Cerebral Oxygenation in Patients With OSA: Effects of Hypoxia at Altitude and Impact of Acetazolamide

Study Questions:

Can acetazolamide mitigate the altitude-related reduction in cerebral oxygenation in obstructive sleep apnea (OSA) patients?

Methods:

Men and women ages 20-80 years with known OSA on continuous positive airway pressure (CPAP) were recruited in 2008. Exclusions included ambulatory nocturnal oxygen desaturation (>3%), mild OSA (apnea/hypopnea index [AHI] <10) after withdraw of CPAP; unstable cardiovascular, pulmonary, or medical conditions; or drugs that interfere with sleep or breathing. Nocturnal polysomnography was performed at baseline and at altitudes listed. Subjects received acetazolamide (500 mg/d) or placebo in a randomized, placebo-controlled, double-blind, crossover fashion at the two altitudes. Subjects discontinued CPAP at baseline and during two different trips (3 days each) to 1,860 (2 days) m and 2590 m (1 day), each trip separated by a 2-week washout. Cerebral tissue oxygenation (CTO) was measured by near-infrared spectroscopy.

Results:

A total of 75 subjects were recruited and after exclusions, agreement to participate, and technical issues, 18 patients (one woman) completed the study. Study subjects were middle-aged (average 61 years [58-65]), overweight, and body mass index was 32 kg/m2 (31-38). The average AHI after CPAP withdraw was 57.3/hour (46.5-67.3). Acetazolamide increased CTO and SpO22 at 2590 m by mean values of 2% (95% confidence interval [CI], 0%-4%) and 2% (95% CI, 1%-3%), respectively, and reduced the AHI by 23.4/hour (95% CI, 14.0-32.8/hour) (p < 0.05, all changes).

Conclusions:

The authors concluded that acetazolamide can partially improve CTO in patients with sleep apnea.

Perspective:

Hypoxia associated with sleep breathing disorders may impair CTO. Nocturnal arterial oxygen saturation can be improved in patients with OSA treated with acetazolamide during high altitude stays. Metabolic acidosis associated with consequences of acetazolamide can lead to hyperventilation and increased oxygenation. There remains a concern for reduction of cerebral blood flow due to potential vasoconstriction from hyperventilation and hypocapnia. This is the first study to show that acetazolamide does not have undesirable reduction in cerebral blood flow, and in fact, partially improves CTO at altitudes in patients with severe OSA.

Keywords: Spectroscopy, Near-Infrared, Overweight, Vasoconstriction, Hyperventilation, Body Mass Index, Polysomnography, Continuous Positive Airway Pressure, Hypocapnia, Confidence Intervals, Oxygen, Sleep Apnea, Obstructive


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