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乙酰唑胺预防REM睡眠呼吸暂停中通气驱动撤除：随机对照试验

Acetazolamide to prevent ventilatory drive withdrawal in REM sleep apnoea: a randomised controlled trial
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本研究为随机、双盲、交叉设计，纳入11例REM优势型阻塞性睡眠呼吸暂停（OSA）患者，比较乙酰唑胺500mg（首夜半量）与安慰剂各3晚的效果。结果显示，乙酰唑胺显著降低呼吸暂停低通气指数（AHI）35.5%和低氧负担35.9%，但未改善REM期通气驱动低谷，而是通过降低上气道可塌陷性和增强肌肉反应性起作用。

要点

  • 乙酰唑胺显著降低REM优势型OSA的AHI和低氧负担，但未消除通气驱动低谷。
  • 机制上，乙酰唑胺改善上气道塌陷性和肌肉反应性，而非通气驱动。
  • 适用于REM优势型OSA，但效果温和，需权衡获益与风险。

核心结论

  • 乙酰唑胺中度改善REM OSA，主要通过改善上气道生理功能，而非缓解通气驱动低谷。

研究设计与样本

  • 随机、双盲、交叉设计，11例REM优势型OSA患者（REM AHI/非REM AHI≥2），乙酰唑胺500mg（首夜半量）或安慰剂各3晚，洗脱期1周。

主要发现

  • 与安慰剂相比，乙酰唑胺降低AHI 35.5%（95%CI 23.1%-46.3%），低氧负担降低35.9%（95%CI 21.1%-48.4%），p<0.001。
  • REM期通气驱动第一十分位变化+0.1 L/min（95%CI -1.0至1.3），p=0.8，无显著差异。

关键数值与推荐

  • 呼气驱动下通气量增加+1.4 L/min（95%CI 1.2-1.8），p<0.001。
  • 通气对驱动斜率增加+32%（95%CI 25-41%），p<0.001；颏舌肌对驱动斜率增加+0.33 %max/(L/min)（95%CI 0.13-0.54），p=0.001。

临床怎么用

  • 临床可考虑用于REM优势型OSA，但需监测疗效和不良反应，因未改善通气驱动机制。

局限性

  • 样本量较小，为11例，且为短期干预（3晚），长期疗效和安全性未知。

以上解读依据论文摘要（全文未开放获取或许可不允许翻译转载）。

原文

Background Obstructive sleep apnoea (OSA) pathogenesis during rapid-eye movement (REM) sleep has been linked to dips in ventilatory drive and downstream genioglossus hypotonia. The carbonic anhydrase inhibitor acetazolamide is known to increase ventilatory drive and improve OSA severity. Therefore, we tested the effect of acetazolamide on REM-predominant OSA severity (apnoea hypopnoea index (AHI) and hypoxic burden, co-primary outcomes) and underlying physiological mechanisms (ventilatory drive, ventilation and pharyngeal muscle activity). Methods 11 participants with REM-predominant OSA per baseline polysomnography (REM AHI/non-REM AHI&ge;2) were allocated to receiving acetazolamide 500 mg for three nights (first night at half dose) or placebo according to a randomised, crossover, double-blind design. Detailed physiological polysomnography with recording of diaphragm and genioglossus electromyography was conducted after each intervention, with a 1-week washout in between. Results As hypothesised, acetazolamide reduced AHI by 35.5% (95% CI 23.1% to 46.3%) and hypoxic burden by 35.9% (95% CI 21.1% to 48.4%) vs placebo (p<0.001), meeting the primary endpoint. Mechanistic analysis in REM revealed that, unexpectedly, acetazolamide did not mitigate dips in ventilatory drive versus placebo (first decile (+0.1 (&ndash;1.0 to 1.3) L/min, p=0.8). Rather, acetazolamide reduced collapsibility (increased ventilation at eupneic drive: +1.4 (1.2 to 1.8) L/min) and raised muscle responsiveness (ventilation vs drive slope: +32 (25 to 41) % ventilation/drive , p<0.001; genioglossus versus drive slope: +0.33 (0.13 to 0.54) %max/(L/min), p=0.001). Conclusions Acetazolamide modestly improved REM OSA, with meaningful improvements in upper airway physiology, but failed to mitigate the dips in ventilatory drive responsible for REM OSA. Trial registration number NCT05589792 .

来源：Thorax，查看原文。版权归原作者所有。

引用

  1. Thorax：Acetazolamide to prevent ventilatory drive withdrawal in REM sleep apnoea: a randomised controlled trial
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供执业医师工作参考，不替代临床判断；数值与分级以指南原文为准。