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


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


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


METHODS
29 adults with previous HAPE.


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


METHODS
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.


CONCLUSIONS
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.
Maggiorini
Marco
M
University Hospital Zürich, Zürich, Switzerland; Université de Bruxelles, Brussels, Belgium. klinmax@usz.unizh.ch
Brunner-La Rocca
Hans-Peter
HP
Peth
Simon
S
Fischler
Manuel
M
Böhm
Thomas
T
Bernheim
Alain
A
Kiencke
Stefanie
S
Bloch
Konrad E
KE
Dehnert
Christoph
C
Naeije
Robert
R
Lehmann
Thomas
T
Bärtsch
Peter
P
Mairbäurl
Heimo
H
D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000187:drug effects; D000328:Adult; D000532:Altitude Sickness / Q000503:physiopathology / Q000517:prevention & control*; D001784:Blood Gas Analysis; D002243:Carbolines / Q000627:therapeutic use*; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D003907:Dexamethasone / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006439:Hemodynamics; D006801:Humans; D008297:Male; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use; D011654:Pulmonary Edema / Q000503:physiopathology / Q000517:prevention & control*; D015222:Sodium Channels / Q000378:metabolism; D000068581:Tadalafil; D014665:Vasodilator Agents / Q000627:therapeutic use*
D002243:Carbolines; D010726:Phosphodiesterase Inhibitors; D015222:Sodium Channels; D014665:Vasodilator Agents; D000068581:Tadalafil; D003907:Dexamethasone; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; C517381:PDE5A protein, human