Acute effects of zolpidem, triazolam and flunitrazepam on arterial blood gases and control of breathing in severe COPD

Abstract

Patients with severe chronic obstructive pulmonary disease (COPD) commonly complain of insomnia, but hypnotic drugs are generally not recommended due to their depressant effect on the respiratory centres. The aim of this study was, therefore, to compare the effects of a single dose of the benzodiazepine hypnotics, triazolam 0.25 mg and flunitrazepam 1 mg, and a new imidazopyridine compound, zolpidem 10 mg, in hypercapnic COPD patients. Twelve stable COPD patients (mean ± SD arterial oxygen tension (Pao2) 9.3 ± 0.8 kPa and arterial carbon dioxide tension (Paco2) 5.9 ± 1.9 kPa) were included in the study. The following measurements were performed before and 2 h after drug administration: Pao2 and Paco2, minute ventilation (V̇E), mouth occlusion pressure (P0.1), rebreathing CO2 tests with ventilatory response to carbon dioxide stimulation (ΔV̇E/ΔPaco2) and mouth occlusion pressure response to carbon dioxide stimulation (ΔP0.1/ ΔPaco2). The measurements were performed in a randomized, double-blind fashion, each patient receiving a single dose of each drug on three different days, separated by a one week interval. No difference was noted between control measurements and those taken 2 h after administration of zolpidem in the following parameters: Pao2, Paco2, V̇E, P0.1, ΔV̇E/ΔPaco2 and ΔP0.1/Paco2. Two hours after administration of triazolam and flunitrazepam, a significant difference was noted in V̇E for triazolam and for flunitrazepam. After flunitrazepam administration, a significant decrease in Paco2 (6 ± 1.8 at baseline versus 7 ± 0.4 kPa), and ΔV̇E/Paco2 (0.44 ± 0.20 at baseline versus 0.31 ± 0.21 l·min-1·kPa) were observed. Pao2 also decreased after flunitrazepam from 7.8 ± 1 to 7.4 ± 0.9 kPa. This study demonstrates that when given at a single equivalent dose, the hypnotic drug zolpidem has no significant effect on arterial blood gases and control of breathing in severe COPD patients, in contrast to triazolam and flunitrazepam.