Review Question - QID 107840

This patient presents with lethargy, change in mental status, slurred speech, jaundice, and asterixis after TIPS procedure for cirrhosis, highly suggestive of hepatic encephalopathy. The first line therapy is nonabsorbable disaccharides such as lactulose. If this fails antibiotic therapy with rifaximin can be added (neomycin is no longer routinely used).

Hepatic encephalopathy (HE) is a potentially reversible condition characterized by progressive neuropsychiatric impairment due to the GABAergic effects of toxic metabolites that accumulate due to hepatic failure. Patients may present with mental status changes, flapping tremor, and mood and behavioral disturbances. Treatment is targeted at reducing the generation of nitrogenous metabolites. Treatment is centered around lactulose (nonabsorbable disaccharides that generate H+ and sequester ammonia as ammonium in the gut), and non-absorbable antibiotics such as neomycin and rifaximin. The order of treatment is to first try lactulose and to then add rifaximin if lactulose alone does not work.

When approaching this question it is most important to first make the correct diagnosis. Looking at the patient's presentation it seems he is suffering from delirium. If you correlate this with his history of hepatitis C then it is likely that he is suffering from liver failure and is unable to metabolize ammonia. The diagnosis is finally confirmed with symptoms beginning after a TIPS procedure. A TIPS procedure bypasses the liver to relieve pressure on the portal system. In doing this the liver is unable to metabolize metabolic products such as ammonia and hepatic encephalopathy ensues. Once the diagnosis is made, choosing the correct management is simply based on knowing the order in which to begin interventions. The first intervention is lactulose which decreases the absorption of ammonia via acidification of gut contents. If this fails, the next step is to begin rifaximin with the lactulose to kill off gut flora and decrease the production of ammonia.

Video A shows a patient with asterixis, a pathognomonic finding in patients with hepatic encephalopathy.

Incorrect Answers:
Answer 1: This is a reasonable approach to a patient suspected of having spontaneous bacterial peritonitis. The patient is afebrile, and has a paracentesis demonstrating neutrophils with less than < 100 cells/mcL. Diagnosis is made based on the clinical presentation, vitals, and a cell count of greater than 250 neutrophils in the paracentesis. Cefotaxime is the drug of choice given its coverage (similar to ceftriaxone) but it renal excretion (these patient's have liver failure!).
Answer 2: Though this patient appears to have significant cirrhotic disease, liver transplantation is considered based on patient's MELD scores. This patient's immediate encephalopathy should be addressed. The best initial step in management for encephalopathy would never be something as invasive as a liver transplant.
Answer 3: Rifaximin is the antibiotic of choice for hepatic encephalopathy as it is very selective for gut flora. However this drug is added AFTER the best initial step in management which is lactulose.
Answer 5: Neomycin is an aminoglycoside that was used as the antibiotic of choice when lactulose therapy failed. It has since been replaced with rifaximin. Neomycin has side effects of nephrotoxicity and ototoxicity and is less specific than rifaximin.

It is a common answer choice on Step exams to choose a low protein diet when it comes to management of hepatic encephalopathy. It has been demonstrated though that protein restriction is not beneficial to these encephalopathic patients (1).