Makindo Medical Notes

💉 Protamine sulfate is used to reverse the anticoagulant effects of unfractionated heparin (UFH) and partially those of low molecular weight heparins (LMWH). It is especially important during heparin overdose, cardiac surgery, and obstetric delivery.

📖 About

• Protamine sulfate is a purified mixture of simple proteins originally derived from the sperm of wild salmon 🐟 (now also produced synthetically/recombinantly).
• Always check the BNF for the most up-to-date dosing guidance.

⚙️ Mode of Action

• ➕ Protamine is a positively charged protein that binds to the negatively charged heparin molecules.
• 🔒 This neutralises heparin activity and forms a stable complex, which is then cleared by the reticuloendothelial system.
• ⏱️ Onset: within 5 minutes, duration ~2 hours.

💊 Indications / Dose

• Heparin reversal (UFH overdose or after surgery) 🩸: → 1 mg protamine per 80–100 units of UFH administered in the preceding 15 minutes. → Max single dose: 50 mg.
• LMWH overdose (e.g., enoxaparin): Partial reversal (about 60% of activity neutralised).
• Administration: Give slowly IV, max rate 5 mg/min, to reduce risk of hypotension/anaphylaxis.

🔗 Interactions

• 📖 See BNF for full list.
• ⚠️ Interaction risk with protamine-containing drugs (e.g., NPH insulin, protamine-zinc insulin, certain beta-blockers).

⚠️ Cautions

• 🚨 Can cause severe hypotension, bradycardia, pulmonary hypertension, and even cardiovascular collapse if given too rapidly or in high doses.
• ⚡ Risk factors for reactions: high/repeated dosing, prior exposure, NPH insulin use, fish allergy, previous vasectomy, severe LV dysfunction, abnormal pulmonary haemodynamics.
• 🛡️ Vasopressors and resuscitation equipment should be immediately available.
• ❌ Should not be given if bleeding occurs without prior heparin exposure.

⛔ Contraindications

• 🚫 See BNF for details.
• Hypersensitivity to protamine or protamine-containing products.

😬 Side Effects

• ⬇️ Hypotension, flushing, bradycardia.
• 🌡️ Histamine release → rash, itching, urticaria.
• ⚠️ Anaphylaxis (rare but life-threatening).
• 🫁 Pulmonary hypertension and non-cardiogenic pulmonary oedema (rare).

📚 References

• BNF: Protamine Sulfate
• MHRA safety updates on protamine use.
• Cardiac surgery / obstetric anaesthesia protocols (RCOA).