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Preliminary Communication |

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

Tsogyal D. Latshang, MD; Yvonne Nussbaumer-Ochsner, MD; Rahel M. Henn, BMS; Silvia Ulrich, MD; Christian M. Lo Cascio, MD; Bruno Ledergerber, PhD; Malcolm Kohler, MD; Konrad E. Bloch, MD
JAMA. 2012;308(22):2390-2398. doi:10.1001/jama.2012.94847.
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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

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Figures

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Figure 1. Patient Flow
Grahic Jump Location

aPatients were allocated to 1 of 4 altitude exposure sequences by letting them select 1 of the available study time slots according to preference. Neither the patient nor the coordinator was aware of the sequence details at the time of allocation. CPAP indicates continuous positive airway pressure; /h, events per hour; ODI, oxygen desaturation index.

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Figure 2. Effects of Acetazolamide at Altitude
Grahic Jump Location

Median differences (and 95% CIs) between outcomes assessed during treatment with acetazolamide plus autoadjusted continuous positive airway pressure (autoCPAP) minus corresponding values on placebo plus autoCPAP are shown for studies at 1630 m and 2590 m, respectively. AHI indicates apnea/hypopnea index; SpO2, oxygen saturation; 1/h, events per hour. Polarity of axes is selected for each outcome so that a favorable effect of acetazolamide is shown to the right of the vertical line representing zero difference.

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