Acetazolamide to prevent ventilatory drive withdrawal in REM sleep apnoea: a randomised controlled trial.

The carbonic anhydrase inhibitor acetazolamide is known to increase ventilatory drive and improve OSA severity.

碳酸酐酶抑制剂乙酰唑胺已知可以增加通气驱动并改善OSA的严重程度。

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).

因此，我们测试了乙酰唑胺对REM主导型OSA严重程度（呼吸暂停低通气指数（AHI）和低氧负荷，主要共同结果）和潜在生理机制（通气驱动、通气和咽部肌肉活动）的影响。

Methods

11 participants with REM-predominant OSA per baseline polysomnography (REM AHI/non-REM AHI≥2) were allocated to receiving acetazolamide 500 mg for three nights (first night at half dose) or placebo according to a randomised, crossover, double-blinddesign.

根据基线多导睡眠图（REM AHI/非REM AHI≥2），11名REM主导型OSA患者被分配接受乙酰唑胺500毫克，连续三个晚上（第一晚为半剂量）或安慰剂，采用随机、交叉、双盲设计。

Detailed physiological polysomnography with recording of diaphragm and genioglossus electromyography was conducted after each intervention, with a 1-week washout in between.

每次干预后，都进行了详细的生理多导睡眠图记录，包括膈肌和下颌舌骨肌肌电图，并在之间进行了1周的洗脱期。

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.

正如所假设的，与安慰剂相比，乙酰唑胺将AHI降低了35.5%（95% CI 23.1%至46.3%）并将低氧负荷降低了35.9%（95% CI 21.1%至48.4%）（p<0.001），满足了主要终点。

Mechanistic analysis in REM revealed that, unexpectedly, acetazolamide did not mitigate dips in ventilatory drive versus placebo (first decile (+0.1 (-1.0 to 1.3) L/min, p=0.8).

在REM中的机制分析显示，出乎意料的是，与安慰剂相比，乙酰唑胺并没有减轻通气驱动的下降（第一十分位数（+0.1（-1.0至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).

相反，乙酰唑胺降低了塌陷性（在正常通气驱动下增加通气：+1.4（1.2至1.8）L/min）并提高了肌肉反应性（通气与驱动斜率：+32（25至41）%通气/驱动，p<0.001；下颌舌骨肌与驱动斜率：+0.33（0.13至0.54）%最大值/（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.

乙酰唑胺适度改善了REM OSA，对上气道生理学有显著改善，但未能缓解导致REM OSA的通气驱动下降。

trial_registration_number

NCT05589792.

NCT05589792。