Inhaled nitric oxide in acute respiratory failure: dose-response curves

Intensive Care Med. 1994 May;20(5):319-27. doi: 10.1007/BF01720903.


Objective: To determine the dose-response curve of inhaled nitric oxide (NO) in terms of pulmonary vasodilation and improvement in PaO2 in adults with severe acute respiratory failure.

Design: Prospective randomized study.

Setting: A 14-bed ICU in a teaching hospital.

Patients: 6 critically ill patients with severe acute respiratory failure (lung injury severity score > or = 2.5) and pulmonary hypertension.

Interventions: 8 concentrations of inhaled NO were administered at random: 100, 400, 700, 1000, 1300, 1600, 1900 and 5000 parts per billion (ppb). Control measurements were performed before NO inhalation and after the last concentration administered. After an NO exposure of 15-20 min, hemodynamic parameters obtained from a fiberoptic Swan-Ganz catheter, blood gases, methemoglobin blood concentrations and intratracheal NO and nitrogen dioxide (NO2) concentrations, continuously monitored using a bedside chemiluminescence apparatus, were recorded on a Gould ES 1000 recorder. In 2 patients end-tidal CO2 was also recorded.

Results: The administration of 100-2000 ppb of inhaled NO induced: i) a dose-dependent decrease in pulmonary artery pressure and in pulmonary vascular resistance (maximum decrease--25%); ii) a dose-dependent increase in PaO2 via a dose-dependent reduction in pulmonary shunt; iii) a slight but significant decrease in PaCO2 via a reduction in alveolar dead space; iv) a dose-dependent increase in mixed venous oxygen saturation (SVO2). Systemic hemodynamic variables and methemoglobin blood concentrations did not change. Maximum NO2 concentrations never exceeded 165 ppb. In 2 patients, 91% and 74% of the pulmonary vasodilation was obtained for inhaled NO concentrations of 100 ppb.

Conclusion: In hypoxemic patients with pulmonary hypertension and severe acute respiratory failure, therapeutic inhaled NO concentrations are in the range 100-2000 ppb. The risk of toxicity related to NO inhalation is therefore markedly reduced. Continuous SVO2 monitoring appears useful at the bedside for determining optimum therapeutic inhaled NO concentrations in a given patient.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Acute Disease
  • Administration, Inhalation
  • Adult
  • Aged
  • Aged, 80 and over
  • Analysis of Variance
  • Dose-Response Relationship, Drug
  • Female
  • Hemodynamics / drug effects
  • Humans
  • Hypertension, Pulmonary / drug therapy
  • Hypertension, Pulmonary / epidemiology
  • Hypertension, Pulmonary / physiopathology
  • Male
  • Middle Aged
  • Nitric Oxide / administration & dosage*
  • Prospective Studies
  • Respiration, Artificial
  • Respiratory Insufficiency / drug therapy*
  • Respiratory Insufficiency / epidemiology
  • Respiratory Insufficiency / physiopathology


  • Nitric Oxide