title: Heparin neutralization with methylene blue, hexadimethrine, or vancomycin after cardiopulmonary bypass.
abstract: 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 micrograms/mL), methylene blue (13.5, 27.0, 135.1, 202.7, 270.3, 337.8, 405.4, 473.0, 540.5, and 810.8 micrograms/mL), hexadimethrine (6.8, 13.5, 20.3, 27.0, 81.1, and 135.1 micrograms/mL), or vancomycin (13.5, 27.0, 135.1, 270.3, 540.5, and 810.8 micrograms/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 micrograms/mL and at hexadimethrine concentrations of 81.1 and 135.1 micrograms/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.
authors.affiliation: Department of Anesthesiology, Emory University School of Medicine, Emory Clinic, Atlanta, Georgia 30322, USA.
authors.forename: M
authors.initials: M
authors.lastname: Kikura
authors.forename: M K
authors.initials: MK
authors.lastname: Lee
authors.forename: J H
authors.initials: JH
authors.lastname: Levy
mesh_terms: D001777:Blood Coagulation / Q000187:drug effects; D002315:Cardiopulmonary Bypass; D005112:Extracorporeal Circulation; D005260:Female; D006493:Heparin / Q000097:blood; D006494:Heparin Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D019763:Heparin Lyase; D006583:Hexadimethrine Bromide / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D007616:Kaolin; D008297:Male; D008751:Methylene Blue / Q000008:administration & dosage / Q000627:therapeutic use*; D008875:Middle Aged; D011133:Polysaccharide-Lyases; D011479:Protamines / Q000008:administration & dosage / Q000627:therapeutic use; D014640:Vancomycin / Q000008:administration & dosage / Q000627:therapeutic use*; D014914:Whole Blood Coagulation Time
chemical_list: D006494:Heparin Antagonists; D011479:Protamines; D007616:Kaolin; D006583:Hexadimethrine Bromide; D014640:Vancomycin; D006493:Heparin; D011133:Polysaccharide-Lyases; D019763:Heparin Lyase; D008751:Methylene Blue