Background. Cardiopulmonary bypass (CPB) surgery initiates systemic inflammatory response syndrome, which in 2-10% of all cases can be considerably severe, known as post-perfusion syndrome. Different therapeutic interventions that can reduce inflammatory reactions during CPB have been used, in a hope for improvement of patients' outcome. Preliminary data suggests that extracorporeal hemadsorption may reduce inflammatory responses and produces a long-lasting anti-inflammatory effect. Glucocorticoids, on the other hand, have been used for a long time during open heart surgery for relief of systemic inflammation after CPB.
The aim of our study was to compare the effects of intraoperative extracorporeal hemadsorption, methylprednisone, and usual care during complex cardiac surgery on CPB, for inflammatory responses and oxidative stress (paraoxonase1, PON1), as well as hemodynamics, and perioperative course.
The hypothesis of the study was that selective extracorporeal hemadsorption during extracorporeal blood circulation in complex cardiac surgery affects postoperative immune status and protective mechanisms by modulating the systemic inflammatory response and anti-inflammatory parameters more effectively than methylprednisolone.
Methods. Seventy-six patients assigned to elective complex cardiac surgery with prolonged CPB (>90 min.) were enrolled in the study and randomized into three study groups: methylprednisolone group (1g of Methylprednisolone in CPB priming solution; n = 20), Cytosorb group (CytoSorb cartridge installed in CPB circuit; n = 20), and control group (usual care, no methylprednisolone, no CytoSorb during CPB, n = 20). The final analysis included 60 patients. Pro-inflammatory (TNF-, IL-1, IL-6, IL-8) and anti-inflammatory (IL-10) cytokines, complement C5a, C-reactive protein, procalcitonin, albumin, and fibrinogen levels, leukocyte numbers, CD64 and CD163 expression by immune cells, as well as paroxonase 1 and lipid status, were analyzed before anesthesia induction, after CPB and surgery, 24 h and 48 h after surgery, and on postoperative day 5. Additionally, fluid/blood products, catecholamine and insulin use, hemodynamic parameters and postoperative complications, including 30-day mortality were recorded.
Results. Methylprednisolone group, compared to Cytosorb and control group, had significantly lower levels of TNF- (by the end of surgery, p <0,001), IL-6 (up to 48h after surgery, p <0,001), and IL-8 (up to 24h after surgery, p <0,016), as well as CRP and fibrinogen (from 24 h after surgery until 5 days afterwards, p<0,016), and PCT (24 h after surgery and on 5th postoperative day, p<0,016). CD64 expression on monocytes was highest in Cytosorb group and lasted until the 5th postoperative day (p <0,016). IL-10 concentration (until the end of surgery) and CD163 expression on monocytes (up to 48 hours after surgery) were highest in methylprednisolone group (p <0,016, for all measurements between the three groups). The Cytosorb group had the least need for noradrenaline during surgery, but this did not reach statistical significance. There were no significant differences between the three groups with respect to PON1 activity and all other recorded parameters of hemodynamics and clinical outcome of patients.
Conclusions. Intraoperative methylprednisolone more effectively ameliorates inflammatory responses during CPB surgery compared to Cytosorb and usual care. However, methylprednisolone did not provide greater hemodynamic stability, or less fluid/blood, catecholamine or insulin use, less perioperative atrial fibrillation or infections, with no differences in short-term patient outcome. Extracorporeal hemadsorption, compared to usual care, results in a higher long-term expression of CD64 on monocytes and a higher, but short-term expression of CD163 on granulocytes. Hemadsorption with CytoSorb is safe and well tolerated. The activity of PON1 decreases after CPB, otherwise neither the use of methylprednisolone nor hemadsorption significantly affects the activity of PON1 compared to standard treatment during CPB.
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