Differences in midazolam-induced breathing patterns in healthy volunteers.

Sex differences, and the influence of drug dosage and additional upper airway obstruction were studied in midazolam-induced breathing patterns and sedation in 30 healthy volunteers (8 males and 22 females). After administration of 0.1 mg.kg-1 midazolam (8 male and 8 female subjects), the rib cage (RC) motion increased in 6 males and the abdominal wall (ABD) motion and SaO2 decreased in all males. In contrast, the RC and ABD motions and SaO2 decreased in all females. Snoring and loss of consciousness occurred in 7 males and in 2 females. There were significant differences in the RC motion, SaO2, the incidence of snoring and the sedative state between male and female subjects. A bolus dose of 0.5 mg of flumazenil completely antagonized the sedative effect of midazolam and restored the breathing pattern, whereas it did not completely restore SaO2. A higher dose (0.2 mg.kg-1) of midazolam was administered to an additional 8 females. It caused a loss of consciousness in all subjects and increased the RC motion in only one subject. Partial obstruction of the nasal cavity was effected with cotton balls in the remaining 6 females who were sedated with 0.1 mg.kg-1 midazolam. An increase in the RC motion occurred similar to that observed in males. These findings suggest a difference in midazolam-induced sedation and breathing patterns between male and female subjects with midazolam administration on a mg.kg-1 basis.