Effect of acetazolamide on obstructive sleep apnea in highlanders: a randomized, placebo-controlled, double-blinded crossover trial

<bold>Introduction:</bold> Acetazolamide (ACZ) improves obstructive sleep apnea (OSA) at sea level and apnea in newcomers exposed to high altitude. However, the effect of ACZ on sleep-disordered breathing in highlanders remains unclear. <bold>Methods:</bold> In a randomized, placebo-controlled, double-blind crossover trial, fourty-one patients with moderate-to-severe OSA permanently living in Lhasa (3650m) recieved either 500mg/day ACZ or placebo for 2 weeks each, separated by a 1-week washout between interventions. Overnight lab-polysomnography, self-reported sleep and clinical evaluation were carried out in before and at the end of each treatment period. The primary outcome was the difference in apnea/hypopnea index (AHI) between ACZ and placebo. <bold>Results:</bold> The per-protocol analysis included 34 participants with mean±SE age 37±1years and BMI 25.2±0.4kg/m2. With placebo, mean±SE values for total AHI, obstructive AHI and mean oxygen saturation were 50.8±4.8/h, 45.7±3.8/h and 83.2±0.5%, respectively. With ACZ, the corresponding values were 34.8±4.8/h, 27.6±3.8/h, and 85.8±0.5% (P<0.05 all vs. placebo). In the intention-to-treat analysis (41 patients), ACZ decreased total AHI by a mean of 13.1/h (95%CI, 4.2 to 22.0), obstructive AHI by 15.2/h (95%CI, 8.3 to 22.0), and increased SpO2 by 2.6% (95%CI, 1.8 to 3.4) (P<0.05 all vs. placebo). Both objective sleep and subjective sleep quality were improved with ACZ. <bold>Conclusion:</bold> In highlanders with OSA, ACZ significantly reduced the severity of sleep-disordered breathing and improved nocturnal oxygenation, as well as sleep quality. ACZ may be an alternative treatment for highlanders with OSA when positive airway pressure is not available.