Inhaled nitric oxide treatment for preterm infants with hypoxic respiratory failure
Authors: R. Smyth
Journal: Thorax (2000)

Background.Inhaled nitric oxide improves oxygenation and lessens the need for extracorporealmembrane oxygenation in full-term neonates with hypoxaemic respiratory failure and persistent pulmonary hypertension, but potential adverse effects are intracranial haemorrhage and chronic lung disease.We investigated whether low-dose inhaled nitric oxide would improve survival in premature neonates with unresponsive severe hypoxaemic respiratory failure, and would not increase the frequency or severity of intracranial haemorrhage or chronic lung disease.Methods.We did a double-blind, randomised controlled trial in 12 perinatal centres that provide tertiary care.80 premature neonates (gestational age ≤34 weeks) with severe hypoxaemic respiratory failure were randomly assigned inhaled nitric oxide (n=48) or no nitric oxide (n=32, controls).Our primary outcome was survival to discharge.Analysis was by intention to treat.We studied also the rate and severity of intracranial haemorrhage, pulmonary haemorrhage, duration of ventilation, and chronic lung disease at 36 weeks' postconceptional age.Findings.The two groups did not differ for baseline characteristics or severity of disease.Inhaled nitric oxide improved oxygenation after 60 min (p=0.03).Survival at discharge was 52% in the inhalednitric-oxide group and 47% in controls (p=0.65).Causes of death were mainly related to extreme prematurity and were similar in the two groups.The two groups did not differ for adverse events or outcomes (intracranial haemorrhage grade 2-4, 28% inhaled nitric oxide and 33% control; pulmonary haemorrhage 13% and 9%; chronic lung disease 60% and 80%).Interpretation.Low-dose inhaled nitric oxide improved oxygenation but did not improve survival in severely hypoxaemic premature neonates.Low-dose nitric oxide in the most critically ill premature neonates does not increase the risk of intracranial haemorrhage, and may decrease risk of chronic lung injury.(Lancet 1999;354:1061-5) Early compared with delayed inhaled nitric oxide in moderately hypoxaemic neonates with respiratory failure: a randomised controlled trialThe Franco-Belgium Collaborative NO Trial Group Background.Inhaled nitric oxide improves oxygenation in severely hypoxaemic term neonates, which lessens the need for extracorporeal-membrane oxygenation.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 (≥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).The 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-oxide group and 95 (40 preterm) in the control group.The decline in oxygenation 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 unit, but this was also significant only in near-term neonates (6[3] vs 7[3] days, p=0.05, on August 15,