Both tadalafil and dexamethasone may reduce the incidence of high-altitude pulmonary edema: a randomized trial

Ann Intern Med. 2006 Oct 3;145(7):497-506. doi: 10.7326/0003-4819-145-7-200610030-00007.


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. identifier: NCT00274430.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3',5'-Cyclic-GMP Phosphodiesterases / drug effects
  • Adult
  • Altitude Sickness / physiopathology
  • Altitude Sickness / prevention & control*
  • Blood Gas Analysis
  • Carbolines / therapeutic use*
  • Cyclic Nucleotide Phosphodiesterases, Type 5
  • Dexamethasone / therapeutic use*
  • Double-Blind Method
  • Female
  • Hemodynamics
  • Humans
  • Male
  • Phosphodiesterase Inhibitors / therapeutic use
  • Pulmonary Edema / physiopathology
  • Pulmonary Edema / prevention & control*
  • Sodium Channels / metabolism
  • Tadalafil
  • Vasodilator Agents / therapeutic use*


  • Carbolines
  • Phosphodiesterase Inhibitors
  • Sodium Channels
  • Vasodilator Agents
  • Tadalafil
  • Dexamethasone
  • 3',5'-Cyclic-GMP Phosphodiesterases
  • Cyclic Nucleotide Phosphodiesterases, Type 5
  • PDE5A protein, human

Associated data