Ventilatory effects of single, high-dose triazolam in awake human subjects

Abstract

The respiratory-depressant effect of the benzodiazepine-derived hypnotic triazolam was investigated with a single oral dose at two and three times the usual dosage in 62 awake normal subjects. A randomized, double-blind protocol compared the following groups: (1) placebo, (2) triazolam, 1.0 mg, (3) triazolam, 1.5 mg, and (4) morphine, 0.15 mg/kg. Differences between predrug and postdrug administration were compared. Minute ventilation (Ve), end-tidal PCO2, and the ventilatory response to CO2 (Ve/PCO2) were preserved with both 1.0 mg and 1.5 mg triazolam compared with placebo. Triazolam caused an increase in breathing frequency (+21% to 50%; p less than 0.05) as a result of a shortening of inspiratory time. Triazolam was associated with a higher Ve corrected for CO2 production and Ve/PCO2 compared with morphine. We concluded that a single dose of triazolam at two and three times the usual level does not cause respiratory depression in awake, normal subjects but does alter respiratory cycle timing causing an increase in breathing frequency.