Systemic inflammatory activation during cardiac Surgery. Influence of cardiopulmonary bypass management and patient factors

Sammanfattning: Cardiac surgery with cardiopulmonary bypass is accompanied by a prominent systemic inflammatory and hemostatic activation, which may contribute to postoperative complications. Aims: To investigate if selection of cardiopulmonary bypass (CPB) system and management of cardiotomy suction (CTS) and mediastinal shed blood (MSB) affect systemic inflammatory response. Further, to study if CTS blood has hemodynamic effects and if the effects can be modulated by cellsaver-processing. Finally, to investigate the prevalence of gene polymorphisms associated with increased tumor necrosis factor (TNF-alpha) production in coronary artery bypass grafting (CABG) patients and whether these polymorphisms influence the magnitude of the postoperative inflammatory response.Materials and methods: In four prospective studies, inflammatory and hemostatic markers were analyzed. I: 41 patients were randomized between a conventional CPB system and a system with closed circuit, complete heparin-coating and a centrifugal pump. II: Cardiotomy suction blood and mediastinal shed blood were randomly retransfused or discarded in 29 CABG patients. III: 25 CABG patients were randomized to retransfusion of unprocessed or cellsaver-processed suction blood during cardiopulmonary bypass and systemic vascular resistance was registered. IV: TNF gene polymorphisms were analyzed in 86 CABG patients. In 45 of the patients the relation between TNF gene polymorphisms and inflammatory response was evaluated. Results: I: The mean concentrations of complement C3a, Bb, sC5b-9, interleukin-8, polymorphonuclear-elastase and tissue plasminogen activator antigen were all significantly lower in the group with a closed, heparin-coated circuit and a centrifugal pump. II: Plasma concentrations of IL-6, and C3a increased significantly less when CTS and MSB was discarded. III: Retransfusion of CTS blood induced a significant transient reduction in systemic vascular resistance. The peak reduction was less pronounced in the group receiving cellsaver-processed blood. There was a significant correlation between cytokine and complement activation in CTS blood and peak reduction of systemic vascular resistance. IV: 30 % of the patients carried the TNFA2 allele and 45% were TNFB2 homozygous. Plasma levels of inflammatory markers did not differ significantly between genetically high and low TNF-alpha producers.Conclusions: Cardiac surgery induces a prominent inflammatory reaction. A CPB system with a closed circuit, complete heparin-coating and a centrifugal pump reduces inflammatory and fibrinolytic activation. CABG performed without retransfusion of moderate volumes of CTS blood or MSB reduces the inflammatory reaction. CTS blood is vasoactive and affects systemic vascular resistance. The effect is proportional to the inflammatory activation in CTS blood. Processing the CTS blood with a cellsaver device reduces the effect on vasculture. The prevalence of the investigated TNF gene polymorphisms did not significantly differ from what previously have been reported from normal populations and do not affect inflammatory response in low-risk CABG patients.