Four patterns of response to inhaled nitric oxide for persistent pulmonary hypertension of the newborn

Pediatrics. 1996 Oct;98(4 Pt 1):706-13.

Abstract

Objective: To determine the clinical role of inhaled nitric oxide (iNO) in the treatment of persistent pulmonary hypertension of the newborn (PPHN).

Study design: Prospective open observational clinical study.

Setting: A regional cardiac and pediatric intensive care unit.

Methods: Twenty-five consecutive near-term neonates (> 35 weeks gestation) with severe PPHN (oxygenation index [OI] > 25) were given a trial of iNO of 20 ppm for 20 minutes. Neonates who showed a greater than 20% improvement in PaO2 as well as a decrease in the OI to below 40 were defined as responders and continued on this therapy.

Results: Four patterns of response emerged to the iNO therapy: Pattern 1 neonates (n = 2) did not respond to the initial trial of iNO-one survived. Pattern 2 neonates (n = 9) responded to the initial trial of iNO, but failed to sustain this response over 36 hours, as defined by a rise in the OI to > 40. Six survived, five with extracorporeal membrane oxygenation. Pattern 3 neonates (n = 11) responded to the initial trial of iNO, sustained this response, and were successfully weaned from iNO within 5 days--all survived to discharge. Pattern 4 neonates (n = 3) responded to the initial trial of iNO, but developed a sustained dependence on iNO for 3 to 6 weeks. All three died and lung histology revealed severe pulmonary hypoplasia and dysplasia. These neonates (pattern 4) not only required iNO for a longer period of time than did the sustained responders (pattern 3), but they required significantly higher doses of iNO during their first 5 days of iNO therapy.

Conclusions: Early responses to iNO may not be sustained. Neonates with pulmonary hypoplasia and dysplasia may have a decreased sensitivity and differing time course of response to iNO when compared with patients who have PPHN in fully developed lungs.

Publication types

  • Clinical Trial
  • Comparative Study

MeSH terms

  • Administration, Inhalation
  • Biopsy
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Infant, Newborn
  • Lung / abnormalities
  • Lung / pathology
  • Male
  • Nitric Oxide / administration & dosage*
  • Nitric Oxide / adverse effects
  • Persistent Fetal Circulation Syndrome / drug therapy*
  • Persistent Fetal Circulation Syndrome / pathology
  • Prospective Studies
  • Respiration, Artificial
  • Respiratory System Agents / administration & dosage*
  • Respiratory System Agents / adverse effects
  • Treatment Outcome

Substances

  • Respiratory System Agents
  • Nitric Oxide