Hepatic encephalopathy therapy

Corticosteroid therapy for patients with alcoholic hepatitis (steatonecrosis) with or without hepatic encephalopathy... 

Lactulose is the foundation of pharmacologic therapy to prevent and treat hepatic encephalopathy because its unique mechanism binds ammonia in the gut and facilitates its excretion. 

Drug therapy for portal hypertension and cirrhosis can alleviate symptoms and prevent complications but it cannot reverse cirrhosis. Drug therapy is available to treat the complications of ascites, varices, spontaneous bacterial peritonitis, hepatic encephalopathy, and coagulation abnormalities. 

Lactulose is the foundation of pharmacologic therapy to prevent and treat hepatic encephalopathy. It is a non-digestible synthetic disaccharide laxative that is hydrolyzed in the gut to an osmotically-active compound that draws water into the colon and stimulates defecation. Lactulose also lowers colonic pH, which favors the conversion of ammonia (NH3) to ammonium (NHf).48 Ammonium is ionic and cannot cross back into systemic circulation it is eliminated in the feces. Lactulose is usually initiated at 15 to 30 mL two to three times per day and titrated to a therapeutic goal of two to four soft bowel movements daily.20 49 50... 

Antimicrobial resistance to rifamycins develops rapidly both in vitro and in vivo [65,85,86], As a consequence, all the three members of the family (i.e. rifampicin, rifabutin and rifapentine) are used clinically as components of combination therapies [65,87], Being structurally related, rifaximin could share this potential. And indeed resistance rates, recorded in fecal strains of Enterobacteriaceae, Enterococcus, Bacteroides, Clostridium and anaerobic cocci, ranged between 30 and 90% after short-term (5 days) antibiotic (800 mg daily) treatment [82], A similar pattern was observed in 10 patients with hepatic encephalopathy after treatment with rifaximin 1,200 mg/day for 5 days [80]. 

Berk DP, Chalmers T Deafness complicating antibiotic therapy of hepatic encephalopathy. Ann Intern Med 1970,73 393-396. 

Conn HO, Bircher J Hepatic Encephalopathy Syndromes and Therapies. Bloomington, Medi-Ed Press, 1994. 

Dasarathy S Role of gut bacteria in the therapy of hepatic encephalopathy with lactulose and antibiotics. Indian J Gastroenterol 2003 22(suppl 2) S50-S53. 

Hepatic cirrhosis and ascites In these patients, sudden alterations of electrolyte balance may precipitate hepatic encephalopathy and coma. Do not institute therapy until the basic condition is improved. 

It is important to note that, even more than in heart failure, overly aggressive use of diuretics in this setting can be disastrous. Vigorous diuretic therapy can cause marked depletion of intravascular volume, hypokalemia, and metabolic alkalosis. Hepatorenal syndrome and hepatic encephalopathy are the unfortunate consequences of excessive diuretic use in the cirrhotic patient. 

Lactulose (Constulose, Generlac, Enulose, Others) [Laxative/ Osmotic] Uses Hepatic encephalopathy constipation Action Acidifies the colon, allows ammonia to diffuse into colon Dose Acute hepatic encephalopathy. 30-45 mLPO qlh until soft stools, then tid-qid Chronic laxative therapy 30-45 mL... 

Treatment goals for hepatic encephalopathy include provision of supportive care, identification and removal of precipitating factors, reduction in the nitrogenous load from the gut and optimisation of long-term therapy. 

L-dopa, a precursor of the neurotransmitters norepinephrine and dopamine, was introduced into HE therapy by J.D. Parkes et al. in 1970. The results were good. As yet, there is still no accepted opinion on the use of this substance. Piracetam, as a nootropic substance, led to a clear improvement in typical electrical brain activities in animals displaying hepatic damage and symptoms of encephalopathy. Similarly, a double-blind randomized cross-over study with the nootropic agent centropheno-xine partly showed positive effects in psychometric testing. Bromocriptine, an agonist of the dopamine receptor, was also used in 1980 for chronic hepatic encephalopathy. (146,163) Application of L-carnitine (6 g/day orally, divided into two doses, for 4 weeks) leads to a marked reduction of hyperammonaemia and a clear improvement in clinical symptoms of HE in cirrhotic patients. (119) (s. p.49)... 

Cadranel, J.F., El Younsi, M., Pidoux, B., Zylberberg, P., Benhamou, Y., Valla, D., Opolon, P. Flumazenil therapy for hepatic encephalopathy in cirrhotic patients a double-blind pragmatic randomized, placebo study. Eur. X. Gastroenterol. Hepatol. 1995 7 325-329... 

Freund, H., Yoshimura, N., Fischer, J.E. Chronic hepatic encephalopathy. Long-term therapy with a branched-chain amino-acid-enriched elemental diet. X. Amer. Med. Ass. 1979 242 347-349... 

Stauch, S., Kircheis, G., Adler, G., Becker, K., Ditschuneit, H., Gortelmeyer, R., Hendricks, R., Heuser, A., Karoff, C., Malfertheiner, R, Mayer, D., Rosch, W, Steffens, J. Oral L-ornithine-L-aspartate therapy of chronic hepatic encephalopathy results of a placebo-controlled double-blind study. X. Hepatol 1998 28 856-864... 

As far as the costs are concerned, a one-year course of prophylactic treatment including the necessary follow-up checks and possible early treatment of commencing water retention is less expensive than 3 or 4 days hospitalization. This solely economic viewpoint is hkewise true for prophylactic measures used in hepatic encephalopathy as well as for its early diagnosis and successful therapy at the practitioner s surgery. 

Etacrynic acid, especially in combination with spironolactone and xipamide, markedly enhances natriuresis and diuresis. The dosage is increased as required (e.g. 1 X 25 mg or 50 mg to 2 x 50 mg per day). With a low-dose application in the form of a combined diuretic therapy, there is usually no risk of hepatic encephalopathy developing. The effect of etacrynic acid sets in at the ascending branch of the loop of Henle (active chloride transport). Renovascular resistance is lowered due to enzymatic activity, presumably as a result of a rise in the release of prostaglandin. 

A 55-year-old man with maxillary sinus cancer declined conventional therapy and opted to treat his condition with hydrazine sulfate obtained via the Internet. He had followed the recommended regimen for 4 months when he developed fulminant hepatorenal failure, hepatic encephalopathy, and profound coagulopathy. He died of severe gastrointestinal hemorrhage. 

Valproate-induced fatal liver failure developed in a 29-year-old woman with Friedreich s disease (78). The first symptoms (apathy during febrile upper airways infection) occurred after 2 months of therapy at a dosage of 20 mg/kg. The drug was withdrawn 10 days later, when she had hepatic encephalopathy and a severe bleeding diathesis supportive treatment was provided but she died after 4 weeks. 

Neomycin is not usually administered parenter-ally to animals because of nephrotoxicity and ototoxicity. Only 3% of a dose of neomycin is absorbed following p.o. administration it is, therefore, used in the therapy of coliform enteritis in small and large animals. It is available as tablets, boluses and water additives, in many different combinations with antibiotics, corticosteroids and anticholinergic agents. It can also be used to decrease nitrogenous waste production by the normal gastrointestinal flora in animals with hepatic encephalopathy. Neomycin is not absorbed through the skin, so it is frequently utilized as the antibacterial constituent in ophthalmic formulations (especially in combination with bacitracin and polymyxin B) and in preparations for the treatment of otitis externa in small animals. 

Seizures occur more infrequently in horses than in dogs and cats. Seizures are seen in adult horses from brain trauma, bacterial meningitis, viral encephalitis and, rarely, hepatic encephalopathy or vascular accidents. Convulsions are seen in young neonatal foals with NMS as a result of brain hypoxia and in Arabian foals aged 3-9 months (idiopathic Arabian epilepsy). Anticonvulsant therapy is used to prevent the spread of the seizure focus, increase (raise) the seizure threshold and decrease the electrical excitement of abnormal... 

The mainstay of therapy of hepatic encephalopathy involves therapy to lower blood ammonia concentrations, and includes diet therapy, lactulose, and antibiotics alone or in combination with lactulose. 

Hepatic encephalopathy is a common complication of cirrhosis and requires clinical vigilance and treatment with dietary restriction, elimination of central nervous system depressants, and therapy to lower ammonia levels. 

Nitrogen requirements for the patient with liver failure are not unlike those of normal subjects, but intolerance to protein is common, and protein restriction has been used successfully as part of the therapy. A dilemma arises when the diet becomes so restrictive that malnutrition results, and the patient becomes susceptible to infection and other comphcations. Overzealous use of protein to correct nutritional deficits invariably results in hepatic encephalopathy. 

There has been considerable interest in the use of vegetable-protein diets in the chronic management of patients with cirrhosis and hepatic encephalopathy. Enthusiasm for this therapy is based on the reduced amounts of AAAs and methionine in vegetable protein. The... 

Kanamycin can be administered orally as adjunctive therapy in cases of hepatic encephalopathy. The dose is 4 to 6 g/day for 36 to 72 hours quantities as large as 12 g/day (in divided doses) have been given. It is ototoxic and nephrotoxic. Like neomycin, its oral administration can cause malabsorption and superinfection. 

Lactulose also is used to treat hepatic encephalopathy. Patients with severe liver disease have an impaired capacity to detoxify ammonia coming from the colon, where it is produced by bacterial metabolism of fecal urea. The drop in luminal pH that accompanies hydrolysis to short-chain fatty acids in the colon results in trapping of the ammonia by its conversion to the polar ammonium ion. Combined with the increases in colonic transit, this therapy lowers circulating ammonia levels. The therapeutic goal in this condition is to give sufficient amounts of lactulose (usually 20 to 30 g, 3 to 4 times per day) to produce two to three soft stools a day with a pH of 5 to 5.5. 

The oral administration of neomycin (usually in combination with erythromycin base) has been employed primarily for preparation of the bowel for surgery. For therapy of hepatic encephalopathy, a daily dose of 4 to 12 g (in divided doses) by mouth is given, provided that renal function is normal. Because renal insufficiency is a complication of hepatic failure and neomycin is nephrotoxic, it is used rarely for this indication. Lactulose is a much less toxic agent and is preferred. 

---