Effect of Acetazolamide and AutoCPAP Therapy on Breathing Disturbances Among Patients with Obstructive Sleep Apnea Syndrome Who Travel to Altitude: a Randomized Controlled Trial

Context: Many patients with obstructive sleep apnea syndrome (OSA) living near sea level travel to altitude, but this may expose them to hypoxemia and exacerbation of sleep apnea. The treatment in this setting is not established.

Objective: To evaluate whether acetazolamide and autoadjusted continuous positive airway pressure (autoCPAP) control breathing disturbances in OSA patients at altitude.

Design, Setting, And Participants: Randomized, placebo-controlled, double-blind, crossover trial involving 51 patients with OSA living below an altitude of 800 m and receiving CPAP therapy who underwent studies at a university hospital at 490 m and resorts in Swiss mountain villages at 1630 m and 2590 m in summer 2009.

Interventions: Patients were studied during 2 sojourns of 3 days each in mountain villages, 2 days at 1630 m, 1 day at 2590 m, separated by a 2-week washout period at less than 800 m. At altitude, patients either took acetazolamide (750 mg/d) or placebo in addition to autoCPAP.

Main Outcome Measures: Primary outcomes were nocturnal oxygen saturation and the apnea/hypopnea index; secondary outcomes were sleep structure, vigilance, symptoms, adverse effects, and exercise performance.

Results: Acetazolamide and autoCPAP treatment was associated with higher nocturnal oxygen saturation at 1630 m and 2590 m than placebo and autoCPAP: medians, 94% (interquartile range [IQR], 93%-95%) and 91% (IQR, 90%-92%) vs 93% (IQR, 92%-94%) and 89% (IQR, 87%-91%), respectively. Median increases were 1.0% (95% CI, 0.3%-1.0%) and 2.0% (95% CI, 2.0%-2.0). Median night-time spent with oxygen saturation less than 90% at 2590 m was 13% (IQR, 2%-38%) vs 57% (IQR, 28%-82%; P < .001). Acetazolamide and autoCPAP resulted in better control of sleep apnea at 1630 m and 2590 m than placebo and autoCPAP: median apnea/hypopnea index was 5.8 events per hour (5.8/h) (IQR, 3.0/h-10.1/h) and 6.8/h (IQR, 3.5/h-10.1/h) vs 10.7/h (IQR, 5.1/h-17.7/h) and 19.3/h (IQR, 9.3/h-29.0/h), respectively; median reduction was 3.2/h (95% CI, 1.3/h-7.5/h) and 9.2 (95% CI, 5.1/h-14.6/h).

Conclusion: Among patients with OSA spending 3 days at moderately elevated altitude, a combination of acetazolamide and autoCPAP therapy, compared with autoCPAP alone, resulted in improvement in nocturnal oxygen saturation and apnea/hypopnea index.

Trial Registration: clinicaltrials.gov Identifier: NCT00928655.