An Adjusted Calculation Model Allows for Reduced Protamine Doses without Increasing Blood Loss in Cardiac Surgery
04 February 2015
02 June 2015
13 August 2015 (online)
Background Heparin dosage for anticoagulation during cardiopulmonary bypass (CPB) is commonly calculated based on the patient's body weight. The protamine–heparin ratio used for heparin reversal varies widely among institutions (0.7–1.3 mg protamine/100 IU heparin). Excess protamine may impair coagulation. With an empirically developed algorithm, the HeProCalc program, heparin, and protamine doses are calculated during the procedure. The primary aim was to investigate whether HeProCalc-based dosage of heparin could reduce protamine use compared with traditional dosages. The secondary aim was to investigate whether HeProCalc-based dosage of protamine affected postoperative bleeding.
Patients and Methods We consecutively randomized 40 patients into two groups. In the control group, traditional heparin and protamine doses, based on body weight alone, were given. In the treatment group, the HeProCalc program was used, which calculated the initial heparin bolus dose from weight, height, and baseline activated clotting time and the protamine dose at termination of CPB.
Results We analyzed the results from 37 patients, after exclusion of three patients. Equal doses of heparin were given in both groups, whereas significantly lower mean doses of protamine were given in the treatment group versus control group (211 ± 56 vs. 330 ± 61 mg, p < 0.001). Postoperative bleeding was less in the HeProCalc group (280 ± 229 mL) as compared with the control group (649 ± 279 mL). However, this difference was not found statistically significant (p = 0.074).
Conclusion HeProCalc-based dosage of heparin and protamine allowed for reduced protamine use after CPB compared with when conventional calculations were used. Furthermore, HeProCalc-based regimen for heparin reversal suggested less postoperative bleeding, although the difference between the groups was not statistically significant.
- 1 Gravlee GP. Cardiopulmonary Bypass: Principles and Practice. 3rd ed. Philadelphia, PA: Lippincott; 2008
- 2 Finley A, Greenberg C. Review article: heparin sensitivity and resistance: management during cardiopulmonary bypass. Anesth Analg 2013; 116 (6) 1210-1222
- 3 Olsson P, Lagergren H, Ek S. The elimination from plasma of intravenous heparin. An experimental study on dogs and humans. Acta Med Scand 1963; 173: 619-630
- 4 Baker MS, Skoyles JR, Shajar FM, Skinner H, Richens D, Mitchell IM. Can lean body mass be used to reduce the dose of heparin and protamine for obese patients undergoing cardiopulmonary bypass?. J Extra Corpor Technol 2005; 37 (2) 153-156
- 5 Noui N, Zogheib E, Walczak K , et al. Anticoagulation monitoring during extracorporeal circulation with the Hepcon/HMS device. Perfusion 2012; 27 (3) 214-220
- 6 Ni Ainle F, Preston RJ, Jenkins PV , et al. Protamine sulfate down-regulates thrombin generation by inhibiting factor V activation. Blood 2009; 114 (8) 1658-1665
- 7 Khan NU, Wayne CK, Barker J, Strang T. The effects of protamine overdose on coagulation parameters as measured by the thrombelastograph. Eur J Anaesthesiol 2010; 27 (7) 624-627
- 8 Cobel-Geard RJ, Hassouna HI. Interaction of protamine sulfate with thrombin. Am J Hematol 1983; 14 (3) 227-233
- 9 Porsche R, Brenner ZR. Allergy to protamine sulfate. Heart Lung 1999; 28 (6) 418-428
- 10 Butterworth J, Lin YA, Prielipp RC, Bennett J, Hammon JW, James RL. Rapid disappearance of protamine in adults undergoing cardiac operation with cardiopulmonary bypass. Ann Thorac Surg 2002; 74 (5) 1589-1595
- 11 Palmer K, Ridgway T, Al-Rawi O, Poullis M. Heparin therapy during extracorporeal circulation: deriving an optimal activated clotting time during cardiopulmonary bypass for isolated coronary artery bypass grafting. J Extra Corpor Technol 2012; 44 (3) 145-150
- 12 Aziz KA, Masood O, Hoschtitzky JA, Ronald A. Does use of the Hepcon point-of-care coagulation monitor to optimise heparin and protamine dosage for cardiopulmonary bypass decrease bleeding and blood and blood product requirements in adult patients undergoing cardiac surgery?. Interact Cardiovasc Thorac Surg 2006; 5 (4) 469-482
- 13 Hofmann B, Bushnaq H, Kraus FB , et al. Immediate effects of individualized heparin and protamine management on hemostatic activation and platelet function in adult patients undergoing cardiac surgery with tranexamic acid antifibrinolytic therapy. Perfusion 2013; 28 (5) 412-418
- 14 Runge M, Møller CH, Steinbrüchel DA. Increased accuracy in heparin and protamine administration decreases bleeding: a pilot study. J Extra Corpor Technol 2009; 41 (1) 10-14
- 15 Guffin AV, Dunbar RW, Kaplan JA, Bland Jr JW. Successful use of a reduced dose of protamine after cardiopulmonary bypass. Anesth Analg 1976; 55 (1) 110-113
- 16 Miyashita T, Nakajima T, Hayashi Y, Kuro M. Hemostatic effects of low-dose protamine following cardiopulmonary bypass. Am J Hematol 2000; 64 (2) 112-115
- 17 Ferraris VA, Brown JR, Despotis GJ , et al; Society of Thoracic Surgeons Blood Conservation Guideline Task Force; Society of Cardiovascular Anesthesiologists Special Task Force on Blood Transfusion; International Consortium for Evidence Based Perfusion. 2011 update to the Society of Thoracic Surgeons and the Society of Cardiovascular Anesthesiologists blood conservation clinical practice guidelines. Ann Thorac Surg 2011; 91 (3) 944-982
- 18 Koch CG, Li L, Duncan AI , et al. Morbidity and mortality risk associated with red blood cell and blood-component transfusion in isolated coronary artery bypass grafting. Crit Care Med 2006; 34 (6) 1608-1616