Inhaled nitric oxide for high-altitude pulmonary edema

N Engl J Med. 1996 Mar 7;334(10):624-9. doi: 10.1056/NEJM199603073341003.


Background: Pulmonary hypertension is a hallmark of high-altitude pulmonary edema and may contribute to its pathogenesis. When administered by inhalation, nitric oxide, an endothelium-derived relaxing factor, attenuates the pulmonary vasoconstriction produced by short-term hypoxia.

Methods: We studied the effects of inhaled nitric oxide on pulmonary-artery pressure and arterial oxygenation in 18 mountaineers prone to high-altitude pulmonary edema and 18 mountaineers resistant to this condition in a high altitude laboratory (altitude, 4559 m). We also obtained lung-perfusion scans before and during nitric oxide inhalation to gain further insight into the mechanism of action of nitric oxide.

Results: In the high-altitude laboratory, subjects prone to high-altitude pulmonary edema had more pronounced pulmonary hypertension and hypoxemia than subjects resistant to high-altitude pulmonary edema. Arterial oxygen saturation was inversely related to the severity of pulmonary hypertension (r=-0.50, P=0.002). In subjects prone to high-altitude pulmonary edema, the inhalation of nitric oxide (40 ppm for 15 minutes) produced a decrease in mean (+/-SD) systolic pulmonary-artery pressure that was three times larger than the decrease in subjects resistant to such edema (25.9+/-8.9 vs. 8.7+/-4.8 mm Hg, P<0.001). Inhaled nitric oxide improved arterial oxygenation in the 10 subjects who had radiographic evidence of pulmonary edema (arterial oxygen saturation increased from 67+/-10 to 73+/-12 percent, P=0.047), whereas it worsened oxygenation in subjects resistant to high-altitude pulmonary edema. The nitric oxide-induced improvement in arterial oxygenation in subjects with high-altitude pulmonary edema was accompanied by a shift in blood flow in the lung away from edematous segments and toward nonedematous segments.

Conclusions: The inhalation of nitric oxide improves arterial oxygenation in high-altitude pulmonary edema, and this beneficial effect may be related to its favorable action on the distribution of blood flow in the lungs. A defect in nitric nitric oxide synthesis may contribute to high-altitude pulmonary edema.

Publication types

  • Clinical Trial

MeSH terms

  • Administration, Inhalation
  • Adult
  • Altitude Sickness / complications
  • Carbon Dioxide / analysis
  • Echocardiography, Doppler
  • Female
  • Humans
  • Hypertension, Pulmonary / complications
  • Hypertension, Pulmonary / diagnostic imaging
  • Hypertension, Pulmonary / drug therapy
  • Lung / blood supply
  • Lung / diagnostic imaging
  • Male
  • Middle Aged
  • Nitric Oxide / therapeutic use*
  • Oxygen / blood
  • Pulmonary Edema / drug therapy*
  • Pulmonary Edema / etiology
  • Pulmonary Edema / physiopathology
  • Radiography
  • Radionuclide Imaging


  • Carbon Dioxide
  • Nitric Oxide
  • Oxygen