[Acute effect of lorazepam on respiratory muscles in stable patients with chronic obstructive pulmonary disease]

Benzodiazepines are known to cause muscle hypotonia, but their effects on respiratory muscle function, particularly on diaphragm, have not yet been studied. Our aim was to look for any effect of lorazepam on respiratory muscle function in patients with chronic obstructive pulmonary disease (COPD). Nine stable COPD patients (mean +/- SD forced expiratory volume in one second (FEV1) 0.91 +/- 0.31 l) were included in the study. The following measurements were performed before and 1 hour after lorazepam administration (doses: 1.5 to 2 mg) by sublingual route: forced vital capacity (FVC), FEV1, maximal voluntary ventilation (MVV), arterial oxygen tension (PaO2), arterial carbon dioxide tension (PaCO2), minute ventilation (Ve), tidal volume (Vt), respiratory rate (f), inspiratory time/inspiratory plus expiratory time (Ti/Ttot)-, mean inspiratory flow (Vi), maximal inspiratory (MIP) and expiratory (MEP) pressures, maximal pleural pressure (Pplmax), transdiaphragmatic pressures (Pdi) and skeletal muscle strength and endurance. As expected, no change was noted in FVC, FEV1, FEV1/FVC (Table-1). Besides stability of expiratory flows, this denotes no change in collaboration in spite of the sedative effects of lorazepam. There was a 20% decrease in Ve, due to a Vt reduction and a small increase in PaCO2. These could be explained by the central effects of benzodiazepines. Skeletal muscle strength and endurance decreased significantly (22 and 50% respectively-Table 2), in accordance with the previously reported muscular actions of this pharmacological group. Respiratory muscle function parameters, MIP, MEP, MVV and Ppl showed significant reductions (10 to 20 per cent), as was the case with diaphragmatic function measured by Pdi (Muller maneuver with abdominal protrussion and maximal open-glottis expulsive maneuver) (Table 3). This study demonstrates that a single lorazepam dose reduces strength and endurance of respiratory muscle in chronic stable COPD patients.