Removal of Cytokines During Extracorporeal Circulation in Cardiac Surgery

Study Overview
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Brief Summary
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The aim of this study is to prove that using a CytoSorb(TM) filter in the cardiopulmonary circuit attenuates the inflammatory response to extracorporeal circulation in patients undergoing cardiac surgery. The hypothesis is that removing cytokines from patients' blood by the CytoSorb device significantly improves circulation and outcome in patients undergoing on-pump cardiac surgery.

Detailed Description
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Cardiac surgery with cardiopulmonary bypass (CPB) induces an inflammatory response due to contact of patients' blood with foreign surfaces like tubes or the oxygenator, ischemic-reperfusion injury and surgical trauma. Inflammation is modulated by cytokines, especially, interleukins. The extent of cytokine release is further related to the duration of bypass and the amount of operating field suction. This results in a systemic inflammatory response syndrome (SIRS) with the risk of multiple organ dysfunction (MOD). Also in patients treated with extracorporeal membrane oxygenation (ECMO) an activation of the inflammation system is seen and accompanied with an increase of cytokine levels. The cytokine concentration correlates with the severity of the immune reaction and can be a predictor of the outcome of the patient. As severe SIRS and MOD significantly increase mortality, the attenuation of the inflammatory response is supposed to reduce morbidity and mortality after cardiac surgery. For adult cardiac surgery and patients who are treated with an extracorporal assist device, a tool for cytokine elimination and attenuation of the inflammatory response seems to be beneficial. In our study we are going to investigate if the use of the CytoSorb device can improve the outcome of patients undergoing elective coronar artery bypass and heart valve surgery.

Official Title
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Reduction of Inflammation Reaction to Extracorporeal Circulation in Cardiac Surgery by Interleukin Dialysis

Conditions
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Coronary Artery Disease, Heart Valve Diseases

Intervention / Treatment
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* Device: CytoSorb device


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: undergoing elective coronar bypass AND heart valve surgery expected duration of bypass more than 120 min Exclusion Criteria: age under 18 years of age pregnancy medication that interacts with the immune system (e.g. steroids, immune suppressors) patients with diagnosed immunodeficiency (e.g. HIV/AIDS) heparin induced thrombocytopenia type II patients that decline participation

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: With CytoSorb device<br>Patients randomised to this arm are treated with the CytoSorb device during bypass. | Device: CytoSorb device<br>* In 20 patients the CytoSorb device will be installed into the extra corporeal circuit. A blood flow of 400ml/min is provided by an roller pump of the heart lung machine in a parallel stream to the main circulation.<br>* Other names: polymer beads adsorbent;|
| No Intervention: Withouot device<br>Patients randomised to this arm are treated without the CytoSorb device during bypass. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of levels of cytokines during procedure compared to baseline | parameters to be measured are: interleukin (IL) 1, interleukin 6, interleukin 8, interleukin 10, tumor necrosis factor-alpha | 1) 5 minutes before bypass 2) 2 hours after begin of bypass, 3) at the end of bypass, approximately 3 hours after begin of bypass, 4) 6 hours after bypass 5) 24 hours after bypass | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of hemodynamic parameters during procedure compared to baseline | Hemodynamic and respiratory parameters such as mean arterial pressure, heart rate and peripheral oxygen saturation are recorded. In addition thermodilution parameters (stroke volume variability, global end diastole volume, extravascular lung water index, cardiac index, systemic vascular resistance) are measured. Volume and catecholamine therapies are managed by an algorithm based on thermodilution parameters. | 1) 5 kinutes before bypass 2) 2 hours after begin of bypass, 3) at the end of bypass, approximately 3 hours after begin of bypass, 4) 6 hours after bypass 5) 24 hours after bypass | 
| Thromboelastometry | At the end of extracorporeal circulation a rotation thromboelastometry analysis is performed and the clotting time (CT), the clot formation time (CFT), the maximum clot firmness (MCF) in In- and Ex-Tem and the MCF in Fib-Tem are measured. Based on an institutional algorithm the coagulation therapy is performed according to the results of the thromboelastometry. | at the end of bypass, approximately 3 hours after begin of surgery | 
| Change of cognitive and emotional state in comparison to condition before surgery | To evaluate, if the use of the cytokine-filter has any influence on cognitive function or the emotional state, the patients perform the mini-mental state examination and answer questions of the Geriatric Depression Scale questionaire. Results before and 24 hours after end of bypass are recorded. | 1)one day before surgery 2) 24 hours after bypass | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CytoSorb(TM), cytokines, inflammation, cardiac surgery, extracorporeal bypass