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

Abstract

To investigate the hypothesis that 0.3 mg flumazenil administered to healthy unpremedicated patients at the end of deep surgical sevoflurane/remifentanil anaesthesia would expedite recovery. Flumazenil, an imidazobenzodiazepine derivative, antagonizes the hypnotic/sedative effects of benzodiazepines on γ-aminobutyric acid receptors. However, endogenous benzodiazepine ligands (endozepines) were isolated in mammalian tissues of individuals who had not received benzodiazepines. Twenty-four healthy unpremedicated patients, scheduled to undergo elective surgery requiring general anaesthesia, were randomly allocated to receive either a single dose of 0.3 mg flumazenil (n = 14) or placebo (n = 10) intravenously at the end of the surgical procedure just before the discontinuation of the volatile anaesthetic. After study drug administration, the authors compared various recovery parameters in the flumazenil and control groups. Median time to spontaneous respiration, eye opening on verbal command, extubation and time to date of birth recollection was significantly shorter in the flumazenil group than in the control group [2.5 min (2.0-3.0) vs. 7.0 min (6.8-8.3), 3.4 min (3.0-4.0) vs. 8.1 min (6.9-10.2), 4.0 min (3.0-5.0) vs. 9.0 min (7.0-10.8) and 4.7 min (4.0-5.0) vs. 10.3 min (8.0-12.0), respectively]. Administration of a single dose of 0.3 mg flumazenil to healthy unpremedicated patients at the end of sevoflurane/remifentanil anaesthesia results in earlier emergence from anaesthesia and significantly expedites recovery. This could redefine the role of flumazenil in general anaesthesia, implicating endozepine-dependent mechanisms.