European journal of anaesthesiology. Supplement
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Eur J Anaesthesiol Suppl · Jan 1988
Review Randomized Controlled Trial Clinical TrialFlumazenil: US clinical pharmacology studies.
Flumazenil, a benzodiazepine antagonist, blocks the central effects of benzodiazepines by competitive interaction at the receptor site. Two double-blind, placebo-controlled, randomized studies in healthy volunteers (110/study) were performed to determine the minimal effective dose of flumazenil required to reverse the sedative, psychomotor and amnesic effects of benzodiazepines used to produce conscious sedation. Conscious sedation was produced by i.v. diazepam (12-30 mg) in one study and i.v. lorazepam (0.045 mg kg-1) in the other. ⋯ While the mean duration of reversal produced by the lower doses was comparable, the 0.2 mg dose resulted in the greatest between subject variability and only partial rather than complete reversal. Two further double-blind, placebo-controlled studies were done in healthy volunteers (45/study) to evaluate the safety of flumazenil 1.0 mg or placebo given i.v. to reverse midazolam-induced sedation in subjects who had been treated for up to 14 days with either oral diazepam or triazolam. No clinically significant changes were noted in laboratory test values, electrocardiograms or vital signs monitored for up to 36 h after flumazenil or placebo in any pre-treatment group.
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Eur J Anaesthesiol Suppl · Jan 1988
Randomized Controlled Trial Comparative Study Clinical TrialThe efficacy of flumazenil versus physostigmine after midazolam-alfentanil anaesthesia in man.
The effects of flumazenil and physostigmine were studied in adult surgical patients recovering from midazolam-alfentanil anaesthesia. Thirty-two patients were anaesthetized with midazolam (0.2 mg kg-1 and 0.36-0.66 mg kg-1 h-1 by infusion) and alfentanil (0.15 mg kg-1 and 0.03-0.15 mg kg-1 h-1 by infusion), vecuronium, 50% nitrous oxide in oxygen, intubated and ventilated. The midazolam and alfentanil infusions were stopped at the end of surgery. ⋯ The time-course of test scores and orientation were similar to that of sedation. No serious side-effects or haemodynamic changes were observed after flumazenil. After physostigmine, seven patients had an increase in heart rate to 140 beats min-1 and blood pressure decreased in three patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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Eur J Anaesthesiol Suppl · Jan 1988
Randomized Controlled Trial Clinical TrialEffects of flumazenil on post-operative recovery after total intravenous anesthesia with midazolam and alfentanil.
Midazolam and alfentanil were infused in a totally i.v. anesthetic technique (TIVA) to patients undergoing hysterectomy. Correlations of midazolam plasma concentrations and effects were made during recovery. Due to the high doses of midazolam administered during TIVA, metabolism and not redistribution mainly governed the duration of effects post-infusion. ⋯ The effect of the benzodiazepine antagonist flumazenil on post-operative performance after total i.v. anaesthesia with midazolam and alfentanil was studied. A bolus dose of flumazenil, 1.0 mg i.v., significantly improved recovery during the first post-operative hour but was followed later by resedation. The reduction in sedation followed by improvement in ventilation, without reduction of analgesia, demonstrated that antagonism of hypnosis is the primary factor in enhancing recovery from total i.v. anaesthesia.