Early compared with delayed inhaled nitric oxide in moderately hypoxaemic neonates with respiratory failure: a randomised controlled trial

Background Inhaled nitric oxide improves oxygenation in severely hypoxaemic term neonates, which lessens the need for extracorporeal-membrane oxygenat ion. Improvement in other relevant outcomes remains unknown, and safety of inhaled nitric oxide is uncertain In preterm neonates. We did a randomised controlled trial to assess use of inhaled nitric oxide in preterm and near- term neonates. Methods We randomly assigned 204 preterm (<33 weeks) and near-term (greater than or equal to 33 weeks) neonates with oxygenation indices from 12.5 to 30.0 and 15 to 40, respectively, 10 parts per million (ppm) inhaled nitric oxide (n=105) or control ventilation therapy without nitric oxide (n=99). T he primary endpoint was the oxygenation index at 2 h. Analysis was done by intention to treat. Findings 12 neonates were excluded, leaving 97 (45 preterm) in the nitric-o xide group and 95 (40 preterm) in the control group. The decline in oxygena tion index at 2 h was greater in the nitric-oxide group than in the control group (IQR 6.2 [median 8.4] vs -2.9 [12.4], p=0.005), but was significant only in near-term neonates (p=0.03). Survivors assigned nitric oxide spent fewer days on mechanical ventilation and in the neonatal intensive-care uni t, but this was also significant only in near-term neonates (6 [3] vs 7 [3] days, p=0.05, and 9 [6] vs 12 [9] days, p=0.02, respectively). Interpretation Low-dose inhaled nitric oxide early in the course of neonata l respiratory failure improves oxygenation and shortens duration of mechani cal ventilation and the length of stay in intensive care. Inhaled nitric ox ide was not, however, significantly beneficial in preterm neonates.