Flumazenil vs. placebo in hepatic encephalopathy in patients with cirrhosis: a meta-analysis.
BACKGROUND
Randomized controlled trials testing flumazenil in hepatic encephalopathy have shown conflicting results.


OBJECTIVE
To compare flumazenil and placebo in hepatic encephalopathy in patients with cirrhosis.


METHODS
An overview of randomized controlled trials comparing flumazenil and placebo in hepatic encephalopathy in patients with cirrhosis was performed. For each end-point, heterogeneity and treatment efficacy were assessed by Peto and Der Simonian methods. As most trials were crossover in nature, a sensitivity analysis was performed including the two treatment periods.


RESULTS
Six double-blind randomized controlled trials, including 641 patients (326 treated with flumazenil and 315 with placebo), were identified. The treatment duration ranged from 5 min to 3 days. Heterogeneity tests between control groups were not significant. The mean percentages of patients with clinical improvement (five trials) were 27% in treated groups and 3% in placebo groups. This difference was significant by both methods (Peto: odds ratio=6.15; 95% confidence interval, 4.0-9.5; P < 0.001; Der Simonian: mean rate difference, 29%; 95% confidence interval, 17-41; P < 0.001). The mean percentages of patients with electroencephalographic improvement were 19% in treated groups and 2% in placebo groups. This difference was significant only with the Peto method (odds ratio=5.8; 95% confidence interval, 3.4-9.7; P < 0.001). The sensitivity analysis showed similar results.


CONCLUSIONS
This meta-analysis shows that flumazenil induces clinical and electroencephalographic improvement of hepatic encephalopathy in patients with cirrhosis.
Goulenok
C
C
Service d'Hépato-Gastroentérologie, Hôpital Pitié Salpêtrière, Paris, France.
Bernard
B
B
Cadranel
J F
JF
Thabut
D
D
Di Martino
V
V
Opolon
P
P
Poynard
T
T
D003128:Coma / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology; D004311:Double-Blind Method; D004569:Electroencephalography; D005260:Female; D005442:Flumazenil / Q000627:therapeutic use*; D006501:Hepatic Encephalopathy / Q000150:complications* / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D008103:Liver Cirrhosis / Q000150:complications* / Q000503:physiopathology; D008297:Male; D016017:Odds Ratio; D018579:Patient Selection; D010919:Placebos; D016032:Randomized Controlled Trials as Topic; D012107:Research Design; D011795:Surveys and Questionnaires; D016896:Treatment Outcome
D010919:Placebos; D005442:Flumazenil