Early, Low-Dose Pulmonary Surfactant Administration in Infants with Post-Cardiotomy Acute Respiratory Distress Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial

Abstract Background: ​ Acute respiratory distress syndrome (ARDS) following cardiopulmonary bypass (CPB) in infants is associated with high morbidity and mortality, driven in part by surfactant dysfunction. While exogenous surfactant is a mainstay for neonatal respiratory distress syndrome, its efficacy in pediatric ARDS remains unproven. This study tested the hypothesis that early, low-dose surfactant therapy improves outcomes in infants with post-cardiotomy ARDS. Methods: ​ In this single-center, double-blind, randomized, placebo-controlled trial, we enrolled infants (≤3 months; weight ≤6 kg) who developed moderate-to-severe ARDS (PaO₂/FiO₂ ≤300 mmHg by PALICC-2 criteria) within 6 hours after CPB. Participants were randomly assigned (1:1) to receive a single endotracheal dose of surfactant (15 mg/kg) or an equivalent volume of saline placebo within 24 hours postoperatively. The primary outcome was the duration of invasive mechanical ventilation. Secondary outcomes included lengths of pediatric intensive care unit (PICU) and hospital stay, oxygenation indices, and safety. Results: ​ Between August 2023 and August 2025, 128 infants were included in the intention-to-treat analysis (65 surfactant, 63 placebo). Groups were well-balanced at baseline. Surfactant administration significantly reduced ventilator duration (69.0 ± 49.6 h vs. 106.2 ± 89.7 h; mean difference –37.1 h, 95% CI –61.2 to –13.0; P < 0.01) and shortened PICU stay (14.3 ± 7.8 d vs. 17.9 ± 8.2 d; P < 0.05) and hospital stay (22.0 ± 11.0 d vs. 26.0 ± 9.1 d; P < 0.05). The surfactant group demonstrated a 26.3% reduction in total hospitalization costs (160.45 ± 44.00 vs. 217.71 ± 155.56 ×10³ CNY; P = 0.005) and exhibited superior lactate clearance (1.19 ± 0.55 vs. 1.58 ± 1.01 mmol/L; P < 0.01) and PaO₂/FiO₂ ratios (292.0 ± 126.3 vs. 229.5 ± 85.6; P < 0.01) at 48 hours. No surfactant-related adverse events occurred. Subgroup analyses suggested enhanced benefit in neonates (≤28 d) and low-birth-weight infants (