ClinCalc Pro
Menu
Calculators Drugs Pathways AI Dx Donate Get the App
Heparin Reversal / Cardiac Surgery Pregnancy: Use only if essential — limited data; short-term procedural use in peripartum cardiac surgery

Protamine Sulphate (Heparin Reversal)

Brand names: Protamine Sulphate 1%

Adult dose

Dose: 1 mg protamine neutralises approximately 80-100 units UFH. Post-cardiopulmonary bypass: 1 mg per 100 units heparin given in past 2-3 hours. IV slow injection over 10 minutes. Maximum 50 mg per injection.
Route: Intravenous slow injection over 10 minutes
Frequency: Single dose or repeated as per ACT monitoring
Max: 50 mg per single dose
Positively charged protein — binds negatively charged heparin to form inactive complex. Widely used after cardiac surgery (post-bypass reversal). Check ACT after administration. Excess protamine has anticoagulant effect — do NOT overdose.

Paediatric dose

Route: IV slow injection
Frequency: Per protocol
Max: 1 mg per 100 units UFH
Same weight-based calculation as adults. Specialist paediatric cardiac surgery only. Slow injection critical — adverse reactions more common with rapid administration.

Dose adjustments

Renal

No dose adjustment required

Hepatic

No dose adjustment required

Clinical pearls

  • NPH insulin allergy risk: NPH (neutral protamine Hagedorn) insulin contains protamine as a carrier protein. Patients on NPH insulin have ~50-fold higher risk of protamine allergy. Warn anaesthesia team pre-cardiac surgery if patient uses NPH insulin. Consider using insulin analogues (glargine, detemir) perioperatively.
  • Excess protamine anticoagulation: paradoxically, too much protamine has anticoagulant effects (inhibits platelet aggregation and thrombin activity). ACT monitoring guides dosing — target ACT returning to baseline (pre-heparin). Do not redose blindly.
  • LMWH reversal: protamine reverses anti-IIa activity of LMWH completely but only ~60% of anti-Xa activity. For enoxaparin: 1 mg protamine per 1 mg enoxaparin (if within 8h); 0.5 mg protamine per 1 mg enoxaparin (if 8-12h). A second dose may be needed.
  • Heparin rebound: after cardiac surgery, heparin sequestered in tissues may be released hours after protamine administration — 'heparin rebound' causes recurrent anticoagulation. Monitor ACT for 4-6 hours post-reversal. Second protamine dose may be required.
  • Slow injection mandatory: rapid IV protamine causes histamine release, complement activation, and severe hypotension. Always inject over 10 minutes. Premedication with antihistamine considered in high-risk patients (NPH insulin, fish allergy).

Contraindications

  • Hypersensitivity to protamine
  • NPH insulin-dependent diabetics or previous protamine exposure (higher allergy risk)
  • Fish allergy (protamine derived from fish sperm — cross-reactivity possible)

Side effects

  • Hypotension (most common — rate-related; give slowly over 10 minutes)
  • Bradycardia
  • Anaphylaxis/anaphylactoid reactions (higher risk in NPH insulin users, previous protamine exposure, fish allergy)
  • Pulmonary hypertension (mechanism unclear — complement activation)
  • Paradoxical anticoagulation (excess protamine — anticoagulant effect)
  • Nausea

Interactions

  • Heparin — pharmacological antagonism (therapeutic interaction — reversal)
  • LMWH — partially reversed by protamine (protamine neutralises anti-IIa but NOT anti-Xa activity of LMWH; only ~60% reversal)

Monitoring

  • ACT (activated clotting time — before and after protamine)
  • Blood pressure during infusion
  • Signs of allergic reaction
  • Haemostasis assessment post-bypass

Reference: BNFc; BNF 90; BNFc; Cardiothoracic Anaesthesia Society Guidelines; AAGBI Guidelines; SPC Protamine Sulphate 1%. Verify against your local formulary and the latest BNF before prescribing.

Related

Curated clinical cross-links plus same-class fallbacks.

Calculators
Pathways