Protamine-to-Heparin Ratio for Effective Reversal in Open-Heart Surgery Post-Cardiopulmonary Bypass

Abstract

Introduction: Heparin is routinely administered to achieve anticoagulation during cardiopulmonary bypass (CPB) in open-heart surgery. Protamine sulfate is used to neutralize heparin; however, inappropriate dosing may result in adverse events such as hypotension and paradoxical bleeding. Determining the optimal protamine-to-heparin (P:H) ratio is therefore essential to ensure effective reversal while minimizing complications. This study aims to identify the effective P:H ratio necessary for adequate heparin reversal. Methods: This retrospective study included adult patients who underwent open-heart surgery with CPB at Lampang Hospital between January 2022 and June 2023. Patients were stratified into three groups based on their P:H ratios: <1, =1, and >1. The P:H ratio was calculated using the initial heparin dose administered prior to the initiation of CPB. The primary outcome was the effective heparin reversal, defined as an activated clotting time (ACT) ≤ 10 sec above baseline or within 80-180 sec five min post-protamine administration. Secondary outcomes included determining the minimum effective P:H ratio that resulted in acceptable postoperative blood loss, and evaluating 8-h postoperative blood loss, blood product transfusion volumes, and 24-h reoperation rates due to bleeding. Results: A total of 539 patients were analyzed. Effective heparin reversal, based on post- protamine ACT values, was achieved across all groups with no significant differences observed. Eight-hours postoperative blood loss, blood transfusions, and 24-h reoperation rates were comparable among three groups, with no statistically significant differences. A P:H ratio of approximately 0.94-0.95 was sufficient to maintain acceptable postoperative blood loss and transfusion requirements, comparable to the median values observed in this study. Conclusion: This study found no significant differences in heparin reversal efficacy or blood loss among groups receiving varying protamine doses. Heparin reversal efficacy was defined as achieving an ACT of ≤10 sec above baseline or within the range of 80-180 sec, measured five min after protamine administration. However, a P:H ratio of 0.94-0.95 may indicate effective heparin neutralization