The Effects of Midazolam in Propofol-Induced Anesthesia

To the Editor: Oxorn et al. concluded that the addition of 0.030 mg/kg of midazolam did not alter the hypnotic dose of propofol in patients undergoing elective dilation and curettage. They did, however, report a statistically significant shorter induction time (43.8 s) for the combination than for propofol alone (74.7 s) (P < 0.003). We and others [1,2] have shown approximately 45% reduction of the hypnotic dose of propofol by using a concurrent dose of 0.020 mg/kg midazolam (frax;1;10 of the 50% effective dose), and we conclude that midazolam and propofol were significantly synergistic for their hypnotic effect. The explanation for the different conclusions is probably based on methodology. Our protocol mandated specific times for administration of drugs to allow for peak effect. IV midazolam's hypnotic effect peaks in 3 min. Propofol's peak effect occurs in 2 min. Consequently, the drugs are staggered by 1 min to produce coinciding peak effects. Our study [3] demonstrated that the 90% effective dose for propofol was 1.03 mg/kg when 0.020 mg/kg of midazolam was added. Clearly, Oxorn et al. did not wait for the peak effect and began titrating extra propofol too soon in the midazolam group. As a result, only shorter induction times demonstrated in their study reflect hypnotic midazolampropofol synergy. Oxorn, et al. used unnecessarily high doses of propofol 2.4 mg/kg in the combined group with midazolam.030 mg/kg because, according to our data, 90% of the midazolam group would have been induced after 1.03 mg/kg. The absence of propofol-midazolam synergy with the other points measured by the authors does not contradict hypnotic synergism because different components of anesthesia have different mechanisms. H. Ronald Vinik, MD Department of Anesthesiology; University of Alabama; Birmingham, AL 35233