Comparison of LISA and INSURE techniques for surfactant administration: a multicentre retrospective study

Abstract NIV and early targeted endotracheal surfactant administration play a pivotal role in the treatment of RDS and other respiratory conditions in neonates. LISA and INSURE are the most widely used techniques for surfactant delivery. This multicentre retrospective registry-based cohort study, conducted in three Southern Italy Neonatal Intensive Care Units between January 2024 and March 2025, aimed to compare their effectiveness. Neonates who received NIV soon after birth and rescue surfactant via either INSURE or LISA were included. Treatment failure was defined as the need for a second dose of surfactant or the need for intubation and mechanical ventilation within 72 h of life. The secondary outcomes were the incidence of BPD at 36 weeks post-menstrual age or at discharge and impact of the applied NIV mode on outcomes within the LISA subgroup. Sixty-one neonates were enrolled: 29 LISA group (48%) and 32 INSURE group (52%). No significant differences were observed in the need for a second surfactant dose (LISA 38% vs INSURE 19%, p = 0.095) or mechanical ventilation within the first 72 h of life (LISA 17% vs INSURE 9%, p = 0.460). BPD incidence was low and comparable between groups (LISA 7% vs INSURE 3%, p = 0.600). In LISA-treated neonates, HFNC, nCPAP, and NIPPV showed comparable effects on primary and secondary outcomes, while oxygen supplementation duration was significantly shorter with NIPPV ( p = 0.014). Conclusion : LISA and INSURE are equally effective modalities for surfactant administration in neonates with no significant differences. What Is Known: • Less invasive surfactant administration (LISA) is currently recommended by the latest European guidelines as the preferred method for surfactant delivery in spontaneously breathing infants on non-invasive ventilation (NIV). • Previous studies suggested that LISA and INSURE have similar safety and effectiveness, with comparable short- and long-term outcomes. What is New: • In this study, the need for a second dose of surfactant was explicitly considered as a marker of LISA failure. • LISA and INSURE techniques are comparable in reducing the need for mechanical ventilation and have similar major clinical outcomes, including BPD. There was a trend toward a higher rate of surfactant retreatment in the LISA group, without reaching statistical significance (p = 0.095). This was not associated with increased intubation or adverse outcomes, suggesting a potential stepwise non-invasive management strategy rather than true therapeutic failure.