Flumazenil in the treatment of acute hepatic encephalopathy in cirrhotic patients: a double blind randomized placebo controlled study

Aims. The aim of this study was to evaluate the effects of flumazenil on he patic encephalopathy in patients with liver cirrhosis. Patients and methods. in the double blind randomized, placebo controlled st udy, 54 patients with hepatic encephalopathy grade III-IV were randomly ass igned to receive either flumazenil 2 mg iv (group A) or placebo (group B); conventional treatment with branched-chain amino acid, saline, glucose, and lactulose was administered in both groups. A 24-hour observation period wa s established. Clinical improvement was defined as a 3 point decrease in th e Glasgow coma score at any time within 24 hours. Results. Clinical improvement was obtained in 22/28 patients in group A and in 14/26 in group B (p<0.05) improvement was observed within the first six hours in 21/22 patients in group A and only in 3/14 in group B. Mortality rate was not different between group A and B; however: all 6 non-responders in group A and only 5 out of 12 in group B died within 24 hours. Among pat ients with post-bleeding encephalopathy, 11 out of 17 in group A and only 2 out of 14 in group B improved (p<0.001). Conclusions. Flumazenil may exert a beneficial effect in a subset of patien ts with acute hepatic encephalopathy; encephalopathy associated with bleedi ng is more likely to respond to flumazenil; responders to the treatment usu ally improve within the first 6 hours while lack of response usually repres ents a bad prognostic sign.