Ulinastatin's Anti-inflammatory Reaction in Cardiac Surgery

Study Overview
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Brief Summary
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The purpose of the present study is to determine whether ulinastatin, urinary anti-trypsin inhibitor, attenuates cardiopulmonary bypass (CPB)-activated systemic inflammatory response in cardiac surgery with CPB. Serial measurements and analysis of several inflammatory cytokines (bactericidal permeability increasing protein, interleukin-6, tumor necrosis factor-α)as well as markers of cardiac injury, renal impairment and oxygenation profile will be performed to determine ulinastatin's efficacy.

Detailed Description
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Applying aortic cross-clamp (ACC) and cardiopulmonary bypass (CPB) for cardiac surgery produces variable systemic inflammatory reactions. As a common complication of those reactions, pulmonary dysfunction, which usually indicated by postoperative hypoxemia, is frequently associated with cardiac surgery employing CPB and has been used as a major predictor of morbidity and mortality. Circulating humoral and cellular factors are involved in the development of the systemic inflammatory reactions including organ dysfunction. So far, many studies analyzed the concentration of inflammatory marker (cytokine) to determine the degree of systemic inflammatory responses in various conditions. Ulinastatin has anti-inflammatory activity and suppresses the infiltration of neutrophils. Previous studies suggested ulinastatin's cytoprotective effect against ischemia-reperfusion injury in major organs and its inhibition of inflammatory marker production. The purpose of the present study is to determine ulinastatin's possible protective efficacy of in attenuating CPB-activated systemic inflammatory response regarding postoperative cardiac, renal and pulmonary dysfunction in cardiac surgery with CPB. Serial measurements and analysis of several inflammatory cytokines, such as bactericidal permeability increasing protein (BPI), interleukin (IL)-6, tumor necrosis factor (TNF)-α, as well as markers of cardiac injury, renal impairment and oxygenation profile, such as creatine kinase-MB (CK-MB), troponin I (TnI), C-reactive protein (CRP), arterial O2 tension /inspired O2 fraction (PaO2/FiO2 ratio), will be performed to this purpose.

Official Title
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Effect of Ulinastatin on Postoperative Systemic Inflammatory Response in Cardiac Surgery

Conditions
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Cardiovascular Disease

Intervention / Treatment
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* Drug: ulinastatin
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: elective cardiac surgery employing CPB Exclusion Criteria: urgent/emergency surgery, previous heart surgery, combined CABG and valve surgery, age > 75 yrs, left ventricular ejection fraction < 0.45, diabetes treated with insulin, active gastropathic disorder, treatment for chronic obstructive pulmonary disease, preoperative use of steroids postoperative re-operation due to bleeding control pre and postoperative renal replacement therapy left ventricular assist device implantation

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 75 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: placebo<br>normal saline, same amount, iv | Drug: placebo<br>* placebo (the same amount of normal saline) iv before the initiation of CPB<br>* Other names: normall saline;|
| Active Comparator: ulinastatin<br>5000 unit/kg iv | Drug: ulinastatin<br>* ulinastatin 5000 unit/kg iv before the initiation of CPB<br>* Other names: ulistin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| bactericidal permeability increasing protein |  | 5-30 min before the end of anesthesia | 
| interleukin-6 |  | 5-30 min before the end of anesthesia | 
| tumor necrosis factorTNF-α |  | 5-30 min before the end of anesthesia | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Creatine kinase-MB |  | before anesthesia, 24 hour after the end of anesthesia | 
| troponin I |  | before anesthesia, 24 hour after the end of anesthesia | 
| C-reactive protein |  | before anesthesia, 24 hour after the end of anesthesia | 
| serum creatinine |  | before anesthesia, 24 hour after the end of anesthesia | 
| PaO2/FiO2 ratio |  | before anesthesia, 24 hour after the end of anesthesia | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ulinastatin, systemic inflammation, cardiac surgery, cardiopulmonary bypass