A RISK-BENEFIT ASSESSMENT OF NATURAL AND SYNTHETIC EXOGENOUS SURFACTANTS IN THE MANAGEMENT OF NEONATAL RESPIRATORY-DISTRESS SYNDROME

Alveolar surfactant is central to pulmonary physiology. Quantitative a nd qualitative surfactant abnormalities appear to be the primary aetio logical factors in neonatal respiratory distress syndrome (RDS) and ex ogenous replacement of surfactant is a rational treatment. Available e xogenous surfactants have a natural (mammal-derived lung surfactants) or synthetic origin. Pharmacodynamic and clinical studies have demonst rated that exogenous surfactants immediately improve pulmonary distens ibility and gas exchange; however, this is achieved more slowly and wi th more failures with synthetic surfactants. The ensuing advantageous haemodynamic effects are not so striking and they include an inconveni ent increased left to right ductal shunt. Two strategies of administra tion have been used: prophylactic or rescue therapy to treat declared RDS. All methods of instillation require intubation. In addition to th e early benefits (improved gas exchange and reduced ventilatory suppor t) the incidence of classical complications of RDS, especially air lea k events, is decreased except for the uncommon problem of pulmonary ha emorrhage. The incidence of bronchopulmonary dysplasia is neither unif ormly nor significantly reduced although the severity appears to be le ssened. The overall incidence of peri-intraventricular haemorrhages is not diminished although separate trials have shown a decreased rate. The most striking beneficial effect of exogenous surfactants is the in creased survival (of about 40%) of treated very low birthweight neonat es. A small number of adverse effects has been described. The long ter m outcome of survivor neonates with RDS treated with surfactants versu s control neonates with RDS not treated with surfactants is similar in terms of physical growth, at least as good in terms of respiratory st atus, with a similar or slightly better neurodevelopmental outcome. Th ere is no clear benefit of exogenous surfactant therapy in extremely p remature infants (<26 weeks gestational age, birthweight <750g). The p otential risks of contamination, inflammatory and immunogenic reaction and the inhalation of platelet activating factor remain a theoretical concern of surfactant therapy which has not been confirmed in clinica l practice. The optimal timing of treatment favours prophylaxis over r escue treatment and early rescue treatment rather than delayed therapy . Meta-analyses suggest the clinical superiority of natural surfactant extracts over a synthetic one (colfosceril palmitate). The economic i mpact of surfactant therapy is favourable and the costs per quality-ad justed life year (QALY) for surviving surfactant treated infants are l ow. In conclusion, the mid and long term benefit/risk ratio clearly fa vours the use of exogenous surfactants to prevent or to treat RDS in n eonates who have a gestational age of >26 weeks or a birthweight of >7 50g, especially with the prophylactic strategy using natural surfactan t extracts.