Midazolam premedication reduces propofol dose requirements for multiple anesthetic endpoints.
OBJECTIVE
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 x kg(-1) (PM; n = 13) or saline placebo (PO; n = 11) i.v. as premedication. Twenty minutes later, anesthesia was induced by propofol infusion at 30 mg x kg(-1) x 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).
Wilder-Smith
O H
OH
Nociception Research Group Berne University, Switzerland. o.wildersmith@anes.azn.nl
Ravussin
P A
PA
Decosterd
L A
LA
Despland
P A
PA
Bissonnette
B
B
D000328:Adult; D000771:Anesthesia, Intravenous; D018686:Anesthetics, Intravenous / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004569:Electroencephalography / Q000187:drug effects; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives; D008297:Male; D008874:Midazolam; D008875:Middle Aged; D016343:Monitoring, Intraoperative; D010147:Pain Measurement / Q000187:drug effects; D011229:Preanesthetic Medication; D015742:Propofol / Q000008:administration & dosage; D011446:Prospective Studies
D018686:Anesthetics, Intravenous; D006993:Hypnotics and Sedatives; D008874:Midazolam; D015742:Propofol