Reversal of the central effects of midazolam by intravenous flumazenil after general anesthesia and use of a long-acting opioid in hospitalized patients: report of a multicenter double-blind clinical study. The Flumazenil in General Anesthesia in Hospitalized Patients Study Group II

Abstract

A double-blind clinical trial was conducted to evaluate the efficacy and safety of flumazenil, a benzodiazepine antagonist, in 146 hospitalized patients, who had had general anesthesia induced by midazolam and a long-acting opioid. Ninety-eight patients received flumazenil and 48 received placebo. Administered postoperatively at a mean intravenous dose of 0.84 mg (range: 0.2 mg to 1 mg), flumazenil reversed benzodiazepine-induced sedation to a greater extent than did placebo. At 5 minutes posttreatment, 61 (76%) of 80 flumazenil-treated patients and 7 (18%) of 40 placebo-treated patients had attained a score of 4 or 5 on the Observer's Assessment of Alertness/Sedation Scale, indicating that they were drowsy or fully awake and alert. This level of arousal was maintained for the full 180-minute posttreatment assessment period in 79% of flumazenil-treated patients. Between-group differences in mean change from baseline in level of alertness were statistically significant (P < 0.01) until 60 minutes posttreatment, when the spontaneous recovery of placebo-treated patients resulted in declining intergroup differences. The global efficacy rating (based on the physician's general impression of the effectiveness of the reversal of sedation 5 minutes after test drug administration) was good or excellent in 64 (80%) of the 80 flumazenil-treated patients and 5 (13%) of the 40 placebo-treated patients evaluated. Flumazenil, compared with placebo, was not associated with an increased frequency of operative-site pain, and no serious adverse effects of this benzodiazepine antagonist were reported. The most frequent adverse experiences in both treatment groups were nausea, shivering, and operative-site pain. Vomiting, dizziness, and injection-site reactions were also reported in > or = 5% of patients treated with flumazenil.