Exposure of Salvaged Blood to Inflammation and Oxidative Stress: the Effect of Different Anticoagulant Regimes (HECICS)

Study Overview
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Brief Summary
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The primary aim of this randomized controlled study is to determine whether the use Anticoagulant Citrate Dextrose Solution--Formula A (ACD-A) in cell salvage reduces inflammation and oxidative stress in cell saver blood compared to heparin. The secondary aim is to determine whether any differences in activation can be correlated to any differences in postoperative clinical outcome.

Detailed Description
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The first primary outcome of this study is the difference in concentration of pro- and anti-inflammatory markers and markers of oxidative stress in the cell-free fraction of the centrifugate of the unwashed autologous blood/anticoagulant mixture in the cell saver reservoir, after correction for cardiopulmonary bypass (CPB) time up to the start of the first washing cycle and contact time of the anticoagulant (either ACD A or heparin) with the saved blood: total antioxidant status (TAS) Total thiols in proteins (TTP) oxidized LDL (oxLDL) Pro-inflammatory markers: interleukins (IL), IL-6, IL-8, myeloperoxidase (MPO) Anti-inflammatory marker: IL-10 The second primary outcome of this study is the difference in direct quality of the washed, salvaged red blood cells (RBC): Blood smear: evaluation by light microscopy Osmotic fragility Haemoglobin and hematocrit Free haemoglobin Free iron Lactate pH Confounding factors (CPB duration, contact time of anticoagulant with saved blood, time since first washing cycle in case of multiple washing cycles) will be controlled for. Secondary outcome: The difference in concentration of the same pro/anti-inflammatory and oxidative stress markers in patient plasma preoperatively vs immediately before and after transfusion of cell saver blood (2 to 3 hours after transfusion and before extubation or transfusion of allogenous blood). C-reactive protein (CRP) TAS, TTP oxLDL IL-6, IL-8, IL-10 MPO Markers for hemolysis in patient plasma preoperatively vs immediately pre- and post-transfusion of the salvaged RBC (indirect quality of the washed salvaged RBC). Free Hb Free iron, ferritin, transferrin Haptoglobin Hepcidin

Official Title
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Exposure of Salvaged Blood to Inflammation and Oxidative Stress: the Effect of Different Anticoagulant Regimes. Heparin vs Citrate in Cellsaver (HECICS).

Conditions
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Intra Operative Bleeding, Blood Salvage

Intervention / Treatment
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* Drug: ACD-A
* Drug: Heparin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Elective cardiac revascularization surgery patients: subgroup analysis for on pump coronary artery bypass grafting (CABG) off pump CABG (OPCABG) Exclusion Criteria: Urgent procedures Severe shock Active infection Inflammatory diseases Active neoplasia Immune suppressive drugs Active or recent renal replacement therapy (RRT) Anticoagulation or anti-aggregation therapy that hasn't been timely interrupted according to guidelines (12,13) Need for allogenous blood transfusion before completion of data collection Massive peroperative bleeding that cannot be safely managed while collecting study data

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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: citrate<br>A quantity of 20 ml ACD-A per 100 ml of collected blood is used to prevent coagulation in the cell savage process. Pre-prepared ACD-A solutions is available (composition of ACD-A solution used: 22.0 g sodium citrate dehydrate, 24.5 g glucose monohydrate, 8.0 g citric acid monohydrate per 1000 ml of water | Drug: ACD-A<br>* use of ACD-A as anticoagulant after blood salvage during cardiac surgery<br>* Other names: Anticoagulant Citrate Dextrose Solution--Formula A;|
| Active Comparator: heparin<br>A heparinised saline solution of 25,000 IU of heparin per 1 litre of intravenous normal saline (0.9% NaCl) solution is used with a dosage of 20 ml of solution per 100 ml of collected blood. This type of solution is not commercially available and is made locally. This solution is used in the cell salvage process to prevent coagulation. | Drug: Heparin<br>* use of heparin as anticoagulant after blood salvage during cardiac surgery<br>* Other names: heparin sodium;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| difference in concentration of pro- and anti-inflammatory markers and markers of oxidative stress in the cell-free fraction of the centrifugate of the unwashed autologous blood/anticoagulant mixture in the cell saver reservoir | measurement of: TAS: total antioxidant status TTP: total thiols in proteins oxLDL: oxidized LDL Pro-inflammatory markers: IL-6, IL-8, myeloperoxidase (MPO) Anti-inflammatory marker: IL-10 | maximum 3 hours post-operatively | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The second primary outcome of this study is the difference in direct quality of the washed, salvaged RBC: | The second primary outcome of this study is the difference in direct quality of the washed, salvaged RBC: Blood smear: evaluation by light microscopy Osmotic fragility Haemoglobin and hematocrit Free haemoglobin Free iron Lactate pH | maximum 3 hours post-operatively |