Respiratory distress syndrome (RDS) in newborn neonates is characterised by deficient secretion of
surfactant from type III alveolar cells. Administration of
surfactant to airways acutely decreases the degree of
respiratory failure and increases the survival rate in neonates with RDS. Clinically available
surfactants are
lipid extracts derived from animal lung lavage or from whole lung. Synthetic
surfactants contain
phospholipids or additional spreading agents. An optimal exogenous
surfactant would be efficacious, nontoxic and nonimmunogenic, resistant to
oxidants and proteolytic agents, widely available at reasonable cost and manufactured with little batch-to-batch variability.
Surfactant has been instilled into the airways as a bolus infusion through the endotracheal tube. In addition,
surfactant may be given by aerosolisation or continuous infusion into the airways. Suggested dosages range from 50 to 200 mg/kg. Exogenous
surfactant is cleared from the epithelial lining fluid (ELF) mainly by alveolar epithelial cells, although alveolar macrophages and the central airways may also contribute to clearance of the
drug. Only small quantities of
surfactant actually enter the blood stream. A significant fraction of
surfactant is taken up, processed, and secreted back into the alveolar space by type II alveolar cells. This process is termed recycling.
Phosphatidylglycerol, given to small premature neonates as a component of exogenous human
surfactant, has an apparent pulmonary half-life of 31 +/- 3 hours (n = 11). The apparent pulmonary half-life of the main
surfactant component
dipalmitoyl phosphatidylcholine is 45 hours (n = 3) and that of
surfactant protein A is about 9 hours (n = 4). A relationship between the dose of exogenous
surfactant and its concentration in the ELF has been demonstrated. Some neonates with RDS respond poorly to
surfactant therapy. The reasons for this include insufficient levels of
surfactant in the ELF, uneven distribution of exogenous
surfactant, inability of exogenous
surfactant to enter the metabolic pathways, inhibition of surface activity by plasma-derived
proteins, or inactivation of
surfactant as a result of
proteases,
phospholipases, or
oxygen free radicals. In addition,
surfactant therapy may be ineffective in neonates with
respiratory failure caused by factors other than
surfactant deficiency. The efficacy of exogenous
surfactant can be improved by increasing the dosage of
surfactant and by administration of
surfactant very early in
respiratory failure.