Inhaled nitric oxide for premature infants with severe respiratory failure.
BACKGROUND
Inhaled nitric oxide is a controversial treatment for premature infants with severe respiratory failure. We conducted a multicenter, randomized, blinded, controlled trial to determine whether inhaled nitric oxide reduced the rate of death or bronchopulmonary dysplasia in such infants.


METHODS
We randomly assigned 420 neonates, born at less than 34 weeks of gestation, with a birth weight of 401 to 1500 g, and with respiratory failure more than four hours after treatment with surfactant to receive placebo (simulated flow) or inhaled nitric oxide (5 to 10 ppm). Infants with a response (an increase in the partial pressure of arterial oxygen of more than 10 mm Hg) were weaned according to protocol. Treatment with study gas was discontinued in infants who did not have a response.


RESULTS
The rate of death or bronchopulmonary dysplasia was 80 percent in the nitric oxide group, as compared with 82 percent in the placebo group (relative risk, 0.97; 95 percent confidence interval, 0.86 to 1.06; P=0.52), and the rate of bronchopulmonary dysplasia was 60 percent versus 68 percent (relative risk, 0.90; 95 percent confidence interval, 0.75 to 1.08; P=0.26). There were no significant differences in the rates of severe intracranial hemorrhage or periventricular leukomalacia. Post hoc analyses suggest that rates of death and bronchopulmonary dysplasia are reduced for infants with a birth weight greater than 1000 g, whereas infants weighing 1000 g or less who are treated with inhaled nitric oxide have higher mortality and increased rates of severe intracranial hemorrhage.


CONCLUSIONS
The use of inhaled nitric oxide in critically ill premature infants weighing less than 1500 g does not decrease the rates of death or bronchopulmonary dysplasia. Further trials are required to determine whether inhaled nitric oxide benefits infants with a birth weight of 1000 g or more.
Division of Neonatal and Developmental Medicine, Department of Pediatrics, Stanford University School of Medicine, Palo Alto, Calif 94304, USA. vanmeurs@stanford.edu
Krisa P
KP
Van Meurs
Linda L
LL
Wright
Richard A
RA
Ehrenkranz
James A
JA
Lemons
M Bethany
MB
Ball
W Kenneth
WK
Poole
Rebecca
R
Perritt
Rosemary D
RD
Higgins
William
W
Oh
Mark L
ML
Hudak
Abbot R
AR
Laptook
Seetha
S
Shankaran
Neil N
NN
Finer
Waldemar A
WA
Carlo
Kathleen A
KA
Kennedy
Jon H
JH
Fridriksson
Robin H
RH
Steinhorn
Gregory M
GM
Sokol
G Ganesh
GG
Konduri
Judy L
JL
Aschner
Barbara J
BJ
Stoll
Carl T
CT
D'Angio
David K
DK
Stevenson
D000280:Administration, Inhalation; D001997:Bronchopulmonary Dysplasia / Q000517:prevention & control*; D002543:Cerebral Hemorrhage / Q000209:etiology; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D007235:Infant, Premature, Diseases / Q000188:drug therapy* / Q000401:mortality / Q000628:therapy; D019102:Infant, Very Low Birth Weight; D007969:Leukomalacia, Periventricular / Q000209:etiology; D008297:Male; D009569:Nitric Oxide / Q000009:adverse effects / Q000627:therapeutic use*; D010100:Oxygen / Q000097:blood; D012121:Respiration, Artificial; D012127:Respiratory Distress Syndrome, Newborn / Q000150:complications; D012131:Respiratory Insufficiency / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D016037:Single-Blind Method; D016896:Treatment Outcome
D009569:Nitric Oxide; D010100:Oxygen