Both Tadalafil and Dexamethasone May Reduce the Incidence of High-Altitude Pulmonary Edema

A Randomized Trial

3 October 2006 | Volume 145 Issue 7 | Pages 497-506

Background: High-altitude pulmonary edema (HAPE) is caused by exaggerated hypoxic pulmonary vasoconstriction associated with decreased bioavailability of nitric oxide in the lungs and by impaired reabsorption of alveolar fluid.

Objective: To investigate whether dexamethasone or tadalafil reduces the incidence of HAPE and acute mountain sickness (AMS) in adults with a history of HAPE.

Design: Randomized, double-blind, placebo-controlled study performed in summer 2003.

Setting: Ascent from 490 m within 24 hours and stay for 2 nights at 4559 m.

Patients: 29 adults with previous HAPE.

Intervention: Prophylactic tadalafil (10 mg), dexamethasone (8 mg), or placebo twice daily during ascent and stay at 4559 m.

Measurements: Chest radiography was used to diagnose HAPE. A Lake Louise score greater than 4 defined AMS. Systolic pulmonary artery pressure was measured by using Doppler echocardiography, and nasal potentials were measured as a surrogate marker of alveolar sodium transport.

Results: Two participants who received tadalafil developed severe AMS on arrival at 4559 m and withdrew from the study; they did not have HAPE at that time. High-altitude pulmonary edema developed in 7 of 9 participants receiving placebo and 1 of the remaining 8 participants receiving tadalafil but in none of the 10 participants receiving dexamethasone (P = 0.007 for tadalafil vs. placebo; P < 0.001 for dexamethasone vs. placebo). Eight of 9 participants receiving placebo, 7 of 10 receiving tadalafil, and 3 of 10 receiving dexamethasone had AMS (P = 1.0 for tadalafil vs. placebo; P = 0.020 for dexamethasone vs. placebo). At high altitude, systolic pulmonary artery pressure increased less in participants receiving dexamethasone (16 mm Hg [95% CI, 9 to 23 mm Hg]) and tadalafil (13 mm Hg [CI, 6 to 20 mm Hg]) than in those receiving placebo (28 mm Hg [CI, 20 to 36 mm Hg]) (P = 0.005 for tadalafil vs. placebo; P = 0.012 for dexamethasone vs. placebo). No statistically significant difference between groups was found in change in nasal potentials and expression of leukocyte sodium transport protein messenger RNA.

Limitations: The study involved a small sample of adults with a history of HAPE.

Conclusions: Both dexamethasone and tadalafil decrease systolic pulmonary artery pressure and may reduce the incidence of HAPE in adults with a history of HAPE. Dexamethasone prophylaxis may also reduce the incidence of AMS in these adults.

ClinicalTrials.gov identifier: NCT00274430

Editors' Notes Context Very few trials have evaluated ways to prevent high-altitude pulmonary edema (HAPE). Contribution In this double-blind trial, 29 adults with a history of HAPE were randomly assigned to receive prophylactic tadalafil, dexamethasone, or placebo during a 24-hour ascent and 2-day stay at 4559 m. Compared with placebo recipients, adults taking dexamethasone less often experienced acute mountain sickness and those taking either dexamethasone or tadalafil less often had HAPE. Cautions The trial involved a small number of selected adults who rapidly ascended to a high altitude. Implications Either tadalafil or dexamethasone might help prevent HAPE in mountaineers with a history of pulmonary edema. —The Editors

 

Author and Article Information

From University Hospital Zürich, Zürich, University Hospital Basel, Basel, and Kantonsspital Chur, Chur, Switzerland; Université de Bruxelles, Brussels, Belgium; and Medical Clinic VII, University of Heidelberg, Heidelberg, Germany.

Acknowledgments: The authors thank the study participants; the hut keepers and the Sezione Varallo of the Club Alpino Italiano for providing an excellent research facility at the Capanna Regina Margherita; Sonja Engelhardt, Christiane Herth, and Hanna Bosshard for expert technical assistance; and Toshiba Switzerland AG for providing ultrasonic equipment.

Grant Support: By the Hartmann-Müller Foundation, the Pierluigi Crivelli Foundation, and the Anna Fedderson-Wagner Fonds (Switzerland).

Potential Financial Conflicts of Interest: None disclosed.

Requests for Single Reprints: Marco Maggiorini, MD, Intensive Care Unit, Department of Internal Medicine, University Hospital Zürich, Rämistrasse 100, CH-8091 Zürich, Switzerland; e-mail, klinmax{at}usz.unizh.ch.

Author Contributions: Conception and design: M. Maggiorini, H.-P. Brunner-La Rocca, P. Bärtsch, H. Mairbäurl.

Analysis and interpretation of the data: M. Maggiorini, H.-P. Brunner-La Rocca, S. Peth, A. Bernheim, S. Kiencke, K.E. Bloch, R. Naeije, P. Bärtsch, H. Mairbäurl.

Drafting of the article: M. Maggiorini, S. Peth, P. Bärtsch, H. Mairbäurl.

Critical revision of the article for important intellectual content: M. Maggiorini, H.-P. Brunner-La Rocca, K.E. Bloch, R. Naeije, P. Bärtsch, H. Mairbäurl.

Final approval of the article: M. Maggiorini, H.-P. Brunner-La Rocca, M. Fischler, T. Böhm, A. Bernheim, S. Kiencke, K.E. Bloch, T. Lehmann, R. Naeije, P. Bärtsch, H. Mairbäurl.

Provision of study materials or patients: M. Maggiorini, A. Bernheim.

Statistical expertise: M. Maggiorini.

Obtaining of funding: M. Maggiorini, P. Bärtsch, H. Mairbäurl.

Administrative, technical, or logistic support: M. Maggiorini, H.-P. Brunner-La Rocca, T. Böhm, C. Dehnert, P. Bärtsch, H. Mairbäurl.

Collection and assembly of data: M. Maggiorini, H.-P. Brunner-La Rocca, S. Peth, M. Fischler, T. Böhm, A. Bernheim, S. Kiencke, K.E. Bloch, C. Dehnert, R. Naeije, T. Lehmann.

Current Author Addresses: Dr. Maggiorini: Intensive Care Unit, Department of Internal Medicine, University Hospital Zürich, Rämistrasse 100, CH-8091 Zürich, Switzerland.

Drs. Brunner-La Rocca, Bernheim, and Kiencke: Department of Cardiology, University Hospital Basel, Petersgraben 4, CH-4031 Basel, Switzerland.

Drs. Peth, Dehnert, Bärtsch, and Mairbäurl: Medical Clinic VII, Sports Medicine, University Hospital Heidelberg, Im Neuenheimer Feld 410, D-69120 Heidelberg, Germany.

Dr. Fischler: Department of Internal Medicine, University Hospital Zürich, Rämistrasse 100, CH-8091 Zürich, Switzerland.

Dr. Böhm: Department of Radiology, Kantonsspital, CH-7000 Chur, Switzerland.

Dr. Bloch: Division of Pneumology, Department of Internal Medicine, University Hospital Zürich, Rämistrasse 100, CH-8091 Zürich, Switzerland.

Dr. Naeije: Department of Physiology, Erasme Campus CP 604, 808 Lennik Road, B-1070 Brussels, Belgium.

Dr. Lehmann: Department of Internal Medicine, Kantonsspital, CH-7000 Chur, Switzerland.

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