Acetazolamide and AutoCPAP Therapy for Patients with Obstructive Sleep Apnea Syndrome Who Travel to

Acetazolamide and AutoCPAP Therapy for Patients with Obstructive Sleep Apnea Syndrome Who Travel to Altitude
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Rebecca M. Baron
M.D., Pulmonary Division, Brigham and Women's Hospital
Joseph Loscalzo
M.D., Ph.D., Chairman, Department of Medicine, Brigham and Women's Hospital, Hersey Professor of the Theory and Practice of Medicine, Harvard Medical School, Boston

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[TD]Obstructive sleep apnea (OSA) manifests as repeated nocturnal airway closures producing episodic hypoxemia; it can lead to systemic hypertension, pulmonary hypertension, cardiac arrhythmias, and daytime hypersomnolence. It is widely believed that continuous positive airway pressure (CPAP) is currently the most effective therapy for OSA. With transition from sea level to moderate to high altitude, it has been reported that patients with untreated OSA experience worsened hypoxemia, sleep-disordered breathing, and secondary consequences, and that acetazolamide partially improves OSA at high altitude. Latshang and colleagues (2012), therefore, set out to determine whether autoadjusted CPAP (autoCPAP) combined with acetazolamide would provide superior benefit for OSA subjects with a brief exposure to moderate altitude, compared with autoCPAP alone.


A total of 51 subjects with moderate to severe OSA ascended from low to moderate altitude for 3 days twice; they received autoCPAP plus acetazolamide on one trip, and autoCPAP plus placebo on the other trip. The primary outcomes were nocturnal oxygen saturation and the apnea/hypopnea index (AHI) measured by polysomnography. The investigators found that at moderate altitudes (2590 m and 1630 m, compared with baseline 490 m), autoCPAP plus acetazolamide resulted in higher nocturnal oxygen saturations and an improved AHI compared with autoCPAP alone, with an even greater benefit of acetazolamide observed at the higher altitude. There were additional benefits of autoCPAP plus acetazolamide, including improved sleep efficiency, fewer nocturnal arousals, fewer symptoms of mountain sickness, and lower blood pressure. Mild side effects of acetazolamide were reported in 30% of subjects and included altered taste and paresthesias, although there were no reported serious adverse events.
Strengths of the study include the randomized, placebo-controlled, crossover design and analysis of the effect of autoCPAP combined with acetazolamide versus autoCPAP alone, given prior data supporting a partial benefit of acetazolamide in treating OSA exacerbations at moderate altitude. Unanswered questions with regard to the study relate to the sole use of autoCPAP: it is uncertain whether autoCPAP is necessary for benefit, or whether use of fixed CPAP settings would be sufficient. Additionally, the investigators acknowledge that they studied only middle-aged male subjects at moderate altitude for 3 days, and, therefore, it has not been evaluated whether the findings apply to a broader population of patients who might reside at higher altitudes for longer periods of time. Interestingly, the mechanism of enhanced benefit of the combination of acetazolamide and autoCPAP is uncertain but might relate in part to amelioration of altitude-induced pulmonary edema that, in turn, can exacerbate OSA. Regardless of the precise mechanism, this study demonstrates a superior benefit of autoCPAP plus acetazolamide in alleviating OSA at moderate altitude compared with autoCPAP alone and supports the notion of prescribing additional support for OSA patients at risk for altitude-related exacerbations.

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[TD="class: contentReference"] Reference

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[TD="class: contentBody"]Latshang TD et al. Effect of acetazolamide and autoCPAP therapy on breathing disturbances among patients with obstructive sleep apnea syndrome who travel to altitude: A randomized controlled trial. JAMA 2012;308:2390. [PMID: 23232895] [Full Text]
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