A placebo-controlled trial of flumazenil given by continuous infusion in severe benzodiazepine overdosage.

Abstract

A controlled trial was performed to study the effect and any adverse reactions of continuously infused flumazenil in severe benzodiazepine overdosage. The study comprised 51 adults admitted to an intensive care unit with poisoning. Enrollment criteria were unconsciousness on admission and a clear response within 5 min after an i.v. bolus injection of 1 mg flumazenil. The level of consciousness was assessed according to a modified Glasgow coma scale immediately before and at defined intervals up to 12 h after injection. A double-blind infusion was started 15 min after the bolus injection and administered for 5 h. The patients were randomly allocated to one of three groups: a group given flumazenil 0.5 mg/h, a group given flumazenil 0.1 mg/h and a placebo group. The groups were comparable in age, sex and toxicological laboratory results. There were no significant differences between the groups in the average coma score on admission or 15 min after the bolus injection. In the flumazenil 0.5 mg/h group the level of consciousness remained unchanged between the 15-min recording and the subsequent assessments. In the two other groups the level of consciousness decreased significantly during the course of the infusion. The infusions were well tolerated. It is concluded that a continuous infusion of 0.5 mg of flumazenil per hour can prevent relapse into coma in patients with severe benzodiazepine poisoning aroused with a single injection of the antagonist.