any increase in cancer risk but a consistent finding of increased numbers of drug related deaths and
suicide.
Malpractice law suits and substance abuse are two precursor events that have a strong association with
suicide among anesthesiologists. One study reported that 4 of 185 anesthesiologists being sued for medical
malpractice attempted or committed suicide. 23 In Alexander’s study, drug abuse was the most frequent method of
suicide among anesthesiologists. 18
WELLNESS
It is estimated that half of the mortality in the US is premature. Many of these lives could have been
preserved with the modification of just 10 behaviors - tobacco use, dietary pattern, physical activity level, alcohol
consumption, exposure to microbial agents, exposure to toxic agents, use of firearms, sexual behavior, motor vehicle
crashes, and illicit use of drugs.
One of the greater challenges for busy anesthesiologists is to balance the demands and stress of practice
with the time necessary for wellness maintenance. A recent article describes the value of a proactive wellbeing
program towards decreasing stresses and improving coping in a group of anesthesia residents. 24
The importance of wellness has also been recognized by the ASA. The ethical guidelines of the ASA state
that anesthesiologists are obliged to maintain their “physical and mental health and special sensory capabilities”.
25
With this in mind, the ASA has developed a “Health and Wellness in Action” initiative whose primary mission is
to promote the health and welfare of ASA members.
BIBLIOGRAPHY
1. US Dept Labor Bureau of labor statistics. Fatal Occupational Injuries and Nonfatal Occupational Injuries
and Illnesses, 2008. http://www.bls.gov/iif/ Accessed 5/22/2012
2. McGregor DG: Occupational exposure to trace concentrations of waste anesthetic gases. Mayo Clin Proc
2000; 75: 273-7
3. Katz JD: Radiation exposure to anesthesia personnel: the impact of an electrophysiology laboratory.
Anesthesia and Analgesia 2005; 101: 1725-6
4. Ismail S, Khan F, Sultan N, Naqvi M: Radiation exposure to anaesthetists during interventional radiology.
Anaesthesia 2010; 65: 54-60
5. Gander PH, Merry A, Millar MM, Weller J: Hours of work and fatigue-related error: a survey of New
Zealand anaesthetists. Anaesth Intensive Care 2000; 28: 178-83
6. Gawande AA, Zinner MJ, Studdert DM, Brennan TA: Analysis of errors reported by surgeons at three
teaching hospitals. Surgery 2003; 133: 614-21
7. Rothschild JM, Keohane CA, Rogers S, Gardner R, Lipsitz SR, Salzberg CA, Yu T, Yoon CS, Williams
DH, Wien MF, Czeisler CA, Bates DW, Landrigan CP: Risks of complications by attending physicians after
performing nighttime procedures. Journal of the Americal Medical Association 2009; 302: 1565-72
8. Gravenstein JS, Cooper JB, Orkin FK: Work and rest cycles in anesthesia practice. Anesthesiology 1990;
72: 737- 742
9. Wallace MS, Ashman MN, Matjasko MJ: Hearing acuity of anesthesiologists and alarm detection.
10. Clark DC, Gibbons RD, Daugherty SR, Silverman CM: Model for quantifying the drug involvement of
medical students. Int J Addict 1987; 22: 249-71
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11. Bissell L, Jones RW: The alcoholic physician: a survey. Am J Psychiatry 1976; 133: 1142-6
12. Canavan DI, Baxter LE, Sr.: The twentieth anniversary of the Physicians' Health Program of the Medical
Society of New Jersey. N J Med 2003; 100: 27-9
13. Gaba DM: Crisis resource management and teamwork training in anaesthesia. Br J Anaesth 2010; 105: 3-6
14. Gazoni FM, Durieux ME, Wells L: Life after death: the aftermath of perioperative catastrophes. Anesthesia
and Analgesia 2008; 107: 591-600
15. De Oliveira GS, Jr., Ahmad S, Stock MC, Harter RL, Almeida MD, Fitzgerald PC, McCarthy RJ: High
incidence of burnout in academic chairpersons of anesthesiology: should we be taking better care of our leaders?
16. Talbott GD, Gallegos KV, Wilson PO, Porter TL: The Medical Association of Georgia's Impaired
Physicians Program. Review of the first 1000 physicians: analysis of specialty. JAMA 1987; 257: 2927-30
17. Collins GB, McAllister MS, Jensen M, Gooden TA: Chemical dependency treatment outcomes of residents
in anesthesiology: results of a survey. Anesth Analg 2005; 101: 1457-62
18. Alexander BH, Checkoway H, Nagahama SI, Domino KB: Cause-specific mortality risks of
anesthesiologists. Anesthesiology 2000; 93: 922-30
19. Menk EJ, Baumgarten RK, Kingsley CP, Culling RD, Middaugh R: Success of reentry into anesthesiology
training programs by residents with a history of substance abuse. Journal of the Americal Medical Association 1990;
263: 3060-2
20. Skipper GE, Campbell MD, Dupont RL: Anesthesiologists with substance use disorders: a 5-year outcome
study from 16 state physician health programs. Anesthesia and Analgesia 2009; 109: 891-6
21. Travis KW, Mihevc NT, Orkin FK, Zeitlin GL: Age and anesthetic practice: a regional perspective. Journal
of Clinical Anesthesia 1999; 11: 175- 186
22. Katz JD: Anesthesiologists are living longer- or are they? Anesthesiology 2003; 99: 1285
23. Birmingham PK, Ward RJ: A high-risk suicide group: the anesthesiologist involved in litigation. Am J
Psychiatry 1985; 142: 1225-6
24. Saadat H, Snow DL, Ottenheimer S, Dai F, Kain ZN: Wellness program for anesthesiology residents: a
randomized, controlled trial. Acta Anaesthesiol Scand
25. American Society of Anesthesiologists. Guidelines for the ethical practice of Anesthesiology .
http://www.asahq.org/publicationsAndServices/standards/10.pdf. Accessed 5/22/2012
DISCLOSURE
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A Fire in the Operating Room: It Could Happen to You

Jan Ehrenwerth, M.D. New Haven, Connecticut
In the days when flammable anesthetic agents were frequently used, fire and explosion hazards were of paramount
importance to the anesthesiologist. Although most operating room personnel do not consider fires a major safety
hazard, in reality many fires occur in the operating room every year. It has been estimated by the ECRI (Emergency
Care Research Institute) that there are approximately 500-600 operating room fires every year in the United States.
About 10% of these produce serious injury to patients or operating room personnel. Therefore, it is incumbent upon
all those who work in the operating room to be aware of how to prevent fires and what to do if one should occur.
The Fire Triad

In order for a fire to occur, three elements must come together at the same time. These elements are known as the
fire triad. They include; (1) heat, or an ignition source; (2) fuel; and (3) an oxidizer. In the operating room, the heat
source is commonly the electrosurgical unit (ESU), a laser, or a fiberoptic light cord. There are many elements that
can provide fuel for an operating fire. These include paper drapes, plastics, gauze dressings, endotracheal tubes, the
patient’s hair, linens and gel mattress pads. The common oxidizers in the operating room are oxygen, air and nitrous
oxide.
A fire is actually the chemical reaction of fuel rapidly combining with oxygen with the resultant release of heat and
light energy. Prevention is clearly better than extinguishing a fire. Fires can be prevented by isolating the various
legs of the fire triad. This can be done by minimizing the amount of oxygen or nitrous oxide that is delivered to the
patient. It should be remembered that oxygen and nitrous oxide support combustion equally well. Therefore, a
mixture of 50% nitrous oxide and 50% oxygen is virtually the same as 100% oxygen. Oxygen and nitrous oxide are
oxidizers and not explosive gases. Examples of explosive gases are cyclopropane, hydrogen and methane.
Keeping heat sources away from flammable materials is another important safety precaution. It should be
remembered that an ESU tip remains hot for a few seconds after the instrument has been deactivated. Similarly, ends
of fiberoptic cables can retain significant amounts of heat after being disconnected from their light source.
Therefore, it is important to be careful where one places the end of a fiberoptic cord. Lasers should be immediately
placed in standby mode and ESUs placed in an appropriate holder when they are not in use. Finally, volatile liquids
must be allowed to dry since the vapors can be quite flammable.
There are many dangers from a fire. Obviously, heat can cause burns to the patient or operating room personnel. Of
great importance is that smoke from the fire can necessitate that the room be evacuated. Depending on what is
burning, toxic products can be given off by the combustion of various materials. Many of these products such as
carbon monoxide, ammonia, cyanide, isocyanates and hydrogen chloride are quite toxic. They can cause chemical
and physical irritation to the tracheal-bronchial system but more important, they can cause asphyxia.
Being prepared for a fire and knowing what to do if one should occur are key elements of a fire safety program.
Knowing the location of fire extinguishers and having fire drills will enable all operating room personnel to become
familiar with proper procedures. Operating room personnel should be familiar with the location of alarm boxes, gas
shut-offs, and fire extinguishers. People should realize that it is important to immediately call for help, decide who is
going to fight the fire, when it will be appropriate to leave the room and how to care for the patient during the fire. If
drapes are burning, they must be removed as most OR paper drapes are impervious to water. Therefore, the fire will
burn on the underside and dousing them with water will not extinguish the fire. Having sources of battery powered
portable lighting available is also extremely important.
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Types of OR Fires
Operating room fires can be classified into two types: those that occur in the patient and those that occur on the
patient. Fires that occur
in the patient would include airway fires such as ignition of an endotracheal tube or a fiberoptic bronchoscope or an
intra-abdominal fire. Fires occurring on the patient include ignition of drapes or surface fires that are fueled by
supplemental oxygen.
One of the ignition sources in the operating room is the laser. Laser is an acronym for Light Amplification by
Stimulated Emission of Radiation. The laser light is produced when energy is aimed at the "lasing medium". The
lasing medium then becomes the name of the laser. For instance, electrical energy aimed at carbon dioxide
molecules is a carbon dioxide laser. The light produced by a laser is known as coherent radiation. Coherent light can
be focused into very small spots with a very high power density.
There are a number of different types of lasers. These include the argon laser which is used in eye and dermatologic
procedures. The energy produced by this laser is absorbed by hemoglobin and melanin and has a tissue penetration
of 0.5 to 2.0mm. The KTP (frequency doubled YAG) laser produces energy that is absorbed by hemoglobin and has
a tissue penetration of 0.5 to 2.0mm. The dye laser has wave lengths that are tunable for different applications. The
Nd:YAG laser has tissue penetration of 2-6mm and can be used for tumor debulking particularly in the tracheal-
bronchial tree. Its energy can be transmitted through a fiberoptic cable which enables it to be used in a "contact"
mode. The CO2 laser produces energy that is absorbed by water. It is used where precision is needed and has
negligible tissue penetration. Also there is minimal heat dissipated to the surrounding tissues. The helium neon laser
(He-Ne) is a very low power laser. Its red light is used for aiming the CO2 and the Nd:YAG lasers.
Fires in the Patient

The most serious fire in the patient is an endotracheal tube fire. Although the ET tube can be ignited by
electrocautery, it is more common for a fire to occur as a result of it being struck by a laser. Wolf and colleagues
showed that the red rubber, the polyvinyl chloride (PVC), and the silicone endotracheal tubes all have a
flammability index of less than 25% oxygen. Therefore, these tubes are not appropriate when doing surgery in and
around the airway.
Before specific laser resistant tubes were developed, many practitioners wrapped endotracheal tubes with various
kinds of foil or copper tape. Today, this is a dangerous practice and should be avoided. There are many
complications associated with wrapping tubes which include kinking of the tube and having unprotected parts of the
tube exposed where layers of tape fail to overlap. In the event that an endotracheal tube should be set on fire, it is
important to immediately disconnect the tube or the inspiratory hose from the anesthesia machine. This will usually
result in the fire going out since the oxidizer has been removed from the fire. Simultaneously the surgeon should
remove the ET tube, and saline or water poured into the airway. The patient is mask ventilated and then reintubated.
Next, bronchoscopy is performed so that the airway can be inspected and any pieces of foreign material removed.
These fires can be quite devastating as an endotracheal tube ignited by a laser with high concentrations of oxygen
essentially turns into a "blow torch" with resultant burns to the lungs, trachea, and esophagus.
Upper Airway Surgery

When anesthetizing patients for upper airway surgery, a number of anesthetic techniques are possible. One can use
jet ventilation either through a metal bronchoscope or a catheter inserted through the cricoid membrane. In this
circumstance, there is no tracheal tube in the airway to burn. However, the FIO2 is not controllable as it is dependent
on a venturi mechanism that entrains room air which is delivered to the patient. Complications of this technique
include hypoventilation, barotrauma and aspiration. The surgery can also be performed using an endotracheal tube
that is specifically resistant to the type of laser being used. The tube should have two cuffs and they should be filled
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with saline that has been colored with methylene blue. This allows the surgeon to know when one of the cuffs has
been ruptured.
If the carbon dioxide laser is being used, then the LaserFlex™ (Mallinkrodt) ET tube is an excellent choice. The
tube consists of a double cuff and a flexible metal shaft that is highly resistant to the CO2 laser. This tube, however,
is not resistant to the Nd:YAG laser. If the Nd:YAG laser is to be used in the upper airway, then a special laser
resistant tube called Lasertubus™ (Rusch, Inc.) can be used. The Lasertubus™ consists of a soft rubber shaft that is
covered by a corrugated silver foil which is then covered by a Merocel™ sponge covering. The MerocelTM when
moistened with saline will consume laser energy if it is struck. It also dissipates the laser light and the silver foil
prevents the laser light from penetrating the shaft of the tracheal tube. It is critical that the MerocelTM covering be
kept moist at all times. This tube also consists of a double cuff design. Only a portion of the tube is laser resistant
and it is important that this part of the tube always remains in the surgical field.
The electrocautery can also be a source of ignition during upper airway surgery. A typical example would be during
a tonsillectomy on a child with an uncuffed tracheal tube. The anesthetic mixture, which may contain oxygen and
nitrous oxide, can readily leak around the tracheal tube and be present in sufficient concentrations that the
electrocautery could cause a fire at the operative site. In these cases, it is recommended that oxygen be mixed with
air and the FIO2 be kept as low as possible. The surgeon can also put wet pledgets around the tracheal tube;
however, it must be remembered that if the pledgets dry out they can also be a source of fuel for a fire.
Lower Airway Surgery

When doing surgery on the lower airway, the Nd:YAG laser is frequently employed. The surgeon usually passes a
laser fiber through the suction port of the fiberoptic bronchoscope. This bronchoscope may then be passed either
through a PVC tracheal tube or through a rigid metal bronchoscope. If the fiberoptic bronchoscope is passed through
a tracheal tube a PVC tube can be used. There is no special tube for this type of surgery. Indeed the fiberoptic cable
passes through the inside of the tracheal tube. Therefore, it is essential to keep the inspired oxygen as low as
possible (preferably <30%) and titrate the oxygen saturation to between 90-95%. Also, the endotracheal tube should
be placed just below the vocal cords so that the tip is as far away from the operative site as possible.
If the rigid metal bronchoscope is used, then obviously there is no tracheal tube in the airway. The patient is then
ventilated with a form of venturi which will entrain room air. Therefore, the inspired oxygen is not precisely
controllable. The FIO2 will usually vary between 40-60%. It should be remembered that in either circumstance, the
cover of the fiberoptic bronchoscope is plastic and can easily burn especially in an oxygen enriched environment.
Laser Safety
There are other safety considerations when using the laser. Reflected laser light can cause retinal damage. The
patient's eyes should be covered with wet eye packs and all personnel in the room must wear goggles that are
specific for the laser being used. These goggles frequently have a color tint, which may make it difficult to monitor
skin color changes. Also, all windows should be covered with black window shades and warning signs should be
posted on all doorways to the operating room. There is also potential damage to the respiratory track from vaporized
tissue which may contain chemical toxins or virus particles in the laser "plume". It is recommended that special
(high filtration) masks be worn by OR personnel during these types of procedures.
Another place where a fire could occur in the patient is during laparoscopic surgery. Even though the abdomen is
inflated with CO2, after about 30 minutes of nitrous oxide anesthesia, the N2O can diffuse into the abdomen and
reach levels that could support combustion. Neuman et al studied this phenomenon and found that at 30 minutes the
mean nitrous oxide concentration was 36%. However, in certain patients, the nitrous oxide concentration was as
much as 47%. Bowel gas contains two potentially flammable gases. These are methane and hydrogen. The reported
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maximum concentration of methane in bowel gas is 56% and hydrogen 69%. 56% methane would require 47%
nitrous oxide in carbon dioxide to support combustion. Since that was the maximum concentration found in the
study, this presents a relatively small hazard. However, 69% H2 will burn in concentrations of nitrous oxide of 29%
or greater. Therefore, if the surgeon should accidentally enter the bowel during laparoscopy which contained a high
percentage of hydrogen, a fire could occur. The nitrous oxide would support combustion, the hydrogen would be the
fuel, and the electrocautery would provide the heat source. Greilich et al reported a fire in which a tank of 14%
carbon dioxide and 86% oxygen was accidentally used to inflate the abdomen instead of pure carbon dioxide. When
the surgeon activated the electrocautery, a fire ensued. The pin index for tanks with 100% CO2 is the same for any
tank with greater than 7% CO2.
Another kind of fire that occurs in the patient is the ignition of a tracheal tube during a tracheostomy. A critically ill
intubated patient will be receiving supplemental oxygen. A surgeon may use the electrocautery to enter the trachea.
This is an extremely dangerous practice since the tracheal tube is frequently in the field while supplemental oxygen
is being delivered to the patient. The ESU then provides a source of heat and a number of fires have resulted.
Decreasing the inspired oxygen would obviously be a safety factor; however, this may not be possible in this patient
population. Also, unless the patient is ventilated with decreased inspired oxygen content for at least a minute, the
higher concentration of oxygen will continue to be present in the trachea. It is far better that the surgeon use a
scalpel or scissors to enter the trachea, instead of the ESU. This will greatly reduce the risk of a tracheal fire.
Fires on the Patient

The other type of operating room fire is one that occurs on the patient. Most commonly these are associated with
monitored anesthesia care (MAC) for head and neck cases where the patient is administered supplemental oxygen
either by a face mask or a nasal cannula. The surgeon then drapes the field such that there is a build up of 100%
oxygen under the drapes and in close proximity to the operative site. This oxygen, in certain circumstances, can then
diffuse directly into the operative site so that when the electrosurgery pencil or the laser is used, a fire can be started.
There are many potential objects that could provide fuel for the fire. These include paper drapes, gauze sponges,
plastic tubing from the oxygen mask, and even the patient’s facial hair. It is important to remember that oxygen is a
drug. Therefore, the need for supplemental oxygen as well as the concentration of oxygen needs to be titrated in
each patient. Frequently, by reducing the amount of sedation given to the patient, the use of supplemental oxygen
can be eliminated. The oxygen can be diluted with room air and titrated to keep the patients oxygen saturation
between 90-95%. The drapes should be arranged so that the oxygen does not build up underneath the operative site.
The drapes should be arranged in a fashion that forms an open tent so that the oxygen will be diluted with room air.
Since oxygen is slightly heavier than room air, as long as there is some way for the oxygen gas to get in and out, it
will tend to flow towards the ground.
Another potential strategy to minimize the risk of fire is to discontinue the use of supplemental oxygen several
minutes before the surgeon uses the laser or the ESU. This will give any oxygen that has built up time to dissipate
which would greatly reduce the risk of fire. However, this may be difficult to do if there is frequent use of the ESU
or laser. Also, it is difficult to predict how long it would take for the oxygen to dissipate. Therefore, the newest
recommendation from the Anesthesia Patient Safety Foundation and the ECRI Institute, is to secure the airway with
an LMA or endotracheal tube when the patient needs supplemental oxygen for a head and neck procedure. There are
a few exceptional cases when there is a need to communicate with the patient (i.e. awake craniotomy or carotid
endarectomy). In these cases the FiO2 should be less than 30 percent.
Volatile prep solutions provide another potential source of fuel for a fire. Solutions such as isopropyl alcohol are
frequently used by surgeons as skin prep. These solutions could pool in certain areas and remain liquid for a
considerable period of time. Additionally, these solutions will vaporize and the resulting vapor, especially in an
oxygen enriched atmosphere, is highly flammable.
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DuraPrep™ is a skin prep that is very popular in many hospitals. It consists of Iodofor and 74% isopropyl alcohol. It
appears that the very high concentration of alcohol is not appreciated by many surgeons and operating room
personnel. If the solution is not allowed to dry completely before beginning surgery, then the alcohol will provide a
potential fuel for a fire. In 2001, Barker & Polson reported on just such a case. A patient was having a burr hole
craniotomy under MAC anesthesia. The patient was receiving supplemental oxygen and the head was prepped with
the Iodofor and alcohol solution. When the surgeons made the skin incision, the electrosurgical unit was activated
and a "pop" sound was heard. In very short order, smoke and a ball of flames engulfed the patient's head and
shoulders. The fire was quickly extinguished, but the patient suffered burns to the face and neck area. In a laboratory
re-creation of the event, Barker and Polson discovered some interesting facts. By duplicating the setup in the
operating room, they were able to re-create the fire. However, if there was no flow of supplemental oxygen, there
was no fire. If the alcohol-based prep solution was not used, again there was no fire and finally, if the closed space
where the oxygen was allowed to build up was not present, again there was no fire. This illustrates an essential fact,
that although operating room fires are a rare event, when the key elements come together at precisely the same time,
a fire is easily started. Also, in the presence of an oxygen enriched atmosphere, the fire will spread almost
instantaneously.
In 2004 four cases of fires in the CO2 canister of the anesthesia machine were reported. These canisters have melted
or actually caught on fire. In at least one case there was a serious patient injury. The common elements included use
of a CO2 absorbent that was desiccated (Baralyme™), SevofluraneTM, and low O2 flows. Apparently a breakdown of
SevofluraneTM occurred, and there was a very exothermic reaction, which caused a fire. Laster et.al. demonstrated
that when desiccated BaralymeTM interacts with SevofluraneTM there is a sustained temperature increase to 200
degrees C, and in one case to over 300 degrees C. In contrast, with IsofluraneTM and DesfluraneTM there was only a
transient increase in temperature to 100 degrees C. AmsorbTM is a newer CO2 absorbent that does not contain strong
alkali, and does not react with SevofluraneTM. Therefore, it would not pose a fire hazard.
In 2010 Laudanski and colleagues reported two cases of a ventilator circuit that caught on fire. This was associated
with a wire that was used to heat the gases in the circuit. In this type of circuit this is a risk of melting wires,
insulation, and/or tubing that can lead to a fire.
Extinguishing a Fire
If a fire should develop, it is important to know how to extinguish it as rapidly as possible. Breaking the fire triad is
extremely important. Therefore, removing the oxidizer by disconnecting the oxygen or the circuit from the patient,
will frequently extinguish the fire. Burning drapes should be removed as quickly as possible and once on the floor,
they can then be extinguished. It should be remembered that impervious paper drapes will repel water and the fire
will actually burn on the underside of the drapes. Therefore, attempting to throw water on these burning drapes
would be useless. Although most operating rooms have a sprinkler system, the sprinklers are usually not activated
in cases of OR fires. This is because the sprinklers are rarely located over the operating room table, and they are also
heat activated. OR fires tend to give off a lot of smoke and toxic products of combustion, but not necessarily enough
heat to activate the sprinklers.
It is important that all operating room personnel are familiar with fire extinguishers. They are classified into three
basic types. Class A is used for wood, paper, cloth and plastics. Class B is used to extinguish flammable liquids or
grease, and Class C are used for energized electrical equipment. Many fire extinguishers are classified to be used in
two or all three types of fires. Halon is a fire extinguisher commonly found in operating rooms. It is a
bromofluorohydrocarbon and can be used on Class B & C fires and on many Class A fires as well. It is a highly
effective fire extinguisher and can be used safely around electronic equipment. However, because it is a
fluorocarbon, it is no longer being manufactured. Newer, environmentally friendly substitutes are now available.
Carbon dioxide fire extinguishers are useful for Class B & C fires and can also be used in Class A fires. The blast of
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carbon dioxide gas has liquid and solid components that rapidly vaporize, which leads to a cooling and smothering
of the fire. Carbon dioxide extinguishers do not leave a residue which could damage electronic equipment, but the
cold may cause freezing if it came into contact with exposed skin. Pressurized water can be used in hand held fire
extinguishers or from the large fire hoses located in the operating room corridors. If a corridor fire hose is used, it
can deliver up to 50 gallons of water a minute. These devices are best used by the fire department unless a patient or
OR personnel is in need of immediate rescue. Obviously, these devices would cause extreme damage to electronic
equipment. All fire extinguishers have advantages and disadvantages. When considering all of these factors, the CO2
fire extinguisher is probably the best for an operating room fire.
When using a fire extinguisher, the acronym "PASS" should be remembered. This stands for Pull the pin to unlock
the handle of the fire extinguisher; Aim the nozzle of the fire extinguisher at the base of the fire; Squeeze the handle
to activate the fire extinguisher and release the agent; Sweep the stream of the extinguisher over the base of the fire.
Case Studies
A couple of case scenarios of actual OR fires will help to illustrate some of the points that have been made. In one
instance during a neurosurgical procedure, the laser and the electrosurgery unit were both in use during the case. The
surgeon picked up the ESU while the laser was lying on the drapes. He mistakenly stepped on the laser pedal which
immediately ignited the drapes and subsequently the mattress and gel pad. A fire was started which produced very
toxic smoke and forced all of the OR personnel to leave the OR. They subsequently had to crawl back into the room,
disconnect the patient from the anesthesia circuit and pull the patient and the table out of the room. This case
illustrated the value of being absolutely certain of which pedal activates which device. Also, when a laser is in use,
once it is set down, the laser should be put in the standby mode immediately. Similarly, when an electrosurgery unit
is not in use, the pencil should be placed in a plastic holder.
Another case involved a trauma patient for an exploratory laparotomy. The electrosurgical pencil became draped
over the side of the table and the button was inadvertently activated. This immediately set the drapes on fire.
Although initially the fire appeared small, within a few seconds the flames had engulfed the left side of the patient.
Attempts by the OR staff to extinguish the fire were unsuccessful and the fire department arrived approximately 15
minutes later and extinguished the fire. A review of the incident revealed that the OR staff had no plan for dealing
with the situation, they couldn't find the fire extinguishers, the fire cabinets were blocked by equipment and the OR
sprinkler system was not activated. Once again, the fact that the ESU pencil was not placed in the holder contributed
significantly to this fire.
ASA Practice Advisory Recommendations
The ASA practice advisory makes a number of recommendations on the prevention of OR fires. First the OR team
must determine if a high risk situation exists. If there is a high fire risk then each person is given a specific task on
how to prevent a fire, and what they will do in the event a fire occurs. All fire management equipment must be
readily available. Prevention is the most important part of the equation. The anesthesiologist and the surgeon must
collaborate during the procedure to minimize an oxygen rich environment. The drapes must be configured to avoid
oxidizer buildup, and flammable skin preps must be dry before draping. Many institutions have instituted a “prep
time out” to insure that all flammable solutions have dried and there is no pooling of prep solutions. This must be
completed prior to draping the patient. The surgeon should be notified if an oxidizer and ignition source are in
proximity, and time allowed for the oxidizer to dissipate before using the ESU or laser.
The team should be aware of early signs of a fire such as a pop, flash, or smoke. If these occur, the surgery must be
stopped immediately, and everyone carries out their assigned task. If it is an airway fire, then simultaneously stop
the flow of gases and remove the ET tube. Saline is poured in the airway and burning materials are removed. If the
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fire is on the patient, then the fire is extinguished with water or saline, and the burning drapes are removed and
thrown on the floor. The patient is then given supportive care, and the degree of injury is assessed. Finally, the scene
is preserved, and hospital and local regulatory reporting requirements are followed.
All OR personnel must be vigilant to potential operating room fires. Clearly, prevention is better than trying to deal
with an established fire. It is however, incumbent upon OR personnel to be prepared. This includes fire drills, being
familiar with the type and location of fire extinguishers, having an evacuation plan, knowing where gas and
electrical shutoffs are located, and being able to rapidly call for help, sound a fire alarm and communicate with other
OR personnel. Only by working together to keep all three legs of the fire triangle from coming together, can OR
fires be prevented.
REFERENCES
1. Abbott Laboratories: “Dear Healthcare Provider”( letter) Nov 17, 2003

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6. Burgess GE, LeJeune FE. Endotracheal tube ignition during laser surgery of the Larynx Arch Otolaryngol
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7. Cameron BG, Ingram GS. Flammability of drape materials in. Anaesthesia 1971;26:281-288
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10. Castro BA, Freedman LA, Craig WL, Lynch C. Explosion within an anesthesia machine: BaralymeR , high
fresh gas flows and sevoflurane concentration. Anesthesiology 2004; 101:537-39.
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Dioxide During Robot-Assisted Radical Prostatectomy: Case Report and Literature Review. European Urology
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18. ECRI. Laser-resistant tracheal tubes (evaluation). Health Devices 1992;21:4-14

19. ECRI. Lasers in medicine - an introduction. Health Devices 1984;13:151-178
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Stoelting RK, Cahalan MK, Stock MC, 6th Edition, Lippincott, Williams & Wilkins; Philadelphia 2009.
21. Fatheree RS, Leighton BL. Acute respiratory syndrome after an exothermic baralymeR-sevoflurane reaction.
22. Geffin B, Shapshay SM, Bellack GS, et al. Flammability of endotracheal tubes during Nd:YAG laser
application in the airway. Anesthesiology 1986;65:511-515
23. Greilich PE et al. Intraabdominal fire during laparoscopic cholecystectomy. Anesthesiology 1995; 83:871-874,
24. Gupte SR. Gauze fire in the oral cavity: a case report. Anesth Analg 1972;51:645-646
25. Hirshman CA, Smith J. Indirect ignition of the endotracheal tube during carbon dioxide laser surgery. Arch
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Anesthesiology, 1993; 78:875-879
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DISCLOSURE
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Update from the Anesthesia Quality Institute

Richard P. Dutton, M.D., M.B.A. Park Ridge, Illinois
Introduction
Anesthesiology is the safest of all medical disciplines, with a ‘failure’ rate of fewer than 1 in 10,000 cases and a
history of interest in patient outcomes that dates back more than a century. Landmarks include Rovenstine’s
promulgation of collected anesthesia case records in the 1930s,1 Beecher and Todd’s examination of perioperative
mortality in the 1950s,2 and creation of the Anesthesia Patient Safety Foundation, the Foundation for Anesthesia
Education and Research and the Anesthesia Closed Claims Project in the 1980s. In 2000 the Institute of Medicine
published To Err is Human, calling attention to preventable errors in healthcare and initiating a focused effort to
improve.3 Anesthesiology was singled out as the medical discipline which had done the most to improve patient
safety. In 2009 the American Society of Anesthesiologists took another step forward by founding the Anesthesia
Quality Institute (AQI). The AQI’s mission is to improve patient outcomes through development of a national
anesthesia registry.4
The AQI created the National Anesthesia Clinical Outcomes Registry (NACOR) in 2010 to capture basic data on
every case, every day from participating practices, and the Anesthesia Incident Reporting System (AIRS) in 2011 to
capture detailed information from individual cases of interest. Data is collected from anesthesia practices of all
types and sizes and aggregated to create benchmarks for clinical outcomes. Benchmarks encompass all aspects of
anesthesia quality including operational efficiency, safety, and patient experience. Practices contributing to the AQI
receive quarterly summaries of their own data, as well as comparators based on practice size and type drawn from
the whole of NACOR. Aggregated information describes the practice of anesthesiology in the United States, and is
distributed to ASA and subspecialty society leaders; Anesthesia in the US 2012 is available for download from the
AQI website at www.aqihq.org. NACOR reports are designed to facilitate practice management, and to address
burgeoning regulatory requirements from the federal government and the Joint Commission.
This Refresher Course Lecture will provide a brief overview of the structure, mechanics and current status of the
AQI, NACOR and AIRS, and will present some snapshots of aggregated national data.
Data Acquisition
The AQI gathers information about the specialty of anesthesiology. This includes published reports in the scientific
literature, business articles and reports, and internal ASA communications. The most important sources of data,
however, are NACOR and AIRS. Participation in the AQI is open to every anesthesiology practice in the United
States, and any provider in the world can submit case reports to AIRS. There is no requirement for a
minimum level of technology or the use of software from any specific vendor. ASA members
receive a substantial discount for participation in NACOR.
Practices wishing to join the AQI begin by signing a Business Associate agreement that outlines the extent of
information to be shared and the rights and responsibilities of both parties towards that data. The AQI is accredited
as a Patient Safety Organization by the Agency for Healthcare Research and Quality (AHRQ), and the
confidentiality of data contributed to the AQI is protected by both federal law and the Illinois Medical Studies Act.
The AQI collects all data in de-identified form, and is further bound by its practice agreements to preserve the
confidentiality of all patients, facilities, providers and groups.
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NACOR is designed to accumulate data through periodic electronic reporting. Participating practices complete an
online demographic survey that describes their organization, the facilities they work in, and the members of the
group. This provides context for all subsequent case-specific data. AQI works with the practice to build links
between their existing software (billing systems, hospital systems, QM programs) and NACOR. The goal is to
collect whatever case-specific electronic data exists, without requiring new data entry by working anesthesiologists.
Data contributed to the AQI is entirely deidentified. Patient names and numbers are removed, and facilities and
providers are recorded by code numbers.
At present, every anesthesia practice uses electronic billing software, and the AQI works with vendors of these
products to enable periodic reporting. A participating practice is NOT required to have an anesthesia information
management system (AIMS). It is expected that electronic anesthesia records will advance over time, and AQI is
aiming for a future state in which a large amount of case-specific data is available through such systems. In the
meantime, the AQI is working with practices and vendors to design, improve and deploy electronic systems to
facilitate the aggregation of clinical data. One function of AQI is to develop consensus-based standards for defining
and reporting relevant outcomes in anesthesiology, and to share these with the healthcare information technology
industry. A second important function is to advise anesthesia practices on which elements of patient care are most
important to measure, and make them aware of technologies that may facilitate electronic data collection.
The AQI began recruiting participant practices in late 2009, and as of June 1, 2012 has signed agreements with 160
groups. These practices represent the breadth of anesthesiology in the United States, including a mix of academic
and private groups, large and small practices and both single-center and multi-hospital corporations. Forty out of
fifty states are represented, and these practices include more than 8000 anesthesia providers working in more than
1100 different surgical facilities.
NACOR began collecting case-specific data in January, 2010, and currently includes records on more than 4.5
million cases. Information available from every case includes the date, location and duration of surgery; the specific
surgical and anesthesia procedures performed; the patient’s age, sex and primary diagnosis; the anesthesia coverage
model; and the specific providers involved.
Many AQI Participant Practices contribute
further electronic information based on their
local software systems. Additional data may
includes quality improvement forms (safety
and complications), patient experience (nausea
and vomiting, pain management, satisfaction),
operational efficiency (length of stay,
readmission or upgrades of care) and detailed
information about the case itself (medications
used, procedures performed, patient vital signs,
fluid management). Departments of
Anesthesiology that are contributing AIMS
data to the Multicenter Perioperative Outcomes
Group (MPOG; http://mpog.med.umich.edu/)
can arrange to have this same data transmitted
simultaneously to NACOR, thus reaping both
research and quality management benefits from
the same information.
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Reporting
AQI reports data to a variety of stakeholders (Figure 1). AQI participating practices receive quarterly online reports
from NACOR which include their own submitted data (trended over time) and aggregated national benchmarks.
Features of the reports allow the practice to ‘slice and dice’ their data to examine specific facilities, providers, cases
or patient types. Reports can be constructed out of multiple variables, and displayed to the level of the individual
practitioner. This allows the practice to use NACOR data for federal and hospital requirements (such as PQRS
submission and for the Joint Commission), and allows individuals to use NACOR data for maintenance of
certification and licensure. Outcome benchmarks can be created based on the peer groups of greatest relevance (for
example: hospital-affiliated surgery centers in the Southeast US). Member practices can construct reports on their
own, or can request specific reports and analysis from the AQI. The NACOR database is accessible for academic
research projects by application to the AQI Data Use Committee.
AQI is working with ASA Committees and anesthesia subspecialty societies to provide custom reports.
Collaborations with AQI can take many forms, but one model is illustrated by the relationship between the AQI and
the Society for Ambulatory Anesthesia (SAMBA). Anesthesia practices with a large proportion of ambulatory cases
can contract with SAMBA to receive ambulatory-specific reports – based on data collected in NACOR – that offer
greater granularity for this subspecialty area. SCOR is a software “front-end” offered by SAMBA that facilitates
rapid collection of case data at the point of care and submission to NACOR. Groups participating with both AQI
and SAMBA will gain added value in understanding the ambulatory component of their practice. More information
is available at http://www.sambahq.org/.
Limitations of NACOR
In reviewing the data that follows, the reader should remember that garbage in = garbage out. Data in NACOR is
accumulated from hundreds of facilities, each with its own unique mix of patients, operations and providers. Data
transmission is through dozens of different electronic systems, many of which use unique definitions for outcomes
of interest. The greatest value of NACOR data to an individual practice is examination of their own outcomes over
time. Development of benchmarks requires unification of disparate data without full knowledge of its heterogeneity,
and interpretation of benchmark data should be undertaken with a grain of salt.5 This is why the demographic
information collected from each practice is so important: it allows an understanding of the context of data collection
at individual sites. For some common elements NACOR data is highly reliable (e.g. surgical case times). For other
elements, such as the occurrence of postoperative nausea and vomiting, there are no standard definitions to draw on
and many different ways of collecting the data. Benchmarks in this area will be less solid, although trends over time
within a single practice – sharing a common definition and level of risk – will remain useful.
Another concern is the potential bias among practices that are participating in NACOR. It is likely that early
adopters are those groups which already put significant value on data collection and analysis, and are best able to
apply the quality management lessons learned. This might bias NACOR towards better performing groups and
lower aggregated rates of major complications.
Anesthesiology as a Specialty
The American Medical Association reports 42,000 anesthesiologists in its records, but does not report how many of
them are engaged in full-time clinical practice. Of these, more than 80% are ASA members. These providers work
in more than 40,000 ORs in 6,000 acute care hospitals and countless ambulatory surgery centers and physician
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offices. At least 70% of all operations are performed on an ambulatory basis, with variable participation of an
anesthesiologist based on local history and economics. There are regions of the country in which less than 5% of all
endoscopies are done under monitored anesthesia care, and other areas where this number approaches 100%. (As an
aside, this appears to be driven as much by the efficiency which an anesthesiologist can bring to an endoscopy
practice as by fee-for-service billing.) In more traditional inpatient settings, perioperative patients account for up to
two-thirds of hospital revenues.
The average practicing anesthesiologist in the US is 50 years old. 25% of anesthesiologists in NACOR are women,
but this percentage increases in more recent graduating classes; 40% of PGY-1 residents are women. 73% of
anesthesiologists in NACOR are certified by the American Board of Anesthesiology. 85% report working full-time,
for an average of about 50 hours per week. Recent work force projections suggest an ongoing nationwide shortage
of anesthesiologists through 2020, as a slight decline in discretionary surgery due to the deflated economy is
balanced by those leaving practice.6 Surgical volume has increased a steady 3-4% per year for the past two decades,
and this is unlikely to change in the years ahead.
More than 5000 anesthesiology residents are currently in training at 131 accredited programs. About 37% will
continue into fellowships, with the last available numbers showing more than 200 pain fellows, 100 cardiothoracic
fellows, 150 pediatric anesthesia fellows, and 62 critical care fellows. Others are pursuing extra training in
obstetrics, transplant, trauma and other disciplines that are non-ACGME approved. It is not known how many are
pursuing bench research or supplemental training in public policy, statistics, business or epidemiology.
Demographics of Anesthesia Practice
Participating practices in the AQI range from three person private practices up to groups which include more than
100 anesthesiologists. Median practice size is around 20. While the majority of practices are private corporations,
at least 20 academic departments are
current participants, and
approximately 50 % of AQI
anesthesiologists report some time
spent teaching residents, student
nurses, or anesthesiologist
assistants.
65% of providers in NACOR are

anesthesiologists and 35% are nurse
anesthetists. This represents a bias
in NACOR relative to the
approximately 50:50 nationwide
ratio of these professions. 63% of
the practices in NACOR work with
NAs and 10% with AAs; the
remainder are physician-only
groups. The care team model of one
physician medically directing some number of residents, AAs or NAs is dominant in NACOR, representing more
than 75% of all cases.
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On average, practices in NACOR report deriving 7% of their income from direct contracts with a hospital, 5% from
“self-pay” patients, and 56% from Medicare or Medicaid. There is substantial variability in these numbers from
group to group, however. 42% of practices report operating an acute pain management service.
Thirty percent of NACOR facilities are medium community hospitals (100-500 beds), accounting for almost half of
all the cases reported. 25% of facilities are freestanding ambulatory surgery centers and another 15% are hospital
associated outpatient surgery facilities; these two groups account for 22% of all cases. Large community and
university hospitals represent only 10% of all NACOR facilities, but perform 24% of all cases (Figure 2).
Demographics of Anesthesia Cases
Approximately 10% of all patients in NACOR are 18 years or younger; 38% are aged 19-49; 26% are 50-64; 19%
are 65-79; and 7% are 80 years or older. The average anesthesia practice will soon see far more geriatric than
pediatric patients. Figure 3 shows the distribution of male and female patients by age in NACOR.
Two thirds of the cases in NACOR

were performed under general
anesthesia, 22% as monitored
anesthesia care, and 10% with spinal
or epidural (Figure 4). Peripheral
nerve block was the primary anesthetic
in less than 5% of cases. It is possible
that these numbers will shift as
ultrasound-guided regional techniques
become more popular.
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ASA physical status increases with age (Figure 5). One third of 50 year old patients are ASA III or greater. This
proportion rises to more than 60% by age 80.
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Clinical Outcomes
One or more measures of clinical quality are reported by about three-quarters of NACOR participants, representing
more than 80% of cases in the registry (Figure 6). Not surprisingly, serious adverse outcomes are more common in
less healthy patients.
The most common outcome measures are the procedure codes for timely administration of antibiotics, observation
of sterile precautions during central line placement, and maintenance of intraoperative normothermia. These
measures— incentivized by the Center for Medicare and Medicaid Services in the Physician Quality Reporting
System—are reported by more than three quarters of NACOR participants, with a generally low rate of failure.
Business or efficiency metrics are electronically captured and transmitted to NACOR by about 20% of participating
practices. These measures include case cancellations, unplanned admissions or upgrades in care, prolonged
intraoperative delays, and extended time in the Post Anesthesia Care Unit.
Minor intraoperative events, such as transient hypotension, abnormal laboratory values or minor dysrhythmias, are
also captured by about 20% of practices. Postoperative nausea and vomiting and difficulties with pain management
would also fall into this category. Within the cases done by these groups, these events have a cumulative occurrence
of about 5 %. Not surprisingly, this is one area where there are many different ways of defining and measuring these
outcomes. Postoperative nausea and vomiting, for example, can be recorded at the end of a case, at PACU
discharge, or in a post-discharge phone call; can be based on a patient, nurse, or provider report; and can be purely
subjective or purely objective (e.g. based on use of a specific medication for treatment). Comparison of data across
practices is difficult, and the national “benchmark” should be taken with a grain of salt.
Serious adverse events, defined as those that cause patient harm or serious risk of harm, have been reported in about
0.5% of the approximate million-plus cases done by the groups that have electronic reporting of these occurrences.
Definitions of these are relatively standardized, based on the recommendations of ASA’s Committee on
Performance and Outcome Measures. Serious adverse events range from dural puncture headache to peripheral
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nerve injury to stroke and myocardial infarction. Perioperative death—the ultimate adverse event—is reported by
these same groups, and provides a crude all-cause mortality of 0.05%, or about 1 in 10,000 anesthetics.
As yet these numbers are too small for statistical analysis, other than the obvious observation that anesthesia is
generally safe. While committed to the long-term development of outcome benchmarks, the AQI intends to move
cautiously in reporting them. Because the frequency is so low, and the consequences of disclosure are serious, any
public reporting of major adverse events will require unified definitions, risk adjustment across reporting locations,
and selected auditing of submitted data. For the time being, detailed reports about major adverse outcomes will be
confined to the private quality management reports shared between the AQI and participating practices. In the long
run, however, it is likely that NACOR will become the definitive reference for outcome data about our profession.
Future Initiatives of the AQI
The primary mission of AQI will remain expansion of NACOR. This will occur through ongoing recruitment of
new practices and increasing the quantity and depth of data collected from current participants. As technology
advances, the NACOR model of continual passive collection of existing clinical data will become progressively
more powerful. The AQI works with more than two dozen information technology vendors to develop reporting
bridges between their software and NACOR. Many anesthesia billing systems and AIMS already include standard
AQI reporting routines. The ongoing dialog between vendors and anesthesia practices will lead to gradual and
incremental standardization of anesthesia outcomes, data formats, and reports; the AQI is perfectly positioned to
facilitate this discussion, and the AQI website has already become an important resource for software developers
and hospital quality managers.
AQI will encourage increased understanding of patient outcomes beyond the usual horizon of PACU discharge. The
adequacy of pain management and the incidence of nausea following discharge after ambulatory surgery are
important to patients, and will be of increasing interest to external regulators. Thirty-day post-procedure mortality is
a standard in many other specialties, and the increasing scientific interest in longer-term outcomes such as cognitive
function or cancer recurrence will drive a demand for this kind of data. At present there are no software systems in
place that can track these outcomes, but the AQI is committed to their development.
The Anesthesia Incident Reporting System
A nationwide benchmarking registry such as NACOR is the ultimate example of top-down quality management, but
there is great value in “bottom-up” reporting as well. Discussion of interesting cases is the cornerstone of the
morbidity and mortality conference, and remains a powerful educational tool. This explains AQI’s creation of the
Anesthesia Incident Reporting System (AIRS). The object is to collect unusual cases and events directly from the
point of care. The mechanism is a simple online form that can be submitted confidentially from any internet-capable
computer (smartphone and tablet applications are under development). Submission to AIRS is protected from legal
discovery by AQI’s status as a Patient Safety Organization. Case submissions are periodically reviewed by a
committee of experts. Cases with unique teaching potential are de-identified and presented monthly in the ASA
NEWSLETTER. All cases are periodically analyzed for common features, and aggregated to identify trends in
patient safety. AIRS currently includes “sub-modules” for reporting postoperative respiratory depression, incidents
related to drug shortages, and pediatric incidents. More modules are under development. AIRS can be accessed at:
https://www.aqiairs.org.
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In the first full year of operation, AIRS has collected hundreds of incidents from practitioners across the United
States and Canada. Reported events have ranged from death due to hemorrhage to minor case disruptions caused by
the lack of needed equipment. Published case studies from AIRS have covered topics including anaphylaxis,
medication errors, the hazards of neuro-monitoring, and bullying behavior in the operating room. At least one
recurring theme in equipment failure – automated blood pressure cuff default to manual mode – has been referred to
the Society for Technology in Anesthesia and to the Anesthesia Patient Safety Foundation for further action.
Similar activity is expected as incidents related to drug shortages accumulate.
Summary
The AQI is an important resource for anesthesiologists and their practices. Data from AQI helps shape ASA
committee work, educational products and advocacy efforts. The goal of NACOR and AIRS is nothing less than a
complete picture of anesthesia practice in the United States, empowering anesthesiology as the leader in patient
safety. More information on the AQI, including educational material on quality management and anesthesia
information technology, can be found on its website at www.aqihq.org.
References
1. Rovenstine EA. “A method of combining anesthetic and surgical records for statistical purposes,” Part IV,
Chapter 3 in Baehne GW (ed) Practical applications of the punched card method in colleges and universities.
New York: Columbia University Press, 1935, pps 301-8.
2. Beecher HK, Todd DP. A study of the deaths associated with anesthesia and surgery: based on a study of 599,
548 anesthesias in ten institutions 1948-1952, inclusive. Ann Surg. 1954;140:2-35.
3. Kohn LT, Corrigan JM, Donaldson MS (eds). To Err is Human: Building a Safer Health System. Washington:
National Academies Press, 2011.
4. Dutton RP. Pro: The AQI model for data collection. ASA Newsletter, May, 2010.
5. Glance LG, Neuman M, Martinez EA, Pauker KY, Dutton RP. Performance Measurement at a "Tipping Point"
Anesth Analg. 2011; 112; 958-966.
6. The Anesthesia Quality Institute. Anesthesia in the US 2012, available online from
https://ecommerce.asahq.org/p-556-anesthesia-in-the-united-states-2012.aspx?
DISCLOSURE
Sangart, Inc. ,Self, Consulting Fees
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Crossing the Patient Safety-Medical Liability Chasm
Karen B. Domino, M.D., MPH-Moderator Seattle, Washington

Cor Kalkman, M.D., Ph.D. Utrecht, The Netherlands
Timothy B McDonald, M.D. Chicago, Illinois
Anesthesia Safety: Challenges and Future Directions
“…Anesthesiology is an example of a complex, high-risk, dynamic patient care system in which there has been
notably reduced error… anesthesiologists confronted the safety issues presented by the need for continuing vigilance
during long operations but punctuated by the need for rapid problem evaluation and action… By a combination of
technological advances … standardization of equipment, and changes in training, they were able to bring about
major, sustained, widespread reduction in morbidity and mortality attributable to the administration of anesthesia…”
These flattering words about our specialty’s achievement in reducing the incidence of adverse events in the
perioperative period can be found in the landmark report that triggered the patient safety revolution: the Institute of
Medicine’s ‘To Err is Human” (1999). 1 Indeed, anesthesiology’s safety record has gone from the 1:1,500 mortality
rate reported in the Beecher & Todd study in 1954 2 to 1:250,000 for a healthy ASA 1 patient undergoing anesthesia
reported by Lienhart in 2006.3
The original focus of anesthesia safety efforts was on improving the safety of anesthesia delivery: designing safer
anesthesia machines and prevention of oxygen pipeline misconnection (pin index system). In the late 1980’s pulse
oximetry and capnography became the cornerstones of anesthesia monitoring, which has resulted in the near
abolishment of hypoxic brain injury due to unrecognized esophageal intubation and the rapid detection of any
problems with ventilation and oxygenation. Ironically, these monitors became widely accepted despite lack of high
level evidence that they indeed reduce the incidence of death and major morbidity4. Subsequently, airway
management improved dramatically in the 1990’s with the development of new devices to secure the airway such as
the laryngeal mask, fiberoptic endoscopy, and the first publication of the ASA difficult airway algorithm in 19935.
These developments in airway management have clearly contributed to a decrease of death and brain injury due to
failed intubation.
The formation of the Anesthesia Patient Safety foundation (APSF) in 1985 was another first for Anesthesiology,
while around the same time the ASA Closed Claims Project started their investigations of adverse events using
closed malpractice insurance files. This endeavor has greatly increased our understanding of potential causes and
mechanisms of rare catastrophic perioperative events.
The last decade has seen substantial growth in full-scale simulation to teach anesthesia residents. It is no longer
considered ethically acceptable to teach a young resident an invasive procedure (be it central venous cannulation, or
fiberoptic intubation) for which a validated simulation model is available. Full scale simulation using physiological
‘model driven’ patient mannequins and life actors playing the various members of the surgical team can prepare
residents for the management of rare and potentially catastrophic events. Moreover, it can simultaneously teach
important non-technical skills, such as leadership in crisis, teamwork and communication.
These achievements during the last 4 decades are impressive and encouraging, but we should carefully consider
safety risks that have not been adequately controlled, as well as the specific challenges for perioperative safety
today. For example, we know in detail how patients died from anesthesia in the 1960’s and 70’s, but what about
today? In France, Lienhart et al. investigated 4200 death certificates from patients who died in the perioperative
period and found that 0.69 deaths in 100,000 were totally related to anesthesia while 4.7 in 100,000 were partially
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related to anesthesia. As expected, age and ASA physical status were strong predictors of mortality. The death rate
increased from 1 in 250,000 for a healthy ASA I patient to 1 in 1800 for sick ASA IV patients, respectively.
Intraoperative hypotension and anemia associated with postoperative ischemic complications were strong predictors
of mortality. Also, deviations from standard practice and teamwork factors contributed to anesthetic mortality. In the
Netherlands, Arbous et al. performed a case-control study of more than 800,000 patients undergoing anesthesia
between 1995 and 1997.6 Cases were patients who died or remained comatose within 24 h of the procedure (n=807),
while controls survived without postoperative coma. In a multivariate analysis, documented equipment check with
protocol and checklist, direct availability of the anesthesiologist, no change of anesthesiologist during the case,
presence of a full-time anesthetic nurse in the room, presence of two persons at emergence, reversal of anesthesia
and postoperative pain medication - as opposed to no pain medication - all decreased the risk for injury.
Serious adverse events as a result of drug swaps and ‘wrong route’ continue to occur. This has resulted in pressure
from regulatory bodies in many countries to adhere to double check procedures when drawing up medication and
when administering the drug. Table 1 shows a series of procedures suggested by Orser and Byrick to reduce the risk
of medication error in anesthesia.7
Table: Preventing medication error in anesthesia 7 (adapted from UK report by National Health Service
2004)
1. Anesthesiologists should be aware of the risks of drug errors and ensure that checking procedures are in
place. Errors often occur in situations of haste, distraction or fatigue.
2. Lighting of the operating room environment is critical for safety. In situations of reduced lighting, specific
arrangements should be made for checking anesthetic drugs.
3. Drug storage arrangements should be consistent in all anesthetic care delivery units.
4. Ampoules should be read and re-read before drugs are drawn up into a syringe. Errors are unlikely to be
detected once the syringe is prepared.
5. Ideally, drugs are prepared by the person who will administer them, immediately before use.
6. Syringes should be labelled with the name and concentration.
7. Syringes intended for an emergency should be stored away from the immediate work area.
8. The international colour-coded syringe labelling system should be used.
9. Consider using pre-filling syringes for emergency drugs that are prepared by the pharmacy unit to assure
quality of contents and accurate labelling.
10. Pharmacists should regularly visit the operating rooms to ensure safe drug use.
11. When drug manufactures, packaging and formulation changes, anesthesiologists should be alerted to the
change before the drugs are provided in the operating rooms.
Imaging – Anesthesia has recently embraced imaging, in particular the use of ultrasound to identify neural and
vascular structures and to evaluate perioperative cardiac function. At least for central venous access, this practice
has been shown to result in a reduced rate of complications. 8,9
Role of non-technical factors in anesthesia safety
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It is increasingly clear that non-technical factors are as important as technical innovations to improve patient safety.
For example, the Joint Commission reported that problems with communication were a leading root cause in more
than 60% of sentinel events.10
Fig 1: Communication is the leading root cause of all sentinel events.
Source: Joint Commission on Accreditation of Healthcare Organizations.10
Handover – Patient harm can result from inadequate handovers and there is widespread consensus that robust,
structured handover processes are critical for safe patient care.11 Each time a patient is transferred between hospital
locations (emergency room, ward, operating room, recovery room, intensive care unit) and when doctors and nurses
change shifts, critical patient information needs to be handed over. Current handover processes have been described
as unstructured, informal and error prone. Moreover, the number of handovers in hospitals has increased
dramatically as a result of recent limitations in the maximum number of resident duty hours. This policy is intended
to increase patient safety by reducing the impact of fatigue and sleep deprivation on quality of care. However, an
increase in the number of handovers is the unavoidable consequence. There has been tremendous activity in
studying ways to improve handovers during the last 2 years.12 Checklists may improve the reliability of handovers.
In hospitals that have electronic patient records (EPRs), a promising approach is to support the various verbal
handover processes with software tools that can combine specific handover items such as to-do lists, daily goals, and
concerns, with automatically extracted data from the EPRs.13 Such systems may relieve the stress on residents of
handing over their patients to the incoming resident. However, there is no ‘one size fits all’ solution to the problems
of handover. The process entails more than just information transfer. Redesign of handover can benefit from
frontline staff input to ensure that new techniques fit into existing practices and settings. With the “video-reflexive”
technique developed by Iedema et al., handover encounters are videotaped and played back to the practitioners
involved for analysis and discussion. This ‘ bottom-up’ reflection on one’s daily practice by watching the recorded
handovers with medical and nursing staff uncovered previously unrecognized clinical and operational problems. The
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resulting improvement strategies had a high level of practitioner ownership and improved coordination of care and
strengthened junior– senior communication.14
Checklists
Checklists have been used in high-risk industries for decades. They take away the reliance on memory for routine
safety checks and allow one to focus on the specifics of the case. After initial professional reluctance, checklists are
now an integral part of perioperative care throughout the world. The Harvard surgeon Atul Gawande, popularized
the use of checklists in healthcare with his book The Checklist Manifesto.15 Two recent studies suggest that using
perioperative checklists reduces perioperative mortality. The Haynes study was an uncontrolled ‘before-after’
observational design. In eight hospitals around the world (Toronto, Canada; New Delhi, India; Amman, Jordan;
Auckland, New Zealand; Manila, Philippines; Ifakara, Tanzania; London, England; and Seattle, WA) they observed
a reduction of mortality from 1.5% before the checklist was introduced to 0.8% afterward.16 This unusually large
effect size has been attributed to a powerful Hawthorne effect.17 de Vries et al. compared a comprehensive surgical
safety system that uses checklists throughout the entire perioperative process (Surgical Patient Safety System,
SURPASS) in 6 Dutch hospitals in a controlled before-after design. Five hospitals not using SURPASS served as
controls. Complication rate decreased significantly from 27.3 to 16.7% and in-hospital mortality decreased from
1.5% to 0.8% for an absolute risk reduction of 0.7 percentage points (95% CI, 0.2 to 1.2). In the control hospitals
there were no changes in these outcomes.18 van Klei et al. investigated the effect of implementing the WHO
checklist on surgical mortality in a university hospital and found a small effect on mortality, that was proportional to
the level of checklist adherence.19
Multi-component safety interventions.
Prevention of central line infections - Pronovost et al. implemented an evidence-based protocol to decrease the rate
of catheter-related infections in ICU’s in Michigan (hand washing, using full-barrier precautions during the insertion
of central venous catheters, cleaning the skin with chlorhexidine, avoiding the femoral site if possible, and removing
unnecessary catheters). A before-after analysis of 1981 ICU-months of data from 103 ICU’s ( a total of 375,757
catheter-days) showed a decrease in the median rate of catheter-related bloodstream infection per 1000 catheter-days
from 2.7 infections at baseline to zero 3 months after the intervention (P≤0.002). The mean rate per 1000 catheter-
days decreased from 7.7 at baseline to 1.4 at 16 to 18 months of follow-up (P<0.002).
Culture - One of the less tangible, but important aspects of safety is that of organizational culture. There is evidence
from several high-risk industries that a negative safety culture results in a higher rate of adverse incidents. There are
now several validated instruments to measure culture via self-assessment, such as the SAQ.20 Certain behaviors that
are not captured by self-assessment questionnaires may only be discovered by close ‘ethnographic’ observation of
daily clinical practice. A patient safety program designed to improve teamwork and culture improved safety climate
scores in a large cohort of 71 intensive care units.21. Definitive proof that such interventions will result in improved
patient outcomes is currently not available. In 74 Veterans Administration hospitals, participation in the Medical
Team Training program was associated with an 18% reduction in annual mortality compared with a 7% decrease
among the 34 facilities that had not yet undergone training.
Standardization – Clinicians are known to highly value their professional autonomy. If this results in excess practice
variability, it may result in suboptimal care. Standardization has been proposed as a solution to increase ‘value’ by
improving outcomes and reduce costs. The key may be to standardize whenever possible, but at the same time to
allow clinicians enough discretion to be able to depart from the standard whenever that is in the patient’s interest.
Such deviations need to be documented in the patient chart.
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Conclusions - Anesthesiology has obtained remarkable safety, at least for healthy patients undergoing surgery of
minor to moderate complexity. There is, however, still considerable room to reduce adverse events and improve
perioperative outcomes in sicker and more complex patients. Many of the proposed changes are not ‘rocket science’
and have been implemented in other high-risk industries decades ago. They are mostly non-technical in nature and
focus on improving communication and teamwork, combined with more acceptance of - and adherence to -
standardization including the use of checklists for repetitive tasks where forgetting to check an item can have
dramatic consequences for the patient.
Topic 1 References
1. Institute of Medicine. Kohn LT, Corrigan JM, Donaldson MS (eds). To Err Is Human: Building a Safer
Health System. Washington: National Academy Press; 2000
2. Beecher HK, Todd DP. A study of the deaths associated with anesthesia and surgery: based on a study of
599, 548 anesthesias in ten institutions 1948-1952, inclusive. Ann Surg 1954; 140:2–35
3. Lienhart A, Auroy Y, Péquignot F, Benhamou D, Warszawski J, Bovet M, Jougla E. Survey of anesthesia-
related mortality in France. Anesthesiology 2006; 105:1087–97
4. Moller JT, Johannessen NW, Espersen K, Ravlo O, Pedersen BD, Jensen PF, Rasmussen NH, Rasmussen
LS, Pedersen T, Cooper JB. Randomized evaluation of pulse oximetry in 20,802 patients: II. Perioperative
events and postoperative complications. Anesthesiology1993; 78:445–53
5. Practice guidelines for management of the difficult airway. A report by the American Society of
Anesthesiologists Task Force on Management of the Difficult Airway. Anesthesiology 1993; 78:597–602
6. Arbous MS, Meursing AEE, van Kleef JW, de Lange JJ, Spoormans HHAJM, Touw P, Werner FM,
Grobbee DE. Impact of anesthesia management characteristics on severe morbidity and mortality.
Anesthesiology 2005; 102:257–68
7. Orser BA, Byrick R. Anesthesia-related medication error: time to take action. Can J Anaesth 2004; 51:756–
60
8. Bodenham A. Reducing major procedural complications from central venous catheterisation. Anaesthesia
2011; 66:6–9
9. Lamperti M, Bodenham AR, Pittiruti M, Blaivas M, Augoustides JG, Elbarbary M, Pirotte T, Karakitsos D,
LeDonne J, Doniger S, Scoppettuolo G, Feller-Kopman D, Schummer W, Biffi R, Desruennes E, Melniker
LA, Verghese ST. International evidence-based recommendations on ultrasound-guided vascular access.
Intensive Care Med 2012. doi:10.1007/s00134-012-2597-x
10. Brown JP. Closing the communication loop: using readback/hearback to support patient safety. Jt Comm J
Qual Saf 2004; 30:460–4
11. Nagpal K, Vats A, Lamb B, Ashrafian H, Sevdalis N, Vincent C, Moorthy K. Information transfer and
communication in surgery: a systematic review. Ann Surg 2010; 252:225–39
12. Kalkman CJ. Handover in the perioperative care process. Curr Opin Anaesthesiol 2010; 23:749–53
13. Raptis D, Fernandes C, Chua W, Boulos P. Electronic software significantly improves quality of handover
in a London teaching hospital. Health Informatics J 2009; 15:191–8
14. Iedema R, Merrick E, Kerridge R, Herkes R, Lee B, Anscombe M, Rajbhandari D, Lucey M, White L.
Handover-Enabling Learning in Communication for Safety (HELiCS): a report on achievements at two
hospital sites. Med J Aust 2009; 190:S133–6
15. Gawande A. The Checklist Manifesto: How to get things right. 209 London: Profile Books (GB); 2011
16. Haynes AB, Weiser TG, Berry WR, Lipsitz SR, Breizat AHS, Dellinger EP, Herbosa T, Joseph S, Kibatala
PL, Lapitan MCM, Merry AF, Moorthy K, Reznick RK, Taylor B, Gawande AA, for the Safe Surgery Saves
Lives Study Group. A surgical safety checklist to reduce morbidity and mortality in a global population.
New Engl J Med 2009; 360:491–9
17. McCambridge J, Kypri K, Elbourne DR. A surgical safety checklist. N Engl J Med 2009; 360:2373–5
holders.
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18. de Vries EN, Prins HA, Crolla RMPH, Outer den AJ, van Andel G, van Helden SH, Schlack WS, van Putten
MA, Gouma DJ, Dijkgraaf MGW, Smorenburg SM, Boermeester MA for the SURPASS Collaborative
Group. Effect of a comprehensive surgical safety system on patient outcomes. N Engl J Med 2010;
363:1928–37
19. van Klei WA, Hoff RG, van Aarnhem EEHL, Simmermacher RKJ, Regli LPE, Kappen TH, van
Wolfswinkel L, Kalkman CJ, Buhre WF, Peelen LM. Effects of the introduction of the WHO “Surgical
Safety Checklist” on in-hospital mortality: a cohort study. Ann Surg 2012; 255:44–9
20. Sexton JB, Helmreich RL, Neilands TB, Rowan K, Vella K, Boyden J, Roberts PR, Thomas EJ. The Safety
Attitudes Questionnaire: psychometric properties, benchmarking data, and emerging research. BMC Health
Serv Res 2006; 6:44
21. Sexton JB, Berenholtz SM, Goeschel CA, Watson SR, Holzmueller CG, Thompson DA, Hyzy RC,
Marsteller JA, Schumacher K, Pronovost PJ. Assessing and improving safety climate in a large cohort of
intensive care units. Crit Care Med 2011; 39:934–9
Communicate Openly – Resolve Early
When patients suffer harm related to the delivery of anesthesia services, anesthesiologists are often ill prepared to
respond to patients and their family members. Honest and effective communication following harm helps to
maintain trust between the anesthesiologist and patient, and is best provided as soon after the harm event as
reasonably possible. Otherwise, every hour that goes by without effective communication can constitute more harm
to the affected parties.
Honest and effective communication after a harmful adverse event is not just the right thing to do, but the smart
thing to do as well. Patient and families sue, in large part, because they perceive a lack of transparency,
abandonment, or “cover-up”. A recent study revealed that 70% of all lawsuits were dismissed after both sides shared
all pertinent and relevant clinical information. A transparent process with open lines of communication and
disclosure of all pertinent information can mitigate those patient and family perceptions and prevent lawsuits at the
outset.
Disclosure of the facts and circumstances, including the admission of errors or mistakes, is a multifaceted process
that requires careful planning, preparation, and coordination by anesthesiologists, surgeons, other proceduralists, and
hospital or clinic administrators. Given its complexity, anesthesiologists understandably fear that an inadequate or
poorly executed disclosure of medical error or mistake will only serve to frustrate the care professionals, patients
and families, potentially ruin the reputation of the organization and other individuals involved in the event, and
encourage lawsuits.
Therefore, successful adverse event or patient harm event response programs that include the “full disclosure” of
medical error rely heavily on the integration between clinical services, organizational risk management, and the risk
management arm of professional liability carriers, if applicable, for individuals involved in the event.
This integration ensures that the various “stakeholders” are “on board” with the process or at least aware of the plan
for communication after adverse events. In order to provide a consistent approach to adverse events for physicians,
patient and families, all of the steps involved in the response to harm should be preapproved by all stakeholders
before implementation of a “full disclosure” process. In addition, since not all care professionals are adept at
communicating in the early phases following serious harm, it is wise for anesthesiologists to seek out the availability
of communication support services within their organization during the “preapproval” phase of the full disclosure
implementation program.
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The communication after harm occurs generally falls into 3 phases: immediate, intermediate, and final or follow-up
phase. See Table 1. The extent to which the patient’s anesthesiologist is involved in a disclosure communication will
vary on a case-by-case basis. Nonetheless, it is critical that the anesthesiologist participate in the post event
communication if anesthesia services were in any way associated with the unexpected outcome. For the immediate
phase of communication, this may require close coordination with anesthesiology associates and those managing a
busy operating room or clinic so that the anesthesiologist is provided the time to engage in these important
discussions. Given the natural tendency for care professionals to intentionally or unintentionally point blame at
others, the anesthesiologist’s presence is mandatory for the early phase communication if his/her care was at all
associated or arguably related to the harm event, and if other providers, such as the surgeon, intend to discuss the
events. The presence of the anesthesiologist may mitigate the risk of “finger pointing” during the initial disclosure
conversation, although the anesthesiologist should always be prepared for the possibility and plan for an appropriate
response in the event finger pointing occurs.
Table 1. Phases of Communication Follow Patient Harm Events
Immediate Express empathy

Do not make promises you cannot keep
Disclose “known” facts
Assure non-abandonment
Identify person[s] [liaison] for follow-up
Listen
Intermediate Ensure liaison presence
Listen
Continue to express empathy
Disclose facts discovered during investigation
Ask and answer questions
Apologize if consensus exists about error or substandard care causing harm
Offer ongoing contact
Final or follow-up phase Ensure liaison presence
Listen
Answer additional questions
Express empathy, apologize if indicated
Discuss process improvement measures
Offer ongoing contact and support
It is important for anesthesiologists to recognize that “disclosure” is a process and not a single event, and some harm
events or unexpected outcomes may require multiple meetings until resolution occurs. During the first meeting, only
the findings surrounding the incident that are reasonably certain and unlikely to change as the investigation proceeds
are communicated to the patient and/or family. The information provided to the patient at each step in the
communication is guided by the “balance beam” approach, described by Pichert and Hickson, which considers the
facts of the case as they are revealed during the investigation, and may ultimately involve an apology and
admissions of unreasonable care and accountability. This approach guides the timing and content of the disclosure
meetings and “balances” the benefit of early disclosure against the risk of prematurely disclosing information and
conclusions that may later turn out to be incorrect. Prior to admitting unreasonable care, it is mandatory that the
anesthesiologist discuss the possibility with his/her professional liability carrier or the organization’s risk manager.
It is also critical that the anesthesiologist understand the difference between “empathy” and “apology”. Empathy is
the understanding or sharing of another’s emotions and feelings and is a necessary element of all effective
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communication related to patient harm events. An “apology” on the other hand is expressing remorse for a mistake
that has caused harm. Apologies carry legal implications and should only be offered when the facts are clear and
agreed upon by stakeholders with knowledge of the events.
Example of expression of empathy: “I am sorry your loved one passed away during the emergency surgery
this morning.”
Example of apology: “I am sorry we gave your loved one a medication to which we should have known she was
allergic. Giving her that medication caused the cardiac arrest she suffered in the OR today.”
Throughout the communication, anesthesiologists should remain mindful of patient expectations following harm
events. Numerous studies now demonstrate that patient and families want:
1. Recognition and appreciation of the harm they have suffered.
2. Acceptance of responsibility by those responsible.
3. Honest and understandable discussion of facts.
4. Plans for future prevention if preventable.
5. Assurance of follow-up and non-abandonment
From the follow-up perspective, patients and families often feel very disrespected when they receive a bill for
anesthesia care that they understand falls well below the “standard of care” – i.e. wrong site surgery or wrong site
regional block. Therefore, it is imperative that the anesthesiologist have a system in place that ensures patients are
not billed for improper anesthesia care. Furthermore, they should not promise patients that “future care will be
handled” or “provided free” if they are not in a position and empowered to make sure that happens. Finally, since
disclosure is a process and not a single event, some of the most rewarding and useful discussions can occur months
or years after a harm event, and the anesthesiologist should take advantage, in certain cases, to circle back with
patients and families long after the initial discussions – much learning and healing for all parties can come from such
contact.
Topic 2 References
McDonald TB, Helmchen LA, Smith KM, Centomani N, Gunderson A, Mayer D, Chamberlin WH. Responding to
patient safety incidents: the seven pillars. Qual Saf Health Care 2010; 19(6):e11
Vincent C, Young M, Phillips A. Why do patients sue doctors? A study of patients and relatives taking legal action.
Lancet 1994; Jun 25; 343(8913):1609-13
Golann D. Dropped medical malpractice claims: their surprising frequency, apparent causes, and potential remedies.
Health Affairs 2011; Vol 30 No 7:1343-50
Pichert JW, Hickson GB, Vincent C. Communicating about unexpected outcomes and errors. In: Carayon P, ed.
Handbook on Human Factors and Ergonomics in Healthcare and Patient Safety. Hillsdale (NJ): Erbaun Associates;
2007:579-98
holders.
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How to Avoid a Lawsuit After an Adverse Outcome: Lessons from the Closed Claims Project
Although adequate medical knowledge is essential for good patient care and to avoid adverse outcomes, not all
adverse outcomes can be prevented, and medical misadventures occur. Besides good care, good communication and
documentation can help you avoid a lawsuit if an adverse outcome occurs. There is a clear relationship between
malpractice claims and communication failures between physician and patient.1,2 Patients who sue are more likely to
be unhappy with the interpersonal relationship with their physician than the outcome of care.3 Recently, institutions
have initiated programs to enhance communication between physicians, patients, and families, such as “full
disclosure” of medical errors.4-9 Over 35 states in the U.S., have passed “apology laws” allowing health care
workers to apologize to patients without the apology being used as evidence of medical negligence.5,8 Although the
ultimate effect of disclosure policies on medical malpractice is unclear, preliminary evidence suggests that some
health care systems have reported a reduction in lawsuits and claims payments.6,7 This lecture will review error
communication, disclosure of information, and other important factors that may help avoid a lawsuit in the advent of
a poor patient outcome.
Why Patients File Lawsuits?

A common reason patients file a lawsuit is the need for an explanation or information that they perceive may be
purposely withheld.2,3 Patients report greater satisfaction and are less likely to sue if they perceive the physician as
communicative, caring, honest, personal, and apologetic (if appropriate).10,11 Other factors that increase the
likelihood of a lawsuit include television advertising by law firms, recommendations by other health care
professionals to seek legal advice, and financial constraints.3,12 Patients’ calls to law firms are often initiated after
receiving a notice of unpaid bills from a collection agency.
Some physicians get sued more often than others. A high risk group of 2-8% of physicians in a particular specialty
accounted for more than 50% of malpractice claims.13 High risk physicians do not have inferior skills or more
complicated patients, but instead have inadequate communication skills with patients and their families, especially
when a complication occurs.14,15
Follow-up After an Adverse Outcome

Poor follow-up after an adverse outcome leaves patients with the impression that you do not care about their
welfare, that your time is more important than their health, and that perhaps not everything possible was done on
their behalf to treat the complication. Although anesthesiologists have very busy work schedules during these times
of “high efficiency” and a focus on “decreased turnover times”, follow-up of patients and their complications with
appropriate referral should occur with proper documentation. Failure to recognize the deterioration in the patient’s
condition and failure to investigate with appropriate intervention increases liability exposure. Follow-up
demonstrates to patients and juries that you are a professional and care about the welfare of your patient. Even
though it may be uncomfortable to see patients after an adverse occurrence, particularly when there was some
potential inadequacy of care on your part, follow-up is an essential part of handling adverse outcomes. One study on
medical malpractice and the reasons patients and/or their relatives file claims showed that only 15.6 – 37.1% of
patients were satisfied with the amount of information provided about an adverse outcome, the clarity and accuracy
of explanation, whether the explanation was delivered sympathetically, and with the overall view of the
explanation.2 Similar results were found in a study of 45 plaintiffs’ depositions of medical malpractice where 32%
of the depositions contained statements concerning patient desertion by the physician, 29% with devaluing patient
and/or family views, 26% with delivering information poorly, and 13% with failing to understand the patient and/or
family perspective.16
Informed Consent
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Although consent is frequently an issue in medical malpractice claims, it is rarely the sole reason for the lawsuit, and
is usually associated with an adverse outcome. The consent issue has been likened to an anniversary card: “obtaining
one does not guarantee you a good time, but you’re asking for it if you don’t get one.” Consent issues may arise for
a variety of reasons: 1) inadequate disclosure of the risks of a procedure – e.g., risk of post-dural puncture headache
after a subarachnoid block; 2) failure to obtain consent for a procedure – e.g., performance of a regional technique
under general anesthesia; or 3) documentation of refusal of care where a patient refuses your recommendations –
e.g., patient with severe chronic obstructive pulmonary disease and congestive heart failure refuses a regional
technique for ankle surgery. Items for consent discussion should include common complications, as well as any rare
devastating complication that the typical patient would find important to make a decision on a particular treatment.
However, they should not be used to list all possible complications, as patients would lose sight of the major
concerns. Documentation on the medical chart of the risks and benefits discussion with patients is key to minimizing
medicolegal issues surrounding consent. Certain states or malpractice liability companies have a requirement for a
separate anesthesia consent form with a patient signature.
Issues surrounding preoperative evaluation in closed claims usually involve 1) lack of documentation of an airway
examination in cases of unsuspected difficult intubation; and 2) lack of follow-up on abnormal preoperative tests
(frequently ordered by other healthcare providers) in cases where the delay in diagnosis, treatment, or consultation
resulted in harm to the patient (e.g. chest x-ray with new cancerous lesion or abnormal EKG with a subsequent
perioperative myocardial infarction). These issues emphasize the importance of performing and documenting a
thorough preoperative evaluation, and addressing any abnormal test results with appropriate treatment, consultation,
or referral.
Changing of the Guard or “Handoffs” with Poor Communication

In this age of same day surgery admissions and outpatient surgery, the frequency of one anesthesia health care
provider doing the history and physical while another provides the anesthetic is an everyday occurrence. Pertinent
medical information may be lost, or specific patient promises may not be honored when poor communication
occurs. Thorough documentation of any discussions with patients regarding their health history or specific wishes
regarding their anesthetic management should help to avoid this problem. Patients may assume that both parties
effectively communicated with each other, and that they have no need to repeat their questions, concerns, or
information provided to the first anesthesiologist. Any unusual issues should be communicated directly between
health care providers. Similar strategies of good documentation and direct communication during “handoffs” during
operations should improve patient care and minimize liability exposure.
Documentation (or Lack Thereof)

Inadequate documentation of the preoperative history and physical and consent, intraoperative events, postoperative
care and follow-up, and critical events are a common cause of lawsuits being settled in favor of the plaintiff.17 The
medical record is your line of communication with other physicians and health care professionals, and it is also the
legal record. Routine care such as a preoperative history and physical and intraoperative care should be documented
on the standard forms provided by your hospital/anesthesia group with your signature and date as this demonstrates
good care. Although one may not have time to document during a crisis, a thorough detailed description of the
events and actions taken should be written at the first available opportunity. Although basic charting of vital signs
and medications should be recorded on the anesthesia record for intraoperative critical events, additional
documentation should also be done in the medical record in the progress note section as most other specialties do not
understand or feel comfortable with the anesthetic record, and it may be lost during storage. Electronic
documentation has the added advantage of not being “thinned” from the chart. Only list the facts - events as they
occurred - and do not speculate about etiology of the damaging event. As many claims are not filed until more than a
year has passed since the event, the documentation also serves as a reminder to you regarding specific details that
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may otherwise be forgotten. If an event is not documented, the judge and/or jury, and possibly even you, will be less
convinced that it ever occurred, and it leaves the impression that you are not careful.
Altering the Medical Record

Perhaps one of the most damaging actions a health care provider can do after an adverse outcome is to alter or
falsify the medical record.18, 19 Revelation of this behavior leaves the judge and/or jury with the impression of a
dishonest and incompetent anesthesiologist/anesthetist whose medical record and testimony cannot be trusted. That
impression combined with a significant patient injury leads the average person to assume fault on the part of the
health care provider. Any additional information that the anesthesiologist wants to place in the chart should be done
on progress notes, with entry date and time noted. Never cross out incorrect information after an adverse event – but
rather note any pertinent corrections in the progress notes. Law firms may send the medical records for ink analysis
to determine if alterations have been made.
Maligning by Other Healthcare Providers

One of the under-appreciated, but more common, reasons for plaintiffs filing claims is the insinuation by other
healthcare professionals that there was a maloccurrence.12,14,16 One study found that 17 of 31 plaintiffs reported that
other healthcare professionals had either directly or indirectly suggested that the care provided by the defendant had
caused the patient injury.17 Of these 17 claims, 71% of the “other healthcare professionals” alleging maloccurrence
were the subsequent consultants who were brought into the case because of the adverse occurrence. For
anesthesiologists, one of the potential avenues for miscommunication about an adverse occurrence is through the
surgeon. Therefore, the anesthesiologist should always accompany the surgeon for any discussions with the
patient/family. “Charting-wars” with surgeons or other healthcare providers should be avoided as this behavior
makes everyone involved look incompetent and only weakens defense of a case should a claim be subsequently
filed.
Summary
Good communication and documentation can help you avoid a lawsuit if an adverse outcome occurs. Empathetic
communication, effective error disclosure, informed consent, preoperative evaluation, careful handoffs, and
documentation are all important.
Topic 3 References
1. Hickson GB, Jenkins AD: Identifying and addressing communication failures as a means of reducing
unnecessary malpractice claims. NC Med J 2007; 68:362-4
2. Vincent C, Young M, Phillips A: Why do people sue doctors? A study of patients and relatives taking legal
action. Lancet 1994; 343:1609-13
3. Hickson GB, Clayton EW, Githens PB, Sloan FA: Factors that prompted families to file medical
malpractice claims following perinatal injuries. JAMA 1992; 267:1359-63
4. McDonald TB: Error disclosure: Within a principled approach to adverse events. American Society of
Anesthesiologists Newsletter 2009 ; 73(5):20-2
5. Gallagher TH, Studdert D, Levinson W: Disclosing harmful medical errors to patients. N Engl J Med 2007;
356:2713-9
6. Pelt JL, Faldmo LP: Physician error and disclosure. Clin Obstet Gynecol 2008; 51:700-8
7. Levinson W: Disclosing medical errors to patients: A challenge for health care professionals and
institutions. Patient Education and Counseling 2009; 76:296-9
8. McDonnell WM, Guenther E: Narrative review: Do state laws make it easier to say “I’m Sorry”? Ann
Intern Med 2008; 149:811-5
9. Gallagher TH: A 62-year-old woman with skin cancer who experienced wrong-site surgery: review of
medical error. JAMA 2009; 302:669-77
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10. Duclos CW, Eichler M, Taylor L, Quintela J, Main DS, Pace W, Staton EW: Patient perspectives of
patient-provider communication after adverse events. Int J Qual Health Care 2005; 17:479-86
11. Levinson W, Roter DL, Mullooly JP, Dull VT, Frankel RM: Physician-patient communication. The
relationship with malpractice claims among primary care physicians and surgeons. JAMA 1997; 277:553-9
12. Huycke LI, Huycke MM: Characteristics of potential plaintiffs in malpractice litigation. Ann Intern Med
1994; 120:792-8
13. Sloan FA, Mergenhagen PM, Burfield WB, Bovbjerg RR, Hassan M: Medical malpractice experience of
physicians. Predictable or haphazard? JAMA 1989; 262:3291-7
14. Hickson GB, Clayton EW, Entman SS, Miller CS, Githens PB, Whetten-Goldstein K, Sloan FA:
Obstetricians’ prior malpractice experience and patients’ satisfaction with care. JAMA 1994; 272:1583-7
15. Entman SS, Glass CA, Hickson GB, Githens PB, Whetten-Goldstein K, Sloan FA: The relationship
between malpractice claims history and subsequent obstetric care. JAMA 1994; 272:1588-91
16. Beckman HB, Markakis KM, Suchman AL, Frankel RM. The doctor-patient relationship and malpractice:
Lessons from plaintiff depositions. Arch Intern Med 1994; 154:1365-70
17. Gorney M, Martello J. The genesis of plastic surgeon claims. A review of recurring problems. Clin Plast
Surg 1999; 26:123-31.ix.
18. Bean RV. Altering records: discrediting your best witness. J Med Assoc GA 1998; 82:63- 4
19. Pennachio DL. Alter records, lose the case. Med Econ 2003;80:40,43-4
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Crossing the Patient Safety-Medical Liability Chasm

Timothy B McDonald, M.D. Chicago, Illinois
When patients suffer harm related to the delivery of anesthesia services, anesthesiologists are often ill prepared to
respond to patients and their family members. Honest and effective communication following harm helps to
maintain trust between the anesthesiologist and patient and is best provided as soon as the harm event as reasonably
possible. Otherwise, every hour that goes by without effective communication can constitute more harm to the
affected parties.
Honest and effective communication after a harmful adverse event is not just the right thing to do but the smart thing
to do as well. Patient and families sue, in large part, because they perceive a lack of transparency, abandonment, or
“cover-up”. A recent study revealed that 70% of all lawsuits were dismissed after both sides shared all pertinent and
relevant clinical information. A transparent process with open lines of communication and disclosure of all pertinent
information can mitigate those patient and family perceptions and prevent lawsuits at the outset.
Disclosure of the facts and circumstances, including the admission of errors or mistakes, is a multifaceted process
that requires careful planning, preparation, and coordination by anesthesiologists, surgeons, other proceduralists and
hospital or clinic administrators. Given its complexity, anesthesiologists understandably fear that an inadequate or
poorly executed disclosure of medical error or mistake will only serve to frustrate the care professionals, patients
and families, potentially ruin the reputation of the organization and other individuals involved in the event, and
encourage lawsuits.
Therefore, successful adverse event or patient harm event response programs that include the “full disclosure” of
medical error rely heavily on the integration between clinical services, organizational risk management, and the risk
management arm of professional liability carriers, if applicable, for individuals involved in the event.
This integration ensures that the various “stakeholders” are “on board” with the process or least aware of the plan for
communication after adverse events. In order to provide a consistent approach to adverse events for physicians,
patient and families, all of the steps involved in the response to harm should be preapproved by all stakeholders
before implementation of a “full disclosure” process. In addition, since not all care professionals are adept at
communicating in the early phases following serious harm it is wise for anesthesiologists to seek out the availability
of communication support services within their organization during the “preapproval” phase of the full disclosure
implementation program.
The communication after harm occurs generally falls in 3 phases: immediate, intermediate, and final or follow-up
phase. See Table 1. The extent to which the patient’s anesthesiologist is involved in a disclosure communication will
vary on a case-by-case basis. Nonetheless, it is critical that they participate in the post event communication if
anesthesia services were in any way associated with the unexpected outcome. For the immediate phase of
communication this may require close coordination with their anesthesiology associates and those managing a busy
operating room or clinic so that the anesthesiologist is provided the time to engage in these important discussions.
Given the natural tendency for care professionals to intentionally or unintentionally point blame at others, the
anesthesiologist’s presence is mandatory for the early phase communication if their care was at all associated or
arguably related to the harm event and other providers, such as the surgeon, intend to discuss the events. Their
presence may mitigate the risk of “finger pointing” during the initial disclosure conversation although they should
always be prepared for the possibility and plan for an appropriate response in the event that occurs.
Table 1. Phases of Communication Follow Patient Harm Events

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Immediate Express empathy

Don't make promises you cannot keep
Disclose “known” facts
Assure non-abandonment
Identify person[s] [liaison] for follow-up
Listen
Intermediate Ensure liaison presence
Listen
Continue to express empathy
Disclose facts discovered during investigation
Ask and answer questions
Apologize if consensus exists about error or
substandard care causing harm
Offer ongoing contact
Final or follow-up phase Ensure liaison presence
Listen
Answer additional questions
Express empathy, apology if indicated
Discuss process improvement measures
Offer ongoing contact and support
It is important for anesthesiologists to recognize that “disclosure” is a process and not a single event and some harm
events or unexpected outcomes may require multiple meetings until resolution occurs. During the first meeting, only
the findings surrounding the incident that are reasonably certain and unlikely to change as the investigation proceeds
are communicated to the patient and/or family. The information provided to the patient at each step in the
communication is guided by the “balance beam” approach, described by Pichert and Hickson, which considers the
facts of the case as they are revealed during the investigation and may ultimately involve an apology and admissions
of unreasonable care and accountability. This approach guides the timing and content of the disclosure meetings and
“balances” the benefit of early disclosure against the risk of prematurely disclosing information and conclusions that
may later turn out to be incorrect. It is mandatory that anesthesiologist discuss the possibility of an admission of
unreasonable care with their professional liability carrier or the organizations risk manager prior to doing so.
It is also critical that the anesthesiologist understand the difference between “empathy” and “apology”. Empathy is
the understanding or sharing of another’s emotions and feelings and a necessary element of all effective
communication related to patient harm events. An “apology” on the other hand is expressing remorse for a mistake
that has caused harm. Apologies carry legal implications and should only be offered when the facts are clear and
agreed upon by stakeholders with knowledge of the events.
Example of expression of empathy: “I am sorry your loved one passed away during the emergency surgery
this morning.”
Example of apology: “I am sorry we gave your loved one a medication to which we should have known they
were allergic. Giving her that medication caused the cardiac arrest she suffered in the OR today.”
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Throughout the communication, anesthesiologists should remain mindful of patient expectations following harm
events. Numerous studies now demonstrate that patient and families want:
1. Recognition and appreciation of the harm they have suffered.
2. Acceptance of responsibility by those responsible.
3. Honest and understandable discussion of facts.
4. Plans for future prevention if preventable.
5. Assurance of follow-up and non-abandonment
From the follow-up perspective, patients and families often feel very disrespected when they receive a bill for
anesthesia care that they understand falls well below the “standard of care” – i.e. wrong site surgery or wrong site
regional block. Therefore, it is imperative that anesthesiologist have a system in place that ensures patients are not
billed for improper anesthesia care. Furthermore, they should not promise patients that “future care will be handled”
or “provided free” if they are not in a position and empowered to make sure that happens. Finally, since disclosure is
a process and not a single event, some of the most rewarding and useful discussions can occur months or years after
a harm event and the anesthesiologist should take advantage, in certain cases, to circle back with patients and
families long after the initial discussions – much learning and healing for al parties can come from such contact.
References:
McDonald T et al. Responding to Patient Safety Incidents: The Seven Pillars. Qual Saf Health Care. 2010. 19e11.
Vincent C, Young M, Phillips A. Why do patients sue doctors? A study of patients and relatives taking legal action.
Lancet. 1994. Jun 25; 343(8913):1609-13.
Golann D. Dropped Medical Malpractice Claims: Their Surprising Frequency, Apparent Causes, and Potential
Remedies. Health Affairs. 2011, Vol 30 No 7, 1343-1350.
Pichert JW, Hickson GB, Vincent C. Communicating about unexpected outcomes and errors. In: Carayon P. ed.
Handbook on Human Factors and ergonomics in healthcare and patient safety. Hillsdale (NJ): Erbaun Associates.
2007:579-598.
DISCLOSURE
All speakers have indicated that he or she has no significant financial relationship with the manufacturer of a
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Changing Physician Behavior: Must We Accept the “Herding Cats” Metaphor?
Nancy L. Glass, M.D., MBA, FAAP Houston, Texas
We pride ourselves on practicing high-quality medicine, appropriate for each patient, in an environment fraught with
sicker patients and overwhelming time pressures. Increasingly, anesthesiologists are being “told” what to do and
how to do it, to improve patient care. At the same time, our hospitals and facilities are introducing new protocols,
new technologies, and electronic records, while frustrating us in other ways by limiting our access to desired
equipment or medications. National drug shortages have compounded the challenges and increased our frustrations.
If we were to review the charts of our own patients, we would probably find deviations from recommended
protocols and practice standards, even by very accomplished practitioners. Why is that?
How can clinical leaders facilitate the acceptance and compliance with new protocols and standards by their groups?
And what about the irascible colleague who refuses to cooperate—what do you do about that person? How do you
bring them “on board?” What can our leaders and hospitals do to help the “regular” clinician feel more positive
about all of the necessary practice changes, and more likely to cooperate?
What is the Problem?
Even though our patients are cared for within complex institutions or networks, at the actual point of care, you and I
make the individual decisions about which procedures and therapies our patients get. And most of us do not work as
employees of the larger organization. We either work for an academic unit affiliated with the hospital, or we work
within a private practice group, so there may not be a defined authority of the hospital administrators “over” the
doctors. Up to the present time, clinicians have been protective of our professional autonomy—to a fault. We
believe that we are providing the treatment our patients need—based on our training and experience, our patients’
values and expectations, and on the resources available. We are less comfortable acknowledging that we also make
decisions based on financial incentives, convenience, time pressures, and other influences in our work environment.
In this presentation, I will discuss some of the reasons that we resist efforts by “management” to get us to change
our behaviors. To some extent, we continue practicing our individualistic styles because there is no definitive data
that tells us that one course of treatment is superior to another. Sometimes there is uncertainty about the nature of
the condition itself, or how it is progressing. Or perhaps we’re being asked to change our practice to prevent a
complication so rare that we’ve never seen it! But even when there IS definitive data to show that one treatment
strategy is optimal, we resist being told that we should change our behaviors.
What is the Department Chief to do? How can he/she affect change in individual practice patterns to positively
influence outcomes? Are we dealing with “problem doctors” or “problem systems”? Even more difficult is the
position of the non-physician manager at the hospital. How can he/she gain the cooperation and participation of
physicians in affecting change in practice patterns within the organization? Wouldn’t it be easier to herd a thousand
cats cross-country from New York to San Francisco? How can we as front-line providers feel better about all of the
changes swirling in our environment?
Changing Individual Behaviors
No discussion of changing individual efforts is complete without looking at motivation. One useful framework for
considering individual motivations in the workplace is that described by psychologist David McClelland. His
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research indicated that most individuals are primarily motivated by one of three factors: affiliation (the desire to be
liked and appreciated, to build positive relationships), achievement (the highest possible standards for personal
performance), or power (the desire to influence others and to have a say in how things are done). Recognizing the
motivators of those in one’s group gives the effective leader the chance to frame the desired behavior in such a way
that the individual is more likely to cooperate. We will consider some specific anesthesia-related examples of these
motivators, and how they might influence a practitioner’s behavior and view of the new initiatives.
How might you recognize How to engage or

Motivator Characteristics
this individual? energize this person
Sets own goals, takes personal Show data; share individual’s
Achievement Motivated by good results responsibility, likes to do things outcomes compared with
alone or closely direct others benchmark
Motivated by positive Joins groups, likes to work with Assign to multi-disciplinary
Affiliation relationships, wants to be others, demonstrates personal group; may function as
liked interest in colleagues cheerleader for new initiative
Provide opportunities to lead
Seeks and enjoys positions of
Wants to influence others, or to develop best practices
power or responsibility; always
Power (Influence) make decisions, guide within a group; may be an
has an opinion at the staff
activity effective champion for
meeting(!)
needed change
Financial incentives have been proposed as a way of getting individuals to adopt particular practices. Medicare is
implementing Pay for Performance, P4P, to ensure that certain key initiatives are achieved, such as antibiotics
within an hour of incision, or maintenance of normothermia during anesthesia. However, there are serious
drawbacks to the use of financial incentives: they only reward the behaviors specifically targeted, while ignoring
other worthy practices; some “best practices” are harder to measure and observe than others. In addition, the power
of the incentive wanes over time, as the individual comes to “expect” the reward, and begins to consider it part of
his/her base salary. More insidious are the detrimental effects of individual rewards on group functioning,
creativity, and initiative.
One of the most potent ways to change an individual’s behavior is to demonstrate his/her results with respect to the
rest of the peer group, since no one chooses to become the “worst” of the group! In one recent report, Frenzel and
colleagues describe a quality improvement project in which they provided CME content focused on risk factors and
best practices for preventing postoperative nausea and vomiting. Subsequently, they followed the group’s
compliance rates with the guidelines over time. Providing individual practitioners with their own compliance rates,
compared with the group, appeared to enhance acceptance of these best practices over time, at least for the patients
with two or more risk factors. Although medical-decision making can be difficult to analyze, this study and others
demonstrate a positive reinforcing impact of “report cards” on practitioner behavior.
Why Change Efforts Fail
An institution’s efforts, if primarily aimed at changing individual physicians’ behaviors, are doomed to failure. The
change in practice being sought must be viewed as important by physicians for their patients. Planning for change
must be effective and comprehensive and must include all stakeholders; the institution must also demonstrate the
will to carry through with the change initiative and be willing to expend resources to guarantee its success. It is
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amazing to see how often the institution’s will falters in the midst of a difficult or contentious change process.
Failure to deal with conflicting incentives or agendas dooms effective change.
Understanding motivators for individuals is key to designing successful change initiatives. The logical approach—
analyzing data, choosing the best solution, making the necessary changes—is a common way that organizations
impose change. But this model fails to take into consideration the emotions of the workers, and generally only
results in incremental changes. A more effective model—sometimes called the See-Feel-Change Model—
demonstrates to individuals compelling evidence for the need to change behaviors and creates the energizing
emotions necessary to make changes based on personal commitment to patients. This model acknowledges the
power of emotions to support or block change efforts.
And finally, we have all been in situations where we agreed with the change in practice, and yet—the “systems”
issues that would support the change have not been fixed, so that “doing the right thing” is more difficult or
cumbersome or time-consuming than it should be. Not having the right equipment, people, or processes in place
will sabotage an otherwise well-considered change initiative.
Recommended Process for Successfully Introducing Change
Professor John Kotter studied change efforts for years in different sizes and kinds of organizations; and from this
work, developed a model for successful change. I will present his model, as well as strategies specific for
implementation of clinical guidelines, including research on which efforts are more/less effective for clinicians. No
single strategy will work for all situations, and leaders must be alert for “derailers”—situations or individuals that
threaten to slow down or impede the change process.
Kotter also described 8 common errors that leaders make in change initiatives. I will introduce these to the group, as
I believe they provide a powerful framework for leaders, as well as an opportunity for self-reflection about
lackluster change efforts in one’s own institution. He described the critical errors as these: failure to create a sense
of urgency around the need to change, not creating a powerful guiding coalition, lacking a clear vision, failure to
communicate that vision, failure to remove obstacles to performing in the new manner, failure to create short-term
wins, declaring victory too soon, and failure to anchor the new behaviors and practices into the group’s culture.
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Heart of Change Framework
Step 1 Step 2 Step 3 Get Step 4

Increase Build guiding the vision Communicate
urgency team right For buy-in
Shift from talking to doing
Step 5 Step 6 Step 8

Step 7
Empower Create short- Make the
Don’t let up
for action term wins change stick
Source: Heart of Change, by John P. Kotter and Dan S. Cohen, Boston:

Harvard Business School Press, 2002
Summary
Introducing change in practice into complex multi-disciplinary medical systems is a challenge! In this presentation,
I will cover change at both the individual and group level, providing participants with a framework for planning, and
for incorporating individual motivation into change initiatives. The presentation will also provide an opportunity for
participants to reflect on successful and unsuccessful change initiatives in his/her own hospital.
The successful leaders in our specialty for the future will be those who effectively engage and motivate a diverse
workforce to embrace change, creating departments that are able to respond quickly to shifting medical, regulatory,
and political landscapes.
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Selected References
There is a wealth of literature on this topic, both in the standard business literature as well as (increasingly) in the
more traditional medical literature. The references listed here are just a start—those that I have found useful or
interesting.
Bohmer R, Changing physician behavior. HBS 9-699-124, 2000.
Cohen MM, Eustis MA, Gribbins RE, Changing the culture of patient safety: leadership’s role in health care quality
improvement. Joint Commission Journal on Quality and Safety. 29(7): 329-335, 2003.
Frenzel JC, Kee SS, Ensor JE, Riedel BJ et al, Ongoing provision of individual clinican performance data improves
practice behavior. Anesth Analg 111(2): 515-519, 2010.
Grol R and Grimshaw J. Evidence-based implementation of evidence-based medicine. Journal on Quality

Improvement 25 (10): 503-513, 1999.
Edmondson AC, Framing for learning: lessons in successful technology implementation. California Management
Review, 45(2), 2003. (or, Reprint CMR247).
Ferris TG, Dougherty D, Blumenthal D and Perrin JM, A report card on quality improvement for children’s health
care. Pediatrics 107(1): 143-155, 2001.
Forthman MT, Wooster LD, Hill WC, et al, Insights into successful change management: empirically supported
techniques for improving medical practice patterns. American Journal of Medical Quality 18(5):181-189, 2003.
Green PL and Plsek PE, Coaching and leadership for the diffusion of innovation in health care: a different type of
multi-organization improvement collaborative. Journal on Quality Improvement 28(2): 55-68, 2002.
Hosler FW and Nadle PA, Physician-Hospital Partnerships: incentive alignment through shared governance within
a performance improvement structure. Journal on Quality Improvement 26(2): 59-73, 2000.
Kinney CF and Gift RG, Building a framework for multiple improvement initiatives. Journal on Quality
Improvement 23(8): 407-423, 1997.
Kotter, John P, Leading change: Why transformation efforts fail. HBR 4231, 1995.
Kotter John P, Leading Change. Harvard Business School Press, 1996.
Kotter, John P and Cohen, Dan S, The Heart of Change: Real Life Stories of How People Change Their
Organizations. Harvard Business School Press, 2002.
Sainfort F, Karsh, BT, Booske BC, Smith MJ, Applying quality improvement principles to achieve healthy work
organizations. Journal on Quality Improvement 27(9):469-483, 2001.
Solberg LI, Brekke ML, Fazio CJ, et al, Lessons from experienced guideline implementers: attend to many factors
and use multiple strategies, Journal on Quality Improvement 26(4):171-188, 2000.
holders.
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Solberg, LI, Guideline implementation: What the literature doesn’t tell us. Journal on Quality Improvement 26(9):
525-537, 2000.
Weber V, Joshi MS, Effecting and Leading Change in Health Care Organizations. Journal on Quality Improvement
26(7):388-399.
Hannenberg. AA, Overview: Pay for Performance in Anesthesiology,

www.asahq.org/Washington/P4PPanel102405Hannenbergpdf.pdf
DISCLOSURE
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"Killing? Or Letting Die? Ethical Issues in Withdrawing/Withholding

Lifesaving Treatment, Continuous Terminal Sedation,
Physician Assisted Suicide and Euthanasia"
Gail A. Van Norman M.D. Seattle, Washington
While instances of resuscitation can be traced back to Biblical times, it was on the battlefields of World War II that
resuscitation first became a practical reality, with the development of open-chest cardiac massage. Kouenhoven
then took lessons learned on the battlefield and developed closed-chest cardiac massage, reporting in 1960 about
increased survivorship of in-hospital cardiac arrest. This and other mid-century medical advancements, such as the
development of mechanical ventilation, lead anesthesiologists to question the ethical implications of invasive and
resuscitative medical care. In the middle 20th century, the World Congress of Anesthesiologist asked the Pope to
address the congress regarding whether patients had a moral right to refuse medical therapy that sustained life, or
whether such a decision would constitute suicide, a mortal sin. In a historic address, the Pope affirmed that persons
were not required by God to pursue all possible therapies in order to prolong life, and that refusal of life-sustaining
treatment was not a form of suicide.
In the context of social upheaval surrounding the Viet Nam War and a dramatic cultural shift in the U.S. celebrating
the human desire toward self-actualization of the 1960’s, questioning traditional authority became commonplace.
The scope of this social skepticism did not leave the medical profession untouched.
Several U.S. medical cases involving the rights of patients to refuse life-saving therapy made national and
international headlines. Two notable cases were that of Karen Ann Quinlan and Nancy Cruzan. Decisions by the
New Jersey State Supreme Court and the U.S. Supreme Court, respectively, established that patients have the right
to refuse medical therapy founded in constitutional guarantees of privacy and noninterference. They further
established that this right extended to all medical care, and not just “extraordinary care.” Federal law established in
1990 that all patients have the right to refuse life-sustaining therapy and that hospitals must not only not inform
patients of those rights, but could not discriminate against them for their decisions. These decisions were reaffirmed
in the long legal wrangling surrounding the case of Terry Schiavo in 2005.
Withdrawing/Withholding Life-Sustaining Care
Although both legal and ethics experts agree that both withdrawing and withholding life-sustaining treatments from
competent patients who express a desire to do so, or from patients for whom surrogate decision makers express a
desire to do so is acceptable, there is still both confusion and controversy about these practices. Some of the
controversy arises out of a past tradition in medicine that set the saving of life above concepts such as quality of life
and patient autonomy. Other conflicts arise because physicians mistakenly believe that both of these practices are
ethically the same as “killing” or “euthanasia,” although clinical ethics experts generally agree that they are not.
These misconceptions are perpetuated by confusing terms in the medical literature that appear to equate them to
euthanasia by referring to withdrawing/withholding of life-sustaining care as “passive euthanasia.” “Euthanasia”
however, is by definition an action, and therefore the term is both inaccurate, and an oxymoron.
Double Effect
The principle of double effect is also misunderstood by physicians and other health care workers, and leads to
frequent misunderstandings about ethical boundaries in end of life care. In cases of “double effect”, a physician
must be taking an action intended for ‘good’, but for which it is understood that a foreseen, even probable, but
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unintended consequence is not ‘good’ (e.g. death). This differs from merely accepting that a rare—and therefore
generally unanticipated--reaction to a medication might be death, in that with double effect, death is both a foreseen
and predictable outcome. The physician, however, does not have death as a goal, but rather feels that some other
goal requires that death be risked, and that in fact the goal may not even be achievable unless death occurs. The
classic example is that of a physician seeking to provide tolerable pain relief for a patient who is requiring very high
doses of narcotic. In order to provide pain relief, an increase in dose may, or is even likely to, produce fatal
respiratory depression. But a lesser dose does not lead to pain relief. The patient and physician accept that the
higher dose should be given for the purpose of relieving pain, but is likely to result in death, too. This so-called
double effect is ethically (and legally) recognized and acceptable.
Physician-Assisted Suicide and Euthanasia
A majority of Americans support PAS for terminally ill patients, and a small but significant portion supports
euthanasia (EU) under similar circumstances. In European countries, public acceptance of PAS and EU appears to
be higher across many societies: in Britain, 84% of the public favors PAS and EU. Yet physicians are not formally
educated or trained regarding either PAS or EU, and are ill-equipped to meet this extraordinary shift in health care
policy and public opinion. Studies demonstrate that physicians from specialties frequently involved in end-of-life
decision-making (e.g. intensivists, palliative care specialists, and oncologists) are the most uniformly opposed to
PAS and EU, while patients of these specialists are most likely to favor PAS--a critical discordance between patients
and their providers.
Failing to understand the underlying causes of patient requests for PAS and EU has lead to false assertions and
misdirected policies regarding these practices. Many physicians and legislative groups, for example, contend that the
public interest in PAS and EU is based on a fear of inadequate clinical treatment of pain at end-of-life, and that
therefore investing substantial financial and educational resources towards developing better pain control at end-of-
life will reduce or eliminate the need to consider such measures. Yet studies consistently show that loss of
independence, loss of “meaning,” and psychological, rather than physical suffering are the primary driving
influences behind the desire for options of PAS and EU. If this is true, concentration of substantial human and
financial resources on new pain management strategies is likely to have only a limited potential for addressing these
concerns, and a better understanding of factors actually influencing patient
decisions will be critical in refocusing policies, funding, and care initiatives to more effective strategies to meet the
medical and social needs of patients at end of life.
To date, most studies of attitudes towards PAS and EU as end-of-life options have focused on patients and families
whose members are under treatment for catastrophic disease and on the physicians involved in treating those
conditions, rather than on the “walking well” population. Nevertheless these studies reveal some interesting
findings about what influences a patient’s or physician’s acceptance of these practices.
For both patients and physicians, a primary influence on individual attitudes towards PAS and EU appears to be
“religiosity,” a term referring to a measure of a person’s religious belief, dedication and activities (as opposed to
their religion, which is the specific set of rituals, stories, symbols and doctrine they use to express their religiosity).
The higher the individual scores on a standard “religiosity” scale, the lower their acceptance or desire for PAS or
EU. And physicians’ religious attitudes appear to differ significantly from those of their patients, and of the general
public. Many authors assert that the drive toward PAS and EU in Western countries is related to a general decline in
religious practices, but individual attitudes do not necessarily reflect broader societal choices. And it is the broader
society that determines legislation and public policies that affect health care funding and medical practice. In
Switzerland, which has the most liberal legislation of all the Western countries regarding assisted suicide, public
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surveys indicate that religiosity is surprisingly high, with over 75% of citizens identifying themselves as religious,
for example
Depression appears to be prevalent in the terminally ill population, but a connection of depression to requests for
PAS and EU has not been clearly established despite many studies attempting to do so. In addition, studies of
decision-making capacity of terminally ill patients have generally failed to demonstrate that the presence of
depression in this population adversely affects competence in a significant way.
Income and education are known to affect individual attitudes towards PAS and EU, but very little is known about
cross-cultural, gender, and ethnicity factors that favor social acceptance of PAS and EU among Western populations
and physicians. Recent studies suggest they play a significant role. In addition, nationality and legislative
acceptance of PAS and EU may not merely reflect the public view, but may actually enhance or deter individual
acceptance of these interventions as end-of-life choices.
Ethical concerns regarding PAS and EU often focus on the risks to vulnerable populations: will elderly, less
educated, economically disadvantaged, or minority groups be disproportionately encouraged to seek PAS or EU?
PAS is now legal in three of the United States, and in some European countries (Belgium, the Netherlands,
Lichtenstein). More than ten years of experience in Oregon appears to show that patients who seek PAS and EU in
general are more likely to be white, and of higher socio-economic and educational background than those who do
not. This may, of course, be a reflection of which populations have the broadest access to health care in general.
Will physicians use legalized power to be involved in PAS and/or EU to victimize the vulnerable? Surveys have
shown that physician participation in PAS and EU is surprisingly common throughout the world, including the
United States, even when such activities are illegal: 36% of Australian surgeons report giving drugs to hasten death,
3.7% of U.S. oncologists admit to performing EU, and 10.8% to PAS prior to its legalization, 38% of German
physicians admit to performing EU at some time, and 7.4% of surveyed UK physicians reported giving drugs with
the intention of hastening death. In none of these countries was either PAS or EU legal at the time of the surveys. A
2005 NEJM study reported that 0.4% of cases involved ending a life without explicit request, a number that was cut
in half by legalization and regulation. If anything, some authors suggest that legalization of PAS and EU may
provide an opportunity for oversight that reduces abuses, rather than encourages them.
Terminal Sedation
A number of authors have suggested that PAS and EU have become unnecessary solutions to the problem of
untreatable suffering, at least in the terminally ill, because physicians have the capacity to essentially render a
patient unconscious, or “terminal sedation.” Both the ethics of terminal sedation and the details of the procedure
itself (generally using such medications as barbiturates, propofol, and/or benzodiazepines) have been the subject of
increasing interest in the palliative medicine literature. In surveys of physician groups in which the acceptance of
EU is quite low (approximately 9%), acceptance of the procedure of terminal sedation is very high (≥ 94%),
reflecting a general belief that it is morally different than ‘killing.’ Yet at least some ethicists do not agree that a
substantial moral difference between the two exists, arguing that premeditated and permanent obliteration of
“personhood,” even with a patient’s consent, is not significantly different than permanent premeditated obliteration
of personhood by causing biological death—certainly the presence of a beating heart no longer serves as a reliable
marker of continued life, if we are to accept brain death as a legal, moral and medical marker of death under other
circumstances.
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Summary
An increasingly challenging ethical landscape faces physicians involved in end-of-life care, as well as patients,
legislators, and the general public. Most anesthesiologists encounter end-of-life ethics and decision-making at some
point in their careers: whether as participation in organ transplantation, palliative care specialists, intensivists—or as
patients or their family members. Greater knowledge and understanding of the ethical and legal aspects of end-of-
life care is important for anyone in clinical medical practice, and for anesthesiologists in particular, as we are
increasingly likely to be asked to provide education to our patients and families, or to participate in some activity
that ethically challenges the boundaries of life, death, and the concepts of killing and letting die.
DISCLOSURE
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The Art and Science of Disclosing Adverse Events to Patients:

An Anesthesiologist’s Perspective
Allen N. Gustin, Jr., M.D., F.C.C.P. Chicago, Illinois
Introduction of Disclosure Concepts: Disclosure is defined as the act of making secret information known. This
concept has gained enormous attention in healthcare over the years. Since the 1999 landmark Institute of Medicine
report “To Err is Human,” evolving healthcare innovations have intended to reduce harmful patient events through
education and systems improvement.1 In 2001, the Joint Commission instituted Standard 2.90 R.I. (Rights of the
Individual), requiring the disclosure of all “unanticipated outcomes” to patients.2 Following this requirement, eight
states now mandate the disclosure of unanticipated outcomes and more than thirty states encourage disclosure by
providing legal protection for portions of what is disclosed to patients. Further encouragement for disclosure
continues with the 2009 update for the National Quality Forum,3 the Full Disclosure Working group of the Harvard
Hospitals (2006),4 and the Institute for Healthcare Improvement (2010).5 All of these groups recognize that
disclosure conversations are difficult to perform. Disclosure conversations with patients have been deemed an
uncomfortable experience by physicians and many physicians are unable to carry out disclosure discussions
effectively.6 Emphasizing this issue, ongoing research efforts have shown that marked differences exist in how
patients and physicians perceive the effectiveness of disclosure communications. One study by Chan found that
patients rated the quality of the disclosure poor in forty percent of cases while the majority of the associated
physicians rated the same disclosure experience as very positive.7 Previous research indicates that when healthcare
workers do disclosure adverse events to patients, critical portions of the unanticipated outcome (why the adverse
event happened and what is being done to prevent it from occurring again) are not disclosed. All physicians (from
surgeons to anesthesiologists) should be skilled when participating in disclosure conversations with patients.
Definitions: The phrase “unanticipated outcome” is a term that Joint Commission uses to refer to outcomes of care
that are different from what healthcare workers and patients expect.8 Unanticipated outcomes are essentially
synonymous with adverse events. An adverse event is best defined as an injury that is caused by medical
management that results in measurable disability. It is important to recognize that the occurrence of an
unanticipated outcome or an adverse event does not necessarily mean that there was a breakdown in the process of
delivering healthcare. Research suggests that the vast majorities of unanticipated outcomes are not due to errors,
thus are not preventable. A medical error is defined as an inaccurate or incomplete diagnosis and/or treatment of a
disease. A medical error (as opposed to an unanticipated outcome or adverse event) is viewed, as a breakdown in
the process of delivering healthcare and that someone should be held accountable. The near miss is an unplanned
event that does not result in injury, illness, or damage; but has the potential to do so. Near misses are usually not
disclosed but should alert healthcare environments to potential system issues that may lead to adverse events later.
Ethicists have debated this issue significantly. At the moment, some ethicists have feared that disclosure of the near
miss might render more psychological suffering to the patient. However, other institutions are disclosing all near
misses to the patients.
Barriers to Disclosure: Physicians fear that disclosure will lead to litigation. Imbalances continue to exist between
the push for full transparency in healthcare and the risk management approach to minimizing liability. Ethicists and
many professional organizations agree that unanticipated outcomes associated with healthcare should be disclosed to
patients. Multiple studies confirm that unanticipated outcomes are common and that disclosure of these events to
patients is frequently inadequate. While historically, the disclosure literature has focused primarily on the potential
impact of disclosure on litigation, recent standards such as the National Quality Forum Safe Practice on Disclosure
and the Harvard Working Group’s White Paper on disclosure emphasizes that effective disclosure is a fundamental
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component of patient-centered care.3,4,9 The risk management aspects of disclosure are now viewed only as
secondary considerations. The other issues associated with not wanting to do disclosure: physicians fear of
litigation, loss of reputation, feelings of shame and embarrassment, insufficient tools and training, and a perceived
lack of support form the systems in which physicians practice.10
Facilitators to Disclosure: Patients report that full disclosure of an unanticipated outcome, especially those due to
a medical error, increases their satisfaction with care, reinforces trust in their physician, and results in more positive
emotional response to the event.11 Many of the studies have surveyed patients and found that patients desire a
consistent set of information after an unanticipated outcome that results from a medical error. This set of
information includes the following: an explicit statement that an error occurred, what the error was, why the error
happened, how any recurrence of that error will be prevented, and an apology for the unanticipated outcome.11 This
set of information represents what is considered a “disclosure conversation.” For patient autonomy to be respected,
disclosure must be performed. Disclosure supports the right of patient decision making.12,13
Failed Disclosures: Failed disclosures can have a wide range of consequences. Failed disclosures can impair
patient’s decision-making capacity, reduce a patient’s trust in healthcare, and decrease patient’s satisfaction with any
healthcare received.
Patients Needs: Patients surveyed from a general sample say that when things go wrong with health care, they need
disclosure, an apology, information about what happened, and how it can be prevented from happening again to
another patient.14 These findings suggest that for errors resulting in harm, breakdown in access to and the
relationships with the clinician may be more troubling to a patient than any technical error in diagnosis and
treatment. Those studies that considered patient perspectives either pre- or post-injury included reviews of patient
complaints, hospital records, plaintiff’s depositions, criminal prosecutions, malpractice claims, and general patient
surveys or interviews with or without the use of scenarios. The degree of emotional stress and emotional trauma
seemed to vary according to the characteristics of the communication between provider and patient. Patients who
felt good about the communication (respect, active listening, caring, etc.) with their provider experienced less
emotional trauma.14 Literature exists concerning the importance of an apology. Some participants mentioned that
apologies did not routinely happen, but an apology remained important to their resolution process. The nature of the
communication appeared to predict whether the patient continued a relationship with the provider after an event.
That patient who experienced a good communication process with their provider also perceived a “no fault” event
and was more likely to call these events “mistakes” or “complications.” Few studies (if any) have focused
specifically on participant perspectives after the injury. Disclosure and apology, if done well, should not increase
potential liability. On the other hand, disclosure and apology done in an insensitive manner, or not at all, may
ultimately result in deterioration or destruction of trust between the patient and the clinician.
The Apology Law: Fear of lawsuits by healthcare providers is a major factor, which can act as a barrier to
disclosure. Two national surveys designed to assess attitudes toward disclosure revealed that fear of litigation was
the primary reason for both physician and hospital reluctance to disclose errors and unanticipated outcomes.2,15
Lawyers and insurance companies have long warned against apologizing in order to avoid litigation, even though
many states now prohibit a doctor’s expressions of remorse, fault, or causality from being used in court as evidence
of their guilt. This body of legislation, referred to as “I’m sorry” or apology laws, encourages full disclosure of
mistakes or errors in judgment by eliminating the physician’s and the hospital’s fear that any apology admission will
be used against them in a court of law. “I’m sorry” laws are a marked change from existing American law: under the
Federal Rules of Evidence and analogous state provisions, apologies are ordinarily admissible in civil court to prove
liability (Federal Rules of Evidence 801(d)). Some of the states that have apology laws include the following:
Colorado Revised Statute 13-25-135 (2003), Oregon Rev. Stat. 677.082 (2003), Massachusetts ALM GL ch.233,
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23D (1986), Texas Civil Prac and Rem Code 18.061(1999), California Evidence Code 1160 (2000), Florida Stat
90.4026 (2001), Washington Rev Code Wash 5.66.010 (2002), Tennessee Evid Rule 409.1(2003), Ohio ORC Ann
2317.43 (2004), Georgia Title 24 Code GA Annotated 24-3-37.1 (2005), Wyoming Wyo. Stat. Ann. 1-1-130,
Oklahoma 63 OKL. St. 1-1708.1H (2004), Maryland MD Court & Judicial Proceedings Code Ann. 10-920 (2004),
North Carolina General Stat. 8C-1, Rule 413, Hawaii HRS Sec.626-1 (2006), Maine MRSA tit. 2908 (2005), South
Dakota Codified Laws 19-12-14 (2005), West Virginia 55-7-11a (2005), Illinois Public Act 094-0677 Sec. 8-1901,
735 ILL. Comp. Stat. 5/8-1901 (2005), Arizona A.R.S. 12-2605 (2005), Louisiana R.S. 13:3715.5 (2005), Missouri
Mo. Ann. Stat. 538.229 (2005), New Hampshire RSA 507-E:4 (2005), Connecticut Public Act No. 05-275
Sec.9(2005) amended (2006) Conn. Gen. Stat. Ann. 52-184d, Virginia Code of Virginia 8.01-52.1 (2005), Vermont
S 198 Sec. 1. 12 V.S.A. 1912 (2006), Montana Code Ann.26-1-814 (Mont. 2005), South Carolina Ch.1, Title19
Code of Laws 1976, 19-1-190 (2006), Delaware Del. Code Ann. Tit. 10, 4318 (2006), Indiana Ind. Code Ann. 34-
43.5-1-1 to 34-43.5-1-5, Idaho Title 9 Evidence Code Chapter 2 .9-207, Iowa HF 2716 (2006), Nebraska Neb. Laws
L.B. 373 (2007), Utah Code Ann. 78-14-18 (2006), North Dakota ND H.B. 1333 (2007), and Michigan HB 6057
(2009).
Not Only What You Say, But Also How You Say It! Most doctors are uncomfortable even explaining the
circumstances surrounding avoidable complications. For clinicians overwhelmed by self-recrimination, discussing
any adverse event or medical error can be hard. Openness, humility, and conceding medicine’s imperfections are
considered “new concepts in health care.” Studies point to poor patient provider communication, inadequate
delivery of information, and negative interactions with the provider as leading causes of increased litigation. It is
best to maintain the physician/patient relationship, encourage open and honest communication including disclosure
of unexpected medical outcomes, encourage expressions of concern including an apology when appropriate, and
attempt to support the patient’s emotion during this stressful time. Face-to-face discussions, communicating openly
and honestly, and active listening to the patient and patient’s family are further examples of skills that need to be
developed by clinicians for effective communication during disclosure conversations.16 Clinicians are also
encouraged to express concern, empathy, or other appropriate emotions without defensiveness. A clinician may find
that keeping his or her feelings in check and attempting to understand the patient’s perspective is very valuable
during a disclosure conversations. The guidelines go on to state that a physician’s concern about legal liability that
might result from full disclosure should not affect a physician’s decision to deal candidly with a patient.
“The Pioneers.” Have Those Organizations Who Routinely Disclosure Adverse Events Experienced More
Litigation? The answer is NO! Having realized the benefits of apologizing, several hospital systems throughout
the country (in conjunction with their attorneys and insurance carriers) have implemented full disclosure policies. A
disclosure policy is a procedure that is carried out when an unanticipated outcome occurs. These organizations have
trained their staff and their health care professionals in how to apologize and even engage in settlement offers. Since
the University of Michigan Health System adopted its program in 2002, the number of medical malpractice claims
has dropped each year, their attorney fees have declined significantly, and the university has reduced its claims-
processing period by more than 50 percent.17 The VA Medical Center in Kentucky mandated that all adverse events
be disclosed to their Veterans. Much speculation was suggested that lawsuits would rise in number when in
actuality, no increase in awards or numbers of suits has occurred.18 McDonald at the University of Illinois at
Chicago has found that when disclosure of unanticipated outcomes does occur routinely, then patients are less likely
to sue and actually are far more forgiving toward the healthcare provider/facility.19
Lessons Learned from Healthcare Systems with Active Disclosure Practices. Adopted from the Lecture
“Disclosing Medical Errors: Best Practices from the Leading Edge”20 Virginia Mason Medical Center
(VMMC), Seattle, Washington, adopted the Toyota Lean model as the basis for its healthcare center operations. The
Toyota Lean focuses on transparency and visibility. VMMC turned the medical centers into a system where:
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everyone is considered a safety inspector, anyone can report a safety concern (and the process stops immediately),
and the system is continuously mistake proofing. When VMMC introduced the Toyota Lean Model, the medical
center averaged thee patient safety alerts a month and now they average well over 300 reports a month. Lessons
learned include the following: the VMMC staff sees that the nature and number of errors that occur and the staff
knows what to expect when an adverse event occurs. VMMC shared stories in order to overcome fear by being
transparent. VMMC felt that too many physicians and other VMMC staff ware faltering and had too many excuses.
Now, the medical center feels that they have buy in from the entire clinical staff of the medical center. University of
Illinois at Chicago Medical Center (UIC), Chicago, Illinois, developed a process where an investigation beings after
an unanticipated outcome in order to determine whether a further investigation is warranted. If the error and the
case meet criteria for an apology with full disclosure, then the apology is delivered. If a remedy is offered, a liaison
is created between the patient, the family, and the claims department. If the claim is large, then the organization
must decide how to the claim will travel through he administrative approval process. The UIC outcomes: family
who experienced an error at UIC continued to seek care in that facility, patient safety has overall improved, and the
time it takes for clinicians to receive critical test results has been reduced. Overall, the lessons learned at UIC:
persuade your lawyers that disclosure is the right thing to do ethically, legally, and financially. UIC recognizes that
shifting the culture of an organization is not easy and it can take time. University of Michigan Health System
(UMHS), Ann Arbor, Michigan, developed a system based on the following guiding principles: compensate patients
and families when UM has made an error, fight to defend themselves when their care was reasonable, and
systematically use mistakes as tools for learning along with making any needed changes to their system.17 Michigan
Compiled Law 600.2912 stipulates that before a claim can be filed against any health practitioner or facility in
Michigan, the patient is required to present details of their claim in writing. This allows UMHS time to review the
claims within three months or less. Then, UMHS’s Medical Liability Review Committee reaches conclusions about
the reasonableness of the care delivered and its impact on the patient’s outcome. UMHS is able to handle many of
these claims long before the claim might enter into the legal system. UMHS’s lessons learned: hospital leaders
won’t easily embrace this unquestioningly, start with small successes and publicize them widely in order to gain the
confidence of the leadership, have courage and appreciate the significance of what you are asking people to do, be
willing to hold the line both ways, and sometimes you need to tell patients that they won’t be compensated because
the care was reasonable. Kaiser Permanente Healthcare System developed a six-step statement principle to guide
physicians in communicating with patients and their families after an adverse outcome or medical error. Step 1:
Always care for the patient. Step 2: Communicate about the unanticipated adverse outcome. Step 3. Report to
appropriate parties. Step 4. Check the medical record. Step 5. Follow-up and provide closure. Step 6. Support the
patient care team (physicians, nurses, pharmacists, etc.). Kaiser created the healthcare ombudsman/mediator. This
is a person that is specially trained in disclosure and is an internal/neutral/confidential line of communication
between the family/patient and the healthcare system. Kaiser’s lessons learned: treat staff as respectfully as you
would treat your patients, engage your leaders in the process, and teach others who may have been involved in the
medical errors to respond as part of the team. Geisinger Health System, a Pennsylvania healthcare system, covers
patient care in 41 counties. In 2002, the Pennsylvania state passed the Medical Care Availability and Reduction of
Error Act. This law requires that a patient who sustained injury as a result of medical negligence by a healthcare
provider must be afforded a prompt investigation and fair compensation. Every effort must be made to reduce the
errors by identifying the problem and implementing solutions that promote patient safety. Geisinger Health System
developed a process that should make such disclosures routine throughout the health system. Since they
implemented their process, they have experienced an increase in the reporting of serious events and an increase in
number of disclosure conversations between physicians and patients. They have had fewer claims filed than the
national average. They recommend adopting a patient centered practice rather than a legalistic philosophy toward
disclosure. COPIC Insurance Company, a Colorado-based physician-led malpractice carrier, has openly
communicated medical errors to patients since October 2000. The company felt that the tort system destroys the
relationship between physicians and patients. The COPIC system developed the no fault “3R’s” program with
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stands for the following: Recognize an unanticipated event, Respond soon after the event occurs, and Resolve any
related issues. The 3R’s program was partially successful given that Colorado has a very strong apology law.
Overall, the lessons learned are the following: nurturing good relationships with patients is essential, develop strong
relationships with senior management, and have faith in a patient’s ability to forgive their physicians.
There are many other medical facilities/healthcare systems that have had increasing success. This list is not meant
to be all-inclusive, but rather offer a sample of those healthcare systems that have experienced significant success.
References:
1. Kohn LT, Corrigan J, Donaldson MS. To err is human: building a safe health care system. Washington,
DC; National Academy Press. 2000.
2. Lamb RM, Studdert DM, Bohmer RM, Berwick DM, Brennan TA. Hospital disclosure practices: results
of a national survey. Health Affairs 2003 (22): 73-83.
3. National Quality Forum. Safe Practices for Better Healthcare- 2009 Update: A Consensus Report.
Washington, DC: National Quality Forum, 2009.
4. The Full Disclosure Working group. When Things Go Wrong: Responding to Adverse Events. A
Consensus Statement of the Harvard Hospitals. Boston, MA: Massachusetts Coalition for the Prevention of
Medical Errors, 2006
5. Conway J, Federico F, Stewart K, Campbell M. Respectful management of serious clinical adverse events
IHI Innovation series white paper. Cambridge, MA: Institute for Healthcare Improvement, 2010
6. Gallagher T, Studdert D, Levinson W. Disclosing Harmful medical Errors to Patients. New England
Journal of medicine 2007; 356 (2): 2713-19.
7. Chan DK, Gallagher TH, Reznick R, Levinson W. How surgeons disclose medical errors to patients: A
study using standardized patients. Surgery. 2005; 138(5): 851-858.
8. Trombly ST. Dealing with adverse Events, Anesthesia Patient Safety Foundation, Accessed on May 3,
2012: http://www.apsf.org/resource_center/newsletter/2006spring/01adverse_event.htm
9. The Patient Safety Handbook by Barbara J Youngberg, Martin J. Hatlie Published by Jones and Bartlett
Publishers, 2003, page 552.
10. White A, Waterman A, McCotter P, Boyle D, Gallagher T. Supporting healthcare workers after medical
errors: considerations for health care leaders. J Clin Outcomes Manag 2008;15:240 –7
11. Gallagher TH, Denham DR, Leape LL, Disclosing unanticipated outcomes to patients: the art and practice,
J Patient Safety 2007 3(3): 158-65.
12. Lo B. Resolving Ethical Dilemmas: A Guide for Clinicians. 3rd ed. Philadelphia, PA: Lippincott Williams
& Wilkins, 2005
13. Wu AW, Cavanaugh TA, McPhee SJ, Lo B, Micco GP. To tell the truth: ethical and practical issues in
disclosing medical mistakes to patients. J Gen Intern Med 1997;12:770–5
14. Dulcos C, Eichelr M, Taylor L, Quintela J, Main D, Pace W, Staton E. Patient perspectives of patient
provider communication after adverse events. International Journal for quality in Healthcare Care. 2005:
17(6); 479-486.
15. Gallagher TH, Waterman AD, Ebers AG, Fraser VJ, Levinson W. Patients' and physicians' attitudes
regarding the disclosure of medical errors. JAMA. 2003;289:1001-1007.
16. Mazor KM, Simon SR, Gurwitz JH. Communicating with patients about medical errors. Archives of
Internal medicine, 2004 146; 1690-1697.
17. Kachalia A, Kaufman SR, Boothman R, Anderson S, Welch K, Saint S, Rogers MA. Liability claims and
costs before and after implementation of a medical error disclosure program. Ann Intern Med
2010;153:213–21
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18. Gallagher TH, Denham C, Leape L, Amori G, Levinson W. Disclosing unanticipated outcomes to patients:
the art and the practice. J of patient safety. 2007; 3(3): 158-165.
19. Helmchen LA, Richards MR, McDonald TB. How does routine disclosure of medical error affect patients’
propensity to sue and their assessment of provider quality? Evidence from survey data. Med Care, 2010
Nov; 48 (11): 955-961.
20. Shapiro E. Disclosing Medical Errors: Best Practices from the “Leading Edge.” Cambridge, MA: Institute
for Healthcare Improvement, March 2008. http://www.ihi.org/IHI
DISCLOSURE
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Chronic Persistent Pain after Surgery:

Mechanisms and Management Strategies
Timothy J. Brennan, M.D., Ph.D. Iowa City, Iowa
Persistent pain after surgery is more common than previously noted. In this lecture the pathophysiology and
preventative strategies for chronic persistent pain after surgery will be reviewed. The unique pathophysiology and
treatments for amputation pain, post-thoracotomy pain syndromes and persistent pain after joint replacement are
discussed.
Amputation
The greatest incidence of chronic pain may occur after limb amputation. Recent studies report incidences
of 60-80%.1,2 Both chronic stump and phantom limb pain after amputation are challenging clinical problems.
Improving postoperative analgesia attempts to prevent chronic postoperative pain by minimizing pain before and
after surgery. Treatments included local anesthetics, opioids, and others.
The beneficial effect of combined epidural drug combinations in reducing the risk of phantom limb pain
was only demonstrated in one series. Local anesthetic infusions are effective in treating acute perioperative pain
from limb amputation.1,2 However, there is no robust evidence supporting the use of pre-emptive analgesia to
decrease chronic pain after amputation for peripheral vascular disease. Some studies suggest that improved
treatment of acute pain does not affect the development of chronic pain.3 Treatment with gabapentin early after
surgery failed to prevent phantom or stump pain after amputation.4
Thoracotomy
Acute pain has not been consistently evaluated as an associated faction in relation to postthoracotomy pain
syndrome. Acute postoperative pain was related to postthoracotomy pain syndrome in some studies whereas other
investigations could not find this positive factor. Possibly the extent and duration of surgery may influence acute
pain and in turn the extent and duration of surgery may associate with the development of persistent pain. 3,5
Surgical approach and risk of nerve injury are factors associated with persistent pain after thoracotomy.6
There are controversies regarding the prevention of postthoracotomy pain syndrome. Several studies hinted
a preventative effect could be achieved with preincision epidural analgesia;7,8 however, the largest study failed to
find a positive effect.9
Persistent pain after total joint replacement

Chronic pain after joint surgery occurs in as high as ten percent of patients undergoing total knee
arthroplasty or hip replacement.10-12 A variety of factors have been implicated in persistent pain after total joint
replacement. Factors include female gender, younger age, and greater preoperative pain, predicted greater risk of
moderate to severe persistent pain postoperatively. However, the current literature is contradictory regarding all of
these factors and their influence on chronic pain after surgery.11
Risk of nerve injury is rare in chronic pain after joint replacement surgery. However, CRPS-like pain
following total knee arthroplasty has been studied.13 For example, CRPS criteria were met in approximately ten
percent postoperative total knee arthroplasty patients. Greater preoperative pain intensity predicted CRPS at three
and six months following total knee arthroplasty. Preoperative distress also predicted signs of CRPS following total
knee arthroplasty.
One study implicated acute postoperative pain based on a survey that acute postoperative pain, as the
patient recalled, predicted persistent pain complaints 12 to 18 months follow-up.14 While other studies indicated
presurgical pain severity and psychological factors, including pain catastrophizing predicted postsurgical pain at six
weeks follow-up.15-23 Other psychological variables are also a significant co-factor in pain after total knee
replacement.12
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Two recent studies have prospectively evaluated in randomized controlled trials, treatment of acute pain
and the prevalence of persistent pain after joint replacement surgery.24 Patients were randomized to ketamine or
placebo during and after surgery for total hip replacement. Ketamine (0.5 mg/kg and 2 mcg/kg/min) reduced opioid
consumption by a modest amount and also decreased a prevalence of patients with persistent pain at rest in the
operated hip at six months. Twenty-one percent of placebo patients experienced pain at rest versus only eight
percent in the ketamine group at 6 months.
A recent study examined the effect of perioperative treatment with pregabalin to decrease the incidence of
postsurgical neuropathic pain.25 Patients undergoing total knee arthroplasty were randomized to receive pregabalin
before and for two weeks after total knee arthroplasty. Patients were followed for neuropathic signs and symptoms.
More than 100 patients were randomized per group and pregabalin reduced the incidence of neuropathic pain, which
was zero in the pregabalin treated group and five percent at six months in the placebo treated group. An opioid-
sparing effect of pregabalin was noted. The authors concluded that perioperative pregabalin decreased the
prevalence of chronic neuropathic pain after total knee arthroplasty.
A third study examined the effect of gabapentin in reducing postoperative pain, opioid consumption, and
persistent pain after total hip replacement surgery.26 A single dose of gabapentin administered either before surgery
or in the immediate postoperative period did not influence acute pain or opioid consumption. Six months after
surgery, the incidence and severity of chronic pain did not differ significantly among groups, demonstrating that a
single dose of gabapentin did not have any beneficial effects in patients undergoing total hip replacement.
Summary
Prevalence rates for chronic pain after surgery vary with procedure and in some cases can be as high as
80%.5,27-29 Importantly, psychological variables may also affect chronic pain after surgery.5,28 Psychological
variables like neuroticism have been suggested to contribute to chronic pain. In addition, fear of long-term
consequences was associated with greater long-term pain six months after major surgery.28 Recent studies noted
attentional bias toward positive stimuli as a risk factor associated with persistent pain after repair of chest wall
deformity as well as pain catastrophizing.30
Conclusion
There have been many links to preoperative pain and persistent postoperative pain in a variety of surgeries.
In joint replacement surgeries, it is arguable whether preoperative pain is a risk factor for predicting postoperative
pain. Psychological variables are also important. Furthermore, the type of pain the patient experiences requires
evaluation of the joint replacement stability and other factors like infection or pain at other sites.
In general, for patients undergoing surgery, preoperative nociceptive testing can predict acute pain and
opioid consumption in the early postoperative period.31 The link to preoperative pain testing and chronic
postoperative pain has not been made. The idea that acute pain after surgery predicts chronic pain has not been
made for joint replacement surgery, nor has improved treatment of acute pain and reduction in the prevalence of
chronic pain after surgery has not been made.
Finally, any study attempting to reduce the incidence of persistent pain must take into account preoperative
psychological variables and extensive preoperative testing. Rigorous follow-up in the acute postoperative period
and follow-up long-term for at least six months must include evaluation of other factors, like age, sex, pain in other
areas of the body, stability of the prosthetic joint and rule out infection. Perhaps stratification into the type of
persistent pain may advance the field.
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References:
1. Nikolajsen L, Ilkjaer S, Christensen JH, Kroner K, Jensen TS: Randomised trial of epidural bupivacaine and
morphine in prevention of stump and phantom pain in lower-limb amputation. Lancet 1997; 350: 1353-7
2. Nikolajsen L, Jensen TS: Phantom limb pain. Br J Anaesth 2001; 87: 107-16
3. Ypsilantis E, Tang TY: Pre-emptive Analgesia for Chronic Limb Pain After Amputation for Peripheral Vascular
Disease: A Systematic Review. Ann Vasc Surg
4. Nikolajsen L, Finnerup NB, Kramp S, Vimtrup AS, Keller J, Jensen TS: A randomized study of the effects of
gabapentin on postamputation pain. Anesthesiology 2006; 105: 1008-15
5. Perkins FM, Kehlet H: Chronic pain as an outcome of surgery. A review of predictive factors. Anesthesiology
2000; 93: 1123-33
6. Wildgaard K, Ravn J, Kehlet H: Chronic post-thoracotomy pain: a critical review of pathogenic mechanisms and
strategies for prevention. European journal of cardio-thoracic surgery : official journal of the European Association
for Cardio-thoracic Surgery 2009; 36: 170-80
7. Senturk M, Ozcan PE, Talu GK, Kiyan E, Camci E, Ozyalcin S, Dilege S, Pembeci K: The effects of three
different analgesia techniques on long-term postthoracotomy pain. Anesthesia and analgesia 2002; 94: 11-5, table of
contents
8. Obata H, Saito S, Fujita N, Fuse Y, Ishizaki K, Goto F: Epidural block with mepivacaine before surgery reduces
long-term post-thoracotomy pain. Canadian journal of anaesthesia = Journal canadien d'anesthesie 1999; 46: 1127-
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9. Ochroch EA, Gottschalk A, Augostides J, Carson KA, Kent L, Malayaman N, Kaiser LR, Aukburg SJ: Long-
term pain and activity during recovery from major thoracotomy using thoracic epidural analgesia. Anesthesiology
2002; 97: 1234-44
10. Roth ML, Tripp DA, Harrison MH, Sullivan M, Carson P: Demographic and psychosocial predictors of acute
perioperative pain for total knee arthroplasty. Pain Res Manag 2007; 12: 185-94
11. Singh JA, Gabriel S, Lewallen D: The impact of gender, age, and preoperative pain severity on pain after TKA.
Clin Orthop Relat Res 2008; 466: 2717-23
12. Sullivan M, Tanzer M, Stanish W, Fallaha M, Keefe FJ, Simmonds M, Dunbar M: Psychological determinants
of problematic outcomes following Total Knee Arthroplasty. Pain 2009; 143: 123-9
13. Harden RN, Bruehl S, Stanos S, Brander V, Chung OY, Saltz S, Adams A, Stulberg SD: Prospective
examination of pain-related and psychological predictors of CRPS-like phenomena following total knee
arthroplasty: a preliminary study. Pain 2003; 106: 393-400
14. Nikolajsen L, Brandsborg B, Lucht U, Jensen TS, Kehlet H: Chronic pain following total hip arthroplasty: a
nationwide questionnaire study. Acta Anaesthesiol Scand 2006; 50: 495-500
15. Baker PN, van der Meulen JH, Lewsey J, Gregg PJ: The role of pain and function in determining patient
satisfaction after total knee replacement. Data from the National Joint Registry for England and Wales. J Bone Joint
Surg Br 2007; 89: 893-900
16. Brander V, Gondek S, Martin E, Stulberg SD: Pain and depression influence outcome 5 years after knee
replacement surgery. Clin Orthop Relat Res 2007; 464: 21-6
17. Brander VA, Stulberg SD, Adams AD, Harden RN, Bruehl S, Stanos SP, Houle T: Predicting total knee
replacement pain: a prospective, observational study. Clin Orthop Relat Res 2003: 27-36
18. Elson DW, Brenkel IJ: Predicting pain after total knee arthroplasty. J Arthroplasty 2006; 21: 1047-53
19. Fisher DA, Dierckman B, Watts MR, Davis K: Looks good but feels bad: factors that contribute to poor results
after total knee arthroplasty. J Arthroplasty 2007; 22: 39-42
20. Forsythe ME, Dunbar MJ, Hennigar AW, Sullivan MJ, Gross M: Prospective relation between catastrophizing
and residual pain following knee arthroplasty: two-year follow-up. Pain Res Manag 2008; 13: 335-41
21. Fortin PR, Clarke AE, Joseph L, Liang MH, Tanzer M, Ferland D, Phillips C, Partridge AJ, Belisle P, Fossel
AH, Mahomed N, Sledge CB, Katz JN: Outcomes of total hip and knee replacement: preoperative functional status
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22. Jones CA, Beaupre LA, Johnston DW, Suarez-Almazor ME: Total joint arthroplasties: current concepts of
patient outcomes after surgery. Rheum Dis Clin North Am 2007; 33: 71-86
23. Jones CA, Voaklander DC, Johnston DW, Suarez-Almazor ME: The effect of age on pain, function, and quality
of life after total hip and knee arthroplasty. Arch Intern Med 2001; 161: 454-60
24. Remerand F, Le Tendre C, Baud A, Couvret C, Pourrat X, Favard L, Laffon M, Fusciardi J: The early and
delayed analgesic effects of ketamine after total hip arthroplasty: a prospective, randomized, controlled, double-
blind study. Anesth Analg 2009; 109: 1963-71
25. Buvanendran A, Kroin JS, Della Valle CJ, Kari M, Moric M, Tuman KJ: Perioperative oral pregabalin reduces
chronic pain after total knee arthroplasty: a prospective, randomized, controlled trial. Anesth Analg 2009; 110: 199-
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26. Clarke H, Pereira S, Kennedy D, Andrion J, Mitsakakis N, Gollish J, Katz J, Kay J: Adding gabapentin to a
multimodal regimen does not reduce acute pain, opioid consumption or chronic pain after total hip arthroplasty.
Acta Anaesthesiol Scand 2009; 53: 1073-83
27. Kehlet H, Jensen TS, Woolf CJ: Persistent postsurgical pain: risk factors and prevention. Lancet 2006; 367:
1618-25
28. Peters ML, Sommer M, de Rijke JM, Kessels F, Heineman E, Patijn J, Marcus MA, Vlaeyen JW, van Kleef M:
Somatic and psychologic predictors of long-term unfavorable outcome after surgical intervention. Ann Surg 2007;
245: 487-94
29. Aggarwal VR, Macfarlane GJ, McBeth J: A high tender point count is associated with the presence of multiple
idiopathic pain disorders: Results from a population study. European journal of pain 2012
30. Lautenbacher S, Huber C, Schofer D, Kunz M, Parthum A, Weber PG, Roman C, Griessinger N, Sittl R:
Attentional and emotional mechanisms related to pain as predictors of chronic postoperative pain: a comparison with
other psychological and physiological predictors. Pain 2010; 151: 722-31
31. Granot M: Can we predict persistent postoperative pain by testing preoperative experimental pain? Curr Opin
Anaesthesiol 2009; 22: 425-30
DISCLOSURE
Cubist, Self, Funded Research, Honoraria ; Pfizer, Self, Honoraria ; Array Pharma, Self, Funded Research ;
Ironwood, Self, Funded Research ; Galleon PHarma, Self, Funded Research, Consulting Fees ; Endo, Self,
Honoraria
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Pain: Mechanism and Activity at the Spinal Cord
James C. Eisenach, M.D. Winston-Salem, North Carolina
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Head, Neck, and Face Pain

Samer N Narouze, M.D., Ph.D. Akron, Ohio
More than 3 million Americans went to hospital emergency rooms seeking relief from headaches and there were
81,000 hospitals admissions, according to the latest Numbers from the Agency for Healthcare Research and
Quality. One-third of the emergency visits and two thirds of the hospital stays were for migraine headaches. 1
The incidence and prevalence of headache in the general population is staggering and emphasis should be placed on
correct diagnosis and treatment rather than on symptomatic management. Will review here the most common
headache disorders encountered in the pain clinic. Each disorder will be described by the International Classification
of Headache Disorders, 2nd edition (ICHD-2) classification and diagnostic criteria.
The ICHD-2 criteria provide a systematic classification for headache and orofacial pain and are divided into three
parts: the primary headaches, the secondary headaches, and cranial neuralgias central and primary facial pain (Table
1). 2
Table 1: ICHD-2 Classification Headings.

Part I: The Primary Headaches
1. Migraine
2. Tension-type headache
3. Cluster headache and other trigeminal autonomic cephalalgias
4. Other primary headaches
Part II: The Secondary Headaches
5. Headache attributed to head and/or neck trauma
6. Headache attributed to cranial or cervical vascular disorder
7. Headache attributed to non-vascular intracranial disorder
8. Headache attributed to a substance or its withdrawal
9. Headache attributed to infection
10. Headache attributed to disorder of homoeostasis
11. Headache or facial pain attributed to disorder of cranium, neck, eyes, ears, nose, sinuses, teeth,
mouth or other facial or cranial structures
12. Headache attributed to psychiatric disorder
Part III: Cranial Neuralgias, Central and Primary Facial Pain and Other Headaches
13. Cranial neuralgias and central causes of facial pain
14. Other headache, cranial neuralgia, central or primary facial pain
PRIMARY HEADACHES:
1. Migraine
1.1 Migraine without aura
A. At least 5 attacks fulfilling criteria B–D
B. Headache attacks lasting 4-72 hours (untreated or unsuccessfully treated)
C. Headache has at least 2 of the following characteristics:
1. unilateral location
2. pulsating quality
3. moderate or severe pain intensity
4. aggravation by or causing avoidance of routine physical activity (e.g., walking or climbing stairs)
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D. During headache at least 1 of the following:

1. nausea and/or vomiting
2. photophobia and phonophobia
E. Not attributed to another disorder
1.2 Migraine with aura

A. At least 2 attacks fulfilling criterion B
B. Migraine aura fulfilling criteria B–C for one of the subforms 1.2.1-1.2.6
C. Not attributed to another disorder
1.2.1 Typical aura with migraine headache

B. Aura consisting of at least 1 of the following, but no motor weakness:
1. fully reversible visual symptoms including positive features (e.g., flickering lights, spots or lines) and/or
negative features (ie, loss of vision)
2. fully reversible sensory symptoms including positive features (e.g., pins and needles) and/or negative
features (ie, numbness)
3. fully reversible dysphasic speech disturbance
C. At least two of the following:
1. homonymous visual symptoms and/or unilateral sensory symptoms
2. at least one aura symptom develops gradually over ≥5 minutes and/or different aura symptoms occur in
succession over ≥5 minutes
3. each symptom lasts ≥5 and ≤60 minutes
D. Headache fulfilling criteria B–D for 1.1 Migraine without aura begins during the aura or follows aura within 60
minutes
1.2.3 Typical aura without headache

As 1.2.1 except:
B. Aura consisting of at least 1 of the following, with or without speech disturbance but no motor weakness:
1. fully reversible visual symptoms including positive features (eg, flickering lights, spots or lines) and/or
negative features (ie, loss of vision)
2. fully reversible sensory symptoms including positive features (ie, pins and needles) and/or negative features
(ie, numbness)
D. Headache does not occur during aura nor follow aura within 60 minutes
2. Tension-type headache (TTH)
2.1 Infrequent episodic tension-type headache

A. At least 10 episodes occurring on <1 day/month on average (<12 days/year) and fulfilling criteria B–D
B. Headache lasting from 30 minutes to 7 days
C. Headache has at least 2 of the following characteristics:
1. bilateral location
2. pressing/tightening (non-pulsating) quality
3. mild or moderate intensity
4. not aggravated by routine physical activity such as walking or climbing stairs
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D. Both of the following:

1. no nausea or vomiting (anorexia may occur)
2. no more than one of photophobia or phonophobia
2.2 Frequent episodic tension-type headache

As 2.1 except:
A. At least 10 episodes occurring on ≥1 but <15 days/month for ≥3 months (≥12 and <180 days/year) and fulfilling
criteria B–D
2.3 Chronic tension-type headache

As 2.1 except:
A. Headache occurring on ≥15 days/month on average for >3 months (≥180 days/year) and fulfilling criteria B–D
B. Headache lasts hours or may be continuous
D. Both of the following:
1. no more than one of photophobia, phonophobia or mild nausea
2. neither moderate or severe nausea nor vomiting
3. Cluster headache and other trigeminal autonomic cephalalgias
3.1Cluster headache
B. Severe or very severe unilateral orbital, supraorbital and/or temporal pain lasting 15-180 minutes if untreated
C. Headache is accompanied by at least 1 of the following:
1. ipsilateral conjunctival injection and/or lacrimation
2. ipsilateral nasal congestion and/or rhinorrhea
3. ipsilateral eyelid edema
4. ipsilateral forehead and facial sweating
5. ipsilateral miosis and/or ptosis
6. a sense of restlessness or agitation
D. Attacks have a frequency from 1 every other day to 8/day
3.1.1 Episodic cluster headache
A. Attacks fulfilling criteria A–E for 3.1 Cluster headache
B. At least two cluster periods lasting 7-365 days and separated by pain-free remission periods of ≥1 month
3.1.2 Chronic cluster headache

A. Attacks fulfilling criteria A–E for 3.1 Cluster headache
B. Attacks recur over >1 year without remission periods or with remission periods lasting <1 month
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SECONDARY HEADACHES:
5. Headache attributed to head and/or neck trauma
5.2.1 Chronic post-traumatic headache attributed to moderate or severe head injury

A. Headache, no typical characteristics known, fulfilling criteria C–D
B. Head trauma with at least 1 of the following:
1. loss of consciousness for >30 minutes
2. Glasgow Coma Scale (GCS) <13
3. post-traumatic amnesia for >48 hours
4. imaging demonstration of a traumatic brain lesion (cerebral hematoma, intracerebral/subarachnoid
hemorrhage, brain contusion, skull fracture)
C. Headache develops within 7 days after head trauma or after regaining consciousness following head trauma
D. Headache persists for >3 months after head trauma
6. Headache attributed to cranial or cervical vascular disorder
6.4.1 Headache attributed to giant cell arteritis (GCA)

A. Any new persisting headache fulfilling criteria C–D
B. At least one of the following:
1. swollen tender scalp artery with elevated erythrocyte sedimentation rate and/or C reactive protein
2. temporal artery biopsy demonstrating giant cell arteritis
C. Headache develops in close temporal relation to other symptoms and signs of giant cell arteritis
D. Headache resolves or greatly improves within 3 days of high-dose steroid treatment
7. Headache attributed to non-vascular intracranial disorder
7.1.1 Headache attributed to idiopathic intracranial hypertension (IIH)

A. Progressive headache with at least 1 of the following characteristics and fulfilling criteria C–D:
1. daily occurrence
2. diffuse and/or constant (non-pulsating) pain
3. aggravated by coughing or straining
B. Intracranial hypertension fulfilling the following criteria:
1. alert patient with neurological examination that either is normal or demonstrates any of the following
abnormalities:
a) papilledema
b) enlarged blind spot
c) visual field defect (progressive if untreated)
d) sixth nerve palsy
2. increased CSF pressure (>200 mm H2O in the non-obese, >250 mm H2O in the obese) measured by lumbar
puncture in the recumbent position or by epidural or intraventricular pressure monitoring
3. normal CSF chemistry (low CSF protein is acceptable) and cellularity
4. intracranial diseases (including venous sinus thrombosis) ruled out by appropriate investigations
5. no metabolic, toxic or hormonal cause of intracranial hypertension
C. Headache develops in close temporal relation to increased intracranial pressure
D. Headache improves after withdrawal of CSF to reduce pressure to 120-170 mm H2O and resolves within 72
hours of persistent normalization of intracranial pressure
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7.4.1 Headache attributed to increased intracranial pressure or hydrocephalus caused by

neoplasm
A. Diffuse non-pulsating headache with at least 1 of the following characteristics and fulfilling criteria C–D:
1. associated with nausea and/or vomiting
2. worsened by physical activity and/or manoeuvres known to increase intracranial pressure (such as Valsalva
manoeuvre, coughing or sneezing)
3. occurring in attack-like episodes
B. Space-occupying intracranial tumour demonstrated by CT or MRI and causing hydrocephalus
C. Headache develops and/or deteriorates in close temporal relation to the hydrocephalus
D. Headache improves within 7 days after surgical removal or volume-reduction of tumour
7.4.2 Headache attributed directly to neoplasm

A. Headache with at least 1 of the following characteristics and fulfilling criteria C–D:
1. progressive
2. localized
3. worse in the morning
4. aggravated by coughing or bending forward
B. Intracranial neoplasm shown by imaging
C. Headache develops in temporal (and usually spatial) relation to the neoplasm
D. Headache resolves within 7 days after surgical removal or volume-reduction of neoplasm or treatment with
corticosteroids
8. Headache attributed to a substance or its withdrawal
8.1.3 Carbon monoxide (CO)-induced headache

A. Bilateral and/or continuous headache, with quality and intensity that may be related to the severity of CO
intoxication, fulfilling criteria C–D
B. Exposure to carbon monoxide (CO)
C. Headache develops within 12 hours of exposure
D. Headache resolves within 72 hours after elimination of CO
8.2 Medication-overuse headache

A. Headache present on ≥15 days/month fulfilling criteria C and D
B. Regular overuse for >3 months of one or more drugs that can be taken for acute and/or symptomatic treatment
of headache
C. Headache has developed or markedly worsened during medication overuse
D. Headache resolves or reverts to its previous pattern within 2 months after discontinuation of overused
medication
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11. Headache or facial pain attributed to disorder of cranium, neck, eyes, ears, nose, sinuses, teeth, mouth or
other facial or cranial structures
11.2.1 Cervicogenic headache

A. Pain, referred from a source in the neck and perceived in one or more regions of the head and/or face, fulfilling
criteria C–D
B. Clinical, laboratory and/or imaging evidence of a disorder or lesion within the cervical spine or soft tissues of
the neck known to be, or generally accepted as, a valid cause of headache
C. Evidence that the pain can be attributed to the neck disorder or lesion based on at least 1 of the following:
1. demonstration of clinical signs that implicate a source of pain in the neck
2. abolition of headache following diagnostic blockade of a cervical structure or its nerve supply using placebo- or
other adequate controls
D. Pain resolves within 3 months after successful treatment of the causative disorder or lesion
CRANIAL NEURALGIAS, CENTRAL AND PRIMARY FACIAL PAIN AND OTHER

HEADACHES
13. Cranial neuralgias and central causes of facial pain
13.1.1 Classical trigeminal neuralgia

A. Paroxysmal attacks of pain lasting from a fraction of a second to 2 minutes, affecting one or more divisions of the
trigeminal nerve and fulfilling criteria B–C
B. Pain has at least 1 of the following characteristics:
1. intense, sharp, superficial or stabbing
2. precipitated from trigger areas or by trigger factors
C. Attacks are stereotyped in the individual patient
D. There is no clinically evident neurological deficit
13.8 Occipital neuralgia

A. Paroxysmal stabbing pain, with or without persistent aching between paroxysms, in the distribution(s) of the greater,
lesser and/or third occipital nerves
B. Tenderness over the affected nerve
C. Pain is eased temporarily by local anaesthetic block of the nerve
13.18 Central causes of facial pain
13.18.4 Persistent idiopathic facial pain

A. Pain in the face, present daily and persisting for all or most of the day, fulfilling criteria B–C
B. Pain is confined at onset to a limited area on one side of the face, and is deep and poorly localized
C. Pain is not associated with sensory loss or other physical signs
D. Investigations including X-ray of face and jaws do not demonstrate any relevant abnormality
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Table 2: Headache with “red flag” symptoms and signs that require further work-up
“Worst headache ever” or “first” headache

Sudden onset of headache (thunderclap headache)
Fever, rash, and/or stiff neck (meningismus)
Papilledema
Dizziness, unsteadiness, dysarthria, weakness, or changes in sensation especially if profound, static, and
occurring for the first time
Migraine auras or other previously experienced neurologic migraine accompaniments lasting longer than 1
hour
Presence of confusion, drowsiness, or loss of consciousness
Headache is triggered by exertion, coughing, bending, or sexual activity
Headache is progressively worsening and/or resistant to treatment
Previously experienced headache characteristics or accompaniments have substantially changed
Persistent or severe vomiting accompanies the headache
Late onset new headache
Headaches beginning after age of 50 are associated with a higher risk of arteritis or intracranial tumors.
Headache occurring in a patient with human immunodeficiency virus or cancer
Frequent emergency department or acute care use
Daily or near-daily use of pain relievers or the need to take more than the recommended dosage of pain
relievers
New Advances in Headache Management:

Calcitonin Gene-Related Peptide (CGRP) antagonists:
CGRP is elevated in external jugular venous blood during acute migraine attacks 3 and stimulation of the trigeminal
ganglion 4.
CGRP antagonism does not cause vasoconstriction, making it safe for patients with migraine who cannot use
triptans (e.g. patients with coronary artery disease or cerebrovascular disease) 5
Although triptans are currently the gold standard for acute migraine treatment, some patients do not respond to them
particularly those with central sensitization or allodynia 6
Currently, two CGRP antagonists have been shown to be effective in acute migraine treatment in randomized
controlled trials, Olcegepant7 and Telcagepant8-10.
Onabotulinumtoxin a (BoNTA) for chronic migraine prophylaxis:
Onabotulinumtoxin A (BoNTA) is now the first medication with US Food and Drug Administration approval
(October 2010) for chronic migraine prophylaxis. Chronic migraine (CM) is defined as headaches at least 15 days
per month and has symptoms that meet criteria for migraine on at least 8 of those days.1
Two recent, phase 3 multicenter studies, the PREEMPT 1 and 2 trials 11,12, evaluated the safety and efficacy of
BoNTA for the treatment CM in adults. 1,384 patients with CM were enrolled in these 2 trials. The trials consist of a
24-week, double-blind, parallel-group, placebo-controlled phase followed by a 32-week open-label phase. All
patients received a minimum dose of 155 units of BoNTA administered at 31 injection sites over 7 head and neck
muscles using a fixed-site, fixed-dose injection paradigm (table 3). 13
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a Each IM injection site = 0.1 mL = 5 Units Botox

b Dose distributed bilaterally
The safety and effectiveness have not been established for the prophylaxis of episodic migraine (14 headache days
or fewer per month) in seven placebo-controlled studies.
The FDA also has placed a “boxed warning” on the anti-migraine drug, onabotulinumtoxinA, marketed as Botox
and Botox Cosmetic. The warning says the effects of the botulinum toxin may spread from the area of injection to
other areas of the body, causing symptoms similar to those of botulism.
Occipital Neurostimulation (ONS):

Occipital neurostimulation (ONS) or greater occipital nerve stimulation offer the potential for a minimally invasive,
low risk, and reversible approach to managing intractable headache disorders contrary to other neuroablative
techniques.
ONS has been used successfully in the treatment of occipital neuralgia 14-17 as well as many primary headache
disorders e.g. migraine18, transformed migraine17, cluster headache18-22, and hemicrania continua19,23. Few reports
also demonstrated its efficacy in secondary headache disorders e.g. cervicogenic headache24, C2-mediated
headaches25, post-traumatic26, and post-surgical headaches27.
The most accepted mechanism of action is that, stimulation of the distal branches of C2 and C3, being the peripheral
anatomical and functional extension of the trigeminocervical complex, may inhibit central nociceptive impulses.28
PET scan studies showed increased regional cerebral blood flow in areas involved in central neuromodulation in
chronic migraine patients with occipital nerve electrical stimulation.29
The ONSTIM study 30, a multicenter, randomized, blinded, controlled feasibility study, evaluated the preliminary
safety and efficacy data on ONS in CM patients with a follow up period of 3 months. Eligible subjects received an
occipital nerve block, and responders were randomized to adjustable stimulation (AS), preset stimulation (PS) or
medical management (MM) groups. 30 Seventy-five of 110 subjects were assigned to a treatment group; complete
diary data were available for 66. A responder was defined as a subject who achieved a 50% or greater reduction in
number of headache days per month or a three-point or greater reduction in average overall pain intensity compared
with baseline. Three-month responder rates were 39% for AS, 6% for PS and 0% for MM. No unanticipated adverse
device events occurred. Lead migration occurred in 12 of 51 (24%) subjects.
Recently, the preliminary results of another prospective, multi-center, double-blind, controlled study (with one year
follow up), were reported. 31 Patients were implanted with a neurostimulation system and randomized to an active or
control group for 12 weeks. Patients then continued in an open-label phase with 24, 48, and 52 week evaluations.
There were significant group differences for all assessments at 12 weeks (p< 0.01). In the active and control groups
respectively, MIDAS headache days decreased by 22.5 and 3.4, total MIDAS scores improved by 64.6 and 20.4,
PAD scores improved by 13.3 and 5.5, VAS scores decreased by 14.1 and 7.0, 35.2% and 11.5% of patients
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achieved a 30% reduction in VAS, 66.7% and 17.2% of patients reported improved QoL, and 51.4% and 19.2%
were satisfied.
The results provide evidence to support safety and effectiveness of occipital neurostimulation for management of
pain and disability associated with chronic migraine.
Sphenopalatine ganglion radiofrequency ablation:

Radiofrequency ablation of the sphenopalatine ganglion is usually performed with the percutaneous infrazygomatic
approach .Once the pterygopalatine fossa is accessed with a radiofrequency needle, sensory stimulation is performed
to produce deep paresthesias behind the root of the nose and then 2 radiofrequency lesions are carried out at 80 oC
for 60 seconds each. 32,33
Narouze et al reported favorable outcome in the treatment of intractable chronic cluster headache. They reported
significant improvement in both mean attack intensity and mean attack frequency for up to 18 months in 15 patients.
However, 46.7% of the patients (7/15) reported change in the headache pattern with return to the episodic form of
cluster headache at a mean follow-up period of 18 months.32
Sphenopalatine ganglion stereotactic radiosurgery:

Stereotactic radiosurgery is another minimally invasive approach for SPG ablation. CT imaging delineates the walls
of the pterygopalatine fossa while the contents of the fossa are better visualized on MRI. It was shown to be helpful
in the treatment of medically refractory cluster headaches (60%). Radiosurgical dose to the SPG ranges from 75Gy
to 80Gy. 34,35
Sphenopalatine ganglion neurostimulation

This technique employed transient neurostimulation with a temporary electrode using the standard lateral
infrazygomatic approach.
Tepper et al. recently demonstrated the effectiveness of electrical stimulation of the SPG for acute treatment of
intractable migraine. In 10 migraine headache trials, acute SPG stimulation resulted in complete relief in 2, partial in
2 and no relief in 6 instances. 36
Ansarina et al. on the other hand reported SPG stimulation for chronic cluster headaches (CCH). In 18 distinct
cluster headache attacks, acute SPG stimulation resulted in complete resolution of the headache in 11, partial
resolution in 3 and no relief in 4 instances. SPG stimulation was noted to result in complete resolution of the
associated autonomic features of cluster and migraine headaches such as nasal congestion and periorbital swelling in
all cases presented with autonomic features. 37
More recently, the safety and efficacy of on-demand SPG stimulation for the acute treatment of CCH were
reported.38 The study design involved a multi-center, dose range finding, with a random insertion of placebo,
multiple headaches, acute treatment study design. All subjects meet the ICHD-II criteria for CCH with a minimum
of 4 headaches/week and are dissatisfied with current treatments. Subjects are implanted with a miniaturized
neurostimulator that provides SPG stimulation. The primary endpoint is acute pain relief by 15 minutes (drop to
'none' or 'mild' on the categorical scale).
Twelve subjects have been implanted with an average procedure time of 90 minutes. Three subjects received pain
relief in 100% of treated headaches. Two subjects received pain relief in 80% and 33% of treated headaches
respectively and two subjects did not receive pain relief.
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DISCLOSURE
Springer, Self, Royalties ; Philips, Self, Consulting Fees
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Clinical Update in Complex Regional Pain
Timothy Lubenow, M.D. Chicago, Illinois
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Spinal Cord Stimulation and Spinal Cord Stimulation of the

Dorsal Root Ganglion: The Evolution of Technology
Timothy Deer, M.D., DAPBM, FIPP Charleston, West Virginia
INTRODUCTION:
Neuromodulation is an area of medicine that is evolving and improving over time. The field involves changing the
function of the neurological system to achieve a change in the perceived or actual function of the nerves, spinal cord
or brain. This can be done by electrical current or drug delivery to the neuroaxis. Some applications of this
technology include pain relief, functional improvement of muscles, reduction of tremor, and in recent years to
impact gastrointestinal, urological, and cardiovascular disease states. The topic of this section will focus on the use
of electrical current to modify the spinal cord and neural pathways. The focus will be on:
1. Conventional applications of Spinal Cord Stimulation (SCS).

2. Stimulation of the Dorsal Root Ganglion (DRG)
3. The potential of High Frequency Stimulation (HFS) of the spinal cord.
4. The Delivery of Percutaneous Paddle Leads.
5. The impact of motion adaptation and sensing on outcomes.
6. Potential advances in the arena going forward.
CONVENTIONAL SPINAL CORD STIMULATION (SCS):
SCIENTIFIC PRINCIPLE
The use of SCS to treat chronic pain involves the strategic placement of a stimulating combination of electrodes
over a neural target in the epidural space. This is achieved by placing the electrodes on a lead attached to an
implanted programmable computer and power source. By using a programmable generator the amplitude, rate,
frequency and shape of the electrical field can be manipulated to create pain relief. The mechanism of neural effect
has been theorized to change the balance of inhibitory to excitatory fiber activity by the gate control process, by
manipulating the number and position of cathodes and anodes on the lead.
PAIN TREATMENT ALGORITHM
The algorithmic treatment of pain is currently the standard of care for improving patients pain levels, function, and
quality of life. In many cases the patient responds to simple techniques such as physical therapy, medications or
injection therapies. In recent years, many experts have recommended the use of SCS much earlier in the algorithm;
namely before a second spine surgery in neurologically stable patients, before chronic high dose opioids in patients
with mixed or neuropathic pain, and in some cases prior to the first back surgery in patients with multi-level disease
or uncertain surgical outcomes. The recent advancement of SCS in the algorithm can be attributed to many
developments. These changes include the simplification of stimulation trialing which now can be done via a
percutaneous skin puncture with no incisions, monitored care and same day discharge. Other major factors include
two recent randomized studies by Kumar and North. Kumar’s study showed that stimulation was superior to
conventional medical treatment alone in patients with a history of failed back surgery with leg pain. North’s study
showed that spinal cord stimulation is superior to a second back surgery in regard to pain relief, satisfaction, and
need to have the other therapy.
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In addition to the evidence based medicine supporting SCS the national problem of opioid addiction and diversion
has led many to recommend neuromodulation as an appropriate choice in the appropriately selected patient.
INDICATIONS AND PATIENT SELECTION:
In the United States, the Food and Drug Administration (FDA) have approved this therapy for the treatment of
moderate to severe pain in the trunk or limbs. The specific indications for which these devices are most commonly
used have been well defined. The most common indication for spinal cord stimulation is failed back surgery
syndrome. Other common reasons patients undergo these surgeries include cervical and lumbar radiculitis, complex
regional pain syndrome, peripheral neuropathies, post herpetic neuralgia, ischemic limb pain, angina, pelvic pain
and other neuropathic and visceral pain syndromes.
Patients are selected for SCS based on pain location, pain quality, and pain intensity. The patients have often failed,
or are not appropriate for, other more conservative methods. The patient should have no untreated coagulation
disorders, have no active infection, have no unstable depression or anxiety, are not actively psychotic, and have an
appropriate response to a SCS trial.
SPINAL CORD STIMULATION: THE PROCEDURE
GENERAL PRINCIPLES
After appropriate patient selection and education the patient should undergo preoperative evaluation for
perioperative risks. Once cleared for trialing, the patient should be interviewed by the anesthesiologists and
stabilized. Preoperative antibiotics are based on local pathogens and susceptibilities. Most common antibiotics
include intravenous vancomycin or a third generation cephalosporin preoperatively, bacitracin or kantrex
intraoperatively. Intraoperative prepping and draping is should be broad and extend well beyond the surgical field.
Positioning should facilitate surgical technique and patient safety and comfort. The decision to use antibiotics post-
operatively is based on physician preference, patient risk profile, and local practices.
IMPLANT METHOD
The use of a percutaneous lead or surgical paddle lead is at the discretion of the implanting physician. Percutaneous
leads are introduced in a less invasive and less dangerous method so are usually preferable, but in some cases such
as those with complex spinal disease, extensive scar tissue, or primary axial back pain a paddle lead may be a better
choice. In those who obtain a percutaneous lead, whether using a cylindrical lead or new paddle constructs, a needle
must be placed appropriately prior to delivering the device.
NEEDLE PLACEMENT
Prior to placing the tuohy needle the implanter should review the preoperative films and develop a strategy for
implant. The plan should include the level of entry, the side of entry and the angle. In the lumbar spine needles are
usually placed into the epidural space at 30 to 45 degrees. A paramedian approach is preferred, with a skin entry
site one and half to two levels below the desired entry space. The needle entry into the epidural space should be two
to three levels below the final lead target. In the cervical spine the needle entry should be below the C7-T1
interspace. Usually at T2-3 or T3-4. In some cases, implanters place the needle in the epidural space at a lumbar
level and deliver the leads to the cervical spine.
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LEAD PLACEMENT
The lead should be driven to the posterior epidural space at the desired level of stimulation. If the patient reports
pain or paresthesia during the placement the lead should be retracted and repositioned. The lead can be guided using
a straight or curved stylet. Fluoroscopic guidance should show good placement on both antero-posterior and lateral
views. The lead placement should be placed based on a strategic target for stimulation.
LEAD TARGET
The physician should understand the target for the led to achieve proper stimulation. Table 1 provides general
targets for spinal cord stimulation.
Table 1. Lead Placement for Anatomical Stimulation
Region Position Target

Cervical C2 Lateral Mandible, Neck, Shoulder
C2-3 Shoulder, Arm
C4-6 Arm, Hand
C7-T2 Anterior Shoulder, Chest
Thoracic T3-T6 Abdominal, Thoracic, Visceral Organs
Thoracic T1-3 Angina, Chest

T4-6 Visceral Abdomen
T7-9 Axial Back
T10 Knee, Hip
T11-12 Leg, Foot
Lumbar L1 Foot, Possible Pelvic Organs

L5-S1 Foot
Nerve Root
Sacral S2-4 Pelvis, Rectum, Perineum
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LEAD PROGRAMMING
Lead design, targeting and epidural anatomy impact the response to SCS. The array and number of the cathode
(negative) and anode (positive) electrodes impact the stimulation pattern. Current is driven into the neural tissue
based on the presence of a cathode. The optimal current delivery occurs when a cathode is surrounded or “guarded”
by an anode on each side. New tripolar constructs have been theorized to deliver current more successfully to the
deep fibers of the cord which are somewhat lateral at the mid to lower thoracic spine. By using a tripolar array
anodes are used laterally to hyperpolarize the nerve roots, so that the cathode can drive current deeper into the cord.
The author prefers the “double guarded cathode approach” placing a lead across midline and then using a + - - +
array to cover the back and both legs. The advent of five column leads may further improve the laterality of
stimulation and again impact long term outcomes in the patient with complex pain patterns.
LEAD ANCHORING
Patient selection, lead placement and proper targeting are important, but once these steps have occurred it is
important to secure the lead so it will not be dislodged. At one point in time this complication was the most
common cause of adverse outcomes, but recent years have seen advances in anchoring. It is very important to
anchor to the fascia and ligament with non-absorbable suture. Mechanical anchors that lock to the lead are valuable
advances in the field to reduce movement. Data has shown that the placement of a strain relief loop in the spinal
incision and pocket can reduce lead strain and improve migration. The highest risks of migration occur in the first
six weeks post implant.
POCKET FORMATION
The position of the pocket is based on patient preference and body habitus. Options include the buttock, abdominal
wall, flank, and chest wall. The depth of the pocket should be appropriate to avoid skin erosion, but should also
assure good communication with telemetry. The most common area for implant currently is in the flank just above
the belt line. The implanter should consider sleeping patterns, shoulder mobility and patient clothing preferences
when planning the pocket. Hemostasis and antibiotic irrigation is important prior to closing the wound.
COMPLICATIONS OF SCS
The most common complications of spinal cord stimulation include lead migration, superficial infection, impedance
abnormalities, wet tap, and nerve irritation. More serious problems include epidural hematoma, epidural abscess,
paraplegia, and death. The number of complications can be reduced by sterile technique, preoperative assessment,
and proper selection.
ADVANCES IN STIMULATION OF THE SPINE:
STIMULATION OF THE DORSAL ROOT GANGLION
The anatomy of the DRG makes it an attractive target for neuromodulation. The structure is a sensory neural body
that contains the soma from primary sensory neurons. The ganglion is located within the bony structure of the spine
just below the pedicle where it reliably lies in all patients, and both transmits and influences sensory neural impulses
traveling from the periphery. The ganglion contains multiple cell types including neurons and glial cells that
change and become hyperexcitable in chronic pain conditions. (Figure 1, with permission of Jeff Kramer, PhD) The
DRG has been a target for injection, surgical interventions and radiofrequency in the past, but with no long standing
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efficacy. The development of new novel leads, delivery tools and multi-channel generators has led to the use of
DRG stimulation as a major advance in the treatment of intractable pain syndromes. The lead shape allows for
selective stimulation of the DRG without encompassing the surrounding structures. (Figure 2, with approval of Jeff
Kramer, PhD) Approval of this therapy has now been given in the European Union, and studies are pending in the
United States.
The presence of hyperexcitable fibers in the DRG appears to lead to selective stimulation of the abnormal areas of
the pain transmission and avoids the over stimulation of fibers that may lead to motor stimulation.
Figure 1.
Figure 2.
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HIGH FREQUENCY METHODS OF SCS:
In the past the variables of SCS included amplitude, pulse width, and rate. Frequency was felt to be a minor variable
and that most patients responded to low frequency stimulation. This concept has recently been challenged. Work
done in the United States, Europe and Australia has suggested that the use of High Frequency Stimulation (HFS)
may give significant relief in those who have primary axial back pain or those with inability to tolerate the feeling of
parasthesia with conventional stimulation. HFS involves the use of leads, similar to conventional systems, placed
based on anatomical strategies noted above. In these implants there are no parathesias created. The efficacy of
these exciting new devices will be determined based on a new study approved by the Food and Drug Administration
(FDA). The frequency used in these devices approach 10, 000 Hz, but may also be used to deliver more standard
frequencies. Currently no studies exist to determine the value of mixing or cycling low frequency and high
frequency settings in the setting of mixed or complex pain syndromes.
PERCUTANEOUS PADDLE DELIVERY:
The choice of delivering a cyndrilical lead via a needle approach or a paddle lead via a laminotomy open approach
has been complicated based on the risk to benefit ratio. In many cases, a paddle lead has been placed although only
a small capacity of the lead has been needed. A need to deliver a more efficient lead via a percutaneous approach
has been present for some time. In the past several months the approval of a percutaneous sheath to delivery a small
streamlined efficient unidirectional lead has changed this equation. Now the ability to place one or two paddles
without a laminectomy is available to the nonsurgical implanter. The use of hybrid systems with both paddle and
percutaneous leads has recently been presented as an option for patients who suffer from both limb and axial pain.
The availability of percutaneous paddle leads does not totally alleviate the need for surgically placed paddle leads.
The complex paddles with multiple columns are needed in some patients who have failed percutaneous attempts at
stimulation, or require a complicated revision, or who have anatomical spinal challenges. When placing a paddle
lead via a percutaneous approach the needle angle and useo of a paramedian approach are important. (Figure 3,4).
These techniques allow for proper placement of the guidewire to direct the sheath which is placed via the Seldinger
technique. (Figure 5 and 6). The sheath is used to pass the paddle lead to the target. Recent publications have
suggested both favorable safety data, and good initial efficacy data.
Figure 3. Figure 4.
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Stylet slightly
withdrawn
Insert
guide wire
Figure 5.
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Figure 6.
MOTION SENSING AND ADAPTATION:
When a lead is placed in the epidural space, it is used to delivery current to the spinal cord and neural structures.
The spinal cord moves in the cerebral spinal fluid as the patient changes positions. In a small number of patients
this movement of the cord causes difficulty in achieving reliable stimulation. There have been some methods to
achieve a reduction in this variability. Options include hardware to further occupy the space such as paddle leads, or
complex arrays, or new technology.
Among the new technologies, only one has current approval by the FDA. This method involves an implanted
motion sensor that changes stimulation with variances in the patients body position. This implant is a part of the
normal programmable device, and does not change the technique or size. The role in satisfaction with this device
appears quite good, but we have not seen improvements in efficacy or function in any current studies. Further data
may further strengthen the need for more widespread use of these types of devices.
Positional variability does not appear to occur with the DRG implant or the HFS devices. The future of these issues
will depend on the percentage of devices used in clinical practices based on FDA approval and efficacy data on
prospective studies.
FUTURE ADVANCES:
The use of SCS, DRG, HFS, and motion adaptation is very exciting and will continue to improve patient lives and
function. We remain in the early stages of our field, but progress is being made.
There are still many challenges such as MRI compatibility, blue tooth or wireless communication between
telemetery and devices, improvement in battery life and minituratization. These are only a few of the issues we
must continue to work on going forward. This will require collaborative efforts by physicians, scientists, device
manufacturers, governmental bodies, and patients. The future is exciting, but we are starting to see the future in
recent advances. This is an exciting time to be a implanting physician and hopefully will be a better time for
patients who are in need of advanced care.
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SELECTED READING:
Deer, T. Bowman, R. Schocket, M. et. al. The Prospective Evaluation of Safety and Success of a New Method of
Introducing Percutaneous Paddle Leads and Complex Arrays With an Epidural Access System. Neuromodulation:
Technology at the Neural Interface Volume 15, Issue 1, pages 21–30, January/February 2012
Deer, T. Atlas of Implantable Therapies for Pain Management. New York, New York: Springer Science + Business
Media, LLC. 2011
Deer, T. Neurostimulation for the Treatment of Chronic Pain Text Book Series. Elsevier Publishing 2012
Fields, R. D. (2009). New culprits in chronic pain." Sci Am 301(5): 50‐57.
Ross, E. Abejon, D. Improving Patient Experience with Spinal Cord Stimulation: Implications of Position‐
Related Changes in Neurostimulation. Neuromodulation: Technology at the Neural Interface
Early View (Published Online December 2011)
Hogan, Q. H. (2010). "Labat lecture: the primary sensory neuron: where it is, what it does, and why it
matters." Reg Anesth Pain Med 35(3): 306‐311.
Deer T, Masone R. Selection of Spinal Cord Stimulation Candidates for the Treatment of Chronic Pain. Pain
Medicine, Volume 9 Issue S1, Pages S82‐S92
North R, Kidd D, Farraokhi F, Piantadosi S. Spinal cord stimulation versus repeated lumbosacral spine surgery
for chronic pain: a randomized, controlled trial. Neurosurgery. 2005;56(1):98‐106.
Mekhail N, Aeshbach A, Stanton‐Hicks M. Cost Benefit analysis of neurostimulation for chronic pain. Clin J
Pain. 2004 Nov‐Dec:20(6): 462‐8.
Kumar. K, Taylor RS, Jacques L, et.al., Spinal Cord Stimulation versus conventional medical management for
neuropathic pain: A Multicenter randomized controlled trial in patients with failed back surgery syndrome.
Pain (2007); doi:10.1016/j.pain.2007.07.028
Taylor R, Van Buyten J, Buscher E. Spinal cord stimulation for complex regional pain syndrome: a systematic
review of the clinical and cost‐effectiveness literature and assessment of prognostic factors. Eur J Pain. 2006
Feb;10(2):91‐101
Deer T. Current and future trends in spinal cord stimulation for chronic pain. Current pain and headache
reports 2001, (5): 503‐509.
Deer T. A Critical Time for Practice Change in the Pain Treatment Continuum: We need to reconsider the role
of pumps in the patient care algorithm. Pain Medicine. June 2010.
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DISCLOSURE
Bioness, Self, Funded Research, Consulting Fees ; Azur, Self, Consulting Fees ; St. Jude Medical Neuromodulation,
Self, Funded Research, Consulting Fees ; Spinal Modulation, Self, Funded Research, Consulting Fees ; Medtronic,
Self, Consulting Fees ; Vertos Medical, Self, Stock O
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Diagnostic and Therapeutic Imaging

James P. Rathmell, M.D. Boston, Massachusetts
Introduction
Until recent years, use of radiographic guidance in the pain clinic was reserved for major procedures like neurolytic
celiac plexus block. Two forces have been at work, which have led to the widespread use of imaging modalities in
the field of pain medicine. Patients and referring practitioners now expect pain physicians to be familiar with use of
imaging in diagnosing pain conditions. At the same time, pain practitioners have demonstrated the usefulness of
radiographic guidance for guiding precise anatomic placement of needles and catheters. The evidence to support
routine use of radiographic guidance is still evolving. The intuitive appeal of this precise approach has already
caught on to the point where the majority of practitioners now perform most of their injections using fluoroscopic
guidance. In patients with intractable pain associated with metastatic cancer, diagnostic imaging studies has proven
invaluable in the planning and implementation of therapy. The use of fluoroscopy, computed tomography (CT), and
most recently, ultrasound in the pain clinic have all advanced rapidly, yet there is scant evidence that this improves
the safety or efficacy of pain treatment. Herein, we will review the available evidence about the usefulness of
diagnostic imaging and image guidance in planning and delivering pain treatment.
Definition and Scope: Use of Diagnostic Imaging to Improve Safety

Pain is among the most common presenting symptoms that lead patients to seek medical care. Diagnostic imaging is
used broadly to search for the anatomic basis for new onset of many symptoms, including pain. Indeed, diagnostic
imaging is the cornerstone of diagnosis in many cases, such as new onset of sciatica associated with disc herniation.
A broad discussion of the use of diagnostic imaging is beyond the scope of this article, but several examples where
diagnostic imaging can provide critical information for planning treatment will be reviewed.
There is moderate scientific evidence that epidural injection of steroids can speed the resolution of radicular
pain early after acute lumbar disc herniations1,2,3 and this treatment is in widespread use. By extrapolation from the
evidence for lumbar disc herniation, the technique has also been used for pain associated with thoracic and cervical
disc herniations and spinal stenosis. Use of diagnostic imaging to establish the exact anatomic level of disc
herniation was unusual just ten years ago. At that time, most practitioners doing epidural injections were doing so
with no experience in interpreting imaging studies; most often they were using the
blind loss-of-resistance technique to identify the epidural space.4 Conventional
wisdom at that time held that the injection should be placed at the level of the disc
herniation to produce maximal benefit. Most practitioners simply placed epidural
injections guided only by the radiologists report: if there was a disc herniation at C6/7,
then the injection was placed at that level. Reports of spinal cord injury during these
injections began to appear, and a connection between spinal cord injury during
injection and high-grade spinal stenosis was made.4 Indeed, in high grade stenosis of
the central spinal canal from any cause, there is often complete loss of the CSF and
epidural fat surrounding the cord, often with direct pressure on the spinal cord. This is
the case in a few patients with large disc herniations (Figure 1. Cervical MRI in a
patient with a large C6/7 disc herniation that causes significant stenosis of the central
spinal canal. This patient developed neuropathic pain suggestive of minor spinal cord
injury during epidural steroid injection conducted using a blind technique at the C6/7
level. Review of diagnostic imaging studies before injection would have identified this
high grade stenosis and use of fluoroscopy to select a intervertebral level where the
stenosis was less severe may have prevented this injury. A: Axial T1-weighted
magnetic resonance image at the C6/7 level. There is a large central herniated
intervertebral disk that lateralizes to the left (arrow heads). The spinal cord is
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displaced toward the rightposterior portion of the spinal canal (arrows). B:Sagittal T2-weighted image at the midline
of the cervicalspine. There is a large disk herniation at the C6/7 level, causing posterior displacement of the spinal
cord (arrow) and effacement of the cerebrospinal fluid signal anterior to the spinal cord. Reproduced with
permission from Reference 4.) . In such cases, it is critical to recognize the lack of enough space in the posterior
epidural canal to allow for safe needle entry and
placement of the epidural steroid. The use of diagnostic
imaging and careful review of the actual images prior to
epidural injection is now routine. When there is severe
spinal canal stenosis, injection at the stenotic levels is
avoided by using fluoroscopy to guide needle
placement at an anatomic level where prior diagnostic
imaging has demonstrated room for needle entry.
Neurolytic celiac plexus block is another
technique that has moderate scientific evidence from
controlled trials demonstrating reduced pain and
analgesic use in patients with painful intra-abdominal
malignancies, particularly pancreatic cancer. The
complications associated with this technique include
renal trauma, trauma to the large vessels of the
abdomen, and pneumothorax. Diagnostic imaging for
identification and staging of pancreatic cancer is
standard practice worldwide, thus imaging studies are
almost universally available at the time patients are
referred for celiac plexus neurolysis. Analysis of the
diagnostic studies can assist in planning the spinal level
of needle entry, as well as the angle and depth of needle
advancement. These planning measurements are made
on the diagnostic images and used to guide needle
placement during celiac plexus block done
subsequently using either CT of fluoroscopy (Figure 2.
Use of diagnostic computed tomography angiography
study of the abdomen in a patient referred for celiac
plexus block to plan position and depth of needle
placement. The diagnostic CT angiogram can be used
to determine the safest position to place needles and
plan the final depth on needle insertion; these
measurements can then be used to carry ot the block
with either fluoroscopy or CT guidance. Axial image
one centimeter inferior to the origin of the celiac artery
from the anterior aorta, below the inferior reflections of
the pleura. The distance from the anterolateral surface
of the aorta to the skin surface (124 mm) and from the
spinous process to the point of needle entry (41 mm);
similar measurements can be made for placement of the
needle on the right side. Performing the celiac plexus
block somewhat inferior to the celiac artery in this
patient was carried out successfully: the needles were
well below the pleura at this level. Adapted with
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permission from Rathmell JP. Atlas of image guided intervention in regional anesthesia and pain medicine.
Lippincott Williams and Wilkins, Philadelphia, 2012.) . Existing diagnostic studies can be help to avoid adjacent
structures thus improving safety.
Definition and Scope: Use of Image-Guidance to Improve Safety

Early work suggests that image guidance can increase the precision of epidural. One of the most quoted studies
demonstrated that using a blind loss-of-resistance technique correctly identified the epidural space in only 30% of
cases.5 This study has been criticized, as the investigators were not frequent users of the loss of resistance technique.
When experienced physicians placed epidurals in the setting of labor and delivery, the success rose to 61.7% in
comparison to a success rate of 47.7% in those who had performed few injections previously.6 Subsequent
investigators reported successful caudal epidural injection in 97.5% of cases performed using fluoroscopic
guidance.7 Radiographic guidance can be used to display images in multiple planes at all spinal levels, and the
epidural space can be identified the vast majority of the time (Figure 3. Radiographic identification of the lumbar
epdiural space. Lateral radiograph of the lumbar spine during interlaminar lumbar epidural injection. A Tuohy
needle is in place in the L5/S1 interspace extending to the posterior epidural space. Clarity of lateral radiographs of
the lumbar spine is often hindered by the overlying iliac crests. During lumbar interlaminar epidural injection, the
needle can be safely advanced using the lateral radiograph to guide depth. The posterior-most extent of the
ligamentum flavum lies just anterior to the junction of the spinous process with the laminae (red arrows). The needle
can be safely advanced to this depth before starting the LOR technique during the last few millimeters of
advancement through the ligamentum flavum to precisely identify the epidural space. The junction of the spinous
process with the lamina can be easily identified in the lateral radiograph by following the inferior margin of the
spinous processes anteriorly until the junction with the lamina is seen as a line that extends in an inferior and
anterior direction (dashed line). The approximate location of the thecal sac is shown (gray lines indicate the
approximate location of the anterior and posterior aspects of the dura mater). Adapted with permission from
Rathmell JP. Atlas of image guided intervention in regional anesthesia and pain medicine. Lippincott Williams and
Wilkins, Philadelphia, 2012.).
Use of radiographic guidance employing a co-axial technique can also improve the precision of needle
placement, reduce or eliminating the need for redirection of the needle to reach the epidural space.8 By aligning the
axis of the x-ray beam with the final radiographic target, the skin directly overlying the target can be anesthetized,
and a needle passed directly from the skin’s surface to the target at a depth in a single pass. Antero-posterior
radiographs demonstrate the needle position from lateral to medial and cephalad to caudad; lateral radiographs
demonstrate the needle’s depth from the skin’s surface. While radiographic guidance can bring the needle in to close
proximity to the epidural space, only bony structures can be identified using fluoroscopy, thus final needle
advancement into the epidural space requires use of the loss-of-resistance technique. Once the needle is in final
position, epidural location can be confirmed by injecting radiographic contrast. If the contrast spreads in a
characteristic pattern without evidence of vascular flow, then epidural location is confirmed.
Identification of intravascular needle location using fluoroscopy requires special attention. Use of a live or
real-time technique rather than static images is essential. Any contrast placed within a blood vessel will be rapidly
carried away in the blood stream and will no longer be visible on static images taken subsequently. Another
difficulty with use of radiographic guidance is the appearance of confusing patterns of contrast spread, particularly
in patients who have had prior surgery, including fusion masses along the bony spine or scarring in the epidural
space. Use of radiographic guidance does not assure the safety of image-guided injections, but the use of these
techniques has strong face validity as a means to improve safety: if you can directly visualize or more precisely infer
the position of critical structures like blood vessels and the spinal cord, then it stands to reason that these structures
can be avoided with the use of image guidance. Caution is in order: images are often confusing, the skill of
practitioners is variable, and despite there is still little evidence for improved safety with image guidance. A recent
study published by the American Society of Anesthesiologists (ASA) examined closed malpractice claims, in a
subgroup of patients who sustained spinal cord injuries during the course of cervical spinal injections.9 Radiographic
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guidance was more common in those who sustained spinal cord injuries than in those who had cervical procedures
performed without radiographic guidance. Did use of radiographic guidance make spinal cord injury more likely?
Perhaps, but it is equally plausible that injections that led to spinal cord injury, e.g. cervical epidural steroid injection
using an interlaminar technique, were done more often with radiographic guidance. Without knowledge about how
many total injections were done with and without radiographic guidance, there is no means to know the actual
incidence of injury with each method. Nonetheless, the ASA Closed Claims report does demonstrate that direct
trauma to the spinal cord can occur during transforaminal injection, interlaminar epidural injection, and trigger point
injection at the level of the cervical spine, even when image guidance is used.
Intravascular injection can lead to local anesthetic toxicity or catastrophic neural injuries to the brain or
spinal cord. With disciplined use of radiographic guidance, intravascular needle location can be detected before local
anesthetic or steroid is injected. In this way, use of radiographic guidance can improve safety. Intravascular needle
location exceeds 20% during cervical transforaminal injection,10,11 and it is unclear what proportion are intravenous
versus intra-arterial.12 Use of digital subtraction appears to further increase the likelihood of detection of
intravascular injection.13 Intravascular injection is common during cervical transforaminal injection, but the
incidence during other techniques is unclear. The proximity of the vertebral artery during stellate ganglion block and
the proximity of the aorta during celiac plexus block make intra-arterial injection distinctly possibility. Means to
detect intra-arterial needle location before injection must be a routine part of performing these techniques.
Without any direct reporting mechanism, any real estimate of the incidence of injuries occurring during the
course of pain treatment is impossible. The ASA Closed Claims study gives us a glimpse of injuries that can occur.
The incidence of these injuries appears to be low, likely less than 1 in 10,000 injections and perhaps even lower;
while it is difficult to estimate this risk with accuracy, in 2006, nearly 800,000 Medicare patients in the United
States14 underwent epidural injections. Catastrophic neural injuries on record number less than 100. From published
studies, it is clear that the use of common injections for pain treatment has risen exponentially in the United States
during the last decade14 and use of fluoroscopy to guide needle placement during these treatments is now the rule
rather than the exception. We need large-scale, prospective studies that examine the frequency of use of these
treatments and their safety and effectiveness to guide practitioners in making rational treatment decisions.
Mechanism of Causation
Injuries associated with image-guided pain treatment fall into several broad categories. Bleeding and infectious
complications, while devastating, are rare: epidural hematoma and epidural abscess. Use of image-guidance is
unlikely to impact either of these complications, but diagnostic imaging is plays a major role in prompt diagnosis
and treatment. Image guidance does play a critical role in avoiding direct trauma to neural structures and preventing
intravascular or intrathecal injection.
Direct Trauma to Neural Structures

Trauma to neural structures, including spinal nerves, the cauda equina, or the spinal cord itself, have all been
associated with injections used in pain treatment. Specifically, direct needle contact with spinal nerves during
transforaminal injection is common. This may cause a transient paresthesia, which resolves with redirection of the
needle or can lead persistent pain. Transforaminal injection is often carried out to treat radicular pain associated with
foraminal stenosis or nerve compression associated with disc herniation. With these conditions, there is little space
around the spinal nerve to accommodate the injected fluid and the injected fluid may lead to worsened nerve
compression. The spinal cord lies in front of the advancing needle during both transforaminal and interlaminar
epidural injections at the cervical level, and direct needle trauma to the cord can occur.9 Patients with severe central
spinal stenosis may be at particular risk for spinal cord injury, especially when using an interlaminar technique.4
Vascular compromise
Evidence for vascular compromise has arisen in two areas: paraplegia following neurolytic celiac plexus block15,16
and catastrophic neural injuries associated with injection of particulate steroid during cervical transforaminal
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injection.17 celiac plexus block is commonly carried out at the T12/L1 vertebral level. Injectate is placed over the
anterolateral vertebral bodies or around the anterolateral aspect of the aorta. The artery of Adamkiewicz arises from
the posterolateral aspect of the aorta, most often on the left between the T10 and L2 vertebral levels, in close
proximity to where the injectate is placed for celiac plexus block. This artery often provides critical blood supply to
the anterolateral spinal cord at the low thoracic level and compromise can lead to spinal cord ischemia or infarction.
The injection of neurolytic solution in this region has been hypothesized to lead to vasospasm of this critical
reinforcing artery, and there is at least one case of transient paraplegia.15 The neurologic insult is more often
permanent. While the mechanism may by arterial spasm and resultant ischemia, it seems more plausible that spinal
cord injury is the result of intra-arterial injection of the neurolytic solution.
Catastrophic neural injury following intra-arterial injection of particulate steroid has been well-described
with transforaminal injections,17 stellate ganglion block,9 and cervical facet injections18. Several mechanisms of
injury have been postulated, including arterial spasm or dissection, but no evidence to support these alternate
mechanisms has appeared. The most likely mechanism is direct intra-arterial injection of steroid particles that
occlude the end-arteriolar circulation, leading to ischemia and infarction. During transformaminal injection,
injection into the spinal medullary arteries can lead to spinal cord infarction, and injection in to the vertebral artery
can lead to stroke involving the posterior cerebral, resulting in cortical blindness, cerebellar infarction and death
from intracranial hypertension. Direct injection in to the vertebral artery can also occur with stellate ganglion block
or high cervical facet injections. Studies in experimental animals strongly support this mechanism of injury19,20 as do
case reports.18 In anesthetized swine, injection of particulate steroid into the vertebral artery resulted in massive
posterior circulation stokes on MRI and persistent coma without return of spontaneous respiratory;19 in contrast,
intra-arterial injection of the non-particulate steroid dexamethasone caused no apparent injury. In a report of a man
receiving a C1/C2 intra-articular facet injection with particulate steroid, intra-arterial injection into the vertebral
artery resulted in a fatal posterior circulation stroke18. These publications strongly support the mechanism of injury
of particulate steroid causing end-arteriolar occlusion.
Prevention of Direct Trauma to Neural Structures

Neural structures cannot be directly visualized using fluoroscopy. Their position must be inferred from their typical
proximity to bony structures that can be seen. Prevention of trauma starts with review of available diagnostic studies
and careful planning of needle placement for the injection. Severe spinal stenosis caused by cervical
spondyloarthropathy or disc herniation can lead to complete effacement of the epidural fat and spinal fluid
surrounding the spinal cord. Needle entry into the spinal canal at such a severely stenotic level can lead to direct
cord trauma, even without dural puncture.4 Interlaminar epidural injection at severely stenotic levels should be
avoided. In a similar fashion, severe spinal foraminal stenosis can lead to neural compression when even small
volumes of injectate are placed within the foramina. The only means to avoid neural injury is to monitor any
symptoms reported during injection, and to slow or halt the injection if symptoms appear.
The use of deep sedation or general anesthesia during the conduct of pain treatment techniques has been the
subject of much debate.21 Proponents hold that sedation improves safety by assuring that the patient will remain
relatively immobile when the needle is in close proximity to critical structures; opponents point out that deep
sedation eliminates the ability of the patient to report contact with neural structures, eliminating any possibility of
using the patient’s early report of symptoms as an early warning sign of impending neural injury. In the ASA Closed
Claims study, use of deep sedation unresponsiveness was associated with an increase in the probability of permanent
spinal cord injury during pain treatment at the cervical spinal level.9 When the patient does report a paresthesia, the
practitioner should suspect contact with a spinal nerve if the pain is localized to an extremity or the spinal cord if the
patient reports both upper and lower extremity pain. If this occurs, the needle should be withdrawn and redirected.
The spinal cord can be entered without producing neural injury; however, if the spinal cord is penetrated and any
substance is injected, it is likely that neurologic injury will occur. The neuronal disruption caused by placing
injectate into the substance of the cord appears to be what causes the most severe injury, rather than direct trauma
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caused by needle entry alone. However, if an arterial structure within the cord is disrupted, bleeding into the cord
can also produce significant injury.
Once the needle is in final position, it is critical to use images obtained in multiple planes to establish the
final needle position. An AP image tells little about the needle’s depth, while a lateral image tells little about the
medial to lateral deviation of the needle. Combining the two images, an accurate measure of the needle’s position in
three dimensions can be reconstructed.
Use of ultrasound has gained rapid acceptance for performing peripheral nerve blocks for surgical
anesthesia.22 Ultrasound can be used to directly visualize superficial neural structures, like the brachial plexus. The
success rate of many peripheral nerve blocks has improved with use of ultrasound. It is less clear if ultrasound will
improve the safety of these techniques.23 Direct intraneural injection and intravascular injection can still occur with
the use of ultrasound. In pain treatment, use of ultrasound has not advanced as rapidly. Pain practitioners have been
using fluoroscopy for years and fluoroscopy allows direct and precise visualization of the bony elements of the
neuraxis. Use of ultrasound to image neuraxial stuctures is limited by the echogenicity of the bony elements of the
spine, preventing direct visualization of many structures. Nonetheless, the safety of several pain treatment
techniques may be improved by the use of ultrasound. Stellate ganglion block is foremost among these. The position
of the great vessels of the neck, the thyroid gland, the esophagus, and the vertebral artery can only be inferred from
the position of the bony elements of the spine using fluoroscopy (Figure 4. Stellate ganglion block. Anatomy
relevant to stellate ganglion block as seen on ultrasound. Transverse (short-axis) ultrasound view at the level of the
transverse process of C7. Note that the vertebral artery can be seen anterior to the echogenic transverse process at
the level of C7. The vertebral artery cannot be seen clearly at the C6 level on ultrasound, as it lies posterior to the
echogenic transverse process within the foramen transversarium. At the level of C7, the superior margin of the
thyroid is seen just lateral to the trachea. The dashed arrow indicates the optimal trajectory for placing a needle
using an in-plane approach, for example, placing the needle in a lateral to medial direction with the shaft in the
transverse plane of the ultrasound image. Ultrasound image courtesy of Urs Eichenberger MD, PhD, University
Department of Anesthesiology and Pain Therapy, University Hospital of Bern, Bern, Switzerland, 2011.) These
structures can be directly visualized using ultrasound. Techniques for using ultrasound to safely perform this block
have been described.24 The use of ultrasound is likely to quickly replace the use of fluoroscopy based for stellate
ganglion block. The position of the pleura during
intercostal block can only be inferred from the position
of the inferior margin of the rib during intercostal nerve
block when using fluoroscopy. The pleura and the
neurovascular bundle can both be seen directly using
ultrasound, facilitating precise placement of the
injectate adjacent to the intercostal nerve while
avoiding penetration of the pleura. If a pneumothorax is
suspected following injection, M-mode ultrasound
provides a simple bedside means to detect even the
smallest air collections.25
Prevention of Intra-arterial Injection

Prevention of intravascular injection relies on the
ability to identify when the tip of a needle or catheter
lies within a vascular structure before local anesthetic
or particulate steroid is administered. The
consequences of intravascular injection depend on the
vascular structure into which the injectate is placed and
the nature of the injectate. Local anesthetic and
neurolytic solutions are often administered in relatively
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large doses for specific procedures – in pain treatment, doses of local anesthetic large enough to produce systemic
toxicity are employed only during less common procedures, like celiac plexus block. Conventional means for
detecting intravascular injection rely on visual evidence of blood on aspiration or detection of signs and symptoms
associated with intravascular injection. Local aesthetics can produce unique symptoms when injected into the blood
stream, including tinnitus, circumoral paresthesias, and metallic taste – but these symptoms do not occur reliably,
particularly with more potent agents like bupivacaine. The addition of epinephrine to the injectate in small
concentrations, e.g. 1:200,000, can lead to an increase in heart rate following intravascular injection, but this also
can be unreliable, particularly in those with cardiac disease receiving beta-blockers. Local anesthetic toxicity can
occur after either intravenous or intra-arterial injection; recognition and treatment have been discussed in detail in
previous reviews. 26
Intra-arterial injection of particulate steroid can lead to devastating neurologic injury. Radiographic
guidance lends a unique and sensitive means to detect intravascular needle or catheter location, and this approach
can be used to prevent inadvertent injection of local anesthetic or steroid into a vascular structure. Injection of
radiographic contrast into a vascular structure can only be detected reliably by using a live technique. If contrast is
injected followed by obtaining a single, static image thereafter, any contrast that was injected intravascularly will
have been carried away from the site of injection by the passing blood flow. The contrast must be injected under
continuous x-ray exposure. The use of digital subtraction improves visualization of vascular structures by
subtracting the baseline image and leaving only those structures that are in motion as the image sequence is taken
(Figure 5. Posterior-Anterior view of the cervical spine during C7/T1 transforaminal injection, including a digital
subtraction sequence after contrast injection. An anteroposterior view of an angiogram obtained after injection of
contrast medium, prior to planned transforaminal injection of corticosteroids. A: Image as seen on fluoroscopy. The
needle lies in the left C7/T1 intervertebral foramen. Contrast medium outlines the spinal nerve (large arrow). The
radicular artery appears as a thin tortuous line of contrast passing medially from the site of injection (small arrow).
B: Digital subtraction angiogram reveals that the radicular artery (small arrow) extends to the midline to join the
anterior spinal artery and much of the contrast is located in the correct location surrounding the spinal nerve (large
arrow). Reprinted from
Rathmell JP, Aprill C,
Bogduk N. Cervical
transforaminal injection
of steroids.
Anesthesiology.
2004;100:1,597, with
permission.) Live
fluoroscopy, with or
without digital
subtraction, increases the
sensitivity of detecting
intravascular needle
location. In one series,
20% of cervical
transforaminal injections
were identified with live
fluoroscopy,10 while only
20% had evidence of
blood return on
aspiration.11 The addition
of digital subtraction
increases the sensitivity
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for detection of intravascular location.13 After intravascular needle position has been ruled out using contrast
injection and a live x-ray technique, it is critical to assure that the needle position does not move. Attaching a short,
flexible extension tubing to the needle at the start of the procedure allows the practitioner performing the injection to
attach and detach syringes to the catheter without touching the needle, thus reducing the chance of any change in
needle position before the particulate steroid is administered. Using this combination of live x-ray and radiographic
contrast, there have been no reports of neural injury attributed to particulate steroid. It is important to remain
vigilant, as patient movement and confusing patterns of contrast spread can easily be missed and intravascular
needle position could be overlooked.
Prevention of Intrathecal Injection

Use of radiographic guidance and injection of small volumes of radiographic contrast can also be used to identify
when a needle has penetrated the dura. Injection of subarachnoid local anesthetic will lead to a sensory and motor
block when administered at the lumbar level and total spinal anesthesia accompanied by respiratory arrest when
injected at the cervical level. While the topic of ongoing debate, intrathecal injection of particulate steroid
preparations may lead to neurotoxicity. Practitioners must learn to recognize the characteristic patterns of epidural
and intrathecal contrast spread. It is also important to recognize unusual patterns like the loculated posterior contrast
collections that signal subdural injection.27 During epidural steroid injection, it is wise to abort the procedure before
placing steroid when either subdural or intrathecal needle position is suspected.
Treatment and When to Seek Consultation

Prevention of injury is the only reliable means to assure the safety of image-guided pain interventions. Once either
direct trauma to neural structures or intra-arterial injection of particulate steroid has occurred, there is no effective
means to improve the outcome. Immediate, supportive care should be given, including airway management,
hemodynamic resuscitation, and treatment of seizures. Diagnostic imaging should be obtained when feasible to
establish the location, nature and magnitude of the injury. Thereafter, transfer to the care of a neurologist or
neurosurgeon for supportive care is likely the best route. In the case of spinal cord injury, there is some evidence
that use of high dose intravenous steroids following traumatic spinal cord transection can improve neurologic
outcome 28,29 and on this basis some experts advocate treatment of spinal cord injury secondary to needle trauma or
ischemia in the same way. Permanent, disabling spinal cord injury is more the most likely long-term outcome.9
After acute stabilization, most patients will need rehabilitation aimed at regaining functional capacity.
Summary
The use of image guidance has become a routine and integral component of pain treatment, however, there is
insufficient scientific evidence to judge whether this has improved safety. The logical appeal is overwhelming, to
the point that it is now unlikely that scientific comparisons of most techniques with and without radiographic
guidance will ever be conducted. This manuscript is meant to be a pragmatic discussion of what we know about the
utility of imaging in improving the safety of interventional pain treatments. This analysis can also serve to guide
future investigators who set out to understand how to apply new imaging techniques, and in the process how to
rigorously evaluate their usefulness.
References
1
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Sethee J, Rathmell JP. Epidural steroid injections are useful for the treatment of low back pain and radicular
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3
Armon C, Argoff CE, Samuels J, Backonja MM; Therapeutics and Technology Assessment Subcommittee of the
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Renfrew DL, Moore TE, Kathol MH, et al. Correct placement of epidural steroid injections: Fluoroscopic guidance
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El-Khoury G, Ehara S, Weinstein JN, et al. Epidural steroid injection: a procedure ideally performed with
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8
Stevens DS, Balatbat GR, Lee FM. Coaxial imaging technique for superior hypogastric plexus block. Reg Anesth
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Nahm FS, Lee CJ, Lee SH, Kim TH, Sim WS, Cho HS, Park SY, Kim YC, Lee SC. Risk of intravascular injection
in transforaminal epidural injections. Anaesthesia 2010;65:917-21.
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Kim do W, Han KR, Kim C, Chae YJ. Intravascular flow patterns in transforaminal epidural injections: a
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Rathmell JP. Toward improving the safety of transforaminal injection. Anesth Analg 2009;109:8-10.
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McLean JP, Sigler JD, Plastaras CT, Garvan CW, Rittenberg JD. The rate of detection of intravascular injection in
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2009;1:636-42.
14
Manchikanti L, Pampati V, Boswell MV, Smith HS, Hirsch JA. Analysis of the growth of epidural injections and
costs in the Medicare population: a comparative evaluation of 1997, 2002, and 2006 data. Pain Physician
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Wong GY, Brown DL. Transient paraplegia following alcohol celiac plexus block. Reg Anesth 1995;20:352-5.
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Abdalla EK, Schell SR. Paraplegia following intraoperative celiac plexus injection. J Gastrointest Surg
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Rathmell JP, Aprill C, Bogduk N. Cervical transforaminal injection of steroids. Anesthesiology 2004;100:1595-
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Edlow BL, Wainger BJ, Frosch MP, Copen WA, Rathmell JP, Rost NS. Posterior circulation stroke after C1-C2
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Okubadejo GO, Talcott MR, Schmidt RE, Sharma A, Patel AA, Mackey RB, Guarino AH, Moran CJ, Riew KD.
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Dawley JD, Moeller-Bertram T, Wallace MS, Patel PM. Intra-arterial injection in the rat brain: evaluation of
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Bernards CM, Hadzic A, Suresh S, Neal JM. Regional anesthesia in anesthetized or heavily sedated patients. Reg
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DISCLOSURE
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REMS, Pill Mills, Legitimate Opioid Use and the Pain Physician
Rafael Miguel, M.D. Tampa, Florida
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Update on the Pharmacological Management of Chronic Pain

Honorio T. Benzon, M.D. Chicago, Illinois
Opioids
Morphine has a variable oral bioavailability between 30 and 65% (table 1). Its metabolites include morphine-6-
glucuronide which causes additional analgesia, and morphine-3-glucuronide (M3G) which cause adverse effects. Its
hydrophilicity results in the delay in its transport across the blood-brain barrier, slower onset of action, and longer
analgesic effect (4-5h) relative to its plasma ½ life (2-3.5h). This result in less accumulation and improved safety.1
Its metabolism is via the liver end excretion of its metabolites are through the kidneys.
Oxycodone has intrinsic analgesic properties (activation of kappa-opioid receptors) and is predominantly a prodrug.
It is converted by the enzyme cytochrome P450 2D6 to oxymorphone and noroxycodone, an inactive metabolite.
Ten % of the population has lower levels of the enzyme resulting in lower concentrations of the oxymorphone and
higher dosages are required to obtain relief. It has no ceiling dose, minimal side effects, minimal active metabolite,
rapid onset of action, long duration of action, & predictable pharmacokinetics.2 It has a more predictable and slightly
higher bioavailability (>50%) (table 1) than morphine. The oxycodone:morphine ratio is 1:1.5.
Hydromorphone is 3 to 5 times more potent than morphine when given orally and 5 to 7 times as potent when given
parenterally. Its duration of analgesic effect, at 3-4 hours, is similar to morphine (Table 1). Pruritus, sedation,
nausea, and vomiting occur less frequently compared to morphine.3 Its metabolite, hydromorphone-3-glucoronide
(H3G) lacks analgesic property but has neuroexcitatory properties similar to M3G. H3G is produced in small
quantities explaining the relative absence of neuroexcitatory symptoms.
Oxymorphone is available in an immediate and slow-release preparation (OpanaR). It has great affinity for the mu-
and delta opioid receptors with little affinity for the k-opioid receptor.4,5 It causes less histamine release compared to
morphine.6 It’s bioavailability is only 10% due to extensive first-pass hepatic metabolism. Steady-state occurs after
3 days of BID dosing. There is minimal interaction with cytochrome P450 enzymes resulting in less interpatient
variability and fewer drug-drug interactions. Alcohol combined with oxymorphone has been shown to result in an
almost 300% increase in the plasma concentration of the drug.5
Table 1. Selected Opioids: Oral Bioavailability, Half-lives, Duration of Action, & Metabolites
Opioid Availability (%) ½ life (h) Duration (h) Metabolites
Morphine 30-65 2-3 4-5 M6G, M3G
Oxycontin 60-80 4.5 12 Oxymorphone
Noroxycodone
Hydromorphone 24 2.3 3-4 H3G
Oxymorphone 10 9 +/- 3 12 O3G
6-OH-oxymorphone
Methadone 60-95 15-60 (22) 6-8
M6G: morphine-6-glucuronide; M3G: morphine-3-glucuronide; H3G: hydromorphone-3-glucuronide; O3G:
oxymorphone-3-glucuronide
From Benzon HT, Rathmell J, Wu C, Turk DC, Argoff C (Eds). Raj’s Practical Management of Pain. 4th Edn.
Philadelphia: Mosby-Elsevier, 2008, pp 606
Methadone has 60-95% bioavailability, high potency, and a long duration of action. Its potency compared to
morphine ranges from 1:1 to 1:4. Its unpredictable half-life (15 to 60 hours, mean of 22 hours) increases the risk of
accumulation and the need for careful and individualized dosing. The rates of metabolism of methadone vary greatly
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between individuals.7 The cardiac arrythmias include QT prolongation (see Box 1), occurring mostly in patients on
high dose maintenance (>120 mg) for the treatment of addiction.8 A third of fatal methadone overdoses were in
patients who were prescribed methadone.9 Guidelines for its use include elicitation of history of heart disease or
arrhythmia, disclosure of the risk of arrhythmia from methadone, screening pre-ECG, follow-up ECG within 30
days and annually especially for doses greater than 100 mg/day.10
Box 1: Criteria for Normal, Borderline and Prolonged QTc Intervals

QTc (msec) Male Female
Normal <430 < 450
Borderline 431-450 451-470
Prolonged >450 >470
Recommendations based on QTc intervals:10
QTc interval 450-500 ms: discuss risks
>500 ms: reduce methadone dose or discontinue
Hydrocodone has a serum ½ life of 3.8 hours and is metabolized by the liver; it has strong anitussive properties
similar to codeine. Many pharmaceutical products combine hydrocodone and nonopioid analgesics specifically
acetaminophen, these combination products have been shown to cause psychomotor impairment in volunteers.11 The
abuse potential of hydrocodone appears to be similar to oxycodone and is dose-related.12
Codeine is transformed to morphine, via the enzyme cytochrome P450 2D6, and has an NNT of 16.7. Nine percent
of Caucasians do not have the enzyme and do not experience analgesia from codeine.13 Children less than 12 years
of age lack maturity of the enzyme and cannot convert the drug to morphine, experiencing the drug’s side effects
with minimal analgesia.14 Studies showed that some Asians, specifically the Chinese, also lack the enzyme.15
Tramadol is an opioid agonist and a monoaminergic drug. It has a high bioavailability (80-90%) and a dose
dependent analgesic efficacy. An issue is its association with seizure activity, although occuring in less than 1% of
users, especially in patients with a history of alcohol abuse, renal insufficiency, stroke, and head injury. Patients who
are on SSRIs should probably not take tramadol because of the risk of development of serotonin syndrome. The
syndrome is chracterized by the triad of neuromuscular and autonomic hyperactivity, and altered mental status.16
Side Effects: For constipation, methylnaltrexone (RelistorR) is given subcutaneously and works directly in the GI
tract. It appears to be effective in reversing the GI effects of opioids.17 Alvimopan (AdolorR) is given orally and has
been studied for opiate induced bowel dysfunction and for prevention of postoperative ileus.18,19 Opioids affect the
HPA axis and the hypothalamic-pituitary-gonadal axis, causing a decrease in testosterone, estrogen, cortisol,
luteinizing hormone, and follicle-stimulating hormone, and an increase in prolactin. These disturbances can lead to
amenorrhea, irregular menses, galactorrhea, decreased libido, and osteoporosis.20 Opioids may alter the
development, differentiation, and function of immune cells. Repeated administration of opioids may result in opioid-
induced hyperalgesia. A possible mechanism involves neuroplastic changes in both the peripheral and central
nervous systems leading to sensitization of pro-nociceptive pathways.21
Opioids and driving performance: Stable doses of morphine of up to 290 mg are considered non-hazardous with
regards to driving abilities.22 Patients on stable doses of transdermal fentanyl over 2 weeks show no significant
psychomotor impairment when compared to volunteers.23 Patients who have dose increments greater than 30% in
the past 2 days show worsening of their cognitive performance.24 The psychomotor performance and driving ability
of patients on opioids (average, 118 mg morphine) and normal volunteer controls were noted to be similar.25
Efficacy of opioids in different chronic pain syndromes:
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Opioids are the mainstay of treatment for cancer pain.26 Long-acting opioids are preferred and should be
supplemented by short-acting analgesics for breakthrough pain. For low back pain, up to 60% of patients are
prescribed opioids for LBP.27 Patients on opioids include those with greater disability, poorer functioning, greater
distress and suffering, higher functional disability scores, have neurologic signs, dermatomal pain distributions, and
pain radiation.28,29 A meta-analysis that compared the efficacy of different opioids demonstrated a nonsignificant
reduction from baseline and the authors concluded that opioids may be efficacious for short-term relief but long-
term efficacy (> 16 weeks) is unclear.27 For neuropathic pain. Studies showed efficacy of opioids,30,31 short-term
studies provide equivocal evidence while intermediate-term studies demonstrate efficacy of opioids over placebo.32
A placebo-controlled study showed the superiority of morphine over mexiletine in phantom pain.33 The combination
of a gabapentin and an opioid has been shown to result in better analgesia, less side effects, and lower doses of each
drugs.34 For fibromyalgia, tramadol35 or tramadol/acetaminophen36 combination has been shown to be more
effective than placebo.
Anticonvulsants
Gabapentin has few side effects (table 2) and lack drug-drug interactions. Median effective dose ranges from 900 to
1800 mg. Gabapentin has been shown to be effective in PHN, DPN, and SCI.1-3 The combination of gabapentin and
morphine was shown to be more effective than either drug alone and at lower dosages.4 It appears not to effective in
post-amputation and phantom limb pain.5 The combination of gabapentin and nortriptyline was found to be very
effective in neuropathic pain from diabetes and varicella zoster.6
Pregabalin shares the same mode of action as gabapentin but with a more rapid onset of action, linear
pharmacokinetics, fewer dose-related side effects, and BID versus TID dosing. Pregabalin is effective in PHN,
DPN, SCI pain, and fibromyalgia.7-10 In a study on neuropathic pain of different etiology pregabalin was noted to be
effective in this broad range of neuropathic pain syndromes.11 Significant differences were noted in sleep
interference, anxiety and depression subscales, and patient satisfaction between pregabalin and placebo.
Lamotrigine has been shown to be effective in HIV polyneuropathy, DPN, and pain from SCI and central post-
stroke pain (CPSP).12-14 It was noted to be effective in patients with trigeminal neuralgia who were not responsive to
carbamazepine.15 The most common side effect is rash, the incidence is increased in patients taking valproate.
Table 2. Side Effects Common Anticonvulsants and Antidepressants

Gabapentin & pregabalin Dizziness, somnolence, fatigue, weight gain, peripheral
edema
Lamotrigine Rash, Stevens Johnson syndrome
Oxcarbazepine Hyponatremia, low thyroid concentrations
Topiramate Weight loss, cognitive effects
Valproic acid (DepakoteR) Tremor
TCAs Cholinergic effects (dry mouth, sedation, urinary
retention)
Milnacipran Nausea, headache, constipation
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Antidepressants
The NNTs of antidepressants are comparable to opioids and anticonvulsants (table 3). Amitriptyline, nortriptyline,
and desipramine have been shown to be effective in PHN.1-3 Nortriptyline and amitriptyline are both effective in
PHN but nortriptyline has fewer side effects. For DPN, amitriptyline and desipramine appear to be equally effective4
while clomipramine appears to be better than desipramine.5 A combination of gabapentin and nortriptyline – two
generic medications - was found to be very effective in neuropathic pain from diabetes and varicella zoster.6 TCAs,
but not SSRIs, impair driving ability during the first week or during the dose escalation of the drug but performance
returns to baseline after one week. 7,8
Selective Serotonin Reuptake Inhibitors (SSRIs): The antinociceptive effect of SNRIs appears to involve
serotonergic as well as opioidergic (e.g. paroxetine) systems. IN DPN, SSRIs, specifically fluoxetine, appears to be
less effective than amitriptyline or desipramine.4 SSRIs appear to be of minimal benefit in fibromyalgia.
Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs): SNRIs block the reuptake of serotonin and norepinephrine,
with venlaflaxine having increased selectivity for serotonin. Duloxetine has a high and balanced affinity for both
norepinephrine and serotonin reuptake transporters.9 Venlafaxine and duloxetine have been shown to have an
analgesic effect in the nerve constriction model of neuropathic pain.10 Duloxetine is effective in DPN and in
fibromyalgia.11,12
Milnacipran is an SNRI with a greater selectivity for norepinephrine over serotonin, studies showed it to be effective
in fibromyalgia.13-15 The efficacy of milnacipran in fibromyalgia was noted in terms of fatigue, physical
conditioning and discomfort.13 Salutary characteristics of the drug include its lower affinity for the muscarinic,
cholinergic, histaminergic, and alpha-adrenergic receptors, low potential for drug-drug interactions, low protein
binding, lack of activity on the cytochrome P450, and limited hepatic metabolism.15 In a pooled analysis of two
RCTs in fibromyalgia, milnacipram, in doses of either 100 mg/day or 200 mg/day, was noted to be superior to be
placebo in terms of pain relief, improvement in the SF-36 Physical Component summary scores, and patient
satisfaction.16 The IASPNeuP-SIG and the European FNS now consider the SNRIs as an excellent choice for the
treatment of DPN.
Comparison of opioids, anticonvulsants and antidepressants: The NNTs and NNHs of opioids,
anticonvulsants, and antidepressants are in table 3.
Table 3. Numbers-Needed-to Treat (NNT) and Numbers-Needed-to-Harm (NNH) of the Different Drugs
Drugs Numbers-Needed-to-Treat (NNT) Numbers-Needed-to-Harm (NNH)
Opioids 2.1 – 3.8 9
Anticonvulsants 2.9 (DPN); 3.9 (PHN) 3.7 (minor event); NS (major event)
TCAs 2.0 – 2.8 (PHN); 1.3 – 3.4 (DPN); 1.7 (CP) 4.5 (minor); 16 (major adverse event)
SSRIs 6.7 ; 5 (paroxetine); 15.3 (fluxetine) 21-24
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Which drug(s) to use? Based on original studies, review articles, and meta-analyses publications, the
recommended drugs for the different chronic pain syndromes are listed on table 4.
Table 4. Recommended drugs for the different chronic pain syndrome

PHN DPN SCI Fibromyalgia HIV Neuropathy CRPS
Pregabalin Pregabalin Pregabalin Duloxetine Lamotrigine Gabapentin
Gabapentin Gabapentin Gabapentin Pregabalin Gabapentin Ketamine
infusion
Opioid Duloxetine IV lidocaine Milnacipran
Antidepressants Antidepressants Tramadol
Tramadol
Lidoderm patch
Ketamine infusion for CRPS & other chronic pain syndromes: Two randomized double-blind studies
showed the efficacy of ketamine infusion in CRPS. In the first study, 60 patients with CRPS I had ketamine infusion
at1.2 ug/kg/min (5mg/h/70 kg, max: 7.2 ug/kg/min (30 mg/h/70 kg) for 4-5 days.1 There was significant pain relief
but it was lost at 12 weeks; there was no functional improvement. The other study showed statistically significant
reduction in many pain parameters.2 In this study, the patients were given ketamine infusion, for 4 hours (25 mg/h)
daily for 10 days. The maximum rate of infusion was 0.35 mg/kg/h, not to exceed 25 mg/h; clonidine and
midazolam were also given to the patients.2 The efficacy of ketamine infusion in other chronic pain syndromes was
noted in a retrospective study. The infusion was noted to be helpful in patients with CRPS, refractory headaches and
back pain; 25-51% relief was noted over 3 weeks.3 There is a recent report of 3 patients who developed increased
liver enzymes and elevated eosinophils after ketamine infusion for CRPS, 10-20 mg/h infusions, two 100-hour
infusions, 16 days apart.4 The accompanying editorial discussed preclinical data about the possible mechanisms of
liver toxicity from ketamine.5
Prescription Monitoring Programs (PMPs), Risk Evaluation and Mitigation Strategy (REMS).
Patients do not adhere to the prescribed regimen, 34% underuse while 14% overuse the medications.1 A history of
substance abuse, especially with multiple substances, is a predictor of opioid misuse.2,3 A family history of
substance abuse, history of legal problems or a mood disorder are significant predictors of aberrant behavior.2,3
Validated screening questionnaires include the Screener and Opioid Assessment for Patients with Pain (SOAPP),4
the Opioid Risk Tool,5 or the Diagnosis, Intractability, Risk, Efficacy (DIRE)6 may predict aberrant behaviors.
Prescription Monitoring Programs (PMPs) include the collection of prescription data, state controlled processing
with data storage, and rules and regulations for those who have access to the data. As of October 2011, all states in
the US have either operational or enacted PMP legislation, only Missouri and New Hampshire had pending
legislation.7 There are differences between the PMPs from state to state in terms of data collection methods and the
class of drugs that are monitored.8 The National All Schedules Prescription Electronic Reporting Act (NASPER)
provides a source of funding for the states to create and improve prescription drug monitoring databases.9
There has been an epidemic of drug abuse and deaths from prescription opioids,10-12 To decrease drug abuse and
overdose, the FDA established Risk Evaluation and Mitigation Strategies (REMS) to “decrease abuse, misuse,
addiction, and overdose deaths”. Pharmaceutical companies have developed extended-release opioid medications
that are difficult to convert into more rapid-acting forms, i.e., "abuse-deterrent formulations". A new tamper
resistant formulation of Oxycontin is available, a REMS has been developed by the manufacturer of SR
hydromorphone, and a morphine preparation with embedded naltrexone (e.g. EmbedaR) has been developed.
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Last year, the White House came out with a document that included goals to tackle the problem.13 These include the
approval and implementation of REMS for certain long-acting and extended release opioids within 12 months,
legislation in all 50 states establishing PMPs within 36 months, issuance by the FDA of a guidance document
developing abuse deterrent drug formulations and post-market assessment of their performance within 24 months,
and a legislation requiring prescribers applying for DEA registration to complete training on the appropriate use,
proper storage and disposal of schedule II and III opioids.13 The central component of REMS is voluntary prescriber
education program that will be offered by continuing education providers at no cost to the medical professionals.14
Urine Drug Testing (UDT)

Reviewing the results of UDT implies knowledge of drug pharmacology and pharmacokinetics, aspects of urine
collection, and understanding the information that was provided.1 A positive UDT confirms that the patient is taking
the prescribed medication. It also informs the clinician whether the patient is taking illicit drugs as long as the drugs
are not metabolites of the prescribed medication. A UDT can be negative in a compliant patient who is a fast
metabolizer of the drug. UDT cannot be used to estimate blood concentrations or assess efficacy.1-3
The blood levels of opioids are affected by absorption, distribution (which is partly dependent on route of
administration),4,5 metabolism and transport of the drug, and receptor affinity.6-8 The pH of the urine influences the
reabsorption and excretion of drugs in the kidney.9 For example, methadone is excreted at lower urine pH.1
Enzyme-mediated immunoassay (EIA) is used for initial evaluation for UDT; EIA has adequate sensitivity but is not
specific. It cannot identify a specific opioid/metabolite and can result in false negative result by missing compounds
such as oxycodone, methadone, and fentanyl.10,11 EIA also exhibit cross-reactivity with other drugs (over the counter
diet agents and decongestants). Confirmatory testing is usually employed with liquid chromatography/mass
spectrometry or gas chromatography/mass spectrometry. With GC/MS or LC/MS, there is no cross-reactivity or
false negative results because these methods precisely identify the parent drug and its metabolites. In ordering UDT,
the physician should state the drugs that are to be included in the testing and information (name, dose, dosing
frequency) about the prescribed medications.
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Ketamine infusion
1. Sigtermans MJ, van Hilten JJ, Bauer MC, et al. Ketamine produces effective and long-term relief in patients with
complex regional pain syndrome type I. Pain 2009;145:304-311
2. Schwartzman RJ, Alexander GM, Grothusen JR, et al. Outpatient intravenous ketamine for the treatment of
complex regional pain syndrome: a double-blind placebo-controlled study. Pain 2009;147:107-115
3. Patil S, Anitescu M. Efficacy of outpatient ketamine infusions in refractory chronic pain syndrfomes: a 5-year
retrospective analysis. Pain Med 2012;13:263-269
6. Noppers IM, Niesters M, Aarts LPHJ, et al. Drug-induced liver injury following a repeated course of ketamine
treatment for chronic pain in 4RPS type 1 patients: A report of 3 cases. Pain 2011;152:2173-2178
5. Sear JW. Ketamine hepato-toxicity in chronic pain management: Another example of unexpected toxicity or a
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Prescription Monitoring Programs (PMPs), Risk Evaluation and Mitigation Strategy (REMS)
1. Broekmans S, Dobbels F, Milisen K, Morlion B, Vanderschueren S. Pharmacologic pain treatment in a
multidisciplinary pain center: Do patients adhere to the prescription of the physician? Clin J Pain 2010; 26:81-
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2. Turk DC, Swanson KS, Gatchel RJ. Predicting opioid misuse by chronic pain patients. Clin J Pain 2008;24:497-
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3. Chou R, Fanciullo GJ, Fine PG, Miaskowski C, Passik SD, Portenoy RK. Opioids for chronic noncancer pain:
prediction and identification of aberrant drug-related behaviors: a review of the evidence for an American Pain
Society and American Academy of Pain Medicine clinical practice guideline. J Pain 2009; 10:131-46
4. Butler SF, Fernandez K, Benoit C, Budman SH, Jamison RN. Validation of the revised Screener and Opioid
Assessment for Patients with Pain (SOAPP-R). J Pain 2008; 9(4):360-72
5 Webster LR, Webster RM. Predicting aberrant behaviors in opioid-treated patients: preliminary validation of the
Opioid Risk Tool. Pain Med 2005; 6:432-42
6. Belgrade MJ, Schamber CD, Lindgren BR. The DIRE score: predicting outcomes of opioid prescribing for
chronic pain. J Pain 2006; 7:671-81
7. Miguel R. Florida’s response to the prescription drug crisis. ASA Newsletter 2011;75:14-18
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Physician 2009; 12:507-15
9. Manchikanti L, Whitfield E, Pallone F. Evolution of the National All Schedules Prescription Electronic Reporting
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10. Dunn KM, Saunders KW, Rutter CM, et al. Opioid prescriptions for chronic pain and overdose: a cohort study.
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Urine drug testing

1. Nafziger AN, Bertino JS. Utility and application of urine drug testing in chronic pain management with opioids.
Clin J Pain 2009;25:73-79
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3. Bernard JP, Opdal MS, Karinen R, et al. Relationship between methadone and EDPP (2-ethylidene-1,5-dimethyl-
3, 3-diphenylpyrrolidine) in urine samples from Norwegian prisons. Eur J Clin Pharmacol 2007;63:777-782
4. Osborne R, Joel S, Trew D, et al. Morphine and metabolite behavior after different routes of morphine
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Pharmacol Ther 1990;47:12-19
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metaolized drugs. Am J Med 2002;113:746-750
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rapid metabolizers due to CYP2D6 dupliaction. Phramacogenetics J. 2007;7:257-265
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10. Katz N, Fanciullo GJ. Role of urine toxicology testing in the management of chronic opioid therapy. Clin J Pain
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11. Kahan N, Srivastava A, Wilson L, et al. Misuse of and dependence on opioids: study of chronic pain patients.
Can Fam Physician. 2006;52:1081-1087
DISCLOSURE
Pfizer, Consulting Fees
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Evaluating Pain Outcomes
Sean Mackey, M.D., Ph.D. Stanford, California
This refresher course is based on the monograph: Anesthesiology Centric ACLS by Andrea Gabrielli, Michael
F. O’Connor, and Gerald A. Maccioli. It is an approved work product of the ASA’s Committee on Critical
Care, and available at:
The epidemiology of cardiac arrest in the anesthesia world is unique and special. In fact hypoxemic or
dysrhythmic cardiac arrest is rarely observed when sedation, regional or general anesthetics are provided. This
can be attributed to the development of better monitoring, safer medications, adoption of clinical standards and
advances in training. With detailed knowledge of the patient’s medical history, there is an intuitive difference in
a patient’s chance of survival. When cardiac arrest during anesthesia does occur, prompt recognition, and
diagnosis can lead to successful management.
The most recent data of cardiac arrest during anesthesia comes from the Mayo Clinic in Rochester (See Sprung
J, et al. 2002). In this study, cardiac arrest was defined as the requirement for resuscitation with either closed
chest compression or open cardiac message, after the onset of anesthesia in 518,294 patients. Cardiac arrests
after transport to the ICU were not included. The two outcome variables were survival of at least one hour after
initial resuscitation and survival to discharge from the hospital. All probable causes of cardiac arrest were
grouped into three categories: 1) intraoperative hemorrhage, 2) pre-existent cardiac pathology and 3) hypoxia,
both at intubation or extubation. Overall 24 cardiac arrests were determined to be secondary to anesthesia
(0.5/10,000 anesthetics). If one extrapolates this number to the 20 million anesthetics performed annually in the
United States, it translates to at least 1000 patients/year, or about three patients a day going from "sleep" to
cardiac arrest! This number is probably a gross underestimation since the many prestigious academic
institutions in the US and abroad that report their experiences do not necessarily reflect the incidence of this
problem in the “real world,” i.e. outside academic boundaries or abroad.
The impact on favorable outcome of having an anesthesiologist present or immediately available during a
surgical procedure is clear. In a large retrospective review, the adjusted alteration for death and failure to rescue
were greater when care was not directed by a physician anesthesiologist (alteration for death = 1.08, p< 0.04;
alteration for failure to rescue = 1.10, P < 0.01), suggesting that anesthesiologist-directed anesthesia care has a
significant positive effect on the outcome for complications in the OR, and long term mortality (see Silber, et al
2000). Appropriate vigilance and monitoring is often the key to recognition and timely response to such a crisis.
For example, in the late 80s the ASA Closed Claims study reported that 57% of hypoxiarelated deaths could
have probably been avoided simply by improved awareness of life threatening respiratory complications during
anesthesia and the use of pulse oximetry and capnography.
In the perioperative setting, patients typically deteriorate into a pulseless arrest over a period of minutes or
hours, under circumstances wholly dissimilar to other in-hospital or out-of-hospital settings. Consequently,
aggressive measures taken to support patient physiology can avert, avoid, or forestall the need for ACLS.
Additionally, patients in the perioperative period have a different milieu of pathophysiology. For example,
hypovolemia, as a cause of myocardial ischemia, is far more common than transmural infarction from plaque
rupture. Intraoperative myocardial ischemia resulting from an imbalance in O2 delivery and consumption rarely
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evolves to full pump failure or ventricular fibrillation in the operating room. The result is a different spectrum
of dysrhythmias in the operating room than in the ED. The most common cardiac dysrrythmia during general
and neuraxial anesthesia is bradycardia followed by asystole (45%). The other life threatening cardiac rhythms
are severe tachydysrrhythmias including ventricular tachycardia,ventricular fibrillation (14%), and pulseless
electrical activity (7%). Remarkably, in 33% of the cases the heart rhythm is not fully assessed or documented
Chang es in ACLS
Animal models of circulatory crisis and of CPR demonstrate that hyperventilation is almost invariably
associated with worsened survival. Ventilation at 20 breaths a minute is associated with significantly lower
survival than ventilation at 12 breaths/minute. As a whole, these studies emphasize the principle: in a low flow
state the duration of increased intrathoracic pressure is proportional to the ventilation rate and inversely
proportional to blood pressure, coronary and cerebral perfusion. Recent versions of the ACLS guidelines
have recommended lower levels of ventilatory support. This is the rationale driving the development of
technologies to ventilate patients using negative pressure.
Cardio v ersio n: S pecial Considerations

• Immediate cardioversion is indicated for a patient with serious signs & symptoms related to the tachycardia or
if ventricular rate is > 150 bpm (Table 2)
• Always be prepared to externally pace patients who are being cardioverted, as some will convert into a very
bradycardic rhythm.
• Biphasic defibrillators are more effective and utilize less energy than monophasic defibrillators. Thus biphasic
defibrillators have almost completely replaced the monophasic defibrillators discussed in older versions of
ACLS.
Rhythm Energy Sequence Monophasic Energy Sequence Biphasic PSVT 50 J, 100 J, 200 J, 300 J, 360 J 100 j
A Flutter 50 J, 100 J 50 J Atrial Fibrillation 200 J, 300 J, 360 J 50 J, 100 J Over the past two decades, there has
been increased interest in preserving vital organ perfusion during CPR and restoring it as quickly as possible
after there is a return of spontaneous circulation (ROSC). There are multiple animal studies and case series that
have suggested that vasopressin or higher doses of epinephrine may be superior to the standard doses of
epinephrine recommended in ACLS. Larger clinical studies have failed to demonstrate any consistent benefit
to either alternative, but have also not documented worsening of outcome associated with their use. Several of
the algorithms in the work product incorporate vasopressin in addition to epinephrine, as it is the opinion of the
authors that the combination of the two drugs is likely superior to either alone in those clinical settings.
Avoiding ACLS is as important as performing it well. The monograph offers the algorithms below as
reasonable approaches to the management of patients with LV shock and RV shock. Cardiac arrest in
perioperative patients typically occurs as a consequence of either hypoxemia or the progression of a circulatory
process. Avoiding cardiac arrest requires successfully managing acute anemia, hypoxemia, and all contributing
factors to cardiac output: preload, contractility, and afterload. Anesthesiologists are masters of recognizing and
treating hypoxemia. Consequently the focus of the remainder of this document will be on the management of
cardiopulmonary interactions and the circulation in the rapidly decompensating patient. Traditional ACLS is
intended for caregivers summoned to aid a patient who has suddenly collapsed. In the perioperative setting, the
list of causes is substantially larger, and ACLS needs to be managed concurrently with the anesthetic and
operation.
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Co mmo n Causes o f A CLS ev ents in the perio perativ e setting Anesthetic

o Intravenous anesthetic overdose
o Inhalation anesthetic overdose
o Neuraxial block with high level sympathectomy
o Local anesthetic systemic toxicity
o Malignant hyperthermia
o Drug administration errors
Respiratory
o Hypoxemia
o Auto PEEP
o Acute Bronchospasm
Cardiovascular
o Vasovagal reflex
o Hypovolemic and/or hemorrhagic shock
o Tension Pneumothorax
o AnaphylacticReaction
o Transfusion Reaction
o Acute Electrolyte Imbalance (high K)
o Severe Pulmonary Hypertension
o Increased intraabdominal pressure
o Pacemaker failure
o Prolonged Q-T syndrome
o Acute Coronary Syndrome
o Pulmonary Embolism
o Gas embolism
o Oculocardiac reflexes
o Electroconvulsive therapy
Reco g nizing cardiac arrest in the OR
- EKG with pulseless rhythm (V-tach, V-fib)
- Loss of pulse X 10 seconds
- Loss of end-tidal CO2
- Loss of plethysmograph
B LS /A CLS in the OR – S o me key po ints to remember . . .
- CPR for patients under general anesthesia need not be preceded by “Annie! Annie! Are you okay?”
- Instruct appropriate personnel to start effective CPR.
- Discontinue the anesthetic and surgery
- Call for help, defibrillator
- Bag mask ventilation if ETT not in place followed by immediate
endotracheal intubation if feasible FiO2 = 1.0
- Don't stop CPR unnecessarily! Capnography is a more reliable indicator of ROSC than carotid
or femoral arterial pulse palpation.
- Capnograph to confirm advance airway positioning and effective CPR
- Hand ventilate rate 8 -10, VT to chest rise, TI one second with 100% oxygen – assess for
obstruction, if none, institute mechanical ventilation. If obstruction, suction, fiberoptic bronchoscopy,
consider exchanging the airway. Continue CPR.
- Open all IVs to wide open
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Anaphylaxis
Anaphylaxis is a rare but important cause of circulatory collapse in the perioperative period. While
there is a wide range of minor allergic reactions, hypotension, tachycardia and bronchospasm can be
more easily followed by vasogenic shock when the offending agent is administered as a rapid
intravenous bolus, the most common route of drug administration during anesthesia. The
preponderance of anaphylaxis in perioperative patients is caused by a small number of drugs.
Anaphylactic shock has been identified as a coexisting or major indeterminate factor for dysrhythmic
cardiac arrest during anesthesia occurring in 2.2 to 22.4 per 10,000 anesthetics with 3% to 4% of them
being life threatening.
N euro axial Anesthesia

Cardiac arrest in association with neuraxial (spinal or subarachnoid block) anesthesia remains the most
mysterious cause of morbidity and mortality in the perioperative period. Its existence would be controversial,
except that is has been well documented as an occurrence in younger, otherwise healthy patients undergoing a
variety of clinical procedures. Its pathophysiology remains a mystery. Clinically, the only unifying feature of
this syndrome is the degree of surprise among the caregivers of these patients. Various hypotheses have been
put forward over the years, invoking unrecognized respiratory depression, excessive sedation concurrent with
high block, under appreciation of both the direct and indirect circulatory consequences of a high spinal
anesthetic, and ‘failure to rescue’ with airway management and drugs. Hypoxemia from hypoventilation does
not appear to be the cause, as there are case reports documenting adequate saturation in these patients. Thus
there is a substantial amount of basic science and clinical interest in the effects of high spinal anesthesia on the
sympathetic innervation of the heart and the circulation.
The most recent North American review of the epidemiology of cardiac arrest during neuraxial
anesthesia indicates the prevalence of cardiac arrest at 1.8 per 10,000 patients (neuraxial), with more
arrests occurring in patients with spinal anesthesia versus epidural (2.9 vs. 0.9 per 10,000 ; P = 0.041)
(Anesth Analg 2005;100:855-
865). In 46% (12/46) of the cases cardiac arrest was associated with recurrent specific surgical events
(cementing of joint components, spermatic cord manipulation, manipulation of a broken femur, and rupture of
amniotic membranes). In 54% (14/26), the anesthetic technique, i.e. subarachnoid block contributed directly to
the arrest. The choice of vasopressors during neuraxial anesthesia is still being debated.
Treatment o f Cardiac A rrest A sso ciated w ith N euraxial Anesthesia

- Discontinue anesthetic or sedation infusion
- Ventilate with 100% Oxygen, intubate trachea
- Begin CPR if patient has significant bradycardia or is pulseless >10sec
- Treat bradycardia with 1mg Atropine
- Treat with at least 1 mg epinephrine IV (up to 0.1mg/kg)
- Consider concurrent treatment with 40 u vasopressin
N.B. – the full monograph covers a variety of other scenarios, which are not
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included in this handout due to space limitations. These include:

o Local Anesthetic Overdose
o Gas embolism
o Tachycardia
o Bradycardia
o Obstretric Patients
D ifferential D iag no sis fo r perio perativ e PEA o r

A sy sto le: 8 H & 8T
Hypoxia Trauma/hypovolemia
Hypovolemia Tension Pneumothorax
Hyper-vagal Thrombosis of Coronary
Hydrogen Ion Tamponade
Hyperkalemia Thrombus in Pulmonary Artery
Malignant Hyperthermia Long QT syndrome
Hypothermia Toxins (anaphylaxis)
Hypoglycemia Pulmonary HTN
REFERENCES
www.asahq.org/clinical/Anesthesiology-CentricACLS.pdf - 2008-02-19
2005 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular
care. Part 4: Adult Basic Life Support. Circulation 2005;112:IV-18-IV-34. Lagasse RS: Anesthesia safety:
Model or myth? A review of the published literature and analysis of current original data. Anesthesiology 2002;
97:1609-1617
Biboulet P, Aubas P, Dubourdieu J, Rubenovitch J, Capdevila X, d'Athis F. Fatal and non-fatal cardiac arrests
related to anesthesia. Can J Anesth 2001; 48:326-332 .
Olsson GL, Hallen B. Cardiac arrest during anaesthesia. A computer-aided study in 250,543 anaesthetics. Acta
Anaesthesiol Scand 1988; 32:653-664
Newland MC, Ellis SJ, Lydiatt CA, et al. Anesthetic-related cardiac arrest and its mortality. A report covering
72,959 anesthetics over 10 years from a US teaching hospital. Anesthesiology 2002;97:108-115
Runciman WB, Morris RW, Watterson LM et al. Crisis management during anaesthesia: Cardiac arrest. Qual
Saf Health Care 2005; 14:e14
Silber JH, Kennedy SK, Even-Shoshan O, et al. Anesthesiologist direction and patient outcomes.
Tinker JH, Dull DL, Caplan RA, Ward RJ, Cheney FW. Role of monitoring devices in prevention of anesthetic
mishaps: a closed claims analysis. Anesthesiology 1989;71:541-546
Sprung J, Warner ME, Contreras MG, et al. Predictors of survival following cardiac arrest in patients
undergoing non-cardiac surgery: a study of 518,294 patients at a tertiary referral center. Anesthesiology 2002;
99:259-269
Kopp SL, Horlocker TT, Warner ME, et al. Cardiac arrest during neuraxial anesthesia: frequency and
predisposing factors with survival. Anesth Analg 2005;100:855-865
Keenan RL, Shaprio JH, Dawson K. Frequency of anesthetic cardiac arrest in infants: effect of pediatric
anesthesiologists. J Clin Anesth 1991;3:433-7
Flick RP, Sprung J, Harrison TE, et al. Perioperative cardiac arrests in children between 1988 and 2005 at a
tertiary referral center: a study of 92,881 patients. Anesthesiology 2007;106:226-37
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DISCLOSURE
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Cancer Pain: State of the Art 2012 ASA Meeting
Allen W. Burton, M.D. Houston, Texas
Introduction:
“We don’t beat the Reaper by living longer. We beat the Reaper by living well.” Professor Randy Pausch
declared this statement during his famous last lecture at Carnagie Mellon University prior to his death from
pancreatic cancer in 2008. (Pausch 2008) As opposed to the widely utilized WHO approach of utilizing opioids
first, many now advocate a mechanism based approach to cancer pain treatment. Old dogma treated cancer pain as a
problem mainly toward the end of life situation in the context of metastatic, progressive disease, whereas new data
shows pain to be problematic throughout the cancer care cycle. (Ahmedzai 2007) The effective management of
these acutely painful surgeries and related treatments may limit the development of chronic pain states in long-term
survivors.(Burton 2007) Effective treatment strategies include multidisciplinary, multimodal care utilizing: (1)
combinations of long acting opioids for constant pain with short acting opioids for incidental pain; (2) ‘adjuvant’
co-analgesics including non-steroidal anti-inflammatories, anticonvulsants, antidepressants, and topical agents to
optimize analgesia and minimize opioid doses thereby reducing concomitant opioid related side effects; (3)
prophylactic treatment of constipation, nausea, and other common troublesome symptoms;(4) interventional options
for pain control including: nerve blocks, spinal infusions, vertebral augmentation, and other procedures. Lastly (5),
psychological evaluation and support must not be overlooked. This monograph will focus on the role of procedures
in context of the overall cancer treatment and in the overall context of palliative care. Traditional analgesic
procedures will be discussed in addition to briefly highlighting neurodestructive procedures, vertebro and
kyphoplasty, fracture stabilization, tumor ablation, and others. Finally, the decision making relating to the role,
timing, and special risks of procedures in the cancer patient will be highlighted. This monograph is devoted to the
science and decision making aspects of interventional cancer pain techniques; for a “how” to do it approach, the
interested reader is directed to either Rathmell or Brown’s excellent atlas’of interventional pain procedures.
(Rathmell JP 2006, Brown DL 2006)
Decision Making:
In traditional pain management teachings, several arbitrary distinctions are usually created. Cancer pain,
chronic pain (so called “non-malignant” pain), and acute pain are viewed as distinct clinical entities with unique
treatment strategies. In fact, these distinct clinical entities represent slightly different aspects of common
pathophysiologic states which blend together in a disease continuum. Therefore, there is much overlap in
appropriate therapeutic approaches to “cancer pain.” For example, optimal acute pain management for cancer
surgery may be important to the patient’s overall outcome in the avoidance of chronic pain and perhaps even
improved survival. (Vila 2007)
When considering the need for procedural intervention in the patient with progressive cancer, the decision
making algorithm is complex, but generally comes down to a decision algorithm which includes failure to achieve
adequate pain relief through pharmacological means and pain anatomically susceptible to an intervention. (Swarm
2007) These issues usually generate a referral to an interventionalist, often-but not necessarily-an anesthesiologist.
Often, patient’s pharmacologic options have been exhausted and the referral for an intervention occurs very far
along in their disease process, essentially at the very end stages of life. However, this traditional approach-the WHO
tier ladder, placing interventions on the fourth step is not always in the patient’s best interest. (Ahmedzai SH 2007,
Burton 2007) In many cases of localized, severe pain-the risk and benefit ratio swings in favor of an interventional
pain relieving procedure well prior to exhausting the pharmacological approaches. Typically, the procedure will not
substitute for the ongoing use of other pain control modalities entirely, but can improve pain relief and allow for a
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reduction in systemic medications and their side effects. The interventional specialist must determine if a procedure
is likely to provide tangible benefit and ensure there is no contraindication to the procedure (ie- pancytopenia,
hemodynamic instability, etc.). Finally, especially in terms of spinal infusions, advanced planning for home care
and appropriate follow-up care is critical. (Mercadante 1994)
Spinal Infusions:
Two broad groups of patients, those with poor pain relief in spite of numerous analgesic trials and those
with unacceptable side effects from analgesics may benefit from neuraxial analgesic infusions. (Crul 1991, Smith
2002, Burton 2004, Smith 2005) There have been many reports of successful analgesia with epidural and intrathecal
infusion. In our center, we have moved almost exclusively to the intrathecal route (except in the immediate
postoperative period) (Burton 2004). The reason for favoring the intrathecal route is economic; we have seen
similar analgesia with much lower infusion rates/volumes- whereas the epidural infusion regularly uses 10 or more
cc’s per hour, the intrathecal usually runs at 0.5 cc’s per hour- saving numerous resources in addition to having to
change external bags much less often. The clinical equivalence of the intrathecal and epidural routes has been
confirmed by other groups. (Mercadante 2008) Neuraxial infusions can be implemented in a variety of ways and
with various medications and equipment as outlined below.
In patients with progressive disease and a short survival time, a percutaneous catheter, portacath, “DuPens”
percutaneous catheter, or tunneled “epidural” catheter (usually placed in the intrathecal space) with an external
pump may be most cost effective, and most easily adjustable in the home care setting.(Crul 1991) Recent meta-
analysis of complications related to home, external intrathecal catheters reveals a low rate of serious complications.
The rate of superficial infection was 2.3%, deep infection 1.4%, with the authors calculating that every 71st patient
had a deep infection after 54 days of therapy, with the risk of bleeding and neurological injury 0.9% and 0.4%
respectively. (Aprili 2009) Therefore, in cancer pain patients with a short life expectancy, with adequate home
resources, and external intrathecal catheter can be considered an effective and low-cost option. One decision
making algorithm published by our group is shown in figure 1. (Phan 2005)
Patients being considered for an implanted pain pump will need a trial infusion in many ways similar to the
external infusion described above. Issues around pump implantation and management are covered in a nice “how
we do it” article by Smith and Coyne. (Smith 2003) These patients will generally have a longer life expectancy or
in some cases chronic cancer pain in a non-terminal setting. The optimal medication for infusion is a matter for a
longer monograph, however expert poly-analgesic recommendations exist and have been recently updated. (Deer
2007) In terms of chronic versus cancer pain, the main difference is a more rapid, aggressive dose and drug titration
in the cancer patients. In our center, our preferred first line is often hydromorphone alone or in combination with
bupivacaine. In refractory cases, ziconotide may be added or substituted as a potent non-opioid neuraxial analgesic.
(Rauck 2009)
Other Cancer Analgesic Procedures:

Vertebroplasty (VP) is the injection of a painful, fractured vertebral body with bone cement, generally
polymethylmethacrylate (PMMA). Kyphoplasty (KP) adds the placement of balloons into the vertebral body with
an inflation/deflation sequence to create a cavity and perhaps restore height prior to the cement injection. These
procedures are performed in a percutaneous fashion on an outpatient (or short stay) basis, usually with monitored
anesthesia care/heavy sedation. The mechanism of action is unknown, but is postulated that stabilization of the
fracture leads to analgesia.
The procedure is indicated for painful vertebral compression fractures due to osteoporosis or malignancy. The ideal
candidate has severe axial (non-radiating) pain due to a fractured vertebrae. Patients failing a short course of
conservative therapy, including analgesics and bracing, are generally considered good candidates for one of these
procedures. Patients with painful fractures more than one year old are not likely to obtain substantial benefit from
VP or KP, unless there is evidence of a fracture non-union (such as edema on MRI or a positive bone scan). Pain
relief is seen in around two-thirds of patients, and even those with advanced disease may find significant
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improvement in quality of life. (Fourney 2003, Hentschel 2005, Burton 2005) In patients with advanced metastatic
disease, these procedures can be combined with local tumor ablation and/or sequenced with spinal radiation therapy
as needed. (Georgy 2009) Finally, patients with painful spinal metastasis and neurological compromise may be
candidates for spinal surgery up to and including vertebrectomy which in many cases provides significant
improvement in quality of life and may increase lifespan as well. (Choi 2009)
Tumor Ablation (Radiofrequency/Cryoablation)/Cementoplasty:

Local tumor ablation with or without addition of bone cement is a recent addition to the cancer pain
treatment armamentarium. Several studies show favorable local pain relief following tumor ablation. Studies are
underway to determine which technique is optimal (Callstrom 2002). When a fracture is impending due to
extensive lytic involvement, then bone cement may be injected into this void created by the tumor ablation. This is
often done in the hip, femur, and pelvis. (Munk 2009)
Neurosurgical ablative:
In some cases of pain refractory to aforementioned techniques, including spinal analgesic infusion, ablative
neurosurgical techniques may be useful. Overall, the use of these techniques has dropped precipitously over the
years-presumably as other effective pain control therapies have been implemented. In many centers, it can be
difficult to find the local neurosurgical expertise to perform some of these procedures. The most commonly used
procedures include anterolateral cordotomy for lateralized pain, midline myelotomy for pelvic pain, rhizotomy
and/or dorsal root entry zone lesioning for plexopathic pain, and finally various ablative procedures used in the past
include pituitary ablation for bone pain, and others. Many authors and centers, particularly outside of the US, view
the cordotomy as a valuable technique in managing refractory cancer pain. (Raslan 2008) Techniques mainly used
experimentally or in chronic pain states include deep brain stimulation or cortical stimulation. (Fenstermaker 1999)
Surgical:
In many pathologic cancer pain states, surgical techniques may be highly effective as palliative techniques.
These include vertebrectomy for metastatic disease in selected cases-as mentioned earlier in this paper, fixation of
pathologically fractured long bones. (Choi 2009) Viscerally, placement of venting gastrostomy and feeding
jejunostomy tubes, or diverting ostomies may provide effective palliation of visceral symptoms associated with
gastric outlet obstruction. (Easson 2007) Other shunting procedures may be helpful with malignant pleural effusions
or ascites. More recently, a variety of less invasive stenting procedures have been developed for the bronchus,
esophagus, and many hollow viscera. (Sharma 2009)
Neurolytic Blocks
In many cases, clinicians may wish to, where feasible, perform a “test block” with local anesthetic to
ensure that the patient obtains analgesia from the block and does not find the sensory changes uncomfortable.
(Lamacraft 1997) Unfortunately, the down side of a “test block” is that the amount of pain relief obtained with the
neurolytic block may fall short of that achieved with the local anesthetic block.
With head and neck cancers, the pain is often diffuse and crossing tissue planes/nerve distributions making
the role of neurolytic blocks limited. Some patients will have focal pains that are amenable to the following blocks:
peripheral trigeminal (ie- supraorbital, mental), trigeminal, sphenopalatine, glossopharyngeal, occipital and
superficial cervical plexus. (Varghese 2002)
Visceral pain has a discrete innervation which makes it amenable to neurolytic blockade. For upper
abdominal pain associated with pancreatic, liver, or gastric tumor the celiac plexus block has been advocated.
Numerous approaches and medications have been tried and compared in the literature with good support for
favorable clinical outcomes in more than two-thirds of patients undergoing the block (Eisenberg 1995). In our
center, we use a posterior approach guided by fluoroscopy, with two needles placed in the retrocrural space. We
inject local anesthetic followed by 50-100% alcohol or 8-10% phenol solution up to 20 cc’s volume. Other
approaches that have been advocated include transgastric via an endoscope and anterior with ultrasound guidance
(Moore 2009, Burton 2009). The anterior approach with ultrasound is very exciting for potential application at the
bedside in a hospice setting. (Bhatnagar 2008) The majority of patients undergoing celiac block will experience
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orthostatic hypotension due to visceral vasodilatation and diarrhea due to unopposed parasympathetic effect.
Neurologically, there is a small risk of paraplegia. (Davies 1993)
For pain in the pelvic viscera, the superior hypogastric, more recently the inferior hypogastric plexus block,
and the Ganglion Impar block have been described and utilized-although not as widely as the celiac block (Plancarte
1997, Schultz 2007). The superior hypogastric block should cover pain coming from the bladder, uterus, vagina,
prostate, urethra, testes, descending colon, and rectum. An anterior approach has also been described for patients
who cannot lie prone. (Mishra 2008) The inferior hypogastric plexus lies anterior to the sacrum at approximately
the S2 level, and may provide pain relief for rectal pain according to recent case reports. The Ganglion of Impar
lies just anterior to the sacrococcygeal junction and is easily blocked with an injection just anterior to the sacrum.
This procedure often provides pain relief for perineal pain without risk of incontinence. (Plancarte 1997)
Risks of neurolytic blocks nearly always include deafferentation pain, which is the main reason neurolytic
blockade is not used in the chronic pain setting. Further, with the celiac plexus block there is a risk of paralysis-
probably due to anterior spinal artery vasospasm and infarct. With the hypogastric plexus block, we have seen
several cases of lower extremity hip flexor weakness due to inadvertent spread of neurolytic agent to the psoas
muscle with a partial denervation of the lumbar plexus (unpublished data). We have modified our technique to
ensure medial needle placement and medial dye spread prior to neurolytic injection. As neurolytic blocks are
relatively rare, the incidence of complication is difficult to determine, but weakness or paralysis are felt to occur
with less than 5% incidence and perhaps less than 1%, although they clearly are reserved for the patient with
progressive cancer and refractory pain.
Other special circumstances include neurolysis of peripheral nerves including the intercostals or other
peripheral branches. Intercostal neurolysis can produce short term relief, with one author finding a median duration
of effect to be three weeks, although in their series of 25 patients one-third had analgesia until the end of life.
(Wong 2007) These authors found optimal outcomes using a diagnostic block, followed by a 10% phenol injection
in those obtaining relief with the diagnostic block.
Subarachnoid or epidural neurolysis has been done in highly refractory cases where bladder and bowel
function are already compromised. Slatkin reported four cases of phenol saddle blocks with reasonably good
outcomes, with the use of 0.6-1 ml of 6% phenol in glycerin injected via subarachnoid injection in cases of highly
refractory pelvic cancer pain. (Slatkin 2003) This report also nicely reviews the literature.
Neurolytic blocks are often extremely helpful in patients with advanced cancer, debilitation, and severe,
refractory pain syndromes.
Conclusions
As opposed to the automatic WHO approach of utilizing opioids first, many now advocate a mechanism
based approach to cancer pain treatment. Old dogma relegated cancer pain as a problem toward the end of life
situation with metastatic, progressive disease, whereas new data shows pain to be problematic throughout the cancer
care cycle. The effective management of these acutely painful surgeries and related treatments may limit the
development of chronic pain states in long-term survivors. Effective treatment strategies include multidisciplinary,
multimodal care utilizing: (1) combinations of long acting opioids for constant pain with short acting opioids for
incidental pain; (2) ‘adjuvant’ co-analgesics including NSAIDS, anticonvulsants, antidepressants, and topicals to
minimize opioid doses and concomitant opioid related side effects; (3) prophylactic treatment of constipation,
nausea, and other symptoms;(4) interventional options for pain control including: nerve blocks, parenteral infusions,
spinal infusions, palliative XRT, palliative chemotherapy, psychological assessment with support, and surgery in
combination for optimal patient quality of life.
Finally, in cases of indolent cancer or remission, cancer pain syndromes effectively become chronic pain
states in nearly all aspects. Thus, in these situations, optimal success will be seen through the use of chronic pain
multidisciplinary assessment and treatment strategies. The goals of treatment in chronic post-cancer pain or
“success” are slightly altered from the “Freedom from cancer pain” label above the WHO ladder to the more
realistic: “Optimal functioning, optimal analgesia, and effective coping with ongoing pain.”
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This author views the WHO ladder concept as outdated and vastly oversimplified in 2010, and advocates a
mechanism based use of all the above therapies in context of the patient’s pain syndrome. More resource
commitment to support ongoing research into unrelieved cancer pain is essential. (Brawley 2009)
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Varghese BT, Koshy RC, Sebastian P, Joseph E. Combined sphenopalatine ganglion and mandibular nerve,
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Figure 1. Decision making for neuraxial infusions in refractory cancer pain. (Phan 2005)
DISCLOSURE
Medtronic, Self,Consulting Fees ; Boston Scientific, Self, Consulting Fees ; Stryker, Self, Consulting Fees ; Azur,
Self, Honoraria ; Cadence, Self, Honoraria ; Cephalon, Self, Honoraria ; Neurogesx, Self, Honoraria ; Pfizer, Self,
Honoraria ; Pricara, Self, Honoraria ; Vapo
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Complications in Interventional Pain Medicine

Richard W. Rosenquist, M.D. Cleveland, Ohio
Introduction
Contemporary pain management is founded on appropriate diagnostic evaluation followed by multimodal treatment
incorporating medical, psychological, physical and interventional modalities. The use of interventional therapies in
this context has seen meteoric growth in both the type and volume of interventional procedures used to treat chronic
pain conditions. Incomplete or inadequate treatment responses to current treatment modalities have fostered
ongoing research and the introduction of many new treatment modalities. While new interventional techniques have
improved outcomes in some patients, they have also been associated with severe complications. These include
commonly reported complications such as pneumothorax, headache, back pain, bleeding, drug toxicity and infection
as well as reports of catheter, lead or device breakage, methylmethacrylate migration, granuloma development,
direct neural trauma, stroke and death. This refresher course addresses complications related to interventional pain
treatments and suggests methods for their avoidance when appropriate.
Scope of the Problem
The relative risk associated with interventional pain therapies has been steadily increasing in concert with the
increase in medical judgment and technical skill required to use them effectively. In a 2004 publication derived
from data maintained within the American Society of Anesthesiologists Closed Claims Project, Fitzgibbon et al.1
identified and described issues and trends in liability related to chronic pain management by anesthesiologists. The
authors reviewed the closed claims database between 1970 and 1999 to identify liability related to chronic pain
management. They excluded all claims related to acute pain management. They compared outcomes and liability
characteristics of 284 pain management claims to 5,125 surgical/obstetric claims. Claims related to chronic pain
management increased over time in concert with the growth in pain medicine. They accounted for 2% of the claims
in the 1970’s, 3% in the 1980’s and 10% of all claims in the 1990’s. Payments for chronic pain management claims
were lower than surgical/obstetric claims from 1970-1989. During the 1990’s, there was no difference in size of
payments between chronic pain management and surgical/obstetric claims. Almost one-third of chronic pain
management claims resulting in payment in the 1990’s involved a permanent and disabling injury as compared to
only 17% from 1979-1989 although this difference was not considered statistically different. In 64% of chronic pain
management claims, the injury became apparent after discharge from the treatment facility. Of the 284 chronic pain
management claims in the database, 276 involved invasive procedures. Epidural steroid injections accounted for
83% of injections and 40% of all chronic pain management claims. Peripheral and autonomic blocks accounted for
36% of the block claims. The most common complication of blocks was pneumothorax. The most common
complications involving epidural steroids were nerve injury, infection and headache. Claims related to ablative
procedures involved unintentional nerve injury in 47% of the cases. Infection or retained catheter fragments were
the most common complications related to implantation or removal of devices, while the most common outcome of
claims related to maintenance of devices was death or brain damage. In 2010, Rathmell et al, 2 compared cervical
procedures to other chronic pain claims collected from 2005 through 2008 in the ASA Closed Claims Database. The
data in this manuscript is notable not only for the dramatic number of claims related to cervical procedures, but the
fact that there were more claims entered for chronic pain in a four year period than the entire previous review of
chronic pain claims for a 30 year period. There were 64 cervical procedure claims (22%) among 294 chronic pain
claims. Cervical procedure claims occurred more often among women and in healthier individuals. The most
common diagnoses included cervical radicular pain (50%) and neck pain of musculoskeletal origin (28%), CRPS
(11%) and spinal stenosis (5%). Ninety-one percent of the cervical procedures were blocks with (67%) being
epidurals, (11%) stellate ganglion blocks, (9%) trigger point injections and (3%) intra-articular facet injections. In
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eighty percent of the cases, the damaging event was directly related to the procedure; needle trauma to the cord
(31%), cord infarction/stroke after intra-arterial injection (14%), dural puncture (6%), compressive hematoma (5%),
infection or abscess (5%), high block/total spinal (5%), inadvertent intravascular injections of local anesthetic (3%)
and pneumothorax (3%). General anesthesia or sedation was used in (67%) of cervical procedure claims with spinal
cord injuries, but only (19%) of cervical procedure claims without spinal cord injuries. In claims with information
regarding radiographic guidance, it was used in (76%) of cases with spinal cord injury. The authors found evidence
of contrast use with radiographic guidance in (57%) of claims with spinal cord injury compared with (17%) of
claims without spinal cord injury after a cervical procedure. Further study is needed to develop approaches to
prevent catastrophic neurologic injuries occurring during pain procedures at the cervical level and to clarify the role
that general anesthesia and/or sedation may have in the occurrence and severity of injury. Although data in these
studies is limited to that available from closed claims, the trends identified provide valuable insight into the larger
picture of significant complications associated with interventional pain procedures and in particular cervical
interventional pain procedures that have limited evidence to support their use.
Injections (Trigger Point, Facets, Epidural Steroid ± Associated Agents, Other)
Injections are performed with the greatest frequency and have the greatest number of complications. Trigger point
injections have been associated with a variety of significant complications including, bleeding, local infection,
epidural abscess,3 seizure, myotoxicity4 and pneumothorax.5 Facet injections are performed less commonly, but have
been associated with significant complications as well. Those reported in the medical literature include infection,6,7
pneumothorax1, spinal cord injury and death.8,.9,10 The medical literature is sparse concerning other complications
that may have occurred in association with facet injection, but hematoma and nerve injury would not be unexpected.
The largest and most devastating group of complications has been associated with performance of epidural steroid
injections. Although common, the occurrence of accidental dural puncture is less threatening than other reported
complications. Some practitioners have advocated the use of the transforaminal approach as a means of avoiding
dural puncture. A cases series of transforaminal injections published in 2000 using both fluoroscopy and contrast
confirmation identified 0/322 procedures with dural puncture, although the incidence of transient headache in the
same study was reported at 3.1%.11 Another prospective series performed at two academic medical centers using an
interlaminar approach reported a 0.8% incidence of dural puncture with only 25% of cases being performed with
fluoroscopy and contrast confirmation.12 Epidural hematoma has been reported at all levels of the spine following
epidural injections and has an estimated incidence of 1:150,000.13 There have been numerous reports of epidural
hematoma occurring after epidural steroid injection.14,15,16,17 In general, if anticoagulant agents are avoided as
described in the ASRA guideline for neuraxial anesthesia or limited to NSAIDs alone, the risk of epidural hematoma
is felt to be unchanged from the norm.12,13 Infection involving the epidural space, discitis, meningitis and
osteomyelitis has been reported following epidural steroid injection.18 Epidural abscesses occur spontaneously with
an incidence that has been reported as 0.33-1.96:10,000 admissions per year19 or related to epidural catheterization
with a reported incidence of 1:1930 catheters.20,21 The incidence of epidural abscess development related to
performance of epidural steroid injections has not been reported. However, there are numerous case reports
identifying epidural abscess development.22,23,24,25,26,27,28 This complication is more insidious as it develops after the
patient has left the treatment facility and may not be promptly discovered or reported by the patient. Underlying
medical illnesses and impaired immune function may increase the risk of this complication, which is most
commonly produced by Staphylococcus aureus species. In those with significant immune compromise, prophylactic
antibiotics at the time of the procedure may be warranted. Neuropathic pain may develop following epidural steroid
injection and has been hypothesized to be the result of nerve root irritation caused by the steroid solution or damage
to the spinal cord or nerve roots without dural puncture by minor compression of neural elements.29 Direct trauma to
the spinal cord in association with performance of cervical, thoracic and lumbar epidural steroid injections has been
reported in procedures performed with and without fluoroscopic imaging.30 Those cases associated with
demonstrable spinal cord injury have been associated with permanent neurological injury. A variety of methods to
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avoid this type of devastating complication including avoiding sedation, using imaging, contrast or a local anesthetic
test dose have been suggested, although significant injury has occurred despite use of all currently recommended
safety measures. Tripathi et al., reported a case of paraplegia after intracord injection during attempted epidural
steroid injection in an awake patient under fluoroscopic guidance.31 In the case report, they comment “it seems
fluoroscopy guidance may not prevent intrathecal perforation or spinal cord penetration.” In a letter to the editor
regarding this article published in May 2006, Drs. Munir, Rastogi and Nedeljkovic comment that the implications of
this statement cannot be understated and reiterate the fact fluoroscopy does not protect patients from injection
related complications.32 This is corroborated in the Anesthesia Patient Safety Foundation newsletter published in
2005 that analyzed 13 claims related to complications after cervical epidural steroid injections.33 Twelve of 13 cases
had been performed with fluoroscopic guidance. In recent years, transforaminal approaches to epidural steroid
injections including both lumbar and cervical approaches have been associated with a growing number of severe
complications including blindness, stroke, spinal cord injury and death.34,35,36,37,38,39 The exact etiology of these
devastating injuries is not clear, but has been variously theorized to be the result of radicular artery spasm, vascular
injury or intravascular injection of particulate steroid into medullary or vertebral arteries. Although an outright
recommendation to abandon this approach has not been advocated, modifications in needle choice, needle location,
imaging and drug administration have all been proposed. At the present time, needle placement in a dorsal portion
of the foramen where medullary vessels are less likely to be located is being proposed as one means of reducing risk.
Other imaging approaches to reduce the risk include the use of live fluoroscopy during injection of contrast at a
minimum along with digital subtraction angiography (DSA) if it is available. The use of DSA will improve the
sensitivity for detecting intravascular injection.40 Some clinicians have advocated injecting local anesthetics prior to
injecting a steroid medication and the use of non-particulate steroids such as Dexamethasone as a means of avoiding
these complications. Initial outcome data examining the use of this Dexamethasone is limited and suggests that it
may not work as well as traditional long lasting preparations.41,42 A 2011 dose-response trial for Dexamethasone
demonstrated meaningful improvement in radicular pain at 12 weeks after injection with parallel improvements in
disability, impression of change and satisfaction measures. There was no difference in efficacy for Dexamethasone
4 mg compared to 8 or 12 mg.(Ahadian 2011 RAPM)43 In addition, there have been some reports of flushing after
the use of Dexamethasone in this setting with the occurrence more common in females than males.44 The frequency
of complications related to transforaminal steroid injections has garnered the attention of the FDA and there is an
ongoing effort on their part to understand the problem and collaborate with physicians to develop recommendations
to reduce the risk of complications. Finally, co-administration of opioids, local anesthetic or both occurred in 61%
of claims reported in the ASA closed claims epidural steroid injection cases and death or brain damage occurred
only in epidural steroid injection cases that involved local anesthetics with or without opioids in the injection.1
Blocks (Peripheral, Axial, Neuraxial, Autonomic)
The most common complication following the performance of blocks is pneumothorax and accounted for 51% of all
block claims in the ASA closed claims database. Other complications include infection, nerve injury, dural puncture,
vascular injury, hematoma, seizure and death. 45,46,47,48,49
Diagnostic Procedures (Discography)
Diagnostic discography continues to be used as a diagnostic procedure. While the performance, interpretation and
utility of this diagnostic procedure remains controversial, the technical performance of the procedure has been
associated with complications. These include direct neural trauma, dural puncture, vascular injury, drug reaction,
disc herniation and infection. 50,51,52,53,54,55 Of these, infection is the most common complication. Meticulous
technique and the use of a two-needle technique are well accepted means of reducing infectious risk.56 Both
intravenous or intradiscal antibiotics have been utilized as infection prophylaxis although the relative success of
using either approach individually or in a combined fashion has not been defined.
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Ablative Procedures (Radiofrequency ablation, IDET, Coblation, Chemical)
The performance of neuroablative procedures has been associated with a variety of complications. The common
complications of infection, hematoma and direct nerve injury as reported with other nonablative procedures are
expected. However, complications reported with ablative techniques may also be produced by heat injury outside of
the desired area of effect in the case of radiofrequency ablation or IDET and unexpected spread of the neurolytic
agent in the case of chemical denervation.57 The most commonly reported complications related to IDET include
disc herniation and nerve root injury. 58,59 In addition, a case report of a broken IDET catheter migrating intradurally,
producing radiculopathy and requiring surgical removal has been published. There have also been reports of spinal
cord injury due to inappropriate lead placement. Major neurologic injury has been reported in relation to the
performance of neurolytic celiac plexus blocks with both alcohol and phenol and in one series had an incidence of
1:683.60 The mechanism of injury may be related to vascular injury, vascular injection of the neurolytic agent or
direct neural trauma. 61,62,63,64
Disc Decompression, Nucleoplasty and Laser Discectomy
There is growing interest in the use of devices to reduce disc volume as an alternative to microdiscectomy or open
discectomy in patients with contained disc herniation. A variety of techniques have been used including mechanical
devices that remove small amounts of disc material, lasers and plasma-mediated ablation. Complications following
the performance of these procedures have included mechanical failure of a Dekompressor unit resulting in four
inches of the probe remaining in the patient after removal of the probe and epidural fibrosis.65,66 As with any
percutaneous procedure, complications such as localized pain, infection, bleeding and nerve injury have also been
reported.67,68
Vertebroplasty and Kyphoplasty
Despite the controversies surrounding the use of vertebroplasty and kyphoplasty, these techniques are still in
widespread use and for well selected patients, the outcomes are excellent. These procedures have been associated
with a wide variety of devastating complications including; spread into the spinal canal, late collapse after
vertebroplasty,69 migration of cement mass,70 pulmonary migration of cement,71 and lumbar artery
pseudoaneurysm.72 These procedures require great care in patient selection and technique to optimize outcomes.
Implantation, Maintenance or Removal of Devices (Intrathecal, Epidural, Spinal Cord

Stimulation)
The use of devices to facilitate drug delivery into the epidural or subarachnoid spaces or provide analgesia via
electrical stimulation of the spinal cord has seen significant growth related to the treatment of both non-cancer and
cancer related pain. Complications have resulted from implantation, maintenance and removal of these devices.
Nerve injury, infections, retained catheter fragments or equipment failure are the most common complications
related to implantation and removal of devices.73,74 A prospective study by Follett and Naumann identified frequent
procedure related complications and underscored the need for careful surgical technique and adherence to implant
guidelines.75 Complications occurring with maintenance of devices were related to pump programming errors, drug
overdose, drug error, concomitant administration of other central nervous system depressants and toxicity or
granuloma formation related to chronic intrathecal drug administration.1,76,77,78,79,80,81 The incidence of granuloma
formation has not been reported, but may be much higher than expected as a result of slow growth and lack of
immediate symptom development. In addition, a recent study has suggested that non-cancer pain patients receiving
intrathecal opioids have an increased risk of mortality.82 Regular evaluation of equipment performance, patient
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function and response to treatment to facilitate detection and treatment of complications at the earliest opportunity is
important.
Training in Pain Medicine and Interventional Procedures
The role of training in the incidence and severity of complications related to interventional pain procedures has not
been examined. The range of training received prior to the performance of interventional procedures is highly
variable and ranges from fellowship trained pain medicine physicians with board certification to physicians with
some exposure during residency to physicians from non-interventional specialties taking weekend courses to learn
interventional procedures to improve the revenue stream of their practice. In addition, there are non-physician
providers with no formal pain training or certification who are performing the entire range of interventional pain
procedures including vertebroplasty and spinal cord stimulation. In most cases, the public lacks sufficient
sophistication to inquire about the extent of training or board certification prior to undergoing procedures. In other
cases, there may be active misrepresentation of credentials. In the case of free standing offices, there may be no
mechanism to examine the training or certification of individuals providing pain care. In the hospital setting, the
credentials committee may choose to establish a low or high standard in granting privileges to perform
interventional pain procedures. In addition, various states have established certain criteria through the medical
boards to regulate pain medicine or establish standards. The net effect of these efforts to improve care and reduce
complications remains to be seen.
Avoiding Complications
The ability to avoid complications prospectively is a desirable goal for pain medicine. This includes the need to
maintain high standards throughout our practices and to participate in ongoing education. There are fundamentals
such as using good sterile technique for the handling of medications and performance of interventional procedures.
We need to examine new procedures from multiple perspectives including anatomy, physiology, pharmacology and
others prior to performing them on humans to determine what complications might occur and how best to avoid
them. We also need to develop consistent approaches that represent best practices in order to reduce the risks to our
patients. This may include the use of algorithms or checklists to standardize approaches. However, even if these
are developed and used, we must constantly question each step along the way and look for ways to improve further.
In most cases, if an unusual circumstance is encountered such as aspiration of blood or vascular runoff during
injection of contrast, it is reasonable to consider stopping the procedure and either performing it again later the same
day or rescheduling for another day. There is no substitute for good judgment and few chronic pain procedures are
emergent.
Conclusions
Interventional therapies provide pain relief to some of our most complicated patients, but are accompanied by the
opportunity to produce disastrous consequences. It is critical that we continue to examine the complications
associated with these procedures and develop clear criteria for patient selection, training and technical performance
to provide the greatest potential to produce the desired outcomes. We must be acutely aware of unusual or
unexpected symptoms or images before, during or after procedures and aggressive in diagnosing and treating
complications as they arise. Furthermore, we must educate our patients about the potential complications that may
develop following discharge so that they may promptly seek appropriate medical care. Finally, we must
systematically examine treatment outcomes and complications in our own practices, through reports in the medical
literature and through systems like the ASA closed claims database so that awareness may be raised, disturbing
patterns recognized and improvements in patient selection and technique promoted to the medical community.
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DISCLOSURE
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Peripheral Nerve Stimulation, Peripheral Nerve Field Stimulation

and Combination Techniques
Marc A. Huntoon, M.D. Nashville, Tennessee
Introduction
Peripheral nerve stimulation (PNS) is a means of treating pain or dysfunction of a nerve by direct electrical
stimulation. In recent years, the stimulation of small nerves that are not named has become popular as well, with
most authors describing this as either subcutaneous or peripheral nerve field stimulation (PNFS). (1) Unfortunately,
for all peripheral nerve stimulation techniques, there are no placebo-controlled, double-blind large scale trials, and
the mechanisms of action remain poorly understood. Likewise, the ability to design these types of trials is extremely
difficult because of the fact that the paresthesias induced by the technique can be felt, unmasking any placebo
treatment. In the original experiments of PNS described in Wall and Sweet’s classic article, (2) the authors treated
each other’s infraorbital nerves to test for the presence of analgesia. They then further tested the tenets of the gate
control theory (3) in a small case series. The fascinating narrative lost within these first experiments is that, in spite
of attempts to treat conditions that would classically be considered “central” pain states, they had some success
using PNS. This idea challenges some of our current concepts about treating the area of the nervous system proximal
to the site of injury. Early technological breakthroughs in PNS gradually led to different designs of leads and
generators, but this has unfortunately not been sustained. Even in the year 2012, there is no complete system that is
designed for PNS implantation, and the entire practice is essentially the “off-label” use of different leads and
generators which in large part were not designed for peripheral applications. Spinal cord stimulation, conversely, has
a whole host of potential electrodes (surgical paddle, percutaneous cylindrical, and hybrid), extensions, and both
rechargeable and primary cell generators. Spinal cord stimulation however, is not easily adapted for long term
coverage of narrow targets such as the pain of the low back, distal feet, and trunk areas. The ongoing difficulty in
targeting the axial back or trunk is partially due to the small size of the representative sensory homunculus fibers in
the dorsal spinal cord, as well as the location of these fibers deep to and comingled with other neural targets.(4) It is
not uncommon, despite charge- steering techniques, where positive charges in one area can move the area of
stimulation away from the “guarded’ area, to have concurrent activation of other fibers such as those in the trunk or
abdomen. These unwanted stimulations can be painful to the patient or, at the least, irritating. Therefore if a single
nerve is involved ( e.g. the ulnar nerve in a patient status post ulnar nerve transposition for cubital tunnel
entrapment, or a discrete area such as a patch of hyperalgesic skin in the distribution of the supraorbital nerve, the
area may be more selectively targeted with PNS. Peripheral nerve field stimulation (PNFS) has become popular for
similar reasons, often as an adjunctive technique usually in combination with either SCS or PNS. Many implanters
are driven by personal successes or failures, with little consensus of how best to utilize the various techniques.
Because of the lack of research and resulting shortcomings in evidence- based practice, many combinations have
been tried in case series.(5) Despite the fact that the combination of various stimulation methods is not yet evidence-
based, there are theoretical reasons for trying. For example, it is known that concomitant administration of the
GABA-b agonist baclofen to a group of SCS non-responding animals with a mononeuropathy produced in lab
conditions can turn the animals into responders. This effect is probably due to the fact that one of the mechanisms
by which SCS produces analgesia is through GABA-ergic systems.(6) Building upon the idea that combinations of
therapies might be able to harness different neural pathways or neurotransmitters/peptides is appealing because of
the complex neurobiology involved. Multiple possible combinations of different neuroaugmentation techniques
might therefore be considered, including: 1) spinal cord stimulation (SCS) and peripheral nerve field stimulation
(PNFS); 2) SCS and PNS; 3) PNS and PNFS; 4) intraspinal drug delivery systems (IDDS) and SCS; 5) IDDS and
PNFS; and 6) IDDS and PNS.
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Peripheral Nerve Stimulation

PNS has many shortcomings that are largely related to the intraneural topography and local anatomy of the
peripheral nerve. Sunderland (7) originally described the cross sectional topography of the named nerves of the
upper extremity, noting that the internal fascicular arrangement was key. Nerves have either motor, sensory or
mixed fascicles, that change in relative location, number and size within a matter of a few millimeters in some cases
Nerves also translocate with movement of the extremity, within their neurovascular bundles and between fascial
planes. Thus, fixed electrodes that are incapable of moving with the nerve are difficult to keep in contact
with the small and variable target fascicles. Problems that may arise because of this relationship include: 1)
permanent lead migration/loss of capture and loss of analgesia (8); 2) Undesirable motor stimulation and resultant
muscle contractions that are painful or otherwise functionally problematic with position change (9); 3) technology
that is poorly designed/non-optimal for the long term application of same for PNS and with unclear safety and
durability (10-12); 4) The lack of a reliable system for trialing and poor patient selection (8,9); 5) Difficulties with
insurance approval and disproportional payments relative to other neuromodulation techniques favoring SCS. (9). A
recent study looked at issues of cross-sectional anatomy more closely; specifically, the effects of the fascicle
perineurial thickness, diameter, and position within the nerve trunk on axonal excitation thresholds and neural
recruitment. Recent experimental work on a human model (femoral nerve) within a circumferential cuff electrode
showed that stimulation characteristics are complicated. Target fascicle stimulation was highly dependent upon the
cross-sectional area. As the thickness of the perineurium or the diameter of the fascicle increased, the threshold for
electrical activation also increased. Within the internal nerve fascicular configuration, a large neighbor fascicle next
to the target fascicle effected activation of the stimulated nerve fascicle by as much as 80% +/- 11%. (13)
Recently, the development of percutaneous ultrasound-guided technique has allowed a trial of stimulation to be
performed prior to permanent implantation. (10-12 ) In some patients, low threshold or stimulation below the
sensory threshold has been possible. (12 )
Peripheral nerve stimulation has proven to be remarkably resilient with the passage of time in many patients. Van
Calenbergh et al. retrospectively examined a group of 11 patients that had been chronically implanted with
peripheral nerve stimulators (radiofrequency coupled) over a period of 22 years period. They invited these eleven
patients to participate in the study. Four had previously been explanted, one patient had died of causes unrelated to
their peripheral nerve problem, and one patient declined participation due to the large distance of their home from
the study center. Of the 5 patients in this retrospective look, the patients universally had sustained excellent
outcomes with demonstrable long-term improvement in their pain, functionality and analgesic usage when the
stimulators were on. Minimal complications were noted over time. (14) Eisenberg et al treated 46 patients with well-
established nerve pain syndromes. They noted good outcomes in 78% of patients, while 22% had poor results. The
visual analogue scale pain scores decreased from 69 + 12 prior to surgery to 24 + 28 post operatively. (15) The
major pathologies treated in the study were: 1) Nerve injuries after knee or hip surgeries; 2) entrapment syndromes;
3) chronic persistent neuropathic pain after nerve graft surgeries ; or 4) needle-stick injuries to nerves. (15)
Revisions were still a major problem in the Cleveland Clinic series, where on average, 1.6 revisions were required
per patient, not including battery replacements. (8 )
Patient Selection
Neuromodulation techniques are generally envisioned as advanced therapies which are applied after the
failure of standard neuropathic pain algorithms, physiotherapy, and other conservative therapies. The results of
previous pharmaceutical trials, interventional pain procedures, physical therapy techniques including transcutaneous
electrical stimulation (TENS) and cognitive behavioral techniques for pain management should be included in the
medical history. A review of any previous opioid or narcotic medications, dependency or addiction issues is
mandatory. A thorough physical examination focusing on neurological and musculoskeletal areas is necessary. The
exam may note sensory or motor neurological changes in specific dermatomal or peripheral nerve distributions,
presence or absence of allodynia, hyperesthesia, hypesthesia, or hyperalgesia. Signs and symptoms of complex
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regional pain syndrome (vasomotor, sudomotor, or trophic changes, tremor, guarding ) should be elicited
Electrodiagnostic studies are often performed for staging purposes but may be normal in primary pain syndromes.
Diagnostic/therapeutic nerve blocks are regarded as important to ascertain the involvement of a specific nerve, and
can be an extension of the physical examination. For example, one might block the suspected nerve utilizing
ultrasound guidance to visualize the presence or absence of a neuroma at the site of injury, and place local anesthetic
medication proximal to the site of entrapment or injury. This can demonstrate the contribution of that specific nerve
to the overall pain syndrome. A recently published protocol utilizes local anesthetic coupled with clonidine for
neural blockade. (10 ) Clonidine has immune modulatory effects that may modulate perineural inflammatory
markers such as cytokines. In patients with neural injuries, Lavand’homme et al. noted prolonged relief of
neuropathic pain with clonidine treatment. (16)
Peripheral Nerve Field Stimulation
Peripheral nerve field stimulation has exploded in popularity as an outgrowth of peripheral nerve stimulation more
recently. PNFS has also been termed subcutaneous nerve stimulation, but the taxonomy was recently
discussed in a special editorial by Levy. (1 ) In PNFS, the smaller unnamed fibers in the periphery within
the subcutaneous tissue and above the deeper muscular layer are targeted. Electrode arrays are classically
placed via a percutaneously placed needle “where it hurts”. The cutaneous afferents that are targets of PNFS are
involved in transmission of pain, and there is some thought that the electrical field produced may be able
to treat not only neuropathic pain, but even nociceptive pain. The mechanism(s) by which PNFS works
remain obscure and yet to be defined. It is likely that local blood flow is altered, neurotransmitter release
and or uptake is effected, neural transmission is effected through cell membrane depolarization, and
potentially by augmentation of peripheral adenosine (17) or central opioidergic pathways that are activated
in similar fashion as transcutaneous electrical nerve stimulation . (18,19)
Analgesic “Tolerance”
In some cases, the effects of stimulation seem to fade over time, with many patients reporting the analgesia
from stimulation is not as potent as it was in the beginning. Although a true pharmacologic tolerance is not likely,
some of the neurobiological findings that can be inferred from electro-acupuncture and transcutaneous electrical
stimulation may be operative. There is evidence that adenosine is released during acupuncture in mice, and that
injection of an agonist of adenosine A-1 receptor replicates the observed analgesia. (17) Further, electro-acupuncture
releases cholecystokinin (CCK) into the spinal perfusate which can be reversed with CCK-8 antiserum. (20)
Interestingly, one of the proposed models of opioid-induced hyperalgesia involves the release of CCK into the rostal
ventral medulla. (21) Thus the role of CCK antagonists in the evolution of declining analgesia from PNS should be
investigated.
Combination SCS and PNFS

Recently, the issue of ‘crosstalk” or the ability of two electrodes in separate locations to be used to
communicate between each other has been discussed. In most concepts of this, the patient receives one or more SCS
electrodes and usually more than one subcutaneous PNFS electrodes. Programming is such that anodes are placed on
one lead and one or more cathodes on the other lead and a larger area of stimulation may be captured in the
perceived paresthesia. Mironer and colleagues studied this idea in 20 patients who had primarily low back pain (>
60% axial). The patients received a SCS midline eight contact electrode programmed as a guarded cathode with
quadripolar electrodes placed perpendicular to the SCS lead in the subcutaneous tissue at the patient’s site of
greatest axial back pain. The subcutaneous field stimulation leads were programmed as alternating cathodes and
anodes. Patients received either program 1, which was SCS alone, program 2, which was the PNFS lead alone and
program 3 both leads simultaneously. In this phase of the experiment, 15 of 19 patients preferred the combined
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program. In a second part of the study, program #1 was SCS and PNFS independently programmed; program #2
epidural anode and PNFS cathode; and program #3 was epidural cathode and PNFS anode. In this study, all patients
were blinded, and programming was done with all PNFS contacts active and only the “sweet spot” contacts active
on the SCS lead. Patients in the second study preferred cycling between programs one and two. (5)
Combination of SCS and PNS

Little has been studied in this area. The author has studied this concept in two patients (unpublished).
Both patients had percutaneous placement of leads epidurally (SCS) and peripherally via ultrasound-guidance
(PNS). Both patients preferred the combination of modalities over either modality alone when they were
blinded to which was activated.
Combination of IDD and SCS

Excitatory amino acids, e.g. glutamate, contribute to the “wind-up” of wide dynamic range (WDR)
neurons in the dorsal horn of the spinal cord. It is also known that local dysfunction of gamma-amino-butyric
acid (GABA) systems occurs in neuropathic pain states, and that SCS can elicit release of GABA in the dorsal
horn and inhibit the hyperexcitability of the WDR. SCS can also induce release of adenosine, serotonin and
norepinephrine. (22) In addition, it is known that acetylcholine release is impaired in nerve injured animals.
SCS effects on animals are blocked in part by atropine and antimuscarinic agents, suggesting that SCS works
through a muscarinic cholinergic mechanism.(23) Spinal cord stimulation responders release significantly
more acetylcholine. As clonidine works in part through intraspinal release of acetylcholine, drugs such
as clonidine or baclofen may be able to augment the response to SCS if applied intrathecally.(22) This concept
was applied in 10 patients with the majority responding to the combinations of either intrathecal baclofen or
intrathecal clonidine in combination with SCS. (23)
Conclusion
As single modality therapies have not been wholly successful, combinations of available implantable therapies
may be utilized more frequently in the future. PNS and PNFS are powerful and effective techniques in their own
right, which remain to be fully exploited in the treatment of painful syndromes.
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DISCLOSURE
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Blood and Pus: Hemorrhagic and Infectious Complications of Neuraxial Anesthesia

Terese T. Horlocker, M.D. Rochester, Minnesota
Spinal Hematoma
The actual incidence of neurologic dysfunction resulting from hemorrhagic complications associated with
neuraxial blockade is unknown; however, recent epidemiologic studies suggest the incidence is increasing (1). In a
review of the literature between 1906 and 1994, Vandermeulen et al. (2) reported 61 cases of spinal hematoma associated
with epidural or spinal anesthesia. In 87% of patients, a hemostatic abnormality or traumatic/difficult needle placement
was present. More than one risk factor was present in 20 of 61 cases. Importantly, although only 38% of patients had
partial or good neurologic recovery, spinal cord ischemia tended to be reversible in patients who underwent laminectomy
within eight hours of onset of neurologic dysfunction.
It is impossible to conclusively determine risk factors for the development of spinal hematoma in patients
undergoing neuraxial blockade solely through review of the case series, which represent only patients with the
complication and do not define those who underwent uneventful neuraxial analgesia. However, large inclusive
surveys that evaluate the frequencies of complications (including spinal hematoma), as well as identify subgroups of
patients with higher or lower risk, enhance risk stratification. In the series by Moen et al. (3) involving nearly 2 million
neuraxial blocks, there were 33 spinal hematomas. The methodology allowed for calculation of frequency of spinal
hematoma among patient populations. For example, the risk associated with epidural analgesia in women undergoing
childbirth was significantly less (1 in 200,000) than that in elderly women undergoing knee arthroplasty (1 in 3600,
p<0.0001). Likewise, women undergoing hip fracture surgery under spinal anesthesia had an increased risk of spinal
hematoma (1 in 22,000) compared to all patients undergoing spinal anesthesia (1 in 480,000).
Overall, these series suggest that the risk of clinically significant bleeding varies with age (and associated
abnormalities of the spinal cord or vertebral column), the presence of an underlying coagulopathy, difficulty during
needle placement, and an indwelling neuraxial catheter during sustained anticoagulation (particularly with standard
heparin or LMWH). They also consistently demonstrate the need for prompt diagnosis and intervention. Practice
guidelines or recommendations summarize evidence-based reviews. However, the rarity of spinal hematoma defies a
prospective-randomized study, and there is no current laboratory model. As a result, the consensus statements developed
by the American Society of Regional Anesthesia and Pain Medicine represent the collective experience of recognized
experts in the field of neuraxial anesthesia and anticoagulation (4). They are based on case reports, clinical series,
pharmacology, hematology, and risk factors for surgical bleeding. An understanding of the complexity of this issue is
essential to patient management.
Oral Anticoagulants
Clinical experience with patients who, congenitally, are deficient in factors II, IX, or X suggests that a factor
activity level of 40% for each factor is adequate for normal or near-normal hemostasis. Bleeding may occur if the level
of any clotting factor is decreased to 20% to 40% of baseline. The PT is most sensitive to the activities of factors VII
and X and is relatively insensitive to factor II. During the first few days of therapy, the PT reflects primarily a
reduction of factor VII, the half-life of which is approximately 6 hrs. After a single dose, marked prolongation of the
INR may occur, although adequate factor levels are still present. However, with additional doses, an INR greater than
1.4 is typically associated with factor VII activity less that 40% (and the potential for inadequate clotting) (5).
Few data exist regarding the risk of spinal hematoma in patients with indwelling epidural catheters who are
anticoagulated with warfarin. The optimal duration of an indwelling catheter and the timing of its removal also remain
controversial. Odoom and Sih (6) performed 1000 continuous lumbar epidural anesthetics in vascular surgical patients
who were receiving oral anticoagulants preoperatively. The thrombotest (a test measuring factor IX activity) was
decreased (but not below 10% activity) in all patients prior to needle placement. Heparin was also administered
intraoperatively. Epidural catheters remained in place for 48 hours postoperatively. There were no neurologic
complications. While these results are reassuring, the obsolescence of the thrombotest as a measure of anticoagulation
combined with the unknown coagulation status of the patients at the time of catheter removal limit the usefulness of these
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results. Therefore, except in extraordinary circumstances, spinal or epidural needle/catheter placement and removal
should not be performed in fully anticoagulated patients.
There were no symptomatic spinal hematomas in two smaller series with a total of nearly 700 patients
undergoing neuraxial block in combination with warfarin anticoagulation perioperatively (6-8). In both studies,
epidural catheters were left indwelling approximately two days. The mean international normalized ratio (INR) at the
time of catheter removal was 1.4, although in a small number of patients the INR was therapeutic (2.0-3.0). A large
variability in patient response to warfarin was also noted, demonstrating the need for close monitoring of the
coagulation status. There were no spinal hematomas in a series of 11,235 patients receiving epidural analgesia after
total knee replacement (9). Patients received warfarin (5-10 mg) starting the night of surgery. Epidural catheters were
removed within 48 hrs. The mean INR in a subset of 1030 patients at the time of catheter removal was 1.5 (range, 0.9-
4.3); the INR was less than 1.5 in nearly 40% of patients. These series suggest that not only the INR but also the
duration of warfarin therapy must be considered and that prolongation within the first 48 hrs may represent a
significant increase in risk.
Intravenous and Subcutaneous Standard Heparin

The safety of neuraxial techniques in combination with intraoperative heparinization is well documented, providing no
other coagulopathy is present. In a study involving over 4000 patients, Rao and El-Etr (10) demonstrated the safety of
indwelling spinal and epidural catheters during systemic heparinization during vascular surgery. However, the heparin
was administered at least 60 minutes after catheter placement, level of anticoagulation was closely monitored, and the
indwelling catheters were removed at a time when circulating heparin levels were relatively low. A subsequent study in
the neurologic literature by Ruff and Dougherty (11) reported spinal hematomas in 7 of 342 patients (2%) who underwent
a diagnostic lumbar puncture and subsequent heparinization. Traumatic needle placement, initiation of anticoagulation
within one hour of lumbar puncture and concomitant aspirin therapy were identified as risk factors in the development of
spinal hematoma in anticoagulated patients. Subsequent studies using similar methodology have verified the safety of this
practice, provided the monitoring of anticoagulant effect and the time intervals between heparinization and catheter
placement/removal are maintained.
Low-dose subcutaneous standard (unfractionated) heparin is administered for thromboprophylaxis in patients
undergoing major thoracoabdominal surgery and in patients at increased risk of hemorrhage with oral anticoagulant or
low molecular weight heparin (LMWH) therapy. There are nine published series totaling over 9,000 patients who
have received this therapy without complications(12), as well as extensive experience in both Europe and United
States without a significant frequency of complications. There are only five case reports of neuraxial hematomas,
four epidural (2,13) and one subarachnoid,(14) during neuraxial block with the use of subcutaneous heparin.
The largest study of thrice daily unfractionated heparin involved 768 epidural catheter placements. Sixteen
patients from this group had a positive match for hemorrhage codes on their discharge records, with none of the
episodes being identified within a major hemorrhage category. Laboratory value analysis failed to reveal changes in
the aPTT values of significance (4). The safety of neuraxial blockade in patients receiving doses greater than 10,000 U
of UFH daily or more than twice-daily dosing of UFH has not been established. Although the use of thrice-daily UFH
may lead to an increased risk of surgical-related bleeding, it is unclear whether there is an increased risk of spinal
hematoma. If thrice-daily unfractionated heparin is administered, techniques to facilitate detection of new/progressive
neurodeficits (eg, enhanced neurologic monitoring occur and neuraxial solutions to minimize sensory and motor
block) should be applied.
Low Molecular Weight Heparin

Extensive clinical testing and utilization of LMWH in Europe over the last ten years suggested that there was not an
increased risk of spinal hematoma in patients undergoing neuraxial anesthesia while receiving LMWH
thromboprophylaxis perioperatively (2,15). However, in the five years since the release of LMWH for general use in the
United States in May 1993, over 60 cases of spinal hematoma associated with neuraxial anesthesia administered in the
presence of perioperative LMWH prophylaxis were reported to the manufacturer (16,17). Many of these events occurred
when LMWH was administered intraoperatively or early postoperatively to patients undergoing continuous epidural
anesthesia and analgesia. Concomitant antiplatelet therapy was present in several cases. The apparent difference in
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incidence in Europe compared to the United States may be a result of a difference in dose and dosage schedule. For
example, in Europe the recommended dose of enoxaparin is 40 mg once daily (with LMWH therapy initiated 12 hours
preoperatively), rather than 30 mg every twelve hours. However, timing of catheter removal may also have an impact. It
is likely that the lack of a trough in anticoagulant activity associated with twice daily dosing resulted in catheter removal
occurring during significant anticoagulant activity. Importantly, there are no data to suggest that the risk of spinal
hematoma is increased with specific LMWH formulations (16). The incidence of spinal hematoma in patients
undergoing neuraxial block in combination with LMWH has been estimated at 1 in 40,800 spinal anesthetics and 1 in
3100 continuous epidural anesthetics (18). It is interesting in that the frequency of spinal hematoma in this series is
similar to that reported by Moen et al (3) for women undergoing total knee replacement with epidural analgesia.
Indications for thromboprophylaxis as well as treatment of thromboembolism or MI have been introduced.
These new applications and corresponding regional anesthetic management warrant discussion (19). Several off-label
applications of LMWH are of special interest to the anesthesiologist. LMWH has been demonstrated to be efficacious
as a “bridge therapy” for patients chronically anticoagulated with warfarin, including parturients, patients with
prosthetic cardiac valves, a history of atrial fibrillation, or preexisting hypercoagulable condition. The doses of
LMWH are those associated with DVT treatment, not prophylaxis, and are much higher. An interval of at least 24
hours is required for the anticoagulant activity to resolve.
Dabigatran
Dabigatran etexilate is a prodrug that specifically and reversibly inhibits both free and clot-bound thrombin. The
drug is absorbed from the gastrointestinal tract with a bioavailability of 5%(20). Once absorbed it is converted by
esterases into its active metabolite, dabigatran. Plasma levels peak at two hours. The half-life is eight hours after a
single dose and up to 17 hours after multiple doses. It is likely that once daily dosing will be possible for some
indications because of the prolonged half-life. Because 80% of the drug is excreted unchanged by the kidneys, it is
contraindicated in patients with renal failure(21). Dabigatran prolongs the aPTT, but its effect is not linear and
reaches a plateau at higher doses. However, the ecarin clotting time (ECT) and thrombin time (TT) are particularly
sensitive and display a linear dose response at therapeutic concentrations. Reversal of anticoagulant effect is
theoretically possible through administration of recombinant factor VIIa, although this has not been attempted
clinically(21). Indeed, product labeling suggests that dialysis may be considered for patients with significant
bleeding due to dabigatran.
Rivaroxaban
Rivaroxaban is a potent selective and reversible oral activated factor Xa inhibitor, with an oral bioavailability of
80%. After administration, the maximum inhibitory effect occurs one to four hours, however, inhibition is
maintained for 12 hours. The antithrombotic effect can be monitored with the PT, aPTT and Heptest, all of which
demonstrate linear dose effects. Rivaroxaban is cleared by the kidneys and gut. The terminal elimination half-life is
nine hours in healthy volunteers and may be prolonged to 13 hours in the elderly due to a decline in renal function
(hence a need for dose adjustment in patients with renal insufficiency and contraindicated in patients with severe
liver disease).
Rivaroxaban was approved in the United States for thromboprophylaxis following total hip or knee
replacement in 2011. Overall, clinical trials comparing rivaroxaban (5- 40mg mg daily, with the first dose six to
eight hours after surgery) with enoxaparin (40 mg, beginning 12 hours before surgery) demonstrate similar rates of
bleeding and comparable efficacy. While a “regional anesthetic” was performed in over half of the patients included
in the clinical trials, no information regarding needle placement or catheter management was included. Although
there have been no reported spinal hematomas, the lack of information regarding the specifics of block performance
and the prolonged half-life warrants a cautious approach.
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Table 1 Recommendations for Management of Patients Receiving Neuraxial Blockade and Anticoagulant
Drugs
Warfarin Discontinue chronic warfarin therapy 4–5 days before spinal procedure and evaluate INR.
INR should be within the normal range at time of procedure to ensure adequate levels of all
vitamin K-dependent factors. Postoperatively, daily INR assessment with catheter removal
occurring with INR< 1.5
Antiplatelet No contraindications with aspirin or other NSAIDs. Thienopyridine derivatives
medications (clopidogrel and prasugrel) should be discontinued 5-7 days and ticlopidine 14 days prior
to procedure. GP IIb/IIIa inhibitors should be discontinued to allow recovery of platelet
function prior to procedure (8 hours for tirofiban and eptifibatide, 24–48 hours for
abciximab).
Thrombolytics/ There are no available data to suggest a safe interval between procedure and initiation or
fibrinolytics discontinuation of these medications. Follow fibrinogen level and observe for signs of
neural compression.
LMWH Delay procedure at least 12 hours from the last dose of thromboprophylaxis LMWH dose.
For "treatment" dosing of LMWH, at least 24 hours should elapse prior to procedure.
LMWH should not be administered within 24 hours after the procedure. Indwelling
epidural catheters should be maintained only with once daily dosing of LMWH and strict
avoidance of additional haemostasis altering medications, including NSAIDs.
Unfractionated SQ There are no contraindications to a neuraxial procedure if total daily dose is less than
heparin 10,000 units. For higher dosing regimens, increase neurologic monitoring and cautiously
co-administer antiplatelet medications.
Unfractionated IV Delay needle/catheter placement 2–4 hours after last dose, document normal aPTT.
heparin Heparin may be restarted 1 hour following procedure. Sustained heparinization with an
indwelling neuraxial catheter associated with increased risk; monitor neurologic status
aggressively.
Dabigatran Discontinue 5-7 days prior to procedure; for shorter time periods, document normal TT.
First postoperative dose 24 h after needle placement and 6 hours post catheter removal
(whichever is later).
Rivaroxaban According to European guidelines, 22-26 hours should elapse between discontinuation of
rivaroxaban and neuraxial block in patients with normal renal function. Longer intervals
are required in patients with renal insufficiency. Indwelling neuraxial catheters are
contraindicated due to the “boxed warning”. Four to six hours is recommended between
spinal block and initiation of rivaroxaban therapy postoperatively.
Antiplatelet Medications
Antiplatelet medications are seldom used as primary agents of thromboprophylaxis. However, many orthopedic
patients report chronic use of one or more antiplatelet drugs. Although Vandermeulen et al (2) implicated
antiplatelet therapy in 3 of the 61 cases of spinal hematoma occurring after spinal or epidural anesthesia, several
large studies have demonstrated the relative safety of neuraxial blockade in both obstetric, surgical and pain clinic
patients receiving these medications (22-24). In a prospective study involving 1000 patients, Horlocker et al (24)
reported that preoperative antiplatelet therapy did not increase the incidence of blood present at the time of
needle/catheter placement or removal, suggesting that trauma incurred during needle or catheter placement is neither
increased nor sustained by these medications. The clinician should be aware of the possible increased risk of spinal
hematoma in patients receiving antiplatelet medications who undergo subsequent heparinization (11). Ticlopidine
and clopidogrel are also platelet aggregation inhibitors. These agents interfere with platelet-fibrinogen binding and
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subsequent platelet-platelet interactions. The effect is irreversible for the life of the platelet. Platelet dysfunction is
present for 5-7 days after discontinuation of clopidogrel and 10-14 days with ticlopidine.
Prasugrel is a new thienopyridine that inhibits platelets more rapidly, more consistently, and to a greater
extent than do standard and higher doses of clopidogrel. In the United States, the only labeled indication is for acute
coronary syndrome in patients intended to undergo percutaneous coronary intervention. After a single oral dose,
50% of platelets are irreversibly inhibited, with maximum effect two hours after administration. Platelet aggregation
normalizes in 7-9 days after discontinuation of therapy. The labeling recommends that the drug “be discontinued at
least 7 days prior to any surgery”.Platelet glycoprotein IIb/IIIa receptor antagonists, including abciximab (Reopro ®),
eptifibatide (Integrilin ®) and tirofiban (Aggrastat ®), inhibit platelet aggregation by interfering with platelet-
fibrinogen binding and subsequent platelet-platelet interactions. Time to normal platelet aggregation following
discontinuation of therapy ranges from eight hours (eptifibatide, tirofiban) to 48 hours (abciximab). Increased
perioperative bleeding in patients undergoing cardiac and vascular surgery after receiving ticlopidine, clopidogrel and
glycoprotein IIb/IIIa antagonists warrants concern regarding the risk of anesthesia-related hemorrhagic complications.
Anesthetic Management of the Anticoagulated Patient

The decision to perform spinal or epidural anesthesia/analgesia and the timing of catheter removal in a patient
receiving thromboprophylaxis should be made on an individual basis, weighing the small, though definite risk of
spinal hematoma with the benefits of regional anesthesia for a specific patient. Alternative anesthetic and analgesic
techniques exist for patients considered to be at an unacceptable risk. The patient’s coagulation status should be
optimized at the time of spinal or epidural needle/catheter placement, and the level of anticoagulation must be
carefully monitored during the period of epidural catheterization (Table 1). It is important to note that patients respond
with variable sensitivities to anticoagulant medications. Indwelling catheters should not be removed in the presence of
a significant coagulopathy, as this appears to significantly increase the risk of spinal hematoma (2,3). In addition,
communication between clinicians involved in the perioperative management of patients receiving anticoagulants for
thromboprophylaxis is essential in order to decrease the risk of serious hemorrhagic complications. The patient should
be closely monitored in the perioperative period for signs of cord ischemia. If spinal hematoma is suspected, the
treatment of choice is immediate decompressive laminectomy. Recovery is unlikely if surgery is postponed for more
than 10-12 hours; less than 40% of the patients in the series by Vandermeulen et al. (2) had partial or good recovery of
neurologic function.
Meningitis and Epidural Abscess

Bacterial infection of the central neuraxis may present as meningitis or cord compression secondary to abscess
formation. Possible risk factors include underlying sepsis, diabetes, depressed immune status, steroid therapy,
localized bacterial colonization or infection, and chronic catheter maintenance. Bacterial infection of the central neural
axis may present as meningitis or cord compression secondary to abscess formation. The infectious source for
meningitis and epidural abscess may result from distant colonization or localized infection with subsequent
hematogenous spread and CNS invasion. The anesthetist may also transmit microorganisms directly into the CNS by
needle/catheter contamination through a break in aseptic technique or passage through a contiguous infection. An
indwelling neuraxial catheter, though aseptically sited, may be colonized with skin flora and consequently serve as a
source for ascending infection to the epidural or intrathecal space.
Historically, the frequency of serious CNS infections such as arachnoiditis, meningitis, and abscess following
spinal or epidural anesthesia was considered to be extremely low- cases were reported as individual cases or small
series (25,26). However, recent epidemiologic series from Europe suggest that the frequency of infectious
complications associated with neuraxial techniques is increasing (3,27). In a national study conducted from 1997 to
1998 in Denmark, Wang et al (28) reported the incidence of epidural abscess after epidural analgesia was 1:1930
catheters. Patients with epidural abscess had an extended duration of epidural catheterization (median 6 days, range 3-
31 days). In addition, the majority of the patients with epidural abscess were immunocompromised. Often the
diagnosis was delayed; the time to first symptom to confirmation of the diagnosis was a median of five days. S. aureus
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was isolated in 67% of patients. Patients without neurologic deficits were successfully treated with antibiotics, while
those with deficits underwent surgical decompression, typically with only moderate neurologic recovery. It is difficult
to determine why the frequency of symptomatic epidural abscess was so high in this series. Since perioperative
antithrombotic therapy was involved in most cases, it is possible that the epidural abscesses were infected “micro”
epidural hematomas, but this is not strongly supported by the diagnostic imaging studies and neurosurgical findings.
In the series by Moen et al (3) there were 42 serious infectious complications. Epidural abscess occurred in 13
patients; nine (70%) were considered immunocompromised as a result of diabetes, steroid therapy, cancer or
alcoholism. Six patients underwent epidural block for analgesia following trauma. The time from placement of the
epidural catheter to first symptoms ranged from 2 days to 5 weeks (median 5 days). Although prevailing symptoms
were fever and sever backache, five developed neurologic deficits. All seven positive cultures isolated S. aureus.
Overall neurologic recovery was complete in 7 of 12 patients. However, four of the five patients with neurologic
symptoms did not recover. Meningitis was reported in 29 patients for an overall incidence of 1:53,000. A documented
perforation of the dura (intentional or accidental) occurred in 25 of 29 cases. In the 12 patients in whom positive
cultures were obtained, alpha-hemolytic streptococci were isolated in 11 patients and S. aureus in one.
These large epidemiologic studies represent new and unexpected findings regarding the demographics,
frequency, etiology and prognosis of infectious complications following neuraxial anesthesia. Epidural abscess is most
likely to occur in immunocompromised patients with prolonged durations of epidural catheterization. The most
common causative organism is S. aureus, which suggests the colonization and subsequent infection from normal skin
flora as the pathogenesis. Delays in diagnosis and treatment result in poor neurologic recovery, despite surgical
decompression. Conversely, patients who develop meningitis following neuraxial blockade typically are healthy and
have undergone uneventful spinal anesthesia. Furthermore, the series by Moen et al (3) validates the findings of
individual case reports of meningitis after spinal anesthesia- the source of the pathogen is mostly likely to be the upper
airway of the proceduralist. While the frequency of serious infectious complications is much higher than reported
previously, the results may be due to differences in reporting and/or clinical practice (asepsis, perioperative antibiotic
therapy, duration of epidural catheterization)
Meningitis after Dural Puncture and Neuraxial Anesthesia

Dural puncture has long been considered a risk factor in the pathogenesis of meningitis. Exactly how bacteria cross from
the blood stream into the spinal fluid is unknown. The presumed mechanisms include introduction of blood into the
intrathecal space during needle placement and disruption of the protection provided by the blood-brain barrier. Initial
investigations were performed over 80 years ago (29). Subsequent clinical studies reported conflicting results regarding
the causal relationship between dural puncture during bacteremia and meningitis However, the protective effect of
antibiotic administration prior to lumbar puncture was suggested (30,31).
Epidural Abscess after Epidural Anesthesia

Several relevant studies have specifically examined the risk of epidural abscess in patients receiving epidural anesthesia
and/or analgesia. Bader et al. (32) investigated the use of regional anesthesia in women with chorioamnionitis. Three
hundred nineteen women were identified from a total of 10,047 deliveries. Of the 319 women, 100 had blood cultures
taken on the day of delivery. Eight of these had blood cultures consistent with bacteremia. Two hundred ninety-three of
the 319 patients received a regional anesthetic, in 43 patients antibiotics were administered prior to needle or catheter
placement. No patient in the study, including those with documented bacteremias, had infectious complications. In
addition, mean temperatures and leukocyte counts in patients who received blood cultures showed no significant
differences between bacteremic and nonbacteremic groups. These authors continue to administer spinal and epidural
anesthesia in patients with suspected chorioamnionitis because the potential benefits of regional anesthesia outweigh the
theoretical risk of infectious complications.
The safety of epidural analgesia in 75 patients admitted to the intensive care unit was prospectively evaluated by
Darchy et al (33). There were no epidural abscesses. However, five of nine patients with positive cultures of the catheter
insertion site also had positive catheter tip cultures (epidural catheter infection); Staphylococcus epidermidis was the most
commonly cultured microorganism. Local infection of the catheter site was treated with catheter removal, but antibiotic
therapy was not specifically prescribed. Concomitant infection at other sites, antibiotic prophylaxis, and duration of
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epidural analgesia were not risk factors for epidural-analgesia related infections. The authors noted that the presence of
both erythema and local discharge is a strong predictor of local and epidural catheter infection.
Epidural anesthesia and analgesia in a patient with a known systemic or localized infection remains controversial.
Jakobsen et al (34) retrospectively reviewed the records of 69 patients with abscesses or wound infections who underwent
epidural catheter placement for surgical debridement over a seven year-period. Several patients had more than one catheter
inserted. Catheters were left indwelling for a mean of nine days. On 12 occasions (eight patients) the catheter was
removed because of local infection. None of the patients demonstrated signs or symptoms of neuraxial infection. The
authors concluded that epidural anesthesia is relatively safe for patients requiring repeated surgical treatment of localized
infection. In contrast, Bengtsson et al. (35) reported three epidural catheter-related infections in patients with cutaneous
wounds over a four year-period. All patients were treated with antibiotic therapy; one patient underwent transcutaneous
drainage of an epidural abscess. However, there were no neurologic deficits. It is difficult to determine the actual risk of
epidural abscess in patients with chronic localized infections who undergo epidural catheter placement due to the small
number of patients studied and the rarity of this complication. Therefore, the clinician must maintain vigilance in
neurologic monitoring to assure early recognition and treatment.
Neuraxial Blockade in the Immunocompromised Patient

Large series have demonstrated that patients with immunodeficiencies are at increased risk for infectious
complications compared to those with intact immune function. However, there are few investigations which have
evaluated the frequency of meningitis or epidural abscess within a specific immunodeficient population (3,27,36).
Table 2. Infectious Complications following Neuraxial Anesthesia in the Immunocompromised

Patient
• The attenuated inflammatory response within the immunocompromised patient may diminish the clinical signs
and symptoms often associated with infection and result in a delay in diagnosis and treatment.
• The range of microorganisms causing invasive infection in the immunocompromised host is much broader than
that affecting the general population and includes atypical and opportunistic pathogens.
• Early and effective therapy is paramount in optimizing neurologic outcome- consultation with an infectious
disease specialist is advised.
• Prolonged antibiotic therapy (weeks-months) is often required because of persistent and immunologic
deficiencies.
• Since eradication of infection is difficult once established, prevention of infection is paramount in caring for
immunocompromised patients.
From: Horlocker, et al 2006, with permission
Herpes Simplex Virus

Herpes simplex virus type 2 (HSV-2) infection is an incurable, recurrent disease characterized by asymptomatic periods
alternating with recrudescence of genital lesions. The primary infection is associated with viremia and can be accompanied
by a variety of symptoms, including fever, headache, and rarely aseptic meningitis. In contrast, recurrent or secondary
infections present as genital lesions without evidence of viremia. When obstetric patients present for delivery with
evidence of active HSV-2 infection, cesarean section is recommended to avoid exposing the neonate to the virus during
vaginal delivery. Neuraxial block in these patients is controversial because of the theoretical potential of introducing the
virus into the CNS. However, there are little data to support these concerns.
Human Immunodeficiency Virus

The risk of performing neuraxial block in patients infected with human immunodeficiency virus (HIV) is largely
undetermined. Approximately 40% of patients with the diagnosis of acquired immune deficiency syndrome (AIDS)
have clinical signs of neuropathy, and 70% to 80% have neuropathic changes present at autopsy. Since the virus infects
the CNS early in the disease, it is unlikely that neuraxial block would result in new CNS transmission. However, the
neurologic symptoms associated with HIV infection such as aseptic meningitis, headache, and polyneuropathy would be
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indistinguishable from those related to regional technique. Hughes et al. (37) reported safe administration of neuraxial
block to 18 HIV-infected parturients. The patients studied showed no postpartum change in immune, infectious or
neurologic status. Avidan et al. (38) and Bremerich et al.(39) also reported a low complication rate for parturients
with HIV infection on antiretroviral therapy who underwent spinal anesthesia. However, in all three series (with a
combined total of 117 patients), the patients were relatively healthy and in the early stage of their disease. The
effects of anesthesia on patients with more advanced disease are unreported.
Aseptic Technique
Although previous publications have repeatedly recommended meticulous aseptic technique, only recently have
standards for asepsis during the performance of regional anesthetic procedures been defined (40) (Table 3).
Handwashing remains the most crucial component of asepsis; gloves should be regarded as a supplement to- not a
replacement of- handwashing (41). The use of an antimicrobial soap reduces bacterial growth and reduces the risk of
bacteria being released into the operative field should gloves become torn or punctured during the procedure. An
alcohol-based antiseptic provides the maximum degree of antimicrobial activity and duration. Prior to washing, all
jewelry (rings, watches, etc) should be removed; higher microbial counts have been noted in health care workers
who do not routinely remove these items before handwashing. Sterile gloves protect not only patients from
contamination, but also health care workers from blood-borne pathogens and are required by the Occupational
Safety and Health Administration (40). Glove leaks are more likely to occur with vinyl compared to latex gloves
(24% vs. 2), with contamination of the health care workers’ hands noted following the leaks in 23% of cases (42).
Conversely, the use of gowns does not further reduce the likelihood of cross contamination in an intensive care unit
setting compared to gloves alone. At this time, there are insufficient data to make recommendations regarding
routine use for single injection or temporary neuraxial/peripheral catheter placement. However, placement of an
indwelling permanent device, such as a spinal cord stimulator, warrants the same asepsis as a surgical procedure,
including gowns, hats, and antibiotic pretreatment (40,43).
Surgical masks, initially considered a barrier to protect the proceduralist from patient secretions and blood,
are now required by the Center for Disease Control due to the increasing number of cases of post spinal meningitis,
many of which result from contamination of the epidural or intrathecal space with pathogens from the operator's
buccal mucosa (3,44-47). A recent ASA Practice Advisory also recommends the wearing of masks (48).
Antiseptic Solutions
Controversy still exists regarding the most appropriate and safe antiseptic solution for patients undergoing neuraxial
and peripheral techniques. Povidone iodine and chlorhexidine gluconate (with or without the addition of isopropyl
alcohol) have been most extensively studied (49,50). In nearly all clinical investigations, the bactericidal effect of
chlorhexidine was more rapid and more effective (extending its effect hours following its application) than povidone
iodine. The addition of isopropyl alcohol accelerates these effects. Chlorhexidine is effective against nearly all
nosocomial yeasts, and bacteria (gram-positive and gram-negative); resistance is extremely rare. It also remains
effective in the presence of organic compounds, such as blood. It must be noted that chlorhexidine-alcohol labeling
contains a warning against use as a skin preparation prior to lumbar puncture. The FDA has not formally approved
chlorhexidine for skin preparation prior to lumbar puncture because of the lack of animal and clinical studies
examining the neurotoxic potential of chlorhexidine, not due to a number of reported cases of nerve injury. Indeed, it
is important to note that there are no cases of neurotoxicity with either chlorhexidine or alcohol (40). Therefore, as a
result of its superior effect, alcohol-based chlorhexidine solutions are considered the antiseptic of choice for skin
preparation before any regional anesthetic procedure (40).
Anesthetic Management of the Infected or Febrile Patient

In summary, several clinical and laboratory studies have suggested an association between dural puncture during
bacteremia and meningitis. The data are not equivocal, however. The clinical studies are limited to pediatric patients
who are historically at high-risk for meningitis. Many of the original animal studies utilized bacterial counts that were
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far in excess of those noted in humans in early sepsis, making CNS contamination more likely. Despite these
conflicting results, it is generally recommended that except in the most extraordinary circumstances, central neuronal
block should not be performed in patients with untreated bacteremia. Patients with evidence of systemic infection may
safely undergo spinal anesthesia, if antibiotic therapy is initiated prior to dural puncture, and the patient has demonstrated a
response to therapy, such as a decrease in fever. Placement of an indwelling epidural (or intrathecal) catheter in this group
of patients remains controversial; patients should be carefully selected and monitored for evidence of epidural infection
(51).
The attenuated inflammatory response within
the immunocompromised patient, including patients
with HSV and HIV, may diminish the clinical signs
and symptoms often associated with infection.
Likewise, the range of microorganisms causing
invasive infection in the immunocompromised host is
much broader than that affecting the general
population and includes atypical and opportunistic
pathogens. Consultation with an infectious disease
specialist is advised to facilitate initiation of early and
effective therapy (36). Meticulous aseptic technique,
including hand-washing with chlorhexidine, wearing
of mask and sterile gloves by the proceduralist, skin asepsis with chlorhexidine and antibiotic pretreatment for the
placement of permanent devices, is critical to the prevention of infectious complications related to regional
anesthesia (40).
All patients with an established local or systemic infection should be considered at risk for developing infection
of the CNS. A delay in diagnosis and treatment of even a few hours significantly worsens neurologic outcome. Bacterial
meningitis is a medical emergency. Mortality is approximately 30%, even with antibiotic therapy. The clinical course of
epidural abscess progresses from spinal ache and root pain, to weakness (including bowel and bladder symptoms) and
eventually paralysis. The initial back pain and radicular symptoms may remain stable for hours to weeks. However, the
onset of weakness often progresses to complete paralysis within 24 hours. Although the diagnosis was historically made
with myelogram, radiologic examination such as CT scan, or more preferably MRI, is currently recommended. A
combination of antibiotics and surgical drainage remains the treatment of choice. As with spinal hematoma, neurologic
recovery is dependent on the duration of the deficit and the severity of neurologic impairment before treatment.
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3. Moen V, Dahlgren N, Irestedt L. Severe neurological complications after central neuraxial blockades in Sweden
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12. Liu SS, Mulroy MF. Neuraxial anesthesia and analgesia in the presence of standard heparin. Reg Anesth Pain
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13. Sandhu H, Morley-Forster P, Spadafora S. Epidural hematoma following epidural analgesia in a patient
receiving unfractionated heparin for thromboprophylaxis. Reg Anesth Pain Med 2000;25:72-5.
14. Greaves JD. Serious spinal cord injury due to haematomyelia caused by spinal anaesthesia in a patient treated
with low-dose heparin. Anaesthesia 1997;52:150-4.
15. Bergqvist D, Lindblad B, Matzsch T. Low molecular weight heparin for thromboprophylaxis and
epidural/spinal anaesthesia--is there a risk? Acta Anaesthesiol Scand 1992;36:605-9.
16. Horlocker TT, Wedel DJ. Neuraxial block and low-molecular-weight heparin: balancing perioperative analgesia
and thromboprophylaxis. Reg Anesth Pain Med 1998;23:164-77.
17. Horlocker TT, Wedel DJ, Benzon H, et al. Regional anesthesia in the anticoagulated patient: defining the risks
(the second ASRA Consensus Conference on Neuraxial Anesthesia and Anticoagulation). Reg Anesth Pain Med
2003;28:172-97.
18. Schroeder DR. Statistics: detecting a rare adverse drug reaction using spontaneous reports. Reg Anesth Pain
Med 1998;23:183-9.
19. Geerts WH, Bergqvist D, Pineo GF, et al. Prevention of venous thromboembolism: American College of Chest
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20. Weitz JI, Hirsh J, Samama MM. New antithrombotic drugs: American College of Chest Physicians Evidence-
Based Clinical Practice Guidelines (8th Edition). Chest 2008;133:234S-56S.
21. Eriksson BI, Quinlan DJ, Weitz JI. Comparative pharmacodynamics and pharmacokinetics of oral direct
thrombin and factor xa inhibitors in development. Clin Pharmacokinet 2009;48:1-22.
22. CLASP: a randomised trial of low-dose aspirin for the prevention and treatment of pre-eclampsia among 9364
pregnant women. CLASP (Collaborative Low-dose Aspirin Study in Pregnancy) Collaborative Group. Lancet
1994;343:619-29.
23. Horlocker TT, Bajwa ZH, Ashraf Z, et al. Risk assessment of hemorrhagic complications associated with
nonsteroidal antiinflammatory medications in ambulatory pain clinic patients undergoing epidural steroid
injection. Anesth Analg 2002;95:1691-7.
24. Horlocker TT, Wedel DJ, Schroeder DR, et al. Preoperative antiplatelet therapy does not increase the risk of
spinal hematoma associated with regional anesthesia. Anesth Analg 1995;80:303-9.
25. Baker AS, Ojemann RG, Swartz MN, Richardson EP, Jr. Spinal epidural abscess. N Engl J Med 1975;293:463-
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26. Ready LB, Helfer D. Bacterial meningitis in parturients after epidural anesthesia. Anesthesiology 1989;71:988-
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27. Ericsson M, Algers G, Schliamser SE. Spinal epidural abscesses in adults: review and report of iatrogenic cases.
Scand J Infect Dis 1990;22:249-57.
28. Wang LP, Hauerberg J, Schmidt JF. Incidence of spinal epidural abscess after epidural analgesia: a national 1-
year survey. Anesthesiology 1999;91:1928-36.
29. Weed LH, Wegeforth P, Ayer JB, Felton LD. The production of meningitis by release of cerebrospinal fluid
during an experimental septicemia. JAMA 1919;72:190-3.
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30. Carp H, Bailey S. The association between meningitis and dural puncture in bacteremic rats. Anesthesiology
1992;76:739-42.
31. Teele DW, Dashefsky B, Rakusan T, Klein JO. Meningitis after lumbar puncture in children with bacteremia. N
Engl J Med 1981;305:1079-81.
32. Bader AM, Gilbertson L, Kirz L, Datta S. Regional anesthesia in women with chorioamnionitis. Reg Anesth
1992;17:84-6.
33. Darchy B, Forceville X, Bavoux E, Soriot F, Domart Y. Clinical and bacteriologic survey of epidural analgesia
in patients in the intensive care unit. Anesthesiology 1996;85:988-98.
34. Jakobsen KB, Christensen MK, Carlsson PS. Extradural anaesthesia for repeated surgical treatment in the
presence of infection. Br J Anaesth 1995;75:536-40.
35. Bengtsson M, Nettelblad H, Sjoberg F. Extradural catheter-related infections in patients with infected cutaneous
wounds. Br J Anaesth 1997;79:668-70.
36. Horlocker TT, Wedel DJ. Regional anesthesia in the immunocompromised patient. Reg Anesth Pain Med
2006;31:334-45.
37. Hughes SC, Dailey PA, Landers D, et al. Parturients infected with human immunodeficiency virus and regional
anesthesia. Clinical and immunologic response. Anesthesiology 1995;82:32-7.
38. Avidan MS, Groves P, Blott M, et al. Low complication rate associated with cesarean section under spinal
anesthesia for HIV-1-infected women on antiretroviral therapy. Anesthesiology 2002;97:320-4.
39. Bremerich DH, Ahr A, Buchner S, et al. [Anesthetic regimen for HIV positive parturients undergoing elective
cesarean section]. Anaesthesist 2003;52:1124-31.
40. Hebl JR. The importance and implications of aseptic techniques during regional anesthesia. Reg Anesth Pain
Med 2006;31:311-23.
41. Saloojee H, Steenhoff A. The health professional's role in preventing nosocomial infections. Postgrad Med J
2001;77:16-9.
42. Olsen RJ, Lynch P, Coyle MB, et al. Examination gloves as barriers to hand contamination in clinical practice.
Jama 1993;270:350-3.
43. Rathmell JP, Lake T, Ramundo MB. Infectious risks of chronic pain treatments: injection therapy, surgical
implants, and intradiscal techniques. Reg Anesth Pain Med 2006;31:346-52.
44. Couzigou C, Vuong TK, Botherel AH, et al. Iatrogenic Streptococcus salivarius meningitis after spinal
anaesthesia: need for strict application of standard precautions. J Hosp Infect 2003;53:313-4.
45. Molinier S, Paris JF, Brisou P, et al. [2 cases of iatrogenic oral streptococcal infection: meningitis and
spondylodiscitis]. Rev Med Interne 1998;19:568-70.
46. Schneeberger PM, Janssen M, Voss A. Alpha-hemolytic streptococci: a major pathogen of iatrogenic meningitis
following lumbar puncture. Case reports and a review of the literature. Infection 1996;24:29-33.
47. Trautmann M, Lepper PM, Schmitz FJ. Three cases of bacterial meningitis after spinal and epidural anesthesia.
Eur J Clin Microbiol Infect Dis 2002;21:43-5.
48. Horlocker TT, Birnbach DJ, Connis RT, et al. Practice advisory for the prevention, diagnosis, and management
of infectious complications associated with neuraxial techniques: a report by the American Society of
Anesthesiologists Task Force on infectious complications associated with neuraxial techniques. Anesthesiology
2010;112:530-45.
49. Birnbach DJ, Stein DJ, Murray O, et al. Povidone iodine and skin disinfection before initiation of epidural
anesthesia. Anesthesiology 1998;88:668-72.
50. Kinirons B, Mimoz O, Lafendi L, et al. Chlorhexidine versus povidone iodine in preventing colonization of
continuous epidural catheters in children: a randomized, controlled trial. Anesthesiology 2001;94:239-44.
51. Wedel DJ, Horlocker TT. Regional anesthesia in the febrile or infected patient. Reg Anesth Pain Med
2006;31:324-33.
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DISCLOSURE
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Lower Extremity Nerve Blocks
Admir Hadzic, M.D., PhD. New York, New York

The purpose of this refresher course lecture is to discuss trends, common techniques, indications, management and
means of preventing complications with lower extremity peripheral nerve blocks. The techniques of US guided
lower extremity NBs are still evolving. The techniques to four most common PNBs presented in this syllabus were
agreed upon by a group of 26 international collaborators/universities. The full listing of the contributors can be
found at: http://www.nysora.com/peripheral_nerve_blocks/3347-our-contributors.html
permission. Reprinting or using individual refresher course lectures contained herein is strictly prohibited without permission from
the authors/copyright holders.
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FEMORAL NERVE BLOCK

Indications: Surgery on femur, anterior thigh, and knee
Abbreviations: FN= Femoral Nerve, FA= Femoral Artery, FV= Femoral Vein
Transducer Placement Cross-Sectional Anatomy
Patient Position: Supine Tips:

Transducer: 8-16 MHz, linear array When FN is not seen, track fascia iliaca
Transducer placement: Femoral crease, medially towards FA to identify FN.
parallel and inferior to inguinal ligament. For analgesia, catheters may be placed
Needle: 22G 5cm short bevel needle (8-10 underneath fascia iliaca.
cm for obese patients) Beware: Risk of falls due to motor weakness
Nerve stimulation response: Quadriceps of quadriceps muscle.
muscle contraction
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Ultrasound Images
US Initial depth setting: 4 cm. Technique:

Local Anesthetic (LA): 15-20 mL Needle Insertion: In plane, lateral to medial,
Ideal view: Fascia Iliaca and FN (out of plane less common)
Key Anatomy: Femoral nerve lateral to Ideal spread of LA: Beneath fascia iliaca
femoral artery, below fascia iliaca around femoral nerve
Number of injections: One
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SCIATIC NERVE BLOCK

Indications: Surgery at and below the knee
Abbreviations: GMM= Gluteus Maximus Muscle, ScN= Sciatic Nerve, IT= Ischial Tubercle, GT= Greater
Trochanter
Patient Position: Prone, lateral or oblique Tips:

(shown) Needle should enter the sheath of the ScN
Transducer: 6-16 MHz, Linear (shown) or either at the lateral or medial aspect of nerve.
curved in larger patients Significant amount of transducer pressure
Transducer Placement: Gluteal crease, the may be required to image ScN.
highest crease if more than one The cross-sectional anatomy shown can be
Needle: 21 G 10cm short bevel needle used as a reference for both transgluteal and
Nerve stimulation response: Twitch of foot subgluteal techniques.
or calf
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Ultrasound Images
US Initial depth setting: 5cm (highly Technique:

dependent on patient size) Needles insertion: In plane, lateral to medial,
Local Anesthetic (LA): 15-20 mL (out of plane in larger patients)
Ideal view: Sciatic nerve in epineural sheath Ideal spread of LA: Around the nerve
(grey arrows) Number of injections: One to two.
Key anatomy: Sciatic nerve, gluteus maximus
muscle
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POPLITEAL BLOCK
Indications: Surgery on ankle, achilles tendon, and foot
Abbreviations: BFM= Biceps Femoris Muscle, CPN=Common Peroneal Nerve, PA=Popliteal Artery, PV= Popliteal
Vein, ScN=Sciatic Nerve, SmM= Semimembranosus Muscle, StM=Semitendinosus Muscle, TN=Tibial Nerve
Patient Position: Prone, oblique (shown) or Tips:

supine Injection can be made also more proximally at
Transducer: 8-16 MHz, linear array either medial or lateral aspect of ScN under
Transducer Placement: Transverse at the epineural sheath.
base of the popliteal fossa 4-5cm above After injection, scan proximally-distally to
popliteal crease assure the LA spread around TN and CPN.
Needle: 22 G 5-8cm short bevel needle Catheter best placed within epineural sheath.
Nerve stimulation response: Twitch of foot
or toes
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Ultrasound Images
US Initial depth setting: 4cm Technique:

Local Anesthetic (LA): 15-25 mL Needle insertion: In plane or out of plane
Ideal View: Where ScN starts diverging into Ideal spread of LA: Around ScN, or between TN
TN and CPN and CPN
Key Anatomy: Popliteal artery, ScN Number of injections: One or two
superficial and lateral to it, femur, common X-Needle path for out of plane approach
epineural sheath of ScN
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SAPHENOUS NERVE BLOCK

Indications: Supplement to popliteal or sciatic blocks for surgery below the knee.
Abbreviations: FA= Femoral Artery, Mediallas M. (Vastus), SaM= Sartorius Muscle, SaN= Saphenous Nerve
Patient Position: Supine with leg abducted Tips:

and externally rotated When localization of FA proves difficult, start
Transducer: 8-16 MHz, linear array scanning more proximally and trace FA to mid-
Transducer Placement: Transverse view at thigh.
medial aspect of lower thigh to mid-thigh level Consider out of plane approach in larger
Needle: 22 G 5-8cm short bevel needle patients.
Nerve stimulation response: If used, A simple infiltration of LA at the site of incision
paresthesia of medial aspect of lower leg can is simple and often adequate for surgery on foot
be elicited and ankle.
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Ultrasound Images
Technique:
US Initial depth setting: 3cm Needle Insertion: In plane
Local Anesthetic (LA); 10-15 mL Ideal spread of LA: Around or underneath the
Ideal view: Artery below the sartorius muscle artery, between vastus medialis and sartorius
Key Anatomy: Femoral artery below muscle
Sartorius muscle, nerve often not visualized Number of injections: One or two
TREATMENT OF LOCAL ANESTHETIC TOXICITY , MONITORING OF NEEDLE PLACEMENT &

INJECTION
Treatment of Local Anesthetic Toxicity:

1) Airway, hyperventilation, 100% 02
2) Abolish convulsions (Diazepam, Midazolam, Propofol)
3) Intralipids (1.5 mL/kg over 1 minute (~100mL), then continuous infusion 0.25mL/kg/min (~500 mL over
30 mins)
4) CPR/ ACLS, consider cardiopulmonary bypass
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Dermatomes:
DISCLOSURE
BBraun, Self, Consulting Fees, Honoraria ; Pacira, Self, Consulting Fees ; LifeTech, Self,
Consulting Fees ; Macosta Medical USA, Self, Equity Position
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Local Anesthetics: Mechanisms, Toxicities and Controversies From a Clinical Perspective
John F. Butterworth, IV, M.D. Richmond, Virginia
General Considerations
Western medicine discovered regional anesthesia in 1884 when Köller and Gartner produced topical cocaine
anesthesia of each other’s corneas.1-3 Advances in the field have resulted from safer local anesthetic compounds
(LAs), better LA adjuncts, better needles and infusion devices, more reliable techniques for nerve localization
(permitting greater clinical reliability despite reduced LA doses), safer sedation techniques, and more effective
resuscitation, techniques. This review will focus on recent information regarding LA mechanisms,
pharmacodynamics, and toxicity, highlighting the potential clinical implications when they are apparent.
LA Structures and Chirality

All “classical” LAs have many features in common, notably a substituted
benzene ring at one end of the molecule and a tertiary amine nitrogen at the opposite
end (Figure 1).2-5 Chiral carbons are designated with an asterix (*) on Figure 1. The
designation as an ester or an amide is determined by a chemical link in the middle
portion of the molecule. All LAs other than ropivacaine and levobupivacaine are
provided as racemic mixtures (e.g. mepivacaine) or have no chiral carbons (e.g.
lidocaine). Other compounds that produce local or regional anesthesia have widely
varying structures. Many of these compounds have been shown to inhibit voltage-
gated Nav channels, confirming that their mechanism of clinical action could be the
same as “classical” LAs. These compounds include: general anesthetics, α2 agonists,
tricyclic antidepressants, alcohols, and nerve toxins.4-12 Perhaps one of these “non-
traditional” Nav channel antagonists will prove safer or more effective than
traditional LAs.13,14
Voltage-gated Na (Na v) Channels

When applied to a peripheral nerve LAs bind Nav channels on axons, preventing
Nav channels from “opening” and inhibiting initiation and propagation of Na currents
and action potentials.4,5 Taylor demonstrated that LAs inhibit Na currents in 1959 yet
anesthesia textbooks continued to include other discredited mechanisms of LA action
for more than 30 years! Nav channels are large, integral membrane proteins
containing 1 larger α-subunit and 1 or 2 smaller β-subunits. The α-subunit, the site of
ion conduction and drug binding, includes roughly 2000 amino acids and 4 “domains,” each with 6 α-helical,
membrane-spanning segments.5 β-subunit forms regulating multiple channel activities have been identified. Some β-
subunit forms regulate channel insertion into the plasma membrane, and the voltage-dependence and kinetics of α-
subunit gating.15,16
Humans have 7 functional genes that code for neuronal Nav channel α-subunits and 2 that code for Nav α-
subunit isoforms in muscle.17 Separate, specific Nav isoforms (gene products) predominate on unmyelinated axons,
nodes of Ranvier, and small dorsal root ganglion nociceptors, and unique forms are found in skeletal (Nav 1.4) and
cardiac muscle (Nav 1.5). Nav isoforms may have differing drug affinities.17 Alternative splicing of gene products
can yield additional variation, as was demonstrated for Nav 1.7 channels in human DRG.18 Some isoforms may be
particularly important in the pathophysiology of chronic pain syndromes.19 Nav 1.7 accumulates in painful human
neuromas. Nav 1.8 increases in DRG in animal models of inflammatory pain. Increased numbers of Nav 1.9 appear
in painful diabetic neuropathy. Nav 1.3 expression increases in dorsal root ganglia after peripheral nerve injury and
in human neuromas formed after injury.
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Nav channels exist in at least 3 states in vivo: “resting,” “open,” and “inactivated,” as was first described by
Hodgkin and Huxley.4,5 During action potentials Nav channels “open” briefly, allowing Na ions to flow into the cell,
depolarizing the plasma membrane. After a few milliseconds, Nav channels “inactivate” and Na flux ceases.
Mammalian myelinated fibers require no contribution from K currents for membrane repolarization, and Nav
channels return to the “resting” conformation with repolarization. 4,5 Such “voltage gating” of channel states likely
results from small movements of paddle-shaped, voltage-sensing amino acid sequences, and there is likely
additional voltage-sensing that regulates the ion “selectivity filter of the Nav.19,20 But, the Nav story may be more
complex with genetic variants. Patients with Nav variants in which “resurgent” Na currents appear during
repolarization, presumably from a lack of convention inactivation, may present with a paroxysmal extreme pain
disorder (Nav 1.7), paramyotonia congenital (Nav 1.4), and long-QT3/sudden infant death (Nav 1.5), depending on
which isoform is abnormal.12Mechanisms of Local Anesthesia by “Classical” LAs
LA binding has been localized to specific regions of the α-subunit.13 There is also evidence that drug binding
may be influenced by α-subunit segments lining the ion-conducting pore of the channel.14 Binding of different LAs
may induce differing conformational changes in the channel.15 While LA interactions with varying Nav isoforms
have not been systematically compared, some isoforms are more LA resistant than others. For example, lidocaine
more potently inhibited unmyelinated nociceptive neurons in “knock out” mice lacking Nav 1.8 as compared to wild
type mice in which Nav 1.8 was present.16 LA inhibition of Na currents increases with repetitive depolarizations,
often called “use-dependent” block., a phenomenon believed to underlie antiarrhythmic and antiepileptic effects.4,5
Repetitive depolarizations increase the likelihood that a LA will encounter “open" or “inactivated” Nav channels
rather than “resting” channels with less LA affinity.4,5,17 Alternatively, LAs may
preferentially modulate Nav channel movements associated with opening events.18
When the quaternary lidocaine derivative QX-314 is applied intracellularly, this
membrane impermeant agent powerfully inhibits Na currents.4,5 Compare the structures
in Figure 2, noting QX-314’s positively-charged nitrogen (note the “+”) and QX-314’s
extra ethyl moiety. An increasing number of studies suggest that QX-314 and other
drugs may gain entrance to the cytoplasm through vanilloid TRPV1 channels, after
TRPV1 activation by pain, lidocaine or capsaicin.19-23 TRPV1 channel activation
underlies nociception in primary sensory afferent fibers.24
LA Actions at Sites Unrelated to Na v Channels or Nerve Block

LAs have low potency and are relatively nonselective. LAs solubilize and disrupt
membranes. LAs bind and inhibit a variety of channels (including KATP, Ca release,
voltage-gated K, Ca, and HERG), enzymes (including mitogen activated kinases,
adenylyl cyclase, and phosphorylases), receptors (nicotinic acetylcholine, NMDA, β-
adrenergic, TRPV1, bradykinin B2, 5-HT3), and signaling mechanisms (G-protein-mediated signaling).4,31-33 LA
binding to these sites could contribute to spinal or epidural anesthesia, positive or negative effects of systemically
absorbed LAs, or could have no importance whatsoever!33 Circulating LAs have profound effects on coagulation,
inflammation, microcirculation; immune responses to infection and malignancy, postoperative gastrointestinal
function, and analgesia.354-38 Infused LAs relieve neuropathic pain, and improve analgesia. Infused LAs shorten
hospital lengths of stay as effectively as epidural analgesia. Lidocaine inhibits cardiac ischemia and reperfusion
injury in mice by an antiapoptotic effect.39 LAs inhibit kinesis and promote apoptosis, effects that could reduce
cancer metastasis or promote chondrolysis after prolonged intraarticular infusion, respectively.40,41
LA Pharmacodynamics
LA Volumes and Concentrations during Nerve Block
During clinical regional blocks, only a vanishingly small fraction of the injected LA molecules will be bound by
Nav channels specifically or even by neurons generally.42 Most drug molecules will be bound by other tissues or
removed by the blood stream. Clinical regional anesthesia will not arise unless conduction is blocked over a
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sufficient length of nerve. This “critical length” exceeds 2 cm (far longer than the 3 Ranvier nodes specified in
textbooks) except at very increased LA concentrations.43 Extent and duration of LA effects can be loosely correlated
with LA content of nerves in animal experiments.42, 44-46 There is debate as to whether volume, concentration, or
mass (volume x concentration) of drug is paramount in determining the success of blocks. In rat sciatic nerve blocks,
lower volumes of more concentrated lidocaine produce shorter latencies and longer durations.46 Nevertheless, human
studies generally find that anesthesia quality improves with increasing mass of drug, whether achieved by increasing
volume or concentration!47,48 Despite the increasing use of ultrasound, accidental intravenous injection remains a
risk, despite direct visualization of injections and reduced volumes of injectate.
Maximum doses
It is ridiculous to speak of one, universal, “safe” maximal dose of a LA compound, yet textbooks and regulatory
agencies persist in this folly.49 The maximal tolerable dose depends on many factors, including the site, rate, and
duration of LA administration, additives, patient weight and body habitus, pregnancy, and the presence of disease.
The same LA dose given for intercostal blocks produces greater peak LA concentrations than when given for plexus
or epidural blocks.3,50 A LA concentration in blood produced by a sudden, accidental bolus iv injection may produce
CNS toxicity; the same concentration gradually produced by slow absorption of LA during a perineural infusion
may have no discernible adverse effects.
LA Potency and Duration

Nerve-blocking potency of LAs increases with increasing molecular weight and increasing lipid solubility.50-52
Larger, more lipid-soluble LAs bind Nav channels with greater affinity, are highly protein-bound in blood, and less
readily “washed out” from nerves than smaller, less lipid-soluble LAs. Increased lipid solubility also associates with
increased protein binding, longer duration of action, and an increased potency at CV toxicity. Think of the profound
reduction in potency, onset delay, and duration of block that result from a methyl for butyl substitution (mepivacaine
vs bupivacaine, see Figure 1).
LA Speed of Onset
Generally, the onset of clinical regional anesthesia slows with increasing LA lipid solubility (compare
mepivacaine to bupivacaine and chloroprocaine to tetracaine). Curiously, many textbooks view pKa as inversely
related to delay of onset despite contradictory data!4,53 Chloroprocaine, the agent with the largest pKa, has the
shortest latency of onset of all.53
Differential Sensory Nerve Block
A nerve block sufficient to block incisional pain will impair motor function.2-4 Greater LA concentrations are
required to block impulses in C fibers than in Aδ or Aβ fibers.44,54 Smaller fibers can be blocked at lower
concentrations of LA than larger fibers of the same type.2 Bupivacaine and ropivacaine are relatively selective for
sensory fibers.55 As previously noted, differing Nav channel forms have distinct affinities for LAs and other
compounds, and specific Nav channel gene products are found in unmyelinated nerves, motor nerves, and dorsal root
ganglia, offering the tantalizing possibility of selective drugs.20,22,56,57
Other Factors Influencing LA Activity
Many factors influence the quality of local and regional anesthesia, including the dose, site of administration,
temperature, pregnancy, and additives. In general, the fastest onset and shortest duration of anesthesia occur with
intrathecal or subcutaneous injections; a slower onset and longer duration are obtained with plexus and peripheral
nerve blocks.4,50 Pain on injection of warmed LAs is less than with room temperature LAs, which hurt less than
refrigerated LAs.58 Pregnancy increases both spread of neuraxial anesthesia and neuronal susceptibility to LAs.4,59,60
LA Additives and LA Mixtures

The most popular LA additives in anesthesia practice (epinephrine, clonidine, opioids, NaHCO3, dextrose, and
steroids) are variously added to increase the safety, quality, distribution, duration, and speed of onset of anesthesia,
and to reduce blood loss.3-4,50 Clonidine and other α2-adrenergic agonists have LA properties and prolong the
duration of nerve blocks produced by lidocaine and mepivacaine.3,11 NaHCO3 increases the fraction of LA molecules
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that are uncharged, increases the apparent LA potency, and speeds the onset of some nerve blocks.3,5,,61 Bicarbonate
also reduces the pain of local infiltration.62 Opioids are commonly added to spinal or epidural LAs. Mixing of LAs
has long been popular; e.g., mepivacaine is often mixed with bupivacaine in the hope of decreasing the latter’s onset
delay. Nevertheless, data are sparse and most often indicate that mixtures yield onset delays and durations
approximating the mean of the component LAs. Toxicity of mixed LAs appears to be additive.63
There are persisting misconceptions about epinephrine. One is that LA-epinephrine solutions are unsafe in
patients at risk for coronary artery disease. However, in high-risk patients, epinephrine reduces LA concentrations
in blood without producing tachycardia, arrhythmias, or myocardial ischemia.64 Another misconception is that
epinephrine is unsafe in digital nerve blocks. Review of the published medical literature shows no amide LA-
epinephrine combination ever having been linked to gangrene after digital block. LA solutions containing
epinephrine are now widely used by dermatologists and hand surgeons for digital nerve blocks.65
LA Blood Concentrations, Protein Binding, Metabolism, and Pharmacokinetics

In blood, all LAs are partially protein-bound, primarily to α1-acid glycoprotein (AAGP) and secondarily to
albumin.2,50 LA affinity for AAGP increases with hydrophobicity and decreases with protonation.66 Extent of protein
binding increases with increasing concentrations of AAGP. Protein binding and AAGP concentrations decline
during pregnancy.67 During longer infusions of LA, concentrations of serum binding proteins progressively
increase.68 There is considerable first-pass uptake of LAs by lung.69 Ester LAs undergo rapid hydrolysis in blood,
catalyzed by pseudocholinesterase.2,3,50 Procaine and benzocaine are metabolized to p-aminobenzoic acid (PABA).
Amide LAs undergo oxidative N-dealkylation in the liver (by cytochrome P450).2,3,50 Amide LA clearance depends
on hepatic blood flow, hepatic extraction, and enzyme function; clearance is reduced by drugs and conditions that
decrease hepatic blood flow such as β-adrenergic or H2-receptor blockers, and heart or liver failure.2,3,50
Toxic Side Effects of LAs

LAs can produce a long list of toxic side effects of which the following types seem to be associated with the
greatest frequency of misconception and confusion.
Methemoglobinemia
Generations of textbooks have described the unique and predictable production of methemogloblinemia at
prilocaine doses >600 mg in adults.50 In fact, lower doses given to healthy patients will produce toxic
methemoglobinemia.70 Perioperative methemogloblinemia in North America more commonly results from
benzocaine, dehydration, or and other drugs than from prilocaine!71 Thus, topical benzocaine (formerly ubiquitous
in endoscopy suites) has been removed from the formularies of many hospitals.
Allergy
Textbooks state (without providing data) that there is greater risk of allergy to ester than amide LAs,
particularly to those LAs metabolized to p-aminobenzoic acid (procaine and benzocaine).50 True LA allergy is rare.
Despite an apparent “allergic” or even anaphylactoid reaction, only a rare tested patient will have a IgE immune
responses to preservative-free LAs.72-74 Allergy to LAs must be distinguished from allergy to other agents (e.g. latex,
antibiotics, paralytics, blood products) and other conditions that are common in the perioperative patient.75
Cardiovascular (CV) Toxicity
LA-associated death after cocaine or tetracaine topical anesthesia was formally studied by a national
commission in the 1930s. After eighty years many important, fundamental issues remain unsettled, including: 1.
What are the mechanisms of LA CV toxicity? 2. Do all LAs produce CV toxicity by one mechanism? 3. Which
animal model best mimics clinical LA systemic toxicity (LAST)?76,77
Laboratory studies provide insight into why bupivacaine appears to have a greater propensity to produce severe
LAST than most other LAs. Bupivacaine binds cardiac Nav channels more avidly and longer than lidocaine.3-5 R(+)
isomers bind cardiac Nav channels more avidly than S(-) isomers (levobupivacaine and ropivacaine).78 LAs inhibit
cardiac conduction with the same rank order of potency as for nerve block.79 LAs produce myocardial depression.80
LAs bind and inhibit cardiac Ca and K channels, but at concentrations greater than needed to inhibit Nav
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channels.3.4,80 LAs bind β-adrenergic receptors and antagonize epinephrine stimulation of adenylyl cyclase.81,82 LAs
produce CNS excitation, tachycardia, and hypertension at lower doses and concentrations than those associated with
cardiac depression. In animal experiments, most LAs will only produce CV toxicity at blood concentrations greatly
exceeding those producing seizures; however, experimental and clinical reports suggest a reduced margin of safety
for bupivacaine.2,3,83 In dogs, supraconvulsant doses of bupivacaine more commonly produce arrhythmias than
supraconvulsant doses of ropivacaine or lidocaine.83 Animals premedicated with midazolam or diazepam (or
receiving general anesthesia) may manifest bupivacaine LAST as CV collapse without convulsions.84
In animals, the rank order of potency for cardiac toxicity appears to be the same as for nerve block.85,86 Both
programmed electrical stimulation and epinephrine elicit more arrhythmias with bupivacaine than with lidocaine or
ropivacaine.87-89 When given LAs to the point of extreme hypotension, dogs given lidocaine were resuscitated, but
required continuing infusion of epinephrine to counteract LA-induced myocardial depression. After bupivacaine or
ropivacaine, some dogs required only electrical defibrillation; others could not be resuscitated using the full ACLS
armamentarium.87-89 Studies in pigs also show that bupivacaine (compared to lidocaine) may have a greater relative
potency for both arrhythmogenesis and for myocardial depression, but that the potency ratio for arrhythmogenesis is
much greater (16:1) as compared to their relative potency at nerve block .90
Chondrotoxicity
In recent years there has been increasing use of LA infusions into surgical wounds for postoperative pain control.
Some patients who have received LA infusions into joint spaces have developed long term adverse outcomes related
to chondromalacia, and this has resulted in litigation against physicians, and suppliers of LAs and wound infusion
pumps. There is an increasingly large literature on the adverse effects of LA infusions on articular cartilage and a
growing consensus that prolonged exposure (days) of articular cartilage to LAs may be ill-advised.91-93
Treatment of LA Toxicity
Serious degrees of methemoglobinemia are treated with oxygen and methylene blue 1 mg/kg IV. Anaphylactoid
reactions may require epinephrine and steroids. Minor LA reactions will terminate spontaneously. Severe LAST
requires active treatment and adherence to a check-list protocol likely increases patient safety.94 LA-induced
seizures require maintenance of adequate ventilation and oxygenation and protection of the patient from injury.
Seizures may be terminated with IV midazolam (0.05-0.10 mg/kg), propofol (0.5-1 mg/kg), or perhaps intravenous
lipid.3,77,95,96 If LA intoxication produces CV depression, hypotension may be treated by infusion of vasopressors
(phenylephrine 0.5-5 mcg/kg/min, norepinephrine 0.02-0.2 mcg/kg/min, or vasopressin 2-20 units IV). If cardiac
arrest is present, it is reasonable to follow the guidelines for Advanced Cardiac Life Support. Epinephrine and/or
vasopressin may be required, and there is controversy as to which is the better choice in this setting.96,97,98 A survey
of academic anesthesia departments in the USA confirmed inadequate understanding and no consensus regarding
resuscitation drugs for LAST.99
With unresponsive LA CV toxicity, IV lipid should be administered and cardiopulmonary bypass (or other
forms of mechanical cardiopulmonary support) should be considered.100-103Animal experiments and human case
reports describe the ability of lipid infusion to resuscitate animals from bupivacaine LAST, even after
"conventional" resuscitative efforts (including ventilation with oxygen, chest compressions, and ACLS drugs) have
proven unsuccessful.012,104 Lipid’s mechanism of action is not clear, although the prevailing opinion is that the LA is
absorbed into a “lipid sink.”There is also evidence that certain lipids may antagonize the binding of LAs to the Nav
channel.105 Lipid appears effective for over-dosage with lipophilic compounds other than LAs such as bupropion and
lamotrigine, and has also been used for lidocaine overdoseage in the critical care unit.106,107 Some now speculate that
lipid therapy should be initiated for incipient LA toxicity (e.g. for CNS symptoms) before conventional drug
treatments.95,96 No toxic side effects of lipid resuscitation have been reported in adults.
Summary
After 125 years the place of both LAs and regional blocks in medical practice remains secure, at least until
better agents and techniques are identified. Some features of local and regional anesthesia are well understood.
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Peripheral nerve blocks almost certainly result from LA inhibition of Nav channels in axonal membranes. Curiously,
the relative clinical potency of the various LAs remains poorly defined.108 The mechanisms of spinal and epidural
anesthesia are unclear. LAs may produce CV toxicity by more than 1 mechanism: more potent agents (bupivacaine)
have greater propensity for arrhythmias and conduction disturbances than less potent agents (lidocaine); all LAs at
increased concentrations will produce myocardial depression. Avoiding LAST is clearly preferable to treating it, and
ultrasound guidance may help us reduce (but not remove) the risk during regional nerve blocsk.109 Meanwhile, the
reported successes with lipid resuscitation suggest that we have a simple and safe treatment for LAST at hand.
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DISCLOSURE
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Local Anesthetic Toxicity:

Optimal Management to Avoid Neurotoxic Injury and Treat Cardiac Arrest
Kenneth Drasner, M.D. San Francisco, California
Continued reports of major and minor neurologic sequelae following central neuraxial blockade have
renewed concern regarding the potential toxicity of currently available local anesthetic agents. These reports, along
with the experimental literature, have led to modifications in clinical practice. This lecture will summarize some of
this clinical experience and the experimental findings that form the basis of these modifications, with particular
emphasis on the rational selection of a local anesthetic for short-duration outpatient spinal anesthesia. In addition,
the lecture will review the issue of local anesthetic systemic toxicity, focusing on the recent development of lipid
rescue for bupivacaine cardiotoxicity, and the extension of lipid resuscitation beyond cardiotoxicity, and beyond
treatment of the local anesthetics.
ANESTHETIC NEUROTOXICTY
Cauda equina syndrome and continuous spinal anesthesia (CSA).

In 1991, reports of cases of cauda equina syndrome following continuous spinal anesthesia (CSA) created
concern regarding the potential neurotoxicity of local anesthetics (1). Most involved lidocaine administered through
microcatheters, though some occurred with other anesthetics and/or macro (epidural) catheters. In all of these cases,
there was evidence of a restricted sacral block that required repetitive doses of local anesthetic to achieve an
adequate level of anesthesia, and it was hypothesized that the combination of maldistribution and the high dose of
anesthetic led to neurotoxic concentrations in the subarachnoid space. Studies performed with models of the
subarachnoid space (2), and other in vitro (3-6) and in vivo (7,8) investigations provided support for this mechanism
of injury. Most critically, administration of anesthetic in a restricted sacral pattern could induce functional loss that
closely paralleled clinical injury and caused histologic damage consistent with impairment.
In response to these reported injuries, spinal microcatheters were removed from the U.S. market. However,
they remain available in some countries, while CSA is still practiced in the U.S. using epidural equipment, and this
technique is commonly used when dural puncture accidentally occurs during epidural placement. It is therefore
essential that the practitioner appreciate the factors that may contribute to neurotoxicity, and how they impact
clinical management of an intrathecal catheter. Most critically, the clinician should limit the combined anesthetic
dosage used to achieve surgical anesthesia to the maximum amount reasonable to administer as a single
intrathecal injection.
Continuous Spinal Anesthesia: Guidelines for Anesthetic Administration

• Insert the catheter just far enough to confirm and maintain placement.
• Use the lowest effective local anesthetic concentration.
• Place a limit on the dose of local anesthetic to be used.
• Administer a test dose and assess the extent of any sensory and motor block.
• If maldistribution is suspected, use maneuvers to increase the spread of local anesthetic (change the
patient’s position, alter the lumbosacral curvature, switch to a solution with a different baricity).
• If well-distributed sensory anesthesia is not achieved before the dose limit is reached, abandon the
technique.
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Risk associated with repetitive injection after failed spinal.

As with CSA, inadequate sensory block with single-injection spinal anesthesia is often the result of
maldistribution. Under such circumstances, there is also the potential for repeat injections to distribute in the same
pattern resulting in neurotoxic concentrations of anesthetic within a restricted area of the subarachnoid space.
Review of the closed claims database (9) and subsequent case reports (10) have confirmed these concerns.
Based on these considerations, there have been suggestions for management of a failed spinal that include
assessment of the likelihood of technical error and adjustment of dosage for the second injection (9). However,
adherence to these recommendations imparts significant delay, as one must allow sufficient time for achievement of
near-maximal block prior to assessment of sensory anesthesia. A more efficient and safer alternative strategy is to
assume that the injected anesthetic has been administered intrathecally. Accordingly, similar to the strategy used for
CSA, the practitioner should simply limit the combined anesthetic dosage to the maximum amount reasonable to
administer as a single intrathecal injection.
Injury associated with inadvertent subarachnoid injection of an “epidural” dose.

There is a third circumstance under which excessive doses of anesthetic might be delivered into the
subarachnoid space—accidental injection of a dose intended for epidural administration. In the 1980s, reports of
deficits associated with apparent subarachnoid administration of chloroprocaine with bisulfite generated concern
that injury might occur if epidural doses of this anesthetic solution are administered intrathecally. Beginning in
1992, similar cases have been reported with lidocaine (11), expanding this concern to include an anesthetic once
considered the gold standard of safety. These cases serve to reinforce the critical importance of the test dose and
fractional administration of anesthetic during performance of epidural anesthesia. Additionally, should high
doses of an anesthetic be administered through a misplaced catheter, repetitive withdrawal of small volumes (4-5
ml) of CSF and replacement with saline should be considered, regardless of the anesthetic.
Injury following single-injection lidocaine spinal anesthesia.

The aforementioned volley of clinical reports provides compelling evidence that injury can result if high
doses of any anesthetic are administered intrathecally. More surprising, two subsequent reports raised suspicion that
neurologic deficits might occur with administration of lidocaine at doses recommended for single-injection spinal
anesthesia (12,13). One was a case report of cauda equina syndrome following intrathecal injection of 100 mg of
lidocaine with epinephrine (13). The second was a prospective study of regional anesthesia from France (12). In a
database that included roughly 10,000 lidocaine spinals, there were eight cases of persistent deficits following
single-injection spinal anesthesia that could not be explained on any other basis. All of these injuries occurred with
relatively high doses (≥75mg); two of these cases were permanent, both of which followed injection of the
maximum recommended clinical dose (100 mg). The lack of an alternative etiology and the occurrence of injury at
the high end of the dose range make toxicity the most likely explanation (14), and argue that the potential benefit of
using a dose higher than 75 mg of intrathecal lidocaine would seem inadequate to override the added risk.
Transient neurologic symptoms (TNS) following single-injection lidocaine spinal anesthesia.

In 1993, Schneider and colleagues reported four cases in which transient pain/dysesthesia followed routine
administration of conservative doses of intrathecal lidocaine (15). These symptoms were initially called “transient
radicular irritation”, but this term was later abandoned in favor of “transient neurologic symptoms” or “TNS”,
owing to the lack of certainty regarding their etiology. In this initial report, all four patients were in lithotomy
position, which led the authors to postulate that this position put stretch on the nerve roots of the cauda equina,
reducing blood flow, and potentiating toxicity (15). A follow-up study documented a 37% incidence of TNS with
spinal lidocaine, but a near-zero incidence with bupivacaine (16). Abundant data from numerous studies have
subsequently confirmed these findings, and have established the co-factors that contribute to the occurrence of
symptoms. In addition to lithotomy, positioning for knee arthroscopy and outpatient status markedly enhance risk
(17,18). While self-limited, the pain can be quite severe, often exceeding that induced by the surgical procedure.
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Importantly, TNS is not associated with sensory loss, motor weakness, or bowel or bladder dysfunction. The
etiology and significance of these symptoms remains to be established, but discrepancies between factors affecting
TNS and experimental animal toxicity cast doubt that TNS and persistent neurologic deficits represent opposite
extremes on a single spectrum of toxicity. While these recent issues have led to restricted use for spinal anesthesia,
lidocaine remains a popular agent for all other applications, including epidural anesthesia.
Chloroprocaine spinal anesthesia: back to the future?

The problems associated with lidocaine spinal anesthesia, particularly the high incidence of TNS have led
many clinicians to abandon the use of this anesthetic for spinal anesthesia. While there are reports describing the use
of low-dose bupivacaine combined with fentanyl (19), many practitioners report a high failure rate with this
technique, and complete recovery may still be delayed. Of other available options, neither procaine (20) nor
mepivacaine (21) appear to offer sufficient advantage with respect to TNS.
Despite a rather blemished past, considerable attention has been focused on the possibility of using
chloroprocaine to fill this anesthetic void. Introduced into clinical practice over 50 years ago, chloroprocaine never
evolved as a spinal anesthetic agent, perhaps related to the development and marketing of the amide, lidocaine. In
any case, reports of neurologic deficits associated with possible intrathecal injection of epidural chloroprocaine in
the early 80s raised concern regarding the potential neurotoxicity of this anesthetic, which, until recently, would
have subdued any enthusiasm for deliberate intrathecal administration.
The dissatisfaction with spinal lidocaine encouraged Kopacz and colleagues to re-investigate the use of
spinal chloroprocaine. Their rigorous systematic volunteer studies documented effective spinal anesthesia with
little, if any, risk of TNS (22-26). Duration of effect was shorter with chloroprocaine than with an equal dose of
lidocaine (23), and institutional discharge criteria were achieved more rapidly than with lidocaine (23), procaine
(22), or low-dose bupivacaine (26). As expected, anesthesia could be prolonged or enhanced by co-administration of
fentanyl (25) or epinephrine (24). However, an unexpected and worrisome finding was the occurrence of “flu-like”
symptoms in volunteers receiving chloroprocaine containing epinephrine (24), the etiology of which remains
obscure. Several small clinical reports have confirmed the suitability of chloroprocaine for outpatient spinal
anesthesia, both in terms of its short duration and low risk of TNS (27,28), though the published data regarding
chloroprocaine as a spinal anesthetic is limited, and certainly insufficient to establish safety. However, the evolving
“off-label” clinical experience with this drug is fairly substantial. Whether this unpublished information provides
adequate evidence of safety is a judgment that needs to be made by the individual anesthetist. However, should
chloroprocaine be used for spinal anesthesia, the available data and clinical experience would suggest that the
solution should be bisulfite-free, the dose limited to 60 mg, and the use of epinephrine be avoided.
ANESTHETIC CARDIOTOXITY AND LIPID RESCUE
Historical context
The most feared complication associated with administration of local anesthetics is the profound effect that
these agents can have on cardiac conduction and function. In the past, it was conventional wisdom that the
cardiovascular system is more resistant than the central nervous system to toxic effects of modern local anesthetics.
It was also well accepted that prompt treatment of CNS toxicity, particularly maintenance of ventilation and
oxygenation, could avert catastrophe. This conventional wisdom was called into question by a sentinel case
reported by Prentiss, in which administration of etidocaine for caudal anesthesia in a healthy 31-yr-old male was
associated with near simultaneous convulsions and cardiac arrest. Shortly thereafter, a seminal editorial by Albright
incorporated Prentiss’ case, along with five others, to support the concept that these long acting lipid-soluble
anesthetic agents (etidocaine and bupivacaine) could induce profound cardiac toxicity preceding or concurrently
with CNS toxicity, and independent of hypoxia (29). Although this suggestion met with considerable resistance,
cases of bupivacaine-induced cardiac collapse continued to occur. By early 1983, the FDA had received reports
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from the pharmaceutical industry of twelve cases of cardiac arrest, ten fatal, associated with the use of bupivacaine
in obstetrics, most associated with the use of the 0.75% solution. In response, the package labeling was modified,
and a “Dear Doctor” letter was sent stating that the 0.75% solution of bupivacaine was no longer to be used for
obstetrical anesthesia, nor any concentration to be used for intravenous regional anesthesia or paracervical block.
This communication also stressed the importance of an adequate test dose, and injection of anesthetic in incremental
doses. In addition to putting into play these changes in clinical practice, the occurrence of these cases stimulated an
enormous literature, which has provided evidence for the distinctive cardiotoxicity of these agents. The most likely
mechanism seems to relate to the nature of bupivacaine’s interaction with cardiac sodium channels (30). Simply put,
recovery from bupivacaine blockade during diastole is relatively prolonged, making it far more potent with respect
to depressing the maximum upstroke velocity of the cardiac action potential (Vmax) in ventricular cardiac muscle.
As a result, bupivacaine has been labeled a “fast-in, slow-out” local anesthetic, which likely creates conditions
favorable for unidirectional block and reentry. Other mechanisms may contribute to bupivacaine’s cardiotoxicity,
including disruption of atrioventricular nodal conduction, depression of myocardial contractility, and indirect effects
mediated by the central nervous system (31). This cardiotoxicity has obviously been the driving force for
development of the single enantiomer anesthetics, ropivacaine and levo-bupivacaine. Unfortunately, despite these
pharmaceutical advancements and the aforementioned modifications in clinical practice, cardiotoxicity has remained
a concern, and with the exception of cardiopulmonary bypass, treatment options have been largely ineffective.
Lipid Rescue
Recently, a series of clinical events, insightful observations, systematic experimentation, and astute clinical
decisions have identified a practical and apparently effective therapy for bupivacaine cardiotoxicity. Additionally,
this therapy appears to have applications that go well beyond the initial problem of bupivacaine cardiotoxicity,
finding application in the treatment of other manifestations of local anesthetic systemic toxicity, as well as
resuscitation from cardiotoxicity secondary to a wide variety of toxicological challenges.
After learning of a case of apparent cardiotoxicity from only 22 mg of bupivacaine in a patient with
carnitine deficiency (32), Weinberg postulated that this metabolic derangement led to enhanced toxicity due to the
accumulation of fatty acids within the mitochondria. He then hypothesized that administration of lipid would
potentiate cardiotoxicity. However, experiments he conducted to test this hypothesis demonstrated protection rather
than enhancement of bupivacaine’s cardiotoxicity by lipid. Encouraged by this serendipitous finding, he instituted a
series of deliberate systematic investigations in rats (33) and dogs (34), which clearly demonstrated the potential
efficacy of intravenous lipid for treating the highly-resistant cardiotoxicity of bupivacaine.
Clinical confirmation came eight years after Weinberg’s initial studies. Faced with a patient who developed
cardiotoxicity refractory to standard ACLS after receiving 20 mL 0.5% bupivacaine and 20 mL 1.5% mepivacaine
for an interscalene block, Rosenblatt administered a 100 mL bolus of 20% Intralipid® (35). The patient
subsequently responded to defibrillation, ultimately making a complete recovery. A subsequent report by Litz
provided additional confirmation, while extending the potential utility of this treatment to cardiotoxicity induced by
ropivacaine (36). Several reports soon followed, including a report by Spence suggesting that lipid may have utility
in treating local anesthetic CNS toxicity (37), as well as others suggesting efficacy in treating toxicity induced by
other classes of compounds. With respect to the latter, laboratory investigations have demonstrated utility for
resuscitation from cardiotoxicity secondary to various compounds including verapamil (38) and clomipramine (39),
and there are anecdotal clinical reports of successful resuscitations from bupropion-induced cardiovascular collapse
(40) and multiform ventricular tachycardia provoked by haloperidol (41). And its potential utility may be predictable
based on physiochemical properties of the toxic compound (42).
The mechanism by which lipid is effective is incompletely understood, but it’s predominant effect is almost
certainly related to its ability to extract bupivacaine (or other lipophilic drugs) from aqueous plasma or tissue targets,
thus reducing their effective concentration (“lipid sink”). Alternatively, or additively, bupivacaine has been shown
to inhibit fatty acid transport at the inner mitochondrial membrane, and lipid might act by overcoming this
inhibition, and thus serve to restore energy to the myocardium.
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Although the mechanism is uncertain, and numerous questions remain, the evidence is more than sufficient
to warrant administration of lipid in cases of systemic anesthetic toxicity. The timing of lipid is somewhat
controversial, though the trend over time has been toward earlier use. While it is has been argued that infusing lipid
at the earliest signs of systemic toxicity could result in unnecessary treatment of some patients, it seems imprudent
to wait until severe cardiovascular dysfunction is evident. With respect to treatment of severe cardiac toxicity, there
is evidence to suggest that vasopressin is best avoided (42). The literature is inconsistent with respect to
epinephrine, the data demonstrating both benefit and potential deleterious effects (43-48). Nonetheless, it is
reasonable to conclude that epinephrine might be useful in augmenting the return of spontaneous circulation, but
high doses are probably to be avoided, the drug preferably administered in the 10-100 mcg bolus range, at least
initially. Most critically, it should be evident that solutions of 20% lipid should be stocked and readily accessible
in any area where local anesthetics are administered, as well as locations where overdoses from any lipophilic
drug might be treated. And importantly, propofol should not be administered for this purpose, as the relatively
enormous volume of this solution required for lipid therapy (~200 ml) would deliver potentially lethal quantities of
propofol. However, small does of propofol might be appropriate for seizure control, particularly in the case where
there would be a delay in administering a benzodiazepine.
Many critical issues have yet to be adequately addressed in this rapidly developing area, including
identification of the most effective lipid emulsion (49-51) and optimal dosage parameters. Timely information on
this topic, as well as downloadable treatment protocols, can be found at lipidrescue.org, a website established and
maintained by Guy Weinberg. Additionally, a recent issue of Regional Anesthesia and Pain Medicine (March-April
2010) contains a collection of articles developed by an ASRA Practice Advisory Panel (52-57). The summary
recommendations from this group (56) are available for download without subscription at journals.lww.com/rapm.
The recommendations from this manuscript for treatment of systemic toxicity and the level of evidence for each
intervention are presented in the following table.
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Recommendations for Treatment of Local Anesthetic Systemic Toxicity (LAST)

• If signs and symptoms of LAST occur, prompt and effective airway management is crucial to preventing hypoxia
and acidosis, which are known to aggravate LAST (I; B).
• If seizures occur, they should be rapidly halted with benzodiazepines. If benzodiazepines are not readily
available, small doses of propofol or thiopental are acceptable. Future data may support the early use of lipid
emulsion to treat seizures (I; B).
• Although propofol can stop seizures, large doses further depress cardiac function; propofol should be avoided
when there are signs of cardiovascular compromise. (III; B). If seizures persist despite benzodiazepines, small
doses of succinylcholine or similar neuromuscular blocker should be considered to minimize acidosis and
hypoxia (I; C).
• If cardiac arrest occurs, we recommend standard Advanced Cardiac Life Support, with the following
modifications:
o If epinephrine is used, small doses (10 to 100 mcg boluses in the adult) are preferred (IIa; C)
o Vasopressin is not recommended (III; B)
o Avoid calcium channel blockers and beta-adrenergic receptor blockers (III; C)
o If ventricular arrhythmias develop, amiodarone is preferred (IIa; B); treatment with local anesthetics
(lidocaine or procainamide) is not recommended (III; C)
• Lipid emulsion therapy (IIa; B):
o Consider administering at the first signs of LAST, after airway management
o Dosing:
 1.5 mL/kg 20% lipid emulsion bolus
 0.25 mL/kg/min infusion, continued for at least 10 minutes after circulatory stability is
attained.
 If circulatory stability is not attained, consider re-bolus and increasing infusion to 0.5
mL/kg/min
 Approximately 10 ml/kg lipid emulsion for 30 minutes is recommended as the upper limit
for initial dosing.
• Propofol is not a substitute for lipid emulsion (III; C)
• Failure to respond to lipid emulsion and vasopressor therapy should prompt institution of cardiopulmonary
bypass (CPB) (IIa; C). Because there can be considerable lag in beginning CPB, it is reasonable to notify the
closest facility capable of providing it when cardiovascular compromise is first identified during an episode of
LAST.
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16. Hampl KF, Schneider MC, Ummenhofer W, Drewe J. Transient neurologic symptoms after spinal anesthesia.
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17. Pollock JE, Neal JM, Stephenson CA, Wiley CE. Prospective study of the incidence of transient radicular
irritation in patients undergoing spinal anesthesia. Anesthesiology 1996;84:1361-7.
18. Freedman JM, Li DK, Drasner K, Jaskela MC, Larsen B, Wi S. Transient neurologic symptoms after spinal
anesthesia: an epidemiologic study of 1,863 patients. Anesthesiology 1998;89:633-41.
19. Ben-David B, Solomon E, Levin H, Admoni H, Goldik Z. Intrathecal fentanyl with small-dose dilute
bupivacaine: better anesthesia without prolonging recovery [see comments]. Anesth Analg 1997;85:560-5.
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21. Liguori GA, Zayas VM, Chisholm MF. Transient neurologic symptoms after spinal anesthesia with
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22. Gonter AF, Kopacz DJ. Spinal 2-chloroprocaine: a comparison with procaine in volunteers. Anesth Analg
2005;100:573-9.
23. Kouri ME, Kopacz DJ. Spinal 2-chloroprocaine: a comparison with lidocaine in volunteers. Anesth Analg
2004;98:75-80.
24. Smith KN, Kopacz DJ, McDonald SB. Spinal 2-chloroprocaine: a dose-ranging study and the effect of added
epinephrine. Anesth Analg 2004;98:81-8.
25. Vath JS, Kopacz DJ. Spinal 2-chloroprocaine: the effect of added fentanyl. Anesth Analg 2004;98:89-94.
26. Yoos JR, Kopacz DJ. Spinal 2-chloroprocaine: a comparison with small-dose bupivacaine in volunteers.
Anesth Analg 2005;100:566-72.
27. Sell A, Tein T, Pitkanen M. Spinal 2-chloroprocaine: effective dose for ambulatory surgery. Acta
28. Casati A, Danelli G, Berti M, Fioro A, Fanelli A, Benassi C, Petronella G, Fanelli G. Intrathecal 2-
chloroprocaine for lower limb outpatient surgery: a prospective, randomized, double-blind, clinical
evaluation. Anesth Analg 2006;103:234-8.
29. Albright GA. Cardiac arrest following regional anesthesia with etidocaine or bupivacaine. Anesthesiology
1979;51:285-7.
30. Clarkson CW, Hondeghem LM. Mechanism for bupivacaine depression of cardiac conduction: fast block of
sodium channels during the action potential with slow recovery from block during diastole. Anesthesiology
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31. Bernards CM, Artu AA. Hexamethonium and midazolam terminate dysrhythmias and hypertension caused by
intracerebroventricular bupivacaine in rabbits. Anesthesiology 1991;74:89-96.
32. Weinberg GL, Laurito CE, Geldner P, Pygon BH, Burton BK. Malignant ventricular dysrhythmias in a
patient with isovaleric acidemia receiving general and local anesthesia for suction lipectomy. J Clin Anesth
1997;9:668-70.
33. Weinberg GL, VadeBoncouer T, Ramaraju GA, Garcia-Amaro MF, Cwik MJ. Pretreatment or resuscitation
with a lipid infusion shifts the dose-response to bupivacaine-induced asystole in rats. Anesthesiology
1998;88:1071-5.
34. Weinberg G, Ripper R, Feinstein DL, Hoffman W. Lipid emulsion infusion rescues dogs from bupivacaine-
induced cardiac toxicity. Reg Anesth Pain Med 2003;28:198-202.
35. Rosenblatt MA, Abel M, Fischer GW, Itzkovich CJ, Eisenkraft JB. Successful use of a 20% lipid emulsion to
resuscitate a patient after a presumed bupivacaine-related cardiac arrest. Anesthesiology 2006;105:217-8.
36. Litz RJ, Popp M, Stehr SN, Koch T. Successful resuscitation of a patient with ropivacaine-induced asystole
after axillary plexus block using lipid infusion. Anaesthesia 2006;61:800-1.
37. Spence AG. Lipid reversal of central nervous system symptoms of bupivacaine toxicity. Anesthesiology
2007;107:516-7.
38. Tebbutt S, Harvey M, Nicholson T, Cave G. Intralipid prolongs survival in a rat model of verapamil toxicity.
Acad Emerg Med 2006;13:134-9.
39. Harvey M, Cave G. Intralipid outperforms sodium bicarbonate in a rabbit model of clomipramine toxicity.
Ann Emerg Med 2007;49:178-85, 85 e1-4.
40. Sirianni AJ, Osterhoudt KC, Calello DP, Muller AA, Waterhouse MR, Goodkin MB, Weinberg GL, Henretig
FM. Use of lipid emulsion in the resuscitation of a patient with prolonged cardiovascular collapse after
overdose of bupropion and lamotrigine. Ann Emerg Med 2008;51:412-5, 5 e1.
41. Weinberg G, Di Gregorio G, Hiller D, Hewett A, Sirianni A. Reversal of haloperidol-induced cardiac arrest
by using lipid emulsion. Ann Intern Med 2009;150:737-8.
42. French D, Smollin C, Ruan W, Wong A, Drasner K, Wu, AH. Partition constant and volume of distribution as
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43. Di Gregorio G, Schwartz D, Ripper R, Kelly K, Feinstein DL, Minshall RD, Massad M, Ori C, Weinberg GL.
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44. Weinberg GL, Di Gregorio G, Ripper R, Kelly K, Massad M, Edelman L, Schwartz D, Shah N, Zheng S,
Feinstein DL. Resuscitation with lipid versus epinephrine in a rat model of bupivacaine overdose.
45. Mayr VD, Mitterschiffthaler L, Neurauter A, Gritsch C, Wenzel V, Muller T, Luckner G, Lindner KH,
Strohmenger HU. A comparison of the combination of epinephrine and vasopressin with lipid emulsion in a
porcine model of asphyxial cardiac arrest after intravenous injection of bupivacaine. Anesth Analg
2008;106:1566-71.
46. Hicks SD, Salcido DD, Logue ES, Suffoletto BP, Empey PE, Poloyac SM, Miller DR, Callaway CW,
Menegazzi JJ. Lipid emulsion combined with epinephrine and vasopressin does not improve survival in a
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47. Hiller DB, Gregorio GD, Ripper R, Kelly K, Massad M, Edelman L, Edelman G, Feinstein DL, Weinberg
GL. Epinephrine impairs lipid resuscitation from bupivacaine overdose: a threshold effect. Anesthesiology
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48. Harvey M, Cave G, Prince G, Lahner D. Epinephrine injection in lipid-based resuscitation from bupivacaine-
induced cardiac arrest: transient circulatory return in rabbits. Anesth Analg 2010;111:791-6.
49. Mazoit JX, Le Guen R, Beloeil H, Benhamou D: Binding of long-lasting local anesthetics to lipid emulsions.
50. Li Z, Xia Y, Dong X, Chen H, Xia F, Wang X, Dong H, Jin Z, Ding X, Papadimos TJ, Xu X: Lipid
resuscitation of bupivacaine toxicity: Long-chain triglyceride emulsion provides benefits over long- and
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51. Ruan W, French D, Wong A, Drasner K, Wu, AHB. A mixed (long- and medium-chain) triglyceride lipid
emulsion extracts local anesthetic from human serum in vitro more effectively than a long-chain emulsion.
Anesthesiology 2012;116:334-9
52. Butterworth JFt. Models and mechanisms of local anesthetic cardiac toxicity: a review. Reg Anesth Pain
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toxicity: a review of published cases, 1979 to 2009. Reg Anesth Pain Med;35:181-7.
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55. Mulroy MF, Hejtmanek MR. Prevention of local anesthetic systemic toxicity. Reg Anesth Pain Med
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188-93.
DISCLOSURE
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Perioperative analgesia and effect on patient outcomes
Spencer S. Liu, M.D. Seattle, Washington
Introduction
Provision of high quality perioperative analgesia has become recognized as an important goal. However,
ability of analgesia to improve outcomes remains controversial. 1 A key component of this continuing controversy
is that individual clinical trials need large patient sample sizes due to the current relatively low incidences of major
postoperative morbidity. Thus, this lecture will focus on studies with large subject samples to evaluate effects of
postoperative analgesia on major postoperative outcomes. Most discussed evidence involves epidural analgesia, as
this is the most studied regional anesthesia/analgesia technique for major postoperative outcomes. Furthermore, the
lecture will discuss effects of regional analgesia on patient oriented outcomes. As anesthesia and perioperative care
become increasingly safe, these patient oriented outcomes may assume greater importance.
Effect of regional analgesia on major morbidity

Epidural analgesia
Mortality
Meta-analyses: The largest meta-analysis of RCTs was published in 2000 (CORTRA) and included 141 RCTs
(through Jan 1, 1997) with 9,559 patients undergoing a variety of surgical procedures 2. This meta-analysis
examined effects of neuraxial block (spinal anesthesia, epidural anesthesia, and epidural analgesia) vs general
anesthesia, but results from this meta-analysis likely apply to perioperative epidural analgesia as 66 of the RCTs
with 4,498 of the patients utilized epidural anesthesia and analgesia. This meta-analysis observed a reduction in
mortality with neuraxial blockade (1.9% vs 2.8%, OR 0.7 with 95% CI 0.54 to 0.9) and specifically for thoracic
epidural blocks (1.5% vs 2.9%) and orthopedic procedures. An smaller meta-analysis of mixed but primarily major
vascular surgery by Beattie et al in 2001 noted a non-significant reduction in mortality (3.1 vs 4.4%) 3.
Several procedure specific meta-analyses have been conducted, and all report inconclusive effects on
mortality with epidural analgesia for open abdominal aortic surgery 4, coronary artery bypass grafting 5, abdominal
surgery 6, and hip and knee replacement surgery 7.
Randomized Controlled Trials: The most recent large RCT was conducted in 2011 in 654 patients undergoing
cardiac surgery that were randomized to combined general/thoracic vs general anesthesia. 8 This RCT did not note
any differences between groups in mortality (0.6 vs 0.3%). 2 large RCTs have been performed in non-cardiac
surgery patients. In 2001, the Veterans Affairs Cooperative Studies Program (VACS) randomized 984 patients (all
or mostly men) undergoing 4 types of surgery (aortic, gastric, biliary, or colon) to combined general/epidural
anesthesia followed by epidural morphine vs general anesthesia followed by systemic opioid treatment 9.
Approximately 85% of the epidurals were placed at the thoracic level. Overall mortality rates were similar between
groups (4 vs 3.4%). In 2002, the Multicentre Australian Study of Epidural Anesthesia (MASTER) trial 10 enrolled
915 high risk patients (prospectively defined in the protocol) who had undergone mixed abdominal surgical
procedures and were randomized to combined general/epidural anesthesia followed by 72 hours of postoperative
epidural analgesia (low thoracic or high lumbar placement) with local anesthetic and opioids vs general anesthesia
followed by systemic opioid treatment. This RCT was limited by poor protocol compliance, as only 225/447
patients fully adhered to the epidural analgesia protocol. Overall mortality rates were again similar between groups
(5.1 vs 4.3%).
Clinical registries: In 2008, a propensity score analysis of a single institution electronic registry of 259,037 patients
undergoing mixed surgery reported a significant reduction in 30 day mortality in patients selected for epidural
anesthesia/analgesia (n=56,556) of 1.7% vs 2%. 11 In 2004, a 5% random sample of the Medicare claims database.
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Patients undergoing a variety of surgical procedures were stratified to the presence (n=12,780 subjects) or absence
(n=55,943) of coding for postoperative epidural analgesia. 12 After adjusting for comorbidities, age, gender, and
hospital size, regression analysis revealed that the presence of postoperative epidural analgesia was associated with a
significantly lower incidence for both 7-day (0.5 vs 0.8%, OR = 0.52 with 95% CI 0.38 to 0.73) and 30-day (2.1 vs
2.5%, OR = 0.74 with 95% CI 0.63 to 0.89) mortality 12. There was a significantly lower mortality in patients who
received postoperative epidural analgesia for higher-risk procedures (e.g., lung resection, colectomy) but not lower-
risk procedures (e.g., total knee replacement, hysterectomy) or in patients with lower comorbidity indices. Although
the number of patients from these registry analyses is impressive, these data are limited by retrospective nature,
accuracy of coding for complications, and degree of association between epidural analgesia and outcomes.
Summary statement: There is modest but consistent evidence for reduction of mortality with epidural analgesia
for non-cardiac procedures. The largest meta-analysis observed a reduction with neuraxial block. Procedure
specific meta-analyses and individual RCTs have not noted an effect from epidural analgesia but lack sufficient
sample size due to the relatively low incidence of mortality (0.2-5%). Analysis of clinical registries offers large
patient numbers and a modest association between epidural analgesia and reduced mortality.
Cardiovascular
Approximately 100 million adults worldwide undergo non-cardiac surgery annually, and nearly half of the
patients are estimated to have cardiac risk factors 13. As such, it is estimated that nearly 500,000-900,000 patients
will suffer a perioperative cardiovascular complication 13. Uncontrolled postoperative pain may contribute to
cardiac morbidity through activation of the sympathetic nervous system, surgical stress response and coagulation
cascade. Experimental data suggest that thoracic epidural anesthesia with local anesthetics can reduce sympathetic
activation and provide a favorable balance of myocardial oxygen, but lumbar epidural anesthesia may not provide
the same physiologic benefits as thoracic epidural anesthesia 14,15.
Meta-analyses: Six meta-analyses were identified that examined efficacy of epidural analgesia on cardiovascular
events 2,3,16-18. The largest was the previously described CORTRA meta-analysis that reported a non-significant
decrease in the risk of myocardial infarction (0.9% vs 1.3%). It should be noted that the majority of patients
received lumbar epidural or spinal anesthesia, which may not provide the physiologic benefit of TEA.
Three smaller but more specific meta-analyses examining the efficacy of postoperative epidural analgesia
and cardiovascular events suggest a benefit for epidural analgesia and TEA in particular for open major vascular
procedures. The meta-analysis by Popping in 2008 in abdominal and thoracic procedures noted a significant
reduction in myocardial infarction with primarily thoracic epidural analgesia (2.6 vs 4.6%). Beattie et al noted a
significantly lower incidence of myocardial infarction in those who received epidural analgesia (rate difference = -
3.8% with 95% confidence interval of -7.4% to -0.2%; p = 0.049) primarily in vascular surgery patients (579 out of
632 patients), and analgesic subgroup analysis revealed that TEA but not LEA provided a significant reduction in
the rate of myocardial infarction (3.6% vs 8.5%, rate difference = -5.3% with 95% CI of -9.9% to -0.7%). A similar
but more procedure specific meta-analysis of open abdominal aortic surgery with 1,224 patients (through June 2004)
noted significant reduction in risk of cardiovascular complications (RR 0.74 with 95% CI 0.56-0.97) and myocardial
infarction (RR 0.52 with 95% CI 0.29 to 0.93) with epidural vs systemic analgesia 4. Subgroup analysis again
indicated that only TEA and not lumbar epidural analgesia was associated with reduced risk of myocardial
infarction. These findings would support the experimental data demonstrating physiologic cardiac benefits of
thoracic but not necessarily lumbar epidural analgesia. Another procedure specific meta-analysis examined 28
RCTs with 2731 patients undergoing coronary artery bypass surgery with or without TEA. 5 Myocardial infarction
was not reduced with an odds ratio of 0.81, but significant reduction in risk of dysrhythmias was noted with TEA
(RR 0.68 with 95% CI 0.5-0.93). Other procedure specific meta-analyses examining effects of epidural analgesia on
abdominal, and hip and knee replacement surgery concluded that there was insufficient evidence to analyze
cardiovascular complications. 6,7,17
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Randomized Controlled Trials: The large RCT of 654 patients undergoing cardiac surgery did not note any
differences between groups in myocardial infarction (4.9% in both groups). 8 The VACS trial did not note a
significant reduction in cardiovascular complications (myocardial infarction, heart failure, dysrhythmias, severe
hypotension) with use of epidural morphine (8.6 vs 11.2%) for all patients 9. However, the abdominal aortic surgery
subgroup (n=374) had significantly lower incidences of cardiovascular complications (9.8 vs 17.9%, p=0.03)
primarily due to reduction in myocardial infarction (2.7 vs 7.9%, p=0.05). The MASTER trial did not note
significant differences between groups.
Summary statement: There is consistent evidence that thoracic epidural analgesia may reduce the risk of
cardiovascular complications, especially myocardial infarction, in patients undergoing open major vascular surgery
and dysrhythmias in patients undergoing cardiac surgery. This is likely due to a higher underlying rate of
cardiovascular complications for this surgical population (4-37%).
Pulmonary
Postoperative pulmonary complications (PPCs) are as common as cardiac complications for patients
undergoing non-cardiac procedures, and may carry the same risk of increased mortality and length of hospital stay
19
. The pathophysiology of postoperative pulmonary complications (PPC) after surgery is multifactorial and may
include disruption of normal respiratory muscle activity from either surgery or anesthesia, a reflex inhibition of
phrenic nerve activity with subsequent decrease in diaphragmatic function, and uncontrolled postoperative pain 20.
Epidural analgesia will confer superior analgesia thus improving voluntary pulmonary function 21. Segmental block
from thoracic epidural anesthesia may result in increased tidal volume and vital capacity related in part to improved
pain control and also to interruption of the reflex inhibition of phrenic nerve activity, thus improving diaphragmatic
activity.
Meta-analysis: In the CORTRA study, neuraxial block in mixed surgical procedures was associated with
significantly decreased risk of pneumonia (3.1% vs 6%, OR 0.61 with 95% CI 0.48-0.76) especially with TEA (OR
0.48 with 95% CI 0.35 to 0.67) vs spinal anesthesia or lumbar epidural anesthesia (OR 0.76 with 95% CI 0.55-1.04)
2
. This finding would support the underlying potential physiologic benefit for TEA for reducing PPCs. This finding
was confirmed in the 2008 meta-analysis (n=5,904) by Popping et al that noted a significant reduction in pneumonia
with primarily thoracic epidural analgesia (8 vs 12%) in patients undergoing abdominal or thoracic surgery. 18
More procedure specific meta-analyses were also identified. Use of TEA in coronary artery bypass surgery
(n=2,731) was associated with significantly decreased risk of PPC (RR 0.53 with 95% CI 0.4 to 0.69). 5 Use of TEA
in open abdominal aortic surgery (N= 861) was associated with significantly decreased risk of respiratory failure
(RR 0.63 with 95% CI 0.51-0.79) 4.
Randomized Controlled Trials: The large RCT of 654 patients undergoing cardiac surgery did not note any
differences between groups in pulmonary complications (9.2 vs 5.8%). 8The VACS study observed a non-significant
reduction in respiratory failure for all patients in the epidural group (9.9% vs 14%) 9. However, subgroup analysis
of the abdominal aortic surgery subgroup (n=374) noted a significant reduction in respiratory failure with use of
epidural analgesia (14% vs 28%, p<0.01). The MASTER study (N=915) found observed similar findings with a
lower incidence of respiratory failure in the epidural analgesia group for high risk patients undergoing mixed
abdominal surgical procedures (23 vs 30%, p=0.02) 10. As described above, most epidurals were placed at the
thoracic level for both RCTs.
Summary statement: There is consistent evidence from meta-analyses and large RCTs that thoracic epidural
analgesia reduces risk of postoperative pulmonary complications, especially in high risk surgery.
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Gastrointestinal
Postoperative ileus is very common after abdominal surgery (>90% in many series) and may increase
resource utilization by prolonging hospital stay 22. Although the pathophysiology of postoperative ileus is
multifactorial, primary mechanisms include neurogenic (spinal, supraspinal adrenergic pathways), inflammatory
(i.e., local inflammatory responses initiate neurogenic inhibitory pathways), and pharmacologic (e.g., opioids)
mechanisms 23. Epidural analgesia provides superior pain control and marked sparing of opioid consumption 21.
Sympathetic block from epidural local anesthetics may attenuate postoperative reflex inhibition of GI motility.
Suppression of the surgical stress response and systemic absorption of epidural local anesthetics may reduce the
inflammatory response to attenuate postoperative ileus 22,23. Consistent with these mechanisms, experimental data
consistently indicate that epidural analgesia with local anesthetics shortens time of intestinal paralysis, increases the
strength of colonic contractions, and does not impair anastomotic healing or increase risk of anastomotic leakage 24.
Meta-analysis: A Cochrane Library meta-analysis that included 22 RCTs with 1,023 patients undergoing
abdominal surgery 25 and a meta-analysis from 2007 (n=806) both noted consistent reduction in postoperative ileus
with epidural analgesia with local anesthetics.
Summary statement: There is consistent evidence from meta-analysis that epidural analgesia with local
anesthetics hastens return of postoperative GI function after abdominal surgery by 24 to 37 hours.
Cancer recurrence
The immune system is critical for ability to detect and eliminate cancer cells. Current evidence suggests a
primary role for NK cells for “elimination, equilibrium, escape” process. The immune system is initially able to
eliminate cancer cells. However, natural selection over time results in resistant cancer cells that are contained in an
equilibrium state. Disruption to the immune system, such as surgical stress, may tip the equilibrium into an escape
phase that allows metastases. Multiple perioperative factors may be involved in the equilibrium/escape phase, and
regional anesthesia/analgesia may play a protective role. 26 Laboratory evidence indicates that acute pain suppresses
NK cell activity, increase adrenergic activity, and is associated with tumor development in animals. Conversely,
relief of postoperative pain reduces postoperative metastasis in rats. Proposed mechanisms for beneficial effects of
regional anesthesia/analgesia include attenuation of perioperative immunosuppression, decreased use of volatile and
opioid agents, and improved tissue oxygenation. There are currently no prospective large scale RCTs specifically
designed to support or refute this theoretical benefit. Most current evidence is either observational or post-hoc re-
analysis of a RCT designed for a different hypothesis. Initial data were very favorable for the ability of regional
anesthesia/analgesia to reduce risk of cancer metastasis, however subsequent data were more equivocal (Table). 27,28
Summary statement: There is a lack of evidence from well designed prospective studies to support or refute a
role for regional anesthesia/analgesia and cancer recurrence.
Effect of regional analgesic technique on patient oriented outcomes

As risk of major perioperative complications decrease, patient oriented outcomes are increasingly being
viewed as valuable. Indeed, patient oriented outcomes such as postoperative pain or nausea are consistently rated as
top priorities in patient surveys. Unfortunately, there are few validated tools for measuring patient evaluation of
such outcomes, as most tools are uni-dimensional and do not recognize patient preferences for different
combinations of outcomes and linked side effects. 29
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Epidural Analgesia
Analgesia: Two meta-analyses have compared epidural analgesia to systemic analgesia for mixed surgical
procedures.9,10 For both meta-analyses, epidural analgesia (compared to systemic opioids including intravenous
patient-controlled analgesia [IV PCA]) provided statistically superior analgesia at rest and with activity for all types
of surgery through postoperative day (POD) 4. Greater improvements were noted when the regimen included local
anesthetics and when level of epidural catheter matched site of surgery (e.g., thoracic catheter for thoracic surgery).
Multiple procedure specific meta-analyses have also been published13-16, and all consistently note statistically
significantly lower pain scores with epidural techniques.
Side effects: The meta-analyses from 2003 and 2005 also reported on incidences of side effects. As expected
epidural and IV PCA analgesia offered different profiles of side effects with epidural analgesia associated with
significantly reduced risk of nausea and sedation but significantly higher incidences of pruritus, urinary retention,
and motor block. When continuous epidural analgesia was compared to patient controlled epidural analgesia,
patient controlled epidural analgesia offered a reduced risk of side effects with significantly lower incidences of
nausea and motor block but greater incidence of pruritus.
Summary statement: Epidural analgesia provides superior analgesia to any form of systemic opioid including IV
PCA delivery for at least the first 3 POD for a variety of surgical procedures. Use of local anesthetics can maximize
this efficacy. Side effect profiles differ between regimens
Continuous peri-neural analgesia

Analgesia and side effects
A meta analysis published in 2006 (19 RCTs with 603 patients) compared continuous peri-neural analgesia
vs. mixed systemic opioids (13 of 19 RCTs used IV PCA).25 Peri-neural analgesia, which can be used on an
ambulatory basis27, provided statistically superior analgesia at rest and with activity for 48-72 hours with a reduction
in risk of nausea, sedation, pruritus but increased risk of motor block.
Functional outcomes and Length of hospital stay

Several recent RCTs suggest that use of perineural analgesia can be used to shorten length of stay of major
orthopedic procedures such as total shoulder, knee, and hip replacement by nearly 30 %. 30-32 After total shoulder
replacement, patients were randomized to saline or ropivacaine via an interscalene catheter. Patients receiving
ropivacaine achieved prospectively defined discharge criteria in 21 vs 51 hrs (p<0.001). After total knee
replacement surgery, patients were randomized to saline or ropivacaine via a femoral nerve catheter. Patients
receiving ropivacaine achieved prospectively defined discharge criteria in 25 vs 71 hrs (p<0.001). After total hip
replacement surgery, patients were randomized to saline or ropivacaine via a lumbasr plexus catheter. Patients
receiving ropivacaine achieved prospectively defined discharge criteria in 29 vs 51 hrs (p<0.001). Long term
investigations have also followed these same patients out for a year after surgery to determine if early superiority in
functional outcomes with regional analgesia is preserved. However, no differences in health related quality of life
were noted between groups. 33 A recent RCT randomizing patients to TEA/GA vs GA for off-pump CABG noted
that TEA resulted in better analgesia, less sedation, faster time to tracheal extubation, and shorter length of ICU and
hospital stay. 34
Ambulatory surgery now comprises 60-70% of surgical volume. Regional analgesia also appears to have
similar salutatory effects for ambulatory surgery. Patients undergoing shoulder or foot/ankle ambulatory surgery
were randomized to receive either patient controlled regional analgesia with ropivacaine (via interscalene or
popliteal catheter) versus patient controlled intravenous analgesia with morphine. Patients receiving regional
analgesia had statistically superior pain control, less side effects, and greater degrees of independent activity for the
first 3 days after surgery. 35 Indeed, recent case series suggest that use of perineural analgesia can convert total
shoulder, hip, and knee replacement from fully hospitalized to ambulatory surgery stays. 36-38
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Summary statement: Meta analysis indicates that continuous peri-neural analgesia provides superior analgesia
for up to 48 hours after surgery with reduced side effects when compared to systemic opioids. Recent clinical trials
suggest use of perineural analgesia may decrease hospital stay for major orthopedic procedures and improve
functional status at home after ambulatory surgery.
Summary and Future Directions

Regional analgesia has modest beneficial effect on mortality. Epidural analgesia reduces cardiopulmonary
complications in major open procedures such as open aortic repair. Epidural analgesia with local anesthetic
containing solutions consistently reduces duration of ileus after open abdominal procedures. Beneficial effects have
been reduced by current low rates of postoperative complications and increased use of minimally invasive surgery
such as laparoscopic colectomy. 39 Effects of regional anesthesia/analgesia on cancer recurrence are of great interest
but await high quality prospective data. Patient oriented outcomes have become an increasingly important field for
investigation. Epidural analgesia consistently provides superior analgesia to systemic opioids and a different
package of side effects. Perineural analgesia consistently provides superior analgesia and reduced side effects
compared to systemic analgesia and may reduce length of stay after major orthopedic procedures.
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14. Taniguchi M, Kasaba T, Takasaki M: Epidural anesthesia enhances sympathetic nerve activity in
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20. Warner DO: Preventing postoperative pulmonary complications: the role of the anesthesiologist.
21. Wu CL, Cohen SR, Richman JM, Rowlingson AJ, Courpas GE, Cheung K, Lin EE, Liu SS:
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22. Mythen MG: Postoperative gastrointestinal tract dysfunction. Anesth Analg 2005; 100: 196-204
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16 Suppl 2: 54-60
24. Fotiadis RJ, Badvie S, Weston MD, Allen-Mersh TG: Epidural analgesia in gastrointestinal
surgery. Br J Surg 2004; 91: 828-41
25. Jorgensen H, Wetterslev J, Moiniche S, Dahl JB: Epidural local anaesthetics versus opioid-based
analgesic regimens on postoperative gastrointestinal paralysis, PONV and pain after abdominal surgery. Cochrane
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26. Gottschalk A, Sharma S, Ford J, Durieux ME, Tiouririne M: Review article: the role of the
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27. Gottschalk A, Ford JG, Regelin CC, You J, Mascha EJ, Sessler DI, Durieux ME, Nemergut EC:
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113: 27-34
28. Myles PS, Peyton P, Silbert B, Hunt J, Rigg JR, Sessler DI: Perioperative epidural analgesia for
major abdominal surgery for cancer and recurrence-free survival: randomised trial. BMJ 2011; 342: d1491
29. Liu SS, Wu CL: The effect of analgesic technique on postoperative patient-reported outcomes
including analgesia: a systematic review. Anesth Analg 2007; 105: 789-808
30. Ilfeld BM, Le LT, Meyer RS, Mariano ER, Vandenborne K, Duncan PW, Sessler DI, Enneking
FK, Shuster JJ, Theriaque DW, Berry LF, Spadoni EH, Gearen PF: Ambulatory continuous femoral nerve blocks
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placebo-controlled study. Anesthesiology 2008; 108: 703-13
31. Ilfeld BM, Vandenborne K, Duncan PW, Sessler DI, Enneking FK, Shuster JJ, Theriaque DW,
Chmielewski TL, Spadoni EH, Wright TW: Ambulatory continuous interscalene nerve blocks decrease the time to
discharge readiness after total shoulder arthroplasty: a randomized, triple-masked, placebo-controlled study.
32. Ilfeld BM, Ball ST, Gearen PF, Le LT, Mariano ER, Vandenborne K, Duncan PW, Sessler DI,
Enneking FK, Shuster JJ, Theriaque DW, Meyer RS: Ambulatory continuous posterior lumbar plexus nerve blocks
after hip arthroplasty: a dual-center, randomized, triple-masked, placebo-controlled trial. Anesthesiology 2008; 109:
491-501
33. Ilfeld BM, Shuster JJ, Theriaque DW, Mariano ER, Girard PJ, Loland VJ, Meyer S, Donovan JF,
Pugh GA, Le LT, Sessler DI, Ball ST: Long-term pain, stiffness, and functional disability after total knee
arthroplasty with and without an extended ambulatory continuous femoral nerve block: a prospective, 1-year follow-
up of a multicenter, randomized, triple-masked, placebo-controlled trial. Reg Anesth Pain Med 2011; 36: 116-20
34. Caputo M, Alwair H, Rogers CA, Pike K, Cohen A, Monk C, Tomkins S, Ryder I, Moscariello C,
Lucchetti V, Angelini GD: Thoracic epidural anesthesia improves early outcomes in patients undergoing off-pump
coronary artery bypass surgery: a prospective, randomized, controlled trial. Anesthesiology 2011; 114: 380-90
35. Capdevila X, Dadure C, Bringuier S, Bernard N, Biboulet P, Gaertner E, Macaire P: Effect of
patient-controlled perineural analgesia on rehabilitation and pain after ambulatory orthopedic surgery: a multicenter
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36. Ilfeld BM, Wright TW, Enneking FK, Mace JA, Shuster JJ, Spadoni EH, Chmielewski TL,
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37. Ilfeld BM, Gearen PF, Enneking FK, Berry LF, Spadoni EH, George SZ, Vandenborne K: Total
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38. Ilfeld BM, Gearen PF, Enneking FK, Berry LF, Spadoni EH, George SZ, Vandenborne K: Total
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Table: Summary data from studies examining effects of regional analgesia on cancer recurrence.
DISCLOSURE
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Ultrasound-Guided Regional Anesthesia
Brian D. Sites, M.D. Lebanon, New Hampshire
Ultrasound Objectives:
There are essentially 4 primary objectives of the anesthesiologist conducting an ultrasound-guided nerve block.
1. Unequivocally image the nerve or plexus.

2. Identify collateral structures such as arteries or pleura.
3. Visualize the needle tip as it approaches the target and avoid collateral structures.
4. Confirm effective perineural spread of local anesthetic.
The ability to accomplish these tasks depends significantly upon the operator’s understanding and interaction with
the ultrasound machine.
Background Terminology:
Ultrasound is defined as sound waves that are at a frequency of 20,000 cycles per second or Hertz (Hz) or higher.
Most transducers used for UGRA are between 4 and 13 million Hz or 4 to 13 megahertz (MHz).
An ultrasound wave is produced when an electrical signal is placed across piezoelectric crystals that force the
crystals to vibrate. This vibration is then conducted through the body. All ultrasound waves are characterized by a
specific wavelength and frequency. The relationship between these variables is c is proportional to (λ)*(f), where c
= the propagation velocity and is presumed to be 1540 m/sec in the human body. Therefore, if c is held constant,
then to increase the frequency of an ultrasound wave, the wavelength would have to proportionately decrease. This
concept is at the core of UGRA since different frequency probes are used for different blocks.
Two additional and important concepts are ultrasound resolution and attenuation. Attenuation is the loss of
ultrasound wave energy as it travels through tissue. Generally, a lower frequency wave will attenuate less at a given
distance in comparison to a higher frequency wave. Thus, the lower frequency ultrasound wave will penetrate
deeper into the patient. Axial resolution, or the ability to identify two or more points in space (one lying in front of
the other), is between one to two wavelengths. This means that the lower frequency (larger wavelength) ultrasound
beam will penetrate deeper but will lack the resolution of the higher frequency and smaller wavelength beam.
Imagine (not image) if all structures reflected ultrasound to the same degree!
This is very interesting theoretical discussion. When ultrasound travels into the body and reflects off of an object,
some of the energy will return to the transducer. When this mechanical energy strikes the transducer, the
piezoelectric crystals vibrate again. This time, however, they convert mechanical energy back into electrical energy.
By convention, the more of this mechanical energy converted, the whiter or more echogenic the structure will
appear. Therefore, the physician identifies structures and pathological conditions by identifying various sine quo
non-shades of grey! If all structures reflected ultrasound to the same degree, all structures would appear the same
shade of grey and we would not have any useful clinical information. It would be like going to the opera and
hearing only one tone for 2 hours. No fun.
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To be more scientific, ‘targets’ for UGRA are generated based on the concepts of reflection and impedance.
Impedance can be referred to as the tendency of a medium to conduct ultrasound. When a sound wave travels
through an object and contacts an adjacent object with a different acoustic impedance, a demarcation is formed. An
example would be nerve tissue surrounded by adipose tissue. At these interfaces between objects with different
acoustic impedances, reflection occurs. This is known as Snell’s law. The larger the difference in acoustic
impedances between structures, the greater the reflection. Interfaces that are highly reflective are displayed as white
or hyperechoic. Examples include fascial planes, bones, and some nerves. Interfaces that weakly reflect ultrasound
waves are darker or hypoechoic. Examples of hypoechoic structures include muscle, fat, and some nerves. Blood
vessels are anechoic and appear black. The fundamental clinical challenge in UGRA is that many of the neural
structures lie in close proximity to other structures that have similar acoustic impedances. Thus, it can be
challenging to make a positive identification because these structures will appear similar and lack a clear acoustic
interface (black on white). The great example of this is the challenge of distinguishing tendon from nerve in the
distal arm or leg. Cardiac imaging is much easier secondary to the clear demarcation between blood filled
chambers (black) on myocardium (whiter).
Basic Imaging Techniques:
Structures of interest can be imaged either in the short-axis (cross-section) or the long-axis. A short-axis view
becomes a long-axis view when the transducer is turned 90 degrees in either direction. In general, regional
anesthesiologists prefer to image nerves and blood vessels in short axis. This is because the operator has a
simultaneous anterior-posterior and lateral-medial perspective. In the long axis view, the lateral-medial perspective
is lost.
Two techniques have emerged in the literature with respect to needle insertion. The needle can be inserted utilizing
the in-plane approach. Here, the needle is inserted parallel to the footprint of the transducer such that it is visualized
in long-axis, allowing full needle visualization. Alternatively, the needle can be inserted perpendicular to the
transducer footprint, generating a short-axis view of the needle. The major drawback to this out-of-plane approach
is that a short-axis view of a block needle appears as a small dot that can be very difficult to see. In addition, the
operator is often unable to confirm the exact location of the needle tip. There are two drawbacks to the in-plane
approach. First, it is likely that the needle will need to travel through more tissue, thus possibly increasing patient
discomfort. Second, given the very thin nature of the ultrasound beam, it can be very challenging to maintain
constant needle imaging throughout the entire procedure.
The ten steps of peripheral UGRA are to (Adopted from ASRA Guidelines1):
1. Visualize key landmark structures including muscles, fascia, blood vessels, and bone
2. Identify the nerves or plexus on short axis imaging
3. Confirm normal anatomy or recognize anatomical variation(s)
4. Plan for the safest and most effective needle approach
5. Use the aseptic needle insertion technique
6. Follow the needle under real-time visualization as it is advanced toward the target
7. Consider a secondary confirmation technique, such as nerve stimulation
8. When the needle tip is presumed to be in the correct position, inject a small volume of a test solution
9, Make necessary needle adjustments to obtain optimal perineural spread of local anesthesia
10. Maintain traditional safety guidelines of frequent aspiration, monitoring, patient response, and
assessment of resistance to injection
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Systematic and methodical scanning can improve target image quality and needle image quality:
ASRA recommended scanning techniques:
1. Find landmark vascular structure (possibly assisted by color Doppler), bone, or muscle
2. Find nerve or plexus on short-axis imaging (transverse scan)
3. Place machine focus on target structures
4. Place depth setting at 1 cm deep to target structures
5. Adjust gain, time gain compensation (TGC), and frequency as necessary
6. Initiate the P.A.R.T. maneuvers to optimize image quality
a. PRESSURE: varying degrees of transducer pressure on skin

b. ALIGNMENT: sliding movement of the transducer to define the
lengthwise course of the nerve
c. ROTATION: the transducer is turned in either a clockwise or
counterclockwise direction to optimize the image
d. TILTING: the transducer is tilted in both directions in order to
maximize the angle of incidence of the ultrasound beam with the target nerve
7. Scan anticipated needle trajectory with color Doppler to identify unsuspected vascularity.
Focus
Most ultrasound machines have a focus button. The focus is usually indicated by an icon on the screen that can be
moved up or down by button control. The idea is that when you place the focus of the ultrasound beam over the
target, then the beam is at its narrowest point at this location. The narrow beam results in the best axial and lateral
resolution for a given ultrasound frequency. In practical terms, this means that image will be the sharpest at this
location.
Depth
The scanning depth is set to just 1 cm below the target because this will result in the largest image on the screen as
well optimization of the frame rate. Slower frame rates can blur the image when there is needle, tissue, or
transducer motion. The reason why frame rates improve with depth setting minimization is that the ultrasound
waves are forced to travel less distance, meaning that they will return to the transducer in a shorter period of time.
Given that the definition of frame rate is the frequency (rate) at which an imaging device produces unique
consecutive images, then if you increase the number of images per second (by decreasing depth), the temporal
resolution must improve. This translates into less blurriness with movement, which is a nice added feature to an
ultrasound-guided block.
Gain and Frequency
As mentioned earlier, attenuation refers to the loss of ultrasound energy as it travels into the body. This loss of
energy mostly results from tissue absorption that generates heat. This is why the ultrasound appearance of deeper
structures appears degraded and more hypoechoic. The gain controls on the ultrasound machine try to compensate
for this degradation in the ultrasound image. There is usually an overall gain button that will make the entire image
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brighter or darker as well as a set of dials called time gain compensation (TGC). These dials control the gain at
specified depths. The typical settings are to increase the TGC for the deeper aspect of the image and decrease the
TGC for the more superficial component. The frequency of the transducer is also directly related to the degree of
attenuation. The higher the frequency of the ultrasound system, the more attenuation. The general rule is to use the
highest frequency linear transducers for the superficial blocks such as the interscalene and supraclavicular.
Transducers that penetrate deeply tend to be the curved transducers that are made for abdominal and obstetrical
applications. These transducers are great for neuraxial and proximal sciatic blocks. Most transducers can be toggled
between a range of settings for various degrees of penetration. Trial and error is the best recommendation. That is,
when your target is identified, change the scanning frequency (penetration) using the machine interface and see what
generates the best image.
P.A.R.T.
The above ASRA suggestions build on the aforementioned primary opening objectives. The P.A.R.T. maneuvers are
very important for both optimizing the quality of the image for both the needle and target structures. There are no
simple rules that mandate which one of the maneuvers will work best. Each patient is different and the operator is
encouraged to systematically go through the maneuvers for every procedure.
Color Doppler
This is an amazing technology that helps to distinguish artery from vein as well as unseen vascular structures within
the trajectory of the needle. It is very important to understand a central limitation of Doppler technology. The
Doppler equation accounts for the velocity and directionality of blood. For velocity measurements to be accurate,
the blood flow must be parallel to the ultrasound beam. It turns out that it is a good thing that we are not interested
in velocity measurements, since most of the relationships between our ultrasound beams and blood flows are
perpendicular. Take, for example, the interscalene block. Here we are imaging the carotid and IJ in short axis, so
there is in essence a 90-degree relationship. If you analyze these vascular structures with color Doppler, it may
appear that there is no flow (no color). Given that the patient is unlikely to be dead, this is an artifact error based on
the beam and flow generating a 90-degree relationship. Obviously, we do not need color flow to identify the
carotid. However, many of the branches that could be punctured such as the transverse cervical or lateral circumflex
arteries may be picked up much easier with color Doppler compared to the naked eye. The simple solution to deal
with the above problem is to tilt the transducer through various angles to establish a different angle relationship
between an area of interrogation and the ultrasound beam. Even though the exact velocity measurements will be
inaccurate, all we really care about is establishing that something either is or is not a blood vessel.
Quality Issues:
Although there are many novice behaviors and quality issues associated with UGRA, I would like to emphasize the
need to confirm screen orientation. One of the significant quality compromising behaviors that we have identified at
Dartmouth-Hitchcock Medical Center is confusion over screen orientation with respect to patient anatomy. To
address this, the ASRA initiative on ultrasound-guided regional anesthesia has made these suggestions:
Before needle insertion, each neural structure should be referenced to key landmark structures in the anterior-
posterior and lateral-medial planes. However, because of the bilateral nature of the peripheral nervous system,
variations in patient positioning, differing presets of various ultrasound systems, and the nuances of individual
techniques, it would be difficult to standardize the correlation of sidedness of the screen with an anatomical location.
This is in contrast to transesophageal echocardiography, where, in the transgastric short-axis view of the left
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ventricle (for example), the anterior aspect of the left ventricle can be standardized to be on the bottom of the screen.
Therefore, the Joint Committee recommends this simple procedure for correlation of the ultrasound screen with
patient sidedness in any patient position.
1. After the application of the transducer onto the patient’s skin, the landmark structure or peripheral
nerve is identified. The primary operator states that the top of the ultrasound screen correlates with the
patient’s skin. To confirm this, pressure is applied with a finger onto the skin. This area should be
visualized being compressed on the ultrasound screen.
2. For patients in any position, the operator states that screen left represents a defined anatomical aspect
of the patient (e.g., cephalad). To confirm this, the primary operator again applies pressure with a
finger at this defined site. A corresponding indentation should be visualized on the left aspect of the
ultrasound screen. If indentation occurs on screen right the operator must turn the transducer 180
degrees. After such a correction, the operator should return to step 1 until correct imaging has been
obtained and confirmed.
I hope this handout helps. If you have any comments or questions, please feel free to email me at
brian.d.sites@gmail.com.
Reference:
1. Sites BD, Chan, VW, Neal JM, Weller R, Grau T, Koscielniak-Nielsen, ZJ, Ivani, G. The American
Society of Regional Anesthesia and Pain Medicine and the European Society of Regional Anaesthesia and
Pain Therapy Joint Committee Recommendations for Education and Training in Ultrasound-Guided
Regional Anesthesia. 2009;34:40-46.
DISCLOSURE
Philips, Inc., Consulting Fees
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Multimodal Analgesia for Perioperative Pain Management:

Lecture to Hospital Protocols
Asokumar Buvanendran, M.D. Chicago, Illinois
Multimodal analgesia is achieved by combining analgesics that act by different mechanisms, which result
in additive or synergistic analgesia with reduced adverse effects secondary to the administration of individual
analgesics1. Opioids have long been the mainstay of postoperative analgesia, but the addition of adjuvant
medications permits the use of lower doses of opioids while addressing pain by alternative mechanisms.
Synergistically or additively these adjuvants enhance analgesia provided by opioids and reduce potential adverse
effects. Additionally, acute opioid tolerance has been described and a correlation between high dose intraoperative
opioid administration necessitates increasing postoperative opioid requirements but this may be avoided by the use
of a multimodal perioperative anesthesia and analgesia model2.
Ambulatory surgery encompasses the majority of surgical procedures currently performed in the United
States. The number of procedures performed on an ambulatory basis has increased due to improvements in surgical
technology, anesthetic techniques, and pharmacology- specifically analgesic agents. There is an increasing trend of
performing more painful procedures on an outpatient basis3. Inadequate management of pain or side effects from
medications (such as opioids) can lead to decreased patient satisfaction and delays in discharge. Multimodal
analgesia captures the effectiveness of individual agents in optimal dosages that maximize efficacy and minimize
side effects. The principals are based on constructing a multimodal analgesia strategy that, in addition to regional or
local anesthesia, includes scheduled administration of non-opioid analgesics (e.g. acetaminophen, non steroidal anti-
inflammatory [NSAID], or cyclooxygenase [COX]-2 inhibitors) and using oral opioids only for breakthrough pain.
These regimens must be tailored to individual patients, keeping in mind the procedure being performed, side effects
of individual medications, and patients’ pre-existing medical conditions. Anesthesiologist are challenged to provide
anesthesia and analgesia using the foundations of multimodal analgesia in order for patients to attain rapid recovery
and discharge from the hospitals4,5.
Though there are various classes of drugs for multimodal therapy-the ability to combine them in an effective
manner to provide the optimal outcome for the surgical patients is critical. By implementing procedure-specific
regimens composed of NSAIDs, acetaminophen, and short-acting opioids many patients will have improved
analgesia following mild to moderately painful procedures. The use of steroids, anticonvulsants, and NMDA
receptor antagonists should be considered based on the amount of postoperative pain that is anticipated and patients
co-existing medical conditions. Infusions, such as α2 agonists, β-blockers, and local anesthetics, may also prove
useful in more painful procedures. To facilitate quicker onset of analgesics, utilizing new routes of administration
(e.g. intranasal ketorolac) should become increasingly popular. Their use should also be emphasized, as many have
already demonstrated fewer side effects. As advancements in pharmacology and equipment improve, so should the
anesthesiologist’s ability to provide a safe, balanced, multi-modal analgesic regimen for a variety of surgical
procedures.
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1. Kehlet H, Dahl JB: The value of “multimodal” or “balanced analgesia” in postoperative pain treatment.
Anesth Analg 1993; 77: 1048-1056.
2. Williams B, Buvanendran A. Non-opioid adjuvants in multimodal therapy for acute perioperative pain.
Adv Anesth 2009; 27: 111-142
3. Joshi GP. Multimodal Analgesia Techniques for Ambulatory Surgery. International Anesthesiology
Clinics 2005; 43(3): 197-204.
4. Buvanendran A, Thillainathan V: Preoperative and postoperative anesthetic and analgesic techniques for
minimally invasive surgery of the spine. Spine 2010; 15: S274-80.
5. Buvanendran A, Tuman KJ, McCoy DD, Matusic B, Chelly JE: Anesthetic techniques for minimally invasive
total knee arthroplasty. J Knee Surg 2006; 19: 133-6.
DISCLOSURE
Pzifer, Funded Research ; NIH, Funded Research ; Cumberland, Funded Research
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Clinical Pathways for Total Joint Arthroplasty:

Essential Components for Success
James R. Hebl, M.D. Rochester, Minnesota
Clinical Pathways: An Overview

The term clinical pathway refers to a multidisciplinary process of mutual decision-making that results in the
organized care of a well-defined group of patients during a well-defined period of time.[1, 2] Clinical pathways
were first introduced in the 1980’s when escalating medical costs pressured physicians to decrease resource
utilization without jeopardizing patient safety or clinical outcomes. At that time, pathways were typically
procedure-specific (e.g., coronary artery bypass grafting, total knee arthroplasty) and tailored to a specific
institution.[3, 4] As a result, tremendous variability often existed from one institutional clinical pathway to another,
making clinical comparisons between pathways and formal scientific study exceedingly difficult.
Despite this variability, it is generally agreed upon that clinical pathways provide several distinct advantages. These
include the ability to (1) provide coordinated care between departments and across patient care units; (2) standardize
patient care and reduce hospital length-of-stay; (3) convert typical inpatient (i.e., same-day admission) procedures to
outpatient (i.e., same-day discharge) procedures; (4) prompt change in the care process to better emphasize patient
outcomes and cost containment; (5) control hospital costs; and (6) serve as a marketing tool with the public or with
third-party payers.[5]
Despite these challenges, this review will summarize the important components of a successful clinical pathway and
attempt to evaluate the impact of differing clinical pathways on major perioperative outcomes after total joint
arthroplasty. Perioperative outcomes that will be evaluated include postoperative complications, hospital length-of
stay, clinical outcomes, and medical costs.
Clinical Pathway Components

Effective clinical pathways for major orthopedic surgery include the coordination and standardization of several
patient care activities during the pre-, intra-, and postoperative period. Essential components of some of the most
effective orthopedic clinical pathways are listed in Table 1.
Preoperative Patient Education

Major orthopedic surgery can be a stressful and anxiety-provoking experience for most patients. Bondy and
colleagues [6] examined the effect of anesthesia patient education on preoperative anxiety and found that a detailed
patient education program may have several beneficial effects. Preoperative patient education may significantly
relieve patient anxiety and emotional stress by providing a better understanding of the perioperative process (e.g.,
preoperative evaluation, hospital admission process, anesthetic options, expected clinical course) and establishing
clear expectations with regard to hospital length-of-stay and the discharge process (e.g., dismissal to home vs.
rehabilitation swing-bed vs. nursing home). Because patients have a better understanding of the perioperative
process, they will often present for surgery with increased confidence in the therapeutic plan and a willingness to
more actively participate in their care. Increased participation often results in greater patient satisfaction and
potentially improved perioperative outcomes. However, the extent to which patient education influences
postoperative outcomes is somewhat unclear.[7-9] McDonald and colleagues [8] demonstrated that preoperative
patient education may result in a modest benefit in preoperative anxiety. However, this benefit failed to persist on
Postoperative Day (POD) 2 or at the time of hospital discharge. A review of the Cochrane Database on this topic
fails to demonstrate that preoperative patient education has a significant impact on postoperative clinical outcomes
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(e.g., postoperative pain, functional outcomes, hospital length-of-stay) in patients undergoing total hip or total knee
arthroplasty.
Multimodal Analgesia
Patients undergoing total knee and total hip arthroplasty experience significant postoperative pain.[10] Severe pain
occurs in 60% of patients and moderate pain in up to 30% of patients undergoing total knee arthroplasty. Failure to
provide adequate analgesia may impede early physical therapy and rapid rehabilitation,[11] which are both
important factors for maintaining joint range of motion and facilitating hospital discharge.[12] In an effort to avoid
many of the side effects commonly associated with opioid-induced analgesia, clinicians have begun adopting
multimodal therapeutic regimens. Multimodal analgesia has become an important concept in the field of modern
pain management.[12-17] The concept is designed to combat pain perception along several pathways of signal
transmission, including the surgical site and surrounding tissues, local sensory nerves, and central nervous system.
Advantages include superior analgesia secondary to the synergistic effects of multiple agents acting via different
pathways, the ability to limit parenteral opioid administration, and minimizing opioid-related side effects. Several
investigations have demonstrated the beneficial effects of multimodal analgesia,[14-16] including its value in
patients undergoing major orthopedic joint replacement surgery.[17-24]
Table 1. Essential Clinical Pathway Components
Preoperative
• Preoperative patient education program
• Appropriate management of preoperative pain and psychological symptoms (fear, anxiety, depression)
Intraoperative
• Development of a comprehensive multimodal analgesic regimen
• The use of peripheral nerve blockade and continuous perineural catheters
• Postanesthesia Care Unit (PACU) algorithms for the management of acute postoperative pain
Postoperative
• Standardized method of pain assessment on the nursing floors and pain score documentation within the medical
record
• Early and accelerated rehabilitation regimen
• Development of an integrated and multidisciplinary Acute Pain Service
• Staff education regarding the importance of pain management
• Written protocols for acute postoperative pain management
Several medications may be used as part of a multimodal analgesic pathway. Specifically, the use of
acetaminophen,[25] non-steroidal anti-inflammatory agents,[26] selective cyclooxygenase-2 inhibitors,[18]
pregabalin,[21] and ketamine,[22] have all been shown to have analgesic benefits in patients undergoing joint
replacement surgery. Most experts recommend using multiple agents during the pre- and postoperative period in
small quantitative doses to maximize the analgesic effect while minimizing associated side effects. Documented
benefits include superior postoperative analgesia,[18, 22, 25, 26] reduced supplemental opioid requirements, [18, 21,
22, 25, 26] fewer opioid-related side effects,[13, 18] improved joint range-of-motion,[18, 21] fewer postoperative
sleep disturbances,[18] shorter time to achieve hospital discharge criteria,[21] improved functional mobility,[22] and
a lower incidence of chronic neuropathic pain.[21]
Finally, poorly controlled acute postoperative (i.e., nociceptive) pain may contribute to the development of chronic
neuropathic pain or complex regional pain syndrome after total joint arthroplasty.[27] Nikolajsen and colleagues
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examined the Danish Hip Arthroplasty Registry and found that 12% of patients continue to experience moderate-to-
severe pain 12-18 months after surgery.[28] Similarly, up to 13% of total knee arthroplasty patients may experience
moderate-to-severe pain 12-months after surgery.[29] Additional risk factors for the development of chronic
postoperative pain include preoperative pain for greater than 1-month, an increased intensity of preoperative pain,
and a patient history of preoperative fear, anxiety or depression.[29, 30] Poorly controlled postoperative pain has
also been shown to impede global recovery and lower the reported quality of life 6-months after surgery.[31]
Therefore, clinical pathways that integrate (1) a comprehensive multimodal analgesic regimen to adequately manage
pre- and postoperative pain; and (2) a comprehensive psychiatric program to manage preoperative psychological
symptoms may have a significant benefit in improving long-term clinical and psychiatric outcomes.
Peripheral Nerve Blockade and Continuous Perineural Catheters

Many treatment regimens for managing severe postoperative orthopedic pain include significant doses of parenteral
opioids. These treatment regimens are commonly associated with significant opioid-related side effects such as
sedation, nausea, vomiting, ileus, and urinary retention that can adversely effect patient outcomes and prolong
hospital length-of-stay.[19] Therefore, clinical pathways that minimize (or eliminate) opioid administration may
significantly reduce opioid-related side effects and improve postoperative patient outcomes.
The integration of regional anesthesia and peripheral nerve blockade into clinical pathways for orthopedic surgery is
an essential step to minimize opioid use and improve perioperative outcomes. Both single-injection [32-35] and
continuous [36-40] peripheral nerve block techniques have been shown to provide superior analgesia, reduce
supplemental opioid requirements, decrease opioid-related side effects, and improve functional outcomes after total
joint arthroplasty. In a recent meta-analysis of 19 articles and 603 patients, Richman and colleagues [41] also
demonstrated that patients receiving continuous peripheral nerve blockade have superior analgesia, fewer opioid-
related side effects (nausea, vomiting, pruritus, sedation), and improved patient satisfaction when compared to
traditional intravenous opioids alone. Although single-injection techniques have been shown to be superior to
placebo or systemic analgesia [32-35], comparison studies have shown that single-injection blocks fail to provide
the extended benefits of continuous perineural catheters.[37, 42, 43] Continuous peripheral nerve block techniques
have also been shown to have similar analgesia – but a more desirable side effect profile – when compared to
epidural analgesia.[44] A recent review by Fowler and colleagues [44] demonstrated that patients receiving
peripheral nerve blocks had less urinary retention and fewer episodes of postoperative hypotension when compared
to patients receiving neuraxial techniques.
A primary concern regarding the use of peripheral nerve blockade is the risk of neurologic complications.
Barrington and colleagues [45] recently performed a prospective audit of more than 7,000 peripheral nerve blocks
performed at 9 Australian hospitals. Overall, they identified a neurologic injury rate of 0.5%. However, only 10%
of these injuries were attributed to peripheral nerve blockade suggesting that the vast majority of perioperative nerve
injuries have a non-anesthesia related etiology. The nerve injury rate attributed to peripheral nerve blockade was
found to be 0.04% − a rate similar to other large-scale investigations.[46, 47] Jacob and colleagues [48] have also
demonstrated that neither the type of intraoperative anesthesia (general versus neuraxial) nor the use of peripheral
nerve blockade was associated with an increased risk of perioperative nerve injury in 12,329 patients undergoing
total knee arthroplasty. Rather, bilateral surgical procedures and total tourniquet time were found to be associated
with an increased risk of nerve injury.[48]
Standardized Pain Assessment and Documentation, Pain Management Protocols and Staff
Education
In 2001, the Joint Commission declared pain as the “Fifth Vital Sign” and instituted Pain Management Standards for
accredited ambulatory care facilities, behavioral health care organizations, critical access hospitals, home care
providers, hospitals, office-based surgery practices, and long-term care providers.[49] The standard requires health
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care providers to (1) Appropriately assess and manage pain; (2) Document pain management interventions and
subsequent reassessments; (3) Perform pain screenings during initial patient assessments; and (4) Educate patients
and their families about pain management. Benhamou [50] and Fletcher [51] report that similar guidelines and
recommendations have been put forward by the Royal College of Surgeons, the French Ministry of Health, the
French Society of Anesthesia and Intensive Care, the European Task Force on Pain Management, and the
International Association for the Study of Pain. The overwhelming consensus is that each of these interventions
should be considered essential components to any clinical pathway designed to optimize pain management and
patient care. Despite these recommendations, the literature suggests that pain remains under-treated in both U.S.
[52] and European [53] health care facilities – in part, because of a lack of adherence to previously published
standards and guidelines.
Early and Accelerated Rehabilitation

An early and accelerated rehabilitation program should also be integrated into clinical pathways designed for total
hip and total knee arthroplasty patients. A review of the literature suggests that early and accelerated rehabilitation
may have a major impact on improved perioperative outcomes in orthopedic patients.[9, 55] Munin and colleagues
[55] demonstrated that early inpatient rehabilitation resulted in a shorter hospital length-of-stay and a more rapid
attainment of short-term functional outcomes after joint replacement surgery when compared to a delayed
rehabilitation program. Pour and colleagues [9] also examined the impact of an accelerated pre- and postoperative
rehabilitation program versus a standard regimen on functional outcomes after total hip arthroplasty. Patients
randomized to the accelerated pathway were seen earlier on the day of surgery and more frequently on subsequent
postoperative days (twice daily versus once daily). There was also a greater emphasis on oral analgesics (versus
intravenous patient-controlled analgesia) in patients receiving accelerated rehabilitation. In addition to a shorter
hospital length-of-stay, accelerated pathway patients were able to walk for longer distances, had improved pain
control, and reported higher patient satisfaction at the time of hospital discharge.[9]
Finally, Mahomed and colleagues [56] have demonstrated that rehabilitation after total hip or total knee arthroplasty
does not need to be restricted to the inpatient setting. Home-based rehabilitation programs may provide similar
degrees of postoperative analgesia, functional outcomes, and patient satisfaction at a significantly lower cost when
compared to hospital-based regimens.[56]
Clinical Pathways and Perioperative Outcomes

The goal of most clinical pathways is to provide standardized, evidence-based care to patients in such a way as to
minimize the variability of care provided by individual providers. This process has the potential to significantly
enhance the quality, improve the safety, and reduce the cost associated with surgical procedures. Several clinical
pathways have been reported in the literature for patients undergoing total joint arthroplasty [1, 4, 19, 20, 57-59];
with no two pathways being identical. As a result, comparison of clinical pathways is exceedingly difficult –
forcing systematic reviews or meta-analyses that examine the topic to comment on the “concept” of clinical
pathways versus their individual component parts. Barbieri and colleagues [1] recently performed a systematic
review of clinical pathways used for joint replacement surgery. The review examined 22 studies and included 6,316
patients. The aggregate results demonstrated a significant reduction in postoperative complications (deep venous
thrombosis, pulmonary embolism, manipulation, superficial infection, deep infection, heel decubitus ulcers), a
shorter hospital length-of-stay, and lower hospital costs in patients undergoing clinical pathways versus standard
care.[1] Publications from the University of California – Irvine, the University of Utah, and the Mayo Clinic are
described below; and represent typical examples of clinical pathways developed for orthopedic surgical patients.
Clinical Pathways for Total Joint Arthroplasty

Skinner and colleagues [57] performed a retrospective, case-controlled investigation of 102 patients undergoing total
hip or total knee arthroplasty at the University of California – Irvine. They compared a multimodal clinical pathway
that incorporated COX-II inhibitors, tramadol, dexamethasone, acetaminophen, and intra-articular bupivacaine to
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patients receiving “standard management” with patient-controlled analgesia and intravenous opioids. Importantly,
the authors did not incorporate regional anesthesia or peripheral nerve blockade as a component of the clinical
pathway. Clinical endpoints were evaluated during POD 1 through 4. For patients receiving the clinical pathway,
opioid requirements were reduced 66% for total hip arthroplasty (POD 2 only) and 68% for total knee arthroplasty
(POD 3 only). Although VAS pain scores were no different among total hip arthroplasty patients, patients
undergoing total knee arthroplasty reported lower VAS pain scores on POD 2 and at the time of hospital discharge.
Implementation of the clinical pathway resulted in no differences in perioperative complications. Hospital length-
of-stay was reduced in only total knee arthroplasty patients undergoing the clinical pathway (4.0 vs. 4.9 days;
P<0.02). [57]
In contrast to clinical pathways not incorporating regional anesthesia [57] – multimodal regimens utilizing
peripheral nerve blockade have been shown to consistently reduce hospital length-of-stay, improve perioperative
analgesia with fewer opioid medications, facilitate postoperative rehabilitation, and reduce opioid-related side
effects.[19, 20, 58] Peters and colleagues [58] performed a retrospective analysis of 100 patients undergoing total
hip and total knee arthroplasty at the University of Utah.[58] The clinical pathway included a multimodal analgesic
regimen (sustained-release oxycodone, COX-II inhibitors, and acetaminophen), intraoperative regional anesthesia
with intrathecal opioids, and an ultrasound-guided femoral nerve catheter (total knee arthroplasty patients only) for
extended postoperative analgesia. Prior to wound closure, patients undergoing both total hip and total knee
arthroplasty received <1 mg/kg of 0.25% bupivacaine injected into the deep and subcutaneous tissues by the
orthopedic surgeon. A multimodal oral analgesic regimen was then continued into the postoperative period.
Control patients were managed with intraoperative general or spinal anesthesia (within intrathecal morphine),
continuous femoral nerve blockade (total knee arthroplasty patients only), and postoperative patient-controlled
analgesia with intravenous opioids. Patients receiving the clinical pathway had significantly lower pain scores at
rest on POD 1 and 2, lower opioid requirements, improved ambulation during rehabilitation sessions, and reduced
hospital length-of-stay. There were no differences in perioperative complications when comparing clinical pathway
to control patients. Overall, the investigators concluded that the development and implementation of a
comprehensive clinical pathway combined with early and aggressive physical therapy improves perioperative
outcomes, shortens hospital length-of-stay, and allows patients to achieved physical therapy goals earlier when
compared to non-clinical pathway patients.[58]
Finally, Hebl and colleagues have described the development and implementation of the Mayo Clinic Total Joint
Regional Anesthesia (TJRA) Clinical Pathway in patients undergoing both minimally-invasive [19] and traditional
[20] total hip and total knee arthroplasty. The TJRA Clinical Pathway incorporates preoperative patient education, a
multimodal analgesic regimen emphasizing peripheral nerve blockade, standardized PACU algorithms, pain
assessments, and medical record documentation, pain management protocols, and a standardized postoperative
physical therapy regimen for patients undergoing total joint arthroplasty. Similar to most clinical pathways, the
TJRA Clinical Pathway was developed by a multidisciplinary group of Mayo Clinic surgeons, anesthesiologists,
pharmacists, nurses, and physical therapy staff based upon their collective experience and exposure to physicians
and practice models outside the institution. Although the basic principles of the pathway have remained unchanged
(e.g., preoperative patient education, multimodal analgesia, peripheral nerve blockade, pain management protocols),
its individual components are continually being evaluated and modified as necessary based upon changes in clinical
practice.
Limitations of Clinical Pathways

Effective perioperative pain management is not without potential consequences. In 2001, the Joint Commission on
Accreditation of Healthcare Organizations (JCAHO) declared pain as the 5th vital sign and mandated that pain
management become an integral component of all patient care activities as a condition of hospital accreditation. As
a result, many institutions implemented aggressive pain management protocols that were guided by patient reports
of pain intensity as quantified by a numeric pain scale. Although numeric pains scales may be useful to monitor
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pain trends within a given patient, these subjective methods of pain assessment are an extremely poor guide for
directed analgesic management. In fact, because these subjective and often non-reproducible pain scales do not take
into consideration patient comorbidities or associated medication risks, adverse outcomes such as oversedation and
respiratory depression may lead to catastrophic outcomes – including death.[70, 76, 77]
Vila and colleagues [78] demonstrated the potential negative impact of implementing a hospital-wide pain
management protocol that treats pain based upon patient self-reports. After implementation of a numeric pain
treatment algorithm, the number of adverse drug reactions secondary to opioid oversedation more than doubled
when compared to pre-implementation values (24.5 vs. 11 adverse events per 100,000 inpatient hospital days;
P<0.001). A decreased level of consciousness preceded 94% of events, emphasizing the importance of careful
clinical assessment and ongoing patient monitoring while managing pain.[78] Overmedication in preparation for an
imaging study,[70] overmedication after discharge from the ICU ,[70] and the first 24 hours after surgery [77]
appear to be the clinical scenarios or time periods in which patients are at greatest risk for respiratory depression and
oversedation.
Finally, clinical pathways that incorporate regional anesthesia and peripheral nerve blockade may increase the
likelihood of residual motor blockade – which may impede early mobilization, increase the risk of patient falls, and
prolong hospital length-of-stay.[43, 79-82] Kandasami and colleagues [80] recently reported a fall rate of 2% in
patients undergoing total knee arthroplasty with the use of femoral nerve blockade. Fall-related injuries included
wound dehiscence (n=4) and periprosthetic fracture (n=1). Hospital length-of-stays were extended 10 to 42 days
secondary to complications from the fall. However, it has been argued that residual motor blockade is a
multifactorial phenomenon – and cannot be entirely attributed to regional anesthesia. In addition to local anesthetic-
induced quadriceps weakness, it is believed that motor block can occur secondary to surgical pain, muscle spasm,
joint stiffness, swelling, dysesthesias, or other surgical factors.[83] Regardless of the cause, anesthesia providers
need to play their role in minimizing the risk of residual motor blockade in patients undergoing total hip and total
knee arthroplasty. Clinical pathways that incorporate peripheral nerve blockade need to do so in such a way that the
benefits of regional anesthesia are achieved (i.e., identifying the optimal local anesthetic, dose, and concentration);
while the contemporary concerns of delayed rehabilitation, prolonged hospital length-of-stay, and increased hospital
costs are avoided.
Summary
Total hip and total knee arthroplasty are two of the most commonly performed surgical procedures in the United States
with increased volumes expected over the next several decades. Clinical pathways represent a standardized,
evidence-based approach to patient care designed to enhance the quality, improve the safety, and reduce the cost
associated with surgical procedures. Clinical pathways for total joint arthroplasty have been shown to significantly
improve the perioperative outcomes of patients undergoing joint replacement surgery. Effective clinical pathways
include preoperative patient education, a multimodal analgesic regimen, peripheral nerve blockade, standardized
pain assessment and medical record documentation, pain management protocols, staff education, and early and
accelerated rehabilitation. Potential clinical benefits include superior postoperative analgesia, fewer opioid-related
side effects, earlier ambulation, improved joint range-of-motion, fewer postoperative complications, and reduced
hospital length-of-stays. The financial benefits of clinical pathways include a reduction in both total hospital and
direct medical costs. However, further study is needed to determine precisely which component(s) of a
comprehensive clinical pathway are most active in contributing to these clinical and financial benefits.
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36. Edwards ND, Wright EM. Continuous low-dose 3-in-1 nerve blockade for postoperative pain relief after total knee
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37. Singelyn FJ, Deyaert M, Joris D, et al. Effects of intravenous patient-controlled analgesia with morphine, continuous
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total knee arthroplasty. Anesth Analg 1998;87(1):88-92.
38. Ganapathy S, Wasserman RA, Watson JT, et al. Modified continuous femoral three-in-one block for postoperative
pain after total knee arthroplasty. Anesth Analg 1999;89(5):1197-1202.
39. Kaloul I, Guay J, Cote C, et al. The posterior lumbar plexus (psoas compartment) block and the three-in-one femoral
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40. Siddiqui ZI, Cepeda MS, Denman W, et al. Continuous lumbar plexus block provides improved analgesia with
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41. Richman JM, Liu SS, Courpas G, et al. Does continuous peripheral nerve block provide superior pain control to
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Anesthesia Hotline Service. Anesthesiology 2002;97(5):1274-1280.
48. Jacob AK, Mantilla CB, Sviggum HP, et al. Perioperative nerve injury after total knee arthroplasty: regional
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49. Commission J. Pain Management Standards. 2001; Available at:
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50. Benhamou D, Berti M, Brodner G, et al. Postoperative Analgesic THerapy Observational Survey (PATHOS): a
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51. Fletcher D, Fermanian C, Mardaye A, et al. A patient-based national survey on postoperative pain management in
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52. Apfelbaum JL, Chen C, Mehta SS, et al. Postoperative pain experience: results from a national survey suggest
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57. Skinner HB, Shintani EY. Results of a multimodal analgesic trial involving patients with total hip or total knee
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58. Peters CL, Shirley B, Erickson J. The effect of a new multimodal perioperative anesthetic regimen on postoperative
pain, side effects, rehabilitation, and length of hospital stay after total joint arthroplasty. J Arthroplasty 2006;21(6
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81. Klein SM, Nielsen KC, Greengrass RA, et al. Ambulatory discharge after long-acting peripheral nerve blockade:
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DISCLOSURE
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Practical Regional Anesthesia: Making It Work in the Real World
Michael F. Mulroy, M.D. Seattle, Washington
Introduction Despite many documented advantages of regional anesthesia (RA), its utilization remains at the
15-30% level in current practice.1 Reasons cited are the additional time and expertise required for this skill, often
leading to resistance by surgeons and hospitals concerned with efficiency. This review will address some of the
reasons we should pursue greater application of regional techniques, as well as practical tips to improve your
personal success and your institutional and surgical acceptance.
Why should we work to make it work? – Reasons to do regional more often

Although general anesthesia has become easier and safer with modern drugs and monitoring devices,
regional anesthesia offers significant advantages to offset the additional work required to perform blocks.
“Old” News- There is at least one meta-analysis that suggests that intraoperative use of regional techniques can
reduce mortality and morbidity2, but the majority of data focuses on the improved benefits in the perioperative
period when regional techniques are used or continued for post-operative analgesia. The evidence is established that
epidural opioid-local anesthetic infusions provide superior post-operative pain relief compared to traditional
systemic opioids after major abdominal, vascular and thoracic surgery 3 4 5, and appear to reduce cardiac6,
respiratory7, and gastrointestinal8 morbidity. After major orthopedic joint replacements, nerve blocks and continuous
peripheral nerve catheters consistently provide superior analgesia and improved rehabilitation for these increasingly
common painful operations in our aging population9 10 and may even reduce hospital costs.11 In outpatient surgery
(now over 60% of our volumes), regional provides better analgesia and less nausea12, and has the potential to
provide faster discharge.13 14 The use of long-acting blocks and continuous catheters provides superior analgesia in
this population also15 16, and allows faster return to normal sleep and activity patterns.17 18
Recent Developments- There is a suggestion that development of chronic pain19 or cancer recurrence20 can be
reduced when RA is used. Chronic pain is reported to develop in 10-50% of patients after hernia, thoracotomy, or
breast surgery, and the incidence appears to be reduced if aggressive effective multimodal analgesia techniques
(including RA) are employed compared to standard opioid therapy. More recent interest has focused on the
potential role of RA in modifying cancer progression. The natural stress response to surgery inhibits cellular
immunity and increases pro-angiogenic factors that may reduce resistance to cancer spread or growth. The
reduction in the neuroendocrine response associated with RA may reverse these tendencies, and reports have
suggested a reduction in recurrence or mortality in breast21, melanoma22, and colon23 cancer operations, though the
data are equivocal for prostate and other cancers; further research is ongoing.
“Breaking News”-. The Centers for Medicare and Medicaid Services (CMS) has developed an incentive pay
system that rewards performance on several perceived “quality measures”, including 12 clinical process based
scores and 8 “patient-experienced” based scores. Thirty percent of scores used for Value Based Purchasing (VBP)
are derived from 18 patient satisfaction questions, 6 of which relate to pain control experiences.24 In an increasingly
competitive hospital reimbursement environment, we may actually see hospital administrations (and surgeons!)
expressing more interest in superior pain control regimens. Recent ASA Guidelines for Acute Pain Management25
help show the path to improvement, and they include RA extensively. And many hospital administrators are asking
if RA analgesia techniques can help reduce post-operative delirium and falls by avoiding opioids.
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Table 1. Meta-Analyses of Regional Anesthesia Outcomes

Overall Morbidity Lower morbidity, 30% lower mortality Rodgers et al., BMJ 2000
Liu, Wu, Anesth Analg 2007
Pain relief Epidural superior, esp. thoracic Block et al. , JAMA 2003
Wu et al, Anesthes 2005
Cardiac Lower incidence of myocardial infarction with Beattie et al., AA 2001
complications thoracic infusions
Respiratory Fewer complications, infections with epidural Ballantyne et al, AA 1998
Gastrointestinal Faster return of function Steinbrook et al. AA 1998
Continuous Better pain relief with catheters, faster Richman et al, AA 2006
Catheters rehabilitation in European experience Ilfeld, AA 2011
Then Why Don’t We? – Reasons Regional is Challenging

Despite these advantages, however, surveys suggest regional techniques are employed in less than 30% of
surgical procedures.1 26 Surveys of post-operative pain scores suggest that there has been no improvement in patient
analgesia despite the availability of these superior techniques in the last 15 years.27 28 Despite the superior pain
relief for outpatients, nerve blocks are used in less than 15% of knee operations and less than 25% of shoulder
surgeries.29
As mentioned above, the main reasons are the issue of time and surgeon acceptance. Surgeon acceptance
can be improved if we overcome the time issues as well as documenting the advantages listed above. A 2004 survey
of Canadian orthopedic surgeons revealed that although they recognized the advantages of better pain control and
fewer complications, they encouraged their patients to have regional blocks only 40% of the time, based on
perceived delays in induction.30 Surgeons were more likely to recommend regional anesthesia for procedures for
which they themselves would prefer regional!31 In our practice we have found that they are more likely to accept RA
when they find that they get fewer postoperative phone calls. Hopefully, we will discuss several steps that can help
overcome all these issues in this presentation.
Opportunities for Improvement

There are “six p’s” that can help us improve personally, and as a team/institution.
Improve our personal proficiency. The first step for most of us is to improve our own success rates so that we
are more efficient and reliable, and our surgeons are more willing to accept regional interventions. This lecture is
not an attempt to improve performance on specific blocks: there are multiple presentations and workshops that
provide that function in the program. Many other opportunities are also available now in terms of workshops,
especially with the recent increasing popularity of ultrasound guidance for nerve blocks. Workshops and courses are
available virtually every month in every corner of the country (see ASA website Calendar of Meetings,
www.asra.com/education, as well as www.nysora.com).
Should you incorporate ultrasound? Nerve stimulation is still an efficient technique and traditional surface
and bony landmarks are still the basis of spinal and epidural anesthesia. Ultrasound guidance has not risen to be “the
standard”, but there are increasing data that it facilitates speed and accuracy of block performance,32 33 although
further information is needed to assess the potential improved safety possible when the needle is visualized directly.
There are now excellent reviews of ultrasound technology34 35, and a plethora of companies competing to produce
high quality imaging devices. Many anesthesiologists have gained renewed confidence in blocks because of the
ability to visualize the nerves, and an improved success rate when they have the chance to see “live” the variations
of anatomy that may have accounted for previous failures with traditional techniques.
Some basic principles can improve success regardless of the technique used:
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a) Plan for success. Choose simple and reliable blocks at the start, such as spinal, femoral and axillary (and
even supraclavicular with ultrasound). Avoid the complex techniques requiring a knowledge of Euclidian geometry,
such as the traditional infraclavicular and proximal sciatic. Also, pick blocks that fit your surgeons’ needs, such as
femorals for the total knee replacements, thoracic (rather than lumbar) epidurals for upper abdominal surgery, and
popliteal fossa blocks for the painful foot surgeries that benefit from prolonged analgesia. When appropriate, use
fast onset local anesthetics, such as chloroprocaine or lidocaine. With lidocaine or mepivacaine, though the data are
confusing, consider adding 1 mL NaHCO3 to each 10 mL of local anesthetic to speed onset (don’t try this with
bupivacaine!).36
b) Prepare yourself and your work area before doing your first attempt.
i) Know the anatomy of the nerve and its surroundings first, particularly the easily identifiable landmarks such as
prominent bones (C6 tubercle for interscalene) or arteries (axillary and femoral). Review the anatomy books,
websites and recent articles on techniques and hazards, and go to one of the many workshops mentioned above.
ii) Prepare your equipment beforehand. Have your drugs, gloves, trays, and resuscitation equipment all in one area
on a cart so that you do not waste time assembling them (or forget an essential item).
iii) This includes a workspace, such as a block room or corner of the PACU where monitors, oxygen and
equipment are available.
c) Practice as much as possible. Develop an efficient style. With either nerve stimulator or paresthesia
technique, search for the nerve in a logical fashion, usually confining the needle movement to small steps in one
plane that is perpendicular to the perceived path of the nerve (useful for interscalene, distal sciatic). Or start next to
an artery (axillary, femoral) and walk in small steps away from it. For ultrasound techniques, use the “phantom”
models to acquire dexterity with needle visualization, and practice scanning the anatomy on yourself, your
colleagues, and your partners. More IS better.
d) Finally, Persist. All new technical procedures have an inevitable failure rate37 on the initial learning
curve, including ultrasound.38 Acknowledge early failures and move rapidly to “plan B”, but don’t give up after the
first ten attempts. Particularly, don’t succumb to the temptation to try another approach – they all work pretty well
when you get past the first struggles, and you will only be climbing onto the bottom rung of another learning curve!
Improve our “team” proficiency Two other “p”s

e) Personnel are critical. You will need help with the blocks, at several stages.
i) First, education of the patient is critical, and if it is done preoperatively, it is a great time saver. This may require
enlisting your pre-anesthesia clinic staff or a partner to explain the procedure and prepare the patient before arrival.
Or even on the day of surgery, a discussion before the “rushed” start of a block is helpful. In the best scenarios, your
surgeon will tell the patient about the block!
ii) Secondly, you will need hands to help position, monitor, and sedate the patient, and perhaps even to inject local
anesthetic when your hands are busy with needle and ultrasound probe. This may be a partner or a PACU or
Admitting nurse, most of whom are very interested in participating in procedures, especially when they see it will
make their job in PACU easier! Additional personnel (such as a “floating” anesthesia staff or a designated “block
team” in a large or academic practice) can allow the block to start even earlier.
iii) Finally, you will need a team to follow up with your patients at home or on the wards. Creating a successful
perioperative pain management program requires a 24/7 commitment, which is far easier when you have colleagues
or a team nurse who are equally committed to ensuring adequate relief and correction of any defects in doses,
pumps, or side effects.
f) Finally, Processes are essential. Success in initiating an ongoing RA program depends on procedural
steps to reduce the time for placement of blocks and allow for onset of local anesthetic action. General principles
for efficiency can be adapted from business models, like the “Toyota Production System” that Boeing has adopted.
i) First, create “Standard work” and expectations. Establish, for example, a pattern that “every knee replacement
gets a femoral nerve block”. Then the surgeon starts that discussion in his or her office, and the patient arrives
expecting a block. The anesthesia pre-operative visit confirms and explains the plan, and the admitting nurse on the
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day of surgery knows that the patient needs to be on a stretcher, the team needs to be called early, and the necessary
equipment is ready when the anesthesiologist arrives. The block is done in the same way, with the same equipment
and drugs, every day, so the same supplies are stocked and ready. The OR, PACU, and ward nurses are not
“surprised” by a numb limp extremity, and the physical therapists know to test for return of motor function before
starting ambulation. Every patient has one, every care provider knows. (In our hospital, every total knee
replacement receives multimodal oral analgesics, spinal anesthesia for surgery, a femoral nerve catheter that is
turned off for 16 hours to allow physical therapy on POD1 and removed on POD2, and rapid transition to oral
analgesics on POD1) This saves time on a daily basis, and potentially improves safety because everyone is aware
of the pathway.
ii) The process must be “Transparent”. The surgeon’s pre-op orders confirm the request for the block. The
anesthesia plan confirms it, documents standard information in a standard form, and has a template in the
computerized orders for management of the patient monitoring, drug administration, and infusion maintenance. The
process is visible and clear to all the participants.
iii) Externalizing the set-up away from operating room is essential to Eff iciency S teps:
improving efficiency. The exact mechanism will vary depending on local 1) Create “standard work”
situations, but there are many opportunities: the Cleveland Clinic has 2) Make the plan “transparent to
published their pathway for arthroplasties as one example.39 A central the entire team
principle is that to avoid any delays in the operating room process, the block 3) Perform blocks away from the
is performed in a separate area – a block room40, the admitting area, or a operating room
corner of the PACU where necessary monitors and equipment are already 4) Centralize equipment to block
available. The use of the block room actually decreases the “anesthesia area
41
controlled time” in the operating room itself and does not significantly
delay the transfer of the patient to the operating room.42 If standard
equipment is ready, in many hospitals the block can be performed by the same anesthesia team while the operating
room is being cleaned and instruments opened.
iv) A critical component of this process is measuring the actual times involved. In our institution, the known time
for admission, IV placement, and block performance is added together and then subtracted from the anticipated time
the OR will be ready, thus dictating the time the patient will arrive and the anesthesia team will start working. If this
is before the previous patient leaves the OR, obviously alternative teams are needed. And a system has to be in
place to signal the anesthesia technicians (or other support) to assemble the block cart and ultrasound, and call the
anesthesiologist to begin the process.
Apply Efforts Efficiently – pick the best returns for the time. In the process of introducing RA into a
practice where it is not used frequently, choose the procedures with the highest benefits and fewest drawbacks- the
“low-hanging fruit”.
a) Frequently this is the orthopedic service, where the surgeons find that traditional analgesia limits their
patients’ rehabilitation and causes many adjustments of medication (i.e., phone calls) to produce analgesia without
debilitating nausea and vomiting. They are grateful if you can help, and this usually means starting with simple
single-injection femoral nerve or psoas compartment blocks with long-acting drugs for total hip and knee
replacements. Once this procedure is recognized to have advantages, adding a sacral nerve block to provide more
effective analgesia, or a continuous catheter technique to prolong the benefits is much easier to negotiate with the
orthopedic team.
b) Thoracic epidural analgesia requires more time, but is so clearly advantageous to the major vascular and
thoracic surgery patient that the surgeons often request it. Expanding the use of epidural analgesia is usually
dependent on the efficiency steps described above, but a post-operative pain service with epidural infusions as the
mainstay is usually rapidly recognized by the ward nurses, the administration, and the surgeons as being worth the
additional time required for the initial insertion for a catheter.
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c) Outpatient surgery, particularly orthopedic procedures, is another opportunity for increasing the use of
regional techniques. For the painful outpatient procedures (anterior cruciate ligament repair, rotator cuff surgery,
complex foot surgery, open fracture repairs), single injection femoral, popliteal fossa or interscalene blocks can
again be done quickly before the procedure, and allow a comfortable first night for most patients. Initially (if a
block room is not available) it is often expedient to place a block with a long-acting anesthetic and then proceed
with a “quick” general or spinal anesthetic rather than waiting for the slower onset of the block. With this approach,
the surgery begins rapidly, but narcotics can be avoided and patients arrive in PACU alert and pain-free, ready for
rapid discharge. Again, once this advantage is recognized (as well as the risks of intraarticular infusions43), many
orthopedic surgeons are delighted to accept a slightly longer time for the insertion of a continuous catheter which
can extend the analgesia (and the period in which they do not get phone calls for inadequate pain relief). Once these
practices are in place, it becomes easier to advance the use of regional techniques to many other procedures.
Summary Regional techniques offer many advantage to our inpatients and outpatients. Simple steps to
improve our efficiency and reliability can lead to greater success and surgeon and patient acceptance, and bring
these documented benefits to a higher percentage of our patients. Equally important, this is an opportunity for
anesthesia providers to assume a more critical and indispensible role in the medical center. As we move to an era of
Accountable Care Organizations (and the concept of a “Surgical Home”) and more external estimations of the
presumed “quality” of our care environment, RA can extend our visibility and impact and ensure we are part of the
perceived “value” of a patient experience.
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DISCLOSURE
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Regional Anesthesia and the Trauma Patient

Laura Clark M.D. Louisville, Kentucky
Objectives:
Learning Objectives:
1. Choose techniques of never blockade that would be applicable to the trauma patient
2. Explain the current rationale of the beneficial effects of pain relief to the trauma patient
3. Discuss the practical problems in the trauma population such as compartment syndrome, nerve injury
4. Apply continuing catheters and multiple catheters in the trauma patient with multiple injuries and operations
Overview of Trauma Physiology

1. Why pain relief is important
i) Minimize opioid need
(1) Minimize side effects
(2) Respiratory depression
(3) Excessive sedation precluding assessment
ii) Minimize immune suppression
2. Physiology of pain in the trauma patient

i) Hormonal , biochemical
ii) Hypermetabolic response
iii) Proinflammatory state
(1) NF-Kappa Beta
iv) Neurochemistry
(1) Neurotransmitters
(2) Inflammatory mediators
(a) Interleukins
(b) Cytokines
3. The differences in the pain in trauma versus pain in elective surgery

i) Advantages of regional anesthesia : How regional anesthesia and analgesia can be beneficial
ii) The role of multimodal therapy in pain relief in trauma
4 . Additional benefits of regional anesthesia and local anesthetics on perioperative outcome

v) Alternative effects –systemic absorption
(1) Intravenous effects of local anesthetics
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Regional Anesthesia in Other Environments

i) Ambulance
ii) Emergency Room
iii) Battlefield
Chronic Pain in the Trauma Patient

i) Traumatic Amputation
(1) Phantom Limb Pain
ii) TheChronic Pain Patient with Acute Pain
Practical Problems in Trauma Patients
(1) Consent
(2) Positioning
(3) Performing Regional Anesthesia in the presence of nerve injury
(4) The trauma patient with Coagulopathy
(5) Compartment syndrome
Situations Unique to the Trauma Patient
(1) Thoracic Trauma

(a) Treatment of Pain from Rib fractures
(i) Paravertebral
(ii) Epidural
Peripheral Nerve Block and Peripheral Catheters
(1) Single Shot vs Continuous Catheter(s)

(a) Indications
(2) Upper Extremity Blocks and Catheters
(3) Lower Extremity Blocks and Catheters
(4) Ultrasound and Nerve Stimulators \
(5) Complications
Case Examples of Application of Regional Analgesia
(1) Multiple Catheters and Blocks in the Polytrauma Patient

(2) Case of Traumatic Amputation with Prolonged Quad Catheters
(3) Simultaneous Surgery on Bilateral Upper Extremity Trauma
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DISCLOSURE
Covidien ,Honoraria ; Cadence ,Honoraria
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Continuous Peripheral Nerve Blocks

Brian M. Ilfeld, M.D., M.S. San Diego, California
Introduction. Continuous peripheral nerve blocks (CPNB) consists of a catheter that is percutaneously inserted
adjacent to a peripheral nerve, followed by local anesthetic administration via the catheter. Therefore, the terms
“perineural local anesthetic infusion” and CPNB are often used synonymously. The maximum duration of a single-
injection peripheral nerve block is currently 8-24 hours. Therefore, when a prolonged neural blockade is desired,
CPNB provides an option.
Indications. CPNB is used to prolong intraoperative surgical anesthesia; treat intractable hiccups; induce
sympathectomy and vasodilation to increase blood flow following a vascular accident, digit transfer/replantation or
limb salvage; alleviate the vasospasm of Raynaud's disease; and treat peripheral embolism. CPNB can provide
analgesia during transportation following trauma, or waiting for surgical treatment. Reports describe CPNB to treat
chronic pain, such as intractable phantom limb pain, pain from terminal cancer and trigeminal neuralgia, and
complex regional pain syndrome. However, the most common indication is providing postoperative analgesia (the
only indication validated with randomized, controlled clinical trials [RCT]).
Most providers use CPNB exclusively for surgical procedures that are expected to result in pain not easily controlled
with less-invasive analgesic techniques because there are intrinsic risks with the techniques,1 or in patients with an
intolerance to alternative analgesics (e.g., opioid-induced nausea). Although recommendations for the use of various
catheter locations for specific surgical procedures exist, there is little published data specifically illuminating this
issue. In general, axillary, cervical paravertebral (CPVB), infraclavicular, or supraclavicular infusions are used for
surgical procedures involving the hand, wrist, forearm, and elbow (infraclavicular the most effective); interscalene,
CPVB and intersternocleidomastoid catheters are used for surgical procedures involving the shoulder or proximal
humerus (interscalene optimal risk-benefit ratio); thoracic paravertebral catheters are used for breast or thorax
procedures; psoas compartment catheters are used for hip surgery; fascia iliaca, femoral, and psoas compartment
catheters are used for knee or procedures thigh (occasionally hip surgery, although this is somewhat controversial);
and popliteal or subgluteal catheters are used for surgical procedures of the leg, ankle, and foot (popliteal optimal
risk-benefit ratio). CPNB has been described in hundreds of pediatric patients, although it is not as thoroughly
validated as in adults.
Patient Selection. Little published data is available regarding the balancing of potential perineural infusion risks
and benefits for patients with significant comorbidities. Investigators often exclude patients with known hepatic or
renal insufficiency, in an effort to avoid local anesthetic toxicity. For infusions that may effect the phrenic nerve and
ipsilateral diaphragm function (e.g. interscalene or cervical paravertebral catheters), patients with heart or lung
disease are often excluded since continuous interscalene local anesthetic infusions have been shown to cause
frequent ipsilateral diaphragm paralysis. Although the effect on overall pulmonary function may be minimal for
relatively healthy patients,2 practitioners must be aware of the possible related risks and be prepared to manage
complications.
Catheter Insertion (Nerve Stimulation). Various catheter insertion techniques have been used, inducing
paresthesias, eliciting a facial “click”, and fluoroscopic guidance. However, most reports involve electrical
stimulation. One common technique involves giving a bolus of local anesthetic via an insulated needle to provide a
surgical block, followed by the introduction of a “nonstimulating” catheter. Many studies report a high success rate
using this procedure,3-6 but the catheter tip may be unknowingly misplaced during insertion.7,8 To help counter this
risk, the perineural catheter may be first inserted, followed by a local anesthetic bolus via the catheter itself.9-12
Unfortunately, this technique requires waiting at least 15 minutes for block onset/failure, followed by removal of the
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catheter/dressing, re-preparation, and catheter reinsertion for failed a failed insertion.13 In addition, a partial block is
possible suggesting the catheter tip is not optimally located, but often precluding replacement using electrical
current.
Alternatively, catheters which deliver current to their tips have been developed in an attempt to improve initial
placement success rates.14 These catheters provide feedback on the positional relationship of the catheter tip to the
target nerve prior to local anesthetic dosing. There is data to suggest that in the area of the popliteal fossa, using
stimulation during catheter advancement results in the catheter tip being placed closer to sciatic nerve.15-18 The
clinical relevance is questionable femoral and interscalene catheters. 19-27 Regrettably, stimulating catheters
guarantee neither a complete surgical block nor an effective postoperative infusion.21,28-30 Furthermore, an
acceptable muscle contraction may not always be obtained during catheter insertion;21,31-34 and, stimulating catheters
often require an increased insertion time and cost more than their non-stimulating counterparts,18 resulting in many
questioning their cost-benefit ratio. Finally, the minimal acceptable current resulting in a muscle contraction remains
unknown.
Also remaining unknown is the optimal distance to insert the catheter past the needle tip. However, increasing the
insertion distance is correlated with an increased the risk of catheter coiling, and perhaps the ultimate distance
between the catheter and target nerve.35 With catheter insertion over 5 cm, numerous catheter knots have been
reported;36 and, a maximum insertion of 5 cm appears warranted. Likewise, remaining unknown is the optimal
minimum insertion distance; but, studies suggests that 0-1 cm results in a minimal risk of secondary block failure,6
but possibly an increased risk of subsequent dislodgement.
Catheter Insertion (Ultrasound). The limited length of this article precludes an in-depth discussion of
ultrasound-guided perineural catheter insertion; but, the information is available elsewhere.37 While ultrasound
guidance would intuitively seem to increase the accuracy of catheter tip location, identifying the catheter tip is often
challenging. Multiple practitioners observe the location of injected fluid,38 an agitated fluid/air mixture,39 or simply
air.40,41 For most anatomic locations, ultrasound-guided insertion decreases insertion time and associated discomfort
compared with an electrical technique (and provide at least similar analgesia). 31,32,34,42-45 The majority of reports of
combining ultrasound and nerve stimulation suggest little benefit,39,46-50 Currently, insufficient data are available to
determine either the optimal techniques/equipment for these insertion modalities, as well as their associated risks
and benefits.37
Infusates. The majority of perineural infusion publications have involved bupivacaine or ropivacaine, although
levobupivacaine and shorter acting agents have been reported. While the available data suggests bupivacaine and
levobupivacaine are more potent than ropivacaine,51 all three provide similar analgesia within human trials, although
the ropivacaine concentration is often increased up to 50% to compensate for decreased potency.51,52 When a
bupivacaine perineural infusion is paused, the motor and sensory effects greatly outlast those of ropivacaine.52 This
is often important when titrating dose to limit undesired CPNB effects. Also unknown is whether the primary
determinant of CPNB effects is only local anesthetic dose/mass, or if volume (rate) and/or concentration have an
influence.53-55 Currently, additional research is warranted, and no optimal concentration/rate combination may be
recommended for all anatomic locations.56 For bupivacaine/levobupivacaine and ropivacaine, the most-commonly-
cited concentrations are between 0.1-0.125% and 0.1-0.2%, respectively. Unfortunately, no adjuvants—such as
clonidine, epinephrine, and opioids—have been found to improve analgesia and/or decrease undesirable CPNB-
related side effects; and infusing solely long-acting local anesthetic appears warranted.
Local Anesthetic Delivery Regimens. Currently available data suggest that following procedures producing
moderate-to-severe pain, providing patients with the ability to self-administer local anesthetic doses increases
perioperative benefits and/or decreases local anesthetic consumption. Unfortunately, insufficient information is
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available to base recommendations on the optimal basal rate, bolus volume, or lockout period accounting for the
many variables that my effect these values (e.g. catheter type, location, surgical procedure). Until recommendations
based on prospectively-collected data are published, practitioners should be aware that investigators have reported
successful analgesia using the following with ropivacaine (0.2%) or bupivacaine (0.125%): a basal rate of 5 (lower
extremity) or 8 (upper extremity) mL/h; a bolus volume of 2 – 5 mL; and a lockout duration of 20 – 60 min.
Additionally, the maximum safe dose remains unknown. However, multiple investigations involving patients free of
renal or hepatic disease have reported blood concentrations within acceptable limits—and an absence of toxicity
symptoms/signs—following multiple weeks of perineural infusion with similar dosing schedules.57,58
Infusion Pumps. There is no single optimal infusion pump for every clinical scenario; and, therefore, pump
preference is usually dictated by desired device characteristics.59 Although elastomeric infusion pumps cannot match
their electronic counterparts in delivering a basal infusion rate within ±5% expected for the entire infusion duration,
whether the increased variability is clinical significant—or in which clinical situations it is relevant—remains
unknown.59 Providing an adjustable basal infusion rate permits titration of local anesthetic dose for inadequate
analgesia, an insensate extremity, undesired side effects (e.g., muscle weakness),60 or maximizing infusion duration
(e.g., ambulatory patients with a set reservoir volume). Furthermore, multiple clinical benefits are provided with a
patient-controlled bolus option, such as increasing analgesia and decreasing opioid consumption. Electronic pumps
provide an adjustable basal rate, patient-controlled bolus doses, and a variable bolus lock-out period.59 And, while
most elastomeric devices include a fixed basal infusion rate, a few provide similar flexibility to electronic pumps.
Elastomeric pumps are often preferred for their smaller size and lighter weight; lack of audible alarms; disposability;
and silent operation (electronic pumps may disturb patient sleep). In addition, elastomeric devices with no bolus
dose capability and a manufacturer-fixed basal rate are usually less costly. However, inexpensive disposable
“cassettes” provide sterile infusion for individual patients utilizing reusable electronic pumps. A few disposable
electronic pumps are available. At least within the United States, the infusion pump/reservoir must now be filled
under a laminar flow workbench.61 Of note, at least within the United States, there are no national guidelines
regarding the maximum safe CPNB duration.61
Ambulatory Perineural Infusion. While length limitations of this article preclude an extensive discussion of
ambulatory CPNB, this information is available elsewhere.59 Ambulatory perineural infusion may be provided to
outpatients using a portable pump. Perineural infusion is often provided for ambulatory surgery without an overnight
hospital stay;59 but may also shorten hospitalization duration,62,63 and/or bestow benefits following discharge to
either a rehabilitation facility or home.6,58 Ultrasound guidance—with its demonstrated decreased insertion time—is
often beneficial in high-turnover ambulatory centers where time constraints are often severe.31,34,45,64 Patient
selection criteria are often more stringent for ambulatory CPNB since outpatients are rarely directly monitored; and
not all patients desire or are capable of accepting the additional responsibility of caring for the catheter and pump
system. Patients with hepatic or renal insufficiency are often excluded from ambulatory CPNB to decrease the risk
of local anesthetic toxicity. Caution is warranted during interscalene and cervical paravertebral infusion (frequently
induce diaphragm weakness) for obese individuals and those with heart/lung disease who may not be able to
compensate for mild hypoxia and/or hypercarbia.
Ambulatory perineural infusion may reduced time until discharge readiness;6,29,62,65 and, in select cases, actual
discharge.62,63 Early discharge after total knee arthroplasty may decrease hospitalization-related costs.66 However,
caution is warranted prior to allowing discharge with a continuous posterior lumbar plexus and femoral nerve block
given that these catheters are associated with an increased risk of falling.67 Nonetheless, relatively small published
series document the feasibility of total joint arthroplasty with only a single-night hospital stay—or even on an
outpatient basis—when patients are provided CPNB at home.68-72
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Benefits. The most-common indication for CPNB is to provide postoperative pain control, and it appears that most
CPNB benefits are dependent upon successfully improving analgesia.56 RCT-documented benefits include decreased
postoperative pain, supplemental analgesic requirements, opioid-related side effects, sleep disturbances,
dissatisfaction, discharge readiness, actual discharge, and inflammatory markers. In addition, an accelerated
resumption of passive joint range-of-motion is documented following total knee arthroplasty procedures with 48-72
hours of continuous femoral perineural infusion. Analgesia is most impressive when the perineural infusion effects
the entire innervation of the surgical site; as is often the case for shoulder and foot procedures (interscalene and
sciatic perineural catheters, respectively).4,7,62 Unfortunately, even though brachial plexus infusions (theoretically)
cover the entire surgical site for procedures at or distal to the elbow, they provide less impressive analgesia.73.
Severely lacking are RCT-documented benefits of continuous axillary,74 supraclavicular,75 and transversus
abdominus plane blocks.56 And, while the benefits of infraclavicular infusion are validated,73 analgesia is often less-
than-optimal unless a high enough dose of local anesthetic is administered, frequently rendering the extremity
insensate. Similarly, for surgical sites innervated by multiple nerves (such as the knee, hip and ankle), a single
perineural usually provide less-than-optimal analgesia without the concurrent use of additional analgesics.6,29,55
While a lumbar epidural provides roughly equivalent analgesia to femoral perineural infusion for hip and knee
arthroplasty, CPNB results in a more-favorable side-effect profile without the risk of epidural hematoma during
concomitant anticoagulant administration.76-78
While the evidence for CPNB benefits during the infusion is vast,56 there are few studies documenting benefits
following catheter removal. Exceptions include increased health-related quality-of-life in one study79 (but not five
others);80-84 improved analgesia after a few days5,85,86 or six months;87 faster tolerance of passive knee flexion
resulting in earlier discharge from rehabilitation centers;77,78,85 and more-rapid resumption of lavatory use and
unassisted standing.85 Noticeably absent is evidence of medium- or long-term improvements in measures of health-
related quality-of-life.80-84,88
Complications. Relatively minor CPNB-related complications occur at a frequency similar to single-injection

peripheral nerve blocks.89 In contrast, severe and permanent infusion-related injuries are uncommon. Unfortunately,
generalizations are difficult given the multiple anatomic locations for perineural infusion as well as diverse
equipment and techniques. For example, the incidence of secondary block (infusion) failure reported by three
different trials includes 1%,90 20%,7 and 50%.9 Catheter insertion-related complications include inaccurate catheter
tip placement; and—in extremely rare cases—intraneural, intrathecal, epidural, intravascular, and even interpleural
catheter insertion. Complications during the perineural infusion include catheter obstruction or dislodgement;
catheter site fluid leakage; infusion pump disconnection, malfunction, or undesired pause; allergic reaction or simply
skin irritation to the catheter dressing and/or liquid adhesive; and, catheter-induced brachial plexus irritation. One of
the most common complications is an insensate extremity that may be unnerving to patients, hinders rehabilitation,
and often believed to be a risk factor for injury.54,55 In such cases, pause the infusion until sensory perception
returns, and then restarted the infusion at a lower basal rate. Conversely, breakthrough pain or persistent inadequate
analgesia may be treated with patient-controlled bolus doses and increasing the basal infusion, respectively.
More serious—and remarkably uncommon—complications include systemic local anesthetic toxicity; myonecrosis
with repeated large boluses of bupivacaine; retroperitoneal and peri-catheter hematoma formation; catheter knotting,
retention, shearing, or breakage; a prolonged Horner’s syndrome; and lower lobe collapse during infusions affecting
the phrenic nerve. In patients with preexisting neuropathy and/or diabetes, limited evidence suggests that prolonged
local anesthetic exposure may increase the risk of nerve injury. Infusions affecting the femoral nerve is associated
with an increased risk of falling following knee and hip arthroplasty.67 Catheter site infection and abscess are rare
(infection incidence 0-3%;91,92 but most reports <1%),11,89,93 although inflammation (3-4%)1,90,94 and bacterial
colonization (6%-57%) are more common. Risk factors include the absence of perioperative antibiotic prophylaxis,
male sex, axillary/femoral catheter insertion, and presence in an intensive care unit.1 The infection risk is also
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correlated with infusion duration;1 but, nevertheless, a minimal incidence of infection has been reported for CPNB
during inter-continental transportation for up to 34 days95 and provided at home for up to 83 days.58
Because all surgical procedures are associated with a variable incidence of nerve injury—regardless of the
application of a regional anesthetic/analgesic—it is often problematic to determine what percentage (if any) of a
new-onset neurologic deficit is attributable to CPNB. Keeping this limitation in mind, the incidence of transient
adverse neurologic symptoms associated with CPNB is 0-1.4% for interscalene,1,11,89,90 0.4-0.5% for femoral,1,96 and
0-1.0% for sciatic catheters.1,90,96,97 Another study reported a 0.2% incidence of neurologic deficits lasting longer
than 6 weeks in nearly 3,500 catheters from multiple anatomic locations.90 In this latter study, it remains unknown
if the deficits resolved after the 6-week study period; but multiple prospective investigations report that the
overwhelming majority of neurologic symptoms present at 4-6 weeks resolve spontaneously within three months of
surgery.1,11,89 Long-term and/or permanent nerve injury has occurred.98 Five large,1,11,89,96,97 prospective series that
followed patients for at least three months reported 3 cases of unresolved adverse neurologic events.89,96,97 These
investigations combined (4,148 total subjects) suggests the risk of neurologic injury lasting longer than nine months
associated with CPNB is 0.07% (all of the risk may not be conclusively attributed to the perineural
infusion).1,11,89,96,97 While ultrasound-guidance may decrease the incidence of many/most of these reported
complications,99 to date there are few data supporting this proposition;100,101 and case reports suggest that completely
abolishing such events is unlikely.102-104
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Anaesthesist 2002; 51: 547-551
99. Swenson JD, Davis JJ: Ultrasound-guided regional anesthesia: why can't we all just stay away from the nerve?
100. Neal JM: Ultrasound-guided regional anesthesia and patient safety: An evidence-based analysis. Reg Anesth
Pain Med 2010; 35: S59-S67
101. Hebl JR: Ultrasound-guided regional anesthesia and the prevention of neurologic injury: fact or fiction?
102. Neal JM, Wedel DJ: Ultrasound guidance and peripheral nerve injury: is our vision as sharp as we think it is?
Reg Anesth Pain Med 2010; 35: 335-337
103. Reiss W, Kurapati S, Shariat A, Hadzic A: Nerve injury complicating ultrasound/electrostimulation-guided
supraclavicular brachial plexus block. Reg Anesth Pain Med 2010; 35: 400-401
104. Cohen JM, Gray AT: Functional deficits after intraneural injection during interscalene block. Reg Anesth Pain
Med 2010; 35: 397-399
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DISCLOSURE
Kimberly-Clark, Self, Honoraria ; Summit Medical, Self, Funded Research ; Smiths Medical, Self, Funded Research
; Teleflex Medical, Self, Funded Research ; Baxter Healthcare, Self, Funded Research
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Current Concepts and Controversies in Acute Pain Management

Eugene R. Viscusi, M.D. Philadelphia, Pennsylvania
Acute pain management continues to be challenging. Studies have demonstrated continued unmet needs with the
majority of patients experiencing significant pain at some point following surgery.1 Analgesic gaps (periods of
breakthrough pain) continue to be a problem for most patients. There is increasing awareness to opioid related side
effects and the need to minimize opioids generally through the use of multimodal analgesic techniques. Opioid
related respiratory depression and sleep apnea are now major considerations in the postoperative period. At the
other end of the opioid spectrum, we have the challenge of managing postoperative pain in the presence of opioid
tolerance and chronic opioid use. There is also an emerging theme of chronic pain following surgery.
Multimodal Analgesia
Historically, we have relied heavily on opioids as single agents for postoperative pain. While opioids are potent and
effective analgesics, this comes at the price of opioid related side effects. Patients typically balance side effects with
pain relieve –often requesting less pain relief rather than suffer opioid related nausea and vomiting.2 Further,
opioids have limited efficacy for some types of pain particularly visceral and neuropathic pain. Acute postoperative
pain is usually a mixed pain syndrome with multiple components and hence may not be relieved well with opioids
alone.
The concept of multimodal analgesia entered the acute pain literature in the early 1990’s when Kehlet described the
benefits of “balanced” analgesia.3 Today, multimodal analgesia, the application of two or more analgesics acting at
different pain pathways and by different mechanisms, is considered standard practice to enhance analgesia and
minimize reliance on opioids. The ASA Guidelines on Acute Pain Management support the use of nonopioids as
around the clock agents with opioids as supplemental agent. The most commonly employed agents are local
anesthetics, acetaminophen, NSAIDs, COX-2 selective inhibitors, gabapentin and pregabalin, and ketamine. While
these agents may be viewed as less potent than opioids, emerging information suggests they may be able to play a
more significant role than previously thought.4 Opioid minimalization is at the heart of many of the challenges and
controversies in acute pain management. Future acute pain management is likely to rely much less on opioids.
Opioid Related Respiratory Depression and Sleep Apnea
The effects of opioids on respiration are well known. In recent years there has been increasing awareness to critical
respiratory events.5,6 The emphasis place on “pain the 5th vital sign” by the Joint Commission several years back
may have increased the use of opioids in the hospital setting in an attempt to improve pain assessments. The
increasing incident of sleep apnea, often blamed on the increasing obesity in our society, is also considered a risk
factor for opioid use.
Obstructive sleep apnea (OSA) is usually associated with obesity, snoring or other signs of airway obstruction. Yet,
the majority of patients with OSA are undiagnosed and many are not obese.7 Further, OSA may coexist with central
sleep apnea (CSA).8 Further, it has been demonstrated that patients with OSA may develop respiratory depression
from opioids but that it is in fact on a central basis and not obstructive.9 Up to 5% of long term opioid dependent
patients will exhibit CSA.10 (Chronic opioid use also suppresses REM sleep which may share a similar basis.)
Opioids are potent analgesics and remain the most widely used analgesics for postoperative pain at this time.
Hence, we will be dealing with these challenges for the foreseeable future.
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While respiratory depression (RD) is a serious problem, definitions of RD vary widely. Reported incidences range
from 1% to approximately 40%.11 However, these definitions include transient oxygen desaturation or transient
respiratory rates below 10 breaths per minute. While these events should not be taken lightly, it is difficult to
predict which or how many of these events will progress to critical situations requiring intervention. In one series of
over 2000 patients with standard patient controlled analgesia settings, the incident of critical respiratory depression
was 0.1-0.3%.12 The controversy here is determining if and what type of monitoring is appropriate for patients
receiving opioids and how to minimize opioid use.
An ASA task force provided guidance on managing patients with OSA.13 There are no specific analgesic
recommendations but rather favor minimal opioids use and multimodal analgesia. Local anesthetic techniques are
encouraged. One specific recommendation is to avoid discharge to an unmonitored setting until there is no further
risk of respiratory depression.
There are various monitoring techniques recommended for the OSA patient but no definitive approach. Pulse
oximety is generally recommended although capnometry may be a more sensitive indicator. Observational
monitoring in the PACU with an OSA prescreening tool may have a role in risk stratifying patients who would
benefit from the most aggressive monitoring.14 The STOP-Bang scoring system has also shown merit in identifying
at-risk patients.15
Using the STOP-Bang questionnaire, one team of investigators found 41.5% of a standard preoperative elective
population had OSA. These investigators also identified a ten-fold increase in pulmonary and cardiac complications
in patients with OSA.16 Clearly, patients with OSA may benefit from advance planning. Early identification is key.
This allows planning an anesthetic to minimize reliance on opioids both intra- and postoperatively as well as
designing an appropriate multimodal approach with appropriate monitoring.
Emerging Views on Opioids
Mu-opioid receptors are ubiquitous within the CNS and at peripheral sites. The analgesic action of opioids within
the CNS is well known. Opioid adverse events are related to both central and peripheral receptors. Peripheral
opioid receptors have a role in ileus, constipation, hormonal regulation, tumor growth, angiogenesis and
immunological function. While long term opioid use has clear risks, there is emerging evidence that the short term
use of opioids may have significant consequences. Use of opioids for as little as one month may produce lasting
changes in the brain.17 Elderly patients given opioids for postoperative pain are at risk for long term opioid use.18
Opioids may reduce survival after cancer surgery.19 Perioperative plans that reduce opioids have been shown to
increased cancer survival in surgery for breast cancer, prostate cancer and possibly bowel cancer. These typically
involve regional anesthetic techniques (paravertebral blocks, epidurals). Opioids are known to enhance
angiogenesis leading to tumor growth and to inhibit the immunological response which may alter survival. Recent
work in rodents with peripheral opioid antagonism demonstrated an inhibition of tumor growth.20
Opioid Tolerance and Hyperalgesia
Long term use of opioids is known to produce tolerance or decreased efficacy requiring dose escalation. Some
patients on chronic opioids also exhibit hyperalgesia or altered pain sensitivity.21 As a group, patients on chronic
opioid therapy for pain or methadone maintenance are well known to present significant postoperative pain
challenges.
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For these patients in the postoperative period, increased opioid requirements are expected but often pain is
unrelieved with opioids alone.22 Opioid tolerant patients benefit from aggressive multimodal analgesia with regional
anesthetic techniques. Recently, ketamine has shown efficacy in this setting. In opioid tolerant spine surgery
patients, Loftus and colleagues demonstrated that pre- and intra-operative ketamine reduced pain and opioid
requirements in the immediate postoperative period and up to six weeks following surgery.23,24,25 Low dose
ketamine is now commonly employed in opioid tolerant patients. There is some controversy as to when and where
ketamine should be administered. Loftus and colleagues demonstrated benefit from pre and intraop administration.
Postoperative ketamine infusion is a useful adjunct in multimodal analgesia for these patients but further studies are
warranted to evaluate dosing and duration of treatment.
Chronic Pain Following Surgery
Chronic pain may be a consequence of surgery. Until recently, normal resolution of acute pain was expected to be a
routine occurrence. There is a significant burden of long-term pain following surgery. The incidence following
thoracotomy and radical mastectomy may exceed 50%. The incidence following inguinal hernia repair is 19-40%.
There is now an understanding that healing with neuronal plasticity may occur resulting in chronic postsurgical pain
(CPSP). CPSP has been linked to severity of acute pain.26 Following thoracotomy, patients who experience pain of
greater intensity and for a longer duration had a higher risk of persistent pain. Kehlet has identified not only intense
acute pain but also, nerve injury and intense inflammatory response as associated factors.27
Surgery often results in an intense peripheral inflammatory response (peripheral sensitization) as a consequence of
the release of local inflammatory mediators. This “inflammatory soup” causes peripheral sensitization that results in
central sensitization (the release of central inflammatory mediators) which in turn results in further pain
sensitization.28 Even in the presence of total neuronal blockade, there is still a central humoral response to
peripheral inflammation. Hence, local anesthetic techniques alone cannot inhibit this process of central
sensitization.
Total knee arthroplasty has a reported incidence of CPSP approaching 9%. A recent study utilizing a complex
multimodal regimen with pregabalin for total knee arthroplasty showed a marked reduction in chronic neuropathic
pain.29 While this is one study, it provides a basis for the potential use of multimodal analgesia as an approach to
reducing the prevalence of CPSP. Still, another study with chronic pain following total joint arthroplasty supports
that patients may have underlying vulnerabilities such as major depression or chronic pain elsewhere.30 There is
some evidence correlating CPSP to individual pain response with experimental pain models.31
In a number of surgical models, perioperative pregabalin either alone or within a complex multimodal regimen has
been shown to reduce pain in the immediate postoperative period and in some studies in the months following
surgery.32-37 Recently, intraoperative lidocaine infusion was shown to reduce chronic pain following breast
surgery.38
Ultimately chronic post-surgical pain is likely to be multifactorial in origin. Current best evidence suggests that a
multimodal analgesic approach may offer the best current approach for reducing long-term pain after surgery. If at-
risk individuals can be identified in the future, targeted approaches might be possible.
Conclusions
Acute pain management continues to be challenging. While significant strides have been made in many areas,
specific patient populations and surgical pain models remain underserved. Multimodal analgesia is now recognized
as a standard of care and is familiar to our surgical colleagues. The most current literature supports opioid reduction
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techniques and multimodal analgesia from the preoperative period and through the recovery period. Integration of
multimodal analgesia into our anesthetic plan will promote early utilization both pre- and intra-operative to
maximize the benefits. The emerging information on opioids suggests that these agents will likely play a lesser role
in our future approaches to acute pain management.
References
1. Apfelbaum JL, Chen C, Mehta SS, et al. Postoperative pain experience: results from a national survey suggest
postoperative pain continues to be undermanaged. Anesth Analg 2003;97:534-40
2. Gan TJ, Lubarsky DA, Flood EM, et al. Patient preferences for acute pain treatment. Brit J Anaesth
2004;92:681-8
3. Kehlet H, Dahl JB. The value of “multimodal” or “balanced analgesia” in postoperative pain treatment.
Anesth Analg 1993;77:1048-56
4. Moore RA, Derry S, McQuay HJ, et al. Single dose oral analgesics for acute postoperative pain in adults.
Cochrane Database of Systematic Reviews 2011, Issue 9
5. Weinger MB. Dangers of postoperative opioids: APSF workshop and white paper addresses prevention of
postoperative respiratory complications. APSF Newsletter 2006-07;21:61, 63-7
6. Overdyk FJ. Letter to the editor: Postoperative opioids need system-wide overhaul. APSF Newsletter 2009-
10;244, 61
7. Young T, Evans L, Finn L, et al. Estimation of clinically diagnosed proportion of sleep apnea syndrome in
middle-aged men and women. Sleep 1997;20:705-6
8. Badr MS, Toiber F, Skatrud JB, et al. Pharyngeal narrowing/occlusion during central sleep apnea. J Appl
Physiol 1995;78:1806-15
9. Bernards CM, Knowlton SL, Schmidt DF, et al. Respiratory and sleep effects of remifentanil in volunteers
with moderate obstructive sleep apnea. Anesthesiology 2009;110:41-49
10. Ecker DJ, Jordan AS, Merchia P, et al. Central sleep apnea: pathophysiology and treatment. Chest
2007;131:595-607
11. Overdyk FJ, Carter R, Maddox RR, et al. Continuous oximetry/capnometry monitoring reveals frequent
desaturation and bradypnea during patient-controlled analgesia. Anesth Analg 2007;105:412-8
12. Viscusi ER, Sicardi M, Damaraju CV, et al. The safety and efficacy of fentanyl iontophoretic transdermal
system compared with moprhine intravenous patient-controlled analgesia for postoperative pain management:
an analysis of pooled data from three randomized, active-controlled clinical studies. Anesth Analg
2007;105:1428-36
13. ASA Task Force on Perioperative Management of Patients with OSA Anesthesiology 2006;104:1081-1952
14. Gali B, Whalen FX, Schroeder DR, et al. Identification of patients at risk for postoperative respiratory
complications using a preoperative obstructive sleep apnea screening tool and postanesthesia care assessment.
Anesthesiology 2009;110:869-77
15. Chung F, Yegneswaran B, Liao P, et al. STOP questionnaire: a tool to screen patients for obstructive sleep
apnea. Anesthesiology 2008;108:812-21
16. Vasu T, Doghramji K, Cavallazzi R, et al. Obstructive sleep apnea syndrome and postoperative
complications. Arch Otolaryngo Head Neck Surg 2010;136:1020-4
17. Younger JW, Chu LF, D’Arcy NT, et al. Prescription opioid analgesics rapidly change the
human brain. Pain 2011;152(8):1803-10
18. Alam A, Gomes T, Zheng H, et al. Long-term analgesia use after low-risk surgery: a retrospective cohort
study. Arch Intern Med 2012;172(5):425-30
19. Lennon FE, Moss J, Singleton PA. The u-opioid receptor in cancer progression: is there a direct effect?
Anesthesiology 2012;116(4):1-6
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Current Controversies in Adult Outpatient Anesthesia
Jeffrey L. Apfelbaum, M.D. Chicago, Illinois
Introduction
The fast paced world of ambulatory anesthesiology continues to present anesthesiologists with an ever-
changing array of challenges. This Refresher Course will provide an update on current controversial issues in adult
outpatient anesthesia, including fast tracking; preoperative assessment, evaluation, and preparation; recent changes
to ASA Basic Anesthesia Monitoring Standards; ramifications of recent changes to Interpretative Guidelines issued
by the Center for Medicare and Medicaid Services (CMS) on our practice; and computer assisted personalized
sedation. Additionally we will consider a variety of “breaking news” areas of controversy which may include topics
such as patients with obesity/modified metabolic syndrome; advances in and recommendations to enhance
perioperative communication; treatment decisions for patients with coronary artery stents; opportunities to
incorporate one’s personal outcomes data into your patient care plan; choice of anesthetic on cancer recurrence
rates; and the effects of drug shortages on ambulatory surgical care.
Fast Tracking: Eliminating Intensive Post-Operative Care in Same Day Surgery Patients Using
Short Acting Fast Emergence Anesthetics
Many anesthetics have the pharmacokinetic and pharmacodynamic advantages of a shorter duration of
action and a more rapid rate of recovery which permit a faster emergence from anesthesia compared with their
predecessors. Showing the value of these agents is required to increase their acceptance and foster further
development. Less than 30 years ago, it was unthinkable that patients would be able to return home on the day of
surgery. Today, advances in surgery and anesthesiology make it possible to perform the vast majority of all surgical
procedures, safely and effectively on an ambulatory basis, with many patients ready to be reunited with their
families within minutes of emergence from anesthesia. In today’s cost sensitive healthcare environment, the
processes of ambulatory surgical care must be continually re-evaluated to take advantage of advances in medicine
and to optimize the efficiency of the surgical center without detriment to patient safety and satisfaction.
Traditionally, ambulatory surgical patients go from the operating room to the postanesthesia care unit or recovery
unit ( a highly specialized intensive care unit) for their immediate postoperative recovery from anesthesia and then
to a second stage recovery unit (SSRU) for preparation for home readiness. By its very nature as a specialized ICU,
the PACU is an expensive, labor-intensive environment. After a set of recovery criteria 1, 2, 3 are met in the PACU,
the patient is usually transferred to the SSRU. In the SSRU, the patient-to-nurse ratio is considerably higher (i.e.,
nursing care in the SSRU is less labor intensive) than in the PACU. Only basic monitoring and observation are
performed as the patient and his or her escort are prepared for home readiness. Because of the rapid recovery of
patients undergoing anesthesia with the shorter acting, faster emergence anesthetics, some have questioned if all
ambulatory surgical patients need to receive intensive postoperative care in the PACU setting or whether “first
stage” recovery from anesthesia can be achieved safely while still in the operating room (at least for some patients),
thereby resulting in enormous potential savings.
The “SAFE” study evaluates the impact of selective patient bypass of the PACU on both the outcomes of
ambulatory surgical patients and the use of resources in the surgical arena.4 This study was designed to evaluate the
rapid recovery of patients undergoing ambulatory surgery using short-acting, fast emergence anesthetic agents and
to determine if policies and procedures could be developed that would allow patients to safely bypass first stage
post-anesthesia care units (PACU) and whether such changes in the recovery paradigm would result in financial
savings for the surgical center. Five community based facilities (hospitals or surgery centers) participated in this
prospective observational study. While in the operating room at the end of the surgical procedure, anesthesiologists
were asked to assess all ambulatory surgical patients for recovery using standardizing discharge criteria typically
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used at the end of a PACU stay (Table 1). If the patient met the discharge criteria, they were transferred from the
OR directly to the less labor intensive second stage recovery unit (SSRU). Financial data were provided from all
five sites detailing all costs associated with the recovery process. Clinical data on every elective ASA 1, 2 and 3
ambulatory surgical patient were collected over a three month period. During month one, data collected established
a baseline of case mix, time stamps, adverse events, bypass rates, and financial profile. During month two, an
educational intervention was provided on a multi-disciplinary basis to all units in the surgical center discussing the
implications of the bypass paradigm. After implementation of the paradigm (month three) weekly feedback reports
were provided to the site featuring the key outcomes of the study, and these reports were distributed to the health
care providers. Nearly 5,000 patients were entered into the study. The overall bypass rate increased from 15.9% in
the baseline month to 58.9% in the month following the educational intervention (p < 0.0001). The change in
process in this study went beyond reducing time spent in the PACU to eliminating the time spent in the PACU while
not increasing the time spent in the operating room or SSRU. In fact, the average (SD) time spent in the SSRU was
significantly shorter for patients who bypassed the PACU than for those who did not bypass the PACU. There were
no significant differences in other parameters of patient outcome. Annualized savings ranged from $50,000 to
$160,000 per site.
The Hows And Whys Of Preoperative Evaluation
The continued growth of outpatient surgery has created new roles for the anesthesiologist which seemingly
demands skills in addition to "giving a good anesthetic." The times from induction to emergence are no longer the
only important role for the perioperative physician. Particularly in the freestanding and office environments, it is
often the anesthesiologist who is most involved in the direct medical care of the patient; we are the physicians who
must insure that the patient is appropriately screened, evaluated, and informed prior to the day of surgery. Indeed,
the anesthesiologist/patient relationship which sometimes develops often takes on a primary care quality. Although
sometimes difficult to arrange, the preoperative interview and evaluation by a consultant anesthesiologist
(particularly in high risk patients) can be extraordinarily beneficial. In addition to lessening anxiety about the
surgery and anesthesia, in most cases, the anesthesiologist will be able to identify potential medical problems in
advance, determine their etiology, and if indicated, initiate appropriate corrective measures. In most facilities, the
goal is to resolve preoperative problems well in advance of the day of surgery, thereby minimizing the numbers of
both cancellations and complications.
At the present time, there are several commonly used approaches to screening patients for ambulatory
surgery. These include: (1) facility visit prior to the day of surgery, (2) office visit prior to the day of surgery, (3)
telephone interviews/no visit, (4) review of health survey/no visit, (5) preoperative screening and visit on the
morning of surgery, (6) computer assisted information gathering, and (7) the use of telemedicine technology. Each
system has its own advantages and disadvantages.
Should Patient Age or ASA Physical Status Influence Case Selection?
Although the vast majority of individuals scheduled for outpatient surgery are relatively healthy (ASA
Physical Status 1 and 2), practitioners are constantly being pressured by third party payors to consider "simple
outpatient surgery" for patients with significant baseline co-morbidities. A survey of members of the Society for
Ambulatory Anesthesia (SAMBA) revealed that half the respondents felt that their practice “pushes the envelope of
patient safety by performing outpatient surgery on patients with serious pre-existing conditions,” and that 40% of
respondents felt that their practice “pushes the envelope of patient safety by performing complex or lengthy surgical
procedures on outpatients.” In the past, many individuals had arbitrarily stated that freestanding ambulatory surgical
facilities were severely limited in the type of patients they could anesthetize, particularly with regard to age and
physical status. Clinical experience, however, suggests otherwise. In a retrospective study of over 1,500 cases of
patients anesthetized for ambulatory surgery, Meridy5 was unable to demonstrate an age-related effect on the
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duration of recovery or the incidence of postoperative complications. Additionally, a retrospective review of cases
performed at the Methodist Ambulatory Surgicare Center in Peoria, Illinois between 1981 and 1985 demonstrated an
unanticipated admission rate of 1.1% for patients over the age of 60 compared to an overall unanticipated admission
rate of 0.8%. With regard to the issue of physical status, in a prospective study involving over 13,000 patients at a
freestanding ambulatory surgical center, Natof 6 concluded that ASA 3 patients whose systemic diseases were well
controlled preoperatively were at no higher risk for postoperative complications than ASA 1 or 2 patients.
Furthermore, in 1987, the Federated Ambulatory Surgery Association (FASA) published the results of a survey
involving over 87,000 patients and concluded that there appeared to be little or no cause and effect relationship
between pre-existing disease and the incidence of perioperative complications7 Chung examined predictors of
adverse events in ambulatory surgery in the elderly, as well as factors contributing to prolonged stay after
ambulatory surgery in elderly patients. This data demonstrated that outpatient surgery is safe in this patient
population, with elderly patients sustaining more minor cardiovascular events than their younger counterparts, and
less postoperative nausea and vomiting, pain, and drowsiness.8, 9. It is clear that geriatric and higher risk (physical
status 3 and 4) patients may be considered acceptable candidates for outpatient surgery if their systemic diseases are
well controlled and the patient’s medical condition is optimized preoperatively.
The Inappropriate Patient - Who's OK And Who's Not
There are few data to reliably categorize the inappropriate adult surgical outpatient. As anesthesiologists
have become more experienced with the anesthetic management of the problem surgical outpatient, the list of
"inappropriate" patients has dwindled. We must individualize our decision with regard to each patient; with few
exceptions, the appropriateness of a case for outpatient surgery is determined by a combination of factors including
patient considerations, surgical procedure, anesthetic technique, and anesthesiologist's comfort level.
At the University of Chicago Medical Center, we have distinguished several groups of patients who may
not be appropriate candidates for ambulatory surgery. As one might expect, this list is frequently modified to adapt
to the ever-changing conditions of our social and medicolegal environment.
• Unstable ASA Physical Status 3 and 4: At the present time we are reluctant to proceed with elective ambulatory
surgery in a medically unstable patient. Instead, we use our anesthesia perioperative medicine clinic (APMC) to
screen these patients, and together with the primary care surgeon or interventionalist, establish a plan to proceed
with the surgery or intervention after medical stabilization. Contrary to the original "ground rules" of ambulatory
surgery, studies involving hundreds of thousands of patients seem to suggest that neither increasing age nor the
presence of stable pre-existing disease affect the incidence of postoperative complications in the surgical outpatient.
• Malignant Hyperpyrexia: In our facility, overnight hospitalization and observation is usually indicated for patients
with a history of malignant hyperpyrexia or with identified susceptibility to malignant hyperpyrexia. However,
patients who are well educated, have a good understanding of their disease process, and have ready access to
medical care may be treated as outpatients by some centers.
• Complex Morbid Obesity/Complex Sleep Apnea: Although patients who have a history of sleep apnea or who
are morbidly obese without systemic disease are acceptable candidates for ambulatory surgery, we prefer overnight
hospitalization and postoperative observation for morbidly obese surgical patients with significant pre-existing
cardiac, pulmonary, hepatic or renal compromise or those patients with a history of complex sleep apnea. Practice
guidelines for the perioperative management of patients with obstructive sleep apnea have recently been developed
by the American Society of Anesthesiologists and offer recommendations for preoperative evaluation, preoperative
preparation, intraoperative management, postoperative management, and “site” of surgery (inpatient vs.
outpatient).10
• Acute Substance Abuse: Because of the increased likelihood of acute untoward cardiovascular responses when
one administers an anesthetic to a patient who has recently abused illicit drugs, we preoperatively counsel these
patients and inform them that any sign of recent drug abuse on the day of surgery will result in immediate
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cancellation of their anesthetic. We tell them that no elective surgical procedure "is worth dying for" and encourage
their preoperative participation in a rehabilitation program.
Anesthesiology directed perioperative medicine clinics are used to optimize the medical condition of a
patient in preparation for surgery. These clinics have been shown to enhance patient safety11, improve patient
satisfaction 12,13, minimize preoperative consultation14, and reduce day of surgery case cancellations and case
postponements.15
Changes to the ASA Standards for Basic Anesthesia Monitoring
For the first time in nearly a decade, there has been a significant change to the ASA Standards for Basic
Anesthesia Monitoring.16 The standard for monitoring of ventilation has undergone significant revision:
V ENTILA TION: 3.2.4: During regional anesthesia (with no sedation) or local anesthesia (with no sedation), the
adequacy of ventilation shall be evaluated by continual observation of qualitative clinical signs. During moderate or
deep sedation the adequacy of ventilation shall be evaluated by continual observation of qualitative clinical signs
and monitoring for the presence of exhaled carbon dioxide unless precluded or invalidated by the nature of the
patient, procedure, or equipment. Many physicians have asked if these standards apply to cases where sedation is
administered in “out of operating room” locations. The Centers for Medicare and Medicaid (CMS) Revised Hospital
Anesthesia Services Interpretative Guidelines seemingly provide guidance on this issue. The first section in these
Interpretative Guidelines is entitled “Types of Anesthesia Services” and the first “bullet” in this section begins as
follows: A nesthesia services, which include both anesthesia and analgesia, are provided along a continuum, ranging
from the application of local anesthetics for minor procedures to general anesthesia for patients who require loss of
consciousness as well as control of vital body functions in order to tolerate invasive operative procedures. This
continuum also includes minimal sedation, moderate sedation/analgesia (“conscious sedation”), monitored
anesthesia care (MA C), and regional anesthesia.
CMS Issues Revised Hospital Anesthesia Services Interpretive Guidelines
CMS has recently issued significant revisions to the Anesthesia Services Interpretive Guidelines.16 These
included significant revisions to the CMS compliance requirements for both pre and post anesthesia evaluations, as
well as a requirement that heretofore, ALL anesthesia and sedation services (including mild, moderate, and deep
sedation) , regardless of providers MUST be organized into a single anesthesia service under the direction of a
qualified doctor of medicine or doctor of osteopathy. Specific portions of these Interpretive Guidelines will be
addressed during the presentation.
Computer- Assisted Personalized Sedation (CAPS)
Ethicon Endo-Surgery, Inc. has recently developed a computer-assisted personalized sedation system (trade
name SEDASYS®) According to the manufacturer, “the SEDASYS® System is the first computer-assisted
personalized sedation (CAPS) system designed for physician/nurse teams to provide minimal-to-moderate sedation
levels with propofol. By integrating drug delivery and patient monitoring, the SEDASYS® System enables
physician/nurse teams to deliver personalized sedation. It automatically detects and responds to signs of over-
sedation (oxygen desaturation and low respiratory rate/apnea) by stopping or reducing delivery of propofol,
increasing oxygen delivery and automatically instructing patients to take a deep breath. The device is currently an
investigational device limited by U.S. law to investigational use only.”17
On May 28, 2009, the Anesthesia and Respiratory Therapy Devices Advisory Committee of the US Food and
Drug Administration (FDA) concluded its deliberations and recommended to the FDA that the SEDASYS® device
be approvable for the administration of propofol by physician/nurse teams for the initiation and maintenance of
minimal to moderate sedation during screening and diagnostic procedures in patients undergoing colonoscopy and
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esophagoduodenoscopy procedures with the following conditions:

1) The device may only be used in adult patients (ASA I, II, and III) 70 years old or younger;
2) The device may only be used in the presence of a 3 person clinical team where one person shall have the sole
responsibility of monitoring the patient, the device and managing the patient's airway. This dedicated person must
have advanced training and at least the skills of a nurse;
3) Physicians utilizing the device must complete training in advanced airway management, pharmacology of
propofol and opioids, patient selection, monitor training (such as SpO2 monitoring), device set-up and maintenance
with the training provided by a clinician with credentials to provide deep sedation to general anesthesia. In addition,
there needs to be a program established for ongoing maintenance of training;
4) The manufacturer must complete all post-marketing studies as proposed at the time of the Advisory Panel
hearing.
5) The product launch is “controlled.”
On several occasions, representatives of the company have suggested that the device is compliant with
ASA guidelines on sedation/analgesia by non-anesthesiologists; as a result of this claim both medical professionals
and lay people have occasionally erroneously concluded that the device is consistent with ASA standards,
guidelines, statements and/or policies.18 Indeed, some individuals have mistakenly concluded that ASA has
“endorsed” the product. However, this conclusion is erroneous. In the AANA-ASA Joint Statement Regarding
Propofol Administration (April 14, 2004) the ASA position regarding the use of propofol is clearly stated as
follows:19
“W henever propofol is used for sedation/anesthesia, it should be administered only by persons trained in the
administration of general anesthesia, who are not simultaneously involved in these surgical or diagnostic procedures.
This restriction is concordant with specific language in the propofol package insert, and failure to follow these
recommendations could put patients at increased risk of significant injury or death.”
In April, 2010, Johnson & Johnson, the parent company of Ethicon-Endo Surgery, Inc., announced that the
FDA sent the company a “not approvable” letter for the SEDASYS® Computer Assisted Personalized Sedation
System. The company has recently appealed this decision. During the session, we will review many of the specifics
of this device and present an update on its current approval status.
Summary
Today there is a continued trend to expand the indications for ambulatory surgery. Because outpatient
anesthesia is a break from our traditional training, we are constantly being confronted with the need for change in
our clinical practice patterns. We have recognized that the needs of the surgical outpatient may be very different
from the inpatient and are now trying to adapt our practice patterns to meet the psychologic and pharmacologic
requirements of the compacted perioperative management the outpatient receives. This Refresher Course has
focused on some of the controversial problems which we as practicing clinicians must deal with every day in our
practice of ambulatory anesthesia for adult patients.
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101
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TABLE 1. DISCHARGE CRITERIA
• Awake, alert, oriented, responsive (or return to baseline)

• Minimal pain
• No active bleeding
• Vital signs stable (not likely to require pharmacologic intervention)
• Minimal nausea
• No vomiting
• If nondepolarizing neuromuscular blocking agent used, patient can perform sustained five second head lift
• Oxygen saturation of 94% on room air (three minutes or longer) OR return of oxygen saturation to baseline
or higher in order to be eligible to bypass Phase I recovery (PACU), the patient must meet ALL of the
above criteria, and in the judgment of the anesthesiologist, be capable of transfer to the step-down unit,
with appropriate care and facility for patient management at that location
DISCLOSURE
holders.
505
Page 5
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qualities, and postoperative determinants. Pain 2011;152:566-73
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experimental pain studies. Anesthesiology 2010:112:1494-502
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of life after major spinal surgery. J NeurosurgAnesthesiol 2012;24(2):121-6
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patients undergoing robotic-assisted laparoscopic radical prostatectomy. J Urology 2010;76(5):122-4
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pain intensity after laparoscopic cholecystectomy. J Clin Anesth 2012;24:175-8
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DISCLOSURE
Cadence, ACEIRx, Pacira, Consulting Fees, Adolor, Funded Research
holders.

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2012 Refresher Course Lectures

Washington District of Columbia

October 13-17, 2012

© American Society of Anesthesiologists. All rights reserved.

Current Controversies in Adult Outpatient Anesthesia

Jeffrey L. Apfelbaum, M.D. Chicago, Illinois

The Hows And Whys Of Preoperative Evaluation

Should Patient Age or ASA Physical Status Influence Case Selection?

The Inappropriate Patient - Who's OK And Who's Not

Changes to the ASA Standards for Basic Anesthesia Monitoring

CMS Issues Revised Hospital Anesthesia Services Interpretive Guidelines

Computer- Assisted Personalized Sedation (CAPS)

esophagoduodenoscopy procedures with the following conditions:

10. Gross JB, et al. Anesthesiology 2006; 104(5):1081-1093.

TABLE 1. DISCHARGE CRITERIA

• Awake, alert, oriented, responsive (or return to baseline)

Girish P. Joshi, MB BS, MD, FFARCSI Dallas, Texas

Table 1: Comorbidities Associated With Obesity

Table 3: STOP-BANG Scoring System

Sedation and Analgesia in the Obese and OSA Patients

Induction of General Anesthesia

Maintenance of General Anesthesia

Nausea and Vomiting Prophylaxis

Intraoperative Fluid Management

Emergence From Anesthesia

Post-PACU Discharge Care

Care After Discharge Home

Preoperative Evaluation of the Adult Outpatient

Models for Systematic Preoperative Evaluation

Previous Coronary Interventions: Stents and Cardiac Rhythm Devices

Cardiac Rhythm Devices

Preoperatively, the following information should be obtained (ASA Practice Advisory):

5. Likelihood of device interference

STOP-BANG (Chung 2008)

3. Observed 7. Neck circumference greater than 40 cm?

Rapid Insulin Aspart 15 min 45-90 min 3-5 hrs

Long Insulin Glargine ~1 hr - up to 24 hrs

Long Insulin Detemir ~3 hrs ~6-8 hrs up to 24 hrs

Management of MH and MH-Susceptible Patients in the Ambulatory Setting

Diseases Associated with MH

Clinical Features of Acute MH

The most important aspects of treatment of acute MH are listed in Table 2.

Preparing Your Ambulatory Surgery Center for Unexpected Acute MH

Anesthesia for MH Susceptible Patients in the Ambulatory Setting

Table 1. Suggested Emergency MH Cart Supplies

Refrigerated drugs and solutions

Table 2. Treatment of Acute MH

Ongoing Monitoring and Treatment:

Douglas G. Merrill M.D. MBA Lebanon, New Hampshire

The Role of the Medical Director

Evidence Based Medicine and Clinical Outcome Measurement

Matching chosen metrics to goals

Process Improvement and Benchmarking: AQI and SCOR!

Business Decision Making

Table 1: Useful Outcome Metrics to Consider for an Ambulatory Surgery Center

Ultrasound-guided Regional Anesthesia for Ambulatory Patients

Local Anesthetics and Adjuvants

Upper Extremity US-Guided Peripheral Nerve Blocks

Lower Extremity US-guided Peripheral Nerve Blocks

Indwelling Catheter Techniques