The role of acetazolamide in sleep apnea at sea level: a systematic review and meta-analysis.

Abstract

BACKGROUND\nThe recognition of specific endotypes as drivers of sleep apnea suggests the need of therapies targeting individual mechanisms. Acetazolamide is known to stabilize respiration at high-altitude but benefits at sea-level is less well understood.\n\n\nMETHODS\nAll controlled studies of acetazolamide in obstructive sleep apnea (OSA) and/or central sleep apnea (CSA) were evaluated. The primary outcome was the apnea-hypopnea index (AHI).\n\n\nRESULTS\nFifteen trials with a total of 256 patients were pooled in our systematic review. Acetazolamide reduced the overall AHI (mean difference [MD] -15.82, 95% CI: -21.91 ∼ -9.74, p < 0.00001) in CSA (MD -22.60, 95% CI: -29.11 ∼ -16.09, p < 0.00001), but not in OSA (MD -10.29, 95% CI: -33.34 ∼ 12.77, p = 0.38). Acetazolamide reduced the respiratory related arousal index (MD -0.82, 95% CI: -1.56 ∼ -0.08, p = 0.03), improved partial arterial of oxygen (MD 11.62, 95% CI: 9.13 ∼ 14.11, p < 0.00001), mean oxygen saturation (MD 1.78, 95% CI: 0.53 ∼ 3.04, p = 0.005), total sleep time (MD 25.74, 95% CI: 4.10 ∼ 47.38, p = 0.02), N2 sleep (MD 3.34, 95% CI: 0.12 ∼ 6.56, p = 0.04) and sleep efficiency (MD 4.83, 95% CI: 0.53 ∼ 9.13, p = 0.03).\n\n\nCONCLUSIONS\nAcetazolamide improves the AHI and several sleep metrics in CSA. The drug may be of clinical benefit in patients with high loop gain apnea of various etiologies and patterns. The existence of high heterogeneity is an important limitation in applicability of our analysis.\n\n\nSYSTEMATIC REVIEW REGISTRATION\nRegistry: PROSPERO, Identifier: CRD42020163316, URL: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020163316.