Changes in respiratory pattern after repeated doses of diazepam and midazolam in healthy subjects

Abstract

Changes in respiratory pattern and arterial PCO2 after three repeated intravenous sedative doses of midazolam 0.05 mg/kg or diazepam 0.15 mg/kg were studied in eight healthy male volunteers in a randomized double-blind crossover design. In order to reduce the influence of the measuring equipment, we utilized a noninvasive computerized technique to measure respiratory variables. Both drugs caused equal changes in breathing pattern with a decrease in tidal volume, an increase in respiratory rate and an unaltered minute ventilation. These alterations in breathing pattern were associated with CO2 retention. Respiratory changes were mainly induced by the first injection of either drug. Despite increased plasma drug concentrations, subsequent doses did not cause further changes in respiratory variables except for an increase in PCO2 after the second dose of midazolam. The clinical significance of these changes in PaCO2 in otherwise healthy individuals is probably limited. The duration of the subjective sensation of sedation was longer after diazepam than after midazolam.