Early versus delayed selective surfactant treatment for neonatal respiratory distress syndrome

Background Clinical trials have confirmed that surfactant therapy is effective in improving the immediate need for respiratory support and the clinical outcome of premature newborns. Trials have studied a wide variety of surfactant preparations used either to prevent (prophylactic or delivery room administration) or treat (selective or rescue administration) respiratory distress syndrome (RDS). Using either treatment strategy, significant reductions in the incidence of pneumothorax, as well as significant improvement in survival, have been noted. It is unclear whether there are any advantages to treating infants with respiratory insufficiency earlier in the course of RDS. Objectives To compare the effects of early versus delayed selective surfactant therapy for newborns intubated for respiratory distress within the first two hours of life. Planned subgroup analyses included separate comparisons for studies utilizing natural surfactant extract and synthetic surfactant. Search methods We searched the Oxford Database of Perinatal Trials, MEDLINE (MeSH terms: pulmonary surfactant; text word: early; limits: age, newborn: publication type, clinical trial), PubMed, abstracts, conference and symposia proceedings, expert informants, and journal handsearching in the English language. For the updated search in April 2012 we searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, 2012, Issue 1) and PubMed (January 1997 to April 2012). Selection criteria Randomized and quasi-randomized controlled clinical trials comparing early selective surfactant administration (surfactant administration via the endotracheal tube in infants intubated for respiratory distress, not specifically for surfactant dosage) within the first two hours of life versus delayed selective surfactant administration to infants with established RDS were considered for review. Data collection and analysis Data regarding clinical outcomes were excerpted from the reports of the clinical trials by the review authors. Subgroup analyses were performed based on type of surfactant preparation, gestational age, and exposure to prenatal steroids. Data analysis was performed in accordance with the standards of the Cochrane Neonatal Review Group. Main results Six randomized controlled trials met selection criteria. Two of the trials utilized synthetic surfactant (Exosurf Neonatal) and four utilized animal-derived surfactant preparations. The meta-analyses demonstrate significant reductions in the risk of neonatal mortality (typical risk ratio (RR) 0.84; 95% confidence interval (CI) 0.74 to 0.95; typical risk difference (RD) -0.04; 95% CI -0.06 to -0.01; 6 studies; 3577 infants), chronic lung disease (typical RR 0.69; 95% CI 0.55 to 0.86; typical RD -0.04; 95% CI -0.06 to -0.01; 3 studies; 3041 infants), and chronic lung disease or death at 36 weeks (typical RR 0.83; 95% CI 0.75 to 0.91; typical RD -0.06; 95% CI -0.09 to -0.03; 3 studies; 3050 infants) associated with early treatment of intubated infants with RDS. Intubated infants randomized to early selective surfactant administration also demonstrated a decreased risk of acute lung injury including a decreased risk of pneumothorax (typical RR 0.69; 95% CI 0.59 to 0.82; typical RD -0.05; 95% CI -0.08 to -0.03; 5 studies; 3545 infants), pulmonary interstitial emphysema (typical RR 0.60; 95% CI 0.41 to 0.89; typical RD -0.06; 95% CI -0.10 to -0.02; 3 studies; 780 infants), and overall air leak syndromes (typical RR 0.61; 95% CI 0.48 to 0.78; typical RD -0.18; 95% CI -0.26 to -0.09; 2 studies; 463 infants). A trend toward risk reduction for bronchopulmonary dysplasia (BPD) or death at 28 days was also evident (typical RR 0.94; 95% CI 0.88 to 1.00; typical RD -0.04; 95% CI -0.07 to -0.00; 3 studies; 3039 infants). No differences in other complications of RDS or prematurity were noted. Only two studies reported on infants under 30 weeks' gestation. Decreased risk of neonatal mortality and chronic lung disease or death at 36 weeks' postmenstrual age was noted. Authors' conclusions Early selective surfactant administration given to infants with RDS requiring assisted ventilation leads to a decreased risk of acute pulmonary injury (decreased risk of pneumothorax and pulmonary interstitial emphysema) and a decreased risk of neonatal mortality and chronic lung disease compared to delaying treatment of such infants until they develop worsening RDS.