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 and qualitative surfactant abnormalities appear to be the primary aetiological factors in neonatal respiratory distress syndrome (RDS) and exogenous replacement of surfactant is a rational treatment. Available exogenous surfactants have a natural (mammal-derived lung surfactants) or synthetic origin. Pharmacodynamic and clinical studies have demonstrated that exogenous surfactants immediately improve pulmonary distensibility and gas exchange; however, this is achieved more slowly and with more failures with synthetic surfactants. The ensuing advantageous haemodynamic effects are not so striking and they include an inconvenient increased left to right ductal shunt. Two strategies of administration have been used: prophylactic or rescue therapy to treat declared RDS. All methods of instillation require intubation. In addition to the early benefits (improved gas exchange and reduced ventilatory support) the incidence of classical complications of RDS, especially air leak events, is decreased except for the uncommon problem of pulmonary haemorrhage. The incidence of bronchopulmonary dysplasia is neither uniformly nor significantly reduced although the severity appears to be lessened. 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 increased survival (of about 40%) of treated very low birthweight neonates. A small number of adverse effects has been described. The long term outcome of survivor neonates with RDS treated with surfactants versus control neonates with RDS not treated with surfactants is similar in terms of physical growth, at least as good in terms of respiratory status, with a similar or slightly better neurodevelopmental outcome. There is not clear benefit of exogenous surfactant therapy in extremely premature infants (< 26 weeks gestational age, birthweight < 750 g). The potential 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 clinical practice. The optimal timing of treatment favours prophylaxis over rescue 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 impact of surfactant therapy is favourable and the costs per quality-adjusted life year (QALY) for surviving surfactant treated infants are low. In conclusion, the mid and long term benefit/risk ratio clearly favours the use of exogenous surfactants to prevent or to treat RDS in neonates who have a gestational age of > 26 weeks or a birthweight of > 750 g, especially with the prophylactic strategy using natural surfactant extracts.