Flumazenil reduces the hypnotic dose of propofol in male patients under spinal anesthesia

Abstract

Purpose. Flumazenil has been reported to produce a partial benzodiazepine-agonist-like effect in some psychopharmacological examinations. This study investigated the effect of flumazenil on the hypnotic activity of propofol in 60 men scheduled for minor surgical procedures done under spinal anesthesia.

Methods. After a steady state of spinal anesthesia had been reached, patients were pretreated with saline or flumazenil, 5 μg·kg⁻¹, followed by the administration of saline or midazolam, 10 μg·kg⁻¹. Then, 250 μg·kg⁻¹·min⁻¹ of propofol was infused until hypnosis was achieved. Loss of response to a simple command with a slight stimulus, served as the end-point for hypnosis. Immediately after achievement of the end-point, propofol infusion was discontinued, and a 2-ml venous blood sample was obtained from the dorsal pedis vein to determine plasma propofol concentration.

Results. Flumazenil significantly decreased the dose of propofol required and the time required to achieve hypnosis compared with values in the control group (55 ± 10 [mean ± SD] vs 71 ± 14 mg and 212 ± 42 vs 268 ± 48 s, respectively; P < 0.05), whereas flumazenil attenuated the effect of midazolam in reducing the plasma concentration of propofol at hypnosis (2.9 ± 0.5 and 2.5 ± 0.6 μg·ml⁻¹, respectively; P < 0.05).

Conclusion. These results suggested that flumazenil may potentiate the hypnotic properties of propofol, despite flumazenil having an antagonistic effect on the enhanced hypnotic activity of propofol induced by the coadministration of midazolam.