1. Intraoperative Protamine Reactions Rebecca Tisdale, T4

2. Intraoperative protamine reactions  Protamine  Nitrogenous alkaline protein from salmon sperm  2/3’s arginine(++++), complexes with sulfate groups of heparin  2 active sites: one neutralizes heparin, 1 exerts mild anticoagulatory effect  Uses: antidote for heparin overdose, during CPB, NPH insulin

3. Intraoperative protamine reactions  Protamine dosing(varies widely)  Protamine titration tests at end of CPB to determine amount of heparin still remaining  1 mg/100 units of heparin separated into 2 doses: initial dose(75% total) after CPB and second dose(25% total) after reinfusion of blood from bypass circuit  ***give over 5 minutes or longer

4.  Adverse reactions(0.06%-10.7%)  Peripheral cardiovascular changes Systemic hypotension Increased pulmonary artery pressure  Pulmonary changes: Bronchospasm  Thrombocytopenia  Cutaneous: Severe angioedema, erythema, pruitis, flushing  Other: Chills, fever, nausea, vomiting, chest pain Intraoperative protamine reactions

5.  Risk factors:  Insulin use  Vasectomy  Fish allergy  Previous exposure  Rapid rate of infusion Intraoperative protamine reactions

6.  Treatment  If patient at risk, consider non-heparin based CPB, OPCPB, heparinase, foregoing heparin reversal  Mild hypotension is often improved by slowing/stopping protamine infusion and increasing IVF’s  Consider phenylephrine, ephedrine Intraoperative protamine reactions

7.  Treatment(cont)  May need to reheparinize and return to CPB  Inotropic support: epinephrine, milrinone, isoproterenol  Nebulized albuterol if bronchospasm, elevated airway pressure Intraoperative protamine reactions

8.  Alternatives to protamine  Hexadimethrine(Polybrene) synthetic polycation 1.1-2 times more potent Systemic hypotension when adminstered rapidly Renal toxicity  Heparinase Bonded to exit filter Systemic administration Intraoperative protamine reactions

9.  References  Kaplan, Joel A.. Kaplan: Essentials of Cardiac Anesthesia, 1st ed.. 1. Philadelphia: Saunders, 2008.  Miller, Ronald D.. Miller's Anesthesia. 7th ed. New York : Churchill Livingstone, 2009. 1902-1904.  Porsche, Renate, and Zara Brenner. "Allergy to protamine sulfate." Heart and Lung. 28.6 (1999): 418-428. Intraoperative protamine reactions