Reversal of the central effects of midazolam by intravenous flumazenil after general anesthesia in outpatients: a multicenter double-blind clinical study. The Flumazenil in General Anesthesia in Outpatients Study Group I.
In a US double-blind, multicenter study, flumazenil, a benzodiazepine antagonist, administered postoperatively in a mean intravenous dose of 0.67 mg (range, 0.2 to 1 mg), was superior to placebo in reversing sedation and other central nervous system effects of benzodiazepines in outpatients recovering from general anesthesia induced by midazolam, fentanyl or sufentanil, and nitrous oxide. Within 5 minutes after administration of flumazenil, sedation was reversed in 94% (87 of 93) of flumazenil-treated patients, compared with 13% (6 of 46) of placebo-treated patients. The criterion response (Observer's Assessment of Alertness/Sedation Scale score of 4 or 5) that was achieved at 5 minutes was maintained in 79 (93%) of 85 patients throughout the 180-minute observation period. Psychomotor performance, measured by the Finger-to-Nose Test, was rated as normal at 5 minutes posttreatment for 77% (71 of 92) of flumazenil-treated patients, and 4% (2 of 46) of placebo-treated patients. The reversal of amnesia, as determined by the Picture Recall Test was less consistent. Patients given flumazenil did not experience more pain at the operative site or require more analgesic medication than did those given placebo. Nausea (flumazenil 24%; placebo 15%), dizziness (flumazenil 12%; placebo 2%), and vomiting (flumazenil 10%; placebo 9%) were the most frequent adverse effects in each group. In conclusion, flumazenil provided prompt arousal from benzodiazepine-induced sedation and was well tolerated.
D000293:Adolescent; D000328:Adult; D000368:Aged; D000553:Ambulatory Care; D000768:Anesthesia, General; D002490:Central Nervous System / Q000187:drug effects*; D004311:Double-Blind Method; D005260:Female; D005442:Flumazenil / Q000494:pharmacology*; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D011939:Mental Recall / Q000187:drug effects; D008874:Midazolam / Q000037:antagonists & inhibitors*; D008875:Middle Aged; D011597:Psychomotor Performance / Q000187:drug effects
D005442:Flumazenil; D008874:Midazolam