• Because of the increased risk of perioperative morbidity and mortality, patients with acute hepatitis should have any elective surgery postponed until the acute hepatitis has resolved, as indicated by the normalization of liver tests.
  
• Isoflurane and sevoflurane are the volatile agents of choice because they preserve hepatic blood flow and oxygen delivery. Factors known to reduce hepatic blood flow, such as hypotension, excessive sympathetic activation, and high mean airway pressures during controlled ventilation, should be avoided.
  
• In evaluating patients for chronic hepatitis, laboratory test results may show only a mild elevation in serum aminotransferase activity and often correlate poorly with disease severity.
  
• Approximately 10% of patients with cirrhosis also develop at least one episode of spontaneous bacterial peritonitis, and some patients may eventually develop hepatocellular carcinoma.
  
• Massive bleeding from gastroesophageal varices is a major cause of morbidity and mortality, and, in addition to the cardiovascular effects of acute blood loss, the absorbed nitrogen load from the breakdown of blood in the intestinal tract can precipitate hepatic encephalopathy.
  
• The cardiovascular changes observed in the patient with hepatic cirrhosis are usually that of a hyperdynamic circulation, although clinically significant cirrhotic cardiomyopathy is often present and not recognized.
  
• The effects of hepatic cirrhosis on pulmonary vascular resistance vessels may result in chronic hypoxemia.
  
• Hepatorenal syndrome is a functional renal defect in patients with cirrhosis that usually follows gastrointestinal bleeding, aggressive diuresis, sepsis, or major surgery. It is characterized by progressive oliguria with avid sodium retention, azotemia, intractable ascites, and a very high mortality rate.
  
• Factors known to precipitate hepatic encephalopathy in patients with cirrhosis include gastrointestinal bleeding, increased dietary protein intake, hypokalemic alkalosis from vomiting or diuresis, infections, and worsening liver function.
  
• Following the removal of large amounts of ascitic fluid, aggressive intravenous fluid replacement is often necessary to prevent profound hypotension and kidney failure.

The prevalence of liver disease is increasing in the United States. Cirrhosis, the terminal pathology in the majority of liver diseases, has a general population incidence as high as 5% in some autopsy series. It is a major cause of death in men in their fourth and fifth decades of life, and mortality rates are increasing. Ten percent of the patients with liver disease undergo operative procedures during the final 2 years of their lives. The liver has remarkable functional reserve, and thus overt clinical manifestations of hepatic disease are often absent until extensive damage has occurred. When patients with little hepatic reserve come to the operating room, effects from anesthesia and the surgical procedure can precipitate further hepatic decompensation, leading to frank hepatic failure.

Coagulation in Liver Disease

In stable chronic liver disease, the causes of excessive bleeding primarily involve severe thrombocytopenia, endothelial dysfunction, portal hypertension, renal failure, and sepsis (see Chapters 32 and 51). However, the hemostatic changes that occur with liver disease may cause hypercoagulation and thrombosis, as well as an increased risk of bleeding. Clot breakdown may be enhanced by an imbalance of the fibrinolytic system.

Chronic liver disease is characterized by the impaired synthesis of coagulation factors, resulting in prolongation of the prothrombin time (PT) and international normalized ratio (INR) (Table 33-1). However, the anticoagulant factors (protein C, antithrombin, and tissue factor pathway inhibitor) are also reduced and may balance out any effect of a prolonged PT. This may be confirmed by assessing thrombin generation in the presence of endothelial-produced thrombomodulin. Adequate thrombin production requires an adequate number of functioning platelets. If the platelet count is >60,000/μL, coagulation may well be normal in a patient with severe cirrhosis.

The patient with cirrhosis will typically have hyperfibrinolysis. However, there is a delicate balance between the activators and inactivators that regulate the conversion of plasminogen to plasmin, and, therefore, individual laboratory tests may not give a true picture of the state of fibrinolysis. The thromboelastography (TEG®), rotational thromboelastometry (ROTEM®), and Sonoclot® technologies are the optimal methods of demonstrating the global state of the coagulation system at a specific moment in time in any patient with liver disease (see Chapter 51).

Acute Hepatitis

Acute hepatitis is usually the result of a viral infection, drug reaction, or exposure to a hepatotoxin. The illness represents acute hepatocellular injury with a variable degree of cellular necrosis. Clinical manifestations depend both on the severity of the inflammatory reaction, and, more importantly, on the degree of necrosis. Mild inflammatory reactions may present merely as asymptomatic elevations in the serum transaminases, whereas massive hepatic necrosis presents as acute fulminant hepatic failure.

Viral Hepatitis

Viral hepatitis is most commonly due to hepatitis A, hepatitis B, or hepatitis C viral infection. At least two other hepatitis viruses have also been identified: hepatitis D (delta virus) and hepatitis E (enteric non-A, non-B). Hepatitis types A and E are transmitted by the fecal-oral route, whereas hepatitis types B and C are transmitted primarily percutaneously and by contact with body fluids. Hepatitis D is unique in that it may be transmitted by either route and requires the presence of hepatitis B virus in the host to be infective. Other viruses may also cause hepatitis, including Epstein-Barr, herpes simplex, cytomegalovirus, and coxsackieviruses.

Patients with viral hepatitis often have a 1- to 2-week mild prodromal illness (fatigue, malaise, low-grade fever, or nausea and vomiting) that may or may not be followed by jaundice. The jaundice typically lasts 2-12 weeks, but complete recovery, as evidenced by serum transaminase measurements, usually takes 4 months. Because clinical manifestations overlap, serological testing is necessary to determine the causative viral agent. The clinical course tends to be more complicated and prolonged with hepatitis B and C viruses relative to other types of viral hepatitis. Cholestasis (see below) may be a major manifestation. Rarely, fulminant hepatic failure (massive hepatic necrosis) can develop.

The incidence of chronic active hepatitis (see below) is 3% to 10% following infection with hepatitis B virus and at least 50% following infection with hepatitis C virus. A small percentage of patients (mainly immunosuppressed patients and those on long-term hemodialysis regimens) become asymptomatic infectious carriers following infection with hepatitis B virus, and up to 30% of these patients remain infectious with the hepatitis B surface antigen (HBsAg) persisting in their blood. Most patients with chronic hepatitis C infection seem to have very low, intermittent, or absent circulating viral particles and are therefore not highly infective. Approximately 0.5% to 1% of patients with hepatitis C infection become asymptomatic infectious carriers, and infectivity correlates with the detection of hepatitis C viral RNA in peripheral blood. Such infectious carriers pose a major health hazard to operating room personnel.

In addition to “universal precautions” for avoiding direct contact with blood and secretions (gloves, mask, protective eyewear, and not recapping needles), immunization of healthcare personnel is highly effective against hepatitis B infection. A vaccine for hepatitis C is not available; moreover, unlike hepatitis B infection, hepatitis C infection does not seem to confer immunity to subsequent exposure. Postexposure prophylaxis with hyperimmune globulin is effective for hepatitis B, but not hepatitis C.

Drug-Induced Hepatitis

Drug-induced hepatitis (Table 33-2) can result from direct, dose-dependent toxicity of a drug or drug metabolite, an idiosyncratic drug reaction, or a combination of these two causes. The clinical course often resembles viral hepatitis, making diagnosis difficult. Alcoholic hepatitis is probably the most common form of drug-induced hepatitis, but the etiology may not be obvious from the history. Chronic alcohol ingestion can also result in hepatomegaly from fatty infiltration of the liver, which reflects impaired fatty acid oxidation, increased uptake and esterification of fatty acids, and diminished lipoprotein synthesis and secretion. Acetaminophen ingestion of 25 g or more usually results in fatal fulminant hepatotoxicity. A few drugs, such as chlorpromazine and oral contraceptives, may cause cholestatic-type reactions (see below). Ingestion of potent hepatotoxins, such as carbon tetrachloride and certain species of mushrooms (Amanita, Galerina), also may result in fatal hepatotoxicity.

Because of the increased risk of perioperative morbidity and mortality, patients with acute hepatitis should have elective surgery postponed until the illness has resolved, as indicated by the normalization of liver tests. In addition, acute alcohol toxicity greatly complicates anesthetic management, and acute alcohol withdrawal during the perioperative period may be associated with a mortality rate as high as 50%. Only emergent surgery should be considered for patients presenting in acute alcohol withdrawal. Patients with hepatitis are at risk of deterioration of hepatic function and the development of complications from hepatic failure, such as encephalopathy, coagulopathy, or hepatorenal syndrome.

Laboratory evaluation of the patient with hepatitis should include blood urea nitrogen, serum electrolytes, creatinine, glucose, transaminases, bilirubin, alkaline phosphatase, and albumin, platelet count, and PT. Serum should also be checked for HBsAg whenever possible. A blood alcohol level is useful if the history or physical examination is compatible with ethanol intoxication. Hypokalemia and metabolic alkalosis are not uncommon and are usually due to vomiting. Concomitant hypomagnesemia may be present in chronic alcoholics and predisposes to cardiac arrhythmias. The elevation in serum transaminases does not necessarily correlate with the amount of hepatic necrosis. The serum alanine aminotransferase (ALT) is generally higher than the serum aspartate aminotransferase (AST), except in alcoholic hepatitis, where the reverse occurs. Bilirubin and alkaline phosphatase are usually only moderately elevated, except with the cholestatic variant of hepatitis. The PT is the best indicator of hepatic synthetic function. Persistent prolongation of longer than 3 sec (INR > 1.5) following administration of vitamin K is indicative of severe hepatic dysfunction. Hypoglycemia is not uncommon. Hypoalbuminemia is usually not present except in protracted cases, with severe malnutrition, or when chronic liver disease is present.

If a patient with acute hepatitis must undergo an emergent operation, the preanesthetic evaluation should focus on determining the cause and the degree of hepatic impairment. Information should be obtained regarding recent drug exposures, including alcohol intake, intravenous drug use, recent transfusions, and prior anesthetics. The presence of nausea or vomiting should be noted, and, if present, dehydration and electrolyte abnormalities should be anticipated and corrected. Changes in mental status may indicate severe hepatic impairment. Inappropriate behavior or obtundation in alcoholic patients may be signs of acute intoxication, whereas tremulousness and irritability usually reflect withdrawal. Hypertension and tachycardia are often also prominent with the latter. Fresh frozen plasma may be necessary to correct a coagulopathy. Premedication is generally not given, in an effort to minimize drug exposure and not confound hepatic encephalopathy in patients with advanced liver disease. However, benzodiazepines and thiamine are indicated in alcoholic patients with, or at risk for, acute withdrawal.

Intraoperative Considerations

The goal of intraoperative management is to preserve existing hepatic function and avoid factors that may be detrimental to the liver. Drug selection and dosage should be individualized. Some patients with viral hepatitis may exhibit increased central nervous system sensitivity to anesthetics, whereas alcoholic patients will often display cross-tolerance to both intravenous and volatile anesthetics. Alcoholic patients also require close cardiovascular monitoring, because the cardiac depressant effects of alcohol are additive to those of anesthetics; moreover, alcoholic cardiomyopathy is present in many alcoholic patients.

Inhalation anesthetics are generally preferable to intravenous agents because most of the latter are dependent on the liver for metabolism or elimination. Standard induction doses of intravenous induction agents can generally be used because their action is terminated by redistribution rather than metabolism or excretion. A prolonged duration of action, however, may be encountered with large or repeated doses of intravenous agents, particularly opioids. Isoflurane and sevoflurane are the volatile agents of choice because they preserve hepatic blood flow and oxygen delivery. Factors known to reduce hepatic blood flow, such as hypotension, excessive sympathetic activation, and high mean airway pressures during controlled ventilation, should be avoided. Regional anesthesia, including major conduction blockade, may be employed in the absence of coagulopathy, provided hypotension is avoided.

Chronic Hepatitis

Chronic hepatitis is defined as persistent hepatic inflammation for longer than 6 months, as evidenced by elevated serum aminotransferases. Patients can usually be classified as having one of three distinct syndromes based on a liver biopsy: chronic persistent hepatitis, chronic lobular hepatitis, or chronic active hepatitis. Patients with chronic active hepatitis have chronic hepatic inflammation with destruction of normal cellular architecture (piecemeal necrosis) on the biopsy. Evidence of cirrhosis is either present initially or eventually develops in 20% to 50% of patients. Although chronic active hepatitis seems to have many causes, it occurs most commonly as a sequela of hepatitis B or hepatitis C. Other causes include drugs (methyldopa, isoniazid, and nitrofurantoin) and autoimmune disorders. Both immunological factors and a genetic predisposition may be responsible in most cases. Patients usually present with a history of fatigue and recurrent jaundice; extrahepatic manifestations, such as arthritis and serositis, are not uncommon. Manifestations of cirrhosis eventually predominate in patients with progressive disease. In evaluating patients for chronic hepatitis, laboratory test results may show only a mild elevation in serum aminotransferase activity and often correlate poorly with disease severity. Patients without chronic hepatitis B or C infection usually have a favorable response to immunosuppressants and are treated with long-term corticosteroid therapy with or without azathioprine.

Anesthetic Management

Patients with chronic persistent or chronic lobular hepatitis should be treated similarly to those with acute hepatitis. In contrast, those with chronic active hepatitis should be assumed to already have cirrhosis and should be treated accordingly (see below). Patients with autoimmune chronic active hepatitis may also present with problems related to other autoimmune manifestations (such as diabetes or thyroiditis) or long-term corticosteroid therapy that they have likely received.

Cirrhosis is a serious and progressive disease that eventually results in hepatic failure, and the most common cause of cirrhosis in the United States is chronic alcohol abuse. Other causes include chronic active hepatitis (postnecrotic cirrhosis), chronic biliary inflammation or obstruction (primary biliary cirrhosis, sclerosing cholangitis), chronic right-sided congestive heart failure (cardiac cirrhosis), autoimmune hepatitis, hemochromatosis, Wilson’s disease, α1-antitrypsin deficiency, nonalcoholic steatohepatitis, and cryptogenic cirrhosis. Regardless of the cause, hepatocyte necrosis is followed by fibrosis and nodular regeneration. Distortion of the liver’s normal cellular and vascular architecture obstructs portal venous flow and leads to portal hypertension, whereas impairment of the liver’s normal synthetic and other diverse metabolic functions results in multisystem disease. Clinically, signs and symptoms often do not correlate with disease severity. Manifestations are typically absent initially, but jaundice and ascites eventually develop in most patients. Other signs include spider angiomas, palmar erythema, gynecomastia, and splenomegaly. Moreover, cirrhosis is generally associated with the development of three major complications: (1) variceal hemorrhage from portal hypertension, (2) intractable fluid retention in the form of ascites and the hepatorenal syndrome, and (3) hepatic encephalopathy or coma. Approximately 10% of patients with cirrhosis also develop at least one episode of spontaneous bacterial peritonitis, and some patients eventually develop hepatocellular carcinoma.

A few diseases can produce hepatic fibrosis without hepatocellular necrosis or nodular regeneration, resulting in portal hypertension and its associated complications with hepatocellular function often preserved. These disorders include schistosomiasis, idiopathic portal fibrosis (Banti’s syndrome), and congenital hepatic fibrosis. Obstruction of the hepatic veins or inferior vena cava (Budd-Chiari syndrome) can also cause portal hypertension. The latter may be the result of venous thrombosis (hypercoagulable state), a tumor thrombus (eg, renal carcinoma), or occlusive disease of the sublobular hepatic veins.

Preoperative Considerations

The detrimental effects of anesthesia and surgery on hepatic blood flow are discussed below. Patients with cirrhosis are at increased risk of deterioration of liver function because of their limited functional reserves. Successful anesthetic management of these patients is dependent on recognizing the multisystem nature of cirrhosis (Table 33-3) and controlling or preventing its complications.

Gastrointestinal Manifestations

Portal hypertension leads to the development of extensive portosystemic venous collateral channels. Four major collateral sites are generally recognized: gastroesophageal, hemorrhoidal, periumbilical, and retroperitoneal. Portal hypertension is often apparent preoperatively, as evidenced by dilated abdominal wall veins (caput medusae). Massive bleeding from gastroesophageal varices is a major cause of morbidity and mortality, and, in addition to the effects of acute blood loss, the absorbed nitrogen load from the breakdown of blood in the intestinal tract can precipitate hepatic encephalopathy.

The treatment of variceal bleeding is primarily supportive, but frequently involves endoscopic procedures for identification of the bleeding site(s) and therapeutic maneuvers, such as injection sclerosis of varices, monopolar and bipolar electrocoagulation, or application of hemoclips or bands. In addition to the risks posed by a patient who is physiologically fragile and acutely hypovolemic and hypotensive, anesthesia for such endoscopic procedures frequently involves the additional challenges of an encephalopathic and uncooperative patient and a stomach full of food and blood. Endoscopic unipolar electrocautery may adversely affect implanted cardiac pacing and defibrillator devices.

Blood loss should be replaced with intravenous fluids and blood products. Nonsurgical treatment includes vasopressin, somatostatin, propranolol, and balloon tamponade with a Sengstaken-Blakemore tube. Vasopressin, somatostatin, and propranolol reduce the rate of blood loss. High doses of vasopressin can result in congestive heart failure or myocardial ischemia; concomitant infusion of intravenous nitroglycerin may reduce the likelihood of these complications and bleeding. Placement of a percutaneous transjugular intrahepatic portosystemic shunt (TIPS) can reduce portal hypertension and subsequent bleeding, but may increase the incidence of encephalopathy. When the bleeding fails to stop or recurs, emergency surgery may be indicated. Surgical risk has been shown to correlate with the degree of hepatic impairment, based on clinical and laboratory findings. Child’s classification for evaluating hepatic reserve is shown in Table 33-4. Shunting procedures are generally performed on low-risk patients, whereas ablative surgery, esophageal transection, and gastric devascularization are reserved for high-risk patients.