• Angela Jerath, Qi Joy Yang, K Sandy Pang, Nikita Looby, Nathaly Reyes-Garces, Tijana Vasiljevic, Barbara Bojko, Janusz Pawliszyn, Duminda Wijeysundera, W Scott Beattie, Terrence M Yau, and Marcin Wąsowicz.
• From the Department of Anaesthesia and Pain Medicine, Toronto General Hospital University Health Network, Toronto, Ontario, Canada.
• Anesth. Analg. 2018 Dec 1; 127 (6): 1323-1332.

BackgroundTranexamic 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.MethodsThis 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.ResultsTXA 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.ConclusionsUsing a pharmacokinetic model, we propose a simple new TXA dosing regimen that optimizes maximal antifibrinolysis and avoids excessive drug dosing.

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