Ulinastatin Improves and Prevents Cardiac Dysfunction Induced by Cardiopulmonary Bypass by Reducing Cardiac Endothelial Permeability
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Sponsor
- Enrollment
- 236
- Locations
- 1
- Primary Endpoint
- Cardiac function
Study Overview
Brief Summary
This project explores the role and mechanism of ulinastatin in preventing cardiac dysfunction caused by cardiopulmonary bypass by reducing cardiac endothelial permeability through clinical research. Our previous basic research has found that inhibiting the TK/B1R/ARNT/MMP3/iNOS signaling axis in the acute phase of cardiac R/I can reduce the permeability of cardiac endothelial cells, reduce cardiac edema and improve cardiac function (this part has been completed) . This study intends to investigate the effects of ulinastatin on 24-hour cardiac function and prognosis in patients undergoing cardiac surgery undergoing cardiopulmonary bypass (cardiac function, inflammatory indicators, coagulation function, capillary leakage indicators, 28-day survival time, CCU time). At the same time, we observed the dynamic changes of TK/B1R/MMP3 during cardiopulmonary bypass in patients undergoing cardiac surgery and explored its relationship with prognosis, as well as the effect of ulinastatin intervention on TK/B1R/MMP3 before and after cardiopulmonary bypass.
Detailed Description
- Baseline Period Visit 1 (within 24 hours before surgery)
- Sign informed consent
- Check inclusion/exclusion criteria
- Demographic data (sex, age, occupation, etc.)
- Past medical history (stroke, hypertension, diabetes, dyslipidemia, coronary heart disease, diabetes, etc.) and medication history in the past 3 months
- Vital signs (temperature, pulse, respiration, blood pressure)
- Preoperative ECG
- Preoperative echocardiography
- Laboratory tests (blood routine, blood glucose, blood lipids, liver and kidney function, myocardial enzymes, blood electrolytes, coagulation function)
- Concomitant therapy
- Adverse events
- Intraoperative cardiopulmonary bypass
- Record vital signs and various physiological indicators in the operating room.
- Routinely perform central venous puncture to establish venous access and monitor central venous pressure, and radial artery puncture to monitor invasive arterial pressure.
- After general anesthesia and endotracheal intubation, routine blood chemistry and arterial blood gas analysis were performed.
- After collecting the above blood samples for testing, the remaining blood was centrifuged, and the plasma was frozen at -80°C for subsequent testing (levels of CRP, IL-6, IL-10, TNF-α, TK/B1R/MMP3, etc.).
- Conventional treatment group: On the basis of general anesthesia, the extracorporeal circulation circuit was routinely prefilled. Management of CPB includes blood gas acid-base electrolyte management, anticoagulation management, invasive arterial blood pressure monitoring, MAP in the range of 50-80 mmHg, hematocrit maintained at 20-25%, and non-pulsatile flow rate of 2.0-2.4 L/min/ m2. During cardiopulmonary bypass, the dose of unfractionated heparin for anticoagulation through a central venous catheter is 300-400 U/kg, with additional doses as necessary to achieve and maintain an activated coagulation time (ACT) between 480 and 600 seconds. After isolation from cardiopulmonary bypass, heparin-induced anticoagulation was reversed with protamine. Surgical procedures include coronary artery bypass grafting, heart valve replacement, aortic replacement, etc.
- Ulinastatin group: On the basis of conventional treatment, administered in accordance with the instructions or previous study doses (general anesthesia with endotracheal intubation, after cardiopulmonary bypass transfer started): 10,000 U/kg Ulinastatin (Guoyao Zhunzi H19990134 , Guangdong Tianpu Biochemical Pharmaceutical Co., Ltd., Guangzhou, China) was dissolved in 50 ml of normal saline for 1 hour through central venous infusion.
After cardiopulmonary bypass
- operation time
- Vital signs (temperature, pulse, respiration, blood pressure)
- Routine blood chemistry and arterial blood gas analysis
- Document vasoactive drug use
- 24 hours, 72 hours, 7 days after surgery
- Vital signs (temperature, pulse, respiration, blood pressure)
- Bedside echocardiography
- Laboratory tests (blood routine, blood sugar, blood lipids, liver and kidney function, myocardial enzymes, coagulation function, etc.)
- After collecting the above blood samples for testing, the remaining blood is centrifuged, and the plasma is frozen at -80°C for later testing (levels of CRP, IL-6, IL-10, TNF-α, TK/B1R/MMP3, etc.)
- Capillary leak indicators
- Document treatment regimen (including vasoactive drug use, etc.)
- Follow-up period
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to 70 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Voluntarily sign the informed consent;
- •Age ≥18 years old and ≤70 years old;
- •Patients receiving cardiopulmonary bypass
- •Patients undergoing heart valve replacement surgery, major vascular surgery, and other cardiac surgery
Exclusion Criteria
- •Severe cardiac insufficiency before surgery (EF<50%, cardiogenic shock);
- •Patients with adverse events during surgery (such as cardiac arrest, etc.);
- •Solid organ or bone marrow transplant recipients;
- •pregnant women;
- •Have a history of allergy to ulinastatin or any of its ingredients;
- •Suffering from autoimmune diseases, tumors, or received high-dose hormones, immunosuppressive drugs, etc. within 2 months;
- •The researcher judges that it is not suitable to participate in this research.
Arms & Interventions
Conventional treatment group
Cardiac surgery patients undergoing cardiopulmonary bypass are not treated with ulinastatin
Intervention: saline (Other)
Ulinastatin
Cardiac surgery patients undergoing cardiopulmonary bypass are treated with ulinastatin
Intervention: Ulinastatin (Drug)
Outcomes
Primary Outcomes
Cardiac function
Time Frame: 24 hours
Echocardiographic detection
Inflammatory marker
Time Frame: 24 hours
Detection of CRP
Inflammatory markers
Time Frame: 24 hours
Detection of IL6
TK/B1R/MMP3 signaling
Time Frame: 24 hours
Detection levels of tissue kallikrein, B1R and MMP3
POD-postoperative delirium
Time Frame: 7 days
Assessment Method for the ICU (CAM-ICU
Secondary Outcomes
- Survival time(28 days)
Investigators
Qin Zhang
phd
Tongji Hospital