Synthetic surfactant for respiratory distress syndrome in preterm infants

Background This section is under preparation and will be included in the next issue. Objectives To assess the effect of intratracheal administration of synthetic surfactant in premature newborns with established respiratory distress syndrome (RDS). Search methods Searches were made of the Oxford Database of Perinatal Trials, Medline (MeSH terms: pulmonary surfactants; limits: age groups, newborn infant; publication types, clinical trial), previous reviews including cross references, abstracts, conference and symposia proceedings, expert informants, and journal handsearching in the English language. Selection criteria Randomized controlled trials which compared the effect of synthetic surfactant treatment to routine management in the treatment of preterm infants with respiratory distress syndrome. Data collection and analysis Data regarding clinical outcome including the incidence of pneumothorax, pulmonary interstitial emphysema, pulmonary hemorrhage, patent ductus arteriosus, necrotizing enterocolitis, apnea of prematurity, intraventricular hemorrhage (any grade, and severe intraventricular hemorrhage), bronchopulmonary dysplasia, neonatal mortality, bronchopulmonary dysplasia or death, retinopathy of prematurity (any retinopathy, and retinopathy greater than Stage 3), mortality at hospital discharge, mortality to one year of age, and cerebral palsy (any, and moderate/severe cerebral palsy) was excerpted from the report of the clinical trials by the reviewer. Data were analyzed according to the standards of the Cochrane Neonatal Review Group. Main results Six randomized controlled trials of synthetic surfactant treatment of established respiratory distress syndrome were identified. Five of the studies used Exosurf Neonatal (a synthetic surfactant composed of dipalmitoylphosphatidylcholine, hexadecanol and tyloxapol); one small study utilized a mixture of dipalmitoylphosphatidylcholine (DPPC) and phosphatidylglycerol (PG). Treatment with intratracheal Exosurf Neonatal in premature infants with established respiratory distress syndrome improves pulmonary gas exchange and decreases the requirement for ventilatory support. In individual trials, the use of Exosurf Neonatal resulted in a statistically significant reduction in pneumothorax, patent ductus arteriosus, bronchopulmonary dysplasia (BPD), BPD or death at 28 days, and mortality. Similar results are seen when these large trials of Exosurf Neonatal are analyzed in conjunction with the smaller trial of dry powdered DPPC and phosphatidylglycerol (PG). The meta-analysis supports a decrease in the risk of pneumothorax (typical relative risk 0.64, 95% CI 0.55, 0.76, typical risk difference -0.09, 95% CI -0.12,-0.06), a decrease in the risk of pulmonary interstitial emphysema (typical relative risk 0.62, 95% CI 0.54, 0.71, typical risk difference -0.12, 95% CI -0.16, -0.09), a decrease in the risk of patent ductus arteriosus (typical relative risk 0.90, 95% CI 0.84, 0.97; typical risk difference -0.06 95% CI -0.10, -0.02), a decrease in the risk of intraventricular hemorrhage (typical relative risk 0.88, 95% CI 0.77, 0.99; typical risk difference -0.04, 95% CI -0.08, -0.00), a decrease in the risk of bronchopulmonary dysplasia (typical relative risk 0.75, 95% CI 0.61, 0.92; typical risk difference -0.04, 95% CI -0.06, -0.01), a decrease in the risk of neonatal mortality (typical relative risk 0.73, 95% CI 0.61, 0.88; typical risk difference -0.05, 95% CI -0.07, -0.02), a decrease in the risk of bronchopulmonary dysplasia or death at 28 days (typical relative risk 0.73, 95% CI 0.65, 0.83; typical risk difference -0.06, 95% CI -0.11, -0.05), a decrease in the risk of mortality prior to hospital discharge (typical relative risk 0.79, 95% CI 0.68, 0.92; typical risk difference -0.05, 95% CI -0.07, -0.02) and a decrease in the risk of mortality during the first year of life (typical relative risk 0.80, 95% CI 0.69, 0.94; typical risk difference -0.04, 95% CI -0.07, -0.01). Treatment with synthetic surfactant increases the risk of apnea of prematurity (typical relative risk 1.20, 95% CI 1.09, 1.31; typical risk difference 0.08, 95% CI 0.04, 0.12). Authors' conclusions Intratracheal administration of synthetic surfactant to infants with established respiratory distress syndrome has been demonstrated to improve clinical outcome. Infants who are treated with synthetic surfactant have a decreased risk of pneumothorax, a decreased risk of pulmonary interstitial emphysema, a decreased risk of intraventricular hemorrhage, a decreased risk of bronchopulmonary dysplasia, a decreased risk of neonatal mortality, a decreased risk of mortality prior to hospital discharge and at 1 year of age. Infants who receive synthetic surfactant treatment for established RDS have an increased risk of apnea of prematurity.