Adults: Protamine Sulfate should be given as a slow intravenous injection over about 10 minutes. No more than 50 mg should be given in any one dose. The dose depends on the amount and type of heparin to be neutralised, the route it was given by, and the time since the last dose, because heparin is continuously being excreted. Ideally, the dose needed to neutralise heparin should be guided by blood coagulation studies or calculated from a protamine neutralisation test. In gross excess, protamine itself acts as an anticoagulant.
Neutralisation of unfractionated (UF) heparins: 1 mg of protamine sulfate will usually neutralise at least 100 international units of mucous heparin or 80 units of lung heparin. The dose should be reduced if more than 15 minutes have passed since the intravenous injection. For example, if 30 to 60 minutes have passed since heparin was injected intravenously, 0.5 to 0.75 mg of protamine sulfate per 100 units of mucous heparin is recommended. If two hours or more have passed, give 0.25 to 0.375 mg per 100 units of mucous heparin. If the patient is on an intravenous infusion of heparin, stop the infusion and give 25 to 50 mg of protamine sulfate by slow intravenous injection. If the heparin was given subcutaneously, give 1 mg of protamine sulfate per 100 units of mucous heparin. Of this, 25 to 50 mg is given by slow intravenous injection and the balance by intravenous infusion over 8 to 16 hours. To reverse UF heparin after cardiopulmonary bypass, either a standard dose of protamine may be given as above, or the dose may be titrated against the activated clotting time. Patients should be monitored carefully, using either the activated partial thromboplastin time or the activated clotting time, checked 5 to 15 minutes after protamine sulfate is given. Further doses may be needed, because protamine is cleared from the blood more rapidly than heparin.
Neutralisation of low molecular weight (LMW) heparins: A dose of 1 mg per 100 units is usually recommended, but the manufacturer's own guidelines should be consulted. The anti-Xa activity of LMW heparins may not be completely reversible with protamine sulfate and may persist for up to 24 hours after administration. LMW heparins also have a longer half-life (about twice that of UF heparin), and this should be borne in mind when estimating the protamine sulfate dose against the time since the last heparin dose. In theory, the dose of protamine sulfate should be halved once one half-life has passed since the last LMW heparin dose. For LMW heparin given subcutaneously, intermittent injections or a continuous infusion of protamine sulfate have been recommended, since absorption may continue from the subcutaneous depot. Patients should be monitored carefully. Further doses may be needed because protamine is cleared from the blood more rapidly than heparin, especially low molecular weight heparin.
Elderly: There is no current evidence that the recommended dose needs to change.
Children: Safety and efficacy in children have not been established. Not recommended.
