Hepatic Encephalopathy

GENERAL PRINCIPLES

• Hepatic encephalopathy is the syndrome of disordered consciousness and altered neuromuscular activity that is seen in patients with acute or chronic hepatocellular failure or portosystemic shunting.

• Hepatic encephalopathy is classified according to the underlying disease into the following:

î Type A: Resulting from ALF

î Type B: Resulting from portosystemic bypass or shunting

î Type C: Resulting from cirrhosis³⁶

• The grades of hepatic encephalopathy are dynamic and can rapidly change.

î Grade I: Sleep reversal pattern, mild confusion, irritability, tremor, asterixis

î Grade II: Lethargy, disorientation, inappropriate behavior, asterixis

î Grade III: Somnolence, severe confusion, aggressive behavior, asterixis

î Grade IV: Coma

• Precipitating factors include medication noncompliance to lactulose, azotemia, FHF, opioids or sedative-hypnotic medications, acute GI bleeding, hypokalemia and alkalosis (diuretics and diarrhea), constipation, infection, high-protein diet, progressive hepatocellular dysfunction, and portosystemic shunts (surgical or TIPS).

DIAGNOSIS

• Asterixis (flapping tremor) is present in stage I through III encephalopathy. This motor disturbance is not specific to hepatic encephalopathy.

• The electroencephalogram shows slow, high-amplitude, and triphasic waves.

• Determination of blood ammonia level is not a sensitive or specific test for hepatic encephalopathy.

TREATMENT

Medications include nonabsorbable disaccharides (lactulose, lactitol, and lactose in lactase-deficient patients) and antibiotics (neomycin, metronidazole, and rifaximin).

• Lactulose, 15-45 mL PO (or via nasogastric tube) bid-qid, is the first choice for treatment of hepatic encephalopathy. Lactulose dosing should be adjusted to produce three to five soft stools per day. Oral lactulose should not be given to patients with ileus or possible bowel obstruction. In the acute phase, a starting dose of 30 mL every 1-2 hours is recommended. This can then be transitioned to every 4 hours, 6 hours, and then 8 hours once the patient starts having bowel movements.

• Lactulose enemas (prepared by the addition of 300 mL lactulose to 700 mL distilled water) may also be administered in patients who cannot tolerate oral intake.

• Rifaximin is an oral nonsystemic broad-spectrum antibiotic that is used at a dose of 550 mg PO bid with no serious adverse events. In a placebo-controlled trial, rifaximin reduced the risk of hepatic encephalopathy and the time to first hospitalization over a 6-month period.