Methylene blue for neutralization of heparin

Patients with protamine allergy present a difficult dilemma when reversal of heparin is required for excessive bleeding. Premedication with steroids and antihistamines has not been shown to effectively prevent anaphylactic reactions in patients with hypersensitivity to protamine. Other heparin antagonists are either not available or are too toxic for human use. This report describes a patient in whom methylene blue was used effectively to neutralize heparin and decrease bleeding due to heparinization. In vitro testing was then done to further define the interaction of heparin and methylene blue. This testing demonstrated that methylene blue neutralized heparin levels of 1 u/ml as well as 10 u/ml. Methylene blue acted as an anticoagulant when present at levels of 3000 micrograms/ml. However, it acted as a coagulant when present in intermediate levels of 800 micrograms/ml and 1600 micrograms/ml. The plasma levels necessary for neutralization of heparin levels of 1 unit/ml (the levels achieved in patient therapeutically anticoagulated) are easily achieved using doses routinely used in treatment of methemoglobinemia. Although the toxicity of methylene blue has been well defined at the lower doses of 2-4 mg/Kg, work still needs to be done to determine safety of the drug at the higher doses necessary to neutralize heparin levels achieved in bypass patients.