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Accepted Manuscript
AGA Clinical Practice Update: Surgical Risk Assessment and PerioperativeManagement in Cirrhosis
Patrick G. Northup, Lawrence S. Friedman, Patrick S. Kamath
PII: S1542-3565(18)31075-9DOI: 10.1016/j.cgh.2018.09.043Reference: YJCGH 56114
To appear in: Clinical Gastroenterology and HepatologyAccepted Date: 24 September 2018
Please cite this article as: Northup PG, Friedman LS, Kamath PS, AGA Clinical Practice Update:Surgical Risk Assessment and Perioperative Management in Cirrhosis, Clinical Gastroenterology andHepatology (2018), doi: https://doi.org/10.1016/j.cgh.2018.09.043.
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AGAClinicalPracticeUpdate:Surgical
RiskAssessmentandPerioperative
ManagementinCirrhosis
Patrick G. Northup, Lawrence S. Friedman, Patrick S. Kamath Correspondence: Patrick G. Northup, MD Division of Gastroenterology and Hepatology University of Virginia JPA and Lee Str, MSB 2145 Charlottesville, VA 22908-0708 [email protected] 434.243.2718 (O) 434.244.9454 (F) Word Count: 5,555 Short Title: Surgical Risk in Cirrhosis CPU Grant Support: None Disclosures: None
Author Contributions: All authors were responsible for the design, composition, and editorial review of the manuscript.
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Abbreviations ASA American Society of Anesthesiologists
BCLC Barcelona Clinic Liver Cancer
CTP Child-Turcotte-Pugh
HCC Hepatocellular carcinoma
HVPG Hepatic vein pressure gradient
INR International normalized ratio
MELD Model for end-stage liver disease
NASH Nonalcoholic steatohepatitis
NSAID Nonsteroidal anti-inflammatory drug
TIPS Transjugular intrahepatic portosystemic shunt
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Despite worldwide increases in the prevalence of chronic liver disease due to viral
hepatitis and NASH, patients with cirrhosis are living longer with more advanced
disease because of improved medical and surgical management.1 As a result, they are
at risk for other diseases and morbidities that patients with cirrhosis might not have
experienced in past decades. Patients with cirrhosis now have a significant lifetime risk
of HCC and obesity-related diseases, and they may require emergent or elective
surgical procedures other than liver transplantation. Early reports of outcomes of
standard surgical procedures in patients with cirrhosis described intolerable mortality
rates as high as 67%2. Improved management and better selection of patients with
cirrhosis have led to improved surgical survival and the development of new risk
prediction algorithms. Nevertheless, the evaluation and treatment of the patient with
cirrhosis in whom an invasive surgical procedure is planned is not standardized, and
there are no definitive prospective trials to provide clarity to clinicians in assessing
patients in the preoperative period and managing them in the postoperative period. The
modern literature on surgical risk stratification in cirrhosis patients consists of case
reports, small series, and only a few serious attempts to stratify risk. This review
summarizes the available data and recommendations based on expert opinion on how
best to predict surgical outcomes and optimize the condition of patients with cirrhosis
who undergo surgical procedures. Table 1 summarizes our recommendations.
The Unique Pathophysiologic Risks in the Patient with Cirrhosis
The pathophysiology of chronic liver disease and portal hypertension predisposes the
patient with cirrhosis to complications related to surgical procedures. A comprehensive
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review of this pathophysiology is beyond the scope of this article3, 4, but several points
warrant emphasis. The patient with cirrhosis generally has protein synthetic dysfunction
that progresses as the liver disease advances and results in the malnutrition/sarcopenia
syndrome, which hinders wound healing and physical recovery from a surgical
procedure. Portal hypertension also progresses with advancing cirrhosis, thereby
raising the risk of surgical bleeding complications involving the collateral circulation,
especially in the splanchnic system in the thoracic and peritoneal cavities. Splenic
sequestration, in addition to a possible contribution from thrombopoietin deficiency,5
leads to peripheral thrombocytopenia, which can interfere with primary hemostasis.
Disruptions in secondary hemostasis (coagulation) and fibrinolysis can lead to a
propensity to either bleeding or clotting, and the net effect can be difficult to predict on
the basis of traditional laboratory testing.4 Current systems of deceased donor organ
allocation in the United States6 result in the selection of liver transplant recipients who
are likely to have renal dysfunction, which complicates fluid management and leads to
reduced renal excretion of drugs; hepatic protein synthetic dysfunction may also impair
hepatic drug metabolism. The result is a change in the pharmacokinetic handling of
medications. All of these pathophysiologic alterations lead to a significant potential for
morbidity and mortality related to surgery. Primary hepatic resection, usually for
malignancy, is particularly hazardous in this population, can acutely exacerbate all of
the aforementioned pathophysiologic changes due to a further reduction in liver mass,
and may thereby increase the postoperative risk of rapidly progressive hepatic failure.
Predicting Surgical Risk in a Patient with Cirrhosis
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Surgical procedures are classified broadly as those that are lifesaving, such as
cardiovascular or cancer surgery and emergency interventions, and those that are
carried out to improve a patient’s quality of life. The challenge for the care team is to
assess the surgical risks before deciding whether the procedure can be carried out
safely, should be delayed until the patient has undergone liver transplantation, or is
best avoided completely, especially in the high risk patient who may not be a liver
transplant candidate. Surgical and consultative teams must also consider the idea of
futility in their decision-making process7. If the surgical risk is much higher than the
chance of a good outcome from the perspective of the patient, then the procedure
should be considered futile and avoided regardless of the patient’s degree of liver
disease. For example, Teh, et al. showed that cirrhotic patients undergoing surgery
categorized preoperatively as American Society of Anesthesiologists (ASA) class V
(see later) had a median survival of two days, a 90% mortality rate at 14 days, and a
100% mortality rate at 90 days8. The risk of postoperative mortality and complications
is related to the degree of hepatic dysfunction, comorbidities, type of surgical
procedure, and expertise of the management team. Of these factors, the severity of
the liver disease appears to be the most important factor in determining mortality risk.
The severity of liver disease has traditionally been assessed in the literature by the
Child-Turcotte- Pugh (CTP) score (Child-Pugh class)9 and the Model for End-stage
Liver Disease (MELD) score. Table 2 summarizes the components of the various
severity scales that are used in practice.
CTPScoreandASAPhysicalStatusClassification
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Historically, the CTP score has been used to stage the degree of liver dysfunction and
severity of portal hypertension in patients with cirrhosis; this system has largely
withstood the test of time. Pre-MELD score era studies showed a good correlation
between the Child-Pugh class (combined with other variables) and surgical mortality10.
In general, patients with Child-Pugh class A cirrhosis may undergo surgery in the
absence of thrombocytopenia or clinically significant portal hypertension; only selected
patients with Child-Pugh class B cirrhosis are elective surgical candidates; and patients
with Child-Pugh class C cirrhosis are not considered candidates for elective surgery.
Recent analyses, however, show less of a correlation between the Child-Pugh class
and surgical outcomes, likely because of low numbers of patients with Child-Pugh class
C cirrhosis included in modern series, in part due to avoidance of surgery in patients
with decompensated cirrhosis.11 Nevertheless, the presence of ascites (a component of
the CTP score but not the MELD score), especially massive ascites, correlates with
poor surgical outcomes in many analyses. Because of the somewhat subjective nature
of estimating the severity of ascites and encephalopathy, use of the CTP score for
surgical risk stratification has been largely supplanted by the MELD score, which
encompasses the objective liver function-dependent components of the CTP score that
have been found to be predictive of outcomes (see below).12 The MELD score is less
effective in describing the occasional patient with severe portal hypertension but
preserved hepatic synthetic function; in these patients, the CTP score may be a more
useful tool in those patients.
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The ASA physical classification system has been used in some form since the early
1940s as a gross measure of the risk of administering anesthesia for surgical
procedures.13 The system classifies patients into illness levels that correlate roughly
with surgical outcomes in some circumstances, but the ASA score is generally thought
of as a measure of comorbidity or disease severity rather than a direct predictor of
outcome, particularly in patients with cirrhosis.14 The classification system also suffers
from poor interobserver variability and is somewhat subjective. Moreover, there is no
category for moderate disease, only for mild and severe disease. Despite these
weaknesses, the ASA classification is still used widely for risk stratification before
invasive procedures in the general surgical population, and it has been studied as a
predictive factor in case series of patients with cirrhosis.
MELDScore
Initially developed to predict mortality after placement of a transjugular intrahepatic
portosystemic shunt (TIPS),15 the MELD score was later introduced as a means of
prioritizing organ allocation for liver transplantation. The MELD score is calculated using
the international normalized ratio (INR), serum bilirubin level, and serum creatinine
level. Patients with a preoperative MELD score < 16 have lower postoperative mortality
rates than those with higher scores.16 One study demonstrated a linear increase in
postoperative mortality with an increase in MELD score. This large, single-center,
retrospective study of patients with cirrhosis who underwent cardiovascular, orthopedic,
or major abdominal surgery showed that the mortality rate increased steadily up to 90
days following major surgery with increasing MELD scores.8 A higher ASA class and
age > 70 years were also predictive of mortality. It is important to emphasize that the
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patients in this study were carefully selected for surgery after exclusion of significant
comorbidity. Mortality could be predicted at 7 days, 30 days, 90 days, one year, and
long-term with a combination of the MELD score, ASA class, and age. Using these data,
the postoperative mortality risk in patients with cirrhosis can be determined with use of
an online calculator (Mayo Postoperative Surgical Risk Score):
https://www.mayoclinic.org/medical-professionals/model-end-stage-liver-disease/post-
operative-mortality-risk-patients-cirrhosis. One advantage of this calculator over the
MELD score alone is that it includes age and ASA class, which give the model more
granularity and greater predictive value than MELD alone. The MELD-Na score has not
been studied as a predictor of surgical outcomes in patients with cirrhosis.
Risks of Specific Surgical Procedures in Patients with Cirrhosis
Many case series in the literature, some with historical controls, address the
characteristics of various surgical procedures and associated mortality in patients with
cirrhosis. Among the different types of surgery, hepatobiliary surgery is perceived to
have the highest risk of liver-related mortality and morbidity. Abdominal surgery and
possibly thoracic surgery in the presence of portal hypertension are significant risk
factors as well, but whether violation of the abdominal or thoracic cavity is a specific risk
factor in and of itself or whether these procedures increase surgical risk because they
are more invasive and disruptive of the splanchnic vasculature and collaterals is
unknown. Therefore, patients undergoing evaluation for surgery in the presence of
cirrhosis require careful selection and extensive discussion involving the patient and
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family prior to the procedure. The urgency of the procedure, although not often a
controllable variable, is an important predictor of outcomes. In the general population,
emergency surgery for any indication carries a significantly higher risk for morbidity and
mortality than non-emergent procedures.17 This trend has been shown in small series of
patients with cirrhosis as well.18, 19 Based on the aforementioned small and retrospective
studies, patients who undergo an emergency procedure should expect at least a two-
fold increased relative risk of morbidity and mortality that will not be directly represented
by MELD-based predictive models (although some models do incorporate emergency
surgery as a risk factor).20
Improvements in surgical technique and medical management have had a positive
effect on surgical mortality and morbidity rates. For example, a case series of patients
with cirrhosis undergoing non-shunt celiotomy published in 1984 showed a 30%
mortality rate, which correlated with the Child-Pugh class.21 By comparison, a series
published in 2010 from a center with extensive experience in surgery in patients with
cirrhosis reported a 7% mortality rate for abdominal procedures that was not well
predicted by the CTP score but did correlate with the MELD score and serum albumin
level.11 The authors of the latter study suggested that use of a laparoscopic approach
was associated with a decreased rate of postoperative complications but acknowledged
possible selection bias. There is also an unquantifiable but significant contribution of
case experience and multidisciplinary management in the improved surgical outcomes
in patients with cirrhosis over the past decades. Several case series have suggested
that, compared with more invasive approaches, laparoscopic and other minimally
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invasive surgical techniques may lead to favorable outcomes in patients with cirrhosis22-
26. The lack of concurrent risk-adjusted controls and the small size of most reports make
definitive, evidence-based recommendations speculative at best. Similarly, aside from
strict avoidance of outdated traditionally hepatotoxic inhalational anesthetic agents, no
studies have compared anesthesia techniques in patients with cirrhosis, so decisions
regarding the choice of an anesthetic agent must be made on a case-by-case basis. As
an example, spinal and epidural anesthesia are known to reduce hepatic blood flow but
there are no specific studies addressing anesthesia risk comparing spinal anesthesia to
other modalities in cirrhosis patients.
PrimaryHepaticResection
Hepatic resection for HCC is typically considered only in patients with Barcelona
Clinic Liver Cancer (BCLC) stage 0 (early) HCC.27 Stage 0 is defined as a tumor < 2
cm in diameter, excellent patient performance status, and normal liver function (Child-
Pugh class A) without portal hypertension. A surrogate marker for the lack of portal
hypertension in this population is a peripheral platelet count > 100,000/mcL. Other
studies have identified the absence of clinically significant portal hypertension by an
hepatic venous pressure gradient (HVPG) < 10 mm Hg28 or the absence of venous
collaterals on cross-sectional abdominal imaging along with the absence of
esophageal varices on upper endoscopy. The use of liver stiffness measurement
(e.g., by transient elastography) to guide decisions regarding hepatic surgical
resection has been suggested, but optimal cutoff values have not been validated. In
one series, a liver stiffness measurement below 22 kPa was established as the
optimal cutoff level for selecting patients for surgery.29 A liver stiffness measurement
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of > 22 kPa had greater sensitivity and higher negative as well as positive predictive
value in predicting patients likely to experience postoperative hepatic decompensation
compared to an HVPG > 10 mm Hg. Much lower cutoff values, ranging from 12 to 15
kPa, have also been proposed.30 A MELD score < 9 may also be used to select
patients for hepatic resection, because such patients have an excellent prognosis
following resection.31
Cholecystectomy
Routine abdominal imaging (ultrasonography and other cross-sectional modalities) may
show a thickened gallbladder wall in patients with cirrhosis, particularly in patients with
ascites. The finding typically reflects fibrotic thickening associated with cirrhosis rather
than the edema seen in acute cholecystitis. In fact, in a cirrhotic patient with acute
abdominal pain, a misdiagnosis of acute cholecystitis is not uncommon. In general,
elective cholecystectomy should be delayed in patients with cirrhosis who are
candidates for a liver transplantation. If urgent surgery must be carried out and the
diagnosis of acute cholecystitis is certain, patients should be referred urgently to a
center with experience in carrying out cholecystectomy in patients with cirrhosis;
however, we do not recommend cholecystectomy in patients with Child-Pugh class C
cirrhosis or refractory ascites. Such patients are also generally not candidates for
percutaneous cholecystostomy, unless they are critically ill, due to the presence of
ascites and a high risk of infections and procedural complications. In non-critically ill
patients, endoscopic transpapillary gallbladder drainage may be carried out if technically
feasible to relieve symptoms, but expertise in the technique is required.32
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Laparoscopic cholecystectomy has been associated with a higher mortality rate in
patients with cirrhosis compared with non-cirrhotic patients in a population-based study
in the United States.24 There is also an increased requirement for conversion of
laparoscopic cholecystectomy to open cholecystectomy in patients with cirrhosis. In the
setting of laparoscopic cholecystectomy, the MELD score correlates well with mortality
risk but not with the risk of complications from the surgical procedure itself.33
Laparoscopic cholecystectomy has not been compared with open cholecystectomy in a
prospective study, but in a single retrospective study using historical controls, the
laparoscopic approach appeared to be preferable when technically feasible.34
AbdominalWallHerniaRepair
Patients with cirrhosis are prone to abdominal hernias because of the presence of
ascites and, to a lesser extent, abdominal organomegaly. Symptomatic hernias are
common, especially in the setting of significant ascites, and control of ascites is key to
successful hernia repair. Because the ascites inevitably recurs quickly, a single large-
volume paracentesis prior to a surgical procedure does not provide adequate
preoperative control of ascites. Medical control of clinically apparent ascites with
diuretics, as per practice guidelines, prior to a surgical hernia repair is required in a
patient with decompensated cirrhosis in order to prevent recurrent ascites
postoperatively. Selected surgical candidates may benefit from preemptive placement of
a TIPS in order to control ascites prior to surgery. Recurrent ascites leads to impaired
wound healing and risks possible dehiscence. For this reason, efforts should be
undertaken to avoid recurrent ascites in the postoperative period and may include
frequent postoperative paracentesis and careful diuretic therapy while attempting to
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avoid renal injury. In selected patients continuous pigtail catheter drainage of ascites
postoperatively may prevent pressure on the hernia repair.
Several studies have examined risk factors for mortality after hernia surgery, but most
relevant studies are uncontrolled and include a heterogeneous population (for example,
elective and emergency cases). Both the MELD score12 and the Child-Pugh class
combined with the ASA class14 have been advocated for hernia surgery risk
stratification, but neither appears to be optimal in all cases.
The emergent presentation of an incarcerated hernia is a special challenge in a patient
with cirrhosis and is the most common indication for emergency surgery in this
population and a major risk factor for poor outcomes.17-19 Because of the significant
increase in mortality and morbidity associated with emergency operations in patients
with cirrhosis, some authors have advocated elective hernia repair in patients with
cirrhosis in order to prevent an emergent presentation. A single-center prospective case
series without controls reported on patients listed for liver transplantation who presented
for elective umbilical hernia repair.25 Thirty patients eventually underwent elective
surgery, and most had Child-Pugh class B or C cirrhosis, with a median MELD score of
12. Two patients had prolonged hospital stays due to complications, but the remainder
did not experience a direct surgical complication. The authors concluded that elective
umbilical hernia repair is preferable to emergency repair in patients with cirrhosis and
ascites. The lack of controls in this series makes broad conclusions difficult and the
frequency of emergency incarceration in patients with cirrhosis with a stable abdominal
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hernia is unknown. Surgical and medical teams should determine the safety and risk-
benefit ratio of elective hernia surgery carefully in this population.
Cardiovascular Surgery
The need for cardiovascular surgery is increasing in patients with cirrhosis as
nonalcoholic steatohepatitis (NASH), usually accompanied by components of the
metabolic syndrome (which are also risk factors for cardiovascular disease), has
become a leading cause of cirrhosis in the developed world 35. Cardiovascular surgery,
especially for an urgent indication, can be life-extending, even in patients with significant
complications from cirrhosis. Cardiovascular operations, especially those requiring
cardiac bypass and extracorporeal circulation, pose unique physiologic challenges for
the patient, including hyperfibrinolysis, platelet activation, and the need for
anticoagulation during and frequently after the procedure. Nevertheless, studies are
limited with regard to the optimal management of patients with cirrhosis and these
intraoperative and postoperative issues.36, 37 Case series and cohort studies using
historical controls show relatively high morbidity and mortality rates in patients with
cirrhosis who undergo cardiac surgery.35, 38, 39 Most cardiac surgery teams use
viscoelastic testing such as thromboelastography or rotational thromboelastometry40 in
the management of patients undergoing these operations, an approach that seems
clinically reasonable because the technology has been tested extensively in persons
with cirrhosis.41
Several prospective and retrospective case series without controls and with historical
controls have evaluated the value of the MELD and CTP scores in predicting outcomes
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after cardiac surgery, but the data are limited by small numbers of patients, inclusion of
only patients cleared for surgery, and a vast preponderance of patients with
compensated cirrhosis with a low MELD score.42-47 Overall, elective coronary artery
bypass graft surgery is associated with mortality rates ranging from 4% to 70%, which
correlate with the MELD score and the Child-Pugh class. In general, a MELD score ≥
13.546 or a CTP score > 747 is considered a contraindication to cardiac surgery. No
specific studies have compared the various surgical approaches. A small study of
patients undergoing aortic valve replacement48 showed no significant difference in
mortality between transcatheter aortic valve replacement and surgical aortic valve
replacement. Coronary angiography and cardiac catheterization are performed routinely
in patients with cirrhosis undergoing liver transplant evaluation and appear to be
relatively safe in this population. Based on a single uncontrolled case series, transfusion
of plasma to prophylactically “correct” the INR prior to the procedure cannot be
recommended49. There are sparse data on the use of antiplatelet agents after coronary
stent placement and after cardiac surgery in patients with cirrhosis, but available studies
suggest an increase in the risk of variceal and non-variceal bleeding when these
patients receive dual antiplatelet therapy.50, 51
BariatricSurgery
Obesity is the most common risk factor for cirrhosis in developed countries, and NASH
cirrhosis is among the most common indications for listing patients for liver
transplantation. Weight loss through lifestyle changes benefit patients with obesity and
NASH but is difficult to achieve52. Bariatric surgery may be carried out at expert centers
in patients with compensated cirrhosis but without clinically significant portal
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hypertension. Even in skilled hands, the risk of complications is increased compared
with that in the general population53-56 although studies regarding risk stratification of
cirrhotic patients prior to surgery are lacking. However, patients with decompensated
cirrhosis or with clinically significant portal hypertension are at highest risk for adverse
outcomes and are not candidates for bariatric procedures. Several centers have
reported the outcomes of sleeve gastrectomy preformed at the time of liver
transplantation. Such a combined procedure in highly selected patients is associated
with durable weight loss and a lower risk of the metabolic syndrome57, 58 after liver
transplantation. A sleeve gastrectomy, which involves resection of the greater curvature
of the stomach, does not add significant morbidity to the liver transplant procedure and
is not associated with intestinal malabsorption postoperatively, which is a particular
concern in the prevention of perioperative graft rejection that could result from
malabsorption of immunosuppression medications. Weight loss following the procedure
is gradual, and endoscopic access to the biliary tract is preserved should the patient
develop post-transplant biliary complications. A few centers have reported case series
of Roux-en-Y gastric bypass59 and sleeve gastrectomy after liver transplantation,60 but
because of small numbers of patients, we cannot make conclusions about safety and
efficacy.
OtherSurgicalProcedures
Table 3 lists risk stratification tools used for various surgical procedures in the setting of
cirrhosis. The data are derived primarily from small case series, and limited conclusions
can be made on the accuracy of the predictive models for many of the operations.
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Preoperative and Perioperative Evaluation and Management of the
Patient with Cirrhosis
Surgical procedures that are generally considered safe in the medical population
without significant comorbidities may pose great risk in the patient with decompensated
cirrhosis. Early involvement of an experienced multidisciplinary medical and surgical
team is an absolute key to success. Earnest and data-driven risk discussions with both
the patient and the surgical teams are a critical prerequisite for an informed decision
about surgical procedures in this population, and the discussion should begin as early in
the process as possible. For patients undergoing elective or semi-elective procedures,
ascites should be controlled, variceal bleeding risk reduced, and acute hepatic
encephalopathy treated preoperatively, with continuation of medical therapy to prevent
recurrent hepatic encephalopathy. With the aging of the population and the increasing
prevalence of obesity, NASH, and diabetes mellitus, the patient with cirrhosis is likely to
have non-hepatic risk factors for surgical complications as well. No specific studies have
examined whether non-hepatic comorbid risk factors such as cardiopulmonary disease
are additive or multiplicative to the risk imparted by liver disease. Clinical experience
suggests, however, that class III obesity and cardiopulmonary disease are risk factors
for morbidity and mortality independent of the severity of liver disease. Similarly, most of
the major risk stratification scores do not include age, but the extremes of age are
known to be independent risk factors for medical and surgical complications. In fact,
both the CTP and MELD scores are predictive of surgical outcome only in patients who
are otherwise satisfactory candidates for surgery and have no other important
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comorbidities. Therefore, cardiology and pulmonary consultations are frequently needed
for these complex patients.
Elective operations in patients with cirrhosis should generally be avoided until the liver
disease can be optimized. Progressive decompensation is well described in the
postoperative period in patients with previously fully compensated cirrhosis. For chronic
viral hepatitis and autoimmune hepatitis, strict adherence to antiviral and
immunosuppressive therapy is required in order to avoid viral resistance and relapse,
respectively, and elective or semi-elective surgery may be delayed until therapy is
completed in order to avoid an interruption in treatment. Alternative routes of drug
administration may be necessary such as the use of intravenous administration of
corticosteroids in patients with autoimmune hepatitis who are unable to take oral
medications.
Ascites
Ascites should be managed aggressively, as recommended by practice guidelines,61
prior to surgical procedures, if possible. Ascites can restrict pulmonary function and
delay perioperative recovery of lung function. Patients with ascites are also at risk of
pulmonary aspiration during induction of anesthesia. Therefore, in patients with
symptomatic ascites, large-volume total abdominal paracentesis should be performed
preoperatively, with intravenous administrative of albumin in a dose of 6-8 grams for
each liter of ascitic fluid removed. Once oral medications are tolerated, daily antibiotic
prophylaxis can be resumed in patients with a history of spontaneous bacterial
peritonitis and patients with a low ascitic total protein concentration, as per practice
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guidelines. In patients who are not able to take oral medications, third-generation
cephalosporins such as ceftriaxone, can be administered prophylactically in a dose of 1
g every 24 hours intravenously until oral intake of prophylactic antibiotics is possible
again. Preoperative thoracentesis is only recommended in patients with moderate to
large pleural effusions that compromise respiratory function. Administration of
intravenous fluid and blood products should be limited perioperatively to avoid
increasing extracellular volume, ascites, and portal venous pressure.62
Only a few case reports and uncontrolled case series have assessed the benefit of
preemptive TIPS placement prior to surgery to reduce the risk of collateral vessel and
intra-abdominal variceal bleeding intraoperatively63-65 Although a decrease in the need
for intraoperative blood transfusions following TIPS placement is claimed, the available
studies have been uncontrolled and the frequency of complications, such as hepatic
encephalopathy, following TIPS placement is not reported. In contrast, a retrospective
study of liver transplantation performed in patients who had undergone placement of a
TIPS prior to transplantation compared with concurrent controls who had not undergone
preoperative TIPS placement showed no difference in red blood cell or plasma
transfusion requirements between the two groups.66 Moreover, in a patient undergoing
non-transplant surgery, a TIPS that is misplaced into the right atrium, inferior vena cava,
or mesenteric veins may adversely affect future liver transplantation.67 Therefore, due to
unproven efficacy, lack of published evidence, potentially high complication rates, and
significant added expense, preemptive TIPS placement prior to a surgical procedure
cannot be recommended as a routine practice.
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HemostasisandCoagulation
Protocol transfusion strategies based on preoperative platelet counts and the INR are
generally ineffective in reducing intra- and postoperative bleeding. Patients with
cirrhosis are known to be in a state of “rebalance” in that deficits in procoagulant factors
are offset by deficits in anticoagulant proteins synthesized by the liver4. Therefore, they
are not necessarily predisposed to severe bleeding.68 In fact, as liver disease advances,
progressive protein C deficiency leads to a thrombophilic state in some patients.69
These observations argue strongly against preoperative protocol transfusions in most
patients with cirrhosis. The INR is not predictive of bleeding complications in patients
with cirrhosis, and “prophylactic” preoperative fresh frozen plasma transfusions are not
recommended.70
Although thrombocytopenia is common in patients with cirrhosis, in vitro71 and
retrospective cross-sectional studies72 have shown that platelet counts above
50,000/mcL are adequate to allow clot formation in most patients with cirrhosis.
Prophylactic transfusions to raise the platelet count to higher levels are unlikely to be
beneficial and may expose the patient to complications of transfusions, volume
overload, or unexpected thrombosis. In recent years, thrombopoietin analogues
(romiplostim) and receptor agonists (eltrombopag, avatrombopag, and lusutrombopag)
have been developed for the treatment of thrombocytopenia due to idiopathic
thrombocytopenic purpura. Eltrombopag is also labeled for use in patients with cirrhosis
due to chronic hepatitis C to allow increasing platelet counts during antiviral therapy with
interferon73. Only avatrombopag and lusutrombopag are approved for the general
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thrombocytopenia related to liver disease. In patients with cirrhosis, avatrombopag and
lusutrombopag were effective in raising platelet counts above 50,000 / mcL in phase 3
clinical trials when given prior to invasive procedures compared with placebo74, 75.
Notably, the rates of bleeding events in both pivotal studies were equivalent in the study
drug and placebo arms, thus raising questions about the need for elevating the platelet
count prior to most invasive procedures. Moreover, thrombotic events have occurred
with the use of these agents in patients with liver disease, and the drugs should be used
with caution. At this time, there is no clear guidance in the literature on when to use
these agents preoperatively in patients with cirrhosis, but it would seem reasonable to
consider their use in patients undergoing an elective procedure associated with a high
bleeding risk if the baseline platelet count is less than 50,000 / mcL. Special attention
should be paid to the potential for thrombotic events such as portal vein and other deep
vein thromboses. Further clinical studies with these agents are ongoing.
Low fibrinogen levels are associated with an increased bleeding risk,76 and levels < 100
mg/dL are associated with a risk of inhibiting clot formation in patients with cirrhosis.
Fibrinogen can be replaced with low-volume cryoprecipitate transfusions, which do not
significantly increase plasma volume. Although no controlled trials of the efficacy of
fibrinogen transfusion in patients with cirrhosis have been undertaken, it seems
physiologically reasonable to replete fibrinogen levels with infusions of cryoprecipitate
prior to high-risk surgical procedures to allow the substrate for adequate clot formation.
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Viscoelastic testing (thromboelastography and rotational thromboelastometry) to guide
intraoperative transfusions is available at large centers and has been shown to
decrease the need for red blood cell and plasma transfusions in the general surgical
population77 and specifically in patients with cirrhosis.78 If available, viscoelastic testing
should be considered prior to and during surgical procedures in patients with cirrhosis to
help guide a rational transfusion strategy. Details about these testing modalities are
available elsewhere40.
PainControl
Because of altered drug metabolism and elimination, patients with cirrhosis are at
especially high risk of medication-related toxicity. Opiates should generally be used at
lower than standard doses and at longer dosing intervals than in the general population.
Although randomized controlled trials have not been performed in patients with
cirrhosis, hydromorphone and transdermal fentanyl may be the preferred agents.79
Protein binding and hepatic metabolism are the primary determinants of benzodiazepine
elimination, and only short-acting benzodiazepines such as midazolam should be used.
Tramadol, which has favorable hepatic metabolism,80 or acetaminophen,81 in a dose of
no more than 2 g daily, is also recommended despite the misconception that
acetaminophen, even in small doses, is contraindicated in patients with cirrhosis. On the
other hand, avoid routine use of NSAIDs, which can impair renal blood flow in patients
with cirrhosis.82 Similarly, oral combination products containing either acetaminophen or
NSAIDs, especially when combined with a narcotic, should not be used and can lead to
accidental toxicity or overdose in a patient who is unaware that acetaminophen is a
component of the product.
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Avoid constipation in patients with cirrhosis in order to minimize flares of hepatic
encephalopathy in the postoperative period. Polyethylene glycol solution may be used
daily to maintain bowel regularity. In the absence of comparative trials, rifaximin may be
preferable in patients with hepatic encephalopathy who undergo primary bowel surgery,
because it generally causes less bowel distension than lactulose.
RescueLiverTransplantation
Prior to a surgical procedure, it is important to determine whether or not the patient will
be a candidate for liver transplantation in the future. In patients who, for whatever
reason, are not potential candidates for liver transplantation, it is vital that this position
be made clear before proceeding with surgery to avoid the need for the patient’s family
and the medical team to readdress this issue if the patient’s condition deteriorates
postoperatively. If the patient is a candidate for liver transplantation, a decision should
be made as to whether the planned surgery can be postponed until the patient has
undergone liver transplantation. Elective operations such as orthopedic procedures may
be best deferred despite uncertainty as to the length of time the patient will be on the
liver transplant waiting list. When a procedure cannot be delayed because of the
adverse impact on the patient’s quality of life, the liver transplant evaluation should be
completed prior to the anticipated surgery, if possible. Making a decision regarding liver
transplant candidacy is not easy and depends in part on how quickly the liver transplant
evaluation can be completed if the patient deteriorates following surgery and how likely
the patient will be to undergo transplantation in the near future. In general, if the
postoperative mortality risk is calculated to be > 15% at 3 months (using an appropriate
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risk calculator, as described earlier) or if the MELD score is > 15 (a score predictive of
increased mortality16), preoperative evaluation for liver transplantation is recommended.
Conclusions
Invasive surgery is frequently required in the patient with cirrhosis, in whom
perioperative management is challenging. Although morbidity and mortality rates
correlate with progression of portal hypertension in this population, the MELD score
and, to a lesser extent, CTP score (and Child-Pugh class) can provide some prediction
of risk in counseling patients and their families. A multidisciplinary approach to these
patients is critical for optimizing all phases of perioperative care, including planning,
preoperative evaluation, intraoperative management, and postoperative recovery. The
data in the literature are limited in scope, usually lack risk-matched controls, and are
based largely on single-center experiences; therefore, evidence-based
recommendations are mostly lacking. Study of larger cohorts with matched controls and
randomized controlled trials are needed to improve our understanding and management
of this challenging population.
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Table 1: Recommendations for Preoperative Risk Assessment and Perioperative
Management in Patients with Cirrhosis
Target audience Gastroenterologists, hepatologists, general surgeons, surgical
subspecialists, anesthesiologists, critical care physicians, and
other clinicians seeing patients with cirrhosis.
Target population Patients with cirrhosis undergoing invasive non-liver transplant
surgical procedures.
Baseline factors
common in patients
with cirrhosis
potentially
contributing to
surgical risk
Significant malnutrition; portal hypertension, raising the risk of
bleeding complications; thrombocytopenia, coagulation, and
fibrinolytic abnormalities; renal dysfunction; impaired hepatic
drug metabolism and elimination; increased susceptibility to
infection; decreased effective intravascular volume and
susceptibility to acute renal injury; potential for a thrombophilic
state and predisposition to venous thromboembolism.
Preoperative
surgical mortality
risk assessment
tools
CTP score, MELD score, ASA Physical Status Classification,
Mayo Postoperative Mortality Risk Calculator in Patients with
Cirrhosis
Postoperative
complications of
surgical procedures
more common in or
Hepatic decompensation and worsening of liver synthetic
function; acute worsening of portal hypertension and associated
complications, including ascites, hepatic encephalopathy, and
portal hypertensive bleeding; wound healing difficulties and
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unique to patients
with cirrhosis
dehiscence; pulmonary complications – pleural effusions and
pneumonia; other infections, including bacterial peritonitis;
increased risk of intraoperative and perioperative bleeding;
multiple organ failure.
Best practice advice
(BPA)
BPA 1: Due to the profound effects of hepatic synthetic
dysfunction and portal hypertension, patients with cirrhosis are at
increased risk of death after all invasive surgical procedures
compared with the healthy general population. It is not entirely
clear how much the risk attributed to cirrhosis is additive to
traditional cardiopulmonary risk factors studied in the general
population. Patients with cirrhosis undergoing all but the most
emergent surgical procedures should be risk stratified and
counseled on the magnitude of that risk.
BPA 2: In patients considered for surgery, use the CTP score
(Child-Pugh class), MELD score, Mayo Postoperative Mortality
Risk Score, or another validated risk stratification system. There
is no single definitive risk stratification system to determine
operative risk in all patients with cirrhosis, and we recommend
using multiple methods.
BPA 3: The type and anatomic site of the proposed surgical
procedure is important in risk stratification. The clinical teams
must incorporate the surgical procedure itself into discussions of
risk with patients. Procedures associated with higher surgical risk
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include hepatobiliary surgery, such as primary liver resection,
other intra-abdominal procedures, thoracic surgery, and
cardiovascular procedures. Avoid elective cholecystectomy if
possible and if required, it should be carried out in centers with
expertise in this population.
BPA 4: Surgical risk is continuous, and there are no absolute
cutoff values for excluding patients with cirrhosis from surgical
procedures. The patient and the surgical and medical teams
caring for the patient must weigh the potential benefits and risks
collaboratively. Patients should be referred to a surgical team
with experience in the care of patients with cirrhosis and portal
hypertension whenever possible. Patients with Child-Pugh class
C (CTP score > 10) or a MELD score > 20 pose a high risk of
postoperative decompensation and death. Avoid or delay until
after liver transplantation, if possible, all but the most urgent and
life-saving procedures in this population.
BPA 5: TIPS is not routinely recommended prior to surgical
procedures in patients with cirrhosis and portal hypertension with
abdominal collaterals. Small uncontrolled case series have
demonstrated the ability to decompress collateral vessels with
TIPS preoperatively in patients requiring deep pelvic and colonic
resections; however, the absolute benefit of TIPS over
conservative management is not established.
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BPA 6: The special case of primary liver resection in a patient
with cirrhosis, usually for malignancy, has been studied more
thoroughly than other general surgical procedures. Data support
the safety profile of segmental liver resections in patients without
clinically significant portal hypertension, as indicated by an
HVPG < 10 mm Hg. A validated surrogate measure of lack of
clinically significant portal hypertension is the absence of venous
abdominal collaterals on imaging or of esophageal varices on
endoscopy, peripheral blood platelet count > 100,000/mcL, or
hepatic transient elastography values of < 23kPa.
BPA 7: There are no established preoperative safety thresholds
for common laboratory values related to bleeding and clotting.
The INR is not predictive of procedural bleeding risk in patients
with cirrhosis. We do not recommend protocol transfusions to a
target INR in patients with cirrhosis. In vitro studies suggest that
a platelet count > 50,000/mcL is adequate to generate thrombin
and provide stable clot formation, and retrospective clinical
studies show an increased bleeding tendency in patients with a
platelet count lower than this threshold. The literature provides
no evidence to support protocol transfusions, but critically ill
patients with plasma fibrinogen levels < 100 mg/dL have more
bleeding events. Handle coagulation management on a case-by-
case basis preferably using viscoelastic testing directed therapy,
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and avoid needless transfusions or volume overload.
BPA 8: Involve a skilled medical team with experience in treating
patients with cirrhosis in the postoperative management of
patients with cirrhosis, and obtain early consultation to help avoid
progressive complications. Achieve optimal control of ascites,
variceal bleeding risk, and hepatic encephalopathy prior to
surgery, if possible. Monitor renal and hepatic function at least
daily in the postoperative period.
BPA 9: Aggressively avoid exacerbations of portal hypertension
and associated complications in the postoperative period.
Appropriate measures include close monitoring of renal function
and avoidance of volume excess or depletion. Excess volume
can increase the risk of variceal and other portal hypertensive
bleeding.
BPA 10: Due to disturbed metabolism and elimination, patients
with cirrhosis are at especially high risk for medication-related
complications. Generally, use opiates at lower doses and with
longer dosing intervals than in the general population. Use only
short-acting benzodiazepines. Avoidance of constipation should
be a priority in the management of these patients to minimize
flares of hepatic encephalopathy in the postoperative period. In
patients who can take medications orally, rifaximin generally
causes less bowel distension than nonabsorbable disaccharides
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(lactulose).
BPA 11: Avoid medications that might be toxic in patients with
portal hypertension and cirrhosis. Do not use NSAIDs because
they can impair renal blood flow. Patients with cirrhosis,
especially those with heavy alcohol use, can be susceptible to
acetaminophen toxicity at doses lower than those that may
cause toxicity in the general population. Do not prescribe
combination opiate / acetaminophen pain relievers to take home
after surgery because the patient may be unaware of the
presence of acetaminophen in various over-the-counter products
and unintentional acetaminophen overdose and hepatotoxicity
can result.
BPA 12: The gallbladder wall may appear thickened on imaging,
which may lead to the erroneous diagnosis of acute cholecystitis.
A diagnosis of acute cholecystitis should be made only in the
appropriate clinical setting, usually in the presence of biliary pain.
There is a significant risk of complications after cholecystectomy
in patients with cirrhosis. Avoid elective cholecystectomy in a
patient with confirmed cirrhosis. Refer patients who require
cholecystectomy to a surgical team with experience in invasive
procedures in the cirrhotic population.
BPA 13: Except for incarceration that cannot be manually
reduced or suspected strangulation with bowel ischemia or
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gangrene, abdominal hernia surgery should be avoided in the
patient with cirrhosis and ascites unless the ascites is completely
controlled medically. Wound dehiscence, peritonitis, and poor
outcomes frequently occur when ascites recurs after hernia
surgery.
BPA 14: Patients who experience hepatic decompensation after
surgery may become candidates for liver transplantation. The
MELD score cutoff value for selecting patients for a liver
transplant evaluation before elective surgery is not clear. We
recommend preoperative liver transplant evaluation when the
predicted postoperative three-month mortality rate is greater than
15% as reflected by surgical risk stratification models or when
the MELD score is ≥ 15.
BPA 15: Centers with expertise in surgery in cirrhotic patients
may perform bariatric surgery in this population, but clinically
significant portal hypertension is a contraindication to the
operation. In highly selected patients with obesity and
decompensated cirrhosis undergoing liver transplantation, a
sleeve gastrectomy at the same time as liver transplantation is
an option.
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Table 2: CTP Score, ASA Physical Status Classification, and MELD Score:
Descriptions and Definitions
Predictive Model Formula/Description Reference
CTP score Encephalopathy grade: none (1), stage 1-2
(2), stage 3-4 (3)
Ascites level: absent (1), slight (2),
moderate or severe (3)
Serum albumin (g/dL): >3.5 (1), 2.8-3.5
(2), <2.8 (3)
Total bilirubin (mg/dL): <2 (1), 2-3 (2), >3
(3)
INR: < 1.7 (1), 1.7-2.3 (2), >2.3 (3)
Total points are calculated:
5-6: class A
7-9: class B
10-15: class C
9
ASA classification Class 1: normal healthy patient
Class 2: mild systemic disease
13
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Class 3: severe systemic disease that is
not life-threatening
Class 4: severe systemic disease that is a
constant threat to life
Class 5: moribund and not expected to
survive without the operation
Class 6: brain-dead patient/organ donor
MELD score = 3.78 × ln (serum bilirubin in mg/dL) +
11.2 × ln (INR) + 9.57 × ln (serum
creatinine in mg/dL) + 6.43
Final score is rounded to the nearest
whole number
Patients on renal replacement therapy are
assigned a serum creatinine value of 4.0
mg/dL
72
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Table 3: Predictive Models Used in Patients with Cirrhosis Undergoing Various
Surgical Procedures
Surgical Procedure Predictive Model
All surgical procedures MELD score (continuous risk),16 MELD
score, age, ASA (continuous risk),8 MELD
score < 1412
Liver cancer resection HVPG < 10 mm Hg,28 MELD score < 9,31
liver transient elastography < 22 kPa30
Cholecystectomy CTP score (continuous risk),33 Child-Pugh
class A+B,83 Child-Pugh class A,74 MELD
score < 1514
Abdominal wall herniorrhaphy CTP score (continuous risk)14 and MELD
score < 1312
Coronary artery bypass grafting CTP score < 847 or MELD score < 13.546
Bariatric surgery Child-Pugh class A56
Lung cancer resection Child-Pugh class A84
Colonic resection MELD score < 985
General orthopedic procedures MELD score (continuous risk)77
Lumbar spine surgery CTP score < 686
Intracranial neurosurgery CTP score (continuous risk)87
Head and neck cancer resections Child-Pugh class A,80 MELD score < 1081