What is the dose of protamine sulfate for reversal of heparin (unfractionated heparin) anticoagulation?

From the Guidelines

Protamine sulfate should be dosed at 1 mg for every 100 units of heparin given in the previous 2–3 hours, with a maximum single dose of 50 mg, as recommended by the most recent and highest quality study 1. The dose of protamine sulfate for heparin reversal is crucial in clinical practice, and the most recent guideline recommends dosing protamine according to the dose of heparin infused over the preceding 2–3 hours 1.

• The recommended dose is 1 mg of protamine sulfate for every 100 units of heparin given in the previous 2–3 hours, with a maximum single dose of 50 mg 1.
• If the activated partial thromboplastin time (aPTT) remains elevated, a repeat administration of protamine at a dose of 0.5 mg protamine per 100 units of unfractionated heparin may be considered 1.
• The medication should be administered by slow intravenous injection at a rate not exceeding 5 mg per minute to avoid hypotension, bradycardia, or anaphylactic reactions.
• Continuous cardiac and blood pressure monitoring is essential during administration.
• Protamine works by binding to heparin molecules to form a stable complex that lacks anticoagulant activity.
• It's essential to note that excessive protamine can itself act as an anticoagulant, so accurate dosing based on the timing and amount of heparin given is crucial.
• After administration, coagulation studies should be performed to confirm adequate reversal, and additional doses may be needed if anticoagulation persists.

From the FDA Drug Label

Each mg of protamine sulfate neutralizes approximately 100 USP heparin units. Protamine sulfate injection should be given by very slow intravenous injection over a 10-minute period in doses not to exceed 50 mg Because heparin disappears rapidly from the circulation, the dose of protamine sulfate required also decreases rapidly with the time elapsed following intravenous injection of heparin. For example, if the protamine sulfate is administered 30 minutes after the heparin, one-half the usual dose may be sufficient

The dose of protamine sulfate for heparin reversal is 1 mg of protamine sulfate per 100 USP heparin units. The dose should be administered slowly over a 10-minute period and should not exceed 50 mg. The required dose decreases over time as heparin is metabolized, with a suggested reduction to half the usual dose if administered 30 minutes after heparin injection 2 3.

• Key considerations:
  • Dose calculation based on heparin units
  • Slow administration over 10 minutes
  • Maximum dose of 50 mg
  • Decreasing dose requirement over time
  • Guidance by blood coagulation studies

From the Research

Dose of Protamine Sulfate for Heparin Reversal

• The dose of protamine sulfate for heparin reversal is a critical aspect of managing patients undergoing cardiac surgery with cardiopulmonary bypass (CPB) 4.
• A study published in 2016 found that a low protamine-to-heparin dosing ratio (0.8) resulted in less postoperative blood loss and lower transfusion rates compared to a high dosing ratio (1.3) 4.
• The study suggested that abundant protamine dosing is associated with increased postoperative blood loss and higher transfusion rates in cardiac surgery 4.
• Another study published in 1979 found that only 0.4% of patients required additional protamine sulfate for residual heparin after cardiopulmonary bypass 5.
• A 2017 study found that individualizing heparin and protamine dosing using a Hemostasis Management System (HMS) led to reductions in blood product usage, including packed red blood cells, fresh frozen plasma, cryoprecipitate, and platelets 6.
• The optimal dose of protamine sulfate for heparin reversal may depend on various factors, including the patient's coagulation status, the type and dose of heparin used, and the specific surgical procedure being performed 4, 6, 7.

Key Findings

• A low protamine-to-heparin dosing ratio (0.8) is associated with less postoperative blood loss and lower transfusion rates compared to a high dosing ratio (1.3) 4.
• Individualizing heparin and protamine dosing using a Hemostasis Management System (HMS) can lead to reductions in blood product usage 6.
• The type and dose of heparin used, as well as the patient's coagulation status, can impact the optimal dose of protamine sulfate for heparin reversal 4, 6, 7.