Effects of intravenous midazolam on the work of breathing

Midazolam at sedative doses induces an increase in upper airway resistance, but its effects on the work of breathing have not been established. The flow-resistive work of breathing and pulmonary resistance (RL) of eight healthy volunteers were measured, with either midazolam 0.1 mg/kg or placebo in a random order. Esophageal pressures were measured using a balloon-tipped catheter, airflow using a pneumotachograph. Total resistive work expressed per minute (WTOT) and per liter of ventilation (WTOT/VE), and their inspiratory (WI) and expiratory (WE) components were determined. No change was observed after placebo injection. Five minutes after midazolam injection, an increase was observed in WTOT (from 3 +/- 0.4 J/min [mean +/- SEM] at control to 6.3 +/- 1.1 J/min; P < 0.01) and in WTOT/VE (from 360 +/- 30 mJ/L at control to 1250 +/- 120 mJ/L; P < 0.01), involving both WI and WE components. An increased inspiratory RL was observed from 13.7 +/- 2.6 cm H2O.L-1.s-1 at control to 32.8 +/- 3.9 cm H2O.L-1.s-1 after midazolam. Changes in inspiratory RL were correlated to changes in WI and WI/VE (r = 0.574, P < 0.001; and r = 0.762, P < 0.001, respectively). Our results suggest that airway obstruction plays a major role in the increased work of breathing observed during sedation with midazolam.