Worsening of pulmonary gas exchange with nitric oxide inhalation in chronic obstructive pulmonary disease

Lancet. 1996 Feb 17;347(8999):436-40. doi: 10.1016/s0140-6736(96)90011-2.


Background: Inhalation of nitric oxide (NO) causes selective pulmonary vasodilation and improves arterial oxygenation in acute respiratory distress syndrome. But some patients do not respond or gas exchange worsens when inhaling NO. We hypothesised that this detrimental effect might be related to the reversion of hypoxic vasoconstriction in those patients where this mechanism contributes to ventilation-perfusion (V(A)/Q) matching.

Methods: We studied 13 patients with advanced chronic obstructive pulmonary disease (COPD). We compared their responses to breathing room air, NO at 40 parts per million in air, and 100% O2. Changes in pulmonary haemodynamics, blood gases, and V(A)/Q distributions were assessed.

Findings: NO inhalation decreased the mean (SE) pulmonary artery pressure from 25.9 (2.0) to 21.5 (1.7) mm Hg (p = 0.001) and PaO2 from 56 (2) 53 (2) mm Hg (p = 0.014). The decrease in PaO2 resulted from worsening of V(A)/Q distributions, as shown by a greater dispersion of the blood-flow distribution (logSD Q) from 1.11 (0.1) to 1.22 (0.1) (p = 0.018). O2 breathing reduced the mean pulmonary arterial pressure to 23.4 (2.1) mm Hg and caused greater V(A)/Q mismatch (logSD Q, 1.49 [0.1]). The intrapulmonary shunt on room air was small (2.7 [0.9]%) and did not change when breathing NO or O2.

Interpretation: We conclude that in patients with COPD, in whom hypoxaemia is caused essentially by V(A)/Q imbalance rather than by shunt, inhaled NO can worsen gas exchange because of impaired hypoxic regulation of the matching between ventilation and perfusion.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Humans
  • Hypertension, Pulmonary / physiopathology
  • Hypoxia / physiopathology
  • Lung Diseases, Obstructive / physiopathology*
  • Lung Diseases, Obstructive / therapy
  • Male
  • Middle Aged
  • Nitric Oxide / administration & dosage
  • Nitric Oxide / adverse effects*
  • Nitric Oxide / therapeutic use
  • Oxygen Inhalation Therapy
  • Pulmonary Circulation / drug effects
  • Pulmonary Gas Exchange / drug effects*
  • Ventilation-Perfusion Ratio / drug effects


  • Nitric Oxide