Angela Jerath1,2, Qi Joy Yang3, K Sandy Pang3, Nikita Looby4, Nathaly Reyes-Garces4, Tijana Vasiljevic4, Barbara Bojko4, Janusz Pawliszyn4, Duminda Wijeysundera1,2, W Scott Beattie1,2, Terrence M Yau5, Marcin Wąsowicz1,2. 1. From the Department of Anaesthesia and Pain Medicine, Toronto General Hospital University Health Network, Toronto, Ontario, Canada. 2. Department of Anaesthesia, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada. 3. Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada. 4. Department of Chemistry, University of Waterloo, Waterloo, Ontario, Canada. 5. Division of Cardiovascular Surgery, Toronto General Hospital University Health Network, Toronto, Ontario, Canada.
Abstract
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.
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.
Authors: Jean Wong; Ronald B George; Ciara M Hanley; Chadi Saliba; Doreen A Yee; Angela Jerath Journal: Can J Anaesth Date: 2021-05-15 Impact factor: 5.063
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Authors: Tobias Kammerer; Philipp Groene; Sophia R Sappel; Sven Peterss; Paula A Sa; Thomas Saller; Andreas Giebl; Patrick Scheiermann; Christian Hagl; Simon Thomas Schäfer Journal: Transfus Med Hemother Date: 2020-11-09 Impact factor: 3.747