Inhaled nitric oxide in premature infants--a meta-analysis

The role of inhaled nitric oxide (iNO) in the treatment of severe hypoxemic respiratory failure of term neonates has been firmly established in several randomized trials. In contrast, the use of iNO in premature newborns has remained controversial. As of 1999, there are data of three randomized controlled trials involving a total of 210 infants below 33 weeks of gestation. None of the trials was able to demonstrate a benefit of iNO with respect to mortality or chronic lung disease. We performed a meta-analysis of the three published trials. Of 111 infants receiving iNO, 44 deaths were observed, compared to 40 of 99 control infants (p = 0.91). The odds ratio in favor of iNO was 0.97 (95% confidence interval 0.54-1.75). There was also no significant difference for treatment failure, defined as death or chronic lung disease (iNO: 32 of 111 infants versus control: 34 of 99, p = 0.39, odds ratio 0.77, 95% confidence interval 0.41-1.45). The rates of intracranial hemorrhage were similar in both groups (35 of 111 infants receiving iNO vs 25 of 99 controls, p = 0.33, odds ratio 1.37, 95% confidence interval 0.69-2.74). We conclude that the use of inhaled nitric oxide may improve oxygenation but not survival in preterm infants with severe hypoxemic respiratory failure.