• Erik R Strauss, Shuhui Li, Reney Henderson, Ross Carpenter, Dong Guo, Kiruphagaran Thangaraju, Upendra Katneni, Paul W Buehler, GobburuJogarao V SJVSDepartment of Pharmacy Practice and Science, Center for Translational Medicine, University of Maryland School of Pharmacy, Baltimore, MD., and Kenichi A Tanaka.
• Division of Cardiovascular Anesthesia, Department of Anesthesiology, University of Maryland School of Medicine, Baltimore, MD. Electronic address: estrauss@som.umaryland.edu.
• J. Cardiothorac. Vasc. Anesth. 2022 Aug 1; 36 (8 Pt A): 2473-2482.

ObjectivesTo examine the pharmacokinetics (PK) and pharmacodynamics of a tranexamic (TXA) regimen designed for cardiac surgery with cardiopulmonary bypass (CPB).DesignA pilot study quantifying TXA concentrations, fibrinolysis markers, and a plasmin- generation (PG) assay. For comparison, PG assay was performed on pooled normal plasma (PNP) with varying TXA concentrations.SettingA single-center, tertiary, academic medical center.ParticipantsTwenty patients undergoing cardiac surgery with CPB for valve surgery and/or coronary artery bypass grafting.InterventionTXA 100 mg/h infusion for 5 hours starting before incision; 1 g TXA in CPB prime and 1 g TXA at CPB end prior to heparin reversal.Measurements And Main ResultsThe PK fit a 2-compartment disposition model. TXA concentrations were above 15 mg/L in all patients during CPB through 2 hours post-TXA infusion. During and after CPB, the TXA regimen decreased the median peak PG by 60% (95% confidence interval [CI], 56%-62%). Lowest median peak PG occurred 15 minutes postprotamine. Peak median D-dimer level of 1.24 (0.95-1.71; 95% CI) mg/L occurred at 15 minutes postprotamine and baseline-adjusted ΔD dimer correlated with increased CPB time (p = 0.004) and lower TXA level (p = 0.001). The median 24-hour chest tube output was 447 (330-664; 95% CI) mL. PG assay on PNP revealed a plateau inhibition at 5 mM TXA (786 mg/L).ConclusionsThis regimen, with total perioperative dose of 2.5 grams, provided TXA concentrations above 15 mg/L for all patients from CPB initiation through 2 hours post-TXA. PG was significantly inhibited (p < 0.0001) during and after CPB, with maximum inhibition measured at 15 minutes after protamine administration.Copyright © 2021 Elsevier Inc. All rights reserved.

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