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

Inflammation Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00426192
• Other study ID #: AN-01
• Status: Active, not recruiting
• Phase: Phase 4
• First received: January 3, 2007
• Last updated: January 23, 2007
• Start date: October 2003
• Est. completion date: November 2004

Study information

• Verified date: January 2007
• Source: University Hospital, Saarland
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 52
• Est. completion date: November 2004
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 35 Years to 80 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Inflammation

Intervention

Drug:
• i.v. mannitol

Procedure:
• hemofiltration

Locations

Country	Name	City	State
Germany	University of Saarland, Department of Anesthesiology, Intensive Care Medicine and Pain Therapy	Homburg/Saar	Saarland

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital, Saarland	Else Kröner Fresenius Foundation

Country where clinical trial is conducted

Germany, 

References & Publications (5)

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. — View 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. — View 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. Review. — View 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. — View Citation

Ziegenfuss T, Wanner GA, Grass C, Bauer I, Schüder 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	LPS-stimulated cytokine release
Primary	LPS-stimulated CD14 exppression density