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Randomized Controlled Trial
. 2023 Mar;27(1):173-180.
doi: 10.1007/s11325-022-02593-3. Epub 2022 Mar 14.

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

Bachar Ahmad  1 , Abdulghani Sankari  2   3   4 , Mehdi Eshraghi  1 , Ahmad Aldwaikat  1 , Hossein Yarandi  5 , Salam Zeineddine  1   6 , Anan Salloum  1   6 , M Safwan Badr  1   6
Affiliations
Randomized Controlled Trial

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

Bachar Ahmad et al. Sleep Breath. 2023 Mar.

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).

Keywords: Ambien; Central sleep apnea; Polysomnography; Sleep-disordered breathing; Zolpidem.

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Conflict of interest statement

Conflict of interest The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Primary endpoint and main clinical outcomes following zolpidem treatment for n = 10 participants for R-ArI, AHI, and total ArI, and n = 8 for CAHI. CAHI for the two participants with CAHI < 5 events/hour at baseline who were recruited based on the presence of narrow CO2 were not included in the analysis. Gray and white boxplots represent the interquartile ranges and medians (solid lines) of the number of events for the no treatment condition and the zolpidem condition, respectively. The dashed lines represent the mean number of events, and individual data points are overlayed on the boxplots. *P-value ≤ 0.05. R-ArI; respiratory arousal index, ArI: arousal index, AHI: apnea–hypopnea index; CAHI: central apnea–hypopnea index
Fig. 2
Fig. 2
Effect of zolpidem on the arousal threshold calculated (n = 4). Symbols represent individual participants, and horizontal bars represent the group average for each treatment condition. No statistical significance was found in the crossover analysis
Fig. 3
Fig. 3
Effect of Zolpidem on the CO2 reserve for n = 8 participants. Symbols represent individual participants, and horizontal bars represent the group average for each treatment condition. No statistical significance was found in the crossover analysis
See this image and copyright information in PMC

References

    1. Tietjens JR, Claman D, Kezirian EJ et al. (2019) Obstructive sleep apnea in cardiovascular disease: a review of the literature and proposed multidisciplinary clinical management strategy. J Am Heart Assoc 8(1):e010440. 10.1161/JAHA.118.010440 - DOI - PMC - PubMed
    1. Drager LF, McEvoy RD, Barbe F, Lorenzi-Filho G, Redline S (2017) INCOSACT Initiative (International Collaboration of Sleep Apnea Cardiovascular Trialists) Sleep apnea and cardiovascular disease: lessons from recent trials and need for team science. Circulation 136(19):1840–1850. 10.1161/CIRCULATIONAHA.117.029400 - DOI - PMC - PubMed
    1. Aurora RN, Chowdhuri S, Ramar K, et al. The treatment of central sleep apnea syndromes in adults: practice parameters with an evidence-based literature review and meta-analyses. Sleep. 2012;35(1):17–40. Published 2012 Jan 1. 10.5665/sleep.1580 - DOI - PMC - PubMed
    1. Bradley TD, Logan AG, Kimoff RJ et al. (2005) Continuous positive airway pressure for central sleep apnea and heart failure. N Engl J Med 353(19):2025–2033. 10.1056/NEJMoa051001 - DOI - PubMed
    1. Bordier P, Lataste A, Hofmann P, Robert F, Bourenane G (2016) Nocturnal oxygen therapy in patients with chronic heart failure and sleep apnea: a systematic review. Sleep Med 17:149–157. 10.1016/j.sleep.2015.10.017 - DOI - PubMed

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