BACKGROUND Recent studies indicate that standard doses of hypnotics reduce or do not change the apnea-hypopnea index (AHI) or pharyngeal muscle activity. A 1-month trial of nightly zopiclone (7.5mg) modestly reduced the AHI versus baseline without changing other sleep parameters or next-day sleepiness. RESEARCH QUESTION This study aimed to determine the effects of high-dose zopiclone (15mg) on AHI, arousal threshold, genioglossus muscle responsiveness and next-day alertness in selected people with obstructive sleep apnea (OSA) (low-moderate arousal thresholds without major overnight hypoxemia). We hypothesised that high-dose zopiclone would yield greater increases in arousal threshold and therefore larger reductions in AHI but may come at the expense of increased hypoxemia and next-day impairment. STUDY DESIGN and methods: 28 participants (AHI=29±20events/h) suspected to have low-moderate arousal thresholds were studied during two in-laboratory polysomnographies, separated by 1-week, with an epiglottic pressure catheter and genioglossus intramuscular electrodes. Participants received 15mg of zopiclone or placebo at each visit according to a double-blind, randomized, cross-over design. Each morning subjective sleepiness and alertness via a driving simulator task were assessed. RESULTS The AHI did not change from placebo to zopiclone (-1.5events/h, 95% CI: -6.6, 3.5events/h; p=0.54). Arousal threshold, genioglossus muscle responsiveness and most other sleep parameters and measures of next-day sleepiness and alertness also did not change with zopiclone. INTERPRETATION A single night of treatment with high-dose zopiclone does not systematically reduce the AHI or increase the arousal threshold in selected people with OSA. The mechanisms for these unexpected findings require further investigation.

中文翻译：

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大剂量佐匹克隆对 OSA 严重程度、上呼吸道生理和警觉性影响的随机试验

背景 最近的研究表明，标准剂量的催眠药会降低或不改变呼吸暂停低通气指数 (AHI) 或咽肌活动。一项为期 1 个月的夜间佐匹克隆 (7.5mg) 试验在不改变其他睡眠参数或第二天嗜睡的情况下适度降低了 AHI 与基线相比。研究问题 本研究旨在确定高剂量佐匹克隆 (15mg) 对特定阻塞性睡眠呼吸暂停 (OSA) 患者的 AHI、觉醒阈值、颏舌肌反应性和次日警觉性的影响（低中度觉醒阈值，无重大过夜）低氧血症）。我们假设高剂量佐匹克隆会产生更大的觉醒阈值增加，因此 AHI 减少更大，但可能以增加低氧血症和次日损伤为代价。研究设计和方法：28 名参与者（AHI = 29±20 事件/小时）被怀疑具有中低唤醒阈值，在两次实验室多导睡眠监测中进行了研究，间隔 1 周，使用会厌压力导管和颏舌肌肌内电极。根据双盲、随机、交叉设计，参与者在每次访问时接受 15 毫克佐匹克隆或安慰剂。每天早上通过驾驶模拟器任务评估主观嗜睡和警觉性。结果 从安慰剂到佐匹克隆，AHI 没有变化（-1.5 个事件/小时，95% CI：-6.6，3.5 个事件/小时；p=0.54）。佐匹克隆的觉醒阈值、颏舌肌反应性和大多数其他睡眠参数以及次日嗜睡和警觉性的测量也没有改变。解释 使用高剂量佐匹克隆进行一晚治疗并不能系统地降低特定 OSA 患者的 AHI 或增加觉醒阈值。这些意外发现的机制需要进一步调查。