Guidelines for Rational and Cost-Effective Use of iNO Therapy in Term and Preterm Infants

Inhaled nitric oxide (iNO) is an effective but costly therapy for infants with hypoxemic respiratory failure. The approved and solidly evidence-based indication is for treatment of late preterm and term infants with persistent pulmonary hypertension of the newborn (PPHN); however, off-label use of iNO has become widespread. Although iNO treatment of infants with congenital diaphragmatic hernia constitutes one of the approved indications, available evidence from randomized trials suggests marginal if any efficacy. Rescue therapy in preterm infants with severe respiratory failure has been studied extensively and is not supported by data from a number of controlled trials. Such use is widespread, but should be discouraged. There may be a subgroup of such infants with pulmonary hypoplasia and documented PPHN who may benefit from this treatment, but the data are limited. Several studies have examined the use of iNO for prevention of chronic lung disease with inconsistent results. This promising application requires more study before it can be recommended. There may be a role of iNO in treating infants with pulmonary hypertension complicating severe bronchopulmonary dysplasia, but there are limited data on long term outcomes. Alternate therapies such as sildenafil may be beneficial in this specific population as well as in other causes of pulmonary hypertension. Rational use of this expensive treatment will maximize cost:benefit and avoid potential exposure to unknown adverse effects not balanced by documentable benefits.