COMPARISON OF 0.7 MG AND 1 MG PROTAMINES ON ACTIVATED CLOTTING TIME AND BLEEDING IN OFF-PUMP CORONARY ARTERY BYPASS PATIENTS: A MULTICENTER STUDY
DOI:
10.54443/morfai.v5i3.3051Published:
2025-05-28Downloads
Abstract
Background: Optimal anticoagulation management is crucial for graft patency and minimizing postoperative complications in off-pump coronary artery bypass grafting (OPCAB), a widely performed surgical procedure for coronary artery disease. The role of protamine in neutralizing heparin and its impact on activated clotting time (ACT) and postoperative bleeding remain unclear. This study compared the effects of two protamine doses (0.7 mg and 1 mg per 1 mg of heparin) on ACT and bleeding outcomes in patients who underwent OPCAB. Methods: This multicenter, single-blind, randomized controlled trial was conducted from February to April 2025 and included 50 patients undergoing OPCAB at Dr. Hasan Sadikin General Hospital and Santosa Hospital Central. Patients were randomized into two groups: Group 1 received 0.7 mg of protamine per 1 mg of heparin, and Group 2 received 1 mg of protamine per 1 mg of heparin. The primary outcomes were post-protamine ACT levels and postoperative bleeding at 1, 4, and 12 h. The secondary outcomes included the need for colloid and crystalloid fluid administration. Results: The results showed No significant difference was observed in the ACT between the two groups after protamine administration (p = 0.541). However, postoperative bleeding was significantly lower in the 0.7 mg group than in the 1 mg group at all postoperative time points (p < 0.05). The 1 mg protamine group required significantly more colloid infusion during the procedure (p = 0.001), suggesting greater hemodynamic instability associated with higher protamine doses. Conclusions: A protamine dose of 0.7 mg per 1 mg of heparin was associated with less postoperative bleeding than the standard 1 mg dose, without significant differences in ACT. These findings suggest that lower doses of protamine may be preferable in OPCAB to reduce bleeding risk while maintaining effective heparin neutralization. Further studies are needed to refine the protamine dosing protocols for cardiac surgery.
Keywords:
Protamine, Off-Pump Coronary Artery Bypass Grafting, Activated Clotting Time, Postoperative Bleeding, AnticoagulationReferences
Vervoort D, Lee G, Ghandour H, Guetter CR, Adreak N, Till BM, et al. Global cardiac surgical volume and gaps: trends, targets, and way forward. Ann Thorac Surg Short Reports. 2024;2(2):320-4.
Marczin N, Raja SG. Off-pump coronary artery bypass grafting. AME Med J. 2020; 1:1-5.
Yanagawa B, Puskas JD. Off-pump coronary artery bypass grafting. Oper Tech Thorac Cardiovasc Surg. 2016; 21(1):2-19.
Saha KK, Sangwan DK, Shroff PK, Deval MM, Saha KK, Jacob RV, et al. Off-pump coronary artery bypass grafting using continuous heparin infusion. Indian Heart J. 2016; 68(6):798-802.
Murugesh WR, Prasad SS, Ramachandrappa Sujay K, Dinesh Kumar US. Is a fixed low-dose protamine better at reducing postoperative bleeding in off-pump coronary artery bypass grafting? Asian Cardiovasc Thorac Ann. 2021; 29(9):922-7.
O’Carroll-Kuehn BU, Meeran H. Management of coagulation during cardiopulmonary bypass. Contin Educ Anaesth Crit Care Pain. 2007; 7(6):195-8.
Mondal S, Abuelkasem E, Vesselinov R, Henderson R, Choi S, Mousa A, et al. Protamine dosing and its impact in cardiac surgery transfusion practice—A retrospective bi-institutional analysis. Transfusion (Paris). 2024; 64(3):467-74.
Boer C, Meesters MI, Veerhoek D, Vonk ABA. Anticoagulant and side-effects of protamine in cardiac surgery: a narrative review. Br J Anaesth. 2018; 120:914-27.
Cossu A, Suelzu S, Pala G, Portoghese M, Columbanu V, Sales G, et al. Impact of different dosage of protamine on heparin reversal during off-pump coronary artery bypass: a clinical study. Cardiac. J. 2015; 1:1-6
Lee MH. Can the minimum protamine dose to neutralize heparin at the completion of cardiopulmonary bypass be significantly lower than the conventional practice? J Extra-Corporeal Technol. 2021;1:1-5
Ho LTS, McVey MJ, Kuiper GJAJM, Gross PL, Karkouti K. Analysis of the effect of varying protamine-to-heparin ratio on coagulation. Br J Anaesth. 2021; 127(4):e128-30.
Simone F, Nardelli P, Licheri M, Frau G, Redaelli M, Monaco F, et al. Less is more: We are administering too much protamine in cardiac surgery. Ann Card Anaesth. 2021; 24(2):178-82.
Miles LF, Burt C, Arrowsmith J, McKie MA, Villar SS, Govender P, et al. Optimal protamine dosing after cardiopulmonary bypass: The PRODOSE adaptive randomised controlled trial. PLoS Med. 2021; 18(6): 1-7.
Lee MH, Beck M, Shann K. Protamine dose to neutralize heparin at the completion of cardiopulmonary bypass can be reduced significantly without affecting post-operative bleeding. J Extra-Corporeal Technol. 2023; 55(3):105-11.
Salenger R, Arora RC, Bracey A, D’Oria M, Engelman DT, Evans C, et al. Cardiac surgical bleeding, transfusion, and quality metrics: Joint consensus statement by the Enhanced Recovery After Surgery Cardiac Society and Society for the Advancement of Patient Blood Management. Ann Thorac Surg. 2024;1:1-6.
Rancati V, Scala E, Ltaief Z, Gunga MZ, Kirsch M, Rosner L, et al. Challenges in patient blood management for cardiac surgery: a narrative review. J Clin Med. 2021;10:1-7.
Palta S, Saroa R, Palta A. Overview of the coagulation system. Indian J Anaesthesia. 2014; 58:515-23.
Bartoszko J, Karkouti K. Managing the coagulopathy associated with cardiopulmonary bypass. J Thromb Haemost. 2021; 19(3):617-32.
Levy JH, Ghadimi K, Kizhakkedathu JN, Iba T. What’s fishy about protamine? Clinical use, adverse reactions, and potential alternatives. J Thromb Haemost. 2023; 21:1714-23.
License
Copyright (c) 2025 Andika Ahadyat Lukman Wiriaatmaja , Reza Widianto Sudjud , Budiana Rismawan
This work is licensed under a Creative Commons Attribution 4.0 International License.
Downloads
How to Cite
