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Previous Volume 355:354-364 July 27, 2006 Number 4 Next

	Full Text PDF PDA Full Text PowerPoint Slide Set Editorial by Stark, A. R. Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited E-mail When Letters Appear PubMed Citation

ABSTRACT

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. (ClinicalTrials.gov number, NCT00006401 [ClinicalTrials.gov] .)

Source Information

From the Pediatric Heart Lung Center, University of Colorado School of Medicine, and Children's Hospital — both in Denver (J.P.K., J.D.S., S.H.A.); the University of Alabama at Birmingham, Birmingham (G.R.C., M.B.); Vanderbilt University Medical Center, Nashville (W.F.W.); Utah Valley Regional Medical Center, Provo, Utah (D.R.G.); the University of North Carolina, Chapel Hill (C.L.B.); Magee Women's Hospital, University of Pittsburgh, Pittsburgh (C.H.); the University of Oklahoma, Oklahoma City (K.C.S.); Duke University, Durham, N.C. (R.L.A.); Pennsylvania Hospital of the University of Pennsylvania Health System, Philadelphia (V.K.B., J.S.G.); the University of Iowa, Iowa City (T.N.G.); Medical University of South Carolina, Charleston (W.M.S.); Loma Linda University, Loma Linda, Calif. (H.C.); Children's Hospital, Minneapolis (R.J.C.); Children's Hospital, St. Paul, Minn. (M.C.M.); St. Joseph's Hospital, Phoenix (D.C.H.); the University of Connecticut, Farmington (M.P.); and the University of Southern California, Los Angeles (S.S.).

Address reprint requests to Dr. Kinsella at the Division of Neonatology, Box B-070, Children's Hospital, 1056 E. 19th Ave., Denver, CO 80218-1088, or at john.kinsella{at}uchsc.edu.

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