Clinical Trial Comparing Heparin and Protamine Fixed and Titrated Doses in Cardiac Surgery With Cardiopulmonary Bypass
- Conditions
- Cardiac SurgeryCardiopulmonary BypassAnticoagulation
- Interventions
- Registration Number
- NCT01267487
- Lead Sponsor
- SANE-Society of Anesthesiology
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 240
- Patients submitted to an Elective Cardiac Surgery with Cardiopulmonary Bypass
- Age 18 to 75 years-old
- 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)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- FACTORIAL
- Arm && Interventions
Group Intervention Description Titrated doses plus PO protamine Heparin and protamine titration Same as "titrated doses" arm, plus continuous infusion of 25mg/ hour of protamine during first 6 PO hours Fixed doses plus placebo Heparin fixed doses 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. Fixed doses plus PO protamine Heparin fixed doses Intraoperative fixed dose schemes (as in "fixed doses plus placebo" group) plus continuous infusion of 25mg/hour of protamine during first 6 PO hours Fixed doses plus PO protamine PO continuous infusion of 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 Titrated doses plus PO protamine PO continuous infusion of Protamine Same as "titrated doses" arm, plus continuous infusion of 25mg/ hour of protamine during first 6 PO hours Titrated doses plus placebo Heparin and protamine titration 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.
- Primary Outcome Measures
Name Time Method Mediastinal blood drainage (ml) 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.
- Secondary Outcome Measures
Name Time Method Transfusion of blood components First 24 PO hours We measured the incidence(%) of transfusion of Packed Red Blood Cells, Plasma or Platelet during first 24 PO hours
Trial Locations
- Locations (1)
Instituto de Cardiologia do Rio Grande do Sul
🇧🇷Porto Alegre, Rio Grande do Sul, Brazil