Combination Therapy Alleviates Sleep Apnea at High Altitudes

Adding the respiratory stimulant acetazolamide (Diamox) to automated continuous positive airway pressure (autoCPAP) gave patients with obstructive sleep apnea better nocturnal oxygen saturation and lower apnea indices when they were at high altitudes, a randomized, placebo-controlled study found.

“Effect of Acetazolamide and AutoCPAP Therapy on Breathing Disturbances Among Patients With Obstructive Sleep Apnea Syndrome Who Travel to Altitude” is published in the Dec. 12 Journal of the American Medical Association.

Read abstract.

The combination led to a 1% (95% CI 0.3 to 1, P<0.001) increase in nocturnal oxygen saturation at an altitude of 1,630 meters — 1 mile — and to a 2% (95% CI 2.0 to 2.0, P<0.001) increase at an elevation 0f 2,590 meters (1.6 miles), according to Konrad E. Bloch, MD, and colleagues from University Hospital of Zurich in Switzerland.

In addition, the median reductions in the apnea/hypopnea index at those two elevations were 3.2 per hour (95% CI 1.3 to 7.5, P<0.001) and 9.2 per hour (95% CI 5.1 to 14.6, P<0.001), respectively, the researchers reported.

Many patients with obstructive sleep apnea enjoy recreational activities involving travel to mountainous areas, and if they normally reside in low altitudes, they can experience exacerbations of their condition.

In a previous study, these researchers found that acetazolamide, which typically is used to remedy acute mountain sickness, helped maintain oxygen saturation among patients with sleep apnea at high altitudes, but failed to fully control breathing and disturbances of sleep.

Therefore, to see if combining the pharmacologic therapy with computer-controlled CPAP would produce better results, they enrolled 51 patients with a verified diagnosis of obstructive sleep apnea.

The participants were predominantly male, with a median age of 63 and a median body mass index of 33. All were receiving CPAP therapy.

They had moderate-to-severe sleep apnea, which was almost exclusively obstructive rather than central.

Baseline assessments were done in Zurich, which lies at an altitude of 490 meters (about 1,600 feet), while the moderately high altitude assessments were done in two Alpine locations.

During 3-day trips to the higher elevations, participants were given either 750 mg acetazolamide or placebo in addition to their CPAP treatment.

Along with improvements in oxygen saturation and the apnea/hypopnea index, benefits also were seen with the combination treatment in sleep efficiency and length of deep, non-REM sleep.

Polysomnographic evaluations suggested that worsening of the apnea among patients receiving placebo was primarily because of increases in central apnea/hypopnea events, while obstructive events appeared to remain stable.

Daytime sleepiness did not differ significantly between the acetazolamide and placebo groups and performance on psychomotor tests was similar, although the active treatment group reported less nocturnal wakefulness.

The active treatment also was associated with decreases in weight and blood pressure (P<0.001) and with improvements at the highest altitude on various measures of pulmonary function such as forced vital capacity and forced expiratory volume in 1 second (P<0.001).

These findings reflected the effects of treatment on preventing the accumulation of fluid in the lungs, which can happen even in healthy individuals at very high altitudes, the researchers explained.

Small numbers of participants reported side effects of unpleasant taste and paresthesias with the relatively high doses of acetazolamide used in the study, but no severe adverse events were seen.

The optimal dosage remains to be established, the researchers noted.

“The combined therapy with acetazolamide and autoCPAP provided an almost complete control of sleep apnea at altitude and a better oxygenation than autoCPAP alone with a major reduction in the time spent with an oxygen saturation less than 90%,” they wrote.

At 2,590 meters, oxygen saturation was below 90% for 13% of the time with active treatment, compared with 57% of the time with placebo (P<0.001).

“Alleviating hypoxemia at rest and during exercise at altitude by acetazolamide may potentially contribute to reducing the risk of adverse effects of altitude exposure, in particular in patients with [obstructive sleep apnea] and cardiovascular comorbidities,” they concluded.

Limitations of the study included its predominantly male, middle-age population whose comorbidities were stable, so it is unknown if the effects extend to other groups or to even higher altitudes.

Source: Journal of the American Medical Association

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