PERIOPERATIVE MANAGEMENT OF PATIENTS WITH ASYMPTOMATIC OR CHRONIC LIVER DYSFUNCTION

The goal of perioperative management of patients with asymptomatic elevations in aminotransaminase, alkaline phosphatase, or bilirubin levels or those with preexisting chronic liver disease is prevention of acute liver failure or further hepatic deterioration. Acute liver failure, defined by encephalopathy in the setting of acute liver injury (e.g., viral hepatitis, toxin ingestion, idiosyncratic drug reaction, sepsis, or shock), is further categorized into hyperacute, acute, or subacute forms based on the time interval between the onset of jaundice and encephalopathy (0 to 7 days, 8 to 28 days, >28 days, respectively).^[192] Patients with the hyperacute form of acute liver failure tend to have a more favorable survival rate (35%), whereas those with the acute and subacute form have poorer prognoses, with mortality rates of 93% and 86%, respectively.^[192] It is therefore imperative to identify perioperative risks and direct therapy to minimize hepatotoxicity and maximize hepatic oxygen delivery. For example, drugs such as acetaminophen or combined drugs such as acetaminophen/hydrocodone probably should not be administered to patients with asymptomatic elevation of liver enzyme test results or chronic liver dysfunction. In patients with cholelithiasis and biliary tract obstruction, it may be prudent to limit the use of opiates preoperatively because they have been reported to cause spasm of the choledochoduodenal sphincter (sphincter of Oddi) and a subsequent increase in intrabiliary tract pressure.^{[193] [194]} These effects appear to be more pronounced for fentanyl, morphine, and meperidine and less severe for opiate agonistantagonists. ^{[193] [194]} Intraoperatively, opiates may be used with the recognition that the possible development of sphincter of Oddi spasm can be treated directly with naloxone or by relaxing smooth muscle tone with either glucagon or nitroglycerin^{[194] [195]} (which induces release of nitric oxide).^{[196] [197]}

Remifentanil appears to have a similar effect as other opiates on the sphincter of Oddi. Fragen and colleagues^[198] studied remifentanil given to six healthy adult

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Patients with more advanced liver disease (e.g., Child-Pugh class B or C cirrhosis) require an anesthetic plan designed to maximize hepatic oxygen delivery and prevent and treat the complications of encephalopathy, cerebral edema, coagulopathy, hemorrhage, and portal hypertension. Hepatic encephalopathy commonly occurs in patients with chronic liver disease because of the accumulation of circulating neurotoxins such as unmetabolized ammonia, gut-derived false neurotransmitters, γ-aminobutyric acid (GABA), and endogenous GABA receptor agonists; altered neurotransmission by the excitatory neurotransmitter glutamate; or altered cerebral energy homeostasis. ^[199] Clinically, hepatic encephalopathy is manifested by neuropsychiatric abnormalities ranging from subtle personality changes and cognitive dysfunction to more advanced depression of consciousness, delirium, and coma. Clinical signs include abnormalities in psychometric testing and apraxia, as well as the more severe findings of asterixis, hyperreflexia, and decerebration. When hepatic encephalopathy occurs with acute liver failure, it often has a rapid onset and is invariably complicated by cerebral edema. Cerebral edema develops as a result of the osmotic effect of accumulated glutamine producing astrocyte cell swelling or as a result of cerebral vasodilation caused by loss of autoregulation, or because of both mechanisms.^[200] These patients invariably require urgent liver transplantation.

A multitude of factors may precipitate hepatic encephalopathy in patients with chronic liver disease. Potassium levels should be monitored and hypokalemia treated to decrease the effect of decreased potassium levels on renal production of ammonia. Arterial pH should be maintained near normal because systemic alkalemia is also noted to increase the diffusion of ammonia across the blood-brain barrier, which can potentially worsen the degree of encephalopathy.^[199] Effective circulating blood volume should be maintained and anemia corrected to maintain hepatic oxygenation and promote the metabolism of circulating toxins. Benzodiazepines should be used judiciously because they may activate the central GABA-benzodiazepine receptor ligand and worsen hepatic encephalopathy. In this regard it should be noted that all psychoactive drugs will have potential deleterious effects on hepatic encephalopathy by further suppressing a vulnerable central nervous system. Hepatic encephalopathy is also a recognized complication of the TIPS procedure.^[201]

When patients remain obtunded or comatose after anesthesia and surgery, therapy is often directed toward decreasing ammonia production. Lactulose is administered either by nasogastric tube or by enema to create an osmotic, cathartic effect and to lower intestinal pH, thereby decreasing the survival of ammonia-producing bacteria.^[151] Flumazenil, a specific antagonist of central benzodiazepine receptors, can improve the level of consciousness in selected cirrhotic patients with severe hepatic encephalopathy.^[202]

Perioperative hemorrhage in patients with significant liver dysfunction may occur because of bleeding diatheses or the complications of portal hypertension (or both). Synthetic hepatic function, as measured by the INR, is useful to assess the severity of the coagulopathy and to gauge therapy, including the subcutaneous administration of vitamin K, transfusion of fresh frozen plasma, use of recombinant factor VII or other factors, and plasmapheresis.^[192] In patients with acute liver failure, plasmapheresis may have potential benefit because it promotes rapid correction of coagulopathy while minimizing volume overload, but at this time no large prospective controlled studies have validated this practice. ^[203]

Hemorrhage may also occur as a result of gastrointestinal bleeding from rupture of esophageal or gastric varices as a complication of portal hypertension. Intraoperatively, it is advisable to avoid the placement of a transesophageal echocardiography probe to avoid initiation of bleeding in patients with esophageal varices. Pharmacologic therapy for acute esophageal variceal bleeding includes use of the combination of vasopressin and nitroglycerin, somatostatin, or octreotide, a synthetic analog of somatostatin.^{[204] [205]}

Portal hypertension may also lead to the development of ascites. Ascites occurs with advanced liver disease secondary to renal retention of sodium and water and localization of this excess fluid in the peritoneal cavity because of portal hypertension. In addition to the general measures of sodium and water restriction and diuretic therapy, therapeutic paracentesis may be indicated if a patient presents for surgery with tense ascites.^[206] Relief of

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The hepatopulmonary syndrome, which is defined by the triad of end-stage liver disease, increased alveolar-arterial gradient, and intrapulmonary vascular dilation, is characterized by the clinical features of digital clubbing, cyanosis, dyspnea, platypnea, and orthodeoxia, in addition to the other clinical characteristics of portal hypertension. Orthodeoxia, defined as arterial oxygen desaturation that is more pronounced in the upright position and relieved by recumbency, is a common phenomenon of hepatopulmonary syndrome.^[208] The pathogenesis of hepatopulmonary syndrome is considered to be primarily related to intrapulmonary vascular dilation diagnosed by contrast-enhanced echocardiography, perfusion lung scanning, or pulmonary arteriography. Current pharmacologic therapy for this disorder is limited; however, orthotopic liver transplantation may lead to a reversal of these pulmonary changes.

Figure 55-7 Transjugular intrahepatic portal-systemic shunt (TIPS) procedure. A stent (or stents) is passed through the internal jugular vein over a wire into the hepatic vein (A); dilated esophageal varices (EV) are apparent. The wire and stent or stents are then advanced into the portal vein (B), after which blood can pass through the portal vein into the hepatic vein and bypass and decompress dilated esophageal veins (C). (Reproduced with permission from www.med.umich.edu/1libr/topics/liver09.htm.)