Natural surfactant (Surfactant TA, Survanta, CLSE, SF-RI 1, Curosurf and human surfactant obtained from amniotic fluid) therapy for RDS in very premature infants has been evaluated in 17 controlled clinical trials. Uniformely intratracheal surfactant administration caused a decreased intensity of mechanical ventilation during the first hours (reduced inspiratory pressure, reduced oxygen requirements) as an immediate effect of surfactant administration. Metanalysis reveals barotraumatic pulmonary complications mainly, pneumothorax and pulmonary interstitial emphysema to occur less frequently in surfactant-treated infants in virtually all trials; an increased incidence of survival without bronchopulmonary dysplasia following surfactant treatment was observed in 10 controlled clinical trials. The incidence of other complications of prematurity (intracranial hemorrhage, patent ductus arteriosus and necrotizing enterocolitis) was unchanged following natural surfactant treatment. Dosing of natural surfactant is still under investigation, however recent data indicate that the initial dose should not be less than 100 mg/kg b.w. and retreatment should be given to infants with unsatisfactory response (i.e. fraction of inspired oxygen (FiO2) > 40%). Timing of surfactant treatment still remains controversial, Prophylactic treatment shortly following birth has been compared with rescue-treatment, i. e. surfactant administration to infants suffering from manifest RDS in most studies 4 - 8 h after birth. Conflicting data from 5 controlled trials may be interpreted as follows: prophylactic treatment seems to be favourable for extremely premature infants (GA less-than-or-equal-to 26 weeks) and rescue treatment seems to be adequate for infants of 27 - 30 weeks of gestation. Intratracheal surfactant instillation in very premature infants did not result in an improved lung function for 24 h to 48 h in all patients. Ten - 25% of study infants were reported to be ''non-responders'', i.e. infants without sustained decrease in oxygen requirements (i.c. FiO2 > 40%). Various factors may be operative including congenital bacterial infections (sepsis or pneumonia), lung hypoplasia and cardiac failure. Inactivation of surface properties of natural surfactant caused by a leakage of proteins across the alveolar-capillary membrane was observed in experimental and clinical studies. Current investigations focus on a combination of postnatal steroids and surfactant treatment to improve lung function and outcome in ''non-responders''. As long as any controlled clinical studies are being published, this approach remains experimental. Up to now, any controlled clinical trials have been performed to assess different modes of artificial ventilation (e. g. high frequency oscillating ventilation versus conventional ventilation) combined with surfactant therapy. Data obtained from premature animals given natural surfactant indicate any advantage with respect to gas exchange and lung histology to result from high frequency ventilation. Further controlled clinical trials are necessary to demonstrate efficacy and hazards of high frequency ventilation, which up to now remains an experimental approach in neonatal intensive care. Severe respiratory disorders in term infants e. g. meconium aspiration syndrome, congenital diaphragmatic hernia, adult respiratory distress-like disorders still represent a challange to neonatal intensive care. Clinical pilot studies indicate beneficial effects on gas exchange in term neonates following surfactant administration. These findings are supported by data from animal models of meconium aspiration syndrome, where an improvement in gas exchange and lung mechanics was demonstrated following surfactant administration. Before applying for routine neonatal intensive care, very carefully controlled clinical trials are mandatory to investigate efficacy and safety of surfactant treatment in term neonates suffering from severe respiratory disorders. Prevention of respiratory distress syndrome in very premature infants by corticosteroids or TRH remains a highly relevant tool. Clinical and experimental studies indicate, that a combination of prenatal steroids and postnatal surfactant results in additive effects and therefore should be further investigated prospectively in clinical trials.
