Inhaled nitric oxide as an adjunct to neonatal resuscitation in premature infants: a pilot, double blind, randomized controlled trial

Abstract

Background: Nitric oxide (NO) plays an important role in normal postnatal transition. Our aims were to determine whether adding inhaled NO (iNO) decreases supplemental oxygen exposure in preterm infants requiring positive pressure ventilation (PPV) during resuscitation and to study iNO effects on heart rate (HR), oxygen saturation (SpO₂), and need for intubation during the first 20 min of life.

Methods: This was a pilot, double-blind, randomized, placebo-controlled trial. Infants 25 0/7-31 6/7 weeks' gestational age requiring PPV with supplemental oxygen during resuscitation were enrolled. PPV was initiated with either oxygen (FiO₂-0.30) + iNO at 20 ppm (iNO group) or oxygen (FiO₂-0.30) + nitrogen (placebo group). Oxygen was titrated targeting defined SpO₂ per current guidelines. After 10 min, iNO/nitrogen was weaned stepwise per protocol and terminated at 17 min.

Results: Twenty-eight infants were studied (14 per group). The mean gestational age in both groups was similar. Cumulative FiO₂ and rate of exposure to high FiO₂ (>0.60) were significantly lower in the iNO group. There were no differences in HR, SpO₂, and need for intubation.

Conclusions: Administration of iNO as an adjunct during neonatal resuscitation is feasible without side effects. It diminishes exposure to high levels of supplemental oxygen.

Fig. 1

NRP algorithm (6th edition) and study procedures

Fig. 2

Study enrollment and randomization

Fig. 3

Oxygen delivery and pre- and post-ductal oxygen saturations during resuscitation. The solid lines (yellow and red) represent average oxygen administered to each group. The interrupted lines (yellow and red) represent pre-ductal (thick) and post-ductal (thin) oxygen saturations in each group. The asterisks represent the highest average oxygen concentration in each group. The blue line represents study gas (ppm)

Fig. 4

Heart rate during resuscitation. The yellow and red lines represent average heart rate for the iNO and placebo groups, respectively. The blue line represents study gas (ppm)