Respiratory depression following diazepam: reversal with high-dose naloxone

The authors compared the effects of naloxone and saline solution on the respiratory changes following diazepam in a double-blind crossover trial in six subjects. Following baseline measurements of respiration, each subject was given diazepam, 15 mg, intravenously. Sixty and ninety-five minutes later each subject received either two doses of naloxone, 15 mg, intravenously, or two doses of the equivalent volume of saline solution. Forty-five minutes after diazepam administration the slopes of the curves of the ventilatory responses to rebreathing carbon dioxide (VE/PETCO2) were depressed to 53 per cent of control (P < 0.05). Following the two doses of naloxone, the slopes of VE/PETCO2 recovered, until, 120 minutes after the second dose of naloxone, slopes had returned to control values. After saline solution, however, slopes remained depressed at 68 per cent of control (P < 0.05). A similar recovery following naloxone was observed in the PETCO2 intercept of the VE/PETCO2 response curve and in the slope of the mouth-occlusion-pressure response curve to rebreathing carbon dioxide. End-tidal carbon dioxide during quiet breathing and during inspiratory resistive-loaded breathing (80 cm H2O/l/s) showed small increases after diazepam, which were not significantly reduced by naloxone. The results of this study show that diazepam produces respiratory depression, and that this may be relieved by large doses of naloxone.