Inhaled nitric oxide therapy in preterm infants with severe respiratory failure

Elevated pulmonary vascular resistance and poor ventilation-perfusion matching commonly exist in preterm infants with severe respiratory distress syndrome (RDS). It has been reported that inhaled nitric oxide (iNO) therapy improves oxygenation and lowers pulmonary artery pressures in preterm infants, decreasing the incidence of chronic lung disease (CLD) and death in premature infants with RDS. iNO relaxes selectively preconstricted pulmonary blood vessels without causing concomitant systemic hypotension. Results of three large multicenter trials dealing with the use of iNO in preterm infants have been recently published, with controversial results. In fact, the National Institute of Child Health and Human Development Neonatal Network Trial suggested that iNO given to critically ill premature infants with a birth weight (BW) =1500 g did not decrease the mortality or the incidence of bronchopulmonary dysplasia (BPD) even if the mortality rates and incidence of BPD were reduced in infants with a birth weight =1000 g. Ballard et al. reported that iNO therapy initiated between 7 and 21 days of age improved the pulmonary outcome in premature infants at risk of BPD. Kinsella et al. reported that among premature newborns with respiratory failure, low-dose iNO (5 p.p.m.) did not reduce the overall incidence of BPD, except among infants with a BW =1000 g and it did reduce the overall risk of brain injury.
On these bases, a group from University of Taiwan conducted a randomized study to determine the effect on oxygenation and the safety of iNO therapy in preterm infants with severe RDS and respiratory failure.
65 preterm infants (BW <1500 g; gestational age, <31 weeks) with severe RDS and respiratory failure requiring mechanical ventilation and an oxygenation index (OI) =25 were randomly assigned to iNO therapy (n=32; the starting dose was 5 p.p.m, while the maximal dose was 20 p.p.m. ) or to placebo (n=33).
Overall, OI was significantly lower (P<0.01) in the iNO therapy group than in the control group at 30min, 3, 12 and 24 h after initiating iNO therapy. Six infants in the iNO-treated group and 10 infants in the control group died (the difference was not statistically significant). There was no difference in incidence of short-term adverse effects, such as pneumothorax, pulmonary hemorrhage or intracranial hemorrhage. No significant differences in the incidences of CLD, intracranial hemorrhage (ICH), patent ductus arteriosus (PDA), retinopathy of prematurity (ROP) or duration of intubation were revealed between the two groups.
Even if limited by a small sample size, these results may suggest that iNO therapy could lead to an improvement in oxygenation without short-term side effects in premature infants with severe RDS and respiratory failure. However, iNO therapy does not significantly reduce mortality rate or the incidences of CLD, ICH, PDA or ROP. Further research is needed to confirm the efficacy and safety of iNO given to premature infants with respiratory failure and a long-term follow-up for neurodevelopmental outcomes is also required.

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