Time course of ventilatory depression after thiopental and midazolam in normal subjects and in patients with chronic obstructive pulmonary disease.

Using a dual isohypercapnic technique, the authors compared the effect on ventilatory control of midazolam (0.2 mg/kg) and thiopental (3.5 mg/kg) in normal volunteers and in subjects with chronic obstructive pulmonary disease (COPD). In normal volunteers the slope of the CO2 response curve decreased from 1.77 +/- 0.16 l . min-1 . mmHg-1 (mean +/- SEM) to a minimum of 1.14 +/- 0.17 l . min-1 . mmHg-1 3.5 min after midazolam, returning to 1.32 +/- 0.21 l . min-1 . mmHg-1 15 min after injection. In the same subjects, the slope of the CO2 response curve fell from 1.89 +/- 0.18 l . min-1 . mmHg-1 to a minimum of 1.37 +/- 0.29 l . min-1 . mmHg-1 one minute after injection of thiopental, returning to 1.69 +/- 0.22 l . min-1 . mmHg-1 15 min after injection. These changes were not statistically significant. In subjects with clinical COPD, the slope of the CO2 response curve decreased from 1.89 +/- 0.63 l . min-1 . mmHg-1 to a minimum of 0.39 +/- 0.19 l . min-1 . mmHg-1 two minutes after injection of midazolam (P less than 0.05 compared with control), while 15 min after injection, the slope recovered to only 0.62 +/- 0.40 l . min-1 . mmHg-1 (P less than 0.05 compared with control). In the same subjects, the slope of the CO2 response curve decreased from 1.53 +/- 0.17 to a minimum of 0.69 +/- 0.25 l . min-1 . mmHg-1 0.5 min after injection of thiopental, recovering to 1.47 +/- 0.28 l . min-1 . mmHg-1 15 min after injection. This was significantly greater than the corresponding slope after midazolam (P less than 0.05). The authors conclude that while the time course of ventilatory depression after thiopental is similar in normal volunteers and in patients with COPD, the ventilatory depression 15 minutes after midazolam is more profound in patients with COPD than in normal subjects.