Effects of acetazolamide on respiratory events and sleep in highlanders with obstructive sleep apnoea: a randomised controlled trial

Introduction Acetazolamide improves sleep apnoea in people living at low altitude and newcomers ascending to high altitude. However, its effects in permanent highlanders with obstructive sleep apnoea (OSA) remain unclear. Methods We analysed data from a randomised, placebo-controlled double-blind crossover trial of 41 patients with untreated moderate-to-severe OSA living in Lhasa (3650 m). Participants received 2-week acetazolamide (500 mg/day) and placebo in randomised order, separated by a 1-week washout. Overnight lab-polysomnography, self-reported sleep and clinical evaluation were carried out at the end of each treatment period. The primary outcome was the difference in apnoea/hypopnoea index (AHI) between acetazolamide and placebo. Results The intention-to-treat analysis including 41 patients, 35 (85%) were male, with a mean±SD age of 37±6 years and a body mass index of 25.2±2.7 kg/m2. Acetazolamide reduced total and obstructive AHI by a mean (95% CI) of 15.5 events/hour (7.1 to 23.9) and 16.6 events/hour (9.9 to 23.4), respectively, corresponding to an approximately one-third reduction in AHI compared with placebo. A similar result was found for the per-protocol population. Mean nocturnal peripheral capillary oxygen saturation increased by 3% (95% CI 2% to 4%) with acetazolamide, rising from 83±3% to 86±3%. Additionally, subjective sleep quality improved by 7% (2% to 13%) with acetazolamide, accompanied by significant increases in non-rapid eye movement stage 2 sleep and sleep efficiency (all p<0.05). Discussion In highlanders with OSA, acetazolamide significantly reduced the severity of sleep-disordered breathing, improved nocturnal oxygenation and subjective and objective sleep quality. Acetazolamide may serve as an adjunctive treatment option, particularly when continuous positive airway pressure therapy is not feasible. Trial registration number ChiCTR2100049304.