Phase 4 Study of Fixed-dose and Titration Schemes of Heparin and Protamine in Cardiopulmonary Bypass Cardiac Surgeries : Evaluation of Post-operatory Blood Loss and Transfusion Requirements
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 240
- 试验地点
- 1
- 主要终点
- Mediastinal blood drainage (ml)
研究概览
简要总结
There are currently several schemes described for anticoagulation with heparin and its reversal with protamine during cardiac surgery with CPB. The oldest, and most used in our routine environment, is the scheme of fixed doses, in which a bolus dose of heparin at the start of CPB is established in IU/kg of body weight and the dose of protamine at the end of CPB is calculated based on the initial dose of heparin administered.
These schemes do not take into account the variability inter-patients and can result in overdose or sub-doses of one or both drugs.
The titration schedule of doses of heparin and protamine through the principle of dose-response curve of Bull promotes individualization of dosage according to the response of each patient. This scheme has been associated with an effective reversal of the effect of heparin after CPB and with reduction of post-operatory bleeding and transfusion.
The restoration of a state of anticoagulation by heparin after its reversal by protamine is called "rebound effect". It is a phenomenon explained by the recirculation of heparin stored in the reticulum-endothelial system and connective tissue, or by free residual concentration of heparin after clearance of protamine. This effect may be present for more than 6 hours of post-operatory and may contribute to increase post-operatory bleeding.
详细描述
The objectives were, primarily, to compare intraoperative fixed versus titrated doses of heparin and protamine in cardiac surgeries with CPB regarding blood loss and transfusion requirements during the first 24 post-operative (PO) hours.
Secondarily, the investigators compared continuous infusion of small doses of protamine (25mg/hour) and placebo during the first 6 PO hours to neutralize heparin rebound effect. The investigators measured KTTP and fibrinogen levels during the first 24 PO hours and also the difference in blood loss and transfusion requirements between the groups.
The study included patients from 18 to 75 years-old submitted to Cardiac surgeries with Cardiopulmonary Bypass.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Prevention
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients submitted to an Elective Cardiac Surgery with Cardiopulmonary Bypass
- •Age 18 to 75 years-old
排除标准
- •Hematocrit < 30
- •INR > 1,3
- •Platelets < 100,000
- •Altered KTTP
- •Receiving Non-fractioned Heparin or Low-Molecular Weight Heparin
- •Renal Insufficiency or Creatinine > 2,0
- •Liver Failure or altered ALT/AST
- •Von Willebrands'disease, Haemophilia, sepsis
- •Use in the past 7 days of antiplatelet-therapy(Ticlopidine or Clopidogrel)
研究组 & 干预措施
Fixed doses plus PO protamine
Intraoperative fixed dose schemes (as in "fixed doses plus placebo" group) plus continuous infusion of 25mg/hour of protamine during first 6 PO hours
干预措施: Heparin fixed doses (Drug)
Fixed doses plus PO protamine
Intraoperative fixed dose schemes (as in "fixed doses plus placebo" group) plus continuous infusion of 25mg/hour of protamine during first 6 PO hours
干预措施: PO continuous infusion of Protamine (Drug)
Titrated doses plus PO protamine
Same as "titrated doses" arm, plus continuous infusion of 25mg/ hour of protamine during first 6 PO hours
干预措施: PO continuous infusion of Protamine (Drug)
Titrated doses plus PO protamine
Same as "titrated doses" arm, plus continuous infusion of 25mg/ hour of protamine during first 6 PO hours
干预措施: Heparin and protamine titration (Drug)
Fixed doses plus placebo
Before CPB, fixed heparin dose of 400 Units per kg of body weight to achieve an Activated Coagulation Time (ACT) > 480 seconds.
Reversal of heparin after CPB using 1 : 1 ratio (1 mg of protamine for each 100 units (1mg) of heparin), plus 0.8 mg/kg of protamine at the end of the surgery.
Continuous infusion of placebo (saline 0.9%) during the first 6 PO hours.
干预措施: Heparin fixed doses (Drug)
Titrated doses plus placebo
Titrated doses of heparin before and during CPB and reversal with protamine after CPB calculated by the construction of individualized Bull's dose-response curve.
Continuous infusion of placebo (saline 0.9%) during first 6 PO hours.
干预措施: Heparin and protamine titration (Drug)
结局指标
主要结局
Mediastinal blood drainage (ml)
时间窗: First 24 PO hours
The mediastinal blood drainage was measured hourly during the first 6 post-operatory (PO) hours, and every 6 hours from the 7th to 24th PO hours.
次要结局
- Transfusion of blood components(First 24 PO hours)