The effect of acetazolamide on sleep apnea at high altitude: A systematic review and meta-analysis

Background: Acetazolamide has been investigated for treating sleep apnea in newcomers ascending to high altitude. This study 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 July 2015 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.