Flumazenil is a competitive
benzodiazepine antagonist that rapidly reverses the residual effects of
benzodiazepines following intravenous
conscious sedation. In a double-blind, multicenter study, postoperative patients who had been sedated with intravenous
diazepam were randomly allocated to receive intravenous doses of
flumazenil (0.4 mg to 1 mg) or placebo. Levels of sedation and
psychomotor impairment were evaluated prestudy, at baseline, and at 6 intervals from 5 to 180 minutes posttreatment. A global evaluation of effectiveness was made at the 5-minute assessment, and memory was assessed at the 180-minute assessment.
Flumazenil (mean dose: 0.73 mg [7.3 ml]) was significantly more effective than placebo (mean dose: 8.9 ml) in reversing sedation,
psychomotor impairment, and
amnesia within 5 minutes after the start of administration. At the 5-minute posttreatment assessment, 84% of 102
flumazenil-treated patients (compared with 42% of 52 placebo-treated patients) experienced complete reversal of sedation. Ninety-two percent of 93
flumazenil-treated patients (compared with 41% of 46 placebo-treated patients) had normal psychomotor function. Reversal of
amnesia at the 5-minute assessment was achieved in 75% of 101
flumazenil-treated patients and in 20% of 51 placebo-treated patients. Statistically significant differences between
flumazenil and placebo were also observed at the 15-minute assessment. Thereafter there were no significant differences between the two treatment groups. Most (70%)
flumazenil-treated patients exhibited no recurrence of sedation during the 180-minute assessment period. The most frequent adverse reaction in the
flumazenil group was
dizziness (6%). There were no serious adverse experiences related to the test
drug.
Flumazenil provided prompt, controlled reversal of residual effects, especially sedation, in the majority (84%) of patients recovering from intravenous
conscious sedation induced by
diazepam. For most (70%) of these
flumazenil-treated patients, the reversal was maintained throughout the 180-minute assessment.