Histopathological correlation with P/F ratios during ARDS in an ovine model treated with extracorporeal arteriovenous carbon dioxide removal (AVCO₂R)

AVCO₂R allows reductions in peak airway pressure, ventilator dependent days, and improves survival in our ovine smoke/burn injury (LD₄₀) model of ARDS. The inflection point of physiologic improvement (PaO₂/FiO₂ > 200) occurs at 48 hours of AVCO₂R treatment, 96 hours post-injury. In this study, we correlated the histopathology with P/F ratio improvements during treatment with AVCO₂R. Adult Suffolk ewes (n=10) received a cotton smoke insufflation (36 breaths) and 40% TBSA III° cutaneous flame burn injury followed by volume-controlled mechanical ventilation. At 40-48 hours post-injury, sheep underwent cannulation of the carotid artery (10-12F) and jugular vein (14F) and were connected to a low-resistance membrane gas exchanger (AVCO₂R). Sheep were euthanized 96 hours post-injury (48 hours AVCO₂R) and lung samples (2-3/animal) were fixed with 10% formalin and stained with hematoxylin-eosin and MOVAT. Pathological findings were graded as absent = 0, minimal = 1, mild = 2, moderate = 3, or severe = 4. We compared lung weights, expressed as a wet:dry ratio, in sheep with no injury (n=4) and to those with smoke/burn injury treated with AVCO₂R. Pulmonary histology after 48 hours of AVCO₂R revealed changes consistent with acute ARDS including mild edema (2.06 ± 1.43), interstitial inflammation (1.39 ± 1.14), atelectasis (1.6 ± .98), minimal hyaline membrane formation, alveolar type II proliferation, and alveolar hemorrhage. No thrombi or fibrosis was observed. Wet:dry ratios showed no significant difference in lung weights between normal and AVCO₂R. AVCO₂R improves survival from smoke/burn induced ARDS without correllative changes in lung histology. However, normalized wet:dry ratios suggest that AVCO₂R reduces fluid transudation to improve gas exchange and outcomes.