Cardiovascular Disease
Conditions
Keywords
ulinastatin, systemic inflammation, cardiac surgery, cardiopulmonary bypass
Brief summary
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
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.
Interventions
DRUGulinastatin
ulinastatin 5000 unit/kg iv before the initiation of CPB
DRUGplacebo
placebo (the same amount of normal saline) iv before the initiation of CPB
Sponsors
Konkuk University Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
25 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | 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
| Measure | Time frame |
|---|---|
| serum creatinine | before anesthesia, 24 hour after the end of anesthesia |
| Creatine kinase-MB | before anesthesia, 24 hour after the end of anesthesia |
| PaO2/FiO2 ratio | 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 |
Countries
South Korea
Outcome results
None listed