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 hepatic encephalopathy in patients with liver cirrhosis. Patients and methods. in the double blind randomized, placebo controlled study, 54 patients with hepatic encephalopathy grade III-IV were randomly assigned 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 was established. Clinical improvement was defined as a 3 point decrease in the 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 patients 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 patients with acute hepatic encephalopathy; encephalopathy associated with bleeding is more likely to respond to flumazenil; responders to the treatment usually improve within the first 6 hours while lack of response usually represents a bad prognostic sign.