Flumazenil in the treatment of acute hepatic encephalopathy in cirrhotic patients: a double blind randomized placebo controlled study.
OBJECTIVE
The aim of this study was to evaluate the effects of flumazenil on hepatic encephalopathy in patients with liver cirrhosis.


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.
Laccetti
M
M
Department of Internal Medicine, Cardarelli Hospital, Naples, Italy.
Manes
G
G
Uomo
G
G
Lioniello
M
M
Rabitti
P G
PG
Balzano
A
A
D003128:Coma / Q000145:classification; D004311:Double-Blind Method; D005260:Female; D005442:Flumazenil / Q000494:pharmacology*; D018757:GABA Modulators / Q000494:pharmacology*; D006470:Hemorrhage; D006501:Hepatic Encephalopathy / Q000188:drug therapy* / Q000209:etiology; D006801:Humans; D008103:Liver Cirrhosis / Q000150:complications*; D017093:Liver Failure / Q000150:complications* / Q000209:etiology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016896:Treatment Outcome
D018757:GABA Modulators; D005442:Flumazenil