Impaired endotoxin inactivation, rather than gut translocation, is associated with organ injury in cardiac surgery with cardiopulmonary bypass

BACKGROUNDS: In patients with cardiac surgery under cardiopulmonary bypass (CPB), postoperative inflammation is a driver of adverse outcomes. Endotoxaemia is one of the factors thought to trigger this inflammatory response. The mechanism behind high endotoxin activity (increased translocation vs. reduced inactivation capacity) has never been elucidated and may imply different therapeutic candidates. OBJECTIVES: We aimed to evaluate, in patients with cardiac surgery with prolonged CPB, mechanisms and consequences of endotoxaemia and the efficacy of haemo-adsorption to reduce the endotoxin burden. DESIGN: Ancillary analysis of a randomised controlled trial. Patients scheduled for cardiac surgery with prolonged CPB were assigned to receive either intra-operative haemo-adsorption or standard of care. Endotoxin mass and activity were measured before surgery, at the end of CPB, 6, 24 and 48 h after the end of surgery. SETTING: Operating room, Amiens University Hospital. PATIENTS: Adults scheduled for cardiac surgery under CPB with an expected CPB time more than 90 min. INTERVENTION: Patients were randomised to receive either haemo-adsorption or standard care during CPB. MAIN OUTCOME MEASURES: Endotoxin activity. RESULTS: Two hundred and ninety-five samples from 66 patients were analysed. Following CPB, we observed a reduction in endotoxin mass accompanied by a relative increase in endotoxin activity. High postoperative endotoxin activity was associated with intra-operative dobutamine requirement, increased postoperative inflammatory biomarkers and organ injury. Endotoxin plasma concentration and activity were not lower in patients treated with haemo-adsoprtion. CONCLUSION: The capacity of individuals to inactivate endotoxin rather than raw endotoxin mass (i.e. Quantity) seemed to be a determinant of endotoxin noxious effect in cardiac surgery and CBP. Haemo-adsorption was not associated with a reduction of endotoxin plasma mass or activity in patients with cardiac surgery under CPB. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04201119NCT04201119.