I Kissin1, H R Vinik, E L Bradley. 1. Department of Anesthesiology, School of Medicine, University of Alabama, Birmingham 35294.
Abstract
STUDY OBJECTIVE: To test the hypothesis that midazolam potentiates thiopental sodium-induced unconsciousness. DESIGN: Randomized, double-blind study. SETTING: A university medical center. PATIENTS: Fifty nonpremedicated ASA physical status I and II adult patients scheduled for eye surgery. INTERVENTIONS: Intravenous (IV) injections of thiopental sodium in doses ranging from 1.0 mg/kg to 4 mg/kg with or without the addition of midazolam 0.02 mg/kg. MEASUREMENTS AND MAIN RESULTS: Inability to open eyes on command was used as an end point of anesthesia and the dose-response curves were determined using a probit procedure. A dose of 0.02 mg/kg, which constitutes less than one-tenth of the hypnotic ED50 value for midazolam, potentiated thiopental sodium anesthesia. The thiopental sodium ED50 value was decreased from 2.4 mg/kg to 1.6 mg/kg (p less than 0.001). Midazolam also reduced individual variability in the response to thiopental sodium. As a result, the thiopental sodium dose that reliably induced any nonpremedicated patient decreased from 6 mg/kg (ED99 of 5.57 mg/kg) to 2.5 mg/kg (ED99 of 2.37 mg/kg). CONCLUSIONS: A subhypnotic dose of midazolam potentiates thiopental sodium-induced unconsciousness. This effect suggests the possibility that midazolam enhances barbiturate binding.
RCT Entities:
STUDY OBJECTIVE: To test the hypothesis that midazolam potentiates thiopental sodium-induced unconsciousness. DESIGN: Randomized, double-blind study. SETTING: A university medical center. PATIENTS: Fifty nonpremedicated ASA physical status I and II adult patients scheduled for eye surgery. INTERVENTIONS: Intravenous (IV) injections of thiopental sodium in doses ranging from 1.0 mg/kg to 4 mg/kg with or without the addition of midazolam 0.02 mg/kg. MEASUREMENTS AND MAIN RESULTS: Inability to open eyes on command was used as an end point of anesthesia and the dose-response curves were determined using a probit procedure. A dose of 0.02 mg/kg, which constitutes less than one-tenth of the hypnotic ED50 value for midazolam, potentiated thiopental sodium anesthesia. The thiopental sodium ED50 value was decreased from 2.4 mg/kg to 1.6 mg/kg (p less than 0.001). Midazolam also reduced individual variability in the response to thiopental sodium. As a result, the thiopental sodium dose that reliably induced any nonpremedicated patient decreased from 6 mg/kg (ED99 of 5.57 mg/kg) to 2.5 mg/kg (ED99 of 2.37 mg/kg). CONCLUSIONS: A subhypnotic dose of midazolam potentiates thiopental sodium-induced unconsciousness. This effect suggests the possibility that midazolam enhances barbiturate binding.