Minimum protamine dose required to neutralize heparin in cardiac surgery: a single-centre, prospective, observational cohort study

PurposeExcess protamine contributes to coagulopathy following cardiopulmonary bypass (CPB) and may increase blood loss and transfusion requirements. The primary aim of this study was to find the least amount of protamine necessary to neutralize residual heparin following CPB using the gold standard assays of anti-IIa and anti-Xa activity. Secondary objectives were to evaluate whether the post-CPB activated clotting time could be used as a surrogate marker for quantifying heparin neutralization. MethodsTwenty-eight consecutive patients undergoing elective cardiac surgery were enrolled. Protamine administration was standardized through an infusion pump at 25 mg & BULL;min(-1). Blood samples were withdrawn prior to and following administration of 150, 200, 250, and 300 mg protamine and analyzed for activated clotting time and anti-IIa and -Xa activity. ResultsFollowing a mean (standard deviation) cumulative heparin dose of 67,700 (19,400) units and a CPB duration of 113 (71) min, protamine requirements varied widely. Eight out of 25 (32%) patients showed complete neutralization of anti-IIa and -Xa activity at the first sampling point (150 mg protamine; protamine:heparin ratio, 0.3 [0.1]). A protamine:heparin ratio of 0.5 (0.2) was sufficient for heparin neutralization in > 90% of patients. After CPB, a low to mid-range activated clotting time correlated well with anti-IIa and -Xa activity. ConclusionsThe protamine:heparin ratio required to neutralize residual unfractionated heparin (UFH) following CPB is variable. A protamine:heparin ratio of 0.3 was sufficient to neutralize UFH in some patients, while a ratio of 0.5 is sufficient to neutralize both residual anti-IIa and -Xa activity in most patients. Larger studies are necessary to confirm these findings and evaluate their clinical implications. Study registrationClinicalTrials.gov (NCT03787641); registered 26 December 2018.

Automated summary

The study aimed to find the minimum amount of protamine required to neutralize residual heparin following cardiopulmonary bypass (CPB), and evaluate whether the activated clotting time can be used as a marker for quantifying heparin neutralization. The results showed that a protamine:heparin ratio of 0.3 was sufficient to neutralize heparin in some patients, while a ratio of 0.5 was sufficient to neutralize anti-IIa and -Xa activity in most patients. Larger studies are needed to confirm these findings.