LISA and ENSURE show similar need for ventilation in preterm neonates with respiratory distress syndrome

UNLABELLED: Surfactant replacement therapy improves outcomes in preterm neonates with respiratory distress syndrome (RDS). While the less invasive surfactant administration (LISA) technique offers advantages over intubate-surfactant-extubate (INSURE), the enhanced INSURE (ENSURE) technique has been proposed to address procedural limitations of INSURE. However, direct comparisons between LISA and ENSURE are limited. This study aimed to compare the effectiveness of LISA and ENSURE in reducing the need for mechanical ventilation within 72 h in preterm neonates with RDS. In this open-label, single-center randomized controlled trial conducted at a tertiary-care hospital in North India, 118 preterm neonates (gestational age 26-35 weeks) requiring surfactant therapy were randomized to receive either LISA or ENSURE. The primary outcome was the need for invasive mechanical ventilation within 72 h of surfactant administration. Secondary outcomes included duration of respiratory support, ventilator-free days, intraventricular hemorrhage (IVH), bronchopulmonary dysplasia (BPD), mortality, and other neonatal morbidities. Baseline characteristics, including gestational age (30.6 vs. 31.3 weeks), birth weight (1442 vs. 1537 g), use of antenatal steroids (91.5% vs. 94.9%), were comparable between the two groups. The need for invasive mechanical ventilation within 72 h was similar in the LISA and ENSURE groups (32.2% vs. 33.9%; relative risk 0.95, 95% CI 0.57-1.59; p = 0.845). The duration of respiratory support, incidence of BPD, and mortality was also comparable. CONCLUSION:  LISA did not reduce the need for invasive mechanical ventilation within 72 h, duration of respiratory support, or neonatal morbidities and mortality compared with ENSURE. TRIAL REGISTRATION: Clinical Trial Registry of India (CTRI/2023/07/055841). WHAT IS KNOWN: •LISA reduces mechanical ventilation and BPD compared with conventional INSURE by preserving spontaneous breathing and avoiding prolonged positive pressure ventilation. •However, consistent superiority over other surfactant delivery techniques has not been demonstrated, with outcomes influenced by technique, expertise, patient selection, and protocol variability. WHAT IS NEW: •ENSURE showed comparable effectiveness to LISA in reducing invasive mechanical ventilation within 72 h. •These findings underscore that a standardized, protocol-driven surfactant strategy may be as important as the choice of technique.