期刊
JOURNAL OF PHYSIOLOGY-LONDON
卷 598, 期 20, 页码 4681-4692出版社
WILEY
DOI: 10.1113/JP280173
关键词
hypnotics; pharmacotherapy and lung; phenotypes; sleep disordered breathing; upper airway physiology
资金
- NeuroSleep, a National Health and Medical Research Council (NHMRC) of Australia Centre for Research Excellence [1060992]
- NHMRC of Australia Fellowship [1116942]
- American Heart Association [19CDA34660137]
- American Academy of SleepMedicine Foundation [188-SR-17]
- National Health and Medical Research Council of Australia [1116942] Funding Source: NHMRC
Key points A decreased respiratory arousal threshold is one of the main contributors to obstructive sleep apnoea (OSA) pathogenesis. Several recent studies have sought to find a drug capable of increasing the respiratory arousal threshold without impairing pharyngeal muscle activity to reduce OSA severity, with variable success. Here we show that zolpidem increases the respiratory arousal threshold by similar to 15%, an effect size which was insufficient to systematically decrease OSA severity as measured by the apnoea-hypopnoea index. Unlike recent physiological findings that showed paradoxical increases in pharyngeal muscle responsiveness during transient manipulations of airway pressure, zolpidem did not alter pharyngeal muscle responsiveness during natural sleep. It did, however, increase sleep efficiency without changing apnoea length, oxygen desaturation, next-day perceived sleepiness and alertness. These novel findings indicate that zolpidem was well tolerated and effective in promoting sleep in people with OSA, which may be therapeutically useful for people with OSA and comorbid insomnia. A recent physiology study performed using continuous positive airway pressure (CPAP) manipulations indicated that the hypnotic zolpidem increases the arousal threshold and genioglossus responsiveness in people with and without obstructive sleep apnoea (OSA). Thus, zolpidem may stabilise breathing and reduce OSA severity without CPAP. Accordingly, we sought to determine the effects of zolpidem on OSA severity, upper airway physiology and next-day sleepiness and alertness. Nineteen people with OSA with low-to-moderate arousal threshold received 10 mg zolpidem or placebo according to a double-blind, randomised, cross-over design. Participants completed two overnight in-laboratory polysomnographies (1-week washout), with an epiglottic catheter, intramuscular genioglossus electromyography, nasal mask and pneumotachograph to measure OSA severity, arousal threshold and upper airway muscle responsiveness. Next-morning sleepiness and alertness were also assessed. Zolpidem did not change the apnoea-hypopnoea indexversusplacebo (40.6 +/- 12.3vs. 40.3 +/- 16.4 events/h (means +/- SD),p = 0.938) or nadir oxyhaemoglobin saturation (79.6 +/- 6.6vs. 79.7 +/- 7.4%, p = 0.932), but was well tolerated. Zolpidem increased sleep efficiency by 9 +/- 14% (83 +/- 11vs. 73 +/- 17%,p = 0.010). Arousal threshold increased by 15 +/- 5% with zolpidem throughout all sleep stages (p = 0.010), whereas genioglossus muscle responsiveness did not change. Next-morning sleepiness and alertness were not different between nights. In summary, a single night of 10 mg zolpidem is well tolerated and does not cause next-day impairment in alertness or sleepiness, or overnight hypoxaemia in OSA. However, despite increases in arousal threshold without any change in pharyngeal muscle responsiveness, zolpidem does not alter OSA severity. It does, however, increase sleep efficiency by similar to 10%, which may be beneficial in people with OSA and insomnia.
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