Cleansing of Suction Blood in Cardiac Surgery for Reduced Inflammatory Response

Study Overview
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Brief Summary
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Cardiac surgery using heart and lung machine produces an inflammatory reaction in the body. This leads in few percent of cases to heart, lung, and kidney disturbances that potentially causes death. White blood cells in contact with the heart and lung machine and external surfaces release mediators partly responsible for this. Blood collected by the suction and the blood remaining in the heart and lung machine after its use, can be cleaned by a cell saver before reinfusion, and this might reduce the inflammatory response.

Detailed Description
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Introduction Cardiopulmonary bypass (CPB) during cardiac surgery induces in all patients a systemic inflammatory response syndrome (SIRS) that is more pronounced than for other surgical procedures. Depending on the severity of this, myocardial dysfunction, respiratory failure, renal and neurological dysfunction, coagulation disturbances and impaired liver function might follow. In worst cases this leads to acute respiratory distress syndrome, disseminated intravascular coagulation, multi organ failure, shock and death. The cause is besides the surgical trauma, the passage of the blood through the extra corporal circulation (ECC) and its pumps and oxygenator, hemodilution, hypothermia, heparin and protamine administration, ischemia and reperfusion, and endotoxemia (LPS) as a cause of intestinal ischemia. The ECC is the main cause of immunological activation and leads in severe cases to the so-called post-perfusion syndrome. This is characterised by increased capillary permeability and intercellular fluid, peripheral vasoconstriction, fever, myocardial edema, diffuse cerebral edema and diffuse hemorrhagic diathesis. This syndrome is considered to be a more severe form of SIRS. Even though most patients have no sequelae after CPB, all patients must be considered to be influenced, in varying degree, by SIRS. High levels of pro-inflammatory cytokines (interleukin (IL)-6, IL-8, IL-1a, IL-1b, tumor necrosis factor (TNF) alfa), have generally been associated with adverse events after CPB. Of importance is also LPS from gram-negative intestinal bacteria, translocating to the systemic circulation during ischemia. Hypothesis Cleansing of suction blood and the remaining blood in the ECC after termination of CPB, reduces the load of inflammatory cells and mediators in the patients' circulation. This potentially diminishes SIRS with a reduction in postoperative organ dysfunction and morbidity. Aim To cleanse suction blood and the remaining blood in the ECC after termination of CPB by means of a cell saver and monitor the influence on inflammatory mediators and the potential clinical benefits. Outcome measures Primary: Concentrations of IL-1B, IL-6, IL-8, IL-10, IL-12p70, TNFa, TNF-R1, TNF-R2, PCT and LPS in patient blood: 6, 24 and 72 hours after termination of CPB. Secondary: Bleeding, need for allogenic blood transfusions and blood products and clinical effect focusing on known complications to cardiac surgery and CPB. Design Prospective randomised clinical trial including 40 patients planned for on-pump coronary artery bypass grafting (CABG). n=20 in the trial group (use of cell saver) and n=20 in the control group (no cell saver). No patients receive postoperative autotransfusion of drain blood. Sample size Estimation based on comparable studies. Anaesthesia and surgery In accordance with current guidelines of the clinic, this includes prophylactic antibiotics (cefuroxime and gentamycin). Cell saver: Medtronic Autolog. Patient exclusion during the trial Patients are excluded in cases of autotransfusion of blood not cleansed by the cell saver, for instance in cases of major blood loss.

Official Title
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Does Cleansing of Suction Blood During Cardiac Surgery With Heart and Lung Machine Reduce the Postoperative Inflammatory Response ?

Conditions
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Systemic Inflammatory Response Syndrome, Coronary Arteriosclerosis

Intervention / Treatment
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* Procedure: Cell saver
* Procedure: No cell saver


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Oral and written informed consent. No limits regarding age or ejection fraction. Exclusion Criteria: Off-pump coronary artery bypass grafting Redo CABG Current infection Antibiotic treatment S-creatinin > 200 micromol/L Antiinflammatory / immuno-modulating treatment: Steroids, immunosuppressive or -stimulating agents (NSAIDs and ASA allowed) Liver disease Immune disease

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 |
| --- | --- |
| Experimental: 1<br>With cell saver | Procedure: Cell saver<br>* Cell saver intraoperatively for coronary artery bypass grafting using cardiopulmonary bypass<br>|
| Active Comparator: 2<br>Without cell saver | Procedure: No cell saver<br>* Conventional suction for coronary artery bypass grafting using cardiopulmonary bypass<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentrations of IL-1B, IL-6, IL-8, IL-10, IL-12p70, TNFa, TNF-R1, TNF-R2, PCT and LPS in patient blood. |  | 6, 24 and 72 hours after termination of CPB. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bleeding |  | Intra- and postoperatively | 
| Need for allogenic blood transfusions and blood products |  | Within submission | 
| Clinical effect focusing on known complications to cardiac surgery and CPB |  | Within submission | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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systemic inflammatory response syndrome, coronary artery bypass grafting, cell saver, interleukins, tumor necrosis factor alfa