Protamine Dosing for 3000 Units of Heparin
For 3000 units of heparin, administer 30-39 mg of protamine sulfate using the standard fixed-dose ratio of 1.0 to 1.3 mg protamine per 100 units of heparin. 1
Standard Dosing Calculation
The American Heart Association recommends administering 1.0 to 1.3 mg of protamine for each 100 units of heparin administered. 1 This translates to:
- Minimum dose: 3000 units ÷ 100 = 30 mg protamine 1
- Maximum dose: 3000 units × 1.3 ÷ 100 = 39 mg protamine 1
One milligram of protamine neutralizes approximately 85-100 units of heparin. 1, 2 The FDA label confirms that each mg of protamine sulfate neutralizes approximately 100 USP heparin units. 2
Time-Dependent Dosing Adjustments
The dose must be adjusted based on time elapsed since heparin administration, as heparin is metabolized with an approximate half-life of 30 minutes. 2
- Within 30 minutes: Use full calculated dose (30-39 mg for 3000 units) 3, 2
- 30-60 minutes after heparin: Reduce to 0.5-0.75 mg per 100 units (15-22.5 mg for 3000 units) 3
- 60-120 minutes after heparin: Reduce to 0.375-0.5 mg per 100 units (11.25-15 mg for 3000 units) 3
- >120 minutes after heparin: Further dose reduction required 3
Administration Guidelines
Administer protamine by slow intravenous injection over 10 minutes to minimize risk of severe hypotension, bradycardia, and anaphylactoid reactions. 3, 2 The maximum single dose should not exceed 50 mg in any 10-minute period. 3, 2
Post-Administration Monitoring
Measure activated clotting time (ACT) or activated partial thromboplastin time (aPTT) 5-10 minutes after protamine administration to confirm adequate heparin reversal. 1, 3
- If ACT/aPTT remains elevated, administer additional protamine at 0.5 mg per 100 units of heparin 3
- Recheck coagulation parameters after each additional dose 1
Critical Safety Considerations
Patients with fish allergies, previous protamine exposure, vasectomy, or protamine-containing insulin use are at increased risk for severe hypersensitivity reactions. 3, 2 Resuscitation equipment and anaphylaxis treatment must be immediately available. 2
Excess protamine has intrinsic anticoagulant properties that can paradoxically worsen bleeding. 3, 4 A recent 2025 randomized controlled trial demonstrated that ratio-based dosing often results in excess protamine administration without clinical benefit. 4
Context-Specific Modifications
For cardiac surgery with cardiopulmonary bypass duration <90 minutes, the fixed-dose ratio method (1.0-1.3 mg per 100 units) is appropriate. 1 For longer procedures, heparin-protamine titration methods or ACT-based dose-response calculations should be used to minimize protamine exposure and reduce bleeding complications. 1