• Hepatic encephalopathy (HE) is a serious, progressive, and reversible metabolic encephalopathy characterized by neuropsychiatric abnormalities and neuromuscular dysfunction that range from mild cognitive and motor impairment to coma and death.
• HE results from the abnormal accumulation of toxic substances that are normally cleared (detoxified) by the liver.

• GI bleeding (excess protein load)
• Sepsis
• Dehydration (excessive diuretics, vomiting, diarrhea)
• Hyponatremia, hypokalemia
• Postsurgical states
• Medication noncompliance
• Sedative use (opiates, benzodiazepines, antidepressants)
• TIPS placement
• Constipation
• Excessive dietary protein

• Elevated levels of ammonia in the presence of an inflammatory response cause astrocyte swelling and fluid accumulation in the brain (cerebral edema).
  • Ammonia is normally converted to urea by the liver; however, with liver failure, ammonia concentrations rise.
  • An alternative pathway in muscle (via glutamine synthetase enzyme) serves to metabolize ammonia to glutamine. Saturation of this secondary pathway leads to accumulation of ammonia in plasma that easily passes through the blood-brain-barrier and comes into contact with astrocytes.
  • Astrocytes convert excess ammonia to glutamine intracellularly. This process will lead to cellular swelling, cerebral edema, and ultimately increased intracranial pressure (ICP).
• Historically, the role of ammonia accumulation has dominated explanations of pathogenesis, but it is now recognized that the pathogenesis is multifactorial. Oxidative stress, endogenous benzodiazepine-like ligands, astrocyte swelling, GABA-like molecules, abnormal histamine and serotonin neurotransmission, endogenous opioids, neurosteroids, inflammatory cytokines, and manganese toxicity are other potential mediators of pathogenicity.

• Assess the severity of HE and treat underlying as well as precipitating causes prior to surgery. Emergent cases may require proceeding with concurrent perioperative management.
• Pharmacokinetic alterations can include: Decreased hepatic metabolism; decreased albumin leading to less protein binding (more free drug available); and increased volume of distribution due to ascites and increased total body water compartments.

Difficulty concentrating, increasing pruritus

Liver transplantation

• Lactulose; first-line therapy with a direct effect on the GI system. It is a nonabsorbable disaccharide that is fermented in the colon and reduces the intestinal production and absorption of ammonia.
• Rifaximin; direct effect on the GI system. A nonabsorbable antibiotic that is very expensive and reserved for patients who are either intolerant or refractory to lactulose. Its cost, however, may be justified by the reduced need for hospitalization.
• Flumazenil; direct neurological therapy. A GABA antagonist that can produce short-term reversal of HE symptoms. Has fallen out of favor secondary to its potential to decrease the seizure threshold and its transient efficacy.
• Metronidazole and neomycin; antibiotics that reduce intestinal ammonia production. However, it lacks data that support its efficacy.
  • Long-term neomycin administration is associated with nephrotoxicity and ototoxicity.
  • Long-term metronidazole administration is associated with peripheral neuropathy.

End stage liver disease

• Overt hepatic encephalopathy (OHE) should be optimized medically and the underlying etiology addressed prior to an elective and possibly an urgent procedure. This may not always be possible, as with GI bleeding (etiology) or other emergent cases.
• Coagulopathy
• Poor nutrition status
• Hypovolemia

• Overt hepatic encephalopathy (OHE). Combination of neurological and neuropsychiatric abnormalities that can be detected by bedside clinical tests.
• Minimal hepatic encephalopathy (MHE). Normal mental and neurological function but abnormal results on formal neuropsychometric testing.
• World Congresses of Gastroenterology Classification System
  • Type A: Associated with acute liver failure. Increased incidence of elevated ICP that can lead to brain stem herniation and death. Thirty percent mortality rate if the ICP is elevated (4).
  • Type B: Associated with portosystemic bypass without intrinsic liver disease
  • Type C: Associated with cirrhosis
• West Haven Criteria. Grades the severity of HE and is based on intellect/behavior as well as level of consciousness and neurological findings.
  • Grade 1 – Trivial lack of awareness; euphoria or anxiety; shortened attention span; impaired performance of addition or subtraction.
  • Grade 2 – Lethargy or apathy; minimal disorientation for time or place; subtle personality change; inappropriate behavior.
  • Grade 3 – Somnolence to semistupor, but responsive to verbal stimuli; confusion; gross disorientation.
  • Grade 4 – Coma (unresponsive to verbal or noxious stimuli).
• Childs–Pugh class score measures lab values (total bilirubin, serum albumin, PT/INR) and clinical symptoms (ascites, hepatic encephalopathy) to assess perioperative mortality risk. Class A is 10%, Class B is 30%, Class C is 82%.
• Model for end-stage liver disease (MELD) score. Originally developed to predict short-term mortality in patients undergoing a TIPS procedure, but currently being used as a predictor for 30-day postoperative mortality and organ allocation in the US (5). It provides an objective measure and is based on laboratory values (INR, bilirubin, creatinine). A score of 5 has a 5% risk; a score of 10 has a 7% risk; a score of 15 has a 11% risk; a score of 20 has a 17% risk; and a score of 25 has a 26% risk.

Admit to ICU if surgery is prolonged, cardiac and/or pulmonary surgery were performed, intraoperative hypotension, excessive blood loss, or Grade III/IV HE.

• Continue preoperative lactulose and antibiotics.
• Carefully titrate sedatives and pain medications to prevent exacerbation.
• Consider hepatology or GI consult.

• Worsening jaundice, encephalopathy, and ascites
• Hepatorenal syndrome
• Development of sepsis and secondary disseminated intravascular coagulation.

• End-Stage Liver Disease
• Hoffman Elimination

572.2

K72.90 Hepatic failure, unspecified without coma

Allyson J.A. Morman , MD

Keith E. Littlewood , MD