Inhaled nitric oxide for the adult respiratory distress syndrome

N Engl J Med. 1993 Feb 11;328(6):399-405. doi: 10.1056/NEJM199302113280605.


Background: The adult respiratory distress syndrome is characterized by pulmonary hypertension and right-to-left shunting of venous blood. We investigated whether inhaling nitric oxide gas would cause selective vasodilation of ventilated lung regions, thereby reducing pulmonary hypertension and improving gas exchange.

Methods: Nine of 10 consecutive patients with severe adult respiratory distress syndrome inhaled nitric oxide in two concentrations for 40 minutes each. Hemodynamic variables, gas exchange, and ventilation-perfusion distributions were measured by means of multiple inert-gas-elimination techniques during nitric oxide inhalation; the results were compared with those obtained during intravenous infusion of prostacyclin. Seven patients were treated with continuous inhalation of nitric oxide in a concentration of 5 to 20 parts per million (ppm) for 3 to 53 days.

Results: Inhalation of nitric oxide in a concentration of 18 ppm reduced the mean (+/- SE) pulmonary-artery pressure from 37 +/- 3 mm Hg to 30 +/- 2 mm Hg (P = 0.008) and decreased intrapulmonary shunting from 36 +/- 5 percent to 31 +/- 5 percent (P = 0.028). The ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen (PaO2/FiO2), an index of the efficiency of arterial oxygenation, increased during nitric oxide administration from 152 +/- 15 mm Hg to 199 +/- 23 mm Hg (P = 0.008), although the mean arterial pressure and cardiac output were unchanged. Infusion of prostacyclin reduced pulmonary-artery pressure but increased intrapulmonary shunting and reduced the PaO2/FiO2 and systemic arterial pressure. Continuous nitric oxide inhalation consistently lowered the pulmonary-artery pressure and augmented the PaO2/FiO2 for 3 to 53 days.

Conclusions: Inhalation of nitric oxide by patients with severe adult respiratory distress syndrome reduces the pulmonary-artery pressure and increases arterial oxygenation by improving the matching of ventilation with perfusion, without producing systemic vasodilation. Randomized, blinded trials will be required to determine whether inhaled nitric oxide will improve outcome.

Publication types

  • Clinical Trial
  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Blood Pressure / drug effects
  • Cardiac Output / drug effects
  • Drug Evaluation
  • Epoprostenol / administration & dosage
  • Epoprostenol / pharmacology
  • Female
  • Humans
  • Hypertension, Pulmonary / drug therapy
  • Hypertension, Pulmonary / physiopathology
  • Infusions, Intravenous
  • Male
  • Middle Aged
  • Nitric Oxide / administration & dosage*
  • Nitric Oxide / pharmacology
  • Oxygen / blood
  • Partial Pressure
  • Pulmonary Gas Exchange / drug effects
  • Respiratory Distress Syndrome / drug therapy*
  • Respiratory Distress Syndrome / physiopathology
  • Ventilation-Perfusion Ratio / drug effects


  • Nitric Oxide
  • Epoprostenol
  • Oxygen