Reversal of flunitrazepam with flumazenil: duration of antagonist activity

The duration of action, dose requirements and efficacy of flumazenil, a specific benzodiazepine antagonist, were evaluated in 50 patients scheduled for orthopaedic surgery under local anaesthesia and flunitrazepam sedation. Fifteen minutes after injection of flunitrazepam 0.03 mg kg-1 the patients received placebo or flumazenil i.v. in a randomized, double-blind and titrated fashion. At selected time intervals, sedation, anterograde amnesia, muscular hypotonia, orientation in time and space, comprehension and collaboration were evaluated. Compared with placebo, flumazenil promptly reversed sedation for 30 min, hypotonia for 45 min and anterograde amnesia for 60 min, and improved orientation and collaboration for 60 min. However, after 90 min significant recurrent sedation was observed, while anterograde amnesia reappeared after 60 and up to 120 min. No side-effects were noted at any time. The dose of flumazenil required for reversal of flunitrazepam sedation was 0.35 +/- 0.15 mg (mean +/- SD).