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Protamine (Protamine Sulfate) - Summary



Protamine sulfate can cause severe hypotension, cardiovascular collapse, noncardiogenic pulmonary edema, catastrophic pulmonary vasoconstriction, and pulmonary hypertension.  Risk factors include high dose or overdose, rapid administration (see WARNINGS  and DOSAGE AND ADMINISTRATION ), repeated doses, previous administration of protamine, and current or previous use of protamine-containing drugs (NPH insulin, protamine zinc insulin, and certain beta-blockers).  Allergy to fish, previous vasectomy, and severe left ventricular dysfunction and abnormal preoperative pulmonary hemodynamics also may be risk factors.  In patients with any of these risk factors, the risk to benefit of administration of protamine sulfate should be carefully considered.  Vasopressors and resuscitation equipment should be immediately available in case of a severe reaction to protamine.  Protamine sulfate should not be given when bleeding occurs without prior heparin use.



Protamines are simple proteins of low molecular weight that are rich in arginine and strongly basic.

Protamine Sulfate Injection, USP is indicated in the treatment of heparin overdosage.

See all Protamine indications & dosage >>


Published Studies Related to Protamine

Pharmacokinetics and pharmacodynamics of insulin lispro protamine suspension compared with insulin glargine and insulin detemir in type 2 diabetes. [2009]
CONCLUSIONS: Following a single 0.8 U/kg dose in T2DM patients, ILPS, G, and D

Nocturnal glucose metabolism after bedtime injection of insulin glargine or neutral protamine hagedorn insulin in patients with type 2 diabetes. [2008]
morning... INTERPRETATION: Nocturnal variations of EGP and Rd explain the reduced

Can extra protamine eliminate heparin rebound following cardiopulmonary bypass surgery? [2004]
loss... CONCLUSIONS: Postoperative protamine infusion was able to almost totally abolish

Effects of differing rates of protamine reversal of heparin anticoagulation. [1996]
changes were more likely to accompany rapid versus slow protamine administration... CONCLUSIONS: Significant declines in systemic VO2 and hemodynamic perturbations

Protamine use during peripheral vascular surgery: a prospective randomized trial. [1995]
routine heparin reversal with protamine... CONCLUSIONS: Although protamine effectively reverses heparin anticoagulation, its

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Clinical Trials Related to Protamine

Cardiac Surgery: In Vivo Titration of Protamine [Completed]
Safe use of cardiopulmonary bypass (CPB) requires massive doses of intravenous unfractionated heparin. At end-CPB, residual heparin is neutralized with intravenous injection of protamine sulfate. This prospective, randomized, controlled study will be conducted in 82 voluntary subjects admitted for elective, first intention, cardiac surgery requiring cardiopulmonary bypass. Each will be randomly assigned to one of two groups. The control group will be submitted to a standard protamine infusion of 1. 3mg :100U of the total heparin dose given during bypass. The test group will receive an infusion of protamine (over 15 minutes) until activated clotting time (ACT) values (determined every 3 minutes) depict a plateau, sign that the optimal protamine to heparin ratio has been attained. The investigators hypothesize this new in vivo titration method to be as efficient as the standard protocol (adequacy of heparin neutralization, % heparin rebound, bleeding, and transfusion), and potentially safer by its ability to prevent protamine overdose and its deleterious impact on platelet function. 15 Principal Objective Evaluate a new in vivo method of titration of protamine sulfate. Secondary Objective Evaluate the impact of this method on the adequacy of heparin neutralization by measuring: 1. platelet count 2. postoperative bleeding 3. transfusion exposure a 4. incidence of heparin rebound

Clinical Trial Comparing Heparin and Protamine Fixed and Titrated Doses in Cardiac Surgery With Cardiopulmonary Bypass [Completed]
There are currently several schemes described for anticoagulation with heparin and its reversal with protamine during cardiac surgery with CPB. The oldest, and most used in our routine environment, is the scheme of fixed doses, in which a bolus dose of heparin at the start of CPB is established in IU/kg of body weight and the dose of protamine at the end of CPB is calculated based on the initial dose of heparin administered. These schemes do not take into account the variability inter-patients and can result in overdose or sub-doses of one or both drugs. The titration schedule of doses of heparin and protamine through the principle of dose-response curve of Bull promotes individualization of dosage according to the response of each patient. This scheme has been associated with an effective reversal of the effect of heparin after CPB and with reduction of post-operatory bleeding and transfusion. The restoration of a state of anticoagulation by heparin after its reversal by protamine is called "rebound effect". It is a phenomenon explained by the recirculation of heparin stored in the reticulum-endothelial system and connective tissue, or by free residual concentration of heparin after clearance of protamine. This effect may be present for more than 6 hours of post-operatory and may contribute to increase post-operatory bleeding.

Protamine in Cardiac Surgery and Haemostasis [Completed]
Protamine is used after Cardiopulmonary Bypass (CPB) to reverse the anticoagulant effects of heparin and restore coagulation. Convincing evidence from in-vitro and in-vivo studies suggest that an overdose of protamine has anticoagulant effects which might lead to bleeding complications. Heparin levels usually decrease during cardiac surgery with CPB. Therefore, a protamine regimen based on the initial heparin dose before CPB might lead to overdose of protamine. In contrast, a protamine regimen based on the actual heparin concentration may avoid this condition. The investigators compare both regimens of protamine dosing in patients undergoing complex surgery with CPB and assess its effect on the amount of protamine given, markers of the coagulation system, utilization of blood products and perioperative blood loss.

Comparing Angiomax to Heparin With Protamine Reversal in Patients OPCAB [Completed]
The purpose of this study is to examine the safety and efficacy of Angiomax as an alternative anticoagulant to heparin with protamine reversal in patients undergoing off-pump coronary artery bypass graft surgery.

Comparison of Two Basal Insulins for Patients With Type 2 Diabetes (IOOY) [Completed]
The purpose of this study is to examine the effectiveness and safety of insulin lispro protamine suspension (ILPS) as compared to insulin detemir as basal insulin therapy in adults with type 2 diabetes. A gatekeeper strategy will be employed for sequentially testing the secondary objectives.

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Page last updated: 2013-02-10

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