Abstract / Summary
Abstract Introduction Sepsis commonly causes acute respiratory distress syndrome (ARDS), and immune hyperactivation may be a causal link. Ventilator-induced lung injury (VILI) is common in ARDS, and VILI may potentiate organ dysfunction in severe sepsis. We used a porcine model of abdominal sepsis-associated ARDS to test whether ventilation strategy could impact systemic inflammation and organ dysfunction. Methods Female Yorkshire pigs (6–8 months) underwent ischemia–reperfusion (I/R) injury of the small bowel and fecal clot implantation or sham laparotomy. The abdominal sepsis animals were ventilated with a volume-controlled (VC) mode using the ARDS-Net low tidal volume (LVt) method to set and adjust the mode, and applied at two time points. Late LVt, was applied once PaO 2 /FiO 2 was ≤300, and Early LVt was applied immediately following injury. The third lung protective group used the airway pressure release ventilation (APRV) mode set and adjusted with the time-controlled adaptive ventilation (TCAV) method, also applied immediately after injury. Animals were supported for 48 h using standardized resuscitation protocols and euthanized. Physiologic variables, clinical lab data, lung histology, and plasma proteome were assessed. Results Sham animals showed no evidence of sepsis or ARDS, whereas all experimental animals developed septic shock, requiring fluid resuscitation and vasopressors. Both LVt groups developed ARDS as measured by PaO 2 /FiO 2 ratio by the study end (Late LVt: 129.9±16.0; Early LVt: 205.2±24.2), while the Early APRV group did not (429.4±59.4). The Sham and experimental groups all had similar proteomes at baseline. The proteomes diverged over time and ended in three distinct groups: Sham, Late LVt/Early LVt, and Early APRV. The most significantly differentially expressed proteins distinguishing the groups were involved in the immune and inflammatory response, with APRV having the lowest inflammatory signature. Conclusion In a porcine model of abdominal septic shock we found that animals ventilated with a higher mean airway pressure strategy (APRV) had decreased plasma proteomic signatures of inflammation compared to those ventilated with a conventional low tidal volume strategy. Our findings are hypothesis generating and not directly translatable to the clinical setting. Future studies should focus on further elucidating a link between VILI and its effect on systemic inflammation and organ dysfunction.