Lactulose and combination therapy of hepatic encephalopathy: the role of the intestinal microflora.

Lactulose is the most frequently utilized agent in the treatment of hepatic encephalopathy because of its efficacy and the fact that it has few serious side effects. How this nonabsorbable disaccharide works has been a matter of controversy, but evidence suggests that metabolism by the enteric flora is necessary for its mechanism of action. When the intestinal flora metabolized lactulose, bacterial incorporation of nitrogen increases as does the bacterial mass. The presence of a carbohydrate and the acidic environment caused by the production of organic acids also act to reduce the breakdown of other nitrogen-containing compounds to ammonia and other potential cerebral toxins. The administration of lactulose to humans causes an increase in fecal nitrogen, but very little increase in ammonia nitrogen. Most of the nitrogen is contained in the fecal bacterial and the soluble fractions of stool. The administration of lactulose causes a reduction in the urea production rate consistent with a reduced entry of ammonia into portal blood, but it does not appear to directly inhibit urea degradation. Other nonabsorbable saccharides, particularly those contained in dietary fiber, appear to have effects similar to those of lactulose. There is some evidence that neomycin can be given with lactulose to cause an additive effect in the treatment of hepatic encephalopathy. This effect is most prominent in patients who have not responded adequately to lactulose alone. At this point, the other antibiotics studied do not appear to have additive effects with lactulose.