Inhaled nitric oxide in preterm infants undergoing mechanical ventilation.
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] .).
Ballard
Roberta A
RA
Children's Hospital of Philadelphia, Philadelphia 19104, USA. ballard@email.chop.edu
Truog
William E
WE
Cnaan
Avital
A
Martin
Richard J
RJ
Ballard
Philip L
PL
Merrill
Jeffrey D
JD
Walsh
Michele C
MC
Durand
David J
DJ
Mayock
Dennis E
DE
Eichenwald
Eric C
EC
Null
Donald R
DR
Hudak
Mark L
ML
Puri
Asha R
AR
Golombek
Sergio G
SG
Courtney
Sherry E
SE
Stewart
Dan L
DL
Welty
Stephen E
SE
Phibbs
Roderic H
RH
Hibbs
Anna Maria
AM
Luan
Xianqun
X
Wadlinger
Sandra R
SR
Asselin
Jeanette M
JM
Coburn
Christine E
CE
D000280:Administration, Inhalation; D000367:Age Factors; D001997:Bronchopulmonary Dysplasia / Q000453:epidemiology / Q000517:prevention & control*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D007235:Infant, Premature, Diseases / Q000401:mortality / Q000628:therapy*; D019102:Infant, Very Low Birth Weight; D007902:Length of Stay; D008171:Lung Diseases / Q000628:therapy*; D008297:Male; D009569:Nitric Oxide / Q000008:administration & dosage* / Q000009:adverse effects; D012121:Respiration, Artificial / Q000009:adverse effects; D016019:Survival Analysis
D009569:Nitric Oxide