EVALUATION OF PROTAMINE DOSING STRATEGIES FOLLOWING CARDIOPULMONARY BYPASS
Justine Bur, Amanda Sowder, Hetal Patel
AdventHealth Orlando-Orlando, FL
OBJECTIVE: Compare the impact of low, medium, or high protamine dosing on bleeding outcomes following cardiopulmonary bypass assisted cardiac surgery.
BACKGROUND: Protamine is used to reverse the anticoagulant effects of heparin after cardiopulmonary bypass (CPB). Improper dosing of protamine may lead to increased postoperative bleeding. Although it is paramount to have an appropriate protamine-to-heparin dosing ratio, evidence remains weak on guiding optimal dosing and inconsistencies exist between guidelines. At our institution, protamine dosing is routinely based off the initial heparin bolus. To our knowledge, no studies have compared protamine-to-heparin dosing ratios in otherwise healthy patients undergoing initial, elective CPB-assisted cardiac surgery.
METHODS: A single centered, retrospective analysis was performed at a major tertiary referral hospital. Healthy adults aged 18 to 75 years old who underwent CPB-assisted coronary artery bypass graft or valve repair or replacement, with or without concomitant left atrial appendage ligation, MAZE, or myectomy were included. Exclusion criteria included chronic kidney disease or dialysis, liver dysfunction, hematologic disorders, pregnancy, or cancer. Patients were also excluded if they received non-packed red blood cell products in the operating room (OR). Primary endpoints included 24-hour chest tube output and 24-hour postoperative allogeneic transfusion requirements. Secondary endpoints included reintubation within 24 hours and operative re-exploration within 24 hours due to postoperative bleeding. All endpoints were measured after disposition from OR to the intensive care unit. Outcomes were evaluated based on low (<1:1), medium (1:1), and high (>1:1) protamine-to-heparin dosing ratios based on initial heparin and protamine boluses administered.
RESULTS: Seventy of the 267 patients screened between February 2023 and January 2025 were included in the analysis. Patients were median age 60 years, median BMI of 28.6 kg/m2 and 42 (60%) were male. At baseline, median pre-operative labs included: hemoglobin 13.6 g/dL, hematocrit 40.3%, platelets 240,000/μL, ACT 107 seconds, INR 1.0 and aPTT 29.6 seconds. Mitral valve replacement, 37 (53%), and repair, 15 (21%), were the most common cardiac surgeries. Median bypass time was 82 minutes. Median heparin and protamine boluses administered were 36,000 units and 320 mg, respectively. Protamine-to-heparin dosing ratios were characterized as follows: 32 (46%) patients comprised low, 28 (40%) comprised medium, and 10 (14%) comprised high. Twenty-four-hour chest tube output for low, medium, and high dose groups totaled 468, 530, and 850 mL, respectively (p=0.136). Of the 36% of patients who received transfusions, median total volume of transfusions for low, medium, and high dose groups were 506, 349, and 473 mL, respectively (p=0.936). No patients were reintubated due to postoperative bleeding within 24 hours and one patient in the high dose group returned to the OR for re-exploration for postoperative bleeding. Lastly, the median time to extubation of low, medium, and high dose groups was 226, 188, and 351 minutes, respectively (p=0.052).
CONCLUSION: This is the first study evaluating association of protamine-to-heparin dosing ratios with bleeding outcomes in otherwise healthy patients undergoing initial, elective CPB-assisted cardiac surgery. Despite the small sample size, there was a trend in increased post-operative 24-hour chest tube output as the protamine-to-heparin ratio increased. Although time to extubation did not statistically differ between groups, the greater time to extubation experienced by the high dose protamine group presents a clinically interesting finding for further exploration.
