Strategies for Protamine Dosing After Anticoagulation in Cardiovascular Surgery

Study Overview
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Brief Summary
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In cardiovascular surgery, patients are anticoagulated with heparin during cardiopulmonary bypass, subsequently, anticoagulation is reversed with protamine to reduce bleeding due to residual heparin-induced coagulopathy, which can last more than four hours. Protamine reverses the effect of heparin by binding to each heparin molecule, therefore an amount of protamine equivalent to residual heparin is required at the time that anticoagulation is desired to be reversed, but generally, the dose of protamine is calculated from the total dose of heparin, ignoring that heparin is metabolized and cleared during of the extracorporeal circulation, this excess of protamine produces anticoagulant effects that increase postoperative bleeding. Residual heparin can be estimated from heparin pharmacokinetic models and therefore, from these models, a dose closer to the amount necessary to reverse the effect of heparin can be estimated, avoiding protamine excess. In this study, a protamine dosage strategy based on residual heparin determined by a pharmacokinetic model of heparin versus total administered heparin will be compared regarding bleeding and use of blood components in the postoperative period.

Official Title
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Comparison of Two Strategies for Protamine Dosing After Anticoagulation in Cardiovascular Surgery Regarding Postoperative Bleeding: Total Heparin Administered Versus Residual Heparin Determined by a Pharmacokinetic Model

Conditions
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Anticoagulant Antagonist Toxicity

Intervention / Treatment
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* Drug: Conventional dose
* Drug: Dosing according residual heparin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients over 18 years of age who undergo scheduled cardiovascular surgery or scheduled urgency at the Shaio clinical foundation in the city of Bogotá, who require extracorporeal circulation. ASA classification, between 1 - 4 Informed consent read and signed by the patient No history of known blood dyscrasia, with INR values <1.5 Platelet count greater than 100,000 No history of heparin-induced thrombocytopenia No history of adverse reaction to protamine No use of dual anti-aggregation therapy acetylsalicylic acid (ASA) + ADP receptor inhibitors (Clopidogrel) at the time of surgery Suspension of ADP receptor inhibitor drugs (Clopidogrel) according to institutional protocol. No use of bridging therapy with tirofiban Patient with chronic use of oral anticoagulants (warfarin, dabigatran), complete the suspension time according to the institutional protocol, No requirement for renal replacement therapy in the last month Patient with BMI between 18 - 41 kg / cm2 Not pregnant Exclusion Criteria: Emergency surgery Anticoagulated patient at the time of the intervention Procedure not performed under extracorporeal circulation. Procedure requiring circulatory arrest and / or profound hypothermia Intraoperative death before protamine administration Inability to complete data collection.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Protamine dosing according the total heparin administrated<br>The protamine dose will be calculated according to the total heparin administered including the heparin dose add during the pump purge, 1 mg of protamine for each 100 IU of heparin | Drug: Conventional dose<br>* Conventional dose used to calculated the protamine dose<br>|
| Experimental: Protamine dosing according the residual heparin determined by a pharmacokinetic model<br>The protamine dose will be calculated according to the residual heparin estimated before the separation of the cardiopulmonary bypass using a pharmacokinetic model, 1 mg of protamine for each 100 IU of residual heparin | Drug: Dosing according residual heparin<br>* In this group the heparin doses will be simulated using a pharmacokinetic model to estimated the residual heparin amount at the end of the surgery, the protamine dose will be calculated using the residual heparin<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| postoperative mediastinal bleeding | total blood collected from the mediastinal chest tubes during the first 24 hours | first 24 hours after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| total blood products transfused | red blood cells, plasma, cryoprecipitate, platelets, fibrinogen, and prothrombin complexes | first 24 hours after surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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heparin, protamine, dose, extracorporeal circulation, cardiopulmonary bypass