Surfactant instillation in spontaneously breathing preterm infants: a systematic review and meta-analysis

Less invasive surfactant therapies (LIST) use surfactant instillation through a thin tracheal catheter in spontaneously breathing infants. This review and meta-analysis investigates respiratory outcomes for preterm infants with respiratory distress syndrome treated with LIST rather than administration of surfactant through an endotracheal tube. Randomised controlled trial (RCT) full texts provided outcome data for bronchopulmonary dysplasia (BPD), death or BPD, early CPAP failure, invasive ventilation requirements and usual neonatal morbidities. Relative risks (RR) from pooled data, with subgroup analyses, were obtained from a Mantel-Haenszel analysis using a random effect model. Six RCTs evaluated LIST: 4 vs InSurE and 1 each vs delayed or immediate intubation for surfactant. LIST resulted in decreased risks of BPD (RR = 0.71 [0.52-0.99]; NNT = 21), death or BPD (RR = 0.74 [0.58-0.94]; NNT = 15) and early CPAP failure or invasive ventilation requirements (RR = 0.67 [0.53-0.84]; NNT = 8 and RR = 0.69 [0.53-0.88]; NNT = 6). Compared to InSurE, LIST decreased the risks of BPD or death (RR = 0.63 [0.44-0.92]; NNT = 11) and of early CPAP failure (RR = 0.71 [0.53-0.96]; NNT = 11). Common neonatal morbidities were not different.

Respiratory management with LIST decreases the risks of BPD and BPD or death, and the need for invasive ventilation. This strategy appears safe, but long-term follow-up is lacking. What is Known: • Initial management of preterm infants with CPAP decreases the risk of death or BPD, but many still require surfactant or invasive ventilation. • Surfactant can be instilled through a tracheal thin catheter while the infant breathes on CPAP, but improvement in BPD is inconsistent between studies. What is New: • Less invasive surfactant therapy (LIST) strategies decrease the risks of BPD, of death or BPD, and of CPAP failure compared to strategies where surfactant is administered through an endotracheal tube. • LIST strategies decrease the risks of the composite outcome of BPD or death and of early CPAP failure when compared to "intubation-surfactant-extubation" approaches.