Early Inhaled Nitric Oxide Therapy in Premature Newborns with Respiratory Failure

John P. Kinsella, Gary R. Cutter, William F. Walsh, Dale R. Gerstmann, Carl L. Bose, Claudia Hart, Kris C. Sekar, Richard L. Auten, Vinod K. Bhutani, Jeffrey S. Gerdes, Thomas N George, W. Michael Southgate, Heather Carriedo, Robert J. Couser, Mark C Mammel, David C. Hall, Mariann Pappagallo, Smeeta Sardesai, John D. Strain, Monika BaierSteven H. Abman

Research output: Contribution to journalArticlepeer-review

321 Scopus citations


BACKGROUND: The safety and efficacy of early, low-dose, prolonged therapy with inhaled nitric oxide in premature newborns with respiratory failure are uncertain. METHODS: We performed a multicenter, randomized trial involving 793 newborns who were 34 weeks of gestational age or less and had respiratory failure requiring mechanical ventilation. Newborns were randomly assigned to receive either inhaled nitric oxide (5 ppm) or placebo gas for 21 days or until extubation, with stratification according to birth weight (500 to 749 g, 750 to 999 g, or 1000 to 1250 g). The primary efficacy outcome was a composite of death or bronchopulmonary dysplasia at 36 weeks of postmenstrual age. Secondary safety outcomes included severe intracranial hemorrhage, periventricular leukomalacia, and ventriculomegaly. RESULTS: Overall, there was no significant difference in the incidence of death or bronchopulmonary dysplasia between patients receiving inhaled nitric oxide and those receiving placebo (71.6 percent vs. 75.3 percent, P=0.24). However, for infants with a birth weight between 1000 and 1250 g, as compared with placebo, inhaled nitric oxide therapy reduced the incidence of bronchopulmonary dysplasia (29.8 percent vs. 59.6 percent); for the cohort overall, such treatment reduced the combined end point of intracranial hemorrhage, periventricular leukomalacia, or ventriculomegaly (17.5 percent vs. 23.9 percent, P=0.03) and of periventricular leukomalacia alone (5.2 percent vs. 9.0 percent, P = 0.048). Inhaled nitric oxide therapy did not increase the incidence of pulmonary hemorrhage or other adverse events. CONCLUSIONS: Among premature newborns with respiratory failure, low-dose inhaled nitric oxide did not reduce the overall incidence of bronchopulmonary dysplasia, except among infants with a birth weight of at least 1000 g, but it did reduce the overall risk of brain injury.

Original languageEnglish (US)
Pages (from-to)354-364
Number of pages11
JournalNew England Journal of Medicine
Issue number4
StatePublished - Jul 27 2006


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