British Journal of Anaesthesia, 115 (S2): ii3–ii14 (2015)

doi: 10.1093/bja/aev380
Clinical Practice

C L I N I CA L P R AC T I C E

Perioperative acute kidney injury

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O. Goren* and I. Matot
Division of Anaesthesiology, Pain, and Intensive Care, Tel Aviv Medical Center, affiliated with Sackler Medical
School, Tel Aviv University, Tel Aviv, Israel
*Corresponding author: E-mail: goren.orr@gmail.com

Abstract
Perioperative acute kidney injury (AKI) is not uncommon and is associated with considerable morbidity and mortality. Recently,
several definition systems for AKI were proposed, incorporating both small changes of serum creatinine and urinary output
reduction as diagnostic criteria. Novel biomarkers are under investigation as fast and accurate predictors of AKI. Several special
considerations regarding the risk of AKI are of note in the surgical patient. Co-morbidities are important risk factors for AKI. The
surgery in itself, especially emergency and major surgery in the critically ill, is associated with a high incidence of AKI. Certain
types of surgeries, such as cardiac and transplantation surgeries, require special attention because they carry higher risk of AKI.
Nephrotoxic drugs, contrast dye, and diuretics are commonly used in the perioperative period and are responsible for a
significant amount of in-hospital AKI. Before surgery, the anaesthetist is required to identify patients at risk of AKI, optimize
anaemia, and treat hypovolaemia. During surgery, normovolaemia is of utmost importance. Additionally, the surgical and
anaesthesia team is advised to use measures to reduce blood loss and avoid unnecessary blood transfusion. Hypotension
should be avoided because even short periods of mean arterial pressure <55–60 mm Hg carry a risk of postoperative AKI. Higher
blood pressures are probably required for hypertensive patients. Urine output can be reduced significantly during surgery and is
unrelated to perioperative renal function. Thus, fluids should not be given in excess for the sole purpose of avoiding or treating
oliguria. Use of hydroxyethyl starch needs to be reconsidered. Recent evidence indicates a beneficial effect of administering
low-chloride solutions.

Key words: acute kidney injury; perioperative complications; perioperative management; surgery

Editor’s key points deterioration leads to accumulation of plasma waste products,

such as urea and creatinine. Acute kidney injury is not an uncom-
• Perioperative acute kidney injury is associated with major
mon disorder and is associated with considerable morbidity and
morbidity and mortality.
mortality. The definition of AKI has changed and evolved over the
• Use of serum creatinine in diagnosis is imperfect, and sev-
years, making the comparison of incidence and prevalence
eral novel biomarkers are under development to improve
among studies difficult. It is estimated that 2–18% of all hospital
detection.
inpatients acquire AKI.1–3 The incidence of AKI is reported to be
• Contributing factors include patient comorbidities, specific
between 22 and 57% in critical care patients.4 5 Unlike the trad-
surgeries, nephrotoxins, fluid and blood management, and
itional belief that patients recovering from AKI usually return to
haemodynamic stability.
their baseline renal function, recent reviews of the literature
show AKI to be a significant risk factor for chronic kidney dis-
ease.6 7 Acute kidney injury is also known to induce distant
The term acute kidney injury (AKI) is used to describe a rapid organ damage, which in turn contributes further to morbidity
deterioration (hours to days) of renal function. This rapid and mortality.8

Accepted: October 3, 2015

© The Author 2015. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved.
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ii3
ii4 | Goren and Matot

Perioperative AKI is a leading cause of morbidity and mortal- The guideline includes a comprehensive review of AKI definition,
ity. It is associated with increased risk of sepsis, anaemia, coagu- risk assessment, diagnosis, prevention, treatment, and renal re-
lopathy, and mechanical ventilation.9 In a prospective study of placement therapy. The group accepted the existing RIFLE and
1200 patients having non-cardiac non-vascular surgery, AKI AKIN criteria for the definition of AKI and proposed simple, prac-
was associated with increased morbidity and mortality.10 A tical criteria of AKI.22 The KDIGO criteria include both a relative
study investigating patients after general surgery reported an and an absolute change of sCr and accept a short (48 h) and an ex-
eight-fold increase in mortality in patients with perioperative tended (7 days) time frame for diagnosis of AKI. The urine output
AKI,11 whereas a more recent large-scale study of patients under- criteria remained practically unchanged. The KDIGO recommen-
going intra-abdominal surgery found that non-AKI patients had a dations relevant to perioperative AKI are discussed in the peri-
30 day mortality of 1.9%, compared with 31% in patients with operative management section.
AKI.12 Notably, mortality is higher in patients with perioperative A comparison of the three different classifications is pre-
AKI even after complete renal recovery.9 sented in Table 1.

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Perioperative AKI is a feared phenomenon with deleterious Despite the continued effort to standardize the definition of
effects. Methods to ameliorate the burden of perioperative AKI AKI using sCr, these methods have several flaws. The increase
are constantly sought. In this review, we discuss definitions of in sCr is late in the course of AKI such that by the time the diag-
AKI, the pathophysiology of AKI relevant to the perioperative nosis is made using standard laboratory methods the disease is
period, and specific considerations of AKI that are of special rele- well established. In addition, sCr can be influenced by volume
vance in the surgical patient. With this knowledge, we consider overload, nutrition, steroids, and muscle trauma.2
methods to identify patients at risk of AKI and review the current Recently, major advances suggest that biomarkers might help
recommended perioperative management aimed to prevent to detect AKI early, identify the aetiology, predict outcome, and
perioperative AKI. tailor specific therapies. Biomarkers are molecules that report
on renal function or damage that relate specifically to different
biological functions of the kidney.23 For example, N-acetyl-β-d-
Definition of acute kidney injury glucosamininidase in the urine is a direct marker of lysosomal
The first attempts to define AKI date back to the 17th century. injury in the proximal tubule, whereas cystatin C in the urine is
Nevertheless, the term acute renal failure appeared for the first a marker of reduced uptake by damaged proximal tubules.23
time in 1951.13 Since then, many definitions have been used by in- Some other promising biomarkers are kidney injury molecule-
vestigators and clinicians, resulting in a lack of clarity and prevent- 1, microalbumin, neutrophyl gelatinase-associated lipocalin,
ing comparable research. A review on the different classification interleukin 18, and liver fatty acid binding protein.23 24 A promis-
systems found more than 35 definitions of acute renal failure.14 ing study conducted in intensive care units (ICUs) showed that
The various definitions attempted to describe diverse aspects of the combined use of the two novel biomarkers insulin-like
AKI. Glomerular filtration rate (GFR) roughly expresses the overall growth factor binding protein 7 and tissue inhibitor of metallo-
function of the different parts of the kidney; a rapid decline in proteinases-2 was a sensitive and fast way to detect AKI.25 A
GFR defines AKI.15 Given that a 24 h urine creatinine clearance similar study showed that insulin-like growth factor binding pro-
test is not straightforward to apply in everyday practice, serum cre- tein 7 and tissue inhibitor of metalloproteinases-2 can also be
atinine (sCr) change from baseline is considered a reasonable sub- used for the detection of post-cardiac surgery AKI.26
stitute and is roughly correlated with the change in GFR (although Several issues remain to be solved before these biomarkers
sCr becomes abnormal only after GFR declines significantly).2 Most can be used in clinical practice. For example, should urinary bio-
definitions use urine output and sCr as markers of renal function markers be normalized to urinary creatinine concentrations?27
because they are unique to the kidney and easily measured. What is their specificity and sensitivity? Can we accurately define
The first publication of consensus criteria for AKI was pub- the sensitivity and specificity when making comparisons with a
lished in 2004. The system was named RIFLE (risk, injury, failure, rather imperfect gold standard, such as sCr? Should a single
loss of kidney function, end-stage renal failure) and used sCr or biomarker or a combination of several be used?24
urine output to define AKI.16 A major issue concerning AKI criteria is their relevance to the
In 2004, the term AKI was proposed as a replacement for the perioperative period. Many surgical patients arrive in hospital with-
former acute renal failure. The change of terms highlighted the out preoperative sCr concentrations. As was mentioned above, this
fact that loss of function and failure are preceded by a structural can lead to over-diagnosis of AKI. On the contrary, when patients
and physiological injury to the kidney. Later, in 2007, a modified do arrive with a preoperative sCr concentration, the opposite can
definition of the RIFLE criteria was published by the Acute Kidney occur because in the immediate postoperative period sCr concen-
Injury Network (AKIN).17 Although the AKIN criteria evolved from trations can be lower than baseline as a result of haemodilution
the RIFLE criteria, a major advance was the understanding that after massive fluid administration and fluid shifts. Comparing
even small changes in sCr concentrations are associated with in- these postoperative and preoperative values can lead to under-
creased morbidity and mortality.18 19 The AKIN criteria allowed diagnosis of AKI and consequently delay treatment.
definition of AKI even without knowledge of baseline sCr. A major concern is whether or not intraoperative urine output
Several studies conducted on postoperative AKI attempted to is reliable as a criterion for AKI. As discussed below, recent stud-
compare the predictive value of the two methods.20 21 Both ies suggest that urine output can be reduced significantly during
schemes predict outcome of AKI with different sensitivity and surgery and is unrelated to perioperative renal function.28 29
specificity. The comparison also highlighted the need to select
baseline sCr carefully when the diagnosis of AKI is based solely
on the net sCr change. If the selected baseline sCr is the first post-
Mechanisms of perioperative acute kidney
operative sCr or the sCr after fluid resuscitation, over-diagnosis of
AKI can occur.21
injury
In 2012, a clinical practice guideline of AKI was proposed by the Causes of AKI were traditionally divided into prerenal, intrinsic,
Kidney Disease: Improving Global Outcomes (KDIGO) Foundation. and postrenal, which provides a convenient classification, but
 Perioperative acute kidney injury | ii5

Table 1 Comparison of the three classifications and staging of acute kidney injury: RIFLE, AKIN, and KDIGO criteria.16 17 22 AKIN, Acute
Kidney Injury Network; GFR, glomerular filtration rate; KDIGO, Kidney Disease: Improving Global Outcomes; RIFLE, risk, injury, failure, loss
of kidney function, end-stage renal failure; RRT, renal replacement therapy; sCr, serum creatinine

Definition RIFLE AKIN KDIGO

system 7 days 48 h

Staging Risk Stage 1 Stage 1

Increased sCr × 1.5 or GFR Increased sCr × 1.5–2 or sCr Increased sCr × 1.5–1.9 that is known or
decrease >25% increase ≥0.3 mg dl−1 presumed to have occurred within the
or or preceding 7 days or sCr increase ≥0.3 mg
urine output <0.5 ml kg−1 h−1 for urine output <0.5 ml kg−1 h−1 dl−1 within 48 h
6h for >6 h or

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urine output <0.5 ml kg−1 h−1 for 6–12 h
Injury Stage 2 Stage 2
Increased Increased Increased sCr × 2–2.9
sCr × 2 or GFR decease >50% sCr × 2–3 or
or or urine output <0.5 ml kg−1 h−1 for ≥12 h
urine output <0.5 ml kg−1 h−1 for urine output <0.5 ml kg−1 h−1
12 h for >12 h
Failure Stage 3 Stage 3
Increased sCr × 3 or GFR decrease Increased sCr × 3 or more or Increased sCr × 3
75% or sCr ≥4 mg dl−1 when sCr is sCr ≥4 mg dl−1 when sCr is in or sCr ≥4 mg dl−1
in acute increase (≥0.5 mg dl−1) acute increase (≥0.5 mg dl−1) or initiation of RRT
or or or GFR decrease to <35 ml min−1 (1.73 m)−2
urine output <0.3 ml kg−1 h−1 for urine output <0.3 ml kg−1 h−1 in patients <18 yr old
24 h or anuria for 12 h for >24 h or anuria for 12 h or
urine output <0.3 ml kg−1 h−1 for ≥24 h or
anuria for ≥12 h

the disease does not always strictly obey these definitions. For are well tolerated.2 Evidence suggests that systemic inflamma-
example, prerenal AKI if profound and lasting will eventually tion leading to tubular injury is responsible for sepsis-associated
lead to intrinsic AKI (secondary AKI).2 15 Intrinsic AKI is better AKI whether or not ischaemia was the initiating factor.30
understood when divided into the major structures of the kidney, Apart from the general mechanisms that are common to AKI
as follows: (i) damage to the renal vasculature from embolic events from various causes, other specific contributions to perioperative
and vasculitides, such as malignant hypertension and haemolytic AKI are of special note in the surgical patient.
uraemic syndrome; (ii) damage to the renal interstitium from
allergic reactions, leukaemia, lymphoma, and bacterial infections;
Co-morbidities
(iii) tubular damage because of secondary AKI, inflammation, ex-
ogenous toxins (contrast dye, antibiotics), and endogenous toxins With the development of surgical techniques and advanced an-
(myoglobin, haemoglobin).15 The most common trigger for AKI in aesthesia delivery and monitoring, surgery on sicker and older
the inpatient population is sepsis.2 30 Major surgery and acute de- patients is more common. These patients suffer from co-morbid-
compensated heart failure are also common reasons for AKI in ities, such as chronic kidney disease, metabolic syndrome, dia-
this population.2 betes mellitus, and cardiovascular and hepatobilliary disease,
The kidney is able to maintain GFR even in the face of chan- all of which are well-documented risk factors predisposing to
ging arterial pressure and volume status. Reduced mean arterial AKI.10–12 32 Male sex is also a risk factor of AKI.11 Other reported
pressure (MAP) initiates a series of systemic and local processes. risk factors in surgical patients are functional dependence,
The sympathetic system is activated, antidiuretic hormone is re- ventilator dependence, chronic obstructive pulmonary disease,
leased, and the renin–angiotensin–aldosterone system increases smoking, bleeding disorders, chronic steroid use, and cancer.12
angiotensin II activity. The net result is water retention, in- A retrospective cohort study evaluated the incidence of AKI in pa-
creased sodium absorption, and the preservation of GFR.15 31 tients admitted to the ICU beds of the postanaesthesia care unit.
Later, if hypoperfusion is not corrected, angiotensin II eventually Independent risk factors of AKI included ASA physical status, Re-
causes vasoconstriction of both the afferent and the efferent ar- vised Cardiac Risk Index, high-risk surgery, and congestive heart
terioles, and as a consequence, reduces GFR.31 These mechan- failure.33 A prospective cohort study conducted in non-vascular,
isms function only as long as MAP is maintained above the non-cardiac surgery patients identified age, diabetes mellitus,
autoregulatory threshold. Below a MAP of 75–80 mm Hg, the auto- Revised Cardiac Risk Index, and ASA status as independent risk
regulatory efficiency declines abruptly.15 factors of AKI.10
A wider and more complex understanding of the mechanisms
of AKI is emerging. The simple ischaemia model alone cannot ex-
plain sepsis- and major-surgery-associated AKI. Haemodynam-
Obesity
ics in sepsis are dominated by a hyperdynamic state, and global Obesity is an excessive accumulation of adipose tissue. Obesity is
renal blood flow may remain intact.30 Decreased perfusion might an epidemic with profound effect on morbidity and mortality.
not be the only reason for major-surgery-associated AKI, because Worldwide, the prevalence of BMI >25 kg m−2 is estimated to be
even prolonged intervals of partial occlusion of the renal artery 37% in men and 38% in women.34 Obesity is a risk factor for AKI
ii6 | Goren and Matot

in general and for perioperative AKI in particular;35 36 it is asso- propofol to attenuate AKI in experimental studies; however,
ciated with metabolic syndrome and can alter renal hemo- such an effect has not been shown in humans.59–62 Recently, a
dynamics.37 The special characteristics of the kidney in the study conducted on 112 patients undergoing valvular heart sur-
obese, known as obesity-related glomerulopathy, include gery and randomized to anaesthesia by either propofol or sevo-
changes in GFR and glomerulomegaly.35 A different understand- flurane showed anaesthesia with propofol to be associated with
ing of the correlation between obesity and atherosclerotic mor- reduced incidence and severity of AKI.63 A study on healthy
bidity can be achieved when the different types and spread of volunteers found that the sympathetic block caused by epidural
adipose tissue are taken into consideration.38 39 Recently, a anaesthesia did not change renal blood flow significantly.64 A
study on ICU trauma patients showed AKI to be correlated with meta-analysis found the incidence of AKI to be lower for neurax-
abdominal fat in particular, as measured by computed ial anaesthesia when compared with general anaesthesia.65
tomography.40 Another meta-analysis evaluated epidural anaesthesia com-
bined with general anaesthesia in cardiac surgery and found a
reduction in AKI in the combined group.66 A recent population-

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Surgery
based historical cohort study found combined general and
In every major operation, a risk for reduction in effective blood neuraxial anaesthesia to have a similar incidence of AKI when
volume or mechanical obstruction exists. Hypovolaemia, low compared with general anaesthesia alone.67
systemic vascular resistance because of anaesthesia or caval
compression, and direct injury to the renal system are all com-
Cardiac surgery
mon events during surgery that can harm the kidney.
Emergency surgery is a risk factor for AKI.11 12 Patients with Acute kidney injury is a significant deleterious consequence of
sepsis presenting to the operating room are at increased risk of cardiac surgery that is associated with increased mortality.19 68
AKI,12 as are patients arriving in the emergency room with sep- The incidence of AKI associated with cardiac surgery can reach
sis.41 Major vascular surgery,42 and cardiac surgery in particu- 30% depending on the definition of AKI.68–70 The mechanisms
lar,43 are well-known risk factors for AKI. Patients undergoing of cardiac surgery-associated AKI are multifactorial and mostly
intraperitoneal surgery in general,11 and exploratory laparotomy related to the use of cardiopulmonary bypass (CPB). Some of
and small bowl resections in particular, are more prone to de- the pathophysiological explanations are ischaemia–reperfusion
velop AKI.12 Lung resection has a relatively high incidence of injury, microembolization, inflammation, decreased renal perfu-
AKI.44 An observational study on cardiac surgery because of sion pressure, haemodilution, and use of nephrotoxic drugs.43
infective endocarditis showed the incidence of postoperative Preoperative chronic kidney disease is the most important risk
AKI to be as high as 59%.45 factor for perioperative AKI in this setting. Other risk factors of
cardiac surgery-associated AKI are age, female gender, preopera-
tive anaemia, perioperative packed red blood cell (PRBC) transfu-
Intra-abdominal pressure
sion, heart failure, emergency surgery, diabetes mellitus,
Increased intra-abdominal pressure is common in ICU patients haemodilution on CPB, duration of CPB, use of an intra-aortic bal-
after abdominal surgery.46 Increased intra-abdominal pressure, loon pump, and valve surgery.43 71 Several risk-predicting models
which is frequently explained by excessive administration of of cardiac surgery-associated AKI have been proposed in order to
fluids,47 48 can cause abdominal compartment syndrome, mech- increase vigilance for high-risk patients.72–74
anically compress the renal veins and constrict the renal arteries Methods to prevent cardiac surgery-associated AKI have been
via activation of the sympathetic system.48 Increased intra-ab- reported with varying degrees of evidence. Preoperative methods
dominal pressure can ultimately lead to reduced renal perfusion include the use of aspirin, avoiding diuretics, maintaining euvo-
and create an ischaemic insult to the kidney and AKI.48 49 Lapar- laemia, avoiding anaemia, use of erythropoietin, and use of
oscopy can also lead to a transient increase in intra-abdominal prophylactic renal replacement therapy. Intraoperative methods
pressure. As a result, during laparoscopy the recorded urine out- are avoiding anaemia and PRBC transfusion, maintaining MAP
put is significantly reduced, and patients can become oliguric above cerebral perfusion pressure, pulsatile perfusion during
despite normovolaemia and normotension. Several studies CPB, preferring off-pump coronary artery bypass grafting, use of
have shown that the observed reduction in urine output during intra-aortic filtration, and use of miniature CPB. The main post-
laparoscopy is not predictive of postoperative AKI in adults50–52 operative strategy to prevent the consequences of cardiac sur-
and in children.53 In the critically ill and in patients’ suffering gery-associated AKI is early use of renal replacement therapy.43
from chronic kidney disease, the duration of pneumoperitoneum Some pharmacological protective agents have been proposed
should be minimized.54 (fenoldepam, statins, human atrial natriuretic peptide, and ne-
siritide) but without conclusive evidence to support their use.43
Recently, remote ischaemic preconditioning was shown to
Anaesthesia
reduce the incidence of cardiac surgery-associated AKI and the
The anaesthetist can influence the risk of AKI in several ways. need for renal replacement therapy in high-risk patients.75
Haemodynamic management (in particular, keeping MAP >55
mm Hg)55 56 and maintenance of euvolaemia are both related to
Paediatric surgery
the occurrence of perioperative AKI. Historically, some haloge-
nated anaesthetics are considered nephrotoxic, such as methox- Data on paediatric perioperative AKI is scarce. Although the neo-
yflurane, which is no longer in routine use.57 Use of sevoflurane is natal period is relatively short, the AKI burden is disproportional-
associated with increased plasma fluoride concentrations and ly high in this age group.76 77 Acute kidney injury in children is
with production of a haloalkene called ‘compound A’; however associated with long-term morbidity and mortality.77–79 The
it has been evaluated extensively and is considered safe to most common cause in neonates and infants is post-cardiac sur-
use.58 Regarding the choice of anaesthetic technique, most re- gery AKI.77 Paediatric AKI is defined in a similar way to adult AKI,
ports concern the beneficial effects of inhaled anaesthetics and with some modifications,80 with the exception of the first days of
 Perioperative acute kidney injury | ii7

life when the neonate’s sCr reflects the mother’s sCr.81 82 Later, mellitus, and old age are all risk factors for aminoglycoside-
neonatal GFR (evaluated as sCr) is correlated with gestational induced nephrotoxicity.15
age and postnatal age in preterm neonates.82 High vigilance for
AKI is necessary in the paediatric population, especially in chil-
Iodinated radiocontrast-induced acute kidney injury
dren admitted to the paediatric ICU. Several methods have
been proposed for the early detection of AKI, but with various de- Contrast dye-induced AKI is a subtype of drug-induced AKI with
grees of success.83–85 Cardiac surgery-associated AKI in children well-defined characteristics. The pathophysiology of contrast
has many risk factors, but the two consistent ones are prolonged dye-induced AKI is a combination of hypoxic and toxic damage
CPB and younger age.85 Currently, the early management of and endothelial dysfunction.15 It is not uncommon for patients
paediatric AKI involves identification of patients at risk, optimiz- to arrive in the operating room after a radiological examination in-
ing volume status, and administering theophylline for neonates volving radiocontrast dye. Contrast dye-induced AKI is associated
suffering from severe asphyxia.22 31 with a significant increase in both short- and long-term mortal-
ity.96 Contrast dye-induced AKI can be prevented by maintaining

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normovolaemia, augmenting urine output, and withholding
Transplantation surgery other nephrotoxic agents. Other strategies include the administra-
tion of sodium bicarbonate and N-acetyl cysteine, although evi-
Transplantation surgery is usually a complex procedure in high- dence is not well established for these treatments.22 97 Patients
risk patients. Acute kidney injury complicates many of these with hypovolaemia are at increased risk of contrast dye-induced
procedures. Transplanted kidneys are susceptible to surgical, AKI. Maintaining effective blood volume is essential before expos-
ischaemic, and drug-related insults predisposing them to AKI. ing patients to the risks of drugs and contrast dye.15 22
However, application of the regular definitions of AKI to a trans- A summary of possible insults predisposing to AKI in the
planted kidney is more problematic considering the post- perioperative period is presented in Fig. 1.
operative changes in sCr concentrations. Moreover, it is not
always possible to differentiate accurately between perioperative
AKI and graft dysfunction.86 Perioperative management
Liver transplantation is a major high-risk surgery. The effects Identification of patients at risk of developing acute
of cirrhosis, nephrotoxicity of some immunosuppressive drugs, kidney injury
and the risks of the surgery are all well-known risk factors for
perioperative AKI. The incidence of post-liver transplantation-re- The first step in preventing and treating AKI is to identify patients
lated AKI varies from 14 to 78% depending on the definition of AKI at risk. Extremes of age, co-morbidities, anaemia, potential hypo-
used, type of transplantation, and patients included in the volaemia, use of contrast dye, use of nephrotoxic drugs, and
study.87–89 However, liver transplantation-related AKI has specif- emergency or high-risk surgery should all alert the anaesthetist
ic diagnostic problems attributable to high bilirubin concentra- to the possibility of perioperative AKI. Some of these risk factors
tions, muscle wasting, oedema, and postoperative use of can be optimized before surgery.
GFR-lowering medications, such as tacrolimus. All can affect
sCr concentrations and under- or overestimate the incidence of Haemodynamic goals
AKI.90 While some risk factors for liver transplantation-related
AKI are similar to other high-risk surgeries, some risk factors The main haemodynamic goal in the perioperative patient is to
are unique.87 89 91 Accordingly, strategies to prevent liver trans- prevent tissue hypoperfusion and thus organ hypoxia. Direct
plantation-related AKI include the use of terlipressin87 and monitoring of tissue hypoxia is not readily feasible in the clinical
avoiding or lowering the dose of tacrolimus after surgery.92 setting. Thus, indirect measures, such as MAP, heart rate variabil-
A small-scale study found the incidence of AKI post-lung ity, and lactate concentrations, are usually used. In the ICU set-
transplantation to be 54%. The incidence of AKI among patients ting, MAP >60–65 mm Hg (>75 mm Hg in patients with chronic
who had a double lung transplant was almost double (87%) the hypertension) is recommended to prevent AKI.98 99 The peri-
incidence in one-lung transplant patients (40%). Intraoperative operative patient has been less extensively investigated. A
hypoxaemia was correlated with AKI.93 meta-analysis showed perioperative haemodynamic optimiza-
tion to reduce postoperative AKI.100 A study conducted on
33 300 non-cardiac surgery patients found that duration of MAP
Drugs <55 mm Hg was independently correlated with AKI.55 A recent
retrospective cohort study conducted on 5127 patients undergo-
Nephrotoxic drugs are a well-established cause of AKI of prere- ing non-cardiac surgery found similar results. The risk of AKI was
nal, postrenal, and intrinsic origin. Nephrotoxic drugs are increased when MAP was <60 mm Hg for >20 min or <55 mm Hg
involved to some extent in AKI in up to 25% of critically ill pa- for >10 min.56 These large-scale studies aid the anaesthetist in
tients.2 94 A large population-based study showed that combina- determining an MAP threshold to be maintained during surgery.
tions of more than two prevalent nephrotoxic drugs (diuretics They also emphasize the importance of the duration of hypoten-
with angiotensin receptor blocker or angiotensin-converting sion, because even short periods have been shown to affect the
enzyme inhibitors and nonsteroidal anti-inflammatory drugs) kidney. Given that autoregulation changes with co-morbidities,
increased the risk of AKI.95 Angiotensin-converting enzyme inhi- future studies should take into account baseline MAP and
bitors and non-steroidal anti-inflammatory drugs, in particular, possibly adopt a more personalized approach to intraoperative
may worsen prerenal AKI because of their influence on compen- arterial pressure management.
satory mechanisms aimed to maintain GFR.15 Aminoglycoside, a
commonly administered antibiotic in the operating room, can
Choice of fluid solution
cause AKI through intracellular processes such as mitochondrial
dysfunction and reduction of protein synthesis. A high dose of Perioperative fluid therapy is aimed to maintain intravascular
aminoglycoside, chronic kidney disease, hypovolaemia, diabetes volume and allow tissue perfusion. Crystalloid solutions include
ii8 | Goren and Matot

Aetiologies of perioperative acute kidney injury

Prerenal:
Preoperative Intraoperative
1. Hypovolaemia 1. Hypovolaemia
Gastrointestinal loses Insensible loses
Haemorrhage Haemorrhage
Third spacing Over diuresis
2. Sepsis 2. Hypotension due to low systemic vascular
resistance (anaesthesia induced)
3. Cardiac failure 3. Low cardiac output (heart failure,

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anaesthesia and CPB induced)
4. Increased intra-abdominal pressure 4. Increased intra-abdominal pressure
5. Cirrhosis, hepatorenal syndrome 5. Aortic cross-clamp
Drugs-non-steroidal anti-inflammatory drugs, angiotensin-converting enzyme
inhibitors, norepinephrine, diuretics.

Intrinsic:
Perioperative
Inflammation
Patient co-morbidities-chronic kidney disease, diabetes mellitus, obesity,
atherosclerosis.
Drug-induced-Antibiotics, aspirin, phenytoin, furosemide, non-steroidal anti
inflammatory drugs, clopidogrel, tacrolimus
Radio-contrast agents
Endogenous nephrotoxins-haemoglobin and myoglobin
Acidosis
Infection
CPB
Anaemia
Packed red blood cell administration
Fluid solutions (hydroxyethyl starch, chloride-rich solutions)

Postrenal:
Preoperative Intraoperative
Tumour Surgical intervention or damage
Prostatic enlargement
Calculi
Blood clots
Neurogenic bladder
CPB-Cardio-pulmonary bypass.

Fig 1 Aetiologies of perioperative acute kidney injury.

normal saline (0.9%) or balanced solutions (Ringer’s lactate, Plas- retrospective study found postoperative hyperchloraemia to be
ma-Lyte, etc.). Colloid solutions include synthetic hydroxyethyl correlated with postoperative AKI.105 The precise clinical implica-
starches (HES), gelatins, and albumin. tions of these results for the incidence of perioperative AKI are
Crystalloid solutions contain different mixtures of electro- not yet clear and are under investigation.106 107
lytes. Saline contains only NaCl, unlike balanced crystalloids, The association of colloid solutions with AKI is controversial.
which are more similar to plasma content. Use of 0.9% saline is Several recent studies report an increase in incidence of AKI and
associated with development of hyperchloraemia. Animal101 renal replacement therapy in critically ill patients infused with
and human experiments102 suggest that saline infusion is corre- HES rather than crystalloids.108–111 These studies evaluated HES
lated with reduced renal blood flow compared with balanced so- solutions with different molecular weights, including the new
lutions. In a large study in the ICU, chloride-restricted fluid low-molecular-weight solutions. Less is known about surgical
management was associated with less AKI and renal replace- patients during the perioperative period. Several studies and
ment therapy.103 Similar results were observed in liver trans- meta-analyses found HES to be a risk factor for AKI,91 112 113
plantation patients, where chloride-liberal fluid administration whereas others did not.114–117 To date, intraoperative use of HES
was a risk factor for postoperative AKI.104 Another large solutions is not recommended in patients with AKI or at risk of
 Perioperative acute kidney injury | ii9

Preoperative:

Identify patients at risk:

Patient related factors- co-morbidities (obesity, CKD, DM, cardiovascular

and hepatobilliary diseases, male sex, obesity,
pulmonary disease, steroid use, cancer,
ASA score, ICU patients, increased intraabdominal
pressure, sepsis, older age and neonates)
Procedure related factors- a. Major surgery (extensive laparotomy

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lung resections, transplantations)
b. Emergency surgery
c. Cardiac surgery
d. Use of contrast dye

Anaemia- Correct anaemia before to surgery when possible according to the patient blood
management protocol.† 139 140 141 142 143 145

Intraoperative:

Choice of fluid solution- a. Avoid HES solutions when possible.† 22 91 108 112 113 117 118 119
b. Balanced crystalloid solutions may prove superior to chloride
rich solutions in preventing AKI.† 103 104 105

Fluid management- a. The use of intraoperative urinary output as a guide to fluid

administration may not be beneficial.† 127 128 129 130
b. Avoid the use of diuretics unless a need to treat volume overload
arises.22 98 135 136 137
c. Use measures during surgery to avoid blood loss and unnecessary
PRBC transfusion.† 139 140 141 142 143 145

Haemodynamic goals- a. Avoid a low MAP even for relatively short periods of time.† 55 56
b. Evidence so far do not recommend the use of one vasopressor
over the other.22
c. Low dose dopamine is no longer considered “renoprotective”
and is not recommended.22 98 148

General considerations- a. Avoid the use of aminoglycosides unless no suitable less

nephrotoxic alternative exists.22

Fig 2 Perioperative management, recommendations prevention of acute kidney injury, and summary. CKD, chronic kidney disease; DM, diabetes mellitus;
HES, hydroxyethyl starch; ICU, intensive care unit; MAP, mean arterial blood pressure; PRBC, packed red blood cell. †This recommendation is based mainly on
observational studies, randomized controlled trials are needed.

AKI.91 108 112 117 118 In a recent paper, Hartog and colleagues119 responds to fluid administration.122–126 Clearance of fluid during
raised concerns regarding the intraoperative use of HES and con- general anaesthesia is only a small fraction of that observed in
cluded that in the absence of proven benefit and considering the conscious volunteers.127 Infusion of crystalloids during anaes-
methodological problems with studies supporting the use of HES, thesia shows reduced clearance and slower distribution28 29
they do not recommend use of HES solutions in any clinical such that intraoperative oliguria may not reflect fluid status or
situation. predict future AKI. A retrospective study in non-cardiac surgical
patients that evaluated risk factors associated with AKI did not
find oliguria to be predictive of postoperative AKI.128 Two pro-
Intraoperative fluid management and urine output
spective randomized studies129 130 that involved bariatric pa-
A common practice to maintain effective blood volume and thus tients and patients undergoing thoracoscopic surgery for lung
kidney perfusion is i.v. hydration. Correcting hypovolaemia is an resection found no correlation between intraoperative urine out-
essential perioperative haemodynamic goal,120 and appropriate put and postoperative AKI. In both studies, intraoperative oli-
hydration is considered important for the avoidance of AKI.22 guria was not predictive of postoperative AKI. Additionally,
121
Intraoperative urine output is often monitored but rarely both studies found no relationship between the amount of
ii10 | Goren and Matot

intraoperative fluids administered (very restrictive vs high- The current KDIGO guidelines state that the evidence so far
volume fluid administration) and intraoperative urine output does not support the use of one vasoactive agent over another.22
or postoperative renal dysfunction. Given that liberal fluid
administration can be correlated with worse postoperative
Vasodilator therapy
outcome,123–125 131 132 the recommendation to maintain, among
other things, urine output of at least 0.5 ml kg−1 h−1 should be re- The rationale behind vasodilator therapy (fenoldepam, atrial
considered.133 134 Urine output in anaesthetized patients may not natriuretic peptide, nesiritide) is to cause renal vasodilatation
be an adequate indicator of fluid balance and is not predictive and increase GFR. Taking into consideration the lack of conclu-
of postoperative AKI in elective surgeries (non-vascular, non- sive beneficial evidence and the potential adverse effects of vaso-
cardiac, and non-transplant). dilator therapy, the common recommendation is against their
use to prevent or treat AKI.22 150
A summary of the major recommendations for prevention of
Use of diuretics AKI is presented in Fig. 2.

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Loop diuretics and mannitol are commonly used during surgery
in an attempt to prevent AKI or treat oliguria and anuria based on Conclusions
experimental studies reporting renoprotective properties of
diuretics. This practice has not been shown to be benefiial.135 Perioperative AKI continues to be a feared consequence of sur-
On the contrary, use of diuretics can be harmful because these gery. It is associated with both short- and long-term deleterious
agents can cause prerenal damage and nephrotoxicity. Diuretics effects. The complexity of perioperative AKI pathophysiology in-
are not recommended except to treat volume overload.22 98 135–137 volves the combined roles of ischaemia and inflammation as
causes of AKI. Novel biomarkers are proposed as a faster and
more accurate way for prompt identification of AKI and could
Anaemia and use of blood products prove beneficial in early intervention to prevent further deterior-
Low haemoglobin concentration reduces the oxygen-carrying ation in renal function. Specific co-morbidities, surgeries, and in-
capacity of the blood. Experimentally, medullary hypoxia plays terventions increase the risk of AKI, such as cardiac or transplant
a central role in the development of AKI.138 A large observational surgery and use of contrast dye. The intraoperative period is un-
study involving non-cardiac surgery patients found preoperative ique in that both anaesthesia and surgery combine to affect renal
anaemia and early postoperative decrements of haemoglobin to function. During surgery, even short periods of hypotension put
be associated with AKI.139 Perioperative anaemia and periopera- the kidney at risk. Urine output does not predict postoperative
tive PRBC transfusions are risk factors for AKI in cardiac sur- AKI. Careful selection and use of i.v. fluids and vasopressors
gery,140–143 such that every unit of transfused blood increases and appropriate blood management are important to prevent
the incidence of cardiac surgery-associated AKI by 10–20%.141 perioperative AKI.
The extent to which this increase is attributable to the deleteri-
ous effects of PRBC transfusions or is a surrogate marker for an Authors’ contributions
extensive surgery is not known. A synergism between the effects
of anaemia and PRBC transfusion may also play a role in this Drafted the manuscript: O.G.
complex mechanism of injury.140 141 Additionally, stored PRBCs Reviewed and revised the manuscript: I.M.
can cause organ damage and are associated with reduced oxy- Approved the final manuscript: O.G., I.M.
gen-carrying capacity.141 144 It is therefore advisable to optimize
patients’ preoperative haemoglobin status as suggested by the Declaration of interest
recent ‘patient blood management’ protocol,145 while using mea-
sures during surgery to reduce blood loss and avoid unnecessary None declared.
PRBC transfusion.

References
Use of vasopressors
1. Lewington AJP, Cerdá J, Mehta RL. Raising awareness of
The role of vasopressors in preventing AKI is not entirely clear. acute kidney injury: a global perspective of a silent killer.
The benefit of vasopressor use in the setting of AKI is mainten- Kidney Int 2013; 84: 457–67
ance of renal perfusion pressure within autoregulatory limits. 2. Bellomo R, Kellum JA, Ronco C. Acute kidney injury. Lancet
Nevertheless, concerns about renal vascular vasoconstriction 2012; 380: 756–66
and side-effects cause clinicians to refrain from their use. Nor- 3. Nash K, Hafeez A, Hou S. Hospital-acquired renal insuffi-
epinephrine constricts renal arterioles and reduces renal blood ciency. Am J Kidney Dis 2002; 39: 930–6
flow (but not GFR).146 Nonetheless, it is commonly used and is 4. Thakar CV, Christianson A, Freyberg R, Almenoff P,
considered safe and effective.98 147 Vasopressin in addition to Render ML. Incidence and outcomes of acute kidney injury
norepinephrine did not show clinical benefit.147 Epinephrine in intensive care units: a Veterans Administration study.
has a prominent α-adrenoreceptor-mediated effect in the kidney. Crit Care Med 2009; 37: 2552–8
Epinephrine is more rarely used, mainly because of its potential 5. Hoste EA, Bagshaw SM, Bellomo R, et al. Epidemiology of
to cause tachycardia, lactataemia, and hyperglycaemia.147 acute kidney injury in critically ill patients: the multination-
Low-dose dopamine can enhance urine output through its al AKI-EPI study. Intensive Care Med 2015; 41: 1411–23
diuretic effect but is no longer considered renoprotective and is 6. Kline J, Rachoin J-S. Acute kidney injury and chronic kidney
not recommended for treatment of AKI.22 98 148 Compared with disease: it’s a two-way street. Ren Fail 2013; 35: 452–5
norepinephrine, dopamine is associated with more adverse 7. Chawla LS, Kimmel PL. Acute kidney injury and chronic kid-
events.149 Phenylephrine is a potent vasoconstrictor, but with a ney disease: an integrated clinical syndrome. Kidney Int 2012;
profound α-adrenergic activity that causes vasoconstriction. 82: 516–24
 Perioperative acute kidney injury | ii11

8. Yap SC, Lee HT. Acute kidney injury and extrarenal organ 27. Ralib AM, Pickering JW, Shaw GM, et al. Test characteristics of
dysfunction: new concepts and experimental evidence. urinary biomarkers depend on quantitation method in
Anesthesiology 2012; 116: 1139–48 acute kidney injury. J Am Soc Nephrol 2012; 23: 322–33
9. Bihorac A, Yavas S, Subbiah S, et al. Long-term risk of mortal- 28. Hahn RG. Volume kinetics for infusion fluids. Anesthesiology
ity and acute kidney injury during hospitalization after 2010; 113: 470–81
major surgery. Ann Surg 2009; 249: 851–8 29. Norberg A, Hahn RG, Li H, et al. Population volume kinetics
10. Biteker M, Dayan A, Tekkeşin AI, et al. Incidence, risk factors, predicts retention of 0.9% saline infused in awake and iso-
and outcomes of perioperative acute kidney injury in flurane-anesthetized volunteers. Anesthesiology 2007; 107:
noncardiac and nonvascular surgery. Am J Surg 2014; 207: 24–32
53–9 30. Prowle JR, Bellomo R. Sepsis-associated acute kidney injury:
11. Kheterpal S, Tremper KK, Heung M, et al. Development and macrohemodynamic and microhemodynamic alterations
validation of an acute kidney injury risk index for patients in the renal circulation. Semin Nephrol 2015; 35: 64–74

Downloaded from https://academic.oup.com/bja/article/115/suppl_2/ii3/272807 by guest on 25 October 2020

undergoing general surgery: results from a national data 31. Symons JM. Moving beyond supportive care—current status
set. Anesthesiology 2009; 110: 505–15 of specific therapies in pediatric acute kidney injury. Pediatr
12. Kim M, Brady JE, Li G. Variations in the risk of acute kidney Nephrol 2014; 29: 173–81
injury across intraabdominal surgery procedures. Anesth 32. Pascual J, Liaño F, Ortuño J. The elderly patient with acute
Analg 2014; 119: 1121–32 renal failure. J Am Soc Nephrol 1995; 6: 144–53
13. Eknoyan G. Emergence of the concept of acute renal failure. 33. Abelha FJ, Botelho M, Fernandes V, Barros H. Determinants
Am J Nephrol 2002; 22: 225–30 of postoperative acute kidney injury. Crit Care 2009; 13: R79
14. Kellum JA, Levin N, Bouman C, Lameire N. Developing a con- 34. Ng M, Fleming T, Robinson M, et al. Global, regional, and na-
sensus classification system for acute renal failure. Curr Opin tional prevalence of overweight and obesity in children and
Crit Care 2002; 8: 509–14 adults during 1980–2013: a systematic analysis for the Global
15. Sharfuddin AA, Weisbord SD, Palevsky PM, Molitoris BA. Acute Burden of Disease Study 2013. Lancet 2014; 384: 766–81
kidney injury. In: Taal MW, Chertow GM, Marsden PA, 35. Suneja M, Kumar AB. Obesity and perioperative acute kidney
Skorecki K, Yu ASL, Brenner BM, eds. Brenner and Rector’s The injury: a focused review. J Crit Care 2014; 29: 694.e1–6
Kidney. Philadelphia, USA: Elsevier, 2012; 1044–99 36. Varrier M, Ostermann M. Novel risk factors for acute kidney
16. Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P. Acute injury. Curr Opin Nephrol Hypertens 2014; 23: 560–9
renal failure – definition, outcome measures, animal models, 37. Kwakernaak AJ, Toering TJ, Navi G. Body mass index and body
fluid therapy and information technology needs: the Second fat distribution as renal risk factors: a focus on the role of renal
International Consensus Conference of the Acute Dialysis haemodynamics. Nephrol Dial Transplant 2013; 28: 42–9
Quality Initiative (ADQI) Group. Crit Care 2004; 8: R204–12 38. Alexopoulos N, Katritsis D, Raggi P. Visceral adipose tissue
17. Mehta RL, Kellum JA, Shah SV, et al. Acute Kidney Injury Net- as a source of inflammation and promoter of atheroscler-
work: report of an initiative to improve outcomes in acute osis. Atherosclerosis 2014; 233: 104–12
kidney injury. Crit Care 2007; 11: R31 39. Romero-Corral A, Sert-Kuniyoshi FH, Sierra-Johnson J, et al.
18. Chertow GM, Burdick E, Honour M, Bonventre JV, Bates DW. Modest visceral fat gain causes endothelial dysfunction in
Acute kidney injury, mortality, length of stay, and costs in healthy humans. J Am Coll Cardiol 2010; 56: 662–6
hospitalized patients. J Am Soc Nephrol 2005; 16: 3365–70 40. Shashaty MG, Kalkan E, Bellamy SL, et al. Computed tomog-
19. Lassnigg A, Schmidlin D, Mouhieddine M, et al. Minimal raphy-defined abdominal adiposity is associated with acute
changes of serum creatinine predict prognosis in patients kidney injury in critically ill trauma patients. Crit Care Med
after cardiothoracic surgery: a prospective cohort study. 2014; 42: 1619–28
J Am Soc Nephrol 2004; 15: 1597–605 41. Medeiros P, Nga HS, Menezes P, Bridi R, Balbi A, Ponce D.
20. Bang J-Y, Lee JB, Yoon Y, Seo H-S, Song J-G, Hwang GS. Acute Acute kidney injury in septic patients admitted to emer-
kidney injury after infrarenal abdominal aortic aneurysm gency clinical room: risk factors and outcome. Clin Exp
surgery: a comparison of AKIN and RIFLE criteria for risk pre- Nephrol 2015; 19: 859–66
diction. Br J Anaesth 2014; 113: 993–1000 42. Wald R, Waikar SS, Liangos O, Pereira BJ, Chertow GM,
21. Englberger L, Suri RM, Li Z, et al. Clinical accuracy of RIFLE Jaber BL. Acute renal failure after endovascular vs open re-
and Acute Kidney Injury Network (AKIN) criteria for acute pair of abdominal aortic aneurysm. J Vasc Surg 2006; 43:
kidney injury in patients undergoing cardiac surgery. Crit 460–6
Care 2011; 15: R16 43. Vives M, Wijeysundera D, Marczin N, Monedero P, Rao V.
22. Kidney Disease: Improving Global Outcomes (KDIGO) Acute Cardiac surgery-associated acute kidney injury. Interact
Kidney Injury Work Group: KDIGO clinical practice guideline Cardiovasc Thorac Surg 2014; 18: 637–45
for acute kidney injury. Kidney Int Suppl 2012; 2: 1–138 44. Ishikawa S, Griesdale DE, Lohser J. Acute kidney injury after
23. Charlton JR, Portilla D, Okusa MD. A basic science view of lung resection surgery: incidence and perioperative risk fac-
acute kidney injury biomarkers. Nephrol Dial Transplant tors. Anesth Analg 2012; 114: 1256–62
2014; 29: 1301–11 45. Legrand M, Pirracchio R, Rosa A, et al. Incidence, risk factors
24. Kokkoris S, Pipili C, Grapsa E, Kyprianou T, Nanas S. Novel and prediction of post-operative acute kidney injury follow-
biomarkers of acute kidney injury in the general adult ICU: ing cardiac surgery for active infective endocarditis: an
a review. Ren Fail 2013; 35: 579–91 observational study. Crit Care 2013; 17: R220
25. Kashani K, Al-Khafaji A, Ardiles T, et al. Discovery and valid- 46. Malbrain ML, Chiumello D, Pelosi P, et al. Prevalence of intra-
ation of cell cycle arrest biomarkers in human acute kidney abdominal hypertension in critically ill patients: a multicen-
injury. Crit Care 2013; 17: R25 tre epidemiological study. Intensive Care Med 2004; 30: 822–9
26. Meersch M, Schmidt C, Van Aken H, et al. Urinary TIMP-2 and 47. Kirkpatrick AW, Ball CG, Nickerson D, D’Amours SK. Intraab-
IGFBP7 as early biomarkers of acute kidney injury and renal dominal hypertension and the abdominal compartment
recovery following cardiac surgery. PLoS ONE 2014; 9: e93460 syndrome in burn patients. World J Surg 2009; 33: 1142–9
ii12 | Goren and Matot

48. Dalfino L, Tullo L, Donadio I, Malcangi V, Brienza N. Intra-ab- 67. Nash DM, Mustafa RA, McArthur E, et al. Combined general
dominal hypertension and acute renal failure in critically ill and neuraxial anesthesia versus general anesthesia: a popu-
patients. Intensive Care Med 2008; 34: 707–13 lation-based cohort study. Can J Anesth 2015; 62: 356–68
49. Demarchi AC, de Almeida CT, Ponce D, et al. Intra-abdominal 68. Karkouti K, Wijeysundera DN, Yau TM, et al. Acute kidney in-
pressure as a predictor of acute kidney injury in post- jury after cardiac surgery. Focus on modifiable risk factors.
operative abdominal surgery. Ren Fail 2014; 36: 557–61 Circulation 2009; 119: 495–502
50. Nishio S, Takeda H, Yokoyama M. Changes in urinary output 69. Rosner MH, Okusa MD. Acute kidney injury associated with
during laparoscopic adrenalectomny. BJU Int 1999; 83: 944–7 cardiac surgery. Clin J Am Soc Nephrol 2006; 1: 19–32
51. Nguyen NT, Perez RV, Fleming N, Rivers R, Wolfe BM. Effect 70. Englberger L, Suri RM, Connolly HM, et al. Increased risk of
of prolonged pneumoperitoneum on intraoperative urine acute kidney injury in patients undergoing tricuspid valve
output during laparoscopic gastric bypass. J Am Coll Surg surgery. Eur J Cardiothorac Surg 2013; 43: 993–9
2002; 195: 476–83 71. Kumar AB, Suneja M. Cardiopulmonary bypass-associated

Downloaded from https://academic.oup.com/bja/article/115/suppl_2/ii3/272807 by guest on 25 October 2020

52. Koivusalo AM, Pere P, Valjus M, Scheinin T. Laparoscopic acute kidney injury. Anesthesiology 2011; 114: 964–70
cholecystectomy with carbon dioxide pneumoperitoneum 72. Thakar CV, Arrigain S, Worley S, Yared JP, Paganini EP. A clin-
is safe even for high-risk patients. Surg Endosc Other Interv ical score to predict acute renal failure after cardiac surgery.
Tech 2008; 22: 61–7 J Am Soc Nephrol 2005; 16: 162–8
53. Gómez Dammeier BH, Karanik E, Glüer S, et al. Anuria during 73. Mehta RH, Grab JD, O’Brien SM, et al. Bedside tool for predict-
pneumoperitoneum in infants and children: a prospective ing the risk of postoperative dialysis in patients undergoing
study. J Pediatr Surg 2005; 40: 1454–8 cardiac surgery. Circulation 2006; 114: 2208–16
54. Joshi GP, Cunningham A. Anesthesia for laparoscopic and 74. Birnie K, Verheyden V, Pagano D, et al. Predictive models for kid-
robotic surgeries. In: Barash PB, Cullen BF, Stoelting RK, ney disease: improving global outcomes (KDIGO) defined acute
Cahalan MK, Stock MC, Ortega R, eds. Clinical Anesthesia. kidney injury in UK cardiac surgery. Crit Care 2014; 18: 606
Philadelphia, USA: Lippincott Williams & Wilkins, 2013; 75. Zarbock A, Schmidt C, Van Aken H, et al. Effect of remote is-
1257–73 chemic preconditioning on kidney injury among high-risk
55. Walsh M, Devereaux PJ, Garg AX, et al. Relationship between patients undergoing cardiac surgery: a randomized clinical
intraoperative mean arterial pressure and clinical outcomes trial. JAMA 2015; 313: 2133–41
after noncardiac surgery: toward an empirical definition of 76. Hui-Stickle S, Brewer ED, Goldstein SL. Pediatric ARF epi-
hypotension. Anesthesiology 2013; 119: 507–15 demiology at a tertiary care center from 1999 to 2001. Am J
56. Sun LY, Wijeysundera DN, Tait GA, Beattie WS. Association of Kidney Dis 2005; 45: 96–101
intraoperative hypotension with acute kidney injury after 77. Ball EF, Kara T. Epidemiology and outcome of acute kidney
elective noncardiac surgery. Anesthesiology 2015; 123: 515–23 injury in New Zealand children. J Paediatr Child Health 2008;
57. Mazze RI. Methoxyflurane revisited: tale of an anesthetic 44: 642–6
from cradle to grave. Anesthesiology 2006; 105: 843–6 78. Greenberg JH, Coca S, Parikh CR. Long-term risk of chronic
58. Kharasch ED. Adverse drug reactions with halogenated kidney disease and mortality in children after acute kidney
anesthetics. Clin Pharmacol Ther 2008; 84: 158–62 injury: a systematic review. BMC Nephrol 2014; 15: 184
59. Lee HT, Ota-Setlik A, Fu Y, Nasr SH, Emala CW. Differential 79. Mammen C, Al Abbas A, Skippen P, et al. Long-term risk of
protective effects of volatile anesthetics against renal ische- CKD in children surviving episodes of acute kidney injury
mia–reperfusion injury in vivo. Anesthesiology 2004; 101: in the intensive care unit: a prospective cohort study. Am J
1313–24 Kidney Dis 2012; 59: 523–30
60. Sindhvananda W, Phisaiphun K, Prapongsena P. No renal 80. Akcan-Arikan A, Zappitelli M, Loftis LL, Washburn KK,
protection from volatile-anesthetic preconditioning in Jefferson LS, Goldstein SL. Modified RIFLE criteria in critical-
open heart surgery. J Anesth 2013; 27: 48–55 ly ill children with acute kidney injury. Kidney Int 2007; 71:
61. Fukazawa K, Lee HT. Volatile anesthetics and AKI: risks, me- 1028–35
chanisms, and a potential therapeutic window. J Am Soc 81. Askenazi D. Evaluation and management of critically ill chil-
Nephrol 2014; 25: 884–92 dren with acute kidney injury. Curr Opin Pediatr 2011; 23:
62. Luo C, Yuan D, Li X, et al. Propofol attenuated acute kidney 201–7
injury after orthotopic liver transplantation via inhibiting 82. Gallini F, Maggio L, Romagnoli C, Marrocco G, Tortorolo G.
gap junction composed of connexin 32. Anesthesiology Progression of renal function in preterm neonates with ges-
2015; 122: 72–86 tational age < or = 32 weeks. Pediatr Nephrol 2000; 15: 119–24
63. Yoo YC, Shim JK, Song Y, Yang S-Y, Kwak Y-L. Anesthetics 83. Goldstein SL, Chawla LS. Renal angina. Clin J Am Soc Nephrol
influence the incidence of acute kidney injury following 2010; 5: 943–9
valvular heart surgery. Kidney Int 2014; 86: 414–22 84. Hassinger AB, Wald EL, Goodman DM. Early postoperative
64. Suleiman MY, Passannante AN, Onder RL, Greene- fluid overload precedes acute kidney injury and is asso-
Helms WF, Perretta SG. Alteration of renal blood flow during ciated with higher morbidity in pediatric cardiac surgery pa-
epidural anesthesia in normal subjects. Anesth Analg 1997; tients. Pediatr Crit Care Med 2014; 15: 131–8
84: 1076–80 85. Zappitelli M. Preoperative prediction of acute kidney injury—
65. Rodgers A, Walker N, Schug S, et al. Reduction of post- from clinical scores to biomarkers. Pediatr Nephrol 2013; 28:
operative mortality and morbidity with epidural or spinal 1173–82
anaesthesia: results from overview of randomised trials. 86. Cooper JE, Wiseman AC. Acute kidney injury in kidney trans-
Br Med J 2000; 321: 1493 plantation. Curr Opin Nephrol Hypertens 2013; 22: 698–703
66. Bignami E, Landoni G, Biondi-Zoccai GG, et al. Epidural anal- 87. Hilmi IA, Damian D, Al-Khafaji A, et al. Acute kidney injury
gesia improves outcome in cardiac surgery: a meta-analysis following orthotopic liver transplantation: incidence, risk
of randomized controlled trials. J Cardiothorac Vasc Anesth factors, and effects on patient and graft outcomes. Br J
2010; 24: 586–97 Anaesth 2015; 114: 919–26
 Perioperative acute kidney injury | ii13

88. Barri YM, Sanchez EQ, Jennings LW, et al. Acute kidney injury is independently associated with increased morbidity and
following liver transplantation: definition and outcome. mortality: a propensity-matched cohort study. Anesth
Liver Transpl 2009; 15: 475–83 Analg 2013; 117: 412–21
89. Utsumi M, Umeda Y, Sadamori H, et al. Risk factors for acute 106. Young JB, Utter GH, Schermer CR, et al. Saline versus Plasma-
renal injury in living donor liver transplantation: evaluation Lyte A in initial resuscitation of trauma patients: a rando-
of the RIFLE criteria. Transpl Int 2013; 26: 842–52 mized trial. Ann Surg 2014; 259: 255–62
90. Agarwal B, Davenport A. Difficulties in diagnosing acute 107. Shaw AD, Bagshaw SM, Goldstein SL, et al. Major complica-
kidney injury post liver transplantation using serum cre- tions, mortality, and resource utilization after open abdom-
atinine based diagnostic criteria. World J Hepatol 2014; 6: inal surgery: 0.9% saline compared to Plasma-Lyte. Ann Surg
696–703 2012; 255: 821–9
91. Hand WR, Whiteley JR, Epperson TI, et al. Hydroxyethyl 108. Serpa Neto A, Veelo DP, Peireira VG, et al. Fluid resuscitation
starch and acute kidney injury in orthotopic liver trans- with hydroxyethyl starches in patients with sepsis is asso-

Downloaded from https://academic.oup.com/bja/article/115/suppl_2/ii3/272807 by guest on 25 October 2020

plantation: a single-center retrospective review. Anesth ciated with an increased incidence of acute kidney injury
Analg 2014; 120: 619–26 and use of renal replacement therapy: a systematic review
92. Mukhtar A, Mahmoud I, Obayah G, et al. Intraoperative terli- and meta-analysis of the literature. J Crit Care 2014; 29: 185.e1–7
pressin therapy reduces the incidence of postoperative 109. Perner A, Haase N, Guttormsen AB, et al. Hydroxyethyl
acute kidney injury after living donor liver transplantation. starch 130/0.42 versus Ringer’s acetate in severe sepsis. N
J Cardiothorac Vasc Anesth 2015; 29: 678–83 Engl J Med 2012; 367: 124–34
93. Ishikawa S, Griesdale DE, Lohser J. Acute kidney injury with- 110. Myburgh JA, Finfer S, Bellomo R, et al. Hydroxyethyl starch or
in 72 hours after lung transplantation: incidence and peri- saline for fluid resuscitation in intensive care. N Engl J Med
operative risk factors. J Cardiothorac Vasc Anesth 2014; 28: 2012; 367: 1901–11
943–7 111. Zarychanski R, Abou-Setta AM, Turgeon AF, et al. Associ-
94. Bentley ML, Corwin HL, Dasta J. Drug-induced acute kidney ation of hydroxyethyl starch administration with mortality
injury in the critically ill adult: recognition and prevention and acute kidney injury in critically ill patients requiring
strategies. Crit Care Med 2010; 38: S169–74 volume resuscitation: a systematic review and meta-ana-
95. Lapi F, Azoulay L, Yin H, Nessim SJ, Suissa S. Concurrent use lysis. JAMA 2013; 309: 678–88
of diuretics, angiotensin converting enzyme inhibitors, and 112. Bayer O, Schwarzkopf D, Doenst T, et al. Perioperative fluid
angiotensin receptor blockers with non-steroidal anti-in- therapy with tetrastarch and gelatin in cardiac surgery—a
flammatory drugs and risk of acute kidney injury: nested prospective sequential analysis. Crit Care Med 2013; 41:
case-control study. Br Med J 2013; 346: e8525 2532–42
96. Brown JR, Malenka DJ, DeVries JT, et al. Transient and per- 113. Kashy BK, Podolyak A, Makarova N, Dalton JE, Sessler DI,
sistent renal dysfunction are predictors of survival after per- Kurz A. Effect of hydroxyethyl starch on postoperative kid-
cutaneous coronary intervention: insights from the ney function in patients having noncardiac surgery.
Dartmouth Dynamic Registry. Catheter Cardiovasc Interv Anesthesiology 2014; 121: 730–9
2008; 72: 347–54 114. Endo A, Uchino S, Iwai K, et al. Intraoperative hydroxyethyl
97. Solomon R, Dauerman HL. Contrast-induced acute kidney starch 70/0.5 is not related to acute kidney injury in surgical
injury. Circulation 2010; 122: 2451–5 patients: retrospective cohort study. Anesth Analg 2012; 115:
98. Joannidis M, Druml W, Forni LG, et al. Prevention of acute 1309–14
kidney injury and protection of renal function in the inten- 115. Martin C, Jacob M, Vicaut E, Guidet B, Van Aken H, Kurz A. Ef-
sive care unit: expert opinion of the working group for neph- fect of waxy maize-derived hydroxyethyl starch 130/0.4 on
rology, ESICM. Intensive Care Med 2010; 36: 392–411 renal function in surgical patients. Anesthesiology 2013;
99. Leone M, Asfar P, Radermacher P, Vincent JL, Martin C. Opti- 118: 387–94
mizing mean arterial pressure in septic shock: a critical re- 116. Van Der Linden P, James M, Mythen M, Weiskopf RB. Safety
appraisal of the literature. Crit Care 2015; 19: 101 of modern starches used during surgery. Anesth Analg 2013;
100. Brienza N, Giglio MT, Marucci M, Fiore T. Does perioperative 116: 35–48
hemodynamic optimization protect renal function in surgi- 117. Gillies MA, Habicher M, Jhanji S, et al. Incidence of post-
cal patients? A meta-analytic study. Crit Care Med 2009; 37: operative death and acute kidney injury associated with
2079–90 i.v. 6% hydroxyethyl starch use: systematic review and
101. Wilcox CS. Regulation of renal blood flow by plasma chlor- meta-analysis. Br J Anaesth 2014; 112: 25–34
ide. J Clin Invest 1983; 71: 726–35 118. Godin M, Bouchard J, Mehta RL. Fluid balance in patients
102. Chowdhury AH, Cox EF, Francis ST, Lobo DN. A randomized, with acute kidney injury: emerging concepts. Nephron Clin
controlled, double-blind crossover study on the effects of 2-L Pract 2013; 123: 238–45
infusions of 0.9% saline and Plasma-Lyte® 148 on renal 119. Hartog CS, Natanson C, Sun J, Klein HG, Reinhart K. Con-
blood flow velocity and renal cortical tissue perfusion in cerns over use of hydroxyethyl starch solutions. Br Med J
healthy volunteers. Ann Surg 2012; 256: 18–24 2014; 349: g5981
103. Yunos NM, Bellomo R, Hegarty C, Story D, Ho L, Bailey M. As- 120. Lobo SM, de Oliveira NE. Clinical review: what are the best
sociation between a chloride-liberal vs chloride-restrictive hemodynamic targets for noncardiac surgical patients?
intravenous fluid administration strategy and kidney injury Crit Care 2013; 17: 210
in critically ill adults. JAMA 2012; 308: 1566–72 121. Sanders G, Mercer SJ, Saeb-Parsey K, Akhavani MA,
104. Nadeem A, Salahuddin N, El Hazmi A, et al. Chloride-liberal Hosie KB, Lambert AW. Randomized clinical trial of intra-
fluids are associated with acute kidney injury after liver venous fluid replacement during bowel preparation for sur-
transplantation. Crit Care 2014; 18: 625 gery. Br J Surg 2001; 88: 1363–5
105. McCluskey SA, Karkouti K, Wijeysundera D, Minkovich L, 122. Cannesson M, Pestel G, Ricks C, Hoeft A, Perel A. Hemo-
Tait G, Beattie WS. Hyperchloremia after noncardiac surgery dynamic monitoring and management in patients
ii14 | Goren and Matot

undergoing high risk surgery: a survey among North Ameri- 136. Yang B, Xu J, Xu F, et al. Intravascular administration of man-
can and European anesthesiologists. Crit Care 2011; 15: R197 nitol for acute kidney injury prevention: a systematic review
123. Lobo DN, Bostock KA, Neal KR, Perkins AC, Rowlands BJ, and meta-analysis. PLoS ONE 2014; 9: e85029
Allison SP. Effect of salt and water balance on recovery of 137. Tagawa M, Ogata A, Hamano T. Pre- and/or intra-operative
gastrointestinal function after elective colonic resection: a prescription of diuretics, but not renin-angiotensin-system
randomised controlled trial. Lancet 2002; 359: 1812–8 inhibitors, is significantly associated with acute kidney in-
124. Brandstrup B, Tønnesen H, Beier-Holgersen R, et al. Effects of jury after non-cardiac surgery: a retrospective cohort
intravenous fluid restriction on postoperative complica- study. PLoS ONE 2015; 10: e0132507
tions: comparison of two perioperative fluid regimens: a 138. Rosenberger C, Rosen S, Heyman SN. Renal parenchymal
randomized assessor-blinded multicenter trial. Ann Surg oxygenation and hypoxia adaptation in acute kidney injury.
2003; 238: 641–8 Clin Exp Pharmacol Physiol 2006; 33: 980–8
125. Nisanevich V, Felsenstein I, Almogy G, Weissman C, Einav S, 139. Walsh M, Garg AX, Devereaux PJ, Argalious M, Honar H,
Matot I. Effect of intraoperative fluid management on out-

Downloaded from https://academic.oup.com/bja/article/115/suppl_2/ii3/272807 by guest on 25 October 2020

Sessler DI. The association between perioperative hemoglo-
come after intraabdominal surgery. Anesthesiology 2005; bin and acute kidney injury in patients having noncardiac
103: 25–32 surgery. Anesth Analg 2013; 117: 924–31
126. Jacob M, Chappell D, Rehm M. Clinical update: perioperative 140. Karkouti K, Grocott HP, Hall R, et al. Interrelationship of pre-
fluid management. Lancet 2007; 369: 1984–6 operative anemia, intraoperative anemia, and red blood cell
127. Olsson J, Svensén CH, Hahn RG. The volume kinetics of ace- transfusion as potentially modifiable risk factors for acute
tated Ringer’s solution during laparoscopic cholecystec- kidney injury in cardiac surgery: a historical multicentre co-
tomy. Anesth Analg 2004; 99: 1854–60 hort study. Can J Anesth 2014; 62: 377–84
128. Kheterpal S, Tremper KK, Englesbe MJ, et al. Predictors of 141. Karkouti K. Transfusion and risk of acute kidney injury in
postoperative acute renal failure after noncardiac surgery cardiac surgery. Br J Anaesth 2012; 109: i29–i38
in patients with previously normal renal function. 142. Haase M, Bellomo R, Story D, et al. Effect of mean arterial
Anesthesiology 2007; 107: 892–902 pressure, haemoglobin and blood transfusion during car-
129. Matot I, Dery E, Bulgov Y, Cohen B, Paz J, Nesher N. Fluid diopulmonary bypass on post-operative acute kidney in-
management during video-assisted thoracoscopic surgery jury. Nephrol Dial Transplant 2012; 27: 153–60
for lung resection: a randomized, controlled trial of effects 143. Karkouti K, Wijeysundera DN, Yau TM, et al. Influence of
on urinary output and postoperative renal function. erythrocyte transfusion on the risk of acute kidney injury
J Thorac Cardiovasc Surg 2013; 146: 461–6 after cardiac surgery differs in anemic and nonanemic pa-
130. Matot I, Paskaleva R, Eid L, et al. Effect of the volume of fluids tients. Anesthesiology 2011; 115: 523–30
administered on intraoperative oliguria in laparoscopic bar- 144. Cohen B, Matot I. Aged erythrocytes: a fine wine or sour
iatric surgery: a randomized controlled trial. Arch Surg 2012; grapes? Br J Anaesth 2013; 111: i62–70
147: 228–34 145. Goodnough LT, Shander A. Patient blood management.
131. McArdle GT, McAuley DF, McKinley A, Blair P, Hoper M, Anesthesiology 2012; 116: 1367–76
Harkin DW. Preliminary results of a prospective randomized 146. Hoogenberg K, Smit AJ, Girbes AR. Effects of low-dose dopa-
trial of restrictive versus standard fluid regime in elective mine on renal and systemic hemodynamics during incre-
open abdominal aortic aneurysm repair. Ann Surg 2009; mental norepinephrine infusion in healthy volunteers. Crit
250: 28–34 Care Med 1998; 26: 260–5
132. Holte K, Klarskov B, Christensen DS, et al. Liberal versus re- 147. Bellomo R, Wan L, May C. Vasoactive drugs and acute kidney
strictive fluid administration to improve recovery after lap- injury. Crit Care Med 2008; 36: S179–86
aroscopic cholecystectomy: a randomized, double-blind 148. Friedrich JO, Adhikari N, Herridge MS, Beyene J. Meta-ana-
study. Ann Surg 2004; 240: 892–9 lysis: low-dose dopamine increases urine output but does
133. Grocott MP, Mythen MG, Gan TJ. Perioperative fluid manage- not prevent renal dysfunction or death. Ann Intern Med
ment and clinical outcomes in adults. Anesth Analg 2005; 2005; 142: 510–24
100: 1093–106 149. De Backer D, Biston P, Devriendt J, et al. Comparison of dopa-
134. Chappell D, Jacob M, Hofmann-Kiefer K, Conzen P, Rehm M. mine and norepinephrine in the treatment of shock. N Engl J
A rational approach to perioperative fluid management. Med 2010; 362: 779–89
Anesthesiology 2008; 109: 723–40 150. Zacharias M, Mugawar M, Herbison GP, et al. Interventions
135. Karajala V, Mansour W, Kellum JA. Diuretics in acute kidney for protecting renal function in the perioperative period.
injury. Minerva Anestesiol 2009; 75: 251–7 Cochrane Database Syst Rev 2013; 9: CD003590

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