A Tough Egg to Crack

A 68-year-old woman presented to the emergency department with altered mental status. On the morning prior to admission, she was fully alert and oriented. Over the course of the day, she became more confused and somnolent, and by the evening, she was unarousable to voice. She had not fallen and had no head trauma.

Altered mental status may arise from metabolic (eg, hyponatremia), infectious (eg, urinary tract infection), structural (eg, subdural hematoma), or toxin-related (eg, adverse medication effect) processes. Any of these categories of encephalopathy can develop gradually over the course of a day.

One year prior, the patient was admitted for a similar episode of altered mental status. Asterixis and elevated transaminases prompted an abdominal ultrasound, which revealed a nodular liver and ascites. Paracentesis revealed a high serum-ascites albumin gradient. The diagnosis of cirrhosis was made based on these findings. Testing for viral hepatitis, autoimmune hepatitis, hemochromatosis, and Wilson’s disease were negative. Although steatosis was not detected on ultrasound, nonalcoholic fatty liver disease (NAFLD) was suspected based on the patient’s risk factors of hypertension and type 2 diabetes mellitus. She had four additional presentations of altered mental status with asterixis; each episode resolved with lactulose.

Other medical history included end-stage renal disease (ESRD) requiring hemodialysis. Her medications were labetalol, amlodipine, insulin, propranolol, lactulose, and rifaximin. She was originally from China and moved to the United States 10 years earlier. Given concerns about her ability to consistently take medications, she had moved to a long-term facility. She did not use alcohol, tobacco, or illicit substances.

The normalization of the patient’s mental status after lactulose treatment, especially in the context of recurrent episodes, is characteristic of hepatic encephalopathy, in which ammonia and other substances bypass hepatic metabolism and impair cerebral function. Hepatic encephalopathy is the most common cause of lactulose-responsive encephalopathy, and may recur in the setting of infection or nonadherence with lactulose and rifaximin. Other causes of lactulose-responsive encephalopathy include hyperammonemia caused by urease-producing bacterial infection (eg, Proteus), valproic acid toxicity, and urea cycle abnormalities.

Other causes of confusion with a self-limited course should be considered for the current episode. A postictal state is possible, but convulsions were not reported. The patient is at risk of hypoglycemia from insulin use and impaired gluconeogenesis due to cirrhosis and ESRD, but low blood sugar would have likely been detected at the time of hospitalization. Finally, she might have experienced episodic encephalopathy from ingestion of unreported medications or toxins, whose effects may have resolved with abstinence during hospitalization.