The impact of ventilation mode on systemic inflammation and organ dysfunction in a porcine model of abdominal sepsis-associated acute respiratory distress syndrome.

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 PaO₂/FiO₂ 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 PaO₂/FiO₂ 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.