Lung-protective ventilation suppresses plasma levels of cell-free DNA in porcine experimental postoperative sepsis

Abstract

Introduction Mechanical ventilation affects systemic inflammation where protective ventilation attenuates the response [1]. Plasma levels of cell-free DNA (cfDNA) increase and have prognostic value in sepsis [2]. In the present study, the effect of tidal volume and PEEP on arterial and transorgan levels of cfDNA was investigated in a porcine postoperative sepsis model. Methods Two groups of anaesthetised pigs were ventilated with either protective ventilation (VT 6 ml/kg, PEEP 10 cmH2O; n = 20) or controls (VT 10 ml/kg, PEEP 5 cmH2O; n = 10) for 7 hours. An artery, the hepatic vein, the portal vein and the jugular bulb were catheterized. Continuous endotoxin infusion at 0.25 μg/kg/hour for 5 hours was started after 2 hours of laparotomy that simulated a surgical procedure. Results The group receiving protective ventilation showed lower levels of cfDNA in arterial blood compared with controls (P = 0.02). Transhepatic levels of cfDNA were higher compared with trans-splanchnic levels during the experiment (P = 0.02), but this effect was attenuated in the group receiving protective ventilation. No difference between the groups was detected in blood samples from the jugular bulb. Conclusion In experimental postoperative sepsis, protective ventila tion suppresses arterial levels of cfDNA. The liver seems to be a significant contributor to systemic cfDNA levels, an effect that is suppressed during protective ventilation.