What dose of protamine sulfate is needed to reverse 5,000 units of heparin administered intravenously?

Protamine Sulfate Dosing for Heparin Reversal

For immediate reversal of 5,000 units of intravenous heparin, 50 mg of protamine sulfate should be administered intravenously.

Dosing Calculation

• The standard dosing for protamine sulfate is 1 mg per 100 units of heparin received when administered within 30 minutes of heparin administration 1, 2
• For 5,000 units of heparin administered intravenously, the calculation is:
  • 5,000 units ÷ 100 units/mg = 50 mg protamine sulfate 1, 2
• This dose should not exceed the maximum recommended single dose of 50 mg 1, 3

Administration Method

• Protamine sulfate should be administered by very slow intravenous injection over a 10-minute period to minimize adverse effects 2, 3
• Rapid administration can cause severe systemic hypotension, bradycardia, and anaphylactoid reactions 2, 4
• The drug can be given undiluted or diluted in D5W or normal saline if necessary 3

Time-Dependent Dosing

• If more time has elapsed since heparin administration, the protamine dose should be reduced according to this schedule 1:
  • < 30 minutes: 1.0 mg/100 units heparin (full dose of 50 mg for 5,000 units)
  • 30-60 minutes: 0.5-0.75 mg/100 units heparin (25-37.5 mg for 5,000 units)
  • 60-120 minutes: 0.375-0.5 mg/100 units heparin (18.75-25 mg for 5,000 units)

  • 120 minutes: 0.25-0.375 mg/100 units heparin (12.5-18.75 mg for 5,000 units)

Monitoring After Administration

• Blood coagulation studies should be performed 5-10 minutes after protamine administration to confirm adequate reversal 2, 3
• If coagulation parameters remain abnormal, additional protamine may be considered, though with caution due to increased risk of adverse effects 2

Potential Adverse Effects

• Hypersensitivity reactions may occur, particularly in patients with:
  • Known fish allergies
  • Previous exposure to protamine
  • Protamine-containing insulin 1, 2
• Protamine itself has weak anticoagulant properties at high doses, which may paradoxically worsen bleeding if overdosed 5, 6
• Hemodynamic effects including hypotension, decreased cardiac output, and reduced systemic oxygen consumption have been documented 7, 4

Special Considerations

• The FDA-approved protamine sulfate product specifies that each mg neutralizes not less than 100 USP Heparin Units 3
• Newer approaches to calculating protamine dosing based on activated clotting time (ACT) may reduce overall protamine exposure but are not yet standard practice 8

Therefore, for immediate reversal of 5,000 units of IV heparin, the correct answer is (e) 50 mg protamine sulfate.