title: Early inhaled nitric oxide therapy in premature newborns with respiratory failure.
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].).
authors.affiliation: Pediatric Heart Lung Center, University of Colorado School of Medicine, and Children's Hospital, Denver, USA. john.kinsella@uchsc.edu
authors.forename: John P
authors.initials: JP
authors.lastname: Kinsella
authors.forename: Gary R
authors.initials: GR
authors.lastname: Cutter
authors.forename: William F
authors.initials: WF
authors.lastname: Walsh
authors.forename: Dale R
authors.initials: DR
authors.lastname: Gerstmann
authors.forename: Carl L
authors.initials: CL
authors.lastname: Bose
authors.forename: Claudia
authors.initials: C
authors.lastname: Hart
authors.forename: Kris C
authors.initials: KC
authors.lastname: Sekar
authors.forename: Richard L
authors.initials: RL
authors.lastname: Auten
authors.forename: Vinod K
authors.initials: VK
authors.lastname: Bhutani
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Gerdes
authors.forename: Thomas N
authors.initials: TN
authors.lastname: George
authors.forename: W Michael
authors.initials: WM
authors.lastname: Southgate
authors.forename: Heather
authors.initials: H
authors.lastname: Carriedo
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Couser
authors.forename: Mark C
authors.initials: MC
authors.lastname: Mammel
authors.forename: David C
authors.initials: DC
authors.lastname: Hall
authors.forename: Mariann
authors.initials: M
authors.lastname: Pappagallo
authors.forename: Smeeta
authors.initials: S
authors.lastname: Sardesai
authors.forename: John D
authors.initials: JD
authors.lastname: Strain
authors.forename: Monika
authors.initials: M
authors.lastname: Baier
authors.forename: Steven H
authors.initials: SH
authors.lastname: Abman
mesh_terms: D000280:Administration, Inhalation; D001724:Birth Weight; D001997:Bronchopulmonary Dysplasia / Q000453:epidemiology / Q000517:prevention & control*; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D019102:Infant, Very Low Birth Weight; D020300:Intracranial Hemorrhages / Q000517:prevention & control; D007969:Leukomalacia, Periventricular / Q000517:prevention & control; D008171:Lung Diseases / Q000628:therapy*; D008297:Male; D009569:Nitric Oxide / Q000008:administration & dosage* / Q000009:adverse effects; D012121:Respiration, Artificial / Q000009:adverse effects; D012127:Respiratory Distress Syndrome, Newborn / Q000401:mortality / Q000628:therapy*; D016019:Survival Analysis
chemical_list: D009569:Nitric Oxide