Strategies for Protamine Dosing After Anticoagulation in Cardiovascular Surgery

Summary

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.

Timeline

Start

2020-11-15

Primary completion

2021-11-20

Completion

2021-11-22

Publications

• Background Puis L, Milojevic M, Boer C, De Somer FMJJ, Gudbjartsson T, van den Goor J, Jones TJ, Lomivorotov V, Merkle F, Ranucci M, Kunst G, Wahba A; EACTS/EACTA/EBCP Committee Reviewers. 2019 EACTS/EACTA/EBCP guidelines on cardiopulmonary bypass in adult cardiac surgery. Interact Cardiovasc Thorac Surg. 2020 Feb 1;30(2):161-202. doi: 10.1093/icvts/ivz251. No abstract available.
• Background Delavenne X, Ollier E, Chollet S, Sandri F, Lanoiselee J, Hodin S, Montmartin A, Fuzellier JF, Mismetti P, Gergele L. Pharmacokinetic/pharmacodynamic model for unfractionated heparin dosing during cardiopulmonary bypass. Br J Anaesth. 2017 May 1;118(5):705-712. doi: 10.1093/bja/aex044.
• Background Meesters MI, Veerhoek D, de Jong JR, Boer C. A Pharmacokinetic Model for Protamine Dosing After Cardiopulmonary Bypass. J Cardiothorac Vasc Anesth. 2016 Oct;30(5):1190-5. doi: 10.1053/j.jvca.2016.04.021. Epub 2016 Apr 28.

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