Sections View Full Chapter Figures Tables Videos Full Chapter Figures Tables Videos Supplementary Content + Print Section ++ For further information, see CMDT Part 16-11: Cirrhosis + Key Features Print Section ++ ++ Essentials of Diagnosis ++ Stage 1: mild confusion Stage 2: drowsiness Stage 3: stupor Stage 4: coma A revised staging system known as SONIC (Spectrum Of Neurocognitive Impairment in Cirrhosis) encompasses absent, covert, and stages 2 to 4 encephalopathy ++ General Considerations ++ A state of disordered central nervous system function resulting from failure of the liver to detoxify noxious agents of gut origin because of hepatocellular dysfunction and portosystemic shunting Ammonia is the most readily identified toxin but is not solely responsible for the disturbed mental status Precipitants of hepatic encephalopathy Gastrointestinal (GI) bleeding—increases the protein in the bowel and rapidly precipitates hepatic encephalopathy Constipation Alkalosis Potassium deficiency induced by diuretics Opioids, hypnotics, and sedatives Medications containing ammonium or amino compounds Paracentesis with consequent hypovolemia Hepatic or systemic infection Portosystemic shunts (including transjugular intrahepatic portosystemic shunts) In one study, risk factors for hepatic encephalopathy in patients with cirrhosis included a higher serum bilirubin level and use of a nonselective β-blocker, whereas a higher serum albumin level and use of a statin were protective ++ Demographics ++ Alcoholic liver disease and chronic hepatitis C are the most common etiologies of cirrhosis + Clinical Findings Print Section ++ ++ Symptoms and Signs ++ Metabolic encephalopathy characterized by Day–night reversal Asterixis, tremor, dysarthria Delirium Drowsiness, stupor, and ultimately coma In patients with cirrhosis, may be precipitated by an acute hepatocellular insult or an episode of GI bleeding Clinical diagnosis supported by asterixis, elevated serum ammonia with exclusion of other causes of delirium Covert hepatic encephalopathy is characterized by mild cognitive and psychomotor deficits EncephalApp A smartphone app that uses the “Stroop test” (asking the patient to name the color of a written word rather than the word itself, even when the word is the name of a different color) Has proved useful for detecting covert hepatic encephalopathy ++ Differential Diagnosis ++ Metabolic encephalopathy, especially hyponatremia, hypoglycemia, or chronic kidney disease CNS infection Altered mental status from medication effects, particularly if they are hepatically metabolized + Diagnosis Print Section ++ ++ Laboratory Tests ++ Liver biochemical tests often consistent with advanced chronic liver disease Serum (and cerebrospinal fluid) ammonia level is generally elevated Role of neuroimaging tests (eg, cerebral positron emission tomography, magnetic resonance spectroscopy) is evolving + Treatment Print Section ++ ++ Medications ++ Purge blood from the GI tract with 120 mL of magnesium citrate by mouth or nasogastric (NG) tube every 3–4 hours until the stool is free of gross blood, or by administration of lactulose Lactulose Initial dose is 30 mL three or four times daily orally Titrate so that the patient produces two or three soft stools per day Administer rectally if patient cannot take orally: lactulose 200 g/300 mL in a solution of saline or sorbitol as a retention enema for 30–60 min; it may be repeated every 4–6 hours Bowel cleansing with a polyethylene glycol colonoscopy preparation is also effective in patients with acute overt hepatic encephalopathy and may be preferable Neomycin sulfate, 0.5–1 g orally every 6 or 12 hours for 7 days Controls the ammonia-producing intestinal flora Side effects include diarrhea, malabsorption, superinfection, ototoxicity, and nephrotoxicity, usually only after prolonged use Alternative antibiotics Rifaximin, 550 mg orally twice daily Metronidazole, 250 mg orally three times daily Patients who do not respond to lactulose may improve with a 1-week course of an antibiotic in addition to lactulose Probiotic agents may have some benefit Avoid opioids and sedatives metabolized or excreted by the liver If agitation is marked, oxazepam, 10–30 mg (not metabolized by the liver) may be given cautiously orally or by NG tube Correct zinc deficiency, if present, with oral zinc sulfate, 600 mg/day in divided doses Sodium benzoate, 5 g twice daily, ornithine aspartate, 9 g three times daily, and L-acyl-carnitine, 4 g orally daily, may lower blood ammonia levels, but less is known about these drugs than lactulose Flumazenil is effective in about 30% of severe hepatic encephalopathy, but the drug is short-acting and intravenous administration is required ++ Therapeutic Procedures ++ Withhold dietary protein during acute episodes When the patient resumes oral intake, protein intake should be restricted to 60–80 g/day as tolerated, and vegetable protein is better tolerated than meat protein Use of special dietary supplements enriched with branched-chain amino acids is usually unnecessary except in occasional patients who are intolerant of standard protein supplements + Outcome Print Section ++ ++ Complications ++ Hypernatremia can develop from intensive lactulose use ++ When to Admit ++ Inability to care for self or follow medical instructions + References Print Section ++ + +Asrani SK et al. 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