Inhaled nitric oxide for respiratory failure in preterm infants

Abstract

Inhaled nitric oxide (iNO) is effective in term infants with hypoxic respiratory failure. The pathophysiology of respiratory failure and the potential risks of iNO differ substantially in preterm infants, necessitating study in this population. To determine the effect of treatment with iNO on death, bronchopulmonary dysplasia (BPD), intraventricular hemorrhage (IVH), and neurodevelopmental disability in preterm newborn infants with respiratory disease. Standard methods of the Cochrane Neonatal Review Group were used. MEDLINE, EMBASE, Healthstar and the Cochrane Central Register of Controlled Trials (The Cochrane Library) were searched covering the years from 1985 to 2010. In addition, the abstracts of the Pediatric Academic Societies were also searched. Randomized and quasi-randomized studies in preterm infants with respiratory disease that compared the effects of iNO gas to control, with or without placebo were eligible. Standard methods of the Cochrane Neonatal Review Group were used. Fourteen randomized controlled trials of inhaled nitric oxide therapy in preterm infants were found. The trials have been grouped post hoc into three categories depending on entry criteria; entry in the first three days of life based on oxygenation criteria, routine use in preterm babies with pulmonary disease, and later enrolment based on an increased risk of BPD. No overall analyses were performed.Nine trials of early rescue treatment of infants based on oxygenation criteria demonstrated no significant effect of iNO on mortality or BPD. Three studies with routine use of iNO in infants with pulmonary disease also demonstrated no significant reduction in death or BPD [typical RR 0.93 (95% CI 0.86 to 1.01)] although this small effect approached significance. Later treatment with iNO based on the risk of BPD (two trials) demonstrated no significant benefit for this outcome in analyses which are possible using summary data.There is no clear effect of iNO on the frequency of all grades of IVH or of severe IVH. Early rescue treatment was associated with a non-significant 20% increase in severe IVH.No effect on the incidence of neurodevelopmental impairment was found. iNO as rescue therapy for the very ill preterm infant does not appear to be effective. Early routine use of iNO in preterm infants with respiratory disease does not affect serious brain injury or improve survival without BPD. Later use of iNO to prevent BPD might be effective, but requires further study.