Perioperative Medicine

Anesthesia, Intensive Care and Pain in Neonates
and Children
Marinella Astuto
Pablo M. Ingelmo Editors
Perioperative
Medicine
in Pediatric
Anesthesia
Anesthesia, Intensive Care and Pain
in Neonates and Children
Series editor:
Antonino Gullo
Marinella Astuto
Ida Salvo
Marinella Astuto • Pablo M. Ingelmo
Editors
Perioperative Medicine
in Pediatric Anesthesia
Editors
Marinella Astuto Pablo M. Ingelmo
UCO di Anestesia e Rianimazione Department of Anesthesia
AO-U Policlinico di Catania MUHC Montreal Children’s Hospital
Catania McGill University
Italy Montreal, QC
Canada
ISSN 2281-1788 ISSN 2281-1796 (electronic)

Anesthesia, Intensive Care and Pain in Neonates and Children
ISBN 978-3-319-21959-2 ISBN 978-3-319-21960-8 (eBook)
DOI 10.1007/978-3-319-21960-8
Library of Congress Control Number: 2015955168
Springer Cham Heidelberg New York Dordrecht London

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Foreword
For some readers, the title of this book might raise a main question: why a book
on perioperative medicine in pediatric anesthesia. The reply is in the understand-
ing that the anesthesia practice has evolved from a limited environment such as
the operating room to the whole perisurgical care, starting from the time a patient
is referred by the surgical treating team till the time the infant-child has recov-
ered and is back with his own family and community. Therefore, it would make
sense that pediatric anesthesiologists apply this concept to their own milieu. The
introduction of sophisticated technology in endoscopic surgery and the better
understanding of the pathophysiology of neonatal surgical stress emphasize the
role of the anesthesiologist as a perioperative physician. For example, there has
been an expansion of regional anesthesia applied to pediatric surgery as a result
of improved and more reliable imaging techniques together with better training.
This has allowed a better quality of analgesia and accelerated recovery. Other
examples are the interactions of pediatric anesthesiologists with respiratory
physiologists and neuroscientists to better understand the control of breathing
and neurobehavioral development, thanks to major development in modern
molecular biology and physiology. Also, better monitoring has allowed complex
surgeries to be performed on an outpatient basis, and over the years a greater
proportion of surgical operations are safely performed on an outpatient basis.
Each chapter stresses the scientific principles necessary to understand and man-
age various situations encountered in pediatric anesthesia from a multidisci-
plinary point of view.
I commend Drs. Astuto and Ingelmo, both pediatric anesthesiologists in two
large pediatric institutions in Italy and Canada, respectively, who have assembled an
international group of illustrious experts to dissect the topic of perioperative pediat-
ric medicine and to present the various aspects of pediatric anesthesia care, from
preoperative preparation of the child, education of the family and optimization of
medical, physical, nutritional and psychological functions, to perioperative man-
agement of specific conditions. The last four chapters are dedicated to acute and
chronic pain and to the impact of anesthesia and surgery on the infant brain. Overall,
v
vi Foreword
these chapters will guide not only the trainee, but also the experienced and seasoned
clinicians who are interested in expanding their knowledge on topics of relevant
importance.
Francesco Carli, MD, MPhil

Department of Anesthesia
MUHC, Montreal General Hospital, McGill University,
Montreal, QC, Canada
Preface
Perioperative clinical outcomes in procedures involving infants and children have

dramatically improved in recent years. Various factors may be responsible for those
benefits such as emerging of new technologies, standardized anesthesia protocols,
minimally invasive surgeries, improvements in acute postoperative care, and wide-
spread use of perioperative safety standards, to mention just a few.
Traditionally, surgeons coordinate perioperative care of patients undergoing sur-
gery. In some European countries, most of the perioperative care relies on anesthe-
siologists and pediatricians. Perioperative medicine becomes a multidisciplinary
speciality aiming to provide continuum of care with coordinated interventions in the
preoperative, intraoperative, and postoperative periods. The collaboration among a
variety of doctors and nurses with specific pediatric training in pediatric environ-
ments allows the development of multidisciplinary clinical care pathways incorpo-
rating multiple evidence-based interventions.
With this book, we aim to provide a comprehensive overview of current practices
in pediatric perioperative care. In all sections, from the preoperative care to the
consequences of anesthesia and surgery through the perioperative care during sur-
gery and in special clinical conditions, we look for practical answers to the most
common questions of pediatric perioperative care.
This book was possible due to the efforts of an exquisite list of anesthesiologists,
pediatricians, and surgeons from Europe and North America. This international
team of contributors ranges from worldwide experts who had changed the way we
care for our patients to young specialists who will lead the future of perioperative
medicine. We are truly and deeply grateful for their collaboration and friendship.
There has been a progressive accumulation of good evidence related to periop-
erative care in the last decade. A long series of well-designed studies now permit an
evidence-based approach to pediatric perioperative care. However, translation of
research findings and guidelines into clinical practice remains a significant barrier
affecting real clinical scenarios. Differences in type of surgeries, ages, interven-
tions, clinical settings, and their interaction justify the need of establishing proce-
dure-specific perioperative programs. Perioperative care is a multidimensional
phenomenon, requiring multimodal management plan and strategies. It is evident
that not a single specialist is able to provide solutions in all circumstances.
Perioperative medicine gives us a unique opportunity to re-imagine the
vii
viii Preface
anesthetic-surgical-pediatrician relationship. This partnership should not continue

to be experienced as independent entities divided by the operating theater “blood-
brain barrier,” but as a united team working towards the shared goal of optimal
patient trajectory throughout the perioperative process to normality.
Catania, Italy Marinella Astuto, MD

Montreal, QC, Canada Pablo Mauricio Ingelmo, MD
Acknowledgments
I would like to express my deep gratitude to Professor Gullo for his patient guidance
and enthusiastic encouragement of my work.
I would also like to thank my dear friend Dr. Pablo Ingelmo for his invaluable
support throughout the planning and development phases of this book. Finally, I
thank all the authors who honored me with their contributions.
Prof. Marinella Astuto M.D.
I wish to thank my wife, Francesca, and my sons, Matteo and Marco, for their
patient support. I also wish to thank Prof. Miguel Angel Paladino and Prof. Roberto
Fumagalli for their mentorship in shaping my clinical and academic career, and to
the KISS group to make it valuable. Finally, this would not be possible without my
friends: Walter, Marinella, and Pierre.
Pablo M. Ingelmo M.D.
ix
Contents
1 Perioperative Medicine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
Gabriele Baldini
Part I Perioperative Care Before Surgery
2 Preoperative Evaluation in Pediatric Anesthesia . . . . . . . . . . . . . . . . 11

Giovanni Mangia, Caterina Patti, and Paola Presutti
3 Preoperative Preparation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21
Luciano Bortone, Luca La Colla, and Marinella Astuto
4 Preoperative Consideration in Common Pathological
and Nonpathological Conditions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39
Marinella Astuto, Gianpaolo Serafini, Simonetta Baroncini,
Fabio Borrometi, Luciano Bortone, Cristina Ceschin,
Andrea Gentili, Elisabetta Lampugnani, Giovanni Mangia,
Luisa Meneghini, C. Minardi, Giovanni Montobbio,
Francesca Pinzoni, Barbara Rosina, Carlotta Rossi,
Marina Sammartino, Emre Sahillioğlu, Rita Sonzogni,
Valter Sonzogni, Simonetta Tesoro, Costanza Tognon,
Tiziana Tondinelli, Nicola Zadra, and Pablo M. Ingelmo
Part II Perioperative Care During Surgery
5 Perioperative Care in Day Hospital Surgery. . . . . . . . . . . . . . . . . . . . 55

Simonetta Tesoro and Laura Marchesini
6 Perioperative Care in Remote Locations . . . . . . . . . . . . . . . . . . . . . . . 75
Maria Sammartino, Fabio Sbaraglia,
and Francesco Antonio Idone
7 Perioperative Care in Paediatric Orthopaedic Surgery . . . . . . . . . . . 87
A.U. Behr
8 Perioperative Care of the Pediatric Neurosurgical Patient . . . . . . . . 115
Massimo Lamperti
xi
xii Contents
9 Pain After Surgical Correction of Congenital Chest

Wall Deformities. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 131
Robert Baird and Pablo M. Ingelmo
10 General Approach to Abdominal and Pelvic Procedures. . . . . . . . . . 137
Jean-Francois Courval
Part III Perioperative Care in Special Situations and Conditions
11 Perioperative Care of Children with a Difficult Airway . . . . . . . . . . 147

Alan Barnett and Thomas Engelhardt
12 Perioperative Care of Children with Neuromuscular Disease. . . . . . 159
Fabrizio Racca and Chiara Robba
13 Perioperative Care of Children with a Metabolic Disease . . . . . . . . . 175
Veyckemans Francis and Scholtes Jean-Louis
14 Perioperative Care of Children with OSA. . . . . . . . . . . . . . . . . . . . . . 187
Gianluca Bertolizio and Karen Brown
15 Perioperative Care of Children with Trauma . . . . . . . . . . . . . . . . . . . 213
Leonardo Bussolin
16 Perioperative Care of Children with Cancer. . . . . . . . . . . . . . . . . . . . 229
Navi Virk, B. Senbruna, and Jerrold Lerman
17 Perioperative Care of Children with Cerebral Palsy
and Behavioral Problems . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 259
Martin Jöhr and Thomas M. Berger
18 Perioperative Care of Neonates with Airway Obstruction . . . . . . . . 273
Pierre Fiset and Sam J. Daniel
Part IV Important Techniques for Perioperative Care
19 Vascular Access in the Perioperative Period . . . . . . . . . . . . . . . . . . . . 285

Thierry Pirotte
20 US-Guided Nerve Targets . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 341
Giorgio Ivani and Valeria Mossetti
21 Noninvasive Hemodynamic and Respiratory Monitoring
During the Perioperative Period. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 379
Brian Schloss and Joseph D. Tobias
Part V Early and Long Term Consequences of Anesthesia

and Surgery
22 Negative Behaviour After Surgery . . . . . . . . . . . . . . . . . . . . . . . . . . . . 403

Marta Somaini and Pablo M. Ingelmo
Contents xiii
23 Acute Pain Management and Prevention . . . . . . . . . . . . . . . . . . . . . . 417

Sylvain Tosetti
24 Long-Term Consequences of Anesthesia (and Surgery)
on the Infant Brain. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 437
Tom Giedsing Hansen
25 Prevention of Chronic Postsurgical Pain . . . . . . . . . . . . . . . . . . . . . . . 447
Gonzalo Rivera
Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 455
Contributors
Marinella Astuto Anesthesia, Intensive Care, University of Catania, Policlinico

Hospital, Catania, Italy
Dipartimento di Anestesia e Rianimazione, Ospedale Universitario Policlinico,
Catania, Italy
Robert Baird, MDCM, MSc, FRCSC, FACS Department of Pediatric Surgery,
MUHC, Montreal Children’s Hospital, McGill University, Montreal, QC, Canada
Gabriele Baldini, MD, MSc Department of Anesthesia, Montreal General
Hospital, McGill University Health Center, Montreal, QC, Canada
Alan Barnett Department of Surgery, Radiology, Anaesthesia and Intensive Care,
The University of the West Indies, Mona, Jamaica, West Indies
Simonetta Baroncini Dipartimento di Anestesia e Rianimazione Pediatrica,
Ospedale S. Orsola-Malpighi, Università di Bologna, Bologna, Italy
A. U. Behr Istituto di Anestesia e Rianimazione, Azienda Ospedaliera Università,
Padova, Italy
Thomas M. Berger Neonatal and Pediatric Intensive Care Unit,
Children’s Hospital, Luzern, Switzerland
Gianluca Bertolizio Department of Anesthesia, Montreal Children’s Hospital,
McGill University, Montreal, QC, Canada
Fabio Borrometi Servizio di Cure Palliative e Terapia del Dolore,
Ospedale Santobono Pausilipon, Napoli, Italy
Luciano Bortone First Service of Anesthesia and Intensive Care, Parma Hospital,
Parma, Italy,
Dipartimento di Anestesia e Rianimazione, Azienda Ospedaliera di Parma,
Parma, Italy
Karen Brown Department of Anesthesia, Montreal Children’s Hospital,
xv
xvi Contributors
Leonardo Bussolin Department of Neuroanesthesia and Neurointensive Care,

Pediatric Trauma Center, Pediatric Hospital Meyer, Florence, Italy
Cristina Ceschin Servizio di Anestesia e Rianimazione, Dolo Hospital,
Mirano, Italy
Jean-Francois Courval Anesthesia Department, Montreal Children’s Hospital,
Sam J. Daniel, MD, FRCPC Department of Pediatric Surgery and
Otolaryngology, Montreal Children’s Hospital, MUHC, McGill University,
Thomas Engelhardt Department of Anaesthesiology, Royal Aberdeen
Children’s Hospital, Aberdeen, UK
Pierre Fiset, MD, FRCPC Department of Anesthesia, Montreal Children’s
Hospital, MUHC, McGill University, Montreal, QC, Canada
Veyckemans Francis, MD Anesthesiology, Cliniques universitaires St Luc,
Université Catholique de Louvain, Bruxelles, Belgium
Andrea Gentili Dipartimento di Anestesia e Rianimazione Pediatrica,
Ospedale S. Orsola-Malpighi, Università di Bologna, Bologna, Italy
Tom Giedsing Hansen, MD, PhD Department of Anesthesiology and Intensive
Care – Pediatric Section, Odense University Hospital, Odense, Denmark
Institute of Clinical Research – Anesthesiology, University of Southern Denmark,
Odense, Denmark
Francesco Antonio Idone Department of Anesthesia and Intensive Care,
Catholic University of Sacred Heart, Training Hospital “A. Gemelli”, Rome, Italy
Pablo M. Ingelmo, MD Department of Anesthesia, Montreal Children’s
Hospital, MUHC, McGill University, Montreal, QC, Canada
Giorgio Ivani Anesthesiology and Intensive Care, Regina Margherita
Children Hospital, Turin, Italy
Scholtes Jean-Louis, MD Anesthesiology, Cliniques universitaires St Luc,
Université Catholique de Louvain, Bruxelles, Belgium
Martin Jöhr Pediatric Anesthesia, Department of Anesthesia, Luzerner
Kantonsspital, Luzern, Switzerland
Luca La Colla First Service of Anesthesia and Intensive Care, Parma Hospital,
Parma, Italy
Massimo Lamperti, MD Anesthesiology Institute, Cleveland Clinic Abu Dhabi
(CCAD), Abu Dhabi, United Arab Emirates (UAE)
Elisabetta Lampugnani Dipartimento di Anestesia e Rianimazione,
IRCCS Ospedale dei Bambini G. Gaslini, Genova, Italy
Contributors xvii
Jerrold Lerman, MD, FRCPC, FANZCA University of Rochester, Rochester,

NY, USA
Giovanni Mangia Department of Anesthesia, San Camillo Hospital, Rome, Italy
Laura Marchesini, MD Department of Anesthesia, Analgesia and Intensive
Care, University of Perugia, Perugia, Italy
Luisa Meneghini Dipartimento di Anestesia e Rianimazione, Università di
Padova, Padova, Italy
C. Minardi Dipartimento di Anestesia e Rianimazione, Università di Padova,
Padova, Italy
Giovanni Montobbio Dipartimento di Anestesia e Rianimazione, IRCCS
Ospedale dei Bambini G. Gaslini, Genova, Italy
Valeria Mossetti Anesthesiology and Intensive Care, Regina Margherita Children
Hospital, Turin, Italy
Caterina Patti Surgeon Freelancer, Rome, Italy
Francesca Pinzoni Dipartimento di Anestesia Pediatrica, Ospedali Civili,
Brescia, Italy
Thierry Pirotte Department of Anesthesia, Cliniques universitaires Saint-Luc,
Université catholique de Louvain – UCL, Brussels, Belgium
Paola Presutti Department of Anesthesia, San Camillo Hospital, Rome, Italy
Fabrizio Racca, MD Anesthesiology and Intensive Care Unit, S.C. Anestesia e
Rianimazione Pediatrica Azienda Ospedaliera SS Antonio Biagio e Cesare Arrigo
Hospital, Alessandria, Italy
Gonzalo Rivera, MD Department of Anesthesia, Clinica Las Condes, Santiago,
Chile
Chronic Pain Service, Department of Anesthesia, The Montreal Children’s
Hospital, McGill University, Montreal, QC, Canada
Chiara Robba Anesthesiology and Intensive Care Unit, SS Antonio Biagio e
Cesare Arrigo Hospital, Alessandria, Italy
Barbara Rosina Dipartimento di Anestesia Pediatrica, Ospedali Civili,
Brescia, Italy
Carlotta Rossi Servizio di Anestesia e Rianimazione, Dolo Hospital,
Mirano, Italy
Emre Sahillioğlu Department of Anesthesiology and Reanimation,
Acibadem University, Istanbul, Turkey
Maria Sammartino Dipartimento di Anestesia e Rianimazione, Ospedale
Universitario A. Gemelli, Università Cattolica del Sacro Cuore, Rome, Italy
xviii Contributors
Department of Anesthesia and Intensive Care, Catholic University of Sacred Heart,

Training Hospital “A. Gemelli”, Rome, Italy
Fabio Sbaraglia Department of Anesthesia and Intensive Care, Catholic
University of Sacred Heart, Training Hospital “A. Gemelli”, Rome, Italy
Brian Schloss, MD Department of Anesthesiology and Pain Medicine,
Nationwide Children’s Hospital, Columbus, OH, USA
Department of Anesthesiology and Pain Medicine, The Ohio State University,
Columbus, OH, USA
B. Senbruna, MD University of Rochester, Rochester, NY, USA
Gianpaolo Serafini Anestesia e Rianimazione 1, Fondazione IRCCS Policlinico
S. Matteo, Università di Pavia, Pavia, Italy
Marta Somaini, MD Department of Anaesthesia and Intensive Care, Niguarda
Ca’ Granda Hospital, Milan-Bicocca University, Milan, Italy
Valter Sonzogni Primo Servizio di Anestesia e Rianimazione, Ospedali Riuniti di
Bergamo, Bergamo, Italy
Rita Sonzogni Primo Servizio di Anestesia e Rianimazione, Ospedali Riuniti di
Bergamo, Bergamo, Italy
Simonetta Tesoro, MD Sezione di Anestesia, Analgesia e Rianimazione,
Dipartimento di Medicina Clinica e Sperimentale, Università di Perugia, Perugia,
Italy
Department of Anesthesia, Analgesia and Intensive Care, University of Perugia,
Perugia, Italy
Joseph D. Tobias, MD Department of Anesthesiology and Pain Medicine,
Nationwide Children’s Hospital, Columbus, OH, USA
Department of Anesthesiology and Pain Medicine, The Ohio State University,
Columbus, OH, USA,
Department of Pediatrics, The Ohio State University, Columbus, OH, USA
Costanza Tognon Dipartimento di Anestesia e Rianimazione, Università di
Padova, Padova, Italy
Tiziana Tondinelli Dipartimento di Anestesia, Ospedale S. Camillo, Rome, Italy
Sylvain Tosetti, MD Anaesthesia Department, The Montreal Children’s Hospital,
Navi Virk, MD University of Rochester, Rochester, NY, USA
Nicola Zadra Dipartimento di Anestesia e Rianimazione, Università di Padova,
Padova, Italy
Perioperative Medicine
1
Gabriele Baldini
1.1 What Is Perioperative Medicine?
Perioperative medicine is the practice of medicine that relates to and encompasses

all aspects of care provided to patients from the moment surgery is considered the
primary treatment to when patients are discharged from the hospital after the opera-
tion [1, 2]. It is considered a multidisciplinary speciality that aims to provide con-
tinuum of care with coordinated and evidence-based interventions in the preoperative,
intraoperative, and postoperative period with the ultimate goals to prevent the
occurrence of adverse outcomes, timely diagnose and treat perioperative complica-
tions (timely rescue) [3], and optimize surgical recovery.
1.2 Patients, Surgery, and Complications
Complications not only delay surgical recovery and increase healthcare costs but
can also determine patients’ survival [4, 5]. In the last years, significant advance-
ments in surgical care have been achieved. Despite advancements in anesthesia and
surgical care have significantly attenuated the stress response associated with sur-
gery, complications still occur in a significant proportion of patients. This demon-
strates that the development of postoperative complications mainly depends on the
interaction between patient’s physiologic reserve and the metabolic and inflamma-
tory response induced by surgery [6]. Consequently, improvement of perioperative
care by optimizing patients’ physiologic reserve and medical needs, and
G. Baldini, MD, MSc

Department of Anesthesia, Montreal General Hospital,
McGill University Health Center, Montreal, QC, Canada
e-mail: gabriele.baldini@mcgill.ca
© Springer International Publishing Switzerland 2016 1

M. Astuto, P.M. Ingelmo (eds.), Perioperative Medicine in Pediatric Anesthesia,
Anesthesia, Intensive Care and Pain in Neonates and Children,
DOI 10.1007/978-3-319-21960-8_1
2 G. Baldini
minimizing organ dysfunction caused by surgery, might significantly reduce adverse

outcomes and further accelerate surgical recovery.
1.3 A Model of Perioperative Medicine: Learning

from Enhanced Recovery After Surgery (ERAS)
Programs
Traditionally, surgeons coordinate perioperative care of patients undergoing sur-

gery. Enhanced recovery after surgery (ERAS) programs are multidisciplinary clini-
cal care pathways incorporating multiple evidence-based preoperative,
intraoperative, and postoperative interventions designed to decrease the surgical
stress response, enhance recovery, and improve outcomes (Fig. 1.1). They have
been successfully adopted by a variety of surgical specialities, and they have shown
to decrease hospital stay and reduce postoperative complications without increasing
readmission rates [7]. As consequence, variability in perioperative clinical practice
has been reduced, and collaboration among a variety of medical specialities, such as
anesthesiologists, surgeons, internists, physiotherapists, and dieticians, increased.
For these reasons, ERAS programs can be considered a well-proven clinical model
of perioperative care that encompasses many of the perioperative care principles.
Mid-thoracic epidural anesthesia/analgesia Preadmission counseling

No nasogastic tubes Fluid and carbohydrate loading
Prevention of nausea and vomiting No prolonged fasting
Avoidance of salt and water overload No/selective bowel preparation
Early removal of catheter Antibiotic prophylaxis
Thromboprophylaxis
Early oral nutrition Postoperative Preoperative
No premedication
Non-opioid oral
analgesia/NSAIDs ERAS
Short-acting anesthetic
Early mobilization Intraoperative agents
Stimulation of gut motility
Mid-thoracic epidural anesthesia/analgesia
Audit of compliance
and outcomes No drains
Avoidance of salt and water overload
Maintenance of normothermia (body warmer/warm intravenous fluids)
Fig. 1.1 Enhanced recovery after surgery (ERAS) for abdominal surgery: perioperative elements.
Published by Varadhan KK et al Crit Care Clin 2010;26:527–47– Fig. 3. Components of
ERAS. – Elsevier Inc
1 Perioperative Medicine 3
ERAS programs have been effectively developed also for pediatric patients [8–12],
but further studies are warranted to establish their safety in this population.
1.4 Areas of Perioperative Medicine
1.4.1 Preoperative Phase
1.4.1.1 Preoperative Risk Assessment and Optimization

Patients’ comorbidities are one of the main determinants of postoperative complica-
tions. In the preoperative period, the aim of perioperative medicine is to assess pre-
operative risk and optimize functional reserve and preoperative conditions that
delay surgical recovery and increase the risk of morbidity and mortality. Ideally,
once high-risk patients have been identified, multidisciplinary meeting should dis-
cuss the efficacy of alternative treatments to surgery to avoid the occurrence of
surgical adverse events without affecting patients’ care [13]. If surgery remains the
best treatment, preoperative strategies to optimize patients’ comorbidities should be
adopted to minimize adverse outcomes [13].
1.4.1.2 Pre-habilitation
In the preoperative phase physicians should also take the opportunity to com-
mence lifestyle changes by supporting adolescent or adult patients with smoking
and alcohol cessation programs, improve nutritional status and functional capacity.
Recovering from surgery takes longer than expected. Even in absence of surgical
complications, physiological and functional capacities are reduced by 20–40 %
after surgery and take time to return to baseline values. Surprisingly, even following
a relatively invasive surgical procedure such as ambulatory laparoscopic cholecys-
tectomy, more than 50 % of patients do not recover to baseline activity levels 1
month after surgery [14]. Pre-habilitation programs aim at improving functional
capacity and physiologic reserve before surgery and are becoming popular and
effective preoperative strategies to help adult patients recover faster from surgery
[15–17]. They include preoperative multimodal interventions such exercise train-
ing, nutrition supplement, and relaxation techniques for a period of 3–4 weeks, and
they have demonstrated to be more effective than rehabilitation programs interven-
ing only in the postoperative phase [18]. Although pre-habilitation programs
enhance functional exercise capacity and reduce hospital stay, it remains unclear if
they positively affect clinical outcomes [17].
1.4.2 Intraoperative Phase
Anesthesia care plays a pivotal role to attenuate surgical stress and minimize organ
dysfunction associated with surgery. Several intraoperative interventions directly
controlled by anesthesiologists [19], such as avoidance of hypothermia and deep
anesthesia, glycemic control, optimal fluid management, adequate hemodynamic
4 G. Baldini
monitoring, and appropriate analgesia, have shown to improve clinical outcomes

and accelerate the early and intermediate phase of surgical recovery [20].
1.4.3 Postoperative Phase
1.4.3.1 Intensity of Postoperative Care

Postoperative care of surgical patients is essential to ensure adequate surgical recov-
ery. Determining the intensity of postoperative care is pivotal as early recognition
and treatment of postoperative complications has been shown to significantly reduce
surgical mortality [5]. The intensity of postoperative care should be determined
considering patient’s preoperative risk and the invasiveness of the surgery.
Admission to intensive care units or high dependency units should be reserved for
high-risk patients or for complicated surgeries.
1.4.3.2 Postoperative Pain Management

Postoperative acute pain management must ensure optimal analgesia, minimizing
opioid side effects and facilitating early mobilization. The introduction of acute
pain services has facilitated the management of surgical patients with inadequate
pain control or with adverse events related to common analgesia techniques. It has
also improved patients’ satisfaction and accelerated hospital discharge. The use of
ultrasound-guided regional analgesia techniques for inpatients and outpatients has
increased and successfully improved postoperative pain control. Indeed, also ambu-
latory patients can be comfortably and safely discharged home with continuous
peripheral nerve blocks.
1.4.3.3 Hemodynamic Management and Echocardiography

Perioperative hemodynamic management is essential to guarantee optimal organ
perfusion and oxygen delivery. The use of cardiac output monitoring was typically
limited in cardiac patients during the intraoperative and postoperative period or for
critically ill patients admitted to intensive care units. Recently, the widespread use
of perioperative echocardiography and noninvasive cardiac output monitors outside
the operating room has gained popularity even in patients undergoing noncardiac
surgery. Thanks to these devices physicians can now administer intravenous fluids
based on more objective and accurate measures of hypovolemia, facilitating the
hemodynamic management of high-risk surgical patients [21] and hemodynami-
cally unstable patients [3]. In the perioperative period, echocardiography can also
be utilized as diagnostic tool, for example, to identify preoperative cardiopulmonary
conditions that can influence the management of surgical patients.
1.4.3.4 Noncardiac Ultrasound

The use of ultrasound in the perioperative period is gaining popularity also to mange
patients without cardiac conditions. For example, ultrasound-guided peripheral
nerve blocks are considered standard of care in many institutions; bedsides, ultra-
sound of the lungs guides physicians to promptly diagnose and treat postoperative
Preoperative Intraoperative Postoperative
Preoperative risk assesment Temperature control Intensity of postoperative care

Cardiovascular Depth of Anesthesia Analgesia
Respiratory Glycemic control Hemodynamic monitoring
Renal Fluid management Noncardiac ultrasound
OSA Hemodynamic monitoring Chronic pain
Metabolic Analgesia
Nutritional
Optimization
Anemia
OSA
Diabetes Mellitus
Functional status (pre-habilitation)
Nutritional
Mental
Pharmacological
Smoking and alcohol cessation
Fig. 1.2 Areas of perioperative medicine
respiratory complications such as pulmonary edema, lung consolidation, pleural

effusion, and pneumothorax [22]; ultrasound assessment of the gastric content pro-
vides important information about the individual risk of aspiration before the induc-
tion of anesthesia [23–26].
1.4.3.5 Chronic Postsurgical Pain

Chronic postsurgical pain (CPSP) can affect a significant proportion of surgical
patients even following minor surgical procedures. Although the incidence of CPSP
is higher after certain surgeries than others, uncontrolled severe acute surgical pain
represents one of the main risk factors associated with the development of CPSP
[27]. Identification of patients at higher risk of CPSP, nerve-sparing surgical tech-
niques, and prevention and treatment of acute postoperative pain represent periop-
erative interventions that must be considered in every surgical patient to decrease
the occurrence of this physically, mentally, and socially disabling condition [28].
Figure 1.2 summarized the most important areas of perioperative medicine dis-
cussed in this section.
1.5 Perioperative Medicine: A Natural Extension

of Anesthesiology?
Anesthesiologists possess extensive perioperative knowledge and skills to be con-

sidered the ideal perioperative physician [6]. While many anesthesiologists have
already identified themselves as perioperative physicians (some anesthesiology
6 G. Baldini
departments have already entitled their departments “Department of Anesthesia and

Perioperative Medicine”), others still consider their practice limited to the operating
room. This mixed vision can be attributed to several reasons, such as workforce and
economic issues, absence of a cohesive and consensus-based perioperative medi-
cine curricula, and lack of a formal and recognized training [1, 2, 29].
Despite these considerations, it is unquestionable that anesthesiologists should
start looking beyond the intraoperative period, as they have done in critical care and
pain management [6]. Improvements of anesthetic knowledge and advancements in
anesthesia care have made the delivery of anesthesia a safer practice. Consequently
the need of anesthesiologists in every operating room has started to be considered
not essential, and many institutions, especially in the North America, have already
tried to replace anesthesiologists with physicians’ assistants, certified nurse anes-
thetists, and other nonphysician figures. If anesthesiologists continue to exclusively
practice in the operating room, the speciality of anesthesiology will be at risk
of being undervalued, the role of the anesthesiologists underestimated, and periop-
erative medicine might be practiced by other specialities (e.g., internal medicine,
surgery).
However, before being considered a true perioperative speciality, anesthesiology
must face important challenges. The residency program should be redesigned by
implementing a robust perioperative curriculum that considers the continuum of
care and clearly defines the required, basic, intermediate, and advanced competen-
cies that a perioperative physician must have. For this purpose, collaboration with
other specialities such as internal medicine, cardiology, and respirology is essential,
and it must be intensified during the residency training to improve anesthesiolo-
gists’ perioperative knowledge. Alternatively, a perioperative fellowship program
could be offered to those anesthesiologists who specifically want to support patient’s
care throughout the entire perioperative period and obtain advance perioperative
knowledge and skills [29]. Finally, expanding the horizons of anesthesia beyond the
operating theatre will provide strong basic science and clinical knowledge to
improve perioperative care.
In conclusion, perioperative medicine aims to provide continuum of care with
coordinated and evidence-based interventions in the preoperative, intraoperative,
and postoperative period with the ultimate goals to reduce morbidity and mortality
and accelerate surgical recovery.
References
1. Rock P (2000) The future of anesthesiology is perioperative medicine. Anesthesiol Clin North
America 18(3):495–513, v
2. Carli F (2001) Perioperative medicine. Are the anesthesiologists ready? Minerva Anestesiol
67(4):252–255
3. Yang H (2015) Perioperative medicine: why do we care? Can J Anaesth 62(4):338–344
4. Khuri SF, Henderson WG, DePalma RG, Mosca C, Healey NA, Kumbhani DJ (2005)
Participants in the VANSQIP. Determinants of long-term survival after major surgery and the
adverse effect of postoperative complications. Ann Surg 242(3):326–341; discussion

341–323
5. Ghaferi AA, Birkmeyer JD, Dimick JB (2009) Variation in hospital mortality associated with
inpatient surgery. N Engl J Med 361(14):1368–1375
6. Grocott MP, Pearse RM (2012) Perioperative medicine: the future of anaesthesia? Br J Anaesth
108(5):723–726
7. Greco M, Capretti G, Beretta L, Gemma M, Pecorelli N, Braga M (2014) Enhanced recovery
program in colorectal surgery: a meta-analysis of randomized controlled trials. World J Surg
38(6):1531–1541
8. Howard F, Brown KL, Garside V, Walker I, Elliott MJ (2010) Fast-track paediatric cardiac
surgery: the feasibility and benefits of a protocol for uncomplicated cases. Eur J Cardiothorac
Surg 37(1):193–196
9. Mattioli G, Palomba L, Avanzini S, Rapuzzi G, Guida E, Costanzo S, Rossi V, Basile A,
Tamburini S, Callegari M, DellaRocca M, Disma N, Mameli L, Montobbio G, Jasonni V
(2009) Fast-track surgery of the colon in children. J Laparoendosc Adv Surg Tech A 19(Suppl
1):S7–S9
10. Reismann M, Arar M, Hofmann A, Schukfeh N, Ure B (2012) Feasibility of fast-track ele-
ments in pediatric surgery. Eur J Pediatr Surg 22(1):40–44
11. Reismann M, Dingemann J, Wolters M, Laupichler B, Suempelmann R, Ure BM (2009) Fast-
track concepts in routine pediatric surgery: a prospective study in 436 infants and children.
Langenbecks Arch Surg 394(3):529–533
12. Reismann M, von Kampen M, Laupichler B, Suempelmann R, Schmidt AI, Ure BM (2007)
Fast-track surgery in infants and children. J Pediatr Surg 42(1):234–238
13. Glance LG, Osler TM, Neuman MD (2014) Redesigning surgical decision making for high-
risk patients. N Engl J Med 370(15):1379–1381
14. Feldman LS, Kaneva P, Demyttenaere S, Carli F, Fried GM, Mayo NE (2009) Validation of a
physical activity questionnaire (CHAMPS) as an indicator of postoperative recovery after
laparoscopic cholecystectomy. Surgery 146(1):31–39
15. Durrand JW, Batterham AM, Danjoux GR (2014) Pre-habilitation. I: aggregation of marginal
gains. Anaesthesia 69(5):403–406
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Clin 33(1):17–33
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Part I
Perioperative Care Before Surgery
Preoperative Evaluation in Pediatric
Anesthesia 2
Giovanni Mangia, Caterina Patti, and Paola Presutti
2.1 Introduction
The preoperative assessment is the process of evaluating the patient’s clinical condi-
tion, aimed to define the risks and eligibility for anesthesia and surgery. The infor-
mation needed to make decisions comes from the anamnesis, the physical exam,
and the complementary test collected by a multidisciplinary team including sur-
geons, nurses, pediatricians, and anesthetists.
The preoperative evaluation defines the physical status of the child, foresees the
surgical and anesthetic risks, prescribes preoperative tests and therapies or special
preparation, and provides information regarding the perioperative care. It also helps
to make appropriate use of hospital resources and programs the surgical activities
based on the clinical characteristic and the risk of the patients.
Although other medical specialists may provide additional information in decid-
ing the eligibility of a patient for anesthesia, the preoperative evaluation is an anes-
thesiologist’s responsibility. Only an anesthesiologist can define the eligibility for
anesthesia.
2.2 Operating Risk Stratification
The clinical risk is the probability of a patient presenting “damage or inconvenience

caused, even if unintentionally, by the medical care given during the hospitalization
period, that causes a prolongation of hospitalization, a health status deterioration or
G. Mangia (*) • P. Presutti

Department of Anesthesia, San Camillo Hospital, Rome, Italy
e-mail: mangia.giovanni@fastwebnet.it
C. Patti
Surgeon Freelancer, Rome, Italy

DOI 10.1007/978-3-319-21960-8_2
12 G. Mangia et al.
death” [1]. The negative outcome of a surgery depends on several factors including
the patient condition, comorbidity, and the type of surgery (Table 2.1).
The American Society of Anesthesiologist Physical Status classification
(ASA-PS) is routinely used for risk prediction [2–4] in the perioperative period.
The NARCO-SS score developed by Clavien for adult patients is a risk assess-
ment system that includes both pre- and intraoperative information [5] and has
been recently adapted for pediatric population [6, 7]. Additionally, the use of
local and regional epidemiological data may contribute to further identify specific
risk [8].
The ASA-PS is the most frequently used system to evaluate the preoperative
physical status. Five classes can be distinguished: I normal healthy patient, II patient
with mild systemic disease, III patient with severe systemic disease that limits activ-
ity but not incapacitating, IV patient with incapacitating disease that is a constant
threat to life, and V moribund patient not expected to survive 24 hours with or with-
out surgical operation. In the event of an emergency operation, an E is placed after
the physical status class. The main advantage of this system is its simplicity.
However, its interrater reliability is subjected to an open discussion. [2–4]. Younger
age (infants and children with less than 3 years of age) and higher ASA-FS (III to
V) were strongly correlated with a higher risk of anesthesia-related cardiac arrest
[9–14].
The NARCO is a score risk system based on the preoperative neurological status
(N), airway (A), respiratory (R), cardiac activity (C), and other items (O). The total
score is supplemented by a score of surgical severity (SS), with the identification of
two categories (A and B) according to surgery invasiveness. It is thereby obtained
an overall risk score (low, moderate, high, higher) and information on the postop-
erative care level (day surgery, PACU, PICU). This system shows a more accurate
prediction rate of adverse events and care intensification – escalation, morbidity,
and mortality – compared with the ASA-PS [5].
Weinberg et al. and Wood et al. studied the predictors of perioperative complica-
tions 30 days after surgery [6, 7]. Prematurity, ASA-PS >3, cardiac surgery, neuro-
surgery, major orthopedic interventions need for intraoperative transfusion of
albumin and/or red blood cells, surgery lasting more than two hours, and SpO2 less
than 96 % were associated with postoperative complications and reoperations.
Table 2.1 Johns Hopkins surgery risk classification system (JHSRCS)

JHSRCS
status Description Example
1 Noninvasive procedure, minimal Excision of lesion of the skin
risk
2 Procedures limited in their Inguinal hernia repair, diagnostic
invasive nature mild risk laparoscopy
3 More invasive procedures Open abdominal procedures
moderate risk, moderate blood
loss
4 Procedures posing significant risk Planned postoperative intensive care, open
thoracic procedure, intracranial procedure
2 Preoperative Evaluation in Pediatric Anesthesia 13
2.3 Timing and Organization of the Preoperative

Evaluation
The timing of the preoperative evaluation could be influenced by the demographic

characteristics, the institutional organization, the patient’s clinical condition, and
the surgical procedure. The organizational system used for the clinical evaluation
and preoperative risk stratification and clinical planning varies among institutions
and type of intervention [15].
Hospitalization of healthy children for a preoperative evaluation the day before
surgery should be considered as improper in most minor elective surgical proce-
dures. A day hospital stay does not reduce costs nor does it save time because the
patient should be evaluated again on the day of surgery [16].
The ASA-PS can provide suggestions on the timing of preoperative visit [17].
The ASA Task Force on Preanesthesia Evaluation suggested that for low-risk
patients undergoing low grading procedures, preanesthesia could be performed the
same day of the surgery [18]. The “one-stop anesthesia” modality is a clinical path-
way designed for day surgery procedures (Fig. 2.1). This modality reduces the
access to the hospital for day surgery interventions with significant social, psycho-
logical, and economic advantages. It is also characterized by a high diagnostic accu-
racy and a high parents’ satisfaction [19–23]. The “one-stop anesthesia” is a
modification of the “one-stop surgery” where patients are screened before the pro-
cedure by external specialists [24, 25].
The preoperative evaluation of high-risk patients and/or scheduled for major sur-
gery should be performed before the day of surgery [23, 26]. Nurses and the pedia-
trician have a central role on the screening and preparation of the surgical patient
independent of the type of surgery [27–30].
The preoperative risk stratification has organizational consequences including
the care settings (in hospital, day of surgery), the postoperative care levels (e.g.,
PACU, PICU, etc.), and the selection of the institution (hospital vs ambulatory sur-
gery center) [31].
2.4 Medical History and Physical Examination
The preoperative assessment should precede any request of laboratory and instru-
mental tests. The anamnesis usually takes advantage of questionnaires, submitted
to parents, in a “face-to-face” procedure, by phone, online, or compiled at home
[32, 33] (Appendix A). As an assessment support, it is also possible to use a specific
software, which helps to reduce the amount of preoperative tests [34]. The medical
history should provide information of all the present and past medical problems. It
should include extensive information of medication intake including natural medi-
cines. Any allergic reaction to food, medications, or other substances (e.g., latex)
must be addressed.
When looking for information regarding previous anesthesia experiences, it is
extremely important to focus the airway management and respiratory or cardiovas-
cular complications. It is also important to consider the postoperative consequences
14 G. Mangia et al.
Steps and timing

Outpatients Dept Outpatients Dept
Deskwork,
Private Visit Private Visit Admission Day Surgery Anaesthetist
Web,
Emergency Emergency consultation room
Anaesthetist consultation room
Day Service Day Service
Pre-hospitalization
Compilation clinical
filing and anesthesia
Indications Choice of timing
questionnaire.
for surgery anethesia visit
Delivery of information
leaflet and PLS letter
One-Stop:preanesthesia
assessment done day of
surgery
WHO
Surgeon Surgeon -nurse Anesthesist Anesthesist
Fig 2.1 Clinical pathways “one-stop anesthesia”
of anesthesia and surgery like nausea and vomiting, pain or unsettled behavior (i.e.,
emergence delirium) during awakening, and behavioral changes persisting days or
weeks after surgery.
The family history should include information of genetically transmitted diseases
(malignant hyperthermia, neuromuscular disease, etc.), cases of unexplained deaths,
bleeding disorders, passive smoking, or other environmental or social conditions.
The preoperative evaluation can also be an opportunity to observe the parent’s
behavior and the relations within the family, with indications of the possible preop-
erative anxiety level.
A thorough assessment of the airway; the cardiovascular, respiratory, and ner-
vous system; and the state of hydration should be performed before any procedure
including anesthesia. The physical examination should take into account the aware-
ness of the motor, cognitive, language, and social development of the child [35].
The physical examination may vary according to the age of the patients. The
physical examination of infants should be flexible, in order to take advantage of the
periods in which the child is quiet or asleep, to auscultate the lungs or heart in the
parents’ arms. Better collaboration results can be achieved with a pacifier, a smile,
a comforting speech, and the use of toys or custom distraction.
Toddlers can be active, curious, or, conversely, shy or less cooperative. Much of
the neurological and musculoskeletal assessment may be inferred from the child
observation when playing and walking into the visit room. The anxiety reduction
can be achieved with a demonstration of the instrument use on the parent or on his
reassuring object (e.g., his moppet, favorite toy, etc.).
Providing preschool child’s simple explanations of the evaluation phases is
always useful. Inviting them to count, explain the colors, talk about a favorite activ-
ity, and externalize your approval is all useful strategies during the evaluation.
The school-age children willingly cooperate during the examination. They
appreciate the information regarding what you do and why you are doing it.
Teenagers may show concern about their developing body. The choice of per-
forming the physical exam with the parents belongs to the patient.
The body weight and length should be measured and compared with the reference
values. During the first 4 years of life, there is a rapid growth rate. The height, with
minimal difference between the sexes, increases on average, by 24 cm in the first
year of life, by 11 cm in the second year, by 8 cm in the third, and by 7 cm in the
fourth. Babies double the birth weight around the 5th months. Their weight triples
around the 1st year and quadruples around the 2nd year. From four years old to the
beginning of puberty, the growth is more restrained and relatively constant in time.
The stature increase is on average 5–6 cm per year in both male and female children.
The weight gain per year varies between 1,770 and 2,800 grams [36]. The Pediatric
Early Warning Score (PEWS) could be useful in children with abnormal physical
examination and/or in emergency situation and may provide additional clinical ele-
ments for the evaluation of children undergoing urgent surgical procedures [37].
2.5 Preoperative Tests
Preoperative test and radiological studies should not be requested on a routine basis
[16]. The indications for these investigations should be documented and based on
the information derived from the medical history and physical exam and/or justified
by the proposed surgical procedure.
The American Academy of Pediatrics stated, “preoperative tests should be
ordered only when they can provide added value, i.e., when there is a reasonable
certainty that they will reveal, or better define the clinical conditions that are rele-
vant to the planned anesthesia and/or may affect the anesthesia or surgical out-
come” [38]. Specific tests could be requested for diagnostic purposes (e.g., a cardiac
ultrasound for exclusion of unknown congenital heart disease), for therapeutic pur-
poses (e.g., allergy tests to exclude cross allergy conditions), and when it is appro-
priate to have baseline value (i.e., concentration of Hb in a potentially bleeding
operation) [39].The usefulness of routine preoperative laboratory tests for one-day
surgery in healthy children was confirmed from some Italian authors since several
years [40].
Several national societies produced guidelines and recommendations for the pre-
operative tests. The National Institute for Health and Clinical Excellence (NICE –
UK) suggested to avoid request routine test for patients younger than 16 years ASA1
scheduled for elective surgery grade 1 and 2 [41]. For the Italian Society of Pediatric
and Neonatal Anesthesia and Intensive Care (SARNePI), the “systematic prescrip-
tion of complementary tests in children should be abandoned, and replaced by a
selective and rational prescription, based on the patient history and clinical examina-
tion” [16]. Those recommendations are based on non-randomized cohort studies
with concurrent or historical controls, retrospective case-control studies or case
series without control groups. A previous blood test (within 6 months) should only
be repeated in case of significant changes on the previous clinical conditions.
There is no justification for the routine examination of hemoglobin and hemato-
crit before minor surgery, and it should be restricted to potentially bleeding surgical
cases [42]. The incidence of anemia in children is rare and occurs more easily in
infants younger than 1 year. Moreover, the presence of a certain level of anemia
does not affect the decision to proceed with surgery [43, 44].
16 G. Mangia et al.
The determination of blood glucose cannot predict the blood glucose concentra-
tion at the time of induction. Numerous studies have actually shown a minimum risk
of hypoglycemia in children even after prolonged fasting.
The measurement of plasma electrolytes is not justified in asymptomatic chil-
dren and should be required only in the presence of vomiting, diarrhea, use of
diuretics, or other conditions associated with acid-base modifications [45].
There is consensus on the uselessness of nonselective coagulation screening. This
test should be restricted to patients with history of coagulopathy and/or as a baseline
measure for procedures with high risk of significant bleeding. The routine request of
coagulation tests before ENT surgery or central blocks remains one of the most con-
troversial topics of the perioperative care. Most studies show low sensitivity, speci-
ficity, and predictive value of partial thromboplastin activated time, prothrombin
time, and thrombin time [46–50]. Moreover, false-positive aPTT prolongation is
commonly associated to nonspecific antiphospholipid antibodies often present in
children with ENT infections or after vaccination [48, 49]. Standardized question-
naires have shown better sensitivity and negative predictive values than aPTT as
coagulation screening before surgery. However, it is difficult to find hemorrhagic
signs in small children. The impossibility of obtaining a family history of one or both
parents’ may compromise the reliability of the questionnaire [51].
Routine request of a preoperative ECG is not recommended in healthy chil-
dren [52]. The SARNePI recommended the request of a preoperative ECG even-
tually associated to a cardiac ultrasound in case of pathologic/uncertain heart
murmur, suspicion of congenital heart disease, obstructive sleep apnea, severe
scoliosis, bronchopulmonary dysplasia (BPD), neuromuscular disease, and in
neonates/infants under 6 months of life [16]. The ECG in newborns and infants
can detect conduction abnormalities, such as long QT syndrome (LQTS) and the
Wolff-Parkinson-White one (WPW) [53]. Investigating maternal factors and fetal
factors associated to sudden infant death (smoking, alcohol, intrauterine hypoxia,
prone position while asleep, and passive smoke) should be also part of the stan-
dard preoperative evaluation. Some congenital heart diseases have asymptomatic
evolution during the first weeks after birth [54]. A recent study reveals that up to
30 % of babies and infants with congenital heart disease were discharged from
the hospital without diagnosis [55]. Routine physical exam looking for a con-
genital heart disease between the sixth and eighth week of life is highly
recommended.
The chest radiography adds little information to the history taking and to the clinical
examination, and its systematic request is not longer justified [56]. A chest radiograph
could be indicated after the physical examination and when the medical history supports
the need of additional information or in case of chronic lung disease, bronchial pulmo-
nary dysplasia (BPD), severe asthma, neuromuscular disease, severe scoliosis, etc.
Conclusion
The preoperative assessment is the process of evaluating the patient’s clinical
condition, aimed to define the risks and eligibility for anesthesia and surgery.
The preoperative evaluation is mandatory before any diagnostic or therapeutic
procedure requiring anesthesia or sedation. The preoperative evaluation should
provide the elements to select a shared and individualized perioperative plan.
The prescription of complementary tests in children should be selective and

based on the patient history and clinical examination. The preoperative evalua-
tion is an anesthesiologist’s responsibility, and only an anesthesiologist can
define the eligibility for anesthesia.
2.6 Appendix A
18 G. Mangia et al.
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Preoperative Preparation
3
Luciano Bortone, Luca La Colla, and Marinella Astuto
3.1 Non-pharmacological Preparation
Preparation of the child and his/her family for anesthesia and surgery should begin
when the surgeon sets the date and type of surgery for the child. Pediatricians also
have an important role in preparing children and families for anesthesia and surgery.
Once it has been ascertained that the child is in good physical condition for surgery,
the pediatrician will help the family deal with the surgery in terms of cognitive,
emotional, and logistical elements [1].
3.1.1 Preoperative Anxiety
Since more than half of children develop anxiety in the preoperative period, close coop-
eration between the pediatrician, surgeon, anesthesiologist, nurses, and nonmedical
personnel is essential for a positive perioperative experience for the child and his/her
family. Preoperative anxiety in children could be assessed by the modified Yale
Preoperative Anxiety Scale (mYPAS), containing 27 items grouped into five categories
(activity, emotional expressivity, state of arousal, vocalization, and use of parents) [2].
There are two distinct components of anxiety: a transient state anxiety, variable
over time and intensity, characterized by a sense of tension, apprehension,
L. Bortone • L. La Colla
First Service of Anesthesia and Intensive Care, Parma Hospital, Parma, Italy
Dipartimento di Anestesia e Rianimazione, Azienda Ospedaliera di Parma, Parma, Italy
e-mail: lbortone@ao.pr.it
M. Astuto (*)
Anesthesia, Intensive Care, University of Catania, Policlinico Hospital, Catania, Italy
Dipartimento di Anestesia e Rianimazione, Ospedale Universitario Policlinico, Catania, Italy
e-mail: marinella.astuto@gmail.com

DOI 10.1007/978-3-319-21960-8_3
22 L. Bortone et al.
nervousness, and worry, and a stable trait anxiety, more or less constant over time,
linked to individual differences in the propensity to develop anxiety. The development
of preoperative anxiety in children depends on many factors, such as awareness of the
disease and the need for surgery, fear of separation from parents, the feeling of lack of
control and the unpredictable character of the event that is about to happen, infant
temperament, previous experience in a hospital environment, and the emotional state
of the parents. Risk factors for the development of preoperative anxiety include being
a preschooler, a shy and introverted character, previous surgeries, relationships with
health personnel related to previous hospitalizations, the presence of anxious parents,
and having participated in preparation programs prior to the intervention [3].
Some children are able to verbalize their fears explicitly; others express them
through behavioral changes, such as crying, agitation, tremor, stoppage of play,
increased muscle tone, and even real attempts to escape. Preoperative anxiety is
associated with increased circulating catecholamines [4].
High levels of preoperative anxiety may adversely affect the postoperative period,
with higher incidence of pain as well as short- and long-term behavioral changes such
as emergence delirium, enuresis, sleep disorders, nightmares, apathy, eating disor-
ders, and separation anxiety [5]. In clinical practice, one can predict the occurrence
of adverse postoperative effects based on the levels of preoperative anxiety. High
levels of preoperative anxiety, with a particularly stressful induction of anesthesia and
reduced doses of anxiolytics, cause the development of anxiety and behavioral disor-
ders in the postoperative period, even a few months after hospitalization [6].
Low levels of preoperative anxiety are associated with a good postoperative
behavioral outcome. It is useful to prevent and treat anxiety in the child and parents
through a comprehensive and multidisciplinary approach that accompanies the
child and his/her family from the admittance to the hospital until the time of induc-
tion of anesthesia. Fundamental moments are represented by preoperative visits by
the surgeon and anesthesiologist; preparation for the intervention by psychologists
or play specialists; strategies adopted in the operating theater before induction of
anesthesia, namely, premedication; and the parental presence in the operating room.
The preoperative visit is a “psychologically” important part of preparation for
surgery. Parents express their concern about anesthesia often in the presence of the
child; they are more often frightened by the risks related to anesthesia than the sur-
gery. The very detailed description of the proposed anesthetic technique with its
potential complications can generate a particularly strong state of anxiety. The data
about the emotional state of the parents after a more or less detailed interview with
the anesthesiologist are conflicting; some studies report levels of tension, depres-
sion, and irritability associated with higher preoperative detailed information, while
others conclude that patients and parents informed in detail about the anesthesia and
its risks are not more anxious than those less well informed.
As a general rule, it is reasonable to adapt the type of information to the psycho-
logical characteristics and the “receptivity” of the patient and the parents. A family
looking for comprehensive information will benefit from a detailed anesthetic inter-
view, while parents with negative attitudes toward potentially dangerous situations
will react with stress and anxiety to a conversation full of details.
3 Preoperative Preparation 23
The anesthesiologist must be prepared to deal with parents and children with
ideas, life views, and religions differing from their own in order to avoid verbal
conflict which could result in an increase in preoperative anxiety for the family.
Our goal is to bring the child to surgery as peaceful as possible. The informed
consent provides adequate information to parents about the anesthetic procedure
and the infrequent possible risks. A good method of requesting consent can help
reduce the anxiety of the parents and the child. To say that anesthesia is as risky
as traveling by train is different from saying that, although rarely, anesthesia can
be fatal.
3.1.2 Preparation for Surgery
Programs destined for pediatric anesthesia preparation aim to reduce the anxiety of
children and parents prior to surgery. By using play and games in the hospital, in
which the child has full control, they can reduce their fears and teach them tools to
deal with otherwise extremely stressful experiences [7].
Over the last 50 years, there have been different patterns of preparation. The
“informative” approach was used in the 1960s. It was aimed to encourage emotional
expression and to establish a relationship of trust between the medical staff, child,
and family. “Modeling” techniques were developed in the 1970s and were based on
the ability of the child and his parents to experience anesthesia and surgery through
video simulations with dolls. In the 1980s, “coping” techniques included the active
involvement of the child and were designed to promote adaptation and the ability to
cope with a critical situation. Currently, in pediatric hospitals, that objective is pur-
sued by specialized support staff through a multimodal approach. Play experiences
and information on the procedures are explored together with the description of the
feelings that the young patient will experience. In addition, the child is given the
opportunity to examine and manipulate the instruments that will be used in the
operating room.
The development of coping techniques is considered the gold standard of psy-
chological preparation, followed by modeling, play therapy, visiting the operating
room, and the distribution of informative material. Compared to other methods
(such as modeling and distribution of informative materials), the preparation of the
child through coping is associated with lower levels of preoperative anxiety at the
day of surgery and at the time of separation from their parents before entering the
operating theater [3].
The choice and timing of the preparation program must be based on the age,
maturity, and cognitive capacity of the child. Age greater than or equal to 6 years old
is an indication to apply the program over five days before the surgical procedure,
in order to ensure that the child has time to process the information received and to
complete the process of coping. Children over the age of 6 years who underwent
psychological preparation one week preoperatively showed decreased levels of anx-
iety during and immediately after preparation, followed by a reduction in stress
during the five days prior to surgery [8]. On the other hand, children aged between
3 and 5 years old gradually acquire the ability to discern fantasy from reality. The
skill is not yet present in those younger than three, and therefore, the application of
preparation programs based on reality may be useless if not counterproductive by
increasing anxiety.
The success of the preoperative preparation can be compromised by past bad
experiences of the child in hospital. In this case, the preparation, in addition to not
adding any information, could produce an exaggerated emotional response and
worsen the anxiety state.
The parents’ anxiety influences the psychological condition of their child.
Hence, it is optimal that the preparatory projects actively involve the family of the
young patient. Watching explanatory movies can reduce preoperative anxiety in
parents.
Kain et al. [9] proposed a preparation project focused on the family called
“ADVANCE.” They demonstrated that this approach reduces the anxiety of both the
child and parents before and during induction of anesthesia. Also ADVANCE was
proved as effective as midazolam in the management of children undergoing induc-
tion and was associated with faster discharge from the recovery room and lower
doses of analgesics during the postoperative period. This approach, however, is very
costly and requires appropriate health personnel.
Fortier and Kain introduced a new web-based approach for children and their
families to impact perioperative pain and anxiety [10].
Music therapy is considered necessary at the time of separation of the child from
the parents upon entering the operating theater, while it does not seem useful to
reduce anxiety during induction of anesthesia [11].
Recently, new techniques have been tested. Seiden et al. have compared mid-
azolam to a “tablet-based interactive distraction” (TBID) in children aged 2–11
years old. They found that TBID reduced perioperative anxiety, emergence delir-
ium, and time to discharge and increased parental satisfaction in patients undergo-
ing ambulatory surgery [12].
Play specialists in our hospital prepare children before surgery, with a parent
present (www.giocamico.it). Aided by two puppets, they teach the children how to
use the oximeter, the pressure cuff, the electrocardiogram patches, facemask, and
intravenous cannula. The play specialists show pictures of the instruments and pro-
vide explanations on what happens in the operating room. They also show the chil-
dren and their parents how all the people they meet will be dressed upon entering
the operating theater. The preparation is offered to all boys and girls aged between
5 and 11 years old, a few days before surgery. For older children, a book with photos
and drawings is used. Children are also offered the opportunity to test the diagnostic
and therapeutic tools (Fig. 3.1).
Specialists also prepare children who have to undergo painful procedures in
sedation analgesia.
Also promising is the preparation of children aged 5–10 years old for MRI. The
aim is to reduce the number of MRI done under general anesthesia (Fig. 3.2).
Fig. 3.1 Play preparation for anesthesia by Giocamico
3.1.3 Parental Presence During Induction of Anesthesia (PPIA)
In 1985, an ophthalmic surgeon, Adrian While, wrote in the British Medical Journal
that he had not been allowed to accompany his 3-year-old daughter to the operating
room for induction and argued that parents should be admitted to the operating
room to help their child. Gauderer indicated that virtually all parents, given a choice,
went into the operating room with their children; only two parents had a fainting
spell. Nurses, anesthesiologists, and surgeons were excited about this new approach,
which appeared to be safe, simple, and effective [13]. A study by Kain compared
PPIA to drug preparation and demonstrated that children who were premedicated
had a lesser degree of anxiety at the time of separation before induction compared
to the control group and to the PPIA group [14]. In another study, the presence of a
parent in the room did not reduce the anxiety of the child who had already received
midazolam, while there was a reduction in the anxiety of the parents and their
greater satisfaction [15].
Nevertheless, it seems that children aged older than 4 and anxious parents might
get some benefit from PPIA [9].
Fig 3.2 Play preparation

for MNR by Giocamico®
Lerman believes that the presence of the parents is not an undeniable right but
rather a therapeutic option to facilitate the induction of anesthesia to be used at the
sole discretion of the anesthesiologist [16]. Despite this theory, there is no doubt
that some children (such as those with special needs, very anxious, or subjected to
multiple hospitalizations) may actually benefit from PPIA, which should ideally be
preceded by a preparation program for parents.
In our experience, of over 15 years, we propose that one of the parents accompa-
nies the child into the operating room for induction of anesthesia, excluding preg-
nant moms, parents with health problems, and anxious parents to whom we explain
that their presence could increase the child’s anxiety and create problems for the
staff. When the parent comes into the room, the preschoolers are normally premedi-
cated with midazolam, while older children can choose, in agreement with the par-
ent, whether or not to have premedication. They can also choose the type of induction
of anesthesia, inhalation or intravenous, which helped in the choice by the anesthe-
siologist. A staff member accompanies the parent in every moment of his stay in the
operating room.
Different “side effects” of PPIA have been described in the literature: parents
taking their children out of the operating room, parents who faint, and even parents
who want the anesthesiologist to discontinue anesthesia and awaken their child.
Hence, it is important to select the right parents (excluding, e.g., those who are anx-
ious) and possibly make them undergo a preparation process. In addition, it is
important to have a staff member always close to the parent. This member will
escort the parent outside the operating room at the end of induction or whenever the
child’s condition changes and the parents’ presence might be distracting or disrup-
tive to the induction of anesthesia.
Hospitalization before surgery and prolonged preoperative fasting represent for
the child an additional source of discomfort. At our hospital, young patients can be
admitted 1–2 h before surgery. Regarding preoperative fasting, it is necessary to
minimize the fasting hours (especially in smaller patients) in accordance with the
directions of the American Society of Anesthesiology for healthy pediatric patients
undergoing elective surgery (see below). In particular, the reduction in fasting hours
is not associated with an increased gastric residual volume, or indirect index of risk
of aspiration pneumonia. Furthermore, a less restrictive fasting regimen reduces
dehydration, increases hemodynamic stability during anesthesia, facilitates venous
vascular access, guarantees glucose homeostasis, reduces irritability in the young
patient, and increases the overall satisfaction of the child and parents.
The pain from venipuncture is one of the greatest fears of the hospitalized pedi-
atric patient. The pain generated by venipuncture is classified as moderate to severe.
The procedure should be reduced to the absolute minimum, such as preoperative
blood tests prescribed only on the basis of anomalies detected in the patient history
or by physical examination [17]. The intravenous line needed for the surgery is
normally placed after induction of anesthesia when the child is asleep and the veins
well dilated. However, if the child prefers an intravenous induction, it is recom-
mended to apply an anesthetic cream over the skin of the most visible veins 40
minutes before the surgery.
3.2 Pharmacological Preparation
The second part of this chapter will briefly review only the most widespread routes
of administration of the most common drugs that are currently used for pharmaco-
logical preparation of children before surgery.
The goals of premedication in children are the reduction in anxiety, block of
autonomic (especially vagal) reflexes, reduction of airway secretions, amnesia, pro-
phylaxis against pulmonary aspiration of gastric contents, facilitation of induction
of anesthesia, and possible analgesia and to potentially mitigate the stress response
and prevent malignant cardiac arrhythmias [18].
A list, although not necessarily exhaustive, of the main indications for premedi-
cation in children includes:
• Children/teenagers who already show a high degree of anxiety

• Children who cannot be separated easily from the parent
• Cases in which the anesthesiologist thinks that PPIA is not of benefit
• Children with previous experience of surgery, perhaps characterized by a nega-
tive memory or discomfort
• Children with neurological and behavioral disorders
• Children with comorbidities requiring smooth induction, possibly without crying
or agitation (e.g., patients with cardiac disease)
Before examining the most frequently used drugs for premedication, it should be
noted that its risks are respiratory depression, loss of airway reflexes, paradoxical
response to the drug, and obviously potential allergic reactions. These risks are gen-
erally influenced not only by age but also by underlying medical conditions (further-
more in this chapter, we refer to elective surgery, but there are special circumstances
such as full stomach, head or abdominal trauma, etc., that require different consider-
ations). Although risks are mainly connected to a relative overdose (or coadministra-
tion of another drug) and can therefore be minimized using a high degree of attention,
the conditions that may require close monitoring after premedication are:
• Upper airway obstruction and/or obstructive sleep apnea syndrome

• Neurological disorders
• Dysphagia or gastroesophageal reflux
• Infants
• Heart disease (especially cyanotic heart defects)
The goal of premedication in children should be individualized: a mild sedation,

while not able to eliminate anxiety completely, can be effective in a child who is not
very agitated and could therefore make the induction mild and pleasant. Conversely,
a heavier sedation may be necessary in the case of a very agitated child.
The factors to be considered when choosing the drug(s) are therefore age, weight,
medication history of the patient (allergies), comorbidities, expectations of the child
and family, level of psychological maturity, anxiety, and cooperativeness.
Table 3.1 Drugs and doses Drug Route Dose (mg/kg)

commonly administered for
Midazolam Oral 0.3–0.7 (up to 20 mg)
premedication
Nasal 0.2
Rectal 0.5–1
Intramuscular 0.1–0.15
Ketamine Oral 3–8
Nasal 3–6
Rectal 5–10
Intramuscular 2–5
Clonidine Oral 0.002–0.004
Nasal 0.002–0.004
Rectal 0.002–0.005
Dexmedetomidine Oral 0.001–0.004
Nasal 0.001–0.004
Another important point to consider is the route of administration of the drug.

Although parenteral administration (especially intravenous) can be faster, can be
more effective, and have a greater predictability in terms of clinical response, the
majority of pediatric anesthesiologists refrain from this route of administration
unless there is a venous access in place. In fact, most of the children reported needle
puncture as their worst experience in hospital.
For this reason, enteral or transmucosal premedication is better accepted by the
child, parents, and hospital staff. A noteworthy exception to this general rule
(according to the experience of the authors) is for children born with spina bifida
who generally do not have sensitivity in the buttock region. The same children on
the other hand are often hostile to inhalation induction, often already have experi-
ence during previous surgeries. The doses of the two main drugs (midazolam and
ketamine) used intramuscularly as premedication in Italy are disclosed in Table 3.1.
In spite of the relative abundance of literature about the different drugs/routes of
administration, we can state that the ideal drug (or the ideal combination of drugs)
for premedication in children has unfortunately yet to be invented. In this brief
review, we will focus on oral, nasal, and rectal routes by examining midazolam, α-2
agonists, and ketamine.
3.2.1 Oral Route
Although the oral route of administration does not always produce predictable and
consistent effects because of fluctuations in the bioavailability and a substantial
first-pass effect, it still remains the most accepted and widespread way of adminis-
tration [19].
Although in the past it was feared that oral premedication might increase gastric
residual volume and therefore increase the risk of reflux with subsequent inhalation,
this was later denied, as long as a large amount of fluid is not ingested [20].
3.2.1.1 Midazolam
Midazolam administered orally still remains the method of choice in 90% of cases
in the USA according to a recent survey [21]. The usual dose of 0.5 mg/kg up to a
maximum of 20 mg causes a constant anxiolysis in the presence of a large safety
margin, whereas the increase above 0.5 mg/kg does not result in an increase of its
sedative or anxiolytic properties [22]. The sedative and anxiolytic effect starts after
10’ and is present after 20’ in the vast majority of children [23]. The peak effect is
observed at 30’, but after 45’ the effect on separation anxiety starts to disappear
[24], even with a possible sedative/light anxiolytic effect up to 2 h.
The effect on awakening times seems to be minimal, while there have been con-
flicting data on discharge time over years. A recent review [25] has shown that
premedication with midazolam 0.5 mg/kg 30’ before surgery reduces separation
anxiety at induction but does not increase recovery times, while opposite results
were found in a previous study [26].
It is essential for the anesthesiologist to be careful about the timing of midazolam
administration to prevent the child from arriving in the operating room not properly
sedated (due to either a late or an early administration). In this last case, however, a
re-administration of midazolam at a reduced dose (e.g., 0.25 mg/kg) can be
attempted.
The main problem of oral midazolam is its bitter taste. In 1998, the FDA approved
a syrup with a more pleasant taste and a lower pH than the intravenous formulation,
thus increasing its bioavailability. A coadministration with a more pleasant tasting
syrup may be useful.
In another study, oral midazolam did not result in an increased frequency of
delirium and agitation after awakening [26]. On the other hand, the effects on
behavioral outcomes such as nightmares, nocturnal enuresis, etc., are contradictory.
Doses greater than 0.5 mg/kg are associated with side effects such as alterations in
balance, posture, vision, and dysphoric reactions in the postoperative period [26].
Of note, these reaction can easily be controlled and antagonized by the administra-
tion of flumazenil 10 μg/kg up to 1 mg iv.
Midazolam (0.5 mg/kg) has been compared to clonidine (4 μg/kg) for premedi-
cation in children undergoing tonsillectomy and has been found to be better in terms
of preoperative anxiety and postoperative analgesia, with no difference in awaken-
ing and discharge times [27]. When compared to oral ketamine 5 mg/kg, midazolam
has displayed similar effects but with a better recovery and discharge profile [28].
Similarly, a better sedation and anxiolysis has been observed with midazolam
(0.5 mg/kg) compared to the combination diazepam-droperidol (0.25 mg/kg each)
[29]. After sevoflurane anesthesia, midazolam was found to be as effective as cloni-
dine and melatonin in reducing postoperative agitation [30].
3.2.1.2 Ketamine
Despite its marked first-pass effect, the usual dose of 6 mg/kg makes the children
quiet and calm at the time of separation from their parents within 30’ and provides
good conditions at the time of induction [31]. Oral ketamine does not generally
produce effects like tachycardia, respiratory depression, agitation during
awakening, or nightmares [23], even though episodes of hallucinations and laryngo-

spasm have been reported [32].
3.2.1.3 α2-Agonists
In recent years, there has been a sort of “rediscovery” of α2−agonists although cloni-
dine has been used for years for premedication in children. It has anxiolytic, seda-
tive, and analgesic properties, tastes better than midazolam, and displays a high rate
of satisfaction among both the medical care team and parents.
Clonidine results in sedation, amnesia, perioperative hemodynamic stability, and
intraoperative (in terms of reduction of anesthetics) and postoperative analgesia,
when orally administered at the dose of 1–4 μg/kg. In addition, premedication with
clonidine 4 μg/kg before adenotonsillectomy was as effective as the administration
of fentanyl 3 μg/kg perioperatively as far as postoperative analgesia (VAS and mor-
phine consumption) was concerned [33]. The effectiveness of premedication with
clonidine in reducing postoperative pain has been confirmed by a Cochrane meta-
analysis in 2014 [34].
Due to its pharmacodynamic effect, clonidine produces a state of sedation more
similar to fatigue and physiological sleep when compared to midazolam. This is
also demonstrated by the ability of patients to be easily awakened to perform a vari-
ety of cognitive tests [35, 36].
One of the disadvantages of premedication with clonidine is its markedly delayed
onset, up to 90’. Still, many pediatric anesthesiologists accept this delay as it is
largely offset by its beneficial perioperative clinical effect. In particular, what is
valued and desirable in pediatric anesthesia is its reduction of sympathetic outflow
without the simultaneous reduction of compensatory homeostatic reflexes. In fact,
although bradycardia and hypotension are potentially dangerous side effects, they
do not actually occur if the total dose of clonidine is below 10 μg/kg.
The more recently introduced dexmedetomidine is an α2-agonist with an α2/α1
specificity eight times greater than clonidine (1600:1 vs. 200:1). This greater selectiv-
ity, together with its limited cardiorespiratory effects, could theoretically offer some
advantages even though data are still limited. Preliminary and retrospective data indi-
cate that dexmedetomidine can be used for both premedication and procedural seda-
tion at a dose of 1–4 μg/kg [37]. An important paper comparing premedication with
oral midazolam(0.5 mg/kg), oral clonidine (4 μg/kg), and transmucosal dexmedeto-
midine (1 μg/kg) showed no difference in terms of anxiety and postoperative sedation
but greater intraoperative hemodynamic stability and reduced postoperative pain in
the clonidine and dexmedetomidine group compared to midazolam [38].
3.2.2 Nasal Route
The drugs most frequently administered through the nasal route are midazolam,
ketamine, and more recently dexmedetomidine.
Nasal absorption is usually faster than the oral route. It is generally true that any
side effects (such as respiratory depression) could occur more rapidly, and
therefore, this route of administration should only be used when there is personnel
with equipment readily available to intervene.
Traditionally premedication through the nasal route included both drops and sprays.
Considering the widespread diffusion of devices such as atomizers, nowadays sprays
seem more widespread than drops. For this reason, a proper and precise dose must be
administered to generate a rapid and predictable onset. The only real disadvantage of
nasal sprays is the possible uncomfortable feeling for patients which can sometimes be
associated with anxiety and fear, even though the discomfort linked to nasal adminis-
tration of midazolam can be reduced by pre-administration of a lidocaine puff.
3.2.2.1 Midazolam
At the dose of 0.2–0.3 mg/kg, nasal midazolam has proven effective in the reduction
of separation anxiety and during induction, while not increasing recovery and dis-
charge times even after short surgeries. In a direct comparison between 0.2 mg/kg
and 0.3 mg/kg, the higher dose resulted in a higher efficacy without an increase in
side effects [39].
Nasal midazolam (0.5 mg/kg) has been compared to a combination of ketamine-
midazolam and has proven as effective as the combination in reducing separation
anxiety in all patients even if its effect took twice as much time (5 min vs. 2.5 min)
as the combination of drugs [40].
In a comparison between midazolam 0.2 mg/kg and dexmedetomidine 1 μg/kg,
both administered nasally, both drugs were similar with respect to separation anxi-
ety, but midazolam was superior for the achievement of satisfactory conditions dur-
ing induction of anesthesia [41].
Nasal midazolam 0.2 mg/kg has been recently compared to two different doses
of intranasal ketamine (0.5 and 3 mg/kg, respectively) and was superior to ketamine
in reducing preoperative anxiety in pediatric patients [42].
3.2.2.2 Ketamine
Nasal ketamine has been used as premedication in pediatric patients. In doses up to
6 mg/kg, it has been proven effective in reducing separation anxiety and during
mask induction, without increasing recovery times.
The addition of nasal ketamine 2 mg/kg after oral administration of midazolam (both
used for premedication) is superior to intranasal alfentanil 10 μg/kg for reduction of pre-
operative anxiety and quality of recovery (agitation) after sevoflurane anesthesia [43].
Ketamine (10 mg/kg) has been compared to nasal midazolam (0.2 mg/kg) and
their combination (7.5 mg/kg and 0.1 mg/kg, respectively). Even though sedation
was adequate in the midazolam group, reduction of separation anxiety and, above
all, compliance during the insertion of venous cannula were superior in the two
ketamine groups, with no significant differences between the combination and ket-
amine alone [44].
Nasal clonidine 4 μg/kg has been proven to be as effective as the same dose adminis-
tered orally, even with a paradoxically lower onset [45]. It has been proven effective
not only as premedication but also to treat agitation/hallucination episodes following

oral midazolam administration, as well as to treat hypertension preoperatively [46].
A prospective, randomized trial compared clonidine 4 μg/kg vs. midazolam
0.3 mg/kg and showed that even though midazolam produced a faster onset of seda-
tion, both drugs displayed a similar onset of anxiolysis with reduced side effects in
the clonidine group [47].
Dexmedetomidine displays the same properties as clonidine with greater selec-
tivity on presynaptic receptors. At the same dose, it is actually more effective when
administered nasally rather than orally in terms of sedation, anxiety reduction, and
tolerability of the mask during induction [48]. Dexmedetomidine has been shown to
have analgesic properties since 2 μg/kg administered before induction can reduce
the EC50 of sevoflurane (LMA positioning) by 21 % [31].
When compared at low doses (1 μg/kg) with oral midazolam (0.2 mg/kg) as a
premedication before general anesthesia, it confers (despite its slower onset) a sig-
nificantly greater degree of sedation at the time of separation from parents, greater
compliance with the application of the mask, and a reduced incidence of shivering
and excitement in the postoperative period. Notably, while about one third of chil-
dren in the midazolam group showed signs of nasal irritation, this side effect was
not present in any child in the dexmedetomidine group [49].
3.2.3 Rectal Route
3.2.3.1 Midazolam
The effective dose of rectally administered midazolam ranges from 0.3–0.5 mg/kg
[50, 51]. The effective dose shown to make mask induction acceptable by a child is
0.35 mg/kg, even though 1 mg/kg did not seem to increase PACU discharge times
[51]. The dose usually administered in our center is 0.5 mg/kg up to 20 mg.
3.2.3.2 Ketamine
The ketamine dose used in most of the literature ranges from 5 to 10 mg/kg. A study
by Tanaka et al. compared different doses of rectal ketamine within this range to
midazolam 1 mg/kg. They showed that only ketamine 10 mg/kg and midazolam
1 mg/kg resulted in a significantly greater proportion of children with reduced sepa-
ration anxiety and mild induction. On the other hand, ketamine 10 mg/kg resulted
in a longer recovery when compared to lower doses [52]. Low doses of the (S+)
enantiomer did not show any benefit compared to the combination ketamine-
midazolam or rectal midazolam 0.75 mh/kg [53].
The most frequently tested drug is clonidine. When administered rectally, it has a
half-life similar to that in adult patients. The rectal route is associated with an almost
total (95%) bioavailability and a time-to-peak plasma concentration of 50 minutes,
and even though only 20 minutes after the rectal administration of clonidine 2.5 μg/
kg, a plasma concentration in the range known as effective in adults is reached [54].
Clonidine 5 μg/kg resulted in a significant reduction of postoperative pain after

adenotonsillectomy when compared to midazolam 0.3 mg/kg, together with a mod-
erately increased sedation during the first 24 h after surgery. This finding was in
agreement with the finding of a parental preference for a sedated child [35].
3.3 Preoperative Fasting
The awareness about fasting before surgery has increased over time even in pediat-
ric anesthesia. While solids leave the stomach following zero-order kinetics (slower
emptying), liquids follow a first-order kinetics (faster emptying).
After combining different studies on gastric emptying in children, it has been
shown that clear liquids can be ingested up to 2 h before surgery without any prob-
lem. Children should be encouraged to drink clear fluids (including water, pulp-free
juice, and tea or coffee without milk) up to 2 h before elective surgery. Rather than
ensuring a minimal fasting interval has been achieved, it is important to encourage
patients to keep drinking up until 2 h before surgery in order to reduce their discom-
fort and improve their well-being [55, 56].
It remains common practice to avoid solid food for at least 6 h before elective
surgery. There is no clear benefit to reduce the fasting time for solids below 6 h.
Cow’s milk and formula are generally treated as solids (proteins coagulate once in
the stomach), while breast milk is considered for the most part similar to a liquid
and therefore requires a time of fasting somewhat intermediate between that for
solids and liquids. It is recommended to finish breast feeding 4 h before anesthesia
and to stop infant formula 4–6 h prior to anesthesia depending on the age. Both
cow’s milk and powdered milk are considered as solid food [55, 56].
There is no consensus on the effects of the trauma on the stomach empty times.
The volume of gastric contents may depend on the nature of the trauma, but gastric
content may not be related to the length of fasting. Gastric volume is better linked
to the interval between the last meal and the trauma. Thus, the injured child should
be considered as a patient with a full stomach [57].
However, in malnourished or debilitated patients and patients with important
comorbidities, as well as in emergency situations, fasting times must be individual-
ized and optimized according to the individual case. An increasing number of
minor surgical procedures are done under sedation in the emergency department or
in other suites outside the operating theater. The available literature does not pro-
vide sufficient evidence to conclude that pre-procedure fasting results in a decreased
incidence of adverse outcomes in children undergoing either moderate or deep
sedation [58].
For more extensive discussion regarding the preoperative fasting, we recommend
the guidelines of the American Society of Anesthesiologists and of the European
Society of Anaesthesiology [55, 56].
Acknowledgments The authors would like to thank Carolyn David for her support and English
review of the chapter.
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Preoperative Consideration in Common
Pathological and Nonpathological 4
Conditions
Marinella Astuto, Gianpaolo Serafini, Simonetta Baroncini,

Fabio Borrometi, Luciano Bortone, Cristina Ceschin,
Andrea Gentili, Elisabetta Lampugnani, Giovanni Mangia,
Luisa Meneghini, C. Minardi, Giovanni Montobbio,
Francesca Pinzoni, Barbara Rosina, Carlotta Rossi,
Marina Sammartino, Emre Sahillioğlu, Rita Sonzogni,
Valter Sonzogni, Simonetta Tesoro, Costanza Tognon,
Tiziana Tondinelli, Nicola Zadra, and Pablo M. Ingelmo
4.1 Upper Respiratory Infections: URI
Adverse respiratory events are of the most frequent causes of perioperative morbid-
ity and mortality in children undergoing general anesthesia [1, 2]. Children with
recent upper respiratory tract infections (upper respiratory infections – URI), under-
going general anesthesia, have an increased risk of complications such as lung and
M. Astuto (*)
Anesthesia, Intensive Care, University of Catania, Policlinico Hospital, Catania, Italy
Dipartimento di Anestesia e Rianimazione, Ospedale Universitario Policlinico, Catania, Italy
e-mail: astmar@tiscali.it
G. Serafini
Anestesia e Rianimazione 1, Fondazione IRCCS Policlinico S. Matteo, Università di Pavia,
Pavia, Italy
S. Baroncini • A. Gentili
Dipartimento di Anestesia e Rianimazione Pediatrica, Ospedale S. Orsola-Malpighi,
Università di Bologna, Bologna, Italy
F. Borrometi
Servizio di Cure Palliative e Terapia del Dolore, Ospedale Santobono Pausilipon, Napoli, Italy
L. Bortone
First Service of Anesthesia and Intensive Care, Parma Hospital, Parma, Italy
Dipartimento di Anestesia e Rianimazione, Azienda Ospedaliera di Parma, Parma, Italy

DOI 10.1007/978-3-319-21960-8_4
40 M. Astuto et al.
airway laryngospasm, bronchospasm, hypoxia, atelectasis, and post-extubation

airway obstruction [3–6].
Respiratory symptoms, eczema or a family history of asthma, rhinitis, and
exposure to passive smoking were associated with an increased risk of adverse
respiratory events [6].
The risks of respiratory complications, especially laryngospasm, are age related,
with a relative risk reduction of 11 % for each year of increasing age [7]. The risk
of bronchospasm is ten times higher in patients with nocturnal dry cough and a his-
tory of eczema, a disease frequently associated with atopy, wheezing, and asthma
[8]. Symptoms of respiratory infection such as cough, purulent nasal secretions, and
fever within two weeks prior to surgery are associated with an increased frequency
of respiratory adverse events [6].
Propofol anesthesia was associated with a lower incidence of perioperative respi-
ratory complications, particularly that of laryngospasm, when compared with sevo-
flurane maintenance [6].
Instrumentation of the airways (endotracheal tube or LMA) is an independent
risk factor for the occurrence of adverse respiratory events, especially laryngo-
spasm. LMA was associated with a higher risk of laryngospasm when compared
with the face mask, but with a lower risk when compared with the endotracheal
tube. [6, 9–11].
C. Ceschin • C. Rossi
Servizio di Anestesia e Rianimazione, Dolo Hospital, Mirano, Italy
E. Lampugnani • G. Montobbio
Dipartimento di Anestesia e Rianimazione, IRCCS Ospedale dei Bambini G. Gaslini,
Genova, Italy
G. Mangia • T. Tondinelli
Dipartimento di Anestesia, Ospedale S. Camillo, Rome, Italy
L. Meneghini • C. Minardi • C. Tognon • N. Zadra
Dipartimento di Anestesia e Rianimazione, Università di Padova, Padova, Italy
F. Pinzoni • B. Rosina
Dipartimento di Anestesia Pediatrica, Ospedali Civili, Brescia, Italy
M. Sammartino
Dipartimento di Anestesia e Rianimazione, Ospedale Universitario A. Gemelli,
Università Cattolica del Sacro Cuore, Rome, Italy
E. Sahillioğlu
Department of Anesthesiology and Reanimation, Acibadem University, Istanbul, Turkey
R. Sonzogni • V. Sonzogni
Primo Servizio di Anestesia e Rianimazione, Ospedali Riuniti di Bergamo, Bergamo, Italy
S. Tesoro
Sezione di Anestesia, Analgesia e Rianimazione, Dipartimento di Medicina Clinica
e Sperimentale, Università di Perugia, Perugia, Italy
Department of Anesthesia, Analgesia and Intensive Care, University of Perugia,
Perugia, Italy
P.M. Ingelmo
Deparment of Anesthesia, Montreal Children’s Hospital, MUHC, McGill University,
4 Preoperative Consideration in Common Pathological and Nonpathological Conditions 41
The preoperative administration of salbutamol (2.5 mg in children weighing < 20 kg,

5 mg in those > 20 kg) in children with recent URI reduced the incidence of respiratory
adverse events, such as laryngospasm, bronchospasm, and desaturation (<95 %) and
severe cough by at least 35 % [12]. This data confirmed previous observations in
children with asthma [13, 14].
In conclusion, children at high risk for perioperative respiratory adverse events
should be systematically identify during the preoperative assessment. The following
factors were associated with an increased risk of perioperative respiratory adverse
events:
• History of recent respiratory tract infection

• Onset of wheezing during physical activity
• More than three episodes of wheezing in the last 12 months
• Nocturnal dry cough
• History of eczema
• Asthma or family history of asthma
• Rhinitis
• Exposure to secondhand smoke
Children with the risk factors listed above, but with moderate symptoms (clear
runny nose, dry cough), may benefit from an anesthetic approach that includes:
• Preoperative premedication with salbutamol

• Induction and maintenance with propofol anesthesia
Surgical procedures of children with purulent rhinitis, productive cough, lower

respiratory tract involvement, and general symptoms (fever > 38.5 ° C, headache, mal-
aise, poor feeding, irritability) should be postponed for 2–3 weeks [3, 6, 15–17].
4.2 Asthma and Bronchial Hyperresponsiveness
The inflammation of the airways is a distinctive feature of asthma. The inflamed

airway become hyperreactive to irritating stimuli. In patients with asthma, many
procedures routinely used in anesthesia, such as laryngoscopy and tracheal intuba-
tion, may induce bronchospasm.
An episode of intraoperative bronchospasm is a serious adverse event and can
make ventilation difficult or impossible. It also produces hypercapnia, acidosis,
hypoxia, and, rarely, cardiovascular collapse and death. The airways are more
prone to bronchospasm within 6 weeks after an attack of asthma. A thorough
preoperative optimization of medical treatment may prevent or limit asthma
complications. Thus, a recent exacerbation of asthma that has required hospital-
ization or emergency therapy within 6 weeks of surgery precludes elective
surgery [18, 19].
Asthma is characterized by episodes of variable and intermittent airway obstruc-
tion, and children present tachypnea, wheezing, and coughing and use accessory
42 M. Astuto et al.
Table 4.1 Stepwise management in children aged 5–12 years

Level Step Steroids Add therapy
1 Mild intermittent No Inhaled short-acting β2-agonist as required
asthma
2 Regular preventer Up to 400 mcg/die LABA
therapy BDP
3 Initial add-on Up to 400 mcg/die LTRA
therapy BDP
4 Persistent poor Up to 800 mcg/die LABA/LTRA/aminofillina
control BDP
5 Continuous or Other doses of BPD Use daily steroid tablet in lowest dose
frequent (≥800 mcg/die) and providing adequate control
use of oral per os steroids
steroids
Patients should start treatment at the step most appropriate to the initial severity of their asthma. Check
concordance and reconsider diagnosis if response to treatment is unexpectedly poor. BPD beclometha-
sone dipropionate, LABA long-acting β2-agonist, LTRA leukotriene-receptor antagonist
respiratory muscles. Older children may complain of shortness of breath, wheezing,

or discomfort. [20].
The diagnosis of asthma could be done in a patient with four or more episodes of
wheezing per year, associated to a parent with asthma, atopic dermatitis, or sensiti-
zation to inhalant allergens, and two of the following: food sensitization, wheezing
outside of infectious episodes, or eosinophilia [21].
Most radiological studies have a reasonable positive predictive value, but poor
negative predictive value [22]. A chest radiograph is rarely useful in mild asthma,
but may be useful in more severe cases to exclude acute infection, hyperinflation, or
pneumothorax in an acute exacerbation [18]. Similarly, a computed tomography
(CT scan) can show bronchomalacia or a dilation of bronchial wall in children with
chronic asthma [23, 24].
Pulmonary function tests as flow expiratory volume (FEV1) are able to determine
the degree of reversibility of respiratory resistance and to measure the extent of
improvement after treatment in collaborative children usually beyond 7 years of age
[18]. Diurnal variation in FEV1 may indicate poor disease control. In general, pul-
monary function tests are still of limited use in the preoperative evaluation children
with asthma [25].
The differential diagnosis are fixed obstructions, suppurative lung diseases (cys-
tic fibrosis, ciliary dyskinesia), post viral bronchitis, and bronchial or tracheomala-
cia. In these circumstances asthma may be misdiagnosed [26, 27].
It is essential to establish the severity and measures for control asthma because
both aspects are closely linked. Asthma of mild severity, but poorly controlled, may
seem harsh in terms of frequent and persistent symptoms. In contrast, severe asthma
may seem well controlled but requires high doses of inhaled corticosteroids to
maintain control. Poorly controlled asthma is defined by various aspects such as the
frequency of symptoms, the use of symptomatic drugs, frequent emergency admis-
sions, and the use of oral corticosteroids (Table 4.1) [20, 22].
A difficult asthma is a poorly controlled asthma despite high doses of inhaled ste-
roids (≥800 μg/day of beclomethasone dipropionate (BDP) or belonging to levels 4
and 5). Although some asthmatic children may be unresponsive to steroids, the most
common reasons for a “difficult asthma” are the low compliance to treatment, inade-
quate technical capacity with the inhaler, or an incorrect diagnosis of asthma [28].
A small group of children with severe asthma may be at risk of life. Those chil-
dren may have a poorly controlled asthma or a “fragile” asthma with asthma attacks
of sudden onsets, which simulate an asphyxiating or anaphylactic reaction. A his-
tory of serious recent exacerbations especially if they required admission to the ICU
is indicative that a child is particularly vulnerable to a sudden attack, which may be
precipitated by nonsteroidal analgesics or anesthetic vapors [29].
Children who take medication only during exacerbation should start taking the
same drugs (inhaled β2-agonists or oral medications) and doses used during exacer-
bation, on a regular basis 3–5 days before surgery [30]. The benefits on airway
reactivity are evident after 6–8 h with a maximum effect between 12 and 36 hours.
Children receiving asthma medication on regular basis should continue with
usual administered treatment. The administration of β2-agonists (e.g., salbutamol)
before the induction of anesthesia may prevent the increase of airway resistance
associated with halogenated anesthesia [13] and URIs [12].
Children under steroid medication and those who have been taking steroids in
the previous two months should receive corticosteroids as during exacerbation (e.g.,
prednisone 1 mg · kg−1 · day−1) [30]. There is no need for perioperative supplemental
doses of steroids as inhaled steroids alone do not cause adrenal suppression [31].
Finally, a child with “difficult” asthma who regularly takes bronchodilators and/or
corticosteroids may require an intensification of the frequency of bronchodilators, an
increase in the dosage of corticosteroids, or occasionally all these measures [28].
4.3 Bronchopulmonary Dysplasia (BPD)
Bronchopulmonary dysplasia (BPD) is the most common cause of chronic lung

disease in infants.
It mostly affects premature infants weighting about 1000 g at birth that still need
oxygen therapy for more than 28 days and after the 36 gestational week [32, 33].
Northway first described BPD in 1967 in a group of infants with respiratory fail-
ure after prolonged mechanical ventilation and administration of high concentra-
tions of oxygen [33]. The lung of these infants presented emphysema, atelectasis,
fibrosis, epithelial metaplasia, and marked hypertrophy of smooth muscles in the
airways and pulmonary vessels.
The uses of less aggressive ventilation modes and postnatal surfactant therapy
have significantly reduced the severity of respiratory distress syndrome and, conse-
quently, the severity of BPD. Actually BDP is characterized mainly by pulmonary
inflammation a decrease of the process of septation of the alveoli and an alteration
in vascular development [34–36], with a framework characterized by diffused X-ray
opacity [37].
44 M. Astuto et al.
The triad airway obstruction, bronchial hyperreactivity, and lung hyperinflation

determine inhomogeneous distribution of ventilation, reduced compliance, increased
work of breathing, and gas exchange impairment [38]. The clinical manifestations
of BPD are tachypnea, wheezing, coughing, frequent febrile episodes, episodes of
desaturation, and bradycardia [38, 39].
Patients with BPD have high respiratory resistance, decreased lung volumes,
lower functional residual capacity, airway obstruction, and lung hyperinflation.
During the first year of life, infants with BPD are at increased risk of laryngospasm,
bronchospasm, and desaturation due to bronchial hyperreactivity. Moreover bron-
chial secretions may lead to occlusion of the endotracheal tube. Finally, in the pres-
ence of hypothermia, pain, acidosis, or hypoxia, infants with BPD may develop
pulmonary hypertension resulting in pulmonary hypoperfusion, hypoxemia, and
cardiac failure [40].
These respiratory alterations are mostly evident during the first 3 years of life.
After 5–8 years infants with a medium form of severe BPD can be asymptomatic,
while the airway’s hyperresponsiveness may persist.
Nutritional support and therapy with bronchodilators, antibiotics, diuretics, and
corticosteroids should be optimized before surgery [40]. Preoperative echocardiog-
raphy is recommended, in order to assess cardiac contractility and the presence of
an associated right ventricular dysfunction [37, 40]. If a BPD patient is taking
diuretics, the concentration of electrolytes should be evaluated before surgery [40].
Patients with BPD may require monitoring and ventilation up to 24–48 hours
after surgery. The risks of general anesthesia with intubation in infants with BPD
may possibly be reduced or prevented by the use of regional anesthesia techniques
and/or with the use of a laryngeal mask airway (LMA) [19, 41].
4.4 Allergies
In most industrialized countries, the immediate hypersensitive reactions to anesthetics

and drugs used in the perioperative period are being reported with increasing fre-
quency. Muscle relaxants and latex are the two main causes responsible for these
intraoperative allergic events [42, 43]. In most cases, the reactions are of immunologic
origin (IgE-mediated reactions, anaphylactic reactions) or due to the direct stimula-
tion of histamine release (anaphylactoid reactions) [44, 45].
The clinical history may reveal a history of atopy and allergy to medications, to
latex, or to tropical fruits.
Atopy is a hereditary predisposition in which the patient synthesizes IgE anti-
bodies to various allergens: pollen, dust, animal hair, and foods. Clinically it pres-
ents with asthma, allergic rhinitis, conjunctivitis, fever, and eczema [46]. Gualdagen
H et al. suggested an association between anaphylactic shock during anesthesia and
atopy. The basophils of atopic patients easily release histamine [47]. Atopy may be
a risk factor when drugs that induce histamine release (atracurium, mivacurium,
etc.) are injected rapidly.
Table 4.2 Groups of patients at risk for developing latex allergy

Group Incidence %
Spina bifida [87, 88] 18–72
Urogenital tract malformations [89] 17–71
Repeated gastrointestinal tract surgery [90, 91] 17–20
Extensive or repeated neurosurgical procedures [92] 36
More than five surgical procedures at neonatal stage or before the age of one [93] 55
Atopic subject [49] 9–36
Tetraplegic patients a
History of anaphylactic reaction of unknown etiology [94] a
Allergy to fruits and vegetables, especially the tropical variant [95] 35–55
a
Numerous case reports with no objective definition of a percentage than the general population
An unexplained episode characterized by cardiovascular collapse, broncho-

spasm, and edema, during a previous anesthesia, could be interpreted as an allergic
reaction. Allergy to local anesthetics is quite exceptional. In a series of 208 patients
who had a suspected reaction to local anesthetics, IgE-mediated mechanism was
demonstrated in only four cases. In other patients, the causes were vasovagal phe-
nomena, possible reactions to additives, panic episodes, or intervascular injection of
adrenaline [48]. There is a high incidence of cross-reactions between neuromuscular-
blocking agents. It is recommended to avoid administering neuromuscular-blocking
agents to patients with previous allergic reactions to this class of drugs before an
allergy test has been performed.
Preoperative identification of patients at risk is the first element of prevention
against latex allergy. In the operating room, the main objective is to ensure the
patient at risk avoids coming in contact with latex, for, e.g., the gloves. The preven-
tion of this contact and/or the repeated exposure to latex is the cornerstone in pre-
venting patients from developing anaphylaxis during surgery[49–53].
The incidence of latex allergy in the pediatric population varies from 0.8 to 6.7 %
(Table 4.2). Common features of groups at risk of presenting an allergic reaction are
atopy, early contact with latex (within the first year of life), and the frequent and
prolonged exposure to latex [54, 55]. An allergy skin tests with specific IgE + before
surgery could be justified in [56]:
• Patients with a documented allergy to an anesthetic drugs or latex

• Patients with a history of unexplained reactions during general anesthesia
(i.e., severe hypotension, bronchospasm, edema)
• Patients who claim to have an allergy toward local anesthetics
• Patients who belong to a group at high risk for latex allergy (Table 4.2)
The skin prick test (SPT) remains the gold standard for IgE-mediated reactions
evaluation. To prevent a false-negative result due to the depletion of mast cells, STP
should be performed 6 weeks after an acute allergic event. The sensitivity to latex is
46 M. Astuto et al.
70–100 % and specificity of 74–100 %. Muscle relaxant allergy sensitivity is greater

than 95 %, and specificity is still a matter of debate [52, 57]:
The radioallergosorbent test (RAST) is an in vitro-specific IgE test and is currently
restricted to the diagnosis of anaphylaxis to muscle relaxants, thiopental, or latex. The
RAST sensitivity to latex varies between 53 and 97 % with specificity of 33–87 %.
The RAST specificity may not exclude a false-negative case of latex sensitization.
Nevertheless, because of the absence of the risk of anaphylaxis and the simplicity of
execution, the RAST is one of the most widely used test. Some studies report that
serum levels of IgE are well correlated with the number of surgeries. The patient is
considered sensitized if the IgE antibody concentrations of > 0:35 kU / L [54, 58].
Some studies support the prophylaxis with diphenhydramine, cimetidine, and
methylprednisolone [18, 54]. Pharmacological prophylaxis may only mitigate early
immune response or may not prevent anaphylaxis at all [58, 59]. However, there is
no evidence to support the use of pharmacological premedication [60].
The term latex-safe defines a path that must be applied to patient with latex
allergy during the perioperative period. Latex-safe strategies designed to prevent
patients at risk to be in contact with latex must be a priority of health-care facilities
[49, 54, 61]. The term latex-free defines an instrument or tool in which the manufac-
turer certifies the absolute absence of latex [60].
If the patient presented a severe allergic reaction of unknown origin, character-
ized by unexplained hypotension or circulatory collapse, bronchospasm, and edema
during a previous general anesthesia, it is recommended to adopt a latex-safe envi-
ronment with a regional anesthesia technique or general anesthesia without
neuromuscular-blocking drugs [46, 62].
4.5 Heart Murmurs
Heart murmurs are a common finding in childhood, and about 50–72 % of these
murmurs are normal or innocents [63, 64]. Every child with a heart murmur requires
a thorough clinical examination with assessment of peripheral pulses, blood pres-
sure, and SaO2, ECG, and in selected cases an echocardiography [65–67].
The anamnesis should look for history of prematurity, the presence of congenital
malformations, respiratory symptoms including repeated infections, cyanosis, chest
pain, syncope, or family history of sudden death. Table 4.3 includes some useful
questions to determine the clinical effect of a murmur [68].
The physical examination includes auscultation of the heart, both when
supine or sitting, as the intensity of an innocent murmur increases in the supine
position for increased end-diastolic volume and stroke volume. The intensity of
the most of the pathological murmurs doesn’t vary during changes on the
patient position. The only exception is the murmur of the hypertrophic cardio-
myopathy (HCM), which increases in intensity from supine to sitting position
[69]. Table 4.4 shows the characteristics of innocent murmurs and pathological
ones [64, 65, 70].
Both arms’ brachial pulses in infants or radial pulses in children should be exam-
ined and compared with femoral pulses. Small femoral pulses, especially if discrep-
ant with respect to the quality of brachial or radial or associated with radio-femoral
Table 4.3 Evaluation of the Children

clinical effects a murmur [68]
Does he/she run? Like peers?
Is he/she calmer or slower than peers?
Cyanosis
Does he/she turn blue? During feeding/when crying?
Does he/she lose consciousness?
Does he/she stop playing and squat?
Infant
Is feeding prolonged?
Does he/she sweat during normal care?
Does he/she have swollen eyes in the morning?
Table 4.4 Characteristics of innocent murmurs and pathological ones [64, 65, 70]
Murmur Characteristics
Innocent Systolic or a continuous
Increases and decreases
Mild or moderately mild (2/6 or less)
Increase in intensity from sitting to supine position
Pathological Diastolic, pansystolic, or late systolic
Generally intense (3/6 or more)
Associated with tremors
Associated with signs or symptoms of heart disease
Does not vary significantly going from sitting to supine position (except
CMI murmur)
delay, are suggestive of aortic coarctation or aortic arch obstruction and require
further investigation [66].
The value of ECG and chest radiography in the diagnosis of congenital heart
disease is limited. Both tests have a very low sensitivity and specificity. Chest
X-rays also expose the child to ionizing radiation and its routine application can be
defined as inappropriate in an asymptomatic child [71–73].
ECG has a low sensitivity in identifying congenital heart lesions in children with
asymptomatic heart murmur.
Echocardiography remains the gold standard for diagnosis of congenital heart
disease and its role in the diagnosis of asymptomatic murmurs has changed radi-
cally in the last 10 years. In the presence of a murmur, it is recommended to perform
an echocardiogram if [65–67]:
• The child is less than 1 year old.

• The murmur has the characteristics of a pathological murmur.
• Signs and symptoms of heart disease are presented.
• There is evidence on the ECG of right or left hypertrophy.
Nonurgent surgery in infants under 1 year of age, with pathological murmur,

and/or signs and symptoms of congenital heart disease, and/or ECG with evidence
of right or left hypertrophy, should be delayed until an echocardiogram with a car-
diology consultation identifies or excludes a pathological condition [64, 68].
48 M. Astuto et al.
4.6 Vaccination
Vaccination represents the most efficient and reliable prevention of primary infec-
tious diseases [74].
Anesthesia and surgery may interfere with the immune response [75–77].
However, the immune-modulatory effect of general anesthesia and surgery may not
modify the efficacy of recently given vaccine [31, 78–81].
Adverse effects to vaccines can occur on the day of administration during the
following 90 days [82]. The most common complications of vaccination (fever,
malaise, crying, pain) can be wrongly interpreted as particularly infectious compli-
cations after surgery. Then there are two questions that need to be answered [81]:
1. Should vaccination be postponed in children scheduled for surgery?

2. Should anesthesia be postponed in recently vaccinated children?
There are no clear answers to these questions [83]. The Italian Schedule of
Vaccination from Ministry of Health did not provide recommendations regarding
anesthesia or surgery [74]. The handbook on vaccinations of Great Britain states
that “anesthesia and surgery are not contraindications to routine immunization but
in some of these situations, additional precautions may be required” like in case
of asplenia or splenic dysfunction [84]. The Australian handbook on vaccinations
specifies “that surgery should be postponed for a week after an inactivated vaccine
and three weeks after a live attenuated vaccine”. A vaccination should be post-
poned for a week after an operation under general anesthesia [85]. The Ministry
of Health of New Zealand stated that “there is no evidence that anesthetic reduces
the immune response to a vaccine or increases the risk of adverse events following
immunization (AEFI).”
Immunization with inactive vaccines should be avoided for 3 days prior to an
anesthetic (12 days for a live vaccine such as MMR) in case an AEFI occurs and
results in the postponement of the anesthetic [86].
It seems reasonable to accept that there is a risk, albeit vague and theoretical,
associated with anesthesia in recently vaccinated children. This small risk can be
reduced to zero by ensuring that surgery, anesthesia, and vaccinations do not coin-
cide. The following has been recommended [83]:
• Postpone an elective procedure that requires anesthesia rather than vaccination,

especially in neonates and infants.
• Postpone vaccinations, one week after general anesthesia.
• Postpone anesthesia to a week after vaccination with inactivated vaccine (diph-
theria, tetanus, pertussis (DTPa)), inactive polio vaccine (IPV), Haemophilus
influenzae type b (Hib) vaccine, and vaccine against meningitis C.
• Postpone anesthesia to three weeks after vaccination with live attenuated vac-
cine: measles, mumps, rubella (MMR), polio, and BCG (against TB).
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Part II
Perioperative Care During Surgery
Perioperative Care in Day Hospital
Surgery 5
Simonetta Tesoro and Laura Marchesini
5.1 Introduction
The pediatric patient is best suited for intervention in outpatient surgery since he/she
rarely suffers from severe systemic disease and the procedures most commonly per-
formed are minor surgery. During the last ten years, many procedures, previously
performed as inpatient, were shifted to outpatient bringing many benefits for both
patients and national health systems. The minimum separation of the child from the
family, the decreased risk of in-hospital infections, and the necessary active participa-
tion of parents caring for their children are the main benefits of the day-surgery (DS)
patient. Reduction in costs for institutions and the greater availability of beds and staff
for more severe cases represent the advantages for health systems.
A surgical procedure and anesthesia should be understood as processes at risk
requiring high-quality performances providing maximum safety and reduced hospi-
talization. Advances in the field of anesthesia and surgery and the increasing need to
reduce health-care costs have encouraged DS also in patients previously excluded.
The evolution of techniques, such as minimally invasive surgery and the introduc-
tion of new drugs together with high levels of professional competence and organi-
zational skills, allows to create a care pathway that leads to high-quality performance
associated with the highest levels of safety.
The effectiveness and efficiency of the care pathway depend on two factors: clinical
practice and the organizational model. Best clinical practice is the ability to administer
the most appropriate care derived from the best scientific evidence available throughout
S. Tesoro, MD (*)
Sezione di Anestesia, Analgesia e Rianimazione, Dipartimento di Medicina Clinica e
Sperimentale, Università di Perugia, Perugia, Italy
Department of Anesthesia, Analgesia and Intensive Care, University of Perugia, Perugia, Italy
e-mail: simonettatesoro@gmail.com
L. Marchesini, MD
Department of Anesthesia, Analgesia and Intensive Care, University of Perugia, Perugia, Italy
DOI 10.1007/978-3-319-21960-8_5
56 S. Tesoro and L. Marchesini
the care pathway. In other words, the clinical appropriateness is the ability to choose the
“right procedure,” the “right patient,” and the “right time.” Choosing the “right environ-
ment” is part of organizational appropriateness that may be national, regional, or insti-
tutional, in which the “right professionals” bring their skills with the proper evaluation
and synthesis of evidence and allow application in the specific organizational model
[1]. This will lead to high quality, high performance, and a high turnover rate.
This chapter reviews the fundamental concepts concerning the most appropriate
care for safe and effective outpatient anesthesia.
5.2 Epidemiology
The number of pediatric outpatient procedures has increased by almost 50 % during
the period 1996–2006 [2]. In 2012, 64 % of pediatric surgical activity was per-
formed on an outpatient basis in France [3].
The data show a large day-surgery activity worldwide; however, there are few
scientific societies that have specific Guidelines or Recommendations for the man-
agement of pediatric DS from a clinical and organizational point of view. The
Association des Anesthésistes Réanimateurs Pédiatriques d’Expression Française
(ADARPEF) published the French Guidelines in 2010 [4].
A systematic review of the literature showed that the rate of perioperative compli-
cations related to anesthesia for the various types of pediatric DS was overall very
low [5]. Specifically, there appeared to be no deaths related to DS anesthesia. As for
the occurrence of adverse cardiorespiratory intra- and postoperative (within 24 hours)
events, a 19–24 % incidence was recorded for various procedures. Adverse events
included laryngospasm, bronchospasm, desaturation <90 %, bradycardia, arrhyth-
mia, hypotension, or hypertension requiring therapeutic intervention. As for bleed-
ing, another major adverse event, the incidence within the first 24 hours was low even
for adenotonsillectomies (0.6 % tonsillectomy, <1 % adenoidectomy). Bleeding in
adenotonsillectomies was recorded at one week with an incidence of 5/826 patients,
of these 4 to 5 were recorded as major bleeding [6]. The incidence of other periopera-
tive complications may vary according to the type of surgery. For example, in strabis-
mus surgery, there is an incidence of 34–79 % of postoperative nausea and vomiting
(PONV), where the incidence of 16–36 % in the pool of procedures [7].
Another complication is the perioperative/postoperative agitation that may occur
in 11–25 % of cases [8].
Complications in pediatric DS are very low with a tendency toward zero for very
serious complications. However, if not managed properly, may cause the loss of
benefit of the care process.
In this chapter, the paragraph Special Considerations will focus on patients under-
going adenotonsillectomy with a higher incidence of postoperative complications.
5.3 Organizational Aspects
The organizational aspect plays an important role in the success of the care pathway
and the different models adopted by the numerous national health systems. An
5 Perioperative Care in Day Hospital Surgery 57
organizational model is the set of rules used to carry out the activities, protocols, or
procedures. To date, there is no scientific evidence proving the superiority of an
organizational model over another. Any facility that provides services in DS should
use an organizational model created according to local legislation and the available
resources. In any case, the care pathway must be accredited by the standards of
accreditation of health facilities in order to minimize clinical risks.
There are three organizational models:
1. Free-standing DS unit with acceptance, wards, operating rooms, and indepen-

dent administrative offices, geographically linked or not to a referral hospital
2. DS unit located inside a hospital organizational structure in a continuous cycle
either public or private
3. Beds dedicated to DS incorporated in the inpatient unit
In the last two organizational models, use of the operating room can be sched-
uled together with other units or there may be operating rooms exclusively for DS.
As previously stated, there is no great organizational model; however, the division
of inpatients and outpatients leads to better care due to the different needs of the
patients undergoing DS, including rapid turnover. When children must be cared for
in an adult unit, they should be nursed in customized and specifically designed pedi-
atric day-care units; a separate area must be organized for them and their parents/
caregivers.
Another important organizational aspect is the perioperative environment in
which the patient and the family are welcomed. It should be comfortable, practical,
and designed for children, with a multidisciplinary staff able to handle the children
and families from both a clinical and psychological point of view [9].
The word “outpatient” does not mean minor procedure but rather a complex
process that requires detailed organization and optimal clinical management of the
whole perioperative period. The anesthesiologist, responsible for the pivotal
moments, must have adequate experience and training in the care of infants and
children.
The key role in all major care processes, particularly in DS, is the multidisciplinary
team of professionals who collaborate according to protocols and standardized proce-
dures, the reference physicians being the surgeon and the anesthesiologist.
5.4 Selection Criteria
Appropriate patient selection is the cornerstone of DS. Factors contributing to the

selection are related to the patient, the procedure, and the social context.
5.4.1 Patient
5.4.1.1 ASA Physical Status

Children with no known systemic diseases and classified as American Society of
Anesthesiologists Physical Status I and II are eligible for DS.
However, children classified as ASA III, with good control of the disease, can be
eligible for DS, at the discretion of the unit that is in charge. It is advisable to present
them as the first case in order to have more time for monitoring prior to discharge.
There is little scientific evidence on this topic, so recommendations are consid-
ered from a methodological point of view, grade IV recommendations, or experts’
opinion.
Specifically, patients with seizure disorders under control can be regarded as
outpatients. In the case of anticonvulsant therapy, the therapeutic range should be
controlled as well as the functionality of organs that could be implicated in the
metabolism of chronic therapy drugs or anesthesia, including liver and kidney func-
tion in case of valproic acid administration.
Blood glucose in patients with diabetes mellitus should be closely monitored
during hospitalization, and regular food and fluid intake should be reestablished
prior to discharge.
In some circumstances, such as the presence of stable chronic diseases, early
discharge is recommended to avoid complications related to hospitalization. This is
the case in patients with immunosuppressive diseases in which hospitalization could
trigger hospital-acquired infection or patients psychologically disturbed, mentally
retarded, in which the distance from home could generate major trauma.
Obesity, OSA (obstructive sleep apnea syndrome), and sleep disorders, with or
without associated adenotonsillar hypertrophy, are more and more frequently found
in the pediatric population, and very often these children undergo adenotonsillec-
tomy. For special assessment and management of these patients, see the paragraph
Special Considerations.
5.4.1.2 Age
Age itself is not an absolute contraindication to DS. However, because of the
increased risk of respiratory complications in infants, children born at term (over
38 weeks) less than one month old are excluded [10]. It remains at the discretion
of the structure whether to admit patients in DS under 1 month of age who will
undergo surface interventions such as frenulectomia lingual or finger supernumer-
ary, usually without complications. The former preterm children should not be
included in the DS program unless they are in excellent condition and have passed
the 60 weeks postconceptual age (PCA) [11] for increased risk of postoperative
apnea and bradycardia [12]. More recent studies [13, 14] have shown that apnea
occurs in 25 % of infants but that this is inversely related to PCA: in patients with
PCA > 60 weeks, the incidence is <5 %, and 44–46 weeks PCA are sufficient to
prevent postoperative apnea and bradycardia. The incidence of apnea and brady-
cardia is low after 52 weeks PCA. Literature data show that after 60 weeks, PCA
former preterm children may be admitted to DS provided that they will not be
subject to situations that could increase the risk of apnea (i.e., anemia) and that
there will be postoperative monitoring depending on postconceptual age.
Specifically, with PCA <46 weeks, continuous monitoring is required for at least
12 hours, excluding the possibility to be admitted to DS. Between 46 and 60 weeks
PCA, six hours of monitoring could be enough.13
Because of the instability of these children and the need for possible intensive
postoperative monitoring, these patients should be treated in high specialty level III
hospitals.
5.4.1.3 Malignant Hyperthermia

Treatment in DS may not be completely ruled out for patients with suspected or
known susceptibility to malignant hyperthermia, if trigger-free anesthesia is per-
formed and postoperative monitoring of at least 6–8 hours is guaranteed [15].
However, it may be safer to monitor for at least 12 hours in view of late-onset reac-
tion due to the use of new-generation halogenated anesthetics (sevoflurane and des-
flurane) and the possibility that stress alone could trigger this adverse reaction.
5.4.1.4 Sudden Infant Death Syndrome

It is contraindicated to admit siblings of children who have died from SIDS as out-
patients unless they have passed 60 weeks PCA, although there is no evidence of a
correlation between anesthesia and SIDS [16].
5.4.1.5 Sickle Cell Disease

Patients with thalassemia may be admitted in DS.
5.4.1.6 Incidental Heart Murmurs

Patients with severe heart disease are excluded from DS. There is a large pediatric
population in which occasionally a heart murmur is found. An innocent murmur
typically soft, early systolic with no abnormal symptoms or signs is eligible for
DS. The murmur varies in intensity with position. Regardless of DS, a murmur in a
child <1 year of age, loud or continuous murmurs, all diastolic, pansystolic, late
systolic, and other signs as failure to thrive, recurrent chest infections, syncope,
cyanosis or hypertension require more in-depth investigation.
5.4.1.7 Upper Respiratory Infection (URI)

Upper respiratory tract infection (URI) is common in the pediatric patient and
poses a dilemma whether to proceed with surgery, particularly in the DS regime.
URI is associated with an increased incidence of respiratory complications in
anesthesia: cough, desaturation, bronchospasm, and laryngospasm. Although
these can be readily managed and without sequelae [17–19], preoperative evalua-
tion on the day of surgery must focus on the general health of the patient and
assess whether the patient is feverish, tired, overwhelmed, with disordered breath-
ing and tachycardia. The preoperative saturation control could be discriminatory
to evaluate whether the infection is confined to the upper respiratory tract or if it
involves the lower respiratory tract. Other risk factors for respiratory complica-
tions in patients with URI are use of the endotracheal tube, prematurity, asthma,
exposure to secondhand smoke, copious secretions, nasal congestion, and airway
surgery [20].
Surgery should be postponed for two weeks when a child is symptomatic with or
without association of additional risk factors [21].
When symptoms are mild or moderate:
• Age < one year: postpone

• Age > 1 year: consider other risk factors and evaluate the risk/benefit of the pro-
cedure [22]
5.4.1.8 Asthma
Asthma is the most common chronic disease in children but may not be considered
a contraindication to DS. If the disease is adequately controlled with therapy and
there are no other risk factors such as respiratory tract infections, the patient can be
treated by slightly increasing the basic therapy. The administration of beta-agonists
is recommended in the immediate preoperative period. At discharge, there should
be no breath sounds and eupnea. In case of poor control of the disease or in the pres-
ence of severe asthma (requiring daily therapy), DS is not recommended for the
patient.
5.4.2 Procedure
Each structure can define the list of procedures to be performed in DS, according to
local legislation. In general, all surface interventions and all diagnostic tests requir-
ing analgosedation or anesthesia are recommended for DS. In the past, criteria
regarding the general characteristics of the procedures were defined [23]:
• No intracranial, intrathoracic, or major intraabdominal surgery

• Minimal risk of bleeding
• Ability to adequately control pain at home
• Simple nursing care that can be provided by parents
• No major limitation on the child’s activity
The duration of the procedure (two hours considering the cutoff) is not a con-
traindication to discharge, provided that 4 hours of postoperative observation are
guaranteed. Discharge is not excluded even for orthopedic operations requiring
cast; however, it is recommended to avoid motor block. With the increase in mini-
mally invasive techniques in pediatrics, an increasing number of children undergo
laparoscopic surgery. In literature, there are many papers proving the feasibility
of laparoscopic procedures in DS; however, the lack of large randomized con-
trolled clinical trials does not allow to draw strong recommendations on the fea-
sibility of interventions classified as DS. The most frequent appears to be the
correction of inguinal hernia in the newborn or infant, often ex-premature. The
indication is to diagnose and treat metachronous contralateral hernia in a single
session without surgical exploration. These patients require endotracheal
intubation.
The final decision remains at the discretion of the multidisciplinary team, based
on the patient’s general conditions, the anesthetic technique adopted, the surgical
time, and the satisfaction of discharge criteria after 4–6 hours of observation.
Performing laparoscopy as the first case of the session is recommended.
5.4.3 Social Factor
Parents have an active role in care management. They should be responsible and be
able to communicate and get to the hospital by themselves. The possibility of reach-
ing a hospital within 1 hour (50 km) is recommended. Weather and other obstacles
that could cause delay in reaching the hospital should also be taken into account.
5.5 Patient Preparation and Premedication
The surgeon is the first professional who meets the patient, posing indication for
surgery and defining the eligibility for DS, based on the type of procedure.
The preoperative evaluation, carried out under the direct responsibility of the
anesthesiologist, consists of clinical evaluation of the patient before anesthesia is
performed. The evaluation of an outpatient is the same as that of an inpatient (to this
regard, see Chap. 2).
The benefits, with regard to DS, resulting from a preoperative anesthetic assess-
ment include the safety of perioperative care with improved outcome and reduction
of complications. Indeed, it is through an adequate preoperative evaluation that the
patient can be clinically and socioculturally framed, and, if necessary, preoperative
investigations can be prescribed.
In DS, a preoperative evaluation allows the anesthesiologist to declare eligible
this path to care. It also provides information on the anesthetic technique of postop-
erative pain management and home care, the timetable for the day, and how to
behave with regard to fasting and therapies. It allows to have informed written
consent.
As for the organization and manner of the preoperative visit, it is up to each indi-
vidual to find the best feasible organizational model: preprepared questionnaires for
the anamnesis filled out by the parents or primary care physician, or for ASA I and
II patients, evaluation could be performed the morning of surgery (one-stop anes-
thesia). There is no scientific evidence on the “timing” of the evaluation, although it
is recommended in proximity of the operation, especially in patients younger than 2
years of age, when the physiological evolution is fast. A very important develop-
mental phase, both from the medical history and clinical point of view, is the differ-
ence between non-walking and walking.
The use of a well-written and understandable (cultural mediators) brochure on
the conduct of the entire process is recommended to avoid misunderstandings or
cancelations that could alter an organization built on detail. Cancelation or
non-presentation of the patient has a high cost for the institution [24], so many actu-
ally call the day before to check on the health of the child (patient medically fit) and
remind the parents about arrival time, place of admission, and preoperative fasting.
Proper detailed and written information for parents has the power to reduce paren-
tal anxiety. It has been shown that children with anxious parents are more likely to
display signs of perioperative anxiety themselves [25]. It is important that the child is
aware of what he/she will experience and provide a correct explanation of all stages of
the day, in particular, the oral premedication, induction, and awakening and the pos-
sibility of minimum postoperative pain. Tools such as videotapes, brochures with ani-
mated characters, or even a guided tour of the unit could be helpful.
5.5.1 Fasting
The most common complications in DS are PONV and agitation on awakening.

Keeping a child fasting from midnight means inducing and then awakening an irri-
tated child because of thirst and hunger and in addition with a gastric residual vol-
ume greater than 0.4 ml/kg with a pH less than 2.5. This increases the risk of
aspiration, PONV, and agitation on awakening. Clear liquids should be adminis-
tered 2–3 hours before induction so that the gastric residual volume will reduce and
the pH will increase [26, 27].
Please refer to the Guidelines [28] and Chap. 3.
5.5.2 Premedication
The three main goals of premedication are the reduction of preoperative anxiety,
easy separation from parents, and easy induction either intravenously or by mask.
There are several techniques of premedication, pharmacological and not, but none
can take the place of the other. In addition, “one cannot fit like a glove for all.” It
depends on previous experience, age and character of the child, ability of the parents
to control their anxiety, and the experience of the team.
For example, in children undergoing repeated procedures requiring anesthesia,
very often the presence of a parent at the moment of induction is of great help and
usually the child asks not to be sedated but to have a parent with him/her. That in
this case can become a valuable ally for the team and can help smooth the experi-
ence for the child, for the staff, and for themselves. In other cases, the parental pres-
ence at induction could create more problems to the parents who see their child
having “strange reactions”. If the induction is to be done in the presence of the
parents, it must be planned with adequate counseling.
The presence of a parent at induction will be of help in reducing the child’s anxi-
ety. Children under 6 months generally do not require premedication, but some
practical precautions could help maintain the child’s comfort such as maintaining
the child dressed and wrapped in his/her blanket, or using a pacifier.
If you opt for intravenous induction, the use of anesthetic ointments (EMLA) for
venipuncture is recommended; however, using EMLA to eliminate pain during veni-
puncture does not eliminate the fear of needles.
In our experience, patients should be adequately premedicated because this will

facilitate the work of the staff, who will have a calm and collaborative patient able
to separate from his/her parents and enter the operating room.
5.5.3 Pharmacological Premedication
The ideal premedication is one that does not interfere with the recovery and the
discharge.
Oral administration is the most widely used, but for more reluctant children,
intramuscular administration can be used.
Midazolam is the benzodiazepine of choice for premedication, exploiting its main
anxiolytic and, most of all, anterograde amnesia effects. It can be administered through
different routes and dosage depending on the route chosen. The most widely used is the
oral route at a dose of 0.5 mg/kg (max 15 mg). Because of its bitter taste, it should be
given with sugar or fruit juice without pulp. The oral onset is 10–30 min. In children
less collaborative, the intranasal route can be used at the same dose as the oral route.
Ketamine is usually used in cases of poor collaboration during oral therapy assump-
tion and is administered parenterally. It can be taken orally at a dose of 6 mg/kg or
intramuscularly 2–4 mg/kg to achieve a sedative effect in 10–15 minutes.
5.6 Anesthesia
The purpose of DS is rapid recovery in order to quickly reach the criteria of dis-
charge and minimize side effects of anesthesia.
In light of this need, the anesthetic conduct should aim to discharge patients as
quickly as possible. The main complications that may interfere with discharge
include PONV, behavioral disorders, and respiratory and cardiovascular complica-
tions. The choice anesthetic technique depends on several factors, including the
type of surgery and the patient’s conditions. When treating a pediatric population,
local or regional anesthesia is rarely performed in the absence of sedation. Therefore,
it is important to find the anesthetic technique with the lowest impact on recovery
times and with minimal side effects so as not to delay discharge. A recent system-
atic review [29] did not provide strong evidence on reduction of side effects, such as
PONV and behavioral disturbances, using induction and maintenance of intrave-
nous anesthesia with propofol compared to inhaled anesthesia.
5.6.1 Drugs
When choosing an inhaled induction, which is of great help with noncollaborative

children or with difficult intravenous access, the drug most widely used today is
sevoflurane that ensures fast and smooth induction with minimum side effects.
Another halogenated agent that can be used is halothane, but this is disappearing
from operating theaters because it is linked to hepatitis and sensitizes the myocar-
dium to catecholamines.
As for intravenous medications, propofol or thiopental is to be preferred because

recovery from other agents, such as benzodiazepines and ketamine, is too long.
The use of muscle relaxants is not precluded in DS, as long as they are antago-
nized based on the monitoring of the neuromuscular junction. Currently, sugam-
madex, that can antagonize neuromuscular block when using nondepolarizing
aminosteroid muscle relaxants. Its use is registered in the pediatric field [30] and
can be a viable alternative to neostigmine, to eliminate the possibility of side effects
such as PONV and increased secretions.
There is limited space today for the pediatric use of succinylcholine, which can
be used in emergency situations, but is not recommended routinely in pediatrics
because of its numerous side effects (triggers malignant hyperthermia, life-threaten-
ing hyperkalemic cardiac arrest, masseter muscle rigidity).
Opioids are not ideal for pediatric day cases as they may produce ventilatory
depression, excessive sedation and PONV. Intraoperative opioids with shorter dura-
tion of action, such as fentanyl and remifentanil, are recommended. The most
important side effects are rigidity of the chest, for which slow administration is
recommended, and overdose, for which an adequate titration is recommended.
5.6.2 Locoregional Anesthesia
The use of local anesthetics in pediatric anesthesia is recommended at the minimum

effective dose. The success of regional anesthesia means administering the right
dose of the right drug in the right place, particularly in DS where the primary benefit
of locoregional anesthesia is postoperative pain relief without unwanted motor
block [31]. Its applicability depends on the type of surgery, the experience of the
team, and the means/tools available.
In children, administration of locoregional anesthesia without sedation is very
rare. A major benefit of combined general and regional anesthetic technique is that
general anesthesia or sedation can be maintained at a lower level and perioperative
opioid requirements can be reduced. In addition, use of local anesthetics at an anal-
gesic and non-anesthetic dose is recommended.
Ultrasound-guided blocks allow a minimum dose of local anesthetic while
reducing the risk of systemic toxicity and accidental intravascular administration
of the drug.
Some current regional anesthetic techniques that may be successfully used in this
context are:
5.6.3 Spinal Block
The duration of spinal anesthesia is much shorter in small children than in adults
and may not be sufficient for bilateral procedures. It is not recommended in
DS because of poor postoperative analgesic coverage compared to alternative
techniques.
5.6.4 Caudal Block
This block represents the most commonly used regional technique in children and
can be used successfully for all subumbilical procedures. To achieve adequate
postoperative pain relief without unwanted postoperative motor block, the correct
concentration of long-lasting local anesthetics needs to be used. Ivani et al. [32]
have shown that administration of 1 ml/kg of levobupivacaine 0.25 % and ropiva-
caine 0.2 % produces adequate postoperative analgesia. The limitation of the tech-
nique is the duration of effective analgesia when used in surgery involving the
lower thoracic dermatomes (inguinal hernia and hydrocele repair) because of its
known regression to craniocaudal fashion. The risk for urinary retention is
approximately 2 % and is similar to that after general anesthesia without caudal
block [33].
5.6.5 Ilioinguinal/Iliohypogastric Nerve Block
The use of this block has been popular in association with inguinal hernia and
hydrocele repair. Weintraud et al. demonstrated that with traditional landmark-
based technique, the local anesthetic is deposited at a suboptimal anatomical loca-
tion [34]. Thus, this block should be performed under ultrasound guidance to
achieve an acceptable success rate as well as to avoid unintentional puncture of the
nearby peritoneum and bowel. Using ultrasound guidance, the volume of local anes-
thetic needed for a successful block is slightly less than 0.1 ml/kg. Its limit is ade-
quate analgesia for orchidopexy. Even if perfect ultrasound-guided ilioinguinal/
iliohypogastric nerve block has been performed, it will not influence the testicular
pain that is responsible for the deep, nauseating pain that represents the major prob-
lem after orchidopexy. For testicular pain, it is necessary to anesthetize the lower
thoracic segments.
5.6.6 Paravertebral Block
It represents a useful alternative to ilioinguinal/iliohypogastric nerve block for

inguinal hernia and is more effective for orchidopexy when performed at a low tho-
racic level. At this level, the low risk of unintentional pleural puncture is almost
completely abolished. It is most frequently used as a unilateral technique.
5.6.7 Lower and Upper Extremity Nerve Blocks
The aim is to avoid the motor block. A longer duration is often desirable, so the use
of continuous peripheral catheter technique is becoming increasingly popular, and
recent publications describe the use in outpatients. However, these techniques are
best applied in slightly older children [35] and in the absence of motor block.
5.6.8 Penile Block
Indicated for circumcision, this block can be used also for postoperative analgesia
following minor hypospadias repair.
5.6.9 Opioids as Adjuvants in Locoregional Anesthesia
Use of morphine to increase the duration of locoregional anesthesia in outpatients is

discouraged.
The most effective drug to prolong the analgesic effect of the caudal block is
ketamine (S-ketamine 1 mg/kg), but the use of clonidine (1 mcg/kg) has not been
excluded.
For peripheral blocks, only clonidine has been found to be effective in prolong-
ing the block.
5.6.10 Fluid Therapy
For short-term procedures (<1 h), it may not be necessary to administer intraopera-

tive fluids as long as the child drinks clear liquids up to two hours before induction.
In DS, it is desirable to restore spontaneous oral hydration as soon as possible, but
some authors have shown that children forced to drink tend to vomit more fre-
quently than those that resume oral hydration spontaneously [36]. Intraoperative
hydration could have a rationale for interventions at high risk of PONV, such as
strabismus and adenotonsillectomy in which pain could limit swallowing or in
infants and babies when even the minimum interval of fasting necessary for admin-
istration of anesthesia appears to be long (3 hours). In any case, administration of
polyelectrolyte solutions is recommended, leaving glucose solutions for very young
children more prone to hypoglycemia.
5.6.11 Airway
The choice of airway management should be assessed on a case-by-case basis

depending on the procedure, the patient’s age, and the experience of the anesthe-
siologist. Sedation is required for many outpatient interventions, so it may be
sufficient to maintain spontaneous or assisted breathing by face mask. The laryn-
geal mask airway (LMA) helps maintain airway patency unless endotracheal intu-
bation is obtained. In the past, intubation was not recommended in DS patients
because of the risk of post-extubation croup. Today, with the use of muscle relax-
ants and a safe antagonist and next-generation devices, the risk is very low. It
usually occurs within 1 hour from extubation; therefore, a closer postoperative
monitoring is recommended.
5.6.12 Temperature
Even for short interventions, monitoring and precautions should be taken to keep
the body temperature stable in pediatric patients by heating the operating room,
using mattresses or blankets, and administrating heated fluids.
5.7 Analgesia
Pain control is a cornerstone in pediatric surgery whether dealing with inpatients or

outpatients. The challenge is to provide a pain-free emergence and recovery by
starting analgesics in the intraoperative period, especially when using a rapid recov-
ery anesthesia as in DS.
Patients should be discharge after adequate analgesia has been achieved.
Furthermore, medications to control pain at home should be prescribed. All tech-
niques and medications available can be used, as long as these do not increase the
side effects and allow postoperative analgesia. The multimodal approach is proba-
bly the gold standard of therapy because it exploits the power of the drugs. Each
drug with a different mechanism of action can be used at a lower dose.
The most commonly used analgesic drug is paracetamol (acetaminophen). The
recommended dose is 10–15 mg/kg every 6 hours, reaching a maximum daily dose
of no more than 100 mg/kg [37]. It can be considered the base drug that can be
associated with other therapies for the multimodal approach. Oral administration is
the most effective route because of its predictable systemic absorption. When pos-
sible, oral use should be encouraged. Another recommendation is the dosing inter-
val, which must be respected even at night, especially in DS patients requiring stable
pain coverage.
The NSAIDs are not contraindicated in pediatrics. Acetylsalicylic acid is no
longer used because of its association with the Reye syndrome. The main side
effect of NSAIDs is platelet antiaggregation. Oral use is encouraged. The most
frequently used are ibuprofen 5–10 mg/kg and ketorolac 0.3–0.5 mg/kg which
can be used parenterally. Ketoprofene can be used parenterally in 1–2 mg/kg
dose [38].
5.7.1 Locoregional Anesthesia
Locoregional anesthesia appears to meet the requirements of good management of

postoperative analgesia in DS. Correctly used regional anesthetic techniques are
feasible and often associated with superior postoperative analgesia when compared
to other options [39].
It is the analgesic of choice since it blocks pain transmission, and produce ade-
quate analgesia up to 6–8 hours. A major benefit of a combined general and regional
anesthetic technique is the reduction in perioperative opioid requirements and,
consequently, reduced postoperative emesis. Kokinsky [40] shows that the adminis-
tration of fentanyl 1 mcg/kg to children undergoing outpatient surgery under gen-
eral anesthesia combined with a caudal block did not improve analgesia but caused
a very significant increase in PONV compared to saline placebo (36 vs. 0 %).
Using continuous peripheral catheter appears very promising in order to extend
analgesia after the return home.
5.8 Postoperative Nausea and Vomiting
Postoperative nausea and vomiting (PONV) are the most common complica-
tions in anesthesia. The medical complications of PONV include pulmonary
aspiration, dehydration, electrolyte imbalance, fatigue, and wound disruption.
Postoperative vomiting (POV) is an expensive complication in DS because it
delays discharge, it causes discomfort in the patient and causes anxiety in both
the children and parents, and increases medical care.
Eberhart [41] identified 4 independent predictors of POV: duration of surgery
>30 minutes; age > 3 years; history of POV in the patient, parent, or sibling; strabis-
mus surgery; and ear-nose-throat surgery. Based on the presence of 0,1, 2, 3, 4 fac-
tors, the risk of POV was 9 %, 10 %, 30 %, 55 %, and 70 %, respectively. The
incidence of POV when prophylaxis was not used was 3.4 %, 11.6 %, 28.2 %, and
42.3 %, respectively, in the presence of 0, 1, 2, or 3 factors.
The management approach is multifactorial and involves proper preoperative
preparation, risk stratification, and rational selection of antiemetic prophylaxis.
The main factor in preoperative preparation for reducing PONV is to avoid pre-
operative dehydration and encourage the patient to take clear liquids up to two hours
before induction. PONV can be reduced by avoiding nitrous oxide and volatile
anesthetics and by reducing postoperative opioids. However, a recent Cochrane
study29 showed that there is no PONV reduction when comparing intravenous anes-
thesia to inhalation anesthesia in outpatients.
The rational selection of antiemetic prophylaxis is derived from a proper risk
stratification in the pediatric population.
The most recent guidelines [42] identify, according to risk stratification, the most
effective single antiemetic therapy and combination therapy regimens for PONV
prophylaxis for most pediatric patients at high risk for POV.
Children who are at moderate or high risk of POV should receive a combination
therapy with at least 2 prophylactic drugs from different classes.42
• Ondansetron 0.05 mg/kh + dexamethasone 0.015 mg/kg

• Ondansetron 0.1 mg/kg + droperidol 0.015 mg/kg
• Tropisetron 0.1 mg/kg + dexamethasone 0.5 mg/kg
New data on pharmacokinetics of ondansetron in children <2 years of age are

now available. Dolasetron is not recommended for cardiac arrhythmia risk. Caution
should be used when administering 5-HT3 antagonist in children with prolonged

QT syndrome.
The incidence of post-discharge nausea and vomiting (PDNV) in children is
20 % after tonsillectomy.
In a recent review by Hohne [43], for outpatients who had short anesthesia with
surgery lasting less than 30 min, with rare use of perioperative opioids, a single
prophylaxis is recommended; for strabismus or ear-nose-throat surgery or high-risk
patients, a double prophylaxis is to be preferred.
5.9 Discharge
Reduction of hospitalization times (pre- and postoperative) is the most effective tool
to reduce the cost of the care process. However, time of observation reductions
should not affect the safety of patients, therefore the phase of postoperative observa-
tion should be ensured by the standards of accreditation which include taking care
of the patient from admission to discharge (chapter access to care and continuity of
care -ACC 1- Joint Commission [44]). Currently, especially in the fast track of sur-
gery at short cycle, the focus has increasingly shifted to the process of taking charge
of the patient even at home.
Discharge is the culmination of DS care and, as all other phases, consists of two
components: clinical management and organizational management.
Modalities for discharge vary depending on the type of organizational model
adopted. There are facilities where patients are transferred from the recovery room
to a hospital ward (short-stay area) where they are discharged. Others are discharged
directly from the recovery room.
In any case, clinical criteria for discharge must be respected. Scoring sys-
tems make the discharge process easier and more efficient. The Aldrete scor-
ing system and postanesthetic discharge scoring system (PADSS) [45] have
received widespread consensus in assessing postanesthetic recovery
(Table 5.1).
The first is essentially based on the assessment of vital signs (respiratory and
cardiovascular) and is used for recovery from anesthesia for the assessment of res-
toration of consciousness, protective reflexes, and motility. It is indicated for recov-
ery phase I, that is, for the discharge of the patient from the recovery room to the
ward for observation. The second system evaluates the vital parameters in a single
item and associates the evaluation of other functions that can ensure the restoration
of activities which will allow the return home, such as the ability to stand stably, the
presence of nausea and vomiting, adequate pain control, and bleeding of the surgi-
cal wound. The PADSS is used for discharge home phase II recovery. Patients
achieving a total score of 9 or 10 are considered fit for transfer or discharge to the
next phase of recovery.
Recently, the Société Française d’Anesthésie et de Réanimation (SFAR) pub-
lished a prospective observational study in which PADSS is applied in the pediatric
Table 5.1 Aldrete scoring Respiration

system
Able to take deep breath and cough = 2
Dyspnea/shallow breathing = 1
Apnea = 0
O2 saturation
Maintains >92 % on room air = 2
Needs O2 inhalation to maintain O2 saturation > 90 % = 1
O2 saturation >90 % even with supplemental oxygen = 0
Consciousness
Fully awake = 2
Arousable on calling = 1
Not responding = 0
Circulation
BP ± 20 mmHg pre-op = 2
BP ± 20–50 mmHg pre-op = 1
BP ± 50 mmHg pre-op = 0
Activity
Able to move 4 extremities = 2
population, defining Ped-PADSS pediatric discharge score in ambulatory surgery

[46] (Table 5.2).
An analysis of the literature does not provide data on the minimum time of post-
operative observation. Previously, a postoperative observation period of at least 4
hours was required; today, as reported by SFAR, 95 % of patients have the Ped-
PADSS ≥9 after two hours of observation. A more recent study [47] including 1060
children and using Ped-PADSS, 97.2 % of children could be discharged one hour
after returning from the operating room, and 99.8 % of children were dischargeable
two hours after. Therefore, it is advisable, but not required, that patients remain in
the hospital for at least four hours postoperatively, but the time may vary depending
on the organizational model, as long as the scoring system is used and patients are
fully satisfied at discharge.
Discharge must be decided by the surgeon or the anesthesiologist but, according
to the Joint Commission Accreditation, can be carried out by educated and empow-
ered personnel according to the procedure in use in the institution.
The child should be entrusted to a responsible adult who can take the patient
back to the hospital for any need. Means of transportation and/or the possibility of
a telephone to call for help should be available.
Postoperative management indications must be written, may be differenti-
ated by type of procedure, should be handed to the parents or the adult respon-
sible, and explained in a comprehensible manner with the aid of a mediator, if
needed.
Table 5.2 Postanesthetic Vital signs

discharge scoring system
BP and pulse within 20 % pre-op = 2
(PADSS)
BP and pulse within 20–40 % pre-op = 1
BP and pulse within >40 % pre-op = 0
Activity
Steady gait, no dizziness, or meets pre-op level = 2
Requires assistance = 1
Unable to ambulate = 0
Nausea and vomiting
Minimal/treated with p.o. medication = 2
Moderate/treated with parenteral medication = 1
Severe/continues despite treatment = 0
Pain
Controlled with oral analgesics and acceptable to patient:
Yes = 2
No = 1
Surgical bleeding
Minimal/no dressing changes = 2
Moderate/up to two dressing changes required = 1
Severe/more than three dressing changes required = 0
Prescriptions for pain therapy, including the rescue dose, must be clear and pre-
cise. Could the family report difficulty in finding the first home administration, the
structure should provide it.
A telephone follow-up could be made the day after surgery to determine the
frequency of complications, including minor ones not requiring hospitalization, and
to report on the child’s condition and resumption of daily activity (information on
meals, sleep disorders, recovery motor activity). Monitoring pain control at home is
also part of patient care according to the standards of the Joint Commission of
Accreditation.
5.10 Special Consideration for Tonsillectomy
Tonsillectomy is the most performed pediatric surgery in the world. As previously

stated, it is one of the interventions with increased incidence of minor postoperative
complications, as well as major complications. Common complications are:
• Respiratory
• PONV
• Hemorrhage
Because of the higher incidence of complications, the indication for surgery in

DS varies according to criteria related to the patient, but also to the organization and
to the legislation of the institutions. The criteria attached to the patient for which the
tonsillectomy with or without adenoidectomy can be performed in DS are:
• Age > 3.
• ASA I and II.
• Lack of comorbidities that may increase the risk of respiratory complications
(OSAS, severe obesity, craniofacial deformities, neuromuscular disorders with
pharyngeal hypotonia, signs of heart failure or pulmonary hypertension, meta-
bolic diseases, recent upper or lower respiratory tract infections). The presence
of just one of these conditions is enough to exclude the patient from DS.
• Normal coagulation tests.
Any facility deciding to perform ATC surgery must adhere to a specific protocol
and must have the ability to shift the patient to inpatient and provide intensive care
for 24 hours. For children under three years of age or with comorbidities (see
above), surgery is recommended in hospitals with ICU. If surgery is performed in
DS, some special precautions must be considered:
• Consensus among the surgeon, anesthesiologist, and parents on postoperative

course.
• At least 6 hours of postoperative surveillance is recommended to check absence
of pharyngeal bleeding, assess and treat postoperative pain, prevent and treat any
PONV, and ensure resumption of feeding. Any adverse event observed during
surveillance may lead to conventional admission.
• Prophylaxis for PONV: these patients are at high risk of PONV, so a combination
therapy with at least two prophylactic drugs from different classes is recommended.
• Plan adequate postoperative analgesia for at least a few days after surgery: the
importance of systematic scheduled administration of paracetamol and a rescue
dose for at least a few days. NSAID prescription following tonsillectomy is not
widespread recomended due to a suspected elevation of hemorrhage risk, even if
Cardwell in a systematic review [48] concluded that NSAID do not increase
bleeding after tonsillectomy/adenoidectomy procedures.
• Specific and detailed instructions about food (cold, smooth, and nonspiced) and
drinks (cold and nonacid).
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Perioperative Care in Remote Locations
6
Maria Sammartino, Fabio Sbaraglia,
and Francesco Antonio Idone
A significant number of children receive some kind of nonoperating room anesthe-

sia (NORA) for painful or uncomfortable procedures [1]. Several advantages are
reported for NORA even if risks and adverse events are described by some authors
[1, 2]. Determination of safety standards in this particular pediatric field must be
considered a priority in clinical research to ensure high quality of care.
The current status of pediatric NORA is even undefined because of the wide
overlapping in literature with sedation, the variety of locations (with different levels
of intensity of care), the different techniques utilized, and the performers involved.
In the matter of this last point, there is a strong debate about who should be perform-
ing sedation in children [3, 4], which reflects the existence of an evolving situation
that does not concern the objective of this chapter.
Independendtly of the degree, the provider must be able to choose a comfortable
sedation plan, and to manage adverse events related to drugs and techniques utilized
[5]. The Joint Commission for Accreditation of Healthcare Organization has stated
that every provider has to be able, when needed, to rescue the patient for that level
of sedation and for one deeper level [6]. Our intent is to examine current practice,
highlighting potential gray areas in the three steps of anesthesia: pre-procedural
assessment, anesthesiological management, and discharge.
M. Sammartino (*)
Dipartimento di Anestesia e Rianimazione, Ospedale Universitario A. Gemelli, Università
Cattolica del Sacro Cuore, Rome, Italy
e-mail: marinasammartino@libero.it
F. Sbaraglia • F.A. Idone

DOI 10.1007/978-3-319-21960-8_6
76 M. Sammartino et al.
6.1 Pre-procedural Assessment
NORA is required for several diagnostic and therapeutic procedures. The feasibility
in these cases is dependent on a multidimensional evaluation by the anesthesiolo-
gist, who will consider the clinical status of the child, the invasivity (pain, duration,
risks, etc.) of the procedure, and the location facilities.
Even if there are not absolute contraindications to procedural sedation outside
the operating room, the quality of care of the operating room should be transferred
also to a remote location.
Location of NORA should be overviewed by the anesthesiologist before the pro-
cedure. The setup should guarantee the presence of a certain number of items that
could be remembered with the acronym SOAPME (Table 6.1). An adequate number
of sockets are important to connect monitors, suction, infusion pumps, etc. Also a
reliable contact trough phone, pager, or mobile is mandatory. Whether one of these
standards is missing, performing NORA is not safe, even if dealing with a mild
sedation.
Children who have to undergo the procedures should be evaluated concerning
their physical and behavioral status (just as for anesthesia in the operating room),
and the correlated suitability for sedation should be investigated. The history should
include comorbidities and previous hospitalization, sedation or general anesthesia,
current therapies, relevant familiar history, and possible allergies. Particular atten-
tion should be dedicated to the risk of obstructive sleep apnea, for obese or snoring
children [7]. Physical examination should include auscultation of the heart and
lungs and evaluation of the neck and airways. Evidence specific for children regard-
ing identification and management of difficult airways is limited [8]. Nevertheless,
a systematic approach for children can be developed from experience with adults in
the operating room using the acronym LEMON (Table 6.2).
Table 6.1 SOAPME mnemonic acronym

S Suction Suction device with child-sized suction catheters
O Oxygen Availability of adequate oxygen delivery
A Airway Age-appropriate airway equipment
P Pharmacy Sedation and emergency drugs
M Monitors Standard monitors for vital parameters (SaO2, EKG, NiBP, EtCO2)
E Equipment Special equipment in child size
Table 6.2 LEMON mnemonic acronym

L Look at him Look for external indicators for difficult airways
E Evaluation Evaluate mouth opening, thyromental distance, mandibular space
M Mallampati Mallampati score
O Obstruction Signs of airway obstruction or OSAS
N Neck Neck mobility
6 Perioperative Care in Remote Locations 77
Table 6.3 Fasting rules by 2h Clear liquids

ASA [71]
4h Breast milk
6h Infant formula and light meal
8h Fatty food or meat
Certain patient factors have been associated with failed sedations, like the pres-
ence of upper respiratory infection (URI) that mainly causes cancellation and
rescheduling of the procedure. URIs are responsible of higher incidence of compli-
cations, but serious events are rare in literature [9]. Whether infectious secretions
are present, the operation should be postponed at least for 2 weeks.
During pre-anesthesiological assessment, provider must present the sedation/
anesthesia plan to parents and child (depending on the age) describing the benefits
(minimizing pain, anxiety, and physiological trauma) and the possible risks often
agent specific but commonly including potential for airway compromise, hypoxia,
and vomiting. An informed consent has to be signed by both parents.
The patient fasting status is a key consideration when assessing the risk index.
The American Society of Anesthesiologists (ASA) suggestions for fasting in chil-
dren undergoing sedation for elective procedures are universal and are showed in
Table 6.3. However, the degree of fasting for urgent/emergent procedures is contro-
versial, and disparate recommendations have been proposed by the ASA and the
American College of Emergency Physicians [10, 11].
Evidence regarding the optimum duration of fasting required to reduce risk of
aspiration during sedation is limited [12]. No relationship has been proved between
the duration of fasting prior to procedural sedation and the amount of content found
in the stomach [13–17]. Furthermore, there are some evidences that the more is the
fasting, the more is the residual gastric volume [18].
Approach to fasting time needs some flexibility when facing with pathologies
that modify children metabolism or digestive tract mobility. In some cases, as in
concomitance of dumping syndrome [19], the provider should consider that the risk
of hypoglycemia is more important than the risk of aspiration. On the other hand, a
slow emptying, as in the case of achalasia or ileus, requires a longer fasting [20].
As reported by recent recommendations of the Italian Society of Pediatric and
Neonatal Anesthesia, the systematic use of complementary tests in children, should
be replaced by a selective prescription, based on the preoperative evaluation [21].
6.2 Anesthesiological Management
Differently from inside the operating room, anesthesiological management cannot

be based only on patient status and on the procedure, but it should be decided also
on the actual environment.
Flexibility is a key factor in the good outcome of NORA. Most of the procedures
are scheduled in remote locations, which often do not guarantee a wide space of
action and cannot allow the use of some drugs or equipment. Anesthesiologists have
to tailor an anesthesia service to the particular requirements imposed by the actual
context. For example, procedures performed directly in neonatal intensive care unit
often do not allow the use of halogenated vapors for the absence of adequate anes-
thesia machines, vaporizers, and scavenger systems so that only intravenous drugs
can be utilized; MRI and many radiologic exams do not allow to remain close to the
patient, reducing the direct control on his ventilation and other vital signs; dentistry
and endoscopy oblige the anesthesiologist to share airways with the co-workers
(more challenging when outside the operating room); some electrophysiological
retinal exams require a dark room without possibility to look at the child, etc. In
these challenges, a right choice of drugs and an efficient and reliable monitoring is
essential for a safe outcome.
Although respiratory adverse events are the most common [2, 22], a basic hemo-
dynamic monitoring (EKG, NiBP) is recommended in every patient, independent
from procedure, location, and clinical status. If deep sedation is performed, or if a
patient has significant underlying illness, vital signs should be measured at least
every 5 min.
Experience and evidence suggest that respiratory complications are the most
reported and are likely to occur within 5–10 min after administration of intravenous
medications and immediately after the procedure when the painful stimuli are removed.
Provided that continuous visual observation of the face, mouth, and chest wall
movements is not reliable, adequate respiratory monitoring is recommended
throughout the procedure [23, 24]. The use of SaO2 is mandatory but does not give
a value in real time. EtCO2 monitoring, on the contrary, better by Microstream
Sensor particularly in neonates, is strongly recommended [25]. Microstream moni-
tors have a sampling chamber of 15 mcl and work well even with low flow of 50 ml.
EtCO2 monitoring is increasingly available in many settings for non-intubated
patients and may be helpful to assess ventilation during sedation and analgesia.
Increases in EtCO2 may be detected in children undergoing respiratory depression
before hypoxemia is noted, particularly in those who are receiving supplemental
oxygen. Different approaches to preoxygenation and to the use of continuous sup-
plemental oxygen during procedural sedation are reported in literature [26]. A FiO2
higher than 0.21 can allow to maximize O2 lung storage [27] and a longer mainte-
nance of a good level of PaO2 during occurrence of apnea. However, continuous
supplemental oxygen can delay desaturation and apnea detection unless capno-
graphic monitoring is available [28]. Furthermore, there is no evidence that preoxy-
genation or increasing FiO2 is associated with improved safety in NORA [29].
An additional monitoring is represented by the cerebral activity monitoring. The
most utilized technology is the bispectral index (BIS). It is able to quantify the level
of consciousness ranging from 0 (no brain activity) to 100 (alert), obtained by con-
tinuous EEG monitoring through probes placed on the forehead. It has shown good
sensitivity in children older than 6 months, and it can be useful to guide adequate
drug administration and to avoid overdosage [30] that could delay awakening. It
should be considered that BIS index is not sensitive to drugs that have site effect out
of the cerebral cortex, as ketamine, dexmedetomidine, remifentanil, and N2O [31].
Other brain activity monitoring devices, as entropy [32] and cerebral state index
[33], are under validation for pediatric age, but results are even controversial.
Table 6.4 Definitions to describe the depth of sedation

Minimal sedation The patient responds normally to verbal commands. Cognitive
function and coordination may be impaired, but ventilatory and
cardiovascular function is unaffected
Moderate sedation/ The patient has depression of consciousness but can respond
analgesia purposefully to verbal commands either alone or accompanied by
light touch. Maintains airways and adequate ventilation without
intervention. Cardiovascular function is maintained
Deep sedation The patient cannot be easily aroused but responds purposefully to
noxious stimulation. May require assistance to maintain airway and
adequate ventilation. Cardiovascular function is usually maintained
General anesthesia The patient cannot be aroused. May require airway assistance and
ventilation. Cardiovascular function may be impaired
Table 6.5 Principal routes of administration

Inhalation Halogenated, N2O
Intravenous All opiates, propofol, midazolam, ketamine, flumazenil, naloxone
Intramuscular Ketamine, benzodiazepine
Rectal Ketamine, benzodiazepine
Intranasal Midazolam, flumazenil, dexmedetomidine, fentanyl, ketamine
Buccal Midazolam, ketamine, sufentanil, dexmedetomidine
Transmucosal Fentanyl
Various drugs and techniques can be chosen: clinicians who administer sedation
must understand the pharmacology of the drugs used. Because sedation is a con-
tinuum in which responses to medications vary greatly upon developmental, behav-
ioral, and clinical status, type of procedure, need to cover painful maneuvers or only
immobility, clinicians must identify the appropriate level of sedation/analgesia for
the single child (Table 6.4). Careful titration of the chosen medication is often nec-
essary to safely achieve the desired depth of sedation. A wide range of short-acting
sedative-hypnotic and analgesic medications are available [24, 34, 35], and many of
these agents have multiple routes of administration (Table 6.5). Procedures that are
not painful and require only immobility can usually be performed with sedation
alone. Children undergoing painful procedures require also analgesia. It has to be
underlined that every performer must be able to deal with possible complications,
and competence in emergency airway management is mandatory [5, 24, 36].
6.3 Inhalation Techniques
Historically, children have been anesthetized in operating rooms by halogenated

vapors. The increasing demand of procedures in NORA has transferred this tech-
nique even outside of the operating room. The recent attention to the environmental
pollution and to the occupational safety has restricted the use of inhalation anesthe-
sia inside the locations equipped by specific scavenger systems.
The most used vapor in this field is sevoflurane that guarantees a safe profile for
maintenance of spontaneous breathing and stabile hemodynamic. It is also advantageous
for its rapid onset and the possibility to find a venous access in not cooperating children.
It can be used trough facial mask or even by nasal probes, very useful in procedures
performed on the eyes or on the face where the mask could result cumbersome.
Other halogenated (as desflurane or isoflurane) are not indicated for this use, due
to their irritating effect on the tracheobronchial system, when used in spontaneous
ventilation.
Nitrous oxide (N2O) is an old gas which recently has been proposed again, in a
new formulation. It is commercialized as a mixture with O2 50 % in portable tanks.
It is delivered through a demand valve mask or continuous flow system [37]. Because
the demand valve mask requires cooperation and may be difficult to be activated by
smaller children, N2O is used primarily in patients older than 4 years of age. To pre-
vent excessive exposure, dedicated facial masks connected with a scavenger system
can be utilized. A continuous delivery system (a mask strapped over the nose and/or
mouth) has been used in younger children with variable success. This system indeed
is more frequently associated with emesis [38, 39]. N2O provides good analgesia,
sedation, amnesia, and anxiolysis [40, 41], and it is a widely used analgesic for acute,
short-term pain relief in a diverse range of clinical situations. Contraindications to
nitrous oxide include nausea and vomiting and trapped gas within body cavities (e.g.,
bowel obstruction, pneumothorax, middle ear infection). Deeper sedation than antic-
ipated can occur with prolonged inhalation and when N2O is combined with opioids
or benzodiazepines [42]. It is reported that fasting is not mandatory using 50 % N2O/
O2 mixture [43]. In the absence of a clear evidence, every physician should identify
the best choice according to his experience or skill.
6.4 Intravenous Techniques
Children are usually afraid of needles, and often in NORA, there is no possibility to
use inhalation induction, so the cooperation of the child for finding a venous access
is important. Application of anesthetic transdermic cream 45 min earlier can be very
useful, in association with administration of midazolam 0.4–0.5 mg/kg (for a maxi-
mum of 15 mg) by mouth or better through the more rapid nasal route, thanks to the
high mucosal vascularization [44].
Over the last decade, intravenous techniques are developed even in pediatrics
with successful outcome. The marketing of new short-acting drugs and the safer
profile of pharmacodynamics allows to calibrate anesthesia in real time with respect
to the procedure.
The development of pediatric pharmacokinetic models for target-controlled infu-
sion (TCI), Paedfusor and Kataria, has been a further boost to better utilize propofol
in children.
TCI technique is particularly advantageous in NORA, allowing to perform seda-
tion in spontaneous breathing assuring a constant propofol plasma concentration
[45]. When compared with manual controlled infusion or intermittent bolus, TCI
provides reduced apnoeic events and shorter awakening time [46].
For these reasons, propofol currently is the commonest intravenous agent (alone
or in combination) administered in NORA. Safety profile is very comfortable even
in smaller children [47], despite propofol infusion syndrome has been described
after longer or high-dose infusion [48]. However, high doses administered by mis-
take for short procedures have not shown fatal outcome, despite a transient altera-
tion in the metabolic pattern [49].
Remifentanil shows a pharmacokinetic profile even more advantageous in gen-
eral anesthesia due to the efficacy of plasmatic esterases, which seems already
mature even in premature babies [50]. Among opiates, remifentanil is the most indi-
cated for a rapid recovery and discharge, even if the apnoeic effect requires a strict
capnographic monitoring when spontaneous breathing is performed.
Outside the operating room, other opioids have proven useful. Alfentanil has
been utilized by bolus in association with propofol or midazolam in short painful
procedures as bone marrow aspiration or lumbar puncture [51]. Opioids with longer
half-life are less recommended, as unique sedation agent, due to the increased inter-
individual variability and difficult titration. Recently sufentanil has been experi-
mented successfully in a preliminary study by nasal route in dentistry [52], but this
technique still needs major validation.
Ketamine, which came back to our attention in the last years, provides sedation,
analgesia, and immobilization while usually preserving upper airway muscle tone and
spontaneous breathing [53–55]. Its use in small doses in association with hypnotic
agents is common, particularly for the possibility of administration by several routes.
Dexmedetomidine can be considered the future of sedation also in NORA. It
causes minimal respiratory depression and, in healthy children, has been found gen-
erally safe and effective for nonpainful procedures [56], and in some sedation ser-
vice, it is already the preferred agent for diagnostic imaging [57, 58].
Further molecules are going to be investigated. Among these, remimazolam, an
ultra short-acting benzodiazepine, is actually in phase II and represents something
new on the horizon [59, 60].
Ketofol, a combination of propofol and racemic ketamine mixed in the same
syringe, for sedation and analgesia in short procedures is still under investigation.
The best ratio between the two drugs is not yet well established: a ratio of 1:3 for
bolus and 1:4 for infusion seems to be a reliable combination [61].
Reversing agent availability is mandatory during NORA, but their use should be
limited to rare and specific situations. Flumazenil, antagonist of benzodiazepines,
could be useful even in the absence of venous access [62]. Naloxone should be used
with extreme prudence as suggested by American Academy of Pediatric Committee
on Drugs guidelines on the use in children [63].
6.5 Complementary Techniques
Complementary and alternative medicines are described for sedation in children.

Sweetening agents like sucrose has been utilized to reduce stress response in neo-
nates [64], as well as the simply sensorial stimulation from skin-to-skin contact with
the mother [65].
Hypnotherapy, acupuncture, and Chinese traditional medicine are proposed as

alternative treatment, but evidence is very poor. Certainly the creation of a reassur-
ing environment and a good interaction with patient and parents assures an easy
approach to NORA.
6.6 Discharge
After the procedure, children need a stay in recovery room during which monitoring
must be carried out. As reported above, minor adverse events are common in the
first minutes after the end of the procedure when stimuli associated with the proce-
dure are removed [24], but serious adverse events rarely occur after 25 min from the
final drugs administration [66].
Sedation scales modified for children are used to assure a safe discharge: the
University of Michigan Sedation Scale (UMSS) [67], the Dartmouth Operative
Conditions Scale [68], and the Modified Maintenance of Wakefulness Test-MMWT
[69] are the unique scales validated in children.
NORA requires specific criteria for the discharge of the patients, which should
be approved by local protocols. As general suggestion, we have to achieve different
requirements in case of inpatient or outpatient procedures.
Inpatients may not need a long stay in recovery room (some procedures are car-
ried out even at bedside), and clinical and multiparametric monitoring could con-
tinue at minor intensity in the ward. On the other hand, outpatients need to assess
discharge readiness before leaving the hospital. It is undeniable that a sedation scale
is a useful and simple measure to optimize recovery time.
However, additional elements in this decision should be considered. Several chil-
dren undergoing NORA are affected by neurological or respiratory diseases, and
recovery from anesthesia cannot be ensured by traditional scores; the surgical pro-
cedure can need a longer stay; outdoor logistics (home environment, distance from
medical center, etc.) are also to be considered. Discharge should be based on stan-
dardized criteria, but this general rule should be applied with flexibility. In any case,
it is mandatory that discharge process appears in the chart and that parents get clear
instructions in post-procedural care.
Depending on the procedure, cooperation between anesthesiologist and surgeon/
physician should be desirable at discharge. NORA is a field in rapid growth due to
increasing sensibility to pediatric pain and an increasing offer of diagnostic and,
particularly, therapeutic procedures that can enhance the standard of care: often
these need to be performed outside the operating room necessarily for logistic rea-
sons or preferably for economic motivations.
The increased availability of short-acting drugs along with accurate noninvasive
monitoring and improved sedation training (including simulation programs) has
enabled effective and safe management of sedation also outside the operating room
[70].
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Perioperative Care in Paediatric
Orthopaedic Surgery 7
A.U. Behr
7.1 Clinical Practice
7.1.1 Preoperative Evaluation in Orthopaedic Surgery
The orthopaedic paediatric patient includes all stages of development, from birth to
adolescence, and ranges from a normal healthy child to a child with multiple con-
genital malformations, neuromuscular diseases or metabolic disorders. Children
with cerebral palsy, dysmorphic syndromes, myelomeningocele, trisomy 21, autism
or other congenital or acquired development diseases offer several clinical chal-
lenges to the anaesthetist. The aims of preanaesthetic assessment are to identify the
most appropriate anaesthetic techniques for each case, to ensure the safety of peri-
operative care and an optimal use of resources and to improve the outcome and
patient satisfaction, while considering the individual and person-related risk factors
and circumstances. Many children in the orthopaedic setting are operated in day
surgery and the adequate preparation of the patients and their parents plays an
important role. The healthy child does not usually need any preoperative investiga-
tion or laboratory tests, but the situation changes significantly when congenital
abnormalities or familiar disorders are present. Children with developmental
disorders (Fig. 7.1) frequently experience complications such as seizures, dyspha-
gia or reactive airway diseases, and they need an interdisciplinary assessment for
optimal surgical outcome.
A.U. Behr
Istituto di Anestesia e Rianimazione, Azienda Ospedaliera Università, Padova, Italy
e-mail: astridursula.behr@gmail.com

DOI 10.1007/978-3-319-21960-8_7
88 A.U. Behr
Fig. 7.1 An 8-year-old

(12 kg) female affected by
osteogenesis imperfecta
7.1.2 Ambulatory Orthopaedic Surgery in Children
Ambulatory surgery is a somewhat lighter burden for health services, resulting in

considerable cost reduction and resource saving. Paediatric orthopaedic surgery seems
to be rarely done in an outpatient setting, mainly because of the postoperative pain,
which all parents fear. The anaesthetic management is challenging because young
children lack the ability to communicate pain, and analgesic need is often difficult to
determine. Therefore, provision of adequate postoperative analgesia and parents’ edu-
cation are important elements of the care plan. Inclusion criteria for ambulatory sur-
gery proposed by Khoury et al. [1] are summarised in Table 7.1. Parents must be
adequately informed on how to deal with cast, including possible complications. They
should be given written instruction and a staff contact number should be available as
well. Of the utmost importance is to provide the family detailed information about
postoperative pain management and consequences of regional anaesthesia. For exam-
ple, if the child undergoes a nerve block, parents should be aware of what is an accept-
able time for resumption of active motion. The most frequent orthopaedic ambulatory
procedures are cast change, arthroscopy, closed fracture reduction and manipulation,
hardware removal, percutaneous tenotomies and arthrograms.
7 Perioperative Care in Paediatric Orthopaedic Surgery 89
Table 7.1 Inclusion criteria Social and geographic factors

for orthopaedic paediatric
Surgery schedule compatible with day-care unit
ambulatory surgery
opening hours
Parents able to follow pain management and follow-up
instructions
Availability of a phone at home
Ability to return to hospital in less than 30 min
Surgical criteria
Surgery lasting <90 min
Minimal estimated blood loss or fluid shifts
(<10 % of total BV)
Few operative complications anticipated
Patient conditions
Child of >4 months of age if preterm or born at term if
ageing <4 months
ASA physical status classification I or II
Absence of apnoea syndrome
Adapted from Khoury et al. [1]
7.1.3 Preoperative Fasting and Premedication
Every child has to be treated individually and it is therefore difficult to establish

fixed rules regarding the perioperative anaesthetic management. For preoperative
fasting, the orthopaedic setting shares the same rules of any other surgical specialty,
but in this arena, trauma patients are frequent and the stomach of traumatised chil-
dren is assumed never to be empty. Nonetheless, it may be necessary to treat the
child as fast as possible, mandating for focused attention to advanced airway man-
agement. Preoperative anxiety may be reduced by premedication similarly to other
surgical settings, but non-pharmacological strategies are available as well. Indeed,
there is evidence that the viewing of animated cartoons by paediatric surgical
patients is an inexpensive, easy to administer, comprehensive intervention that can
be very effective in alleviating preoperative anxiety and “needle phobia” in this
special surgical population [2]. Furthermore, it may be useful to apply EMLA tapes
not only at the venous puncture site but also at the insertion site of the plexus or
nerve block.
7.1.4 Procedural Sedation
Anaesthetic services are commonly required for sedation during diagnostic proce-
dures, non-invasive treatment of fractures and other short but painful procedures.
Reposition or manipulation of a fractured limb without sufficient analgesia is inhu-
man, and, to some extent, it is comparable to severe personal injury. Closed reduc-
tion and cast immobilisation in the emergency department are usually eased by deep
sedation to reduce procedure-related stress.
90 A.U. Behr
Deep sedation for both emergent and elective orthopaedic procedures is associ-
ated with several, rare but potentially serious adverse events like apnoea or hypoten-
sion, which require continuous monitoring and several dedicated staff members [3].
Furthermore, in these cases, preoperative fasting is mandatory, and postprocedural
observation in adequate recovery area may be prolonged with relatively long time to
discharge. Performing an analgesic or anaesthetic nerve block (Fig. 7.2) of the inter-
ested area based on anatomical considerations results in lighter sedation, reduced
risks and shorter postoperative observation time. Indeed, the patients can be dis-
charged 2 h after uncomplicated procedures, even with persistent sensory block.
With regard to postoperative pain management, regional anaesthesia combined with
postoperative non-opioid analgesics, like paracetamol, NSAIDs, or weak opioid,
such as codeine or tramadol, are regularly used after ambulatory surgery.
Procedural sedation is also required for non-intrusive approaches for correction
of early-onset scoliosis. This treatment in infants and toddlers is based on sequen-
tial, repeated body cast positioning, which may initiate as early as at 4 months of
age. After the child is positioned on the frame, distraction and derotation of the
spine will be performed in general anaesthesia or deep sedation. Plaster application,
particularly around the hip, should allow bowel and bladder function, avoid skin
breakdown and permit access to epidural or perineural catheters. These infants and
toddlers with scoliosis, as well as other children with chronic diseases, present
repeatedly for surgical or diagnostic procedures and should be treated with particu-
lar sensibility and compassion. Indeed, even a single negative experience can indel-
ibly ruin patient and family attitude toward anaesthesia.
Fig. 7.2 US-guided

infraclavicular nerve block
for non-invasive treatment
of upper limb fracture
7.1.5 Intraoperative Positioning
Anaesthetists, surgeons and nurses are all responsible for the safe positioning of
surgical patients to prevent position-related complications. Paddings, pillows and
special jelly frames are required for achieving the best posture on the surgical bed
and to protect the patient against damage from inadvertent pressure ischemia. Nerve
injuries and skin pressure injuries result from poor positioning, with direct pressure
causing ischemia to that area. Spine surgery involving vertebral fusion and instru-
mentation often requires special operating tables and the patient in a prone position.
Special attention must be paid in these cases, because cardiovascular and respira-
tory functions may be compromised in this position. Body weight should be distrib-
uted unburdening the abdomen in order to minimise venous congestion, and direct
pressure on the eyeballs must be carefully avoided. The arms should not be abducted
or extended greater than 90° from the natural position, and the weight of the arms
should be evenly distributed across the forearm to avoid ulnar nerve compression at
the elbow. Positioning may be even more challenging in children with important
deformities and particular caution is warranted. The use of intraoperative radiologic
imaging is common, radioprotective barriers should be used, and radiation exposure
must be monitored by the anaesthetist, as well.
7.1.6 Intraoperative Warming
The detrimental effects of hypothermia include increased rates of wound infection,

increased blood loss and increased length of stay in recovery room and hospital.
Hypothermia exacerbates blood loss by decreasing platelet function, interfering
with coagulation factors’ activity and slowing vasoconstriction. Therefore, the mon-
itoring of patient’s core temperature is advisable, and several precautions help
maintaining normothermia in the perioperative period. They include active patient
warming using forced-air devices, the preservation of a comfortable temperature in
the operating room at least until the patient is positioned and covered and an ade-
quate warming of intravenous fluids and blood products before infusion [4].
Furthermore, some diseases, such as osteogenesis imperfecta or arthrogryposis
multiplex congenita, may be associated with altered baseline temperature regula-
tion. In these patients, core temperature monitoring is mandatory and special atten-
tion must be addressed to its perioperative maintenance (Fig. 7.3).
7.1.7 Tourniquet
Tourniquets are commonly used in surgery to establish and maintain a bloodless

surgical field, allowing the surgeon to work with greater technical precision and
safety. Nonetheless, the widespread use of tourniquets in orthopaedic surgery in
adults and children is not without risks, and the surgical literature includes numer-
ous reports of injuries and hazards associated with tourniquet overpressurization,
92 A.U. Behr
Fig. 7.3 A 6-year-old

male with intraoperative
forced-air warming
blankets
like pain at the tourniquet cuff site; muscle weakness; compression injuries to blood
vessels, nerves, muscles or skin and extremity paralysis. Underpressurization, vice
versa, may result in blood leakage in the surgical field and venous congestion of the
limb. Overall, the risk of tourniquet-related injuries can be reduced minimising
tourniquet inflation time, using automatic tourniquet instruments and cuffs that
allow accurate pressure delivery, control and monitoring and maintaining tourniquet
cuff pressure near the minimum level required to stop arterial blood flow in the
operated limb. Indeed, significantly lower tourniquet cuff pressures based on limb
occlusion pressure (LOP) and the use of wide contour cuffs can be used effectively
and safely in the paediatric population without compromising the quality of a blood-
less surgical field [5]. LOP is the minimal cuff pressure required to occlude arterial
blood flow into a patient’s limb with a specific tourniquet cuff at a specific moment.
LOP may be determined manually by slowly increasing tourniquet cuff pressure
until distal arterial pulsations cease at the Doppler stethoscope or with a recently
developed automated plethysmographic system. Previous studies in children showed
that tourniquet cuff pressures based on LOP measurements before cuff inflation
significantly decreased mean tourniquet cuff pressures and were sufficient to main-
tain a satisfactory surgical field [6]. Before tourniquet application, a flat rubber ban-
dage named Esmarch’s bandage will be wrapped repeatedly around the limb to
Table 7.2 Recommendations for pneumatic tourniquet use in paediatric limb surgery
1. Use the widest cuff suitable for the selected limb location, and use a contoured cuff able to
match the taper of the thigh
2. Select a limb protection sleeve specifically designed for the selected cuff. If such sleeve is
not available, apply two layers of elastic bandage sized such that its basal compression is
minor than venous pressure (≈20 mmHg) and less than a snugly applied cuff
3. Accurately apply the tourniquet cuff over the sleeve, avoiding fluid collection between the
cuff or the sleeve and the patient’s skin
4. Using the applied cuff, measure the LOP and set tourniquet pressure, respectively, 50, 75 or
100 mmHg above LOP for LOP < 130 mmHg, 131 < LOP < 190 mmHg or >190 mmHg. To
measure the occlusion pressure, use a plethysmographic tourniquet system or a Doppler
stethoscope. For manual measurement, locate an arterial pulse distal to the tourniquet, slowly
inflate the cuff until arterial pulse stops for several heartbeats, then deflate and confirm that the
pulse resumes. Measurement must be done once systemic blood pressure is stable at the level
expected during surgery. Note that the limb should remain horizontal and motionless
5. Exsanguinate the limb by elevation or elastic bandage
6. Inflate the tourniquet cuff and monitor the tourniquet during use
7. If arterial blood flow over the tourniquet cuff is observed, increase cuff pressure in
25 mmHg increments until flow stops
8. Minimise tourniquet inflation time
9. Remove the cuff and the sleeve of the tourniquet immediately after the deflation
Adapted from Reilly et al. [5]
make it bloodless, and a soft dressing will be applied to the limb at the tourniquet
site to avoid wrinkles and blisters (Table 7.2). Adequate exsanguination can also be
achieved by elevation of the limb at 90° or 45° for the upper or the lower extremi-
ties, respectively. Also the anaesthetic conduct may influence the effects of tourni-
quet application. In fact, both the continuous propofol infusion and regional
anaesthesia techniques attenuate lipid peroxidation and decrease tourniquet-related
injuries in paediatric limb surgery [7]. Also intraoperative temperature regulation
may be affected by tourniquet application owing to a combination of decreased heat
loss from the ischemic limb and a reduced heat transfer from the central to the isch-
emic peripheral compartment.
7.1.8 Blood Management
Paediatric patients undergoing major orthopaedic surgery are at risk of significant

intraoperative blood loss. The judicious use of blood transfusion is imperative both
because of limited blood bank supply and because transfusions can lead to various
complications. Awareness of infectious hazards of transfusion prompted a more
thoughtful approach to blood product administration, greater tolerance of asymp-
tomatic anaemia, more attention to medical, preoperative treatment of anaemia and
greater attention to surgical haemostasis. Whenever possible, a cost-effective
approach is based on the identification and treatment of preoperative anaemia, and,
in most circumstances, it can be accomplished with nothing more than oral iron
94 A.U. Behr
therapy. Fortunately, the amount of blood transfused for many surgical procedures
has decreased in recent years. A close observation (or surveillance) of the operative
field helps to estimate blood loss, while the monitoring of vital signs, haematocrit,
urine output and central venous pressure is valuable to assess the adequacy of vol-
ume replacement and are useful tools in blood-sparing strategies [8, 9].
7.1.8.1 Preoperative Donation of Autologous Blood

As the hazard gap between allogeneic and autologous transfusions narrows (the risk
of bacterial infection and mistransfusion are almost the same for the two alterna-
tives), a balanced appraisal of the beneficial and detrimental effects of both is appro-
priate. Importantly, autologous blood donation (ABD) should not be attempted in
children with significant ischaemic cardiac disease or in paediatric patients with an
active infection, because bacteria can contaminate the collected unit and overgrow
during storage. ABD should be discouraged before procedures for which RBC
transfusion is unlikely and in children with needle phobia and limited collaboration
capacity. Erythropoietin proved to be useful in a wide variety of patients, including
preterm infants, children on chemotherapy, children with renal failure and children
undergoing elective major reconstructive surgery, spine surgery, liver transplanta-
tion, cardiac surgery and Jehovah’s witnesses. Erythropoietin stimulates erythropoi-
esis by the bone marrow. Recommended is recombinant erythropoietin, 600 U/kg
sc, once or twice weekly, 3–4 weeks before surgery with supplementation of iron,
vitamin B12, vitamin E and folic acid oral supplementation. Coordination with the
haematology unit, blood bank and the primary patient care team is required to take
full advantage of this therapy, especially if ABD is programmed. Common practice
is to donate one unit per week, but the last unit should be donated at least 5–7 days
prior to surgery to allow plasma proteins to normalise, to restore intravascular vol-
ume and to allow adequate erythropoiesis so that the patient will not be anaemic on
the day of surgery. Banked units of autologous blood may be stored for 35–42 days
in the liquid state. Because of the risk of incorrect patient identification and possible
bacterial contamination, also autologous blood has to be transfused only if strictly
indicated.
7.1.8.2 Intraoperative Blood Recovery and Reinfusion

Acute normovolaemic haemodilution involves withdrawal of a calculated volume of
the patient’s blood after the induction of anaesthesia with simultaneous volume
replacement with crystalloid or colloid infusion. The patient’s own fresh blood is
carefully stored in a refrigerator and reinfused in the final phase of surgery. The two
major advantages of intraoperative haemodilution are the following: blood lost dur-
ing surgery has a low haematocrit and fresh, whole autologous blood is available for
transfusion.
Intraoperative red cell salvage (CS), i.e. the process of collecting shed blood dur-
ing surgery and reinfusing it to the patients, is often used as an effective blood
conservation strategy, and CS has been linked with reduced ABT. The blood recov-
ered from the surgical field will be washed, centrifugated and reinfused. In this way,
infectious and immunologic risks of allogeneic transfusion and the risk of
mistransfusion will be avoided. Intraoperative blood recovery compared with allo-

geneic blood transfusion proved cost saving and cost-effective also in paediatric
orthopaedic surgery [10]. Nonetheless, this CS is not widely used in paediatric
patients, probably because of the capital investment for the devices, the significant
costs of disposable parts and the need for a trained operator. CS may be particularly
useful to minimise allogeneic blood transfusion in scoliosis surgery, and it may also
be used in conjunction with preoperative autologous blood donation, further reduc-
ing the need for allogeneic RBC transfusions. The development of paediatric-sized
equipment should make this technique more widely used and more cost-effective
even in small children. Major contraindications to CS are infection or contamina-
tion of the surgical field, sickle cell disease and surgery for malignancies.
7.1.8.3 Antifibrinolytics
The fibrinolytic system is the most important antithrombotic mechanism that main-
tains vascular patency. Major surgery and trauma cause extensive tissue injury and
release large amounts of tissue activators (tissue plasminogen activator, kallikrein
and urokinase) leading to a shift from physiological fibrinolysis to hyperfibrinoly-
sis, which decreases clot stability and increases tendency to bleeding, leading to
coagulopathy, fibrinogen and clot factor consumption. Antifibrinolytic drugs reduce
fibrin degradation through inhibition of plasmin generation, therefore decreasing
surgical bleeding and the need for transfusion in adults and children [11]. Tranexamic
acid (TXA) is worldwide the most used synthetic antifibrinolytic agent. TXA has a
higher and more sustained antifibrinolytic activity in tissue (i.e. ten times stronger)
compared to ε-aminocaproic acid, and it is more effective at reducing postoperative
and total blood loss in spine surgery. The half-life of TXA is about 80–90 min in
patients with normal renal function, and for this reason, a maintenance infusion or
repeated administration is generally required to achieve an optimal haemostatic
effect. Dosage schemes are not based on pharmacokinetic studies, and there is a
large variability in initial loading dose, varying between 2 and 100 mg/kg and a
continuous infusion of 3–10 mg/kg/h. Our dosage scheme for paediatric population
is 50 mg/kg of intravenous TXA as loading dose (2 g max), followed by an infusion
of 5 mg/kg/h.
7.1.8.4 Transfusion Trigger

The “absolute” threshold for red blood cell transfusion is a controversial topic,
especially in the paediatric population. Most of the actual recommendations are
based on expert opinion or derived from adult studies, and, as observed in adults,
the trend in paediatric patients has been toward a lower absolute transfusion trig-
ger. As important as the preoperative preparation of the patient to optimise the Hb
level is the awareness that there is no universal trigger for the administration of
allogeneic blood products, and clinical decision must be based on the single
patient. In the absence of co-morbidities which compromise organ oxygenation or
limit the compensatory mechanisms for anaemia, Hb levels as low as 7 g/dL are
generally well tolerated and transfusion is recommended if the Hb is lower than
6 g/dL [12].
96 A.U. Behr
7.1.9 Postoperative Care
The absence of a family member, the strange environment, hunger, changes in body
temperature, the presence of peripheral venous access or a cast are factors that may
all contribute to increase the discomfort of the paediatric patient awakening from
anaesthesia. A recovery room that permits awaking in the presence of parents and
adequate pain control is essential in orthopaedic paediatric surgery. Caring for an
alert, calm and cooperative child reduces the workload for nurses in the recovery
room because children who are pain-free are less inclined to be uncooperative, and
it is less likely that they interfere with the operation site (Fig. 7.4), removing dress-
ings, drainage tubes or urinary catheters [13].
7.1.9.1 Pain Treatment

Acute perioperative pain in infants and children is still undertreated, although intra-
operative and postoperative analgesia significantly improved in the last decades.
Intense pain without adequate analgesia will not only cause unacceptable pain at the
time of intervention, it will also produce long-lasting pain memory and behavioural
disorders [14]. Orthopaedic surgery is one of the most painful and it is frequently
described to be more painful than expected. To counteract pain in the immediate
postoperative period in infants and children, an adequate multimodal pain therapy
concept must be implemented, and local or regional anaesthesia (Fig. 7.5) should be
performed whenever possible [15]. Acetaminophen (paracetamol) and NSAIDs are
the most common analgesics prescribed for moderate pain in orthopaedics and they
should be regularly administered after any painful intervention. Regular, round-the-
clock administration of these drugs decreases the need of opioid rescue, and their
intravenous administration assures the analgesic effect before the child is able to do
oral intake. Opioids should be given immediately and sufficiently whenever neces-
sary, and they may be administered by the intravenous, oral, transmucosal and trans-
dermal route. Long-term pain associated with limb-lengthening techniques, like the
Ilizarov frame, or paediatric oncologic orthopaedic surgery, may require oral intake
Fig. 7.4 Ilizarov frame in

a 9-year-old female
affected by Cornelia de
Lange syndrome
Fig. 7.5 Continuous

sciatic nerve block for pain
treatment in septic arthritis
of the ankle
of opioids after hospital discharge. Opioids may also be added to neuraxial anaes-
thesia through the epidural or spinal route for postoperative pain treatment.
Benzodiazepines provide sedative, anxiolytic and amnesic effect; they have no anal-
gesic properties but are synergic with pain medication when muscle spasm is a
component of pain.
Regional anaesthesia in children is an evolving technique with many advantages
in perioperative management compared with systemic analgesia. Indeed, the pro-
found analgesia delivered by regional anaesthesia provides ideal psychological con-
ditions for the recovering children and their family, reducing emergence agitation
and anxiety often present in the orthopaedic setting. Unfortunately, even for estab-
lished regional techniques, such as the caudal block, the evidence for procedure-
specific indications is not currently well defined [16, 17]. Nowadays, we are able to
use regional anaesthesia techniques in more than 80 % of orthopaedic procedures in
children. There is significant evidence on a transition from neuraxial to peripheral
nerve blocks in clinical practice. The main concern regarding single-shot nerve
blocks, even with adjuvant, is the limited duration of analgesia, which is usually
sufficient for a large number of orthopaedic procedures, but insufficient in many
cases of major surgery. Continuous peripheral nerve blocks (CPNBs) are one of the
most recent developments in paediatric regional anaesthesia, and it is a valuable
alternative to parenteral opioids or continuous neuraxial blockade for several types
of surgery [18, 19].
CPNBs proved superior to traditional opioid-based analgesia in terms of
improved analgesia with reduced sedation, nausea, pruritus and length of hospital
stay [20]. The multimodal pre-emptive analgesia involves the use of low concentra-
tion, motor-sparing blocks in conjunction with other analgesics such as opioids,
NSAIDs and acetaminophen. This technique aims to facilitate early ambulation by
providing excellent analgesia without accompanying motor weakness. Dadure dem-
onstrated that CPNBs are feasible in the paediatric setting and that in skilled hands
98 A.U. Behr
they promote prolonged analgesia in the majority of patients without major adverse
events. The most common minor adverse events are catheter-related mechanical
problems dominated by leakage of local anaesthetic around the catheter and cathe-
ter dislodgment [21]. Other minor adverse events are less common in CPNBs com-
pared to continuous epidural infusion.
CPNBs are indicated after major orthopaedic surgery in children, for complex
regional pain syndromes, for phantom limb pain prevention and for managing vaso-
spasm. Ropivacaine is the local anaesthetic most commonly administered in CPNBs,
and the doses for continuous infusion range from 0.2 to 0.4 mg/kg/h at a concentra-
tion of 0.2 %. Specific indications for continuous analgesic treatment include hip,
femoral, tibial and humeral osteotomies; traction of femoral shaft fracture; congeni-
tal foot or hand malformation; limb elongation; osteosynthesis and exostosis; toe,
hand or foot amputation; club foot repair; hallux valgus repair; chronic oncologic
pain but also painful physical therapy after knee and ankle arthrolysis or knee liga-
mentoplasty. Otherwise, painful rehabilitation and physiotherapy are other main
indications to catheter positioning, because only if pain is under control, good reha-
bilitation will be performed [22]. A significant advantage of CPNBs over single
injection nerve blocks is the ability to provide prolonged analgesia with relatively
low doses of local anaesthetics. Patient-controlled regional anaesthesia is feasible
also in paediatric patients, and it was demonstrated that patient-controlled regional
anaesthesia with boluses of ropivacaine 0.2 % provides adequate postoperative
analgesia with smaller doses of ropivacaine or levobupivacaine and lower total
plasma concentrations of local anaesthetics than continuous infusion [23]. Low
doses of local anaesthetics remain an important precaution for potential complica-
tions such as local anaesthetic systemic toxicity (LAST) and permit the use of these
devices even at home after hospital discharge.
7.1.9.2 Compartment Syndrome

Compartment syndrome is a condition in which increased pressure within a closed
compartment compromises tissue function and perfusion within that space. It occurs
most commonly in an osteofascial compartment of the leg or the forearm, but it may
occur in the upper arm, thigh, foot, buttock, hand and abdomen as well. The most
common cause of compartment syndrome is a trauma, usually when a fracture
occurred [24]. Acute compartment syndrome requires prompt diagnosis and man-
agement. Plaster cast immobilisation can cause compartment syndrome and pres-
sure sores. In case of persisting pain, the cast should be removed and the area
carefully examined. Delays in treatment can result in significant disability including
neurological deficit, muscle necrosis, amputation and death. Severe pain and par-
aesthesia are often reported as cardinal symptoms, but many authors consider these
symptoms unreliable, as they are subjective and variable. These symptoms are par-
ticularly difficult to assess at extreme ages or in patients with neurologic compro-
mise, and there is unconvincing evidence that PCA, opioids or RA might delay the
diagnosis of compartment syndrome. Main clinical signs are tense, swollen com-
partments, sensory loss and pulselessness of distal segments. Objective monitoring
may be the measurement of compartment pressure by needle or catheter, the
monitoring of tissue oxygenation by near-infrared spectroscopy (NIRS) or the dos-

age of serum creatine phosphokinase (CK) as an indicator of muscle necrosis [25].
High clinical suspicion, ongoing assessment of patients and compartment pressure
measurements are essential for early diagnosis. The outcome is related to the time
from diagnosis to fasciotomy, which allows tissue decompression and must be per-
formed within 8 h. Delay in diagnosis may be a concern of surgeons when plexus
blockade is performed in cases of fractures. It is important to highlight that com-
partment syndrome is one of the most painful experiences, and it cannot be masked
by opioids or other drugs or diluted concentrations of local anaesthetics used for
postoperative infusion. Nonetheless, it is nowadays inacceptable that the diagnosis
of compartment syndrome is made thank to children’s pain, especially when suffi-
cient diagnostic tools are available [26]. Importantly, surgeries at risk for develop-
ing compartment syndrome must be excluded from ambulatory paediatric
protocols.
7.1.9.3 Fat Embolism

Fat embolism (FES) has been rarely described in paediatric population, only case
reports and small series are published, but it could be a fatal event [27]. The classic
presentation includes neurologic abnormalities such as confusion, drowsiness, leth-
argy, convulsions, coma and hypoxia resulting from impaired respiratory function.
These manifestations usually arise 12–24 h after the injury. A petechial rash on
mucous membranes and skin, mainly of the thorax and neck region, often appears
later, but it could be absent in about 50 % of the cases. Minor symptoms of FES are
fever as high as 38.5 °C, decreased haematocrit, retinal changes and tachycardia.
Patients may show severe hypoxia progressing to acute respiratory distress syn-
drome (ARDS) with pulmonary hypertension. Diagnosis is primarily clinical, but
biological tests (serum lipase presence or elevation in urine or sputum, thrombocy-
topenia or blood coagulation disorders), echocardiography and imaging studies of
brain and chest are useful diagnostic tools. Respiratory failure often dominates the
clinical picture of FES and it represents the main cause of death for these patients.
Treatment is based on supportive pulmonary therapy and on other resuscitative
measures. Severe cases require mechanical ventilation and analgesia, fluids and car-
diovascular supportive therapy. Caution in mobilisation and an early fixation of the
fracture site are suggested to reduce the risk of FES. Despite its low incidence in
children, FES has to be suspected in all patients that show hypoxia and altered con-
sciousness after traumatic long-bone fracture or surgery.
7.1.9.4 Thromboprophylaxis
Venous thromboembolism (VTE) in children is a rare complication mainly because
of limited direct evidence in paediatric population. Besides, about 50 % of currently
available drugs are used unlicensed or off-label in these patients, reflecting the pau-
city of specific trials in children. Most recommendations are extrapolated from
adults, and there is evidence that such approach may, in many circumstances, be
inappropriate [28]. Rates of VTE associated with elective paediatric orthopaedic
procedures seem to have a total incidence of 0.05 %, ranging from 0.02 to 0.33 %
100 A.U. Behr
in the paediatric trauma population [29]. Spine or spinal cord injuries, pelvic frac-
ture and lower extremity fractures have an increased risk for VTE. Although rare,
VTE is associated with 2.2 % mortality rate, while thrombosis recurs in about 8 %
of the cases, and postphlebitic or postthrombotic syndrome occurs in 12–50 % of
the patients. Besides, hospital costs are increased and length of stay in hospital is
frequently prolonged. Interestingly, the development of a VTE is more frequently
related to patients’ co-morbidities, such as metabolic condition or syndrome, obe-
sity, complications of implanted devices, older age and admission as an inpatient,
more than to the kind of surgical procedure [30]. In addition to patients’ age, clini-
cians need to consider factors such as physical development, stage of puberty and
emotional and intellectual development. In absence of clear guidelines for VTE
prophylaxis in paediatrics patient, low dose of unfractionated heparin or low-
molecular-weight heparin combined with intermittent pneumatic compression may
be a good choice in selected high-risk patients.
7.2 Peripheral Paediatric Orthopaedic Surgery
Peripheral paediatric orthopaedic surgery is defined as any surgery on muscles, ten-

dons, bones or joints of children’s limbs from the ileum or scapular to toes or fingers.
Ambulatory surgery may be possible in appropriately selected patients undergoing a
limited number of procedures, but frequently the anaesthetist have to take into account
major orthopaedic surgery with intense postoperative pain. Children with skeletal
abnormalities repeatedly present for orthopaedic procedures and often had previous
experience of operating rooms (Fig. 7.6). Prophylactic, systematic and multimodal
approach for pain control including regional anaesthesia assures high quality of post-
operative analgesia. Regional anaesthesia is very useful in case of peripheral surgery
in children, and it is generally performed in combination with general anaesthesia or
deep sedation. This combination permits to reduce anaesthetic requirements. Most of
Fig. 7.6 Preprocedural

scan for sacral plexus
block in stump regulation
after leg amputation in a
13-year-old female with
Charge syndrome
the anaesthetic agents produce a dose-related decrease in cardiorespiratory mechanics

and central ventilatory control, particularly in neonates, infants and young children.
The reduction of MAC offers several advantages including avoidance of airway
instrumentation, and respiratory assistance is not usually required. Therefore, regional
anaesthesia reduce the need for muscle relaxants, opioids and hypnotics; it allows
smoother and more comfortable emergence, reduced wake-up times, more rapid dis-
charge from recovery and earlier return of appetite. Importantly, RA will decrease the
risks associated with deeper planes of general anaesthesia. Regional anaesthesia pro-
vides profound analgesia for orthopaedic surgery with minimal physiological pertur-
bations and side effects. Spinal, epidural and peripheral nerve blocks are effective in
obtunding the neuroendocrine stress response to surgical trauma, avoiding autonomic,
hormonal, metabolic, immunologic, inflammatory and neurobehavioral conse-
quences. Stress hormones (epinephrine, norepinephrine, adrenocorticotropic hor-
mones, cortisol, prolactin) and blood glucose levels are lower following regional
anaesthesia than after general anaesthesia, independently from opiate analgesia, and
this occurs also when the central or regional block is placed at the end of surgery.
Regional anaesthesia is an effective alternative to systemic analgesics, particularly
when systemic opiates are contraindicated, such as in children at risk of opiate-
induced respiratory depression (acute) or in patients that have become tolerant to their
analgesic effects (chronic pain). General anaesthesia supplemented with pre-emptive
regional anaesthesia produces better operating conditions and reduced risks of surgi-
cal blood loss in children, and this may contribute to shorter operating time. Wound
infiltration with local anaesthetic has additional beneficial effects on the inflammatory
response and stimulates the activity of natural killer cells. Single-shot blocks are lim-
ited by the duration of the local anaesthetic agent used. However, with the recent
development and application of continuous peripheral nerve catheters, prolonged
analgesia is possible. The decision to intubate the trachea or to use a supraglottic
device like a laryngeal mask should be based on the usual criteria, such as a full stom-
ach, intraoperative positioning, need to maintain adequate ventilation and the expected
duration of the surgical procedure. If indicated, the trachea should be intubated before
the block is performed. The difficult airway is not uncommon in children and the
laryngeal mask may be an invaluable alternative. Various types of supraglottic devices
(Fig. 7.7) are widely used for securing and maintaining a patent airway in orthopaedic
surgery as an alternative to tracheal intubation in patients requiring general anaesthe-
sia or very deep sedation. The main advantages of these devices include less or no
need for muscle relaxation and the need for lower doses of anaesthetic drugs.
Furthermore, these airway devices are less invasive and are applicable also in sponta-
neously breathing anaesthetised patients. The supraglottic devices can be inserted also
if the space is limited and in children with head and neck vascular malformations.
Pierre-Robin, Treacher-Collins, Goldenhar, cri-du-chat syndromes, and mucopoly-
saccharidoses are examples of conditions that have been successfully managed with
these devices in different paediatric surgical settings. This approach avoids excessive
airway instrumentation, minimises the risk of trauma and further airway obstruction
due to bleeding or oedema, circumvents the “can’t intubate, can’t ventilate” scenario
and can also act as a conduit to facilitate flexible fibreoptic bronchoscopy for
102 A.U. Behr
Fig. 7.7 Insertion of i-gel

mask for airway
management
diagnostic or interventional purposes and to aid tracheal intubation [31]. The i-gel
airway, an innovative supraglottic non-inflatable device made of a medical-grade ther-
moplastic elastomer (soft, gel-like and transparent), assures a high success rate of
correct positioning at the first attempt, a short median insertion time, good oropharyn-
geal sealing pressure, ease of gastric tube placement and rare postoperative complica-
tions, like blood staining and sore throat. It seems to be safe, efficient and cost-effective
[30, 32], and it may be extremely popular in children undergoing minor therapeutic
and diagnostic procedures or short orthopaedic surgery not requiring controlled ven-
tilation with muscle relaxants, like surgery of the upper and lower limbs.
7.2.1 Upper Limb
All kinds of upper extremity surgery can be managed with brachial plexus blockade,
but these cases are still frequently managed in general anaesthesia in most of the
institutions because of interdisciplinary and other organisational reasons. Forearm
fractures and supracondylar humeral fractures are frequent findings in the paediatric
emergency department, and they may require close reduction or open surgery.
Closed reduction and cast immobilisation are usually facilitated by deep sedation of
the paediatric patients. A variety of techniques have been used to induce analgesia
in children with closed fractures requiring manipulation, including haematoma
block, Bier block (intravenous regional anaesthesia) or peripheral nerve blocks [33].
Each technique has related advantages and disadvantages and the choice must be
tailored on each child. Nonetheless, regional nerve block during manipulation has
several benefits such as the significantly reduced need for sedation and systemic
opiate analgesia, with less nausea and emesis. Motor blockade provides good mus-
cle relaxation and makes the manipulation easier and faster. PNBs have a good
safety profile, particularly with the use of ultrasound guidance, and provide better
pain control in the postoperative period. Importantly, if the surgeon has to change
strategy and convert to open reduction, the anaesthesia is just done and the surgeon
can switch to open osteosynthesis. The duration of analgesia depends on the type of
administered local anaesthetic, and it may last as long as 6 to 8 hours with long-
acting agents like ropivacaine and levobupivacaine.
Elective surgery of the upper limb in paediatric orthopaedics includes correction
of hand disorders like polydactyly, syndactyly and upper limb function and restora-
tion for life care in arthrogryposis like humeral elongation, shoulder arthroscopy in
the adolescent, humeral osteotomy, resection and treatment of tumours of the
cephalic end of the humerus or upper extremity amputation.
All upper extremity blocks may be performed also in children, and in the recent
Pediatric Regional Anesthesia Network (PRAN), it was found that most upper
extremity blocks (82 %) were placed using US guidance [19]. Interscalenic block in
paediatric orthopaedic surgery is less frequently adopted in clinical practice com-
pared to the adult patients, because it is indicated only in case of shoulder luxation,
shoulder arthroscopy in the adolescent, fracture of the proximal humerus and treat-
ment of rare oncological pathologies. The surgical procedures below the mid-
humeral level can be managed with axillary, infraclavicular or supraclavicular
approaches. Infraclavicular and supraclavicular approaches are particularly recom-
mended in patients with injured or fractured arm in order to avoid painful arm
abduction. The supraclavicular approach is preferred because of the easily identified
sonoanatomy, the ability to perform the block with a single injection and the low
incidence of significant complications, but it is imperative to perform it with US
guidance to avoid complications, such as pneumothorax and intravascular
injection.
7.2.2 Lower Limb
Foot, ankle and long-bone osteotomies for correction of congenital or acquired

lower limb abnormalities in children (Fig. 7.8) are common orthopaedic procedures.
Regional anaesthesia in paediatric patients really improved in recent years, thanks
to technical development, the availability of new equipment and increased informa-
tion on the safety and pharmacology of local anaesthetics in children and infants.
Caudal blocks, lumbar epidural and spinal anaesthesia are the neuraxial techniques
applied as single or continuous injection in infants and children for surgery of the
lower limb and the pelvis. Central neuraxial block in young children is character-
ised by remarkable hemodynamic stability, and clinical hypotension is seldom
observed in children younger than 8 years of age [34]. Unlike in adults, in children,
the adoption of ultrasound for central nerve blocks is increasing in clinical practice.
Without considering the better resolution for more superficial structures that is gen-
erally observed in children, the very limited ossification of bony structures allows
good visual resolution of central neuraxial anatomy, perception of the inserted nee-
dle and the spread of injected solutions [35]. Few, small studies proved that there
may be benefits from ultrasound guidance, but there is still insufficient evidence.
Ultrasound imaging during and/or before performing neuraxial block may reliably
104 A.U. Behr
Fig. 7.8 Hardware removal after pelvic osteotomy acc. Salter and femoral varus derotation oste-
otomy in a 4-year-old female (16 kg)
predict the expected depth for loss of resistance, and it may enable dynamic view
during the procedure. For unilateral lower limb surgery in adults, alternatives to
epidural analgesia are CPNBs, and they probably represent the gold standard for
postoperative analgesia after major unilateral surgery. CPNBs are associated with a
reduced incidence of side effects when compared with epidural analgesia, and
anaesthesia is restricted to the involved area [36]. In adults, the use of CPNBs is
increasing in parallel with the evidence for their efficacy. In some meta-analyses,
postoperative analgesia provided with perineural analgesia was superior to opioids
at all time periods and for all catheter locations [37]. Unfortunately, there is extreme
paucity of medical literature regarding feasibility, safety and efficacy of continuous
nerve blockade in the paediatric population. Benefits for children include, even if
performed in general anaesthesia, site-specific analgesia, reduced side effects, early
discharge from hospital and significant reduction in healthcare resource utilisations
[38]. The use of ultrasound guidance is recommended for increasing the success and
safety of both single and continuous peripheral nerve blocks.
The lumbar plexus or psoas compartment block (PSCB) is useful for hip, thigh,
femur and knee surgery (Fig. 7.9). This plexus of nerves travels between the dorsal
and the intermediate portion of the psoas muscle and comprises the ventral rami of
the first four lumbar roots, frequently including a branch of T12. These spinal nerves
divide into ventral and dorsal branches as the plexus runs distally. Relevant nerves
derived from this plexus include femoral, lateral femoral cutaneous and obturator
nerves. The use of PSCB in experienced hands combined with general anaesthesia
is considered a safe technique for open hip reduction and osteotomies for hip dys-
plasia in small children, and it is considered superior to single-shot caudal block for
postoperative analgesia [39]. Compared to epidural anaesthesia, PSCB is associated
with significantly less adverse events and lower total ropivacaine doses and plasma
concentration [40]. A valid and more simple alternative for postoperative pain treat-
ment in pelvic osteotomy may be a catheter surgically placed in the fascia iliaca
compartment with subsequent continuous fascia iliaca block infusing larger vol-
umes of local anaesthetics at lower concentrations [41].
Fig. 7.9 US-guided

continuous PSCB for hip
surgery
More distal types of peripheral surgeries below the knee level, such as leg frac-
ture and foot surgery, like club foot surgery, mostly require saphenous or femoral
(FN) and sciatic nerve (SN) blocks. For anterior knee procedures like knee arthros-
copy, an FN block may be sufficient (Fig. 7.10). However, consideration should be
given to adding an obturator nerve (ON) block for coverage of the medial aspect of
the knee, while lateral femoral cutaneous nerve (LFCN) blockade is advisable
when the lateral aspect of the knee is involved. Similarly, the SN should be blocked
when surgery involves the posterior aspect of the knee, such as in the case of ante-
rior cruciate ligament repair when hamstring allograft is performed. FN block has
been used to provide analgesia for femur fractures in paediatric patients. However,
surgical repair of femur fractures usually requires an incision within the distribution
of the LFCN. Ultrasound-guided LFCN and FN block have been reported in paedi-
atric patients for postoperative analgesia following surgical repair of femur
fractures.
Many complications in infants and non-verbal children are difficult to diagnose
for impossibility to describe their symptoms accurately. Nevertheless, the incidence
of serious complications detected in the PRAN study was extremely small, and no
sequelae lasting >3 months were reported. Problems such as catheter dislodgement,
106 A.U. Behr
Fig. 7.10 US-guided femoral nerve block for knee arthroscopy
kinking and malfunction were especially common, accounting for one-third of all
postoperative adverse events, suggesting that devising better methods of placement
and fixation should be a high priority. This study confirmed the reduced performance
of neuraxial anaesthesia in favour of peripheral nerve blocks for lower limb surgery
in recent years. Peripheral regional anaesthesia proved effective in paediatric patients,
and it was burdened with less complications and adverse events. Most of these pro-
cedures were performed with ultrasound guidance augmenting procedural safety.
7.3 Scoliosis Surgery
Currently, scoliosis is defined as lateral deviation of the normal vertical line of the spine
greater than 10° when measured on a radiograph. Because the lateral curve of the spine
is associated with rotation of the vertebrae, a three-dimensional deformity occurs.
Procedures involving the spinal column and surgery for scoliosis repair became com-
mon in the paediatric age group during the last decades and provide a multitude of
challenges to the anaesthetist. Spinal deformities requiring orthopaedic surgical inter-
vention may be the result of congenital, acquired or traumatic conditions. Children
often present concomitant diseases that affect the cardiovascular and respiratory func-
tion. Operating time may be protracted, significant blood loss is possible and strategies
for blood sparing and blood product management are warranted. Surgical procedures
on the paediatric spine may involve one or several vertebral levels with an incision at
any level of the vertebral column (cervical, thoracic, lumbar, sacral). Further variations
include an anterior approach, a posterior approach or, in the case of thoracic and lum-
bar spine procedures, a combined anteroposterior procedure (Fig. 7.11).
The magnitude of the scoliotic curve is commonly measured using the Cobb
method. Measurement is made from an anteroposterior radiography, identifying all
the vertebrae involved within the curve. The apical vertebra is the one with the
Fig. 7.11 Measurement of scoliosis curve using the Cobb method in a 10-year-old female with
idiopathic scoliosis before and after spinal surgery (Images courtesy of D.A. Fabris Monterumici,
Spine Surgery Unit, University General Hospital, Padua, Italy)
greatest body rotation and displacement from the ideal alignment. The top and bot-
tom vertebrae of the curved or scoliotic segment are then identified. These vertebrae
have the most evident tilt but the least degree of rotation and displacement. They are
located above and below the apical vertebra, respectively. A line is drawn along the
edge of these two vertebrae and extended out. On the top vertebra, the line is drawn
along the upper edge and slopes downward according to the angle of the vertebra.
On the bottom vertebra, the line is drawn along the lower edge in an upward direc-
tion. Perpendicular lines are then drawn from both lines so that they cross at the
level of the apical vertebra. The Cobb angle is the angle formed by these two inter-
secting lines, and if it exceeds 40°, surgery will be frequently indicated. Vertebral
rotation and rib cage deformity usually accompany any lateral curve [42]. There are
various classifications of scoliosis, but from an anaesthetic perspective, the etiologic
classification is more useful. Two main etiological groups of paediatric scoliosis
exist: neuromuscular scoliosis (NMS) secondary to a wide range of underlying
108 A.U. Behr
pathologies such as cerebral palsy, Duchenne muscular dystrophy, spinal muscular

dystrophy, Friedrich ataxia, Marfan syndrome or osteogenesis imperfecta, and idio-
pathic scoliosis (IS), a genetically modulated growth abnormality, which tends to be
more common in girls. While the latter is a diagnosis of exclusion, the former has
defined criteria and subgrouping, of which cerebral palsy is the most common form.
Children with scoliosis of early onset (<5 years) or with independent cardiac or
pulmonary diseases appear to have increased risk of respiratory failure. Vertebral
rotation and rib cage deformity result in distortion in the thorax and can cause
restrictive lung defect, with restriction of lung volume and function for impaired
movement and reduced compliance. In the long term, this may lead to hypoxemia,
hypercarbia, recurrent lung infections and pulmonary hypertension. Spinal instru-
mentation for the treatment of scoliosis is performed when conservative treatment
measures have failed to arrest the progression of the spinal curvature (Fig. 7.12).
Patients with NMS are often younger and sicker at the time of surgery. In addition,
the skeletal deformity is usually more severe and extended than in patients with
idiopathic disease. Children with NMS add mechanical distortion to deteriorating
muscle function, and the natural history of the specific neuromuscular disease must
be considered. In these children, respiratory complications are five times more com-
mon than in patients with IS. Furthermore, pneumonia, pulmonary oedema and
upper airway obstruction are more common when scoliosis is associated with
Fig. 7.12 The same patient with IS before and after spine surgery (Images of D.A. Fabris
Monterumici, Spine Surgery Unit, University General Hospital, Padua, Italy)
mental retardation and developmental delay. Among these patients, those with cere-
bral palsy have the highest complication rate [43, 44].
Surgery for scoliosis correction is a major undertaking associated with signifi-
cant blood loss and cardiac and pulmonary complications related to the effects of
the patient’s distorted anatomy. Important preoperative variables are pulmonary
function, Cobb angle and number of fused vertebra, which may predict the outcome
of the immediate postoperative period. In some medical centres, patients are admit-
ted to the intensive care unit following scoliosis surgery because of the prolonged
anaesthesia, the need for efficient pain control and the known immediate postopera-
tive complications, which are most commonly pulmonary (atelectasis, pneumotho-
rax), gastrointestinal (paralytic ileus) and infective, although the most feared and
unpredictable are the neurological complications. A relationship between intraop-
erative blood loss and postoperative complications was established; ICU admission
for patients with one or more of the above-mentioned complications is probably
justified, but it may be unnecessary in many patients. Co-morbidity, the time of day
and staffing level on the orthopaedic ward should also be taken into account.
Especially in elective paediatric spine deformity surgery, many efforts should focus
on minimising allogeneic blood transfusion. The estimated blood loss (EBL) is
60–150 ml per vertebral segmented fused in children with IS. In children with cere-
bral palsy, this estimation is significantly higher, ranging from 100 to 190 ml per
level while it may reach 200–280 ml per vertebral level in children with DMD. Factors
implicated in the increased blood loss include neuromuscular aetiology, degree of
spine curvature, number of fused spinal segments, weight and height of the patient,
surgical complexity including reoperation and more complex anteroposterior
approach or lumbosacral fusion, coexisting pulmonary disease, intraoperative arte-
rial blood pressure control and dilution coagulopathy [45, 46].
A large-bore intravenous access with a fluid warmer and an arterial line for inva-
sive blood pressure and arterial blood gases monitoring must be routinely applied.
A central line should be placed if massive blood loss is expected (e.g. >1 blood
volume) or if vascular access is limited. The long preparation time and exposure of
an undraped child on the spinal frame may predispose to hypothermia and require
additional effort for maintaining normothermia for optimal clotting and hemody-
namic stability. It will be useful to position a warming blanket underneath the frame
so that warming from below occurs. Some spinal table or frame may negatively
impact cardiac function, and correct positioning without abdominal compression is
important to minimise venous congestion and intraoperative bleeding (Fig. 7.13).
Direct control of bleeding via mechanical occlusion and topical haemostatic agents
may be blood sparing as well. Routine complete blood count, electrolytes and clot-
ting studies must be performed during surgery. Consumption of clotting factors as
well as dilution of clotting factors enhances the blood loss. Normal saline, autolo-
gous blood recovery and transfusion of blood and fresh frozen plasma must be given
according to estimated blood loss, intraoperative blood test results and hemody-
namic status. Patients treated with TXA lost significantly less blood and received
significantly fewer blood transfusions than the control group without significant
differences in intra- and postoperative complications. Controlled hypotension with
110 A.U. Behr
Fig. 7.13 Intraoperative prone position for posterior approach in spine surgery
a targeted mean arterial pressure of 50–60 mmHg is recommended. The use of remi-
fentanil enabled better achievement of permissive hypotension during surgery,
shorter operation times and early postoperative spontaneous ventilation with
reduced need for ICU hospitalisation and no increase in significant complications.
In a retrospective analysis (25 years) of paediatric patients undergoing elective sco-
liosis surgery at the Mayo Clinic [47], a significant change in blood management
strategies was observed with lower transfusion trigger, a significant increase in allo-
geneic RBC transfusion and a significant increase in preoperative autologous dona-
tion and intraoperative autotransfusion. Although the patients had worse baseline
co-morbidities and lower perioperative Hb level, they did not observe any increase
in morbidity or mortality.
Early detection of spinal cord injury during surgery requires intraoperative spinal
cord monitoring with neurophysiologic monitoring of the motor evoked potentials
(MEPs) end somatosensorial evoked potentials (SSEPs). Utility of wake-up test,
consisting in decreasing the depth of anaesthesia almost to awaking and asking the
child to respond to verbal commands, is limited by the fact that it may be conducted
a significant time after neurologic insult and delay the correction of the spinal instru-
mentation; it is less specific and it may be performed only in neurologically normal
children. Somatosensory and motor evoked potentials are useful to record, but they
request specific anaesthetic regimen with monitoring of anaesthetic depth by bispec-
tral analysis (BIS) [48]. Although inhalational anaesthetics and most intravenous
anaesthetics markedly depress SSEPs and MEPs, ketamine and etomidate seem to
enhance the amplitude of both, possibly by attenuating inhibition. During MEP mon-
itoring, neuromuscular blockade must be limited, and in many centres, neuromuscu-
lar blocking drugs are not given after intubation, initial incision and muscle dissection,
especially if children suffered preoperative neuromuscular dysfunction.
Extubation criteria are the commonly accepted: awake, calm and cooperative
patient, hemodynamic stability, negative inspiratory force >20 cm H2O, respiratory
rate <30 min, PaCo2 < 50 mmHg and PaO2 > 70 mmHg with FiO2 < 0.4. No active
bleeding from the operative site or from the drains. Relatively young and healthy
children with IS operated on propofol and remifentanil and fused posteriorly can be
successfully managed in a regular ward in the postoperative period. Postoperative
visual loss in spine surgery is extremely rare, but it remains a dreaded complication
despite significant efforts to identify risk factors and a pathophysiological mecha-
nism. The vast majority of cases are related to ischemic optic neuropathy [49].
Spinal fusion surgery for correction of scoliosis is considered one of the most
invasive procedures performed in paediatrics. Because of the significant length of the
surgical incision and the degree of bony and soft tissue dissection, there may be sig-
nificant postoperative pain, and if it is not treated adequately, it may contribute to
chronic postsurgical pain. In many cases, the experience of pain is relatively transient
and declines predictably over time with recovery from surgery, while in other cases,
pain persists for several months engendering problems in everyday functioning.
Currently, there is an increasing trend toward the use of pre-emptive multimodal
analgesia as well as a significant interest in the application of regional anaesthetic
techniques as a means of controlling pain following spine surgery in children using
intrathecal or epidural single-shot or catheter technique [50]. Effective analgesia is
generally best provided using a pre-emptive multimodality approach, which includes
analgesic agents (paracetamol, NSAIDs, ketamine and opioids), anxiolytic agents
and medications to control muscle spasms. Muscle spasms may be particularly prob-
lematic in patients with underlying cerebral palsy. Options for the provision of anal-
gesia include also the use of patient-controlled analgesia (PCA). Although young
patients or those with developmental disabilities may not be able to activate the
device, nurse-controlled or parent-controlled analgesia may be provided. Using the
device in this manner, the bedside parent or nurse has ready access to a supply of
opioid to provide an immediate rescue dose. Importantly, prior to instituting PCA, an
appropriate level of analgesia must be achieved by careful opioid titration. This is
generally done in the operating room on completion of the surgical procedure. A
choice may be fixed doses of intravenous paracetamol every 6 h, administration of
NSAIDs at fixed intervals and PCA with morphine.
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Perioperative Care of the Pediatric
Neurosurgical Patient 8
Massimo Lamperti
The improvement in diagnosis, treatment, and outcome in infants and children treated
for neurosurgical procedures has increased in the last years due to the new technologies
available for neuromonitoring, standardized protocols for anesthesia maintenance,
improved postoperative acute care, and highly specialized anesthesiologist taking care
of these patients. The anesthesiologist taking care for neurosurgical patients has to keep
in mind that neurological diseases are often long-term diseases and their management
has to include since the beginning patients’ families, psychologists, and an integrated
social care system as these diseases can be associated with mild to severe disabilities.
The developing brain of a child has specific aspects to be considered such as age-
dependent differences in anatomy, metabolism, cerebrovascular physiology, and
locations of neurologic lesions. The perioperative management of children undergo-
ing neurosurgical procedures is based on the acknowledgments of the differences on
the pediatric neurophysiology, the neurosurgical procedures, and treatment of
related complications.
8.1 Neurophysiology of the Pediatric Brain
8.1.1 Cerebral Blood Flow
Cerebral blood flow (CBF) varies with age. CBF of newborns and premature infants
is lower than adults (40–42 ml 100 g−1 min−1), while in term infants and older children,
values become higher than in adults. From 6 months to 3 years, the CBF is thought to
be 90 ml 100 g−1 min−1 and from 3 to 12 years at 100 ml 100 g−1 min−1 [1, 2].
M. Lamperti, MD
Anesthesiology Institute, Cleveland Clinic Abu Dhabi (CCAD), Swing Wing L7-207,
P O Box# 112412, Al Maryah Island, Abu Dhabi, United Arab Emirates (UAE)
e-mail: LamperM@ClevelandClinicAbuDhabi.ae

DOI 10.1007/978-3-319-21960-8_8
116 M. Lamperti
8.1.2 Brain Energy Metabolism
The brain requires large amounts of energy to maintain its cellular integrity and sup-
port neurotransmission. The pediatric brain has a higher glucose consumption
(6.8 mg of glucose per 100 g−1 min−1) compared to an adult brain (5.5 mg per 100 g
100 g−1 min−1). The brain has no reserve of glucose to face this large requirement.
Glucose is stored as glycogen and enters the glial cells (mostly astrocytes) using a
facilitated ATP Na + −K+ transport system. This membrane transport system is lim-
ited by its kinetic constant, and the amount of glucose transported into the astrocytes
actually decreases when the plasma glucose level increases. This could provide
some protection to the brain tissue against excessive intracellular hyperglycemia in
the normal brain. However, the glucose transport system could be altered in case of
brain injury leading to hyperglycemia and secondary brain tissue damage. As a
consequence a tight glycemic control is mandatory to prevent and treat the injured
brain [3, 4].
8.1.3 Cerebral Oxygen Metabolism
With the only exception of the glomic cells in the carotid body, the brain is the organ
with the highest rate of oxygen consumption. It is 3.5 ml O2 × min−1 × 100 g−1 in
adult and 5.5 ml O2 × min−1 × 100 g−1 in children. When this is compared with the
overall oxygen consumption rate of the body (0.3 ml O2 × min−1 × 100 g−1), it is
more evident why the brain is very sensitive to hypoxia. Most of the oxygen con-
sumption in the brain is used to maintain cellular integrity and electrogenesis and
sustain cellular transport mechanism such as reuptake of neurotransmitters. When
the supply of oxygen decreases, electrogenesis is impaired and quickly ceases.
Cerebral autoregulation and cerebrovascular reactivity are impaired and the neuro-
nal integrity is jeopardized. In the presence of hypoxia, ion pump impairment pre-
vents normal membrane repolarization and leaves the neuron in a constant refractory
state. Neuronal integrity is initially maintained, and if oxygen supply is restored,
neuronal function resumes rapidly (zona pellucida). With ongoing lack of oxygen,
however, neuronal viability and integrity deteriorate with increasing duration of
hypoxia (zona penumbra). In this brain tissue area, neuronal damage will become
irreversible if hypoxia persists at normothermia.
8.1.4 Arterial Carbon Dioxide/Oxygen Tension (PaCO2/PaO2)
Arterial PaCO2 has a major vasodilatory effect on cerebral blood vessels, leading to
an increase in CBF, which is linear between a PaCO2 of 3.5 and 8 kPa. At birth, the
cerebrovascular response to changes in PaCO2 is incompletely developed. For this
reason, moderate hypocapnia has mild effects on the newborn brain compared to
adults and CBF has only moderate changes until severe hypocapnia occurs. Brain
ischemia due to hypocapnia is thought to be caused by the effect of pH and CO2 on
8 Perioperative Care of the Pediatric Neurosurgical Patient 117
cerebral vascular tone. The association between hypocapnia and clinical adverse
outcome in various studies in adults and children has resulted in the advice to apply
therapeutic hypocapnia only after careful consideration of the risks and the potential
benefits. Special attention should be given to avoid accidental hypocapnia [5].
Capnography is standard in anesthesia monitoring and to prevent hypo- and
hypercapnia. It is of crucial importance to be aware of the limitations of the end-
tidal measurement of carbon dioxide (ETCO2) in the neonate and small infants.
Although the ETCO2 value is in general lower than the corresponding PaCO2 value,
in some patients, the ETCO2 overestimates PaCO2. The frequent evaluation of the
capillary or arterial blood CO2 trend is mandatory for the prevention of clinical
hypocapnia in long procedures, major surgery, and compromised neonates.
The cerebral vasculature of adults is less sensitive to changes in PaO2 and CBF
does not increase until PaO2 decreases below 50 mmHg, when it increases exponen-
tially. In neonates, CBF is more sensitive to hypoxia and increases even in response
to smaller decreases in PaO2 [6].
8.1.5 Blood Pressure and Cerebral Autoregulation
The lower limits of cerebral autoregulation in neonates are not precisely known, and
there is likely a wide range of variability in infants. Several studies have shown that
the lower limit of cerebral autoregulation for some infants is indeed fairly close to the
definition of hypotension using the infant’s age in gestational weeks although there is
also evidence that some premature infants are able to demonstrate cerebral autoregu-
lation at a MAP level considerably lower than their gestational age in weeks [7, 8].
Vavilala et al [9] found that in infants older than 6 months of age undergoing a sevo-
flurane anesthesia, the lower limit of cerebral autoregulation for mean arterial pressure
(MAP) was found to be 59 mmHg, which was 11 mmHg lower than baseline blood
pressures. The lower limit of cerebral autoregulation of older children was also found
to be 60 mmHg, but was 22 mmHg lower than baseline blood pressures. A study of
children younger than 2 years undergoing sevoflurane anesthesia found that in infants
<6 months of age, the lower limit of autoregulation occurred at 38 mmHg or a 20 %
decrease from baseline awake MAP [10]. In contrast the same authors found that, in
infants older than 6 months, the lower limit of autoregulation did not occur until blood
pressure had decreased 40 %. These studies demonstrate that infants have less cere-
bral autoregulatory reserve and may be at the risk of inadequate cerebral perfusion
following a decrease in blood pressure after anesthetic induction.
Inadequate perfusion from hypotension can lead to partial asphyxia. Most gen-
eral anesthetics are associated with some degree of hypotension, which can be ame-
liorated by surgical stimulation. Prolonged inductions or surgical preparation times
may lead to prolonged periods of hypotension in neonates. Ideally, general anesthe-
sia should decrease cerebral metabolic rate and thus decrease the need for intraop-
erative neuronal substrate. However, it is not known whether common volatile and
intravenous general anesthetics, which are gamma-aminobutyric acid (GABA)
receptor agonists, lead to a lowered cerebral metabolic rate in young infants.
118 M. Lamperti
The difficulties of anesthetizing young infants can be compounded by inaccurate

blood pressure monitoring. It is essential to assure a proper noninvasive blood pres-
sure monitoring during induction and maintenance or before an invasive arterial
monitoring is placed.
8.1.6 Intracranial Pressure
The Monro-Kellie doctrine states that the skull is a closed box containing the brain,
blood, and cerebrospinal fluid (CSF). An increase in volume of one of these compo-
nents, with an increase in intracranial pressure (ICP), will result in a compensatory
reduction in the other components to counteract the change. In the infant, before
cranial suture fusion, decompression can occur through an increase in skull size.
The posterior fontanelle closes at about 6 months of age, and the anterior fontanelle
at around 12–18 months. The final cranial suture closure may be as late as 10 years
old. Increases in intracranial volume can only be accommodated if the change is
gradual. Acute increases, such as after traumatic brain injury, will still result in
raised ICP as in adults.
The infant may not demonstrate signs typically associated with intracranial
hypertension, because the cranium can substantially expand in response to an
expanding intracranial brain mass or process causing hydrocephalus, before coming
to clinical attention. Early in the course, infants and young children often do not
exhibit the traditional signs of intracranial hypertension such as bradycardia, ele-
vated systemic blood pressure, dilation of the pupils, and papilledema. If present,
these signal severe progression with poor outcomes. Neonates and infants may pres-
ent with increased head circumference, bulging fontanelles, widened cranial sutures,
“sundowning” of the eyes, irritability, drowsiness, poor feeding, or lower motor
deficits.
8.1.7 Brain and Inflammation
The brain was thought not to be involved in the inflammatory processes. New
studies suggest that in traumatic brain injury [ 11] subarachnoid hemorrhage
[12], a severe cerebral inflammatory reaction, is activated. Systemic inflam-
matory reactions affect the brain while cerebral inflammatory processes lead
to significant systemic effects. Cerebral ischemia and reperfusion injury are
the main causes of brain damage because of the inflammatory reactions they
start.
Currently, there is no clinical evidence to suggest that direct inflammatory modu-
lation reduces the incidence of mortality or morbidity in patients affected with a
cerebral insult [13]. The secondary effects of an inflammatory reaction such as
hypoxia, hypotension, hyperthermia, and hyperglycemia are known to induce sec-
ondary brain injury and should be prevented.
8.1.8 Pediatric Electrophysiology
Children develop different pathological conditions from adults that are often age
specific. The electroencephalogram (EEG) recording is different in children than
adults because the brain, meninges, skull, scalp, head size, and the child’s behavior
and ability to cooperate all change over time.
Therefore, pediatric EEGs must be recorded and interpreted with special atten-
tion given to the child’s age and developmental level. An EEGer must be aware of
normal age-specific characteristics. For example, the normal pediatric EEG activity
has more variation than the adult EEG. Focalities are not always abnormal but lack
of change between states is abnormal in infants. As EEG varies greatly by age, its
interpretation needs to be conceptually age specific [14–17].
8.1.9 Anesthesia and Neurotoxicity
Data supporting anesthetic neurotoxicity have been presented more than 10 years
ago [18, 19]. Researchers found that exposure of developing rodents to ethanol, a
known N-methyl-D-aspartate (NMDA) receptor antagonist and gamma-
aminobutyric acid (GABA) receptor agonist, during a critical period of develop-
ment resulted in widespread neuroapoptosis of the central nervous system [20].
Most anesthetic agents were studied for their potential negative effects via these
receptors. Further studies tried to confirm the potential role of general anesthetics in
neurodegeneration [21] and long-term deficits in developing monkeys [22–24]. The
histologic changes induced by anesthetics exposure not only damage neurons but
even oligodendrocytes [22].
Although there are evidences, it should be almost impossible to extrapolate those
results to humans as any randomized controlled trial would deserve ethical conse-
quences if the same methods should applied in neonates and children. All studies
reported in the literature on general anesthetics’ neurotoxicity in children are retro-
spective. Most studies supporting the association between neurocognitive outcome
and exposure to anesthetics showed hazard ratios less than 2 [25–28]. At the current
time, retrospective human data remain hypotheses generating, rather than conclu-
sion generating.
8.2 Perioperative Management
8.2.1 Preoperative Assessment
The preoperative assessment of the pediatric neurosurgical patient includes under-

standing of the underlying neurological pathology and a thorough assessment of
any coexisting diseases, medications, intravascular volume status, and anesthetic
history.
120 M. Lamperti
Children with brain tumors can have a variety of signs and symptoms that may
affect the conduct of anesthesia such as drowsiness, lethargy, seizures, cranial nerve
palsies, focal muscle weakness, hypothalamic-pituitary axis hormonal deficiencies,
nausea, and vomiting.
Intracranial hypertension should be kept great consideration, as it can become a
life threatening during induction and early phases of the anesthesia. Intense crying or
screaming or fighting can cause significant elevations in ICP. Premedication with oral
midazolam has shown significant benefits with no respiratory depression or change in
PaCO2. Opioids may produce respiratory depression and should be used with caution in
patients with elevated ICP. Ketamine should be avoided in patients with elevated ICP
as it increases both cerebral blood flow (CBF) and cerebral metabolic rate.
The intravascular blood volume could be contracted because of poor intake or
recurrent vomiting. Children may have abnormal airways because of associated cra-
niofacial abnormalities. Pediatric patients have a higher risk for perioperative respi-
ratory and cardiovascular morbidity and mortality than adults [29].
8.2.2 Induction
Infants and children without intravenous access will undergo inhalational induction.
As volatile anesthetics can increase in CBF, it is important to support or control the
ventilation to prevent the PaCO2 increase and offset the rise in CBF. Non-depolarizing
neuromuscular blocking agent could also be administered to facilitate endotracheal
intubation and prevents the increase of ICP.
Patients with lethargy or nausea and vomiting are at risk for aspiration of gastric
contents and will benefit from a modified rapid sequence induction technique.
8.2.3 Monitoring
Intracranial surgery may be associated with sudden cardiovascular changes and the
potential for rapid blood loss. Routine monitoring includes capnography, pulse
oximetry, electrocardiography, temperature, and invasive arterial pressure. Urethral
catheterization and the measurement of urine output are necessary for prolonged
procedures and especially those associated with diabetes insipidus or the require-
ment for mannitol. A central venous catheter (CVC) provides large-bore access and
allows for central administration of vasoactive drugs and potentially treatment of
venous air embolism (VAE). Readings can be unreliable in small children in the
prone position but trends may be useful.
Precordial Doppler ultrasonography could be useful for VAE detection.
Neurophysiological monitoring may be utilized with the aim to improve out-
come and reduce morbidity by early detection of neurological injury at a point when
damage can be limited or reversed. In brief, the modalities for monitoring include
EEG, somatosensory evoked potentials (SSEPs), motor evoked potentials (MEPs),
and transcranial Doppler (TCD).
8.2.4 Positioning
Proper position of the patient for pediatric neurosurgical procedures is imperative to

ensure both patient safety and comfort. Most patients undergoing neurosurgery are
in a supine position. The flexion of the neck may result in downward migration of
the endotracheal tube or occlusion of jugular venous drainage, causing cerebral
venous hypertension and increased intracranial volume and pressure. The prone
position raises the risk of eye injury from direct ocular pressure and hypoperfusion.
The park-bench position is utilized for lateral or midline incisions and when quick
access to the patient is needed. Appropriate padding and stabilization is required to
prevent stretch, ischemia, and pressure injury to the axilla as well as other parts of
the body. The sitting position requires careful attention to padding pressure points
as well as securing the patient on the bed to ensure patient safety and surgical
stability.
8.2.5 Maintenance of General Anesthesia
Maintenance of anesthesia commonly is accomplished with a balanced anesthetic

technique of opioids, volatile anesthetic, and neuromuscular blockade. Volatile
anesthetics may significantly blunt cerebral autoregulation in a dose-dependent
manner by producing cerebral vasodilatation and exacerbate intracranial hyperten-
sion. Inhalational anesthetics also alter the evoked potentials that are used in neuro-
logical monitoring. These agents are typically avoided or used at low concentration
of 0.5 MAC or less.
Infusions of short-acting opioids such as sufentanil or remifentanil can provide
adequate intraoperative analgesia and rapid emergence, permitting postoperative
neurological assessment. A remifentanil infusion commenced at the induction of
anesthesia can readily be titrated to response and avoids the hypotension and brady-
cardia associated with boluses of remifentanil in children. Remifentanil usually
obviates the need for repeated doses of neuromuscular blocking agents.
Total intravenous anesthesia (TIVA) with propofol may be used in older chil-
dren, but its widespread use in younger children has been limited due to the original
weight restrictions on target controlled infusion devices.
Dexmedetomidine can be used as an adjunct. It does not significantly affect most
intraoperative neurophysiologic monitoring and reduces opioid requirements.
Neuromuscular blockade is typically used unless the case requires intraoperative
assessment of motor nerve function, as in spinal cord or epilepsy surgery.
8.2.6 Fluid Management
Glucose-containing and hypotonic solutions should not be used in pediatric patients.

Hyperglycemia worsens reperfusion injury, and hypotonic infusions increase cere-
bral edema. However, the dangers of hypoglycemia particularly in the neonate or
122 M. Lamperti
ex-premature infant should be considered and blood glucose monitored closely. The
commonly used isotonic crystalloids are Ringer’s lactate and 0.9 % sodium chlo-
ride. Excessive quantities of normal saline can result in hypernatremia and hyper-
chloremic metabolic acidosis. For these reasons, electrolytes and blood glucose
should be monitored especially during long procedures.
Blood loss can be difficult to assess during craniotomies due to constant oozing
onto the surgical drapes and irrigation. There is a potential for sudden and drastic
losses, so cross-matched blood should always be available. Transfusion of 10 ml/kg
of packed red blood cells increases hemoglobin concentration by 2 g/dl. Pediatric
patients are susceptible to dilutional thrombocytopenia in the setting of massive
blood loss and multiple red blood cell transfusions. Administration of 5–10 ml/kg of
platelets increases the platelet count by 50,000–100,000/mm3. The routine use of
the antifibrinolytic agent, tranexamic acid, in surgical procedures with excessive
blood loss, such as posterior spine fusions and craniofacial reconstructive proce-
dures, has been shown to decrease blood loss in pediatric patients [30].
8.2.7 Body Temperature
Mild hypothermia (34–35 °C) decreases in CMRO2 and may help to attenuate raised
ICP. However, it is essential to appreciate the complications of hypothermia (e.g., dis-
ordered coagulation), the importance of normothermia for adequate emergence from
anesthesia, and the time required to rewarm even a mildly hypothermic child, espe-
cially an infant. Fluid warmers, warm air devices, and heated mattresses are required.
8.2.8 Venous Air Embolism (VAE)
VAE is a major risk in patients in sitting position or in those with the head of bed
significantly elevated. Continuous precordial Doppler ultrasound allows early
detection of a VAE and normovolemia minimizes this risk. In case of VAE produc-
ing significant reduction of the ETCO2 and hemodynamic instability, the operating
table must be placed in the Trendelenburg position to prevent further embolism of
intravascular air. Significant rotation of the head can also impair venous return
through a compression of the jugular veins. However these measures can reduce
cerebral perfusion, increased intracranial pressure, and venous bleeding. Special
risks exist in neonates and young infants as right-to-left cardiac mixing lesions can
result in paradoxical emboli.
8.2.9 Postoperative Care
Postoperative care is determined by the complexity of the surgical procedure and

the physiologic alterations that may occur during the operative course. Generally
extracranial procedures usually need routine postoperative care.
Intracranial procedures and other major neurosurgical cases may require postop-
erative care in the pediatric intensive care unit (PICU).
In the past, many clinicians avoided morphine analgesia due to the side
effects of vomiting, sedation, and its potential effect on pupil size. However,
strong opioids provide effective analgesia without increase in complications.
Acetaminophen is usually started intraoperatively and continued regularly after
operation.
8.3 Main Postoperative Complications
8.3.1 Hyponatremia
Hyponatremia is the most common electrolyte disturbance in patients undergoing

neurosurgery. Severe hyponatremia may result in brain swelling and the symptoms
reflect its effects on the central nervous system. Initial symptoms may include head-
ache, nausea, and vomiting; as hyponatremia worsens, mental confusion, seizures,
stupor, and coma may develop.
Hyponatremia of neurosurgical patients is often associated with a syndrome of
inappropriate antidiuretic hormone secretion (SIADH) or with the salt-wasting
brain syndrome (SWS). The differential diagnosis between these two clinical condi-
tions is essential, since treatment strategies are completely different.
Patients with SIADH need fluid restriction of approximately 70 mL/100 kcal
and may need furosemide and/or increased sodium supply due to an excess ADH
secretion. Volume replacement with an isotonic solution and increased sodium
supply are mandatory in the salt-wasting syndrome to prevent severe
dehydration.
8.3.2 Diabetes Insipidus
The removal of brain lesions in the suprasella could affect the pituitary function and
impaired the ADH secretion. The reduced secretion of ADH causes hypernatremia
due to intravascular volume depletion, polyuria, and dehydration. This complication
usually occurs within the first postoperative hours, when the urine output is higher
than 3 ml/kg/h. Patients with diabetes insipidus typically present hypernatremia
(Na > 150 mEq/L), urinary sodium levels below 20 mEq/L, and dehydration.
Treatment is based on the administration of intranasal or intravenous
desmopressin.
8.3.3 Hyperglycemia
This complication can be not uncommon in neurosurgical patients [31] and must be
treated although it is not related to a worse outcome.
124 M. Lamperti
8.3.4 Brain Edema
Surgical manipulation of the brain and nervous tissues may cause perilesional
edema in several grades, impacting the postoperative clinical symptomatology.
There is lack of evidence warranting a benefit of systemic corticosteroid to reduce
brain edema. Corticosteroid adverse effects, such as hyperglycemia, infection, and
slow wound healing, are well known.
8.4 Perioperative Prophylaxis
Perioperative antibiotic prophylaxis by intravenous administration reduces the risk

of surgical wound infection, although there is no consensus on short or extended
time protocol [32]. Postoperative seizure prophylaxis is still debated. The current
consensus is to continue the antiepileptic drugs if the patient had seizures before the
neurosurgical intervention. There is no evidence on the prophylactic use of antiepi-
leptic drugs in patients with brain tumors, and the use of these drugs is highly related
to an increased risk of adverse events [33].
8.5 Main Neurosurgical Conditions in Pediatric Patients
8.5.1 Hydrocephalus and Shunt Procedures
The need for CSF drainage can be caused by an acute or chronic mismatch in cere-
bral fluid content circulation and related increase in ICP. CSF can be diverted com-
monly from cerebral ventricles to the peritoneal cavity or the right atrium. In some
cases, if the CSF circulation is altered by an endoventricular problem, an endo-
scopic third ventriculostomy could be sufficient.
The main problem related to shunt procedures is heat conservation related to a
large skin exposure especially in neonates. Fluid and body warmers and a strict core
body temperature monitoring are mandatory in these patients.
8.5.2 Brain Tumors
Brain tumors are the most common solid tumor of childhood. Two-thirds of them
arise infratentorially. The anesthetic implications of posterior fossa pathology
include an increased likelihood of raised ICP due to CSF outflow obstruction and a
higher occurrence of postoperative airway problems due to perioperative compro-
mise of brainstem respiratory centers and lower cranial nerve function. The hemo-
dynamic response to laryngoscopy and fixation of the head in pins may lead to a
detrimental increase in ICP that should be attenuated by a potent opioid such as
remifentanil.
A reinforced tracheal tube is recommended to aid positioning airway from the

surgical field and avoid kinking associated with positioning and surgery duration. A
throat pack aids in stabilizing the tube position.
Most patients require postoperative monitoring in a high dependency units or
PICU to detect early changes in consciousness and neurological impairment.
8.5.3 Epilepsy Surgery
Medically intractable seizures have now several possible surgical options such as
insertion of vagal stimulator, craniotomy for resection of epileptic foci, or hemi-
spherectomy. Perioperative anesthetic considerations have to deal with develop-
mental delay, perioperative seizures, and coexisting diseases. Intraoperative
neurophysiologic monitoring useful for surgical removal of the epileptic foci can be
impaired by volatile anesthetics. Nitrous oxide can precipitate pneumocephalus
after a recent craniotomy (up to 3 weeks later) and should be avoided until after the
dura is opened.
Awake craniotomy offers the advantage of allowing EEG mapping intraopera-
tively, minimizing unnecessary tissue resection, but this is usually possible only
when children are mature and psychologically prepared to participate in this par-
ticular procedure. In the “sleep-awake-asleep” technique, the patient undergoes
general anesthesia for the surgical exposure. The patient is then awakened for
functional testing, and general anesthesia is recommenced when patient’s col-
laboration is not anymore necessary. Most cooperative patients will tolerate
sedation with propofol or dexmedetomidine. Propofol does not interfere with
EEG, if it is discontinued 20 min before monitoring in children undergoing an
awake craniotomy [34]. Supplemental opioids are administered to provide
analgesia.
Cerebral hemispherectomy techniques for medically intractable seizures have
changed in the last decade, with a trend from anatomic (total) toward minimally
invasive functional resections [35]. Significant intraoperative blood loss and hemo-
dynamic instability of both techniques have an impact on the anesthetic manage-
ment of these patients [36].
8.5.4 Craniosynostosis Repair
Craniosynostosis is the premature fusion of one or more cranial sutures. Single-

suture craniosynostosis usually occurs in otherwise healthy children. Multiple
suture disease often occurs also as part of a craniofacial syndrome such as Apert’s,
Crouzon’s, or Pfeiffer’s.
Techniques for cranial remodeling are varied and involve removal of the skull
vault by the neurosurgical team followed by refashioning by plastic or maxillofacial
surgeons.
126 M. Lamperti
Manipulation of the skull vault alters the skull shape to promote uniform growth
in sagittal and coronal planes. The management of more complex multiple suture
craniosynostosis with craniofacial anomalies has to be referred to tertiary centers.
Anesthetic management of craniofacial surgery has to consider the following
aspects:
1. Blood loss: surgery for correction of these malformations has to be scheduled in

a period of physiological anemia between 2 and 6 months. Bleeding comes from
scalp wounds and bones, making it difficult to quantify accurately as it is hidden
in surgical sponges. Blood products are invariably required perioperatively
according surgical technique used. Tranexamic acid has been recently shown to
attenuate massive blood loss and has been administered in surgical procedures
associated with massive blood loss [37].
2. VAE: the patient is at risk during retraction of the scalp over the orbital ridge as
the scalp veins are at an upper level than the right atrium. The current monitoring
for VAE in neonates and children is precordial Doppler.
3. Oculocardiac reflex: profound bradycardia may result from orbital manipulation.
It usually responds to removal of the stimulus and administration of antimusca-
rinic agents.
4. Airway: surgery below the orbital ridge is associated with excessive facial edema
and may involve the use of a rigid extraction device frame. This may present the
anesthesiologist with problems at the initial and subsequent surgeries.
5. Positioning: this will vary for individual procedures; particular care is needed
around the eyes and to guard against excessive neck extension/flexion.
8.5.5 Congenital Spinal Lesions
Failure of the neural tube to close during the first trimester results in a disease spec-
trum ranging from spina bifida occulta to anencephaly.
The most common conditions presenting for neurosurgical correction are lumbo-
sacral meningoceles. If posterior herniation includes neural structure (myelomenin-
gocele), the distal neurological function is often severely impaired.
These defects require correction within the first few days of life to minimize
bacterial contamination and sepsis. Main aspects in surgery for neural tube defects
repair are:
1. Surgery in the first days after birth.

2. Bleeding: if a skin grafting is required, there may be a need for blood
replacement.
3. Positioning: care must be taken to minimize pressure on the cystic structure,
leading to further damage or rupture. Induction of anesthesia may be carried out
in the lateral decubitus or more commonly supine, with a ring-shaped sponge to
support and relieve pressure from the herniation. Surgery is conducted in the
prone position, and particular care is required to avoid abdominal compression
and venous congestion of the operating site.
4. Latex allergy prevention: children with myelodysplasia have an increased risk of
latex allergy and a latex-free environment is mandatory.
8.5.6 Vascular Malformations
The primary goal of anesthetic management during cerebrovascular surgery is to

optimize cerebral perfusion while minimizing the risk of bleeding. Large arteriove-
nous malformations (AVMs) may be associated with high output congestive heart
failure requiring vasopressors during general anesthesia. Hypertensive crisis after
embolization or surgical resection of the AVMs should be rapidly treated with vaso-
dilators as sodium nitroprusside.
These lesions are often managed by combined neurointerventional and neurosur-
gical approach, which start with endovascular occlusion of the lesion followed by
surgical resection and ending with a postoperative angiography.
Management of patients with Moyamoya syndrome is targeted to optimize cere-
bral perfusion with aggressive preoperative hydration and maintaining normoten-
sion or mild hypertension during surgery and the postoperative period.
Intraoperative normocapnia is essential because both hypercapnia and hypocap-
nia can lead to steal phenomenon from the ischemic region. Intraoperative EEG
monitoring may be utilized during surgery to detect cerebral ischemia. Optimization
of cerebral perfusion should be extended into the postoperative period by maintain-
ing euvolemia and maintaining sedation and analgesia in the PICU to prevent hyper-
ventilation induced by pain and crying.
8.5.7 Neuro-Endoscopy and Anesthesia
Children undergoing third ventriculostomy surgery will be positioned in a Mayfield

headrest. Warmed Ringer’s lactate fluid is used to irrigate the operating site; mea-
suring the volume of fluid infused and drained is imperative to avoid rapid increases
in ICP. Hypertension, arrhythmias, and neurogenic pulmonary edema have been
reported in conjunction with acute intracranial hypertension.
Conclusions
A comprehensive anatomical and physiological acknowledgment of pediatric
brain function is essential to allow the anesthesiologist to maintain a balance in
brain metabolism during anesthesia for neurosurgical procedures.
A specific training and a dedicated team of anesthesiologist, neurosurgeons,
and nurses for those patients are crucial not only for perioperative management
but also to create a special environment for children and their families.
128 M. Lamperti
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2. Mackersie A (1999) Paediatric neuroanaesthesia. Balliere’s Clin Anaesthesiol 13:593–604
3. Feinendegen LE, Herzog H, Thompson KH (2001) Cerebral glucose transport implies indi-
vidualized glial cell function. J Cereb Blood Flow Metab 21:1160–1170
4. Weir CJ, Murray GD, Dyker AG et al (1997) Is hyperglycaemia an independent predictor of
poor outcome after acute stroke? Results of a long-term follow up study. BMJ
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5. Curley G, Kavanagh BP, Laffey JG (2011) Hypocapnia and the injured brain: evidence for
harm. Crit Care Med 39:229–230
6. Krane EJ, Phillip BM, Yeh KK, Domino KB (1986) Anaesthesia for paediatric neurosurgery.
In: Smith RM, Mototyama EK, Davis PJ (eds) Smith’s anaesthesia for infants and children, vol
2006, 7th edn. Mosby, Philadelphia, pp 651–684
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have reduced cerebral blood flow. Pediatrics 114:1591–1596
8. Tyszczuk L, Meek J, Elwell C et al (1998) Cerebral blood flow is independent of mean arterial
blood pressure in preterm infants undergoing intensive care. Pediatrics 102:337–341
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12. Chyatte D, Bruno G, Desai S et al (1999) Inflammation and intracranial aneurysms.
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13:523–528
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102:727–732
Pain After Surgical Correction
of Congenital Chest Wall Deformities 9
Robert Baird and Pablo M. Ingelmo
9.1 Pectus Excavatum
9.1.1 Background
This most common chest wall deformity involves posterior encroachment of the
sternum and lower costal cartilages. While the precise incidence remains subjective,
as many as 1–2 % of individuals may be affected, with boys typically presenting
more frequently. In most instances, patients are asymptomatic and chiefly con-
cerned with their cosmetic appearance; rarely, cardiopulmonary function may be
compromised by the constraints of the chest wall. Some patients will have associ-
ated musculoskeletal conditions – Marfan and Loeys-Dietz syndrome are classic
examples that should be ruled out when clinical suspicions arise [1].
The preoperative assessment of patients with PE involves a complete history and
physical exam, paying particular attention for stigmata of an inheritable musculo-
skeletal condition. Patients should also be screened for metal allergies whenever an
implant is expected. In addition, a CT scan for objective measurement of the defect
and pulmonary function tests and echocardiography are standard evaluations in
R. Baird, MDCM, MSc, FRCSC, FACS (*)

Department of Pediatric Surgery, MUHC, Montreal Children’s Hospital, McGill University,
e-mail: robert.baird@mcgill.ca
P.M. Ingelmo
Department of Anesthesia, Montreal Children’s Hospital, MUHC, McGill University,
e-mail: pablo.ingelmo@mcgill.ca

DOI 10.1007/978-3-319-21960-8_9
132 R. Baird and P.M. Ingelmo
Fig. 9.1 CT scan of a

patient with severe PE
(Haller Index of 7) as
well as significant
sternal tilt
most high-volume centers (Fig. 9.1). Finally, a preoperative visit with the anesthe-
siology team is crucial to review perioperative pain-control strategies.
9.1.2 Surgical Technique
The standard approach to repair of PE is the thoracoscopic-assisted Nuss procedure.

Championed by Dr. Nuss and the team from Virginia, this procedure involves the
transthoracic insertion of a metal bar with affixation to the lateral chest wall [2, 3].
Briefly, after surgical marking and prophylactic antibiotic administration, oblique
skin incisions are made in the anterior axillary line at the point of deepest sternal
depression (typically T5–6). A second small incision is then made in the right chest,
and a port is inserted into the thoracic space followed by gentle insufflation and
insertion of a thoracoscope. A tunneler is then use to dissect from lateral to medial,
entering the chest just medial to the ridge above the point of maximal depression.
Once intrathoracic, the tunneler is then gradually advanced under direct vision
above the pericardium until the opposite chest is reached. Once brought through,
heavy suture material is affixed to both the tunneler and the chosen bar – after it has
been bent to shape. The tunneler is then slowly withdrawn, bringing the suture and
Nuss bar with it. Once the Nuss bar is in position, it is then flipped, immediately
correcting the deformity. Care is then taken to ensure the bar is adequately secured
to the lateral chest – a stabilizer is typically used on one side. Pneumothorax is then
ceased, air is allowed to egress from the chest, and wounds are closed in layers.
An alternative technique for repair of PE involves an open approach to remove
abnormal costal cartilages, performance of a wedge osteotomy to elevate the ster-
num, and insertion of a retrosternal strut to maintain the reconfigured sternum in
place. This modified Ravitch repair continues to have applications in patients with
stiff chest walls or those that have had prior attempts at a chest wall reconstruction.
It remains the procedure of choice for some surgeons [4].
9 Pain After Surgical Correction of Congenital Chest Wall Deformities 133
9.1.3 Analgesic Considerations
Comparative studies have suggested that the Nuss procedure is associated with
increased postoperative pain compared with the modified Ravitch procedure [5–7].
Nonetheless, no differences have been noted in patient satisfaction or overall out-
comes between the two groups [8]. In both cases, the length of hospitalization is
typically dictated by the ability to adequately achieve effective analgesia. A recent
large multi-institutional observational study has demonstrated that pain typically
crescendos at 8/10 (median) during hospitalization and improves to 3/10 before
discharge with a variety of different analgesic techniques [9]. Importantly, this
cohort of patients demonstrates improved body image and perceived ability for
physical activity after surgery [10].
Three main options exist for early postoperative pain relief: thoracic epidural
(TE), patient-controlled analgesia (PCA), and a continuous paravertebral nerve
block (PVNB). Elective repair of pectus excavatum is an ideal indication for
placement of a TE catheter – a recent global survey of 108 pediatric institutions
revealed that 91 % of respondents used thoracic epidurals as the primary mode of
analgesia [11]. While these allow for sparing systemic narcotics, concerns remain
about rare but devastating complications like paraplegia [12]. Older prospective
trials comparing epidural catheters with intravenous PCA have demonstrated
equivalency in pain relief and length of stay [13, 14]. This has resulted in several
centers publishing their preference for PCA, especially given the significant
number of patients with failed epidurals [15, 16]. A recent randomized trial of
110 patients receiving either epidural or PCA revealed a 22 % failure rate for
epidural and an increase in resource utilization for epidural patients with only
modest differences in very early pain scores compared to PCA patients [17]. A
subsequent meta-analysis of available literature confirmed a small improvement
in pain scores through to 48 h after surgery, without significant differences in
secondary outcomes [18].
Thus, it is currently unclear whether epidural or PCA is the optimal analgesic
strategy given the apparent small benefit but small increased risk associated with
epidural. An attractive alternative is a continuous paravertebral nerve block –
potentially marrying the improved analgesia of an epidural without the increased
risk [19]. Two recent retrospective comparisons of PVNB to standard epidural have
suggested equivalent efficacy without the need for urinary catheterization [20, 21].
Clearly, further prospective evaluations of PVNB for pectus excavatum repair are
required prior to widespread adoption.
Chronic pain after Nuss procedure remains a rare but devastating consequence
after an elective operation. Twenty-two percent of anesthesiologists responding to a
survey on the subject disclose referring at least one patient per year for chronic pain
treatment [11]. The true rate of chronic pain after Nuss procedure is difficult to
ascertain as is it not commonly reported in surgical reports. Every effort must be
taken to adequately treat early postoperative pain with multimodal therapy in order
to avoid the transition to long-term pain. Should this occur, dedicated treatment in a
pain clinic should be considered mandatory.
9.2 Pectus Carinatum
9.2.1 Background
This deformity is generally believed to be less common than pectus excavatum,

with centers reporting PC to be half as common as PE [22]. The deformity is
manifest as overgrowth of the cartilaginous costo-sternal junctions. The deformity
can be symmetric or asymmetric and occasionally involves protrusion of the
manubrium as well. It is associated with other musculoskeletal conditions only
very rarely and an extensive workup is typically unnecessary. Unlike PE, the treat-
ment of choice for PC has rapidly become compression bracing. While reports of
corsets and other binders have been in existence for many years, the modern era
of bracing began with the description of dynamic compression bracing from Dr.
Martinez-Ferro in Argentina [23]. This device gradually reduces the anteroposte-
rior chest dimension while allowing room for lateral expansion. It (or variations
of it) has been widely adopted and has made the operative repair of PC much less
frequent [24]. Nonetheless, a subset of patients either desire immediate or delayed
correction while others fail compression bracing and subsequently undergo
surgery.
9.2.2 Surgical Techniques
Pectus carinatum is traditionally treated by the Ravitch procedure [25]. This involves
excision of multiple offending costal cartilages followed by one or several osteoto-
mies to achieve an appropriate chest contour. Typically, a large dissection is required
and a closed-suction drain is left in the operative field and only removed once the
output decreases. More recently, a “reverse Nuss” has been described. Also known
as the Abramson based on its originator, a Nuss bar is passed in front of the defor-
mation and secured under tension to the lateral thoracic wall in order to retract the
protrusion [26]. This technique has shown promise; however further studies are
required before it can be considered generalizable.
9.2.3 Analgesic Considerations
The Ravitch procedure is generally considered to be less painful than the Nuss pro-
cedure [5–7]. As a consequence, less effort has been placed in investigating analge-
sic strategies in the perioperative period. Although the reporting is incomplete,
Fonkalsrud et al. report a series of Ravitch procedures without epidural placement
and minimal analgesics required at the time of discharge to hospital [27]. For
patients undergoing the “reverse Nuss,” the most appropriate analogous operation is
the Nuss and not the Ravitch. As such, the debate about thoracic epidural versus
PCA versus the emerging option of PVNB is highly relevant. Further investigations
will be required to evaluate this patient subset in further detail.
9 Pain After Surgical Correction of Congenital Chest Wall Deformities 135
Conclusions
The correction of a chest wall deformity is very often a pivotal moment in the life
of an adolescent. It is a decision designed to enhance a patient’s quality of life
and self-esteem; the pain associated with this choice should never be underesti-
mated or minimized. Multiple options remain available to the conscientious cli-
nician and ongoing research efforts will continue to clarify optimal analgesic
options that best balance patient comfort with procedural risk. Ultimately, the
choice of pain-control strategy should be based on patient and parental desires
and past experiences, as well as individual and institutional practice patterns.
References
1. Kelly RE (2008) Pectus excavatum: historical background, clinical picture, preoperative evalu-
ation and criteria for operation. Semin Pediatr Surg 17(3):p181–p193
2. Nuss D et al (1998) A 10-year review of a minimally invasive technique for the correction of
pectus excavatum. J Pediatr Surg 33(4):545–552
3. Kelly RE et al (2010) Twenty-one years of experience with minimally invasive repair of pectus
excavatum by the Nuss procedure in 1215 patients. Ann Surg 252(6):1072–1081
4. Fonkalsrud EW, Dunn JC, Atkinson JB (2000) Repair of pectus excavatum deformities: 30
years of experience with 375 patients. Ann Surg 231(3):443
5. Fonkalsrud EW et al (2002) Comparison of minimally invasive and modified Ravitch pectus
excavatum repair. J Pediatr Surg 37(3):413–417
6. Molik KA et al (2001) Pectus excavatum repair: experience with standard and minimal inva-
sive techniques. J Pediatr Surg 36(2):324–328
7. Papic JC et al (2014) Postoperative opioid analgesic use after Nuss versus Ravitch pectus
excavatum repair. J Pediatr Surg 49(6):919–923
8. Nasr A, Fecteau A, Wales PW (2010) Comparison of the Nuss and the Ravitch procedure for
pectus excavatum repair: a meta-analysis. J Pediatr Surg 45(5):880–886
9. Kelly RE et al (2007) Prospective multicenter study of surgical correction of pectus excava-
tum: design, perioperative complications, pain, and baseline pulmonary function facilitated by
internet-based data collection. J Am Coll Surg 205(2):205–216
10. Kelly RE et al (2008) Surgical repair of pectus excavatum markedly improves body image and
perceived ability for physical activity: multicenter study. Pediatrics 122(6):1218–1222
11. Muhly WT, Maxwell LG, Cravero JP (2014) Pain management following the Nuss procedure:
a survey of practice and review. Acta Anaesthesiol Scand 58(9):1134–1139
12. Skouen JS, Wainapel SF, Willock MM (1985) Paraplegia following epidural anesthesia. Acta
Neurol Scand 72(4):437–443
13. Walaszczyk M et al (2011) Epidural and opioid analgesia following the Nuss procedure. Med
Sci Monit 17(11):PH81–PH86
14. Butkovic D et al (2007) Postoperative analgesia with intravenous fentanyl PCA vs epidural
block after thoracoscopic pectus excavatum repair in children. Br J Anaesth 98(5):677–681
15. Peter S, Shawn D et al (2008) Is epidural anesthesia truly the best pain management strategy
after minimally invasive pectus excavatum repair? J Pediatr Surg 43(1):79–82
16. Bogert JN et al (2013) Patient-controlled analgesia-based pain control strategy for minimally-
invasive pectus excavatum repair. Surg Pract 17(3):101–104
17. St Peter SD et al (2012) Epidural vs patient-controlled analgesia for postoperative pain after
pectus excavatum repair: a prospective, randomized trial. J Pediatr Surg 47(1):148–153
18. Stroud AM et al (2014) Epidural analgesia versus intravenous patient-controlled analgesia fol-
lowing minimally invasive pectus excavatum repair: a systematic review and meta-analysis.
J Pediatr Surg 49(5):798–806
19. Qi J, Du B, Gurnaney H, Lu P, Zuo Y. (2014) A prospective randomized observer-blinded study

to assess postoperative analgesia provided by an ultrasound-guided bilateral thoracic paraver-
tebral block for children undergoing the Nuss procedure. Reg Anesth Pain Med.
39(3):208–13
20. Pontarelli EM et al (2013) On-Q® pain pump versus epidural for postoperative analgesia in
children. Pediatr Surg Int 29(12):1267–1271
21. Hall Burton DM, Boretsky KR (2014) A comparison of paravertebral nerve block catheters
and thoracic epidural catheters for postoperative analgesia following the Nuss procedure for
pectus excavatum repair. Paediatr Anaesth 24(5):516–520
22. Westphal FL, Lima LC, Lima Neto JC et al (2009) Prevalence of pectus carinatum and pectus
excavatum in students in the city of Manaus, Brazil. J Bras Pneumol 35(3):221–226
23. Martinez-Ferro M, Fraire C, Bernard S (2008) Dynamic compression system for the correction
of pectus carinatum. Semin Pediatr Surg 17(3):194–200
24. Emil S et al (2012) Pectus carinatum treatment in Canada: current practices. J Pediatr Surg
47(5):862–866
25. Ravitch MM (1949) The operative treatment of pectus excavatum. Ann Surg 129(4):429
26. Abramson H, D’Agostino J, Wuscovi S (2009) A 5-year experience with a minimally invasive
technique for pectus carinatum repair. J Pediatr Surg 44(1):118–124
27. Fonkalsrud EW, Anselmo DM (2004) Less extensive techniques for repair of pectus carina-
tum: the undertreated chest deformity. J Am Coll Surg 198(6):898–905
General Approach to Abdominal
and Pelvic Procedures 10
Jean-Francois Courval
Abdominal and pelvic procedures are characterized by a wide range of pathological

processes which have their unique preoperative considerations, intraoperative man-
agement issues, postoperative pain control techniques, as well as special monitoring
requirements (intraoperative or postoperative). Also typical of these procedures is
the wide age and weight variation which ranges from extreme prematurity with very
low birth weight in neonates to the near adult population who may be morbidly
obese. Adding to this, changing physiology, disease-specific considerations, possi-
ble associated syndromes, and the challenging clinical practice of pediatric anesthe-
siologists involved in such procedures becomes evident. In this context, keeping a
flexible and varied approach, adapted to the clinical settings of abdominal and pel-
vic procedures, is more important than a rigid specific recipe. This chapter will
explore some of the common preoperative, intraoperative and postoperative consid-
erations for the pediatric population in need of an abdominal or pelvic procedure.
10.1 Common Preoperative Considerations
An awareness of possible congenital anomalies or syndromes associated with

abdominal and pelvic procedures is essential in a pediatric practice. Common con-
genital anomalies such as a Meckel’s diverticulum (an embryological remnant of
the omphalomesenteric duct) may not significantly alter anesthetic management;
however, it may completely alter the surgical procedure. A common abdominal pro-
cedure such as an appendectomy for acute appendicitis may be transformed into a
Meckel’s diverticulum resection [1]. On occasion, the likeliness of associated syn-
drome or congenital anomalies will be raised by the age of presentation or clinical
J.-F. Courval
Anesthesia Department, Montreal Children’s Hospital, Montreal, QC, Canada
e-mail: jf.courval@gmail.com

DOI 10.1007/978-3-319-21960-8_10
138 J.-F. Courval
history. Intussusceptions are usually idiopathic; however, if recurrent or occurring

in a child older than 3 years old, the incidence of associated cystic fibrosis, Burkitt
lymphoma, or Peutz-Jeghers syndrome is increased [1]. At the other extreme, the
abdominal pathologies will have significant associated anomalies which will have
an impact on the anesthetic plan. Omphaloceles have been associated with chromo-
somal anomalies, bladder/cloacal exstrophy, neurological and cardiac defects,
Beckwith-Wiedemann syndrome, and Down syndrome. These have significant
anesthetic implications and they must be taken into consideration [2–4].
Trisomy 21 (i.e., Down syndrome) and Beckwith-Wiedemann syndrome are a
reoccurring theme when it comes to abdominal and pelvic procedures. The range of
abdominal and pelvic pathologies that have been associated with either or both is
extensive and includes omphalocele, umbilical hernias, Hirschsprung disease,
Wilms’ tumor, as well as others [3–6]. Specific airway considerations and possible
associated congenital cardiac malformations with their physiological impact will
add to the complexity of the anesthetic management in such patients. VACTERL
(Vertebral, Anal, Cardiovascular, TransEsophageal, Renal, and Limb) anomalies
are another possible association that the pediatric anesthesiologist should be aware
of. A VACTERL association is more common with higher and more complex ano-
rectal malformations; however, in a review by Rollins et al., a complete workup was
felt to be warranted even with more benign lesion such as rectoperineal fistula [7].
Also important to consider is an understanding of the disease process as well as
its possible complications or evolution. This may prompt the pediatric anesthesiolo-
gist to make additional preparation or plan for additional monitoring. Knowing that
complex gastroschisis (commonly associated with bowel atresia) has an increased
risk of morbidity and mortality [2], or that abdominal pathologies such as necrotizing
enterocolitis, appendicitis, anorectal malformations, and intussusception have the
potential to cause bowel necrosis and bowel perforation [1, 8], are good examples.
Anticipating possible complications such as peritonitis and septic shock is very
important and improves the chances of survival of the pediatric patient which could
succumb to associated cardiovascular collapse, renal dysfunction, anemia, thrombo-
cytopenia, and coagulopathy. Knowledge of the potential complications secondary to
chemotherapy or radiotherapy when dealing with the pediatric oncologic abdominal
or pelvic masses is also important. Myocardial damage resulting in cardiac dysrhyth-
mias or acute cardiomyopathy, myelosuppression, hepatic failure, pulmonary fibro-
sis, or neuronal damages are some of the considerations inerrant to the anesthetic
management of this population [6]. The mass or hormonal effects of neoplasm should
also be considered. For example, Wilms’ tumors have been associated with systemic
complications such as hypertension and acquired von Willebrand’s disease; in addi-
tion, vascular extension of this tumor may complicate the surgical procedure as well
as anesthetic management due to possible pulmonary embolism and inferior vena
cava or tricuspid valve obstruction from the mass itself [6].
Finally, electrolytes imbalance and volume status are common perioperative con-
cerns with abdominal and pelvic procedures. Loss of gastrointestinal fluid due to
excessive vomiting or diarrhea with abdominal pathologies such as appendicitis,
intussusception, or pyloric stenosis may lead to abnormal electrolyte values. Certain
10 General Approach to Abdominal and Pelvic Procedures 139
tumor such as Wilms’ tumor may produce excessive amount of renin which can result
in polydipsia and aldosterone-induced wasting of potassium [6]. This may also occur
with pheochromocytoma and the secretion of excessive amount of catecholamines.
Catecholamine secretions have also been associated with hyperglycemia which may
require insulin therapy [9]. The electrolytes anomalies may also be related to genito-
urinary anomalies and renal dysfunction which is common in patient with anorectal
malformations, gastroschisis, or Beckwith-Wiedemann syndrome [4, 10–12]
Hypovolemia may result from various mechanisms: gastrointestinal bleeding third
spacing, and large evaporative loss [3] are common in this patient population.
Although early and aggressive fluid resuscitation (from 50 ml/kg up to 200 ml/kg) has
been reported to improve outcome in sepsis [13], this may prove insufficient in pathol-
ogies such as a toxic megacolon syndrome and enteric bacteremia, where the combi-
nation of fluid as well as vasopressor support may be lifesaving measures [14].
10.2 Intraoperative Management
Overall outcome and complication rate of abdominal and pelvic pathologies have
greatly improved over the past 50 years. Gastroschisis, isolated omphalocele, and
Wilms’ tumor are examples of pathologies that were associated with significant
mortality rate which now have a survival rate of 90 % or more [10, 14]. The reasons
leading to these remarkable improvements are probably multifactorial and multidis-
ciplinary; total parenteral nutrition, neonatal and surgical care, oncology protocols,
better diagnostic tools, identification of associated pathologies, and improved peri-
operative monitoring are some of the factors that may have contributed to these
results. The practice of anesthesia has also evolved significantly over the past years,
and patients have benefited from increased safety protocols and improved monitor-
ing in the operating room.
A better understanding of the risk associated with a full stomach and the serious-
ness of aspiration pneumonitis has led to the adoption of strict rules regarding inges-
tion of fluid or solids during the perioperative period. Unfortunately, these rules
should not be viewed as an assurance of an empty stomach since poor children
compliance or delayed gastric emptying secondary to intestinal obstruction in
pyloric stenosis or intussusception may interfere with normal gastric emptying.
Direct assessment of gastric content with ultrasound has been looked at and may
have future applications; however, it remains unproven at this time [16, 17].
Therefore, anesthesiologists still have to resort to the use of the rapid sequence
induction (RSI) technique to minimize the risk of aspiration during the induction
period. Gastric decompression with a nasogastric tube insertion prior to induction
has been advocated to prevent or minimize the risk of aspiration [4, 18]. However,
the classic RSI may represent a significant challenge in a pediatric population par-
ticularly when patients may be hypovolemic without IV access and may not want to
cooperate for preoxygenation or an awake intubation [14, 16].
As was previously mentioned, Beckwith-Wiedemann and Down syndromes are
frequent consideration with abdominal and pelvic procedures. Airway assessment
140 J.-F. Courval
prior to induction is important in order to evaluate the potential risk of a difficult

intubation. Macroglossia is common with Beckwith-Wiedemann syndrome and
may complicate airway management [4]. Down syndrome has a number of features
which may also lead to difficulty in securing the airway: short neck, macroglossia,
mandibular hypoplasia, cervical spine instability, subglottic stenosis, and poor
cooperation due to possible mental retardation. In addition, Down syndrome patients
may have associated congenital cardiac anomalies and are at risk for bradycardia
with inhalational induction with sevoflurane [19, 20]. Combining all of those clini-
cal features (acute abdomen, full stomach, difficult airway, cervical spine instabil-
ity, congenital heart anomalies, bradycardia on induction, difficult or absent IV
access) and managing these patients becomes a challenge even for the most experi-
ence pediatric anesthesiologist.
Certain pathologies such as pyloric stenosis, gastroschisis, necrotizing enteroco-
litis, or Hirschsprung disease are more prevalent during the neonatal period in
patient who may be born prematurely. Appropriate ventilation becomes very impor-
tant in these patients in order to avoid hypoxemia, oxygen toxicity or barotrauma.
Tidal volume should not exceed 8 ml/kg, and the inspiratory oxygen concentration
should be adjusted to maintain an oxygen saturation of 88–92 % [13]. Pulmonary
hypoplasia should also be considered and may lead to prolonged mechanical venti-
lation and tracheostomy in this population [2, 21]. As an increased number of
abdominal and pelvic procedures are being done laparoscopically, the reduced pul-
monary compliance, increased airway pressure, and increased CO2 load must also
be considered during the operation [22]. In addition, given the relative short dis-
tance between the end of the endotracheal tube and the carina in small pediatric
patients, the increased intra-abdominal pressure from gas insufflation during lapa-
roscopy, can lead to the cephalad displacement of the carina [14] resulting in pos-
sible endobronchial intubation orsevere bronchospasm. Adequacy of ventilation
should also be reassessed postoperatively since the procedure itself may have
impacts on the ventilatory parameters. For example, after primary closure of a gas-
troschisis, the resultant increase in intra-abdominal pressure could negatively affect
postoperative ventilation.
The need for invasive monitoring will vary greatly depending on the abdominal
and pelvic procedure. While certain procedures will be performed with standard
monitoring, others may mandate the full spectrum of what is available in modern
anesthesia (i.e. arterial line, central venous catheter, pulmonary artery wedge cath-
eter, transesophageal echocardiography, etc.). The potential for rapid changes in
hemodynamic stability, need for frequent blood sampling and diagnostic accuracy,
are important factors when deciding which monitors should be added to standard
monitoring. The pediatric anesthesiologists involved in such procedures must be
prepared for potential massive blood loss and sudden hypotension with a Wilms’
tumor invading the inferior vena cava [6] as well as severe hypertensive crisis from
massive catecholamine release associated with secreting neuroblastoma or pheo-
chromocytoma [23, 24]. The maintenance of an adequate mean arterial pressure is
further complicated by the fact that this value will vary depending on the age of the
patient [25]. Invasive monitoring will facilitate perioperative management of
complex intra-abdominal pathologies; however, will this result to improved out-

come remains controversial. With pheochromocytoma going from a perioperative
mortality of 50 to 3 % [9], associating this impressive result solely on improved
monitoring would be an oversimplification since there have been significant con-
comitant improvements in surgical techniques as well as preoperative medical man-
agement. Unfortunately, the entire arsenal of adult invasive monitoring may not be
possible in the pediatric population. It is often necessary to modulate monitoring
according to possible size limitation, technical difficulties, and/or lack of experi-
ence with a specific monitoring device and consider the potential benefit of such
tools [9].
Intraoperative fluid management will vary according to the weight of the patient,
the disease process, the duration of the surgery, as well as the surgical approach.
Losses from third spacing can be minimal for a laparoscopic hernia repair, may
reach 20–30 mL/kg for intussusception [13] or be in excess of 50 mL/kg for necro-
tizing enterocolitis [26]. Adequate evaluation and management of intraoperative
fluid can be a challenge; however, it is important since it may lead to improved
outcome [27]. Unfortunately, the opposite is also true, particularly for patient with
pheochromocytoma. The chronic hypertension in these patients may lead to an
uncertain intravascular volume status and acute myocardial dysfunction. Aggressive
fluid resuscitation in this clinical setting would be unwise and could lead to conges-
tive heart failure or pulmonary edema [9]. It is also important to consider which
fluid will be used to replace losses. By far, crystalloids are the most common fluid
used in abdominal and pelvic procedures. However, colloid, packed red blood cells,
fresh frozen plasma, cryoprecipitate, and others may be indicated depending on the
clinical setting. The importance of early replacement with massive blood loss is of
critical importance. The pediatric anesthesiologist providing care to this population
must keep in mind that massive blood loss may not be a large volume, particularly
in the context of a very low birth weight premature neonate with necrotizing
enterocolitis.
Positioning for gastrointestinal and genitourinary procedures is usually in the
supine or lithotomy position. On occasion, the prone position is encountered for
procedures such as a posterior sagittal anorectoplasty, a procedure introduced by
Peña in 1982 for the correction of anorectal malformation [8]. Particular attention to
pressure points and temperature control during positioning is crucial since this
patient population may have very sensitive skin where minimal pressure may result
in damages and the procedure may be prolonged. When the bowel is exposed as in
gastroschisis or omphalocele, measures to reduce evaporative fluid and heat loss are
essential. Covering the bowel with a sterile plastic wrapping is helpful in that set-
ting, and it also prevents desiccation of the viscera [3, 13]. However, with the intro-
duction of a laparoscopic approach to increasingly complex abdominal and pelvic
procedures, third spacing and evaporative loss have been significantly reduced. An
unfortunate consequence of this approach has been the increased duration of proce-
dures and the potential risk of significant perioperative hypothermia. However, the
overall popularity of the laparoscopic approach has increased to the point that the
McBurney incision for appendicitis is now a rare event in major pediatric centers
142 J.-F. Courval
[1]. With increased experience, the increased surgical duration of laparoscopic pro-
cedure has been steadily reduced, and the gains on length of hospital stay, when
compared to laparotomy, far outweigh the possible increase in surgical time [28].
This tendency toward less invasive correction of various pathologies has been grow-
ing and now mandates that the pediatric anesthesiologist learns to work in environ-
ments outside of the traditional operating room. For example, the correction of
intussusception is now frequently performed in the radiology suite, either pneumati-
cally or with enema. In addition to facilitating the procedure, general anesthesia has
also improved the overall success rate for this approach [6, 29].
10.3 Postoperative Management
When it comes to postoperative care, the postanesthesia care unit (PACU) is where
most patients will recover from their surgery. For most abdominal or genitourinary
procedures, the PACU will be the intermediate step before being discharged home.
The PACU stay is usually limited and discharge home commonly occurs within 3 or
4 h. For some patients, an overnight stay will be required to determine whether the
patient can be discharged home or needs to be admitted for further monitoring.
Down syndrome being commonly associated with many abdominal and genitouri-
nary pathologies, obstructive sleep apnea becomes a significant concern in this
patient population.
There has been a constant push to perform more complex procedure in a day
surgery setting. A combination of improved surgical technique, anesthesia monitor-
ing, and risk stratification has been instrumental in this evolution [30]. The impact
of laparoscopic surgery, interventional radiology, and cardiology has certainly been
impressive over the past two decades in the pediatric as well as the adult population.
The delivery of improved medical care at a lower cost is certainly an incentive for
this approach. Procedures may have become more expensive; however, the short-
ened length of hospital stay offsets this additional cost and contributes to improve
the overall efficiency of care. For example, an appendectomy for acute appendicitis
will now be discharged within 24 h and will only be admitted if prolong antibiotic
therapy is necessary [1]. The complexity of patients observed in the PACU has also
seen a significant increase. This is particularly true in environments where access to
the intensive care unit (ICU) may be limited or at times when the number of admis-
sion to the ICU is unusually large. As discussed above and given the numerous
potential complications, the need for postoperative admission to the pediatric or
neonatal intensive care unit remains. The importance of postoperative risk evalua-
tion and an assessment of possible prolong monitoring must be done early.
Postoperative pain control management for abdominal and pelvic procedures has
improved significantly in the past two decades. High-dose narcotics have been asso-
ciated with postoperative nausea and vomiting which may result in delayed dis-
charge home. Finding the most effective peripheral nerve block to obtain the best
pain relief has been the subject of a number of research projects. The benefits of
peripheral nerve blocks may even be extended after discharge home with the
placement of a catheter connected to an elastomeric pump [31]. In major pediatric

centers, inguinal hernia repair and orchidopexy are now associated with minimal
pain, whereas patients undergoing tonsillectomy are still reported to have signifi-
cant pain up to 7 days postoperatively [32, 33].
Conclusion
When providing anesthesia care to patient undergoing an abdominal or pelvic
procedure, it is important to look for possible associated syndromes and to
understand the disease process. Particular attention to volume status, electrolytes
balance, and blood loss can be challenging and may mandate additional monitor-
ing intraoperatively or postoperatively. Communication with the surgical team
prior to incision will help you anticipate and prepare for potential intraoperative
complications. Finally, in this era, it should be possible to provide excellent pain
relief to the vast majority of these patients and avoid having to resort to high-
dose narcotics.
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Part III
Perioperative Care in Special
Situations and Conditions
Perioperative Care of Children
with a Difficult Airway 11
Alan Barnett and Thomas Engelhardt
11.1 Introduction
Airway problems are a leading cause of perioperative morbidity and mortality in

healthy children without any signs or symptoms of airway anomalies but also fre-
quently encountered in children with an impaired airway [1, 2].
Mortality due to perioperative hypoxia is a consequence of prolonged airway
obstruction. Transient perioperative hypoxia may result in apparent short-term post-
operative morbidity. However, long-term consequences of transient hypoxemia are
only poorly understood.
Neonates and young children are at a particular high risk as are children undergo-
ing emergency procedures [3, 4]. Children in general have a decreased oxygen
reserve and increased oxygen consumption when compared with adults. Their
apnoea tolerance is, therefore, very low (measured in seconds) [5, 6]. Even a tran-
sient airway obstruction develops rapidly into significant hypoxemia and profound
bradycardia compromising the well-being of the child.
This chapter describes essential anatomical and physiological information and
their direct clinical consequences. A pragmatic approach is suggested for the man-
agement of different paediatric airway problems including a list of minimum airway
equipment available.
A. Barnett
Department of Surgery, Radiology, Anaesthesia and Intensive Care,
The University of the West Indies, Mona, Kingston 7, Jamaica, West Indies
T. Engelhardt (*)
Department of Anaesthesiology, Royal Aberdeen Children’s Hospital,
Foresterhill, Aberdeen AB25 2ZN, UK
e-mail: tomkat01@yahoo.com

DOI 10.1007/978-3-319-21960-8_11
148 A. Barnett and T. Engelhardt
11.2 The Paediatric Airway
11.2.1 Anatomical Considerations
As the child develops from birth and progresses to adulthood, there are significant
changes, which occur in the airway and lungs. The head is large relative to the body
in infants and young children, and facial structures are small when compared to the
neurocranium. The oral cavity is small at birth and increases in size in the first year
of life following a substantial growth of the mandible and teeth. The neonatal tongue
is flat with limited lateral mobility.
The larynx is loosely embedded in the surrounding structures when compared
with adults and more anterior. External manipulation allows positioning during
direct laryngoscopy. The epiglottis is long, narrow and frequently U-shaped, obscur-
ing the glottic view on direct laryngoscopy. The glottis is higher in relation to the
spine in neonates (C2/C3) and descends to its usual position at C5 after 2 years. The
vocal cords are shorter in the neonate and comprise about half of the anterior glottis
[7].
The neonatal larynx is thought to be conically shaped and approximately cylin-
drical in an older child. In addition, the larynx is thought to be widest at the supra-
glottic and narrowest at the subglottic level. However, this view has been challenged
in MRI studies indicating that the narrowest part is in fact at the glottis. Most impor-
tantly, the cricoid ring is functionally the narrowest (unyielding) part of the neonatal
airway. The cricoid ring is not circular but has an ellipsoid shape and a mucosal
layer highly susceptible to trauma. Pressure or trauma at the cricoid ring results in
oedema, increase in airway resistance and airway obstruction [8].
Tracheal length is related to the patient’s age and height. Alteration of the head
position changes the tracheal tube position and requires reassessment by clinical or
other means.
11.2.2 Physiological Considerations
Young children have a very low functional residual capacity and increased closing
capacity. In addition, children have a higher oxygen demand as well as increased
carbon dioxide production. The direct consequence is a very low apnoea tolerance
leading to significant hypoxemia and respiratory acidosis. Even optimal pre-
oxygenation does not generate a sufficiently long ‘safety period’. The younger the
child, the less time there is [5, 6].
The laryngeal reflexes are the most powerful protective reflexes in humans and
are designed to prevent pulmonary aspiration. They are functional reflexes. The
recurrent laryngeal nerve and the external and internal branches of the superior
laryngeal nerve (vagus) innervate the larynx. The former supplies the afferent inner-
vation of the subglottic part of the larynx and all muscles with the exception of the
cricothyroid muscle which is innervated by the external branch of the superior
laryngeal nerve. The internal branch of the superior laryngeal nerve provides
11 Perioperative Care of Children with a Difficult Airway 149
sensory innervation to the epiglottis and larynx above the vocal cords. Stimulation
results in coughing, laryngospasm and bradycardia.
The larynx is very sensitive to mechanical or chemical stimulation induced by
liquids or solids. It is relatively insensitive to inhaled irritants such as volatile anaes-
thetic agents [9]. Laryngospasm is defined as complete closure of the larynx. A
mechanical stimulus (secretions/blood/foreign body) is the primary cause and fre-
quently observed in children with upper respiratory tract infections. A ‘true’ or
‘complete’ laryngospasm is in contrast to glottic spasm or ‘partial’ laryngospasm, a
strong approximation of the vocal cords only. A partial laryngospasm leaves a small
lumen at the posterior commissure, potentially allowing minimal oxygenation with
high inflation pressures.
A complete laryngospasm results in silent chest movements but no movement of
the reservoir bag. Face mask ventilation is not possible. In partial laryngospasm,
there is chest movement, but there is a stridulous noise with a mismatch between the
patient’s respiratory effort and the small amount of movement of the reservoir bag
[10].
Laryngospasm must also be differentiated from postextubation stridor, com-
monly due to trauma of the paediatric airway and mucosal injury with subsequent
oedema.
11.2.3 Clinical Consequences of Airway Obstruction
Airway obstruction may occur at any time in the perioperative period in any child
and may be described as either anatomical or functional (Table 11.1).
Anatomical airway obstructions are caused by poor technique such as incorrect
use of the face mask, suboptimal positioning of the patient’s head, mandible and
upper thorax and failure to recognise airway obstruction caused by large adenoids
and tonsils.
Table 11.1 Airway obstructions during anaesthesia are generally divided into anatomical
(mechanical) and functional airway obstructions
Anatomical airway obstructions Functional airway obstructions
Causes Causes
Inadequate head position Inadequate anaesthesia
Poor face mask technique Laryngospasm
Large adenoids/tonsils/obesity Muscle rigidity
Secretions Bronchospasm
Treatment Treatment
Repositioning/reopening/Guedel Deepen anaesthesia
Two-hand/two-person technique Muscle relaxation
Suction Epinephrine
This distinction necessitates different treatments: anaesthetic technique for anatomical airway
obstructions and pharmacological interventions for functional airway obstructions
Simple mouth opening and the application of the ‘triple airway manoeuvre’
(head-tilt, chin-lift, jaw-thrust) or alternatively the use of an appropriately sized
oropharyngeal airway will usually overcome these problems. Mechanical obstruc-
tion due to secretions, blood, regurgitation or foreign bodies necessitates suction
removal under direct vision. Gastric distension secondary to forceful bag-mask ven-
tilation requires decompression by orogastric suctioning. Unexpected subglottic or
other tracheal mechanical obstructions (inhaled foreign bodies) can be overcome by
bypassing with a smaller tracheal tube. Prolonged and/or failed tracheal intubation
attempts in small neonates and small infants result in peripheral lung collapse.
Careful lung recruitment manoeuvres are required in order to restore optimal oxy-
genation and ventilation. If no mechanical obstruction is detected during direct
laryngoscopy and the trachea cannot be intubated, a supraglottic airway device must
be inserted as an alternative in order to overcome any potentially overlooked ana-
tomical supraglottic airway problems [7].
Functional upper airway obstructions are frequent in children and may be caused
by insufficient depth of anaesthesia, laryngospasm or opioid-induced glottic clo-
sure. Functional lower airway obstructions are caused by bronchospasm or opioid-
induced muscle rigidity of the thoracic wall. Treatment options of functional airway
obstructions are primarily pharmacological. Additional hypnotics may be used in
the child without co-morbidities which is not already deeply hypoxic and brady-
cardic. The administration of muscle relaxation overcomes most functional airway
obstructions with the exception of bronchospasm for which epinephrine may be
used in the impending peri-arrest situation [11].
11.3 Classification of the Paediatric Airway
The paediatric airway may be classified under three headings: normal, impaired
normal and an expected difficult airway (Table 11.2). This pragmatic classification
in conjunction with the presented urgency of the situation determines the anaes-
thetic approach.
11.3.1 Normal (Unexpected Difficult)
Children in this category are encountered on a daily basis. These children are usu-
ally healthy and have no previous symptoms or signs indicative of a difficult airway.
Problems encountered are either due to an anatomical (mechanical) or functional
airway obstruction (Table 11.1).
11.3.2 Impaired Normal (Suspected Difficult)
Swelling, trauma and infections can turn the normal airway of otherwise healthy
children rapidly into an impaired normal airway. The severity of symptoms and
Table 11.2 Simple and pragmatic classification of the paediatric airway

Normal paediatric airway: ‘unexpected’ Time: critical
Place: anywhere
Who: anyone
Comment: established paediatric airway
algorithm essential
Impaired normal paediatric airway: Time: urgent
‘suspected’ Place: anywhere, consider transfer to specialist
centre
Who: expertise required, consider ENT
Known abnormal paediatric airway: Time: normally elective, planning essential
‘expected’ Place: paediatric specialist centres only
Who: specialist expertise required, ENT support
essential
After Marin and Engelhardt [12]
The vast majority of children have a normal airway. The known difficult paediatric airway is the
domain of the experienced paediatric anaesthetist
speed of deterioration dictate the urgency and need of the anaesthetic intervention.
The underlying disorder – infectious (epiglottitis), allergic or mechanical (inhaled
foreign body, bleeding tonsil) – requires swift recognition and treatment. Most chil-
dren, however, tolerate a certain delay in order to allow resuscitation, organisation
and preparation of appropriate staff, location and equipment.
11.3.3 Expected Difficult Airway
This refers to children who have a known or obvious difficult/abnormal airway.

Examples include but are not limited to head, neck and airway anomalies. They
may be congenital (associated with syndromes) or acquired (burns, scars), associ-
ated with tumours and other masses and more rare causes such as subglottic and
tracheal disorders or anterior mediastinal mass syndrome.
Unless there is an immediate threat to life or limb, these patients must be trans-
ferred to a specialised hospital with appropriate experience, personnel and equip-
ment available to guarantee optimal safety.
11.3.4 Approach to the Paediatric Airway
The clear distinction between ‘normal’, ‘impaired normal’ and ‘known abnormal’
allows the non-specialist paediatric anaesthetist to determine the optimal approach
to the child requiring airway interventions (Fig. 11.1). Whereas the ‘normal’ paedi-
atric airway may be managed in most centres with appropriate staffing and resources,
the establishment of simple, locally adapted, easy memorisable and rehearsed algo-
rithms is essential for safe paediatric airway management (see below). The acutely
proceed − unexpected
Normal airway YES
difficult airway algorithm
NO
proceed according local

Facilities/expertise YES
algorithm/protocol
NO
proceed - get Help if doubt

Life or limb saving YES
about ability to ventilate
NO
STOP REFER
Fig. 11.1 Flow chart for approaching paediatric airway management (After Marin and Engelhardt
[12])
impaired normal paediatric airway requires experience and skill. If these are avail-
able, the paediatric airway can be managed locally. The gravity of the underlying
disease process (infectious, allergic swelling, trauma or burn) and speed of deterio-
ration will guide the anaesthetic intervention. Resuscitation, organisation and prep-
aration of appropriate staff, location and equipment should be arranged if the
condition of the child allows. All other patients should be transferred to a dedicated
paediatric unit unless intervention is critical. Surgical (ENT) support is required if
the anaesthetist is not experienced enough or has doubts about the ability to oxygen-
ate and ventilate.
11.4 Management of the Paediatric Airway
11.4.1 Managing the Unexpected Difficult Airway
Routine paediatric airway management is usually easy in experienced hands.

However, as outlined above, children have an increased oxygen consumption and a
lower oxygen reserve when compared with adults. Therefore, preparation, regular
training and education are essential to prevent and recognise early unexpected dif-
ficulties in the otherwise ‘normal’ paediatric airway. Time critical concepts are
required based on simple, forward only, easy memorisable, locally adapted and
rehearsed algorithms. Such a simple proposal for the paediatric patient was pub-
lished recently and is reproduced in an adapted form (Fig. 11.2).
Maintenance of the ability to oxygenate and ventilate is the key to successful
airway management. Good daily clinical practice is required to achieve this.
Anatomical/mechanical airway obstructions need to be recognised and treated first
as described. No pharmacological intervention will solve this problem. If the
Unexpected difficult ventilation/oxygenation Unexpected difficult intubation

Basic rules
Ensure adequate level of anaesthesia and muscle paralysis Basic rules
Ensure adequate level of anaesthesia and muscle paralysis
Use laryngeal pressure or BURP
Failed
Failed
Exclude/treat anatomical airway obstruction
Re-open airway / Oro-pharyngeal airway
2-hand/2-person bag-mask-ventialtion Maintain oxygenation, ventilation and anaesthesia
Failed Call for help
Call for help Failed intubation plan A*

Exclude/treat functional airway obstruction Use improved direct laryngoscopic technique/conditions or
Use indirect laryngoscopic technique
Laryngospasm / Opioid rigidity / Bronchospasm / Inflated stomach Limit to 2 intubation attempts
Deepen anaesthesia / Paralyse / i.v. epinephrine / Gastric drain
Failed Failed
Consider
surgery
Maintain oxygenation, ventilation and anaesthesia with LMA
Failed oxgenation plan A
Direct laryngoscopy
Exclude/remove foreign body in / from hypopharynx / larynx Failed intubation plan B
Intubate trachea
Insert LMA
Perform fiberoptic tracheal intubation through the LMA
Failed Limit to 2 intubation attempts
Failed
Failed oxgenation plan B
Insert LMA Maintain oxygenation, ventilation and anaesthesia
Ventilate Emergency Ventilate Emergency

wake-up through surgery wake-up through surgery
LMA* with LMA LMA* with LMA
*In a child with previously no signs, no symptoms and no history of / for a difficult *Rapid sequence induction intubation - Ensure deep anaesthesia and paralysis, oxygenate
airway → invasive ventilation techniques are not needed and ventilate via face mask or via LMA
07-09-2010 – Weiss M, Engelhardt T - Paediatr Anaesth. 2010;20:454-64 07-09-2010 – Weiss M, Engelhardt T - Paediatr Anaesth. 2010;20:454-64
Fig. 11.2 Simplified ‘open-box’ proposal for the management of the unexpected difficult paediat-
ric airway (Adapted from Weiss and Engelhardt [13]). A clear separation between oxygenation/
ventilation problems and difficult intubation is essential. Oxygenation/ventilation (and anaesthe-
sia) must be guaranteed
situation does not improve early, call for help immediately. Recognition and treat-
ment of functional airway obstruction using either an additional dose of hypnotic,
muscle relaxant or epinephrine is essential. Limited and as of yet unpublished evi-
dence suggests that all otherwise normal children can be oxygenated and ventilated
if anatomical and functional airway problems are recognised and treated [11]. An
unexpected foreign body (food/chewing gum – a mechanical obstruction) occluding
the glottis must be removed or bypassed following muscle relaxation. A supraglot-
tic airway device may be helpful in overcoming unexpected/unknown anatomical
airway obstructions. Unexpected difficult tracheal intubation may occur, and simi-
larly a simple, stepwise, forward only and locally adapted algorithm must be in
place. It is essential to realise that repeated traumatic airway instrumentation will
convert a difficult paediatric airway into an impossible situation.
A ‘rescue’ option is frequently incorporated into the management of the ‘cannot
oxygenate-cannot ventilate’ algorithms. Principally, the choice is between a surgi-
cal airway, needle cricoidotomy and rigid bronchoscopy. There is currently only
insufficient evidence to firmly endorse any of these options in children. Emphasis
must be on prevention of this situation in the otherwise normal child through the
early recognition and treatment of anatomical and functional airway obstructions

through dedicated teaching and training.
11.5 Managing the Suspected Difficult (Previously Normal)

Airway
In contrast to the unexpected difficult airway, the suspected (previously normal)

paediatric airway presents unique challenges to the anaesthetist. Previous training
and experience as well as existing facilities dictate the approach. Frequently, there
is sufficient time to allow optimisation of the patient, planning as well as organisa-
tion of additional help.
Optimisation of the patient includes specific treatment directed at the underlying
cause and may include antimicrobial cover in case of bacterial infections, adminis-
tration of corticosteroids in children with croup-like symptoms and inhalational
trauma as well as appropriate resuscitation if required.
Prior to any intervention a short, rapid evaluation, directed at the characteristics
of the onset of the illness and the course of development of respiratory signs, must
be performed in order to exclude trauma and foreign body aspiration. Clinical signs
of acute airway obstruction should be assessed and include stridor, cyanosis, dys-
pnoea, suprasternal recession, use of auxiliary respiratory muscles, presence of
apnoeic episodes as well as the posture of the patient. Frequent observations and
assessments are recommended [14].
A concise plan (method of induction and spontaneous ventilation versus con-
trolled ventilation) needs to be formulated prior to starting induction of anaesthesia,
with all instruments and drugs available and ready to use. The most experienced
anaesthetist should perform airway procedures in the child with the compromised
airway. In life-threatening situations and situations in which there are doubts about
the ability to ventilate, the presence of an experienced (ENT) surgeon ready to inter-
vene immediately is mandatory. Anatomical and functional airway obstructions can
occur at any time and must be treated as previously outlined.
11.6 Managing the Expected Difficult Airway
The management of the expected difficult airway is the domain of the experienced
paediatric anaesthetist and requires a specialised setup. Management of these chil-
dren is challenging. Preparation for a child with an expected difficult airway includes
a quiet environment, anaesthetists proficient in advanced airway management tech-
niques including fibre-optic intubation as well as trained anaesthetic nurses/assis-
tants and suitable paediatric equipment.
Similarly to the previous descriptions, expected difficulties for mask ventilation
and tracheal intubation may need to be catered for separately.
Inhalational induction or incremental doses of intravenous hypnotics (propofol)
can be used to establish a depth of anaesthesia.
Depending on the anaesthetist’s preference and experience, this is followed by

one of the two options for further airway manipulations:
1. (Assisted) spontaneous ventilation using inhalational or total intravenous

anaesthesia
2. Positive pressure ventilation with muscle paralysis (if bag-mask ventilation is
possible)
An experienced ENT surgeon must be on standby ready to intervene if difficulty

with mask ventilation occurs as rigid bronchoscopy or establishing a surgical air-
way may be urgently required.
Direct laryngoscopy should be attempted, and access to the larynx (Cormack and
Lehane grading) must be documented for future anaesthetic interventions.
Fibre-optic tracheal intubation remains the gold standard despite the advent of
alternatives such as videolaryngoscopes or other techniques [15]. It is, therefore,
essential to maintain skills and expertise in fibre-optic intubation in children. A
tracheostomy is the final option and must be considered during complicated and
failed intubation attempts before swelling and bleeding make mask ventilation
impossible. It may be necessary to secure the airway with a prophylactic tracheos-
tomy if a repeated subsequent tracheal intubation is unlikely to succeed [16]. Awake
direct laryngoscopy may only be considered in extreme circumstances (grotesque
hygroma, lymphagioma or tumours of the head and neck). The EXIT procedure
during birth represents a special option to oxygenate the newborn until conventional
or invasive airway has been established [17]. A reversible extubation strategy using
an airway exchange catheter should be planned in patients with a difficult airway
[18].
11.7 Paediatric Airway Equipment
Safe paediatric airway management of the paediatric airway necessitates availabil-

ity of suitable equipment. Safe anaesthesia does not have to be expensive. In every
operating theatre and wherever a child is anaesthetised, there is an essential mini-
mum equipment requirement (Table 11.3). Maker and manufacturer are of little
relevance, but the equipment must be suitable for children and acceptable to the
anaesthetist in charge.
There is an ever expanding range of desirable paediatric airway equipment on the
market, and individual departments need to decide their best options based on their
needs and affordability. These include (but are not limited to) endoscopy masks,
second-generation supraglottic airway devices and videolaryngoscopes. It is essen-
tial that this equipment is regularly maintained and that regular training of all staff
occurs.
In addition, a difficult/emergency airway trolley should be available in every
suite where children are managed. This must be adapted to locally accepted difficult
airway algorithms. A one-stop ‘airway trolley’ may be the best option for some
Table 11.3 Essential minimum airway equipment requirements for paediatric anaesthesia
Equipment Comment
Face masks All age-appropriate sizes must be available
Self-inflating bag Connection possible to face mask
Oropharyngeal airway All age-appropriate sizes must be available
Nasopharyngeal airway All age-appropriate sizes must be available. A tracheal tube may be
cut and used
Supraglottic airway All age-appropriate sizes must be available (1, 1½, 2, 2½, 3, 4 and 5)
device First-generation devices are adequate
Tracheal tube All age-appropriate sizes must be available. If Microcuff tracheal
tubes are used, cuff pressure must be monitored
Direct laryngoscope Selection of straight and curved blades
Alternative laryngoscope Select one alternative option to visualise the larynx
Other equipment Intubating stylet, introducer, gastric drains, tapes and syringes
(throat pack)
Table 11.4 Difficult/ Drawer 1 label: failed oxygenation/ventilation

emergency airway trolley
setup, arrange according to LMA: sizes 1, 1.5, 2, 2.5, 3, 4 and 5 (in duplicate)
locally adapted airway Alternative masks and supraglottic airway devices
algorithm Magill forceps
Drawer 2 label: failed intubation plan A
Selection of ‘alternative’ laryngoscopy blades
(s.a. McCoy, Wisconsin, Miller)
Gum elastic bougies (sizes 5 and 10 F)
Malleable stylet (sizes 2 and 5 F)
Choice of visualisation or intubating aid
(depending on local preference)
Drawer 3 label: failed intubation plan B
Airway exchange catheters of assorted sizes
7 F, ID 2.5 mm; 8 F, ID 3.0 mm; 11 F, ID 4.0
mm; 14 F, ID 5.5 mm; and 19 F, ID 7.0 mm
Endoscopy masks
(Drawer 4 label: rescue)
Cricoidotomy needle kit (Melker) label: age > 8
years
Surgical cricoidotomy kit label: age < 8 years
Different-sized cannulae for cannula cricoidotomy
and connection tubing
Scalpel (x 2)
Tracheal hook
Artery forceps
Surgical gloves
departments, with equipment separated according to age/weight. Other departments

who have a dedicated ‘difficult airway’ trolley for elective procedures may choose
an additional simplified ‘airway rescue’ trolley equipped according to departmental
rescue algorithms. Simplicity is the key to success and overstocking must be avoided
at all costs (Table 11.4).
All paediatric difficult/emergency airway equipment must be regularly checked
and operators must be familiar with its content. Availability and signage must be
guaranteed.
11.8 Summary
Paediatric airway management can be challenging. However, if clear concepts and

local protocols for the management of the unexpected, suspected and expected dif-
ficult airway are established and expertise and training are maintained, significant
airway-related morbidity and mortality can be avoided.
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with Neuromuscular Disease 12
Fabrizio Racca and Chiara Robba
12.1 Introduction
Children with neuromuscular disorders (NMDs) (Table 12.1) are at high risk of
intraoperative and postoperative complications. Indeed, this peculiar group of
patients may have altered vital functions (e.g., weakness of the respiratory muscles,
scoliosis, cardiac involvement), which increase the risk of surgical procedures
requiring general anesthesia (GA) or sedation. Moreover, in children with some
types of NMDs, succinylcholine and halogenated agents can trigger life-threatening
reactions, such as malignant hyperthermia (MH), rhabdomyolysis, or hyperkalemic
cardiac arrest secondary to denervation. On the other hand, survival rate of these
children has progressively improved, increasing the need for surgical procedures
related or unrelated to NMDs.
An intensive, proactive, multidisciplinary approach should be instituted before,
during, and after any surgical procedure requiring GA or sedation. Thus, surgery in
this children population should be performed in a fully equipped hospital with
extensive experience in NMD management.
This chapter will review the pathophysiology of life-threatening complications
of anesthesia in NMDs and the assessment and management of these children
before, during, and after anesthesia.
F. Racca, MD (*)
Anesthesiology and Intensive Care Unit, S.C. Anestesia e Rianimazione Pediatrica Azienda
Ospedaliera SS Antonio Biagio e Cesare Arrigo Hospital, Via Venezia 16,
Alessandria 15100, Italy
e-mail: fracca7766@gmail.com
C. Robba
Anesthesiology and Intensive Care Unit, SS Antonio Biagio e Cesare Arrigo Hospital,
Alessandria, Italy

DOI 10.1007/978-3-319-21960-8_12
160 F. Racca and C. Robba
Table 12.1 Neuromuscular disorders of childhood

1. Motoneuron diseases Spinal muscular atrophy (SMA), SMA with respiratory distress
(SMARD)
Spinobulbar muscular atrophy (Kennedy disease)
Poliomyelitis
2. Peripheral neuropathies Guillain–Barrè Syndrome (GBS)
Chronic inflammatory demyelinating polyneuropathy (CIDP)
Hereditary sensory and motor neuropathies (i.e., Charcot–Marie–
Tooth disease)
Hereditary sensory and autonomic neuropathies (HSAN)
Critical illness polyneuropathy
3. Neuromuscular junction Myasthenia gravis (MG)
diseases Congenital autoimmune myasthenia gravis
Congenital myasthenias
Botulism
4. Muscle Progressive Dystrophinopathies: Duchenne (DMD) and Becker (BMD) type
diseases muscular Limb-girdle muscular dystrophies (LGMD)
dystrophies Facioscapulohumeral muscular dystrophy (FSHD)
Oculopharyngeal muscular dystrophy (OPMD)
Myotonic dystrophy (DM): DM type 1 (DM1), DM type 2 (DM2
or PROMM disease)
Congenital Ullrich CMD, Bethlem myopathy
muscular Emery–Dreifuss dystrophy
dystrophies Merosin-deficient CMD
Alpha-dystroglycanopathies (e.g., Fukuyama CMD)
Congenital Central core disease/malignant hyperthermia
myopathies Nemaline/rod myopathies
Centronuclear/myotubular myopathy
Fiber-type disproportion myopathy
Myofibrillar myopathies
Metabolic Mitochondrial encephalomyopathies
myopathies Glycogen storage disorders (i.e., GSD type II or Pompe disease,
McArdle disease)
Lipid storage myopathies
12.2 Life-Threatening Complications of Anesthesia in NMDS
12.2.1 Respiratory Failure
Respiratory involvement can vary significantly between different NMDs and within
each type of disorder. Reduction of inspiratory muscle strength results initially in
restrictive pulmonary impairment with a progressive decrease of forced vital capac-
ity (FVC). Subsequently, ineffective alveolar ventilation may occur, leading to noc-
turnal hypercapnia and eventually to diurnal hypercapnia. In addition, weakness of
expiratory muscles leads to inadequate clearance of airway secretions.
Hypoventilation, coupled with an impaired cough, predisposes to atelectasis and
respiratory failure. Furthermore, patients with NMDs often experience mild to mod-
erate bulbar dysfunction, affecting their ability to swallow. Children with type 1
12 Perioperative Care of Children with Neuromuscular Disease 161
spinal muscular atrophy (SMA), myasthenia gravis (MG), and with other rapidly
progressive NMDs may develop a more severe bulbar dysfunction with an increased
likelihood of aspiration. Finally, respiratory status can be further impaired by sleep
apneas, nutritional problems, gastroesophageal reflux, or progressive scoliosis. In
patients with compromised respiratory function, anesthetic agents may further
decrease respiratory muscle strength, exacerbating hypoventilation, airway secre-
tion retention, aspiration, and obstructive and central apneas. These conditions may
lead to nosocomial infections, prolonged intubation, tracheotomy, and eventually
death.
12.2.2 Cardiovascular Failure
Several NMDs are associated with cardiac dysfunctions (cardiomyopathies and/or

abnormality of the conduction system) as shown in Table 12.2. However, clinical
manifestations of heart failure are often unrecognized until very late stage, owing to
musculoskeletal limitations. All children with relevant cardiac dysfunctions have a
limited ability to increase cardiac output in response to stress. Consequently, they
are at high risk for perioperative cardiac side effects due to negative inotropic effect
of volatile and i.v. anesthetic agents, positive pressure ventilation, hypoxemia, and
acute anemia. Volatile anesthetics may also induce arrhythmia resulting from sensi-
tization of the heart to catecholamines and from inhibitory effects on voltage-gated
K+ channels. Finally, children with NMDs with respiratory involvement leading to
nocturnal hypoxemia may be affected by right ventricular changes because of pul-
monary hypertension.
Table 12.2 Cardiac dysfunction in children with neuromuscular disorders

Disorder Cardiac dysfunction
Guillain–Barrè syndrome, SMA type 1, Dysautonomia may enhance cardiovascular
a subgroup of hereditary neuropathies instability (i.e., bradycardia, blood pressure shifts)
Dystrophinopathies Dilated cardiomyopathy (very common; broad
spectrum of severity including severe cardiac
failure); arrhythmias and conduction defects (<10 %
of patients)
Limb-girdle muscular dystrophies Arrhythmias and conduction defects (common);
(LGMD) dilated cardiomyopathy (rare in LGMD type 2A,
2D)
Myotonic dystrophies Arrhythmias and conduction defects (common);
dilated cardiomyopathy (rare)
Congenital myopathies Arrhythmias and conduction defects; dilated
cardiomyopathy
Mitochondrial encephalomyopathies Arrhythmias and conduction defects; dilated
cardiomyopathy
Glycogen storage diseases type II Cardiomyopathy (hypertrophic cardiomyopathy in
the infantile form)
Lipid storage myopathies Cardiomyopathy
12.2.3 Malignant Hyperthermia (MH)
It is a rare inherited drug-induced disorder of the skeletal muscle characterized by

an increased muscle metabolism with excessive heat, carbon dioxide and lactate
production, high oxygen consumption, contractures of the muscles, and myofiber
breakdown. It is usually triggered when an MH-susceptible individual is exposed to
a halogenated agent or succinylcholine and in rare cases to strenuous exercise and/
or heat exposure.
12.2.3.1 Patients at Risk

• Diagnosis of ryanodine receptor 1 (RYR1) mutations or central core disease
(CDC)
• Relatives of MH or CCD patients
• Few muscle diseases:
– Central core disease
– Core-rod myopathy
– King–Denborough syndrome
12.2.3.2 Prevention
• Choice of anesthesia: “trigger-free” anesthetic and “clean” anesthesia machine for
halogenated agents. The anesthesia machine must be prepared by using a dispos-
able circuit, a fresh CO2 absorbent, disconnecting the vaporizers and flushing with
O2 at a rate of 10 L min for at least 20 min before use. However, these recommen-
dations are derived from older-style anesthetic machines, and modern anesthetic
workstations may need longer cleaning times to wash out residual inhalational
anesthetics in order to establish an acceptable concentration below 5 ppm.
• Availability of sufficient quantities of dantrolene in order to treat MH: dantrolene
(vials, 20 mg each).
• Adequate intra- and postoperative monitoring: carefully monitoring for signs of
rhabdomyolysis (i.e., serial plasma CK and myoglobin and urine myoglobin),
capnometry, and measurement of body temperature.
12.2.3.3 Management of Acute Crisis

• Discontinue inhalational agents and use non-triggering agents for the remainder
of the procedure.
• Hyperventilate with 100 % oxygen and intubate with endotracheal tube.
• Give dantrolene: loading bolus of 2.5 mg/kg i.v., with subsequent bolus doses of
1 mg/kg i.v. until the signs of acute MH have abated; 1 mg/kg every 6 h should
be continued for 48 h after the last observed sign of acute MH to prevent
recrudescence.
• Give sodium bicarbonate for acidosis.
• Cool the patient (cold saline for infusion, ice to body surface); lavage body cavi-
ties (e.g., stomach, bladder, rectum). Maintain temperature <39 °C.
• Treat hyperkalemia:
– To antagonize the myocardial effects of hyperkalemia, give immediately cal-
cium chloride i.v. (repeat the dose after 5 min if ECG changes persist).
– To shift potassium back into muscle cells hyperventilate, give sodium bicar-
bonate and insulin with 10 % dextrose (monitor finger stick glucose closely).
• Treat dysrhythmias: usually responds to treatment of acidosis and hyperkalemia;
use standard ACLS protocols; calcium channel blockers are contraindicated in
the presence of dantrolene.
12.2.4 Rhabdomyolysis
It is an uncommon but potentially fatal disorder triggered by succinylcholine or

halogenated agents in susceptible patients, characterized by muscle necrosis with
release of intracellular muscle constituents (i.e., myoglobin, potassium, and creatine
kinase) into the circulation. It can be acute, resulting in hyperkalemic cardiac arrest,
or subacute, presenting as dark urine, acute kidney failure, or cardiac arrest in the
postanesthetic care unit.
12.2.4.1 Patients at Risk

• Succinylcholine may cause rhabdomyolysis in almost all neuromuscular dis-
eases but especially if muscles are denervated, progressively dystrophic, or meta-
bolically altered.
• Halogenated agents may cause rhabdomyolysis in patients with myopathies
(especially dystrophinopathies and metabolic myopathies).
12.2.4.2 Prevention
• “Trigger-free” anesthetic and “clean” anesthesia machine for halogenated agents
(see malignant hyperthermia)
• Adequate intra- and postoperative monitoring: carefully monitoring for signs of
rhabdomyolysis up to 12 h postoperatively (i.e., serial plasma CK and myoglobin
and urine myoglobin)

• Treat hyperkalemia (see malignant hyperthermia).
• Prevent heme pigment-induced acute kidney injury:
– Early and aggressive fluid resuscitation with isotonic saline to maintain the
urine output greater than 1 mL/kg/h.
– Loop diuretics may be given to patients who develop volume overload as a
result of aggressive volume administration.
– Alkalinization of urine: administration of an alkaline solution to maintain the
urine pH above 6.5, providing the patient is not severely hypocalcemic and
has an arterial pH less than 7.5 and a serum bicarbonate less than 30 meq/L.
• Treat acute kidney injury: dialysis may be necessary for control of hyperkalemia
and correction of acidosis or for the treatment of volume overload.
12.2.5 Hyperkalemic Cardiac Arrest Secondary to Denervation
It is a cardiac arrest due to hyperkalemia triggered by succinylcholine in the pres-

ence of striated muscle denervation hypersensitivity (upregulation of nicotinic ace-
tylcholine receptors).
12.2.5.1 Pathologies at Risk

• Motoneuron diseases
• Peripheral neuropathies
12.2.5.2 Prevention
Avoid succinylcholine in children with motoneuron diseases or peripheral
neuropathies.

• Use standard ACLS protocols.
• Shift potassium back into muscle cells, give sodium bicarbonate and insulin with
10 % dextrose, and hyperventilate.
• Continue cardiopulmonary resuscitation until serum potassium levels are low-
ered to a near normal level.
12.3 Preoperative Assessment and Management
12.3.1 Neurological Assessment
Detailed diagnosis is essential to assess the risk during surgery and anesthesia.
Thus, preoperative assessment must include a neurological examination to confirm
the diagnosis, when feasible, and to identify the level of progression of the disease
in each patient. However, diagnostic process may be complex and some patients
may lack a definite diagnosis, particularly those manifesting only with isolated ele-
vated creatine kinase levels with or without minor signs. These children are particu-
larly at risk of life-threatening complications related to anesthesia and should be
treated as subjects at highest risk level.
12.3.2 Pulmonary Assessment
In all children with NMDs, preoperative pulmonary evaluation is strongly recom-

mended to assess the risk of respiratory complications and the need for specific
perioperative and postoperative management.
Assessment of respiratory function should include an accurate medical history
and physical examination, a chest x-ray, an evaluation of sleep-disordered breath-
ing, and the measurements of respiratory function and cough effectiveness.
Evaluation of respiratory function and cough effectiveness includes measurement of
FVC, peak cough flow (PCF), and diurnal pulse oximetry (SpO2). SpO2 less than
95 % in room air has been established as a clinically significant threshold of abnor-

mality, requiring carbon dioxide (PCO2) level measurement. Preschool or older
patients with developmental delay may not be able to perform evaluation tests of
respiratory function and cough effectiveness. In these cases, the measurement of the
crying vital capacity (i.e., FVC obtained from a tightly fitted mask over the nose and
mouth with in-line spirometer) can approximate FVC.
It is crucial to optimize the patient’s respiratory status before surgery. When
respiratory function measurements and sleep studies are abnormal, noninvasive
ventilation (NIV) and manual or mechanically assisted cough techniques may be
indicated. Therefore, planning and coordination with the hospital respiratory thera-
pists is crucial. In particular, mechanical insufflator–exsufflator (MI-E) can increase
coughing, promote deep lung inflation, and treat or prevent atelectasis. Consequently,
patients with limited respiratory reserve should be trained in these techniques before
surgery and assisted with these devices during sedation, regional anesthesia, and in
the postoperative period. This strategy is also recommended for patients already
using assisted cough techniques and long-term NIV.
Recently, preoperative training in the use of NIV has been recommended for
patients with Duchenne muscular dystrophy (DMD) with preoperative FVC
<50 % of predicted value and especially for patients at high risk of respiratory
failure, defined by an FVC <30 % of predicted value. Moreover, for children over
12 years of age, if PCF is less than 270 L/min, training in assisted cough tech-
niques is advocated before surgery. This strategy has the potential to be applied to
adults and children with respiratory involvement resulting from diagnosis other
than DMD.
12.3.3 Cardiac Assessment
Children with NMDs should undergo a careful assessment of cardiac function as

well as optimization of therapy before anesthesia or sedation. In all children with
NMDs, an electrocardiogram and echocardiogram should be performed before anes-
thesia or sedation, if not done in the previous 12 months. Moreover, signs or symp-
toms of arrhythmias should be promptly investigated with a Holter test. In addition,
patients with a high degree of AV blocks may need a cardiac pacemaker before GA.
In all patients with severe cardiac dysfunctions, invasive arterial pressure should
be monitored during GA and in the postoperative period.
In children with NMDs without primary myocardial dysfunction (e.g., SMA),
preoperative cardiologic evaluation is suggested only if pulmonary hypertension is
suspected.
12.3.4 Other Issues
Nutritional status should be optimized before surgery. In case of poor nutritional

balance, wound healing can be delayed and the patient could be too weak to ade-
quately clear secretions or maintain ventilation.
Patients with NMDs have an increased sensitivity to premedication drugs, which

could induce apnea and hypoventilation.
For patients chronically treated with steroids (i.e., DMD, MG), consideration has
to be paid to their administration during surgery. In fact, this therapy can suppress
the hypothalamic–pituitary–adrenal axis, and during a phase of stress, such as sur-
gery, the adrenal glands may not respond appropriately.
The preoperative evaluation should also include the assessment for a difficult
intubation due to jaw ankylosis, atrophy of the masseter muscle and/or other masti-
catory muscles, macroglossia, or limited mobility of the cervical spine. If any of
these conditions is present, intubation should be performed taking into account chil-
dren guidelines for difficult airway management.
Moreover, in those patients, obtaining an appropriate intravenous line could be
difficult. Ultrasound may assist peripheral cannulation. Besides, ultrasound-guided
venous access is considered the gold standard for any patient for whom central vas-
cular access is necessary. In this case, a peripherally inserted central venous catheter
utilizing a cephalic or basilic venous approach under ultrasonic guidance may pro-
vide a safe alternative to the standard approach.
In addition, children with NMDs with NMDs are predisposed to hypothermia
because of reduced heat production in atrophic or dystrophic muscle. Negative effects of
hypothermia are preventable by heating the skin with heated blankets or blown hot air.
Postoperative admission to a pediatric intensive care unit (PICU) should be con-
sidered in any patient at risk for respiratory complications, with weak cough, severe
bulbar dysfunction, severe cardiac dysfunction, or morphine infusions. In fact,
PICU setting allows intensive cardiovascular and respiratory monitoring and use of
adjuvant therapy, including NIV and cough-assisted and suctioning devices.
Finally, a very important preoperative issue is to establish whether the benefit of
surgery outweighs the anesthetic risk and discuss risks and benefits of surgical pro-
cedures with the patients and/or their family.
12.3.5 Preoperative Considerations in Specific NMDs
12.3.5.1 Myasthenia Gravis

Pharmacologic therapy should be optimized. If the patient is poorly controlled, a
preoperative course of plasmapheresis or i.v. immunoglobulins could be beneficial.
However, there is little evidence that supports this strategy in order to reduce anes-
thetic complication. Oral anticholinesterase drugs should be continued in the preop-
erative period, except for the day of surgery as they may interfere with muscle
relaxants and enhance bronchial secretions. When oral administration is limited, an
equivalent dosage of intravenous neostigmine should be introduced and continued
until the patient resumes oral therapy.
12.3.5.2 Mitochondrial Myopathies

These patients may have increased lactate levels during periods of physiological
stress. Therefore, preoperative fasting in these patients could be particularly
hazardous. Intravenous isotonic fluid containing dextrose (e.g., 0.9 % sodium chlo-
ride with 5 % dextrose) should be started during preoperative fasting period to allow
maintenance of normoglycemia, as excessive glycolytic oxidation may increase
plasma lactate levels.
In children with NMDs with decreased pulmonary function, GA should be avoided

preferring regional anesthesia whenever possible. If GA is unavoidable, ultrashort-
acting drugs, such as propofol and remifentanil, are preferable and succinylcholine
must be avoided. Furthermore, administration of volatile anesthetics in myopathic
children is usually considered at high risk for life-threatening complications.
12.4.1 Succinylcholine and Halogenated Agents
Four major categories of NMDs (see Table 12.1) should be considered to plan the
safest anesthesia strategy: (1) motoneuron diseases, (2) peripheral neuropathies, (3)
neuromuscular junction diseases, and (4) muscle diseases.
In motoneuron and peripheral nerve diseases, the use of halogenated agents is
permitted, whereas succinylcholine must be avoided.
In children with neuromuscular junction disorders, GA can be performed using
halogenated agents.
In myopathic children, the use of inhaled anesthetics and succinylcholine is clas-
sically considered at high risk for MH or acute rhabdomyolysis. Although only few
muscle diseases carry significant risk of MH such as some rare myopathies due to
mutation of calcium channels (e.g., ryanodine receptor), “central core myopathies,”
King–Denborough syndrome, or other rarer conditions, all children with muscle
disease carry a risk of rhabdomyolysis. Therefore, it is recommended to avoid the
use of succinylcholine and halogenated agents in such children. However, in chil-
dren with mitochondrial myopathies, halogenated agents can be administered.
Some authors agree that faced with a difficult venous access in a patient with myop-
athy, a brief use of inhalation anesthesia is possible as long as the anesthesiologist
is prepared to treat rhabdomyolysis; however, some other authors suggest the use of
ketamine in these circumstances. Although i.m. ketamine is used for adult patients,
an oral or rectal route is preferred for pediatric patients to avoid unnecessary pain
and stress to the child and their family.
12.4.2 Total Intravenous Anesthesia (TIVA)
Whenever inhalation anesthesia must be avoided, GA can be performed using

TIVA. However, it should be minded that respiratory and cardiac depression can
be induced by intravenous anesthetic agents and opioids. Thus, the dose of these
drugs should be carefully titrated to be effective but to avoid excessive respiratory

and cardiac depression. Although the effectiveness of target controlled infusion
(TCI) of propofol compared with manually controlled infusion remains contro-
versial in adults and in children, some authors reported that careful titration of
propofol by TCI enables to evaluate the patient’s sensitivity to propofol in sub-
jects with NMDs.
Moreover, despite its well-known limitation in pediatric patients, the use of
bispectral index monitor (BIS) may prevent the occurrence of awareness and reduce
the risk of drug overdose in children with NMDs.
12.4.3 Nondepolarizing Neuromuscular

Blocking Agents (NMB)
In all children with NMDs, nondepolarizing NMB may show prolonged duration of
neuromuscular blockade, even with short-acting drugs. Thus, most reports recom-
mend to avoid NMBs whenever possible. However, when NMB are necessary, the
dose should be reduced and titrated to effect, neuromuscular function has to be
continuously monitored (e.g., using the train-of-four monitoring), and the effect of
muscle relaxant should be always antagonized. Nevertheless, anticholinesterase
drugs are not recommended because they may lead to hyperkalemia. Therefore,
reversal of rocuronium-induced or vecuronium-induced neuromuscular blockade
by sugammadex could be beneficial in NMDs to eliminate the risk of postoperative
residual muscle paralysis. Finally, the combination of rocuronium and sugammadex
could replace the need for succinylcholine in rapid sequence induction in children
with NMDs.
12.4.4 Regional Anesthesia
There are potential risks with regional anesthesia in children with preexisting
peripheral nervous system diseases. Upton and McComas emphasized that if
these patients are exposed to secondary damages such as injuries from needles or
catheters, ischemic lesions from vasopressors, or toxicity of a local anesthetic, the
probability of neurological damages increases. On the other hand, the use of
regional or local anesthesia offers a significant advantage in terms of avoidance of
anesthetic drugs and reduction of postoperative respiratory complications for all
children with NMDs and mainly in those with reduced pulmonary function. A
significant reduction of the required volume of local anesthetic is possible when
ultrasound and peripheral nerve stimulator are used for nerve identification.
Moreover, the use of ultrasound appeared to reduce the incidence of hematoma
formation following vascular puncture. Therefore, regional anesthesia should be
warranted whenever possible, including patients with preexisting peripheral ner-
vous system disorders.
12.4.5 Anesthetic Considerations in Specific NMDs
12.4.5.1 Guillain–Barrè Syndrome (GBS)

In patients with GBS, anesthesia may be associated with severe complications due
to dysautonomia (i.e., bradycardia, blood pressure swings, and profound hypoten-
sion with sedatives). In patients with autonomic dysfunction, a potential sympa-
thetic blockade resulting from regional anesthesia requires careful control of blood
pressure. Consequentially, a neuraxial blockade should be cautiously administered
to patients with GBS. However, several cases have reported a successful use of epi-
dural and spinal anesthesia in these patients without any case of hemodynamic
instability.
12.4.5.2 Myasthenia Gravis (MG)

Factors potentially enhancing neuromuscular blockade should be avoided (e.g.,
hypothermia, hypokalemia, hypophosphatemia, and several drugs). As local anes-
thetic agents may block neuromuscular transmission, subarachnoid and epidural
anesthesia should be performed using reduced doses and preferably amid local
anesthetics, such as bupivacaine and ropivacaine.
Excess of anticholinesterase drugs may produce flaccid muscle paralysis and
pupil constriction (cholinergic crisis) in patients with MG. Many patients have a
decreased requirement of these drugs in the first 48 h. Thus, intravenous anticholin-
esterase drugs should be administered slowly and cautiously in the postoperative
period. Moreover, meticulous attention to pulmonary toilet is required, particularly
since respiratory secretions may be increased by the anticholinesterase drugs.
Sugammadex, in combination with neuromuscular monitoring, can be used to
reverse rocuronium-induced neuromuscular blockade in patients with MG, thereby
avoiding the need for reversal with acetylcholinesterase inhibitors.
12.4.5.3 Dystrophinopathies
Several studies have shown a delayed onset of nondepolarizing muscle relaxants in
patients with dystrophinopathies. Therefore, a high dose of rocuronium is needed to
shorten the onset time. Reversal of NMB by sugammadex can eliminate the risk of
postoperative residual paralysis, even after a high dose of rocuronium.
12.4.5.4 Myotonic Dystrophy

The anesthetic strategy of choice remains uncertain. Whenever possible, peripheral
nerve or neuroaxis blockade is preferable. When GA is indicated, extreme care
should be taken during all phases of anesthesia. Many authors have proposed the
use of halogenated gases in patients with DM1 and DM2, but others consider safer
to avoid them. Noteworthy, halogenated agents may induce postoperative shivering
which can precipitate myotonia. Moreover, there is an increased sensitivity of DM1
patients against thiopental and propofol. During anesthetic induction, thiopental is
relatively contraindicated due to prolonged respiratory depression. Propofol can be
successfully used both for induction and maintenance of anesthesia, if the dose is
carefully titrated. In these patients respiratory failure may be caused both by weak-
ness and myotonic reactions. Many factors like hypothermia, postoperative shiver-
ing, dyskalemia, mechanical and electrical stimulation, or drugs (i.e., propranolol,
succinylcholine, and anticholinesterase agents) can precipitate myotonic contrac-
tures. The development of myotonia represents an important problem for anesthesia
because, if laryngeal and respiratory muscles are involved, intubation can be diffi-
cult or even impossible. Myotonia occurs for an intrinsic change in the muscle and
not in the peripheral nerve or neuromuscular junction. Thus, it cannot be abolished
by peripheral nerve blockades or neuromuscular blockers. Myotonia may be treated
with midazolam; otherwise, the treatment is mainly preventive, avoiding all trigger-
ing factors. Consequently, a protocol of safe surgical procedure should be adopted
to prevent myotonia. Dyskalemia, triggering drugs, and excessive stress should be
avoided, body temperature should be closely monitored to minimize the risk of
shivering, and succinylcholine should not be administrated. Careful cardiac moni-
toring is needed in all DM1 patients, for their high risk of arrhythmic events, which
may cause sudden death at any age. Finally, these patients have also a propensity to
develop hyperglycemia, dysphagia, and gastroesophageal reflux. Maintaining the
torso of the patient elevated in the postoperative period reduces the risks of
aspiration.
12.4.5.5 Mitochondrial Myopathies

Mitochondrial myopathies consist of a heterogeneous group of disorders caused by
abnormalities in mitochondria leading to muscle weakness, lactic acidosis, and a
variable combination of central and/or peripheral nervous system involvement (sei-
zures, hemiparesis, cortical blindness, ophthalmologic abnormalities, hearing loss),
bulbar dysfunction with impaired swallowing, cardiac dysfunction, hepatic and
renal disease, and defect of insulin secretion. It should be borne in mind that propo-
fol has a mitochondrial depressant effect that can induce lactic acidosis. Moreover,
in these patients also other anesthetic agents such as thiopentone, midazolam, halo-
genated agents, and local anesthetics can cause lactic acidosis interfering with mito-
chondrial function. Nevertheless, it is noted that all these anesthetic agents have
been used with success in patients with mitochondrial myopathies. This suggests
that there is no case for avoiding any particular anesthetic agents in these patients.
However, caution is required with all anesthetic agents. In particular, it would be
seen as pertinent to avoid the prolonged use of propofol for the maintenance of
anesthesia. Moreover, lactic acidosis should be prevented with control of excessive
stress, maintaining normal serum glucose levels, adequate oxygen balance, stable
cardiovascular function, and adequate gas exchange. Finally, the routine periopera-
tive use of lactate-free i.v. fluids in all children with mitochondrial disease undergo-
ing GA is recommended.
12.4.5.6 Glycogenosis Type II (GSDII)

In the infantile form of GSDII, characterized by a significant hypertrophic cardio-
myopathy, decreased cardiac output and myocardial ischemia have been observed
during anesthesia. In fact, stiffness of the hypertrophied ventricular walls can induce
abnormal diastolic relaxation and lead to dynamic left ventricular outflow tract
obstruction, elevated left ventricular end-diastolic pressure, and reduced diastolic
filling. This condition may precipitate as a consequence of a decrease in systemic
vascular resistance, preload, or both eventually induced by anesthetic agents, with
an increased risk of intraoperative cardiac arrest.
12.5 Postoperative Management
12.5.1 Pain Control
Adequate pain control is essential to prevent hypoventilation secondary to splinting

after thoracic, upper abdominal, and spine surgery.
Intravenous opioids should be titrated to provide adequate analgesia and promote
airway clearance minimizing respiratory suppression. This goal is best accom-
plished with preemptive analgesia and using multiple pharmacological agents. Oral
clonidine administered preoperatively has been shown to reduce the requirement for
postoperative analgesics. Moreover, i.v. paracetamol, administered alone or in com-
bination with nonsteroidal anti-inflammatory agents (e.g., ketorolac), has been
shown to reduce the amount of opiates delivered.
Continuous infusion of opioids via epidural catheters can be used when appro-
priate to achieve pain control while minimizing respiratory side effects.
Finally, wound infiltration with local anesthetic solutions and continuous infu-
sion of local anesthetic solutions via peripheral nerve block catheters should be
offered when appropriate as safer alternatives. Peripheral nerve blocks have been
shown to provide postoperative analgesia which is comparable to that obtained with
an epidural technique but with less side effects. These neural structures should be
localized using ultrasound guidance or nerve stimulation techniques.
In case of hypoventilation after opioid administration, adequate ventilation
can be achieved by using NIV or by delaying extubation for 24–48 h. Moreover,
MI-E can also be useful when pain prevents the children from coughing
spontaneously.
12.5.2 Respiratory Management
Postoperative management should be determined by preoperative respiratory func-

tion and the type of surgery performed. Children with normal cough clearance and
relatively preserved muscle function are not at increased risk for postoperative com-
plications. On the other hand, children with decreased respiratory muscle strength
require close monitoring and aggressive respiratory management.
The application of a protocol based on the combination of NIV with MI-E after
extubation for high-risk children with NMDs may provide a clinically important
advantage by averting the need for reintubation or tracheotomy and shortening their
PICU stay.
NIV as bridge support after extubation should be considered for patients with
baseline FVC <50 % of predicted value and should be strongly considered for those
with FVC <30 % of predicted value. Postoperatively the use of assisted cough tech-
niques including the use of MI-E must be considered for any teenage with preopera-
tive PCF <270 L/min. These techniques should be adopted before and after
extubation. Assisted cough technique is obviously also recommended for patients
already using MI-E and NIV preoperatively.
To improve the chance of success, extubation should be delayed until respiratory
secretions are well controlled and SpO2 is normal or baseline in room air.
In patients requiring long-term mechanical ventilation, respiratory support must
be continued in the postoperative period.
Oxygen must be applied with caution in children with NMDs because it can cor-
rect hypoxemia without treating the underlying cause such as hypercapnia, mucus
plugging, and atelectasis. To facilitate appropriate oxygen use, CO2 levels should be
strictly monitored.
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with a Metabolic Disease 13
Veyckemans Francis and Scholtes Jean-Louis
Metabolic diseases are numerous. They can broadly be divided into three categories
depending on their pathophysiology:
• Intoxication by accumulation of a toxic compound that cannot be eliminated:

e.g., hyperammonemia in case of urea cycle anomaly
• Lack of energetic resources due to deficiency in their synthesis or use: e.g., lack
of aerobic ATP in mitochondrial cytopathies
• Storage of complex molecules: e.g., mucopolysaccharidosis
Some overlap is of course possible: for example, both hypoglycemia and hepatic
accumulation of dextrin in case of glycogenosis type III (Cori’s disease). Moreover,
as a rule, the more important the deficit, the earlier the signs and symptoms of the
disorder appear: a mild deficit can thus remain pauci- or asymptomatic for a long
period of time or present with signs, for example, neuropsychiatric problems, that
do not usually trigger search for a metabolic disorder.
The anesthetic consequences of metabolic diseases vary widely: for example, the
main concerns are airway and cardiac related when caring for a child with muco-
polysaccharidosis, adequate steroid coverage in case of congenital adrenal hyper-
plasia, and avoiding increased protein catabolism in the presence of a urea cycle
anomaly. Anesthesiologists care for a child with a metabolic disease only for a short
but critical period of time, the perioperative period, when many factors can jeopar-
dize its fragile equilibrium. They therefore need the help of the child’s caring team
to answer the following questions:
V. Francis, MD (*) • S. Jean-Louis, MD

Anesthesiology, Cliniques universitaires St Luc, Université Catholique de Louvain, Avenue
Hippocrate 10-1821, Bruxelles 1200B-1200, Belgium
e-mail: francis.veyckemans@uclouvain.be

DOI 10.1007/978-3-319-21960-8_13
176 V. Francis and S. Jean-Louis
• What are the direct consequences of the disease regarding the child’s anesthetic
management: upper and lower airway, heart, muscle function, neurodevelop-
mental issues, seizures etc.?
• What is the child’s usual treatment and/or diet?
• What could be the effects of some anesthetic drugs on the organs affected by the
disease?
• What are the possible effects of the perianesthetic period on the child’s metabolic
equilibrium: fever, stress, starvation, etc.?
• What intravenous solution should be used as long as the child is unable to follow
its usual diet: glucose 5, 10, or 20 % with electrolytes?
• What should be specifically monitored: blood glucose, lactates, or ammonium?
• What have been the child’s previous anesthetic experiences?
The first goal of this chapter is to give the reader a frame to help him/her estab-
lish an anesthetic plan adapted to the child’s known or suspected pathology and its
current preoperative status. The second goal is to highlight the importance of devel-
oping a “metabolic reflex” when a child presents with an unusual clinical picture in
the perioperative period. This will be illustrated with a few examples.
13.1 Sources of Information
It is necessary to check the most recent data about a metabolic disease in order to
know its pathophysiology, its usual clinical presentations and outcome, and its treat-
ment, whether curative or symptomatic. This can be done using the paper or elec-
tronic literature, for example:
• Inborn Metabolic Diseases, 5th edition, by Saudubray, van den Berghe & Walter
(Springer, 2012)
• Genetic Syndromes by B Bissonnette & B Dalens (McGrawHill, 2005)
• http://www.rarediseases.org/
• http://orpha.net/
• http://orphanaesthesia.eu
• http://ncbi.nlm.nih.gov/Omim/
or, more simply, “googling.”

When using Google, it is important to remind that the ranking of the links obtained
depends not only on the key word(s) introduced but also on a complex algorithm: the
ranking is thus not linked to the quality of the data and each link should be checked
(origin, date of update or publication, etc.). Moreover, when considering anesthetic
case reports, the information should be interpreted with caution [1] because they
generally describe isolated cases, the scientific value of which is relative:
• Either there was no problem: it could be the result of excellent anesthetic care or
simply a lucky outcome.
13 Perioperative Care of Children with a Metabolic Disease 177
• Or something happened: it is sometimes difficult to determine whether it was

associated with the disease or with borderline anesthetic management.
• In addition, the date of publication should be checked: some were published at a
time when current equipment (e.g., supraglottic airways) or drugs (e.g., short-
acting opiates or muscle relaxants, propofol) were not available yet.
The reviews of large series are therefore the best source of information.
We should also keep in mind that thanks to progress in medicine, the natural his-
tory of some diseases has changed: their evolution can be totally or partially con-
trolled by a strict medical treatment (a special diet, e.g., phenylketonuria), by
intravenous enzyme replacement therapy (e.g., Gaucher’s and Pompe’s disease), and/
or by organ transplantation (e.g., Hurler’s disease) [2, 3]. We currently do not know
yet what the evolution of the cured disease and the side effects of its treatment will be,
neither what are the possible anesthetic implications of their modified condition.
Last, the parents often know very well their child’s disease and can provide the
address of useful website specifically dedicated to the disease. And finally, nothing
is better than a direct contact with the pediatrician in charge of the child: he/she
knows very well both the child and its disease.
13.2 Synthesis of the Informations
The pathophysiology of the disease should be carefully reviewed in the light of anes-
thetic care. In order to make sure everything has been considered, the authors pro-
pose using the NARCO + Age acronym [4] as summarized in Table 13.1. In fact, this
Table 13.1 The NARCO memory tool

Neuromuscular Any developmental delay?
muscles: spasticity, contractures, hypotonia?
Seizures: controlled or not?
Medical treatment?
Airway Difficult intubation/ventilation?
Any risk for regurgitation/inhalation? chronic lung infection?
Signs of obstructive or central sleep apnea?
Respiratory Reactive airway?
Restrictive or obstructive syndrome?
Chronic lung infection?
Cardiovascular Dysrhythmia?
Cardiomyopathy?
Others Special diet?
Tolerates fasting?
Previous anesthesia?
Psychological issues?
Communication
Modified from Malviya et al. [4]
system-based approach was originally designed to evaluate the child’s anesthetic risk
better than the ASA physical status and any other memory jogger can be used such
as ABCD with A for airway, B for brain, C for cardiac, and D for drugs, diet, etc.
But the child’s age should also be taken into account because, as for any pediatric
case, (1) the younger the patient, the higher the risk; (2) young age has its own ana-
tomic, physiologic, and pharmacologic specificities; and (3) because some patholo-
gies become worse with age, for example, mucopolysaccharidosis and mitochondrial
cytopathies.
The anesthesiologist should also keep in mind that a child with a metabolic dis-
ease remains a child: the “metabolic” tree should not hide the forest! The basic
pediatric preoperative evaluation should be undertaken as in any child:
• Personal history: previous anesthesia?

• Allergies?
• Bleeding problem?
• Upper airway: mouth opening? retrognathia? facial asymmetry? midface hypo-
plasia? loose teeth? snoring during sleep?
• Airway reactivity: recent infection? asthma? passive smoking?
• Difficult venous access?
• Cardiopulmonary examination?
The final anesthetic plan should also be adapted to the procedure for which anes-
thesia is needed, whether it is an emergency or not, and whether it will occur in an
operating room or outside the operating theaters area. It should be borne in mind
that an emergency procedure combines the risks of emergency anesthesia (full
stomach) with the effects of fever, hypovolemia, and stress on the child’s metabolic
equilibrium: the child’s pediatrician’s advice and the availability of a high-
dependency bed for the early postoperative period are necessary in this context.
Last but not least, there are psychological issues to consider: as it grows, a child
with a metabolic disease becomes a chronic medical patient with its “special
needs” and phobias (mask, needle) but also with a critical eye on what is done
around him/her. Moreover, compliance with treatment is often a critical issue at the
time of adolescence. In short, a child with a metabolic disease is a fragile person
and taking care of it, and of its family, needs a mix of science, vigilance, and
compassion.
13.3 Example 1: A Urea Cycle Defect
The urea cycle is the succession of six successive enzymatic reactions to transform
ammonia, the result of endogenous and exogenous protein catabolism, in urea
which can be eliminated in the urine. It occurs only in the hepatocytes [5]. N-acetyl
glutamate synthetase (NAGS) is one of the three mitochondrial enzyme participat-
ing to it. NAGS deficiency is transmitted as an autosomal recessive trait (NAGS
gene, 17q21.31) and its prevalence is around 1/70,000. Its clinical signs vary accord-
ing to the importance of the deficit and thus of the patient’s age:
• Neonatal period: difficult feeding, vomiting a few hours after birth, and rapid
evolution to hypotonic coma with seizures if not diagnosed and treated.
• Infancy: anorexia, vomiting, and failure to thrive; these children often undergo
diagnostic esophagogastroscopies before the definitive diagnosis is established.
• Childhood and adolescence: episode(s) of acute decompensation presenting as a
neurologic (encephalopathy, convulsions, ataxia, psychiatric problem), meta-
bolic (coma), or hepatic (cytolysis, Reye-like syndrome) problem precipitated by
a stress such as fever, postoperative period, infection, or administration of val-
proate acid.
The basic principle of the treatment of NAGS is avoiding protein catabolism.

The children therefore need a special diet, the protein content of which is carefully
adapted to the child’s age and decreased in case of infection or stress (e.g., surgery).
They often also receive a daily dose of N-carbamyl glutamic acid (30–250 mg/kg/
day) according to their blood urea and NH3 level. Orthotopic liver transplantation
can be performed to cure the disease.
Anesthetic implications:
• N: according to the child neurologic status

• A: nothing specific to the disease
• R: nothing specific to the disease
• C: nothing specific to the disease
• O
– Special diet: a low-protein and hypercaloric diet should be started 1 or 2 days
before elective surgery.
– Preanesthetic fasting time has to be kept as short as possible; a glucose-
containing solution with electrolytes should be administered at the beginning
of the preanesthesia starving period.
– Monitoring: NH3 (nl <50 μmol/L), glycemia.
– In case of seizures, valproate should not be administered as it inhibits carba-
mylphosphate transferase, another enzyme of the cycle.
– There is no specific contraindication to perform a regional block, which is a
good way to reduce the patient’s perioperative stress response.
– In case of surgery during or following which blood can enter the digestive
tract (e.g., ENT, dental, or gastrointestinal surgery), the gastric content should
be aspirated (nasogastric tube) because ingested blood is an important source
of exogenous protein.
– In case of hyperammonemia, the following should be administered in emer-
gency: IV glucose 20 %, Na-benzoate (0.25–0.5 g/kg/day), Na-phenylbutyrate
(0.5 g/kg/day), and l-arginine (0.25–0.5 g/kg/day). In case of failure or severe
neurologic signs, hemodialysis or peritoneal dialysis should be performed.
13.4 Example 2: A Glycogenosis
In case of glycogenosis type III (also called Cori’s or Forbe’s disease), the absence
of amylo-1, 6-glycosidase impairs complete degradation of glycogen in glucose:
both a risk of hypoglycemia and accumulation of dextrin in hepatic and/or muscular
cells ensue. Both the liver and the muscles are affected in type A while only muscles
cells are affected in form B.
The accumulation of dextrin into the hepatocytes leads to hepatomegaly and pro-
gressively to hepatic fibrosis; in some cases, cirrhosis and hepatic adenomas develop
during adolescence. These patients are often obese because they require frequent
meals to avoid hypoglycemia. Cases of late hypertrophic cardiomyopathy have been
described.
Anesthetic implications [6, 7]:
• N: sometimes hypotonia in infancy; proximal amyotrophy with elevated CPK in

adolescents and adults
• A: macroglossia that may be present
• R: respiratory comorbidities of obesity, asthma and obstructive sleep apnea
• C: echocardiography to rule out cardiomyopathy
• O
– Hepatic function has to be checked; any sign of portal hypertension?
– Difficult venous access and other comorbidities of obesity.
– Preanesthetic fasting time has to be kept as short as possible; a glucose-
containing solution with electrolytes should be administered at the beginning
of the preanesthesia starving period.
– Monitoring: blood glucose level.
– Succinylcholine and use of a surgical tourniquet should be best avoided to
prevent rhabdomyolysis (fragile muscles).
– There is no specific contraindication to perform a regional block but
ultrasound-guided peripheral nerve blocks could be more tricky to perform
because amyotrophy modifies muscular echogenicity.
13.5 A Mitochondrial Cytopathy
The mitochondrion is the main energy provider of the cell and many metabolic
reactions occur at least partly into it: metabolism of glucose (tricarboxylic or
Krebs cycle), lipids (β-oxidation of fatty acids with the carnitine shuttle system),
and protein (urea cycle). In addition, many neurodegenerative diseases (e.g., some
forms of Parkinson or Charcot-Marie-Tooth disease) are now known to be caused
by defects in what can be called the “maintenance functions” of the mitochon-
drion. But the term mitochondrial cytopathy refers mainly to pathologies of the
respiratory chain or oxidative phosphorylation system, a succession of reactions
occurring in the inner membrane of the mitochondrion: it generates an active
proton (H+) and a free electron gradient leading to the production of ATP. The five
protein complexes involved in the respiratory chain are encoded by genes that are
present in the mitochondrial or in the nuclear DNA: their mode of transmission is
complex being either maternal or autosomic dominant or recessive. Moreover,
their phenotypic expression is highly variable depending on the relative distribu-
tion of wild and mutated mitochondria within each cell and on the energetic needs
of the tissue wherein they are distributed (threshold effect) [8]. Mitochondrial
cytopathies are usually called according to acronyms such as MERFF (myoclo-
nus, epilepsy, ragged red fibers), MELAS (mitochondrial encephalopathy, lactic
acidosis, stroke-like episodes), or their discoverer’s name (e.g., Leigh or Kearns-
Sayre’s disease).
A peculiar aspect of the anesthetic care of mitochondrial cytopathies is that many
anesthetic agents do interfere in vitro with the respiratory chain. Those data were
obtained in vitro on wild mitochondria isolated from tissue: their relevance for clini-
cal practice is thus difficult to define taking into account that almost all anesthetic
agents have been used in patients with a mitochondrial cytopathy without observing
major clinical effects. However, they should be kept in mind when planning anes-
thesia, for example:
• Propofol inhibits complexes II and V of the respiratory chain as well as the

intramitochondrial transport of free fatty acids by the carnitine system: a con-
tinuous infusion of propofol is thus considered as contraindicated because it
could induce a propofol infusion syndrome (PRIS) [9]. However small case
series have been published showing no untoward effect of a continuous infusion
of propofol in patients with a mitochondrial cytopathy provided a glucose-con-
taining solution was associated [10]. Recently a case of neurologic deterioration
has been observed after a single dose of propofol given without glucose admin-
istration in a girl with MELAS syndrome but her clinical status was deteriorat-
ing before anesthesia: it is thus difficult to determine whether her metabolic
deterioration would have occurred without propofol [11]. In any case, a glu-
cose-containing solution (6 mg·kg−1·h−1) should always be associated with the
use of propofol in patients with a known or suspected mitochondrial cytopathy,
and their blood lactate level should be monitored if a continuous infusion of
propofol is used.
• Barbiturates, etomidate, and ketamine inhibit complex I.
• Nitrous oxide decreases the activity of complex IV which could favor the local
synthesis of nitric oxide.
• Halogenated agents act, among others, on the GAS-1 gene which encodes a sub-
unit of complex 1 [12]: it is thus possible that children with a mitochondrial
cytopathy are more sensitive to halogenated agents as shown in a series of chil-
dren with complex I dysfunction who needed less sevoflurane to achieve a BIS
level of 60 [13].
• Regarding local anesthetics, lidocaine does not interfere with the respiratory
chain but both isomers of bupivacaine inhibit complex I more than ropiva-
caine [14].
As the mitochondrial cytopathies are all multisystemic and evoluting diseases,

the preoperative evaluation of the patient should look at every organ system. Going
back to the proposed NARCO memory tool:
• N: the patient’s neurologic status needs to be carefully evaluated: seizures and

their level of control? encephalopathy? amyotrophy? contractures? scoliosis?
mental retardation?
– There is no risk of malignant hyperthermia even though one poorly docu-
mented case [15] and an abnormal response to caffeine-halothane contracture
test in one adult with a combined mitochondrial and metabolic myopathy [16]
have been described: abnormal mitochondria are a frequent finding at histo-
logic examination of diseased muscles and the response to contracture tests
can be falsely positive in case of structural muscle disease.
– There is no risk of anesthesia-induced rhabdomyolysis (AIR) when haloge-
nated agents are used.
– In case of muscular signs (amyotrophy, contractures, disuse atrophy), succi-
nylcholine should be best avoided to avoid acute rhabdomyolysis.
• A: nothing specific to the disease; gastroparesis with delayed gastric emptying
can be observed if the gastrointestinal system is involved; this could result in a
“full stomach” situation.
• R: central and/or obstructive apnea should be looked for. A decreased response
to both hypoxia and hypercarbia has been observed in case of Leigh syndrome:
preoperative sedation should thus be used with great care if at all [17]. There are
signs of obstructive or restrictive pulmonary dysfunction in case of chronic
infection (inhalation of saliva or gastric content) and/or scoliosis: pulmonary
function tests are usually impossible to perform but measuring SpO2 on air and
percutaneous CO2 at nighttime can be helpful.
• C: ECG and echocardiography to rule out a cardiomyopathy and dysrhythmias
or conduction disturbances, respectively.
• O [18].
– Any event increasing the patient’s oxygen consumption, such as fever and
infection, could deteriorate its neurologic status [11, 19]; in those cases, the
indication for surgery and anesthesia should be reevaluated with the whole
caring team; in the same way, both preoperative hypo- and hyperthermia, as
well as postanesthetic shivering, should be avoided.
– Liver and kidney function should be checked as well as hemoglobin, platelets,
and electrolytes; in case of unexplained hyponatremia/hyperkalemia, subclin-
ical adrenal insufficiency should be suspected.
– The patient should take its usual treatment (antiepileptics, vitamins, carnitine,
CoQ, etc.) up to the day of anesthesia.
– Preanesthetic fasting time has to be kept as short as possible; a 5–10 %
glucose-containing solution with electrolytes should be administered from the
beginning of the preanesthesia starving period; it is recommended to avoid
any IV fluid solution containing lactates (e.g., Hartmann’s solution) even
though the lactate load is actually very low and such solution has been used
uneventfully in a series of cases [10]; if the child receives a ketogenic diet to
control complex seizures, the neurologist’s advice should be asked regarding
perioperative fluid content.
– Monitoring: blood glucose and lactate level. The basal blood lactate levels of
the patient should be known: it is usually somewhat higher than the upper
limit of normal values; to be valid, the venous blood sample on which lactates
are measured should be withdrawn without applying a tourniquet; blood glu-
cose should be kept within normal limits because both hypo- and hyperglyce-
mia can be deleterious for the mitochondrial function.
– If a non-depolarizing muscle relaxant is used, neuromuscular function should
be carefully monitored because cases of increased sensitivity have been
described [20]; moreover, if muscular signs are present, the train-of-four
should be obtained before administering the muscle relaxant in order to know
the patient’s basal value.
– There is no specific contraindication to perform a regional block, and it is a
good way to reduce the patient’s perioperative stress response; but scoliosis
can make a neuraxial block difficult to perform and should be discussed with
the parents if demyelinating lesions are present; moreover, some patients
present with a paucisymptomatic peripheral neuropathy with a reduction of
motor nerve conduction velocity [21]: the possible effects of a regional block
on these axonal and/or demyelinating lesions are currently unknown.
13.6 Developing a “Metabolic Disease” Reflex
In Western countries, many metabolic diseases are currently detected at birth via a
systematic screening (Guthrie’s test). However, some are not detectable in the neo-
natal period and some children can escape the test for different reasons. Moreover,
a partial metabolic disorder can remain asymptomatic for a long time because it is
compensated by other metabolic pathways or the patient spontaneously adapted its
diet or behavior: for example, patients with a mild form of a urea cycle disorder
spontaneously avoid meat because they feel unwell after eating some (hyperammo-
nemia). But the metabolic disorder can suddenly become symptomatic if the
patient’s fragile metabolic equilibrium is broken following a stressful situation such
as fever, starvation, protein catabolism, etc. These are typical encountered during
the perioperative period. The anesthesiologist should always think “metabolism” in
case of unexplained complication following an apparently uneventful anesthesia
such as delayed awakening or behavioral changes.
There are many causes for delayed awakening after anesthesia, such as:
• Hypothermia
• Overdose [22]
Table 13.2 Easily obtained biological signs to detect an acute meta-

bolic disorder
Diabetes mellitus: ↑ or ↓ blood glucose
Mitochondrial cytopathy: ↑ lactates,
Organic acidemia ↑ lactates, ↓ blood glucose
Urea cycle disorder: ↑ NH4
Hypothyroidism: ↓ blood glucose
Adrenal insufficiency: ↓ blood pressure ↓Na ↓ blood glucose
(Cave: asthmatic, child with a transplanted organ)
• Drug interaction [23]

• Cerebral edema whatever its cause: hyponatremic encephalopathy and trauma
• Cerebral ischemia: sickle cell disease, Moyamoya syndrome, etc.
• Cerebral embolism [24]
• Or an asymptomatic cerebral tumor
In the same way, there are many possible causes for postanesthesia behavioral
changes: they can be the result of one of the above-mentioned cerebral pathologies
or of:
• An idiosyncratic drug reaction [25, 26]

• A hysteric conversion, a diagnosis of exclusion
But they can also be the result of a decompensated metabolic disorder [27, 28].
In those circumstances, the anesthesiologist should not hesitate to obtain a blood
sample to check glucose, electrolyte, ammonium, and lactate levels (see Table 13.2)
and even to ask for a cerebral CT scan and the advice of a neurologist. This will
allow initiate, if necessary, a life-saving symptomatic treatment and the first stage(s)
of a diagnostic workup.
Conclusion
The perioperative care of a child with a metabolic disease is a stressful experi-
ence for its parents and a clinical, and often pharmacologic, challenge for the
anesthesiologist.
A child with a metabolic disease is a fragile person and taking care of it, and
of its family, needs a mix of science, vigilance, and compassion, as well as a
team approach. After anesthesia, we should not forget the child’s future but give
the parents a short report on the technique(s) and precautions used as well as
some practical issues in order to help colleagues to take care of their child in the
future, in elective, as well as in emergency situations.
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Pediatrics 133:e1072–e1076
Perioperative Care of Children with OSA
14
Gianluca Bertolizio and Karen Brown
14.1 Introduction
Sleep-disordered breathing (SDB) represents a spectrum of diseases which involves

up to 13 % of children and includes snoring, central sleep apnea (CSA), obstructive
sleep apnea syndromes, and other sleep-related hypoventilation/hypoxemic condi-
tions [1].
Obstructive sleep apnea (OSA), a disorder of breathing during sleep, is charac-
terized by prolonged partial upper airway obstruction and/or intermittent complete
obstruction that disrupts ventilation during sleep and normal sleep patterns [2].
Most of the obstructive respiratory events in children with OSA occur during
rapid eye movement (REM) sleep [3], when airways are more vulnerable to col-
lapse [4].
14.1.1 Epidemiology
Adult and pediatric OSA differs. In adults between the ages of 30 and 70 years,
OSA affects 20 % of men and 10 % of women.
In children, the prevalence of OSA is 1–6 %, with an equal distribution between
boys and girls [2, 5]. The onset usually occurs between 2 and 8 years of age [5],
coinciding with lymphadenoid hypertrophy [6]. A second peak is reported during
adolescence [7], with boys being more affected than girls [6].
Obstructive apneas have been reported in 36–57 % of infants, with a peak inci-
dence between 2 and 7 weeks of age [8].
G. Bertolizio (*) • K. Brown

Department of Anesthesia, Montreal Children’s Hospital, McGill University,
1001 Boulevard Décarie, Montreal, QC H4A 3J1, Canada
e-mail: gianluca.bertolizio@mcgill.ca

DOI 10.1007/978-3-319-21960-8_14
188 G. Bertolizio and K. Brown
14.1.2 Clinical Presentation
In older children and adolescents, headache, daytime somnolence, and dry mouth are
common signs of OSA. Recent data suggest that daytime sleepiness is more common
than previously thought [9] and its prevalence may be as high as 35 % [10].
Symptoms of childhood OSA include nightly apneic episodes, nighttime snor-
ing, restless sleep, and daytime sleepiness.
Snoring is reported in 3–14 % of children, whereas witnessed apneas are
described in 2–5 % of children younger than 6 years of age [11]. Restlessness, dia-
phoresis, and parasomnias are also reported.
Infants with OSA may present with mouth breathing, excessive waking, labored
breathing, night sweats, and failure to thrive [12]. In infants sleepiness is rarely
reported. Prolonged periods of obstructive hypoventilation are often present, espe-
cially in the premature infant. In the majority of infants with OSA, craniofacial
conditions and adenotonsillar obstruction are identified, whereas obesity is reported
only occasionally.
14.1.3 Risk Factors for OSA
OSA and SDB are more common among former preterm infants [13] and in chil-
dren who reside in disadvantaged neighborhoods [14]. There is a higher incidence
of OSA in children of African-American (AA) ethnicity [13, 15]. Furthermore,
these children demonstrate more severe oxygen desaturation during obstructive
apnea than Latino and Caucasian children [15].
A recent analysis [16] of over 1200 children aged 5–10 years reported that AA
ethnicity and prenatal exposure to tobacco smoke were both significantly associated
with more severe OSA. Of note, over 90 % of the children with severe OSA were
represented by children of AA ethnicity. A limitation of this study was that patients
with associated comorbidities and obesity were excluded.
Obesity is also a risk factor for OSA in children, such that the risk of OSA
increases by 12 % with each 1 kg/m2 increment in body mass index (BMI) [9].
However, the BMI does not linearly correlate with the severity of the OSA [17]. The
prevalence of OSA among obese children ranges between 22 and 40 % [18, 19].
Asthma is also related to OSA [9]: it usually does not affect baseline saturation,
but it may worsen the nadir saturation during REM sleep [20]. Parental history of
adenotonsillectomy and tonsillar hypertrophy are also risk factors for OSA [21].
14.1.4 Consequences of OSA
Children with mild SDB have high prevalence of cognitive impairment [9] and
learning and behavior problems, with the strongest, most consistent associations for
externalizing hyperactive-type behaviors that resemble the attention-deficit/hyper-
activity disorder (ADHD) [2].
14 Perioperative Care of Children with OSA 189
Children with OSA have autonomic dysregulation and altered baroreflex func-
tion [22] and dysregulation of hypothalamus-pituitary-adrenal axis. OSA is associ-
ated with a higher incidence of enuresis [9, 23], especially in girls.
Children with OSA have a significant decrease in exercise tolerance that has
been attributed to a compromise in cardiac function. In particular, recent data show
a reduction of cardiac and stroke volume indexes in children aged 7–12 years with
OSA compared to weight-matched healthy subjects [24].
Furthermore, OSA causes endothelial dysfunction [9], systemic [25] and pulmo-
nary [26] hypertension, and left [27, 28] and right [29, 30] ventricular dysfunction.
Compared to primary snoring, children with OSA demonstrate a larger left ven-
tricular mass index and a greater relative wall thickness [28] and left ventricular
diastolic dysfunction [27]. Compared to age-matched healthy children, patients
with OSA have a higher mean pulmonary artery pressure, a shorter ejection time,
and a lower myocardial performance index [30].
14.2 Diagnosis of OSA
14.2.1 Physical Exam and Medical History
It is widely held that clinical criteria can be used to diagnose OSA. Snoring, in par-
ticular loud snoring, witnessed apnea, mouth breathing, unusual body and head
position during sleep are all associated with OSA [31]. During wakefulness, mouth
breathing may be present. Daytime sleepiness and tiredness are reported. Both obe-
sity and failure to thrive occur [31]. Table 14.1 lists the signs and symptoms
Table 14.1 Signs and symptoms associated with obstructive sleep apnea in children [32]
History
Frequent snoring (≥3 nights/week)
Labored breathing during sleep
Gasps/snoring noises/observed episodes of apnea
Sleep enuresis (especially secondary enuresis) after ≥6 months of continence
Sleeping in a seated position or with the neck hyperextended
Cyanosis
Headaches on awakening
Daytime sleepiness
Attention-deficit/hyperactivity disorder
Learning problems
Physical examination
Underweight or overweight
Tonsillar hypertrophy
Adenoidal facies
Micrognathia/retrognathia
High-arched palate
Failure to thrive
Hypertension
Reproduced with permission.
suggestive of OSA reported by the American Academy of Pediatrics (AAP) [32]. In

the diagnosis of moderate and severe OSA, the clinical evaluation (history and
physical examination) has a poor sensitivity and specificity (59 and 73 %, respec-
tively). Although one study reported a history of snoring every night had a higher
sensitivity (91 %) and specificity (75 %) as well as a positive predictive value of 67
% and a negative predictive value of 94 % [33], this study was limited to Asian
children and therefore may not be applicable to children of other ethnicities.
Several questionnaires have been developed to aid in the diagnosis of OSA,
including the OSA-18 [34] and the Pediatric Sleep Questionnaire (PSQ) [35].
Compared with the gold standard polysomnography (PSG), these detailed question-
naires, often with more than 20 items, have a sensitivity of 78 % and a specificity of
72 % [36]. In a recent study of children with craniofacial disorders, 57 % had posi-
tive PSQ, but only 28 % had PSG findings of OSA [37].
It is evident that the accurate diagnosis and stratification of OSA require that
clinical evaluation be supplemented with a test [38].
14.2.2 Diagnostics Test
Currently, the gold standard for the diagnosis of OSA is a nocturnal, in-laboratory
PSG study [1]. The typical PSG monitoring includes electroencephalography
(EEG), chin and anterior tibial electromyography (EMG), bilateral electrooculogra-
phy, pulse oximetry and photo plethysmography, airflow sensor (nasal pressure
transducer, oronasal airflow thermistor, end-tidal capnography), chest and abdomi-
nal respiratory inductance plethysmography, body position sensor, microphone, and
real-time synchronized video monitoring. Key metrics obtained from PSG are listed
in Table 14.2 [1]. Abnormalities of sleep are quantified with the apnea-hypopnea
Table 14.2 Metrics obtained from polysomnography [1]

Respiratory event Definition
Apnea Complete cessation of flow (drop of peak signal excursion to ≤10 %
of the baseline for more than 90 % of the event duration, for ≥10 s)
Hypopnea (partial Drop of signal by ≥30 % of the baseline for at least two breaths and
apnea) associated with a ≥3 % oxygen desaturation by pulse oximetry or
an arousal
Respiratory effort- Increasing respiratory effort, flattening of the nasal flow waveform,
related arousals or an elevation in the end-tidal PCO2, lasting at least two breaths
(RERAs) and associated to an arousal from sleep
Hypoventilation Period of ventilation ≥25 % of total sleep time characterized by a
PCO2 >50 mmHg
Apnea-hypopnea index The combined total number of apneas and hypopneas per hour of
(AHI) sleep
Respiratory disturbance The combined total number of apneas, hypopneas, and RERAs per
index (RDI) hour of sleep
index (AHI), which computes events related to obstruction [39] and various metrics
of saturation including the nadir saturation and desaturation index. Hypercarbia is a
feature of severe OSA.
Unlike adult OSA, there remains no consensus on the criteria to establish the
diagnosis of OSA in children [35].
The following values are considered abnormal: AHI >5 and a nadir or minimum O2
saturation <92 %. Hypercarbia is defined as a CO2 50 mmHg >10 % sleep time or a
CO2 45 mmHg >60 % sleep time [40]. Other criteria have also been proposed [41, 42].
14.2.3 Cardiorespiratory Studies
Abbreviated cardiorespiratory studies may be performed at home or at the bedside.

These studies limit the recordings to the measurement of oronasal airflow, respira-
tory inductance plethysmography, body position, snoring sounds, electrocardiogra-
phy, transthoracic impedance, and pulse oximetry saturation. They correlate well
with PSG [43].
14.2.4 Oximetry
The incidence of hypoxemia among children with SDB younger than 3 years is
almost 40 %, decreasing by 17 % for each 1-year increase in age [34].
Overnight oximetry, which is potentially more widely available, can be used to
evaluate OSA at the bedside and at home [44].
In a population of children referred to sleep laboratories with a high pretest prob-
ability of OSA, there is a very high probability (99 %) that an abnormal oximetry
will be associated with PSG-proven OSA. However, when applied to the general
population where the pretest probability of OSA is lower, the probability that an
abnormal oximetry is associated with OSA is lower [45].
Desaturation indices (number of desaturation events >4 % below the baseline
saturation) of 2.0, 3.5, and 4.2 correlate with mild, moderate, and severe OSA
(AHI >1, AHI >5, and AHI >10, respectively). Each correlation showed high sensi-
tivity (77.7, 83.8, and 89.1 %, respectively) and specificity (88.9, 86.5, and 86.0 %,
respectively) [46].
An abnormal oximetry trend study has been defined as at least three clusters of
desaturation. The McGill Oximetry Score (MOS) was developed to further stratify
the severity of OSA. It identifies three levels of severity (MOS2, MOS3, and MOS4)
defined as nadir saturations below 90, 85, and 80 %, respectively. The MOS has
been shown to correlate with PSG [47, 48] and may be used as an initial test to
evaluate children with SDB [49, 50]. Constantin et al. [34] compared the MOS to
the OSA-18 questionnaire. An OSA-18 score of 60 (maximum 126) had very low
sensitivity (40 %) but high negative predictive value. Therefore, children with a low
OSA-18 score are unlikely to have OSA. This suggests that whereas a careful clini-
cal evaluation may exclude severe OSA, it cannot reliably stratify OSA severity.
14.2.5 Other Studies
Nap studies have also been proposed but results are conflicting. The use of home
PSG, respiratory polygraphy, nasal resistance, electrocardiogram-based auto-
mated apnea screening, and pulse transit time (PTT) [2, 51] is under investiga-
tion. Similarly, audio and videotaping have shown a sensitivity of 94 %, a
specificity of 68 %, a positive predictive value of 83 %, and a negative predictive
value of 88 %, but they are, like polysomnography, time-consuming to perform
or analyze [52].
Radiologic studies (i.e., X-ray) have been also used, but the sensitivity, specificity,
and positive and negative predictive values of these tests have yet to be reported [2].
Finally, propofol-induced (and possibly dexmedetomidine-induced) sleep endos-
copy [53] and cine MRI [54] have been used to evaluate upper airway dynamics to
identify the site of obstruction in children with OSA.
14.2.6 Future Prospective
Several biomarkers, such as chemokines, inflammatory cells, and others, have been
investigated as predictors of OSA [9, 51], but their clinical application has yet to be
established.
14.3 Anatomical and Physiological Basis of Respiratory

Control
14.3.1 Upper Airway Anatomy and Its Relationship with OSA
Infants and children have a small maxilla and a large occiput, which may predispose
to airway collapsibility. Within the first year of life, both the maxilla and the cra-
nium will grow and promote the stability of pharyngeal architecture [55].
The upper airway is an “X”-shaped passageway, with the mouth and nose as two
distinct entry points, which meet in the pharynx before splitting apart into the larynx
and esophagus.
The upper airway contains different anatomical structures, with different growth
characteristics. The following section gives an overview of the relative importance
of each structure.
14.3.1.1 Nasopharynx
The nose receives support from boney structures and cartilage. Therefore abnor-
malities of these structures may promote obstruction of the nasal airway [56].
The nasal resistance to airflow spontaneously fluctuates in both adult and chil-
dren. In adults, nasal obstruction increases the number of apneas and hypopneas
[57] and worsens the sleep disturbance [58]. In children, nasal resistance is also
affected by body position, increasing in the dependent nostril [59].
In infants, the nasal route of breathing is extremely important as they are prefer-
ential nasal breathers [60]. Indeed infants with unrecognized choanal atresia may
asphyxiate.
14.3.1.2 Mouth and Pharynx

The oral cavity is limited by the hard and soft palate superiorly and the tongue infe-
riorly, and it is bounded laterally and anteriorly by the alveolar process. It opens
posteriorly into the oropharynx and forms the part of the “X” where the nasal and
oral cavities meet.
More inferiorly, the oropharynx continues into the retroglossal region (or “hypo-
pharynx”), which is bounded anteriorly by the tongue and epiglottis, superiorly by
the retropalatal oropharynx, inferiorly by the esophagus and larynx, and posteriorly
and laterally by the pharyngeal constrictors.
During development, the tonsillar and adenoid tissues grow faster than the sur-
rounding structures, encroaching on the airway and predisposing to pharyngeal
obstruction [61].
In normal children, airway closure occurs at the level of soft palate and base of
the tongue, whereas in children with SDB, pharyngeal closure occurs at the level of
tonsils and adenoids [62].
Children with OSA have shown larger soft palate and bigger tonsils and ade-
noids, which narrow the retroglossal pharyngeal space [63]. Adenoid size is an
important determinant in children between 1 and 12 years.
The tongue plays a critical role in the genesis of OSA. The loss of tongue and
neck muscle tone causes the tongue to fall back into the posterior pharynx, often
resulting in partial or complete obstruction [64], especially accentuated in mandibu-
lar hypoplasia. Furthermore, lingual tonsillar abnormalities can also predispose to
airflow obstruction. This is especially important in the child with trisomy 21 [65].
14.3.1.3 Larynx
Below the epiglottis, the upper airway divides into the esophagus, located posteri-
orly, and the trachea, located anteriorly. Abnormalities of this area are rarely associ-
ated with OSA, unless anatomical or neurological abnormalities are present [66].
Redundancy in the arytenoid-aryepiglottic fold area may be associated with
OSA [67]. Tracheomalacia has been also implicated in sleep apnea [68].
14.3.2 Neuronal Control of Breathing in Sleep and Airway

Collapsibility
Two models have been proposed to describe the airway collapsibility [55]: the ana-
tomical balance model and the neural balance model.
The anatomical balance model [69] considers the upper airway as a tube with a
collapsible segment (analogous to the nose, the hypopharynx, and the larynx), sur-
rounded by soft tissue (i.e., tongue) contained in a rigid box (i.e., boney structures).
The pressure at which the pharyngeal airway collapses has been investigated. Two
pressures have been reported: the critical pressure (Pcrit) and the closing pressure
(Pclose). The Pcrit [70] was studied in awake spontaneously breathing children. In
contrast, Pclose [62] was determined in paralyzed, anesthetized, apneic patients.
Pharyngeal collapse (Pcrit) occurs when the surrounding pressure is greater than
the pressure within the airway segment. If the upstream resistance (nose) is low, as
in normal subjects, the downstream (hypopharynx) pressure does not achieve Pcrit
and airway patency is determined by the inspiratory pressure.
This model has been successfully applied in wake adults and children to describe
the dynamic interaction of neuronal and anatomical components in the genesis of
pharyngeal obstruction [70, 71].
In paralyzed and ventilated children, Isono [62] endoscopically evaluated the
static changes of pharyngeal cross-sectional area at different pressures and identi-
fied the Pclose and the anatomical levels at which the airway collapsed.
In the neural balance model [72], airway patency is determined by the balance
between pharyngeal collapsing forces (diaphragm, external intercostal muscles) and
pharyngeal dilator muscles (i.e., the genioglossus muscle, which is the major upper
airway dilator).
The pharyngeal dilator muscles are regulated by:
1. Consciousness: both sleep and general anesthesia decrease the pharyngeal dila-
tor muscle activity relatively more than the diaphragm and external intercostal
muscles, promoting airway collapse.
2. The negative pressure airway reflex.
3. The level of chemical stimuli: pO2, pCO2, and pH.
During wakefulness and non-rapid eye movement (NREM) sleep, activation of

the pharyngeal dilators during inspiration maintains a patent pharyngeal airway.
Transition to sleep results in reduced tone of the pharyngeal dilator and constrictor
muscles [73], with a subsequent increase in airway resistance.
The pharyngeal collapsing forces may overcome the dilating forces, creating a
subatmospheric (negative) pressure in the pharyngeal airway. Pressure receptors
located in the mucosa of the nasopharynx and larynx are stimulated in response to
this subatmospheric pressure (negative pressure reflex) [73], activating the pharyn-
geal dilators to counteract the collapse of the airways [74].
If negative pressure reflex fails, an apnea event occurs, and the subsequent
changes in pO2, pCO2, and pH may stimulate a ventilatory response and an arousal.
Younes introduced the concept of loop gain (LG), which describes the feedback
interaction (loop) between an apnea event, the subsequent increase of pCO2, and the
ventilatory response (gain), which then normalizes the pCO2 to maintain respiratory
homeostasis [75]. If the initial compensatory response overshoots, the resulting hypo-
carbia will cause a second hypopnea/apnea, which will be more severe than the initial
one, and the cycle can perpetuate indefinitely. In normal individuals, this control sys-
tem is stable (LG is <1). In patients with OSA, the system is unstable (LG >1) [76].
In normal children, the risk of obstruction due to anatomic factors such as small
airway size, high nasal resistance, and high chest wall compliance is compensated
by an increased ventilatory drive and decreased airway collapsibility [77]. In chil-

dren with OSA, the neuromotor response to airway collapse has been linked to
respiratory afferent cortical processing deficits [78].
14.4 Special Considerations
14.4.1 Infants and Premature Infants
A detailed description of OSA in infants is beyond the scope of this chapter.

Interested readers are referred to the excellent review of Katz et al. [79]. Whereas in
children high nasal resistance, relative hypoplasia of the mandible and maxilla is an
anatomical feature associated with OSA, in infants, laryngomalacia, choanal atre-
sia, cleft palate, and subglottic stenosis are commonly reported [79]. Adenotonsillar
hypertrophy may become significant beyond 6 months of age; it is more common
among males and preterm or low birth weight infants, and it is associated with high
recurrence rate after surgery [80].
In infants, the site of obstruction is palatal or retroglossal, and it increases during
neck flexion [79]. In a recent retrospective study [81], premature infants represented
the 5.5 % of all surgical patients with SDB. Pulmonary and gastrointestinal comor-
bidities and airway abnormalities were common (40, 29.8, and 19.3 %, respec-
tively). One third of the patients had abnormal preoperative pulse oximetry.
Polysomnographic criteria for OSA in infants have yet to be established, but
OSA should be suspected in any infant with an AHI >2. Furthermore, infants with
laryngomalacia and chronic respiratory distress should be evaluated for SDB [79].
In the majority of infants, symptoms of OSA resolve during development [68].
Nonpharmacological management of OSA includes continuous positive airway
pressure (CPAP), position therapy, and nasopharyngeal intubation. Surgical options
include adenotonsillectomy, supraglottoplasty, lip-tongue adhesion, mandibular
distraction, and tracheostomy [79].
14.4.2 The Obese Child
Several factors contribute to OSA in the obese child [82]. Tonsillar or adenoid hyper-
trophy is reported in 65 % [83]. The adipose tissue, infiltrating the pharyngeal muscles
and the surrounding structures [84], may contribute to the airway collapsibility that
characterizes OSA. Obesity compromises upper airway patency not only by encroach-
ing on the caliber but also by impairing the function of upper airway muscles. Obesity
also decreases the longitudinal tension of the airway and reduces lung compliance and
functional residual capacity, all of which promote pharyngeal airway collapse [85].
Severe obesity and OSA are associated with sleep fragmentation and subsequent
psychomotor impairment, reduced memory recall, and lower spelling scores [86].
In children, obesity carries higher risk of depression [26], suicide, relationship
difficulties, gastroesophageal reflux [87], hepatic diseases, irritable bowel syndrome
[88], metabolic syndrome (note that insulin resistance is present in 30–50 % vs. 4 %
in nonobese adolescents) [89], type 2 diabetes mellitus, fatty liver disease [90],
hypertension, dyslipidemia, and atherosclerosis [91].
Compared to OSA-matched subjects, obese children showed lower cardiac index
volume, stroke volume index, and oxygen consumption at peak exercise capacity
[24].
The risk for the metabolic syndrome (insulin resistance, dyslipidemia, hyperten-
sion, and obesity) increases with every 0.5-unit increment in BMI z score (odds
ratio, 1.55; 95 % CI 1.16–2.08), and it is present in half of the severely obese chil-
dren (BMI z score >2.5) [89].
A retrospective analysis [92] shows that overweight/obese (BMI >27 kg/m2)
children undergoing adenotonsillectomy are more at risk of desaturation, laryngo-
spasm, and perioperative upper airway obstruction. These children are also admitted
more often and hospital stays are longer than healthy children.
Furthermore, adenotonsillectomy has a lower success rate, as residual OSA post-
adenotonsillectomy is present in up to 75 % of obese children [83, 93], with an odds
ratio for persistent OSA of four compared to normal weight children [42].
14.4.3 Syndromes
Syndromes and medical conditions predisposing to OSA in children and adoles-

cents are summarized in Table 14.3 [94].
If mouth breathing and obesity are combined with poor chin development and
long face (adenoidal face), OSA should be suspected [95].
OSA symptoms are common in craniofacial malformations [96]. In a recent
study, PSG (AHI >5) was positive in 28 % of children with craniofacial malforma-
tions [37]. More than 70 % of patients with syndromic craniosynostosis (Apert,
Pfeiffer, and Crouzon) may have OSA (median AHI 12.9), which is severe in most
of the cases [96].
These patients frequently require more complex and invasive airway surgery
such as tongue reduction or lingular tonsillectomy [97].
Children with trisomy 21 are at high risk of having OSA, and the obstruction
may be at several levels in the airway [98, 99]. It has been recently reported that 97
% of these children have abnormal polysomnography, and 59–66 % have moderate
to severe OSA [100]. Compared to normally developed children, patients with tri-
somy 21 show higher MOS and higher EtCO2 at night [101]. At the time of the
adenotonsillectomy, children with trisomy 21 may have already developed clini-
cally significant pulmonary hypertension [102].
The Prader-Willi syndrome is a condition that combines anatomical altera-
tions (dimorphisms, including micrognathia) with obesity. Adenotonsillectomy
has been proposed to treat the OSA, but it is associated with a higher risk of
perioperative complications including delayed emergence, hemorrhage, hypo-
glycemia, laryngospasm, supplemental oxygen administration, and the need for
reintubation [103].
Table 14.3 Syndromes associated with obstructive sleep apnea in children [94]
Craniofacial syndromes Apert syndrome
associated with significant Crouzon syndrome
mandibular or maxillary Goldenhar syndrome (hemifacial microsomia)
hypoplasia Hallermann-Streiff syndrome
Pierre Robin syndrome (Robin sequence)
Rubinstein-Taybi syndrome
Russell-Silver syndrome
Treacher Collins syndrome
Other syndromes featuring Achondroplasia
prominent craniofacial Klippel-Feil syndrome
involvement Larsen syndrome
Saethre-Chotzen syndrome
Stickler syndrome
Velocardiofacial syndrome
Conditions associated with Beckwith-Wiedemann syndrome
macroglossia Down syndrome
Hypothyroidism
Mucopolysaccharide storage disorders (e.g., Hunter, Hurler
syndromes)
Conditions associated with Adenotonsillar hypertrophy
anatomic airway Cleft palate and/or cleft palate repair
obstruction Choanal atresia or stenosis
Fetal warfarin syndrome
Laryngotracheomalacia
Nasal polyps or septal deviation
Pfeiffer syndrome
Vascular ring
Neurologic disorders Cerebral palsy
associated with weakness Cranial neuropathies (e.g., Mobius syndrome, poliomyelitis)
or impaired ventilatory Neuromuscular disorders (e.g., Duchenne, myotonic dystrophies)
control Structural brainstem lesions (e.g., Chiari malformations,
syringobulbia)
Conditions characterized Morbid obesity/metabolic syndrome
by obesity Prader-Willi syndrome
Other conditions Arthrogryposis multiplex congenita
Conradi-Hünermann syndrome
Gastroesophageal reflux
Sickle cell disease
14.4.4 Central Hypoventilation Syndromes
Congenital central hypoventilation syndrome is a sleep-dependent hypoventilation

disorder, which is classically diagnosed at birth but may present late in infancy or
even in adulthood (late-onset central hypoventilation syndrome, LOCHS) [104]. It
is characterized by an impaired response to hypercapnia and an overnight oxygen
saturation trace that differs from the OSA pattern [104]. Mutations of gene PHOX2B
have been identified in patients affected by LOCHS. Exposure to anesthesia may
result in delayed emergence, which may be confused with opioid hypersensitivity or

residual neuromuscular blockade [105]. Postoperative hypoventilation may be the
presenting feature.
Rapid-onset obesity with hypothalamic dysfunction (ROHHAD) is another cen-
tral hypoventilation disorder, which may present in the perioperative period [106].
However, its etiology, pathophysiology, and associated endocrine abnormalities dif-
fer from the LOCHS.
14.5 Medical Treatment of OSA
Several studies are investigating medical treatments for OSA in children [107].
Noninvasive positive pressure ventilation (NIV) is extensively used in adults.
Increasingly NIV is used to treat infants and children with OSA [108].
Since the settings for NIV systems after surgery may differ from the ones used at
home, care must be taken to provide trained staff and monitoring throughout the
hospital admission and immediate access to invasive ventilation in the event of
respiratory deterioration during the postoperative period [109].
The application of high-flow oxygen nasal cannula, weight loss, and positional
therapy (lateral and prone positions versus supine during sleep) are promising therapies
in selected OSA patients, but long-term results are inconclusive or unknown [97, 110].
Dental procedures, such as rapid maxillary expansions and oral appliances, may
be indicated. Two detailed reviews have been recently published [97, 110].
Since inflammation has been shown to play a pivotal role in tonsil and adenoid
hypertrophy [107], immunomodulating drugs such as montelukast may prove use-
ful in the future. Nasal corticosteroids seem to be effective [107, 110] and may be
of short-term benefit allowing optimization prior to adenotonsillectomy. Their long-
term safety has still to be established [110]. Studies on drugs directed to different
biomarkers are under investigation [107].
14.6 Surgical Treatments
The first-line treatment of OSA in children is adenotonsillectomy, which is the most

common surgery performed in the United States (annual caseload 500,000).
Adenotonsillectomy has been shown to improve the AHI, quality of life (QOL),
behavior, and school performance, regardless of the presence of obesity [83].
Adenoidectomy alone has been shown to reduce airway collapsibility [70].
A recent systematic review analyzed the cardiovascular benefits of adenotonsil-
lectomy [111]. Despite the high heterogeneity of the studies, adenotonsillectomy
seemed to have beneficial effects on blood pressure (especially diastolic) and car-
diac function [111].
Similarly, a recent study reported a decrease of mean pulmonary pressure, right
and left ventricular isovolumetric contraction time length, myocardial performance
index values, and an increase of ejection time [30].
Surgical alternatives to adenotonsillectomy have been proposed. In children

older than 5 years, partial tonsillectomy has been shown to decrease pain, improve
the return to a normal diet, decrease the risk of bleeding, and maintain immunologic
function, with minimal risk of regrowth [112].
In fact, residual OSA may occur in 20–40 % [93] of children with severe OSA,
depending on AHI threshold criterion to define severe OSA [113]. Obesity, age >7
years, the presence of asthma, a high presurgical AHI [93] and respiratory distur-
bance index (RDI) [42], AA ethnicity [114], and craniofacial malformation [96] are
risk factors for persistent OSA after surgery.
Adenotonsillectomy, however, is not without risks [107, 115, 116]. Hemorrhage,
cardiorespiratory events, and medication error are the most common complications
(54, 18, and 17 %, respectively) after adenotonsillectomy and are responsible for
half of the mortality events [117, 118]. In particular, children may demonstrate a
delayed onset of respiratory compromise several hours after surgery [42].
In 3–16-year-old children with mild OSA (AHI between 1 and 5), adenotonsil-
lectomy has been shown to give early relief of symptoms and improvement of QOL
compared to conservative clinical observation [119]. However, watchful waiting
also showed significant improvements in QOL after 8 months and may be consid-
ered as an alternative to adenotonsillectomy.
In a recent retrospective analysis of 126 infants with OSA [120], 86 children
underwent a variety of surgical interventions including tonsillectomy, adenoidec-
tomy, and adenotonsillectomy in 35 % of the patients. Comparing these children with
those managed with nonsurgical interventions (watchful waiting, antireflux therapy,
CPAP), surgical interventions showed a similar success rate at 6 months’ follow-up.
A recent large multicenter, single-blind, randomized study, the Childhood
Adenotonsillectomy Trial (CHAT) [114], investigated the outcomes of children
between 5 and 9 years of age undergoing adenotonsillectomy versus a strategy of
watchful waiting. As compared to control, adenotonsillectomy did not improve neu-
rological outcomes (NEPSY attention and executive-function test) at 7 months’
follow-up, but children who underwent early adenotonsillectomy had greater behav-
ioral improvement (caregiver and teacher ratings), quality of life (Pediatric Sleep
Questionnaire and Pediatric Quality of Life Inventory), and PSG indexes (AHI,
change from baseline –1.6 vs. –3.5, p < 0.001). Most importantly, PSG findings nor-
malized in 79 % of children in early-adenotonsillectomy group but also in 46 % of
watchful waiting group. Of note, 59 % of the obese children (BMI z score >1.65)
still manifested severe OSA after surgery (AHI >5).
In children with syndromic craniosynostosis, adenotonsillectomy has been per-
formed to alleviate the symptoms of obstruction, but additional interventions, such
as CPAP therapy, mandibular distraction, and tracheostomy, may be required [96].
A recent study [121] compared CPAP with surgical therapy in OSA patients with
trisomy 21 and mucopolysaccharidoses. It showed a similar 1-year outcome in
terms of PSG, clinical evaluation, Epworth Sleepiness Scale—Children, QOL, and
OSA-18 score.
Tongue base suspension and uvulopalatopharyngoplasty, associated or not with
adenotonsillectomy, have been applied to selected patients and they may be
beneficial. Recently, the European Respiratory Society Task Force has reviewed
their clinical application [97]. Finally, tracheotomy is reserved for severe refractory
patients [40].
14.7 Anesthesia Management of the Patient with OSA
14.7.1 General Recommendations: The American Society

of Anesthesiology Guidelines
The American Society of Anesthesiologists (ASA) recently updated the guidelines

for the management of patients with OSA [122]. It must be noted that these
guidelines:
1. Do not address patients with central apnea, airways abnormalities (i.e., deviated
nasal septum) or obesity not associated with obstructive apnea, and hypersomno-
lence not secondary to sleep apnea.
2. Do not consider children younger than 1 year.
3. Encourage evaluation of OSA with sleep study. In its absence, the ASA endorses
clinical criteria to both diagnose and stratify OSA severity.
4. Recommend that OSA patient to be managed in hospitals that have the facilities
to treat postoperative airway complications.
5. Encourage the use of CPAP perioperatively.
6. Recommend a full reversal of neuromuscular blockade.
7. Highlight that OSA patients are at higher risk of respiratory depression second-
ary to opioids and sedatives.
8. Recommend an accurate assessment of patient in the postoperative period.
9. Encourage a prolonged period of observation. Patients should not be discharged
to an unmonitored setting until they are no longer at risk of postoperative respira-
tory depression. This new recommendation has been introduced in 2014 and
highlights the critical role of postoperative monitoring in reducing the risk of
respiratory complications.
14.7.2 Anesthesia Management Options
The anesthesiologist should plan the anesthesia based on the severity of the OSA. As
mentioned, clinical evaluation with preoperative questionnaires has high negative
predictive value but a very low sensitivity [34]. Tait et al. [123] developed a limited
five-item questionnaire to identify children with SDB at increased risk for periop-
erative adverse respiratory events. The study, however, was not designed to stratify
the OSA severity, and the respiratory events were restricted to the immediate post-
operative period.
Therefore, if sleep study data are not available, the anesthesiologist must assess
airway collapsibility clinically. The risk and benefits of premedication should be
also carefully weighed in children with severe OSA, since significant airway
obstruction and severe oxygen desaturation can occur [124].
The child’s response to anesthesia may be informative as it may unmask OSA by
inducing skeletal hypotonia simulating conditions during REM sleep. During spon-
taneous ventilation, the requirement for positive pressure to maintain pharyngeal
airway patency, a high apneic threshold for carbon dioxide [125], and a heightened
opioid sensitivity are all suggestive of severe OSA and may warrant postoperative
admission and extended period of cardiorespiratory monitoring [126].
The use of local anesthesia may also unmask OSA. In children with OSA, the
application of local anesthesia results in a relatively greater decrease of pharyngeal
cross-sectional area likely from the inhibition of the upper airway dilators [127].
Titration of opioids to the severity of OSA is critical to reduce respiratory complica-
tions (see below).
Finally, supplemental oxygen must always be administered carefully in the
recovery room as in children with severe OSA, their blunted carbon dioxide respon-
siveness may render them more dependent on peripheral respiratory drive [125].
14.8 Specific Guidelines for Anesthesia Management

of the Children Undergoing Adenotonsillectomy
14.8.1 Recommendations for Adenotonsillectomy: Italian

National Program Guidelines, American Academy
of Otolaryngology—Head and Neck Surgery Guidelines,
and American Association of Pediatrics Guidelines
The 2008 Italian National Program Guidelines [128] state that the decision to per-
form adenotonsillectomy should be based on clinical evaluation (i.e., loud snoring,
low hemoglobin saturation) with or without the use of specific questionnaires.
Nocturnal pulse oximetry is recommended as an initial test in children with sus-
pected SDB. PSG is reserved for children with inconclusive pulse oximetry studies
[48]. Adenoidectomy alone is not recommended due to the high recurrence of
symptoms. Intraoperative morphine is not indicated. Multimodal analgesia with
dexamethasone 0.5–1 mg/kg i.v. (max 8 mg), acetaminophen 15 mg/kg p.o. q4 h
around the clock, and codeine 1 mg/kg p.o. q4 h pro re nata are recommended.
However, it must be noted that codeine received a black box warning from FDA in
2013 [39].
Short-term antibiotics are also indicated. The guidelines also recommend post-
operative admission for children younger than 3 years of age.
The American Academy of Otolaryngology—Head and Neck Surgery recom-
mends PSG before adenotonsillectomy be reserved for children with coexisting dis-
eases, such as obesity, trisomy 21, craniofacial abnormalities, neuromuscular
disorders, sickle cell disease, and mucopolysaccharidoses [129]. Importantly, the
results of PSG should be communicated to the anesthesiologist prior to the induc-
tion of anesthesia. Postoperative admission is recommended for patients younger
than 3 years of age and with severe OSA (AHI ≥10 or more obstructive events/h,
oxygen saturation nadir <80 %, or both).
The 2012 American Academy of Pediatrics (AAP) [32] recommends adenotonsil-
lectomy as the first-line treatment for children with OSA. Relative contraindications
are very small tonsils/adenoids, morbid obesity and small tonsils/adenoids, bleeding
disorder refractory to treatment, and a submucous cleft palate. Nocturnal video record-
ing, nocturnal oximetry, daytime nap polysomnography, and ambulatory polysom-
nography are considered valid alternatives to PSG. The guidelines acknowledge that
children may present with chronic rhinorrhea and nasal congestion, even in the
absence of viral infections, which makes airway management more challenging.
Postoperative admission is recommended for patients younger than 3 years of age and
with severe OSA, cardiac diseases due to OSA, failure to thrive, obesity, craniofacial
anomalies, neuromuscular disorders, and current respiratory infection. The AAP iden-
tifies children with a perioperative nadir saturation <80 % and PCO2 >60 mmHg or a
preoperative AHI >24 are at higher risk for postoperative respiratory complications.
14.8.2 Anesthesia Management Options for Children Undergoing

Adenotonsillectomy
Postoperative hospital admission is recommended for children younger than 3 years

or in the presence of comorbidity, a bleeding diathesis, excessive distance from a
hospital, excessive pain, poor oral intake, postoperative vomiting, and an awake
(room air) saturation below 95 %[45].
Elective ICU admission may be considered in case of children less than 24
months with RDI >60 during REM sleep; RDI <60 in REM sleep but associated
with coexisting syndrome or significant neuromuscular disease likely may promote
airway obstruction, failure to thrive, respiratory compromise, central apnea, com-
plex cyanotic or congenital heart disease [130], or MOS4 [45]. In agreement with
AAP practice guidelines, for children with very severe OSA (MOS4) older than 2
years and with no comorbidities, postoperative admission to a monitored setting is
an alternative to pediatric intensive care unit [45].
14.8.2.1 Intraoperative Management

There is neither consensus nor randomized controlled trials regarding the anesthesia
management in children undergoing adenotonsillectomy for OSA. In the setting of
adenotonsillectomy, endotracheal intubation is generally preferred to LMA due to
smaller surgical pharyngeal visualization.
Inhalational induction should be carefully used since the decrease in pharyngeal
muscle tone and longitudinal tension may unmask the airway collapsibility and
require skilled mask airway support. It is therefore mandatory that clinicians per-
form a careful evaluation of the airway before induction and that advanced airway
equipment is immediately available [39]. The application of CPAP through the APL
valve may facilitate the ventilation in skilled hands, and the level of CPAP is propor-
tional to the level and the severity of airway collapsibility [55].
Intravenous induction may result in a collapse of the upper airway, making posi-
tive pressure ventilation difficult. Insertion of an oral airway usually overcomes the
pharyngeal obstruction.
A recent study [131] compared dexmedetomidine-ketamine and sevoflurane-
sufentanil undergoing uvulopalatopharyngoplasty. Dexmedetomidine-ketamine
showed lower pain score, less emergence delirium/agitation, but longer awake time,
higher sedation (Ramsay score), and incidence of desaturation below 95 % in post
anesthesia care unit (PACU).
Since OSA patients have demonstrated higher opioid sensitivity [132] and hypo-
algesia [133], the intraoperative use of short-acting opioids such as remifentanil
may have an advantage in children with severe OSA (MOS 3 and 4). Furthermore
the dose of postoperative morphine should be reduced by 50 % and carefully titrated
as children with MOS 3 and 4 may require only half of the usual opioid dose [50].
As mentioned in the previous section, infiltration of the pharynx with local
anesthesia is discouraged due to the risk of airway collapse. Multimodal analge-
sia with acetaminophen and intraoperative steroids is advantageous to decrease
postoperative pain [115]. The use of nonsteroidal anti-inflammatory drugs in
adenotonsillectomy remains under debate [134]. Finally, the routine use of anti-
biotics is not recommended [115], although postoperative transient bacteremia is
common [135].
14.8.2.2 Postoperative Management

Optimization of postoperative management is critical to reduce respiratory events,
which may be as high as 60 % after adenotonsillectomy [45].
A recent survey from the Society for Pediatric Anesthesia [136] identified at 16
cases of preventable death/neurological injury within 24 h after surgery, which
occurred at home, in PACU, or on the ward [136]. This highlights the need for pro-
longed postoperative monitoring.
Respiratory complications are common during the first night after surgery,
when children with mild and moderate OSA may show a worsening of the symp-
toms [137]. Patients with preoperative RDI >19 or persistent snoring should
undergo PSG follow-up, since they are more at risk of residual OSA [42].
Rhinorrhea, uvular edema, and residual anesthesia may exacerbate postoperative
obstruction [130]. Children may also develop postobstructive pulmonary edema
in the postoperative period [32]. Finally, dehydration involves 5 % of the patients
below 3 years [138].
Conclusions
Pediatric OSA represents a complex disorder with unique pathophysiological
features. Understanding the anatomical and physiological basis of airway col-
lapse in children with OSA is crucial to optimize the anesthesia management of
these patients. The anesthesiologist must be aware that the stratification of the
OSA severity is pivotal to identify patients at high risk for postoperative compli-
cation. Furthermore, extended postoperative monitoring and judicious use of
narcotics should always be considered in these high-risk patients.
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with Trauma 15
Leonardo Bussolin
Trauma injury remains to be a major cause of death and severe disability in children
from 1 to 14 years old.
In pediatric population, traumatic injuries are predominantly blunt, nonpenetrat-
ing. This feature results from a number of reasons reported in Fig. 15.1.
Major and lethal pediatric traumas are relatively rare. This aspect makes difficult
to accomplish guidelines for the management and treatment of pediatric trauma
because most of the publications show small and poor statistically significant popu-
lations of patients.
Mortality for traumatic injury presents three peaks:
1. Immediate: within the first hour, often upon impact and due to injuries which are
incompatible with life (laceration of major intra-thoracic or intra-abdominal ves-
sels, high injury of the cervical spine, rupture of the cardiac chambers, severe
brain injury)
2. Early: within the first two hours after the traumatic event and secondary to inad-
equate establishment, stabilization and control of airway, uncontrolled hemor-
rhage associated with hemodynamic collapse, respiratory failure for pulmonary
contusion and hemorrhage or pneumothorax, and intracranial bleeding
3. Delayed: for complications occurring during hospitalization (sepsis, progressive
respiratory failure, multiorgan failure)
Motor vehicle collisions, pedestrian and bicycle accidents, falls, and burns are
the most common causes of injury in children [1].
The essential factors for obtaining successful management of trauma include the
quick diagnosis and treatment of primary injuries and the avoidance of secondary
L. Bussolin (*)
Department of Neuroanesthesia and Neurointensive Care, Pediatric Trauma Center,
Pediatric Hospital Meyer, Florence, Italy
e-mail: leonardo.bussolin@meyer.it

DOI 10.1007/978-3-319-21960-8_15
214 L. Bussolin
Relatively greater size of Less fatty tissue and

Small body mass internal organs elastic connective
Greater impact energy Organs in proximity

per unit surface area with the bone structures
High rate of blunt

injury
Reduced muscle mass High bone elasticity
Reduced bone
calcification
Fig. 15. 1 Causes of high rate of blunt injury in children
injury. The term platinum 30 min (golden hour for adults), while not evidence based,
refers to an early and critical period in the care of trauma victims, during which the
appropriate management may significantly increase patients’ survival rate.
Early recognition of primary injuries with rapid control of the airway and
replacement of the circulating blood volume remain the cornerstones for a success-
ful resuscitation of the pediatric trauma victim. Secondary injuries, which result
from hypoxia and hypotension, are important determinants of morbidity and mor-
tality after trauma, particularly in the presence of head trauma [2].
Pediatric trauma presents significant challenges regarding the anesthetic man-
agement, because of the anatomical, physiological, and psychological peculiarities
characterizing every step of the development of child that make him a separate
individual for each aspect of clinical care. For this reason, successful treatment of
the traumatized child requires an accurate knowledge of the anatomical and physi-
ological features that distinguish children from adults. These differences differ as
the age increases, with neonates presenting the greatest clinical challenge.
As previously mentioned (Fig. 15.1), children have less fat and more elastic con-
nective tissue with a flexible skeleton placed in close proximity to abdominal and
thoracic structures, which can be injured without external lesions.
The larger body surface area to body mass ratio predisposes children to high heat
loss than adults, potentially resulting in severe hypothermia.
Children have different physiological response to major trauma compared to adults,
since they are able to maintain a near-normal blood pressure until 30–40 % of blood
15 Perioperative Care of Children with Trauma 215
volume is lost. In these situations, the most important monitoring parameters are repre-
sented by the increased heart rate and the decreased tissue perfusion, the latter detected
by the assessment of capillary refill time. The latter is detected by compressing for 5 s
the nail bed, in children, or the sternal region in neonate and infants. The resulting
ischemic area (appearing pallid) should return normally perfused within 2 s. A longer
capillary refill time indicates a condition of tissue hypoperfusion (Fig. 15.2).
Children may not cope well emotionally in the aftermath of an accident. They
need to be managed in a calm, child-friendly environment. The presence of a parent
or psychologist in the resuscitation room may help the trauma team by minimizing
the injured child’s fear and anxieties. It is shown that 25 % of children suffer from
post-traumatic stress disorder after a traumatic event [3].
The most challenging anatomical and functional aspects related to pediatric
trauma concern the airway and pulmonary function. Children have high oxygen
consumption rate, relatively low functional residual capacity, and rapid bradycardic
response to hypoxia. They do not tolerate long apneic periods well. Therefore, accu-
rate airway examination is crucial.
The anesthesiologist should be prepared to encounter the following anatomical
features of pediatric airway:
• A large protuberant occiput creates the natural flexion of the head in young chil-
dren. It predisposes the airway to obstruction and requires careful positioning for
intubation.
• A small oral cavity, large tongue, the presence of adenoids and tonsils, and occa-
sionally loose deciduous teeth may restrict intraoral manipulation, obstruct visi-
bility with direct laryngoscopy, and create predisposition to easy bleeding.
• The larynx is short and positioned relatively high and more anterior. The epiglot-
tis is often U shaped, long, and floppy. This combination may pose potential
difficulties with laryngoscopy, and a short larynx increases the possibility of
endobronchial intubation.
Fig. 15.2 Detection of capillary refill time

216 L. Bussolin
• The commonly accepted knowledge that the larynx in infants and children is fun-
nel shaped with the narrowest point of the funnel at the cricoid ring must be
revised. Litman et al. [4] demonstrated with magnetic resonance imaging scans
that in neonates, infants, and children up to 14 years, the larynx is conical in the
transverse dimension with the apex of the cone at the level of the vocal cord and
cylindrical in the anteroposterior dimension and does not change throughout
development. Subsequently, Dalal et al. [5] confirmed these findings by using
video-bronchoscopy imaging.
The role of the anesthesiologist in the management of pediatric trauma extends

long before the arrival to the operating room. It includes the emergency department,
the radiology suite, the intensive care unit, and the acute pain service. Therefore, pedi-
atric anesthesiologist is involved to provide any or all of these services at any time.
The anesthesiologist may have to take care of traumatized pediatric patients on
following occasions:
1. Initial stabilization in the emergency department

2. Sedation and monitoring for imaging
3. Emergency surgical procedures, such as laparotomy or craniotomy
4. After initial stabilization, to perform anesthesia for the fixation of long bone
fractures
5. Intensive care unit management
6. Pain control during hospitalization, especially using regional analgesia
For all these reasons, a rapid and well-organized trauma team of an injured child
is essential.
15.1 Primary Survey
The main goal of the primary survey is to detect and treat immediate life-threatening
conditions, such as bleeding or hypertensive pneumothorax.
In pediatric trauma, the primary survey is classically presented according to
ABCDEF sequence with some peculiarities:
A: airway + cervical stabilization

B: breathing + ventilation and oxygenation
C: circulation + hemorrhage control
D: disability
E: exposure
F: family
The next step of the assessment is not started until the preceding abnormality has
been managed and corrected.
Before starting any manipulation of the patient, the level of consciousness must
be evaluated by the application of a verbal or slight painful stimulus.
15.1.1 Airway
A number of traumatized patients arrive to the emergency department (ED) already

intubated, and therefore, the duty of the anesthesiologist is to evaluate the airway in
terms of tube size, cuffed/uncuffed, the presence and magnitude of air leak if
uncuffed tube, depth of the tube, breath sounds, ventilation, and oxygenation. Any
chest X-ray done in the ED should be reviewed in order to ascertain the correct posi-
tion of the tracheal tube in mid-trachea and the presence of pneumothorax. If the
patient is not intubated, the assessment of the airway must simply determine the
ability patency. The mouth is opened to visualize the cavity, and, if the patient is
unconscious, the jaw thrust is performed to prevent that the tongue falls back
obstructing the upper airways. At the same time, an appropriate-sized cervical col-
lar is chosen and placed (Fig. 15.3). If an appropriate pediatric cervical collar is not
available, rolled towels or blankets might be carefully placed on either side of
patient’s head in young children and infants.
The airway can be obstructed by blood, foreign bodies, teeth, secretions, and
vomit in the oropharyngeal space, and any effort should be done to remove or suc-
tion them. Throughout the maneuver, the axes of the head, neck, and thorax must be
aligned to prevent any dangerous rotation or extension movements of the cervical
spine.
15.1.2 Breathing
After step A has been completed, breathing must be assessed. If the patient is spon-
taneously breathing, then 100 % high-flow oxygen will be administered by a non-
rebreathing face mask with a reservoir.
If the child is apneic or is making poor respiratory effort, assisted ventilation is
required. When properly performed, bag-valve-mask (BVM) ventilation for a short
period of time is as effective as ventilation via an endotracheal tube. Five ventila-
tions must be performed, and of these, at least two must be effective, eventually with
Fig. 15.3 Mouth opening,

jaw thrust maneuver, and
cervical collar placed
218 L. Bussolin
Table 15.1 Sizing of LMA Size Weight (kg)

1 ≤5
1.5 5–10
2 10–20
2.5 20–30
3, 4, 5 >30
the aid of an oral airway, if the patient is unconsciousness (considering that inserting
an oral airway into a semiconscious child’s mouth may cause gagging and vomit-
ing). In traumatized patient, the insertion of the oral airway should be carried out
directly (without 180° rotation) with the use of a tongue depressor.
If manual or assisted ventilations by facemask are not effective, endotracheal
intubation or insertion of a supraglottic device (laryngeal mask airway (LMA)) has
to be performed.
The use of appropriated-sized LMA has been validated even in the prehospital
care [6]as an alternative in the case of difficult tracheal intubation.
The sizing of LMA is done on the basis of the weight of the patient (Table 15.1).
If intubation is necessary, a fast assessment of the airway should be made before
inducing anesthesia and administration of neuromuscular blocking drug. A plan
should be available in the case of a difficult or failed intubation. A video laryngo-
scope, bronchoscope, or LMA should also be kept handy.
In trauma patient, nasotracheal intubation is contraindicated, especially if an
injury of the cranial base is suspected.
The pediatric trauma victims should always be considered as full stomach
patients, and rapid sequence induction is preferred as the gold standard for airway
management in these patients [7].
In children, the Sellick maneuver may be less effective than in adults, because of
the pliability of laryngeal cartilages.
Severely injured children should be intubated with cuffed endotracheal tubes, even in
the prehospital settings [8, 9]. The size of the cuffed tube is often determined by modi-
fied Cole formula (age [years]/4 + 4) for uncuffed tubes, decreased by half-size for cuffed
tubes. The cuff should be inflated to get a seal at about 25 cm H2O of airway pressure.
For neonates, the sizing of tracheal tube is reported in Table 15.2.
The insertion depth of the tracheal tube is calculated by multiplying by three the
result of modified Cole formula for uncuffed tubes. The proper position of the tra-
cheal tube must be confirmed by the auscultation of breath sounds and by
capnography.
Any destabilization of respiratory parameters (e.g., oxygen desaturation) during
ventilation through the tracheal tube should be carefully considered. For this pur-
pose, the acronym DOPES is used:
D = dislodgment of the tracheal tube with possible accidental removal or deepening

into a bronchus
O = obstruction of the tracheal tube by secretions, vomit, blood, or foreign body
Table 15.2 Sizing of Size Weight (kg)

tracheal tube in neonates
2.5 <1
3 1–2
3.5 >2
P = pneumothorax
E = equipment (e.g., oxygen line)
S = stomach dilatation following entry of air during the manual ventilation
15.1.2.1 Tension Pneumothorax

Tension pneumothorax occurs when trauma to the chest resulted in wall injury with
progressive entry of air that is unable to escape from the pleural space resulting in
increased pressure and lung collapse. Since in children the mediastinum is very
compliant, it shifts earlier in the course, resulting in decreased venous return and
more rapid cardiovascular collapse. This condition leads to a severe condition with
dyspnea, hypotension, increased respiratory rate, ipsilateral hyperresonance, and
reduced breath sounds. The diagnosis of tension pneumothorax is clinical and not
radiological, so the first rule for a correct treatment is to suspect it! Therefore, this
life-threatening situation must be promptly treated by urgent needle thoracostomy
followed by tube thoracostomy.
15.1.3 Circulation
In children, secondary cardiopulmonary arrest, caused by either respiratory or cir-

culatory failure, is more frequent than primary arrests caused by arrhythmias. The
outcome from cardiopulmonary arrest in pediatric patient is poor, and identification
of the antecedent stages of cardiac or respiratory failure is a priority, and therefore,
effective early intervention may be lifesaving.
The management of step C in children presents unique challenges, such as
obtaining the cooperativeness of the child for intravenous placement and the poten-
tial for psychological trauma, smaller veins, and more subcutaneous fat in children,
making both palpating and visualizing veins more difficult. Additional issues
include higher likelihood of hypovolemia upon presentation, lower success rates of
intravenous insertion by first responders with consequent hematomas, bruises, and
nonavailability of these punctured veins for intravenous placement, fractures in the
extremity bones, and hypothermia causing peripheral vasoconstriction.
As previously mentioned, a child with normal blood pressure can be in shock.
The earliest warning signs that a child is in shock include signs of decreased skin
perfusion (capillary refill, temperature, and color), central nervous system perfusion
(lethargy, inappropriate response to painful procedures, and lack of recognition of
parents), and pulses (tachycardia and the presence or absence of pulses). If hypoten-
sion is present with a markedly depressed mental status, the child is in late shock
220 L. Bussolin
with blood loss up to 40 % of blood volume. Waiting until hypotension is present to

begin treating shock is too late.
Obtaining vascular access in a pediatric trauma patient offers unique challenges.
These issues include obtaining the cooperativeness of the child for IV placement
and the potential for psychological trauma, smaller veins, and more subcutaneous
fat in children, making both palpating and visualizing veins more difficult.
Several new devices, such as intraosseous needle systems and techniques such as
ultrasonography to cannulate central and peripheral veins, have improved this
aspect of pediatric trauma management.
Once shock has been identified and intravenous or intraosseous access has
been obtained, resuscitation should be initiated, according to the algorithm shown
in Fig. 15.4.
20 ml/kg
Lactated Ringer
(may repeat 1 or
2 times)
Stable Unstable
hemodynamics hemodynamics
Blood transfusion
Clinical 10 ml/kg
observation packed red cells
(may repeat 1
time)
Unstable
hemodynamics
Surgical
treatment
Fig. 15.4 Resuscitation algorithm

15.1.4 Disability
This step involves a quick assessment of neurologic function which must be repeated
during the secondary survey to monitor for changes in the child’s neurologic status.
The level of consciousness is evaluated by the Glasgow Coma Scale (GCS) adjusted
according to the patient’s age (Table 15.3) or by the rapid application of AVPU acro-
nym (A alert, V verbal, P pain, U unresponsive), considering that P corresponds to
GCS ≤ 8.
15.1.5 Exposure
The final passage of primary survey consists in completely undressing the

patient and performing the log-roll maneuver, in order to detect any superficial
lesion or swelling, while preventing hypothermia and inserting the spinal board
(Fig. 15.5).
Table 15.3 Pediatric Glasgow Coma Scale

>1 year <1 year Score
EYE Spontaneously Spontaneously 4
OPENING To verbal command To shout 3
To pain To pain 2
No response No response 1
MOTOR Obeys Spontaneously 6
RESPONSE Localizes pain Localizes pain 5
Flexion – withdrawal Flexion – withdrawal 4
Flexion – abnormal Flexion – abnormal 3
(decorticate rigidity) (decorticate rigidity)
Extension Extension 2
(decerebrate rigidity) (decerebrate rigidity)
No response No response 1
> 5 years 2–5 years 0–23 months
VERBAL Oriented Appropriate Smiles/coos 5
RESPONSE words/phrases appropriately
Disoriented/confused Inappropriate Cries and is 4
words unconsolable
Inappropriate words Persistent cries Persistent 3
and screams inappropriate crying
and/or screaming
Incomprehensible sounds Grunts Grunts, agitated, and 2
restless
No response No response No response 1
TOTAL PEDIATRIC GLASGOW COMA SCORE (3–15)
222 L. Bussolin
Fig. 15.5 Log-roll maneuver and insertion of the spinal board
15.1.6 Family
The child with trauma, if/when conscious, usually shows a severe distress following
related to fear, pain, separation from parents, and the presence of strangers. The
appropriate management of traumatized child includes not only the life support but
also the psychological support to patient and parents. The aim is to facilitate a good
outcome concerning the behavioral and psychological development of the child.
Based on the age of the child, the main goal is to reassure him/her, allowing
parents to stay close to him/her.
Even the parents are victims of a severe psychological and emotional trauma. For
this reason, it is important that a component of the team establishes an adequate
communicative approach with parents, describing the phases of management.
15.2 Preoperative Evaluation and Management
If possible, an accurate history and clinical examination should represent the first
step of management before administering anesthesia. However, during emergency,
the AMPLE acronym may be feasible.
A = allergies
M = medications
P = past medical history
L = last oral intake and last tetanus immunization

E = events related to the injury
Clinical assessment is crucial in pediatric trauma [10]. During emergency, only

a rapid evaluation of airway, breathing, and circulation may be possible.
The operating room should be prepared by including age-appropriate equipment,
diluting and labeling the medications in age-appropriate doses, raising the ambient
temperature to 26 °C for infants and small children, rapid-infusion devices, fluid
warmers, and infusion pumps.
Imaging and laboratory testing may be very useful in injured children, but they
should not delay emergency procedures. Between all the chest imaging methods,
standard anterior-posterior chest X-rays is a cost-effective screening tool that will
reveal most of the thoracic abnormalities [11].
Routine laboratory tests such as urinalysis or serum dosages are rarely indicated
in pediatric trauma. It is recommended getting blood type, cross matching, and
hematocrit even though the patient is hemodynamically stable. Serial hematocrits
may help in the monitoring of solid organ injuries [12]. Although coagulopathy is
unusually associated with pediatric trauma, PT, PTT, and INR are useful tests in
critically injured patients.
Children with trauma, particularly the smallest, are subject to hypothermia because
of their immature thermoregulation, greater body surface area to body mass ratio,
and fluid and heat loss from exposed surgical sites; therefore, temperature monitor-
ing is mandatory.
Children with a head injury may require arterial and intracranial pressure moni-
toring as well as neurophysiologic monitoring during surgery.
The maintenance of anesthesia does not show any specific aspect. No single
technique or drug is superior to others [13].
15.4 Intraoperative Fluid Management
As mentioned above, children compensate better hemodynamically in the early

stages of injury, and hypotension is a late sign of hemorrhage that may not occur
until 30–40 % of the blood volume is lost. The increase of heart rate and capillary
refill time should not be overlooked, since children have small blood volumes (Table
15.4), and delay in fluid resuscitation may lead quickly to a significant
hypovolemia.
All intravenous fluids should be warmed to 37° to prevent hypothermia.
Resuscitation routinely starts with isotonic crystalloids as the fluid of choice.
The end points of fluid resuscitation in children usually include normalization of
pulse rate and urine output >1 ml/ kg/h.
224 L. Bussolin
Table 15.4 Blood volumes and minimum values of systolic pressure according to age
Age Blood volume (ml/kg) Systolic pressure (mmHg)
0–1 month 90 60
1 month – 1 year 80 70
> 1 year 70 70 + 2 x age (years)
The value of diastolic pressure is approximately 2/3 of systolic pressure
The use of hypertonic saline should be considered when trauma is associated

with a closed head injury [14] by a starting dose of a bolus of 6.5–10 ml/kg, fol-
lowed by an infusion of 0.1–1 ml/kg/h.
Hydroxyethyl starch and albumin have also been used in children with no signifi-
cant adverse effects [15, 16].
Dextrose-containing fluids are usually avoided, because hypotonic solutions may
contribute to the development of cerebral edema and also to avoid the risk of hyper-
glycemia, which is associated with poor neurological outcome in children with a
head injury [17].
15.5 Damage Control Strategy (DCS)
Massive hemorrhage in pediatric trauma is a rare event, although not impossible. Most
studies concern adults, so that clinical decisions either follow adult protocols or are
made according to individual clinical judgment. Deciding on time and volume of blood
transfusion may be difficult in children, as well as the optimal ratio of blood components
(red blood cells, fresh frozen plasma, platelets). Supplemental use of coagulation factors
such as recombinant factor VII and/or cryoprecipitate is advocated if appropriate.
Hemodilution, coagulopathy, acidosis, and transfusion-related complications are
associated with excessive crystalloid infusion and administration of blood products.
Coagulopathy, acidosis, and hypothermia represent the so-called lethal triad, and
the damage control approach is a strategy for preventing this situation. The main
principles of DCS include rapid surgical control of bleeding, permissive modest
hypotension that helps preserving the freshly formed thrombus, minimal use of iso-
tonic colloids with the prevention of hemodilution-related complications, and early
administration of packed red blood cells in combination with plasma and platelets
in a 1:1:1 unit ratio [18].
DCS takes place in three stages (Table 15.5).
15.6 Postoperative Period
Most of the children with major trauma will require monitoring, further stabiliza-
tion, and continuation of mechanical ventilation in the intensive care unit (ICU)
after the initial surgery. Significant fluid shift, acidosis, and soft tissue swelling
could be anticipated with massive blood loss and aggressive fluid resuscitation.
Table 15.5 The three stages of damage control

Operating room – damage control surgery
Rapid hemostasis
Control contamination
Temporary abdominal closure
Intensive care – resuscitation
Rewarming
Correct shock – optimize oxygen delivery
Correct coagulopathy
Correct acidosis
Detect abdominal compartment syndrome
Operating room – second-look laparotomy
Definitive repair
Abdominal closure
The decision to perform extubation in the operating room after major trauma
must be considered carefully. Successful extubation in patients mechanically venti-
lated is dependent on cardiovascular stability, normal acid-base balance, presence of
intact airway reflexes and ability to clear secretions, an intact central inspiratory
drive, ability to exchange gases efficiently, and respiratory muscle strength to meet
the work associated with respiratory demand. In pediatric trauma patients, mecha-
nism of injury, such as facial injury, and the absence of an air leak at the time of
extubation are the strongest factors predicting post-extubation stridor. Children who
cannot be extubated immediately will require transport to the intensive care unit.
Before transport, the anesthesiologist should reassess the patient and ensure hemo-
dynamic stability, adequate oxygenation, and functionality of the monitors.
Intraoperative monitoring should be continued during transport, and the resuscita-
tion drugs should be immediately available. A detailed report containing history and
perioperative events must be given to the intensive care unit team, ensuring the
continuity of care and patient safety.
15.7 Sedation and Analgesia
Also for the treatment of postoperative pain, Sedation and analgesia are required for a
wide range of procedures in pediatric trauma including painful procedures, such as
laceration repair, reduction of bone fractures or joint dislocations, and vascular access,
and nonpainful procedures, such as diagnosting imaging (CT, MRI, X-rays). The pri-
mary purpose of sedation and analgesia is to provide anxiolysis, control of pain, and
movement during the above procedures. Some of these procedures may not require
sedation and analgesia and can be managed with nonpharmacological techniques.
The choice of drug and level of sedation should depend on individual needs and
whether the procedure is going to be painful or nonpainful. Painful procedures
require deeper level of sedation together analgesic, while nonpainful procedures,
such as diagnostic imaging, will need minimal to moderate sedation. The medica-
tion used for sedation and analgesia includes sedative-hypnotics, analgesics, and/or
226 L. Bussolin
dissociative agents to relieve anxiety and pain associated with diagnostic and thera-
peutic procedures in children with injury.
There are two primary methods to relieve anxiety and pain associated with diag-
nostic and therapeutic procedures in children with injury: inhalational technique
with nitrous oxide and/or halogenated agents (sevoflurane) and intravenous tech-
nique by using a wide number of drugs, including sedative-hypnotics, analgesics,
and/or dissociative agents. Commonly used drugs and their adverse event are shown
in Table 15.6 with specific antagonists. Basic pediatric sedation equipment and dos-
ing guide are shown in Fig. 15.6.
15.8 Pain Assessment
Pain evaluation is crucial for an appropriate sedation and analgesia.

Pain assessment in children is challenging, as there is no single tool available
for all age groups; hence, age-appropriate pain assessment scales should be used
(Table 15.7).
Table 15.6 Pharmacological agents used for sedation and analgesia and antagonists [19]
Drugs and dosage Clinical effects Adverse events
Midazolam
0.5–0.75 mg/kg per os Anxiolysis, amnesia, Hypoventilation, apnea, and
0.025–0.1 mg/kg i.v. sedation, hypnotic, paradoxical reactions
0.2 mg/kg intranasal anticonvulsant
Propofol
1 mg/kg followed by 0,5 Sedative with rapid onset and Respiratory depression, apnea,
mg/kg if necessary brief duration of action hypotension, and pain on injection
Ketamine
3–5 mg/kg i.m. Dissociative analgesia and Increase in heart rate and blood
1–2 mg/kg i.v. amnesia pressure, increase in exocrine
secretion
Fentanyl
1–2 μg/kg i.v. or Potent analgesic with no Respiratory depression,
intranasal to repeat every anxiolytic or amnestic effects hypotension, bradycardia
3 min until titration
effect
Morphine
0.2 mg/kg i.v. or 0.3–0.5 Analgesia Respiratory depression, nausea,
mg/kg intranasal vomiting
Naloxone
0.1 mg/kg i.v. to repeat Reversal of respiratory Shorter effect in reversing
every 2 min if necessary depression by opioids long-acting opioids
Flumazenil
0.02 mg/kg i.v. to repeat Reversal of clinical effects of Shorter effect in reversing
every 1 min if necessary benzodiazepines long-acting benzodiazepines
Fig. 15.6 The Broselow system modified for use at the Pediatric Trauma Center at Harborview
Medical Center [19]
Table 15.7 Pain assessment tools in children of different ages

Pain scale Measurement criteria Age group
Premature Infant Pain Profile Assessment of 15 indicators of distress Neonates and
(PIPP) preterm babies
Neonatal Facial Coding Assessment of facial actions Neonates
System (NFCS)
Face, Legs, Activity, Cry and Assessment of distress behaviors in five Children 2
Consolability (FLACC) categories months–7 years
Children’s Hospital of Assessment of distress behavior in six 1–4 years
Eastern Ontario Pain Scale categories
(CHEOPS)
Faces Pain Scale-Revised A series of facial expression illustrating 3–5 years
(FPS-R) different degrees of discomfort, assigned a
numerical score of 1–10
Oucher Scale Six color photos of a child’s face showing 7 years or older
different intensities of pain and a numerical
scale of scores from 0 (no pain) to 100
(worst pain ever)
Visual analog scale A line without markers with end points of School-age
least or greatest values of intensity of pain children
Numerical rating scale Variation of VAS. Numbers (0–10 or 0–100) School-age
(NRS) to rate the pain children
228 L. Bussolin
15.9 Conclusion
Trauma is the leading cause of morbidity and mortality in children. Emergency depart-
ment anesthesiologists are involved in the care of injured children during periopera-
tive treatment. Treatment of the traumatized child requires an accurate knowledge of
the anatomical and physiological features that distinguish children from adults.
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with Cancer 16
Navi Virk, B. Senbruna, and Jerrold Lerman
16.1 Pediatric Cancer Stats
Cancer is the major cause of pediatric mortality and morbidity. It is the second most
common cause of death in children less than 15 years of age [1, 2]. Although the
5-year survival rates exceed 80 %, this leaves chronic and debilitating sequelae for
many of these children [3, 4]. The incidence and types of cancer differ with age and
differ dramatically from adults (Table 16.1). The pediatric anesthesiologist must be
prepared to manage the various conditions associated with cancer patients, as well
as the consequences of cancer therapy modalities. Children with cancer can have
serious multisystem disease and are prone to various toxicities from chemotherapy
and/or radiation therapy and the associated pharmacological treatment.
16.2 Immunomodulatory Effects
Immunosuppression and cancer cell augmentation have been associated with cer-
tain anesthetic agents such as ketamine, inhalant anesthetics, and opioids. Propofol
and nitrous oxide have been shown to confer less immunosuppression. Regional
anesthesia may actually be beneficial in reducing cancer recurrence [5, 6]. Without
stronger evidence, at the current time, we cannot recommend a specific anesthetic
plan that avoids suppressing the immune system and augmenting cancer.
N. Virk, MD • J. Lerman, MD, FRCPC, FANZCA (*) • B. Senbruna, MD

University of Rochester, Rochester, NY, USA
e-mail: navvirk@msn.com; jerrold.lerman@gmail.com

DOI 10.1007/978-3-319-21960-8_16
230 N. Virk et al.
Table 16.1 Incidence (%) of pediatric cancer by age

Age (years) Overall
Type of cancer 0–4 5–9 10–14 15–19 0–19
Leukemias 36.1 33.4 21.8 12.4 25.2
CNS tumors 16.6 27.7 19.6 9.5 16.7
Lymphomas 3.9 12.9 20.6 25.1 15.5
Carcinomas and epithelial tumors 0.9 2.5 8.9 20.9 9.2
Soft tissue sarcomas 5.6 7.5 9.1 8.0 7.4
Germ cell, trophoblastic, and other gonadal tumors 3.3 2.0 5.3 13.9 7.0
Malignant bone tumors 0.6 4.6 11.3 7.7 5.6
Sympathetic nervous system tumors 14.3 2.7 1.2 0.5 5.4
Renal tumors 9.7 5.4 1.1 0.6 4.4
Retinoblastoma 6.3 0.5 0.1 0.0 2.1
Hepatic tumors 2.2 0.4 0.6 0.6 1.1
Miscellaneous neoplasmsa 0.5 0.3 0.6 0.8 0.6
a
Including cardiac tumors
16.2.1 Toxicity of Oncological Therapies
Chemotherapy, radiation therapy, hematopoietic stem cell transplantation (HSCT),

and surgical interventions are mainstays of cancer treatment. All of these modalities
can significantly affect healthy tissue and lead to multiorgan dysfunction. The tox-
icities of pharmacologic agents must be understood and recognized by the anesthe-
siologist in order to optimally manage these children.
16.2.1.1 Chemotherapy
Chemotherapy is one of the cornerstones of cancer treatment. The majority of chil-
dren with cancer who present for anesthesia are or have been submitted to one or
more chemotherapy regimens. These medications can have significant biological
effects on a range of organ systems as well as enzyme function. Therefore, the anes-
thetic must be optimized to address the altered physiology and medication interac-
tions for each child. The greatest concerns pertain to the acute effects of chemotherapy,
although occasionally the effects may persist and alter the child’s susceptibility to
anesthesia years after conclusion of treatment. The effect of chemotherapy on peri-
operative care is determined by the specific agent, its inherent toxicity, and the cumu-
lative dose. The impact of these agents on cardiorespiratory, hematopoietic, and
gastrointestinal systems is most relevant to anesthesia. Table 16.2 provides an over-
view of chemotherapy agents and their association with organ toxicities.
Cardiotoxicity
Cardiotoxicity can manifest as acute or subacute, chronic, and late-onset pathology.
The most common chemotherapy agents that cause cardiotoxicity are anthracy-
clines (doxorubicin, daunorubicin, and epirubicin), mitoxantrone, cyclophospha-
mide, bleomycin, 5-fluorouracil, and paclitaxel [7–9].
16 Perioperative Care of Children with Cancer 231
Anthracyclines and the anthracycline analog, mitoxantrone, impair myocardial

contractility that may lead to cardiomyopathy and congestive heart failure, espe-
cially if mitoxantrone total does exceeds 140 mg/m2 [10]. Anthracycline therapy
enhances the cardiodepressive effects of anesthesia even in children who have nor-
mal resting cardiac function [11]. Dysrhythmias, which develop independent of the
dose administered, may be manifested as sinus tachycardia, supraventricular tachy-
cardia, junctional tachycardia, atrioventricular and bundle-branch block, or ventric-
ular tachycardia. Dysrhythmias may occur as early as few hours after the
administration of these agents [12, 13]. Forty percent of anthracycline-induced
acute toxicity presents as electrocardiographic changes, which include the afore-
mentioned dysrhythmias as well as decreased QRS voltage, and prolongation of the
QT interval, which is characteristic of doxorubicin [7, 13]. With the exception of
decreased QRS voltage, these changes usually resolve within 1–2 months of the
conclusion of therapy. However, sudden death secondary to ventricular fibrillation
may occur. Rare cases of subacute cardiotoxicity resulting in acute failure of the left
ventricle, pericarditis, or a fatal pericarditis-myocarditis syndrome have been
reported particularly in children [14].
Chronic anthracycline cardiotoxicity usually presents as cardiomyopathy. This
sequela depends on the cumulative dose administered. The average reported inci-
dence of congestive heart failure is 0.14 % with doses <400 mg/m2, 7 % with 550
mg/m2, 15 % with 600 mg/m2, and 35 % with 700 mg/m2 total dose of adriamycin
[15, 16].
It is important to understand that anthracycline cardiotoxicity can have a late onset.
A recent review reported occult ventricular dysfunction, heart failure, and arrhythmias
appearing in previously asymptomatic patients more than 1 year after conclusion of
anthracycline therapy [17]. Doxorubicin, in particular, can cause subclinical myocar-
dial injury during preadolescent years, which later, during the period of growth spurt,
impairs growth of the myocardium. In addition to the total dose of anthracyclines,
high-dose radiation to the mediastinum, concurrent cyclophosphamide therapy,
extremes of age, prior myocardial injury, hypertension, valvular heart disease, and
liver diseases play a significant role in the development of cardiotoxicity.
Table 16.2 Common complications associated with chemotherapeutic agents

System toxicity Chemotherapeutic agents
Cardiac toxicity Busulfan, cisplatin, cyclophosphamide, daunorubicin/adriamycin,
5-fluorouracil
Pulmonary toxicity Methotrexate, bleomycin, busulfan, cyclophosphamide, cytarabine,
carmustine
Renal toxicity Methotrexate, l-asparaginase, carboplatin, ifosfamide, mitomycin-C
Hepatotoxicity Actinomycin D, methotrexate, androgens, l-asparaginase, busulfan,
cisplatin, azathioprine
CNS toxicity Methotrexate, cisplatin, interferon, hydroxyurea, procarbazine,
vincristine
SIADH secretion Cyclophosphamide, vincristine
232 N. Virk et al.
Cyclophosphamide is the second agent that can cause myocardial injury. A total
dose of cyclophosphamide in excess of 120 mg/kg administered over 2 days can cause
severe congestive heart failure, hemorrhagic myocarditis, pericarditis, and necrosis.
Conventional daily oral doses of busulfan may cause endocardial fibrosis that
manifests as constrictive cardiomyopathy [18, 19]. In case of preexisting cardiac
disease, the use of interferon may exacerbate the disease. Mitomycin may also
cause myocardial damage if administered over an extended period of time or in
large doses [20]. Paclitaxelin combined with cisplatin has been reported to cause
ventricular tachycardia [21].
If any of the aforementioned agents have been used, the child who presents for
anesthesia care should undergo a thorough cardiac evaluation that may require
echocardiography or nuclear medicine studies. Diastolic dysfunction may present
as an early manifestation of anthracycline toxicity. If the left ventricular ejection
fraction (LVEF) decreases to less than 45 %, it is considered indicative of
anthracycline-induced cardiotoxicity.
The choice of intraoperative monitors should be based on the preoperative symp-
toms and the specific surgical procedure. Invasive arterial blood pressure monitor-
ing and less commonly central venous catheter or transesophageal echocardiography
may be helpful in children with documented cardiac dysfunction. Children who
have received anthracycline therapy can develop acute intraoperative left ventricular
failure refractory to beta-adrenergic receptor agonists under anesthesia. Amrinone
and sulmazole are effective treatments in such cases [22]. Effects of non-
anthracycline chemotherapeutic agents on the heart are summarized in Table 16.3.
Pulmonary Toxicity
Children who have cancer often present with pulmonary complications that may be
the result of the disease itself or its treatment. Respiratory failure arises secondary to
pulmonary metastases or primary lesions, infections, chemotherapy, radiotherapy,
and/or extensive surgical pulmonary resections [23]. The mortality rate in these chil-
dren is as great as 75 % if mechanical ventilation is required [24–26].
Table 16.3 Adverse cardiac effects with non-anthracycline chemotherapeutic agents

Agent Cardiovascular effect
Cyclophosphamide Fulminant CHF secondary to hemorrhagic myocarditis
Acute pericarditis with effusion
Risk increased with dose > 200 mg/m2 and anthracycline
combination
Bleomycin Acute pericarditis
5-Fluorouracil Coronary insufficiency presenting as angina/myocardial infarct due
to coronary spasm
Paclitaxel and docetaxel Asymptomatic bradycardia, severe bradyarrhythmias and
tachyarrhythmias including ventricular fibrillation and asystole,
conduction disorders, myocardial ischemia and infarction;
Overall risk is increased with concomitant cisplatin therapy.
Peripheral edema is due to fluid retention (docetaxel)
The primary chemotherapeutic agents that damage the pulmonary system are
busulfan, cyclophosphamide, paclitaxel, and bleomycin, the last being the most det-
rimental of these.
Bleomycin is known to cause six distinct pathologies:
1. Interstitial pneumonitis that can progress to chronic fibrosis

2. Acute hypersensitivity pneumonitis
3. Acute chest pain syndrome
4. Bronchitis obliterans with organizing pneumonia
5. Pulmonary venoocclusive disease
6. Noncardiogenic pulmonary edema
Bleomycin-induced pulmonary toxicity develops 4–10 weeks after therapy with

an incidence between 0 and 40 %. Nonlethal pulmonary fibrosis is known to occur
in 11–30 % of children with an associated mortality from bleomycin of 2–10 %. As
many as 20 % of children with radiological and histological evidence of bleomycin
toxicity are symptom-free [27]. Risk factors for bleomycin pulmonary toxicity are
old age, cumulative dose >400–450 mg, poor pulmonary reserves, radiotherapy,
uremia, greater inspired oxygen concentrations, and concomitantly administered
other anticancer drugs.
Bleomycin is believed to cause direct cytotoxicity that involves the production of
superoxides and other free radicals. The use of greater concentrations of inspired
oxygen augments this process. Although pulmonary injury is thought to develop
with cumulative dose >400–450 mg, fetal pulmonary fibrosis has been reported
with total doses as low as 50 mg [22]. The fetal injury is believed to occur as type II
pneumocytes replace type I pneumocyte in the alveoli. With continuous exposure,
type II pneumocytes are replaced by cuboidal epithelium. Further, since effective
tissue repair is absent, this leads to the development of fibrosis. The chest X-ray
shows bilateral basal and perihilar infiltrates with fibrosis. The clinical picture
includes fever, cough, dyspnea, bibasilar rhonchi, and rales. Exertional dyspnea
may occur with mild X-ray changes and a normal or low resting PaO2. Arterial
hypoxemia is a common sign of bleomycin toxicity. An increased alveolar-arterial
PO2 gradient and decreased carbon monoxide diffusing capacity (DLCO) are con-
sistent findings in interstitial fibrosis. Pulmonary function testing indicates a restric-
tive lung pattern. Regression of the injury may occur with immediate cessation of
therapy. Steroid therapy has been found to be effective in some cases.
The perioperative inspired oxygen concentration has been a concern in those
who received bleomycin therapy. In one report of patients who were treated with
bleomycin and who received an intraoperative FiO2 > 0.39, five developed ARDS
and subsequently died [28]. In two more recent, larger series, no perioperative pul-
monary complications occurred in patients who received bleomycin and who were
subsequently exposed to intraoperative FiO2 > 0.25 and >0.41 [29, 30]. A recent,
much larger study demonstrated minor pulmonary complications in patients exposed
to inspired FiO2 > 0.40 and >0.25, although none progressed to ARDS or died.
Instead, meticulous fluid balance, duration of surgery, and postchemotherapy forced
234 N. Virk et al.
vital capacity were recognized as significant predictors of postoperative pulmonary

morbidity [31]. In the face of this conflicting evidence, the current recommenda-
tions are to minimize the FiO2 wherever possible to maintain the SpO2 in excess of
90 % and to use intraoperative PEEP.
During preoperative assessment of patients with pulmonary complications chest
X-ray, pulmonary function tests, arterial blood gas analysis, and in some instances
DLCO may assist in identifying the severity of the pulmonary dysfunction. In some
cases, arterial access may facilitate repetitive intraoperative arterial blood gas analy-
ses. Depending on the preoperative presentation and intraoperative course, postop-
erative ventilatory support may be anticipated.
Other chemotherapy agents and their adverse pulmonary effects important to
anesthesia are listed in Table 16.4.
Hepatorenal Toxicity
The renal system is affected by several chemotherapy agents, the most common
and important of which is cisplatin. Approximately 30 % of patients who are
treated with cisplatin develop nephrotoxicity, which is the dose-limiting conse-
quence. The most important measure to prevent nephrotoxicity is adequate hydra-
tion with forced diuresis. Normal saline is a particularly beneficial fluid to infuse
as the large concentration of chloride in the tubules inhibits the hydrolysis of
cisplatin [22]. Renal injury stems from coagulation necrosis of proximal and dis-
tal renal tubular and collecting duct epithelium that reduces the renal blood flow
and glomerular filtration rate (GFR). A single dose of cisplatin of 2 mg/kg or
50–75 mg/m2 produces nephrotoxicity in 25–30 % of patients [32]. Acute renal
failure can occur within 24 h of administration. Chronic decreases in GFR can
also occur. The reported decrease in GFR after 16–52 months of cisplatin therapy
is 12.5 % [33]. Coadministration of other nephrotoxic drugs, such as aminoglyco-
sides, increases the risk of nephrotoxicity. Newer cisplatin analogs, i.e., carbopla-
tin and oxaliplatin, are less nephrotoxic than cisplatin. Other nephrotoxic agents
are listed in Table 16.5.
Table 16.4 Adverse pulmonary effects with non-bleomycin chemotherapy agents

Incidence
Agent (%) Description
Busulfan 4–10 Pulmonary fibrosis, pulmonary alveolar
lipoproteinosis
Cyclophosphamide <2 Pneumonitis with or without fibrosis
Mitomycin <10 Similar to bleomycin
Cytosine arabinoside 5–32 Noncardiogenic pulmonary edema with or without
pleural effusion
Methotrexate 7 Hypersensitivity pneumonitis or
Noncardiogenic pulmonary edema or
Pulmonary fibrosis or
Pleurisy with acute chest pain
Table 16.5 Adverse nephrotoxic effects with non-cisplatinum chemotherapeutic agents

Agent Description
Mitomycin Chronic progressive increase in serum creatinine to microangiopathic
hemolytic anemia
Methotrexate Physical effect because of precipitation of drug within the renal tubules
NSAIDs reduce excretion of methotrexate and therefore should be
avoided [34]
Ifosfamide Acute tubular necrosis and renal failure
Hepatic injury presents as increased liver enzymes, impaired synthetic function

with low protein and coagulation factor synthesis, fatty infiltration of liver, and cho-
lestasis. The cause of the hepatic injury may be due to either the chemotherapy itself
or their metabolites. Among these, l-asparaginase and cytarabine are the most com-
mon chemotherapeutic agents that induce hepatocellular dysfunction, although
cyclophosphamide and mitomycin have been reported to cause dysfunction as well.
The resultant hepatic dysfunction can range from mild to very severe, with associ-
ated ascites, painful hepatomegaly, and encephalopathy.
Neurotoxicity
Chemotherapy can affect central, peripheral, and autonomic nervous systems.
Vincristine is the only known chemotherapeutic agent whose dose is limited by the
presence of neurotoxicity. It can affect all aspects of the nervous system. Central
nervous system toxicity may be manifested as ophthalmoplegia and facial palsy.
Peripheral neuropathy is characterized by depression of deep tendon reflexes and
peripheral paresthesia that progresses proximally over the course of chemotherapy.
Motor dysfunction and gait disorders can also occur. Autonomic dysfunction may
result in orthostatic hypotension, erectile dysfunction, constipation, difficulty in
micturition, bladder atony, and more.
About 50 % of those who receive cisplatin treatment develop neurotoxicity that
depends on the dose administered and the duration of therapy. It usually presents as
peripheral neuropathy in stocking and glove distribution and auditory and visual
impairment. A subclinical, unrecognized neuropathy may cause unexpected com-
plications from regional anesthesia. Recently, a diffuse brachial plexopathy was
reported after an interscalene block in a patient receiving cisplatin [35]. Therefore,
if regional anesthesia is planned, a thorough neurological examination is
warranted.
Severe neurologic consequences have occurred after inadvertent intrathecal
administration of vincristine. Close to 100 fatal or serious irreversible neurologic
injuries have been reported, although the true number of cases is unknown [36].1
Vincristine is an effective intravenous chemotherapeutic agent for leukemia, lym-
phoma, Wilms’ tumor, neuroblastoma, and other tumors. However when injected
intrathecally, it produces either a local motor neuropraxia (resulting in paresis of
1
https://www.ismp.org/newsletters/acutecare/showarticle.aspx?id=58
236 N. Virk et al.
varying severity) or ascending radiculomyeloencephalopathy, coma, and death.

Typically, vincristine is prepared in a syringe for intravenous administration, but
when a patient is scheduled for intrathecal chemotherapy, it has been inadvertently
given along with or in place of the prescribed intrathecal chemotherapy with disas-
trous sequelae. Although there is no strategy to prevent the neurologic injury or
death once intrathecal vincristine has been given, if the error is identified immedi-
ately, then the CSF has been irrigated and flushed with fresh frozen plasma, result-
ing in para- or tetraparesis and only a 15 % mortality [36]. This contrasts with a 100
% mortality without aggressive treatment with plasma. Since 50 % of vincristine is
bound to plasma proteins within 20 min of injection into blood, circulating plasma
in the CSF is believed to bind with vincristine, preventing it from destroying the
neuronal cytoskeleton and inducing neurologic injury or death. The key strategy to
avoid this potentially catastrophic outcome is to never prepare vincristine in a
syringe and to always keep vincristine remote from any intrathecal procedures.
Additional neurotoxic chemotherapy agents are listed in Table 16.6.
Hematological Effects
All lines of hematopoiesis can be affected either by the primary malignancy, metas-
tasis to bone marrow, or chemotherapy. A dysfunctional coagulation cascade can
prolonged PT and PTT times; increase factor I, V, VIII, IX, XI, and fibrinogen deg-
radation products; reduce platelet life span; and decrease antithrombin III activity.
To date, no prospective trials have estimated the minimum platelet count required to
prevent bleeding during specific procedures. The empiric recommendation is to
maintain the platelet count in excess of 50,000 per microliter during the periopera-
tive period. It is essential to correct any preexisting coagulopathy before commenc-
ing surgery.
Anemia is very common in cancer patients. Recommendations differ regarding
the transfusion threshold for packed red blood cell (PRBC). Most recommend a
hemoglobin threshold of <9 g/dl for transfusion in asymptomatic children, with
greater values in symptomatic patients [37]. During perioperative period, the anes-
thesiologist should closely follow the blood loss and guide the decision to transfuse
Table 16.6 Adverse neurotoxic effects with non-vincristine chemotherapy agents

Incidence
Agent (%) Description
Cytarabine 15–37 Cerebellar dysfunction, peripheral neuropathy, seizures,
encephalopathy, myelopathy, pseudobulbar palsy
Ifosfamide 0–10 Cerebellar dysfunction, hemiparesis, coma, extrapyramidal
abnormalities
5-Fluorouracil 0–5 Cerebellar dysfunction, multifocal leukoencephalopathy
Methotrexate 0–2 Meningeal irritation, transient paraparesis, encephalopathy
Paclitaxel 50–70 Peripheral neuropathy, autonomic neuropathy
(high dose)
Procarbazine Cerebral effects: lethargy, depression to psychosis,
peripheral neuropathy
based on age-adjusted estimated allowable blood loss calculations.

Immunocompromised children including infants depending on the institutional pol-
icy; hematopoietic progenitor cell transplant recipients; those with Hodgkin’s dis-
ease, leukemia and lymphoma, aplastic anemia with severe lymphocytopenia, and
solid organ tumors; those receiving nucleoside analog therapy (i.e., fludarabine);
those requiring granulocyte transfusions; and those undergoing intense chemother-
apy require irradiated PRBCs. Accordingly, red blood cell transfusions should be
planned before surgery in collaboration with the treating oncologist [38].
Most children receiving broad-based chemotherapy will experience immunosup-
pression. Chemotherapy, by design, targets rapidly dividing cells, including immune
system cells. For this reason, these children are more susceptible to infections.
Meticulous aseptic techniques are mandatory during all invasive procedures. Wound
healing can also be affected by the absence of neutrophils. Nonetheless, children
whose WBC exceeds 500/mm3 generally have uncomplicated surgical wound heal-
ing. The effect of chronic anemia on surgical wound healing is minimal [39]. Other
factors that complicate wound healing include chemotherapy. The effect of chemo-
therapy depends on the dose and timing of chemotherapy administration, as well as
concurrent radiotherapy.
Myelosuppression caused by chemotherapy is transient and usually resolves
within 1–6 weeks after cessation of treatment.
Hormone and Enzyme Production

The most common hormonal disturbance in children treated for cancer is steroid-
induced adrenal suppression. The stress response may be blunted for 6 months or
greater after therapeutic exogenous corticosteroids. Most children who continue
their usual doses of corticosteroids during surgery have appropriate corticosteroid
levels and can mount an endogenous stress response [40]. Whether they require a
supplemental dose of steroids in the perioperative period remains controversial
[41, 42]. The corticotrophin (ACTH) stimulation test is the definitive test to con-
firm adrenal suppression, but individual testing is labor-intensive, costly, and of
limited predictive value. A recent review (with limited power) determined that
patients with intact hypothalamic-pituitary axis who are receiving physiologic
doses of exogenous steroids more than likely can mount a stress response, whereas
those with dysfunction of the hypothalamic-pituitary axis (e.g., Addison’s disease)
likely cannot mount an endogenous response to steroids and require supplementa-
tion [43]. Current practice in most centers favors supplementing children who have
taken exogenous steroids in the perioperative period. If a child develops unex-
plained intraoperative or postoperative hypotension, particularly if it is unrespon-
sive to a fluid bolus and/or pressors, treatment with hydrocortisone (1.5 mg/kg
intravenously) is definitely warranted.
Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is best
known in association with paraneoplastic syndrome of small cell lung cancer,
which is exceedingly rare in children, but it has been associated with other onco-
logic diseases as well. About 1–2 % of cancer patients develop SIADH. Some
drugs, including vasopressin, carbamazepine, oxytocin, vincristine, vinblastine,
238 N. Virk et al.
cyclophosphamide, phenothiazines, tricyclic antidepressant agents, opioids, and

monoamine oxidase inhibitors, can also induce SIADH [44]. The diagnostic criteria
for SIADH include a serum sodium level <135 mEq/L, plasma osmolality <280
mOsm/kg, urine osmolality >500 mOsm/kg, and urine sodium >20 mEq/L. Patients
who develop SIADH can experience malaise, altered mental status, seizures, coma,
and occasionally death. Focal neurologic findings can occur in the absence of brain
metastases. Acute treatment is indicated if serum sodium concentration is <125
mEq/L. Correction of the hyponatremia should be undertaken slowly, particularly
if the hyponatremia has persisted for several days. The increase in serum sodium
should be ≤20 mEq/L during the first 48 h of treatment. Children who experience
too rapid an increase in the serum concentration of sodium may suffer neurologic
insults and central pontine myelinolysis.
Some chemotherapy agents can interfere with several enzyme activities.
Alkylating agents such as cyclophosphamide inhibit pseudocholinesterase activity.
The effect may persist for 3–4 weeks after the final dose. Accordingly, the use of
succinylcholine may cause prolonged muscle paralysis, and a reduction of the dose
is indicated in such patients [45]. Procarbazine exerts inhibitory effect on mono-
amine oxidase. Because of potential synergistic action, barbiturates, antihistaminic,
phenothiazines, opioids, and tricyclic antidepressants should be used with caution.
16.2.1.2 Radiation Toxicity

Toxicity from radiation is unavoidable, but children are particularly prone to devel-
oping sequelae because of their young age. The duration, dose, and interval of radia-
tion therapy together contribute significantly to the early side effects of the radiation,
whereas the dose and age of the child contribute to the late side effects. In general,
the sequelae develop in the organ being irradiated, although the singular exception
is the development of subsequent solid neoplasms as outlined below [46, 47].
All tissues damaged by radiation are susceptible to inflammation and subsequent
fibrosis. For example, radiation to the neck may cause the tissues to stiffen and
fibrose, which in turn distort and narrow the airway leading to a potentially difficult
airway. Thoracic radiation may affect both the heart and lungs. Cardiac manifesta-
tions may include pericarditis, effusions, cardiomyopathy, valvular fibrosis, and
conduction abnormalities [48]. To minimize cardiac toxicity, radiation doses are
limited to <25–30 Gy. The lungs are particularly at risk for fibrosis. Both fibrosis
and interstitial pneumonitis can occur but are more likely to result from chemora-
diation combination therapy. In the abdomen, radiation may cause progressive
nephrotoxicity at doses exceeding 20 Gy. Gastrointestinal manifestations include
malnutrition, chronic enterocolitis, and bowel obstruction. Whole-brain radiation
may cause long-term diminution in cognitive function and intelligence quotient, the
severity of which depends on the age of onset of the radiation and the magnitude of
the dose. The younger the child and the larger the dose, the greater the impact on
cognitive function, with learning disabilities and memory loss more prominent than
generalized intellectual impairment. Radiation therapy of the sella turcica with
doses that exceed 35–40 Gy may cause pituitary dysfunction manifested by isolated
hypothyroidism and growth retardation to panhypopituitarism. Finally, both
conductive hearing loss and sensorineural hearing loss have been reported after cra-
nial radiation. Other common sequelae of radiation therapy include blistering of the
skin and non-melanoma skin cancer, hair loss, nausea, and anemia. Perhaps the
most worrisome complication after radiation therapy is the risk of developing a
subsequent solid malignant neoplasm. These occur in up to 47 % of children after a
10-year or greater latency period after radiation. The risk of developing a neoplasm
that is distinct from the original primary neoplasm increases the younger the child
at the time of the radiation exposure and the greater the dose of the radiation.
Examples of solid subsequent neoplasms include thyroid, breast, brain, sarcoma,
and others.
16.2.2 Anterior Mediastinal Mass (AMM)
Children with AMMs require general anesthesia and/or sedation for a tissue (lymph
node) biopsy, CT scan or MRI for diagnosis, or indwelling central line for chemo-
therapy [49]. Children with these tumors present a significant risk for anesthesia,
since cardiac arrest has been reported in the past. Understanding the pathophysiol-
ogy of the disease enables the clinician to anticipate complications and prepare the
anesthetic to avoid them.
Four tissue types comprise most AMMs in children: lymphomas, teratomas, thy-
momas, and thyroid with lymphomas being the most common, 45 % of AMMs [49].
The most rapidly growing tumor in the anterior mediastinum is the lymphoblastic
T-cell lymphoma, a non-Hodgkin’s lymphoma, which has a doubling time of only
12–24 h. These children may present with minor findings (e.g., night sweats) that
rapidly progress over 1–2 days to life-threatening problems (e.g., orthopnea, supe-
rior vena cava syndrome). In children, anesthesia is usually required to delimit the
extent of and tumor effects on mediastinal structures in radiology as well as for tis-
sue biopsy and chronic chemotherapy access in the operating room.
The decision to proceed with local, regional, or general anesthesia depends on
the age and level of cooperation of the child, the extent of mediastinal organ involve-
ment, and the access of the node or tumor being biopsied or the planned procedure.
A multidisciplinary team that includes the surgeon, anesthesiologist, and oncologist
should review all radiological and preoperative data before embarking on the
surgery.
Preoperatively, all children should have a chest X-ray (anterior-posterior and lat-
eral views) as well as a preoperative echocardiogram. The latter is particularly help-
ful in determining whether the right atrium, pulmonary artery, pericardium, and
pericardial sac are involved with the tumor. Although echocardiographic examina-
tions are performed awake and cannot rule out compression of these structures dur-
ing anesthesia, they can identify whether the structures may be at risk during
anesthesia.
Those children who can tolerate the surgery under local anesthesia and sedation
are managed in this manner. However, this is not usually possible in younger chil-
dren, in children who cannot tolerate local anesthesia and sedation, and in those
240 N. Virk et al.
whose tumor severely compromises the airway and/or pulmonary artery. In such
instances, a 12–24 h course of intravenous steroids or limited radiation should be
considered and discussed with the oncologists to shrink the tumor to facilitate an
anesthetic and reduce the risk of cardiac arrest [50]. The risks associated with
administering a brief course of steroids or radiation are infrequent but may include
widespread tumor necrosis that may both render the diagnosis of the cell type dif-
ficult and possibly trigger tumor lysis syndrome [51]. Some oncologists are reluc-
tant to treat these children with steroids because of the potential difficulty in
establishing the tissue diagnosis should extensive tumor necrosis ensue. Establishing
the tumor type is critical for determining the treatment regimen for the specific
tumor type. Thus, a balance between the oncologist’s and anesthesiologist’s require-
ments must be sought.
For most children who require a radiological investigation, tumor biopsy, or che-
motherapy access, general anesthesia with spontaneous respiration and avoiding
paralysis are the optimal prescription [49]. If the child cannot lie flat, anesthesia can
be induced and the trachea intubated with the child positioned in the left lateral
decubitus or less desirably, in the sitting position. The trachea should be intubated
at induction of anesthesia to ensure a patent airway should it become necessary to
turn the child prone to reverse circulatory collapse. Tracheal intubation is performed
without muscle relaxation to preserve spontaneous respiration. Spontaneous respi-
ration best preserves the negative intrathoracic pressure gradient to suspend the
tumor above the mediastinal structures and avoid pressure on the pulmonary artery
and right atrium as well as the tracheobronchial tree. Maintaining spontaneous res-
piration preserves negative intrathoracic pressures, although simply induction of
anesthesia may decrease the magnitude of the negative intrathoracic pressure suffi-
ciently to allow the tumor to press on cardiac vessels. Therefore, one must always
monitor the cardiac output (via the capnogram; see below) and be prepared to emer-
gently reestablish circulation. The latter may be achieved by either turning the child
prone or applying one towel clip at the sternal notch and one at the xiphoid junction
in the anesthetized child and lifting the sternum to restore patency of the cardiac
vasculature (usually the pulmonary artery). The capnogram is a very useful monitor
to confirm the adequacy of the pulmonary circulation (and cardiac output); the sud-
den loss of or reduction in the capnogram may herald compression of the pulmonary
artery before systemic cardiovascular sequelae occur. Unless the femoral artery and
vein have been cannulated before induction of anesthesia, it is exceedingly unlikely
that extracorporeal membrane oxygenation could be instituted rapidly enough to
restore the circulation in a child who arrests with an AMM.
16.2.3 Airway Lesions
Mucositis and xerostomia are possible sequelae of chemotherapy/radiation therapy

developing within weeks of beginning treatment. Mucositis and ulcerative lesions
can also occur after hematopoietic stem cell transplant as a part of GVHD. This can
result in pseudomembrane formation, supraglottic edema, friability/bleeding, and
the potential for aspiration [37]. Irradiation of the neck can lead to fibrosis and air-
way distortion (subglottic edema, supra and subglottic stenosis, hypoplasia of the
jaw, and chondronecrosis of the epiglottis, arytenoids, and trachea) [46]. Concerns
for difficult airway, poor LMA seating, and the need for smaller ET tubes may
result. For children who received HSCT and required mechanical ventilation, 30 %
of intubations were reported to be difficult, most often because of bleeding or edema
from mucositis [46].
16.2.4 Neoplasia/Cancer
16.2.4.1 Cardiovascular Effects and Considerations

Although primary cardiac tumors are rare, serious cardiac sequelae may arise from
the cardiotoxic nature of oncological pharmacotherapies. Chemotherapeutic agents
such as anthracyclines, cyclophosphamide, fluorouracil, alkaloids, and asparaginase
are among the commonly utilized cardiotoxic chemotherapies. Their cardiac effects
are cumulative with irradiation, leading to recommendations to limit the dose of
irradiation to 25–30 Gy whenever it is combined with chemotherapy that is cardio-
toxic. Radiation therapy to the thorax can result in pericardial effusions, pericardi-
tis, cardiomyopathy, valvular fibrosis, conduction anomalies, and coronary artery
disease [48, 52].
Children treated with anthracyclines and/or chest irradiation should be followed
with regular echocardiography, especially if they received anthracycline during
infancy, required a dose greater than 240 mg/m2, or received irradiation greater than
40 Gy alone or greater than 30 Gy coupled with anthracycline therapy [53].
16.2.4.2 Pulmonary Effects and Considerations

Pulmonary neoplasms and resultant chemotherapy can result in many pulmonary
complications such as pleural effusions, pulmonary embolus, chylous effusion,
AMM, and pulmonary leukostasis, pneumonitis, pulmonary fibrosis, and pulmo-
nary edema. Pneumonitis commonly has a subclinical presentation and is reversible
up to the point of radiologic changes [54, 55]. Pulmonary fibrosis frequently occurs
during acute treatment but can become manifest months to years after treatment.
Children treated with bleomycin are at risk for exacerbation of pulmonary fibrosis
and restrictive lung disease with high concentrations of inspired oxygen. There
overall risk for pulmonary toxicity with chemotherapy in the children is near 6 %. It
increases to 20 % with the addition of radiation therapy and 25 % in those undergo-
ing HSCT [56, 57]. Bleomycin is the most common and best known culprit for
pulmonary complications, although there are many other agents that are associated
with pulmonary toxicity.
16.2.4.3 Renal Effects and Considerations

Common renal tumors in children include Wilms’ tumor, clear cell sarcoma of the
kidney, malignant rhabdoid tumor, congenital mesoblastic nephroma, and renal cell
carcinoma. Neuroblastoma can infiltrate the kidney leading to obstruction and acute
242 N. Virk et al.
renal failure. Common chemotherapeutic agents that can lead to nephrotoxicity

include cisplatin, carboplatin, ifosfamide, cyclophosphamide, and methotrexate.
Manifestations of toxicity include Fanconi syndrome (ifosfamide), hypomagnese-
mia (cisplatin), SIADH, and radiation nephritis. Careful evaluation and manage-
ment of blood pressure, electrolytes, anemia, and coagulation status is important
when treating children with renal dysfunction that was associated with chemotherapy-
radiation therapy [37].
16.2.4.4 Hepatic Effects and Considerations

Although rare, primary liver tumors in children include hepatoblastoma, sarcoma,
germ cell tumors, and rhabdoid tumors (Table 16.1). Genetic syndromes are associ-
ated with up to 20 % of hepatic neoplasms. Beckwith-Wiedemann syndrome is
associated with neonatal birth weights greater than 4 kg, macroglossia, and ompha-
locele [58]. Commonly these infants have exophthalmos, visceromegaly, hypervis-
cosity syndrome, and hypoglycemia. Careful consideration should be made to the
possibility of difficult airway, glucose monitoring, the need for phlebotomy, and the
possibility of postoperative airway obstruction.
Chemotherapy and radiation can lead to hepatic toxicity and fibrosis; however, it is
usually mild and self-limiting. Sinusoidal obstruction syndrome after HSCT occurs
11–27 % of the time with a high mortality of 19–50 %. Sinusoidal obstruction syn-
drome is characterized by portal hypertension, liver failure, and subsequent multiorgan
failure. For any patients with hepatic dysfunction, it is important to anticipate dimin-
ished biotransformation of anesthetic agents and the possibility of coagulopathy.
16.2.4.5 GI Effects and Considerations

Although primary GI tumors are rare, intra-abdominal masses can lead to obstruction
(intestinal or biliary), intussusceptions, perforation, and hemorrhage. Chemotherapy
toxicity can result in diarrhea, mucositis, neutropenic enterocolitis, stomatitis,
anorexia, and malnutrition/dehydration. Anesthetic considerations include aspiration
risk, vitamin K deficiency, electrolyte disturbances, and fluid status [37].
16.2.4.6 CNS Effects and Considerations

Common central nervous system neoplasms include astrocytomas, ependymomas,
neuroectodermal tumors, and gliomas. Neurotoxicity from chemotherapy is associ-
ated with platinum agents, l-asparaginase, ifosfamide, methotrexate, cytarabine,
etoposide, vincristine, and cyclosporine A. Irradiation of the brain can lead to neu-
rocognitive delays and leukoencephalopathy. Most tumors require resection and the
anesthesiologist should be prepared to manage ICP and treat the possibility of intra-
operative seizures [37]. Supplemental steroid therapy may be necessary for those
who have received steroids either for their tumor or to decrease the ICP.
16.2.4.7 Endocrine Effects and Considerations

Less than 5 % of childhood cancer includes endocrine tumors (Table 16.1). Gonadal
germ cell tumors, thyroid neoplasia, and pituitary masses are the most prevalent
endocrine cancers. The main anesthetic concerns involve the use of steroids for
cancer treatment and the effects of radiation on hormone secretion.
Adrenal suppression is common in patients receiving glucocorticoid treatment,

and stress dose steroids are recommended in any pediatric patient who has received
steroid treatment within 1–2 months of surgery. Radiation can result in growth
hormone and gonadotropin deficiency in doses as low as 20 Gy. Panhypopituitarism
risk increases as the radiation dose rises to approximately 40 Gy [59].
Hypothyroidism can occur 2–4.5 years after radiation in doses up to 20 Gy [60].
16.2.4.8 Hematological Effects and Considerations

Myelosuppression can occur from the effects of the cancer and the chemotherapy.
Anemia, thrombocytopenia, and neutropenia are common manifestations in pediat-
ric cancer. Hyperleukocytosis greater than 200,000/mm3 can increase blood viscos-
ity and cause leukostasis. Caution must be used to maintain appropriate volume
status and avoid excessive transfusion that can exacerbate hyperleukocytosis [61].
Reduction in the treatment dose and the products transfused is standard treat-
ment regimen for myelosuppression. Leukoreduced and irradiated blood products
are recommended in immunocompromised patients susceptible to GVHD. Platelet
transfusion may be indicated for certain procedures. Recommendations for minor
surgical procedures require that platelet counts exceed 20,000/mm3. For major inva-
sive procedures, the platelets counts should be in the range of 40,000–50,000/mm3.
Neurosurgery requires platelet counts of more than 100,000/mm3. Bleeding diathe-
ses, which are common in children with ALL and AML, should be readily corrected
through leukoreduced FFP transfusion if PT/PTT is increased or there is evidence
of surgical bleeding due to coagulopathy [37].
16.2.4.9 Psychiatric Considerations

Neurocognitive and psychiatric changes are often present years after cancer treat-
ment. These can manifest as poor academic performance or emotional trauma. The
greatest effects are noted in children undergoing intrathecal methotrexate and cranial
irradiation. Demographics, support structures, and the child’s involvement in their
care regimen are all critical factors in determining the extent of the emotional trauma.
Children should be given the opportunity to assume an active role in their own
care. Activities such as pretreatment desensitization, role playing, and discussions
with the child about physical and mental expectations are useful to limit the psychi-
atric stress of cancer therapy and surgical intervention. Posttraumatic stress symp-
toms are reported in 33–68 % of children undergoing cancer treatment. It is important
to have an honest discussion with children about what to expect and the possible
outcomes for the treatment and procedures they are undergoing. A preferred anes-
thetic routine may be established for children undergoing multiple procedures [46].
16.2.5 Tumor Lysis syndrome (TLS)
TLS is caused by tumor cell lysis that results in the release of the cell contents.
Tumor cell lysis can be spontaneous or therapy induced (chemotherapy, radiation,
glucocorticoids, tamoxifen, or interferons). The greater the tumor cell burden, the
more severe the presentation. Although TLS is most commonly associated with
244 N. Virk et al.
non-Hodgkin’s lymphoma or acute leukemia, more and more frequently, it is

being reported with other tumors. Cairo and Bishop classified TLS either as a
laboratory or clinical syndrome [62]. Laboratory TLS requires that two or more of
the following metabolic abnormalities occur within 3 days before or up to 7 days
after the initiation of therapy: hyperuricemia, hyperkalemia, hyperphosphatemia,
and hypocalcemia. In contrast, clinical tumor lysis syndrome is present when
laboratory tumor lysis syndrome is accompanied by an increase in plasma creati-
nine concentration, seizures, cardiac dysrhythmias, or death. Acute renal failure
results from the precipitation of urate, xanthine, and phosphate stones in the renal
collecting system. Uric acid can induce acute kidney injury not only by intrarenal
crystallization but also by crystal-independent mechanisms, such as renal vaso-
constriction, impaired autoregulation, decreased renal blood flow, oxidation, and
inflammation [63]. Tumor lysis also releases cytokines that cause a systemic
inflammatory response syndrome and often multiorgan failure [64]. Calcium
phosphate can precipitate throughout the body. Precipitates in the cardiac con-
ducting system can cause serious, possibly fatal dysrhythmias. The risk of TLS is
greater in cases of preexisting chronic renal insufficiency, oliguria, dehydration,
hypotension, and acidic urine. The mainstay of treatment is hyperhydration with
intravenous balanced salt solution (2500–3000 ml/m2/day in children at the great-
est risk for TLS). If the urine output remains poor after achieving an optimal state
of hydration, the use of loop diuretics is recommended, with a target urine output
of at least 2 ml/kg/h. Urinary alkalinization should be avoided because it increases
the solubility of uric acid but decreases the solubility of calcium phosphate, and it
is more difficult to correct hyperphosphatemia than hyperuricemia. Control of the
serum phosphorus concentration may prevent hypocalcemia, which can lead to
life-threatening dysrhythmias and neuromuscular irritability. Asymptomatic
hypocalcemia does not require treatment. At the prospect of sudden death due to
cardiac dysrhythmias, hyperkalemia remains the most dangerous component of
the TLS. Glucose with insulin or beta-agonists can be used as temporizing mea-
sures, and calcium gluconate may be used to reduce the risk of dysrhythmia in the
acute setting.
When the anesthetic prescription is planned for any child who is undergoing
chemotherapy, it is crucial to clarify the risk of developing TLS, its severity, and
instituted treatment with the treating oncologist. NOTE: children who present for
minor surgical or medical procedures with AMMs have a high incidence of hemato-
poietic tumors that are untreated. Do NOT administer dexamethasone for postop-
erative nausea and vomiting until after the biopsy has been taken, and the oncologists
have been consulted because a single dose of dexamethasone may precipitate
TLS. In fact, a single-dose dexamethasone induced a fatal TLS event in a child with
an undiagnosed hematopoietic tumor after adenotonsillectomy [51]. New-onset
TLS usually develops 5–7 days after the induction of therapy. Some treatment regi-
mens have reduced risk for TLS than others. It is rare that those with TLS present
for anesthesia, but when the occasion arises, one should pay close attention to main-
tain adequate hydration and measure plasma potassium concentrations frequently
(e.g., every 4–6 h).
16.2.6 Retinoic Acid Syndrome
Up to 25 % of those with acute promylocytic leukemia receiving all-trans retinoic

acid develop retinoic acid syndrome. It has a 2 % mortality. Retinoic acid syndrome
manifests as respiratory distress, pulmonary infiltrates, pericardial effusions, car-
diac dysfunction, hypotension, and possibly ARF [37].
16.3 Preoperative Evaluation
Preoperative evaluation and testing for the child with cancer must be tailored to the
specific comorbidities and the risks of the individual. Along with a comprehensive
history and physical evaluation, a thorough review of the child’s medical history and
treatment regimen is necessary. Specific interest should be paid to the child who is
at risk for anemia, coagulopathy, and electrolyte abnormalities.
Children are at increased risk for anemia if present with a new diagnosis of
leukemia/lymphoma and recent chemotherapy/radiation/HSCT and are less than
6 months of age. There is a 20 % incidence of hyperleukocytosis in children
with newly diagnosed leukemia. The risk of thrombocytopenia is increased in
children who are newly diagnosed with leukemia (75 % incidence), receive
chemoradiation, have signs and symptoms of DIC, and who present with sple-
nomegaly [53].
Monitoring coagulation via testing is indicated in those who present with sepsis,
vitamin K deficiency, hyperleukocytosis, T-cell ALL, myelomonocytic leukemia,
and acute promyelocytic leukemia and have undergone l-asparaginase treatment. If
platelet counts are sufficient for the type of surgery required, no further testing is
usually indicated.
Common conditions that can lead to electrolyte disturbances include SIADH,
hypercalcemia from bone neoplasms or neuroblastoma, dehydration or malnutri-
tion, renal dysfunction, and tumor lysis syndrome.
16.4 Pediatric Cancer Pain
16.4.1 Definition
Pain is a multidimensional phenomenon with sensory, physiological, cognitive,

affective, behavioral, and spiritual components. It is the most common discomfort
experienced by children with cancer and occurs in almost 89 % of patients in an
advanced stage of the disease [65]. Pain affects all aspects of daily life, including
physical activities, school attendance, sleep patterns, family interactions, and social
relationships and can lead to distress, anxiety, depression, insomnia, and fatigue.
Very often, the severity of the pain is underestimated and inadequately treated
because of the pediatrician’s lack of experience and fear of opioid addiction and
depressed respiration.
246 N. Virk et al.
Pain can be classified according to the pathophysiological mechanism (noci-

ceptive or neuropathic pain), the duration (chronic or acute), the etiology (malig-
nant or nonmalignant), or its anatomic location (somatic or visceral). Most
children with cancer suffer from both chronic pain and acute pain. Chronic pain is
defined as continuous or recurrent pain that persists beyond the expected normal
time of healing, although in children with cancer, it persists secondary to the
ongoing disease process. Acute pain has a sudden onset and short duration. It is
important to distinguish three different kinds of acute pain: incidental pain, “end
of dose” pain, and spontaneous or breakthrough pain. Incidental pain has an iden-
tifiable cause such as movement, weight bearing, coughing, and therapeutic pro-
cedures. “End of dose” pain occurs when the nadir of the analgesic blood level is
less than the minimum effective blood level for analgesia, e.g., toward the end of
a dosing interval. This pain may be eliminated by increasing the dose of the long-
acting opioid during the maintenance period. Breakthrough pain is characterized
by a transient increase in the severity of pain over and above the preexisting base-
line level of pain. It has a sudden onset and is severe in intensity and short in
duration. Although “rescue” doses of opioids are needed to abate the pain, the
likelihood of a positive response is decreased in these children [66]. Approximately
57 % of children with cancer experience breakthrough pain, a pain that may occur
multiple times each day. Children 7–12 years of age appear to be at increased risk
for breakthrough pain [67]. Breakthrough pain independently contributes to
impaired functioning and psychological distress. Children with acute cancer pain
have breakthrough pain as a result of progress of the disease or infection at the
tumor site, development of tolerance to analgesics, drug interactions, decreasing
renal function with the accumulation of nociceptive metabolites (morphine-
3-glucuronide or hydromorphone-3-glucuronide), and/or somatization and psy-
chological distress [68].
To tailor appropriate treatment strategies, it is important to distinguish between
nociceptive pain and neuropathic pain. Nociceptive pain arises from tissue injury.
Activation of nociceptors in either surface tissues (skin, mucosa) or deep tissues
such as the bone, joint, muscle, or connective tissue causes somatic pain, and activa-
tion of nociceptors located in the viscera causes visceral pain. Neuropathic pain is
caused by structural damage and nerve cell dysfunction in the peripheral or central
nervous system. It has rarely been studied in infants, children, and adolescents. The
main causes of neuropathic pain in cancer patients are nerve injury, nerve entrap-
ment, or external compression by any space-occupying lesion; phantom limb pain;
nerve infiltration by cancers; and nerve damage caused by cancer treatment (e.g.,
chemotherapy, radiation).
16.4.2 Pain Assessment
For optimal pain management, it is essential to establish regular, objective pain level
assessment. The pain should be reassessed frequently to evaluate the effectiveness
of treatment and to institute modifications if necessary.
There is no single validated tool to measure persistent pain in children; however,

several tools are available to assess acute pain in children of different ages. Many
pain self-reporting tools can be used in children as young as 3 years. Assessing pain
in preverbal children may present a challenge. In such cases, the severity of a child’s
pain may be best evaluated by parents and/or caregivers who understand their child’s
behavioral responses to pain.
To improve perioperative pain management in children with oncologic disease
who present for repeated surgery, the anesthesia provider should inquire regarding
pain management strategies that have been used previously, as well as the efficacy
of those treatments.
16.4.3 Pain Treatment
Currently there is limited scientific evidence upon which to base pain management
strategies. The WHO and other recommendations are based on low-quality evidence
and rely primarily on expert opinions. The principles of pain management include the
application of the WHO analgesic ladder, appropriate opioid dose escalation, the use
of adjuvant analgesics, and the use of nonpharmacological methods of pain control.
16.4.4 Pharmacological Treatment
The key concepts of pharmacological cancer pain management in children include

using a two-step strategy as opposed to three-step ladder in adults, dosing at regular
intervals, using the appropriate route of administration, and adapting treatment to
the individual child. In the two-step strategy, the severity of pain dictates the choice
of analgesic. For mild pain, acetaminophen and/ or nonsteroidal anti-inflammatory
agents (e.g., ibuprofen) should be considered as first-line treatments, whereas for
moderate to severe pain, an opioid should be the primary intervention. In some situ-
ations, however, the first step can be bypassed based on clinical judgment.
16.4.4.1 Acetaminophen
The dose of oral acetaminophen is 10–20 mg/kg, with repeat dosing according to 12.5
mg/kg every 4 h or 15 mg/kg every 6 h IV (2–12 years old and adolescents <50 kg).
Acetaminophen is safe in neonates, although its metabolism and elimination are
delayed compared with adults. As a result, repeat doses in neonates should
be administered at 6 h rather than 4 h intervals. The total dose should not exceed
90–100 mg/kg (PO) or 75 mg/kg (IV) daily as excessive doses can lead to hepatic
failure. Hepatic damage has been reported after reduced doses when the usual doses
were given to debilitated children, so it is wise to avoid acetaminophen in such cases.
16.4.4.2 Ibuprofen
The dose of oral ibuprofen is 5–10 mg/kg three or four times daily with or after
food. The maximum total daily dose is 40 mg/kg/day. Ibuprofen can upset the
248 N. Virk et al.
gastrointestinal tract, impair renal function, and decrease platelet aggregation. In

children with mildly impaired renal function, the lowest effective dose of ibuprofen
should be used and renal function monitored. Sodium and water retention along
with deteriorating renal function are signs of impending renal failure. In moderate
to severe renal impairment, and in children younger than 3 months, ibuprofen should
not be used. Ibuprofen should also be used with caution in those with impaired
hepatic function as there is an increased risk of gastrointestinal bleeding and in
those with severe liver disease.
In case of moderate to severe pain, opioids are necessary. Unfortunately, fear and
a lack of knowledge about the use of opioids in children often present obstacles to
achieving effective pain relief. Morphine is the medicine of choice for the second
step in the WHO ladder, although other potent opioids may be considered and made
available in order to substitute the opioid because of intolerable side effects. There
is insufficient evidence to recommend any alternative to morphine as the opioid of
first choice. Selection of alternative opioid analgesics should be guided by consider-
ing the safety, availability, cost, and suitability including patient-related factors.
One of the basic and most important principles in managing cancer pain is the
administration of analgesics at regular intervals. It is necessary to achieve and main-
tain steady blood levels of analgesics. Analgesic dosing that is designed on a PRN
basis increases the opioid consumption, fails to satisfactorily control pain, and
invariably leads to alternating periods of under- and overmedication. Prolonged-
release oral formulation, transdermal patches, and intravenous infusions of opioids
are widely used to maintain stable analgesic levels. Tables 16.7, 16.8, and 16.9 pres-
ent the recommended initial doses of opioids according to the child’s age. Dosing is
titrated to effect with no maximum doses listed. If more than four doses of “rescue”
or breakthrough pain medications are needed each day, the background analgesic
dose must be increased. The maximum increase in the dose of opioids over 24 h is
50 % in outpatient settings. Experienced prescribers who monitor the children
closely can increase the dose up to 100 % over 24 h. To transition from parenteral
opioids to oral formulations, it is important to keep the contents of Table 16.10 in
mind, although there are few studies in children that address the equivalence of
opioid dosing.
The pain management has to be adapted to each child. Opioids, unlike the first-
step medications, do not have a maximal (ceiling) dose. Some children require very
large doses of opioids. For breakthrough pain, additional morphine (oral
Table 16.7 Doses for opioids in opioid-naive neonates

Route of
Medicine administration Starting dose
Morphine IV injection 25–50 mcg/kg every 6 h
SC injection
IV infusion Initial IV dose 25–50 mcg/kg and then 5–10 mcg/kg/h
Fentanyl IV injection 1–2 mcg/kg every 2–4 h
IV infusion Initial IV dose 1–2 mcg/kg and then 0.2–1 mcg/kg/h
Table 16.8 Doses for opioids in opioid-naive infants (1 month–1 year)

Medicine Route of administration Starting dose
Morphine Oral (immediate release) 80–200 mcg/kg every 4 h
IV injection 1–6 months: 100 mcg/kg every 6 h
SC injection 6–12 months: 100 mcg/kg every 4 h (max 2.5 mg /
dose)
IV infusion 1–6 months: initial IV dose: 50 mcg/kg, then: 10–30
mcg/kg/h
6–12 months: initial IV dose: 100–200 mcg/kg, then:
20–30 mcg/kg/h
SC infusion 1–3 months: 10 mcg/kg/h
3–12 months: 20 mcg/kg/h
Fentanyl IV injection 1–2 mcg/kg every 2–4 h
IV infusion Initial IV dose: 1–2 mcg/kg and then 0.2–1 mcg/kg/h
Oxycodone Oral (immediate release) 50–125 mcg/kg every 4 h
Table 16.9 Doses for opioids in opioid-naive children (1–12 years)

Medicine Route of administration Starting dose
Morphine Oral (immediate release) 1–2 years: 200–400 mcg/kg every 4 h
2–12 years: 200–500 mcg/kg every 4 h (max
5 mg)
Oral (prolonged release) 200–800 mcg/kg every 12 h
IV injection 1–2 years: 100 mcg/kg every 4 h
SC injection 2–12 years: 100–200 mcg/kg every 4 h (max
2.5 mg)
IV infusion Initial IV dose: 100–200 mcg/kg and then
20–30 mcg/kg/h
SC infusion 20 mcg/kg/h
Fentanyl IV injection 1–2 mcg/kg, repeated every 30–60 min
IV infusion Initial IV dose: 1–2 mcg/kg and then 0.2–1
mcg/kg/h
Hydromorphone Oral (immediate release) 30–80 mcg/kg every 3–4 h (max 2 mg/dose)
IV injection or SC 15 mcg/kg every 3–6 h
injection
Methadone Oral (immediate release) 100–200 mcg/kg
IV injection and SC every 4 h for the first 2–3 doses and then
injection every 6–12 h (max 5 mg/dose initially)
Oxycodone Oral (immediate release) 125–200 mcg/kg every 4 h (max 5 mg/dose)
Oral (prolonged release) 5 mg every 12 h
immediate-release formulation, IV injection, or subcutaneous) and fentanyl may be

administered as frequently as required. The rescue dose of morphine and other opi-
oids, except fentanyl, is 10 % of the total daily baseline dose. If larger breakthrough
doses are required, the regular baseline morphine dose should be increased, guided
by the amount of morphine required to control breakthrough pain. Commonly used
250 N. Virk et al.
Table 16.10 Approximate Medicine Dose ratio (parenteral/oral)

dose ratios for conversion
Morphine 1:2–1:3
between parenteral and oral
dose formulations Hydromorphone 1:2–1:5
Methadone 1:1–1:2
Table 16.11 Usual starting doses for patient-controlled analgesia in children

Initial bolus Continuous Maximum
until analgesia infusion (mcg/ PCA bolus Lockout hourly dose
(mcg/kg) kg/h) (mcg/kg) time (min) (mcg/kg/h)
Morphine 100–200 0–20 (max 10–20 5–10 60–100
1000) (max 1000)
Hydromorphone 2–4 0–4 (max 250) 2–5 5–10 12–20
(max 250)
Fentanyl 0.5–1 0–0.5 (max 50) 0.5–1 5 1.5–2.5
(max 50)
Doses are for children >6 months of age and are capped at 50 kg body weight
opioid regimens include immediate-release oral morphine every 4 h or controlled-

release morphine twice daily, plus a PRN dose of 10 % of the 24-h morphine
requirement as an hourly fast-release breakthrough pain medication. If the child has
IV access, patient-controlled analgesia (PCA) can be administered using a continu-
ous opioid infusion with additional self-administered boluses. If the child is too
young or unable to push the PCA demand button, a nurse-controlled analgesia pro-
tocol can be introduced (NCA) [67]. Children older than 5 or 6 years are capable of
using a PCA. If the PCA bolus dose has to be increased, it should be increased in
increments of 50 %, as in the case of the maintenance dose. For usual PCA starting
doses, refer to Table 16.11 [68].
16.4.4.3 Morphine
Morphine is available as immediate- and slow-release tablets, oral liquids, granules
(to be diluted in water), and injection. Oral long-acting morphine proved to be safe
and effective even in the very young patients. Immediate-release morphine is avail-
able as oral syrup or tablets and can be easily dosed according to weight. Prolonged-
release oral formulations allow for longer dose intervals, therefore improving the
patient’s compliance by reducing dose frequency. Prolonged-release oral formula-
tions of morphine are administered every 8–12 h but are unsuitable for the treatment
of breakthrough pain. Prolonged-release tablets cannot be crushed, chewed, or cut,
but prolonged-release granules can replace prolonged-release tablets in such a case.
Immediate-release tablets are used for titrating morphine dosage for the indi-
vidual child and defining the adequate dose for pain control and can be administered
every 4 h. They are also indispensable for the management of episodic or break-
through pain. Liquid preparations allow for easier dose administration than tablets
in infants and small children. Intravenous morphine can be administered either by
medical stuff or by patient by PCA or NCA.
Table 16.12 Equianalgesic opioid doses

Parenteral dose, Duration of
Opioid agonist IV, SC, IM (mg) Oral dose (mg) PO:IV action (h)
Morphine 10 30 3:1 3–4
Morphine, long-acting – 30 – 12
Hydromorphone 1.5 7.5 5:1 2–3
Fentanyl 0.2 mg – – 2
Oxycodone – 15–20 – 3–5
Oxycodone, long-acting – 20 – 12
The dose in renal impairment should be reduced as follows: mild (GRF 20–50 ml/
min or approximate serum creatinine 150–300 micromol/l) to moderate (GFR 10–20
ml/min or serum creatinine 300–700 micromol/l) by 25 %, and severe (GFR <10 ml/
min or serum creatinine >700 micromol/l) by 50 % or consider switching to alterna-
tive opioid analgesics which have less renal elimination, such as methadone and fen-
tanyl. In hepatic impairment, morphine should be avoided or the dose reduced.
Despite the lack of prospective data, opioid switching or rotation may have a
positive impact on managing dose-limiting side effects of, or tolerance to, opioid
therapy during cancer pain treatment in children [69]. For equianalgesic doses, refer
to Table 16.12.
16.4.4.4 Fentanyl
Fentanyl is a short-acting opioid that can be used by IV infusion or as transdermal
patch as maintenance medication or as IV boluses for breakthrough pain. Some sug-
gest using the intranasal route (an off-label use) for breakthrough pain. The nasal
mucosa is very well vascularized facilitating rapid absorption and the absorbed fen-
tanyl bypasses first-pass metabolism. The pharmacokinetics of nasal fentanyl are
very similar to those of the IV route. However, there are no published studies of
transmucosal fentanyl application systems in children. Consequently, these products
cannot yet be recommended for use in children with cancer and breakthrough pain.
Initial dosing of IV fentanyl for bolus and infusions is described in Tables 16.7,
16.8, and 16.9.
The dose of fentanyl must be reduced in children with impaired renal function:
by 25 % with moderate impairment (glomerular filtration rate (GFR) 10–20 ml/min
or serum creatinine 300–700 micromol/L) and by 50 % with severe impairment
(GFR <10 ml/min or serum creatinine >700 micromol/L). In the case of impaired
hepatic function, fentanyl should be avoided or, at the very least, the dose reduced
as coma may be precipitated.
Transdermal fentanyl patch is indicated as a maintenance analgesic in children
with chronic pain. In a multicenter study in children, transdermal fentanyl was found
to be safe and well tolerated as an alternative to oral opioids [70]. Each transdermal
application of fentanyl is designed to be worn for 72 h. The minimal dose delivers 12
mcg/h of fentanyl. The patch should never be cut to adjust the dose of fentanyl. The
safety and efficacy of transdermal fentanyl patches in children less than 2 years of
252 N. Virk et al.
Table 16.13 Dose conversion to transdermal fentanyl patch (Duragesic)

Current opioid Daily dose (mg/day)
Oral morphine 60–134 135–224 225–314 315–404
IM or IV morphine 10–22 23–37 38–52 53–67
Oral oxycodone 30–67 67.5–112 112.5–157 157.5–202
Oral hydromorphone 8–17 17.1–28 28.1–39 39.1–51
IV hydromorphone 1.5–3.4 3.5–5.6 5.7–7.9 8–10
Oral methadone 20–44 45–74 75–104 105–134
Recommended transdermal fentanyl ↓ ↓ ↓ ↓
patch dose 25 mcg/ h 50 mcg/ h 75 mcg/ h 100 mcg/ h
age have not been established. To guard against accidental ingestion by children,
caution should be exercised when choosing the application site for the transdermal
patch. The dose of fentanyl should be reduced with impaired hepatic and renal func-
tion (see above). When a transdermal patch is initiated, all around-the-clock opioids
should be stopped. The immediate-release morphine equivalent should be available.
The dose of the patch dose may be adjusted after 3 days, based on the amount of
supplemental opioids required during the previous 48 h, using a ratio of 45 mg/24 h
of oral morphine to a 12 mcg/h increase in patch dose. Transdermal fentanyl patch
therapy in children who require less than 60 mg/day of oral morphine or an equian-
algesic dose of another opioid has not been evaluated in controlled clinical trials. For
dose conversion from other opioids to transdermal patch, refer to Table 16.13.
Exposure of the application site and surrounding skin to direct external heat
sources such as heating pads or warming blankets may increase the absorption of
fentanyl and has resulted in fatal overdose of fentanyl, a respiratory arrest and death.
If a child develops a fever or increased core body temperature due to strenuous exer-
tion, they are at risk for increased fentanyl absorption and may require a reduction
in the dose of the transdermal fentanyl patch to preclude complications. The appli-
cation site should be changed as the patch is changed every 72 h.
16.4.4.5 Hydromorphone
Hydromorphone is available as a tablet, an oral liquid, or by injection. Hydromorphone
is a potent opioid with substantive differences between oral dosing and intravenous
dosing. Extreme caution should be used when converting from one route to another.
In converting from parenteral to oral hydromorphone, oral doses may need to be
titrated up to 5 times the IV dose. For dosing ranges, refer to Table 16.9.
The dose of hydromorphone should be reduced in children with moderately or
severely impaired renal function. Treatment should begin with the smallest dose and
titrated according to the child’s response. In the case of impaired hepatic function,
the initial dose should be reduced with all levels of impaired function.
16.4.4.6 Methadone
Methadone has wide interindividual variability in its pharmacokinetics and thus
should only be initiated by practitioners who are experienced with its use. The dose
should be titrated during close clinical observation of the child over several days.
The dose should initially be titrated like other strong opioids. The dose may need to
be reduced by 50 % 2–3 days after the effective dose has been established in order
to prevent adverse effects due to methadone accumulation. Thereafter, dosing
increases should be undertaken at intervals of 1 week or greater, with a maximum
increase of 50 %. For dosing ranges, refer to Table 16.9.
Methadone dose should be reduced or avoided in children with impaired hepatic
function. Significant accumulation of methadone is unlikely in children with renal
failure, as its elimination occurs primarily via the liver. Nevertheless, in children
with severely impaired renal function, the dose should be reduced by 50 % and
titrated to effect.
16.4.4.7 Oxycodone
Oxycodone is available in immediate- and prolonged-release oral formulations. The
dose in cases of moderately to severely impaired renal function should be reduced.
In moderately and severely impaired hepatic function, the dose should be reduced
by 50 % or avoided. When converting from oral morphine to oral oxycodone, an
initial dose conversion ratio of 1.5:1 is a good starting point. Thereafter, titrate the
dose to optimize the level of analgesia. For dosing ranges, refer to Table 16.9.
16.4.4.8 Naloxone
Naloxone is a pure intravenous opioid antagonist that is used to antagonize extreme
effects of an opioid overdose. In the opioid-naive neonate, infant, or child, the dose
to treat apnea after an opioid is 10 mcg/kg followed by 100 mcg/kg if there is no
response. Diagnosis should be reviewed if respiratory function does not improve;
further doses may be required if respiratory function deteriorates. Continuous IV
infusion may be needed (5–20 mcg/kg/h) and should be adjusted according to
response. Smaller doses are required in opioid-tolerant patients: neonate, infant, or
child – 1 mcg/kg titrated over time, e.g., every 3 min, until the child is breathing
spontaneously and maintaining adequate oxygenation; thereafter, a low-dose IV
infusion or intramuscular administration of the same dose that was effective intrave-
nously may be administered to maintain the respiratory rate and level of conscious-
ness until the effect of overdose has resolved. During this period, close monitoring is
required. Caution should be exercised to avoid acute withdrawal symptoms. In the
case of an opioid overdose caused by renally excreted drugs in children with impaired
renal function, extended treatment with a naloxone infusion may be required.
16.4.5 Adjuvant Therapy
Adjuvants have not been widely studied in infants and children. Their use is based
on experience in adult pain management, expert opinion, and several case reports.
The use of corticosteroids and bisphosphonates is not recommended as adjuvant for
pain management in children. The benefits of these medications are unknown and
they carry potential for serious side effects.
254 N. Virk et al.
At present, it is not possible to make a recommendation regarding the use of tri-

cyclic antidepressant and selective serotonin reuptake inhibitors or anticonvulsants
(e.g., gabapentin) as adjuvants in the treatment of neuropathic pain in children. The
benefits remain unclear.
It is also not possible to make recommendations regarding the benefits and risks
of ketamine as an adjuvant to opioids for the management of pain in children.
Ketamine is believed to be a useful adjunctive agent; however, there is a paucity of
evidence regarding its safety and efficacy in children. In one study, ketamine showed
an opioid-sparing effect and improved pain control in children with uncontrolled
cancer pain [71].
Based on the available evidence, no recommendation can be made regarding the
use of other adjuvants, e.g., benzodiazepines and baclofen, in the management of
pain in children with muscle spasm and spasticity.
16.4.6 Nonpharmacological Pain Management
The data on invasive pain management procedures in infants and children are anec-
dotal, and precise indications on who, when, and how they should receive such
treatments remain unclear. Peripheral nerve blocks, catheter-delivered nerve blocks,
and epidurals have been reported to be effective in children suffering from advanced
stage cancer. Neurolytic nerve blocks can also be considered.
Strong emphasis should be placed on supportive, rehabilitative, and integrative
therapies, such as distraction, biofeedback, deep breathing, and self-hypnosis.
Education of both family and the child cannot be overestimated.
16.4.7 Post-op Pain in Cancer Patient
Children with cancer can present at any stage of their disease for surgery. If the
child is opioid-naive, the pain management strategy is similar to that of other chil-
dren without cancer. However, if the child has been chronically exposed to opioids
before surgery, the dose of perioperative opioids may have to be increased to
account for possible resistance to the opioids. Postoperative incidental pain may
also require larger doses of opioids than expected. When appropriate, adjuvants
like acetaminophen and nonsteroidal anti-inflammatory agents can be used to
decrease opioid requirements perioperatively. NMDA receptor antagonists (e.g.,
ketamine) and magnesium infusions may reduce the dose of opioid required to
achieve analgesia in adults chronically exposed to opioids. If the child has been
exposed to PCA opioids, the overall dose of opioids may have to be increased sub-
stantively after surgery. The increased doses vary depending on the child’s resis-
tance to opioids and the surgery performed. If other techniques are used to manage
perioperative pain such as epidural or peripheral nerve blocks with or without a
catheter, the maintenance dose of opioids should continue to avoid the acute opioid
withdrawal.
16.5 Sedation Techniques
Sedation for radiation therapy requires an organized team approach to assure ade-
quate anesthesia for the child with remote and reliable monitoring. These proce-
dures take place in a remote site (radiation oncology) where there is no backup or
support. Accordingly, ALL standard anesthetic requirements must be in place before
embarking on an anesthetic including appropriate preoperative assessment of the
child (fasting) as well as medications, equipment (including resuscitation cart), and
recovery personnel. Anesthesia is usually induced in the radiation suite, and once
the child is stable, the child is left alone for the brief period of radiation administra-
tion while he/she is monitored remotely from the control station. Depending on the
site of radiation, there are a number of anesthetic prescriptions that may be used. In
all cases, the child must remain still but usually can breathe spontaneously. For
children who require a contoured total facemask to pinpoint the radiation beam to
the head, the only source for oxygen and monitoring may be nasal prongs. For those
who have radiation to anywhere but the head, any airway and anesthetic technique
may be used, recognizing that daily serial treatments may be required for up to 60
days. Hence, the least invasive airway management may be preferred.
Several pharmacological options are available to sedate these children, but for
the most part, total intravenous anesthesia with propofol is used by many. Other
approaches include ketamine, midazolam, and dexmedetomidine infusions. Usually
these children have a port or indwelling intravenous access making an intravenous
induction facile. A bolus of intravenous propofol, 2 mg/kg, followed by an infusion
of 250–300 mcg/kg/min (with larger initial infusion rates for younger infants and
those with neurological impairment) should provide immobility while maintaining
spontaneous ventilation. If intravenous access was not available, an inhalational
induction followed by conversion to the intravenous technique once the child is
anesthetized is possible. Standard ASA monitors should include etCO2 via nasal
cannula with supplemental oxygen. Proper positioning and padding with foam
cushions is important. During the treatment, the children are monitored in a control
station adjacent to the radiation suite, and it is paramount that attention is undivided
during the anesthetic to ensure adequate oxygenation and ventilation are main-
tained. With recovery in a room adjacent to the scanner, the child will achieve street
readiness for discharge after a brief recovery from the propofol.
16.6 Conclusion
To assure proper preoperative preparation of a cancer patient who is receiving che-

motherapy, the following tests, taking in consideration clinical presentation, are
suggested: complete blood count, urine analysis, serum electrolytes, fasting blood
sugar, serum BUN, pulmonary function tests, arterial blood PaO2 and PaCO2, serum
osmolality, bilirubin, creatinine, amylase, liver function tests, chest X-ray, and
ECG. Awareness of the side effects of the various chemotherapeutic agents is pru-
dent for safe and comprehensive anesthesia care.
256 N. Virk et al.
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with Cerebral Palsy and Behavioral 17
Problems
Martin Jöhr and Thomas M. Berger
17.1 Introduction
Cerebral palsy (CP) is a general term covering a variety of nonprogressive condi-

tions caused by lesions or anomalies of the brain occurring early in development.
The incidence in children born at term is 1–2.5 per 1,000 live births in the developed
world. The etiology seems to be multifactorial; surprisingly, intrapartum hypoxia is
responsible only for a small proportion of CP cases. In the majority of patients,
antenatal events seem to be responsible: cerebral malformations, prenatal infections
(i.e., toxoplasmosis, rubella, cytomegalovirus, herpes), prenatal strokes, as well as
genetic disorders. CP is the final common end point of damage to the central ner-
vous system during early development [1]. CP is probably more common in chil-
dren born prematurely.
The clinical presentations are highly variable, ranging from subclinical mono-
plegia with normal intellectual capacity to spastic quadriplegia with severe mental
retardation. The motor defects are commonly used for labeling CP: spasticity, dys-
kinesia, and ataxia [2]. Cognitive function may vary from completely normal, to
mild speech difficulties, to severe handicap. Up to 30 % of the patients with CP may
suffer from epilepsy. The overall prognosis of these patients is modest: 3 out of 4
patients experience chronic pain, 1 out of 2 have an intellectual disability, 1 out of 3
develop displacement of the hip, 1 out of 3 are unable to walk, 1 out of 4 have
behavioral disorders, 1 out of 4 have a bladder control problem, and 1 out of 15
require tube feeding [3].
M. Jöhr (*)
Pediatric Anesthesia, Department of Anesthesia, Luzerner Kantonsspital, 6000 Luzern 16,
Switzerland
e-mail: joehrmartin@bluewin.ch
T.M. Berger
Neonatal and Pediatric Intensive Care Unit, Children’s Hospital, 6000 Luzern 16, Switzerland

DOI 10.1007/978-3-319-21960-8_17
260 M. Jöhr and T.M. Berger
The anesthetic management of patients with CP is not well covered in most pedi-
atric anesthesia textbooks, but it has been summarized in several review articles
[4–9].
17.2 Preoperative Evaluation
17.2.1 General Aspects
Developmental delay is common in children with CP, and a thorough assessment of

their motor and cognitive deficits is of paramount importance. Normally, the parents
or caregivers know the patient and his/her preferences best, and the anesthesiologist
should benefit from this knowledge. Some of the key questions concerning severely
handicapped children are: what is he/she able to do, how can he/she communicate,
which preferences does he/she have, and which are signs of discomfort (Fig. 17.1)?
The anesthesiologist should become familiar with all aspects of the patient’s life
including social aspects: where does the patient live, who is caring for him, and what
are the resources of the family [10]? An often underestimated problem is the transi-
tion from pediatric to adult care [11]; while a global assessment including all aspects
of life is common practice in pediatrics, specialists in adult hospitals tend to focus
only on their domain, and important aspects of the patient’s care can thus be missed.
17.2.2 Specific Problems
Gastroesophageal reflux is relatively common among patients with CP and associ-

ated with an increased risk of pulmonary aspiration. The presence of scoliosis may
restrict ventilation (Fig. 17.2), and these patients are also at high risk for pulmonary
Fig. 17.1 A 14-year-old 25 kg severely disabled boy in severe pain. According to his mother,
flexion of the toes is a typical sign of discomfort or pain
17 Perioperative Care of Children with Cerebral Palsy and Behavioral Problems 261
complications. Contractures and deformities have to be taken into account because

they may significantly limit the possibilities to position the patient. Chronic
constipation is common and may lead to rare, but typical, complications, such as
superior mesenteric artery syndrome [12]. In addition, many of these patients have
cognitive impairments that preclude cooperative behavior even in older children.
In adult patients with CP sarcopenia, obesity and sedentary behavior will influence
the perioperative course [13]; a lifelong health program is mandatory for these
patients [14].
17.2.3 Spasticity
A big challenge in patients with CP is controlling spasticity and avoiding contrac-

tures. Pharmacologically, this is often attempted with compounds that modulate
motor tone; e.g., benzodiazepines, baclofen, vigabatrin, or tizanidine. All these
drugs have the potential to cause drowsiness and dose-dependent sedation.
Baclofen is structurally related to GABA. It can be administered orally or intra-
thecally. Especially after the first intrathecal trial injections, careful observation of
the patient is mandatory [15]. Replacement of pumps is required every 5–7 years,
and the pumps have to be refilled at least every 3 months. Baclofen should not be
withdrawn abruptly as this can induce acute withdrawal symptoms.
Vigabatrin is primarily used as an antiepileptic agent; it is a GABA analogue that
inhibits GABA metabolism.
Fig. 17.2 A 15-year-old 12 kg girl scheduled for laparoscopic fundoplication. Positioning is a

challenge. The correct position of the endotracheal tube was verified bronchoscopically
Because of its structural similarity with clonidine, Tizanidine causes sedation,

bradycardia, and hypotension in addition to myorelaxation. It is primarily metabo-
lized by CYP1A2, and blocking this enzyme, e.g., by high doses of ciprofloxacin,
may lead to excessive concentrations of tizanidine.
Botulinum toxin (Botox) is injected directly into the muscle and provides func-
tional denervation lasting several months by preventing presynaptic acetylcholine
release. In addition, Botox can be used in children with excessive salivation [16] or
for controlling bladder detrusor hyperactivity.
Injections into the muscles or into the salivary gland are made under ultrasound
control, most often in sedated or anesthetized children. Provided the total dose is
restricted, severe adverse events are rare [17]. Reported adverse reactions are mostly
related to the sedation procedure and not to the injected compound itself [18].
Neurolytic blocks (also called chemodenervation) are mainly suitable for nerves
predominantly consisting of motor fibers, e.g., the obturator nerve in case of adduc-
tor spasm [19]. To perform these blocks, skilled anesthesiologists use nerve stimula-
tion and ultrasound to identify nerve location. Today, neurolytic blocks have almost
universally been replaced by intramuscular Botox injections. However, selective
neurolytic nerve blocks using phenol (5–12 % solutions) may still have a place as
they provide relief for a period of 4–8 months [20]. Alcohol may be an alternative
to phenol for neurolysis [21].
17.2.4 Epilepsy
Up to 30 % of patients with CP have coexisting epilepsy. Perioperatively, seizure

frequency and duration can be increased because factors enhancing seizure activity,
such as stress, starvation, sleep deprivation, optical stimulation, and hyperventila-
tion, may be unavoidable. On the other hand, most, if not all, anesthetics protect
against convulsive activity [22]. With uninterrupted antiepileptic medication and
good clinical care, increased seizure activity should rarely occur [23].
Valproic acid has been associated with severe bleeding complications [24]. The
mechanisms involved are only poorly understood, but thrombocytopenia and plate-
let dysfunction, as well as deficiencies of several coagulation factors, such as fibrin-
ogen, factor XIII, and especially von Willebrand factor type 1, have been implied
[25, 26]. Preoperative coagulation tests are suggested for children who are on long-
term medication with valproic acid [25]. Another severe complication of valproic
acid use is acute pancreatitis [27].
17.3 Perioperative Management
17.3.1 Positioning and Venous Access
Positioning can be very demanding for obvious reasons; often, an inventive spirit is
needed. Meticulous padding as well as small adjustments in position of all
accessible body parts (e.g., arms, head) is key to avoid pressure sores during pro-
longed surgery. Severely handicapped children may be at high risk to sustain long
bone fractures simply through unskilled positioning.
Venous access can be difficult. In the authors’ practice, an inhalational induction
is often performed allowing careful selection of the optimal puncture site in a quiet
and motionless patient [28]. In the authors’ opinion, this can even be justified in
patients with a history of reflux [29].
17.3.2 Airway Management
Endotracheal intubation is strongly recommended for children with gastroesopha-

geal reflux and prolonged surgery. On the other hand, for many children with cere-
bral palsy and no history of reflux, a laryngeal mask airway (LMA) with a gastric
access, e.g., LMA Supreme® or LMA ProSeal®, can be a valuable airway tool. In
case of scoliosis and severe deformity, optimal positioning for intubation can be
challenging, even if the airway itself is normal. Often, the length of the trachea may
not be as long as expected for age, and auscultation may not reliably allow identify-
ing bronchial main stem intubation. It is the authors’ practice to use fiberoptic con-
trol liberally to verify the correct position of the tip of the endotracheal tube.
Intermittent airway obstruction may occur in some patients with CP – even with-
out anesthesia – because of hypotonia of the pharyngeal muscles; the symptoms
tend to become worse with increasing age [30] and ultimately may lead to a trache-
ostomy in some patients. Perioperatively, special attention must be paid to avoid
anesthetic overhang or benzodiazepine medication. During mask induction, the
skilled practitioner will generally be able to maintain an open airway with jaw thrust
and positive airway pressure.
17.3.3 Thermal Homeostasis
Hypothermia is the most common perioperative complication in children with CP [4].

The etiology is probably multifactorial: undoubtedly, the most important factor in its
pathogenesis is a reduced metabolic rate (“vita reducta”) coupled with exaggerated
losses due to exposure of large areas of the body necessary for many orthopedic inter-
ventions. In addition, these patients often have very little subcutaneous fat tissue to insu-
late against heat loss. Finally, it has been speculated that there may be abnormal
thermoregulatory mechanisms in patients with a compromised central nervous system.
Forced air systems (e.g., Bair Hugger®) are successfully used to prevent periop-
erative hypothermia. In addition to an elevated room temperature, the authors use
two forced air systems in vulnerable patients: one on which the patient is placed and
one that covers the body surface as much as possible. Continuous monitoring of the
patient’s body temperature using rectal, esophageal, or bladder temperature probes
is advisable. With the appropriate use of modern equipment, hypothermia can
almost invariably be prevented.
17.3.4 Pharmacodynamics and Pharmacokinetics
Hypnotics: Patients with CP, as well as many other severely handicapped children,
seem to be much more sensible to hypnotic agents. Frei et al. reported that the MAC
values of halothane are reduced by around 1/3 in children with CP [31]. This is
clearly a pharmacodynamic phenomenon: a lower concentration is needed for a
certain effect. Similarly, less propofol is needed to reach a target BIS value of 40
[32]. This may also be caused by an altered pharmacodynamic response; however,
different pharmacokinetics may also be responsible. Lower BIS values are recorded
in children with cerebral palsy while awake, as well as after exposure to different
sevoflurane concentrations [33]. Other authors, however, have found similar BIS
values before induction among patients with CP when compared with healthy chil-
dren [34]. The reduced requirement for hypnotic agents seems to be a common
phenomenon for most, if not all, severely handicapped children [35]. It is the
authors’ practice to monitor the hypnotic state with an EEG-based monitor, i.e.,
bispectral index (BIS®), in all of these patients despite the fact that the validity of
these monitors has not been tested extensively in this patient population, and an
individual patient may well present with a very low BIS® value before anesthesia
induction.
Opioids: Only limited information is available about the sensitivity to opioids in
patients with CP. It has been speculated that chronic hypoxia increases the sensitiv-
ity to opioids, especially to the respiratory depressant effects of opioids [36].
Children living in high altitude exposed to chronic hypoxic conditions seem to
require less opioids after surgery for sufficient pain relief [37]. Typically, increased
sensitivity to opioids is discussed in the context of obstructive sleep apnea [38]
where it is associated with relevant morbidity and even mortality [39]. There is little
doubt that similar phenomena can be found in children with CP; intermittent noctur-
nal desaturations up-regulate endorphin receptors and enhance sensitivity to opioids
[40]. Therefore, careful dosing and adequate monitoring is very important in this
patient population.
Neuromuscular blocking agents: Surprisingly, children with CP, despite the fact
that they often have a very reduced muscle mass (Fig. 17.3), seem to be resistant to
non-depolarizing neuromuscular blocking agents. Clinically, a given dose has a
shorter duration of action [41]. This resistance does not appear to be related to con-
comitant use of antiepileptic medication [42]. Receptor up-regulation seems to be a
suitable explanation. This also explains the increased sensitivity to succinylcholine
[43]. Hyperkalemia does not seem to be a problem, likely due to a reduced muscular
mass [44]. Despite the fact that the airway is usually normal, difficult intubation is
reported to be more common in severely handicapped patients; insufficient doses of
non-depolarizing neuromuscular blocking agents may be at least in part responsible
in some cases. Given the availability of sugammadex, higher doses of rocuronium,
which provide excellent intubation conditions, have become an attractive option in
patients with CP or other neuromuscular disorders [45].
Fig. 17.3 Despite severe muscular hypotrophy, this boy is remarkably resistant to atracurium
17.3.5 Uncooperative Behavior at Induction
The preoperative visit is of paramount importance; patients at risk for a stormy and
difficult induction should then be recognized. The parents should be asked about
and charts be scrutinized for information concerning previous anesthetics; it is the
authors’ practice to leave a note in the anesthesia chart on the sedative effects of the
premedication and the quality of induction.
Prevention of difficult inductions by using an adequate premedication is of par-
amount importance. It is the authors’ practice to add ketamine to midazolam if
relevant uncooperative behavior can be anticipated [46]. Often, a peaceful induc-
tion can be achieved by gentle conviction of the patient and parental support. In
addition, success is highly dependent on the skill and empathy of the anesthesiolo-
gist. Inhalation of nitrous oxide followed by sevoflurane using a flavored mask
while the child is in his/her preferred position is a good option. In the authors’
institution, an uncooperative child is usually left in his/her hospital bed for induc-
tion [47].
The management of uncooperative behavior at induction includes several
options: postponing surgery, top-up premedication with ketamine, skilful inhala-
tional or intravenous induction using persuasion, and sometimes gentle physical
restraint are all valuable options. The choice of a particular method will depend on
the individual practitioner: extensive experience with pediatric patients, appropri-
ate skills, as well as empathy with the child and the parents are key factors for
success. Often, only a detailed discussion with the parents can disclose the optimal
solution for the individual patient. The authors have induced anesthesia in children
sitting on the floor in the corridor in front of the operating theatre refusing to enter
it. In one child, refusing to enter the hospital, anesthesia was even induced on the
street in front of the hospital. Without doubt, the safest drug under these circum-
stances is ketamine.
17.3.6 Postoperative Analgesia
In patients with CP, pain is not restricted to the perioperative period but rather a
predominant symptom [48]; up to 75 % of young people with CP experience some
pain in a typical week [49]. Possibly as a consequence, pain appears to be more dif-
ficult to treat in this patient population. A first challenge is to recognize whether the
patient is in pain. It is likely that pain is often undertreated in these patients [50]. On
the other hand, because of the difficulties to distinguish pain and other causes of
agitation, overdosing with oversedation can easily occur.
Whenever possible, regional blocks are probably the most elegant way to provide
reliable analgesia in these vulnerable patients; continuous epidural analgesia may
be considered after major surgery, especially in conditions where spasms of the
muscles of the lower extremities can be expected [51].
17.4 Typical Interventions
17.4.1 Orthopedic Surgery
Major orthopedic surgery is commonly undertaken in children with CP [52].

Scoliosis surgery is often extensive involving segments from the high thoracic
region down to the sacrum, and pelvic stabilization will assist in sitting. Intraoperative
monitoring has become commonplace [53]. Postoperative pain relief is challenging;
intrathecal morphine can easily be administered [54], enhances perioperative stabil-
ity, and thus may reduce blood loss [55]. Epidural catheters, positioned intraopera-
tively by the surgeons, have also been successfully used [56].
Hip reconstruction involving pelvic and femoral osteotomies is offered even to
the most debilitated children with the aim to reduce pain, to facilitate positioning,
and even occasionally to allow a sitting position. Palliative surgery, e.g., resection
of the femoral head, is nowadays only rarely performed [57]. Postoperative pain
relief can be provided through lumbar epidural catheters; in the authors’ practice,
however, caudal morphine combined with peripheral nerve blocks, e.g., lumbar
plexus [58] or femoral and/or sciatic nerve blocks, are often used.
Blood loss can be major. Antifibrinolytic agents, e.g., tranexamic acid, are rec-
ommended by most authorities to reduce blood loss [59]; its effectiveness has been
specifically shown in cerebral palsy scoliosis too [60]. However, the pediatric data
covering other types of surgery are still very limited [61].
Latex allergy seems to be a lesser problem nowadays; nevertheless, all children
presenting for repeated surgery are at increased risk (Fig. 17.4) [62]; latex allergy is
not caused by spina bifida per se [63].
17.4.2 Fundoplication and Gastrostomy
Nissen fundoplication is considered as the treatment of choice for children with

gastroesophageal reflux disease. Laparoscopic Nissen fundoplication is offered
Fig. 17.4 Swelling of the lip after contact with latex gloves in an 8-year-old girl
today as the standard procedure, although the evidence of its superiority over open
surgery is limited [64]. The technique involves prolonged pneumoperitoneum with
the patient in a head-up position [65]. Ventilation and PEEP have to be adapted to
counteract the effects of the elevated intra-abdominal pressure. Pneumothorax can
occur by transition of CO2 from the abdominal cavity to the pleural space through
lesions caused by dissection; generally, no specific treatment is required provided
that a sufficiently high PEEP level is maintained [66]. Hemodynamic monitoring is
crucial; the critical phases are the creation of the pneumoperitoneum as well as its
release at the end of surgery. The patients usually develop a transient oliguric state
during the period with elevated intra-abdominal pressure [67]; there is some con-
sensus that this does not require aggressive treatment.
Open Nissen fundoplication is a major upper abdominal intervention with
relevant morbidity and postoperative pain. In retrospective case series, the use
of epidural catheter techniques was associated with a reduced need for postop-
erative ventilation and fewer complications [68] as well as shorter hospital
stays [69].
Gastrostomy is widely accepted as the preferred technique to establish long-term
enteral feeding in patients with severe CP. Nowadays, it is performed as a percuta-
neous endoscopic technique (PEG) in the majority of cases, and a classical open
gastrostomy is only rarely done. A preoperative plain x-ray is recommended in all
children with scoliosis and suspected distortion of the anatomy [70]. The one-step
low-profile percutaneous endoscopic gastrostomy seems to achieve equally good
results compared with the classical approach [71]. In children, the procedure is usu-
ally performed under general anesthesia. Although the procedure is considered to be
minor, and enteral feedings can be restarted within 6 h, pain and discomfort occur
commonly and can be considerable. Careful observation of the patient is required,
as unintended puncture of other visceral structures, e.g., the colon, can occur. In the
authors’ practice, an ultrasound-guided subcostal transversus abdominis plane
(TAP) block, performed following surgery to avoid distortion of the anatomy, is
commonly used for pain control.
Conclusions
Children with CP are vulnerable patients. Intraoperatively, careful positioning,
gaining venous access, maintenance of thermal homeostasis, and correct dosing
are the most challenging tasks. Postoperatively, the liberal use of regional tech-
niques for pain control is a very attractive concept. Precision and meticulous care
is particularly important in these patients to optimize perioperative care and
outcome.
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Perioperative Care of Neonates
with Airway Obstruction 18
Pierre Fiset and Sam J. Daniel
18.1 Presentation
Evaluation and treatment of the newborn presenting with airway dysfunction or

obstruction demands close collaboration between the anesthesiologist, neonatolo-
gist, otolaryngologist, and craniofacial surgeons. Anesthesiologists may be involved
in situations of neonatal lifesaving airway rescue, diagnostic processes under GA,
or more definitive corrective treatment scenarios. These challenging patients may
present with a difficult airway and necessitate the use of specific anesthetic tech-
niques to provide optimal conditions for a precise diagnosis. A comprehensive eval-
uation of each patient is essential. This review will address most of the major
pathologies of the newborn airways with the objective of helping to establish a
rational plan for anesthesia.
18.2 Symptoms and Signs
Stridor, apneas, cyanosis, choking on feeding, chronic cough and aspiration, recur-
rent croup, and failure to thrive are all nonspecific common features of airway
obstruction. Tachypnea might be present with intercostal and suprasternal indraw-
ing, which might be intermittent and triggered by feeding, position, or sleep.
P. Fiset, MD, FRCPC (*)

Department of Anesthesia, Montreal Children’s Hospital, MUHC, McGill University,
e-mail: pierre.fiset@muhc.mcgill.ca
S.J. Daniel, MD, FRCPC
Department of Pediatric Surgery and Otolaryngology, Montreal Children’s Hospital, MUHC,
e-mail: sam.daniel@mcgill.ca

DOI 10.1007/978-3-319-21960-8_18
274 P. Fiset and S.J. Daniel
Some patients present obvious features that immediately suggest a cause for air-
way obstruction: upper or lower mandibular hypodevelopment, protruding tongue,
and facial abnormalities including ear deformities, small mouth opening, and cleft
lip/palate.
The context and timing in which symptoms appear is revealing. Whether those
start immediately at birth, in the context of prematurity, after an endotracheal intu-
bation or progressively in the first days and weeks of life will suggest different pos-
sible etiologies. As part of the initial evaluation of these patients, the significant
presence of comorbidities should be kept in mind.
Bedsides flexible fiber-optic endoscopy (FFE) is universally used as an initial
and basic exam to help determine the diagnosis and conduct.
18.3 Pathologies of the Upper Airway (Above the Glottis

Structures)
The term tongue-based airway obstruction (TBAO) [1] relates to a group of syn-
dromes, pathological presentations, and features that all have in common to cause
obstruction of the neonatal airway based on glossoptosis or macroglossia. The
Pierre Robin sequence, presenting in a spectrum going form an isolated finding to
being associated with a syndrome in 27–82 % of cases, is the most common anom-
aly of that group. It was originally described as an association of micrognathia,
glossoptosis, and obstructive apnea from upper airway obstruction. A good propor-
tion of those patients also have a cleft palate [2].
Treacher Collins and Goldenhar syndromes fall in the TBAO spectrum, as well
as different forms of micro- or retrognathia. Treacher Collins syndrome is a rare
(1:50,000) genetic disorder involving the development of the first and second bran-
chial arches and limited to the head and neck. Bilateral maxillary, zygomatic, and
mandibular hypoplasia is present combined with a small oral aperture, high-arched
palate, and temporomandibular joint abnormalities [3]. The incidence of Goldenhar
syndrome (hemifacial microsomia) is reported to be between 1:35,000 and 1:56,000.
The etiology is unknown, and environmental causes like drug ingestion (vitamin A,
tamoxifen, cocaine, retinoic acid) or alcohol use during pregnancy, maternal diabe-
tes, rubella, or influenza may be in cause, but no genetic etiology has yet been
identified [4, 5]. The unilateral facial hypodevelopment is accompanied by auricular
and ocular defects. Coincident cervical instability and vertebral anomalies are fre-
quent [6].
Macroglossia can be present without an associated mandibular anomaly. In a
recent review, it was associated with Beckwith-Wiedemann syndrome [7] in 46 %
of cases as well as with trisomy 21 and other chromosomal anomalies, hypothyroid-
ism and vascular and lymphatic malformations. It is an isolated finding in about
15 % of cases [8].
Placing the newborn in prone position, bypassing the obstruction with a naso-
pharyngeal airway, or maintaining the patency with a CPAP or BiPaP device are all
part of the initial treatment of these patients. Some will outgrow their obstruction
18 Perioperative Care of Neonates with Airway Obstruction 275
and avoid surgery, but most of them will be brought to the OR for a systematic
evaluation and for a variety of procedures which include mandibular distraction,
tongue-lip adhesion, transmandibular K-wiring, subperiosteal release, or tracheos-
tomy [9].
Lesions of the base of the tongue can be present at birth or increase in size in the
neonatal period causing immediate or progressive signs of airway obstruction.
Possible causes are hemangiomas, teratomas, dermoid cysts, lymphatic or venous
malformations, thyroglossal duct, or vallecular cysts. Depending on the size, they
can compromise airway visualization by direct laryngoscopy.
Nasal obstruction is another cause of neonatal upper airway obstruction. This
can be secondary to choanal atresia, pyriform aperture stenosis, or nasolacrymal
duct mucocele [10]. CHARGE syndrome (Coloboma, Heart defect, Atresia choa-
nae, Retarded growth, Genitourinary abnormalities, and Ear anomalies) is the most
common diagnosis associated with the condition. Bilateral occlusion is also associ-
ated with other syndromes featuring midfacial hypoplasia such as Crouzon, Pfeiffer,
Antley-Bixler, or Apert [11]. These associations may contribute to a difficult airway
situation. Preoperative FFE is especially useful in this situation for establishing
diagnosis and estimating the size, nature, and extent of the lesion. Unilateral cho-
anal atresia is more likely to be isolated, although the presence of associated anoma-
lies should be suspected.
For the anesthesiologist, the common features of the above pathologies are the
potential early airway obstruction during induction and the difficulty to visualize
the larynx and perform endotracheal intubation.
18.4 Supraglottic and Laryngeal Pathologies
Laryngomalacia is the most common cause of inspiratory stridor in the newborn

accounting for 60–70 % of cases. It is frequently classified according to the area of
“collapsus” of the larynx [12]. Interestingly, this relates to the fact that the nature
and severity of the disease are revealed by the action of air movement on supraglot-
tic structures. Optimal conditions for diagnosis and treatment will be provided in a
non-intubated, spontaneously breathing patient. A secondary lesion is present in
63 % of cases, most often tracheomalacia [13]. Gastroesophageal reflux (GERD) is
often present, but it remains unclear whether it is the increased negative pressure
due the obstruction that causes acid to be drawn up to the level of the larynx or it is
the acid reflux that is an independent etiological factor of aggravation. Patients with
laryngomalacia needing surgical treatment may have shortened aryepiglottic folds,
a retropositioned epiglottis, or a prolapsed/redundant arytenoid mucosa[14].
Laryngeal cleft (LC) is labeled as a rare congenital malformation accounting for
0.5–1.6 % of laryngeal anomalies. Four types are described by Benjamin and Inglis
based on the extent of the underdevelopment of the tracheoesophageal septum [15]
(Fig. 18.1). It has been traditionally underdiagnosed but is now reported with
increasing frequency. The type 1 presents with stridor, feeding difficulties, and
recurrent airway infections [16]. Coincidental presence of laryngomalacia may
4
Thoracic
inlet
Fig. 18.1 Benjamin’s and Inglis’ classification of laryngeal clefts. Type 1: Interarythenoid defect,
type 2: extending partially into the cricoid cartilage, type 3 complete seperation of the cricoid
cartilage extending with possible extension into the tracheoesophageal wall. Type 4: common tra-
cheoesophagus with possible extension to the carinal level (From Pezzettigotta SM et al (2008)
Laryngeal Cleft. Otolaryngol Clin North Am 41 (2008) 913–933. Used with permission)
mask the diagnosis and contribute to the severity of symptoms. LC is associated

with other congenital anomalies, mostly gastrointestinal, more than 50 % of the
time [17]. As the proper diagnosis, especially in type 1, is made by probing of the
interarytenoid area, suspension laryngoscopy in a non-intubated, spontaneously
breathing patient is the anesthetic technique of choice.
Laryngeal webs are rare congenital or acquired malformation in which abnormal
fibrous tissue forms anteriorly between two structures within the larynx. They are staged
type 1–4 depending on the degree of severity using either Cohen’s [18] or Benjamin’s
[19] classification (Fig. 18.2). They are most frequently congenital, with associated
anomalies (mostly cardiac, or deletion of 22q11 chromosome) in 51 % of patients [18],
but can be acquired following a surgical procedure, intubation, or infection. Webs can
extend from the supra- to the subglottic area. Their definitive treatment is difficult, as
vocal cords tend to form fibrosis and granulation tissue following surgery.
Vocal cord paralysis is the second most common cause of inspiratory stridor,
accounting for 15–20 % of cases. It can be idiopathic, secondary to central nervous
system immaturity, due to a compression of midbrain structures by either a Chiari
malformation [20] or any lesion occupying space in the cranium and causing a par-
tial herniation of midbrain structures through the foramen ovale [21]. Unilateral
palsy can be seen after head and neck or cardiac surgery. Proper evaluation of the
Fig. 18.2 Cohen’s and Benjamin’s classification of laryngeal webs. Type 1: 35 % or less of the
glottis is involved. Type 2: 35–50 %, Type 3: 50–75 %, Type 4: more than 75 % with extension to
the subglottic area. In Type 2 and 3, may extend into the subglottis and result in subglottic stenosis.
(From Otolaryngol Clin North Am 41 (2008) 877–888. Used with permission)
condition is best done without an endotracheal tube in place. These patients may
require a tracheostomy.
18.5 Subglottic and Tracheal Pathologies
Subglottic stenosis (SGS) is most frequently caused by endotracheal intubation in

the neonatal period. It happens at the level of the cricoid cartilage which is the nar-
rowest point of the pediatric airway. The incidence has decreased in the past 30
years; however, a recent prospective study found that 11.38 % of patients had some
degree of stenosis after intubation [22]. Length of intubation and need for additional
sedation appeared to be key factors for the development of SGS. The congenital
form of SGS is rare, accounting for no more than 10 % of cases. Depending on the
severity of the narrowing, these patients will undergo a variety of treatments: obser-
vation and repeat examination, balloon dilatation, laser therapy, laryngotracheo-
plasty, cricoid split, or partial cricotracheal resection. Not infrequently a tracheotomy
will be done to insure unobstructed breathing and allow healing after a complex
corrective surgery. In the general pediatric population, anesthesiologists should
have a high index of suspicion if an infant cannot be intubated with an age-
appropriate endotracheal tube. The four-grade Cotton-Myers classification of SGS
is based on the relation between the biggest size of endotracheal tube fitting the
airway and the expected size of the tube calculated for age [23].
Infantile hemangiomas are the most common benign vascular tumors in children
and proliferate rapidly in the first year of life. There seems to be an increased risk of
laryngeal hemangioma associated with a “beard” distribution of cutaneous lesions.
Left untreated the mortality associated with subglottic hemangiomas can be as high
as 50 %. Lesions can be found in any part of the airway where they may extrinsi-
cally compromise air entry or grow inside structures, including the trachea. It is a
common differential diagnosis in infants presenting with progressive stridor and
undergoing diagnostic bronchoscopy. Patients with head and neck hemangiomas
should undergo a workup for PHACES (Posterior fossa brain malformations,
Hemangiomas of the face, Arterial Cerebrovascular abnormalities, Eye abnormali-
ties, and Sternal defects.). The use of propranolol has been recently reported to have
significant effects by decreasing the size of the lesions [24]. For a recent up to date
review, see [25]
Tracheomalacia is caused by either the altered structure of the tracheal tissue
architecture or by secondary factors like external compression or inflammatory
response to various insults. It causes variable degrees of respiratory distress due to
the exaggerated collapse of the airway typically during expiration. Bronchoscopic
observation during spontaneous ventilation (functional bronchoscopy) is used to
evaluate the extent and severity of collapsus; however, there is yet no standardized
way to classify the severity. Tracheomalacia might be underdiagnosed in children,
some patients being wrongly labeled as asthmatics. Most patients needing more
careful follow-up have an associated esophageal atresia or an anomaly of the aortic
arch or the supra-aortic vessels causing extrinsic compression [26, 27]. In some
instances, an aortopexy will allow decompression of the trachea, but a conservative
approach is usually indicated in the first 18 months of age [28]. Extrinsic compres-
sion of the tracheal tree can also be caused by a mediastinal mass and a neck mass
from tumoral or cystic origin and treated according to the diagnosis.
Congenital distal tracheal stenosis represents only 0.3–1.6 of all laryngotra-
cheal lesions and is often accompanied by cardiovascular, gastrointestinal, and pul-
monary comorbidities. While patients presenting minimal symptoms can be
observed as the stenotic area may grow to a normal size, those having more severe
symptoms will undergo surgery. A variety of tracheoplasty techniques may be
used: costochondral grafting, resection with end-to-end anastomosis, or slide tra-
cheoplasty [29]. Options for anesthetic airway management include intubation
with the cuff passed in the stenotic area, selective split endotracheal tube with one
side in each mainstem bronchus, selective intubation, bilateral jet ventilation, and
cardiopulmonary bypass [30, 31].
18.6 Anesthetic Management
18.6.1 Emergency Airway Rescue
Situations of airway rescue with impending complete obstruction are emergencies

during which the anesthesiologist must work in close collaboration with the otolar-
yngologist. A variety of airway devices must be available: oro- and nasopharyngeal
airways, appropriate sized supraglottic devices [32], various laryngoscope blades of
sizes 00 and 0, intubation aids like the family of devices labeled as videolaryngo-
scopes, and fiber-optic tracheoscopes. The presence of the otolaryngologist is man-
datory in order to establish an emergency surgical airway if needed. Induction of
anesthesia should be cautious and progressive. The presence of midfacial
deformities or various types of mandibular hypoplasia and macroglossia may impair

proper bag and mask ventilation at a very early stage of induction. Inhalational
induction probably remains the first choice of many anesthesiologists for induction
of anesthesia keeping in mind that the anesthetic administration is more likely to be
interrupted while the airway is secured or when the surgeon is working. TIVA with
short-acting agents like propofol and remifentanil allows a progressive deepening of
anesthetic state, maintenance of spontaneous respiration, and relatively rapid rever-
sal of anesthesia when stopped. An excellent review on the topic has been published
by Sims and von Ungern-Sternberg [33].
18.6.2 Anesthesia for Diagnostic and Therapeutic Procedures
Most patients presenting with a symptomatic airway problem will be first evaluated
with bedside FFE. Even in an awake patient, a good overall evaluation of the airway
down to the level of the glottis can be made, and some pathologies can be identified
for further evaluation under anesthesia. Subsequently, patients are brought to the
OR for detailed visual characterization of obstructive structures and pathologies, as
well as a precise evaluation of the functional mechanics of the airway, ideally and
most of the time during spontaneous breathing. Precise evaluation in that context is
very challenging for the anesthesiologist as the depth of anesthesia needs to be pre-
cisely reached and maintained for the performance of very stimulating procedures
like rigid bronchoscopy or airway suspension while spontaneous breathing is main-
tained. Moreover, during the same diagnostic session, the depth of anesthesia might
have to change significantly as the patient may require, for example, deep levels for
rigid bronchoscopy followed by very light levels of anesthesia in order to observe
the glottis structure behavior in a “sleep-like” state.
A variety of ventilation techniques may be used depending on the context, the
nature, and the extent of the obstruction and the level of comfort of the anesthesiolo-
gist. In a recent retrospective study on the anesthetic management for subglottic
stenosis, Knights et al. found no difference in the outcome between eight different
airway management techniques [34].
Extubation of neonatal intensive care patients after prolonged intubation is often
made in the operating room because of the significant frequency of immediate rein-
tubation in a sometimes difficult context. In our institution, this is done under gen-
eral anesthesia and spontaneous breathing with a flexible endoscope in situ to
observe the laryngeal area.
Patients with TBAO and pathologies of the upper airway and supraglottic area
need careful induction as they might obstruct quite early. Their ability to maintain
some airway patency during anesthesia is useful to help determine the need for fur-
ther intervention, for example, tongue-lip adhesion.
Functional problems like laryngomalacia and tracheomalacia are best evaluated
during spontaneous ventilation. Laryngomalacia may exhibit a complex pattern of
anterior, posterior, and/or circumferential collapse. Subtle changes in aryepiglottic
folds, epiglottic shape, and position of the arytenoid are frequently found in that
condition and subject to surgical correction. These are best evaluated during spon-
taneous breathing without an endotracheal tube in place. Tracheomalacia is
classified according to the degree of collapse during spontaneous breathing during

rigid bronchoscopy. Anomalies like a Class 1 laryngeal cleft could be missed if an
endotracheal tube is in place.
18.6.3 Planning for Postoperative Period
Difficult airway access, surgical interventions, and the use of rigid bronchoscopy
with or without suspension are all factors susceptible to induce swelling of respira-
tory tract structures in the postoperative period. The length of the procedure and
extent of surgical trauma will also be considered in deciding if the patient needs to
remain intubated or to be observed in a high-acuity area like the intensive or acute
care unit. Dexamethasone [35] or l-epinephrine given by aerosol for prevention of
post-extubation laryngeal edema is frequently used.
Conclusion
Management of the newborn obstructed airway is one of the most challenging
situations in an anesthesiologist’s practice. Proper management of these patients
requires skillful manipulation of the airway, optimal ventilation techniques, and
intimate knowledge of pharmacology. Maintenance of airway patency is com-
plexified by the need of providing conditions that will allow proper evaluation of
functional breathing mechanics in order to take optimal surgical decisions.
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Part IV
Important Techniques for Perioperative Care
Vascular Access in the Perioperative
Period 19
Thierry Pirotte
Vascular access is of major importance in the perioperative period. Venous access is

a compulsory element during any type of anesthesia and often an inevitable way to
initiate treatment in critically ill children. Anesthesiologist and pediatricians, as
experts, should master their techniques and have a thorough knowledge of the exist-
ing tools that could assist difficult vascular accesses.
Bedside ultrasound examination and real-time needle guidance are the most
important progress made over the last decade to facilitate vascular access and reduce
complications. A broad range of techniques have been developed far beyond the
puncture of the internal jugular vein [1]. The learning curve to apply these tech-
niques in children, and especially in neonates, is not short and should be followed
carefully as described in this chapter.
19.1 Ultrasound Guidance
Over the last decade, the importance of perioperative ultrasound (US) became obvi-
ous due to the diversity of applications developed in anesthesia: nerve blocks, vas-
cular access, evaluation of the gastric content, or assessment of potential
complications (fluid or air in the thoracic or abdominal cavity).
T. Pirotte
Department of Anesthesia, Cliniques universitaires Saint-Luc, Université catholique de
Louvain – UCL, Brussels, Belgium
e-mail: t.pirotte@uclouvain.be

DOI 10.1007/978-3-319-21960-8_19
286 T. Pirotte
19.1.1 Advantages of Ultrasound Guidance
The use of US for vascular access can be divided in US screening, corresponding to

an evaluation of the subcutaneous anatomy – or sonoanatomy – and real-time US
guidance (USG) of the needle during puncture.
Pre-procedural US screening detects anomalies in vessel size, position, or
patency, as well as anomalies of the surrounding structures (hematoma, ganglions,
etc.) (Fig. 19.1). If the chosen vessel or insertion site presents too much difficulty,
another site is chosen. In comparison with the blind landmark approaches, US tech-
niques detect the difficult puncture before it becomes difficult.
USG of the needle brings the needle tip in the lumen of the vessel without dam-
aging surrounding structures (artery, nerve, pleura), helps the catheterization of the
vessel, and, for central venous access, places the needle tip in an optimal position to
insert the guide wire (GW) (Fig. 19.2).
a b
c d
Fig. 19.1 Pre-procedural US screening to detect anatomical variants. (a) Normal anatomy, (b)
abnormal internal jugular vein (V) position (median to the carotid artery), (c) abnormal surround-
ing structure (*, ganglion), (d) abnormal patency (IJV thrombosis)
19 Vascular Access in the Perioperative Period 287
Fig. 19.2 Role of

a
ultrasound guidance during
vascular puncture. (a) (1)
Guide the needle in the
middle of the vein, (2)
avoid transfixion, (3) avoid
puncturing surrounding
structures, and (b) (4)
catheterize the vessel and
place the needle tip in an
optimal position to insert
the guide wire
Post-procedural screening is used to confirm the correct migration of the GW

and eventually to detect potential life-threatening complications (severe hematoma,
pneumothorax, hemopericardium) (Fig. 19.3).
For vascular access, USG has shown an increase in final success rate and in suc-
cess rate at first attempt and a reduction in complication rate (mainly inadvertent
arterial punctures) and in a number of attempts needed to succeed. These factors are
extremely important in young children and infants where multiple attempts will
lead to potential complications, time consumption, and possible instability (hypo-
thermia, hypotension).
19.1.2 Limitations of Ultrasound Guidance
The availability of the equipment and the learning curve are the two main limita-
tions. The cost of the US machine and the disposable probe covers is consequent but
should be balanced with the cost of more complications and sometimes longer pro-
cedures with blind landmark techniques. The learning curve is short for US screen-
ing but can be much longer for USG and placement of CVC in neonates.
In children, structures are usually superficial offering a nice view of both vessels
and needle. The limit of resolution can however be reached in case of very small
vessels (radial artery in neonates).
Only few pathological situations, like subcutaneous emphysema, may hamper
the use of US.
288 T. Pirotte
a b
c d
Fig. 19.3 Post-procedural US screening. (a) Confirmation of the correct migration of the guide
wire (arrow) in the brachiocephalic vein. (b) Detection of a severe carotid hematoma (arrows). (c)
Left: absence of pneumothorax: positive lung sliding sign in 2D-mode (*, rib); right: seashore sign
in M-mode (arrow, pleural line). (d) Absence of hemopericardium (*, ** empty spaces; RV, LV
right and left ventricles)
19.1.3 Guidelines for Ultrasound Guidance During Vascular Access
Different societies in different countries and continents do recommend the use of

US for vascular access [2–6]. Table 19.1 summarizes their opinion regarding central
and peripheral venous access and arterial access. US screening alone can be useful
but is evaluated as insufficient and thus not recommended. For some techniques like
the subclavian vein puncture, no comparative study is currently found in the litera-
ture, making guidelines impossible or very cautious.
19.1.4 Ultrasound Equipment
High-quality US machines are needed to offer sufficient resolution of small vessels

and a correct view of the nerves. Doppler and Zoom functions are mandatory to
Table 19.1 Guidelines for ultrasound-guided vascular access in children

PVA ART PICC IJV SCV FEM
NICE – UK – 2002 [2] n/a n/a n/a +++ + +
ASA – USA – 2012 [3] n/a n/a n/a +++ + +
ASEcho – USA – 2012 [4] no +D +++ +++ no +
International – 2012 [5] +D ++ +++ +++ +++ +++
SFAR – France – 2014 [6] +D +D n/a +++ no +++
NICE National Institute for Clinical Excellence, ASA American Society of Anesthesiologists,
ASEcho American Society of Echocardiography, International International expert group, SFAR
French Society of Anesthesia and Reanimation, PVA peripheral venous access, ART radial artery,
PICC peripherally inserted central catheters, IJV internal jugular vein, SCV subclavian vein, FEM
femoral vein, +++ strong recommendations, ++ recommendation in most cases, + weak recom-
mendations, + D recommendation in expected difficulties, no no recommendations, n/a not
analyzed
a b c d
Fig. 19.4 High-frequency probes for vascular access. (a) Adult linear, (b) linear small footprint,
(c) linear pediatric “hockey stick” (*, more room for needle handling), (d) curvilinear transfonta-
nellar probe (lower resolution and image distortion)
identify thrombosis and to differentiate or puncture very small vessels. Image stor-
age, diffusion, and sharing should be possible to complete the chard of the patient.
High-frequency (>10 MHz) probes are used because of the usual superficiality of
the vascular structures in children (Fig. 19.4). Linear probes (giving a rectangular
image) are preferred over the curvilinear probes (lower frequency and resolution,
distortion of the image). Small-footprint probes (25 mm) are mandatory to treat
infants and neonates; they give more room for the placement of the needle (the
“hockey stick” probe gives as much space as possible). If the US equipment is
290 T. Pirotte
Fig. 19.5 Comparison of

adult and pediatric
equipment in young
children. Adult probes are
limited to US screening
while small-footprint
pediatric probes can be
used for both US screening
and US needle guidance
limited to a standard adult linear probe (38 mm footprint) and the child is young, at
least US screening should be used (Fig. 19.5). Sterile US probe covers and sterile
gel are needed and disposed with the US machine.
Recent new developments in US technology are:
• Enhanced needle visualization systems (US beam steering)

• Incorporated teaching course in US machines
• Wireless US probes facilitation sterile handling (Acuson™ – Siemens®)
• GPS needle guidance allowing to predict needle track even before skin puncture
(eZGuide™ – eZono®)
19.1.5 Puncture Techniques (Fig. 19.6)
Vessels can be visualized by US in two different planes or “views”: the short-axis

view or SAX shows a round structure and the long-axis view or LAX a long tubular
structure. Patent vessels are anechoic (black) and thrombosed vessels iso- or hyper-
echoic (from grey to white). Veins are easily compressible, their size varies with
Fig. 19.6 Possible ultrasound-guided puncture techniques for vascular access. By combining two
different views of the vessel (SAX and LAX) and two different needle approaches (OOP and IP),
four techniques are formed to puncture vessels
respiration, and they may content valves. Arteries are pulsatile and more difficult to
compress.
US needle guidance can be performed with two different needle-to-probe align-
ments or “approaches”: the out-of-plane approach or OOP when the needle is
inserted perpendicular to the US beam and is seen as a hyperechoic (white) dot and
the in-plane approach or IP when the needle is inserted strictly into and parallel to
the US beam and is seen as a hyperechoic (white) line.
With OOP approaches, the vessel is placed in the middle of the screen to lie
under the middle part of the probe. The needle is inserted at a distance correspond-
ing to the vessel depth with a flat angle (<45°) to appear in the soft tissues above the
vessel (Fig. 19.7). The needle tip is followed by sliding or tilting movements of the
probe (Fig. 19.8). Sliding movements, requiring gel on the skin, are used if the site
offers enough room for movement. Tilting movements are used if room for probe
movement is limited (more frequently in infants and neonates). Probe movements
should always precede needle movements because the appearance of the hyper-
echoic needle tip on the screen is the most obvious pattern recognized by our eyes.
With IP approaches, the probe remains in a stable immobile position while the
needle is inserted exactly parallel and under the length of the probe (Fig. 19.9).
Perfectly inserted, the needle is seen as a bright hyperechoic line. If the needle
292 T. Pirotte
Fig. 19.7 The middle of

the screen is the middle of
the probe. With OOP
needle approaches, placing
the vessel exactly in the
middle of the screen
facilitates the puncture.
The needle is inserted with
a flat angle (α) under the
middle part of the probe to
appear above the vessel (*)
Fig. 19.8 To follow the needle tip during OOP approaches, sliding (left side) or tilting (right side)
movements of the probe are used. Tilting movements more often used in young children when
room for probe movement is limited
moves away from this position, it can disappear completely or partially. Needle (or
probe) position is corrected to have a constant view of the needle tip and shaft.
Four combinations of vein “views” and needle “approaches” are used in clinical
practice depending on the type and size of the vein, the age of the child, and the
preference of the operator:
• SAX view with OOP approach: used frequently for peripheral venous and arte-
rial accesses; for jugular, femoral, and axillary access; and for peripherally
inserted central catheters (PICCs) insertions.
• SAX view with IP approach: used for the access to the internal jugular vein (IJV)
by a posterior approach.
• LAX view with OOP approach: rarely used, only for the infraclavicular access to
the subclavian vein in older children.
• LAX view with IP approach: used for the supraclavicular and infraclavicular
accesses to the brachiocephalic, subclavian, and axillary veins and can also be
used for peripheral accesses when veins are big enough.
19.1.6 Learning Curve
US needle guidance should be trained on gel models, not on patient. Different pro-
fessional gel models exist that reliably simulate the puncture of small vessels but
also the puncture of jugular, femoral, or subclavian veins in children (Fig. 19.10).
After “in vitro” training, the first 5–10 punctures should be supervised by an expe-
rienced colleague. The variability of the learning curve is important depending on
dexterity, three-dimensional orientation, and number of procedures done per week.
19.1.7 Sterile Setting and Ergonomics (Fig. 19.11)
Central venous catheter should be inserted by using maximal barrier precautions

including cap, mask, sterile gloves, and gown and large sterile drapes and a long
sterile probe cover. Transparent sterile drapes are useful to see the anatomy and the
chest movements of the child.
The US machine should be placed in front of the operator allowing an alignment
of hands and US scream.
19.2 Peripheral Venous Access
19.2.1 Indications
A peripheral venous access (PVA) is mandatory for every anesthesia. For elective
surgeries most children will prefer inhalational induction of anesthesia. The PVA is
then placed after the child is asleep but before any manipulation of his airway. The
294 T. Pirotte
b c
Fig. 19.9 To follow the needle during IP approaches, the needle is precisely inserted parallel and
centered under the length of the probe. The needle is seen as an hyperechoic line (a). When com-
pletely lost, the needle can be retrieved by small sliding movements of the probe (b). If the needle
disappears partially during its progression, right-to-left movement of the needle will re-center the
needle under the probe (c)
success rate of PVA in the operation room is high with a success at first attempt
between 68 and 80 % and a rate of impossible access less than 0.5 %, which is 10
times lower than the failure rate in the ward (up to 5 %) [7].
The period between induction and the first intravenous access can be critical.
Children with a possible difficult PVA should be detected during the preoperative
evaluation to allow specific equipment and/or abilities to be prepared for the time of
anesthesia [8] (Table 19.2). Allowing children to drink clear fluids 2 h before anes-
thesia will facilitate the PVA by limiting dehydration. In case a life-threatening
condition occurs before the PVA is found (laryngospasm, major bradycardia or car-
diac), the intraosseous route should be used without delay (see Intraosseous Route).
a b d
Fig. 19.10 Different gel models used for pediatric vascular access training sessions. (a) “Head
and torso,” (b) “pediatric vessels,” and (c) “PICC insertion arm” from Blue Phantom® and (d)
“vascular access child” from Simulab®
a b
Fig. 19.11 Sterility and ergonomy. (a) Long sterile drape and probe covers ensure maximal bar-
rier precautions. (b) Hands and US screen are aligned in front of the operator to facilitate
handling
296 T. Pirotte
Table 19.2 Anticipating a difficult peripheral venous access is of major importance

Difficult PVA Tips and technologies
Young age (2 months–2 years) Experience in pediatric and neonatal anesthesia
Former preterm children Push needle with the thumb (feel the “pop” or
Prolonged illness “click”)
Previous difficult iv access Fill the cannula with saline (faster venous flashback)
No veins seen or palpated preoperatively Wet black skin (increase transparency)
Obesity Warm up the skin
Black skin Take EMLA® cream off 10 min before puncture
Vasoconstriction Transillumination
Dehydration Near-infrared technology
Ultrasonography
Failed PVA after induction of anesthesia
Stable conditions: call for help, use advanced technologies (ultrasound), go to a CVA
Life-threatening condition: call for rapid help, use the intraosseous route
Experience and advanced technologies are sometimes necessary
PVA peripheral venous access, CVA central venous access
In case anesthesia has to be induced intravenously (emergencies, child with a full

stomach, risk of malignant hyperthermia, etc.), a technique – or a combination of
these techniques – should always be used to reduce pain and possible trauma related
to “awake” PVA:
• Application of topical anesthetics: EMLA® cream (lidocaine 2.5 %–prilocaine 2.5

%), Ametop® (tetracaine 4 %), or S-Caine® patch (lidocaine 7 %–tetracaine 7 %)
can be used. The last two have the advantage to anesthetize the skin more rapidly
(within 20–30 min) but have to be removed also earlier (within 30–45 min).
EMLA® cream is applied under an occlusive dressing on two different visible veins
60–90 min before puncture. The maximal application time should never exceed 4
h. Optimal puncture conditions are obtained 5–10 min after wiping the cream of
the skin (disappearance of the vasoconstriction induced by the prilocaine). In neo-
nates, EMLA® is limited to 0.5 g with a maximal application time of 1 h.
• Breathing a mixture of O2 and N2O (with a fraction of N2O between 50 and 70
%) for 3–5 min before puncture causes analgesia and some kind of amnesia.
• Hypnosis techniques for school-age children: the Magic Glove, the Magic Pen,
the on/off button, or the comfortable location can truly help seriously ill children
in case of repeated procedures.
• Infiltration of 0.2–0.5 ml of 1 % lidocaine subcutaneously through an insulin or
intradermal needle will offer analgesia after a short massage of the skin.
Somewhat painful, this technique is mostly used in adolescents.
19.2.2 The Choice of the Vein
The common challenges to find a PVA are encountered between 2 and 18 months of
age (chubby babies) or in case of obesity or multiple previous attempts (blood
a b
c d
Fig. 19.12 Different peripheral venous accesses used in children. (a) Dorsal side of the hand, the
first choice; (b) external jugular vein, an alternative allowing blood samples (supraclavicular com-
pression); (c) epicranial vein, here used during combined hand and foot syndactyly corrections in
Ethiopia; (d) anterior aspect of the wrist, a last and temporary solution
sample or infusions). The most often used puncture sites are listed below and ranked
in order of preference (Fig. 19.12):
• The hand: the first choice in the operating room is a nice vein usually seen or
discerned at the dorsal side of the hand between the fourth and the fifth metacar-
pal bones (sometime between the third and the fourth one) [7]. The second vein
runs at the radial side of the wrist but is highly mobile in young children and
therefore more difficult to puncture.
• The forearm and the antecubital fossa: three major veins run along the forearm –
the cephalic, the median antecubital, and the basilic vein. Veins at the forearm are
difficult to see in young children due to the relatively high fat layer. At the ante-
cubital fossa, veins can be punctured if they are clearly seen or palpated. Veins
should be punctured rapidly under the skin and cannulated over a sufficient dis-
tance to avoid early dislodgment and delay recognition of extravasation. In dif-
ficult cases, USG should be used instead of blind attempts (risk of arterial
puncture or medial nerve damage). At the arm level, basilic–brachial and cephalic
veins can’t be seen or palpated anymore and have to be punctured under USG. At
that level, longer catheter – like PICCs or midlines – has to be used to provide a
sufficient catheterization length (see Peripherally Inserted Central Catheters).
298 T. Pirotte
• The foot: the internal saphenous vein runs at the anterior border of the medial
malleolus and is rarely absent. Ultrasound guidance can be used in case of a
negative palpation. This vein is interesting in case of head and neck surgery
when massive blood loss is expected (e.g., craniostenosis). Small veins at the
dorsum of the foot or the external saphenous vein can also be cannulated.
• The scalp: in neonates, branches of the temporal vein can be prominent on the
frontoparietal aspect of the head. Digital compression is used to increase vein
size and allow cannulation of a short catheter. Shaving the hair locally helps both
puncture and fixation.
• The neck: the external jugular vein is seen in the majority of children. Digital
compression at the lower end of the vein close to the clavicle increases vein size
and prevents the vein from collapsing during inspiration. To gain access, the child
is placed head-down with a rolled towel under the shoulders and the head turned
away from the puncture site. Ultrasound guidance can be used but is rarely needed.
Infusion rate and blood flashback can fluctuate with head position and ventilation.
Gentle traction on the skin after catheter fixation usually helps to get a blood
sample during surgery (can be used as second PVA for this purpose).
• The anterior aspect of the wrist: these tiny and superficial veins are sometimes
the only vein seen in a chubby baby or an obese child. These veins are fragile and
close to other functionally important structures (artery, nerve, tendons). They
represent a last and temporary solution.
19.2.3 Standard Procedure
A rapid evaluation of the four limbs usually detects the most attractive site. A tour-
niquet is placed at the proximal end of the limb without pinching the skin or inter-
rupting the arterial circulation (presence of distal pulse, no skin whitening).
Compression and relaxation of the limb’s muscles (“milking”) can increase vein
filling. In some cases, the vein can only be palpated but not seen. It is advised to
start with distal attempts to allow rescue attempts at a more proximal level without
risking leaks of infused fluid through prior puncture sites. Black skin is disinfected
to increase light reflexion and visualization of superficial veins.
After disinfection, the skin is stretched and the vein immobilized by the non-
dominant hand. Pushing the needle with the thumb helps to feel the “pop” or “click”
when the bevel pierces the wall of the vein. In neonates or hypovolemic children,
venous flashback is sometimes not immediate and can take up to 4 s to appear. It is
therefore important to wait long enough after having felt the “click.” To reduce the
risk of future extravasation, only half of the length of the cannula should be used to
find the vein, allowing the next half to be catheterized into the vein (Fig. 19.13).
Filling the needle with saline can speed up slow blood flows in the needle hub. Once
the flashback is recognized, the needle is pushed one or a few millimeters further to
allow the cannula (shorter than the needle) to enter the vein. After having confirmed
venous flashback into the fully inserted cannula, this one is carefully taped, a few
milliliter of saline is injected manually, and the infusion bag is connected.
In case of difficult access (vein not seen, not palpated), specific technique can be
used:
• Transillumination: by bringing light into the tissues, superficial veins are visualized
as black lines in a pink environment. This technique showing the track but not the
depth of the vein increases success rate in neonates and children less than 3 years
old [9]. Depending on the thickness of the limb, the light-emitting diode (LED) is
placed under or at the side of the vein (Veinlite Pedi®, Vein Finder®, Wee Sight®).
Short application times should be used to prevent potential burns in neonates.
• Near-infrared technology: hemoglobin absorbs more infrared light than the sur-
rounding tissues. Portable devices have been developed to detect superficial
veins and project their position in real time (VeinViewer®, AccuVein®).
Unfortunately the theoretical thickness of skin analyzed (8 mm) seems over-
stated. Deep unpalpable veins are currently not detected by these devices (Fig.
19.14). The efficacy of these devices remains thus controversial with a possible
benefit for black skin [10, 11].
• Ultrasound guidance (USG): ultrasound allows to detect veins that cannot be
seen or palpated. It shows their position, depth, track and patency and can guide
the needle into their lumen. Real-time USG reduces the procedure time and the
number of attempts needed and increases the success rate in case of difficult PVA
[12, 13]. This technique is recommended in these circumstances by different
societies [5, 6]. Some experience is needed in young children to bring the needle
tip in the lumen of such small vessels. USG is much easier in the operating room
after inhalational induction of anesthesia than in the ward when children are
awake. The usual sites for USG peripheral access are the ankle with the internal
saphenous vein (Fig. 19.15) and the antecubital fossa with the basilic or brachial
veins (Fig. 19.16).
Fig. 19.13 Venous access at the dorsal side of the hand. The left hand stretches the skin to immo-
bilize the vein; the needle is pushed by the thumb to feel the “click.” Only half of the needle length
is used to find the vein allowing the next half to be catheterized into the vein (reduced risk of
extravasation)
300 T. Pirotte
Fig. 19.14 Near-infrared

a
technology. Superficial are
clearly shown (a), but
more profound veins are
not pointed out (b)
Fig. 19.15 Ultrasound-guided internal saphenous vein puncture. SAX view of the vein, OOP
needle approach. The skin of the ankle is stretched by a tape to immobilize the vein. *, vein; med
mall, medial malleolus
19.2.4 Complications
19.2.4.1 Phlebitis
Phlebitis is caused by mechanical or chemical irritation of the venous endothelium.
Contributing factors include the material of the cannula (polyurethane is less phle-
bogenic than teflon), the nature of the solution (pH, tonicity, and composition), the
site of insertion (upper limb less prone to phlebitis), and the duration of
catheterization.
19.2.4.2 Extravasation
Depending on the nature, concentration, and volume of fluid injected, extravasation
can lead to a temporary swelling, compartment syndrome, necrosis, or even delayed
limb deformation. It should be prevented by a careful insertion technique (sufficient
length of vein catheterization) and surveillance. In the absence of blood return, cor-
rect cannulation of the vein is confirmed by a manual injection of saline or by a free
flow of the infusion bag placed at a height of 90 cm and this without any subcutane-
ous swelling detected.
Fig. 19.16 Ultrasound-guided basilic vein puncture at the antecubital fossa. SAX view of the
vein, OOP needle approach. Note the proximity of the medial nerve (N) and the brachial artery (A).
V basilic vein
302 T. Pirotte
19.2.4.3 Injection of a Residual Anesthetic Medication

Medication injected at a distance of the cannula can remain in the infusion tubing if
it is not flushed enough. The fact that anesthetic medication (opiates, muscular
relaxant) could remain in the tubing even outside the operating room can be dra-
matic. The next injection through the same infusion site will bring the medication
into the bloodstream with dramatic consequences (apnea, muscular relaxation). It is
therefore advised to flush every medication with a volume corresponding to twice
the volume of both tubing and cannula.
19.2.4.4 Specific Complications

When puncturing vein at the scalp, care must be taken to avoid accidental catheter-
ization of a branch of the superficial temporal artery. Skin whitening around the site
of insertion after a saline test injection is an early sign. The cannula should be
removed immediately and a few minutes of compression applied.
Extravasation or hematoma in the neck area can have major (respiratory) conse-
quences. Therefore, a high degree of suspicion should be kept during the (short) use
of external jugular vein accesses.
At the anterior aspect of the wrist, the medial nerve can be damaged directly by
the needle or indirectly by a hematoma.
19.3 Central Venous Access
19.3.1 Indications
The risk of complications related the central venous catheter (CVC) insertions is
higher in children than in adults. The benefit/risk balance should therefore be ana-
lyzed before every CVC placement. Indications for CVC placement in children are:
• Extensive surgery with potential massive blood loss or hemodynamic instability

• The need to measure the central venous pressure
• Infusion of inotropes
• Infusion of antibiotics or chemotherapy inducing phlebitis (osmolality >500
mOsm, pH <5 or >9)
• Postoperative parenteral nutrition
• Hemodialysis, plasmapheresis
• Neurosurgery is a sitting position (rapid aspiration of air bubbles)
• Lack of peripheral venous access
The experience of the operator and the proper use of USG can, by reducing risks,
increase the benefit/risk balance and allow children to access the CVCs for broader
indications.
19.3.2 General Aspects
19.3.2.1 Equipment and Technique of Insertion

Skin preparation for CVC placement should be done with chlorhexidine (>0.5 %)
with alcohol in children [14]. There is however no consensus for skin disinfection
in a neonate younger than 44 gestational weeks. A Seldinger insertion technique is
usually used during CVCs insertion: small puncture needle, insertion of a soft
metallic guide wire (GW), skin incision, dilation, and introduction of the catheter
over the GW. In neonates and infants, the use of a peripheral intravenous (IV) can-
nula can facilitate the puncture: by having smaller and sharper inner needle tips,
they limit depression of the anterior wall of the vein. Whatever the needle used, a
syringe should always be connected to increase handling, avoid any blood loss, and
prevent air embolism in spontaneous breathing children. In children, it is advised to
insert the GW by its J-shaped end. We know however that the diameter of the
J-shaped end (close to 4 mm) can exceed the diameter of an infant’s veins. Therefore,
the soft straight tip can be used with precaution and under some conditions: gentle
insertion without any force and ideally under fluoroscopy. Before any dilation or
insertion of large-bore catheter, the correct migration of the GW into the chosen
vein should be verified by US or fluoroscopy. US is also used to mobilize and redi-
rect the GW in real time if an aberrant migration is detected (Fig. 19.17). Dilators
are introduced over the GW till a “click” is felt (passage of the wall of the vein) but
not further. If any resistance is felt during dilation, in-and-out movements of the
GW are used to detect immediately any unintentional bending of the GW.
CVCs are in polyurethane or silicone and have single or multiple lumens.
Catheters should be radiopaque and have centimeter graduations and a distal conical
soft end. The size of the CVC depends on the site of insertion and the age/weight of
the child (Table 19.3). The diameter of double-lumen (4 F) catheters is large com-
pared to the veins of neonates or preterm infants and should therefore be used only
if one lumen is insufficient.
The optimal length of insertion depends on the child (age, weight, length), the
approach (site, side, low or high approach), and the mediastinal anatomy (angle and
length of the brachiocephalic vein). Some tables and calculation have been made,
but the data over left-sided approaches are rare [15]. Whatever the insertion site,
verifying the catheter tip position is mandatory.
CVCs are carefully secured to the skin with skin stitches: the goal is to avoid any
catheter withdrawal or kinking without damaging the skin (loose skin stitches are
used and hard plastic clips avoided) (Fig. 19.18).
19.3.2.2 Complications Common to All Sites

CVC-related complications can be classified in immediate, intermediary, or late
complications (Table 19.4). Specific complications linked to the access of the supe-
rior or inferior vena cava (SVC or IVC) will develop late.
304 T. Pirotte
a b
c d
Fig. 19.17 Ultrasound detection and guidance of the guide wire (GW). (a) Anatomy before punc-
ture (RBCV–LBCV right and left brachiocephalic veins, SVC superior vena cava, Ao aortic arch).
(b) Migration of the GW (arrows) from the right subclavian to the LBCV. (c) Withdrawal of the
GW till the J-shaped tip is seen. (d) Insertion of the GW downwards in the SVC
Table 19.3 Size of central venous catheters used depending on the weight, age, and vein size
<1.5 kg Newborn 6 m–4 years 4–10 years >10 years
Single-lumen 2 F (22 3 F (20 ga) 3 F (20 ga) 4 F (18 ga) 5 F (16 ga)
CVC ga)
Double-lumen /a 4F 4F 5F 7F
CVC
PICC 1 F (28 2 F (23 ga) 3F 4F 5F
ga) (vein > 3 mm) (vein > 4 mm) (vein > 5 mm)
Umbilical 3.5 F 5F / / /
catheters
Correspondence between French (F) and gauge (ga) are given. Age: m months, y years
a
Double-lumen 4 F catheters are used in preterm infants only if a single lumen is insufficient
a b
Fig. 19.18 Securing central venous catheters in young children. Loose skin stitches avoid catheter
withdrawal without damaging the skin. (a) Fully inserted right subclavian catheter. (b) Partially
inserted left subclavian catheter; the hard plastic clip is not used to avoid excessive pressure on the
skin
306 T. Pirotte
Table 19.4 Classification of central venous catheter-associated complications

Common complications
Immediate Intermediary Late
Hemorrhage, hematoma Tamponade Catheter occlusion
Arterial puncture Extravascular fluid infusion Thrombosis
Arrhythmia Infection
Extravascular GW migration Catheter rupture
Air embolism Arteriovenous fistula
Specific complications
Access to the SVC Access to the IVC
Pneumothorax Peritoneal fluid infusion
Hemothorax Perimedullar catheter migration
Chylothorax Lower limb ischemia
Portal thrombosisa
SVC superior venous cava, IVG inferior vena cava, GW guide wire
a
For umbilical catheters
Immediate Complications
Arterial puncture is the most frequent complication. Consequences are hematoma,
subsequently difficult or impossible punctures, respiratory difficulties, or develop-
ment of an arteriovenous fistula.
Air embolism occurs mainly at the time of insertion in the spontaneously breath-
ing child.
Extravascular GW migration is more frequent in neonates (fragility of veins and
soft tissues) and/or when the GW is inserted by its straight end.
Intermediary Complications
Tamponade can have atypical presentations in children. It should be suspected in
case of sudden hemodynamic deterioration after CVC placements.
Vessel perforation and extravascular fluid infusion will have consequences
depending on the structure involved, the size of the hole, and the infusion rate.
Repeated contact of the catheter against the vessel wall is a risk factor and should be
avoided by an optimal catheter tip placement.
Late Complications
Catheter occlusion is limited by placing catheters with the lowest number of lumens
required at an optimal insertion depth. Lumens are flushed with saline after every blood
sample or infusion and between infusion of two incompatible medications. Positive pres-
sure connectors are placed on any lumen that is only intermittently used. CVC occlusion
is treated by instillation of alteplase, a recombinant tissue plasminogen activator, during
2 h in the occluded catheter lumen [16]. Alteplase is diluted in a volume of saline corre-
sponding to 110 % of the priming volume of the lumen at the weight-adapted dose of:
• 0.5 mg till 10 kg
• 1 mg from 10 to 30 kg
• 2 mg above 30 kg
The incidence of CVC-related thrombosis is probably underestimated because

the signs are often subclinical. Risk factors in children are:
• Sepsis
• Intracardiac surgery
• Congenital thrombophilia: protein C, protein S, or antithrombin III deficiency,
Factor V Leiden, hyperhomocysteinemia
• Acquired thrombophilia: nephrotic syndrome, varicella, cyanogenic
cardiopathy
• Prolonged parenteral nutrition
The usual treatment of CVC-related thrombosis is the removal of the catheter

combined with administration of heparin or fibrinolytic drugs. In some cases, the
catheter can be left in place to provide local thrombolysis and avoid potential clot
dislodgment.
The risk of catheter-related infection and sepsis is inversely proportional to ges-
tational age (in neonates) and directly proportional to the duration of catheteriza-
tion, the use of parenteral nutrition, or mechanical ventilation. Prevention can be
divided into an optimal placement (maximal barrier precautions, low number of
attempts, and limited duration for placement) and meticulous care for the catheter
(sterility, limited manipulations, renewal of dressing, and infusion tubing). Routine
change of CVCs after a period of time is not advised if no local or systemic infec-
tion signs can be found. Differentiation between catheter infection and contamina-
tion is often difficult: peripheral and central blood cultures and catheter tip culture
may clarify the diagnostic. If fever persists despite catheter change and antibiotics,
endocarditis should be excluded.
Rupture of CVC is rare and almost limited to peripherally inserted central cath-
eters (PICCs): forced attempts to flush blocked lines are a recognized risk. Medially
inserted subclavian CVCs can get stuck in the costoclavicular pinch, where repeated
respiratory movements can lead to erosion and rupture of the catheter.
19.3.3 Access to the Superior Vena Cava
The placement of peripherally inserted central catheters (PICCs) also aiming for the
superior vena cava (SVC) will be discussed in a later paragraph. Any approach in
the neck or around the clavicle carries the risk of pleural puncture. The volume of
cervicothoracic veins is highly dependent on the respiratory cycle. During the inspi-
ratory phase, especially in spontaneous breathing, the vein collapses and the lung
expands, increasing the risks of pneumothorax and lowering the chance of success.
It is therefore advised to use USG or to progress with the needle only during the
expiratory phase.
To avoid tamponade and reduce the incidence of thrombosis, the catheter tip
position in the SVC should be optimal as defined by the cavo-atrial junction. A
308 T. Pirotte
location method should be used during placement to allow sterile repositioning

before catheter fixation. Three methods can be used:
• Fluoroscopy is a versatile and widely used tool. It allows real-time guidance of

the GW from the insertion point to its central position. In case of hindered GW
migration, explanation can be given by the injection of radiopaque agent (phle-
bography). The optimal tip position is the point just above the right atrium
shadow, situated at the thoracic vertebral level T2 or T3, a little lower than the
carina. CVCs inserted from the right side can be left in the lower third of the
SVC, while those inserted from the left side should be placed lower at the cavo-
atrial junction or in the very initial portion of the right atrium in order to have a
vertical position parallel to the SVC walls. Any oblique position or contact with
the vein walls would increase the risk of perforation. To limit irradiation, guid-
ance of the GW down to the SVC is done by US (Fig. 19.17). Fluoroscopy is
only used shortly and with pediatric settings (reduced dose, closed diaphragm,
pulsed X-ray impulse) for the final tip position.
• ECG guidance is a reliable method for tip position. This method will however be
impossible in case of cardiac rhythm disorders or in case of aberrant GW
migration.
• Ultrasonography: the initial part of the SVC can often be seen in the suprasternal
fossa with the usual equipment (high-frequency linear probe). A curvilinear low-
frequency probe is on the other hand needed to examine the right atrium or the
distal part of the SVC. Cardiac ultrasonography for tip positioning requires thus
special equipment, special training, and probably a second operator during place-
ment. This method is not yet validated for accurate CVCs tip positioning.
The presence of a persistent left SVC is observed in 0.3–0.5 % children but can
be 10 times more frequent in children with congenital heart defects. When catheter-
ized, the GW or catheter is seen with fluoroscopy at the left side of the vertebral
column above the heart shadow (Fig. 19.19).
19.3.3.1 The Internal Jugular Vein
Anatomy and Sonoanatomy

The internal jugular vein (IJV) runs at the latero-vertebral site of the neck, alongside
the common carotid artery (CA) in a usual anterolateral position. At its distal end
(where valves can be seen), it keeps a superficial track to reach the subclavian vein
(SCV) and form the brachiocephalic vein (BCV), while the CA follows a deeper
track. At the left side, the thoracic duct drains close to the jugulo-subclavian conflu-
ent increasing the risk of complications. US screening studies show that at the level
of the cricoid:
• The relationship between IJV and CA is highly variable and unpredictable.

• In neutral position, the IJV overlaps the CA in 25–44 % of the cases and can be
found medially in 6 % of the cases. [17]
Fig. 19.19 Presence of a

persistent left superior
vena cava. The catheter
(arrows) inserted in the left
subclavian vein migrates at
the left side of the vertebral
column
Fig. 19.20 The observed

relationship between the
internal jugular vein (IJV)
(V) and the carotid artery
(CA) (A) depends on the
probe position. The vein is
seen lateral (position 1) or
anterior (position 2) to the
artery. During US
screening, the probe
follows the curve surface
of the neck overestimating
the IJV–CA overlapping.
To decrease overlapping
and facilitate the anterior
approach, the probe is held
in a more vertical position
(1)
• When the head is progressively turned away from the puncture site and up to 45°,
the incidence of overlapping increases even more [18]. These data’s should how-
ever be read very carefully because the position of the probe in the neck is often
not clearly defined and can have a major impact on the ultrasonographic findings,
overestimating the real overlap (Fig. 19.20).
310 T. Pirotte
• The diameter of the IJV can be increased by Valsalva maneuver, Trendelenburg

position, and liver compression. These effects are limited in infants less than 1
year of age where the distance IJV – right atrium – is short and the venous system
highly compliant.
For all approaches, the child is placed 15–30° head-down with a rolled towel
under the shoulders to increase venous pressure and reduce the risk of air embolism.
The head is usually turned 30–45° away to give room for the needed approach.
During landmark approaches, the skin over the vessels is stretched cranially by the
nondominant hand to increase anteroposterior diameter of the vein and reduce its
compressibility. For USG approaches, the skin has to be taped because the non-
dominant hand holds the probe [19].
Landmark Approaches
Different “blind” or “landmark-guided” approaches to the IJV can be used in chil-
dren. However, due to the clear recommendation to use US guidance [2–6] (see
Table 19.1), blind approaches should only be used if USG is impossible (no equip-
ment available, insufficient training and experience).
For anterior approach, the needle entry site is the convergence of the sternal and
clavicular heads of the sternomastoid muscle or in infants halfway between the
mastoid and the suprasternal notch. The needle is inserted 30–45° into the skin, just
lateral from the carotid pulse, aiming for the ipsilateral nipple. The exploratory
needle progresses during expiration with small movements, while negative pressure
is created in the syringe.
For posterior approach, the needle entry site is on the lateral border of the cla-
vicular head of the sternomastoid muscle, 1–3 cm (depending on age) above the
clavicle. The needle is advanced underneath the muscle towards the suprasternal
notch. Due to a needle direction towards important surrounding structures, like
nerve roots, trachea, and esophagus, this approach is rarely used blindly in young
children.
Ultrasound-Guided Approaches
US screening is performed in the neck from the cricoid level to the suprasternal
fossa to check the patency of the IJV, the brachiocephalic vein (BCV), and the initial
part of the SVC. Any found anomalies will influence the choice of approach (see
Fig. 19.1). If the IJV is completely collapsing during inspiration, relative hypovole-
mia is suspected and administrating an IV fluid bolus and/or increasing the
Trendelenburg position may improve the chance to succeed.
For the anterior approach, the probe is positioned perpendicular to the neck at
the cricoid level (Fig. 19.21). Structure is followed from medial to lateral: trachea,
thyroid gland, CA, and IJV (seen in a SAX view) [20]. An OOP approach is used
and the needle tip visualized from the skin to its final intraluminal position by slid-
ing or tilting movements of the probe (see Figs. 19.7 and 19.8). In infants and
Fig. 19.21 Ultrasound-guided anterior approach of the IJV in infants: SAX view and OOP needle
approach. The short neck forces the operator to place the probe above the clavicle and use a tilting
movement (arrow) to follow the needle tip during its progression. *, needle insertion point for a
USG posterior approach (SAX-IP)
neonates, the small size and high mobility of the IJV make punctures, even with US,
often difficult. Moreover, the cranial – almost extrathoracic – position of the subcla-
vian artery (SCA) and the lung top (under the distal part of the IJV) increases the
risk of arterial or pleural puncture in this population (Fig. 19.22). Accidental arterial
punctures during blind anterior approaches of the IJV were probably not only due
to carotid but also to subclavian artery punctures. To facilitate GW insertion in these
young children, it is interesting to bring the needle tip in the lowest part of the IJV
or even in the BCV representing the only veins larger than the J-shaped GW.
For the posterior approach, the probe is placed in the same but slightly turned
position offering an oblique SAX view of the IJV. The traditional needle approach,
towards the suprasternal notch, is used by passing the needle under the length of the
probe (IP approach) [1, 21]. This approach is rarely used in young children.
When choosing between anterior or posterior approach, the anatomy of the child
(short neck), the operator preference (OOP or IP approach), but also the IJV–CA
relationship will play a key role. The posterior approach is interesting when the
IJV–CA overlap is important (vein on top of the artery). In that case, the laterome-
dial needle track reduces the risk of carotid puncture (Fig. 19.23).
Regardless of the approach used, the correct GW migration is checked by US
before dilation and insertion of the catheter.
19.3.3.2 Periclavicular Approaches

Central venous catheters can be placed in different veins around the clavicle (Fig.
19.24) [1]:
312 T. Pirotte
a b
c d
Fig. 19.22 Short-axis view of the right IJV during an anterior OOP approach. (a) Needle tip
(arrow) above the vein; (b) needle tip passing the anterior wall; (c) needle tip in the IJV lumen
above the subclavian artery (SCA); (d) needle tip brought in the brachiocephalic vein above the
lung top to facilitate guide wire insertion
• The brachiocephalic vein (BCV), by a supraclavicular approach

• The subclavian vein (SCV), by an infraclavicular approach or, for its distal part,
by the supraclavicular approach
• The axillary vein (AxV), by an infraclavicular transpectoral approach
Each of these approaches has their own advantages and disadvantages and can be
applied to all or a certain age category (Table 19.5). The visualization and puncture
of these veins are possible and already used for years; however, due to the absence
of randomized controlled trials, no recommendations are currently given [2–4, 6].
Only a group of international experts have stated that USG should be used for all the
CVC placements in children [5].
From the neck region, the end of the IJV joins with the SCV to form the BCV or
innominate vein. The right BCV is shorter and makes a steeper intrathoracic angle
compared to the left BCV (Fig. 19.25). The subclavian vessels and BCVs of infants
have a more cranial and superficial position compared to children and adults,
improving US visualization and puncture. By starting with the well-known SAX
a b
Fig. 19.23 Internal jugular vein (IJV)–carotid artery (CA) relationship is important to chose
between anterior or posterior approach of the IJV. With the anterior approach (a), the needle track
is posterior while it is medial with the posterior approach (b). The posterior approach is interesting
when there is a major IJV–CA overlap
Fig. 19.24 Three possible periclavicular approaches: (1) supraclavicular approach of the brachio-
cephalic vein (BCV), (2) infraclavicular approach of the subclavian vein (SCV), and (3) infracla-
vicular approach of the axillary vein (AxV). Clav, clavicle; *, cephalic vein
view of the IJV at the cricoid level, the US probe has to slide caudally to the clavicle
to see the distal part of the IJV with the subclavian artery (SCA) passing under.
When the probe comes in contact with the clavicle, the probe is tilted caudally to
have a view of the BCV behind the clavicle. From this position, the probe is rotated
slightly with its lateral side towards the axilla to see the SCV (Fig. 19.26). The SCA
and the brachial plexus are thus more cranial, separated from the SCV by the ante-
rior scalene muscle.
314 T. Pirotte
Table 19.5 Comparison between three different periclavicular approaches for CVC placement in
children
Approach – Age USG
Targeted vein Guidance categories technique Advantages Disadvantages
Supraclavicular – US All LAX–IP Large and Central approach
brachiocephalic open vein Exit site
vein Easy ! brachial plexus
puncture
Infraclavicular – US/LM Alla LAX–IP Open vein Shadow clavicle
subclavian vein LAX– Safe Orientation
OOPa progression children/
Exit site adolescentsa
Transpectoral – US (Children) SAX– Exit site Depth
axillary vein adolescents OOP Comfort Compressibility
LAX–IP vein
Proximity pleura
US ultrasound, LM landmark
a
The US-guided infraclavicular approach of the subclavian can be more difficult in older children
(visualization of the vein, 3D orientation, initial OOP approach)
Fig. 19.25 Panoramic view of the major veins leading to the superior vena cava (SVC). Note the
difference in length and angulation of the right and left brachiocephalic veins (RBCV–LBCV). SCV
subclavian vein, RL–LL right and left lungs, Clav clavicle, AoA aortic arch, * external jugular vein
From the arm, basilic and brachial veins fuse together to form the AxV, which
receive the cephalic vein just before its passage under the clavicle. The AxV changes
name by passing above the first rib. Above the clavicle, the external jugular vein
coming cranially makes a medial turn to become parallel and fuse with the SCV.
Supraclavicular Access to the Brachiocephalic Vein

Although described with landmark approaches, blind punctures of the BCV have
never been widely used in children. With US, the BCV is probably the largest vein
visible, remaining “open” even in hypovolemic patients. This is a great rescue tech-
nique when other techniques have failed, or in cases of expected difficulties (low-
weight preterm infants, hypovolemia, and IJV or SCV thrombosis). Used electively
in young children, this approach showed excellent results: high success rate even in
neonates, extremely low incidence of arterial puncture, and no cases of
a b
c d
Fig. 19.26 A four-step view of the major cervicothoracic veins above the clavicle. (a) SAX view
of the internal jugular vein (IJV) at the cricoid level. (b) Subclavian artery (SCA) passing under the
distal part of the IJV (probe slided above the clavicle). (c) Brachiocephalic vein (BCV) (probe tilted
cranially above the clavicle). (d) Subclavian vein (SCV) (probe tilted and rotated towards the axilla
above the clavicle). A carotid artery, L lung top, FR first rib, * external jugular vein
pneumothorax [22–24]. Insertion time seems shorten with this technique compared
to the USG infraclavicular access of the SCV [25].
Ultrasound-Guided Approach
The child is placed in a slight Trendelenburg position with a rolled towel under the
shoulders. The head is turned to the opposite side. The 2-step technique to see the
BCV is simple and has a short learning curve: from the cricoid level (IJV), caudal
sliding to reach the clavicle followed by tilting of the probe to look behind the
clavicle (Fig. 19.26). The degree of cranial tilting of the probe required to see the
vein is inversely proportional to the age of the child. The cranial position of the
BCV in infants allows their visualization with a limited probe tilting (Fig. 19.27)
compared to older children where the probe is tilted a lot, often touching the child’s
chin (see Fig. 19.30). A strict in-plane (IP) needle approach is used to monitor
closely the needle tip progression at any moment (vertical and medial direction
towards the mediastinum). The needle should be inserted close to the US probe, not
316 T. Pirotte
Fig. 19.27 Supraclavicular approach of the brachiocephalic vein (BCV). LAX view of the BCV;
IP approach above the clavicle (dotted line). Tilting the probe is often not necessary in infant due
to the cranial position of the vessels. L lung top
too lateral in the supraclavicular fossa, to avoid inadvertent subclavian artery or

brachial plexus damage.
Infraclavicular Access to the Subclavian Vein

The SCV is a short vein (from 1 cm in neonates to 3–4 cm in adolescents) running
from midclavicular to the distal end of the IJV close to the sternoclavicular joint.
The direction of the vein is flat behind the clavicle in children and cranial towards
the cricoid in infants.
To access the SCV, a rolled towel is placed under the shoulders, the head moder-
ately turned away from the puncture site with the arm along the body, and the table
tilted 15–30° head-down. The left SCV is often preferred because it continues into
the BCV in a smoother way compared to the right SCV (Fig. 19.25).
Landmark Approach
The puncture site is below the clavicle, in the deltopectoral groove, at the midcla-
vicular level, where the external jugular vein can sometimes be seen on the other side
of the clavicle. More lateral approaches increase the risk of subclavian artery punc-
ture and brachial plexus injury. The needle is slightly bent in its middle to make it
progress upwards and away from the pleura when passing under the clavicle. The
skin is entered 0.5–1 cm below the lower border of the clavicle to avoid any later
kinking of the catheter. The exploratory needle is advanced only during expiration to
decrease the risk of pleural puncture. When passing under the clavicle, the attached
syringe, maintaining a negative pressure, is lowered and the needle directed to:
• The cricoid or the opposite ear lobe in infants less than 6 months
• The midway between the cricoid and the suprasternal notch in infant over 6 months
• The suprasternal notch in children
The needle should never be inserted over a distance superior to the distance from
the insertion point to the suprasternal notch. Aspiration of blood can only appear
during slow needle withdrawal. If arterial blood is aspirated, SCA puncture is sus-
pected due to too cranial and deep attempts. When inserting the GW, tilting the head
towards the puncture side or compressing the end of the IJV prevents catheter mal-
position in the ipsilateral IJV.
Ultrasound-Guided Approach [26]

The same positioning is used as for the landmark approach, but Trendelenburg posi-
tion will only be used if needed (small or highly collapsible vein). Head rotation
needs sometimes to be increased to allow US probe positioning. Supraclavicular
visualization of the SCV is obtained with a 3-step technique from the SAX view of
the IJV at the cricoid level: sliding down to the clavicle, tilting cranially, and rotat-
ing laterally to the axilla (Fig. 19.26). Pulling the arm downwards flattens the clav-
icle and increases the visible length of the SCV.
Puncture techniques depend on the age category:
• In infants (Fig. 19.28): the cranial, almost extrathoracic, position of the SCV
facilitates US visualization. The end position of the probe showing the SCV will
be from the midclavicular to the cricoid. The needle is inserted with an IP
approach under the clavicle and strictly under the long axis of the probe. The
needle is seen touching and passing under the clavicle. Needle and probe align-
ment is precisely kept because the US shadow under the clavicle will hinder
needle visualization for a short moment. As soon as the needle has passed under
the clavicle, its bevel will reappear, allowing US guidance in the lumen of the
SCV. With experience and when visualization is good, the needle tip is brought
further in the BCV, which is the optimal place to insert the GW. Because the SCV
is fixed under the clavicle and doesn’t collapse under the pressure of the approach-
ing needle, this technique is found very useful in preterm neonates where IJV
punctures are difficult even with USG (Fig. 19.29).
• In children (Fig. 19.30): important tilting of the probe (often touching the child’s
chin) is often needed to get a view of the SCV. The probe is kept above and paral-
lel to the clavicle (no clavicle or shadowing is seen). The focus is set on the SCV
and the initial part of the BCV. The needle insertion point and direction are the
same as that for the landmark approach. The bended needle is inserted below the
clavicle in order to pass under the US probe with an oblique OOP approach.
Once the needle tip (hyperechoic dot) is detected, its cranial progression is
stopped to prevent any inadvertent puncture of the SCA and redirected to the
suprasternal notch becoming almost an IP approach (needle seen partially in its
length). The optimal tip position (centered in the SCV or BCV) is reached before
insertion of the GW.
The migration of the GW is always checked by US before dilation and insertion
of the catheter. If needed, the guide wire is redirected in real time under USG (see
Fig. 19.17). When the GW migrates into the ipsilateral IJV, it can be withdrawn and
reinserted after having used the US probe to compress the distal end of the IJV.
318 T. Pirotte
a d
b c
Fig. 19.28 Infraclavicular approach of the subclavian vein (SCV) in infants. (a) Probe positioned
above the clavicle (dotted line) with a cranial orientation from midclavicular to the cricoid. The
needle is inserted under the clavicle with an IP approach. (b, c) Needle passing under the clavicle
(*), entering the SCV and progressing into the brachiocephalic vein (BCV). (d) Guide wire inser-
tion is easier when the needle tip is positioned at the BCV
Transpectoral Access to the Axillary Vein

The axillary vein (AxV) and artery are found close to each other in the infraclavicu-
lar region. The artery surrounded cranially by the brachial plexus is more cranial
and deeper than the vein. The vessels pass deep under the pectoral muscles and
cross the clavicle at the midclavicular level.
Only used with USG, this approach is the classic approach for “subclavian
accesses” in adults [27]. The difficulty of this technique is that the AxV is deep,
close to the pleura, and highly compressible (inspiration or approaching needle).
Experienced operators have however shown excellent results in adults. Its use in
children is limited and probably only recommended in adolescents. Small needles
from PICC insertion sets can be used to reduce depression of the punctured vein.
The introducer of these sets allows the insertion of most classic pediatric CVCs.
Fig. 19.29 Central venous catheter insertion in preterm neonates (800 g) using two different
approaches. Veins are very small: 1.5 mm for the subclavian (SCV) and 3 mm for the brachioce-
phalic vein (BCV). (a) Infraclavicular approach of the SCV. *, clavicle. (b) Supraclavicular
approach of the BCV. A Subclavian artery. L Lung top. Both approaches are in-plane (IP)
approaches. In both cases, the needle tip is brought in the BCV to insert the guide wire
Transpectoral approaches, by avoiding any bony contact, are comfortable and can
be proposed to older awake children.
Ultrasound-Guided Approaches
Two different approaches can be used depending on the age of the patient and the
preference of the operator:
• The OOP approach (Fig. 19.31): a SAX view of the axillary vessels is obtained
by placing the probe in sagittal oblique position below the clavicle. The clavicle
and its shadow are seen cranially followed by the axillary artery (AxA) and more
caudally and superficially the AxV. The cephalic vein is seen merging in the end
of the AxV just before passing under the clavicle. The needle progression is fol-
lowed through the pectoral muscles, entering the AxV by sliding or tilting the
probe. This approach has the advantage of a constant view of the artery and
pleura and the relative closeness of the insertion site to the clavicle.
• The IP approach (Fig. 19.32): a LAX view of the vein is obtained by placing the
probe in an oblique position from the midclavicular to the axilla, the medial part
of the probe lying on the clavicle. The vein and artery cannot be seen simultane-
ously. It is mandatory to differentiate clearly the AxV from the AxA: the vein is
more caudal and superficial, it is not pulsating but its diameter changes with
320 T. Pirotte
a b
Fig. 19.30 Infraclavicular approach of the subclavian (SCV) in a 10-year-old child. LAX view of
the SCV obtained by tilting the probe cranially above the clavicle (dotted lines). (a) The needle is
inserted under the clavicle with an oblique out-of-plane (OOP) approach. When the needle tip is
seen as a dot (white arrow), the needle is reorientated medially to the sternal notch (black arrow).
(b) By changing needle orientation, the approach becomes almost in-plane (IP), allowing the nee-
dle to appear as a line (white arrows) progressing in the SCV. L lung, * external jugular vein
inspiration, and the cephalic vein merges in its distal portion and valves can be
seen in its lumen. Once the vein is identified, the skin is punctured with a strict
IP approach. The anterior wall of the vein is compressed and the needle flattened
to avoid transfixion. This approach has the advantage of a constant view of the
needle tip and shaft and the disadvantage of a more lateral exit site of the cathe-
ter, reserving this approach to older children.
Whatever the approach used, it is advised to enter the vein close to its passage
under the clavicle because at that point the vein is fixed anteriorly and kept open.
The depth and compressibility of the vein combined with the proximity of the pleura
force the operator to be careful and already experienced in USG.
19.3.3.3 Complications Associated with SVC Catheterization

Immediate complications are:
• Pneumothorax
• Hemothorax
Fig. 19.31 Out-of-plane infraclavicular approach of the axillary vein. SAX view of the vessels
obtained under the clavicle. The vein is punctured close to the clavicle (clav). A axillary artery, V
axillary vein, * cephalic vein
• Catheter malposition: possible malposition when blood can be aspirated are the
thymic, intercostal and azygos veins. The latter, missed on a classic chest X-ray,
will require a profile view. Catheters can also migrate in a persistent left SVC
(see Fig. 19.19). If no blood can be aspirated, migration in the mediastinum,
epidural, or subarachnoid space is possible.
Late complications are:
• Trauma of the thoracic duct (left) or great lymphatic vein (right) leading to yel-
lowish spillage at the insertion point that increases after meals
• Chylothorax, usually caused by venous thrombosis in the area where those lym-
phatic ducts drain
322 T. Pirotte
Fig. 19.32 In-plane infraclavicular approach of the axillary vein. LAX view of the axillary vein
(V) obtained under the clavicle. The vein is punctured close to the clavicle (clav) (arrow). *
cephalic vein
19.3.4 Access to the Inferior Vena Cava
19.3.4.1 The Femoral Vein

The femoral access is useful during reanimation (far from the neck and the chest) but also
when other sites are unavailable. In infants and children, the femoral vein (FV) catheter-
ization shows almost the same incidence of infection and mechanical complications as
SCV or IJV access. This access is also often used for temporary hemodialysis in young
children. Compression in this region is easy in case of venous or arterial hematoma.
Anatomy
The diameter of the FV is around 4 mm at 1 year and 10 mm at the age of nine. The mean
diameter of the vein can be increased by using either a reverse Trendelenburg position, a
firm compression 1–2 cm above the inguinal ligament, or a combination of them [28].
These maneuvers are also useful to check the patency of femoral and iliac veins.
At the level of the inguinal ligament, US examinations have shown high vari-
ability in the position of the FV [29]. Usually medial to the femoral artery (FA), it
can be found completely below the artery in some cases. Distally to the inguinal
ligament, this overlapping increases even more. External rotation of the hip will
reduce this overlapping and bring the vein median to the artery. A small pad can be
placed under the buttocks of infants to give a better exposure of the groin.
The ideal position for the catheter tip is at the intervertebral level L4–L5 or maxi-
mum L3–L4, at distance of the renal veins implantations. The approximative cath-
eter length for an L3 level is 0.14× the size of the child in cm + 1.49 [30].
Landmark Approach
In a reverse Trendelenburg position, the leg of the child is placed in a straight posi-
tion with the hip slightly rotated externally. If available, at least US screening should
be used to compare both the right and left FV (vein size and importance of FA
overlapping). The insertion point is 0.5–1 cm below the inguinal ligament and
0.5 cm medial to the femoral pulse. The needle is inserted with a 30° angle parallel
to the femoral pulse in the direction of the umbilicus. Steeper and deeper puncture
may injure the coxofemoral articulation.
Ultrasound-Guided Approach
The use of USG for the FV access is recommended in children and infants with
strength of recommendation varying from weak to strong [2–6] (see Table 19.1).
USG has shown to, at least, reduce the incidence of arterial puncture and often
reduce the procedure time and increase the success rate [31].
The probe is placed just below and parallel to the inguinal ligament to obtain a
SAX view of the vessels. The image quality is often much lower than in the neck
region, especially in young children. Visualization of the FA bifurcation or the cross
of the saphenous vein indicates a too distal position of the probe. If the FV is located
below the FA, external hip rotation, or even knee flexion (frog-leg position), is
tested to find the optimal leg position to reduce vessel overlapping (Fig. 19.33).
Abdominal or inguinal compression is performed to test the patency of the femoral
and iliac veins (positive if cross section increases). An OOP needle approach is used
to enter the vein in its middle (Fig. 19.34). The probe is tilted towards the legs dur-
ing needle progression to follow the needle tip. Transfixion of the vein can be dif-
ficult to avoid in infants. After insertion, the correct GW migration is checked by US
before dilation and insertion of the catheter.
19.3.4.2 Complication Associated with IVC Catheterization

These specific complications include:
• Extravasation of fluid in the retroperitoneal cavity.

• Catheter migration in the perimedullar space via the left lumbar and epidural
veins. A right FV approach seems to reduce this complication due to the increased
angulation between the femoral and lumbar veins on the right side [32]. Only a
lateral X-ray can detect this rare complication.
324 T. Pirotte
a b c
Fig. 19.33 US screening before femoral vein catheterization. The best leg position to reduce ves-
sel overlapping is searched. (a) Straight leg position (vein often overlapped by the artery); (b)
external rotation of the hip (often the optimal position); (c) external rotation combined with knee
and hip flexion (frog-leg position)
b c
Fig. 19.34 Ultrasound-guided femoral vein puncture. SAX view of the femoral vein (FV) and
OOP needle approach. Probe tilting is used to follow the progression of the needle tip (black
arrow). (a) The FV is median to the femoral artery; (b) US screening with Doppler function; (c)
needle (white arrow) entering the vein
• Lower limb ischemia: in case of inadvertent FA puncture and complete

thrombosis.
• Portal vein thrombosis (see umbilical access).
19.4 Peripherally Inserted Central Catheters
Peripherally inserted central catheters (PICCs) have been used for decades in the
neonatal population for intermediate to long-term IV therapy. New materials (low-
diameter, high-volume catheters) and improved insertion techniques (USG, micro-
introducers) have resulted in PICC now being used for a larger variety of purposes
in a broader pediatric population [33]. PICCs are by definition inserted through a
peripheral vein (usually in the upper limb) and are positioned with their tip in the
lower third of the VCI. Shorter catheters (called midlines) with lengths from 10 to
25 cm can also be used as “improved” peripheral access: their tip, usually in the
axillary or subclavian vein, does not reach a central position. These two catheters
represent interesting alternatives to avoid repeated peripheral venipunctures (source
of significant stress) or the placement of a CVC.
19.4.1 Indications
PICCs are indicated when intermediate- to long-term IV access is needed for

medications (antibiotics, chemotherapy), fluid therapy, blood sampling, or par-
enteral nutrition. Together with the midlines, they complete the available offer of
catheter types that can be adapted to the needs of children. When a child needs
an IV treatment, there is a reflexion on which is the best catheter for him regard-
ing his venous capital, the type of medication, the length of treatment, and the
treatment setting (in the hospital, at home, or both) (Fig. 19.35). midlines can be
Medication Peripheral access Central access

(pH - Osmolality) OK needed
Length of
1 week 2−3 weeks 1−3 months >3 months
treatment
Good Bad At home

In hospital
Context venous venous
treatment
or mixed
capital capital treatment
MID MID PORT

Type of
PVA PICC CVC PICC PICC TCVC
catheter
CVC PICC PICC
Fig. 19.35 Decision-making tree to find the most appropriate type of catheter needed by the child.
Venous capital of the child, type of medications, length of treatment, and treatment setting (in
hospital or ambulatory) are important factors. PVA peripheral venous access, MID midline, PICC
peripherally inserted central catheter, CVC central venous catheter, PORT port-a-cath, TCVC tun-
neled CVC
326 T. Pirotte
used for up to 3 weeks if the child does not need a central venous access (CVA).
PICCs are used if a CVA is needed and/or if the expected length of the treatment
exceeds 3 weeks. PICCs are probably the best option for home therapy or if
the child alternates in hospital treatments and periods at home. PICCs have there-
fore shown their value in long-term treatment (up to 1 year) of oncological
children [34].
PICCs and midlines are compared to more classic catheters in Table 19.6.
Compared to CVCs that usually require GA for insertion, PICCs can often be
inserted with light or even no sedation in school-age children. Serious complica-
tions described with central approaches, such as severe hematoma, pneumotho-
rax/hemothorax, or air embolism, are extremely rare during PICC insertion. The
cost of a PICC catheter is higher than a CVC catheter, but it can be used for a
longer period of time and sometimes allows children to continue their treatment
at home.
Contraindications for PICC placement are few: local skin damage (infection,
burn, radiation), peripheral vein damage (stenosis or thrombosis caused by previ-
ous catheter insertion), or central vein damage (stenosis, thrombosis of the ipsilat-
eral SCV or the SVC) may hinder venipuncture or hamper catheter advancement to
the correct targeted position. An alternative should be considered in children with
chronic renal failure or end-stage renal disease to preserve veins for the formation
of an arteriovenous fistula for dialysis. Technical insertion difficulties are more
frequent in young children (<2 years/12 kg), and experience will be required in this
population.
19.4.2 Catheter Placement
PICC insertions in the forearm or the antecubital fossa by palpation are almost
abandoned due to their association with increased incidences of bleeding, phlebitis,
Table 19.6 Comparison between different peripheral and central venous accesses
PORT or
PVA MID PICC CVC TCVC
Life span Days 2–3 weeks Weeks–months Weeks Months–years
Necessitate GA or No Sometimes Sometimes Always Always
sedation
Insertiona Easy Easy Easy Difficult Difficult
Insertion complications No Rare Rare Potential Potential
Systemic complications No No Less frequent Potential Potential
Removal Ward Ward/home Ward/home Ward Surgery
Cost + ++ +++ ++ ++++
PVA peripheral venous access, MID midlines, PICCs peripherally inserted central catheters, CVC
central venous catheters, PORT port-a-cath, TCVC tunneled CVC
a
Insertion difficulty depends on experience of the operator and age of the child
thrombosis, and discomfort. USG seems mandatory to aim for veins at the arm level
and to reach higher success rates.
19.4.2.1 Sedation
The need for sedation will depend on the experience and confidence of the child.
Children younger than 6 years will often need some kind of sedation or light general
anesthesia (spontaneous breathing with facial or laryngeal masks), while older chil-
dren (>10 years) often accept placement under local anesthesia. In between, differ-
ent protocols have been tested alone or combined: midazolam premedication,
EMLA® cream application, inhalation of 50 % nitrous oxide, and hypnosis.
19.4.2.2 Vein Selection

Three to four veins can be used for PICC insertion at each arm. Variability is how-
ever important and only US screening will help to decide which is the best vein to
catheterize (Fig. 19.36). The choices are usually the following:
• n° 1: The basilic vein: superficial, good diameter, straight course

• n° 2: One of the brachial veins: good diameter, straight course to the axillary vein
but deeper and close to the nerves and artery
• n° 3: The cephalic vein: superficial, small size, and tortuous course below the
clavicle (higher incidence of thrombosis)
19.4.2.3 Catheter Selection

PICCs are made of polyurethane or silicone; the latter is softer and seems to be asso-
ciated with a lower risk of thrombosis even if the literature remains controversial.
The distal end of PICCs can be opened or closed by a valve (Groshong® – Bard). The
advantage of a “closed end” is that the valve prevents any reflux of blood in the cath-
eter, reducing the risk of catheter occlusion. The size of the inserted PICC is chosen
according to the age of the child and the diameter of the vein. To lower the incidence
of thrombosis, only 1/3 of the lumen should be filled by the catheter (Fig. 19.37a):
Fig. 19.36 US screening

at mid-arm level for the
placement of PICCs. The
two most appropriate veins
are (1) the basilic vein and
(2) one of the brachial
veins. H humerus, A
brachial artery, U ulnar
nerve, M medial nerve
328 T. Pirotte
Fig. 19.37 Prevention and

a
detection of PICC-related
peripheral thrombosis. (a)
LAX view of the basilic
vein after PICC insertion.
Sufficient room for blood
flow around the catheter
reduces the risk of
thrombosis. (b) LAX view
of another basilic vein
before puncture. An almost
completed thrombosis, due
to a previous PICC, is
pointed out by the Doppler
analyze b
• PICC 1 F: neonates < 1500 g

• PICC 2 F: neonates > 1500 g
• PICC 3 F: age < 6 years and vein > 3 mm
• PICC 4 F: age > 6 years and vein > 4 mm
• PICC 5 F: age > 10 years and vein > 5 mm (5 F = double lumen)
19.4.2.4 Insertion Technique (Fig. 19.38)

The arm of the child is placed in abduction on a table. After placement of a tourni-
quet, US screening is performed to assess the anatomy of the arm, to chose the best
vein (size and accessibility) and the adapted the catheter size. Maximal barrier pre-
cautions are applied as for any CVC placement including sterile probe cover and gel
for the US equipment. The vein is usually viewed in SAX and punctured with an
OOP needle approach. The tip of the tiny needle is followed entering and catheter-
izing the vein by slow sliding movement of the probe towards the axilla. A guide wire
is inserted into the vein (Seldinger technique), a small incision of the skin is made,
and the dilator and peel-away introducer are placed. “Open-ended” catheters have to
be cut at the appropriate length before insertion. The length is determined by mea-
surement along the course of the vein to the SVC using a tape included in the PICC
set. “Close-ended” catheters are introduced and cut distally after confirmation of the
tip placement by fluoroscopy. Flexion of the patient’s head forwards and towards the
ipsilateral shoulder reduces the risk of advancing the catheter into the jugular veins.
a b
c d
Fig. 19.38 Insertion of a peripherally inserted central catheter on the left arm of a child. (a)
Sterile dressing and positioning during a USG puncture at mid-arm level (SAX–OOP technique).
(b) Insertion of the dilator and introducer over the guide wire. (c) Insertion of the PICC in the peel-
away introducer. (d) Fixation by a suture-free StatLock® above the antecubital fossa
19.4.2.5 Catheter Tip Positioning

A non-central placement of the PICC increases the risk of mechanical and throm-
botic complications. It is therefore advised to avoid blind insertions and to use either
ECG guidance or fluoroscopy. The ideal position is the cavo-atrial junction when
the arm is in adduction with the elbow slightly flexed. Fluoroscopy seems to be the
easiest and most reliable and versatile tool because it shows the cavo-atrial junction
with precision but also helps to direct the PICC from the arm (using phlebography)
to the SVC (Fig. 19.39). Irradiation should however be reduced as much as possible
in children by using adapted doses and short pulsed emission of X-ray and by clos-
ing the diaphragm.
19.4.3 Fixation and Maintenance
PICCs are fixed by a suture-free securing device (StatLock®, BARD) and covered
by a transparent dressing. To increase comfort, the fixation should not reach the
antecubital fossa and can therefore be placed above the insertion point (Fig. 19.38d).
The dressing has to be changed every week and the catheter flushed with 10 ml of
330 T. Pirotte
a b
Fig. 19.39 The use of fluoroscopy during PICC insertions. Precise positioning of the catheter tip
at the cavo-atrial junction (a). Phlebography detecting complete axillary vein thrombosis at the
arm (b) or infraclavicular level (c)
saline every 3 days for “open-ended” catheters and every week for “close-ended”
ones. Different waterproof PICC covers exist and allow children to take a shower or
a bath or even to go for a swim.
The overall rates of complications are low in the pediatric population ranging from
1 to 19 per thousand catheter days (TCD), but only 1/3 are serious requiring antibi-
otic treatment or removal of the PICC. Complication rate increases with patient age
<5 years, double-lumen catheters, and multiple daily uses [35].
19.4.4.1 Mechanical Problems

Mechanical complications are rarely life-threatening but may result in the interrup-
tion of treatment and need for replacement of the PICC [33]. The most frequent
problems are:
• Occlusion of the catheter (0–10 per TCD): caused by a thrombosis, injections of

incompatible drugs, or insufficient flushing after blood samples. Careful flushing
with saline or instillation of fibrinolytic agents reduces the incidence of irrevers-

ible occlusion to less than 2 per TCD.
• Breakage or leakage (0–2 per TCD): usually due to a forceful attempt to unlock
a blocked line with small syringes. PICC should only be flushed with large 10 ml
syringes to reduce the injection pressure. Leakage at the catheter exit site can be
handled by using a repair kit (new connector), while catheter fracture and embo-
lization within the skin will need a radiologic intervention to retrieve the embo-
lized fragment.
• Accidental dislodgment (0.1–3 per TCD): more frequent in the pediatric popula-
tion than in the adult or neonatal population.
19.4.4.2 Infection
The PICC-associated infection rate is low (0.2–6.4 per TCD) [33, 36], much lower
than for classic CVCs and close to the infection rate of long-term devices (ports and
tunneled lines). The risk factors are the length of treatment >21 days, infusion of
parenteral nutrition, children with chronic metabolic diseases, and treatment setting
(intensive care > in hospital > ambulatory).
19.4.4.3 Thrombosis
PICC-related thromboses are rare and can be divided into peripheral thrombosis (at
the arm level) and central thrombosis (as for any CVC) [33, 37]. Peripheral vein
thrombosis (incidence 3–4 per TCD) is often asymptomatic but will hinder future
catheter placements (Fig. 19.37b). Symptomatic PICC-related central thrombosis is
extremely rare (incidence from 0 to 0.2 per TCD).
The specific risk factors are:
• Hematological or oncological disease

• Catheter too large for the vein
• Double-lumen catheter
• Suboptimal, non-central, tip positioning
• History of catheter infection or occlusion
• Long insertion time
19.5 Intraosseous Route
19.5.1 Description
By placing a needle in the medullary cavity, the intraosseous (IO) route gives access
to the systemic circulation by an insertion point that is not collapsable or dependent
on the volemic status of the child. This access is however an urgent and temporary
solution used only if a life-threatening condition occurs when no other venous
access could be found (cardiac arrest, polytrauma, major burns). The IO access is
rapid and does not usually require general anesthesia compared to CVC placements.
It can be used when peripheral access is impossible and waiting for fasting condi-
tions (to place a CVC) represents an excessive risk for the child.
332 T. Pirotte
Fig. 19.40 The intraosseous route. The EZ-IO® electric drill is one of the most friendly devices.
The needle length is appropriate if the 5 mm mark can still be seen when bone contact occurs
Any medication or fluid can be given by this route. Pharmacokinetics of injected

drugs is not known, but the usual posology is advised. Medications are flushed with
5–10 ml of saline. The IO route is used till another (peripheral or central) access is
found and usually withdrawn within 24 h.
19.5.2 Perioperative Indications
The IO route is rarely used in the operating room. Different circumstances occur-
ring after inhalational anesthesia should however be considered as indications if no
venous access is found rapidly: hemodynamic instability, severe laryngospasm or
bleeding compromising the upper airway patency, and impossible venous access in
remote location [38]. IO devices should be present in the operating department,
their location known by everyone, and anesthesiologists should be trained to use
them.
19.5.3 Technique
Three different devices can be used to create an IO route: manually inserted needles
(Cook®), air pressure guns (Bone Injection Gun®), and small electric drills (EZ-
IO®). A better success rate is found when the drilling machines are used, especially
when the operator has almost no experience as most anesthesiologists do [39].
Different sites of insertion can be used in children (distal femur, distal tibia,
proximal humerus, iliac crest), but the easiest and safest site for novice operators is
the proximal part of the tibia. The insertion point is 1–2 cm (0.5–1 cm in neonates)
below and medial to the anterior tibial tuberosity. The needle is pushed through the
skin in contact with the bone (at least 5 mm of the needle should remain outside the
skin), and the drill is then activated till a loss of resistance is felt (Fig. 19.40). The
needle should be firmly fixed into the bone and some blood or bone marrow col-
lected by aspiration. Injection of 5–10 ml of saline should be easy without any sign
of extravasation. The needle is firmly fixed and regular inspection of the surround-
ing skin is performed.
19.5.4 Contraindication
Contraindication for the placement of an IO route can be local (fractured bone, pre-
vious IOR (or attempts) in the same bone within 48 h, local infection) or systemic
(osteoporosis and osteogenesis imperfecta, right-to-left intracardiac shunt).
The most frequent complications are extravasation (4–12 %) and needle dislodg-
ment (8–10 %). Severe complications are rare: compartment syndrome (0.6 %) and
osteomyelitis (0.5 %) [40]. Fractures were described but are extremely rare, and
lesion of the growth plate and fat embolism are theoretical.
19.6 Arterial Access
19.6.1 Indications and Equipment
The placement of an arterial line is indicated in case of surgeries associated with

major blood loss or potential hemodynamic instability (when vasoactive drugs are
expected to be used), but also if difficult perioperative ventilation is foreseen or
postoperative ventilation planned. The most commonly used arteries are the radial
and femoral arteries, but other different sites can be used.
Short cannulas (24 G for neonates and 22 G for children) are usually used, but a
Seldinger method can be chosen for femoral access in older children.
The needle is inserted through the skin with a flat 20° angle, watching for blood
return in its hub. Slow insertion of the cannula prevents vasospasm and arterial
trauma.
The cannula is carefully fixed to avoid both accidental removal and kinking at the
puncture site.
Tubing and transducer are once more flushed with the heparinized solution just
before the connection to the cannula in order to eliminate any bubble of air. A
334 T. Pirotte
transparent dressing is applied to allow visual inspection of the skin proximal and
distal to the entry site to detect early signs of ischemic complications. The heparin-
ized solution should contain 0.5 IU of heparin/ml and be flushed at a constant rate
of 1 ml/h.
Blood samplings are performed very slowly to prevent the vessel from collaps-
ing. After each sample, the tubing is flushed gently by hand with a maximal speed
of 1 ml over a period of 5 s. Any blanching of the skin should reduce even more the
speed of injection.
The arterial line is clearly identified to avoid the accidental intra-arterial injec-
tion of any perioperative medication.
19.6.2 The Radial Artery
The forearm of the child is fixed in a stable horizontal position with the wrist taped
in light extension (the artery could collapse if excessive extension is applied). The
collateral circulation to the hand is checked either by the modified Allen’s test or by
a US screening confirming the presence of a patent homolateral ulnar artery.
For the landmark approach, the pulse is located by pressure on the distal end of
the radius and the skin is puncture close to the skin fold of the wrist. A flat approach
with an angle of 10–20° is used because of the superficiality of the artery. In small
children, the artery is easily transfixed. The access can be gained by slowly with-
drawing the cannula without the inner needle till blood flow is obtained and re-
inserting it in the arterial lumen.
For the USG approach, the radial artery can be followed from the wrist till half-
way of the forearm allowing different insertion sites. The distal approach at the
wrist is the first choice, but more proximal approaches can be used as rescue tech-
niques. A SAX view of the artery is used because LAX views of small vessels are
difficult to obtain and almost impossible to maintain. The artery is punctured with
an OOP needle approach (Fig. 19.41). Correct visualization of the radial artery in
infants is obtained by using the zoom function (Fig. 19.42). To ensure successful
catheterization, the needle tip should be seen progressing into the arterial lumen
over a few millimeters by translating the probe slowly cephalad. An experience will
be required to apply this technique in neonates and infants. The use of USG increases
the success rate at first attempt and reduces finale failure rate [41, 42]. It is therefore
at least recommended when a difficult access is suspected or encountered and in
case of coagulopathy [4–6].
19.6.3 The Femoral Artery
The positioning of the child is the same as for femoral vein catheterization. External
hip rotation, to reduce vessel overlapping, will reduce the risk of arteriovenous fis-
tula creation if the artery is inadvertently transfixed. For infants, a small pad can be
placed under their buttocks to give a better exposure of the groin.
Fig. 19.41 Ultrasound-guided puncture of the radial artery. Arm positioning is of major impor-
tance: the forearm is fixed in a stable horizontal position and the wrist taped in extension. SAX
view of the artery, OOP needle approach
Fig. 19.42 Ultrasound image at the wrist of an infant. The radial artery (arrow) is seen in SAX
above the radial bone (R). Square: the zoom function has to be used to increase visibility of both the
artery and needle. The needle tip progresses in the lumen close to the posterior wall. U ulnar bone
For the landmark approach, the insertion point is situated 0.5–1 cm below the
inguinal ligament on top of the femoral pulse. A 45° approach is used and rapidly
flattened once arterial blood flashback is found.
For the USG technique, the insertion point will be chosen in order to hit the vessel
at the level of the common femoral artery (Fig. 19.43). The artery is catheterized over a
few millimeters under direct vision. After having inserted the cannula or the guide wire,
their correct migration is confirmed by a last US screening. USG seems to increase the
first-attempt success rate and decrease the incidence of hematoma by reducing the risk
of transfixing the artery. US screening can be used postoperatively to confirm the
patency of the femoral artery during the use of the catheter or after withdrawal.
336 T. Pirotte
Fig. 19.43 Ultrasound-guided puncture of the femoral artery. SAX view of the femoral vessels,
OOP needle approach. The needle tip is seen in the lumen of the artery. Square Doppler examina-
tion during US screening, V femoral vein
19.6.4 Other Arteries
The ulnar artery is the largest terminal branch of the brachial artery, but the close
proximity of the ulnar nerve could lead to additional complications if USG is not
used. Cannulation of the ulnar artery should be avoided when cannulation of the
radial artery has already been performed on the same wrist (potential total occlusion
of the arterial supply of the hand).
The posterior tibial artery runs in the retromalleolar grove posterior to the inter-
nal malleolus. It is best palpated with the foot in dorsiflexion.
The dorsalis pedis artery runs on the dorsal aspect of the foot, usually between
the first two metatarsal bones. It is best palpated with the foot in plantar extension.
The temporal artery site is no longer recommended.
The brachial artery should be used with caution due to the absence of collateral
blood flow at its level and the proximity of the median nerve. USG should therefore
be used.
The axillary artery is rarely used, and there is some collateral flow at its level,
but the artery is surrounded by branches of the brachial plexus, which can be injured
by sharp needles.
The most frequent complication is ischemia. The etiology of ischemia is multiple:

vasospasm, thrombosis, and emboli. Ischemic damage is more likely in case of low
cardiac output and/or when vasopressors were used. Vasospasm can occur within
minutes or hours after insertion. Early signs are pallor, delayed refilling time, and
loss or reduced pulse distal to the insertion site. Vasospasm occurs more frequently
in neonates and infants. Either injecting a small dose of lidocaine into the catheter
or warming the contralateral limb to produce reflex vasodilatation can be used. If no
improvement is noticed, the catheter should be removed. The incidence of arterial
thrombosis is directly related to the duration of cannulation and is inversely related
to the weight of the child. Distal embolization of a thrombus formed in the cannula
or proximal embolization of air can occur in case of aggressive flushing. In case of
an ischemic complication, local warming, systemic anticoagulation, topical vasodi-
latation using a nitroglycerine ointment or patch, or a brachial plexus block can be
used.
Local infection is rare if the cannula is left in place for less than 4 days. Multiple
attempts and technical difficulties increase the risk of infection, reason to use USG
in order to reduce the number of attempts. Although there is a theoretical increased
risk of contamination for the femoral site due to the proximity of the perineum, the
incidence of infection is no greater than for radial catheters.
Other potential complications are nerve damage by the needle or by a compres-
sive hematoma, tendon sheath injury, arteriovenous fistula, and accidental intra-
arterial injection of medications.
19.7 Umbilical Access
Umbilical vein and arteries can easily be accessed during the first few days of life.
The umbilical cord contains two arteries and one vein buried within Wharton’s jelly.
The umbilical vein is the recommended emergency access for neonatal resuscitation
and can be used as a central venous route for fluid and drugs administration or blood
samples. The umbilical artery is used for invasive pressure monitoring and arterial
blood gas sampling. Access to the umbilical vessels is done under maximal sterile
conditions: the umbilical cord is cut 2 cm above its skin-covered portion, and the
stump is gently tied using a tissue lace. Contraindications to umbilical vessel cath-
eterization include omphalocele, gastroschisis, peritonitis, and necrotizing entero-
colitis. Umbilical accesses have to be removed before abdominal surgeries. Access
to the superior or inferior vena cava is usually achieved in the operating room after
induction of anesthesia and just before the surgical act.
19.7.1 The Umbilical Vein
Within the body, the umbilical goes cephalad, enters the liver and divides in the
branches: one joins the left branch of the portal vein and the other, called the ductus
arteriosus, bypasses the liver and joins the VCI via the suprahepatic veins. The
umbilical vein is a wide, thin-walled vessel. Before any insertion, the gaping vessel
is cautiously opened and clots removed. The catheter (3.5 F if < 1500 g, 5 F if > 1500
g) is slowly inserted into the upper part of the body. The catheter tip can be placed
in a low or a high position. The low position is used for emergency venous access to
avoid placement of the catheter in the liver. The distance of insertion varies between
338 T. Pirotte
3 cm (preterm) and 5 cm (full term). The ideal tip position is the high position when
the catheter is advanced through the ductus venosus into the IVC, just above the
diaphragm on the chest X-ray. The insertion length can be estimated according to
birth weight (formula: 1.5× kg + 5.5 cm) or by using standardized graphs [43].
19.7.2 The Umbilical Artery
The umbilical arteries turn inferiorly in the abdomen to enter the pelvis and connect
with the internal iliac arteries. These vessels are thick walled and usually have a
degree of spasm. To be catheterized, they need to be carefully dilated using small
forceps. The catheter (3.5 F if < 1200 g, 5 f if > 1200 g) is carefully inserted aiming
the lower part of the body. The catheter tip can be placed in a low or a high position.
The high position is ideal with the tip in the descending aorta, above the diaphragm
at Th7–Th9 level on the X-ray. The insertion length can be calculated according to
birth weight (formula: 3× kg + 9 cm) or using standardized graphs [43]. The low
position is above the aortic bifurcation and below the renal arteries, corresponding
to L3–L4 on the X-ray.
19.7.3 Specific Complications
Some complications are specific to the umbilical access including [44]:
• Infection (omphalitis).
• Thromboembolism with clot: heparin use decreases the incidence of catheter
occlusion but not the risk of aortic thrombosis.
• Vessel trauma (perforation and aneurysm formation).
• Blood flow obstruction resulting in enterocolitis or hepatic necrosis.
• Umbilical vein catheter tip malposition: fluid accumulation in different cavities
(pleura, pericardium, peritoneum), arrhythmia, hepatic hematoma, and portal
vein thrombosis. Portal vein thrombosis can remain asymptomatic for a long
period and be revealed only later by a portal hypertension without cirrhosis [45].
• Umbilical artery catheters: systemic hypertension by renal artery obstruction and
vasospasm with ischemic complications (lower limbs).
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US-Guided Nerve Targets
20
Giorgio Ivani and Valeria Mossetti
There has been a recent increase in the use of regional anesthesia in pediatric
patients; this explosive growth, particularly in the use of truncal blocks, can be
attributed in part to the refinement of anatomically based ultrasound imaging to
facilitate nerve localization. Historically, pediatric regional anesthesia has posed a
significant challenge due to the close proximity of nerves to critical structures and
the need for limiting the local anesthetic volume below toxic levels in children.
Ultrasound guidance, however, allows the visualization of important anatomy and
can help overcome many of these traditional obstacles [1].
This technique, in fact, has brought pediatric regional anesthesia to new levels
improving the quality of anesthetic blockade with faster onset time, longer duration
of blocks, and lower dose of local anesthetics [2].
Although ultrasound may be useful for nerve localization, one of the main ben-
efits is to provide visualization of the dispersion of the local anesthetic within the
desired tissue plains. Ultrasound has been shown to provide adequate landmarks for
determining the location of nerves in children along with a discriminatory approach
to evaluating nerve location and anatomical variations in infants and children. This
technology however requires a significant training and skill for its successful
implementation.
Ultrasound guidance is therefore strongly recommended when performing
peripheral nerve blocks in infants and children [3, 6–8].
This chapter will review a variety of common peripheral nerve and central neur-
axial blocks that can be performed using ultrasound guidance in children. We have
to emphasize that ultrasound guidance is a relative recent innovation to the field of
regional anesthesia; most of the current literature is not evidence based. As a result,
much of the data comes from case reports and case series.
G. Ivani (*) • V. Mossetti (*)

Anesthesiology and Intensive Care, Regina Margherita Children Hospital, Turin, Italy
e-mail: valeriamossetti@libero.it

DOI 10.1007/978-3-319-21960-8_20
342 G. Ivani and V. Mossetti
Our goal is to provide the pediatric anesthesiologist with a comprehensive sum-

mary of the relevant sonoanatomy, techniques, and outcomes of ultrasound guid-
ance for peripheral nerve blocks of the extremities and trunk as well as neuraxial
blocks in pediatric patients based on currently available literature.
20.1 Ultrasound Equipment
Mobile, usually cart-based, echographs consist primarily of a probe (transducer), a

computer that controls the transducer, sends the impulse, receives the echo, and
processes the signal, a visualization system, and a storage device for later digital
editing and printing (Fig. 20.1a, b). The most important part of the echograph is the
transducer which can present different forms depending on its specific use. The
important technical specifications are its axial and lateral resolution and the fre-
quency achieved. Resolution is the ability to discern two dots as being distinct from
each other on the x and y plane: on the (x) axis – which is parallel to the propagation
line of the ultrasonic beam – and on the (y) axis – which is the axis vertical to the
ultrasonic beam. Today, due to technological advancement in signal processing soft-
ware, it is also possible to improve data quality for imaging and to influence the
definition: to reduce the phenomenon of signal attenuation, the reflected signals are
amplified taking into account the delay with which the signal is received, thus
allowing statements as to their depth. Finally, it should be kept in mind that the
ultrasonic beam transmitted from the transducer results in the two-dimensional
Fig. 20.1 Cart-based echographs

20 US-Guided Nerve Targets 343
representation of a three-dimensional object. Therefore, recordings from at least

two sets of planes are required to be able to reconstruct the object in its original
shape [4, 5].
20.2 Minimum Requirements for Regional Anesthesia

Ultrasound Equipment
The ultrasound equipment used in regional anesthesia should be transportable.

Portable units as well as compact scanner systems mounted on a cart are commer-
cially available.
These should meet at least the following requirements: color Doppler to identify
blood vessels and distinguish them from the surrounding tissues, contrast images
(gain), and sufficient storage capacity for images and preferably also for films.
For any ultrasound-guided block technique, a sterile preparation of the probe
with an adhesive sheet and the block area also using sterile gel is recommended
(Fig. 20.2a, b). When a catheter is introduced, it is recommended to completely
wrap the probe with a proper sterile cover (Fig. 20.2c).
20.2.1 Ultrasound Probe
Transducer characteristics, such as frequency and shape, determine ultrasound

image quality. The transducer frequencies used for peripheral nerve blocks range
from 3 to 15 MHz. Linear transducers are most useful for nerve imaging to provide
high-resolution images. For superficial structures (e.g., nerves in the interscalene,
supraclavicular, and axillary regions), it is ideal to use high-frequency transducers
in the range of 10–15 MHz remembering that depth of penetration is often limited
to 2–3 cm below the skin surface.
For visualization of deeper structures (e.g., in the infraclavicular and popliteal
regions), it may be necessary to use a lower frequency transducer (less than or equal
to 7 MHz) because it offers ultrasound penetration of 4–5 cm or more below the
skin surface. However, the image resolution is often inferior to that obtained with a
higher frequency transducer.
Two types of probes are commonly used in children (Fig. 20.3):
• Linear probes (6–13 MHz): the resulting imagine is square, with good resolution
in the near field, but narrow depth; probe frequency is selected according to
nerve depth, 7 MHz for structures deeper than 5 cm, 10 MHz for structures
between 3 and 5 cm deep, 12 MHz for structures maximally 3 cm deep, and
shorter probes such as the Hockey stick probe with a length of 2.5 cm for pedi-
atric use.
• Sector probes (2–5 MHz): the resulting image is trapezoidal, with good resolu-
tion and depth, but structures in the near field are poor imaged.
a b
Fig. 20.2 (a) Adhesive sheet, (b) Sterile gel, (c) Sterile cover
Fig. 20.3 Probes commonly

used in children
To correctly perform a nerve block under ultrasound guidance, it is important to

proceed as follows:
1. Localize the nerve

2. Move the ultrasound probe
3. Move the block needle
20.2.2 Identification of the Structures in Ultrasonography
The term isoechogenic refers to a structure displayed in an ultrasound image with a

certain intensity on a gray scale.
Formations with low echogenicity are called hypoechoic, formations that do not
deliver any echo at all are anechoic, and those formations with high echogenicity
are called hyperechoic. Normally the echogenicity of an investigated structure cor-
responds to its type and composition; however, not every anechoic structure is fluid
nor must every hyperechoic structure be solid.
The terms shadow cone and acoustic enhancement refer to structures that inhibit
the travel of ultrasound, or, respectively, increase its speed. Such situations occur
typically in investigations of bone or calcium structures (e.g., gallstones) and forma-
tions containing liquid (e.g., liver cysts).
Vessels: their identification is of particular importance because it guides to the neu-

rovascular bundle. Vessels appear hypoechoic; discrimination between arteries
and veins and also applying pressure with the probe are possible with color
Doppler: veins are compressible while arteries remain pulsatile; gentle pressure
is needed because during venous compression, intravenous needle tip placement
may be missed.
Muscle: this has a fibrolamellar ultrasonographic appearance with either heteroge-
neous structures with bandlike hyperechoic intramuscular septae or homogenous
structures.
Bones: the cortex of the bone is hyperechoic and the areas behind or deep to the
cortex are completely anechoic.
Fatty tissue: hypoechoic.
Tendons, pleura: hyperechoic.
Local anesthetic: direct observation of the spread of local anesthetic during injec-
tion is mandatory; local anesthetic solution appears anechoic.
Neuronal structures: every nerve has a particular appearance in ultrasonography
with regard to the shape, the echogenicity, and the quantity of connective tissue
present between the nerve fibers.
The proximal parts of the brachial plexus appear as hypoechoic round to oval
structures; by contrast more peripheral nerve structures appear hyperechoic. In the
lower extremity, most of the neural structures appear hyperechoic (Fig. 20.4a, b).
Fig. 20.4 (a) Scanning of

the axilla. (b) A artery, a
N nerve, V vein
b
muscle
N
A V
tendon
bone
20.2.3 Needle Handling
Proper needle handling skills are required for accurate and smooth needle insertion
during ultrasound-guided nerve blocks. If the operator is not ambidextrous and pre-
fers to use the dominant hand to handle the needle and inject local anesthetic, then
the operator must choose a proper body location and orientation in relationship to
the patient.
There are two ways to align the transducer with the needle:
In plane (IP): The transducer is exactly parallel to the needle. In this case it is pos-
sible to see the whole length of the needle and the needle tip. Advantages:
Because the needle tip is visualized, it is possible to position it correctly without
the risk of injuring nerves or vessels. Disadvantages: Since ultrasound has an
extremely narrow beam width, it can be difficult to keep the needle constantly in
view (Fig. 20.5a, b).
Out of plane (OOP): The needle and the transducer are perpendicular to each other.
In this case it is possible to see the cross section of the needle as a hyperechoic
dot, which however can result from any other needle segment and not the tip.
Advantages: The needle cross section is easily identified. Disadvantages: One is
not sure where the tip of the needle is. This potentially carries the risk of injury
to nerves and blood vessels (Fig. 20.6a, b).
20.3 Ultrasound-Guided Regional Anesthetic Techniques
20.3.1 Upper Limb Blocks
Peripheral regional anesthesia is of great utility in children undergoing surgery on

the upper extremities. Many approaches to the brachial plexus have been described;
in children the most commonly performed and reported brachial plexus blockade is
the axillary block. This may be due to the fact that other block sites are situated near
critical structures such as the cervical pleura (supraclavicular and infraclavicular)
and the spinal cord (interscalene). Introduction of ultrasound imaging will likely
greatly increase the performance of brachial plexus blocks in infants and children at
locations besides the commonly described axillary approach by allowing for real-
time visualization of anatomical structures.
Fig. 20.5 In plane approach

Fig. 20.6 Out of plane approach
Fig. 20.7 ca carotid

artery, jv jugular vein
jv
ca
20.3.1.1 Interscalene Approach

The interscalene block is indicated for all upper extremity surgery, but particularly
if the shoulder is involved.
Ultrasound imaging allows visualization of the C5, C6, and C7 nerve roots
between the anterior and middle scalene muscles. In a transverse oblique plane at
the level of the cricoid cartilage and at the posterolateral aspect of the sternocleido-
mastoid muscle, the muscle appears as a triangular-shaped structure overlying the
internal jugular vein and common carotid artery (Fig. 20.7).
The scalene muscles serve as useful landmarks; the anterior scalene lies deep to
the sternocleidomastoid and lateral to the subclavian artery, while the middle and
posterior scalenes are located more posterolaterally. The neurovascular (intersca-
lene) sheath appears as a hyperechoic structure within the interscalene groove. The
Fig. 20.8 (a) Scanning of

the interscalene groove. a
(b) SCM
sternocleidomastoid
muscle, ASM anterior
scalene muscle, MSM
middle scalene muscle, VA
vertebral artery, arrows
roots of brachial plexus
b
SCM
ASM
MSM
VA
trunks and/or roots of the brachial plexus may be visible as round- or oval-shaped
hypoechoic structures. The roots or trunks lie between the scalenus anterior and the
scalenus medius at this level. The prominent internal jugular (anechoic) lies medi-
ally (Fig 20.8a, b).
Interscalenic approach is performed with a high-frequency linear probe; the
transducer position is transverse on neck, 3–4 cm superior to clavicle, over external
jugular vein (Fig. 20.9).
A combined ultrasound-guided nerve stimulating technique may facilitate nerve
localization. Using an in-plane approach and slight redirections to advance the nee-
dle close to the brachial plexus, local anesthetic spread around the nerve roots or
trunks may be visualized. Precise needle placement may limit the dose of local
anesthetic required.
The goal, in fact, is local anesthetic spread around superior and middle trunks of
brachial plexus, between anterior and middle scalene muscle (Fig. 20.10).
Fig. 20.9 IP interscalene

approach
Fig. 20.10 arrows roots

of brachial plexus, yellow
line needle, blue: local
anesthetic, red line spread
of local anesthetic
Ultrasound guidance allows multiple injections around the brachial plexus, there-
fore eliminating the reliance on a single large injection of local anesthetic for block
success as is the case with non-ultrasound-guided techniques. Ability to inject mul-
tiple aliquots of local anesthetic also may allow for the reduction in the volume of
local anesthetic required to accomplish the block.
Due to potential adverse effects including pneumothorax, vertebral artery injec-
tion, and intrathecal injection, the intrascalene block is not common in pediatrics.
Palpation of the interscalene grove often proves challenging in children under gen-
eral anesthesia, and as a result, a recent report states that this block is not recom-
mended for any heavily sedated or anesthetized patient. However, the improvements
in nerve localization made possible due to ultrasound guidance have the potential to
increase the use of this block in children [9–11].
20.3.1.2 Supraclavicular Approach

The supraclavicular block is indicated for all upper extremity surgery, but particu-
larly if the shoulder is not involved; in general indications are arm, elbow, forearm,
and hand surgery.
It is a popular technique for surgery below the shoulder because the onset and
quality of anesthesia are fast and complete.
The proximity of the brachial plexus at this location to the chest cavity and pleura
has been of concern to many practitioners; however, ultrasound guidance has
resulted in a resurgence of interest in the supraclavicular approach to the brachial
plexus. The ability to image the plexus, rib, pleura, and subclavian artery with ultra-
sound guidance has increased safety due to better monitoring of anatomy and nee-
dle placement [12].
The subclavian artery crosses over the first rib between the insertions of the ante-
rior and middle scalene muscles, at approximately the midpoint of the clavicle. The
pulsating subclavian artery is readily apparent, whereas the parietal pleura and the
first rib can be seen as a linear hyperechoic structure immediately lateral and deep
to it, respectively. The rib, as an osseous structure, casts an acoustic shadow, so that
the image field deep to the rib appears anechoic or dark. A reverberation artifact
often occurs, mimicking a second subclavian artery beneath the rib.
The trunks and divisions of the plexus appear as hypoechoic grapelike clusters
laterally and cranially the artery, while a hyperechoic line with dorsal shadowing
indicates the first rib (Fig. 20.11).
With a high-frequency probe in the coronal oblique plane, the plexus divisions
and/or roots are visible lateral to the subclavian artery (Fig. 20.12). Using an in-
plane approach, directing the needle from lateral to medial avoids vascular struc-
tures in contact with the plexus.
The goal is local anesthetic spread around brachial plexus, lateral, and superficial
to subclavian artery.
This approach lends itself to a continuous catheter technique because nerve
structures are close proximity to another.
When compared to other brachial plexus blocks, there is an increased risk of
pneumothorax due to the proximity of the lung parenchyma at the level of this
block. By using an in-plane approach, ultrasound guidance may reduce this risk by
providing clear visibility of the needle shaft and tip, making the supraclavicular
approach one of the most reliable and effective blocks of the brachial plexus
(Fig. 20.13).
20.3.1.3 Infraclavicular Approach

The indications for the infraclavicular approach to the brachial plexus are arm,
elbow, forearm, and hand surgery.
Identification of the arterial pulse on the sonographic image is an easy primary
goal in establishing the landmark. The axillary artery and vein are located deep and
medial to the cords, with the vein positioned medial and caudal to the artery.
The cords of the infraclavicular portion of the brachial plexus appear hyper-
echoic and lateral and/or below the subclavian artery; the pleura is hyperechoic and
FR SA
pleura
pleura
Fig. 20.11 FR first rib, SA subclavian artery, yellow line brachial plexus
Fig. 20.12 IP suprclavicular

approach
SA
FR
Fig. 20.13 SA subclavian artery, FR first rib, Arrows needle, red line spread of local anesthetic
medial. Although all the cords surround the artery, they are not visualized with
equal clarity. The lateral cord is most easily viewed and appears as a hyperechoic
oval structure. In contrast, the posterior and medial cords may be difficult to visual-
ize, in part because the view may be obstructed by the axillary vasculature; the
medial cord lies between the artery and vein while the posterior cord is deep to the
artery. The pectoralis major and minor muscles lie superficial to the neurovascular
bundle and are separated by a hyperechoic lining (perimysium) (Figs. 20.14 and
20.15).
The block is typically performed with the patient in supine position with the head
turned away from the side to be blocked. The arm is abducted to 90° and the elbow
flexed.
The probe is positioned immediately medial to the coracoid process of the scap-
ula under the clavicle in a parasagittal plane so that the plexus can be scanned trans-
versely (the marker on the probe is directed toward the patient’s head). The
transducer is moved in the superior-inferior direction until the artery is identified in
cross section. While the plexus lies quite deep in adults, the structure is much more
superficial in children, making a higher frequency probe optimal (Fig. 20.16).
The needle is inserted in plane cephalad to the probe and redirected when neces-
sary to ensure optimal spread of the local anesthetic around the cords. The goal is
local anesthetic spread around axillary artery; the optimal spread of local anesthetic
should be lateral and below the artery, to include the posterior cord (Fig. 20.17).
MC
AA
LC AV
PC
Pleura
Fig. 20.14 AA axillary artery, AV axillary vein, LC lateral cord, PC posterior cord, MC medial cord
Fig. 20.15 Color Doppler

of the infraclavicular area
Infraclavicular block is well suited for catheter technique because the muscula-
ture of the chest wall helps stabilize the catheter and prevents its dislodgment com-
pared with the more superficial.
The risks of this block are similar to the supraclavicular approach, with the
danger of pneumothorax being most serious. Just as with the supraclavicular
block, an in-plane needle insertion under ultrasound guidance may minimize the
risk by allowing clear visualization of the needle tip and shaft [14, 16]. In
Fig. 20.16 IP
infraclavicular approach
LC MC
AA
AV
PC
Pleura
Fig. 20.17 Spread of local anesthetic, AA axillary artery, AV axillary vein, LC lateral cord,
PC posterior cord, MC medial cord
addition, due to the closer proximity of the cervical pleura to the plexus cords
medially, a lateral puncture site is recommended [19]. Ultrasound imaging may
also be advantageous in avoiding multiple puncture sites and visualizing underde-
veloped structures like the coracoid process that may be difficult to palpate in
children using “blind” techniques [13, 15, 17].
AV
AA
AV
Fig. 20.18 Vascularization of the axilla, AA axillary artery, AV axillary veins
20.3.1.4 Axillary Approach

The axillary approach to the brachial plexus is the most popular technique for chil-
dren; it provides analgesia for forearm and hand surgery.
The axillary brachial plexus block requires access to the axilla. Therefore abduc-
tion of the arm 90° is an appropriate position that allows for transducer placement
and needle advancement. Care should be taken not to overabduct the arm because
that may cause discomfort as well as produce tension on the brachial plexus, theo-
retically making it more vulnerable to needle or injection injury during the block
procedure.
The axillary artery is a useful ultrasound landmark and appears as a circular
anechoic structure adjacent to the biceps and coracobrachialis muscles. The artery
can be associated with one or more axillary veins, often located medially to the
artery; color Doppler is also a helpful tool to identify the axillary vasculature
(Fig. 20.18). Importantly, an undue pressure with the transducer during imaging
may obliterate the veins, rendering veins invisible and prone to puncture with the
needle if care is not taken to avoid it (Fig. 20.19). Surrounding the axillary artery are
three of the four principal branches of the brachial plexus: the median (superficial
and lateral to the artery), the ulnar (superficial and medial to the artery), and the
radial (posterior and lateral or medial to the artery) nerves. These are seen as round
AA
Fig. 20.19 Compression of axillar veins, AA axillary artery
hyperechoic structures, and although the previously mentioned locations relative to

the artery are frequently encountered, there is considerable anatomical variation
from individual to individual.
Three muscles surround the neurovascular bundle: the biceps brachii (lateral and
superficial), the wedge-shaped coracobrachialis (lateral and deep), and the triceps
brachii (medial and posterior). The fourth principal nerve of the brachial plexus, the
musculocutaneous nerve, is found in the fascial layers between biceps and coraco-
brachialis muscles, though its location is variable and can be seen within either
muscle. It is usually seen as a hypoechoic flattened oval with a bright hyperechoic
rim (Fig. 20.20).
A high-frequency linear probe placed perpendicular to the anterior axillary fold
provides a short-axis view of the neurovascular bundle with the biceps brachii and
coracobrachialis muscles lateral and the triceps brachii medial and deep to the
biceps (Fig. 20.21).
An in-plane technique may be used. It is best to use multiple injections with
needle redirections to ensure that the local anesthetic surrounds all the terminal
nerves of the plexus. Due to the close proximity of the axillary vein and artery, mul-
tiple punctures may be necessary to avoid intravascular injection [18] (Figs. 20.22
and 20.23).
M
U
Biceps
AV
AA
MC
R
Coracobrachialis
Triceps
Humerous
Fig. 20.20 Yellow circles nerves, AA axillary artery, AV axillary vein, MC muscolocutaneous
nerve, M median nerve, U ulnar nerve, R radial nerve
Fig. 20.21 IP axillar

approach
20.3.2 Lower Limb Blocks
20.3.2.1 Femoral Nerve Approach

The femoral nerve originates from nerve roots L2, L3, and L4. Femoral nerve block
is an easy block to perform and provides surgical anesthesia and analgesia for the
anterior thigh extending to the knee.
The femoral artery is easily visualized and serves as the principle ultrasound
landmark. With the probe placed perpendicular to the nerve axis (i.e., coronal
oblique) at the level of and parallel to the inguinal crease, the nerve appears lateral
AA AV
Fig. 20.22 Red line spread of local anesthetic. AA axillar artery, AV axillar vein
Fig. 20.23 Axillar

catheter
to the large, circular, and anechoic femoral artery. Color Doppler may be helpful to
identify the femoral vasculature.
If it is not immediately recognized, sliding the transducer medially and lat-
erally will bring the vessel into view eventually. Immediately lateral to the
vessel and deep to the fascia iliaca (separating the nerve from the artery) is the
femoral nerve, which is typically hyperechoic and roughly triangular or oval in
shape. The nerve is positioned in a sulcus in the iliopsoas muscle underneath
the fascia iliaca. Other structures that can be visualized are the femoral vein
(medial to the artery) and the fascia lata (superficial in the subcutaneous layer)
(Fig. 20.24).
FN FA
FV
Fig. 20.24 FN: femoral nerve, FA: femoral artery, FV: femoral vein
a b
Fig. 20.25 IP femoral approach
The nerve spreads soon after its passage below the inguinal ligament, so that low
volumes placed proximally will achieve the best results [20].
Femoral nerve block is performed with a high-frequency linear probe; transducer
position is transverse, close to the femoral crease (Fig. 20.25a, b); the needle is
inserted using an in-plane approach, so that the needle tip can be visualized as it
enters the fascia iliaca (Fig. 20.26). It is important that the needle be placed inside
the fascia iliaca compartment. In a study comparing ultrasound guidance to nerve
stimulator technique, the nerve was visible in all children studied when the probe
was placed parallel and inferior to the inguinal ligament and lateral to the femoral
artery. Ultrasound was also used effectively to visualize the needle tip and facilitate
needle redirections [21].
Because of the proximity to the relatively large femoral artery, ultrasound may
reduce the risk of arterial puncture that often occurs with this block with the use of
non-ultrasound techniques. Although there is no direct evidence to prove that ultra-
sound could reduce this risk, it is the authors’ experience that fewer adverse events
Iliac fascia
FA
FV
Fig. 20.26 FA femoral artery, FV femoral vein, red circle spread of local anesthetic
occurred when this block was performed under ultrasound guidance. In addition,
precise ultrasound imaging of the local anesthetic spread may reduce the need for
larger volumes used when injecting blindly.
20.3.2.2 Sciatic Nerve Block

The sciatic nerve is formed by nerve roots L4 to S3 and innervates the posterior
thigh and leg below the knee, with the exception of the medial portion. A sciatic
block is commonly used for surgical procedures of the foot and ankle, as well as in
combination with a femoral nerve block for patients undergoing knee surgery.
As it leaves the pelvis through the greater sciatic foramen, the sciatic nerve can
be found inferior to the gluteus maximus muscle. The nerve lies between the ischial
tuberosity and the greater trochanter. Curved probes (curvilinear) with moderate-
low frequency (e.g., 2–5 MHz) allow deeper ultrasound beam penetration and are
often necessary in older children. While the medial aspect of the greater trochanter
appears largely hypoechoic, the sciatic nerve is predominantly hyperechoic and is
typically elliptical in a short-axis view (Figs. 20.27, 20.28, and 20.29).
The pathway of the sciatic nerve continues through the posterior popliteal fossa
before bifurcating to form the common peroneal and tibial nerves. A linear probe
transversely oriented in the popliteal crease captures both the tibial and common pero-
neal nerves located medially and laterally, respectively, to the popliteal vessels. This
vasculature, particularly the popliteal artery, serves as useful ultrasound landmarks
(color Doppler may be useful). At the popliteal crease, the tibial nerve is found more
superficial and most adjacent to the artery. However, as the probe is moved cephalad,
the artery becomes deeper and more distant as the tibial nerve moves laterally to join
the common peroneal nerve. At and cephalad to the bifurcation, the sciatic nerve
appears as a large round to flat-oval hyperechoic structure. The biceps femoris muscle
lies superficial to the bifurcating nerves and appears as a large oval-shaped structure
with less internal punctuate areas (hyperechoic spots) than the nerves.
GMM
GT
SN
IT
Fig. 20.27 GMM gluteus maximus muscle, GT greater trochanter, IT ischial tuberosity,
SN sciatic nerve
Fig. 20.28 IP subgluteous

approach
The sciatic nerve is easily located at a midfemoral level and can also be
blocked half way up the thigh. In this area the nerve is largely concealed by the
biceps femoris and medially slightly by the semimembranosus and semitendi-
nous muscles; underneath lies the adductor magnus. At this level it is quite easy
Fig. 20.29 Red line local anesthetic spread
to locate the bellies of the two muscles that encompass the nerve: the biceps
femoris and the adductor magnus. In this plane the nerve appears as a well-
defined, hyperechoic structure that is either triangular or oval in shape. This is an
easy block to perform in children under general anesthesia since it can be per-
formed either in the lateral position or in the supine position with elevation of the
limb (Figs. 20.30 and 20.31).
Ultrasound imaging can be particularly beneficial when using catheter insertion
to confirm the spread of local anesthetic around the nerve (Figs. 20.32, 20.33,
20.34a, b). In addition, ultrasound guidance can be advantageous in instances in
which a blind technique is likely to fail. An example of this was described for
patients with venous malformations. The use of ultrasound in these patients helped
the anesthesiologist avoid vascular puncture during needle placement [22]. Due to
the high degree of variability in the division of the sciatic nerve, ultrasound also
offers considerable advantages in nerve localization when using the popliteal
approach [23, 24].
20.3.2.3 Saphenous Nerve Block

The saphenous nerve is the terminal sensory branch of the femoral nerve. It supplies
innervation to the medial aspect of the leg down to the ankle and foot. Blockade of
the nerve can be sufficient for superficial procedures in this area; however, it is most
useful as a supplement to a sciatic block for foot and ankle procedures that involve
the superficial structures in medial territory. The use of ultrasound guidance has
improved the success rates of the saphenous blocks, compared with field blocks
below the knee and blind transsartorial approaches.
Fig. 20.30 IP midfemoral

approach
sciatic nerve
Fig. 20.31 Sciatic nerve at midfemoral level
It is performed with a high-frequency linear probe; transducer position is trans-

verse on anteromedial mid thigh (Fig. 20.35a, b).
The goal is local anesthetic spread lateral to the femoral artery and deep to the
sartorius muscle (Fig. 20.36).
Although saphenous nerve is a strictly sensory block, an injection of the local
anesthetic in the adductor canal can result in the partial motor block of the vastus
medialis. For this reason, caution must be exercised when advising patients regard-
ing the safety of unsupported ambulation after proximal saphenous block.
Fig. 20.32 Sciatic

catheter
Fig. 20.33 Sciatic

catheter in plane with the
nerve
20.3.3 Truncal Blocks
Truncal blocks are becoming a more popular means of providing analgesia for pro-
cedures in the umbilical or epigastric regions. The ability to visualize relevant mus-
culature and fascial layers with ultrasound offers an advantage over the more
subjective conventional technique of detecting “pops” or “clicks” upon penetration
into fascial compartments. This is particularly beneficial in children due to the close
proximity of nerve and critical abdominal structures. In addition, visualization of
the local anesthetic spread made possible with ultrasonography has the potential to
a b
Fig. 20.34 Sciatic catheters
Fig. 20.35 (a) FA femoral

artery, SN sciatic nerve. a
(b) Colordoppler of the
femoral artery
Sartorius muscle
FA
SN
Femur
b
Fig. 20.36 IP saphenous

nerve block
improve success rates and allow for administration of minimal volumes of local
anesthetic [25, 26].
20.3.3.1 Ilioinguinal-Iliohypogastric Nerve Block

Both the iliohypogastric (IH) and ilioinguinal (II) nerves arise from L1 and emerge
from the upper part of the lateral border of the psoas major muscle. The ilioinguinal
nerve is a smaller nerve and courses caudad to the iliohypogastric nerve.
This block provides analgesia for all surgical procedures in the inguinal area.
Blockade of the II and IH nerves is indicated for analgesia following inguinal
hernia repair because the nerves provide sensory innervation to the skin of the lower
abdominal wall in addition to the upper hip and upper thigh. Because the lateral
cutaneous branch of the IH nerve may pierce the internal and external oblique mus-
cles immediately above the iliac crest, it is worthwhile to block the nerves as proxi-
mal as possible (i.e., posterior to the anterior superior iliac spine) before the nerve
branches (Fig. 20.37).
Ultrasound technique has reduced failure rate and complications (intestinal
puncture, pelvic hematoma) compared to techniques based on anatomical land-
marks and “fascial click.”
The nerves are medial to the anterior superior iliac spine and between the inter-
nal oblique and the transverse abdominal muscle. Both nerves appear hyperechoic,
with oval shape.
Using a linear probe, it should be placed at the highest point of the iliac crest with
the axis facing the umbilicus. This orientation provides a clear view of the relevant
muscle layers and nerves (Fig. 20.38). Using an in-plane approach, a needle is
inserted toward the ilioinguinal and iliohypogastric nerves (Fig. 20.39).
Both nerves are in close proximity to each other; usually one needle tip position
is sufficient for blockade of both nerve (Fig. 20.40).
Fig. 20.37 IC iliac crest,

OE external oblique
muscle, OI internal oblique
muscle, TR transversus
muscle, 1 and 2
ilioinguinal and
iliohypogastric nerves
Fig. 20.38 IOM internal

oblique muscle, TAM
transversus abdominis
muscle, P peritoneum,
ASIS anterior superior iliac
spine, IIN ilioinguinal and
iliohypogastric nerves
The use of conventional techniques for the ilioinguinal nerve block based on
the observance of clicks to determine penetration of the abdominal muscles has
a reported success rate of approximately 70 % [27]. Part of the block failure may
be attributed to inaccurate nerve localization using traditional landmark-based
needle insertion sites and the fascial click method to determine injection. A study
by Wientraud et al. used ultrasonography to determine the actual location of
local anesthetic distribution when it was injected using traditional methods. The
local anesthetic surrounded the nerves in only 14 % of blocks [28]. Thus, the use
Fig. 20.39 IP ilioinguinal/

iliohypogastric nerve block
Fig. 20.40 Red line spread of local anesthetic
of ultrasound guidance to visualize the plane of nerve localization, needle

trajectory, and local anesthetic dispersion offers significant opportunity for
improvement.
Pharmacodynamic studies have demonstrated the efficacy of lower doses of local
anesthetics for managing postoperative pain in children who received these blocks
under ultrasound guidance. The authors also believe that using lower volumes could
reduce the risk of local anesthetic toxicity [26]. The use of lower volumes of local
anesthetic is also supported by a recent pharmacokinetic study that found higher
plasma levels of ropivacaine using ultrasound guidance when compared to a single
pop technique [29].
20.3.3.2 Rectus Sheath Block

The rectus sheath block is generally used in pediatric surgery for umbilical or epi-
gastric hernia correction and for laparoscopic port insertion. For this purpose the
tenth intercostal space nerve in the umbilical region is blocked.
The patient is in supine position. Start by scanning the sonoanatomy of the inves-
tigation area (on the left side and on the right side of the umbilicus) to locate the
rectus abdominis muscle (Fig. 20.41). Then follow the belly of this muscle to its
lateral border; on the outside the aponeuroses of the internal oblique muscle and the
transverse muscle can be identified (Fig. 20.42).
The block is performed with a linear high-frequency probe; the probe is posi-
tioned on the abdomen near the umbilicus in a tangential plane so that the abdomi-
nal muscles can be scanned transversely (the marker on the probe is directed toward
the patient’s right body side) (Fig. 20.43). The blockade is performed bilaterally.
The writers are used to perform this block with the in-plane approach.
Since the tenth intercostal nerve cannot be visualized by ultrasound, the block-
ade is performed by injecting the local anesthetic between the lateral border of the
rectus abdominus muscle and the aponeuroses of the internal oblique muscle and
the transverse muscle [26] (Fig. 20.44).
Umbilicus
RM RM
Fig. 20.41 RM rectus abdominis muscle

20.3.3.3 Transversus Abdominis Plane Block

The TAP is a potential space located between the internal oblique and the transver-
sus abdominis muscles. The thoracolumbar nerve roots, T8–L1, run in the TAP.
The transversus abdominis plane (TAP) block was first described as a landmark-
guided technique involving needle insertion at the triangle of Petit. This is an area
bounded by the latissimus dorsi muscle posteriorly, the external oblique muscle
EO
IO
RM
T
Fig. 20.42 RM rectus muscle, EO external oblique muscle, IO internal oblique muscle, T trans-
versus abdominis muscle, P peritoneum
Fig. 20.43 IP rectus

sheath block
RM
Fig. 20.44 RM rectus muscle, P peritoneum, red line spread of local anesthetic
anteriorly, and the iliac crest inferiorly (the base of the triangle). A needle is inserted
perpendicular to all planes, looking for a tactile endpoint of two pops. The first pop
indicates penetration of the external oblique fascia and entry into the plane between
external and internal oblique muscles; the second pop signifies entry into the TAP
plane between internal oblique and transversus abdominis muscles.
It has been shown to provide good postoperative analgesia for a variety of proce-
dures, as well as chronic neuropathic abdominal wall pain [30]. This block is par-
ticularly useful when a central neuraxial blockade is contraindicated.
The patient is placed in a supine position and the abdomen is exposed between the
costal margin and the iliac crest. A high-frequency linear probe or hockey stick probe
is placed on the abdomen lateral to the umbilicus (Fig. 20.45). The probe can be
shifted laterally to identify the three layers of the abdominal wall. The 3 muscle lay-
ers, external oblique, internal oblique, and transversus abdominis, serve as easily
identified landmarks in an ultrasound image. However, there may not be a clear dis-
tinction between the individual muscles. The external oblique is most superficial and
lies above the internal oblique, followed by the transversus abdominis. Deep to the
muscles, the peritoneum appears as a hypoechoic region. The nerves for this block
have similar echogenicity when compared to the muscles and travel tangentially to
the ultrasound beam axis. As a result, the nerves will not be visualized (Fig. 20.46).
Fig. 20.45 IP TAP block
EO
IO
Fig. 20.46 EO external oblique muscle, IO internal oblique muscle, T transverse abdominis mus-
cle, P peritoneum
Fig. 20.47 TAP transversus abdominis plexus, yellow lines: spread of local anesthetic
Next, a needle is placed at or slightly posterior to the midaxillary line using an

in-plane approach. The needle should be inserted into the plane between the internal
oblique and the transversus abdominis muscles and the local anesthetic is injected
into this potential space. The local anesthetic dispersion will appear as an elliptical
opening of the potential space (Fig. 20.47). If this spread is not observed, it is
important to hydrodissect with small injections of local anesthetic solution or saline
until the exact plane of injection is recognized [31].
20.3.4 Continuous Peripheral Nerve Blocks
Continuous peripheral nerve blocks have been shown to decrease resting and dynamic
pain and reduce opiate requirement, side effects, and sleep disturbance after surgery.
The main indications are for procedures associated with significant prolonged
postoperative pain, to improve peripheral perfusion after microvascular surgery, in
vasospastic disorders involving the limb and for children who have significant pain-
ful conditions to allow physical therapy in chronic regional pain syndrome [32].
For catheter placement, ultrasound techniques with needle guidance method are
used. The ultrasound image will reveal both the target structures and the needle
position; especially designed catheters can be introduced through either a needle or
an intravenous cannula.
Continuous catheter placement

There are two common approaches for catheter placement: the in-plane and out-of-plane
approaches; in the out-of-plane needle approach, the catheter is ideally positioned for
advancement as it exits the tip of the needle parallel to the long axis of the target nerve;
insertion using the in-plane needle approach assumes that the catheter can turn 90° upon
exiting the tip of the needle to be advanced along the long axis of the nerve.
The ultrasound transducer and cord are covered completely inside a sterile sheath.
The technique of continuous catheter placement follows the same principle as the single-shot
injection technique. That is, the procedures for patient positioning, skin preparation and
sterilization, and transducer selection are identical.
In general, a 17 G insulated needle is inserted perpendicular to the ultrasound transducer
(out-of-plane approach) and advanced to contact the target nerve.
Once the needle is deemed in contact with the target nerve (as indicated by nerve movement
and/or nerve stimulation), inject a minimum volume of local anesthetic to distend the
perineural space.
Distention of the perineural space will facilitate catheter threading especially in tight spaces,
e.g., interscalene groove. A 20 G stimulating or non-stimulating catheter is then inserted
3–5 cm into the perineural space.
The catheter is often inserted without real-time ultrasound guidance unless an assistant is
available to hold the ultrasound transducer in place while the principal operator uses one hand
to hold the needle and one hand to thread in the catheter.
It is often difficult to visualize the transverse view of the catheter which appears as a
hyperechoic dot.
After the needle is withdrawn, real-time assessment of local anesthetic spread is recommended
during injection. Circumferential spread indicates that the catheter tip is located in an optimal
position. Suboptimal catheter position may be corrected by withdrawing the catheter a short
distance before further local anesthetic is injected. Securing catheter can be challenging in a
mobile limb; subcutaneous tunneling is an option.
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Intensive Care 35:807–808
Noninvasive Hemodynamic
and Respiratory Monitoring During 21
the Perioperative Period
Brian Schloss and Joseph D. Tobias
21.1 Introduction
The first public display of the delivery of general anesthesia in the ether dome was
quickly followed within 2 years by the first reported case of death related to anes-
thesia in a child. Despite improvements in medications and preoperative prepara-
tion, perioperative morbidity and mortality may still occur [1–4]. Although likely
multifactorial in most instances, the incidence of both is increased in younger pedi-
atric patients (neonates and infants) when compared to older pediatric patients, in
the presence of comorbid diseases and increased American Society of
Anesthesiologists (ASA) status, as well as by a lack of experience or training by the
anesthesia provider [5, 6]. Data from the Australian Incident Monitoring Study
(AIMS) suggested that 46 % of intraoperative cardiac arrests were thought to be
anesthesia related, and of these events, more than half had a preventable factor that
could be identified [7].
The incidence of perioperative morbidity and mortality may be modified by sev-
eral factors, most importantly the presence of personnel with appropriate training in
B. Schloss, MD
Department of Anesthesiology and Pain Medicine, Nationwide Children’s Hospital,
700 Children’s Drive, Columbus, OH 43205, USA
Department of Anesthesiology and Pain Medicine, The Ohio State University, Columbus,
OH, USA
J.D. Tobias, MD (*)
Department of Anesthesiology and Pain Medicine, Nationwide Children’s Hospital,
700 Children’s Drive, Columbus, OH 43205, USA
Department of Anesthesiology and Pain Medicine, The Ohio State University, Columbus,
OH, USA
Department of Pediatrics, The Ohio State University, Columbus, OH, USA
e-mail: Joseph.Tobias@Nationwidechildrens.org

DOI 10.1007/978-3-319-21960-8_21
380 B. Schloss and J.D. Tobias
the provision of anesthesia to infants and children as well as by the use of standard
monitoring and safety devices on the anesthesia machine including continuous elec-
trocardiography, pulse oximetry, end-tidal carbon dioxide (ETCO2), continuous
temperature recording, intermittent measurement of blood pressure, an oxygen ana-
lyzer, and disconnect or low-pressure alarm of the ventilator/circuit system. The
AIMS demonstrated the potential utility of monitoring equipment in early detection
of perioperative adverse events. Of 1256 critical incidents, which occurred in asso-
ciation with general anesthesia, 48 % were initially “human detected” by the vigi-
lance of the anesthesia provider, while 52 % were “monitor detected.” More than
half were detected by either pulse oximetry (27 %) or capnography (24 %) [8, 9].
The remaining events were detected by electrocardiography (19 %), a blood pres-
sure monitoring device (12 %), a low-pressure circuit disconnection alarm (8 %), or
an oxygen analyzer (4 %). The percentage of events picked up by pulse oximetry
would have increased to 40 % had all of the cases used the modulated pulse tone
from the pulse oximeter instead of the tone or “beep” from the electrocardiogram.
The pulse oximeter also functioned as a secondary monitor for identifying respira-
tory events when the primary monitor was either nonfunctional or not in use. These
events included circuit disconnects, circuit leaks, esophageal intubation, aspiration,
pulmonary edema, endotracheal tube obstruction, failure of oxygen delivery,
hypoxic gas mixture, hypoventilation, air embolism, and bronchospasm.
Regardless of the event, these data clearly demonstrate that early detection of
critical events is facilitated and that morbidity and mortality can be decreased by
adherence to the current guidelines for monitoring during anesthesia. The following
chapter discusses current standard for intraoperative monitoring of hemodynamic
and respiratory function, the technology available, and its applications during the
perioperative period. Additionally, potential new technologies which may allow the
continuous, noninvasive measurement of cardiac output, blood pressure, tissue oxy-
genation, oxygen saturation, and the partial pressure of carbon dioxide (PaCO2) are
reviewed and their potential applications in the perioperative period discussed.
21.2 Noninvasive Monitoring of Respiratory Function
A key component of perioperative care involves continuous monitoring of respira-

tory function. During the intraoperative period, it is generally recommended that
this include pulse oximetry, end-tidal carbon dioxide monitoring (ETCO2), and the
use of a precordial stethoscope. Given the risk of end-organ damage related to
hypoxemia, the general focus of perioperative monitoring remains the detection of
changes in oxygenation.
21.2.1 Pulse Oximetry
Although the concept and even early machines were developed in the 1930s and
1940s, the modern generation of pulse oximeters was developed in the 1970s with
21 Noninvasive Hemodynamic and Respiratory Monitoring 381
their widespread introduction into clinical practice in the 1980s. The pulse oximeter
generally consists of a light-emitting diode that emits two wavelengths of light (940
and 640 nm) through the tissue. Oxygenated hemoglobin preferentially absorbs
light at the higher wavelength (940 nm or infrared spectrum), while unoxygenated
hemoglobin absorbs light at the lower wavelength (640 nm or red spectrum) [10].
The detector which collects light after it has traversed the tissue measures the ratio
of absorption to determine the oxygen saturation. Plethysmography is used to iden-
tify the pulsatile signal, thereby eliminating non-pulsatile venous blood and tissue.
The newer generation of pulse oximeters that have been developed over the past
5–10 years has focused on ensuring readings during low flow states, reducing inter-
ference from movement, improving accuracy within the lower saturation range (less
than 90 %), and measuring variant hemoglobins (carboxyhemoglobin, methemo-
globin) through the use of additional wavelengths of light.
In pediatric practice, pulse oximetry must be readily available in any situation
where there is a risk of hypoxemia including perioperative care, sedation, the ICU
setting, and the emergency department. More recently pulse oximetry has been used
not only to identify patients with hypoxemia allowing for earlier therapy but also as
a therapeutic decision-making tool as a means of triaging patients and identifying
those that may need hospital admission [11–13]. Pulse oximetry has also emerged
as a useful monitor during neonatal resuscitation and as a means of screening for
congenital heart disease [14]. As skin color has been shown to be an unreliable indi-
cator of oxygenation, pulse oximetry is being used more frequently during resusci-
tation following delivery [15]. These initiatives have been further pushed by the
mounting data showing the deleterious physiologic effects of both hypoxia and
hyperoxia [16, 17]. Given these concerns, current guidelines recommend oxygen
saturation monitoring in the delivery room for neonates with persistent cyanosis,
when assisted ventilation and supplementary oxygen administration are required, or
when neonatal resuscitation is anticipated (high-risk deliveries) [18].
Most importantly for perioperative care, pulse oximetry remains an essential
monitor during the entire perioperative period and into the postoperative period in
patients with significant comorbid conditions or those receiving continuous opioid
infusions such as patient-controlled analgesia. These recommendations persist
despite the presence of evidence-based medicine which clearly shows a decreased
risk of significant morbidity or mortality during the perioperative period [19].
Despite the lack of definitive data during the perioperative period, reviews of adverse
events during procedural sedation show the potential impact of inadequate monitor-
ing as a causative or contributing factor [20]. In a review of adverse sedation events
derived from the Food and Drug Administration’s adverse drug event reporting sys-
tem, from the US Pharmacopeia, and from a survey of pediatric specialists, the
authors investigated 95 adverse events occurring during procedural sedation.
Successful outcome of the event and subsequent resuscitation defined as prolonged
hospitalization without injury or no harm were associated with the use of pulse
oximetry compared with a lack of any documented monitoring.
As with any monitoring device, effective use requires an understanding of the
technology and its limitations. Pulse oximetry estimates the percent saturation of
Table 21.1 External and Motion artifact

patient-related factors that
Poor perfusion due to hypothermia or decreased cardiac output
affect pulse oximetry
Nail polish and artificial nails
Skin pigmentation
Cardiac arrhythmias
Electromagnetic interference from surgical cautery
Ambient light
Abnormal hemoglobin variants (methemoglobin)
Poor position or application of the probe
Venous pulsation from tricuspid regurgitation
Intravenous dyes (methylene blue)
the hemoglobin and cannot be used as a surrogate measure of the partial pressure of
oxygen in the blood (PaO2). The relationship between PaO2 and oxygen saturation
is affected by many factors including the type of hemoglobin present and the status
of the oxyhemoglobin dissociation curve which can be affected by acid-base status,
temperature, and 2,3-DPG levels. Pulse oximetry is known to be inaccurate during
periods of hypoxemia (saturation less than 85–90 %) and generally reads 98–100 %
when the PaO2 exceeds 100 mmHg, making it ineffective during periods of hyper-
oxia. Moreover, as the saturation does not change regardless of the hemoglobin
concentration, it does not provide information regarding oxygen carrying capacity
or oxygen delivery to the tissues, acid-base status, or ventilation [21, 22].
Furthermore, several patient-related or external factors may interfere with its accu-
racy (Table 21.1), although some of these issues have been addressed to some extent
with the newer generation devices. Newer technology has led to the introduction of
low-perfusion pulse oximetry that provides accurate readings during low-perfusion
states, devices using 6–8 wavelengths of light instead of 2 that can identify abnor-
mal hemoglobin species (carboxyhemoglobin, methemoglobin), improved accuracy
at saturation levels less than 90 %, and alternative sites for monitoring (forehead,
esophageal) [23–26].
21.2.2 End-Tidal Carbon Dioxide Monitoring
End-tidal carbon dioxide (ETCO2) monitoring or capnography displays the patient’s

exhaled carbon dioxide concentration continuously during exhalation with the
ETCO2 being the peak value before the next breath is initiated. Capnometers esti-
mate ETCO2 through the use of infrared technology such that the concentration of
CO2 in the exhaled gas is measured by the absorption of infrared light by CO2.
Following its introduction into anesthesia practice, it has become the standard of
care to continuously monitor ETCO2 whenever general anesthesia is provided.
Additionally, the measurement of ETCO2 via infrared or other technology is stan-
dard of care whenever endotracheal intubation occurs. When used continuously in
the ICU or operating room setting, the technology provides a continuous estimation
of the partial pressure of CO2 (PaCO2) in the blood and serves as a disconnect alarm
during mechanical ventilation, monitoring respiratory rate, and providing informa-
tion regarding pulmonary function via the shape of the capnogram. Abrupt changes
in the ETCO2 such as decreases related to increased dead space may alert the clini-
cian to decreased cardiac output or alterations in pulmonary perfusion related to gas
or pulmonary embolism. Acute increases in ETCO2 may be the initial sign of malig-
nant hyperthermia or other hypermetabolic states.
The normal capnogram has 3 phases of exhalation and one of inspiration, gener-
ally labeled as phases 1–4. Phase 1 is the beginning of exhalation, representing dead
space ventilation and therefore having no ETCO2 present. If there is ETCO2 present
during phase 1, this is indicative of the rebreathing of exhaled gas, which may be
due to inadequate fresh gas flows. Phase 2 is the rapid and steep upslope of the cap-
nogram representing the emptying of alveolar gas with dead space gas. Phase 3 is
the plateau phase, which in the normal state should be relatively horizontal.
Upsloping of phase 3 of the capnogram indicates obstructive lung disease (asthma,
bronchospasm) with differential emptying of alveoli with varying time constants.
With the initiation of inspiration, there is an abrupt decrease of the ETCO2 (phase
4) which should return to 0 mmHg.
The ETCO2 generally correlates in a clinically useful fashion with the PaCO2
with the ETCO2 being 2–4 mmHg lower than the PaCO2. This correlation can be
used clinically to adjust ventilation techniques both in the operating room and the
ICU setting. However, this correlation is dependent on effective matching of venti-
lation with perfusion, and various technology and patient-related factors may inter-
fere with this accuracy [27–31]. Such issues may be particularly relevant in the
practice of pediatric anesthesia where smaller tidal volumes, type of ventilation
(continuous versus intermittent flow), and sampling issues can affect the correlation
of ET and PaCO2.
Although initially introduced for intraoperative care, capnography has been
brought out of the operating room to various clinical arenas. The concern that
changes in pulse oximetry may take 60–90 s after the development of apnea in
patients receiving supplemental oxygen has led some authorities to recommend the
use of continuous ETCO2 monitoring during procedural sedation. While not man-
dated by all of the current guidelines for procedural sedation, ETCO2 monitoring
has been shown to be a beneficial adjunct to monitoring during procedural sedation.
While there may be some discrepancy between the ETCO2 value and the PaCO2
especially when monitoring from a nasal cannula, in many cases a direct correlation
can be demonstrated [32, 33]. The capnograph provides a continuous and real-time
demonstration that air exchange is occurring. If there is upper airway obstruction or
central apnea, this is immediately demonstrated as the capnogram extinguishes [34,
35]. Several clinical studies have demonstrated the early identification of respira-
tory depression using this technology and have clearly indicated its superiority over
pulse oximetry in many clinical scenarios in both pediatric and adult patients [36–
40]. These data have also been supported by a recent meta-analysis, concluding that
episodes of respiratory depression were 17.6 times more likely to be detected by
capnography compared with standard monitoring [41]. Owing to the growing
evidence, the American Society of Anesthesiologists has amended its standards for
basic anesthetic monitoring effective from 2011 to include mandatory ETCO2 mon-
itoring during moderate and deep sedation.
The recent literature and clinical experience clearly demonstrate that capnogra-
phy is not only effective for confirming ETT placement but may also have an
expanded role: the continuous monitoring of tube position in the OR and during
transport and monitoring during procedural sedation as a means for providing the
immediate identification of apnea or upper airway obstruction. It clearly remains the
standard of care for intraoperative monitoring and to document correct endotracheal
tube placement wherever endotracheal intubation occurs. Beyond this, it is rapidly
becoming the standard of care during procedural sedation especially with the recent
revisions of the ASA guidelines. It is also a key monitor in the ICU as a means of
rapidly adjusting minute ventilation during mechanical ventilation and for assessing
patients with respiratory illnesses. It may provide useful information following
endotracheal intubation and during transport as a means of avoiding inadvertent
hyperventilation which may be detrimental in patients with traumatic brain injury
[42]. More recently, it has been suggested that it can be used to judge the adequacy
of resuscitation during cardiac arrest. The depth of chest compression has been
shown to correlate with the ETCO2 values [43]. Additionally, higher ETCO2 values
during resuscitation have been shown to correlate with a greater chance of return of
spontaneous circulation (ROSC). Although initial investigations suggested that an
ETCO2 greater than 10 mmHg predicted ROSC, this value has recently been ques-
tioned suggesting that the goal ETCO2 during resuscitation should be considered
higher, perhaps approaching 25 mmHg [44]. Although ETCO2 was initially applied
only in the presence of an ETT, design modifications and the development of new
devices allow its application in patients with a native airway during spontaneous
ventilation. Given its ability to immediately detect hypercarbia and perhaps respira-
tory depression, it has been suggested that its use during postoperative period to
monitor patients receiving patient-controlled analgesia may lead to the early identi-
fication of respiratory depression prior to the development of respiratory
arrest thereby improving patient safety [45].
21.2.3 Transcutaneous CO2 Monitoring
Transcutaneous CO2 (TC-CO2) devices can also be used to provide a continuous

estimate of PaCO2 in various clinical scenarios. Although introduced for use in the
neonatal population where both transcutaneous CO2 and O2 monitoring have been
used, these devices have also found their way out of the NICU and into the ICU and
OR setting as a means of continuously monitoring ventilation. Their use has been
driven by concerns of clinical scenarios that affect the accuracy of ETCO2 or limit
their use (high-frequency ventilation techniques). In general, these devices apply
heat to the skin at 43–45 °C leading to capillary vasodilatation, increasing the transit
time of blood through the capillary, resulting in a close approximation of capillary
and arterial PaCO2. The vasodilatation of the capillary bed also allows CO2 to
diffuse from the arterial capillary lumen to the membrane of the transcutaneous
monitor. Alterations in temperature affect the solubility of CO2 in blood such that an
increase in the temperature increases the partial pressure of CO2 in the blood and a
higher PaCO2 value or a larger gradient between the actual PaCO2 and the TC-CO2.
Additionally, the higher temperature increases the metabolic rate of the tissues,
thereby further increasing the PaCO2. These factors are corrected by an internal
calibration factor that is used to calculate the TC-CO2 and thereby makes the TC
value an appropriate estimate of the PaCO2. Although used less commonly than
ETCO2 devices, these devices have seen increased used in various clinical scenarios
in both the OR and the ICU setting. These include conventional and high-frequency
mechanical ventilation, in spontaneously breathing patients, during the transport of
critically ill patients, and in other clinical scenarios including apnea testing during
brain death examination and in the assessment of patients with diabetic ketoacidosis
(DKA).
In a cohort of pediatric ICU patients with respiratory failure of various etiolo-
gies, ranging in age from 1 to 40 months, 100 simultaneously obtained sets of arte-
rial, transcutaneous, and end-tidal CO2 values were analyzed [46]. The end-tidal to
arterial CO2 difference was 6.8 ± 5.1 mmHg, while the transcutaneous to arterial
CO2 difference was 2.3 ± 1.3 mmHg, p < 0.0001. The absolute difference between
the end-tidal and arterial CO2 was ≤4 mmHg in 38 of 100 values, while the absolute
difference between the transcutaneous and arterial CO2 value was ≤4 mmHg in 96
of 100 values, p < 0.0001. The same investigators demonstrated the improved accu-
racy and potential application of TC-CO2 monitoring in an older cohort of patients
with respiratory failure who ranged in age from 4 to 16 years of age [47]. A final
study evaluated the accuracy of transcutaneous CO2 monitoring following cardio-
thoracic surgery in infants and children [48]. Given the potential for various physi-
ologic factors including residual shunt and ventilation-perfusion mismatch which
may exist following cardiopulmonary bypass (CPB) and surgery for infants with
congenital heart disease, the authors speculated that ETCO2 would be inaccurate in
this patient population and of limited benefit for continuous monitoring in the pedi-
atric ICU setting. The study population included 33 consecutive patients following
surgery for congenital heart disease. Transcutaneous CO2 monitoring was initiated
if the initial ABG following CPB demonstrated an arterial to end-tidal gradient of 5
mmHg or more. Although the study validated the utility of TC-CO2 monitoring and
its improved accuracy over ETCO2 in this unique patient population, problems with
TC-CO2 monitoring were noted in 3 patients who demonstrated cardiovascular
instability and were requiring dopamine at 20 μg/kg/min and epinephrine at 0.3–0.5
μg/kg/min. The cutaneous vasoconstriction induced by these vasopressors impacted
the accuracy of TC-CO2 monitoring. Other reported ICU and OR applications of
TC-CO2 monitoring have included continuous CO2 monitoring during high-
frequency ventilation, one-lung ventilation, laparoscopic surgery, apnea testing, and
metabolic disturbances where changes in PaCO2 may correlate with acidosis resolu-
tion [49–54]. In such settings, ETCO2 may not be feasible due to the ventilation
technique or inaccurate due to alterations in pulmonary ventilation-perfusion
matching.
Table 21.2 Advantages and disadvantages of transcutaneous and end-tidal devices

Transcutaneous End-tidal
Advantages More accurate than end-tidal in Rapid set-up with no calibration
many clinical scenarios Technically easy to use
Easy to use in both intubated and Confirms intratracheal position of
non-intubated patients ET tube
Accuracy not affected by Provides ventilator disconnect
pulmonary parenchymal disease, alarm.
shunt, ventilation-perfusion Capnogram provides information
inequalities, type of ventilator, and regarding pulmonary function
low tidal volumes
Can be used with high-frequency
types of mechanical ventilation
Disadvantages More labor intensive than end-tidal Less accurate than transcutaneous
devices devices in many clinical scenarios
Requires calibration and placement Accuracy affected by pulmonary
Must be repositioned every 3–4 h parenchymal disease, shunt,
Potential for superficial skin ventilation-perfusion inequalities,
blistering type of ventilator, low tidal
Accuracy affected by decreased volumes, and site of sampling
perfusion or use of vasoconstricting Use in non-intubated patients
agents requires specialized sampling
Increasing, but still limited clinical device (nasal cannula)
experience outside of the neonatal
population
As with all noninvasive monitors, attention to detail regarding specific aspects of

TC-CO2 monitoring is required to ensure the accuracy of the technique. When com-
pared with ET-CO2 monitoring, TC-CO2 monitoring requires a longer preparation
time including a 5-min calibration period prior to placement and then an additional
5–10 min equilibration period after placement on the patient to allow for an equili-
bration between the transcutaneous and arterial CO2 values. The electrode should be
recalibrated and placed at another site every 4 h to avoid burns or blistering of the
skin when the device is warmed to 45 °C, while newer devices that attach to the ear
lobe and are heated to 43 °C have a lower risk of thermal injury and may be left in
place for a longer period of time. While various sites (chest or abdomen) have been
used in neonates and infants, we prefer the volar aspect of the forearm in adults
especially those with obesity. Accuracy may be affected by technical factors related
to the monitor itself including trapped air bubbles, improper placement technique,
damaged membranes, and inappropriate calibration techniques. Patient-related
issues that affect accuracy include variations in skin thickness; the presence of
edema, tissue hypoperfusion, and hypothermia; or the administration of medica-
tions that result in cutaneous vasoconstriction. When considering these noninvasive
monitors of PaCO2, there are advantages and disadvantages to both (Table 21.2).
Given their different clinical utilities, perhaps they should be considered as compli-
mentary rather than competing devices.
21.2.4 Acoustic Impedance Monitoring
The latest addition to the respiratory armamentarium is the rainbow acoustic moni-
toring (RAM, Masimo Corporation, Irvine, California). RAM technology provides
continuous, noninvasive monitoring of respiration rate using an innovative adhe-
sive sensor with an integrated acoustic transducer that is externally applied to the
patient’s neck. The patented technology, known as Signal Extraction Technology
(SET®), separates and processes the respiratory signal to display continuous
acoustic respiration rate. Preliminary studies have suggested that this technology is
responsive to changes in respiratory rate and is superior to capnography in detect-
ing respiratory pauses. Its use of noninvasive adhesive sensors that are applied
externally to the lateral aspect of the patient’s neck may be more easily tolerated
than ETCO2 capturing devices. In a study comparing acoustic monitoring with
capnography in 33 adults in the post-anesthesia care unit following general anes-
thesia, the acoustic monitor and capnometer both reliably monitored ventilatory
rate, while the acoustic monitor more sensitively identified pauses in ventilation
[55]. Although the acoustic monitor was statistically more accurate and more pre-
cise than capnography, the clinical differences were modest without proven clini-
cal significance. The authors concluded that acoustic monitoring may provide an
effective and convenient means of monitoring ventilatory rate in postsurgical
patients. Other studies have demonstrated that respiratory rate monitoring with the
acoustic monitor correlates well with that monitored by capnography and that the
device is better tolerated than other devices such as a facemask for capnography
(Capnomask) [56, 57]. Its preliminary validation and success in these areas have
led to its use in the pediatric population for perioperative monitoring and in the
adult population outside of the operating room [58–60]. While all of these prelimi-
nary studies have suggested that it is better tolerated than capnography by mask or
nasal cannula, other advantages over capnography have yet to be determined.
Further work is needed to delineate its role in perioperative and postoperative
respiratory monitoring.
21.3 Noninvasive Monitoring of Hemodynamic Function
Along with respiratory monitoring (oxygen saturation and ETCO2), the monitoring
of cardiovascular parameters and hemodynamic function remains an integral com-
ponent of standard perioperative monitoring. Although blood pressure monitoring
remains a required component of perioperative care, it fails to provide us with even
more essential information regarding cardiovascular performance including car-
diac output, systemic tissue oxygen delivery, and tissue oxygenation. While these
monitors are not considered essential for perioperative care, there remains great
interest in the technology that would allow us to noninvasively monitor these
parameters.
21.3.1 Cardiac Output Monitoring
The ability to measure cardiac output (CO) at the bedside became a reality in the
1970s, courtesy of the pulmonary artery catheter (PAC) developed by Drs. Swan
and Ganz [61]. While the use of a PAC has failed to decrease mortality, there con-
tinues to be great interest in CO measurement in the operating room and beyond
with the hopes of identifying parameters, which, when altered, will improve out-
come [62]. This is evidenced by a Cochrane Database review which concluded that
optimizing CO in a goal-directed fashion reduces hospital stay, as well as complica-
tions such as respiratory failure, renal impairment, and wound infection [63].
The PAC measures CO by way of the thermodilution technique. Using the ther-
modilution method, an injectate is administered centrally (right atrium) and a down-
stream (pulmonary artery) temperature change is measured. The magnitude of the
change and its rapidity are directly related to CO. Using a variation of the “Stewart-
Hamilton” indicator dilution equation, CO is calculated [62]. Although this method
was introduced over 40 years ago, it generally remains accepted as the most accu-
rate method of measuring CO at the bedside. Precision errors as low as 13 % have
been reported with the use of PACs in animal models [64]. To eliminate the need for
repeated injections which provide only intermittent measures of CO, a PAC was
developed with a coil which sits in the right atrium that warms to slightly greater
than body temperature, thereby warming the blood and eliminating the need for
intermittent injection. Despite their accuracy, PAC use has fallen out of favor with
many clinicians given their invasive nature, which may mitigate any clinical advan-
tage their CO measurements bring. In addition, the size of PACs precludes their use
in small children, while intracardiac shunts mitigate the accuracy of thermodilution
measures of CO, thereby making it even less common among pediatric clinicians.
Transpulmonary thermodilution (TPTD) is another method of CO measurement,
which is similar to the PAC. An injectate is administered centrally and a down-
stream temperature change is measured. However, the technique eliminates some of
the invasiveness of the procedure as the distal measurement is measured in the fem-
oral artery rather than the pulmonary artery. This method is likely equivalent in
accuracy to the PAC, although it remains an invasive option, requiring the use of
specialized central venous and femoral artery catheters [65]. While thermodilution
remains the clinical gold standard in CO measurement, it is invasive and often
impractical. Given the theoretical benefit of optimizing CO in the perioperative
period, newer and less invasive methods of CO measurement are being developed
and evaluated.
Doppler techniques offer a noninvasive alternative for the measurement of
CO. These monitors are based on the Doppler effect, which states that the change in
frequency of a reflected ultrasound signal is proportional to the speed of the reflect-
ing object (blood flow) [66]. These changes in frequency can then be used to calcu-
late velocity and ultimately quantify stroke volume and hence CP. Transthoracic and
transesophageal echocardiography use Doppler ultrasound to accurately measure
CO; however, they require specialized training and their regular use in the operating
room is not feasible [67]. More practical approaches involve esophageal and
transcutaneous (suprasternal) Doppler probes. Esophageal Doppler monitors

(EDM) are a particularly attractive option in the operative room given its relative
ease of placement and lack of interference with most surgical fields. For this reason,
it is far more common than suprasternal probes. An EDM simply involves a probe,
which is placed in the esophagus and is connected to an analyzer. The probe sends
and receives ultrasound signals to the descending aorta, while the analyzer inter-
prets the frequency changes, calculating velocity, which is then used to determine
CO. However, up to one third of CO is diverted away from the aorta prior to the
point of measurement by an EDM. Additionally, the aortic cross-sectional area is
needed to calculate CO based on the measured velocity. These factors are estimated
by the analyzer using the patient’s age, weight, and height. Given these limitations,
it is not surprising that the absolute values of EDM-measured CO are not inter-
changeable with the gold standard of thermodilution [68]. However, EDM does
consistently show high correlations with thermodilution reference methods. This
suggests that EDM may still be useful in the perioperative period by accurately
tracking acute changes in CO.
The pulse contour analysis technique involves calculation of cardiac perfor-
mance based on an arterial waveform tracing. This process necessitates the place-
ment of an arterial catheter and often involves a specialized transducer, which
accompanies the signal analyzer. Pulse contour analysis monitors can be catego-
rized as calibrated and non-calibrated varieties. The available calibrated pulse con-
tour monitors use either TPTD or lithium dilution to measure cardiac output [68].
Uncalibrated devices derive CO purely from waveform analysis without input from
the other forms of CO measurement. The accuracy of pulse contour analysis remains
in question given their significantly smaller body of literature compared with ther-
modilution and Doppler techniques. With this in mind, the studies suggest that cali-
brated pulse contour monitors are more accurate when compared to their uncalibrated
counterparts. In addition, both types have decreased accuracy during periods of
hemodynamic instability [69–73].
Thoracic electrical bioimpedance (TEB) is a completely noninvasive method of
monitoring CO, requiring the placement of several electrodes on the external sur-
face of the thorax. This method assumes that resistance to electrical flow is directly
related to blood volume within the thorax so that changes in this resistance are used
to calculate changes in the intrathoracic blood volume and hence CO. The elec-
trodes are both transmitters and receivers of electrical current, constantly measuring
changes in amplitude. The amplitude changes are caused by changes in thoracic
fluid volume and ultimately related to descending aortic blood flow. An electrocar-
diogram measures ventricular ejection time, and the amount of amplitude change
during ventricular ejection time is directly proportional to stroke volume.
Unfortunately, TEB is prone to errors secondary to pulmonary edema, electrical
interference, patient movement, and skin temperature. As such, TEB has shown
poor correlation with clinical reference standards [74–76].
Bioreactance is a similar technique, which was developed in an effort to improve
on the inaccuracies of TEB. Bioreactance refers to the “phase shift” of voltage,
which occurs specifically during pulsatile blood flow. Given the fact that pulsatile
flow in the thorax is predominantly taking place in the aorta, bioreactance is able to
more accurately measure cardiac output without interference from thoracic fluid
(pulmonary edema). Validation studies suggest that bioreactance is far more accu-
rate than TEB when compared with thermodilution [77–79]. However, more
research is needed before it can be recommended for routine use.
In conclusion, thermodilution techniques remain the clinical gold standard for
cardiac output monitoring. The invasiveness of thermodilution techniques remains
their primary drawback; however, no technology to date has proven itself to be
superior. Doppler-based techniques, specifically transesophageal Doppler, provide
a noninvasive alternative with accuracy that is similar, though not superior, to ther-
modilution. Calibrated pulse contour analysis is superior to its uncalibrated pulse
contour analysis, though both tend to suffer during periods of hemodynamic insta-
bility. Bioreactance is completely noninvasive and shows promising accuracy in
comparison to thermodilution. It is, however, a relatively newer technology when
compared to thermodilution and Doppler counterparts. More research is needed
before meaningful conclusions can be made regarding the clinical utility of bioreac-
tance, while bioimpedance monitors have shown poor accuracy and cannot be rec-
ommended for clinical use.
21.3.2 Electrocardiogram Monitoring
Continuous monitoring of the electrocardiogram (ECG) remains one of the standard

intraoperative monitors during the provision of anesthesia care. Although arrhyth-
mias are uncommon outside of the pediatric cardiac anesthesia arena, bradycardia
may occur due to the administration of volatile anesthetic agents (halothane or sevo-
flurane), hypoxemia, hypothermia, and alterations in intracranial pressure or from
the oculocardiac or trigeminocardiac reflex. Although the negative chronotropic
effect is less with sevoflurane when compared to halothane, bradycardia may still
occur, thereby making continuous ECG monitoring mandatory regardless of the
duration of the anesthetic or sedation event [80]. While many of these bradycardic
responses are self-limiting, treatment may be required when the heart rate fails to
respond to initial therapies such as release of surgical traction or a decrease in the
volatile agent concentration. In most clinical scenarios for the pediatric population,
a 3-lead ECG is used with the demonstration of lead II to facilitate the identification
of P wave morphology and arrhythmia analysis. In adult patients and in specific
pediatric patients, a 5-lead ECG is used to facilitate ischemia detection.
Other applications for ECG monitoring include identification of potentially
lethal electrolyte disturbances including hyperkalemia, rare instances of prolonged
QT syndrome (congenital, acquired, or drug induced), and monitoring for inadver-
tent systemic injection of local anesthetic agents. Over the years, there has been a
dramatic increase in the use of regional anesthesia in infants and children, which has
resulted in the increased administration of local anesthetic agents in the age group.
Given its prolonged duration of action, the long-acting agent, bupivacaine, is fre-
quently used. As it is relatively cardiotoxic when compared with other agents, a
means of identifying inadvertent intravascular or systemic injection is mandatory.

To accomplish this, a small amount of epinephrine is generally added to the solution
as a test dose [81]. Although this was proposed to result in an increase in heart rate
with a high sensitivity, subsequent work demonstrated that when anesthetized with
a volatile anesthetic agent, the sensitivity of a heart rate increase was less than
expected and not adequate to ensure the safety of the technique. [82–84] By using
the T wave, systolic BP, and HR criteria, the positive response rate to an epinephrine
test (0.1 mL/kg of a 1:200,000 solution or 0.5 μg/kg) was 100, 95, and 71 %, respec-
tively, during sevoflurane anesthesia and 90, 71, and 71 % during halothane anesthe-
sia [85].
21.3.3 Near-Infrared Spectroscopy
Near-infrared spectroscopy (NIRS) uses infrared light, a technique similar to pulse

oximetry, to noninvasively estimate brain tissue oxygenation by measuring the
absorption of the light by tissue chromophores (hemoglobin and cytochrome aa3).
Pulsatile flow is not required and therefore the device works during CPB and other
non-pulsatile states such as cardiopulmonary bypass. Based on the relative absorp-
tion of the infrared light at various wavelengths, the specific concentration of the
hemoglobin species can be determined using a modification of the Beer-Lambert
law [86]. There are two basic types of NIRS monitors: a saturation monitor that
measures the difference absorption between oxygenated and unoxygenated hemo-
globin and a concentration monitor that measures the concentration of oxygenated
and reduced hemoglobin and the relative redox state of cytochrome aa3. The satura-
tion monitor is the one used most commonly in clinical practice and the ones that
are currently commercially available for widespread clinical use. To improve the
ease of use, instead of providing the specific concentrations of oxygenated and
unoxygenated hemoglobin, the NIRS monitors provide a single numeric value
known as cerebral oxygenation (rSO2). Cerebral oxygenation monitoring is initiated
by placing a self-adhesive probe over the patient’s forehead. Infrared light is directed
into the cranium from a light source, and two sensors placed at fixed distances from
the light source measure the light after it has passed through extracranial tissue
(proximal sensor) or both extracranial and intracranial tissues (distal sensor).
Clinical evidence supports the correlation of the NIRS number (rSO2) with cere-
bral blood flow (CBF) and oxygenation as changes in rSO2 easily correlate with
clinical changes that alter CBF such as blood pressure, PaCO2, and systemic oxy-
genation. During CPB, rSO2 increases during cooling, with improvements in car-
diac output and oxygen delivery. Cerebral oxygenation (rSO2) decreases
exponentially and in a predictable and reproducible fashion during deep hypother-
mic cardiac arrest. Clearly the rSO2 decreases rapidly during periods of hypoxemia,
hypocarbia, hypoperfusion, or cardiac arrest. In fact, the rSO2 has been shown to be
an earlier and more sensitive indicator of hypoxemia than pulse oximetry [87, 88].
Furthermore, anecdotal experience supports its ability to identify problems related
to cannula positioning during CPB. To date, NIRS monitoring has found the
greatest use during cardiac surgery in both the adult and the pediatric population.
There is accumulating evidence in the adult population which suggests that moni-
toring rSO2 and acting on changes may alter outcome; however, additional studies
are needed to validate these findings in the pediatric population [89–91]. More
recent work has demonstrated the use of the NIRS to determine the autoregulatory
threshold, demonstrating it to be widely altered in critically ill patients and also sug-
gesting that maintenance of blood pressure within the autoregulatory limits alters
outcome [92].
Despite its potential utility, one must also recognize the limitations of cerebral
oxygenation monitoring using rSO2. Unlike pulse oximetry, there is generally no
“normal value” that can be assigned to rSO2. Studies in the pediatric population
have demonstrated a wide variation in the baseline values in patients without clini-
cal signs of cerebral hypoxemia. Our clinical experience demonstrates similar vari-
ability depending on the age of the patient, underlying type of congenital heart
disease, and perhaps head circumference and depth of penetration of the near-
infrared light. Although the development of neonatal and pediatric probes has over-
come some of these issues, NIRS should be regarded as a trend monitor with the
need for additional prospective trials to demonstrate which values constitute true
cerebral hypoxemia and the risk of subsequent neurologic damage. It is likely that
adverse outcomes relate not only to the nadir of the rSO2 but also to the duration of
time spent at low values (the area under the curve). The current literature suggests
that values less than 40 % or an absolute decrease of 20 % (a decrease from an rSO2
value of 64–44 %) from baseline values should alert the clinician to the need for
interventions to reverse potential cerebral hypoxemia. These interventions may
include changing head position, verifying appropriate cannulation placement or
increasing pump flow during CPB, allowing the PaCO2 to increase, and increasing
oxygen delivery (increasing cardiac output, increasing systemic oxygen saturation,
or increasing hemoglobin). If the above measures fail to increase rSO2, based on the
clinical scenario, therapeutic maneuvers to decrease the cerebral metabolic rate for
oxygen may be indicated.
21.3.4 Blood Pressure Monitor
Blood pressure (BP) monitoring in the perioperative period is an obvious necessity.

Fluctuations in hemodynamics are common secondary to anesthetic medications,
surgically induced nociception, fluid shifts, and blood loss. Blood pressure is most
commonly measured with a noninvasive, oscillometric blood pressure (NIBP) cuff
during this period. However, certain clinical scenarios involving wide BP swings or
significant blood loss dictate the use of an arterial cannula. The advantage of an
arterial cannula is its continuous monitoring capability and the ability to draw fre-
quent blood samples for laboratory evaluation. While the arterial cannula is both
reliable and accurate, its advantages are mitigated by its invasive nature, which can
lead to complications such as arterial occlusion, distal ischemia, bleeding, infection,
and unintended injection of medications. However, such complications are rare and
infrequently seen especially when short-term monitoring is used intraoperatively.

More importantly, there may be situations in which an arterial cannula cannot be
placed due to patient-related issues or positioning. Furthermore, the need for an
arterial cannula may not have been anticipated prior to the onset of rapid blood loss
or acute hemodynamic instability. For these reasons, there remains interest in tech-
nology which offers beat-to-beat BP monitoring in a noninvasive fashion.
The most common technique of continuously and noninvasively monitoring BP
was first described by Jan Peñàz in 1973 [93]. Peñàz, a physiologist, described a
technique referred to as “vascular unloading” which employs the use of an inflatable
finger cuff and a distal infrared plethysmograph. The plethysmograph is used to
estimate the blood volume in the finger, while the cuff attempts to maintain that
blood volume at a constant within the finger. The two aspects of the monitor are in
a constant feedback loop as the cuff pressure varies with systole and diastole. This
information is then incorporated into a formula which displays a waveform mimick-
ing an invasive arterial tracing. Modern monitors using variations of Peñàz tech-
nique also incorporate NIBP readings to help calibrate the formula. Although
generally accurate, there are limitations associated with this technique. Fluctuations
in temperature, vascular disease, and the use of vasoactive agents can interfere with
proper readings [94]. Also, as with NIBP devices, the accuracy varies based on cuff
size. Despite these limitations, the technology behind this device is now commer-
cially available. The preliminary clinical data suggests that this may be a promising
technique in the adult and older pediatric population [95, 96].
Another technique for noninvasive continuous blood pressure monitoring is
known as arterial tonometry [97]. This method requires a peripheral artery of a large
diameter which is adjacent to a bony structure. The radial artery is the most com-
mon choice. A tonometer with a pressure sensor is placed over the artery, and pres-
sure is applied until the artery is compressed, but not totally occluded. It is believed
that the pressure between the skin overlaying the artery and the tonometer is a good
approximation of arterial intraluminal pressure. The pressure fluctuations at the skin
are then transmitted into a real-time arterial pressure tracing. While the tonometry
method offers the advantage of a more proximal measurement, one of the major
drawbacks is its reliance on calibration from an NIBP cuff. The tonometry module
must assume that an oscillometric BP measurement is completely accurate, which
can create a significant degree of error. It has also been reported that there is a wide
variation in the oscillometric readings among the different devices from various
manufacturers [98]. Additionally, there can be some difficulty in properly placing a
tonometer directly over the intended artery. For these reasons, tonometry-based
noninvasive blood pressure monitors have not gained widespread popularity and
clinical use.
Pulse transit time is another technique which may have promise for future con-
tinuous noninvasive blood pressure monitoring [99]. This method measures the dif-
ference in propagation time of pulsatile blood at two separate peripheral sites. The
ECG waveform can be used to detect the beginning of a pulse wave, while the actual
distal pulse is detected at two separate sites using plethysmographic waveforms.
These time variations can then be related to systolic blood pressure. The technique
is also cuffless which removes the errors that are common with cuffed methods.
Presently, there is no commercial monitor available that uses the pulse transit time
technique. A recent meta-analysis by Kim et al. examining commercially available
noninvasive blood pressure monitors concluded that the accuracy and precision of
these devices is larger than has been deemed acceptable by the Association for the
Advancement of Medical Instrumentation [100]. To put this conclusion into per-
spective, the meta-analysis stated that if a systolic arterial pressure is measured to
be 100 mmHg using an arterial catheter, the systolic pressure measured by a com-
mercially available noninvasive monitor could range from 74 to 123 mmHg. While
these devices have shown great promise for future use, they will likely require addi-
tional improvements in accuracy before they find a significant foothold in modern
perioperative care.
Conclusions
The years have seen improvements in both the pharmacology and technology of
anesthesia, which have resulted in a decrease in the risks of perioperative mor-
bidity and mortality. Many of these advancements have been linked with the
introduction of standard monitoring during perioperative care to include a con-
tinuous ECG display, pulse oximetry, end-tidal CO2, temperature, and intermit-
tent BP. Additional devices have been introduced for both respiratory and
hemodynamic monitoring, which may fill in some of the deficiencies of the cur-
rently used monitor. These newer devices offer options for transcutaneous CO2
monitoring, NIRS, and continuous noninvasive BP or CO monitoring. However,
prior to their widespread acceptance and integration into perioperative care, evi-
dence-based medicine demonstrating their impact on outcome is needed.
Furthermore, the technology behind some of these devices falls short of the accu-
racy required for clinical decision making. However, we hold firmly to the
knowledge that the early detection of critical events has been shown to decrease
morbidity and mortality. As such, the search continues for monitors that will
supplement the current perioperative armamentarium.
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Part V
Early and Long Term Consequences
of Anesthesia and Surgery
Negative Behaviour After Surgery
22
Marta Somaini and Pablo M. Ingelmo
22.1 Emergence Delirium, Emergence Agitation

and Postoperative Pain
Smessaert et al. [57] introduced the concept of ‘mode of recovery’, describing the
different types of behaviours whilst consciousness is being regained following
anaesthesia and surgery. They described three models of recovery: patients who
made a tranquil and uneventful recovery; patients with moderate degree of restless-
ness; and patients markedly delirious and uncooperative, requiring special care and
restraint. Eckenhoff et al. [21] described the incidence and the aetiology of post-
anaesthetic excitement, studying more than 14,000 patients in recovery room. They
defined as having ‘emergence excitement’ patients who were crying, sobbing,
thrashing about and disoriented upon awakening from general anaesthesia. The lat-
ter entity of this syndrome was considered emergence delirium (ED).
Since the early 1960s, the terms emergence delirium (ED), emergence agitation
(EA), ‘emergence excitement’ and ‘maladaptive postoperative behaviour’ were
often used as synonymous without a clear consensus on definition [4, 48, 65].
Recently, Bortone et al. [8] introduced the term early postoperative negative behav-
iour (e-PONB) that collectively includes different unsettle behaviours after awaken-
ing and differentiates early phase from later postoperative behavioural changes.
The more relevant components of e-PONB have been identified as pain, ED and
EA [4, 8]. Up to 80 % of children undergoing general anaesthesia can experience
M. Somaini, MD (*)
Department of Anaesthesia and Intensive Care, Niguarda Ca’ Granda Hospital,
Milan-Bicocca University, Milan, Italy
e-mail: ma.somaini@gmail.com
P.M. Ingelmo, MD
Department of Anesthesia, Montreal Children’s Hospital, MUHC, McGill University
e-mail: pablo.ingelmo@mcgill.ca

DOI 10.1007/978-3-319-21960-8_22
404 M. Somaini and P.M. Ingelmo
e-PONB depending on clinical setting and on the perioperative management [18,

48, 58].
The standard diagnostic criteria for delirium (Diagnostic and Statistical Manual
of Mental Disorders, Fifth Edition – DSM-V) are disturbances in attention and
awareness (reduced ability to direct, focus, sustain and shift attention) associated
with change in cognition (disorientation, language disturbance) and perceptual dis-
turbance. Sickic and Lerman [56] defined ED as ‘a mental disturbance during the
recovery from general anaesthesia consisting of hallucinations, delusions and con-
fusion manifested by moaning, restlessness, involuntary physical activity, and
thrashing about in bed’.
The most frequently quoted incidence of ED in young children is probably 20 %
[5, 48, 65]. ED occurs during the first 20 min after spontaneous awakening [29, 65].
The onset of this behaviour is almost always within 5 min after awakening and lasts
for about 10–15 min, is self-limiting in almost all cases and never restarts in the
same child [8, 28].
EA is a state of restlessness and mental distress and not all children that have EA
have delirium. A child may be agitated for numerous reasons including pain, hunger
or fear because of the absence of a primary caregiver or unfamiliar surroundings.
‘Agitation’ can be used as a general term that encompasses all of these states, but it
should be avoided on publications that specifically discuss the ED phenomenon [5,
48, 65].
22.2 Consequences of e-PONB
Children with e-PONB are at risk of self-injury or accidental removal of IV cathe-

ters and drainages. It usually requires extra nursing care and eventually supplemen-
tal sedative or analgesic drugs. Also, an unsettle behaviour reduces parental and
caregivers’ satisfaction [48, 63, 66]. Long-term psychological implications of
e-PONB are unclear, but it has been demonstrated that children who show ED whilst
emerging from anaesthesia have a higher risk of developing separation anxiety, apa-
thy, sleep and eating disorders weeks after surgery [24, 37, 59]. Children with
e-PONB could also present nightmares, waking up crying, temper tantrums or more
serious behavioural changes such as the new-onset enuresis [20, 31]. Kain et al.
reported that up to 60 % of children between 1 and 7 years old undergoing elective
outpatient procedures develop negative behaviours on the first day after surgery.
The negative behaviour could persist up to 2 weeks after surgery [31]. The preva-
lence of at least one negative behaviour in children from 6 to 12 years ranged from
a maximum of 80 % (95 % CI 71–90 %) in the first day after surgery 1 to a mini-
mum of 43 % (95%CI 31–56 %) 6 months after elective adenotonsillectomy surgery
[5, 60].
Postoperative pain may be a significant contributing factor to EA when assessing
the cause of a child’s behaviour upon emergence. Inadequate pain relief may cause
EA, particularly after short surgical procedures [19, 23, 26]. However, recent publi-
cations suggested that ED and postoperative pain are independent behaviours with
22 Negative Behaviour After Surgery 405
different trend over the first 30 min after spontaneous awakening from general
anaesthesia [8, 12]. It is important to distinguish ED from pain, since the aetiology
and management are likely to be different [5, 48, 58]. A wrong diagnosis can lead
to the treatment of self-limiting behaviour (ED) and/or to the under-treatment or
delayed treatment of postoperative pain.
22.3 Risk Factors
In 1960, Smessaert et al. described two main factors associated to ED. The first one
was related to the intraoperative period (anaesthesia management, cyclopropane
more than ether or barbiturates) and to the surgical procedures (peripheral surgery
is less frequently associated to ED than intrathoracic or intra-abdominal surgery).
The second one was the individual characteristics of the patient (e.g. sex, age and
temperament), and they hypothesized that the behaviour during emergence from
surgical anaesthesia was primarily influenced by the patient’s personality structure.
They did not consider pain as an essential factor causing delirium [57]. More
recently, e-PONB was associated with the type of anaesthesia; the surgical setting;
the child’s age, experience and temperament; the preoperative anxiety; and the
parental presence during awakening and with the postoperative pain [18, 22].
22.3.1 Age and Gender
Since from 1960s, it was described that the incidence of e-PONB is higher in child-
hood and decreases with age [21]. However, more information provided by recent
literature could not support the inverse relationship between age and incidence of
e-PONB. Different development stages are characterized by different psychological
development. For example, it is unlikely that infants experience separation anxiety,
which is very common in small children between one and three 3 years old. Children
in preschool respond positively to distraction, and older children/adolescents want
to be part in the decision-making process as mechanisms to decrease anxiety [5, 50].
Gender seems to do not affect the incidence of e-PONB. But some authors report
that ED occurs more frequently in male preschool children [18]. As consequence,
the use of age-specific tools may help on a more accurate evaluation, prevention and
treatment of e-PONB.
22.3.2 Parents and Culture
Ethnicity, language and cultural values could influence the report of negative behav-
iour changes. Spanish-speaking Hispanic parents reported lower incidence of nega-
tive behavioural changes compared to English-speaking White parents. Stoicism is
a common cultural value within Hispanic families, and as a consequence, they tend
not to report e-PONB [25].
22.3.3 Preoperative Anxiety
Preoperative anxiety is an independent predictor for postoperative negative behav-

iours. Kain et al. described the strong correlation between preoperative anxiety and
postoperative negative behaviour in young children undergoing general anaesthesia.
The risk of postoperative negative behaviour changes is up to 3.5-fold greater in
children who experienced preoperative anxiety [32, 34, 35].
The identification of anxiety traits before surgery may help to improve the peri-
operative management and prevent e-PONB. Clinical and laboratory parameters
(i.e. heart rate and blood pressure, plasma cortisol concentrations) have been con-
sidered to assess anxiety, but these values had low validity and reliability [5]. The
modified Yale preoperative anxiety scale (m-YPAS) is a validated and reliable tool,
but too complex to be use in a normal busy clinical practice [32].
The induction compliance checklist (ICC) was validated for use during inhala-
tion induction of anaesthesia [33]. Beringer et al. developed the Paediatric
Anaesthesia Behaviour (PAB) score, to quantify the level of anxiety during induc-
tion of anaesthesia. The PAB score identifies children who are distressed during
induction of anaesthesia. They described three behavioural scenarios where chil-
dren could be described as:
1. Happy – calm and controlled. Compliant with induction

2. Sad – tearful and/or withdrawn but compliant with induction
3. Mad – loud vocal resistance (screaming or shouting) and/or physical resistance
to induction requiring physical restraint by staff and/or parents
There was significant correlation between the PAB score and the ICC and
m-YPAS. A high PAB score during induction was associated with increased inci-
dence and intensity of e-PONB in PACU and with the development of behavioural
changes after discharge home [6].
22.3.4 Surgery
The relationship between the type of surgery and the incidence e-PONB is unclear.
Some authors reported that ear, nose and throat surgery, ophthalmologic procedures
[3], genitourinary surgery [43] and surgical procedures in admitted patients [47]
were associated with increased risk of postoperative behavioural changes. On the
contrary, several studies excluded the increase risk of postoperative negative behav-
iour in association with the type of surgery [5].
22.3.5 Inhalation Anaesthesia
Sevoflurane and desflurane, agents with low blood/gas solubility, were associated
with higher incidence of ED and EA when compared with halothane [3, 17, 69].
The faster clearance of sevoflurane and desflurane in the central nervous system
may explain the high incidence of ED after volatile anaesthesia. This hypothesis has
been supported by the increased incidence of postoperative agitation since the intro-
duction of fast-acting volatile agents. The late emergence of cognitive function
compared to other brain functions, such as audition and locomotion, has been con-
sidered the cause of the confusion state [18]. In support of this theory, Bong et al.
recently found that the only significant predictor for ED is the time taken to awake
from general anaesthesia. With every minute increase in wake-up time, the odds of
ED had been reduced by 7 % [7]. Recently, the biphasic effect of sevoflurane has
been described as possible contributing factor to the genesis of ED in young chil-
dren [5]. This drug potentiates GABA alfa-receptor-mediated inhibitory postsynap-
tic currents at high concentrations and blocks these currents at low concentrations
[53].
When compared sevoflurane and desflurane anaesthesia on postoperative behav-
iour, the incidence of ED varied between 10 and 55 %. However, in most of the
studies on the argument, there is no consensus on definition, and the incidence and
magnitude of the postoperative behaviours were measured with not validated scales
to assess ED [11, 12, 64, 68]. Welborn et al. reported 55 % of ED after desflurane
compared with 10 % in the sevoflurane group, in children undergoing ENT surgery
[68]. Cohen assessed the postoperative behaviour of preschool children undergoing
adenotonsillectomy, using a three-point scale (calm, agitated but consolable, very
agitated and inconsolable). There were no significant differences on the incidence
of EA between children receiving sevoflurane (18 %) or desflurane (24 %) [41]. As
well, Valley et al. found a 33 % overall incidence of ED without significant differ-
ences between children receiving sevoflurane or desflurane [64].
Locatelli et al. investigated the incidence of ED, using the PAED. One in four
children undergoing sub-umbilical surgery with sevoflurane or desflurane and effec-
tive regional anaesthesia had ED. They found no differences on incidence of ED
between sevoflurane and desflurane anaesthesia. However, ED had a longer dura-
tion in children receiving sevoflurane anaesthesia [46].
22.3.6 Propofol
The incidence and intensity of ED after propofol anaesthesia were significantly

lower than volatile anaesthetics. The incidence of ED in children undergoing eye
examinations with sevoflurane group was 38 % compared to 0 % for propofol group
[27]. Maintenance with propofol significantly reduces the risk of EA (RR 0.35, 95
% CI 0.25–0.51) when compared with sevoflurane anaesthesia even when children
in propofol groups received sevoflurane induction [15]. Similar results were
obtained when compared to children receiving only sevoflurane or propofol mainte-
nance (RR 0.59, 95 % CI 0.46–0.76) [9, 13, 14, 15, 62].
Different authors investigated the effect of single bolus of propofol at induction
or at the end of the surgery on EA incidence during sevoflurane anaesthesia. Propofol
2 or 3 mg/kg at induction did not reduce the incidence and severity of EA. Instead,
children receiving propofol 1 mg/kg at the end of sevoflurane anaesthesia showed

reduce risk of EA (RR 0.58, 95 % CI 0.38–0.89) [15]. Recently, Costi el at reported
that transition to propofol 3 mg/kg for 3 min at the end of sevoflurane anaesthesia
reduces the incidence and severity of EA. [16]
22.4 Tools to Recognize and Quantify e-PONB
The recognition of pain, ED and EA in the recovery room is clinically relevant,

as different condition should receive different management [4, 8, 48, 65]. Young
children who are unable to verbalize pain, anxiety, discomfort, fear, hunger or
thirst may manifest all these different conditions with similar behaviours.
Moreover, it is possible to observe significant behaviours (pain, ED and EA)
overlap during the first minutes after awakening [58]. The lack of ‘gold standard’
to identify ED and the impossibility of using self-report pain scales during
awaken makes the differentiation between the major components of e-PONB
extremely difficult.
Several observational scales were developed to measure EA, pain and ED in
young children. EA is frequently described using three to five categories [67]. The
most common EA scales (Watcha, Cravero, Aono, etc.) have not been psycho-
metrically tested and include behaviours such as crying, inconsolability and lack
of cooperation. Substantially, these scores describe a generic agitation state, but
they are unable to discriminate between different aetiologies neither to identify
ED [48]. ED should not be diagnosed only on the basis of crying and consolabil-
ity, and then the scales measuring EA should be only used to identify generically
agitated children.
In 2004, Sikich and Lerman developed the Pediatric Anesthesia Emergence
Delirium (PAED) scale, the only tool validated to assess ED in young children [56].
The PAED scale includes five items: ‘Eye contact’, ‘Purposeful actions’, ‘Awareness
of the surroundings’, ‘Restlessness’ and ‘Inconsolability’ (Table 22.1). The items
evaluating consciousness (‘Eye contact’ and ‘Awareness of the surroundings’) and
cognition (‘Purposeful actions’) are domains included in the definition of delirium
reported by the Diagnostic and Statistical Manual of Mental Disorders IV and
V. Instead, ‘Restlessness’ and ‘Inconsolability’ reflect disturbance in psychomotor
behaviour and emotion. They can also be an expression of pain, stress, anxiety or
apprehension. The PAED scale has some limitations. First, the items have objective
criteria, but the score for each one is influenced by subjectivity. Second, as described
by the same authors, the last two items could reflect both pain-linked and ED-linked
behaviours. Third, there is no consensus about the cut-off used to identify ED (from
≥10 to ≥16 depending on the author [48].
Locatelli et al. divided the PAED scales in a delirium-specific score (ED1 – ‘Eye
contact’ and ‘Awareness of the surroundings’ and ‘Purposeful actions’) and in non-
specific delirium score (ED2 – ‘Restlessness’ and ‘Inconsolability’). In their study,
ED1 (≥9 points in ‘Eye contact’ and ‘Awareness of the surroundings’ and ‘Purposeful
actions’) was highly correlated with ED episodes in young children undergoing
Table 22.1 FLACC scale [52]

Face, Legs, Activity, Cry, Consolability scale
Face
0. No particular expression/smile, eye contact and interest in surroundings
1. Occasional grimace or frown, withdrawn, disinterested, worried look to face, eyebrows
lowered, eyes partially closed, cheeks raised, mouth pursed
2. Frequent to constant frown, clenched jaw, quivering chin, deep furrows on forehead, eyes
closed, mouth opened, deep lines around nose/lips
Legs
0. Normal position or relaxed
1. Uneasy, restless, tense, increased tone, rigidity, intermittent flexion/extension of limbs
2. Kicking or legs drawn up, hypertonicity, exaggerated flexion/extension of limbs, tremors
Activity
0. Lying quietly, normal position, moves easily and freely
1. Squirming, shifting back and forth, tense, hesitant to move, guarding, pressure on body
part
2. Arched, rigid, or jerking, fixed position, rocking, side to side head movement, rubbing of
body part
Cry
0. No cry/moan (awake or asleep)
1. Moans or whimpers, occasional cries, sighs, occasional complaint
2. Crying steadily, screams, sobs, moans, grunts, frequent complaints
Consolability
0. Calm, content, relaxed, does not require consoling
1. Reassured by occasional touching, hugging or ‘talking to’ distractible
2. Difficult to console or comfort
Table 22.2 PAED scale (Pediatric Anesthesia Emergence Delirium scale) [9]
Not at Just a Quite a Very
all little bit much Extremely
Child makes eye contact with the caregiver 4 3 2 1 0
Child’s actions are purposeful 4 3 2 1 0
Child is aware of his/her surroundings 4 3 2 1 0
Child is restless 0 1 2 3 4
Child is inconsolable 0 1 2 3 4
sub-umbilical surgery with effective caudal block. Moreover, the incidence of ED1
recognized ED cases (sensitivity 93 %) and non-ED cases (specificity 94 %). In
contrast, ED2 correctly identified non-ED cases (specificity 95 %), but was not reli-
able in identifying ED cases (sensitivity 34 %) [46].
The descriptors used in some EA scales and in the PAED scale may overlap with
those used by pain evaluation tools like the Face, Legs, Activity, Cry, Consolability
(FLACC) scale (Table 22.2) [48]. The FLACC scale is a reliable observational score
to assess pain in young children. It was validated to assess postoperative pain in
fully awake children, observing the child over 5 min and recording the worse behav-
iour of each item [51].
The PAED scale and the FLACC scales overlap three criteria: ‘Inconsolability’,
‘Purposeful actions’ and ‘Restlessness’. High scores on restlessness and inconsola-
bility items, even associated with low scores on ED-specific items, may produce a
false-positive diagnosis of ED [48]. On the other hand, if evaluated with FLACC
scale, facial expression in combination with inconsolability and motor restlessness
may diagnose pain instead of ED.
The categories ‘No eye contact’ and ‘No awareness of surroundings’ are unique
to the PAED scale and considered as the most important items for ED identification
[46, 48, 56]. The association of ‘No eye contact’ and ‘No awareness of surround-
ings’ is strongly correlated to ED episodes with 99 % sensitivity and 63 % specific-
ity during the first 15 min after awakening. The association of ‘Abnormal facial
expression’, ‘Crying’ and ‘Inconsolability’ demonstrates 93 % sensitivity and 82 %
specificity to detect pain during the early postoperative period [28].
22.5 Prevention and Treatment
The treatment of e-PONB should be ideally preventive. Pharmacologic and non-

pharmacologic strategies are largely investigated.
22.5.1 Non-pharmacologic Approach
The strong correlation between preoperative anxiety and postoperative behavioural

supported the use of pharmacological and non-pharmacological preventive strate-
gies. Different strategies to decrease preoperative anxiety have been proposed. They
include decrease sensory stimuli during induction of anaesthesia, distraction and
hypnosis, clown therapy, children and parents preparation with movies, videos or
interactive book [72]. The efficacy of parental presence during induction in reduc-
ing anxiety in children is still controversial [30, 36, 44, 49]. The perioperative infor-
mation and distraction reduce the perioperative anxiety, salivary cortisol
concentrations and postoperative morphine consumption in children [70].
Kain et al. evaluated the ADVANCE strategy (anxiety-reduction, distraction,
video modelling and education, adding parents, no excessive reassurance, coaching
and exposure/shaping) for family preparation [38]. Informed parents are involved in
the distraction of their own child before and during the induction of anaesthesia.
This programme decreases preoperative anxiety of children and the incidence of
ED. Moreover, it was more effective than premedication with midazolam on ED
prevention [18].
Recently, Seiden et al. compared the tablet-based interactive distraction (TBID)
method with midazolam premedication in children undergoing ambulatory surgery.
TBID method reduced perioperative anxiety, incidence of ED and the discharge
time and increased parental satisfaction [55].
22.5.2 Pharmacologic Approach
22.5.2.1 Midazolam
Midazolam is the most common used drug to prevent and treat preoperative anx-
iolysis [34, 35]. However, the efficacy of midazolam on preventing e-PONB or its
long-term sequels is controversial. Few studies supported the use of midazolam
premedication to prevent EA [11, 12, 42, 43]. Other studies reported no effect on
e-PONB [11, 12, 15, 18]. Recently, Chuo et al. showed that intravenous midazolam
0.03 mg/kg just before the end of surgery decreases the incidence of EA in children
undergoing elective strabismus surgery. They suggested that premedication mid-
azolam is unable to reduce e-PONB because its effect may not last enough in longer
procedures [10].
22.5.2.2 Alpha2-Adrenergic Agonists

There is strong evidence that intravenous clonidine or dexmetomidine reduced the
incidence of postoperative e-PONB (overall summary odds ratio 0.28, 95 % CI
0.19–0.40) [10]. It should be consider that most of these studies investigated EA,
and not specifically ED, and no studies investigate the effect on long-term behaviour
changes. The administration of alpha2-adrenergic agonists prolongs the time in
recovery room, but this finding seems to be clinically irrelevant [54].
Mikawa et al. found that 4 mcg/kg clonidine premedication is more effective on
reduce EA when compared with clonidine 2 mcg/kg, midazolam 0.5 mg/kg, diaze-
pam 0.4 mg/kg or placebo [52]. Yao et al. demonstrated that intranasal dexmedeto-
midine premedication (1–2 mcg/kg) significantly reduces incidence and severity of
ED in children aged 3–7 years undergoing general anaesthesia [71].
The mechanism of alpha2-adrenergic agonist on e-PONB is unclear. Some
authors hypothized that clonidine reduces the noradrenaline content in adrenergic
areas of the brain increased by all the inhaled anaesthetics [61].
22.5.2.3 Intravenous Anaesthesia with Propofol

The combination of a propofol infusion and nitrous oxide with an effective regional
block or a low dose of opioid represents the best strategy for the prevention of
e-PONB [5, 8]. Propofol, either as a single bolus at the end of surgery or as an infu-
sion, has been shown to decrease the incidence of ED after sevoflurane anaesthesia
[40, 41].
22.5.2.4 Pain Management

Inadequate pain control remains a potential contributor of e-PONB analgesia and is
considered the first act to prevent negative behaviour changes after awakening [1, 2,
5, 11, 12, 39–41].
Caudal block and loco-regional anaesthesia had been showed to reduce the risk
of EA [2, 39]. As well nonsteroidal anti-inflammatory drug administration decreases
the incidence of e-PONB. Intraoperative fentanyl showed an overall decrease in risk
of EA (RR 0.37, 95 % CI 0.27–0.50) (I2 = 54 %) [26, 15]. The incidence of EA and
pain but not ED can be reduced by fentanyl, but not clonidine, before surgery in
children undergoing lower abdominal surgery with sevoflurane without affecting

awakening and discharge from PACU. Whilst this strategy may reduce both EA and
pain after awakening, it was also associated with a higher incidence of PONV the
day after surgery [8].
The mechanisms of action of opioids on the prevention of e-PONB are unclear.
Fentanyl inhibits neurons of the hypocretin-orexin system in the hypothalamus,
which regulate arousal and maintenance of the awake state [45].
22.5.3 When and How to Treat e-PONB?
Clinicians should consider treating e-PONB according to the severity and duration
of the symptoms and concerns over the safety of the child [5]. However, there is no
evidence that if left untreated the ED episodes have any sequelae in young
children.
Clinicians should consider two aims during e-PONB management: protect the
child from self-injury and second provide a quiet setting where the child can recover.
The parental presence in recovery room does not affect the incidence of ED. Heath
providers in PACU should explain the phenomenon and reassure parents that ED is
self-limiting and their child will return to his/her normal behaviour [5].
If clinicians consider treating e-PONB, they first need to define if the negative
behaviour is the expression of ED, pain or both. If it is clearly an ED episodes
(PAED score ≥10 or the association of ‘No eye contact’ and ‘No awareness of sur-
roundings’), a small bolus of propofol (0.5–1 mg/kg) should be enough to control
the child. If the origin of the distressing behaviours is difficult to understand, fen-
tanyl (1–1.5 mcg/kg) should be the first option as it is possible to control pain and
ED [17, 18].
Conclusion
e-PONB significantly affects the awakening of young children. The recognition
of the different components of e-PONB is clinically relevant but remains a chal-
lenge, even for expert nurses and doctors. Prevention of preoperative anxiety,
propofol anaesthesia, associated with adequate analgesia and an accurate assess-
ment during early period after awakening remain the main tools for the preven-
tion of e-PONB.
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Acute Pain Management and Prevention
23
Sylvain Tosetti
23.1 Introduction
Evaluation, management, and relief of pain are fundamental human rights, whatever
the age of the patient [1]. Postoperative pain could be better understood if we
consider its multiple components: sensorial, affective, behavioural, and cognitive.
Cutaneous sensory receptors appear as early as 7 weeks of gestation, and the
spread all over cutaneous surfaces is complete around 20 weeks of gestation. The
pain perception mediators and the thalamo-cortical connections are functional since
the 24th week of gestation. The release of cortisol, endorphins, and norepinephrine
by the 24th week of gestation suggests conscious suffering [2]. The remodelling
process of nociceptor units during gestation includes an increase amount of recep-
tors [3] resulting in low activation thresholds. The descending inhibitory system is
not completely functional after birth as infants are prone to long-lasting hyperalge-
sia [4] due to central sensitization [5].
The subjective and emotional components are predominant and indissociable;
moreover, the ability to verbalize painful experience (pattern, intensity, and loca-
tion) is a key step in evaluation and then transmission of information to parents and
healthcare workers. Pain assessment, not surprisingly, is one of the major challenges
in paediatric pain especially in neonates, preverbal children, or patient with cogni-
tive impairment.
Despite considerable educational efforts and the publication of pain management
guidelines [6, 7], moderate to severe pain still remains an actual problem both in the
hospital setting and at home [8, 9]. The challenge is to provide “safe effective pain
management comprehensively to all children whatever the procedure, clinical
S. Tosetti, MD
Anaesthesia Department, The Montreal Children’s Hospital, Montreal, QC, Canada
e-mail: sylvain.tosetti@mail.mcgill.ca; sylvain.tosetti@chuv.ch

DOI 10.1007/978-3-319-21960-8_23
418 S. Tosetti
setting, developmental state or comorbidities” [10]. Moreover, postoperative analge-

sia is not just to eliminate pain but improve surgical outcomes and prevent chronicity
allowing rapid return to normal activity levels [11] and overall quality of life [12].
23.2 Assessment of Pain
Appropriate management of pain in children depends on valid and reliable assess-

ments and measurements, and pain should be considered as the “fifth vital sign”.
The essence of pain measurement in the postoperative setting is to provide an inten-
sity value useful to make practical decisions and to guide the therapeutic plan. The
use of self-report tools, the gold standard in postoperative pain evaluation, is not
feasible in infants, young children, and children with cognitive disabilities. Different
observational/behavioural scales have validated to measure acute and procedural
pain in infants and children that can’t rate their own pain experience. Table 23.1
resumes the most commonly used tools in different ages and clinical situation.
The child’s parents are essential members of the treatment team. In the day hos-
pital clinical setting, they are the sole dispenser of analgesic medication once back
home. Dedicated pain assessment tools have been developed for parental postopera-
tive pain management, like the Parents’ Postoperative Pain Measure (PPPM).
Unfortunately, even with such tools and correct assessment of pain condition, par-
ents still give few analgesics medications, mainly due to fear of pain medication’s
adverse effects [13, 14].
Children with special needs remain a vulnerable population at risk of poor pain
control after surgery. The underpinning condition often compromises their ability to
Table 23.1 Examples of pain assessment tools depending on the age and/or situation
Age Self-report scale Hetero-evaluation scale
Premature and infants n/a PIPP-R,COMFORT
Before 3 years n/a FLACC
After 5–6 years Faces, Poker Chips, NRS, FLACC, CHEOPS
VAS
Situation
PACU/ward VAS, Faces, Poker Chips, FLACC, CHEOPS
NRS
PICU/NICU VAS, Faces, Poker Chips, FLACC, CHEOPS, COMFORT
NRS
Children with special needs n/a m-FLACC, NCCPC-PV
At home VAS, NRS (if >5–6 years) PPMP (>2 years)
Adapted from PedIMMPACT [21]
n/a not adapted, COMFORT, PIPP-R Premature Infant Pain Profile-Revised [19], VAS visual ana-
log scale, NRS numerical rating scale, (m-)FLACC (modified-)Face, Legs, Activity, Cry,
Consolability, CHEOPS Children’s Hospital Of Eastern Ontario Pain Scale, NCCPC-PV Non-
communicating Children’s Pain Checklist-Postoperative Version [20], PPPM Parents’ Postoperative
Pain Measure
23 Acute Pain Management and Prevention 419
express pain. The parents of children with cognitive impairment usually develop
unique abilities for the assessment of their child level of discomfort and pain [15, 16].
The use of hemodynamic parameters has not been standardized to assess the
effectiveness of analgesia and hence may be prone to imprecise evaluation and deci-
sion management in the perioperative setting. However, new technologies like the
Analgesia Nociception Index (ANI) and the Pupillary Reflex Dilatation (PRD)
deserve a special attention as alternatives for nociception assessment during sur-
gery. Both ANI and PRD monitor the balance between sympathetic and parasympa-
thetic activities, either through heart rate variability or pupillary diameter evolution
in response to a noxious stimulus. These technologies were used to evaluate the
effectiveness of nerve block [17] and remifentanil [18] in children undergoing
sevoflurane anaesthesia.
23.3 Multimodal Analgesia
The timing of the antinociceptive intervention [22] seems to be less important than
the modality and duration [23, 24]. Preventive analgesia focuses on attenuating the
perioperative noxious stimuli and aims to diminish perioperative pain and analgesic
requirements during and after the surgical period. The key point is a judicious use
of multimodal strategies, targeting different pathways of pain signalling, enhance-
ment, or perpetuation. This may also reduce the short-term morbidity (urinary
retention, constipation, nausea and vomiting, respiratory depression, etc.) as well as
some long-term consequences of the acute nociceptive stimulus like the chronic
postsurgical pain [25].
23.4 Control of Acute Pain
23.4.1 Opioid Analgesics (Table 23.2)
Opioids are an essential tool for the prevention and treatment of moderate to severe
pain in children. Due to its efficacy and versatility, they have a central role in multi-
modal analgesia.
Whenever feasible, the oral administration should be preferred in the postopera-
tive setting. The administration on an as-needed basis (PRN: pro re nata) may pro-
vide less clinical disponibility than on a regular basis (ATC: around the clock) or
continuous infusion.
The adverse effects associated to the use of opioids varies from nausea and vom-
iting, pruritus or constipation to more serious like opioid-induced respiratory
depression (OIRD) and opioid withdrawal after prolonged use. Opioid-naive neo-
nates and infants are at more risk of OIRD reducing doses and increasing the admin-
istration intervals increases the opioid safety margin in those populations [26, 27].
The concomitant use of non-opioid analgesics and regional analgesia techniques
further reduces opioid-related risks. An alternative management to common
420 S. Tosetti
Table 23.2 Examples of dosing for currently used opioids and their routes of administration
Opioid Route Age group Dose/interval
Morphine PO Infants and 100–250 μg/kg q3–4H
children
IV bolus Preterm neonate 25–50 μg/kg q3–4H
Full-term neonate 50–100 μg/kg q3H
Infants and
children
IV infusion Preterm neonate 2–5 μg/kg/h
Full-term neonate 5–10 μg/kg/h
Infants and 15–30 μg/kg/h
children
Hydromorphone PO Infants and 40–80 μg/kg q4H
IV bolus children 10–20 μg/kg q3–4H
IV infusion 3–5 μg /kg/h
Fentanyl IV bolus Infants and 0.5–1 μg/kg q1–2H
IV infusion children 0.5–2 μg/kg/h
IN 1–2 μg/kg q1–2H
Sufentanila IV bolus Infants and 0.1–1 μg/kg
IV infusion children 0.1–2 μg/kg/h
IN aerosol 1–2 μg/kg
Remifentanila IV bolus Infants and 1–2 μg/kg
IV infusion children 0.1–1 μg/kg/hb
Methadone IV bolus Infants and 0.05–0.1 mg/kg
children
Nalbuphine IV bolus Infants and 0.1–0.2 mg/kg
children
Tramadol IV or PO start Infants and 1–2 mg/kg q6H (max 400 mg/
dose children day)
Adapted from the Acute Pain Guidelines of the Montreal Children’s Hospital
PO per os (orally), IV intravenous, PR per rectum (rectally), IM intramuscular, IN intranasal, q
every, H or h hour, m minutes
a
Administration limited to acute care setting
b
Higher infusion rates may be used for a limited time duration (possible link to opioid-induced
hyperalgesia)
opioid-induced side effects is the use of naloxone at low dose as a continuous IV

infusion [28].
23.4.1.1 Morphine
Morphine is a very versatile molecule, dispensable through various routes, of which
PO and IV are the most used in hospitalized patients. The hydrophilic properties of
morphine allow longer duration of analgesia compared to more lipophilic opioids.
The total body clearance of morphine represents 80 % of the adult range 6
months after birth and 96 % by 1 year of age [29]. Morphine undergoes hepatic
metabolism and then renal excretion. Infants and premature neonates may display a
large range of elimination half-life due to immaturity of the glucuronidation mecha-

nism. Half-life may vary from 9 ± 3 h in premature neonates, 6.5 ± 2.8 h in term
neonates, to 2.0 ± 1.8 h in infants and children [26, 27, 30].
23.4.1.2 Fentanyl
Fentanyl is frequently used for acute pain prevention and management during
surgery. It also offers benefits in patients with renal failure or in those at risk of
histamine release. Its high lipid solubility promotes fast IV or IN onset with
peak of action of less than 5 min or 15 min, respectively. New dispersion formu-
lation like oral transmucosal fentanyl citrate (OTFC) may be interesting for
moderately painful procedures of short duration, when IV access is not in place
or not desirable [31].
Fentanyl is commonly used as continuous infusion in PICU and NICU.
Premature babies and infants are at risk of accumulation due to a reduced plas-
matic clearance [32].
23.4.1.3 Sufentanil
Sufentanil is eight to ten times more potent than fentanyl. The clearance of sufentanil
in normal children is twice that in adolescents; thus a greater maintenance regimen
is necessary. In opposition to fentanyl, sufentanil presents less accumulation over
time during continuous infusion, thus offering stable plasmatic levels with shorter
half-life and less postoperative respiratory depression. Its lipophilic properties
promote residual analgesia and diminished postoperative agitation in PACU.
Another advantage is its versatility of use through different routes, like intrana-
sal. A single IN dose as premedication may cover analgesia for short and moder-
ately painful procedures, for example, myringotomies, dressing changes, or tubes
removal [33], with the combined advantage of providing preprocedural anxiolysis
and sedation.
23.4.1.4 Remifentanil
Remifentanil is rapidly metabolized in the plasma by nonspecific esterases and does
not accumulate with prolonged infusions [34]. Those properties allow high titrat-
ability and make remifentanil a useful molecule for short procedures with minimal
post-procedural pain, like cardiac catheterization or biopsies. One drawback is the
potential induction of acute opioid tolerance (AOI) and opioid-induced hyperalge-
sia (OIH) [35] precluding its use during a prolonged time and/or at high dose.
Infusion rates between 0.1 and 0.3 mcg/kg/min seem not to induce AOI or OIH [35].
23.4.1.5 Oxycodone
Oxycodone is 1.5–2 times more potent than oral morphine and is provided in short-
acting and long-lasting PO formulation. The metabolism in patients older than 6
months shows stable values and clearance 50 % higher than adults [36, 37]. Onset,
peak, and duration of action are similar to those of oral morphine, thus rendering
oxycodone a valid option for opioid rotation in the context of opioid-induced hyper-
algesia or due to adverse effects.
422 S. Tosetti
23.4.1.6 Hydromorphone
Hydromorphone is commonly used in the paediatric population due to its renal
elimination as an inactive metabolite and lack of histamine release [38, 39]. It is five
to seven times more potent than morphine with similar onset and duration of action.
Common routes of administration are IV, PO, or epidural. Hydromorphone is also a
popular second-choice molecule when opioid rotation is needed. PCA mode is con-
venient; however one should be careful with conversion calculation and the risk of
errors with small boluses.
23.4.1.7 Methadone
Methadone has been safely used for postoperative pain in children [40], burns [41],
or trauma [42], by IV or PO routes. It is also frequently used for opioid rotation and
treatment of opioid withdrawal syndrome due to its NMDA receptor antagonist
properties [43]. The longer duration of action could represent a double-edged sword,
as side effects related to over dosage would last longer. The administration of meth-
adone in opioid-naive patient should only be initiated in a hospital setting, paying
close attention to side effects and various drug interactions.
Methadone is considered a second-line opioid for acute pain management; how-
ever it could be used as a single bolus co-analgesic for procedures that are relatively
painful in the first 24 h [44] like orchidopexy, as weaning from regional anaesthesia
or in the context of surgery with high nociceptive impact like spinal surgery.
23.4.1.8 Nalbuphine
Nalbuphine is an agonist-antagonist semi-synthetic opioid with pharmacological
potency comparable to morphine, usually indicated in procedures with minimal to
moderate pain intensity. Because of its κ-receptor agonist and μ-receptor antagonist
properties, the risk of respiratory depression associated with μ-receptor is prevented.
The effect on the κ-receptor reduced the incidence of emergence agitation in PACU
[45]. Nalbuphine has minimal effect on bowel or bladder function, characteristics of
interest in ambulatory surgery. On the other hand, nalbuphine has a ceiling effect
above 0.4 mg/kg, and the induced sedation may trigger upper airway obstruction.
23.4.1.9 Tramadol
Tramadol is a weak μ-opioid receptor agonist and a monoaminergic (MAO) reup-
take inhibitor [46, 47]. It is derived from codeine and metabolized in the liver
through the CYP2D pathway [48]. Its MAO properties may play a role in minimiz-
ing the μ side effects like constipation and especially respiratory depression [49].
This makes tramadol an alternative option in children with known risk factor for
OIRD, like obstructive sleep apnoea [50]. It was associated with a similar incidence
of postoperative nausea and vomiting as morphine. It has a similar safety profile
either in patients with neuropathic pain and with nociceptive pain [51].
The recommended IV dose is 1 mg/kg and 100 mg is approximately equivalent
to 10 mg of morphine [52, 53]. It has been effectively used by mouth, IV, IM, cau-
dal/epidural, or local infiltration [54] as well as topical application during tonsil-
lectomy [55]. Tramadol/acetaminophen combination is a convenient analgesic
post-tonsillectomy pain control, especially at home. One consideration to rise is the

theoretical risk of hypoglycemia in predisposed patients and serotoninergic syn-
drome with the concomitant use of selective serotonin re-uptake inhibitors.
23.4.1.10 PCA, NCA, and PARCA (Table 23.3)

The patient-controlled analgesia (PCA) gives autonomy to patients over their pain
control and positively influences the latter through patient’s empowerment [56]. It
is a safe alternative for pain management in children of 6 years old and older. PCA
implies the understanding of the concept, the ability to self-evaluate pain, and the
capacity of activate the dosing device. It is also useful in hospital “frequent flyer”
children younger than 6 years of age with closer monitoring from the acute pain
team.
Table 23.3 Example of PCA/NCA/PARCA

Bolus dose Lockout time Basal infusion 1 h limit (μg /
Drug (μg/kg) (minutes) (μg/kg/h) kg/h)
Children >6 years and appropriate developmental/motor state
Morphine PCA 10–30 6–15 0–4–20c 100–400
Morphine + ketamine PCA 10–30 6–15 0–4–20 100 - 400
(1:1)
Hydromorphone PCAa 2–6 6–15 0–1–5 20–80
Fentanyl PCAb 0.2–0.5 6–8 0–0.1–0.5 2–5
Morphine NCA
Preterm neonates 4 30 0–2–4 50
Term neonates 20 20 0–4–10 100
Infants <2 months
Ward: children >2 months 50 15 0–10–20 100–400
Morphine PARCA
Preterm neonates n/a n/a n/a n/a
Term neonates n/a n/a n/a n/a
Infants < 2 months
Ward: children >2 months 50 15 0–10–20 100–400
Hydromorphone NCAa
Preterm neonates 1 30 0–0.5–1 10
Term neonates 4 20 0–1–2 20
Infants <2 months
Ward: children >2 months 6–10 15 0–1–5 50–100
Fentanyl NCAb
Ward: Children >2 months 0.2–1 15–30 0–0.1–0.5 2–5
Adapted from APS guidelines of the Acute Pain Service of the Montreal Children’s Hospital and
of the Mother and Child Hospital Lyon
PARCA parent-controlled analgesia, n/a non-applicable
a
First line for morphine allergy; first line for renal failure; second line for morphine side effects
b
First line for renal failure; second line for morphine side effects
c
0–4–20 = either no basal infusion or between 4 and 20 μg/kg/h
424 S. Tosetti
Younger children or those unable to manipulate the machine (with special needs
or physical restraint) benefit from proxy-controlled analgesia, usually the nurse in
charge of the patient or a parent. A recent survey of 252 American centres [57]
showed that the vast majority of centres (96 %) would provide PCA but has proxy-
controlled analgesia (nurse or parent) in only 38 %. Indeed, this latter technique
provides excellent pain relief for children unable to use it by themselves but may
create some safety challenges given the subjectivity of the proxy, bypassing the
inherent safety features of analgesics dispensed by the patient itself. The main con-
cern is a slightly augmented incidence of respiratory depression [58], easily detected
by proper monitoring and treatment without major consequences. Parent-/nurse-
controlled analgesia for children with developmental delay is efficient and safe but
implies a reinforced monitoring, strict education of the proxy, and clear, written,
instruction [59].
The standard monitoring includes oxygen saturation and respiratory rate. More
advanced measurements like continuous capnography or breathing sounds through
a microphone placed on the neck may further augment safety and prevent
oversedation.
The use of a background continuous infusion is controversial. The aim is to
improve analgesia through an increase of the plasmatic levels of opioids, especially
during night-time, when patient uses PCA less. The increased risk of respiratory
adverse events may not justify the potential analgesic advantages.
An acute pain team, informed proxy or nursing staff, and an adequate monitoring
increase the safety independently of the modality (PCA, NCA, or PARCA) or the
risk of the patient (opioid tolerant, neonates, OSA, etc.)
23.4.2 Non-opioid Analgesics (Table 23.4)
Non-opioid analgesics could be indicated as a single therapy for mild pain and as
adjuvants for moderate to severe pain [60]. The combination of more than one
non-opioid analgesic may potentiate their respective efficacy and has shown
significant opioid-sparing effects [61]. The early use of non-opioid analgesic
adjuvants is associated with reduced risk of serious postoperative opioid adverse
events (OAE) [62].
23.4.2.1 Acetaminophen (Paracetamol)

Acetaminophen is a common co-analgesic medication in children. The multiple
routes of administration allow an easy adaptation to the patient’s needs. The intra-
venous route gives more reliable plasmatic levels, bioavailability, and a slightly
faster onset time over rectal or oral routes [63].
Acetaminophen exerts its analgesic effects through the inhibition or prostaglan-
din release, as a cannabinoid ligand, enhancing inhibitory descending pathways by
serotoninergic interactions [64]. The administration of acetaminophen is safe in
neonates as far as doses are lowered by 50 % taking in account the longer half-life
(up to 7 h).
Table 23.4 Examples dosing of non-opioid analgesics and routes of administration

Drug Age group Route/dose/interval Max. daily dose
Acetaminophen Term infants PO: 10–15 mg/kg Children <100 mg/kg/
(paracetamol) and children: q4–6H day
PR: 20–40 mg/kg q6H Infants 75 mg/kg/day
Neonates <32 PO/PR: 10–15 mg/kg Neonates <32 w.
wPCA PO/PR: 15–20 mg/kg 40 mg/kg/day neonates
Neonates >32 >32 w.
wPCA 60 mg/kg/day
IV paracetamol Term neonates 7.5 mg/kg q6H 30 mg/kg/day
(propacetamol) Infants and 12.5 mg/kg q6H max 3.75 g/day
children
Ibuprofen Children PO/PR: 5–10 mg/kg <40 mg/kg/day
Term neonatesa q6–8H <30 mg/kg
PO: 5 mg/kg
q12–24H
Ketorolac Childrena IV: 0.5 mg/kg q6–8H <2 mg/kg/day
<5 consecutive days
Sucrose Preterm PO 24 % solution: Doses shouldn’t exceed
neonates 0.5 ml 10/day
Term neonates 1 ml
Dexamethasone All ages IV: 0.1–0.15 mg/kg Single bolus
wPCA weeks post conceptional age, q every, H hour
a
Should be used cautiously <6 months of age and reassessed daily
23.4.2.2 NSAIDs
NSAIDs analgesic effects are mediated by the inhibition of COX-1 and COX-2
activity. As a group, they inhibit the biosynthesis of prostaglandins with the subse-
quent reduction of excitatory amino acids [65]. Due to its opioid-sparing effects,
NSAIDS are effective for the reduction of opioid-induced adverse effects [61, 66].
NSAIDS are useful for the prevention of pain rebound during weaning from regional
analgesia. Parents should be taught to give NSAIDS (and acetaminophen) before
wearing off a regional block [67].
Inadequate pain relief has been associated with the fear of opioids’ adverse
effects at home. The association of oral ibuprofen 10 mg/kg every 8 h and oral
acetaminophen 10–15 mg/kg every 6 h provided similar analgesia than PO mor-
phine, with less respiratory adverse effects in children undergoing tonsillectomy
[68]. It is possible that with adequate information, parents would have a better
adherence to the postoperative pain programmes with non-opioid-based analgesic
plan.
Ketorolac is commonly used intravenously, and more recently, the intranasal
route has also been described [69]. Even if it has been safely used in infants, the
lower age limit is still under debate. The administration of ketorolac 0.5 mg/kg
every 6–8 h was associated with a 17 % incidence of bleeding events (fresh blood in
tubes, surgical wound or intra-abdominal bleeding, blood-positive stools) in small
infants (average 21 days) [70].
426 S. Tosetti
Ketorolac use in infants should be limited to specific cases only for a limited
period with close monitoring of renal function and bleeding events. Ketorolac has
been also contraindicated in children undergoing tonsillectomy due to the increase
risk of postoperative bleeding; however a single postoperative dose lowers PACU
pain scores.
23.4.2.3 Dexamethasone
Dexamethasone is frequently used for the prevention of postoperative nausea and
vomiting and to enhance postoperative analgesia after adenotonsillectomy. A single
dose of 0.15 mg/kg during surgery has been associated with a significant opioid-
sparing effects [71].
23.4.2.4 Ketamine
Ketamine, an NMDA receptor antagonist, is used during the perioperative period as
adjuvant for postoperative analgesia and to prevent opioid-induced hyperalgesia in
the context of major surgery with expected high postoperative opioid requirements
[72]. A Cochrane review showed reduced postoperative morphine requirements and
opioid side effects (PONV) [73], but preventive properties and infusion regime need
to be studied in children as no definitive conclusion has been drawn yet [74]. Even
if the usual ratio of morphine/ketamine is 1:1, the optimal ketamine dose as an
adjunct in PCA has not yet been determined.
23.4.2.5 Clonidine/Dexmedetomidine
Clonidine and dexmedetomidine are both α-2 central agonists with sedative and
analgesic properties. Dexmedetomidine has been associated with the reduction of
postoperative analgesic requirements and reduction in opioid-related adverse effects
after adenotonsillectomy [75].
23.4.2.6 Sucrose
Sucrose 24 % is known to trigger the release of endorphins that contribute to pain
control [76]. Sucking with or without sucrose seems to provide the same effect on
pain reduction [77].
23.4.2.7 Gabapentinoids
Gabapentinoids (gabapentin and pregabalin) are α-2-δ modulators with demon-
strated analgesic activity and opioid-sparing properties in paediatric scoliosis sur-
gery. Preoperative administration 30 min before surgery (10–15 mg/kg, max
600 mg) seems efficient, followed by a dose every 8 h, for 2–4 weeks [78].
23.4.2.8 Lidocaine Infusion

Lidocaine as intravenous infusion has demonstrated analgesic and opioid-
sparing properties in adults (bolus 1.5 mg/kg, followed by 1.5 mg/kg/h).
Currently, there are no paediatric data except a case report of a terminally ill
child successfully treated [79] with an infusion of up to 3 mg/kg/h, without
toxic adverse events.
23.4.3 Regional Anaesthesia
Regional anaesthesia, as part of a multimodal analgesia regimen, could be consid-

ered the standard of perioperative care for various procedures in children. The use
of regional analgesia reduces the peri- and postsurgical stress [80], prevents postop-
erative pain, and allows significant reduction on opioid consumption and opioid-
related adverse events [81–84]. Regional anaesthesia in children is a safe practice in
experienced and well-trained hands [85–87], even when performed asleep [88]. The
use of ultrasound guidance has improved the safety and efficacy of most peripheral
blocks [81].
The timing of block administration (before or after the surgical procedure), the
type (central or peripheral), and the modality (single shot, continuous, PCA) vary
depending on the type of surgery, the conditions of the patient (hospitalized or
ambulatory), and the training of the caregiver.
Epidural blocks represent the most common regional analgesia technique used for
pain prevention and treatment. Neuraxial techniques are effective and safe [87], with a
rate of severe complications for caudal anaesthesia as low as 0.03–0.005 % [85].
Nevertheless, some catastrophic complications have been described following epidural
placement [89] promoting the search for alternatives to central blockade [90, 91].
Current evidence strongly supports the use of peripheral regional anaesthetic
techniques in children. Generally speaking, single-shot blocks could be used for the
majority of ambulatory procedures, providing analgesia for the first 6–12 h.
Ultrasound guidance has improved the visibility of targets and allowed real-time
needle tracking, thus reducing the amount of blind needle paths. Interfascial spread
of local anaesthetics (LAs) allows injection from certain distance of the nerve bun-
dles. The needle is being placed between two fascias, allowing the spread of the
solution towards the target, without needle repositioning. This concept, already
used in blocks like obturator, pectoralis block (PEC 1 + 2), and transversus abdomi-
nis plane block (TAP), can be extended to almost every nerve that courses in between
two fascias, like the saphenous and mid-thigh (between sartorius and vastus latera-
lis) and the median nerve at the forearm (between flexor digitorum superficialis and
profundus), etc.
Continuous peripheral nerve blocks (CPNBs) are indicated in procedures associ-
ated with significant pain for more than 24–48 h [23, 25]. Nowadays, more complex
surgical procedures are performed on an outpatient basis or with shorter hospital
stay, and the use of CPNBs has been extended after hospital discharge [92]. Recently
large case series of children undergoing orthopaedic surgery demonstrated the
safety and efficacy of that technique [93]. The use of CPNBs in the ambulatory set-
ting demands careful preparation and follow-up including troubleshooting protocol
for complications, inadequate analgesia, and/or catheter removal. The logistic of
those services could be too complicated for small-volume facilities.
The continuous infusion is the most common delivery mode of LAs through a
peripheral or a central catheter. Similar to PCA or PARCA, adequately chosen prox-
ies and children may benefit from the patient-/proxy-controlled nerve analgesia
(PCNA) or from the patient-/proxy-controlled epidural analgesia (PCEA) [94, 95].
428 S. Tosetti
Children, especially neonates and infants, require a careful selection of the type
and dosing of LAs to avoid systemic toxicity [83]. L-enantiomers like ropivacaine
and levobupivacaine have safer toxicity profile than bupivacaine [96]. Bupivacaine
combined with epinephrine and injected at low concentration is still widely used but
should be avoided for continuous infusions.
Description of block techniques goes beyond the scope of this chapter [96,
97]. Table 23.5 describes common regional blocks and dosing regimens used in
paediatrics and Table 23.6 some suggested LA doses, volumes, and infusion
protocols.
The use of adjuncts to LA solutions prolongs the duration of action of single-shot
blocks and the efficacy of continuous infusion [98, 99] (Table 23.7).
Table 23.5 Common regional blocks in paediatrics and examples of dosing regimens
Peripheral blocks
Level Site Ropivacaine 0.2 % (2.5–3 mg/
kg)a
Upper limb Brachial plexus: 0.2–0.3 ml/kg (max 15–20 ml)
Interscalene
Supra-/infra-clavicular
Axillar
Median nerve (elbow, forearm) 0.1 ml/kg/nerve (max 5–6 ml)b
Radial nerve (elbow, forearm)
Ulnar nerve (elbow, forearm)
Hand Wrist (median, radial, ulnar) 0.05–0.1 ml/kg/nerve
Digital blocks (max 2–3 ml)b
Lower limb Sacral plexus: 0.2–0.5 ml/kg (max 20–25 ml)
Sub-gluteal
Anterior mid-femoral
Popliteal (lateral approach)
Lumbar plexus: Lumbar
Lumbar (paravertebral) 0.2–0.5 ml/kg (max 20 ml)
Femoral Femoral and saphenous
Saphenous (mid-thigh) 0.2–0.4 ml/kg (max 15–20 ml)
Fascia iliaca 0.2–0.3 ml/kg (max 15 ml)
Obturator 0.1 ml/kg/nerve (max 5 ml)
Lateral femoral cutaneous
Foot Ankle (tibial, saphenous, peroneal) 0.1 ml/kg/nerve (max 5 ml)b
Toe blocks (ring approach)
Thorax PEC blocks 1 + 2 0.2–0.3 ml/kg/site (max
15–20 ml)
Intercostal 0.05–0.1 ml/kg/rib (max
2–3 ml)
Paravertebral 0.1 ml/kg/space
(max 5 ml/space)c
Table 23.5 (continued)

Peripheral blocks
Abdomen TAP subcostal or lateral 0.2–0.3 ml/kg/side
Quadratus lumborum (max 15 ml/side)
Paravertebral lumbar
Umbilical 0.1 ml/kg/nerve (max 5 ml)
Ilio-inguinal, ilio-hypogastric 0.1–0.2 ml/kg (max 10 mld)
Genitalia Penile 0.1 ml/kg/side (max 2.5 ml/side)
Pudendal 0.1–0.2 ml/kg (max 10 ml)
Head and Scalp blocks 0.05–0.1 ml/kg/nerve
neck Peri-orbital (supra/infra) (max 2 ml/nerve)
Peri-auricular (greater/lesser auricular)
Maxillary 0.1–0.2 ml/kg/side (max 10 ml)
PEC pectoralis block 1 + 2, TAP transversus abdominis plane block, LA local aesthetic
a
Alternatively levobupivacaine 0.25 % or dilute bupivacaine at 0.125–0.175 %
b
The solution doesn’t need to spread all over the nerve
c
Could be injected at one space to facilitate the insertion of a catheter
d
Higher volume augments the risk of spread to the femoral nerve
Table 23.6 Examples of infusion guidelines of local anaesthetics and adjuncts

Molecule Solution Limits
Ropivacaine 0.1–0.2 % 0.2 mg/kg/h <1 month
0.3 mg/kg/h <6 months
0.4 mg/kg/h >6 months
Fentanyl 1–2 μg/ml 1–2 μg/kg/h
Sufentanil 0.1–0.2 μg/ml 0.1–0.2 μg/kg/h
Clonidine 1 μg/ml 0.5–1 μg/kg/h
PCEA/PCNA Ropivacaine 0.1–0.2 % 0.1 mg/kg/h + bolus 0.1 mg/kg, lockout
(>5–6 years of age) 10 min
PACEA/NCEA Ropivacaine 0.1–0.2 % 0.2 mg/kg/h + bolus 0.1 mg/kg, lockout
(>1 year of age) 30 min
Adapted from APS Guidelines Mother and Child Hospital Lyon
PCEA patient-controlled epidural analgesia, PCNA patient-controlled nerve analgesia, PACEA
parent-controlled epidural analgesia, NCEA nurse-controlled epidural analgesia
23.4.4 Non-pharmacological Management of Pain and Anxiety
Anxiety and other psychological factors have significant impact on pain intensity and
analgesic requirements. There is growing evidence supporting the benefits of family
centred non-pharmacological techniques during the perioperative period [100].
Many strategies have been described, including videogames or tablet-based dis-
traction [101], clown doctors, child life specialists, and family-based preparation
[102]. Children, especially under the age of 8 years, display a vivid imagination and
caregivers can take clinical advantage of the “magical thinking” and the potent
effect of the context-induced placebo analgesia [103].
430 S. Tosetti
Table 23.7 Common adjuncts to nerve blocks and examples of dosing regimens
Molecule Site of injection Suggested dosing
Morphinea Epidural (caudal, lumbar, or 30–50 μg/kg q12–24H
thoracic)
Intrathecal 3–5 μg/kg (single shot)
Clonidineb Epidural (co-administration) 1–2 μg/kg (single shot)
Peripheral (intravenous 1–2 μg/kg (single shot)
co-injectionc)
Adjunct to continuous infusion 0.5–1 μg/kg/h
of LAs
Dexamethasone Intravenous co-injectionc 0.1–0.15 mg/kg (usually single shot,
up to q8H)
q every, H hours, LAs local anaesthetics
a
Mandatory respiratory monitoring
b
For children >1 year old
c
Intravenous co-injection displays the same efficacy as perinervous injection
Hypnosis is increasingly being recognized as an effective technique for pain con-

trol in the perioperative period. Patients receiving hypnosis present significantly
reduced anxiety level and shortened hospital stay after surgery [104].
23.5 Time to Procedures Specific Strategies?
Paediatric anaesthesia societies have proposed general guidelines for perioperative

pain management [6]. Few specific pharmacological or non-pharmacological inter-
ventions could be used as a sole strategy. There are currently no specific procedure-
related guidelines, as presented by the PROSPECT project (www.postoppain.org)
in adults [105]. This could be due to the fact that most of the efforts were directed
to evaluate specific analgesic methodologies and few studied procedure-specific
solutions. The current heterogeneity of outcomes and methodologies in paediatric
studies precludes an adequate comparison between techniques and development of
robust procedure-specific guidelines [106].
23.6 Analgesia at Home
Most surgical procedures are nowadays performed on an ambulatory regime.

Discharge information and parental education about pain evaluation, analgesic plan,
and rescue medication management are of paramount importance. Not unusually
parents are reluctant to provide rescue medication [9, 107] due to a variety of factors
and misconceptions. A detailed analgesic plan should be part of the postoperative
surgical indications: it should include the doses, timing, and a plan B in case of
inadequate analgesia or adverse effects. Whenever possible, the timing of medica-
tion should fit the child/family activity, for example, synchronizing medication dur-
ing meal times, at bedtime, etc. [108].
Conclusions
Efficient pain relief is of paramount importance in the perioperative care of infants
and children. Postoperative pain in children presents specific physiological, ana-
tomical, psychological, and pharmacological challenges. The analgesic modali-
ties and routes of administration should be adapted to the age, unique anatomy,
developmental status, and physiology. A dedicated acute pain service (APS) team
best provides postoperative pain management, especially in the context of more
complex techniques during admission. Multimodal perioperative pain manage-
ment is a key concept for postoperative pain prevention and treatment. Opioids
are the preferred medication for severe pain. They should be associated with non-
opioid medications, regional anaesthesia/analgesia, and non-pharmacological
strategies. Future research should focus on clinical outcomes other than pain
when evaluating paediatric procedure-specific techniques.
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Long-Term Consequences of Anesthesia
(and Surgery) on the Infant Brain 24
Tom Giedsing Hansen
24.1 Introduction
Very few issues (if any) within pediatric anesthesia have caused so much concern
and emotional gravity than the fact that the past roughly 15 years, a plethora of
animal studies have uniformly shown that exposure to most of the currently used
anesthetics possibly during a vulnerable period of brain development (i.e., brain
growth spurt or peak of synaptogenesis) may lead to neurodegeneration (particu-
larly apoptosis) and abnormal synaptic development [1–4]. Importantly, the
observed morphological abnormalities are associated with functional deficits in
learning and behavior later in life [5]. Initial studies were mainly performed in
immature rodent pups, but more recent studies have included nonhuman primates
(rhesus monkeys) [6–8]. Given the number of neonates, infants, and young children
anesthetized annually worldwide, these findings could have significant public health
implications. Both gamma-aminobutyric acid (GABA) agonists (e.g., inhalational
anesthetics, propofol, benzodiazepines) and n-methyl-d-aspartate (NMDA) antago-
nists (e.g., ketamine and nitrous oxide) are implicated [3, 4]. Although results from
animal studies using opioids, α-2 receptor agonists, and xenon are less overwhelm-
ing – and in some cases/circumstances have indicated that these agents may in fact
possess neuroprotective properties – they are generally inconclusive.
Translating these animal studies into a human clinical context is difficult. How
do various developmental stages of brain development in animal models translate
into humans? The anesthetic techniques and managements used in the majority of
T.G. Hansen, MD, PhD (*)

Department of Anesthesiology and Intensive Care – Pediatric Section,
Odense University Hospital, Odense DK-5000, Denmark
Institute of Clinical Research – Anesthesiology, University of Southern Denmark,
Odense DK-5000, Denmark
e-mail: tomghansen@dadlnet.dk

DOI 10.1007/978-3-319-21960-8_24
438 T.G. Hansen
animal (rodent) studies are extremely different to normal clinical practice, for exam-
ple, the use of supra-clinical doses and long duration of exposure to anesthetic drugs
sometimes resulting in excessively high mortality (20–80 %). Additionally, the use
of multiparameter monitoring and control of airway and respiration are difficult (or
even impossible) due to the small size of the neonatal animals, which also precludes
repeated blood gas and glucose measurements due to small circulating blood vol-
umes [3]. This may be of utmost importance. A recent animal study by Wu et al.
compared the effects of mechanical ventilation and spontaneous breathing on out-
come in 14-day-old rats exposed to isoflurane and sevoflurane. Compared with
mechanical ventilated rats, spontaneous breathing rats had significantly higher mor-
tality, neuroapoptosis, and impaired neurocognitive outcome [9].
24.2 Limitations of Animal or Preclinical Data
The initial animal studies on anesthesia-related neurotoxicity and the developing

brain were never driven by any clear or well-defined associations between general
anesthesia and subsequent specific neurocognitive deficits in humans or the applica-
bility to clinical care of human infants. Additionally, many inherent factors limit the
applicability of animal-derived data to humans. More specifically, ontogenic differ-
ences in neurodevelopment between humans and animals that may impact outcome
are largely unknown. Factors regarding the administration of anesthesia and study
design, for example, differences in anesthetic drug potency between human and
animals, lack of surgical stress, differences in monitoring and correction of physi-
ologic, metabolic, and biochemical aberrations induced by anesthetic drugs and sur-
gery, use of excessively high doses of anesthetics for a long period of time, and use
of agents that are rarely used in modern clinical practice (such as ketamine, isoflu-
rane, and nitrous oxide), may complicate matters [1]. Furthermore, there is a lack of
systematic evidence for the clinical benefits of animal research in general and ani-
mal neuroscience in particular [10].
24.3 Normal Development of Human Brain
Morphology and function of the brain is not a static process but rather a complex,
continuous, and lifelong process. Immediately after birth, the brain is about 25 % of
its adult size and unevenly matured [3, 4]. The brain stem and spinal cord are rela-
tively well developed, whereas the limbic system and cerebral cortex are still imma-
ture. Despite being produced before birth, the cortical neurons are poorly connected,
and most synapses are produced after birth during a peak synaptogenesis where the
rate of cortical synapse formation is estimated to be two million new synapses per
second. At the age of 2 years, the cerebral cortex comprises more than 100 trillion
synapses. The newborn brain contains little myelin, and myelination appears to be
virtually an “automatic or innate” process in that its sequence succession is very
predictable, and it appears that severe malnutrition is the only single individual
24 Long-Term Consequences of Anesthesia (and Surgery) on the Infant Brain 439
environmental factor known to impact myelination. Sensory afferent stimuli before

and after birth differentiate the function of neurons and neural pathways, ensuring
neuroplasticity of the CNS [3, 4]. However, this plasticity may be a two-edged
sword in that it implies that on one hand young children’s brains are more open to
learning and enriching influences on the other they may also be more vulnerable and
susceptible to environmental changes. Selection and formation of active neural cir-
cuits (pruning) occurs throughout life but is much more common in early childhood.
This initial excess of neurons and synapses is followed by significant neuronal death
and decline in synapses. This normal and DNA-programmed cell death or apoptosis
is necessary to ensure normal CNS morphology and function. It is an intimate and
integral part of normal brain development and maintenance. The net result is that
<50 % of neurons survive into adult life. Any interference with this normal apop-
totic process may have detrimental effects to the central nervous system. All com-
monly used anesthetics have been shown in preclinical studies to markedly increase
neuroapoptosis. However, several other studies have subsequently also documented
acute neuronal cell loss, altered dendritic architecture, reduced synaptic density,
destabilization of the cytoskeleton, and cell cycle abnormalities following exposure
to all commonly used general anesthetics [3, 4]. For obvious reasons, it remains to
be proven whether similar anesthesia-induced neurodegeneration occurs in human
clinical settings.
24.4 Human Studies
Relative to the magnitude of animal investigations, the number of human studies is

relatively limited. The majority of these are listed in the reference list and have
recently been reviewed in details elsewhere [11, 12], where more detailed informa-
tion about these studies can be obtained. Fortunately, all these studies have been
inconclusive, that is, it has been very difficult to show whether this animal phenom-
enon has a human corollary [13–26]. In the following, the most important issues
related to the human studies are presented.
24.5 Relevant Human Outcome Measure
It remains to be determined how anesthesia-related neurotoxicity (if it exists) will

reveal itself in humans. Contrary to babies with, for example, fetal alcohol syn-
drome or babies born to mothers on certain antiepileptic drugs in whom distinctive
mental and physical defects are well described, any detrimental effect associated
with anesthetic exposure in infancy must be of a minor nature [3]. Otherwise, it
would be easy to demonstrate and it would most likely have been suspected many
years ago. Therefore, the following questions are of utmost importance: what is a
meaningful outcome measure and when and how do we best measure it? Should we
search for developmental disorders in preschool, learning disabilities (LD) in ele-
mentary school, social disturbances in adolescence, or psychiatric disorders in
440 T.G. Hansen
adulthood, and what relevance has loss of various cognitive functions or early
dementia in the elderly? To what extent are sensorimotor deficits or psychiatric
disorders relevant? More importantly, how well does a single short-term interim
measure performed in early childhood or adolescence adequately predict outcome
later in life, and what are the long-term consequences of that? Currently, we do not
have the answers.
Learning disabilities is a very crude outcome influenced by many underlying
factors, for example, chronic diseases and environmental factors. More importantly,
LD is not a specific neuropsychological outcome measure, but rather a categorical
determination arising from differences between a child’s educational outlook (e.g.,
IQ) and his or her actual achievement. Focusing on the cumulative incidence of LD
implies that follow-up is ceased when an LD is identified, and a priori it is then
thought that the LD will persist and never disappear. This impedes estimation of the
true prevalence of this outcome measure. Further, a child labelled with LD may at
some point in life have a change in achievement placing him or her back in the nor-
mal range. Such an incident will not be detected by the current used study designs.
Assessment of academic performances has a pragmatic advantage over, for exam-
ple, IQ testing or similar in that parents are likely to be more interested in how their
child will do in school. A recent study employing extensive and repeated neurode-
velopmental testing suggested that group testing such as academic performance
may lack sufficient sensitivity to detect smaller, minor, or more subtle neurocogni-
tive impairment between children exposed and children not exposed to anesthesia
compared with individually administered cognitive tests [26]. It has been claimed
that studies using individually administered tests of cognition may be more likely to
be positive into any potential phenotype (e.g., abnormalities in speech and lan-
guage). However, at this point, we do not know under what circumstances individ-
ual cognitive testing are actually also meaningful human outcome measures. Many
of the outcomes used in these studies are interrelated. One question quickly arises:
exactly how different are individually tests of speech and language and school tests?
Certainly, good academic achievements require good speech and language skills
[27].
Attention-deficit hyperactivity disorder (ADHD) has also been tested as a pri-
mary outcome measure to assess for anesthesia-related neurotoxicity [13]. However,
the diagnosis and treatment of ADHD are highly disputed. The diagnosis of ADHD
is afflicted by ascertainment bias as demonstrated by the large variation in its preva-
lence across countries, states, races, genders, and ethnicities. Further, in 2011, two
million more children were diagnosed with ADHD in the USA compared with
2003, and overall one out of five US teenage boys was labelled with an ADHD
diagnosis (more than two-third of these were taking long-term medication such as
dexamphetamine). Thus and because ADHD is associated with an array of psychi-
atric disorders and learning disabilities, its value as an outcome measure in studies
on anesthesia-related neurotoxicity is questionable [28, 29]. Recently, autism spec-
trum disorder has also been used as outcome measure in these types of studies [30].
Similar arguments as just mentioned in relation to ADHD can been applied regard-
ing this outcome measure [31].
24.6 Migration
The degree of migration of study subjects is of major concern in many of the human
cohort studies published thus far. As high a proportion as one-third of the original
cohort has been reported in some series to move such that information from these
individuals could not be retrieved [13, 14]. This is an important issue because sig-
nificant differences between migrants and nonmigrants are well noted in some of
these cohort studies increasing the likelihood for selection biases [32]. Families
with a significantly ill child living in close proximity to a major pediatric center are
less likely to migrate. Furthermore, children with significant comorbidities are more
likely to suffer neurobehavioral problems and require multiple anesthetics.
24.7 Sample Size Issue
The problem surrounding the “sample size issue” was addressed in one of the first
human studies on this topic [23]. Since then it has become increasingly apparent
that sufficiently large sample sizes are needed to detect modest associations among
the multitude of perioperative factors that impact neurocognitive outcomes (see
later). In fact, very few of the current available human cohort studies have large
sample sizes [21, 22]. The introduction of multiple (individual) testings has been
employed to compensate for this fact [19]. However, such an approach carries a
high-risk Type I statistical error, which (as mentioned earlier) may be a particular
risk in the present context in that many of the tests use are interrelated [27]. Similar
problems have been encountered in studies on postoperative dysfunction (POCD) in
the elderly [33, 34]. The reality is that to date, there are no reliable tools available to
test for the presence of POCD, and simply increasing the number of tests to assess
and classify POCD also increases the rate of false-positive classifications.
24.8 Duration and Number of Exposures
Preclinical data suggests that larger anesthetic doses and longer duration may be
associated with greater effects (i.e., poorer outcome) [1–9]. Similarly, human
studies suggest that one single and short-term anesthetic (and surgical) exposure
seems harmless, whereas multiple exposures are associated with poorer outcome
(i.e., increased hazard ratios) [14–26]. However, such an association is not neces-
sarily causal, because children who require multiple surgeries are far more likely
to suffer serious underlying conditions that – as mentioned above – may indepen-
dently impact neurodevelopment. Additionally, the effects from surgeries (e.g.,
stress responses, pain, and neuroinflammation) cannot be disentangled from that
of the anesthetic itself in these studies [11, 12]. Very few studies have focused on
longer exposures/procedures [35, 36]. In these studies, it appears that many other
confounding factors are by far more important than merely exposure to
anesthetics.
442 T.G. Hansen
24.9 Age at Exposure
In preclinical studies, timing of exposure to anesthetic drugs seems to play a pivotal

role in mediating the degree of injury as the brain may have periods of increased
vulnerability during different stages of development [37]. In young rodents, the
period of greatest vulnerability appears to be between postnatal 4 and 10 days
(~PD7) and corresponds to the period of the peak synaptogenesis. In guinea pigs,
this corresponds to mid-gestation, whereas in rhesus monkeys, it corresponds to up
to 35 days of age [3, 4]. In humans, the period of greatest synaptogenesis is thought
to occur during the last trimester and up to 2 to 3 to 4 years postnatally. However,
there is no evidence to support this contention. Additionally, all brain regions may
not develop uniformly, and different regions may be differentially susceptible dur-
ing different stages of development [3, 4, 38, 39]. A free available website was
launched almost 10 years ago to improve accuracy in extrapolating vulnerable peri-
ods between different animal species. This website used more modern models and
the newest brain developmental data (www.translatingtime.net) [38, 39].
Unfortunately, this new bioinformatics method has not yet been implemented in
animal studies on anesthesia-related neurotoxicity. By integrating data from core
developmental stages and events from many mammalians into a statistical model,
these animal models suggest that the developmental stage of, for example, a rodent
cerebral cortex at PD-7 may actually correspond to the maturational stage of the
human brain at the very beginning of third trimester [39]. This may well mean that
animal experiments using 7-day-old rodents may correlate with providing anesthet-
ics to extremely premature babies.
More recent animal studies have shown that neuronal cell death also occurs in
isoflurane- or propofol-exposed adult mice. Two recent studies have demonstrated
that different brain regions are vulnerable at different ages, as neurogenesis peaks at
different ages among brain regions, and that brain regions with ongoing adult neu-
rogenesis (e.g., dentate gyrus and olfactory bulb) seem to be vulnerable far beyond
the previously suggested window of vulnerability, potentially far into adulthood
[40, 41]. Thus, in animals, there may be no such thing as a “safe anesthetic period.”
Still, it is the general belief that the youngest and most immature infants are at
greatest risk. This is unfortunately not reflected in the current human studies pub-
lished so far on this topic as these usually comprise very few neonates and infants.
The few studies that do comprise infants show no differences in outcome following
minor surgeries compared to controls but major differences following major surger-
ies, for example, neurosurgery [21, 22, 35].
24.10 Impact of Surgery
Very few of the available human cohort studies have focused on a single and well-
defined surgery [21, 22]. Rather, most studies have pooled data from multiple sur-
geries (and diagnosis). This is very unfortunate because both surgery and underlying
pathology independently influence subsequent neurocognitive outcome. In infants
undergoing inguinal and pyloric stenosis repair, academic achievements in
adolescence are comparable to the background population [21, 22] and much better
compared to infants undergoing, for example, neurosurgical procedures [35].
24.11 Gender Issue
Another important confounding factor is gender. Gender (male) can influence the
need for surgery, for example, inguinal hernia and pyloric stenosis repair [21, 22].
Interestingly, it is widely recognized that gender independently impact neurobehav-
ioral outcome (and mortality) in later life. Additionally, gender may also influence
an individuals’ susceptibility to toxicity – which is an issue also observed in pre-
clinical studies [3].
24.12 Other Important Factors
The single most important cofactor is the effects of surgery itself. The impact of
stress responses, nociception, and neuroinflammation need much more clarification.
Higher socioeconomic status and particularly parental (maternal) education are
strongly associated with better neurobehavioral outcome and with enhanced capac-
ity to recover from any injury. Interestingly, parental education is more valid than
parental occupation and socioeconomic status as these later are subject to changes
over time, whereas after the age 30 years, parental educational length rarely changes
[42]. Noteworthy, in several of the available human studies, known confounding
factors (e.g., gender, age (birth weight), congenital malformations, maternal age,
and parental level of education) more strongly affect outcome than exposure to
anesthesia and surgery [21, 22].
Many other perioperative factors have the possibility to impact later neurodevel-
opment possibly to a much larger extents than a brief anesthetic exposure in young
life [43]. These include a number of physiological, metabolic, and biochemical fac-
tors induced by general anesthetics and surgery, but also the more important ques-
tions: who, where, when, and how should small children be anesthetized? For more
information about all these issues, the readers are referred to www.safetots.org.
24.13 Ongoing and Future Studies
Currently (i.e., primo 2015), there are at least three ongoing prospective studies. In
the Pediatric Anesthesia and Neuro-Development Assessment (PANDA) study,
about 500 ASA 1 and 2 children scheduled for inguinal hernia repair before 3 years
of age will be compared with an unexposed sibling from a retrospective database.
At the age between 8 and 15 years, children will be extensively assessed neurode-
velopmentally. Initial results from this study are pending.
The GAS study is a multisite, randomized controlled trial (RCT) in which infants
undergoing inguinal hernia repair before 60 weeks postconceptual age are random-
ized to either general anesthesia or regional anesthesia (spinal or caudal) comparing
444 T.G. Hansen
neurodevelopmental outcome. The follow-up time is 5 years. Enrollment has been

completed, but final analysis results are not expected before 2017.
Using an extensive battery of neurocognitive tests (including the operant test bat-
tery used in relation to nonhuman primates), the Mayo Safety in Kids study intends
to compare the performance of children previously exposed to anesthesia before the
age of 3 years with children never exposed. Enrollment is ongoing, but the first
results will not be available before 2016.
24.14 Conclusion
Fortunately, it has proven difficult to demonstrate a human equivalent to the animal

data demonstrating anesthesia-related neurotoxicity in the developing brain. This
fact indicates that the problem most likely is less significant than previously feared.
However, that does not mean that the problem is not important. At this point, we
know that one single and brief anesthetic exposure seems “safe” and that repeated
anesthetic (and surgical) exposures have consistently been associated with poorer
outcomes (LD, ADHD, etc.). Importantly, these associations are not necessarily
causal, as children who require multiple surgeries are far more likely to suffer seri-
ous underlying medical disorders that can impact neurodevelopment. Furthermore,
many other perioperative factors influence neurocognitive outcome, and each and
every one of them more significantly do so than anesthetic/surgical exposures [40].
Very few neonates, infants, and young children undergo unnecessary anesthesia and
surgery. It is ethically unacceptable to subject infants to invasive procedures without
the benefit of anesthesia and analgesia. The decision to delay surgery or a diagnostic
procedure should be made with a clear understanding that any real added risk of
delay is being balanced against a still ambiguous and unknown risk of toxicity.
Other than taking sensible precautions (e.g., briefest possible exposures to anesthet-
ics, usage of regional techniques and possibly more opioids, and ensuring as much
parental contact as possible), there is no need to change current anesthetic clinical
practice and no need to postpone or cancel truly urgent surgeries.
24.15 Author’s Comment
In this author’s mind, it is highly possible that any definite link between anesthetic
drugs or techniques and subsequent neurobehavioral impairment in children will
never be established. Hopefully, in this search for any such potential causality in
perioperative young children exposed to anesthetics, anesthetists, surgery and sur-
geons, their overall outcomes will be improved.
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ultrastructural properties of developing synapses in young rats. Neurotox Res 17:179–188
3. Vutskits L, Davis PJ, Hansen TG (2012) Anesthetics and the developing brain: time for a
change in practice? A pro/con debate. Paediatr Anaesth 22:973–980
4. Vutskits L (2012) General anesthesia: a gateway to modulate synapse formation and neural
plasticity? Anesth Analg 115:1174–1182
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6. Paule MG, Li M, Allen RR et al (2011) Ketamine anesthesia during the first week of life can
cause long lasting cognitive deficits in rhesus monkeys. Neurotoxicol Teratol 33:220–230
7. Slikker W Jr, Zou X, Hotchkiss CE et al (2007) Ketamine anesthesia during neuronal cell death
in the perinatal rhesus monkey. Toxicol Sci 98:145–158
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developing rhesus monkey. Neurotoxicol Teratol 33:592–599
9. Wu B, You S, Zhenq Y et al (2014) Physiological disturbance may contribute to neurodegen-
eration induced by isoflurane or sevoflurane in 14 day old rats. PLoS One 9, e84622
10. Pound P, Bracken MB (2014) Is animal research sufficiently evidence based to be a corner-
stone of biomedical research? BMJ 348:g3387
11. Hansen TG (2013) Neurotoxicity, general anesthesia and the developing brain: what have we
learned from the human studies so far? Curr Anesthesiol Rep 3:175–183
12. Hansen TG (2015) Anesthesia-related neurotoxicity and the developing animal brain is not a
significant problem in children. Paediatr Anaesth 25:65–72
13. Sprung J, Flick RF, Katusic SK et al (2012) Attention-deficit/hyperactivity disorder after early
exposure to procedures requiring general anesthesia. Mayo Clin Proc 87:120–129
14. Wilder RT, Flick RP, Sprung J et al (2009) Early exposure to anesthesia and learning disabili-
ties in a population-based birth cohort. Anesthesiology 110:796–804
15. DiMaggio C, Sun LS, Kakavouli A et al (2009) A retrospective cohort study of the association
of anesthesia and hernia repair surgery with behavioral and developmental disorders in young
children. J Neurosurg Anesthesiol 21:286–291
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exposure to anesthesia and surgery. Pediatrics 128:e1053–e1061
17. Sprung J, Flick RP, Wilder RT et al (2009) Anesthesia for cesarean delivery and learning dis-
ability in a population-based birth cohort. Anesthesiology 111:302–310
18. DiMaggio C, Sun LS, Li G (2011) Early childhood exposure to anesthesia and risk of develop-
mental and behavioral disorders in a sibling birth cohort. Anesth Analg 113:1143–1151
19. Ing C, DiMaggio C, Whitehouse A et al (2012) Long-term differences in language and cogni-
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20. Bartels M, Althoff RR, Boomsma DI (2009) Anesthesia and cognitive performance in children
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Prevention of Chronic Postsurgical Pain
25
Gonzalo Rivera
25.1 Background
Chronic postsurgical pain (CPSP) is conceptualized as pain that extends beyond the
period of normal tissue healing, and it is not explained by the initial pathology or surgi-
cal complications [1]. In practice, a time frame of pain for more than 2–3 months has
gained acceptance as operative definition. The reported prevalence rates range from 5 to
more than 50 % in adult surgical population, depending mainly on the type of surgery
[2]. CPSP can occur after surgeries such as thoracotomy, extremity amputation, and
hysterectomy. However, all procedures including relatively “minor” surgeries (e.g.,
appendectomy or inguinal hernia repair) have been associated with this condition [3, 4].
Even though CPSP is a well-known entity in the adult literature, this is a rela-
tively unstudied complication in the pediatric population [5]. Considering the grow-
ing number of children who undergo surgery every year, there is a necessity to
understand the population at risk, possible predisposing risk factors involved, and
the eventual long-term effects in functionality and development [6].
25.2 Magnitude of the Problem
The prevalence varies with the nature of the surgical insult and time since surgery but
also with the definition criteria used to classify patients with CPSP. Higher preva-
lence rates are reported in studies that include any report of pain regardless of
G. Rivera, MD
Department of Anesthesia, Clinica Las Condes, Santiago, Chile
Chronic Pain Service, Department of Anesthesia, The Montreal Children’s Hospital,
McGill University, 2300 Tupper Street, Room C1117, Montreal, QC H3H 1P3, Canada
e-mail: gonzalo.rivera@mail.mcgill.ca; gon.rivera@gmail.com

DOI 10.1007/978-3-319-21960-8_25
448 G. Rivera
intensity. Lower rates are typically seen when other criteria than pain (e.g., disability)
are also included in the classification [7]. Overall, studies on different pediatric set-
tings suggest that young age at the time of surgery is associated with lower risk of
developing CPSP [8].
It has been reported that 1 year after surgery, 22 % of children developed moderate
to severe (NRS, ≥4) CPSP. This study included children aged 8–18 years who under-
went major orthopedic or general surgery, including thoracotomies and laparoscopies.
The relative risk of having moderate to severe pain 1 year after surgery was 2.5
(CI 0.9–7.5) if patients experience pain ≥3 out of 10 two weeks after discharge [7].
In a retrospective study, 113 children and their parents were enrolled to answer
telephone interviews regarding persistence and characteristic of pain after surgery
in the preceding 3–10 months. Children between ages of 2 and 17 years who had
undergone general, orthopedic, and urologic surgeries were included. Thirteen per-
cent of patients reported the existence of CPSP (average pain level of 4.2 ± 1.5 on a
0–10 NRS) with a median duration of 4.1 months [9].
More specifically, groin pain after inguinal hernia repair is reported to be present
in 3.2–13.5 % (severe pain in 2 %) of patients after 3.2–49 years follow-up [10–12].
The prevalence of CPSP after inguinal hernia repair seems to be lower when surgery
is performed in childhood since adult reported a 10 % incidence of CPSP [6].
Similarly, results from studies of CPSP after sternotomy and thoracotomy have
shown that surgeries during childhood have promising results compared with same
procedures in adults in terms of chronic pain. A recent report on CPSP after ster-
notomy during childhood has shown that pain is present in 21 % of patients (10 %
≥4 on the NRS) after a mean follow-up period of 4 years. In adults, sternotomy is
followed by CPSP in 20–50 % of patients [8]. Comparably, very young age at the
time of surgery was associated with shorter duration of postoperative pain after
thoracotomy due to coarctation of the aorta. The prevalence of postsurgical pain
(>3 months) after thoracotomy was 3.2 % in the youngest group (0–6 years at the
time of surgery), 19.4 % in children aged 7–12 years at the time of surgery, and
28.5 % among those aged 13–25 years at the time of surgery [13].
Spine surgery is associated with variable rates of pain before and after surgery
and has been reported with prevalence rates of CPSP ranging from 11 to 68 %,
1–6 years after surgery [6, 14]. Interestingly, Siebert and colleagues have shown
that adolescents who experienced no pain before and after spine surgery (“no pain
trajectory”) were significantly younger than other groups of patients who experi-
enced pain either before or after surgery [15].
25.3 General Mechanisms and Clinical Presentation
The pivotal factor seems to be the nerve damage during the procedure. However, the
development of CPSP involves biological, psychological, surgical, and genetic fac-
tors interacting in a specific moment [16].
Inflammatory mediators are released by damaged tissue and an inflammatory
cascade is triggered after surgery. Several molecules and compounds act directly
25 Prevention of Chronic Postsurgical Pain 449
on the primary afferent terminals, decreasing their excitation threshold (periph-

eral sensitization) [3]. This response is normal and produces the major part of
the acute postsurgical pain. However, one of the triggers of pain chronicity is
thought to be the peripheral nerve damage. When nerves are transected or
stretched during surgical manipulation, they discharge trains of impulses using
glutamatergic neurotransmission via NMDA receptors to sensitize nociceptive
pathways in the CNS [16]. This effect produces excitotoxic neuronal destruction
and neuroimmune inflammation causing central macrophage activation [17]. All
the process of central sensitization is also accompanied by alterations in gene
expression resulting in changes in function and synaptic connections in the spi-
nal cord [18].
Interestingly, changes derived by this phenomenon are not limited to the spinal
cord. Important alterations in the cortex gray matter and descending systems have
also been documented [17].
While mechanisms of peripheral and central sensitization are initially physio-
logic and protective, under unknown conditions, they become maladaptive and del-
eterious. The transition is complex and not completely understood. From clinical
and epidemiological studies, it is possible to observe that psychosocial and genetic
factors have relevant roles in the occurrence of CPSP in an individual.
Clinically, CPSP can have both inflammatory and neuropathic characteristics.
Usually, inflammatory symptoms (e.g., swelling, redness) decay over time and
respond satisfactorily to NSAIDs. However, neuropathic component may persist for
longer periods and is commonly refractory to regular analgesics [19].
Neuropathic pain is usually continuous, like a superficial burning sensation or
painful cold. It is also described like paroxystic electric shock or very brief stab-
bing pain. The neuropathic pain could be spontaneous or elicited by light mechan-
ical (friction, pressure) or thermal stimulation [20]. One of the cardinal
manifestations of neuropathic pain is allodynia, in which a non-painful stimulus
(e.g., touch) produces pain. A second manifestation is known as secondary hyper-
algesia, in which an increase in pain sensitivity occurs in non-injured areas beyond
the area of initial injury [21]. In the clinical setting in a patient who is suspected
to suffer from CPSP, all these clinical features should be related with the surgical
area or scar.
25.4 Factors Associated with CPSP in Children
It is obvious that only a fraction of patients develop CPSP after surgery. However,
there is no clear way to know what patient in what situation will evolve with
CPSP. In this regard, available literature has highlighted some risk factors for devel-
oping CPSP. Since the majority of the information is provided from studies per-
formed in adults, the interpretation of these data in the context of child care should
be done carefully.
Arbitrarily, it is possible to group the associated factors for developing CPSP
into three main groups: surgical, psychosocial, and patient-related factors.
450 G. Rivera
25.4.1 Surgical Factors
The following surgical factors are linked with an increased likelihood of developing
CPSP: type of surgery (e.g., spine surgery, thoracotomy, amputation, etc.), increased
duration of surgery, low surgical load in a specific surgery center, open surgeries
(vs. video-assisted procedures), pericostal stitches, and evidence of nerve damage.
Whether these factors are causally related to the development of CPSP is not com-
pletely known [16]. Nevertheless, it seems evident that there is a relation between
the magnitude of injured tissues, the probability of nerve damage, and the occur-
rence of CPSP. As a result, adequate training in less invasive surgical techniques
appears warranted. Avoiding an unnecessary surgery is always advisable.
25.4.2 Psychosocial Factors
Preoperative anxiety, post-traumatic stress disorder, introverted personality, pain

catastrophizing, poor social support, and emotional numbness have been associated
with CPSP or with chronic postsurgical disability in adults [22]. There are no clues
to know whether these factors may have the same effect in children. However, it has
been reported that anxiety 6 months after surgery is associated with the maintenance
of pain after 12 months [7]. It is also interesting that parental catastrophizing scores
48–72 h after surgery can predict pain intensity in their children 12 months later
[23]. Adolescents with idiopathic scoliosis who have greater expectations about
changes in self-appearance before spine surgery report more pain and experienced
less reduction in preoperative pain after surgery [14]. Those findings stand out the
intimate relationship between the effect of the psychological “environment” during
perioperative period and the occurrence of persistent pain after surgery. The role of
eventual psychological interventions or therapies in modifying CPSP remains to be
elucidated.
25.4.3 Patient-Related Factors
Experience of pain either before or after surgery is one of the most robust predictors
of chronic pain after surgery in adults [6]. No other patient factor is as consistently
related to the development of future pain problems as pain: “pain predicts pain”
[16]. In a prospective study involving 83 children aged 8–18 years who underwent
major orthopedic and general surgery, patients who reported an NRS pain-intensity
score ≥3 out of 10 2 weeks after discharge were more than three times more likely
to develop moderate/severe CPSP at 6 months (RR 3.3) and more than twice as
likely to develop moderate/severe CPSP at 12 months (RR 2.5) than those who
reported NRS pain score <3 [7]. In this study, the presence of moderate/severe
CPSP was not accompanied by high levels of functional disability for the majority
of children. Approximately 5–15 % of children with chronic pain report pain
-disability of a severity requiring professional attention [24].
As mentioned above, young age at the moment of surgery appears to be a protec-

tive factor for developing CPSP. An immature peripheral and central nervous sys-
tem combined with an enhanced neuronal plastic capacity in the child’s brain may
contribute to a lower risk for developing chronic painful conditions. Tissues are
more indulgent and flexible in children, and therefore many procedures may be less
harmful in children than in adults [8].
Contrary to other pain conditions, in the setting of CPSP, the gender differ-
ence did not appear to influence the occurrence of persistence of pain after
surgery [6, 7].
25.5 Prevention Strategies
Once established, CPSP is very difficult to reverse and complicated to treat.

Therefore, a logical answer seems to be its prevention.
25.5.1 Surgical Technique
The primary focus for prevention needs to be an increased awareness among sur-
geons of ways to avoid intraoperative nerve injury, including careful dissection,
reduction of inflammatory response, and the use of minimally invasive techniques
[17]. Video-assisted procedures can decrease the damage inflicted to nerves com-
monly produced by conventional open surgery.
25.5.2 Pharmacological Therapy
A growing number of studies of preoperative systemic drug interventions have

been conducted. Those trials included adult population who underwent different
surgical procedures such as cardiac surgery, spine surgery, knee arthroplasty, thy-
roidectomy, breast surgery, and thoracotomy to mention a few. A wide variety of
drug classes (NMDA antagonists, lidocaine, alpha-agonists, NSAIDs, steroids,
anticonvulsants, antidepressants, opioids, etc.) administered at a variety of thera-
peutic schemes have been documented [25]. Even if many pharmacological inter-
ventions have some positive effect in reducing postoperative pain, they have failed
to modify consistently the occurrence of CPSP [22]. Exceptions to this are the use
of perioperative ketamine infusions (>24 h) that appear to reduce the incidence of
pain at 3 and 6 months after surgery (mainly abdominal and pelvic surgery) and the
administration of oral pregabalin which resulted in superiority over placebo
(mainly in cardiac surgery and total knee replacement) for pain incidence at
3 months after surgery [26].
Currently, there is no information available concerning the effect of pharmaco-
logical interventions on the incidence of CPSP in children.
452 G. Rivera
25.5.3 Regional Blocks
Although regional techniques are effective in controlling acute postoperative pain

in different surgical settings, their effectiveness in improving long-term outcomes
has been more elusive. In adult population, thoracic epidural anesthesia and para-
vertebral block, respectively, may prevent CPSP after thoracotomy and breast can-
cer surgery in about one out every four to five patients treated [27]. Less consistent
data is available concerning the role of regional blocks in preventing CPSP after
limb amputation. Nevertheless, it has been reported that prolonged postoperative
infusion (median duration of 30 days) of local anesthetics via peripheral nerve
catheters could be useful for reducing the incidence of phantom limb pain 1 year
after surgery [28].
Unfortunately, despite the extensive use of regional blocks in children, including
continuous ambulatory techniques [29], the effect of these procedures for the pre-
vention of CPSP has not been studied.
25.5.4 Other Potential Strategies
Different strategies for CPSP prevention have been implemented in adults. Althaus
et al. have developed a risk index for predicting CPSP considering different periop-
erative factors, such as preoperative pain (same and/or other place than the surgical
site), acute postoperative pain, recent psychological “capacity overload,” and the
presence of stress indicators (sleep disorder, trembling hands, tachycardia, etc.) [2].
They found a strong correlation between the number of positive factors in each
category and the risk of CPSP (e.g., scoring 4≥ the risk is >70 % of CPSP). Naturally,
it is not possible to directly extrapolate these data to children. Nevertheless, this tool
highlights the importance of psychological aspects in predicting CPSP. In this
regard, it is well known that various forms of cognitive behavioral therapies consti-
tute an essential part of the multidisciplinary treatment of many chronic pain condi-
tions in adults and children [30, 31]. Therefore, it can be anticipated that further
psychological research may contribute to improving the prevention and the treat-
ment of chronic pain in children undergoing surgery.
25.5.5 Summary of the Preventing Strategies
The results of studies on preventive multimodal analgesia are equivocal and ori-
ented to adult population. Although sufficient analgesia during the perioperative
period is important for the prevention of CPSP, mere short-term blockage of noci-
ception and control of symptoms have not been shown to eliminate the long-term
problem [22]. The wide variety of treatment protocols used, even in the same surgi-
cal scenario, reflects a current lack of understanding of the critical mechanisms and
temporal aspects of development of CPSP [26]. However, this does not exclude the
possibility that many interventions may be beneficial in pediatric cases. Since the
intensity of acute postoperative pain is the strongest predictor of pain chronicity,

standardized pain evaluation and treatment protocols are recommended.
Psychological questionnaires and interventions that predict the psychosocial fac-
tors in patients that make them susceptible to develop persistent pain should be
designed and implemented [32]. Finally, it is essential to ensure patients and par-
ents are adequately prepared and educated for the surgical event and its
consequences.
25.6 Concluding Remarks
In conclusion, the available evidence suggests that the prevalence of CPSP is lower
if surgery is performed in childhood. When pain is intense and persists, it is likely
to have a neuropathic component. At this moment, the refinement in surgical tech-
niques and an adequate acute postoperative pain management constitute the most
widely accepted prevention strategies in children. Despite advances in the under-
standing of the mechanisms involved and the interplay of risk factors in the adult
population, the management and prevention of persistent postsurgical pain remain
inadequate and poorly studied in children. Further research on the role of presurgi-
cal preparation and postoperative care should be conducted for preventing potential
disabling consequences.
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Index
A ADVANCE
ABCDEF sequence, 216 preparation for surgery project, 24
ABD. See Autologous blood donation (ABD) strategy, 410
Abdominal and pelvic procedures Adverse events following immunization
common preoperative considerations, (AEFI), 48
137–139 AEFI. See Adverse events following
intraoperative management, 139–142 immunization (AEFI)
postoperative management, 142–143 Age at exposure, anesthetic drugs, 442
Acoustic impedance monitoring, 387 α2 Agonists, 31
Acute pain management Airway assessment, 139–140, 217
ambulatory regime, 430 Airway management
assessment tools, 418–419 endotracheal intubation, 263
cutaneous sensory receptors, 417 intermittent airway obstruction, 263
hemodynamic parameters, 419 Airway obstruction
multimodal analgesia, 419 diagnostic and therapeutic procedures,
non-opioid analgesics (see Non-opioid 279–280
analgesics) emergency airway rescue, 278–279
non-pharmacological (see Non- mucositis and xerostomia, 240
pharmacological management, pain) neck irradiation, 241
opioids (see Opioid analgesics) newborn, evaluation and treatment, 273
procedure-specific guidelines, 430 postoperative period, 280
regional anaesthesia (see Regional subglottic and tracheal pathologies,
anaesthesia) 277–278
Acute pain service (APS) team, 431 supraglottic and laryngeal pathologies,
ADARPEF. See Anesthésistes Réanimateurs 275–277
Pédiatriques d’Expression Française symptoms and signs, 273–274
(ADARPEF) TBAO, 274–275
Adjuvant therapy ulcerative lesions, 240
adult pain management, 253 Aldrete scoring system, 69, 70t
anticonvulsants, 254 Alert, verbal, pain, unresponsive (AVPU)
benefits, medications, 253 acronym, 221
benzodiazepines and baclofen, 254 Allergies
gabapentin, 254 atopy, 44, 45
ketamine, 254 causes, 44
selective serotonin reuptake inhibitors, 254 latex allergy, 44, 45
tricyclic antidepressants, 254 latex-safe strategies, 46

DOI 10.1007/978-3-319-21960-8
456 Index
Allergies (cont.) poorly controlled, 42–43

to local anesthetics, 45 regular medication, children, 43
prophylaxis, 46 stepwise management, children, 42
radioallergosorbent test (RAST), 46 steroid medication, children, 43
skin prick test (SPT), 45 Atopy, 40, 44, 45
American Academy of Otolaryngology, Aute respiratory distress syndrome (ARDS), 99
201–202 Autologous blood donation (ABD), 94
American Academy of Pediatrics (AAP), 202 AVMs. See Arteriovenous malformations
American Society of Anesthesiologists (ASA) (AVMs)
guidelines, 200
Analgesia at home, 430
Anatomical, physiological, and psychological B
peculiarities, trauma, 214 Beckwith–Wiedemann syndrome, 138–140
Anesthesia, NMDs BIS. See Bispectral index (BIS)
cardiovascular failure, 161 Bispectral index (BIS), 78
hyperkalemic cardiac arrest, 164 Bladder detrusor hyperactivity, 262
MH, 162–163 Blood pressure (BP) monitoring
respiratory failure, 160–161 arterial cannula, 392, 393
rhabdomyolysis, 163 arterial tonometry, 393
Anesthésistes Réanimateurs Pédiatriques fluctuations, hemodynamics, 392
d’Expression Française invasive arterial tracing, 393
(ADARPEF), 56 pulse transit time, 393–394
Anterior mediastinal mass (AMM) vascular unloading, 393
capnogram, 240 Botulinum toxin (Botox), 262
chemotherapy access, 240 BPD. See Bronchopulmonary dysplasia (BPD)
chest X-ray, 239 Brachial plexus, 428
general anesthesia, 239, 240 Brain edema, 124
local anesthesia and sedation, 239 Brain tumors, 124–125
preoperative echocardiogram, 239 Breathing
respiration and avoiding paralysis, 240 analgesia, 296
sedation, 239 primary survey, trauma
tissue types, children, 239 destabilization/respiratory
tumor biopsy, 240 parameters, 218
Antifibrinolytics, 95 nasotracheal intubation, 218
Anxiety tension pneumothorax, 219
components of, 21 in sleep and airway collapsibility, 193–195
development factors, 22 Bronchopulmonary dysplasia (BPD), 43–44
high levels of, 22 Bronchospasm, 39–41, 44–46
low levels of, 22
transient state, 21
ARDS. See Aute respiratory distress syndrome C
(ARDS) Capnography. See End-tidal carbon dioxide
Arteriovenous malformations (AVMs), 127 (ETCO2) monitoring
Asthma. See also Upper respiratory infections Cardiac dysfunction, neuromuscular
(URI) disorders, 161
bronchodilators, 43 Cardiac output (CO) monitoring
bronchospasm, 41 bioreactance, 389
chest radiograph, 42 Doppler techniques, 388
computed tomography (CT scan), 42 pulse contour analysis technique, 389
corticosteroids, 43 TEB, 389
day-surgery, 60 thermodilution method, 388, 390
diagnosis of, 42 transpulmonary thermodilution (TPTD), 388
flow expiratory volume (FEV1), 42 CBF. See Cerebral blood flow (CBF)
medication, children, 43 Central hypoventilation syndromes, 197–198
Index 457
Central venous catheter (CVC) Cervical collar, 217

access, SVC (see Superior vena cava (SVC)) CHARGE syndrome, 275
classification, complications Chemodenervation, 262
catheter occlusion, 306–307 Chemotherapy
immediate complications, 306 awareness, side effects, 255
intermediary complications, 306 cancer treatment, 230
late complications, 306 cardiotoxicity
risk factors, 307 chronic anthracycline, 231
rupture, 307 complications, 231
treatment, 307 constrictive cardiomyopathy, 232
equipment and technique of insertion, cyclophosphamide, 232
303–305 intraoperative monitors, 232
indications, 302 hematological effects
IVC access (see Inferior vena cava (IVC)) anemia, 235
Cerebral blood flow (CBF), 115 dysfunctional coagulation, 235
Cerebral palsy (CP) meticulous aseptic techniques, 235
anesthetic management, 260 myelosuppression, 235
blood loss, 266 hepatorenal toxicity
cognitive function, 259 cisplatin, 234
epidural catheter techniques, 267 coagulation necrosis, 234
fundoplication, 266–267 hepatic injury, 235
gastrostomy, 267 non-cisplatinum chemotherapeutic
hemodynamic monitoring, 267 agents, 234, 235
hip reconstruction, 266 renal injury, 234
latex allergy, 266 renal system, 234
lesions/anomalies, 259 hormone and enzyme production
motor defects, 259 alkylating agents, 236
orthopedic surgery, 266 SIADH, 235
perioperative management steroid-induced adrenal
airway management (see Airway suppression, 235
management) stress response, 235
analgesia, 266 neurotoxicity
meticulous padding, 262 cisplatin treatment, 235
pharmacodynamics and local motor neuropraxia, 235–236
pharmacokinetics, 264, 265 neurologic consequences, 235
positioning, 262–263 non-vincristine chemotherapy
thermal homeostasis, 263 agents, 236
uncooperative behavior at induction, 265 pulmonary toxicity
venous access, 263 adverse cardiac effects, 232
pneumoperitoneum, 267 bleomycin-induced, 233
pneumothorax, 267 chest X-ray, 234
preoperative evaluation complications, 232
baclofen, 261 non-anthracycline chemotherapeutic
botulinum toxin (Botox), 262 agents, 232
contractures and deformities, 261 non-bleomycin chemotherapy
developmental delay, 260 agents, 234
epilepsy, 262 perioperative inspired oxygen
flexion, toes, 260 concentration, 233, 234
gastroesophageal reflux, 260 primary chemotherapeutic
laparoscopic fundoplication, 261 agents, 233
neurolytic blocks, 262 pulmonary function tests, 234
sarcopenia, 261 Childhood Adenotonsillectomy
spasticity, 261 Trial (CHAT), 199
vigabatrin, 261 Choanal atresia, 275
458 Index
Chronic postsurgical pain (CPSP) D

in children Damage control strategy (DCS), 224, 225
patient-related factors, Day-surgery (DS)
450–451 analgesia
psychosocial factors, 450 locoregional, 67–68
surgical factors, 450 NSAIDs, 67
definition criteria, 447 pain control, 67
glutamatergic neurotransmission, 449 anesthesia
inflammatory mediators, 448 airway management, 66
inguinal hernia repair, 448 caudal block, 65
laparoscopies., 448 drugs, 63–64
nerve damage, 448 fluid therapy, 66
normal tissue healing, 447 ilioinguinal/iliohypogastric nerve
paroxystic electric shock, 449 block, 65
patient classification, 447 locoregional, 64
peripheral and central sensitization, 449 lower and upper extremity nerve
predisposing risk factors, 447 blocks, 65
prevention strategies opioids as adjuvants in locoregional, 66
pain management, 453 paravertebral block, 65
pharmacological therapy, 451 penile block, 66
preventive multimodal spinal block, 64
analgesia, 452 temperature, 67
regional techniques, 452 discharge
surgical technique, 451 aldrete scoring system, 69, 70t
treatment protocols, 452–453 clinical criteria for, 69
secondary hyperalgesia, 449 modalities for, 69
spine surgery, 448 observation period, postoperative, 70
superficial burning sensation, 449 pain therapy prescriptions, 71
thoracotomies, 448 postanesthetic discharge scoring system
Circulation, 124, 163, 219–220, 240, (PADSS), 69–71, 71t
298, 331, 334 postoperative management, 70
Clonidine, 411 recovery from anesthesia, 69
Cobb method, 106 telephone follow-up after, 71
Compartment syndrome, 98–99 tonsillectomy, 71–72
Congenital chest wall deformities vital parameters evaluation, 69
pectus carinatum epidemiology, 56
analgesic considerations, 134 organizational aspect, 56–57
background, 134 patient preparation
Ravitch procedure, 134 fasting, 62
surgical technique, 134 information for parents, 62
pectus excavatum pharmacological premedication, 63
analgesic considerations, 133 premedication, 62–63
preoperative assessment of, 131 preoperative evaluation, 61
reverse Nuss procedure, 134 written and understandable brochure, 61
surgical technique, 132 patient selection
Congenital spinal lesions, 126–127 age, 58–59
Continuous peripheral nerve blocks ASA physical status, 57–58
(CPNBs), 97–98, 427 asthma, 60
CPSP. See Chronic postsurgical incidental heart murmurs, 59
pain (CPSP) malignant hyperthermia, 59
Craniosynostosis repair, 125–126 sickle cell disease, 59
Cri-du-chat syndrome, 101 sudden infant death syndrome
Crystalloids, 141 (SIDS), 59
CS. See Intraoperative red cell upper respiratory tract infection (URI),
salvage (CS) 59–60
Index 459
post-discharge nausea and vomiting parents and culture, 405

(PDNV), 69 preoperative anxiety, 406
postoperative nausea and vomiting propofol, 407–408
(PONV), 68–69 surgery, 406
postoperative vomiting (POV), 68 End-tidal carbon dioxide (ETCO2) monitoring
procedure, 60–61 chest compression, 384
social factor, 61 infrared technology, 382
Developmental delay, 260 partial pressure of CO2 (PaCO2), 382–383
Dexmetomidine, 411 ventilation techniques, 383
Diabetes insipidus, 123 Enhanced recovery after surgery (ERAS)
Disability program, 2–3
chronic pain, 450 Epidural blocks, 427
chronic postsurgical, 450 Epilepsy
cognitive function, 238 surgery, 125
compartment syndrome, 98 valproic acid, 262
neurologic function, 221 ERAS program. See Enhanced recoy after
pain evaluation, 418 surgery (ERAS) program
trauma injury, 213 Esmarch’s bandage, 92
Distal tracheal stenosis, 278 ETCO2. See End-tidal carbon dioxide (ETCO2)
DOPES sequence, 218–219 monitoring
Doppler techniques, 388 Exposure
Down syndromes, 139–140 allergic reaction, 45
Dystrophinopathies, 169 anesthetic/surgical, 444
direct external heat sources, 252
in neonates, 124
E OSA, 188
Early postoperative negative behaviour passive smoking, 40
(e-PONB) primary survey, trauma, 221
children, 404 to secondhand smoke, 41, 45
prevention and treatment “sleep-awake-asleep” technique, 125
non-pharmacologic approach, 410 Extubation, 66, 111, 155, 171, 172, 225, 279
pharmacologic approach, 411–412
risk factors
age and gender, 405 F
inhalation anaesthesia, 406–407 Face, legs, activity, cry, consolability
parents and culture, 405 (FLACC) scale, 409
preoperative anxiety, 406 Face-mask ventilation, 149
propofol, 407–408 Family
surgery, 406 adverse respiratory events, 40
tools, 408–410 anesthesia and surgery, 21, 90
treatment, 412 asthma, 41
Electrocardiogram (ECG) monitoring genetically transmitted diseases, 14
anesthesia care, 390 non-pharmacological techniques, 429
applications, 390 pain, 245
intravascular/systemic injection, 390–391 preoperative anxiety, 21, 23
Emergence agitation (EA) preoperative evaluation, 14
diagnostic criteria, 404 Fasting, preoperative, 34
inadequate pain relief, 404 Fat embolism (FES), 99
restlessness and mental distress, 404 Femoral nerve approach
scales, 408 high-frequency linear probe, 360
Emergence delirium (ED) hyperechoic, 359
definition, 404 surgical anesthesia and analgesia, 358
risk factors ultrasound guidance, 360–361
age and gender, 405 FES. See Fat embolism (FES)
inhalation anaesthesia, 406–407 Fundoplication, 266–267
460 Index
G I
Gastrostomy, 267 Ibuprofen, 425
General anesthesia, infant brain ICP. See Intracranial pressure (ICP)
age, 442 Iliohypogastric (IH) and ilioinguinal (II) nerves
anesthesia-related neurotoxicity, 444 in-plane approach, 367, 369
animal studies, anesthesia-related linear probe, 367
neurotoxicity, 438 local anesthetic, 367, 369
brain development, 437 nerve localization, 368
degree of migration, 441 pharmacodynamic studies, 369
duration and number pharmacokinetic study, 370
of exposures, 441 ultrasound technique, 367
gender issue, 443 Immunomodulatory effects, cancer
human brain, normal development, airway lesions, 240–241
438–439 AMMs (see Anterior mediastinal
human outcome measure, 439–440 mass (AMM))
human studies, 439 cancer cell augmentation, 229
impact of surgery, 442–443 immunosuppression, 229
morphological abnormalities, 437 neoplasia (see Neoplasia/cancer)
neuroprotective properties, 437 retinoic acid syndrome, 245
nociception and neuroinflammation, 443 TLS, 243–244
perioperative factors, 443 toxicity, oncological therapies
sample size issue, 441 (see Oncological therapy)
stress responses, 443 Infantile hemangiomas, 277
synaptogenesis, 437 Infants
Glasgow Coma Score, 221 brain, anesthesia
Glycogenosis, 180 age, 442
Glycogenosis type II (GSDII), 170–171 anesthesia-related neurotoxicity, 444
Goldenhar syndromes, 101, 274 animal studies, anesthesia-related
Guillain–Barrè syndrome (GBS), 169 neurotoxicity, 438
brain development, 437
degree of migration, 441
H duration and number of exposures, 441
Halogenated agents, 163, 167 gender issue, 443
HCM. See Hypertrophic cardiomyopathy human outcome measure, 439–440
(HCM) human studies, 439
Heart murmurs morphological abnormalities, 437
brachial and radial pulses, 46 neuroprotective properties, 437
chest X-rays, 47 nociception and neuroinflammation, 443
clinical effects, 46, 47 normal development, human brain,
ECG, 47 438–439
echocardiography, 47 perioperative factors, 443
hypertrophic cardiomyopathy sample size issue, 441
(HCM), 46 stress responses, 443
innocent and pathological, 46, 47 surgery impact, 442–443
Heat loss, 263 synaptogenesis, 437
Hip reconstruction, 266 CPSP
Hydrocephalus and stunt procedures, 124 patient-related factors, 450–451
Hyperglycemia, 123 psychosocial factors, 450
Hyperkalemic cardiac arrest, 164 surgical factors, 450
Hypertrophic cardiomyopathy (HCM), 46 Inferior vena cava (IVC)
Hypnosis, 430 complications
Hyponatremia, 123 catheter migration, 323
Hypothermia, 263 fluid extravasation, 323
Index 461
lower limb ischemia, 324 Italian National Program Guidelines, 201

portal vein thrombosis, 324 Italian Society of Pediatric and Neonatal
femoral vein Anesthesia and Intensive Care
anatomy, 322–323 (SARNePI), 16
femoral vein catheterization, 323, 324
reverse Trendelenburg position, 323
US-guided femoral vein puncture, J
323, 324 Jaw thrust, 150, 217, 263
Infraclavicular approach JHSRCS. See Johns Hopkins surgery risk
arterial pulse, 351 classification system (JHSRCS)
“blind” techniques, 355 Johns Hopkins surgery risk classification
catheter technique, 354 system (JHSRCS), 12
Color Doppler, 353, 354
indications, 351
local anesthetic spread, 353, 355 K
ultrasound imaging, 355 Ketamine, 30–31
Inhalation anaesthesia, 406–407 Ketorolac, 425, 426
Interfascial spread of local anaesthetics
(LAs), 427
Internal jugular vein (IJV) L
anatomy and sonoanatomy, 308–310 Laryngeal cleft (LC), 275
anterior approach, 310 Laryngeal mask airway (LMA), 66
“blind”/“landmark-guided” approaches, adverse respiratory events, 40
310 dexmedetomidine, 33
posterior approach, 310 gastric access, 263
ultrasound-guided anterior approach, general anesthesia, 44
310–311 sizing, 218
Interscalene approach surgical pharyngeal visualization, 202
carotid artery, 348 Laryngeal webs, 276
internal jugular (anechoic), 349 Laryngomalacia, 275
IP, 349, 350 Laryngospasm, 149
pneumothorax, 350 Larynx, 193
ultrasound imaging, 348 Lateral femoral cutaneous nerve (LFCN), 105
US-guided nerve stimulating technique, Latex allergy, 44, 45, 266
349 Latex-safe strategies, 46
Intracranial pressure (ICP), 118 Lethal triad, 224
Intraoperative bronchospasm, 41 LFCN. See Lateral femoral cutaneous nerve
Intraoperative fluid management (LFCN)
abdominal and pelvic procedures, 141 Limb occlusion pressure (LOP), 92
trauma, 223–224 LMA. See Laryngeal mask airway (LMA)
Intraoperative management Long QT syndrome (LQTS), 16
abdominal and pelvic procedures, 139–142 LOP. See Limb occlusion pressure (LOP)
NMDs, 167–171 Lower limb blocks, USG techniques
OSA, 202–203 femoral nerve approach, 358–361
trauma, 223 saphenous nerve block, 363–364, 366
Intraoperative red cell salvage (CS), 94–95 sciatic nerve block, 361–363
Intraosseous (IO) access LQTS. See Long QT syndrome (LQTS)
complications, 333 Lumbar plexus, 428
contraindication, 333
description, 331–332
devices, 332–333 M
perioperative indications, 332 Macroglossia, 274
technique, 332–333 MAC values of halothane, 264
462 Index
Malignant hyperthermia (MH) Nasal administration

acute crisis management, 162–163 α2-agonists, 32–33
patients at risk, 162 ketamine, 32
prevention, 162 midazolam, 32
McGill Oximetry Score (MOS), 191 Nasopharynx, 192–193
Mental retardation, 259 National Institute for Health and Clinical
MEPs. See Motor evoked potentials (MEPs) Excellence (NICE-UK), 16
Metabolic diseases Near-infrared spectroscopy (NIRS)
biological signs, 184 brain tissue oxygenation, 391
glycogenosis, 180 cerebral hypoxemia, 392
Guthrie’s test, 183 cerebral oxygenation monitoring, 391, 392
mitochondrial cytopathy, 180–183 neurologic damage, 392
perioperative care, 176 Negative behaviour after surgery
reflex, 183–184 EA (see Emergence agitation (EA))
sources, 176–177 ED (see Emergence delirium (ED))
synthesis of, 177–178 e-PONB (see Early postoperative negative
systematic screening, 183 behaviour (e-PONB))
urea cycle disorder, 178–179, 183 postoperative pain (see Postoperative pain,
Midazolam, 30 child’s behaviour)
Mitochondrial cytopathy, 180–183 Neonatal larynx, 148
Mitochondrial myopathies, 166–167, 170 Neonates
Modified Maintenance of Wakefulness Test brain, anesthesia (see Infants)
(MMWT), 82 hypotension, 117
Modified Yale preoperative anxiety scale Microstream Sensor, 78
(m-YPAS), 21, 406 stress response, 81
Mortality Neoplasia/cancer
airway problems, 147 cardiovascular effects and considerations, 241
cancer, 229 CNS effects and considerations, 242
gastroschisis, 138 endocrine effects and considerations,
gender, 443 242–243
general anesthesia, 39 hematological effects and considerations, 243
inflammatory processes, 118 hepatic effects and considerations, 242
perioperative hypoxia, 147 myelosuppression, 243
perioperative medicine, 3, 6 primary GI tumors, 242
pheochromocytoma, 141 psychiatric considerations, 243
postoperative phase, 4 pulmonary neoplasms, 241
pulmonary toxicity, 232 renal tumors, children, 241–242
retinoic acid syndrome, 245 Neurodevelopment
subglottic hemangiomas, 277 academic performance, 440
trauma, 228 humans and animals, 438
for traumatic injury, 213 perioperative factors, 443
Motor evoked potentials (MEPs), 120 Neuro-endoscopy and anesthesia, 127
Mouth, 193 Neurolytic blocks, 262
Multimodal analgesia, 419 Neuromuscular blocking agents (NMB),
Music therapy, 24 168, 264
Myasthenia gravis (MG), 166, 169 Neuromuscular disorders (NMDs)
Myotonic dystrophy, 169–170 anesthesia, life-threatening complications
mYPAS. See Modified Yale preoperative cardiovascular failure, 161
anxiety scale (m-YPAS) hyperkalemic cardiac arrest, 164
MH, 162–163
respiratory failure, 160–161
N rhabdomyolysis, 163
N-acetyl glutamate synthetase (NAGS), intraoperative management
178–179 dystrophinopathies, 169
NARCO memory tool, 177 GBS, 169
Index 463
GSDII, 170–171 induction, 120

MG, 169 maintenance of anesthesia, 121
mitochondrial myopathies, 170 monitoring, 120
myotonic dystrophy, 169–170 positioning, 121
NMB, 168 postoperative care, 122–123
regional anesthesia, 168 preoperative assessment, 119–120
succinylcholine and halogenated venous air embolism (VAE), 122
agents, 167 postoperative complications
TIVA, 167–168 brain edema, 124
postoperative management diabetes insipidus, 123
pain control, 171 hyperglycemia, 123
respiratory management, 171–172 hyponatremia, 123
preoperative assessment and management perioperative prophylaxis, 124
cardiac assessment, 165 vascular malformations, 127
chronic treatment, steroids, 166 NICE-UK. See National Institute for Health
intravenous line, 166 and Clinical Excellence (NICE-UK)
mitochondrial myopathies, 166–167 NIRS. See Near-infrared spectroscopy (NIRS)
myasthenia gravis, 166 NMS. See Neuromuscular scoliosis (NMS)
neurological assessment, 164 Noninvasive hemodynamic monitoring
PICU, 166 applications, 380
premedication drugs, 166 blood pressure (BP) monitoring, 387,
pulmonary assessment, 164–165 392–394
Neuromuscular scoliosis (NMS), 107, 108 cardiac output (CO), 388–390
Neurophysiology, pediatric brain electrocardiogram (ECG), 390–391
anesthesia and neurotoxicity, 119 intraoperative monitoring, 380
arterial carbon dioxide/oxygen tension medications, 379
(Paco2/Pao2), 116–117 NIRS, 391–392
blood pressure, 117–118 Noninvasive respiratory monitoring
brain and inflammation, 118 acoustic impedance monitoring, 387
brain energy metabolism, 116 applications, 380
cerebral autoregulation, 117–118 ETCO2, 382–384
cerebral blood flow (CBF), 115 intraoperative monitoring, 380
cerebral oxygen metabolism, 117 medications, 379
intracranial pressure (ICP), 118 pulse oximetry, 380–382
Neurosurgical patient TC-CO2, 384–386
brain tumors, 124–125 Nonoperating room anesthesia (NORA),
congenital spinal lesions, 126–127 75–82
craniosynostosis repair, 125–126 Non-opioid analgesics
epilepsy surgery, 125 acetaminophen (paracetamol), 424
hydrocephalus and stunt procedures, 124 clonidine and dexmedetomidine, 426
neuro-endoscopy and anesthesia, 127 dexamethasone, 426
neurophysiology, pediatric brain dosing, 424, 425
anesthesia and neurotoxicity, 119 gabapentinoids (gabapentin and
arterial carbon dioxide/oxygen tension pregabalin), 426
(Paco2/Pao2), 116–117 ketamine, 426
blood pressure, 117–118 lidocaine infusion, 426
brain and inflammation, 118 NSAIDs, 425–426
brain energy metabolism, 116 sucrose, 426
cerebral autoregulation, 117–118 Non-pharmacological management, pain
cerebral blood flow (CBF), 115 child life specialists, 429
cerebral oxygen metabolism, 117 clown doctors, 429
intracranial pressure (ICP), 118 context-induced placebo analgesia, 429
perioperative management family-based preparation, 429
body tempearture, 122 psychological factors, 429
fluid management, 121–122 tablet-based distraction, 429
464 Index
Non-pharmacological preparation physical exam and medical history,

parental presence during induction of 189–190
anesthesia (PPIA), 25, 27 radiologic studies, 192
preoperative anxiety epidemiology, 187
components of, 21 infants and premature infants, 195
development factors, 22 medical treatment, 198
high levels of, 22 neuronal control
low levels of, 22 anatomical balance model, 193–194
preoperative visit, 22 anatomic factors, 194–195
“receptivity” of the patient and the loop gain, 194
parents, 22 neural balance model, 194
transient state, 21 pharyngeal dilator muscles, regulation,
for surgery 194
ADVANCE project, 24 obese child, 195–196
age, children, 23–24 respiratory control
coping techniques, 23 larynx, 193
fasting, 27 mouth and pharynx, 193
informative approach, 23 nasopharynx, 192–193
modeling techniques, 23 upper airway anatomy
MRI, 24 and relationship, 192
music therapy, 24 risk factors, 188
parents’ anxiety, 24 surgical treatments, 198–200
play and games, 23–24, 26 syndromes, 196, 197
play specialist, 24 Obstructive sleep apnea syndrome
success of, 24 (OSA), 58
tablet-based interactive distraction Oncological therapy
(TBID), 24 chemotherapy (see Chemotherapy)
NORA. See Nonoperating room anesthesia radiation toxicity, 238–239
(NORA) “One-stop anesthesia” modality, 13
Nuss procedure, 132–134 “One-stop surgery”, 13, 15
Opioid analgesics
adverse effects, 419
O dosing, 419, 420
Obstructive sleep apnea (OSA) fentanyl, 421
adenotonsillectomy, guidelines hydromorphone, 422
AAP, 202 methadone, 422
American Academy of Otolaryngology, morphine, 420–421
201–202 nalbuphine, 422
intraoperative management, 202–203 oral administration, 419
Italian National Program Guidelines, oxycodone, 421
201 PCA/NCA/PARCA, 423–424
postoperative management, 203 remifentanil, 421
anesthesia management sufentanil, 421
ASA guidelines, 200 tramadol, 422–423
options, 200–201 Oral administration
central hypoventilation syndromes, α2-agonists, 31
197–198 intramuscular administration, 63
clinical presentation, 188 ketamine, 30–31
consequences, 188–189 midazolam, 30
diagnosis Orthopaedic surgery
biomarkers, 192 ambulatory surgery, 88–89
cardiorespiratory studies, 191 blood management
diagnostics test, 190–191 antifibrinolytics, 95
Nap studies, 192 intraoperative blood recovery and
oximetry, 191 reinfusion, 94–95
Index 465
preoperative donation of autologous nonpharmacological pain

blood, 94 management, 254
transfusion trigger, 95 optimal pain management, 246–247
fasting, 89 pharmacological treatment, 247–253
intraoperative positioning post-op pain in cancer patient, 254
and warming, 91 sedation techniques, 255
peripheral paediatric treatment, 247
general anaesthesia, 100, 101 Paravertebral thorax, 428
lower limb, 103–106 Parental presence during induction of
MAC, 100, 101 anesthesia (PPIA), 25, 27
regional anaesthesia, 100, 101 Parents’ postoperative pain measure
supraglottic devices, 101 (PPPM), 418
trachea, intubated, 101 PDNV. See Post-discharge nausea and
upper limb, 102–103 vomiting (PDNV)
wound infiltration, 101 Pectoralis (PEC) blocks, 428
postoperative care Pectus carinatum
compartment syndrome, 98–99 analgesic considerations, 134
pain treatment, 96–98 Ravitch procedure, 134
premedication, 89 reverse Nuss procedure, 134
preoperative evaluation, 87 surgical technique, 134
procedural sedation, 89–90 Pectus excavatum
tourniquets, 91–93 analgesic considerations
OSA. See Obstructive sleep apnea paravertebral nerve block (PVNB), 133
syndrome (OSA) patient-controlled analgesia
Outcome human measure, anesthetic drugs, (PCA), 133
439–440 thoracic epidural (TE), 133
Oximetry, 191 Nuss procedure, 132, 133
Oxygen toxicity, 140 preoperative assessment of, 131
surgical technique, 132
Pediatric airway features, 215, 277
P Pediatric anesthesia emergence delirium
Paediatric airway (PAED) scale, 408
anatomical considerations, 148 Pediatric early warning score (PEWS), 15
classification Pediatric intensive care unit (PICU), 123
approaches, 151–152 Pediatric regional anesthesia network
expected difficult airway, 151 (PRAN), 103
impaired normal, 150–151 Periclavicular approaches
normal, 150 advantages and disadvantages, 312
management cervicothoracic veins, 313, 315
equipment, 155–157 CVC placement, children, 312, 314
expected difficult airway, 154–155 infraclavicular access, subclavian vein
suspected difficult, 154 (SCV)
unexpected difficult airway, 152–154 brachial plexus injury, 316
obstruction, clinical consequences, ipsilateral IJV, 317
149–150 puncture site, 316
Paediatric anaesthesia behaviour puncture techniques, age category, 317
(PAB) score, 406 US-guided approach, 317
Pain panoramic view, major veins, 312, 314
adjuvants (see Adjuvant therapy) supraclavicular access, brachiocephalic
assessment vein (BCV)
parental postoperative, 418 brachial plexus damage, 315–316
perioperative care of children, 246–247 cervicothoracic veins, 315
tools, children, 226, 227 in hypovolemic patients, 314
definition, 245–246 transpectoral access, axillary vein (AxV),
measurement, 418 318–320
466 Index
Perioperative care acute pain management, 4

with cancer chronic postsurgical pain (CPSP), 5
anesthesia care, 255 echocardiography, 4
immunomodulatory effects (see hemodynamic management, 4
Immunomodulatory effects, cancer) intensity of, 4
pediatric cancer by age, 229, 230 noncardiac ultrasound, 4–5
pediatric cancer pain (see Pain) preoperative phase
pediatric cancer stats, 229 intraoperative phase, 3–4
preoperative evaluation and testing, 245 pre-habilitation, 3
metabolic diseases risk assessment and optimization, 3
glycogenosis, 180 Perioperative prophylaxis, 124
mitochondrial cytopathy, 180–183 Peripherally inserted central catheters (PICCs)
reflex, 183–184 catheter placement
sources, 176–177 catheter selection, 327
synthesis of, 177–178 catheter tip positioning, 329
urea cycle defect, 178–179 insertion technique, 328, 329
NMD (see Neuromuscular disorders palpation, 326–327
(NMDs)) prevention and detection, 327–328
OSA (see Obstructive sleep apnea (OSA)) sedation, 327
trauma vein selection, 327
anatomical and functional aspects, 215 central vein damage, 326
anatomical and physiological complications
features, 228 infection rate, 331
blunt injury in children, 214 mechanical problems, 330–331
capillary refill time detection, 215 thrombosis, 331
clinical assessment, 223 decision-making tree, 325
coagulopathy, 223 definition, 325
DCS, 224, 225 fixation and maintenance
diagnosis and treatment, primary fluoroscopy, 329, 330
injuries, 213 suture-free securing device, 329
history and clinical examination, 222 hamper catheter advancement, 326
imaging and laboratory testing, 223 indications, 325–326
intraoperative fluid management, local skin damage, 326
223–224 peripheral vein damage, 326
intraoperative management, 223 technical insertion difficulties, 326
mortality for traumatic injury, 213 Peripheral venous access (PVA)
motor vehicle collisions, 213 arterial circulation, 298
pain assessment, 226–227 extravasation, 301
pedestrian and bicycle accidents, 213 hematoma, 302
pediatric management, 214, 216 hypnosis techniques, 296
postoperative period, 224–225 indications, 293–294, 296
post-traumatic stress disorder, 215 near-infrared technology, 299, 300
primary survey, 216–221 phlebitis, 301
routine laboratory tests, 223 puncture sites
sedation and analgesia, 225–226 foot, 298
trauma injury, 213 forearm and antecubital fossa, 297
trauma management, 213 hand, 297
Perioperative medicine neck, 298
anesthesiology and, 5–6 scalp, 298
areas of, 5 wrist, 298
definition, 1 residual anesthetic medication, 302
enhanced recovery after surgery (ERAS) transillumination, 299
program, 2–3 USG, 299–301
patient, surgery and complications, 1–2 PEWS. See Pediatric early warning score
postoperative phase (PEWS)
Index 467
Pharmacodynamics and pharmacokinetics Postoperative pain, child’s behaviour, 404

hypnotics, 264 Postoperative period
neuromuscular blocking agents, 264, 265 airway obstruction, 279
opioids, 264 care of children, trauma, 224–225
Pharmacological premedication Postoperative vomiting (POV), 68
ketamine, 63 POV. See Postoperative vomiting (POV)
midazolam, 63 PPIA. See Parental presence during induction
oral administration, 63 of anesthesia (PPIA)
Pharmacological preparation Prader-Willi syndrome, 196
close monitoring after premedication, 28 PRAN. See Pediatric Regional Anesthesia
drugs and doses, 28, 29 Network (PRAN)
enteral/transmucosal premedication, 29 Preoperative anxiolysis, 411
indications for premedication, 28 Preoperative evaluation
nasal route (see Nasal administration) children care, cancer, 245
oral route (see Oral administration) CP
premedication goal, 28 baclofen, 261
rectal route (see Rectal administration) botulinum toxin (Botox), 262
Pharmacological treatment contractures and deformities, 261
acetaminophen, 247 developmental delay, 260
equianalgesic opioid doses, 251 epilepsy, 262
fentanyl, 251–252 flexion, toes, 260
hydromorphone, 252 gastroesophageal reflux, 260
ibuprofen, 247–248 laparoscopic fundoplication, 261
methadone, 252–253 neurolytic blocks, 262
morphine, 250–251 sarcopenia, 261
naloxone, 253 spasticity, 261
opioids, opioid-naive neonates, 248, 249 vigabatrin, 261
oxycodone, 253 family history, 14
parenteral and oral dose formulations, operating risk stratification
248, 250 American Society of Anesthesiologist
patient-controlled analgesia in Physical Status (ASA-PS), 12
children, 250 Johns Hopkins surgery risk
Pharmacologic approach, e-PONB classification system (JHSRCS), 12
alpha2-adrenergic agonists, 411 NARCO-SS score, 12
fentanyl, 412 physical examination
intravenous anaesthesia with propofol, 411 body weight and length, 15
midazolam, 411 pediatric early warning score (PEWS), 15
pain management, 411–412 preschool children, 14
Pharynx, 193 school-age children, 14
Phenol, 262 teenagers, 14
PICU. See Pediatric intensive care unit (PICU) toddlers, 14
Pierre Robin sequence, 274 preoperative assessment, 13
Platinum 30 min, 214 preoperative test
Play specialists, 24 anemia, 15
Plexus or psoas compartment block blood glucose, 16
(PSCB), 104 chest radiography, 16
Polysomnography, 190 ECG, 16
PONV. See Postoperative nausea and vomiting guidelines and recommendations, 15
(PONV) laboratory tests, 15
Postanesthetic discharge scoring system nonselective coagulation screening, 16
(PADSS), 69–71, 71t plasma electrolytes, 16
Post-discharge nausea and vomiting (PDNV), 69 timing and organization
Postoperative analgesia, 266 “one-stop anesthesia” modality, 13, 15
Postoperative nausea and vomiting (PONV), “one-stop surgery”, 13
68–69 preoperative visit, 13, 14
468 Index
Preparation, preoperative Rapid-onset obesity with hypothalamic

fasting, 34 dysfunction (ROHHAD), 198
non-pharmacological preparation (See Rapid sequence induction (RSI)
Non-pharmacological preparation) technique, 139
pharmacological preparation (See Ravitch procedure, 133, 134
Pharmacological preparation) Rectal administration
Preventive analgesia, 419 α2-agonists, 33–34
Primary injuries, 213, 214 ketamine, 33
Primary survey, trauma midazolam, 33
airway, 217 Regional anaesthesia
bleeding/hypertensive pneumothorax, 216 block techniques and dosing regimens,
breathing, 217–219 428–429
circulation, 219–220 continuous infusion, 427
disability, 221 CPNBs, 427
exposure, 221 epidural blocks, 427
family, 222 infusion guidelines, 427, 429
tension pneumothorax, 219 nerve blocks and dosing regimens,
verbal/slight painful stimulus, 216 427, 430
Prophylaxis, 46 peri-and postsurgical stress, 427
Propofol anaesthesia, 407–408 ultrasound guidance, 427
Propofol infusion, 411 Regional anesthesia, 168
PROSPECT project, 430 Remote locations
PSCB. See Plexus or psoas compartment block anesthesiological management
(PSCB) cerebral activity monitoring, 78
Pudendal, 429 depth of sedation, definitions, 79
Pulse contour analysis technique, 389 EtCO2 monitoring, 78
Pulse oximetry flexibility, 77
description, 380–381 hemodynamic monitoring (EKG,
external and patient-related factors, 382 NiBP), 78
hypoxemia, 381 multiple routes of administration, 79
oxygenated hemoglobin, 381 respiratory monitoring, 78
patient-controlled analgesia, 381 complementary techniques, 81–82
therapeutic decision-making tool, 381 discharge, 82
Puncture techniques inhalation techniques, 79–80
needle tip, 291, 292 intravenous techniques
patent vessels, 290 alfentanil, 81
sites dexmedetomidine, 81
foot, 298 ketamine, 81
forearm and antecubital fossa, 297 Ketofol, 81
hand, 297 propofol, 81
neck, 298 remifentanil, 81
scalp, 298 target-controlled infusion (TCI), 80
wrist, 298 nonoperating room anesthesia (NORA),
sliding movements, 291 75–82
US needle guidance, 291 pre-procedural assessment
failed sedations, 77
fasting status, 77
Q LEMON (Look at him, Evaluation,
Quadratus lumborum, 429 Mallampati, Obstruction, Neck), 76
SOAPME (Suction, Oxygen, Airway,
Pharmacy, Monitors, Equipment), 76
R Retinoic acid syndrome, 245
Radiation toxicity, 238–239 Reverse Nuss, 134
Radioallergosorbent test (RAST), 46 Rhabdomyolysis, 163
Index 469
S Spontaneous ventilation, 279

Sacral plexus, 428 SSEPs. See Somatosensory evoked potentials
Salivation, 262 (SSEPs)
Salt-wasting brain syndrome (SWS), 123 Subglottic stenosis (SGS)
Sciatic nerve block congenital distal tracheal stenosis, 278
biceps femoris muscle, 361 diagnostic bronchoscopy, 278
catheter, 363, 365 endotracheal intubation, 277
IP midfemoral approach, 363, 364 and laryngeal pathologies
IP subgluteous approach, 361, 362 Benjamin’s and Inglis’ classification,
local anesthetic spread, 361, 363 275, 276
Scoliosis surgery Cohen’s and Benjamin’s classification,
apical vertebra, 106–107 276, 277
cerebral palsy, 108 vocal cord paralysis, 276
Cobb method, 106–107 laryngomalacia, 275
estimated blood loss (EBL), 109 and tracheal pathologies, 277–278
extubation criteria, 111 tracheomalacia, 278
intraoperative spinal cord monitoring, 110 Succinylcholine, 163, 164, 167
motor evoked potentials (MEPs), 110 Sudden infant death syndrome (SIDS), 59
neuromuscular scoliosis (NMS), 107, 108 Sugammadex, 264
neurophysiologic monitoring, 110 Superior vena cava (SVC)
preoperative variables, 109 catheter malposition, 321
prone position for posterior approach, 109 cavo-atrial junction, 307
scoliosis, defined, 106 ECG guidance, 308
scoliosis surgery correction, 109 fluoroscopy, 308
scoliotic curve, 106 immediate complications, 320–321
somatosensorial evoked potentials internal jugular vein (IJV) (see Internal
(SSEPs), 110 jugular vein (IJV))
spinal fusion surgery, 111 late complications, 321
spinal instrumentation, 108 periclavicular approaches (see
surgical procedures, 106 Periclavicular approaches)
vertebral rotation and rib cage pleural puncture, 307
deformity, 108 spontaneous breathing, 307
Secondary injuries, 214 ultrasonography, 308
Sedation and analgesia, 78, 81, 127, Surgery
225–226, 255 infants brain, anesthesia, 442–443
SFAR. See Société Française d’Anesthésie et preparation for
de Réanimation (SFAR) ADVANCE, project, 24
Shock, 44, 138, 219–220, 449 age, children, 23–24
SIADH. See Syndrome of inappropriate coping techniques, 23
antidiuretic hormone secretion fasting, 27
(SIADH) informative approach, 23
Sickle cell disease, 59 modeling techniques, 23
SIDS. See Sudden infant death syndrome MRI, 24
(SIDS) music therapy, 24
Skin prick test (SPT), 45 parents’ anxiety, 24
“Sleep-awake-asleep” technique, 125 play and games, 23–24, 26
Sleep-disordered breathing (SDB), 187 play specialist, 24
Société Française d’Anesthésie et de success of, 24
Réanimation (SFAR), 69, 70 tablet-based interactive distraction
Somatosensory evoked potentials (SSEPs), 120 (TBID), 24
Spasticity SWS. See Salt-wasting brain
baclofen, 261 syndrome (SWS)
intrathecal injections, 261 Syndrome of inappropriate antidiuretic
vigabatrin, 261 hormone secretion (SIADH), 123
470 Index
T cart-based echographs, 342

Tablet-based interactive distraction (TBID), 24 curvilinear probes, 289
TAP. See Transversus abdominis plane Doppler and Zoom functions, 288–289
(TAP) block high-frequency probes, 289
Target-controlled infusion (TCI), 80 linear probes, 289
TBID. See Tablet-based interactive distraction needle handling skills, 346–347
(TBID) probes
TC-CO2. See Transcutaneous CO2 (TC-CO2) linear transducers, 343
devices nerve block, 345
TCD. See Transcranial Doppler (TCD) sector, 343
TCI. See Target-controlled infusion (TCI) types, children, 343, 344
Temperature, 263 small-footprint probes, 289
Tension pneumothorax, 219 sterile probe covers and sterile gel, 290
Thermal homeostasis ultrasonography, 345, 346
forced air systems, 263 Ultrasound guidance (USG)
hypothermia, 263 advantages, 286–287
Thermodilution method, 388, 390 applications, 285
Thoracic electrical bioimpedance (TEB), 389 equipment
TIVA. See Total intravenous anesthesia (TIVA) adult and pediatric, young children, 290
Tizanidine, 262 curvilinear probes, 289
Tonsillectomy, 71–72 Doppler and Zoom functions, 288–289
Total intravenous anesthesia (TIVA), 121, high-frequency probes, 289
167–168 linear probes, 289
Tracheal intubation, 41, 102, 150, 153–155, small-footprint probes, 289
218, 240 sterile probe covers and sterile gel, 290
Tracheomalacia, 278 gel models, 293, 295
Tranexamic acid, 266 learning curve, 293, 295
Transcranial Doppler (TCD), 120 limitations, 287
Transcutaneous CO2 (TC-CO2) devices post-procedural screening, 287, 288
advantages and disadvantages, 386 puncture techniques, 290–293
cutaneous vasoconstriction, 385 sterile setting and ergonomics, 293, 295
diabetic ketoacidosis (DKA), 385 sterility and ergonomy, 293, 295
neonatal population, 384 during vascular access, 288, 289
pulmonary ventilation-perfusion Umbilical, 429
matching, 385 UMSS. See University of Michigan Sedation
ventilation techniques, 384 Scale (UMSS)
Transpulmonary thermodilution (TPTD), 388 Uncooperative behavior management, 265
Transversus abdominis plane (TAP) block University of Michigan Sedation Scale
IP TAP block, 372, 373 (UMSS), 82
local anesthetic dispersion, 374 Upper limb blocks, US-guided techniques
needle insertion, 371 axillary approach
neuraxial blockade, 372 anechoic structure, 356
oblique fascia, 372 brachial plexus block, 356
subcostal/lateral, 429 catheter, 357, 359
Treacher-Collins syndrome, 101, 274 compression, 356, 357
Trisomy 21, 138 high-frequency linear probe, 357, 358
Tumor lysis syndrome (TLS), 243–244 in-plane technique, 357
local anesthetic, 357, 359
vascularization, 356
U brachial plexus, 347
Ultrasound (US) equipment infraclavicular approach, 351–355
adult and pediatric, young children, 290 interscalene block approach, 348–350
block technique, 343 supraclavicular approach, 351–353
Index 471
Upper respiratory infections (URI). See also indications and equipment, 333–334
Asthma ischemia, 336, 337
day-surgery, 59–60 local infection, 337
endotracheal tube or LMA, 40 posterior tibial artery, 336
laryngospasm, 40, 41 radial artery, 334, 335
propofol anesthesia, 40 temporal artery, 336
risk factors, 40, 41 ulnar artery, 336
salbutamol, 41 vasospasm, 336–337
symptoms of, 40 bedside ultrasound examination, 285
Urea cycle defect, 178–179 CVC (see Central venous catheter (CVC))
USG regional anesthetic techniques IO route
axillary approach, 356–359 complications, 333
cart-based echographs, 342 contraindication, 333
continuous peripheral nerve blocks, description, 331–332
374, 375 devices, 332–333
lower limb blocks (see Lower limb blocks, perioperative indications, 332
USG techniques) technique, 332–333
truncal blocks PICCs (see Peripherally inserted central
iliohypogastric (IH) and ilioinguinal catheters (PICCs))
(II) nerves, 367–370 portal vein thrombosis, 338
rectus sheath block, 370–372 PVA (see Peripheral venous
TAP, 371–374 access (PVA))
ultrasound equipment (see Ultrasound real-time needle guidance, 285
(US) equipment) ultrasound guidance (see Ultrasound
upper limb blocks (see Upper limb blocks, guidance (USG))
US-guided techniques) umbilical arteries, 338
USG, 341 umbilical vein, 337–338
Vascular malformations, 127
Venipuncture, 27
V Venous air embolism (VAE), 120, 122
Vaccination, 48 Venous thromboembolism (VTE), 99–100
VACTERL association, 138 Ventilation techniques, 279
VAE. See Venous air embolism (VAE) Vocal cord paralysis, 276
Valproic acid, 262 von Willebrand factor type I, 262
Vascular access, perioperative period VTE. See Venous thromboembolism (VTE)
arterial access
axillary artery, 336
brachial artery, 336 W
complications, 336–337 Wolff-Parkinson-White one (WPW), 16
dorsalis pedis artery, 336 WPW. See Wolff-Parkinson-White one
femoral artery, 334–336 (WPW)

Perioperative Medicine

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Anesthesia, Intensive Care and Pain in Neonates

ISSN 2281-1788 ISSN 2281-1796 (electronic)

Library of Congress Control Number: 2015955168

Springer Cham Heidelberg New York Dordrecht London

Printed on acid-free paper

Springer International Publishing AG Switzerland is part of Springer Science+Business Media

Francesco Carli, MD, MPhil

Perioperative clinical outcomes in procedures involving infants and children have

anesthetic-surgical-pediatrician relationship. This partnership should not continue

Catania, Italy Marinella Astuto, MD

Part I Perioperative Care Before Surgery

2 Preoperative Evaluation in Pediatric Anesthesia . . . . . . . . . . . . . . . . 11

Part II Perioperative Care During Surgery

5 Perioperative Care in Day Hospital Surgery. . . . . . . . . . . . . . . . . . . . 55

9 Pain After Surgical Correction of Congenital Chest

Part III Perioperative Care in Special Situations and Conditions

11 Perioperative Care of Children with a Difficult Airway . . . . . . . . . . 147

Part IV Important Techniques for Perioperative Care

19 Vascular Access in the Perioperative Period . . . . . . . . . . . . . . . . . . . . 285

Part V Early and Long Term Consequences of Anesthesia

22 Negative Behaviour After Surgery . . . . . . . . . . . . . . . . . . . . . . . . . . . . 403

23 Acute Pain Management and Prevention . . . . . . . . . . . . . . . . . . . . . . 417

Marinella Astuto Anesthesia, Intensive Care, University of Catania, Policlinico

Leonardo Bussolin Department of Neuroanesthesia and Neurointensive Care,

Jerrold Lerman, MD, FRCPC, FANZCA University of Rochester, Rochester,

Department of Anesthesia and Intensive Care, Catholic University of Sacred Heart,

1.1 What Is Perioperative Medicine?

Perioperative medicine is the practice of medicine that relates to and encompasses

1.2 Patients, Surgery, and Complications

G. Baldini, MD, MSc

© Springer International Publishing Switzerland 2016 1

minimizing organ dysfunction caused by surgery, might significantly reduce adverse

1.3 A Model of Perioperative Medicine: Learning

Traditionally, surgeons coordinate perioperative care of patients undergoing sur-

Mid-thoracic epidural anesthesia/analgesia Preadmission counseling

Prevention of nausea and vomiting No prolonged fasting

Avoidance of salt and water overload No/selective bowel preparation

Early removal of catheter Antibiotic prophylaxis

Avoidance of salt and water overload

Maintenance of normothermia (body warmer/warm intravenous fluids)

1.4 Areas of Perioperative Medicine

1.4.1 Preoperative Phase

1.4.1.1 Preoperative Risk Assessment and Optimization

1.4.2 Intraoperative Phase

monitoring, and appropriate analgesia, have shown to improve clinical outcomes

1.4.3 Postoperative Phase

1.4.3.1 Intensity of Postoperative Care

1.4.3.2 Postoperative Pain Management

1.4.3.3 Hemodynamic Management and Echocardiography

1.4.3.4 Noncardiac Ultrasound

Preoperative Intraoperative Postoperative

Preoperative risk assesment Temperature control Intensity of postoperative care

Fig. 1.2 Areas of perioperative medicine

respiratory complications such as pulmonary edema, lung consolidation, pleural

1.4.3.5 Chronic Postsurgical Pain

1.5 Perioperative Medicine: A Natural Extension

Anesthesiologists possess extensive perioperative knowledge and skills to be con-

departments have already entitled their departments “Department of Anesthesia and

adverse effect of postoperative complications. Ann Surg 242(3):326–341; discussion

5.3 Organizational Aspects

5.4 Selection Criteria

5.4.1.1 ASA Physical Status

5.4.1.3 Malignant Hyperthermia

5.4.1.4 Sudden Infant Death Syndrome

5.4.1.5 Sickle Cell Disease

5.4.1.6 Incidental Heart Murmurs

5.4.1.7 Upper Respiratory Infection (URI)