Protamine Dosing in Cardiac Surgery: Can One Size Fit All?

Abstract

G reater than 1.5 million cardiac surgical procedures are performed globally each year utilizing cardiopulmonary bypass (CPB). 1 Most patients are anticoagulated with unfractionated heparin, a mix of highly sulfated, negatively charged, glycosaminoglycans ranging in size from 3,000 to 30,000 Da, which can be reversed with protamine. 2 Heparin's primary anticoagulant activity occurs through upregulation of antithrombin III's inhibition of factor IIa (thrombin) and factor Xa. 2 Protamine is an isolate of basic polypeptides from fish sperm used clinically to bind to acidic unfractionated heparin and reverse its anticoagulant effect. 3 Despite its extensive use in cardiovascular surgery, important clinical questions remain about protamine. In this month's issue of Anesthesiology, Jain et al. 4 present a randomized controlled trial comparing two protamine dosing strategies in adults after CPB.Although protamine has been used in cardiac surgery since the 1960s, different protocols are used for dosing, and only a few randomized controlled trials in cardiac surgery are available to guide best practice. [5][6][7] Protamine has significant limitations as a reversal agent that include direct anticoagulant properties, hypersensitivity reactions including shock and pulmonary hypertension, and the potential for heparin "rebound." 5,[8][9][10] Protamine is a highly positively charged basic molecule due to its numerous arginine residues comprising two thirds of its structure. 3,11 Protamine's significant positive charge facilitates its avid binding to heparin, neutralizing its anticoagulant effect. Heparin-protamine complexes are then eliminated by liver macrophages. 12 Protamine emerged as the "gold standard" heparin reversal agent for cardiac surgical Image: Adobe Stock.This editorial accompanies the article on p. 98.