Changes in breathing pattern and chest wall mechanics after benzodiazepines in combination with meperidine

The effects of repeated sedative i.v. doses of midazolam and diazepam in combination with meperidine on breathing pattern and thoracoabdominal motion were studied in eight healthy male volunteers. At 20-min intervals in a randomized double-blind crossover design the subjects initially received two doses of midazolam 0.05 mg/kg or diazepam 0.15 mg/kg followed by meperidine 0.5 mg/kg and then naloxone 0.4 mg. Breathing pattern and thoracoabdominal motion were measured non-invasively, utilizing a computerized strain gauge technique. The initial injection of both benzodiazepines caused significant decreases in tidal volume, inspiratory time and expiratory time. There were no significant differences between the two drugs in any of these variables. Minute ventilation, mean inspiratory flow and respiratory timing were not significantly affected. The second injection of both benzodiazepines caused only insignificant additional changes. When meperidine was added, the effects on inspiratory time and tidal volume were small and not significant. However, expiratory time increased and was no longer significantly different from control. The injection of naloxone reversed the meperidine-induced changes only, and the breathing pattern was no longer different from that obtained during benzodiazepines alone. The decrease in tidal volume after the benzodiazepines was almost exclusively mediated by a decrease in the abdominal contribution. Additional doses of benzodiazepines did not enhance these changes. However, meperidine caused a further decrease in the abdominal contribution. This decrease was reversed by naloxone. This indicates that the combination of benzodiazepines and meperidine caused a profound decrease in diaphragmatic performance.