Strategies for Protamine Dosing After Anticoagulation in Cardiovascular Surgery (SEPARATION)

Fundación Clínica Shaio

Status and phase: Unknown; Phase 4

Conditions: Anticoagulant Antagonist Toxicity

Treatments: Drug: Conventional dose; Drug: Dosing according residual heparin

Study type: Interventional

Funder types: Other

Identifiers

NCT04628884

DIB-20-34

Details and patient eligibility

About

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.

Enrollment: 136 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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136 participants in 2 patient groups

Protamine dosing according the total heparin administrated

Active Comparator group

Description:

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

Treatment:

Drug: Conventional dose

Protamine dosing according the residual heparin determined by a pharmacokinetic model

Experimental group

Description:

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

Treatment:

Drug: Dosing according residual heparin