Cytokine Removal in Cardiopulmonary Bypass Patients

Study Overview
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Brief Summary
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Cardiopulmonary bypass (CPB) surgery initiates a systemic inflammatory response induced by extrinsic (e.g. anesthesia, contact activation within the extracorporeal circuit, endotoxemia) and intrinsic (e.g. tissue damage, endothelial cell activation, ischemia-reperfusion injury of myocardium) factors. Monocytes are important players in systemic inflammation and the main producers of pro- and antiinflammatory cytokines. Monocytes activated by the extracorporeal circuit lead to a dysregulation of inflammatory homeostasis, increased levels of proinflammatory plasma mediators such as TNF-a, IL-1β, IL-6 and IL-18 are joined by antiinflammatory cytokines such as IL-10. This strong inflammatory response induces post surgical monocyte immunosuppression which is indicated by an impaired production of ex vivo LPS induced TNF-a production. Also malfunction of the peripheral circulation with increased lactate levels, pronounced fluid accumulation, increased need of vasopressors and cerebral dysfunction are observed. All of these factors may delay weaning from the ventilator, recovery of organ functions and discharge from ICU. Thus measures to decrease the inflammatory process have the potential to improve the perioperative course. Use of cytokine adsorbing circuit during CBP has an effect on circulation cytokine levels for the first 36 hours after surgery and induces a decreased inflammatory response for up to 3 days post surgery.

Detailed Description
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Patients, who have an elective cardiac surgical intervention with an expected CBP duration >120 minutes (e.g.: valve surgery, coronary artery bypass graft (CABG), combined procedures) will be enrolled to the study after given informed consent. Patients, who decline will be asked to collect their secondary outcome data to create a real - life group and increase the number of patients in the control group. In this real - life group no additional blood samples will be taken.

Official Title
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Effect of Cytokine Removal in Cardiopulmonary Bypass Patients Using the Cytosorb ™ Filter

Conditions
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Elective Cardiac Surgical Interventions

Intervention / Treatment
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* Device: CytoSorb


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: elective cardiac surgical intervention with an expected CBP duration >120 minutes Exclusion Criteria: Emergency procedures Heart transplantation Elective left ventricular assist device (LVAD) implantation Pulmonary thromendarterectomy Declined informed consent Serum creatinine > 2mg/dl Body mass index < 18 Age < 18 years Pregnant woman Receiving chemotherapy or diagnosed with any disease state (e.g., AIDS) that has produced leukopenia Receiving antileukocyte drugs Receiving TNF-α Blockers, immunosuppressive drugs (e.g. tocilizumab) CRP > 2mg/dl History of Stroke Bilirubin >2mg/dl

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CytoSorb<br>For the intervention group, the CytoSorb filter will be installed on the CPB machine in a parallel circuit to the body circulation. The flow through the filter will be driven by a roller pump with 200ml.min-1 . | Device: CytoSorb<br> <br> * Other names: ISO 13485:2003;|
| No Intervention: Control<br>No filter will be installed on the CPB machine. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| IL-6 |  | 1. Preoperative 2. Before CBP 3. After CPB 4. 2 hours after CPB 5. 24 hours 6. 48 hours 7. 120 hours |