Early inhaled nitric oxide therapy in premature newborns with respiratory failure.
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].).
Kinsella
John P
JP
Pediatric Heart Lung Center, University of Colorado School of Medicine, and Children's Hospital, Denver, USA. john.kinsella@uchsc.edu
Cutter
Gary R
GR
Walsh
William F
WF
Gerstmann
Dale R
DR
Bose
Carl L
CL
Hart
Claudia
C
Sekar
Kris C
KC
Auten
Richard L
RL
Bhutani
Vinod K
VK
Gerdes
Jeffrey S
JS
George
Thomas N
TN
Southgate
W Michael
WM
Carriedo
Heather
H
Couser
Robert J
RJ
Mammel
Mark C
MC
Hall
David C
DC
Pappagallo
Mariann
M
Sardesai
Smeeta
S
Strain
John D
JD
Baier
Monika
M
Abman
Steven H
SH
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
D009569:Nitric Oxide