Inhaled nitric oxide in preterm infants undergoing mechanical ventilation

N Engl J Med. 2006 Jul 27;355(4):343-53. doi: 10.1056/NEJMoa061088.

Abstract

Background: Bronchopulmonary dysplasia in premature infants is associated with prolonged hospitalization, as well as abnormal pulmonary and neurodevelopmental outcome. In animal models, inhaled nitric oxide improves both gas exchange and lung structural development, but the use of this therapy in infants at risk for bronchopulmonary dysplasia is controversial.

Methods: We conducted a randomized, stratified, double-blind, placebo-controlled trial of inhaled nitric oxide at 21 centers involving infants with a birth weight of 1250 g or less who required ventilatory support between 7 and 21 days of age. Treated infants received decreasing concentrations of nitric oxide, beginning at 20 ppm, for a minimum of 24 days. The primary outcome was survival without bronchopulmonary dysplasia at 36 weeks of postmenstrual age.

Results: Among 294 infants receiving nitric oxide and 288 receiving placebo birth weight (766 g and 759 g, respectively), gestational age (26 weeks in both groups), and other characteristics were similar. The rate of survival without bronchopulmonary dysplasia at 36 weeks of postmenstrual age was 43.9 percent in the group receiving nitric oxide and 36.8 percent in the placebo group (P=0.042). The infants who received inhaled nitric oxide were discharged sooner (P=0.04) and received supplemental oxygen therapy for a shorter time (P=0.006). There were no short-term safety concerns.

Conclusions: Inhaled nitric oxide therapy improves the pulmonary outcome for premature infants who are at risk for bronchopulmonary dysplasia when it is started between 7 and 21 days of age and has no apparent short-term adverse effects. (ClinicalTrials.gov number, NCT00000548 [ClinicalTrials.gov] .).

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Administration, Inhalation
  • Age Factors
  • Bronchopulmonary Dysplasia / epidemiology
  • Bronchopulmonary Dysplasia / prevention & control*
  • Double-Blind Method
  • Drug Administration Schedule
  • Female
  • Gestational Age
  • Humans
  • Infant, Newborn
  • Infant, Premature
  • Infant, Premature, Diseases / mortality
  • Infant, Premature, Diseases / therapy*
  • Infant, Very Low Birth Weight
  • Length of Stay
  • Lung Diseases / therapy*
  • Male
  • Nitric Oxide / administration & dosage*
  • Nitric Oxide / adverse effects
  • Respiration, Artificial* / adverse effects
  • Survival Analysis

Substances

  • Nitric Oxide

Associated data

  • ClinicalTrials.gov/NCT00000548