The effect of oral midazolam and diazepam on respiration in normal subjects

Benzodiazepine have been shown to suppress ventilatory responses to hyperoxic hypercapnia (HCVR) and isocapnic HVR when taken parenterally. Most patients would, however, prefer to take an oral rather than parenteral preparation but the effect of oral benzodiazepine on these ventilatory responses has not been well studied. We therefore studied the effect of oral midazolam (7.5 mg) and diazepam (5 mg) both given orally on resting ventilation and respiratory drive, as assessed by HCVR and HVR. Flumazenil, a specific benzodiazepine antagonist, was administered intravenously to reverse the effect. A mental alertness-drowsiness index in five grades, from 1 (awake and alert) to 5 (asleep), was used to assess the sedation effect. Six normal male subjects, (aged 31 +/- 1.6 yrs) (mean +/- SD), participated in the study. Mean resting ventilation, and ventilatory response to HCVR and HVR were not significantly altered by these drugs when taken orally. Flumazenil also had not significant effect on HCVR and HVR. However the mental alertness-drowsiness index rose from 1 to 2.83 with oral midazolam and reversed to 1.25 with flumazenil. Similarly, this index increased from 1 to 2.25 after oral diazepam and reversed to 1.42 after flumazenil. In conclusion, we found that even though oral midazolam and diazepam produced a significant sedation effect, which was reversed with flumazenil, the drugs had no effect on ventilation at rest and the ventilatory responses to hypoxia and hypercapnia.