Clinical therapeutics
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Clinical therapeutics · Nov 1992
Randomized Controlled Trial Multicenter Study Clinical TrialReversal of central nervous system effects by flumazenil after intravenous conscious sedation with midazolam: report of a multicenter clinical study. The Flumazenil in Intravenous Conscious Sedation with Midazolam Multicenter Study Group I.
Flumazenil, a benzodiazepine antagonist, reverses the residual central nervous system effects of benzodiazepines. In this US double-blind, multicenter study, the efficacy of flumazenil was compared with that of placebo in antagonizing the effects of midazolam, a benzodiazepine used to induce intravenous conscious sedation. The mean dose of flumazenil was 0.7 mg, administered intravenously. ⋯ Flumazenil was well tolerated. Dizziness (10%) and nausea (9%) were the most frequently reported adverse effects. Results of this study demonstrate that flumazenil antagonizes the central nervous system effects of midazolam after intravenous conscious sedation.
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Clinical therapeutics · Nov 1992
Randomized Controlled Trial Multicenter Study Clinical TrialReversal of central benzodiazepine effects by intravenous flumazenil after conscious sedation with midazolam and opioids: a multicenter clinical study. The Flumazenil in Intravenous Conscious Sedation with Midazolam Multicenter Study Group II.
The efficacy and safety of flumazenil in antagonizing the central effects of the benzodiazepine midazolam was demonstrated in patients in whom conscious sedation was induced with midazolam plus an opioid (fentanyl, meperidine, or morphine). In a double-blind, multicenter study, 240 patients were administered flumazenil postoperatively at an average intravenous dose of 0.7 mg (7 ml) and 114 patients were administered an average dose of 9 ml placebo. Complete reversal of sedation was observed in 80% of flumazenil-treated patients and 30% of placebo-treated patients 5 minutes posttreatment. ⋯ Flumazenil was well tolerated, although adverse effects were reported slightly more often than in the placebo group. The most frequent adverse events in both groups were dizziness and nausea. Vital signs were not affected.
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Clinical therapeutics · Nov 1992
Randomized Controlled Trial Multicenter Study Clinical TrialTreatment of benzodiazepine overdose with flumazenil. The Flumazenil in Benzodiazepine Intoxication Multicenter Study Group.
Flumazenil, a specific benzodiazepine antagonist, was evaluated as adjunctive therapy in the management of benzodiazepine overdose. Thirteen emergency departments enrolled 326 patients in this double-blind, placebo-controlled trial; 162 patients were randomly allocated to receive flumazenil (maximum dose, 30 ml, providing 3 mg of flumazenil), and 164 were allocated to receive placebo (maximum dose, 30 ml). A successful response was the attainment of a score of 1 or 2 on the Clinical Global Impression Scale (CGIS), denoting a very much improved or much improved status, 10 minutes after the start of intravenous administration of the test drug. ⋯ This was accomplished irrespective of the presence of coingested drugs. Flumazenil is not recommended for patients with serious cyclic antidepressant poisoning or those who use benzodiazepines therapeutically to control seizure disorders. When used as recommended, however, flumazenil has been shown to have an acceptable safety level.
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Clinical therapeutics · Nov 1992
Randomized Controlled Trial Multicenter Study Clinical TrialReversal 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. ⋯ 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.
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Clinical therapeutics · Nov 1992
Randomized Controlled Trial Multicenter Study Clinical TrialReversal of central benzodiazepine effects by flumazenil after conscious sedation produced by intravenous diazepam. The Flumazenil in Intravenous Conscious Sedation with Diazepam Multicenter Study Group I.
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. ⋯ 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.