Clinical bottom line
Inhaled nitric oxide (iNO) is a targeted pulmonary vasodilator used in the management of pulmonary hypertension (PH) in neonates and infants. It is primarily utilized for its ability to selectively reduce pulmonary artery pressure without causing systemic hypotension. The use of iNO is well-established in term and near-term neonates with hypoxic respiratory failure and evidence of pulmonary hypertension. However, its role in preterm infants and other pediatric populations remains less clear and requires careful consideration of the evidence.
What the evidence shows
Inhaled nitric oxide has been shown to improve oxygenation and reduce the need for extracorporeal membrane oxygenation (ECMO) in term and near-term neonates with persistent pulmonary hypertension of the newborn (PPHN). A systematic review by Barrington et al. (2017) confirmed that iNO significantly reduces the need for ECMO in this population, with a number needed to treat (NNT) of approximately 5 to prevent one ECMO treatment (PMID: 28257568).
For preterm infants, the evidence is less definitive. A Cochrane review by Askie et al. (2017) evaluated the use of iNO in preterm infants and found no significant improvement in survival without bronchopulmonary dysplasia (BPD) (PMID: 28257567). The review highlighted that while iNO may improve short-term oxygenation, it does not appear to confer long-term respiratory benefits in this group.
In infants and older children with other forms of pulmonary hypertension, such as those associated with congenital heart disease, the use of iNO is more variable and often based on individual clinical scenarios. A study by Steinhorn et al. (2016) explored the use of iNO in pediatric patients with PH secondary to congenital heart defects, suggesting potential benefits in specific cases, although larger trials are needed to confirm these findings (PMID: 26820273).
Caveats and uncertainty
While iNO is effective in certain neonatal populations, its use is not without risks. Potential adverse effects include methemoglobinemia and nitrogen dioxide formation, which necessitate careful monitoring. Additionally, the cost of iNO therapy is significant, which may limit its accessibility in some healthcare settings.
The lack of robust evidence supporting the use of iNO in preterm infants and other pediatric populations introduces uncertainty in clinical decision-making. Current guidelines recommend against routine use in preterm infants due to insufficient evidence of benefit. Furthermore, the heterogeneity of studies and patient populations makes it challenging to generalize findings across different clinical contexts.
How this may change practice
The established role of iNO in term and near-term neonates with PPHN is unlikely to change significantly in the near future, given the consistent evidence supporting its efficacy. However, ongoing research may refine its use in preterm infants and other pediatric populations. Clinicians should remain informed about emerging evidence and consider individual patient factors when deciding on iNO therapy.
Future studies may focus on identifying specific subgroups of preterm infants or pediatric patients who might benefit from iNO, potentially leading to more targeted and effective use of this therapy. Additionally, advancements in alternative pulmonary vasodilators or combination therapies could influence the landscape of PH management in neonates and infants.