Bachar Ahmad1, Abdulghani Sankari2,3,4, Mehdi Eshraghi1, Ahmad Aldwaikat1, Hossein Yarandi5, Salam Zeineddine1,6, Anan Salloum1,6, M Safwan Badr1,6. 1. Department of Internal Medicine, Wayne State University School of Medicine, 4646 John R, Detroit, MI, 48201, USA. 2. Department of Internal Medicine, Wayne State University School of Medicine, 4646 John R, Detroit, MI, 48201, USA. asankari@wayne.edu. 3. Department of Internal Medicine, John D. Dingell VA Medical Center, Detroit, MI, USA. asankari@wayne.edu. 4. Department of Medical Education, Ascension Providence Hospital, Southfield, MI, USA. asankari@wayne.edu. 5. Department of Biostatistics, Wayne State University School of Medicine, Detroit, MI, USA. 6. Department of Internal Medicine, John D. Dingell VA Medical Center, Detroit, MI, USA.
Abstract
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 CO2 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 CO2 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 cmH2O, 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 CO2 reserve or increase the arousal threshold. TRIAL REGISTRATION: Clinicaltrials.gov. Sleep and Breathing in the General Population - Chemical Stimuli (NCT04720547).
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 CO2 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 CO2 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 cmH2O, 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 CO2 reserve or increase the arousal threshold. TRIAL REGISTRATION: Clinicaltrials.gov. Sleep and Breathing in the General Population - Chemical Stimuli (NCT04720547).
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