Randomized controlled trial of early compared with delayed use of inhaled nitric oxide in newborns with a moderate respiratory failure and pulmonary hypertension

Objective: To evaluate whether early treatment with inhaled nitric oxide (iNO) will prevent newborns with moderate respiratory failure from developing severe hypoxemic respiratory failure (oxygenation index (OI) >= 40). Study Design: A total of 56 newborns with moderate respiratory failure ( OI between 10 and 30) were randomized before 48 h after birth to early treatment with 20 p.p.m. of iNO (Early iNO group, n = 28) or conventional mechanical ventilation with FiO(2) 1.0 (Control group, n = 28). Infants received iNO and/or high-frequency oscillatory ventilation (HFOV) if they developed an OI>40. Result: 7 of 28 early iNO patients (25%) compared to 17 of 28 control patients (61%) developed an OI>40 (P<0.05). In the Early iNO group mean OI significantly decreased from 22 (baseline) to 19 at 4 h (P<0.05) and remained lower over time: 19 (12 h), 18 (24 h) and 16 at 48 h. In contrast, OI increased in the Control group and remained significantly higher than the Early iNO group during the first 48 h of study: 22 (baseline), 29, 35, 32 and 23 at 4, 12, 24 and 48 h, respectively (P<0.01). Of 17, 6 control patients who developed an OI>40 were successfully treated with iNO. Nine of the remaining eleven control patients and six of seven Early iNO patients who had an OI>40 despite use of iNO responded with the addition of HFOV. One patient of the Early iNO group and two of the Control group died. Median (range) duration of oxygen therapy was significantly shorter in the Early iNO group: 11.5 (5 to 90) days compared to 18 (6 to 142) days of the Control group (P<0.03). Conclusion: Early use of iNO in newborns with moderate respiratory failure improves oxygenation and decreases the probability of developing severe hypoxemic respiratory failure. Journal of Perinatology (2010) 30, 420-424; doi: 10.1038/jp.2009.171; published online 5 November 2009