Effect of Dexamethasone on Nocturnal Oxygenation in Lowlanders With Chronic Obstructive Pulmonary Disease Traveling to 3100 Meters: A Randomized Clinical Trial

Abstract

Importance: During mountain travel, patients with chronic obstructive pulmonary disease (COPD) are at risk of experiencing severe hypoxemia, in particular, during sleep.

Objective: To evaluate whether preventive dexamethasone treatment improves nocturnal oxygenation in lowlanders with COPD at 3100 m.

Design, setting, and participants: 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 [FEV1] >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.

Interventions: 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.

Main outcomes and measures: Difference in altitude-induced change in nocturnal mean oxygen saturation measured by pulse oximetry (Spo2) 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.

Results: Among the 118 patients included, 18 (15.3%) were women; the median (interquartile range [IQR]) age was 58 (52-63) years; and FEV1 was 91% predicted (IQR, 73%-103%). In 58 patients receiving placebo, median nocturnal Spo2 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, Spo2 was 84% (IQR, 83%-85%) and AHI was 39.4 events/h (IQR, 19.3-66.2) (P < .001 both comparisons vs 760 m). In 60 patients receiving dexamethasone, Spo2 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, Spo2 was 86% (IQR, 84%-88%) (P < .001 vs 760 m) and AHI was 24.7 events/h (IQR, 13.2-33.7) (P = .99 vs 760 m). Altitude-induced decreases in Spo2 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.

Conclusions and relevance: 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.

Trial registration: ClinicalTrials.gov Identifier: NCT02450994.

Conflict of interest statement

Conflict of Interest Disclosures: None reported.

Figures

Figure 1.. CONSORT Flowchart

COPD indicates chronic obstructive pulmonary disease.

Figure 2.. Effect of Altitude and Dexamethasone on Clinical and Physiologic Outcomes

A, Mean differences in altitude-induced changes in the first and second nights at 3100 m compared with the corresponding baseline examination at 760 m in patients receiving dexamethasone and placebo. For the top graph, negative changes favor 760 m. For the middle graph, positive changes favor 760 m. For the bottom graph, negative changes favor 760 m. B, Mean differences in altitude-induced changes measured at 3100 m between patients receiving dexamethasone and placebo (treatment effect of dexamethasone). For the top graph, positive changes favor dexamethasone. For the middle graph, negative changes favor dexamethasone. For the bottom graph, positive changes favor dexamethasone. Subjective sleep quality was assessed by a visual analog scale (range, 0 [extremely bad] to 100 [excellent]). Error bars indicate 95% CI. ODI indicates oxygen desaturation index >3% dips in arterial oxygen saturation; Spo2, mean nocturnal oxygen saturation assessed by pulse oximetry; and TIB, time in bed.