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

A Randomized Trial

  1. Marco Maggiorini, MD;
  2. Hans-Peter Brunner-La Rocca, MD;
  3. Simon Peth, MD;
  4. Manuel Fischler, MD;
  5. Thomas Böhm, MD;
  6. Alain Bernheim, MD;
  7. Stefanie Kiencke, MD;
  8. Konrad E. Bloch, MD;
  9. Christoph Dehnert, MD;
  10. Robert Naeije, MD, PhD;
  11. Thomas Lehmann, MD;
  12. Peter Bärtsch, MD; and
  13. Heimo Mairbäurl, PhD
  1. 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.

    Abstract

    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

    Article and Author Information

    • 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.

    Responses to this article

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    Summary for Patients

    • Summaries for Patients:A Comparison of Medications Used to Prevent High-Altitude Pulmonary Edema Ann Intern Med October 3, 2006 145:I-28
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