Postoperative reversal of loss of vigilance following midazolam with the use of the antagonist flumazenil (Ro 15-1788)

Author(s): Freye E, Fournell A


Midazolam, a benzodiazepine with the purportedly shortest half-life of all these compounds, is advocated for the induction of general anesthesia. It is still debatable, however, whether a long-lasting hangover may result in depression of vigilance postoperatively. After midazolam induction (0.18 mg/kg) and enflurane/nitrous oxide/oxygen anesthesia, ten patients received flumazenil (0.8 mg/70 kg) in the postoperative period while another ten received placebo in a double-blind fashion. Continuous recording of EEg activity was performed using the Lifescan monitor, computing the power in the various EEG frequency domains. Additionally, patients were scored with regard to orientation in space and time and their collaboration and comprehension of verbal commands. Compared to placebo, flumazenil induced power in the alpha domain, accompanied by a drop of power in the delta and theta bands. While the increase in alpha activity resolved after 30 min, beta activity increased significantly, an effect that lasted up to the 180th postoperative minute. As with the finding of higher power in the fast-frequency domains, flumazenil patients scored higher with regard to collaboration and comprehension as well as orientation in space and time. 1. When used for induction, midazolam may result in significant depression of vigilance even 120 min after operation. 2. Flumazenil is a specific antagonist with a rapid onset of action. 3. Flumazenil is an antagonist specifically directed to reverse the side-effects of benzodiazepines in a manner similar to naloxone, which is used in opioid overdose.

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