Effect of Dexamethasone on Nocturnal Oxygenation in Lowlanders With Chronic Obstructive Pulmonary Disease Traveling to 3100 Meters
Authors: Michael Furian, Mona Lichtblau, Sayaka S. Aeschbacher, Bermet Estebesova, Berik Emilov, Ulan Sheraliev, Nuriddin H. Marazhapov, Maamed Mademilov, Batyr Osmonov, Maya Bisang, Stefanie Ulrich, Tsogyal D. Latshang, Silvia Ulrich, Talant M. Sooronbaev, Konrad E. Bloch
Journal: JAMA Network Open (2019)

<h3>Importance</h3> During mountain travel, patients with chronic obstructive pulmonary disease (COPD) are at risk of experiencing severe hypoxemia, in particular, during sleep. <h3>Objective</h3> To evaluate whether preventive dexamethasone treatment improves nocturnal oxygenation in lowlanders with COPD at 3100 m. <h3>Design, Setting, and Participants</h3> A randomized, placebo-controlled, double-blind, parallel trial was performed from May 1 to August 31, 2015, in 118 patients with COPD (forced expiratory volume in the first second of expiration [FEV<sub>1</sub>] &gt;50% predicted, pulse oximetry at 760 m ≥92%) who were living at altitudes below 800 m. The study was conducted at a university hospital (760 m) and high-altitude clinic (3100 m) in Tuja-Ashu, Kyrgyz Republic. Patients underwent baseline evaluation at 760 m, were taken by bus to the clinic at 3100 m, and remained at the clinic for 2 days and nights. Participants were randomized 1:1 to receive either dexamethasone, 4 mg, orally twice daily or placebo starting 24 hours before ascent and while staying at 3100 m. Data analysis was performed from September 1, 2015, to December 31, 2016. <h3>Interventions</h3> Dexamethasone, 4 mg, orally twice daily (dexamethasone total daily dose, 8 mg) or placebo starting 24 hours before ascent and while staying at 3100 m. <h3>Main Outcomes and Measures</h3> Difference in altitude-induced change in nocturnal mean oxygen saturation measured by pulse oximetry (Spo<sub>2</sub>) during night 1 at 3100 m between patients receiving dexamethasone and those receiving placebo was the primary outcome and was analyzed according to the intention-to-treat principle. Other outcomes were apnea/hypopnea index (AHI) (mean number of apneas/hypopneas per hour of time in bed), subjective sleep quality measured by a visual analog scale (range, 0 [extremely bad] to 100 [excellent]), and clinical evaluations. <h3>Results</h3> Among the 118 patients included, 18 (15.3%) were women; the median (interquartile range [IQR]) age was 58 (52-63) years; and FEV<sub>1</sub>was 91% predicted (IQR, 73%-103%). In 58 patients receiving placebo, median nocturnal Spo<sub>2</sub>at 760 m was 92% (IQR, 91%-93%) and AHI was 20.5 events/h (IQR, 12.3-48.1); during night 1 at 3100 m, Spo<sub>2</sub>was 84% (IQR, 83%-85%) and AHI was 39.4 events/h (IQR, 19.3-66.2) (<i>P</i> &lt; .001 both comparisons vs 760 m). In 60 patients receiving dexamethasone, Spo<sub>2</sub>at 760 m was 92% (IQR, 91%-93%) and AHI was 25.9 events/h (IQR, 16.3-37.1); during night 1 at 3100 m, Spo<sub>2</sub>was 86% (IQR, 84%-88%) (<i>P</i> &lt; .001 vs 760 m) and AHI was 24.7 events/h (IQR, 13.2-33.7) (<i>P</i> = .99 vs 760 m). Altitude-induced decreases in Spo<sub>2</sub>during night 1 were mitigated by dexamethasone vs placebo by a mean of 3% (95% CI, 2%-3%), and increases in AHI were reduced by 18.7 events/h (95% CI, 12.0-25.3). Similar effects were observed during night 2. Subjective sleep quality was improved with dexamethasone during night 2 by 12% (95% CI, 0%-23%). Sixteen (27.6%) patients using dexamethasone had asymptomatic hyperglycemia. <h3>Conclusions and Relevance</h3> In lowlanders in Central Asia with COPD traveling to a high altitude, preventive dexamethasone treatment improved nocturnal oxygen saturation, sleep apnea, and subjective sleep quality. <h3>Trial Registration</h3> ClinicalTrials.gov Identifier:NCT02450994