Sildenafil citrate for the prevention of high altitude hypoxic pulmonary hypertension: double blind, randomized, placebo-controlled trial

High Alt Med Biol. 2011 Fall;12(3):207-14. doi: 10.1089/ham.2011.0007.

Abstract

Exaggerated hypoxic pulmonary vasoconstriction is a key factor in the development of high altitude pulmonary edema (HAPE). Due to its effectiveness as a pulmonary vasodilator, sildenafil has been proposed as a prophylactic agent against HAPE. By conducting a parallel-group double blind, randomized, placebo-controlled trial, we investigated the effect of chronic sildenafil administration on pulmonary artery systolic pressure (PASP) and symptoms of acute mountain sickness (AMS) during acclimatization to high altitude. Sixty-two healthy lowland volunteers (36 male; median age 21 years, range 18 to 31) on the Apex 2 research expedition were flown to La Paz, Bolivia (3650 m), and after 4-5 days acclimatization ascended over 90 min to 5200 m. The treatment group (n=20) received 50 mg sildenafil citrate three times daily. PASP was recorded by echocardiography at sea level and within 6 h, 3 days, and 1 week at 5200 m. AMS was assessed daily using the Lake Louise Consensus symptom score. On intention-to-treat analysis, there was no significant difference in PASP at 5200 m between sildenafil and placebo groups. Median AMS score on Day 2 at 5200 m was significantly higher in the sildenafil group (placebo 4.0, sildenafil 6.5; p=0.004) but there was no difference in prevalence of AMS between groups. Sildenafil administration did not affect PASP in healthy lowland subjects at 5200 m but AMS was significantly more severe on Day 2 at 5200 m with sildenafil. Our data do not support routine prophylactic use of sildenafil to reduce PASP at high altitude in healthy subjects with no history of HAPE. TRIALS REGISTRATION NUMBER: NCT00627965.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Altitude Sickness / complications
  • Altitude Sickness / physiopathology
  • Altitude*
  • Blood Pressure
  • Double-Blind Method
  • Echocardiography
  • Female
  • Humans
  • Hypertension, Pulmonary / diagnostic imaging
  • Hypertension, Pulmonary / etiology
  • Hypertension, Pulmonary / physiopathology
  • Hypertension, Pulmonary / prevention & control*
  • Hypoxia / physiopathology
  • Intention to Treat Analysis
  • Male
  • Piperazines / adverse effects
  • Piperazines / therapeutic use*
  • Pulmonary Artery
  • Purines / adverse effects
  • Purines / therapeutic use
  • Sildenafil Citrate
  • Sulfones / adverse effects
  • Sulfones / therapeutic use*
  • Systole
  • Vasodilator Agents / adverse effects
  • Vasodilator Agents / therapeutic use*
  • Young Adult

Substances

  • Piperazines
  • Purines
  • Sulfones
  • Vasodilator Agents
  • Sildenafil Citrate

Associated data

  • ClinicalTrials.gov/NCT00627965