Encephalopathy lactulose

Treatment is largely empirical, based on observations that intestinal bacteria and protein loads in the intestinal tract are important in the symptoms of hepatic encephalopathy. Lactulose has long been recognized to reduce the symptoms in chronic hepatic encephalopathy. Antibiotic treatment with a nonabsorbable antibiotic such as neomycin reduces the number of bacteria and is especially helpful in patients with GI bleeding. Protein reduction in the diet also improves encephalopathy reducing dietary protein to the less than 40g/day often needed to improve symptoms may compromise nutrition. Patients with acute encephalopathy require... 

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. 

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... 

Antibiotics with activity against urease-producing bacteria, such as neomycin [42], paromomycin [44] or metronidazole [45], also reduce the production of intestinal ammonia and have proved to be of value. Vancomycin has also been used in patients with lactulose-resistant chronic encephalopathy [46]. The efficacy of neomycin is similar to that of lactulose [42]. However, a small percentage of this drug is absorbed from the gastrointestinal tract and may cause ototoxic and nephrotoxic effects, especially with continuous use over several months [47]. This drug should be used with particular caution by patients with renal insufficiency. The efficacy of metronidazole for... 

Bircher J, Muller J, Guggenheim P, Haemmerli UP Treatment of chronic portal-systemic encephalopathy with lactulose. Lancet 1966 1 890-892. 

Conn HO, Leevy CM, Vlahcevic ZR, Rodgers JB, Maddrey WC, Seeff L, Levy LL Comparison of lactulose and neomycin in the treatment of chronic portal-systemic encephalopathy. A double blind controlled trial. Gastroenterology 1977 72 573-583. 

Lanthier PL, Morgan MY Lactitol in the treatment of chronic hepatic encephalopathy An open comparison with lactulose. Gut 1985 26 415-420. 

Tarao K, Ikeda T, Hayashi K, Sakurai I A Successful use of vancomycin hydrochloride in the treatment of lactulose-resistant chronic hepatic encephalopathy. J Gastroenterol Hepatol 1989 4 284-286. 

Massa MD, Vallerino MD, Dodero MD Treatment of hepatic encephalopathy with rifaximin Double blind, double dummy study versus lactulose. Eur J Clin Res 1993 4 7-18. 

Bucci L, Palmieri GC Double-blind, doubledummy comparison between treatment with rifaximin and lactulose in patients with medium to severe degree hepatic encephalopathy. Curr Med Res Opin 1993 13 109—118. 

After the submission of the manuscript three interesting papers [1-3] dealing with the management of hepatic encephalopathy have been published. A Cochrane systematic review [1] evaluating 30 randomized controlled trials did conclude that antibiotics appear to be superior to nonabsorbable disaccharides in improving symptoms of portal systemic encephalopathy. The authors also emphasized that there is insufficient high-quality evidence to support the use of lactulose or lactitol. A combination of a disaccharide and an antibiotic has been suggested, but not consistently demonstrated to be beneficial [2]. Finally, the use of probiotics has been proposed [3], whose administration could actually follow that of antibiotics. 

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. 

L The answer is a. (Hardman, p 922) Lactulose is a synthetic disaccharide (galactose-fructose) that is not absorbed. In moderate doses, it acts as a laxative. In higher doses, it is capable of binding ammonia and other toxins that form in the intestine in severe liver deficiency and that are believed to cause the encephalopathy. Loperamide is an antidiarrheal opioid lorazepam is a CNS depressant loxapine is a heterocyclic antipsychotic. 

Hepatic encephalopathy 30-45 mL PO tid-qid, or 250 mL PR qid [300 mL of lactulose combined with 700 mL of water] instill via rectal tube, then clamp tube for 45 min. 

Lactulose (certain brands) Prevention and treatment of portal-systemic encephalopathy, including the stages of hepatic precoma and coma. 

Osmotic laxatives (e.g., lactulose, sorbitol) are poorly absorbed or nonabsorbable compounds that draw additional fluid into the GI tract. Lumen osmolality increases, and fluid movement occurs secondary to osmotic pressure. Lactulose is a synthetic disaccharide that is poorly absorbed from the GI tract, since no mammalian enzyme is capable of hydrolyzing it to its monosaccharide components. It therefore reaches the colon unchanged and is metabolized by colonic bacteria to lactic acid and to small quantities of formic and acetic acids. Since lactulose does contain galactose, it is contraindicated in patients who require a galactose-free diet. Metabolism of lactulose by intestinal bacteria may result in increased formation of intraluminal gas and abdominal distention. Lactulose is also used in the treatment of hepatic encephalopathy. 

This is a semisynthetic disaccharide which is not absorbed from the GI tract. It produces an osmotic diarrhoea of low pH, and discourages the proliferation of ammonia-producing bacteria. It is therefore useful in the treatment of hepatic encephalopathy. Osmotic laxatives like lactulose, sorbitol, and lactilol rarely cause significant adverse effects. Glycerol suppositories are useful in softening and lubricating passage of inspissated faeces. 

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... 

Suppression of bowel flora is thought by some to be useful in hepatic encephalopathy. Here, absorption of products of bacterial breakdown of protein (ammonium, amines) in the intestine lead to cerebral symptoms and even to coma. In acute coma, neomycin 6 g/d should be given by gastric tube as prophylaxis, 1-4 g/d may be given to patients with protein intolerance who fail to respond to dietary protein restriction (see also lactulose, p. 640). 

Horsmans, Y., Solbreux, P.M., Daenens, C., Desager, J.R, Geubel, A.R Lactulose improves psychometric testing in cirrhotic patients with sub-clinical encephalopathy. Aliment. Pharmacol Ther. 1997 11 165 — 170... 

Loguercio, C., Abbiati, R., Rinaldi, M., Romano, A., Dei VeccMo Bianco, C., Coitori, M. Long-term effects of Enterococcus faecium SF 68 versus lactulose in the treatment of patients with cirrhosis and grade 1-2 hepatic encephalopathy. X Hepatol. 1995 23 39-46... 

McClain, C.J., Potter, T.J., Kromhout, J.R, Zieve, L. The effect of lactulose on psychomotor performance tests in alcoholic cirrhotics without overt hepatic encephalopathy. J. Clin. Gastroenterol. 1984 6 325-329... 

Riggio, O., Balducci, G., Ariosto, F., Merli, M., Tremlterra, S., Ziparo, V., Capocaccia, L. Lactitol in the treatment of chronic hepatic encephalopathy — a randomized cross-over comparison with lactulose. Hepato-Gastroenterol 1990 37 524-527... 

Uribe-Esquivel, M., Moran, S., Poo, J.L., Munoz, R.M. Invitro and invivo lactose and lactulose effects on colonic fermentation and portal-systemic encephalopathy parameters. Scand. J. Gastroenterol. 1997 32 (Suppl. 222) 49- 52... 

Watanabe, A., Sakai, T., Sato, S., Imai, F., Ohio, M., Arakawa, Y., Tod G., KobayasU, K., Muto, Y., Tsujii, T., Kawasaki, H., Okita, K., Tanikawa, K., Fujiyama, S., Shimada, S. Clinical efficacy of lactulose in cirrhotic patients with and without subclinical hepatic encephalopathy. Hepatology 1997 26 1410-1414... 

Long-term application of lactulose, possibly in shortterm combination with neomycin or paromomycin, is recommended. This is especially true when there are signs of an onset of hepatic encephalopathy. 

Self-monltorlng on the part of the patient makes it possible to identify the beginning of water accumulation in the organism (> 1 litre), a reduced lactulose effect (which is inadequate for intestinal detoxification) and/or a latent phase of hepatic encephalopathy. In such cases, immediate outpatient treatment is generally reliable and swift in its therapeutic success. 

The effects of lactulose and lactitol in daily doses of 18-36 g for 6 months have been evaluated in a prospective, open study in 31 cirrhotic patients with chronic encephalopathy (38). Mean daily stool frequency (2.5 versus 1.7) and the frequency of reported adverse effects (59 versus 14%) were significantly higher with lactulose. Common adverse effects were nausea, intestinal discomfort, flatulence, and diarrhea. 

There has been a systematic review of 30 randomized comparisons in hepatic encephalopathy of lactulose or lactitol with no intervention, placebo, or antibiotics and comparisons of lactulose with lactitol (39). Compared with placebo or no intervention, non-absorbable disaccharides had no statistically significant effect on mortahty, but appeared to reduce the risk of no improvement of hepatic encephalopathy. However, this result might have reflected bias, owing to the poor quality of the majority of the studies. 

---