Midazolam produces dose-dependent decrease in ventilation with 0.15 mg/kg IV producing effect similar to diazepam 0.3 mg/kg IV.
Patients with chronic obstructive pulmonary disease experience even greater midazolam respiratory depression .
Transient apnoea usually follows after rapid injection of large doses of midazolam (>0.15 mg/kg IV) especially in the presence of premedication with opioids.
The incidence of midazolam-induced apnoea reported in published paper ranges from 18-78%. The peak decrease in the slope of the CO2 response curve occurs 3.5 minutes after midazolam (0.2 mg/kg), when given to healthy volunteers and in 2 minutes in COPD patients.
Midazolam respiratory depression in both normal and COPD patients has a slower onset and is more prolonged than with thiopental (3.5 mg/kg).
Midazolam respiratory depression seems to be a CNS effect, since both the ventilatory response to CO2 and the mouth occlusion pressure to CO2 are depressed and there is little effect on respiratory mechanism.
The respiratory effects of midazolam are not reversed by naloxone. Midazolam produces a significant decrease in mean inspiratory flow, resulting in decreased tidal volume (VT). Total lung capacity was decreased during sedation with midazolam.
This ventilatory depression is partly compensated by a decrease in expiratory time producing an increase in respiratory rate. Interestingly, repeated equal doses of midazolam 0.1 mg/kg, seemed to produce less depression, suggesting “tolerance” to the effects of midazolam respiratory depression .
There is evidence that the low sedative doses of midazolam (0.075 mg/kg IV) do not affect the ventilatory response to CO2, suggesting perhaps that in lower doses clinically important midazolam respiratory depression does not occur.