Nocturnal cerebral oxygenation in patients with COPD at altitude: data from a randomized clinical trial of acetazolamide

Patients with chronic obstructive pulmonary disease (COPD) may experience cerebral tissue deoxygenation during altitude travel, especially during sleep. We quantified nocturnal cerebral (CTO) and arterial oxygenation (SpO2) in patients with COPD during a stay at 3100 meters and evaluated the effects of preventive acetazolamide therapy. Patients with moderate to severe COPD, living < 800 meters, underwent nocturnal pulse oximetry and cerebral tissue oximetry by near-infrared spectroscopy at 760 meters and during the first night at 3100 meters. Patients were randomized to 375 mg/day acetazolamide or placebo starting 24 hours before ascent and while staying at 3100 meters. Altitude and acetazolamide effects on CTO and other outcomes were evaluated by mixed linear regression analysis. Forty-three patients, 9 female, mean±SD age 55.4±8.9 years, FEV1 60±13% predicted, were included in the analysis. When ascending from 760 to 3100 meters taking placebo (N=17), CTO and SpO2 decreased from 66.5±1.0% to 63.4±1.0% (P<0.05) and from 90.8±0.4% to 83.7±0.4% (P<0.05), respectively; cerebral (cODI) and arterial (aODI) oxygen desaturation indices (≥4% dips in CTO or SpO2, respectively) increased by a mean(95%CI) of 6.2/h (4.0 to 8.5) and 19.5/h (13.2 to 25.9); (P<0.05). Compared to placebo, the mean CTO (+2.3% [2.2 to 2.5]) and SpO2 (+2.1% [2.1 to 2.2]) were higher and the mean cODI (-4.4/h [-7.3 to -1.5]) and aODI (-15.0/h [-23.1 to -6.9]) were lower in the acetazolamide group, P<0.05 all effects. Patients with COPD travelling to 3100 meters experienced sustained and intermittent nocturnal cerebral deoxygenation related to hypoxemia. Acetazolamide mitigated these altitude-related deoxygenations, albeit not to lowland values. Registry: ClinicalTrials.gov; Identifier: NCT03156231.