Clinical Decision Thresholds for Surfactant Administration in Preterm Infants: a Systematic Review and Network Meta-Analysis

Background:The ideal threshold at which surfactant administration in preterm neonates with respiratory distress syndrome (RDS) is most beneficial is contentious. The aim of this systematic review was to determine the optimal clinical criteria to guide surfactant administration in preterm neonates with RDS. Methods:The systematic review was registered in PROSPERO (CRD42022309433). Medline, Embase, CENTRAL and CINAHL were searched from inception till 16th May 2023. Only randomized controlled trials (RCTs) were included. A Bayesian random effects network meta-analysis (NMA) evaluating 33 interventions was performed. The primary outcome was requirement of invasive mechanical ventilation (IMV) within 7 days of life. Findings:58 RCTs were included. In preterm neonates ≤30 weeks after adjusting for the confounding factor of modality of surfactant administration, an arterial alveolar oxygen tension ratio (aAO2) <0.36 (FiO2: 37-55%) was ranked the best threshold for decreasing the risk of IMV, very low certainty. Further, surfactant administration at an FiO2 40-45% possibly decreased mortality compared to rescue treatment when respiratory failure was diagnosed, certainty very low. The reasonable inference that could be drawn from these findings is that surfactant administration may be considered in preterm neonates of ≤30 weeks' with RDS requiring an FiO2 ≥ 40%. There was insufficient evidence for the comparison of FiO2 thresholds: 30% vs. 40%. The evidence was sparse for surfactant administration guided by lung ultrasound. For the sub-group >30 weeks, nebulized surfactant administration at an FiO2 < 30% possibly increased the risk of IMV compared to Intubate-Surfactant-Extubate at FiO2 < 30% and 40%, and less invasive surfactant administration at FiO2 40%, certainty very low. Interpretation:Surfactant administration may be considered in preterm neonates of ≤30 weeks' with RDS if the FiO2 requirement is ≥40%. Future trials are required comparing lower FiO2 thresholds of 30% vs. 40% and that guided by lung ultrasound. Funding:None.