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

Primary Purpose

Inflammation

Status
Unknown status
Phase
Phase 4
Locations
Germany
Study Type
Interventional
Intervention
i.v. mannitol
hemofiltration
Sponsored by
University Hospital, Saarland
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional prevention trial for Inflammation focused on measuring Immunedefense Suppression, Cardiopulmonary Bypass, Mannitol, Hemofiltration, Cytokines, Receptors, Surface CD14

Eligibility Criteria

35 Years - 80 Years (Adult, Older Adult)MaleDoes not accept healthy volunteers

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

Sites / Locations

  • University of Saarland, Department of Anesthesiology, Intensive Care Medicine and Pain Therapy

Outcomes

Primary Outcome Measures

LPS-stimulated cytokine release
LPS-stimulated CD14 exppression density

Secondary Outcome Measures

Full Information

First Posted
January 3, 2007
Last Updated
January 23, 2007
Sponsor
University Hospital, Saarland
Collaborators
Else Kröner Fresenius Foundation
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1. Study Identification

Unique Protocol Identification Number
NCT00426192
Brief Title
Effects of Hemofiltration and Mannitol Treatment on Cardiopulmonary-Bypass Induced Immunosuppression
Official Title
Mechanisms of Endotoxin-Tolerance of Human Monocytes After CABG-Sugery - Effects of Hemofiltration and Mannitol Treatment
Study Type
Interventional

2. Study Status

Record Verification Date
January 2007
Overall Recruitment Status
Unknown status
Study Start Date
October 2003 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
November 2004 (undefined)

3. Sponsor/Collaborators

Name of the Sponsor
University Hospital, Saarland
Collaborators
Else Kröner Fresenius Foundation

4. Oversight

5. Study Description

Brief Summary
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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Inflammation
Keywords
Immunedefense Suppression, Cardiopulmonary Bypass, Mannitol, Hemofiltration, Cytokines, Receptors, Surface CD14

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
Single
Allocation
Randomized
Enrollment
52 (false)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
i.v. mannitol
Intervention Type
Procedure
Intervention Name(s)
hemofiltration
Primary Outcome Measure Information:
Title
LPS-stimulated cytokine release
Title
LPS-stimulated CD14 exppression density

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
35 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hauke Rensing, MD PhD
Organizational Affiliation
University of Saarland
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Saarland, Department of Anesthesiology, Intensive Care Medicine and Pain Therapy
City
Homburg/Saar
State/Province
Saarland
ZIP/Postal Code
66421
Country
Germany

12. IPD Sharing Statement

Citations:
PubMed Identifier
9315800
Citation
Wan S, LeClerc JL, Vincent JL. Inflammatory response to cardiopulmonary bypass: mechanisms involved and possible therapeutic strategies. Chest. 1997 Sep;112(3):676-92. doi: 10.1378/chest.112.3.676.
Results Reference
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PubMed Identifier
10910482
Citation
Grundmann U, Rensing H, Adams HA, Falk S, Wendler O, Ebinger N, Bauer M. Endotoxin desensitization of human mononuclear cells after cardiopulmonary bypass: role of humoral factors. Anesthesiology. 2000 Aug;93(2):359-69. doi: 10.1097/00000542-200008000-00013.
Results Reference
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PubMed Identifier
12022753
Citation
Wilhelm W, Grundmann U, Rensing H, Werth M, Langemeyer J, Stracke C, Dhingra D, Bauer M. Monocyte deactivation in severe human sepsis or following cardiopulmonary bypass. Shock. 2002 May;17(5):354-60. doi: 10.1097/00024382-200205000-00002.
Results Reference
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PubMed Identifier
9466468
Citation
Kleinschmidt S, Wanner GA, Bussmann D, Kremer JP, Ziegenfuss T, Menger MD, Bauer M. Proinflammatory cytokine gene expression in whole blood from patients undergoing coronary artery bypass surgery and its modulation by pentoxifylline. Shock. 1998 Jan;9(1):12-20. doi: 10.1097/00024382-199801000-00002.
Results Reference
background
PubMed Identifier
10229162
Citation
Ziegenfuss T, Wanner GA, Grass C, Bauer I, Schuder G, Kleinschmidt S, Menger MD, Bauer M. Mixed agonistic-antagonistic cytokine response in whole blood from patients undergoing abdominal aortic aneurysm repair. Intensive Care Med. 1999 Mar;25(3):279-87. doi: 10.1007/s001340050836.
Results Reference
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Effects of Hemofiltration and Mannitol Treatment on Cardiopulmonary-Bypass Induced Immunosuppression

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