Reversal of the central effects of midazolam by intravenous flumazenil after general anesthesia in outpatients premedicated with an opioid and a muscle relaxant: report of a multicenter double-blind clinical study. The Flumazenil in General Anesthesia in Outpatients Study Group II.
Flumazenil was studied in a double-blind multicenter trial to confirm its efficacy and safety in antagonizing the central effects of benzodiazepines after general anesthesia (midazolam, short-acting narcotic, nitrous oxide) with muscle relaxants and selected potent volatile anesthetics as needed. One hundred seventy-two outpatients were randomly assigned to receive either flumazenil or placebo titrated to the point of reversal of sedation or a maximum dose of 1 mg of flumazenil or 10 ml of placebo. The test drug was given intravenously (0.2 mg flumazenil or 2 ml placebo) at 1-minute intervals. Tests of alertness, psychomotor function, and memory were conducted prestudy and at baseline before the administration of flumazenil and at 5-, 15-, 30-, 60-, 120-, and 180-minute intervals after administration. The changes from prestudy or baseline scores were analyzed to compare differences between treatment groups. Seventy-five percent of the 105 flumazenil-treated patients and 14% of the 55 placebo-treated patients who met the qualifications for efficacy evaluations obtained a criterion level of response as measured by the Observer's Assessment of Alertness/Sedation Scale. Most (76%) patients who were alert at 5 minutes maintained their level of wakefulness throughout the 180-minute observation period. All 172 patients were included in evaluations of safety. Fifty percent of 113 flumazenil-treated patients and 31% of 59 placebo-treated patients reported one or more adverse experiences. The most frequently reported were nausea, vomiting, and dizziness. Only 6 adverse effects in the flumazenil group and 1 in the placebo group were considered severe; the remainder were mild or moderate. None were considered serious or potentially serious. Postoperative administration of flumazenil (mean dose, 0.85 mg) safely provided a prompt, controlled reversal of the sedative and psychomotor effects of midazolam in most patients.
D000328:Adult; D000368:Aged; D000556:Ambulatory Surgical Procedures; D000768:Anesthesia, General; D002490:Central Nervous System / Q000187:drug effects*; D004311:Double-Blind Method; D005260:Female; D005442:Flumazenil / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008874:Midazolam / Q000037:antagonists & inhibitors*; D008875:Middle Aged; D009294:Narcotics; D003473:Neuromuscular Nondepolarizing Agents / Q000008:administration & dosage*; D011229:Preanesthetic Medication; D013390:Succinylcholine / Q000008:administration & dosage
D009294:Narcotics; D003473:Neuromuscular Nondepolarizing Agents; D005442:Flumazenil; D013390:Succinylcholine; D008874:Midazolam