Nitric oxide might improve preterm infants respiratory outcome

Inhaled nitric oxide is successfully used in the treatment of in term infants with persistent pulmonary hypertension. Its positive action is exerted through a selective pulmonary vasodilatation which improves oxygenation and reduces the need for extracorporeal membrane oxygenation.

The possibility of applying inhaled nitric oxide therapy to preterm infants at high risk for respiratory complications and bronchopulmonary displasia has also been evaluated. Preliminary works in animals reported that inhaled nitric oxide improves surfactant function and reduces lung inflammation, attenuates hyperoxic lung injury and promotes lung growth. However, most trials in critically ill preterm babies assessed no advantage in preventing bronchopulmonary displasia. Furthermore, they underlined the negative possible outcomes of such a treatment for the vulnerable preterm organism, consisting in exacerbation of hemorrhagic or ischemic brain injury.

A new perspective about the possibility of using nitric oxide for preterm babies is given by the study by Ballard et al., who conducted a randomized, stratified, double-blind, placebo-control clinical trial, involving 21 centres. They hypothesized that a prolonged therapy with nitric oxide might be needed to prevent increased airway resistance, to attenuate hyperoxic injury and to improve surfactant function and lung development.

The design of this large study differs from other similar trials. In the first place, the enrolled infants were undergoing mechanical ventilation between 7 and 21 days of age, while previous studies took into consideration preterm babies with respiratory failure shortly after birth, in the attempt to counteract inflammation and pulmonary hypertension. Conversely, Ballard and colleagues aimed to prevent further negative outcomes. Thus, they focused on infants who were likely to develop bronchopulmonary displasia but they excluded infants whose condition was life-threatening. In the second place, nitric oxide treatment was continued for 24 days, independently on the possible benefits. Eventually, infants in this trial had greater exposure to nitric oxide, in terms of the duration and the peak and total dose, than did infants in other trials.

Analyzing the results, the researchers concluded that 24 days treatment with nitric oxide significantly improved the likelihood of survival and diminished the incidence of bronchopulmonary displasia at 36 weeks. Infants who received nitric oxide were hospitalized for fewer days, required oxygen for a shorter period and had less severe disease. Moreover there was no evidence of short-term deleterious clinical effects of nitric oxide therapy. Anyway, the conclusion of the study still awaits long-term pulmonary and neurodevelopmental outcomes to be followed up through two years of infants' age.

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