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.

AIM:

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.