What is the dosage of protamine to reverse heparin (Heparin Sodium) infusion?

From the Guidelines

To reverse a heparin infusion (gtt), administer protamine sulfate at a dose of 1 mg for every 100 units of heparin received in the previous 2-3 hours, as recommended by the most recent guidelines 1. The maximum single dose should not exceed 50 mg. Protamine should be administered slowly by intravenous injection at a rate not exceeding 5 mg per minute to avoid adverse reactions such as hypotension, bradycardia, or anaphylaxis. If the exact amount of circulating heparin is unknown, a typical initial dose is 25-50 mg. After administration, reassess the patient's coagulation status (PTT or ACT) to determine if additional protamine is needed. Remember that heparin has a half-life of approximately 60-90 minutes, so the amount needed for reversal decreases over time since the last heparin dose. Protamine works by binding to heparin molecules to form a stable complex that lacks anticoagulant activity. Be prepared to manage potential adverse reactions, and have resuscitation equipment available during administration. This approach is supported by guidelines from reputable sources, including the Neurocritical Care Society and the Society of Critical Care Medicine 1, as well as the American Heart Association/American Stroke Association Stroke Council 1.

Some key points to consider when administering protamine sulfate include:

• The dose of protamine sulfate depends on the time from cessation of heparin, with a recommended dose of 1 mg per 100 units of heparin received in the previous 2-3 hours 1.
• The maximum single dose of protamine sulfate should not exceed 50 mg 1.
• Protamine sulfate should be administered slowly by intravenous injection at a rate not exceeding 5 mg per minute to avoid adverse reactions 1.
• The patient's coagulation status should be reassessed after administration to determine if additional protamine is needed 1.

Overall, the use of protamine sulfate to reverse heparin infusion is a well-established practice that is supported by guidelines from reputable sources. By following the recommended dose and administration guidelines, healthcare providers can effectively reverse heparin infusion and minimize the risk of adverse reactions 1.

From the FDA Drug Label

When clinical circumstances (bleeding) require reversal of the heparin effect, protamine sulfate (1% solution) by slow infusion will neutralize heparin sodium. No more than 50 mg should be administered, very slowly, in any 10-minute period Each mg of protamine sulfate neutralizes approximately 100 USP heparin units.

To reverse heparin gtt, the amount of protamine required is based on the amount of heparin to be neutralized.

• Dose calculation: Each mg of protamine sulfate neutralizes approximately 100 USP heparin units.
• Administration: No more than 50 mg of protamine sulfate should be administered, very slowly, in any 10-minute period 2.

From the Research

Protamine Dosing for Heparin Reversal

• The amount of protamine required to reverse heparin can be calculated using various methods, including a mathematical formula based on activated clotting time (ACT) measurements 3.
• A study found that administering 2/3 of the total calculated dose of protamine was sufficient to reverse the anticoagulant effect of heparin, and that the commonly applied 1:1 ratio of protamine to heparin may be higher than needed 4.
• Another study compared a fixed 250-mg protamine dose to a 1:1 protamine-to-heparin ratio-based strategy and found that the fixed dose resulted in less total protamine administered, with no difference in activated clotting time or postoperative bleeding 5.
• The protamine dose response has been studied using activated partial thromboplastin time (APTT) in the presence and absence of heparin, and results suggest that protamine has a wide safety range when neutralizing heparin without exerting its own anticoagulant action 6.
• Individualized heparin and protamine management, using rotational thromboelastometric parameters, has been shown to improve postoperative hemostasis and reduce blood loss compared to activated coagulation time (ACT)-based fixed target heparin and protamine management 7.

Key Findings

• A 1:1 ratio of protamine to heparin may be higher than needed, and administering 2/3 of the total calculated dose of protamine may be sufficient to reverse the anticoagulant effect of heparin 4.
• A fixed 250-mg protamine dose can be effective in reversing heparin, with less total protamine administered compared to a 1:1 ratio-based strategy 5.
• Protamine has a wide safety range when neutralizing heparin, and individualized management can improve postoperative hemostasis and reduce blood loss 6, 7.