eMedicine Specialties > Perioperative Care > Perioperative Care

Perioperative Management of the Patient With Liver Disease

Author: Avital Yehudit O'Glasser, MD, Resident Physician, Department of Internal Medicine, Oregon Health and Sciences Universtiy
Coauthor(s): Sai Praveen Haranath, MBBS, MPH, FCCP, Consultant Physician, Pulmonary and Critical Care Medicine, Kaiser Permanente Medical Center, Walnut Creek, CA; Brintha K Enestvedt, MD, Fellow, Department of Gastroenterology, Oregon Health and Sciences University; Sai Prashanth Haranath, MBBS, Staff Physician, Department of Internal Medicine, Middlesex Hospital; Hari Conjeevaram, MD, MS, Associate Professor, Department of Medicine, Division of Gastroenterology, University of Michigan School of Medicine
Contributor Information and Disclosures

Updated: May 5, 2009

Introduction

The number of patients with cirrhosis who require surgery is on the rise. Despite advances in antiviral therapeutics, the prevalence of cirrhosis secondary to hepatitis C continues to increase, as does the prevalence of cirrhosis due to chronic alcoholic liver disease. Additionally, nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are gaining more attention, especially in association with metabolic syndrome and obesity. At the same time, the amount of medications and treatments aimed at improving survival among patients with cirrhosis has been increasing. Therefore, it can be expected that a growing number of patients with liver disease, both known and as yet undiagnosed and asymptomatic, will undergo surgery.

An estimated 1 in 700 patients admitted for elective surgery has abnormal liver enzyme levels.  Some authors have estimated that as many as 10% of patients with advanced liver disease will undergo surgery in the last 2 years of their lives.1 This article focuses on the challenges of perioperative care of patients with liver disease.
 
Identification of the surgical risk is imperative in the care of any patient. Patients with liver disease are at particularly high risk for morbidity and mortality in the postoperative period due to both the stress of surgery and the effects of general anesthesia. del Olmo et al compared 135 patients with cirrhosis with 86 patients without cirrhosis, all undergoing nonhepatic general surgery.2 At 1 month, mortality rates were 16.3% for patients with cirrhosis compared with 3.5% in the control group. What is further evident in the literature is that decompensated liver disease increases the risk of postoperative complications (eg, acute hepatic failure, sepsis, bleeding, renal dysfunction). Assessing risk in these patients is a challenging but important endeavor. 
 
The liver is vital for protein synthesis, glucose homeostasis, bilirubin excretion, drug metabolism, and toxic removal, among other critical functions. In general, the liver has substantial functional reserve because of its dual blood supply: portal-venous (75%) and hepatic-arterial (25%). Hence, clinical manifestations of liver damage occur only after considerable injury. 

Liver disease comprises a large spectrum of hepatic dysfunction. It includes asymptomatic transaminitis, cirrhosis, and end-stage liver disease. The most common causes of advanced liver disease are chronic viral infections (hepatitis C [HCV] and B [HBV]), alcohol abuse, NAFLD/NASH , autoimmune disease, drugs or toxins, metabolic disorders (eg, alpha-1 antitrypsin deficiency, hemochromatosis, and Wilson disease), and biliary tract diseases.

For excellent patient education resources, visit eMedicine's Hepatitis Center and Liver, Gallbladder, and Pancreas Center. Also, see eMedicine's patient education articles Liver Transplant and Cirrhosis.

Surgical Risk Assessment

Basis for risk assessment
 
Secondary to the loss of hepatic reserve capacity and because of other systemic derangements that are the result of liver dysfunction (such as hemodynamic impairments), patients with liver disease have an inappropriate response to surgical stress. These individuals are accordingly at an increased risk of bleeding, infection, postoperative hepatic decompensation, including hepatic coma or death. Therefore, the decision to perform surgery in these patients must be heavily weighed.

Prediction of surgical risk is based on the degree of liver dysfunction, the type of surgery, and the preclinical status of the patient. The extent of liver dysfunction and type of surgery play key roles in determining a patient’s specific risk. In addition, liver disease can affect almost every organ and system in the body, including the cardiorespiratory and circulatory systems, the brain, the kidneys, and the immune system. 

The extent to which secondary manifestations of liver disease affect these systems may be just as important as the manifestations of primary liver dysfunction in predicting the outcome after surgery. Such comorbid conditions responsible for perioperative morbidity and mortality (eg, coagulopathy, intravascular volume, renal function, electrolytes, cardiovascular status, and nutritional status) should be identified and addressed before surgery. Optimal preparation may decrease death and complications after surgery. Issues to anticipate and address include manifestations of acute liver decompensation including encephalopathy, acute renal failure, coagulopathy, adult respiratory distress syndrome, and sepsis.3,4

Algorithm for a patient with liver disease for wh...

Algorithm for a patient with liver disease for whom surgery is being considered.

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Algorithm for a patient with liver disease for wh...

Algorithm for a patient with liver disease for whom surgery is being considered.


 
Quantitative risk stratification
 
Two risk stratifications schemes have been used to estimate the perioperative risk of patients with cirrhosis: the Child-Turcotte-Pugh score and the Model for End-Stage Liver Disease (MELD) score. 
 
The Child-Turcotte-Pugh (CTP) score incorporates a combination of 3 biochemical elements (ie, prothrombin time [PT], albumin level, and bilirubin level) and 2 clinical features (ie, presence of ascites and encephalopathy) to assess the primary functions of the liver (see the table below). A patient’s score is translated to 1 of 3 CTP classes: A, B, or C, with A reflecting the least severe disease. Patients who are CTP class B and C have worse outcomes and are candidates for liver transplantation.
 
The CTP score was first developed to predict mortality after portocaval shunt surgery, but it has since been used to predict perioperative morbidity and mortality rates for patients undergoing hepatic and nonhepatic intra-abdominal surgeries.1,5,6,7 Patients with CTP class A disease are estimated to have a 10% mortality rate after abdominal surgery. That mortality rate increases to 30-31% for CTP class B and 76-82% for CTP class C.1,7
 
However, the CTP scoring system has been challenged for its ambiguity and interobserver variability because it includes subjective parameters (eg, degree of ascites and encephalopathy). Additionally, all the factors are weighted equally. Patients within a given class are not homogenous but also not distinguished between, a feature for which it has also been criticized.8
 
The MELD score was originally developed to predict short-term mortality for patients undergoing transjugular intrahepatic portosystemic shunt (TIPS) placement. It has since been adopted as the tool to prioritize patients with cirrhosis for liver transplantation. 
 
The MELD score is based on a patient's serum bilirubin, creatinine, and international normalized ratio (INR) for prothrombin time and is calculated from a validated predictive equation, as follows: (3.8 × In bilirubin value) + (11.2 X In INR) + (9.6 In creatinine value), where bilirubin and creatinine values are in milligrams per deciliter (mg/dL) and ln represents natural logarithm.

The MELD score originally included the etiology of liver failure, but this criterion was subsequently dropped from the equation because it was proved prognostically insignificant.  The United Network for Organ Sharing (UNOS) provides an online calculator available at the UNOS MELD calculator.
 
With regard to its original utilization, a MELD score <8 predicts good outcome after TIPS and a score >18 predicts poor outcome, with best outcomes seen in patients with scores <14.  Avoidance of TIPS is generally recommended in patients with a MELD score >24, unless the procedure is used as a measure of last resort to control active variceal bleeding. Since its implementation, the MELD score’s use has been expanded to also predict the risk of mortality and morbidity after other procedures. A MELD score of at least 8 predicts an increased risk of postoperative complications, including death in patients undergoing cholecystectomy9 and cardiac surgery requiring cardiopulmonary bypass.10

Several authors have also shown that the MELD score predicts morbidity and mortality after hepatic resection for hepatocellular carcinoma. Cucchetti et al showed that MELD scores <9 were associated with 0% postoperative liver failure; MELD scores 9-10 were associated with 3.6% postoperative liver failure; and MELD scores >10 were associated with 37.5% postoperative liver failure.11  Teh et al showed that a MELD score less than or equal to 8 was associated with 0% postresection mortality compared  with 29% mortality for MELD scores >8.12
 
In general, the MELD score fairs well compared to the CTP score. However, some might argue that the MELD score may be a more objective predictor of postoperative mortality than the CTP score,9,10,13,14 especially as patients fall along a continuum of values instead of into 3 discrete groups.

The MELD score has been validated as an independent prediction tool to calculate postoperative mortality. A retrospective analysis by Northup et al found that the MELD score was the only statistically significant predictor of 30-day mortality. For example, with a MELD of 5 was associated with 5% risk; 10, with a 7% risk; 15, with an 11% risk; 20, with a 17% risk; or 25, with a 26% risk.15

Teh et al performed a retrospective, multivariate analysis that showed among patients with cirrhosis undergoing multiple types of major surgeries, the MELD but not the CTP score predicted increased mortality at 30 and 90 days, 1 year, and over the long term.16  Age and American Society of Anesthesiologists (ASA) class also predicted postoperative mortality. The MELD was the strongest predictor of mortality after 7 days and over the long term. For example, the 30-day mortality associated with MELD <8 was 5.7% but >50% for MELD score >20.16 The relative risk of mortality also increased 14% for each 1 point increase in the MELD score.
 
Child-Turcotte-Pugh classification of liver disease. (CTP A = 5-6 points, CTP B = 7-9 points, CTP C = 10-15 points)

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Table
Criterion
1 point each
2 points each
3 points each
Ascites
None
Controlled with diuretics
Poorly controlled
Encephalopathy
None
Grade I-II
Grade III-IV
Total bilirubin, µmol/L
(normal = 17.1 µmol/L or 1.0 mg/dL)
< 34
(0-2 mg/dL)
34 – 50
(2-3 mg/dL)
> 50
(> 3 mg/dL)
Albumin, g/L
>35 (>3.5 g/dL)
25-35 (2.5-3.5 g/dL)
<25 (<2.5 g/dL)
INR
<1.7
1.7–2.2
>2.2
Criterion
1 point each
2 points each
3 points each
Ascites
None
Controlled with diuretics
Poorly controlled
Encephalopathy
None
Grade I-II
Grade III-IV
Total bilirubin, µmol/L
(normal = 17.1 µmol/L or 1.0 mg/dL)
< 34
(0-2 mg/dL)
34 – 50
(2-3 mg/dL)
> 50
(> 3 mg/dL)
Albumin, g/L
>35 (>3.5 g/dL)
25-35 (2.5-3.5 g/dL)
<25 (<2.5 g/dL)
INR
<1.7
1.7–2.2
>2.2
 
Other risk stratification systems
 
The ASA physical status class risk stratification system is based on comorbid conditions that are a threat to life or that limit activity and thus helps in predicting preoperative risks. In general, an ASA class greater than 2 increases the risk 1.5- to 3.2-fold.17 The ASA class independently predicted postoperative mortality in patients undergoing hepatic resection for hepatocellular carcinoma.12 Teh et al also found the ASA class significantly predicts increased mortality and morbidity among patients with cirrhosis undergoing major surgery, with ASA class V the strongest predictor of postoperative mortality at 7 days.16 The mortality related to ASA IV was the equivalent of 5.5 MELD points in terms of risk.
 
It is also important to not overlook the preoperative cardiopulmonary evaluation. This is required of any patient, regardless of the functional status of their liver. Cardiac risk stratification should potentially include an assessment of functional capacity (metabolic equivalent [MET] or exercise duration) and stress testing (exercise electrocardiography [ECG], dipyridamole thallium test, or dobutamine stress echocardiography), if it is performed.   Surgery-specific risk also has a pivotal role in cardiac risk assessment. Cardiac surgery performed in patients with cirrhosis is associated with a high surgical mortality rate.10  
 
In 1997, the American College of Physicians (ACP) published guidelines in the form of algorithms for assessing and managing perioperative risks based on the results of the tests mentioned above. The Goldman cardiac risk index is used to predict postoperative pulmonary and cardiac complications.18 It is a classification system based on points assigned to a patient's clinical history, physical findings, ECGs, general medical status (based on arterial blood gases [ABGs], electrolytes, and liver disease), and type of operation.

Preoperative Assessment and Management

Asymptomatic patients
 
The evaluation of any patient undergoing surgery should include thorough history taking and physical examination. In asymptomatic patients, this is an extremely valuable screening tool.  Risk factors (eg, pervious blood transfusions, tattoos, illicit drug use, sexual history, alcohol use, personal history of adverse reaction to anesthesia, and personal or family history of jaundice) for liver disease should be explored.

A complete medication review including other-the-counter (OTC) and herbal agents should be performed. Symptoms or physical signs suggestive of liver dysfunction/disease (eg, hepatosplenomegaly, spider angioma, jaundice, gynecomastia, palmar erythema, scleral icterus, asterixis, encephalopathy) should prompt further examination with liver function tests, coagulation studies, complete blood cell (CBC) counts and metabolic panels. However, routine preoperative testing of liver function is not recommended because of the low prevalence of liver abnormalities in clinically asymptomatic patients.19,20
 
Asymptomatic patients with significantly abnormal liver function should have their elective surgery postponed and their liver disease investigated; their perioperative risk should be reassessed after their liver dysfunction is characterized.21
 
Acuity of liver disease
 
Although most studies have focused on patients with end-stage liver disease or cirrhosis, patients with acute hepatitis have been associated with an increased risk of surgical morbidity and mortality . This also applies to patients with acute alcoholic hepatitis. Patients with these conditions tend to have morbidity rates higher than those with chronic cholestatic disease. Therefore, it is prudent to postpone surgery, especially elective surgery, until transaminitis is resolved.22 Patients with chronic liver disease but with preserved hepatic function may not have an increased operative risk,23  but these individuals need to be closely evaluated nonetheless. 
 
Severity and specific derangements of known chronic liver disease
 
In patients with known liver disease, especially with cirrhosis, optimal preparation for surgery, that appropriately addresses the primary features and secondary manifestations of liver disease may decrease the risk of complications or death after surgery. This includes laboratory tests to assess blood counts, coagulopathy, electrolyte abnormalities, and markers of hepatic synthetic function.
 
Coagulopathy and thrombocytopenia
 
Coagulopathy is one of the primary features of advanced liver disease. In addition to hepatic synthetic dysfunction (all of the coagulation factors with the exception of von Willebrand factor are produced in the liver), malnutrition and vitamin K malabsorption due to cholestasis contribute to this abnormality. Additionally, portal hypertension leads to hypersplenism with resultant platelet trapping and peripheral thrombocytopenia. Vitamin K supplementation and administration of fresh-frozen plasma (FFP) are recommended to correct coagulopathy before surgery. Cryoprecipitate might also be required to reduce the prothrombin time. A prolonged bleeding time can also be corrected with diamino-8-D-arginine vasopressin (DDAVP). Finally, platelet transfusion may be necessary based on the patient’s platelet level and the desired level as dictated by the type of surgery.
 
Ascites
 
Ascites is important to assess and manage before surgery, because it can lead to wound dehiscence, abdominal wall herniation, and respiratory compromise secondary to reduced lung expansion. In a study by Conn, ascites in patients with cirrhosis was associated with a 37-83% mortality rate compared with 11-53% in those without ascites.24 In general, ascites should be treated aggressively with diuretics and/or large-volume paracentesis before surgery.  A low sodium diet is another important component of ascites management. Patients on diuretics need to have their creatinine and electrolytes monitored. 

Ascites fluid can also be removed intraoperatively at laparotomy.23 It is important to take note of the volume of fluid removed and the patient’s baseline renal function and to consider albumin repletement to maintain intravascular volume and prevent paracentesis-induced circulatory dysfunction. Ascitic fluid should also be analyzed to rule out spontaneous bacterial peritonitis. 
 
Encephalopathy
 
Many patients with cirrhosis may have portosystemic encephalopathy at baseline, which increases their risk of postoperative encephalopathy. A retrospective study of 40 patients with chronic liver failure undergoing nonhepatic surgery demonstrated that encephalopathy was associated with an 88% risk of mortality, which was even higher than the 50% risk associated with emergency surgery.25  

Multiple factors in the preoperative and postoperative periods may precipitate encephalopathy, such as infection and/or sepsis, diuretics, hypokalemia, metabolic alkalosis, constipation, use of central nervous system (CNS) depressants such narcotics and benzodiazepines, hypoxia, azotemia, and gastrointestinal bleeding. Addressing the underlying precipitant through correction of electrolyte abnormalities, treatment of infection, management of gastrointestinal bleeding, and restriction of sedatives may help prevent or decrease encephalopathy. Hepatic encephalopathy is also often treated by administering lactulose or poorly absorbed antibiotics such as rifaximin.
 
Renal dysfunction
 
Patients with chronic liver disease are at risk for renal dysfunction at baseline due to the propensity for hemodynamic derangements that increase the risk of renal hypoperfusion. This risk is increased by diuretics, nephrotoxic agents including nonsteroidal anti-inflammatory drugs (NSAIDs), large-volume paracentesis performed without albumin supplementation, infections, and gastrointestinal bleeding. Hepatorenal syndrome is another concerning occurrence in this patient population. 

The risk of renal dysfunction in the postoperative period is increased because of hemodynamic changes and fluid shifts or losses, particularly if ascites fluid is removed at laparotomy. Renal function should be closely monitored pre- and postoperatively, with appropriate measures taken to address or eliminate potential insults. Vasoactive compounds such as midodrine and terlipressin appear to be at least as effective as intravenous albumin in preventing circulatory dysfunction with resultant renal impairment in patients with cirrhosis who have lost third-spaced volume.26,27
 
Pulmonary disease
 
Pulmonary complications of end-stage liver disease include hepatopulmonary syndrome, portopulmonary hypertension, and hepatic hydrothorax. Hepatopulmonary syndrome is associated with vascular shunt, and the risk of hypoxia and ventilation-perfusion mismatch should be addressed before surgery. Portopulmonary hypertension can eventually lead to right heart failure and hypoxia. Hepatic hydrothorax, usually unilateral and in the right hemithorax, can occur and impair ventilation. However, the associated hypoxemia is usually not severe.28 Drainage is usually not recommended because the effusion often rapidly reaccumulates. Finally, the risk of chronic obstructive pulmonary disease (COPD) should be assessed in any patient who has previously smoked tobacco or who has alpha-1 antitrypsin deficiency.
 
Malnutrition
 
Severe malnutrition is associated with an increased need for packed red blood cells, FFP, and cryoprecipitate during liver transplantation. It is also associated with a prolonged postoperative stay. Stephenson et al suggest that preoperative improvement in the patient's nutritional status may improve outcomes.29
 
In patients with end-stage liver disease, parenteral and enteral nutrition should be started, preferably in the preoperative period, because they are expected to have increased energy expenditure after surgery.30  Of importance, certain types of nutritional supplementation may aggravate the tendency for hepatic encephalopathy; therefore, use high-carbohydrate and/or high-lipid supplements with a decreased amino acid content.31 Patients with alcoholic liver disease and Wernicke encephalopathy benefit from preoperative vitamin B1 supplementation. Advanced liver disease can also predispose to hypoglycemia.
 
Disease-specific considerations
 
Patients with autoimmune hepatitis on daily steroids should receive stress-dosed steroids before surgery. D-penicillamide can impair wound healing; patients taking it for Wilson disease should decrease their dose for 1-2 weeks pre- and postoperatively. Wilson disease might predispose to an increased risk of neurologic changes postoperatively. In addition, it is worth noting that patients with a history of alcohol abuse are at increased risk of other complications, including poor wound healing, bleeding, delirium, and infections. Patients who have continued to actively drink are at risk for withdrawal. 

Intraoperative Factors

Anesthesia
 
Impaired hepatic synthetic function and derangement of other hepatic functions are especially pertinent to note when choosing anesthetic and other agents used in the perioperative period.  These changes include decreased synthesis of plasma-binding proteins. Hypoalbuminemia impairs drug binding and metabolism and elevates serum drug levels. Impaired drug metabolism, detoxification, and excretion by the liver can prolong drug half-lives. Thus, the absorption, distribution, metabolism, and excretion of anesthetics, muscle relaxants, analgesics, and sedatives may be affected.
 
Patients with liver disease are more likely than patients without liver disease to have hepatic decompensation with the use of anesthesia.23 General anesthesia reduces total hepatic blood flow, especially the contribution of the hepatic artery. Patients with liver disease tend to have several baseline cardiovascular abnormalities, including decreased systemic vascular resistance and increased cardiac index, which may further affect hepatic blood flow. In addition, catecholamine and other neurohormonal responses are impaired in patients with liver disease; therefore, intraoperative hypovolemia or hemorrhage may not trigger adequate compensatory mechanisms. Anesthetics causing sympathetic blockade further blunt this response. The result of this reduction in hepatic perfusion is a drastic loss of their remaining marginal hepatic function. 
 
Of all the inhaled anesthetics, halothane and enflurane appear to reduce hepatic artery blood flow the most because of systemic vasodilation and a mild negative inotropic effect.23,32,33,34   Halothane is also associated with the greatest risk of hepatotoxicity, with the incidence of fulminant hepatitis approximating 1 case in 6,000-35,000 patients after exposure.35 Isoflurane has fewer effects on hepatic blood flow and less hepatic metabolism ; it is the preferred anesthetic agent in patients with liver disease. Newer haloalkanes, such as sevoflurane and desflurane, also undergo less hepatic metabolism than halothane or enflurane.
 
The drug effects of neuromuscular blocking agents may be prolonged in patients with liver disease because of impaired biliary excretion. Atracurium has been recommended as the agent of choice because it relies on neither the liver nor kidney for excretion.36  Likewise, drugs such as morphine, meperidine, benzodiazepines, and barbiturates should be used with caution because of their dependence on the liver for metabolism. In general, the doses of these agents should be decreased by 50%.37  Fentanyl is the preferred narcotic.38
 
Surgery
 
The type of surgery is potentially an important determinant of postoperative hepatic dysfunction. Because of traction on abdominal viscera, intra-abdominal operations are more likely than extra-abdominal surgeries to cause reflex systemic hypotension and to subsequently reduce hepatic blood flow. Surgeries that result in a large amount of blood loss increase the risk for ischemic hepatic injury. Sufficient surgical hemostasis and autologous platelet-rich plasma have been demonstrated to be useful for prevention of massive hemorrhage.3,7
 
Examples of specific surgeries and considerations
 
Cholecystitis and cholelithiasis are common in patients with liver disease. The odds ratio for perioperative mortality in patients with liver disease who undergo cholecystectomy is 8.47.23 In fact, open cholecystectomy in patients with cirrhosis has been called a formidable operation, although recent studies have demonstrated lowered but still considerable mortality rates in patients with cirrhosis who undergo abdominal surgery. Perkins et al confirmed that a MELD score greater to or equal to 8 predicts an increased risk of postoperative complications in this type of surgery.9
 
However, laparoscopic cholecystectomy can be safely performed in selected patients who have well-compensated cirrhosis and no signs of portal hypertension.23  A case-controlled retrospective review of laparoscopic cholecystectomy in 48 patients with Child-Pugh class A (80% of patients) and Child-Pugh class B cirrhosis demonstrated no increase in morbidity and mortality rates or worsening of outcome compared with control subjects.39 Another small series had similar results40 ;the authors concluded that laparoscopic cholecystectomy is relatively safe in patients with Child-Pugh class A or B cirrhosis. In addition, Ji et al showed that laparoscopic cholecystectomy was associated with lower rates of postoperative complications than open cholecystectomy in patients with cirrhosis matched for disease severity.41
 
A large study of 747 patients from 1990 to 1997 who underwent liver resection demonstrated that mortality was significantly higher in patients with cirrhosis (8.7%) or obstructive jaundice (21%) than in patients with a normal liver (1%; P < 0.001).42  Two groups have also demonstrated that the MELD score predicts risk of postresection morbidity and mortality.12,11
 
Cardiac surgery in patients with cirrhosis is associated with a high operative mortality rate.23 Friedman et al found the following risk factors for operative mortality: obstructive jaundice, hematocrit value <30%, serum bilirubin level >11 mg/dL, malignant biliary obstruction, azotemia, and cholangitis.23  In a small study, patients with cirrhosis and a CTP class A were found to have 0% mortality; B, 50% mortality; and C, 100% mortality after cardiac surgery,43 with another group finding that a CTP score >7 was more sensitive and as specific as the MELD score in predicting poor outcome.10
 
In some parts of the world, parasitic diseases, such as hydatid disease or echinococcosis, may cause liver lesions that need to be surgically removed. In such cases, the surgical technique is important, and sepsis can cause perioperative morbidity.44
 
Emergency surgery
 
Patients undergoing emergency surgery are at substantial risk for liver dysfunction. Intuition suggests, the more urgent the surgery, the less opportunity that is available to correct reversible factors, such as electrolyte abnormalities, coagulopathy, and clinical manifestations of portal hypertension (eg, ascites, hepatic encephalopathy).
 
Emergency surgery is an important predictor of adverse outcome. In a series of 100 patients with cirrhosis who underwent abdominal surgery for a variety of reasons, 80% of nonsurvivors and 40% of survivors who had serious complications had undergone emergency surgery.1 A series of 92 patients with cirrhosis who underwent abdominal surgeries had a 50% mortality rate in association with emergency procedures (22% for CTP class A, 38% for CTP class B, 100% for CTP class C) versus 18% for elective surgery (P = 0.001).7 This study showed that the most accurate predictor of outcome is the patient's preoperative CTP class.

Yet another study demonstrated that patients with cirrhosis had a higher perioperative morbidity and mortality rate with emergency surgery than with elective surgery. Mortality rates significantly differed between the groups (emergency group, 1 mo = 19% mortality rate, 3 mo = 44%; elective group, 1 mo = 17% mortality rate, 3 mo = 21%; P <0.05).13 Finally, a more recent study found that 100% of patients with cirrhosis undergoing emergency died, with a median survival 2 days16 ; all these patients had higher MELD scores and were ASA class V.16
 
Alternatives to surgery
 
Relatively noninvasive techniques or advances in medical management have replaced surgical intervention for many conditions (eg, extrahepatic biliary obstruction, refractory variceal hemorrhage, coronary artery disease). TIPS has become the treatment of choice for managing cases of refractory variceal bleeding, and surgical shunts are created only in special circumstances.

Percutaneous stenting or endoscopic retrograde cholangiopancreatography (ERCP) is now commonly used for biliary strictures and choledocholithiasis. Coronary angioplasty and percutaneous coronary interventions have decreased the need for coronary artery bypass grafting (CABG). The use of proton-pump inhibitors (PPIs) along with antibiotic treatment of Helicobacter pylori has usurped the need for surgical treatment of peptic ulcer disease (PUD) with antrectomy and/or vagotomy.

Postoperative Monitoring

In patients with cirrhosis, liver failure is the most common cause of postoperative death.38 Hepatocellular injury is most commonly due to the effects of anesthesia, intraoperative hypotension, sepsis, or viral hepatitis. A low threshold is generally maintained for postoperative transfer to the intensive care unit (ICU).

Patients must be observed closely for signs of acute hepatic decompensation, such as worsening jaundice, encephalopathy, and ascites. Sedatives and pain medications should be carefully titrated to prevent an exacerbation of hepatic encephalopathy. Renal function should also be monitored because of the risk of hepatorenal syndrome and fluid shifts that occur due to surgery. These patients should also be monitored for surgical site complications such as infections, bleeding, and dehiscence. Early enteral feeding has been suggested to improve outcomes.
 
Serious sequelae of decompensated cirrhosis include severe sepsis and secondary disseminated intravascular coagulation (DIC). These potential complications emphasize the need for maintaining a low threshold for ICU-level monitoring.

Conclusion

Surgery in a patient with liver disease, especially end-stage liver disease with cirrhosis and portal hypertension, poses a formidable challenge for all physicians involved. Targeted interventions before surgery may help to prevent complications and improve outcomes. 

The cornerstones of perioperative management are medical treatment of the complications of liver disease, including coagulopathy, ascites, encephalopathy, and malnutrition. Attention must also be paid to risk factors for infection and renal dysfunction after surgery. Sepsis, coagulopathy, and emergency surgery are most strongly correlated with postoperative mortality.
 
Evolving knowledge of the effects of anesthesia, improving surgical techniques, and use of improved diagnostic tests will help reduce perioperative complications.21 Established risk stratification systems such as the CTP score, the MELD score, and the ASA physical status class should also be used when evaluating a patient with liver disease for potential surgery.  Therefore, a multidisciplinary approach to postoperative care is imperative and should include input from anesthesiologists, surgeons, internists, and hepatologists.

Algorithm for a patient with liver disease for wh...

Algorithm for a patient with liver disease for whom surgery is being considered.

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Algorithm for a patient with liver disease for wh...

Algorithm for a patient with liver disease for whom surgery is being considered.


General considerations are as follows (see Image 1 or above):
 
  • Surgery is contraindicated in patients with CTP class C, high MELD score, ASA class V, acute hepatitis, severe coagulopathy, or severe extrahepatic manifestations of liver disease (eg, acute renal failure, hypoxia, cardiomyopathy).
  • Avoid surgery if possible in patients with a MELD score of greater than or equal to 8 or CTP class B unless they have undergone a thorough preoperative evaluation and preparation.
  • Use caution with sedatives and neuromuscular blocking agents.
  • Optimize medical therapy for patients with cirrhosis.
    • Correct coagulopathy with vitamin K and FFP to achieve prothrombin time within 3 seconds of normal.
    • The goal platelet count is >50-100 × 103/L but may vary depending on the specific surgery.
    • Minimize ascites to decrease risk of abdominal-wall herniation, wound dehiscence, and problems with ventilation.
    • Address nutritional status.
  • Perform close postoperative monitoring
    • Admission to the ICU may be appropriate after prolonged surgeries, intraoperative hypotension, excessive blood loss, or cardiac and/or pulmonary surgery.
    • Monitor for signs of acute liver failure, including worsening jaundice, encephalopathy, and ascites.
    • Monitor renal function.
    • Monitor and correct electrolyte abnormalities, especially hypokalemia and metabolic alkalosis.

Multimedia

Algorithm for a patient with liver disease for wh...
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Media file 1: Algorithm for a patient with liver disease for whom surgery is being considered.
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Algorithm for a patient with liver disease for whom surgery is being considered.

Keywords

perioperative management of the patient with liver disease, perioperative management of hepatic disease, end-stage liver disease, ESLD, end stage liver disease, hepatitis, cirrhosis, hepatorenal syndrome, paracentesis -induced circulatory dysfunction, hepatic tumors, portal hypertension, transjugular intrahepatic portosystemic shunt, TIPS, liver transplantation, hepatic surgery, Child-Turcotte-Pugh score, CTP score, Model for End-Stage Liver Disease score, MELD score, American Society of Anesthesiologists class, ASA class

 


More on Perioperative Management of the Patient With Liver Disease

References
Further Reading
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References

  1. Garrison RN, Cryer HM, Howard DA, Polk HC Jr. Clarification of risk factors for abdominal operations in patients with hepatic cirrhosis. Ann Surg. Jun 1984;199(6):648-55. [Medline]. [Full Text].

  2. del Olmo JA, Flor-Lorente B, Flor-Civera B, et al. Risk factors for nonhepatic surgery in patients with cirrhosis. World J Surg. Jun 2003;27(6):647-52. [Medline].

  3. Mueller AR, Platz KP, Kremer B. Early postoperative complications following liver transplantation. Best Pract Res Clin Gastroenterol. Oct 2004;18(5):881-900. [Medline].

  4. Ziser A, Plevak DJ, Wiesner RH, et al. Morbidity and mortality in cirrhotic patients undergoing anesthesia and surgery. Anesthesiology. Jan 1999;90(1):42-53. [Medline].

  5. Leonetti JP, Aranha GV, Wilkinson WA, Stanley M, Greenlee HB. Umbilical herniorrhaphy in cirrhotic patients. Arch Surg. Apr 1984;119(4):442-5. [Medline].

  6. Cryer HM, Howard DA, Garrison RN. Liver cirrhosis and biliary surgery: assessment of risk. South Med J. Feb 1985;78(2):138-41. [Medline].

  7. Mansour A, Watson W, Shayani V, Pickleman J. Abdominal operations in patients with cirrhosis: still a major surgical challenge. Surgery. Oct 1997;122(4):730-5; discussion 735-6. [Medline].

  8. Trotter JF, Brimhall B, Arjal R, Phillips C. Specific laboratory methodologies achieve higher model for endstage liver disease (MELD) scores for patients listed for liver transplantation. Liver Transpl. Aug 2004;10(8):995-1000. [Medline]. [Full Text].

  9. Perkins L, Jeffries M, Patel T. Utility of preoperative scores for predicting morbidity after cholecystectomy in patients with cirrhosis. Clin Gastroenterol Hepatol. Dec 2004;2(12):1123-8. [Medline].

  10. 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. Aug 2004;2(8):719-23. [Medline].

  11. Cucchetti A, Ercolani G, Vivarelli M, et al. Impact of model for end-stage liver disease (MELD) score on prognosis after hepatectomy for hepatocellular carcinoma on cirrhosis. Liver Transpl. Jun 2006;12(6):966-71. [Medline]. [Full Text].

  12. 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. Dec 2005;9(9):1207-15; discussion 1215. [Medline].

  13. Farnsworth N, Fagan SP, Berger DH, Awad SS. Child-Turcotte-Pugh versus MELD score as a predictor of outcome after elective and emergent surgery in cirrhotic patients. Am J Surg. Nov 2004;188(5):580-3. [Medline].

  14. 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. Jul 2005;140(7):650-4; discussion 655. [Medline]. [Full Text].

  15. [Best Evidence] Northup PG, Wanamaker RC, Lee VD, Adams RB, Berg CL. Model for End-Stage Liver Disease (MELD) predicts nontransplant surgical mortality in patients with cirrhosis. Ann Surg. Aug 2005;242(2):244-51. [Medline]. [Full Text].

  16. Teh SH, Nagorney DM, Stevens SR, et al. Risk factors for mortality after surgery in patients with cirrhosis. Gastroenterology. Apr 2007;132(4):1261-9. [Medline].

  17. Smetana GW. Preoperative pulmonary evaluation. N Engl J Med. Mar 25 1999;340(12):937-44. [Medline].

  18. Lawrence VA, Dhanda R, Hilsenbeck SG, Page CP. Risk of pulmonary complications after elective abdominal surgery. Chest. Sep 1996;110(3):744-50. [Medline]. [Full Text].

  19. Schemel WH. Unexpected hepatic dysfunction found by multiple laboratory screening. Anesth Analg. Nov-Dec 1976;55(6):810-2. [Medline].

  20. Robbins JA, Mushlin AI. Preoperative evaluation of the healthy patient. Med Clin North Am. Nov 1979;63(6):1145-56. [Medline].

  21. Rizvon MK, Chou CL. Surgery in the patient with liver disease. Med Clin North Am. Jan 2003;87(1):211-27. [Medline].

  22. Powell-Jackson P, Greenway B, Williams R. Adverse effects of exploratory laparotomy in patients with unsuspected liver disease. Br J Surg. Aug 1982;69(8):449-51. [Medline].

  23. Friedman LS. The risk of surgery in patients with liver disease. Hepatology. Jun 1999;29(6):1617-23. [Medline]. [Full Text].

  24. Conn M. Preoperative evaluation of the patient with liver disease. Mt Sinai J Med. Jan 1991;58(1):75-80. [Medline].

  25. Rice HE, O'Keefe GE, Helton WS, Johansen K. Morbid prognostic features in patients with chronic liver failure undergoing nonhepatic surgery. Arch Surg. Aug 1997;132(8):880-4; discussion 884-5. [Medline].

  26. [Best Evidence] Singh V, Dheerendra PC, Singh B, et al. Midodrine versus albumin in the prevention of paracentesis-induced circulatory dysfunction in cirrhotics: a randomized pilot study. Am J Gastroenterol. Jun 2008;103(6):1399-405. [Medline].

  27. Singh V, Kumar R, Nain CK, Singh B, Sharma AK. Terlipressin versus albumin in paracentesis-induced circulatory dysfunction in cirrhosis: a randomized study. J Gastroenterol Hepatol. Jan 2006;21(1 pt 2):303-7. [Medline].

  28. Keegan MT, Plevak DJ. Preoperative assessment of the patient with liver disease. Am J Gastroenterol. Sep 2005;100(9):2116-27. [Medline]. [Full Text].

  29. Stephenson GR, Moretti EW, El-Moalem H, Clavien PA, Tuttle-Newhall JE. Malnutrition in liver transplant patients: preoperative subjective global assessment is predictive of outcome after liver transplantation. Transplantation. Aug 27 2001;72(4):666-70. [Medline].

  30. Weimann A, Kuse ER, Bechstein WO, et al. Perioperative parenteral and enteral nutrition for patients undergoing orthotopic liver transplantation. Results of a questionnaire from 16 European transplant units. Transpl Int. 1998;11 suppl 1:S289-91. [Medline].

  31. Wiklund RA. Preoperative preparation of patients with advanced liver disease. Crit Care Med. Apr 2004;32(4 suppl):S106-15. [Medline].

  32. Batchelder BM, Cooperman LH. Effects of anesthetics on splanchnic circulation and metabolism. Surg Clin North Am. Aug 1975;55(4):787-94. [Medline].

  33. Ngai SH. Effects of anesthetics on various organs. N Engl J Med. Mar 6 1980;302(10):564-6. [Medline].

  34. Strunin L. Anesthetic management of patients with liver disease. In: Millward-Sadler GH, Wright R, Arthur MJ, eds. Liver and Biliary Disease. London, UK: Saunders; 1992:1381-91.

  35. Gut J. Molecular basis of halothane hepatitis. Arch Toxicol Suppl. 1998;20:3-17. [Medline].

  36. Maze M. Anesthetics and the liver. In: Miller RD, ed. Anesthesia. 4th ed. Edinburgh, UK: Churchill Livingstone; 1994:1994.

  37. Gholson CF, Provenza JM, Bacon BR. Hepatologic considerations in patients with parenchymal liver disease undergoing surgery. Am J Gastroenterol. May 1990;85(5):487-96. [Medline].

  38. Friedman LS, Maddrey WC. Surgery in the patient with liver disease. Med Clin North Am. May 1987;71(3):453-76. [Medline].

  39. Fernandes NF, Schwesinger WH, Hilsenbeck SG, et al. Laparoscopic cholecystectomy and cirrhosis: a case-control study of outcomes. Liver Transpl. May 2000;6(3):340-4. [Medline]. [Full Text].

  40. D'Albuquerque LA, de Miranda MP, Genzini T, Copstein JL, de Oliveira e Silva A. Laparoscopic cholecystectomy in cirrhotic patients. Surg Laparosc Endosc. Aug 1995;5(4):272-6. [Medline].

  41. Ji W, Li LT, Wang ZM, et al. A randomized controlled trial of laparoscopic versus open cholecystectomy in patients with cirrhotic portal hypertension. World J Gastroenterol. Apr 28 2005;11(16):2513-7. [Medline]. [Full Text].

  42. Belghiti J, Hiramatsu K, Benoist S, et al. Seven hundred forty-seven hepatectomies in the 1990s: an update to evaluate the actual risk of liver resection. J Am Coll Surg. Jul 2000;191(1):38-46. [Medline].

  43. Hayashida N, Shoujima T, Teshima H, et al. Clinical outcome after cardiac operations in patients with cirrhosis. Ann Thorac Surg. Feb 2004;77(2):500-5. [Medline].

  44. Atmatzidis KS, Pavlidis TE, Papaziogas BT, Mirelis C, Papaziogas TB. Recurrence and long-term outcome after open cystectomy with omentoplasty for hepatic hydatid disease in an endemic area. Acta Chir Belg. Apr 2005;105(2):198-202. [Medline].

  45. Alter MJ, Kruszon-Moran D, Nainan OV, et al. The prevalence of hepatitis C virus infection in the United States, 1988 through 1994. N Engl J Med. Aug 19 1999;341(8):556-62. [Medline]. [Full Text].

  46. American College of Physicians. Guidelines for assessing and managing the perioperative risk from coronary artery disease associated with major noncardiac surgery. Ann Intern Med. Aug 15 1997;127(4):309-12. [Medline]. [Full Text].

  47. Armstrong GL, Wasley A, Simard EP, et al. The prevalence of hepatitis C virus infection in the United States, 1999 through 2002. Ann Intern Med. May 16 2006;144(10):705-14. [Medline]. [Full Text].

  48. Burroughs AK, Matthews K, Qadiri M, et al. Desmopressin and bleeding time in patients with cirrhosis. Br Med J (Clin Res Ed). Nov 16 1985;291(6506):1377-81. [Medline]. [Full Text].

  49. Child CG, Turcotte JG. Surgery and portal hypertension. Major Probl Clin Surg. 1964;1:1-85. [Medline].

  50. Farrell GC, Larter CZ. Nonalcoholic fatty liver disease: from steatosis to cirrhosis. Hepatology. Feb 2006;43(2 suppl 1):S99-S112. [Medline]. [Full Text].

  51. Gill RA, Goodman MW, Golfus GR, Onstad GR, Bubrick MP. Aminopyrine breath test predicts surgical risk for patients with liver disease. Ann Surg. Dec 1983;198(6):701-4. [Medline]. [Full Text].

  52. Hall JC, Tarala RA, Hall JL, Mander J. A multivariate analysis of the risk of pulmonary complications after laparotomy. Chest. Apr 1991;99(4):923-7. [Medline]. [Full Text].

  53. Hanje AJ, Patel T. Preoperative evaluation of patients with liver disease. Nat Clin Pract Gastroenterol Hepatol. May 2007;4(5):266-76. [Medline]. [Full Text].

  54. Harville DD, Summerskill WH. Surgery in acute hepatitis. Causes and effects. JAMA. Apr 27 1963;184:257-61. [Medline].

  55. Jackson FC, Christophersen EB, Peternel WW, Kirimli B. Preoperative management of patients with liver disease. Surg Clin North Am. Aug 1968;48(4):907-30. [Medline].

  56. Jacob M, Copley LP, Lewsey JD, et al. Functional status of patients before liver transplantation as a predictor of posttransplant mortality. Transplantation. Jul 15 2005;80(1):52-7. [Medline].

  57. Kroenke K, Lawrence VA, Theroux JF, Tuley MR. Operative risk in patients with severe obstructive pulmonary disease. Arch Intern Med. May 1992;152(5):967-71. [Medline].

  58. Mas A, Rodes J, Sunyer L, et al. Comparison of rifaximin and lactitol in the treatment of acute hepatic encephalopathy: results of a randomized, double-blind, double-dummy, controlled clinical trial. J Hepatol. Jan 2003;38(1):51-8. [Medline].

  59. Millwala F, Nguyen GC, Thuluvath PJ. Outcomes of patients with cirrhosis undergoing non-hepatic surgery: risk assessment and management. World J Gastroenterol. Aug 14 2007;13(30):4056-63. [Medline]. [Full Text].

  60. O'Leary JG, Friedman LS. Predicting surgical risk in patients with cirrhosis: from art to science. Gastroenterology. Apr 2007;132(4):1609-11. [Medline].

  61. Patel T. Surgery in the patient with liver disease. Mayo Clin Proc. Jun 1999;74(6):593-9. [Medline].

  62. Rector RS, Thyfault JP, Wei Y, Ibdah JA. Non-alcoholic fatty liver disease and the metabolic syndrome: an update. World J Gastroenterol. Jan 14 2008;14(2):185-92. [Medline]. [Full Text].

  63. Runyon BA. Management of adult patients with ascites caused by cirrhosis. Hepatology. Jan 1998;27(1):264-72. [Medline]. [Full Text].

  64. Runyon BA. Surgical procedures are well tolerated by patients with asymptomatic chronic hepatitis. J Clin Gastroenterol. Oct 1986;8(5):542-4. [Medline].

  65. Zacks SL, Sandler RS, Rutledge R. A population-based cohort study comparing laparoscopic cholecystectomy and open cholecystectomy. Am J Gastroenterol. Feb 2002;97(2):334-40. [Medline].

  66. Zacks SL, Sandler RS, Rutledge R, Brown RS Jr. Liver disease markedly increases the risk of perioperative death in cholecystectomy patients [abstract]. Hepatology. 1997;26 (program issue):179A.

  67. [Best Evidence] Lerut J, Mathys J, Verbaandert C, et al. Tacrolimus monotherapy in liver transplantation: one-year results of a prospective, randomized, double-blind, placebo-controlled study. Ann Surg. Dec 2008;248(6):956-67. [Medline].

  68. [Best Evidence] Taketomi A, Kayashima H, Soejima Y, et al. Donor risk in adult-to-adult living donor liver transplantation: impact of left lobe graft. Transplantation. Feb 15 2009;87(3):445-50. [Medline].

  69. [Best Evidence] Vanlemmens C, Di Martino V, Milan C, et al for the TRANSCIAL Study Group. Immediate listing for liver transplantation versus standard care for Child-Pugh stage B alcoholic cirrhosis: a randomized trial. Ann Intern Med. Feb 3 2009;150(3):153-61. [Medline].

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Keywords

perioperative management of the patient with liver disease, perioperative management of hepatic disease, end-stage liver disease, ESLD, end stage liver disease, hepatitis, cirrhosis, hepatorenal syndrome, paracentesis -induced circulatory dysfunction, hepatic tumors, portal hypertension, transjugular intrahepatic portosystemic shunt, TIPS, liver transplantation, hepatic surgery, Child-Turcotte-Pugh score, CTP score, Model for End-Stage Liver Disease score, MELD score, American Society of Anesthesiologists class, ASA class

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Contributor Information and Disclosures

Author

Avital Yehudit O'Glasser, MD, Resident Physician, Department of Internal Medicine, Oregon Health and Sciences Universtiy
Disclosure: Nothing to disclose.

Coauthor(s)

Sai Praveen Haranath, MBBS, MPH, FCCP, Consultant Physician, Pulmonary and Critical Care Medicine, Kaiser Permanente Medical Center, Walnut Creek, CA
Sai Praveen Haranath, MBBS, MPH, FCCP is a member of the following medical societies: American College of Chest Physicians
Disclosure: Nothing to disclose.

Brintha K Enestvedt, MD, Fellow, Department of Gastroenterology, Oregon Health and Sciences University
Disclosure: Nothing to disclose.

Sai Prashanth Haranath, MBBS, Staff Physician, Department of Internal Medicine, Middlesex Hospital
Sai Prashanth Haranath, MBBS is a member of the following medical societies: American College of Gastroenterology and New York Academy of Sciences
Disclosure: Nothing to disclose.

Hari Conjeevaram, MD, MS, Associate Professor, Department of Medicine, Division of Gastroenterology, University of Michigan School of Medicine
Hari Conjeevaram, MD, MS is a member of the following medical societies: American Association for the Study of Liver Diseases and American Gastroenterological Association
Disclosure: Nothing to disclose.

Medical Editor

George Y Wu, MD, PhD, Professor, Department of Medicine, Director, Hepatology Section, Herman Lopata Chair in Hepatitis Research, University of Connecticut School of Medicine
George Y Wu, MD, PhD is a member of the following medical societies: American Association for the Study of Liver Diseases, American Gastroenterological Association, American Medical Association, American Society for Clinical Investigation, and Association of American Physicians
Disclosure: Humana Press Consulting fee Consulting; Novartis Consulting fee Review panel membership

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Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Donna Leco Mercado, MD, Director of Medical Consultation, Department of Internal Medicine, Baystate Medical Center; Assistant Professor, Tufts University School of Medicine
Donna Leco Mercado, MD is a member of the following medical societies: Sigma Xi
Disclosure: Nothing to disclose.

CME Editor

Alex J Mechaber, MD, FACP, Associate Dean for Undergraduate Medical Education, Associate Professor of Medicine, University of Miami Miller School of Medicine
Alex J Mechaber, MD, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, and Society of General Internal Medicine
Disclosure: Nothing to disclose.

Chief Editor

William A Schwer, MD, Professor, Department of Family Medicine, Rush Medical College; Chairman, Department of Family Medicine, Rush-Presbyterian-St Luke's Medical Center
William A Schwer, MD is a member of the following medical societies: American Academy of Family Physicians
Disclosure: Nothing to disclose.

 
 
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