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Optimisation of the dosage of tranexamic acid in trauma patients with population pharmacokinetic analysis.
- Source :
-
Anaesthesia [Anaesthesia] 2018 Jun; Vol. 73 (6), pp. 719-729. Date of Electronic Publication: 2018 Feb 07. - Publication Year :
- 2018
-
Abstract
- Tranexamic acid is used both pre-hospital and in-hospital as an antifibrinolytic drug to treat or prevent hyperfibrinolysis in trauma patients; dosing, however, remains empirical. We aimed to measure plasma levels of tranexamic acid in patients receiving pre-hospital anti-hyperfibrinolytic therapy and to build a population pharmacokinetic model to propose an optimised dosing regimen. Seventy-three trauma patients were enrolled and each received tranexamic acid 1 g intravenously pre-hospital. A blood sample was drawn after arrival in the emergency department, and we measured the plasma tranexamic acid concentration using liquid chromatography-mass spectrometry, and modelled the data using non-linear mixed effect modelling. Tranexamic acid was administered at a median (IQR [range]) time of 43 (30-55 [5-135]) min after trauma. Plasma tranexamic acid levels were determined on arrival at hospital, 57 (43-70 [20-148]) min after pre-hospital administration of the drug. The measured concentration was 28.7 (21.5-38.5 [8.7-89.0]) μg.ml <superscript>-1</superscript> . Our subjects had sustained severe trauma; injury severity score 20 (16-29 [5-75]), including penetrating injury in 2.8% and isolated traumatic brain injury in 19.7%. The pharmacokinetics were ascribed a two-compartment open model with body-weight as the main covariate. As tranexamic acid concentrations may fall below therapeutic levels during initial hospital treatment, we propose additional dosing schemes to maintain a specific target blood concentration for as long as required. This is the first study to investigate plasma level and pharmacokinetics of tranexamic acid after pre-hospital administration in trauma patients. Our proposed dosing regimen could be used in subsequent clinical trials to better study efficacy and tolerance profiles with controlled blood concentrations.<br /> (© 2018 The Association of Anaesthetists of Great Britain and Ireland.)
- Subjects :
- Adolescent
Adult
Aged
Aged, 80 and over
Antifibrinolytic Agents adverse effects
Brain Injuries, Traumatic drug therapy
Drug Administration Schedule
Emergency Medical Services
Female
Humans
Injury Severity Score
Male
Middle Aged
Prospective Studies
Tranexamic Acid adverse effects
Young Adult
Antifibrinolytic Agents administration & dosage
Antifibrinolytic Agents pharmacokinetics
Tranexamic Acid administration & dosage
Tranexamic Acid pharmacokinetics
Wounds and Injuries drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1365-2044
- Volume :
- 73
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Anaesthesia
- Publication Type :
- Academic Journal
- Accession number :
- 29411358
- Full Text :
- https://doi.org/10.1111/anae.14184