Adjunctive Therapies for Treatment of Severe Respiratory Failure in Neonates

Nitric oxide in persistent pulmonary hypertension of the neonate ▼ The usage of inhaled nitric oxide in term and near-term neonates had been addressed in a meta-analysis published by 2006 with 14 trials, which were eligible [12]. Oxygenation was improved after introduction of inhaled nitric oxide by about one half, and correspondingly, the oxygenation index decreased at least in infants with neonatal RDS suffering from coexisting persistent pulmonary hypertension of the neonate (PPHN) significantly. However, in the subgroup of babies with congenital diaphragmatic hernia, no significant improvement was observed. This subgroup of neonates presenting often with severe neonatal respiratory failure has been reported to differ considerably from other subgroups with respect to different response to interventions for treating severe neonatal respiratory failure [22]. As a conclusion from the trials on nitric oxide, it does seem reasonable to analyze term neonates or late preterms not only on the basis of need of adjunctive therapies, but also to select carefully underlying disorders leading to severe neonatal respiratory failure. Different pathophysiologies of severe respiratory failure in this distinct age group yield various therapeutic responses depending on the underlying disorder. In the group of preterm neonates, a meta-analysis was published in 2011 reporting on about 2 300 preterms in 11 trials. There was no effect of the routine use of inhaled nitric oxide in these cohorts of preterm neonates with respect to typical neonatal outcome variables: mortality, bronchopulmonary dysplasia (BPD) or severe neurologic disorders including intracranial hemorrhage and periventricular leukomalacia [1]. It thus can be concluded for the use of inhaled nitric oxide that in term neonates with severe respiratory failure excluding congenital diaphragmatic hernia the use of nitric oxide as an adjunctive therapy can be recommended. However, this does not hold true in preterm neonates, mostly suffering from classical neonatal RDS. Severe neonatal pulmonary failure in late preterm or term neonates still represents a major challenge in neonatology. In contrary with a considerable number of controlled clinical trials facing classical neonatal respiratory distress syndrome (RDS), e. g. primary surfactant deficiency syndrome in an immature lung, only a limited number of studies have been published to address this problem in near term or term neonates. Since the beginning 90 s, extracorporeal membrane oxygenation (ECMO) had been getting standard in neonatal intensive care. This trend had been intensified since the publication of a clinical controlled trial and follow-up data from the UK, testing ECMO in term neonates with severe respiratory failure [3]. In parallel with this trend, adjunctive therapies in severe neonatal respiratory failure have been developed facing surfactant administration, e. g. for meconium aspiration syndrome [11], administration of nitric oxide in persistent pulmonary hypertension [4] and high-frequency oscillation ventilation in hypoxic respiratory failure [8]. The data of these studies were convincing with respect to improving gas exchange acutely after introduction of either therapy, however, upon analyses of survival without oxygen requirements or other major clinical outcome variables, only few studies did show efficacy in term neonates suffering from either pathophysiology of respiratory failure.