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Midazolam premedication reduces propofol dose requirements for multiple anesthetic endpoints

Oliver H.G. Wilder-Smith, MBCHB MD^*, Patrick A. Ravussin, MD, Laurent A. Decosterd, PhD, Paul A. Despland, MD and Bruno Bissonnette, MD^¶

^* From the Nociception Research Group Berne University, Berne
the Department of Anaesthesiology Sion Hospital
the Division of Clinical Pharmacology
the Department of Neurology, Lausanne University Hospital (CHUV), Lausanne, Switzerland and
^¶ the Department of Anaesthesia, University of Toronto, Toronto, Canada.

Address correspondence to: Dr. Oliver H.G. Wilder-Smith, The Pain Centre, University Department of Anaesthesiology, Academisch Ziekenhuis Nijmegen, P.O. Box 9101, NL-6500 HB Nijmegen, The Netherlands. Phone: +31–24–361 44 06; Fax: +31–24–361 35 85; E-mail: o.wildersmith{at}anes.azn.nl

Purpose: This study investigates the interactions between midazolam premedication and propofol infusion induction of anesthesia for multiple anesthetic endpoints including: loss of verbal contact (LVC; hypnotic), dropping an infusion flex (DF; motor), loss of reaction to painful stimulation (LRP; antinociceptive) and attainment of electroencephalographic burst suppression (BUR; EEG).

Methods: In a double blind, controlled, randomized and prospective study, 24 ASA I-II patients received either midazolam 0.05 mg•kg^–1 (PM; n=13) or saline placebo (P0; n=11) iv as premedication. Twenty minutes later, anesthesia was induced by propofol infusion at 30 mg•kg^–1• hr^–1. ED₅₀, ED₉₅ and group medians for times and doses were determined and compared at multiple anesthetic endpoints.

Results: At the hypnotic, motor and EEG endpoints, midazolam premedication significantly and similarly reduced propofol ED₅₀ (reduction: 18%, 13% and 20% respectively; P <0.05 vs unpremedicated patients) and ED₉₅ (reduction: 20%, 11% and 20% respectively; P <0.05 vs unpremedicated patients). For antinociception (LRP), dose reduction by premedication was greater for propofol ED₉₅ (reduction: 41%; P <0.05 vs unpremedicated patients) than ED₅₀ (reduction: 18%; P <0.05 vs unpremedicated patients). Hemodynamic values were similar in both groups at the various endpoints.

Conclusions: Midazolam premedication 20 min prior to induction of anesthesia reduces the propofol doses necessary to attain the multiple anesthetic endpoints studied without affecting hemodynamics in this otherwise healthy population. The interaction differs for different anesthetic endpoints (e.g., antinociception vs hypnosis) and propofol doses (e.g., ED₅₀ vs ED₉₅).

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