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Dexamethasone improves pulmonary hemodynamics in COPD-patients going to altitude: A randomized trial


Lichtblau, Mona; Furian, Michael; Aeschbacher, Sayaka S; Bisang, Maya; Ulrich, Stefanie; Saxer, Stéphanie; Sheraliev, Ulan; Marazhapov, Nuriddin H; Osmonov, Batyr; Estebesova, Bermet; Sooronbaev, Talant; Bloch, Konrad E; Ulrich, Silvia (2019). Dexamethasone improves pulmonary hemodynamics in COPD-patients going to altitude: A randomized trial. International Journal of Cardiology, 283:159-164.

Abstract

Background Chronic obstructive pulmonary disease (COPD) may predispose to symptomatic pulmonary hypertension at high altitude. We investigated hemodynamic changes in lowlanders with COPD ascending rapidly to 3100 m and evaluated whether preventive dexamethasone treatment would mitigate the altitude-induced increase in pulmonary artery pressure. Methods In this placebo-controlled, double-blind trial, non-hypercapnic COPD patients living <800 m, were randomized to receive either dexamethasone (8 mg/day) or placebo tablets one day before ascent from 760 m and during a 3-day-stay at 3100 m. Echocardiography was performed at 760 m and after the first night at 3100 m. The trans-tricuspid pressure gradient (RV/RA, main outcome), cardiac output (Q) by velocity-time integral of left ventricular outflow, indices of right and left heart function, blood gases and pulse-oximetry (SpO2) were compared between groups. Results 95 patients, 79 men, mean ± SD age 57 ± 8y FEV1 89 ± 21% pred, SpO2 95 ± 2% were included in the analysis. In 52 patients receiving dexamethasone, RV/RA, Q and SpO2 at 760 and 3100 m were 19 ± 5 mm Hg and 26 ± 7 mm Hg, 4.9 ± 0.7 and 5.7 ± 1.1 l/min, SpO2 95 ± 2% and 90 ± 3% (P < 0.05 all changes). In 43 patients receiving placebo the corresponding values were 20 ± 4 mm Hg and 31 ± 9 mm Hg, 4.7 ± 0.9 l/min and 95 ± 3% and 89 ± 3% (P < 0.05 all changes) between group differences of altitude-induced changes were (mean, 95% CI): RV/RA −4.8 (−7.7 to −1.8) mm Hg, Q 0.13 (−0.3 to 0.6) l/min and SpO2 1 (−1 to 2) %. Conclusions In lowlanders with COPD travelling to 3100 m preventive dexamethasone treatment mitigates the altitude-induced rise in RV/RA potentially along with a reduced pulmonary vascular resistance and improved oxygenation. Abbreviation 6MWD six-minute-walking distance BMI body mass index CI confidence interval COPD chronic obstructive pulmonary disease eNOS endothelial NO synthase FAC fractional area change FEV1 forced expiratory volume in 1 s FVC forced vital capacity GOLD global Initiative for Chronic Obstructive Lung Disease HAPE high altitude pulmonary edema HPV hypoxic pulmonary vasoconstriction mPAP mean pulmonary arterial pressure NO nitric oxide PaO2 partial pressure of oxygen in arterial blood PAP pulmonary artery pressure PAWP pulmonary artery wedge pressure PH pulmonary hypertension Q cardiac output RAP right atrial pressure RV right ventricle RV-ESPAR right ventricular end-systolic pressure-area relation sPAP systolic pulmonary artery pressure SpO2 oxygen saturation SV stroke volume TAPSE tricuspid annular plane systolic excursion RV/RA trans-tricuspid or right ventricular to right atrial pressure gradient Keywords COPD Dexamethasone Hypobaric hypoxia Altitude Pulmonary artery pressure Hemodynamics

Abstract

Background Chronic obstructive pulmonary disease (COPD) may predispose to symptomatic pulmonary hypertension at high altitude. We investigated hemodynamic changes in lowlanders with COPD ascending rapidly to 3100 m and evaluated whether preventive dexamethasone treatment would mitigate the altitude-induced increase in pulmonary artery pressure. Methods In this placebo-controlled, double-blind trial, non-hypercapnic COPD patients living <800 m, were randomized to receive either dexamethasone (8 mg/day) or placebo tablets one day before ascent from 760 m and during a 3-day-stay at 3100 m. Echocardiography was performed at 760 m and after the first night at 3100 m. The trans-tricuspid pressure gradient (RV/RA, main outcome), cardiac output (Q) by velocity-time integral of left ventricular outflow, indices of right and left heart function, blood gases and pulse-oximetry (SpO2) were compared between groups. Results 95 patients, 79 men, mean ± SD age 57 ± 8y FEV1 89 ± 21% pred, SpO2 95 ± 2% were included in the analysis. In 52 patients receiving dexamethasone, RV/RA, Q and SpO2 at 760 and 3100 m were 19 ± 5 mm Hg and 26 ± 7 mm Hg, 4.9 ± 0.7 and 5.7 ± 1.1 l/min, SpO2 95 ± 2% and 90 ± 3% (P < 0.05 all changes). In 43 patients receiving placebo the corresponding values were 20 ± 4 mm Hg and 31 ± 9 mm Hg, 4.7 ± 0.9 l/min and 95 ± 3% and 89 ± 3% (P < 0.05 all changes) between group differences of altitude-induced changes were (mean, 95% CI): RV/RA −4.8 (−7.7 to −1.8) mm Hg, Q 0.13 (−0.3 to 0.6) l/min and SpO2 1 (−1 to 2) %. Conclusions In lowlanders with COPD travelling to 3100 m preventive dexamethasone treatment mitigates the altitude-induced rise in RV/RA potentially along with a reduced pulmonary vascular resistance and improved oxygenation. Abbreviation 6MWD six-minute-walking distance BMI body mass index CI confidence interval COPD chronic obstructive pulmonary disease eNOS endothelial NO synthase FAC fractional area change FEV1 forced expiratory volume in 1 s FVC forced vital capacity GOLD global Initiative for Chronic Obstructive Lung Disease HAPE high altitude pulmonary edema HPV hypoxic pulmonary vasoconstriction mPAP mean pulmonary arterial pressure NO nitric oxide PaO2 partial pressure of oxygen in arterial blood PAP pulmonary artery pressure PAWP pulmonary artery wedge pressure PH pulmonary hypertension Q cardiac output RAP right atrial pressure RV right ventricle RV-ESPAR right ventricular end-systolic pressure-area relation sPAP systolic pulmonary artery pressure SpO2 oxygen saturation SV stroke volume TAPSE tricuspid annular plane systolic excursion RV/RA trans-tricuspid or right ventricular to right atrial pressure gradient Keywords COPD Dexamethasone Hypobaric hypoxia Altitude Pulmonary artery pressure Hemodynamics

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Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Pneumology
Dewey Decimal Classification:610 Medicine & health
Scopus Subject Areas:Health Sciences > Cardiology and Cardiovascular Medicine
Uncontrolled Keywords:Cardiology and Cardiovascular Medicine
Language:English
Date:1 May 2019
Deposited On:25 Jan 2019 10:39
Last Modified:29 Jul 2020 09:19
Publisher:Elsevier
ISSN:0167-5273
OA Status:Closed
Publisher DOI:https://doi.org/10.1016/j.ijcard.2018.12.052
PubMed ID:30638985
Project Information:
  • : FunderSNSF
  • : Grant ID320030_143875
  • : Project TitlePatients with chronic obstructive pulmonary disease at altitude
  • : FunderSNSF
  • : Grant ID32003B_172980
  • : Project TitleAcetazolamide for prevention of altitude related illness in patients with chronic obstructive pulmonary disease (COPD). Randomized, placebo-controlled, double-blind trial.
  • : FunderFP7
  • : Grant ID201502
  • : Project TitleCHILD-INNOVAC - NASAL VACCINATION AGAINST RESPIRATORY INFECTIONS IN YOUNG CHILDREN

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