A Phase 4 interventional study of Heparin fixed doses and PO continuous infusion of Protamine in Cardiac Surgery, Cardiopulmonary Bypass and Anticoagulation, sponsored by SANE-Society of Anesthesiology. Completed at 1 site in Brazil. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2010-12-28.
Sponsored by SANE-Society of Anesthesiology · Phase 4, Interventional, and Prevention
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.
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.
This is the only study on the registry with SANE-Society of Anesthesiology as lead sponsor.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Intraoperative fixed dose schemes (as in "fixed doses plus placebo" group) plus continuous infusion of 25mg/hour of protamine during first 6 PO hours
Drug: Heparin fixed doses · Drug: PO continuous infusion of Protamine
Same as "titrated doses" arm, plus continuous infusion of 25mg/ hour of protamine during first 6 PO hours
Drug: PO continuous infusion of Protamine · Drug: Heparin and protamine titration
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.
Drug: Heparin fixed doses
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.
Drug: Heparin and protamine titration
Fixed doses of 400 units/ kg of patient's body weight before CPB to achieve an ACT \> 480 sec. Supplemental doses of 50mg of heparin if ACT \<480 sec during CPB. Reversal doses of protamine in a 1:1 ratio (1mg of protamine for every mg of heparin administered), plus 0.8mg/kg of protamine at the end of the surgery.
25mg/hour in IV continuous infusion during first 6 PO hours
Titrated doses of heparin during CPB were manually calculated using Bull´s dose-response curve, which was based in periodic assessment of Activated-Coagulation Times (ACT)- baseline ACT, after 2mg/kg of heparin at cannulation and every 15 to 30 minutes during CPB. Reversal doses of protamine were calculated as a 1:1 ratio of the actual estimated heparin concentration (in mg/kg) at the end of CPB, using the Bull´s dose response curve.
Mediastinal blood drainage (ml)
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.
Time frame: First 24 PO hours
Transfusion of blood components
We measured the incidence(%) of transfusion of Packed Red Blood Cells, Plasma or Platelet during first 24 PO hours
Time frame: First 24 PO hours
This study is completed, as verified in Dec 2010. You cannot join it, but the record below documents what was studied.
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