Clinical responses to prolonged treatment of persistent pulmonary hypertension of the newborn with low doses of inhaled nitric oxide

J Pediatr. 1993 Jul;123(1):103-8. doi: 10.1016/s0022-3476(05)81551-3.


We studied the efficacy of low-dose nitric oxide inhalation in nine consecutive patients with severe persistent pulmonary hypertension of the newborn (PPHN) who were candidates for extracorporeal membrane oxygenation (ECMO). All patients had marked hypoxemia despite aggressive ventilator management and echocardiographic evidence of pulmonary hypertension. Associated diagnoses included meconium aspiration syndrome (3 patients), sepsis (3 patients), and congenital diaphragmatic hernia (2 patients). Infants were initially treated with inhaled nitric oxide at 20 ppm for 4 hours and then at 6 ppm for 20 hours. In all infants, oxygenation promptly improved (arterial/alveolar oxygen ratio, 0.077 +/- 0.016 at baseline vs 0.193 +/- 0.030 at 4 hours; p < 0.001) without a decrease in systemic blood pressure. Sustained improvement in oxygenation was achieved in eight patients treated with inhaled nitric oxide for 24 hours at 6 ppm (arterial/alveolar oxygen ratio, 0.270 +/- 0.053 at 24 hours; p < 0.001 vs baseline). One patient with overwhelming sepsis had an initial improvement of oxygenation with nitric oxide but required ECMO for multiorgan and cardiac dysfunction. We conclude that low doses of nitric oxide cause sustained clinical improvement in severe PPHN and may reduce the need for ECMO. However, immediate availability of ECMO is important in selected cases of PPHN complicated by severe systemic hemodynamic collapse.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acute Disease
  • Administration, Inhalation
  • Drug Evaluation
  • Echocardiography
  • Extracorporeal Membrane Oxygenation
  • Humans
  • Infant, Newborn
  • Nitric Oxide / administration & dosage*
  • Oxygen / blood
  • Persistent Fetal Circulation Syndrome / blood
  • Persistent Fetal Circulation Syndrome / diagnostic imaging
  • Persistent Fetal Circulation Syndrome / drug therapy*
  • Respiratory Insufficiency / blood
  • Respiratory Insufficiency / diagnostic imaging
  • Respiratory Insufficiency / drug therapy
  • Time Factors
  • Vasodilator Agents / administration & dosage*


  • Vasodilator Agents
  • Nitric Oxide
  • Oxygen