Carter Sophie G, Carberry Jayne C, Grunstein Ronald R, Eckert Danny J
Neuroscience Research Australia (NeuRA) and the University of New South Wales, Sydney, NSW.
Neuroscience Research Australia (NeuRA) and the University of New South Wales, Sydney, NSW; Adelaide Institute for Sleep Health, Flinders University, Adelaide, SA.
Chest. 2020 Jul;158(1):374-385. doi: 10.1016/j.chest.2020.02.057. Epub 2020 Mar 18.
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 (7.5 mg) modestly reduced the AHI vs baseline without changing other sleep parameters or next-day sleepiness.
This study aimed to determine the effects of high-dose zopiclone (15 mg) on AHI, arousal threshold, genioglossus muscle responsiveness, and next-day alertness in selected people with OSA (low to moderate arousal thresholds without major overnight hypoxemia). We hypothesized 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.
Twenty-eight participants (AHI = 29 ± 20 events/h) suspected to have low to 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 15 mg of zopiclone or placebo at each visit according to a double-blind, randomized, crossover design. Each morning, subjective sleepiness and alertness via a driving simulator task were assessed.
The AHI did not change from placebo to zopiclone (-1.5 events/h; 95% CI, -6.6 to 3.5 events/h; P = .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.
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.
Australian New Zealand Clinical Trials Registry; No.: ACTRN12617000988358; URL: https://www.anzctr.org.au.
研究表明，标准剂量的催眠药可降低或不改变呼吸暂停低通气指数（AHI）或咽部肌肉活动。一项为期1个月的每晚服用佐匹克隆（7.5毫克）的试验与基线相比，AHI略有降低，且未改变其他睡眠参数或次日嗜睡情况。
本研究旨在确定高剂量佐匹克隆（15毫克）对选定的阻塞性睡眠呼吸暂停患者（低至中度觉醒阈值且无严重夜间低氧血症）的AHI、觉醒阈值、颏舌肌反应性及次日警觉性的影响。我们假设高剂量佐匹克隆会使觉醒阈值有更大提高，从而使AHI有更大降低，但可能以低氧血症增加和次日功能损害为代价。
对28名疑似低至中度觉醒阈值的参与者（AHI = 29±20次/小时）进行了两次实验室多导睡眠图检查，间隔1周，使用会厌压力导管和颏舌肌肌内电极。参与者根据双盲、随机、交叉设计，每次就诊时服用15毫克佐匹克隆或安慰剂。每天早晨，通过驾驶模拟器任务评估主观嗜睡和警觉性。
从安慰剂组到佐匹克隆组，AHI未发生变化（-1.5次/小时；95%CI，-6.6至3.5次/小时；P = 0.54）。佐匹克隆治疗后，觉醒阈值、颏舌肌反应性以及大多数其他睡眠参数和次日嗜睡及警觉性指标也未改变。
对于选定的阻塞性睡眠呼吸暂停患者，单晚服用高剂量佐匹克隆不会系统性地降低AHI或提高觉醒阈值。这些意外发现的机制需要进一步研究。
澳大利亚新西兰临床试验注册中心；编号：ACTRN12617000988358；网址：https://www.anzctr.org.au
