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

STUDY OBJECTIVES: The 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 are less well understood. METHODS: All controlled studies of acetazolamide in obstructive sleep apnea and/or central sleep apnea (CSA) were evaluated. The primary outcome was the apnea-hypopnea index. RESULTS: Fifteen trials with a total of 256 patients were pooled in our systematic review. Acetazolamide reduced the overall apnea-hypopnea index (mean difference [MD] -15.82, 95% CI: -21.91 to -9.74, P < .00001) in central sleep apnea (MD -22.60, 95% CI: -29.11 to -16.09, P < .00001), but not in obstructive sleep apnea (MD -10.29, 95% CI: -33.34 to 12.77, P = .38). Acetazolamide reduced the respiratory related arousal index (MD -0.82, 95% CI: -1.56 to -0.08, P = .03), improved partial arterial of oxygen (MD 11.62, 95% CI: 9.13-14.11, P < .00001), mean oxygen saturation (MD 1.78, 95% CI: 0.53-3.04, P = .005), total sleep time (MD 25.74, 95% CI: 4.10-47.38, P = .02), N2 sleep (MD 3.34, 95% CI: 0.12-6.56, P = .04) and sleep efficiency (MD 4.83, 95% CI: 0.53-9.13, P = .03). CONCLUSIONS: Acetazolamide improves the apnea-hypopnea index and several sleep metrics in central sleep apnea. 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. SYSTEMATIC REVIEW REGISTRATION: Registry: PROSPERO; Name: The effect of acetazolamide in patients with sleep apnea at sea level: a systematic review and meta analysis; URL: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020163316; Identifier: CRD42020163316.