Effects of Hemofiltration and Mannitol Treatment on Cardiopulmonary-Bypass Induced Immunosuppression

Study Overview
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Brief Summary
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After cardiac surgery with cardiopulmonar bypass, the LPS-stimulated cytokine response has been previously shown to be depressed. Therefore, in this trial the hypothesis was tested, whether simple immunomodulting interventions like the i.v. adminstration of mannitol of hemofiltration during cardipulmonary bypass can attenuate this immunosuppressing effect.

Detailed Description
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Background Cardiac surgery using cardiopulmonary bypass (CPB) causes a systemic inflammatory response. In addition to this immune response to CPB, a significant impairment of the responsiveness of peripheral blood mononuclear cells (PBMC) to further immunological stimuli has been observed. The aim of our present study was to evaluate the ability of antioxidant therapy with mannitol or hemofiltration during CPB to modulate the observed immunosuppression after CPB. Methods With ethics committee approval, 52 patients undergoing elective CABG-surgery were prospectively enrolled and randomized into 3 groups (control, 50 g mannitol iv, hemofiltration during CPB). Blood samples were taken after induction of anesthesia (T1), 20 min after separation from CPB (T2) and 24 h postoperatively (T3). Expression density of the monocytic surface receptor CD14, HLA-DR expression and cytokine release (TNF- and IL10) after LPS-stimulation were evaluated. Results At T2, the CD14dim cell population was maintained in both intervention groups while in the control group there was a significant decrease of this proinflammatory monocytic phenotype. At T3, all groups developed a significant shift towards the antiinflammatory CD14bright population. No significant differences regarding HLA-DR expression or cytokine release could be demonstrated. Conclusion This study shows that the suppression of the stimulated immune response after CPB can be alleviated by iv administration of mannitol or hemofiltration. In the light of data showing that this depression of the immune response might affect the postoperative course of patients, these results could lead to an improvement of the management of patients undergoing cardiac surgery with CPB.

Official Title
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Mechanisms of Endotoxin-Tolerance of Human Monocytes After CABG-Sugery - Effects of Hemofiltration and Mannitol Treatment

Conditions
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Inflammation

Intervention / Treatment
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* Drug: i.v. mannitol
* Procedure: hemofiltration


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: male patients aged 35-80 elective CABG surgery Exclusion Criteria: previous cardiac surgery ejection fraction < 40% valvular heart disease myocardial infarction during the last 3 months evidence of concomitant malignant or immunologic diseases antecedent medication with corticosteroids or methylxanthines hemoglobin < 12 g/dl body mass index > 30

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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Male

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


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: i.v. mannitol|nan|
|Procedure: hemofiltration|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| LPS-stimulated cytokine release |  |  | 
| LPS-stimulated CD14 exppression density |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Immunedefense Suppression, Cardiopulmonary Bypass, Mannitol, Hemofiltration, Cytokines, Receptors, Surface CD14