Search

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.

The authors compared the respiratory effects of an intravenous infusion of ketamine (1 mg X kg-1) with droperidol (0.1 mg X kg-1), or placebo on three different occasions in a double-blind, randomized fashion in eight healthy volunteers. Breathing pattern, thoraco-abdominal motion, end-expiratory positions of the rib cage and abdomen, arterial hemoglobin oxygen saturation (SaO2), and end-tidal carbon dioxide concentration (FECO2) were continuously measured with noninvasive techniques. During the 1-h monitoring period following drug injection, droperidol produced occasionally significant but clinically unimportant differences in respiratory variables when compared with placebo. In contrast, ketamine induced a significant (P less than 0.001) and persistent increase in minute ventilation (+75%) from 5 to 20 min after start of infusion by increasing both the driving (i.e., tidal volume/inspiratory time [VT/Ti]) and the timing (i.e., inspiratory time/total respiratory cycle time [Ti/Ttot]) components of ventilation (Milic-Emili J, Grunstein MM: Chest 70 (Suppl): 131-133, 1976). This was obtained without any significant change in end-expiratory positions or change in relative rib cage contribution to tidal volume. Despite multiple apneic episodes observed with ketamine, the subjects maintained a stable SaO2 and FECO2, indicating no resting respiratory depression. This study, performed with a noninvasive respiratory monitoring technique, confirms that droperidol infused over 5 min at a clinically used dosage does not cause respiratory depression in healthy subjects, whereas ketamine produces an important ventilatory stimulation.

The purpose of this study was to examine the respiratory depression produced by diazepam and by midazolam. Ventilatory and mouth occlusion pressure responses to CO2 were measured in eight healthy volunteers before and after the intravenous administration of 0.3 mg/kg of diazepam and 0.15 mg/kg of midazolam. The mean ventilatory response to CO2 (mean +/- SEM) decreased after administration of diazepam or midazolam from 2.0 +/- 0.2 to 1.3 +/- 0.1 1.min-1/torr or from 2.1 +/- 0.2 to 1.4 +/- 0.1 1.min-1/torr, respectively. In the same volunteers, the mouth occlusion pressure responses decreased from 0.54 +/- 0.05 to 0.30 +/- 0.04 cm H2O/torr after midazolam and from 0.67 +/- 0.12 to 0.28 +/- 0.07 cm H2O/torr after diazepam. When compared with the control slopes of the ventilatory and mouth occlusion pressure responses, the drug slopes were significantly different. Respiration was similarly depressed after diazepam and after midazolam. That both the ventilatory and mouth occlusion pressure responses to CO2 are equally depressed by intravenous injections of midazolam and of diazepam at equipotent doses suggests a direct depression of the central respiratory drive by these drugs.