Heparin neutralization with methylene blue, hexadimethrine, or vancomycin after cardiopulmonary bypass

There are no clinically available alternatives for reversing heparin in protamine-allergic patients. This study examined the ability of methylene blue, hexadimethrine, and vancomycin to reverse circulating heparin so that these compounds can be carefully examined in future placebo-controlled studies in humans. Heparin activity in blood obtained from extracorporeal circuits was reversed by adding protamine (13.5, 27.0, 81.1, 135.1, and 270.3 μg/mL), methylene blue (13.5, 27.0, 135.1, 202.7, 270.3, 337.8, 405.4, 473.0, 540.5, and 810.8 μg/mL), hexadimethrine (6.8, 13.5, 20.3, 27.0, 81.1, and 135.1 μg/mL), or vancomycin (13.5, 27.0, 135.1, 270.3, 540.5, and 810.8 μg/mL), and activated clotting times (ACTs) were measured with kaolin (n = 18). Heparinase-ACT was obtained to determine complete reversal. Heparin concentrations were 3.3 ± 0.3 U/mL with ACT values of 485 ± 97 s. The ACT at a protamine concentration of 81.1 μg/mL and at hexadimethrine concentrations of 81.1 and 135.1 μg/mL was not statistically different from heparinase-ACT; however, methylene blue or vancomycin did not reverse the anticoagulation at any concentrations. Hexadimethrine can reverse heparin- induced anticoagulation after cardiopulmonary bypass as well as protamine, although methylene blue or vancomycin did not neutralize heparin in vitro.