Inhaled nitric oxide for respiratory failure in preterm infants.
BACKGROUND
Inhaled nitric oxide has been proven effective in term infants with hypoxic respiratory failure. The pathophysiology of respiratory failure, and the potential risks, differ substantially in preterm infants. Analysis of the efficacy and toxicities of inhaled nitric oxide in infants born before 35 weeks is therefore necessary.


OBJECTIVE
To determine whether, in preterm newborn infants (<35 weeks gestation) who have hypoxic respiratory failure, treatment with inhaled nitric oxide improves oxygenation within 2 hours and reduces the rates of death, bronchopulmonary dysplasia, intraventricular hemorrhage, or neurodevelopmental disability


METHODS
Standard methods of the Cochrane Neonatal Review Group were used. We searched MEDLINE, EMBASE, Healthstar and the Cochrane Controlled Trials Register from the Cochrane Library, using the following keywords: nitric oxide, clinical trial, newborn, and covering years from 1985 to 2000. In addition, we searched the abstracts of the Pediatric Academic Societies.


METHODS
Randomized and quasi randomized studies in preterm infants with hypoxic respiratory failure. Administration of inhaled nitric oxide. Clinically relevant outcomes that were analysed included death, bronchopulmonary dysplasia (defined as oxygen dependence at 36 weeks postconceptional age), intraventricular hemorrhage, long term neurodevelopmental outcome and short term effects on oxygenation.


METHODS
Standard methods of the Cochrane Neonatal Review Group were used. Two investigators extracted, assessed and coded separately all data for each study. Any disagreement was resolved by discussion.


RESULTS
Three randomised controlled trials of inhaled nitric oxide therapy in preterm infants were found. One study consisted of infants determined to have a high risk of developing bronchopulmonary dysplasia. The second study consisted of infants with a 50% predicted mortality. The third study included term and preterm infants who had an oxygenation index of between 12.5 and 30, but randomised and analysed separately the preterm infants. No significant effect of inhaled nitric oxide on mortality or bronchopulmonary dysplasia was demonstrated. One study showed a reduction in days receiving assisted ventilation in the nitric oxide group, which was a secondary outcome. There was no evidence of effect on intraventricular hemorrhage incidence. There are no data on long term neurodevelopmental outcome. There may be short term improvements in oxygenation.


CONCLUSIONS
The currently published evidence from randomized trials does not support the use of inhaled nitric oxide in preterm infants with hypoxic respiratory failure. There is a possible reduction in the severity of chronic lung disease (shortened duration of assisted ventilation). Because of lack of power, it is not possible to eliminate the possibility of substantial improvements in outcome. Further studies should be performed.
Barrington
K J
KJ
Pediatrics, Royal Victoria Hospital, 687 av des Pins O, Montreal, P. Quebec, Canada, H3A 1A1. kbarri@po-box.mcgill.ca
Finer
N N
NN
D000280:Administration, Inhalation; D001997:Bronchopulmonary Dysplasia / Q000401:mortality / Q000517:prevention & control; D002543:Cerebral Hemorrhage / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D007231:Infant, Newborn; D007234:Infant, Premature; D007235:Infant, Premature, Diseases / Q000628:therapy*; D009569:Nitric Oxide / Q000008:administration & dosage*; D016032:Randomized Controlled Trials as Topic; D012131:Respiratory Insufficiency / Q000628:therapy*; D014665:Vasodilator Agents / Q000008:administration & dosage*
D014665:Vasodilator Agents; D009569:Nitric Oxide