B60-29 Ventilation Strategy Determines Lung Surfactant Functional Preservation in a Neonatal Lung Injury Model

Rationale

Respiratory Distress Syndrome (RDS) is a major complication of neonatal mechanical ventilation and is driven in part by ventilation-induced lung injury and disruption of lung surfactant. While high-frequency oscillatory ventilation with volume guarantee (HFOV+VG) is considered a lung-protective strategy, its effect on surfactant biophysical performance remains unknown. In addition, aerosolized surfactant delivery has been proposed to improve surfactant distribution and limit mechanical stress compared with bolus instillation, but its functional benefit remains uncertain.

Methods

A neonatal piglet model of ventilation-induced lung injury was established through repeated BAL to induce surfactant depletion. Animals were randomized into four experimental groups combining ventilation strategy and surfactant delivery mode: conventional mechanical ventilation (CMV) with bolus delivery, CMV with aerosolized delivery, HFOV+VG with bolus delivery, and HFOV+VG with aerosolized delivery. Large surfactant aggregates were isolated from BAL. Surfactant biophysical function was assessed using Captive Bubble Surfactometer. Data are presented as median (interquartile range) and analyzed using non-parametric statistics. Global group differences were assessed using Kruskal-Wallis tests with effect sizes estimated by epsilon squared (ε²).

Results

Surface tension differed significantly between groups: 5 seconds after injection, CMV-bolus was 48.6 [45.0-50.0] mN/m, CMV-nebulized 47.5 [37.5-52.0] mN/m, HFOV+VG-bolus 35.2 [29.7-38.5] mN/m, and HFOV+VG-nebulized 44.9 [40.7-46.7] mN/m (H = 8.44, p = 0.038, ε²=0.25), although it was later stabilized and reached equilibrium in all samples. After expansion, re-spreading to equilibrium differed across groups: After 5 seconds, CMV-bolus was 37.8 [26.5-48.5] mN/m, CMV-nebulized 40.7 [23.3-52.1] mN/m, HFOV+VG-bolus 23.1 [22.7-23.4] mN/m, and HFOV+VG-nebulized 23.8 [22.8-25.1] mN/m (H = 10.26, p = 0.016, ε²=0.33). These differences persisted after 5 minutes (CMV-bolus 25.4 [23.0-31.7], CMV-nebulized 29.1 [22.3-41.1], HFOV+VG-bolus 22.4 [22.3-22.9], HFOV+VG-nebulized 22.7 [22.3-22.8] mN/m; H = 8.63, p = 0.035, ε²=0.26). During prolonged dynamic cycling that mimics repetitive breathing, minimum surface tension in the 30th cycle differed significantly across groups: CMV-bolus 16.3 [2.1-19.9] mN/m, CMV-nebulized 11.3 [2.2-20.0] mN/m, HFOV+VG-bolus 2.3 [2.1-2.5] mN/m, and HFOV+VG-nebulized 2.0 [1.6-2.2] mN/m (H = 8.66, p = 0.034, ε²=0.26).

Conclusions

Ventilation strategy was the primary determinant of lung surfactant function. HFOV+VG preserved surfactant adsorption, respreading, and the ability to achieve very low surface tensions during dynamic cycling, whereas CMV was associated with higher and more heterogeneous surface tensions. Aerosolized surfactant delivery did not confer additional functional benefit under the conditions studied, likely because the severity of CMV-induced lung injury outweighed potential delivery-related effects. Overall, these findings highlight HFOV+VG as a particularly effective lung-protective ventilation strategy for preserving surfactant biophysical function in severe ventilation-induced injury

This abstract is funded by: Spanish Ministry of Science and Innovation