(1249) Perfluorocarbon Liquid Lung Rest Improves Compliance in a Swine Model of Extracorporeal Life Support

Introduction: Extracorporeal life support (ECLS) is a life-saving treatment for severe lung injury that can enable “lung rest.” However, current lung rest strategies with gas ventilation can result in inadequate and heterogeneous alveolar recruitment; this may delay lung recovery and risk complications from prolonged ECLS runs. Liquid lung rest (LLR) with perfluorochemicals (PFCs) potentially offers a superior strategy compared to gas ventilation, as liquid can more evenly open the alveoli at lower pressures. We hypothesized that when compared to standard gas rest ventilation, LLR would improve pulmonary compliance and histologically demonstrate increased alveolar opening.

Methods: We induced acute lung injury with oleic acid (0.08 mL/kg) in neonatal pigs (3.5-4.5 kg), followed by cannulation to ECLS. The pigs were placed on rest ventilator settings (PIP 20, PEEP 10, Rate 10, FiO2 40%) and randomized to gas rest ventilation only (n=4) or LLR (n=5). In the LLR group, 5 mL/kg of perfluorooctyl bromide (PFOB) was instilled into the lungs. The pigs were supported on ECLS for 4 hours. At the end of the study, the pigs were euthanized, and samples were taken from the dependent and non-dependent sections of the upper, middle, and lower lobes. Following H&E staining, airspace percentage (A%) was quantified using custom Matlab image processing code. Data (mean±SD) were compared using 2-tailed t-tests.

Results: Static pulmonary compliance decreased significantly following the oleic acid lung injury (baseline: 1.29±0.31 vs. post-injury: 0.61±0.09; p< 0.001). In the gas ventilation group, the pulmonary compliance continued to decrease over the study (0.52±0.18 at 4 hours). By contrast, in the LLR group, pulmonary compliance increased to 0.80±0.16 at 4 hours (p < 0.05, gas ventilation vs. LLR). A% was higher in the LLR group (0.37±0.04) versus the gas ventilation group (0.33±0.02), but the difference was not statistically significant (p=0.16).

Conclusions: In a swine model of acute lung injury requiring ECLS, LLR with 5 mL/kg of PFOB resulted in a higher pulmonary compliance at 4 hours. Its effect on alveolar opening, as evaluated by histology, was inconclusive. Future work will investigate whether the improvement in compliance is sustained beyond 4 hours and whether higher doses of PFOB can provide further benefit.