Effect of Zolpidem on nocturnal arousals and susceptibility to central sleep apnea

Purpose Arousals may contribute to the pathogenesis of sleep-disordered breathing (SDB) and central sleep apnea (CSA). We aimed to determine the effect of the nonbenzodiazepine hypnotic zolpidem on the frequency of respiratory-related arousals and central apnea in patients with moderate-to-severe SDB. We hypothesized that zolpidem decreases the severity of SDB by decreasing the frequency of respiratory-related arousals. Methods Patients with apnea–hypopnea index ≥ 15 events/hour and central apnea–hypopnea index ≥ 5 events/hour underwent a sleep study on zolpidem 5 mg and a sleep study with no medication in a randomized order. The respiratory arousal index was compared between the two studies using a randomized crossover design. Sleep, respiratory, and physiologic parameters, including the CO 2 reserve and the respiratory arousal threshold, were also compared. Results Eleven participants completed the study. Compared to no treatment, zolpidem reduced the respiratory arousal index (39.7 ± 7.7 vs. 23.3 ± 4.4 events/h, P = 0.031). Zolpidem also lowered the total apnea–hypopnea index (55.6 ± 8.5 vs. 41.3 ± 7.5 events/hour, P = 0.033) but did not affect other clinical and physiologic parameters. Compared to control, zolpidem did not widen CO 2 reserve (− 0.44 ± 1.47 vs. − 0.63 ± 0.86 mmHg, P = 0.81). The respiratory arousal threshold did not show a significant change on zolpidem compared to control (− 8.72 ± 2.1 vs. − 8.25 ± 2.81 cmH 2 O, P = 0.41). Conclusion Nocturnal arousals and overall SDB severity were reduced with a single dose of zolpidem in patients with moderate-to-severe sleep-disordered breathing with increased susceptibility for central apnea. Zolpidem did not widen the CO 2 reserve or increase the arousal threshold. Trial Registration Clinicaltrials.gov. Sleep and Breathing in the General Population — Chemical Stimuli (NCT04720547).