Respiratory Depressant Effects of Different Doses of Midazolam and Lack of Reversal with Naloxone-A Double-Blind Randomized Study

Abstract

Conflicting data concerning the ventilatory effects of benzodiazepines may be caused by the large variability in investigational conditions. Respiratory effects of three different intravenous doses of midazolam (0.05 mg/kg, 0.1 mg/kg, 0.2 mg/kg) and placebo were measured in a double-blind and randomized fashion in eight healthy volunteers. The respiratory variables were analyzed by means of a noninvasive method, thereby avoiding interferences associated with the stimulating effects of mouthpiece and nose clip. After injection of midazolam, tidal volume decreased by 40% with the three doses and respiratory frequency increased to the same extent, minute ventilation remained constant. Only the largest dose of the drug produced a significant decrease (P less than 0.05) in O2 saturation that was related to the longer duration of apnea. Intravenous naloxone (0.015 mg/kg) injected 5 min after midazolam did not change any measured respiratory or hemodynamic variable. We conclude that the respiratory effects of midazolam are poorly dose related and not reversed by naloxone. The observed compensatory increase in respiratory frequency which is not noted in other studies, is probably related to the noninvasive measurement technique used.