A Pharmacokinetic and Pharmacodynamic Investigation of an ε-Aminocaproic Acid Regimen Designed for Cardiac Surgery With Cardiopulmonary Bypass
Journal of Cardiothoracic and Vascular Anesthesia
Antifibrinolytics; cardiac surgery; pharmacodynamics; pharmacokinetics; ε-aminocaproic acid
Objective: To investigate the pharmacokinetics and pharmacodynamics of an ε-aminocaproic acid (EACA) regimen designed for cardiac surgery with cardiopulmonary bypass (CPB). Design: Prospective observational study requiring blood sampling to measure EACA concentrations and fibrinolysis markers (fibrinogen, D-dimer, α2-antiplasmin, and tissue plasminogen activator-plasminogen activator inhibitor [tPA-PAI-1] complex). Setting: Single-center, tertiary medical center. Participants: Patients who underwent cardiac surgery with CPB between 2018 and 2019 for aortic or mitral valve replacement/repair or coronary artery bypass grafting. Previous sternotomy patients were included. Intervention: None. Measurements and Main Results: The pharmacokinetics of EACA, during CPB, were described by a 3-compartment disposition model. EACA concentrations were greater than 130 mg/L in all patients after CPB and in most patients during CPB. The D-dimer level trended up and reached a peak median level of 1.35 mg/L of fibrinogen equivalence units (FEU) at 15 minutes after protamine administration. The median change in D-dimer (ΔD-dimer) from baseline to 15 minutes after protamine was 0.34 (–0.48 to 3.81) mg/L FEU. ΔD-dimer did not correlate with EACA concentration intraoperatively, urine output, body weight, glomerular filtration rate, cell salvage volume, and ultrafiltration volume. The median 24-hour chest tube output was 445 (180-1,011) mL. Conclusion: This regimen provided maximum EACA concentrations near the time of protamine administration, with a total perioperative dose of 15 g. Most patients had EACA concentrations greater than the target during CPB. ΔD-dimer did not correlate with EACA concentration. The median 24-hour chest tube output compared well to similar studies that used higher doses of EACA.
Strauss, E., Dahmane, E., Judd, M., Guo, D., Williams, B., Meyer, M., Gammie, J., Taylor, B., Mazzeffi, M., Gobburu, J., & Tanaka, K. (2021). A Pharmacokinetic and Pharmacodynamic Investigation of an ε-Aminocaproic Acid Regimen Designed for Cardiac Surgery With Cardiopulmonary Bypass. Journal of Cardiothoracic and Vascular Anesthesia, 35 (2). http://dx.doi.org/10.1053/j.jvca.2020.07.048