Acetazolamide對於高海拔睡眠呼吸中止症之應用：系統性回顧與統合分析

目標：Acetazolamide除了被應用於預防及治療急性高山症，近年來也經常有研究探討其能否改善初至高海拔地區旅客的夜間睡眠呼吸中止情形，但目前應用acetazolamide治療高海拔睡眠呼吸中止症的成效及有效劑量仍未有共識，主要受限於先前研究樣本數較小及研究間介入的差異，且缺乏相關的統合文獻發表。本研究目的為利用系統性文獻回顧及統合分析方法，探討acetazolamide對於高海拔睡眠呼吸中止症之成效和有效劑量，並比較阻塞型睡眠呼吸中止症患者與健康受試者間是否有療效上的差異。方法：搜尋PubMed、Embase、Scopus、Cochrane Library及Airiti Library等資料庫，最後搜尋時間為 2016 年 10 月，無語言限制。納入條件包含：隨機對照試驗、受試者居住於低海拔地區且無罹患阻塞型睡眠呼吸中止症以外的疾病、試驗執行於海拔 2500 公尺以上地區、試驗介入為acetazolamide並執行睡眠研究。高海拔睡眠呼吸中止症的主要測量指標為睡眠呼吸障礙指數及陣發性睡眠呼吸中止百分比，次要測量指標為夜間血氧飽和度。結果：納入 8 篇文獻做系統性回顧及統合分析，共包含 190 位成人。在健康受試者中，acetazolamide對於睡眠呼吸障礙指數、陣發性睡眠呼吸中止百分比及夜間血氧飽和度的影響分別為減少 34.66 ( 95% 信賴區間 25.01 - 44.30 )與低異質性( p = 0.7，I2 = 0% )、減少 38.56% ( 95% 信賴區間 18.92 - 58.19% )與低異質性( p = 0.24，I2 = 28% )及增加 4.75% ( 95% 信賴區間 1.35 – 8.15% )與高異質性( p < 0.01，I2 = 87% )。在阻塞型睡眠呼吸中止症患者中，acetazolamide對於睡眠呼吸障礙指數及夜間血氧飽和度的影響分別為減少 13.18 ( 95% 信賴區間 9.25 – 17.10 )與低異質性( p = 0.33，I2 = 0% )及增加 1.85% ( 95% 信賴區間 1.08 – 2.62% )與低異質性( p = 0.56，I2 = 0% )。結論：Acetazolamide減少睡眠呼吸障礙指數及陣發性睡眠呼吸中止百分比，並提升夜間血氧飽和度以改善高海拔睡眠呼吸中止症。Acetazolamide對於健康受試者的效果比阻塞型睡眠呼吸中止症患者更佳，就現有研究證據而言，每天250毫克的口服劑量可能是健康受試者的最低有效劑量。

關鍵字

acetazolamide ；海拔；睡眠呼吸中止

並列摘要

Background: Besides the prevention and treatment of acute mountain sickness, acetazolamide has also been recently investigated for treating sleep apnea in newcomers ascending to high altitude. However, the efficacy and optimal dose of acetazolamide for improving sleep apnea at high altitude remain unclear due to the limited number of cases and methodological differences in existing studies and have not been systematically reviewed to date. This systematic review and meta-analysis aimed to assess the effect of acetazolamide on sleep apnea at high altitude, determine the optimal therapeutic dose, and compare its effectiveness in healthy trekkers and obstructive sleep apnea (OSA) patients. Methods: PubMed, Embase, Scopus, Cochrane Library, and Airiti Library databases were searched up to October 2016 for randomized controlled trials (RCTs) performed above 2500 m in lowlanders and that used acetazolamide as intervention in sleep studies. Studies including participants with medical conditions other than OSA were excluded. Results: Eight studies of 190 adults were included. In healthy participants, the pooled mean effect sizes of acetazolamide on Apnea Hypopnea Index (AHI), percentage of periodic breathing time, and nocturnal oxygenation were 34.66 [95% confidence interval (CI) 25.01– 44.30] with low heterogeneity (p = 0.7, I2 = 0%), 38.56% (95% CI 18.92–58.19%) with low heterogeneity (p = 0.24, I2 = 28%), and 4.75% (95% CI 1.35–8.15%) with high heterogeneity (p < 0.01, I2 = 87%), respectively. In OSA patients, the pooled mean effect sizes of acetazolamide on AHI and nocturnal oxygenation were 13.18 (95% CI 9.25–17.1) with low heterogeneity (p = 0.33, I2 = 0%) and 1.85% (95% CI 1.08–2.62%) with low heterogeneity (p =0.56, I2 = 0%). Conclusions: Acetazolamide improves sleep apnea at high altitude by decreasing AHI and percentage of periodic breathing time and increasing nocturnal oxygenation. Acetazolamide is more beneficial in healthy participants than in OSA patients, and a 250 mg daily dose may be as effective as higher daily doses for healthy trekkers.

並列關鍵字

acetazolamide ； altitude ； sleep apnea syndromes

參考文獻

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延伸閱讀

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Acetazolamide對於高海拔睡眠呼吸中止症之應用：系統性回顧與統合分析

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