Effect of intravenous flumazenil on reversal of the central effects of midazolam used with short-acting opioids for general anesthesia in hospitalized patients: report of a multicenter, double-blind clinical study. The Flumazenil in General Anesthesia in Hospitalized Patients Study Group I.

Midazolam, a short-acting benzodiazepine central nervous system (CNS) depressant widely used for the induction and maintenance of general anesthesia, is often supplemented with short-acting opioids for general anesthesia. Administered postoperatively, flumazenil, a specific benzodiazepine antagonist, reverses the CNS sedative effects of midazolam. In a double-blind clinical trial in hospitalized patients, flumazenil, administered postoperatively at an average intravenous dose of 0.89 mg (range: 0.4 mg to 1 mg), was more effective than placebo in reversing sedation and other residual effects of benzodiazepines in patients recovering from general anesthesia induced by midazolam (mean dose 29 mg) in conjunction with fentanyl (mean dose 0.4 mg) or sufentanil (mean dose 0.056 mg). Five minutes posttreatment, 87 (83%) of 124 flumazenil-treated patients and 6 (10%) of 60 placebo-treated patients had attained the criterion response for reversal of sedation. Of these patients, 60% in the flumazenil group, compared with 100% in the placebo group, retained their degree of alertness throughout the 3-hour observation period. Between-group differences were significant until 60 minutes posttreatment, when the effect of the benzodiazepines had spontaneously waned in the placebo group. The Physician's Global Efficacy Rating, providing an overall measure of efficacy 5 minutes after test drug administration, was good or excellent for 86% of the flumazenil-treated patients, as compared with 7% of the placebo-treated patients evaluated. Measurements of psychomotor function and memory also showed significant between-group differences. Flumazenil, compared with placebo, was not associated with a substantially greater frequency of operative-site pain. These results demonstrate that the efficacy and safety of flumazenil were not compromised by the addition of a short-acting opioid to the anesthetic regimen.