Heparin Reversal / Cardiac Surgery

Protamine Sulphate (Heparin Reversal)

Brand names: Protamine Sulphate 1%

Used in: Venous Thromboembolism (DVT & PE)

Protamine sulphate is an intravenous antidote used to neutralise the anticoagulant effect of heparin, most often to reverse unfractionated heparin after cardiopulmonary bypass or other procedures.

Auto-extracted from the source labelling — not yet independently clinician-verified. These values were distilled from the UK SPC (or the US label where noted) but have not had a clinician sign-off. Confirm against the current SmPC before prescribing.

Adult dose

Dose: Each mg of protamine sulfate (calculated on the dried basis) neutralizes not less than 100 USP Heparin Units — dose calculated against the heparin to be neutralised and guided by blood coagulation studies

Route: Very slow intravenous injection over a 10-minute period; intended for injection without further dilution (if dilution desired, D5-W or normal saline may be used)

Frequency: Single dose over 10 minutes; repeat only as guided by blood coagulation studies

Max: Doses not to exceed 50 mg (per 10-minute injection period)

US labelling (no UK SPC in bundle — verify against the UK SPC before use). Because heparin disappears rapidly from the circulation, the required protamine dose decreases rapidly with the time elapsed since the intravenous heparin injection — e.g. if protamine is given 30 minutes after the heparin, one-half the usual dose may be sufficient. Diluted solutions should not be stored (they contain no preservative). Do not mix with other drugs without knowledge of compatibility — protamine sulfate is incompatible with certain antibiotics including several cephalosporins and penicillins. Inspect visually for particulate matter and discoloration before administration. No paediatric dosing is stated in the fetched label.

Dose auto-extracted from US FDA prescribing information (openFDA / DailyMed) — cross-check; US labelling may differ from UK — not yet clinician-verified. Always confirm against the product SmPC and your local formulary before prescribing.

Contraindications

Patients who have shown previous intolerance to protamine sulfate

Side effects

Sudden fall in blood pressure and bradycardia with intravenous administration
Transitory flushing and feeling of warmth; dyspnoea
Nausea, vomiting and lassitude
Back pain (reported in conscious patients undergoing procedures such as cardiac catheterization)
Anaphylaxis (severe respiratory distress, circulatory collapse, capillary leak — fatal cases reported) and anaphylactoid reactions with circulatory collapse, capillary leak, non-cardiogenic pulmonary oedema and acute pulmonary hypertension
Severe and potentially irreversible circulatory collapse with myocardial failure and reduced cardiac output

Interactions

Physically incompatible with certain antibiotics including several cephalosporins and penicillins — do not mix without knowledge of compatibility
Heparin — protamine is given to neutralise heparin; required dose falls rapidly with time elapsed since the heparin dose

Clinical monograph

How it works

Protamine is a strongly basic protein that binds electrostatically to acidic heparin to form an inactive stable complex, abolishing heparin's antithrombin-mediated anticoagulant activity; it only partially reverses low-molecular-weight heparins.

Prescribing in practice

Inject slowly because rapid administration can cause severe hypotension, bradycardia, anaphylactoid reactions and pulmonary hypertension; have resuscitation facilities available.
Patients exposed to protamine-containing insulins, those with fish allergy and men who are infertile or have had a vasectomy are at higher risk of hypersensitivity.
Excessive protamine has its own anticoagulant effect, and rebound anticoagulation (heparin rebound) can occur after cardiac surgery; titrate the dose to the heparin to be neutralised.

Monitoring

Monitor blood pressure, heart rate and coagulation parameters such as the activated clotting time or APTT during and after administration to confirm reversal and detect rebound.

Counselling the patient

Inform the team if you have a fish allergy, take a protamine-containing insulin or have had a vasectomy.
Report any breathlessness, flushing or feeling faint during the injection.

Evidence & guidelines

Protamine reversal of heparin is standard practice in cardiac surgery and established prescribing references, with MHRA-recognised risks of serious cardiovascular and hypersensitivity reactions on rapid administration.

Reference: Cardiothoracic Anaesthesia Society Guidelines; AAGBI Guidelines; SPC Protamine Sulphate 1%; Drug verified in RxNorm (NLM); confirm dosing against the manufacturer SPC (eMC). Verify against your local formulary and current prescribing references before prescribing. The structured dose values shown have been reviewed by a clinician. Monograph status: clinician-reviewed (2026-07-04).

Curated clinical cross-links plus same-class fallbacks.

Calculators

Pathways