Response to inhaled nitric oxide in premature and term neonates

Inhaled nitric oxide (iNO) has emerged as a promising therapeutic agent in the treatment of persistent pulmonary hypertension of the newborn. Several theories exist regarding causes of both response and nonresponse to iNO. Clinical trials differentiate disease entities (primary vs secondary persistent pulmonary hypertension associated with meconium aspiration syndrome, pneumonia or congenital diaphragmatic hernia) and their specific response rates. iNO combined with high-frequency ventilation appears to be superior to inhalation of nitric oxide (NO) during conventional ventilation. Little is known regarding the role of the degree of lung expansion and its modification -- no matter what mode of ventilation is applied. Gestational age plays an important role in relation to the potential adverse effects of NO. Of particular concern in the premature neonate is the effect of NO on bleeding time and the inhibition of platelet aggregation. Those potentially hazardous effects need to be carefully weighed against early intervention with iNO at a comparably low oxygenation index in order to prevent the vicious cycle of hypoxaemia and subsequent increased right-to-left shunting. Further studies are required to determine the optimal timing, mode of delivery and mode of ventilation used with iNO therapy in order to optimise the response of premature and term neonates.