Hepatic encephalopathy/temp

Diet

It has been presumed that excessive protein intake leads to increased generation of ammonia, which, in the setting of severe liver impairment, will accumulate and worsen the hepatic encephalopathy. While very large protein loads (such as gastrointestinal hemorrhage, because blood is rich in protein) are known to precipitate encephalopathy, the need for patients with chronic liver disease to be protein-restricted has been disproven. Indeed, because chronic liver disease is a catabolic state, a protein restricted diet would lead to protein malnutrition and a negative nitrogen balance.

Correction of hypokalemia

Concomitant hypokalemia should be corrected, as hypokalemia increases renal ammonia production and may promote conversion of ammonium into ammonia, which can cross the blood-brain barrier.

Lactulose

Lactulose is a compound that will cause osmotic diarrhea, thus lessening the time available for intestinal bacteria to metabolize protein into ammonia within the bowel. Further, it acidifies the environment in the lumen of the bowel. This promotes the conversion of lumenal ammonia (NH₃) to ammonium (NH₄⁺), which, by virtue of its net charge, should be less readily absorbed into the bloodstream from the bowel lumen. Despite this theoretical and appealing mechanism, a meta-analysis of randomized controlled trials by the international Cochrane Collaboration found benefit, but suggests there is little evidence for its preferred use to treat hepatic encephalopathy. Indeed, any [...] (laxative) that speeds up transit through the bowel, thereby lessening the time available for bacteria to metabolize protein into ammonia, works just as well.

Lactulose can be given rectally for patients who cannot take oral medications. One regimen is 300 mL (200 g) of lactulose syrup (10 g/15 ml) in 1 L of water which is retained for 1 hour, with the patient in the Trendelenburg position.

Antibiotics

Antibiotics may be given to kill bacteria present in the bowel, thereby decreasing bacterial conversion of protein to ammonia (and other toxic substances) there. Although effective, neomycin, a non-absorbable aminoglycoside antibiotic, is essentially contraindicated; it has been found that a proportion of the ingested dose is indeed absorbed due to increased gut permeability, thus increasing the risk of renal failure and hearing loss (i.e., two of the potential side-effects of neomycin). The former side-effect, in particular, is especially worrisome, given the already-increased likelihood of renal failure in cirrhosis and portal hypertension (i.e., hepatorenal syndrome). Metronidazole has also been studied.

Rifaximin

Rifaximin (Xifaxan), received orphan [...] status in 2005 for the treatment of hepatic encephalopathy. In contrast to neomycin, its tolerability profile is comparable to that of placebo. Multiple clinical trials have demonstrated that rifaximin at a dose of 400 mg taken orally 3 times a day was as effective as lactulose or lactitol at improving hepatic encephalopathy symptoms. Similarly, rifaximin was as effective as neomycin and paromomycin. Rifaximin was better tolerated than both the cathartics and the other nonabsorbable antibiotics. A number of concerns remain regarding rifaximin's role in the treatment of hepatic encephalopathy. It remains to be determined whether rifaximin can improve severe encephalopathy symptoms as rapidly as lactulose. There are also concerns regarding the cost-effectiveness of the medication.

Benzodiazepine receptor antagonists

A meta-analysis of randomized controlled trials by the international Cochrane Collaboration found benefit from flumazenil. The doses of flumazenil varied around a median of 2 milligrams over 10 minutes: 'Flumazenil was given as a continuous infusion (12 trials), preceded by bolus injections in two trials. One trial used only bolus injections. Patients received flumazenil at a total dose ranging from 0.2 to 19.5 milligram (median 2 milligram). The median duration of treatment was 10 minutes (range one minute to 72 hours)'. However, the benefit was short.

L-ornithine-L-aspartate

L-ornithine-L-aspartate stimulates the urea cycle, and has shown encouraging results in randomized controlled trials.