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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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https://doi.org/10.1016/j.cgh.2018.09.043

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1 of 47 Northup, et al: Surgical Risk in Cirrhosis CPU 9/28/2018

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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References

1. Mokdad AA, Lopez AD, Shahraz S, et al. Liver cirrhosis mortality in 187 countries

between 1980 and 2010: a systematic analysis. BMC Med. 2014;12:145. Epub

2014/09/23.

2. Aranha GV, Greenlee HB. Intra-abdominal surgery in patients with advanced

cirrhosis. Arch Surg. 1986;121(3):275-7. Epub 1986/03/01.

3. Garcia-Tsao G, Abraldes JG, Berzigotti A, et al. Portal hypertensive bleeding in

cirrhosis: Risk stratification, diagnosis, and management: 2016 practice guidance by the

American Association for the study of liver diseases. Hepatology. 2017;65(1):310-35.

Epub 2016/10/28.

4. Tripodi A, Mannucci PM. The coagulopathy of chronic liver disease. N Engl J

Med. 2011;365(2):147-56. Epub 2011/07/15.

5. Rios R, Sangro B, Herrero I, et al. The role of thrombopoietin in the

thrombocytopenia of patients with liver cirrhosis. Am J Gastroenterol. 2005;100(6):1311-

6. Epub 2005/06/03.

6. Kim WR, Biggins SW, Kremers WK, et al. Hyponatremia and mortality among

patients on the liver-transplant waiting list. N Engl J Med. 2008;359(10):1018-26. Epub

2008/09/05.

7. Fine RL. Futility, the Multiorganization Policy Statement, and the Schneiderman

Response. Perspect Biol Med. 2018;60(3):358-66. Epub 2018/01/30.

MANUSCRIP

T

ACCEPTED

ACCEPTED MANUSCRIPT


8. Teh SH, Nagorney DM, Stevens SR, et al. Risk factors for mortality after surgery

in patients with cirrhosis. Gastroenterology. 2007;132(4):1261-9. Epub 2007/04/06.

9. Pugh RN, Murray-Lyon IM, Dawson JL, et al. Transection of the oesophagus for

bleeding oesophageal varices. Br J Surg. 1973;60(8):646-9. Epub 1973/08/01.

10. Ziser A, Plevak DJ, Wiesner RH, et al. Morbidity and mortality in cirrhotic patients

undergoing anesthesia and surgery. Anesthesiology. 1999;90(1):42-53. Epub

1999/01/23.

11. Telem DA, Schiano T, Goldstone R, et al. Factors that predict outcome of

abdominal operations in patients with advanced cirrhosis. Clin Gastroenterol Hepatol.

2010;8(5):451-7, quiz e58. Epub 2009/12/29.

12. Befeler AS, Palmer DE, Hoffman M, et al. The safety of intra-abdominal surgery

in patients with cirrhosis: model for end-stage liver disease score is superior to Child-

Turcotte-Pugh classification in predicting outcome. Arch Surg. 2005;140(7):650-4;

discussion 5. Epub 2005/07/20.

13. Doyle DJ, Garmon EH. American Society of Anesthesiologists Classification

(ASA Class). StatPearls. Treasure Island (FL)2018.

14. Neeff H, Mariaskin D, Spangenberg HC, et al. Perioperative mortality after non-

hepatic general surgery in patients with liver cirrhosis: an analysis of 138 operations in

the 2000s using Child and MELD scores. J Gastrointest Surg. 2011;15(1):1-11. Epub

2010/11/10.

MANUSCRIP

T

ACCEPTED

ACCEPTED MANUSCRIPT


15. Malinchoc M, Kamath PS, Gordon FD, et al. A model to predict poor survival in

patients undergoing transjugular intrahepatic portosystemic shunts. Hepatology.

2000;31(4):864-71. Epub 2000/03/25.

16. Northup PG, Wanamaker RC, Lee VD, et al. Model for End-Stage Liver Disease

(MELD) predicts nontransplant surgical mortality in patients with cirrhosis. Ann Surg.

2005;242(2):244-51. Epub 2005/07/26.

17. Bohnen JD, Ramly EP, Sangji NF, et al. Perioperative risk factors impact

outcomes in emergency versus nonemergency surgery differently: Time to separate our

national risk-adjustment models? J Trauma Acute Care Surg. 2016;81(1):122-30. Epub

2016/03/10.

18. Andraus W, Pinheiro RS, Lai Q, et al. Abdominal wall hernia in cirrhotic patients:

emergency surgery results in higher morbidity and mortality. BMC Surg. 2015;15:65.

Epub 2015/05/21.

19. Odom SR, Gupta A, Talmor D, et al. Emergency hernia repair in cirrhotic patients

with ascites. J Trauma Acute Care Surg. 2013;75(3):404-9. Epub 2013/10/04.

20. Mullen MG, Michaels AD, Mehaffey JH, et al. Risk Associated With

Complications and Mortality After Urgent Surgery vs Elective and Emergency Surgery:

Implications for Defining "Quality" and Reporting Outcomes for Urgent Surgery. JAMA

Surg. 2017;152(8):768-74. Epub 2017/05/12.

MANUSCRIP

T

ACCEPTED

ACCEPTED MANUSCRIPT


21. Garrison RN, Cryer HM, Howard DA, et al. Clarification of risk factors for

abdominal operations in patients with hepatic cirrhosis. Ann Surg. 1984;199(6):648-55.

Epub 1984/06/01.

22. Xu HW, Liu F, Li HY, et al. Outcomes following laparoscopic versus open major

hepatectomy for hepatocellular carcinoma in patients with cirrhosis: a propensity score-

matched analysis. Surg Endosc. 2018;32(2):712-9. Epub 2017/07/21.

23. Alshahrani AS, Gong GS, Yoo MW. Comparison of long-term survival and

immediate postoperative liver function after laparoscopic and open distal gastrectomy

for early gastric cancer patients with liver cirrhosis. Gastric Cancer. 2017;20(4):744-51.

Epub 2016/12/13.

24. Chmielecki DK, Hagopian EJ, Kuo YH, et al. Laparoscopic cholecystectomy is

the preferred approach in cirrhosis: a nationwide, population-based study. HPB

(Oxford). 2012;14(12):848-53. Epub 2012/11/09.

25. Eker HH, van Ramshorst GH, de Goede B, et al. A prospective study on elective

umbilical hernia repair in patients with liver cirrhosis and ascites. Surgery.

2011;150(3):542-6. Epub 2011/05/31.

26. Pei KY, Liu F, Zhang Y. A matched comparison of laparoscopic versus open

inguinal hernia repair in patients with liver disease using propensity score matching.

Hernia. 2017. Epub 2017/10/27.

27. Llovet JM, Bru C, Bruix J. Prognosis of hepatocellular carcinoma: the BCLC

staging classification. Semin Liver Dis. 1999;19(3):329-38. Epub 1999/10/13.

MANUSCRIP

T

ACCEPTED

ACCEPTED MANUSCRIPT


28. Bruix J, Castells A, Bosch J, et al. Surgical resection of hepatocellular carcinoma

in cirrhotic patients: prognostic value of preoperative portal pressure. Gastroenterology.

1996;111(4):1018-22. Epub 1996/10/01.

29. Rajakannu M, Coilly A, Adam R, et al. Prospective validation of transient

elastography for staging liver fibrosis in patients undergoing hepatectomy and liver

transplantation. J Hepatol. 2017. Epub 2017/08/25.

30. Llop E, Berzigotti A, Reig M, et al. Assessment of portal hypertension by

transient elastography in patients with compensated cirrhosis and potentially resectable

liver tumors. J Hepatol. 2012;56(1):103-8. Epub 2011/08/11.

31. Teh SH, Christein J, Donohue J, et al. Hepatic resection of hepatocellular

carcinoma in patients with cirrhosis: Model of End-Stage Liver Disease (MELD) score

predicts perioperative mortality. J Gastrointest Surg. 2005;9(9):1207-15; discussion 15.

Epub 2005/12/08.

32. Itoi T, Coelho-Prabhu N, Baron TH. Endoscopic gallbladder drainage for

management of acute cholecystitis. Gastrointest Endosc. 2010;71(6):1038-45. Epub

2010/05/05.

33. Bingener J, Cox D, Michalek J, et al. Can the MELD score predict perioperative

morbidity for patients with liver cirrhosis undergoing laparoscopic cholecystectomy? Am

Surg. 2008;74(2):156-9. Epub 2008/03/01.

MANUSCRIP

T

ACCEPTED

ACCEPTED MANUSCRIPT


34. Poggio JL, Rowland CM, Gores GJ, et al. A comparison of laparoscopic and

open cholecystectomy in patients with compensated cirrhosis and symptomatic

gallstone disease. Surgery. 2000;127(4):405-11. Epub 2000/04/25.

35. Shaheen AA, Kaplan GG, Hubbard JN, et al. Morbidity and mortality following

coronary artery bypass graft surgery in patients with cirrhosis: a population-based study.

Liver Int. 2009;29(8):1141-51. Epub 2009/06/12.

36. Lewis JH, Mortensen ME, Zweig S, et al. Efficacy and safety of high-dose

pravastatin in hypercholesterolemic patients with well-compensated chronic liver

disease: Results of a prospective, randomized, double-blind, placebo-controlled,

multicenter trial. Hepatology. 2007;46(5):1453-63. Epub 2007/08/03.

37. Task Force on Patient Blood Management for Adult Cardiac Surgery of the

European Association for Cardio-Thoracic S, the European Association of

Cardiothoracic A, Boer C, et al. 2017 EACTS/EACTA Guidelines on patient blood

management for adult cardiac surgery. J Cardiothorac Vasc Anesth. 2018;32(1):88-120.

Epub 2017/10/17.

38. Bizouarn P, Ausseur A, Desseigne P, et al. Early and late outcome after elective

cardiac surgery in patients with cirrhosis. Ann Thorac Surg. 1999;67(5):1334-8. Epub

1999/06/04.

39. Chou AH, Chen TH, Chen CY, et al. Long-Term Outcome of Cardiac Surgery in

1,040 Liver Cirrhosis Patient- Nationwide Population-Based Cohort Study. Circ J.

2017;81(4):476-84. Epub 2017/02/07.

MANUSCRIP

T

ACCEPTED

ACCEPTED MANUSCRIPT


40. Davis JPE, Northup PG, Caldwell SH, et al. Viscoelastic Testing in Liver Disease.

Ann Hepatol. 2018;17(2):205-13. Epub 2018/02/23.

41. Fleming K, Redfern RE, March RL, et al. TEG-Directed Transfusion in Complex

Cardiac Surgery: Impact on Blood Product Usage. J Extra Corpor Technol.

2017;49(4):283-90. Epub 2018/01/06.

42. Arif R, Seppelt P, Schwill S, et al. Predictive risk factors for patients with cirrhosis

undergoing heart surgery. Ann Thorac Surg. 2012;94(6):1947-52. Epub 2012/08/28.

43. Filsoufi F, Salzberg SP, Rahmanian PB, et al. Early and late outcome of cardiac

surgery in patients with liver cirrhosis. Liver Transpl. 2007;13(7):990-5. Epub

2007/04/12.

44. Jacob KA, Hjortnaes J, Kranenburg G, et al. Mortality after cardiac surgery in

patients with liver cirrhosis classified by the Child-Pugh score. Interact Cardiovasc

Thorac Surg. 2015;20(4):520-30. Epub 2015/01/24.

45. Macaron C, Hanouneh IA, Suman A, et al. Safety of cardiac surgery for patients

with cirrhosis and Child-Pugh scores less than 8. Clin Gastroenterol Hepatol.

2012;10(5):535-9. Epub 2012/01/03.

46. Thielmann M, Mechmet A, Neuhauser M, et al. Risk prediction and outcomes in

patients with liver cirrhosis undergoing open-heart surgery. Eur J Cardiothorac Surg.

2010;38(5):592-9. Epub 2010/04/24.

MANUSCRIP

T

ACCEPTED

ACCEPTED MANUSCRIPT


47. Suman A, Barnes DS, Zein NN, et al. Predicting outcome after cardiac surgery in

patients with cirrhosis: a comparison of Child-Pugh and MELD scores. Clin

Gastroenterol Hepatol. 2004;2(8):719-23. Epub 2004/08/04.

48. Thakkar B, Patel A, Mohamad B, et al. Transcatheter aortic valve replacement

versus surgical aortic valve replacement in patients with cirrhosis. Catheter Cardiovasc

Interv. 2016;87(5):955-62. Epub 2015/12/25.

49. Townsend JC, Heard R, Powers ER, et al. Usefulness of international normalized

ratio to predict bleeding complications in patients with end-stage liver disease who

undergo cardiac catheterization. Am J Cardiol. 2012;110(7):1062-5. Epub 2012/06/26.

50. Krill T, Brown G, Weideman RA, et al. Patients with cirrhosis who have coronary

artery disease treated with cardiac stents have high rates of gastrointestinal bleeding,

but no increased mortality. Aliment Pharmacol Ther. 2017;46(2):183-92. Epub

2017/05/11.

51. Russo MW, Pierson J, Narang T, et al. Coronary artery stents and antiplatelet

therapy in patients with cirrhosis. J Clin Gastroenterol. 2012;46(4):339-44. Epub

2011/11/23.

52. Vilar-Gomez E, Martinez-Perez Y, Calzadilla-Bertot L, et al. Weight Loss

Through Lifestyle Modification Significantly Reduces Features of Nonalcoholic

Steatohepatitis. Gastroenterology. 2015;149(2):367-78 e5; quiz e14-5. Epub

2015/04/14.

MANUSCRIP

T

ACCEPTED

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53. Pestana L, Swain J, Dierkhising R, et al. Bariatric surgery in patients with

cirrhosis with and without portal hypertension: a single-center experience. Mayo Clin

Proc. 2015;90(2):209-15. Epub 2015/02/11.

54. Hanipah ZN, Punchai S, McCullough A, et al. Bariatric Surgery in Patients with

Cirrhosis and Portal Hypertension. Obes Surg. 2018. Epub 2018/08/16.

55. Mosko JD, Nguyen GC. Increased perioperative mortality following bariatric

surgery among patients with cirrhosis. Clin Gastroenterol Hepatol. 2011;9(10):897-901.

Epub 2011/07/26.

56. Shimizu H, Phuong V, Maia M, et al. Bariatric surgery in patients with liver

cirrhosis. Surg Obes Relat Dis. 2013;9(1):1-6. Epub 2012/12/04.

57. Heimbach JK, Watt KD, Poterucha JJ, et al. Combined liver transplantation and

gastric sleeve resection for patients with medically complicated obesity and end-stage

liver disease. Am J Transplant. 2013;13(2):363-8. Epub 2012/11/10.

58. Zamora-Valdes D, Watt KD, Kellogg TA, et al. Long-term outcomes of patients

undergoing simultaneous liver transplantation and sleeve gastrectomy. Hepatology.

2018;68(2):485-95. Epub 2018/02/20.

59. Al-Nowaylati AR, Al-Haddad BJ, Dorman RB, et al. Gastric bypass after liver

transplantation. Liver Transpl. 2013;19(12):1324-9. Epub 2013/09/17.

MANUSCRIP

T

ACCEPTED

ACCEPTED MANUSCRIPT


60. Lin MY, Tavakol MM, Sarin A, et al. Safety and feasibility of sleeve gastrectomy

in morbidly obese patients following liver transplantation. Surg Endosc. 2013;27(1):81-5.

Epub 2012/07/04.

61. Runyon BA, Committee APG. Management of adult patients with ascites due to

cirrhosis: an update. Hepatology. 2009;49(6):2087-107. Epub 2009/05/29.

62. Lieberman FL, Reynolds TB. Plasma volume in cirrhosis of the liver: its relation

of portal hypertension, ascites, and renal failure. J Clin Invest. 1967;46(8):1297-308.

Epub 1967/08/01.

63. Semiz-Oysu A, Moustafa T, Cho KJ. Transjugular intrahepatic portosystemic

shunt prior to cardiac surgery with cardiopulmonary bypass in patients with cirrhosis and

portal hypertension. Heart Lung Circ. 2007;16(6):465-8. Epub 2007/04/21.

64. Schlenker C, Johnson S, Trotter JF. Preoperative transjugular intrahepatic

portosystemic shunt (TIPS) for cirrhotic patients undergoing abdominal and pelvic

surgeries. Surg Endosc. 2009;23(7):1594-8. Epub 2009/03/06.

65. Gil A, Martinez-Regueira F, Hernandez-Lizoain JL, et al. The role of transjugular

intrahepatic portosystemic shunt prior to abdominal tumoral surgery in cirrhotic patients

with portal hypertension. Eur J Surg Oncol. 2004;30(1):46-52. Epub 2004/01/23.

66. Guerrini GP, Pleguezuelo M, Maimone S, et al. Impact of tips preliver

transplantation for the outcome posttransplantation. Am J Transplant. 2009;9(1):192-

200. Epub 2008/12/11.

MANUSCRIP

T

ACCEPTED

ACCEPTED MANUSCRIPT


67. Boyer TD, Haskal ZJ, American Association for the Study of Liver D. The Role of

Transjugular Intrahepatic Portosystemic Shunt (TIPS) in the Management of Portal

Hypertension: update 2009. Hepatology. 2010;51(1):306. Epub 2009/11/11.

68. Tripodi A, Salerno F, Chantarangkul V, et al. Evidence of normal thrombin

generation in cirrhosis despite abnormal conventional coagulation tests. Hepatology.

2005;41(3):553-8. Epub 2005/02/24.

69. Tripodi A, Primignani M, Lemma L, et al. Evidence that low protein C contributes

to the procoagulant imbalance in cirrhosis. J Hepatol. 2013;59(2):265-70. Epub

2013/04/16.

70. Northup PG, Caldwell SH. Coagulation in liver disease: a guide for the clinician.

Clin Gastroenterol Hepatol. 2013;11(9):1064-74. Epub 2013/03/20.

71. Tripodi A, Primignani M, Chantarangkul V, et al. Thrombin generation in patients

with cirrhosis: the role of platelets. Hepatology. 2006;44(2):440-5. Epub 2006/07/28.

72. Seeff LB, Everson GT, Morgan TR, et al. Complication rate of percutaneous liver

biopsies among persons with advanced chronic liver disease in the HALT-C trial. Clin

Gastroenterol Hepatol. 2010;8(10):877-83. Epub 2010/04/07.

73. Afdhal NH, Dusheiko GM, Giannini EG, et al. Eltrombopag increases platelet

numbers in thrombocytopenic patients with HCV infection and cirrhosis, allowing for

effective antiviral therapy. Gastroenterology. 2014;146(2):442-52 e1. Epub 2013/10/16.

MANUSCRIP

T

ACCEPTED

ACCEPTED MANUSCRIPT


74. Terrault N, Chen YC, Izumi N, et al. Avatrombopag Before Procedures Reduces

Need for Platelet Transfusion in Patients With Chronic Liver Disease and

Thrombocytopenia. Gastroenterology. 2018. Epub 2018/05/21.

75. Tateishi R, Seike M, Kudo M, et al. A randomized controlled trial of

lusutrombopag in Japanese patients with chronic liver disease undergoing

radiofrequency ablation. J Gastroenterol. 2018. Epub 2018/08/15.

76. Drolz A, Horvatits T, Roedl K, et al. Coagulation parameters and major bleeding

in critically ill patients with cirrhosis. Hepatology. 2016;64(2):556-68. Epub 2016/04/29.

77. Wikkelso A, Wetterslev J, Moller AM, et al. Thromboelastography (TEG) or

thromboelastometry (ROTEM) to monitor haemostatic treatment versus usual care in

adults or children with bleeding. Cochrane Database Syst Rev. 2016(8):CD007871.

Epub 2016/08/24.

78. De Pietri L, Bianchini M, Montalti R, et al. Thrombelastography-guided blood

product use before invasive procedures in cirrhosis with severe coagulopathy: A

randomized, controlled trial. Hepatology. 2016;63(2):566-73. Epub 2015/09/05.

79. Tegeder I, Lotsch J, Geisslinger G. Pharmacokinetics of opioids in liver disease.

Clin Pharmacokinet. 1999;37(1):17-40. Epub 1999/08/19.

80. Kotb HI, Fouad IA, Fares KM, et al. Pharmacokinetics of oral tramadol in patients

with liver cancer. J Opioid Manag. 2008;4(2):99-104. Epub 2008/06/18.

MANUSCRIP

T

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81. Benson GD. Acetaminophen in chronic liver disease. Clin Pharmacol Ther.

1983;33(1):95-101. Epub 1983/01/01.

82. Laffi G, La Villa G, Pinzani M, et al. Arachidonic acid derivatives and renal

function in liver cirrhosis. Semin Nephrol. 1997;17(6):530-48. Epub 1997/11/14.

83. Fernandes NF, Schwesinger WH, Hilsenbeck SG, et al. Laparoscopic

cholecystectomy and cirrhosis: a case-control study of outcomes. Liver Transpl.

2000;6(3):340-4. Epub 2000/05/29.

84. Iwasaki A, Shirakusa T, Okabayashi K, et al. Lung cancer surgery in patients with

liver cirrhosis. Ann Thorac Surg. 2006;82(3):1027-32. Epub 2006/08/25.

85. Lee JH, Yu CS, Lee JL, et al. Factors affecting the postoperative morbidity and

survival of patients with liver cirrhosis following colorectal cancer surgery. Int J

Colorectal Dis. 2017;32(4):521-30. Epub 2016/12/18.

86. Liao JC, Chen WJ, Chen LH, et al. Complications associated with instrumented

lumbar surgery in patients with liver cirrhosis: a matched cohort analysis. Spine J.

2013;13(8):908-13. Epub 2013/04/02.

87. Chen CC, Hsu PW, Lee ST, et al. Brain surgery in patients with liver cirrhosis. J

Neurosurg. 2012;117(2):348-53. Epub 2012/05/29.

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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

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