On the topic of protamine for heparin reversal, the guidelines suggest calculating the dose based on titration to existing heparin in the blood, which has been associated with reduced bleeding and blood transfusions (a class IIa recommendation). Regarding protamine overdose, the guidelines recommend limiting the ratio of protamine to heparin to less than 2.6 mg to 100 units (also a class IIa recommendation). Total doses higher than that ratio may inhibit platelet function, prolong ACT, and increase the risk of bleeding, according to the evidence.
Patients who require high doses of heparin and have prolonged CPB times may be at risk for heparin rebound; in such cases, the guidelines offer a class IIb recommendation for low-dose protamine infusion at 25 mg/hour for up to six hours after CPB, as part of a blood-conservation program.
Some patients may experience complications associated with protamine reversal. In those who have
anaphylactic reactions (pulmonary hypertension and circulatory collapse shortly after protamine administration), the guidelines offer a class I recommendation to discontinue protamine and apply resuscitative measures, such as restarting CPB with adequate anticoagulation.
Finally, the authors stressed that there is no ideal CPB anticoagulation strategy for patients who cannot take heparin, as heparin and protamine are the gold standard. However, some patients may require bivalirudin. In patients who have received bivalirudin for anticoagulation and are bleeding excessively after CPB, the guidelines call for a combination of modified ultrafiltration, hemodialysis, and recombinant factor VIIa with blood product replacement to improve hemostasis (a class IIb recommendation).