Messineo Ludovico, Sands Scott A, Labarca Gonzalo
Division of Sleep and Circadian Disorders, Department of Medicine, and Department of Neurology, Brigham & Women's Hospital and Harvard Medical School, Boston, Massachusetts; and.
Department of Respiratory Diseases, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.
Am J Respir Crit Care Med. 2024 Dec 15;210(12):1461-1474. doi: 10.1164/rccm.202403-0501OC.
Low arousal threshold and poor muscle responsiveness are common determinants of obstructive sleep apnea (OSA). Hypnotics were hypothesized as an alternative OSA treatment via raising the arousal threshold and possibly genioglossus responsiveness. To examine the effect of common hypnotics on arousal threshold, OSA severity, and genioglossus responsiveness. We searched MEDLINE, Embase, CENTRAL, and ClinicalTrials.gov for randomized clinical trials, and we ran meta-analyses to determine the effect of oral hypnotics on arousal threshold, OSA severity, and genioglossus responsiveness. The Grades of Recommendation Assessment, Development and Evaluation was used to rate the quality of evidence (QoE). The association between post-treatment apnea-hypopnea index (AHI) and arousal threshold percentage reductions was explored in individual patient data meta-analyses (overall sample and low arousal threshold subgroups). On the basis of our analysis (27 studies; 25 for AHI, 11 for arousal threshold, 4 for genioglossus responsiveness), hypnotics minimally raised arousal threshold (mean difference [95% confidence interval], 2.7 [1.5, 3.8] cm HO epiglottic pressure swings; moderate QoE) but did not change OSA severity (-1.4 [-3.5, 0.7] events/h; moderate QoE). Individual patient data meta-analysis ( = 114) showed no association between changes in arousal threshold and AHI, independent of arousal threshold subgrouping. However, people with very low arousal threshold or those who exhibited a 0-25% arousal threshold increase from placebo experienced the greatest, yet still modest, post-treatment AHI reductions (∼10%). Hypnotics did not affect genioglossus responsiveness (high QoE). Further research testing or clinical use of hypnotics as OSA alternative treatments should be discouraged, unless in the presence of comorbid insomnia or as part of combination therapy in individuals with very low arousal threshold.
低觉醒阈值和肌肉反应性差是阻塞性睡眠呼吸暂停（OSA）的常见决定因素。催眠药被认为是一种通过提高觉醒阈值以及可能提高颏舌肌反应性来治疗OSA的替代方法。为了研究常用催眠药对觉醒阈值、OSA严重程度和颏舌肌反应性的影响。我们检索了MEDLINE、Embase、CENTRAL和ClinicalTrials.gov上的随机临床试验，并进行荟萃分析以确定口服催眠药对觉醒阈值、OSA严重程度和颏舌肌反应性的影响。使用推荐评估、发展和评价分级来评定证据质量（QoE）。在个体患者数据荟萃分析（总体样本和低觉醒阈值亚组）中探讨了治疗后呼吸暂停低通气指数（AHI）与觉醒阈值降低百分比之间的关联。基于我们的分析（27项研究；25项针对AHI，11项针对觉醒阈值，4项针对颏舌肌反应性），催眠药仅轻微提高了觉醒阈值（平均差[95%置信区间]，2.7[1.5，3.8]cm HO会厌压力波动；中等QoE），但并未改变OSA严重程度（-1.4[-3.5，0.7]次/小时；中等QoE）。个体患者数据荟萃分析（n = 114）显示，觉醒阈值变化与AHI之间无关联，与觉醒阈值亚组划分无关。然而，觉醒阈值非常低或从安慰剂组出现0 - 25%觉醒阈值升高的患者，治疗后AHI降低幅度最大，但仍较小（约10%）。催眠药不影响颏舌肌反应性（高QoE）。除非存在合并失眠或作为觉醒阈值极低个体联合治疗的一部分，否则应不鼓励进一步开展将催眠药作为OSA替代治疗的研究测试或临床应用。
