乙酰唑胺治疗阻塞性睡眠呼吸暂停和中枢性睡眠呼吸暂停：全面系统评价和荟萃分析。
Acetazolamide for OSA and Central Sleep Apnea: A Comprehensive Systematic Review and Meta-Analysis.
机构信息
Division of Pulmonary, Critical Care and Sleep Medicine, University of California, San Diego, CA.
Sleep and Circadian Medicine Laboratory, Department of Physiology, School of Biomedical Sciences and Biomedical Discovery Institute, Monash University, Melbourne, VIC, Australia; Turner Institute for Brain and Mental Health, Monash University, Melbourne, VIC, Australia.
出版信息
Chest. 2020 Dec;158(6):2632-2645. doi: 10.1016/j.chest.2020.06.078. Epub 2020 Aug 5.
BACKGROUND
Therapy options for OSA and central sleep apnea (CSA) are limited, thus many patients remain untreated. Clinically, acetazolamide is sometimes used for CSA; however, given overlapping pathophysiologic properties of OSA and CSA, we hypothesized that acetazolamide is equally effective for both types. Prior reviews focused on specific subtypes of sleep apnea, study designs, and languages, thus including few studies (typically ≤3) limiting insights.
RESEARCH QUESTION
How efficacious is acetazolamide for sleep apnea, and is its effect modified by sleep apnea type or acetazolamide dose?
STUDY DESIGN AND METHODS
We queried MEDLINE, EMBASE, and ClinicalTrials.gov from inception until March 11, 2019. Any study in which adults with OSA/CSA received oral acetazolamide vs no acetazolamide (control) that reported sleep apnea-related outcomes was eligible, independent of study design or language. Two reviewers independently assessed eligibility and abstracted data. Primary outcomes were apnea-hypopnea index (AHI) and oxygen saturation nadir. Quality of evidence (QoE) was rated with the use of Grades of Recommendation Assessment, Development and Evaluation methods.
RESULTS
We included 28 studies (13 OSA/15 CSA; N = 542; N = 553) that enabled meta-analyses for 24 outcomes. Acetazolamide doses ranged from 36 to 1000 mg/d and treatment duration from 1 to 90 d (median, 6 d). Overall, acetazolamide vs control lowered the AHI by -0.7 effect sizes (95% CI, -0.83 to -0.58; I = 0%; moderate QoE) that corresponded to a reduction of 37.7% (95% CI, -44.7 to -31.3) or 13.8/h (95% CI, -16.3 to -11.4; AHI = 36.5/h). The AHI reduction was similar in OSA vs CSA, but significantly greater with higher doses (at least up to 500 mg/d). Furthermore, acetazolamide improved oxygen saturation nadir by +4.4% (95% CI, 2.3 to 6.5; I = 63%; no evidence of effect modification; very low QoE) and several secondary outcomes that included sleep quality measures and BP (mostly low QoE).
INTERPRETATION
Short-term acetazolamide improved both OSA and CSA. Rigorous studies with long-term follow up are warranted to assess Acetazolamide's value for the chronic treatment of patients with sleep apnea.
CLINICAL TRIAL REGISTRATION
PROSPERO (CRD42019147504).
背景
阻塞性睡眠呼吸暂停（OSA）和中枢性睡眠呼吸暂停（CSA）的治疗选择有限，因此许多患者未得到治疗。临床上，有时会使用乙酰唑胺治疗 CSA；然而，鉴于 OSA 和 CSA 具有重叠的病理生理特性，我们假设乙酰唑胺对这两种类型同样有效。先前的综述侧重于特定类型的睡眠呼吸暂停、研究设计和语言，因此只包括少数研究（通常≤3 项），限制了我们的深入了解。
研究问题
乙酰唑胺治疗睡眠呼吸暂停的效果如何？其效果是否受睡眠呼吸暂停类型或乙酰唑胺剂量的影响？
研究设计和方法
我们检索了 MEDLINE、EMBASE 和 ClinicalTrials.gov 从成立到 2019 年 3 月 11 日的数据。任何纳入成人 OSA/CSA 患者接受口服乙酰唑胺与无乙酰唑胺（对照组）治疗并报告与睡眠呼吸暂停相关的结局的研究均符合纳入标准，无论研究设计或语言如何。两位审查员独立评估纳入标准并提取数据。主要结局是呼吸暂停-低通气指数（AHI）和氧饱和度最低点。使用推荐评估、制定和评价方法（Grades of Recommendation Assessment, Development and Evaluation，GRADE）对证据质量（Quality of Evidence，QoE）进行评级。
结果
我们纳入了 28 项研究（13 项 OSA/15 项 CSA；N=542；N=553），这些研究可进行 24 项结局的荟萃分析。乙酰唑胺剂量范围为 36 至 1000mg/d，治疗持续时间为 1 至 90d（中位数为 6d）。总体而言，乙酰唑胺与对照组相比，AHI 降低了 0.7 个效应大小（95%置信区间为-0.83 至-0.58；I=0%；中等 QoE），相当于降低了 37.7%（95%置信区间为-44.7 至-31.3）或 13.8/h（AHI=36.5/h）。在 OSA 与 CSA 中，AHI 降低的效果相似，但高剂量时降低效果更显著（至少在 500mg/d 以上）。此外，乙酰唑胺可将氧饱和度最低点提高 4.4%（95%置信区间为 2.3 至 6.5；I=63%；无效应修饰的证据；非常低的 QoE），并改善了多项次要结局，包括睡眠质量测量和血压（大多是低 QoE）。
结论
短期乙酰唑胺可改善 OSA 和 CSA。需要进行长期随访的严格研究来评估乙酰唑胺在治疗睡眠呼吸暂停患者的慢性治疗中的价值。
临床试验注册
PROSPERO（CRD42019147504）。
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