The drug is injected intravenously, slowly or drip, under medical and laboratory control of blood coagulability (especially partial platelet generation time (ARTT) or coagulation time (ACT), to bring to a normal, physiological level the ability to coagulate).
In case of an overdose of heparin, a solution of protamine sulfate is injected at a rate of 1 ml (10 mg) for 3 minutes. If necessary, the injections are repeated at intervals of 15-30 minutes, the total dose is usually 5 ml (50 mg) of the solution - injected for 10 minutes. Do not administer more than 150 mg for 1 hour.
With spontaneous bleeding, the daily dose is 5-8 mg / kg, intravenously drip in 2 divided doses at intervals of 6 hours.
The maximum duration of treatment is 3 days.
The dose of the drug depends on the method of administration of heparin. The calculated dose is dissolved in 300-500 ml of 0.9% sodium chloride solution.
With bolus injections of heparin, the dose of protamine sulfate decreases depending on the time elapsed from the administration of heparin, since the latter is continuously removed from the body.
| Time elapsed after heparin injection | The dose of protamine sulfate per 100 ME heparin |
| 15-30 min | 1 - 1.5 mg |
| 30 - 60 min | 0.5-0.75 mg |
| Over 2 hours | 0.25-0.375 mg |
If heparin was injected intravenously, stop infusion of heparin and inject 2.5-3 ml (25-30 mg) of protamine sulfate.
If heparin was administered subcutaneously or intramuscularly - a dose of protamine sulfate is 1.2-1.3 mg per 100 ME heparin.
The first 25-50 mg protamine sulphate should be administered intravenously slowly, the remaining dose - intravenously drip for 8-16 hours.
If the operative intervention used extracorporeal circulation - the dose of protamine sulfate is 1.2-1.3 mg per 100 ME heparin.
Application for neutralization of low molecular weight heparin
Protamine sulfate is used to neutralize low molecular weight heparins (LMWH), but it can not completely eliminate antithrombotic activity: 1 mg of protamine sulfate neutralizes 100 units of anti-Na activity and not more than 60% of anti-Xa activity of low molecular weight heparins. When choosing a dose of protamine sulfate, it is necessary to take into account the amount of introduced low-molecular heparin, the route of its administration, the pharmacokinetics of the drug used, and the time elapsed after the last injection of low-molecular heparin.
Introduce Protamine sulfate intravenously or in the form of infusion slowly - 1 mg protamine sulfate per 100 anti-Xa ME recently introduced low-molecular-weight heparin. 8 hours after the administration of low-molecular-weight heparin, a half dose of protamine sulfate can be used, and after 12 hours the drug will probably not be needed. The duration of preservation of the effect of low molecular weight heparin is due to its intake from the subcutaneous tissue, therefore, an infusion of the calculated dose of protamine sulfate for several hours or repeated administration of a half dose of protamine sulfate with persistent bleeding.
Patients with renal and hepatic insufficiency
In patients with mild to moderate renal insufficiency (CK≥30 mL / min and <60 mL / min), no dose reduction is required, in patients with renal disease insufficiency of severe degree (CC <30 ml / min) dose should be reduced by 25%.
In patients with hepatic insufficiency Protamine sulfate should be used with caution.