Optimal Protamine Dosing for Heparin Reversal in Cardiopulmonary Bypass: A Quasi-Experimental Study in Elective Coronary Artery Bypass Surgery

Abstract

Objectives: Protamine sulfate is routinely administered after cardiopulmonary bypass (CPB) to neutralize heparin; however, conventional 1:1 heparin–protamine dosing may exceed the amount required for effective reversal and contribute to postoperative bleeding and adverse reactions. This study evaluated whether reduced protamine dosing achieves adequate heparin neutralization while maintaining comparable postoperative outcomes in patients undergoing elective coronary artery bypass grafting (CABG). Methodology: This quasi-experimental study was conducted at the Rawalpindi Institute of Cardiology, Rawalpindi, Pakistan, from October 2023 to October 2024. Sixty adult patients undergoing elective CABG with CPB were assigned to receive 30%, 50%, or 100% of the calculated protamine dose (1 mg per 100 IU heparin). Heparin reversal was guided by activated clotting time (ACT) monitoring. Primary outcomes included postoperative chest drain output, length of intensive care unit (ICU) stay, and need for re-exploration due to bleeding. Results: Baseline demographic and operative characteristics were comparable across groups. Post-protamine ACT values were lowest in the 50% protamine group (mean 140 seconds), which also demonstrated the lowest mean postoperative drain output (885.5 mL). No statistically significant differences were observed among groups in drain output, ICU stay, or re-exploration rates (p > 0.05). Four patients (6.7%) required intraoperative crossover to a higher protamine dose, and analyses were conducted on a per-protocol basis. Reduced-dose groups achieved satisfactory ACT reversal without increased postoperative bleeding or morbidity. Conclusion: Reduced protamine dosing, particularly at 50% of the calculated dose, provided effective heparin reversal following CPB in elective CABG patients, with postoperative outcomes comparable to full-dose protamine. These findings support a more conservative, ACT-guided approach to protamine administration. Larger multicenter studies are warranted to confirm optimal dosing strategies.