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Tranexamic Acid Dosing for Cardiac Surgical Patients With Chronic Renal Dysfunction

A New Dosing Regimen

Jerath, Angela, FRCPC, FANZCA, MBBS, BSc*,†; Yang, Qi Joy, MSc; Pang, K. Sandy, PhD; Looby, Nikita, MSc§; Reyes-Garces, Nathaly, MSc§; Vasiljevic, Tijana, BSc§; Bojko, Barbara, PhD§; Pawliszyn, Janusz, PhD§; Wijeysundera, Duminda, PhD, FRCPC*,†; Beattie, W. Scott, PhD, FRCPC*,†; Yau, Terrence M., PhD, FRCSC, MD, MSc, BA; Wąsowicz, Marcin, FRCPC, PhD, MD*,†

doi: 10.1213/ANE.0000000000002724
Hemostasis and Thrombosis: Original Clinical Research Report
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BACKGROUND: Tranexamic acid (TXA) is a common antifibrinolytic agent used to minimize bleeding in cardiac surgery. Up to 50% cardiac surgical patients have chronic renal dysfunction (CRD). Optimal dosing of TXA in CRD remains poorly investigated. This is important as TXA is renally eliminated with accumulation in CRD. High TXA doses are associated with postoperative seizures. This study measures plasma TXA concentrations in CRD cardiac surgical patients for pharmacokinetic modeling and dose adjustment recommendations.

METHODS: This prospective cohort study enrolled 48 patients with stages 1–5 CRD, classified by Kidney Disease Outcome Quality Initiative. Patients were separated into 2 treatment groups. A “low-risk” group underwent simple aortocoronary bypass or single-valve repair/replacement and received a 50 mg/kg TXA bolus. A “high-risk” group underwent redo, aortic, multiple valve or combination surgery and received the Blood Conservation Using Anti-fibrinolytics Trial dosing regimen (loading dose 30 mg/kg, infusion 16 mg/kg/h with 2 mg/kg in pump prime). Primary outcome identified changes in TXA clearance and distribution volume, which provided the rationale for dose adjustment. Descriptive clinical outcomes assessed postoperative seizures, blood loss, ischemic-thrombotic complications, in-hospital mortality, and length of hospital stay.

RESULTS: TXA concentrations were elevated and sustained above the therapeutic threshold for approximately 12 hours in high-risk stages 3–5 groups, in accordance to CRD severity.

CONCLUSIONS: Using a pharmacokinetic model, we propose a simple new TXA dosing regimen that optimizes maximal antifibrinolysis and avoids excessive drug dosing.

From the *Department of Anaesthesia and Pain Medicine, Toronto General Hospital University Health Network, Toronto, Ontario, Canada

Department of Anaesthesia, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada

Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada

§Department of Chemistry, University of Waterloo, Waterloo, Ontario, Canada

Division of Cardiovascular Surgery, Toronto General Hospital University Health Network, Toronto, Ontario, Canada.

Published ahead of print 26 October 2017.

Accepted for publication October 26, 2017.

Funding: This study was supported by Heart and Stroke Foundation of Canada, Merit Award, Department of Anaesthesia, University of Toronto, and Natural Sciences and Engineering Research Council of Canada. The sponsors aided funding of the study and were not involved in the study conduct, analysis, or data interpretation.

The authors declare no conflicts of interest.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website.

Study Registration: ClinicalTrials.gov, NCT01609686.

The study concept was derived by A.J. and M.W. The study was designed by all authors. Tranexamic acid concentration measurement was performed by N.L., N.R.G., T.V., B.B., and J.P. Statistical analysis was conducted by A.J. Pharmacokinetic analysis was conducted by Q.J.Y. and K.S.P. All authors contributed to the study manuscript.

Reprints will not be available from the authors.

Address correspondence to Angela Jerath, FRCPC, FANZCA, MBBS, BSc, Department of Anaesthesia and Pain Medicine, Toronto General Hospital University Health Network, Toronto, Ontario M5G 2C4, Canada. Address e-mail to Angela.Jerath@uhn.ca.

© 2018 International Anesthesia Research Society
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