Inhaled nitric oxide in the neonatal period

Pulmonary hypertension of the newborn is an important cause of hypoxaemia, particularly in the at term or near term neonate. It can occur as a primary condition or secondary to a variety of other diseases. Endogenous nitric oxide is an important modulator of vascular tone in pulmonary circulation. Initial uncontrolled studies indicated that inhalation of nitric oxide resulted in a reduction in pulmonary hypertension, with improvement in oxygenation, but no change in the systemic vascular resistance. There have now been a number of randomised trials performed exploring the efficacy of inhaled nitric oxide. These trials have demonstrated that in at term or near term infants, inhaled nitric oxide reduces the combined end point of death or the need for extracorporeal membrane oxygenation. The significant effect seems due to the reduced extracorporeal membrane oxygenation requirement. No such beneficial effect has been consistently reported in infants with congenital diaphragmatic hernia. Randomised trials have failed to highlight long-term positive results in preterm infants. Inhaled nitric oxide has side effects, although those due to nitrogen dioxide and methaemoglobin formation can be minimised by appropriate nitric oxide delivery. It is important to use the smallest effective nitric oxide dose, continuous nitric oxide and nitrogen dioxide monitoring and frequent methaemoglobin analyses. Careful patient selection should be undertaken, avoiding those at high risk of haemorrhagic complications. Longer term follow-up studies are required to determine the real risk:benefit ratio of inhaled nitric oxide treatment.