The Effects of Oxiris on Systemic Inflammation and Endothelial dysFunction

Overview

CS-AKI occurring in 20% to 70% of cases depending of the type of cardiac surgery. The systemic inflammatory response is often observed and associated with increased risk of AKI. Cardiopulmonary bypass (CPB) induces a complex inflammatory response that has a multifactorial pathogenesis. The inflammatory response is triggered by exposure of the blood to artificial surfaces during extracorporeal circulation, ischemia/reperfusion injuries, translocation of gram-negative bacteria from the intestinal tract, small amounts of LPS in IV solutions. SIRS during CPB with high levels of inflammatory mediators, active complement proteins and LPS provoke endothelial dysfunction- retraction of endothelial cells with increasing vascular permeability and thrombogenic activity, also inflammatory mediators activate leukocytes and they enhance vascular permeability by affecting endothelial cells and vascular basement membrane. The systemic inflammation and endothelial dysfunction are the basis for multiple organ dysfunction syndrome. Vascular integrity damage during cardiac surgery entail redistribution of fluids with interstitial fluid accumulation and require accurate volume control (pertinent removal of "CPB priming volume"), especially in patients with CKD (low GFR) with high risks of AKI.

Specific details of Treatment/Intervention: (prescription and/or therapy, devices, equipment, solutions, product to be used in conducting study: To apply Prismaflex system with oXiris membrane after cardiopulmonary bypass in SCUF modality for CPB priming volume elimination. Duration of procedure: 6 hours Blood flow:150-200 ml/min Anticoagulation: no additional heparinization. According to the features of oXiris membrane: 1. Cytokines, complement, endotoxin adsorptive capacity. 2. Capability of accurate fluid balance management after cardiac surgery and CPB. 3. Reduced demand of anticoagulation therapy for CRRT in patients with high risk of bleeding. The goal of the research: 1. To evaluate effect of adsorption of oXiris membrane on levels of complement (C3a, C5a), pro- and anti-inflammatory cytokines (IL-1β, TNF-α,IL-6,Il-8, IL-10,TGF-β), LPS (EAA levels) after CPB. 2. To evaluate leukocytes activation after CPB and after inflammatory mediators adsorption with oXiris (CD11b/CD18) 3. To evaluate endothelial dysfunction after CPB and after CRRT with oXiris: endothelial/leukocytes interactions (ICAM-1, VCAM-1), biomarkers of endothelial permeability (angiopoetin-2, sFLT-1), biomarkers of endothelial coagulopathy (von Willebrand factor, thrombomodulin) 4. To evaluate effect of volume control with CRRT on CS-AKI and dependence on mechanical ventilation after cardiac surgery, regarding volume overload in patients undergoing CPB with "priming volume" infusion. 5. To evaluate stage and topography of cardiac surgery associated acute kidney injury (creatinine, cystatin C, NGAL, KIM-1, β2-microglobuline) in patients in two arms: oXiris and standard protocol. 6. To evaluate adsorptive and volume control feasible effects of oXiris membrane on volume management (CVP,PAWP), LPS adsorption, reduction of systemic inflammation , endothelium dysfunction and AKI after cardiac surgery with CPB in comparison with standard protocol.