Flumazenil therapy for hepatic encephalopathy in cirrhotic patients: a double-blind pragmatic randomized, placebo study.

OBJECTIVE

To evaluate the effects of flumazenil on hepatic encephalopathy in patients with cirrhosis.

DESIGN

Double-blind randomized study.

SETTING

Liver intensive care unit over a 2-year period.

PATIENTS

Fourteen patients with cirrhosis (median age 54 years, range 41-73 years), comprising 10 men and four women enrolled during 18 episodes of hepatic encephalopathy.

METHODS

Placebo or flumazenil (1 mg at 0.1 mg/min infusion rate) was infused in coded vials. The patients' hepatic encephalopathy was graded clinically and by electroencephalography (EEG).

RESULTS

In eight episodes of hepatic encephalopathy the placebo was infused first and no improvement occurred (0%). During 12 episodes of hepatic encephalopathy, flumazenil was administered and the EEG recording improved within 7 min (range 4-47 min; 12 out of 18 cases; 66 versus 0% for flumazenil versus placebo, respectively; P < 0.01); a modest clinical improvement in hepatic encephalopathy was observed within 83 min (range 30-340 min). The amount of flumazenil infused averaged 0.7 mg (range 0.4-1 mg).

CONCLUSIONS

The infusion of 0.4-1 mg flumazenil results in a modest but rapid improvement in the EEG grading of hepatic encephalopathy and to a moderate but delayed improvement in the clinical grade of hepatic encephalopathy.