Effect of Flumazenil on Bispectral Index Monitoring in Unpremedicated Patients

Abstract

This study demonstrates that flumazenil given to healthy unpremedicated patients during propofol/remifentanil anesthesia significantly increased the BIS value and allowed earlier emergence from anesthesia. This may indicate that flumazenil could be used on a case-by-case basis to reverse endogenous or exogenous endozepines that might play a role during anesthesia.

Effects of γ-Aminobutyric Acid Type A Receptor Modulation by Flumazenil on Emergence from General Anesthesia

“…Human EEG data gathered during recovery from general anesthesia characteristically exhibits an increase in high-frequency power 36–38 . Our results are also consistent with those of Dahaba et al, who determined that flumazenil changed the frontal EEG of patients undergoing intravenous anesthesia towards a pattern more indicative of awakening 39 . In humans, increased power in higher frequency bands is also more indicative of the lighter stages of sleep (such as N1 and REM) 40 more common in the early morning in preparation for waking.…”

Flumazenil expedites recovery from sevoflurane/remifentanil anaesthesia when administered to healthy unpremedicated patients

“…26 Furthermore, in a recent prospective randomized clinical trial, administration of flumazenil intraoperatively during propofol/remifentanil anaesthesia in healthy unpremedicated patients not previously exposed to any benzodiazepine medication significantly increased BIS value. 11 It has also been demonstrated that flumazenil improves recovery of high cortical and neuromotor functions following halothane, enflurane and isoflurane anaesthesia, reduces shivering and improves the overall quality of emergence. 27 References to convulsions and ventricular tachycardia precipitated by flumazenil have been reported in the literature.…”

“…11 Naturally occurring endozepines, or endogenous benzodiazepine receptor ligands, that did not result from environmental contamination with pharmaceutical benzodiazepines have been isolated in different mammalian tissues. 11,21,22 Specifically, endogenous benzodiazepines were detected in potentially physiological concentrations in human cerebrospinal fluid, serum, plasma, urine, ultrafiltrates of patients who had not received benzodiazepines and breast milk of healthy, newly delivered women who were not taking benzodiazepines. [5][6][7][8]23,24 Benzodiazepines of natural origin (NBZDs) have been isolated in medicinal plants and foods.…”

“…The minimum important differences and SDs for sample size calculation were based on published literature. 11 A total of 25 patients were initially enrolled and randomized to receive flumazenil (n ¼ 15) or placebo (n ¼ 10). However, data from 24 patients were included in the subsequent analysis.…”

“…It seems to act as an analeptic agent when administered to patients with hepatic encephalopathy, 9,10 whereas a recent study showed that it significantly increases the bispectral index (BIS) value and allows earlier emergence from anaesthesia when administered to healthy unpremedicated patients during propofol/remifentanil anaesthesia. 11 Incremental intravenous bolus injections of flumazenil 0.1-0.3 mg are considered most effective in the treatment of benzodiazepine overdose, whereas 1 mg is reported as the most frequent maximal dose in humans. 12 The efficacy of a large bolus dose of flumazenil has already been documented.…”