Cleansing of Suction Blood in Cardiac Surgery for Reduced Inflammatory Response

Coronary Arteriosclerosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00159926
• Other study ID #: 959583153
• Secondary ID: 961501172DHF: 03
• Status: Terminated
• Phase: Phase 3
• First received: September 8, 2005
• Last updated: January 4, 2008
• Start date: January 2003
• Est. completion date: February 2004

Study information

• Verified date: November 2007
• Source: Rigshospitalet, Denmark
• Contact: n/a
• Is FDA regulated: No
• Health authority: Denmark: The Regional Committee on Biomedical Research Ethics
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 30
• Est. completion date: February 2004
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Arteriosclerosis
• Coronary Arteriosclerosis
• Coronary Artery Disease
• Myocardial Ischemia
• Systemic Inflammatory Response Syndrome

Intervention

Procedure:
• Cell saver
Cell saver intraoperatively for coronary artery bypass grafting using cardiopulmonary bypass
• No cell saver
Conventional suction for coronary artery bypass grafting using cardiopulmonary bypass

Locations

Country	Name	City	State
Denmark	Department of Cardiothoracic Surgery, Rigshospitalet	Copenhagen

Sponsors (3)

Lead Sponsor	Collaborator
Rigshospitalet, Denmark	Copenhagen Hospital Corporation, Danish Heart Foundation

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	No
Secondary	Bleeding		Intra- and postoperatively
Secondary	Need for allogenic blood transfusions and blood products		Within submission
Secondary	Clinical effect focusing on known complications to cardiac surgery and CPB		Within submission