Optimisation of the dosage of tranexamic acid in trauma patients with population pharmacokinetic analysis

Anaesthesia

Volumn 73, Issue 6, 2018, Pages 719-729

  Grassin Delyle, S ^a,b   Theusinger, O M ^c   Albrecht, R ^d   Mueller, S ^e   Spahn, D R ^f   Urien, S ^g,h   Stein, P ^d,f  

^a LABORATOIRE DES SCIENCES DU CLIMAT ET DE L ENVIRONNEMENT   (France)

^b FOCH HOSPITAL   (France)

^c UNIVERSITY HOSPITAL ZURICH   (Switzerland)

^d Rega Center   (Switzerland)

^e Schutz und Rettung Ambulance Service   (Switzerland)

^f UNIVERSITY HOSPITAL ZURICH   (Switzerland)

^g ASSISTANCE PUBLIQUE HÔPITAUX DE PARIS   (France)

^h UNIVERSITÉ PARIS DESCARTES   (France)

Author keywords

antifibrinolytic agents; pharmacokinetics; tranexamic acid; trauma

Indexed keywords

TRANEXAMIC ACID; ANTIFIBRINOLYTIC AGENT;

ADULT; AGED; ARTICLE; BODY WEIGHT; CENTRAL VOLUME OF DISTRIBUTION; COMPARTMENT MODEL; DRUG BLOOD LEVEL; DRUG EFFICACY; DRUG ELIMINATION; DRUG TOLERABILITY; EMERGENCY WARD; FEMALE; HUMAN; INJURY SEVERITY; LOADING DRUG DOSE; MAJOR CLINICAL STUDY; MALE; PENETRATING TRAUMA; PERIPHERAL VOLUME OF DISTRIBUTION; TRAUMATIC BRAIN INJURY; ADOLESCENT; CLINICAL TRIAL; DRUG ADMINISTRATION; EMERGENCY HEALTH SERVICE; INJURY; INJURY SCALE; MIDDLE AGED; MULTICENTER STUDY; PROSPECTIVE STUDY; VERY ELDERLY; YOUNG ADULT;

ADOLESCENT; ADULT; AGED; AGED, 80 AND OVER; ANTIFIBRINOLYTIC AGENTS; BRAIN INJURIES, TRAUMATIC; DRUG ADMINISTRATION SCHEDULE; EMERGENCY MEDICAL SERVICES; FEMALE; HUMANS; INJURY SEVERITY SCORE; MALE; MIDDLE AGED; PROSPECTIVE STUDIES; TRANEXAMIC ACID; WOUNDS AND INJURIES; YOUNG ADULT;

EID: 85041693813     PISSN: 00032409     EISSN: 13652044     Source Type: Journal    
DOI: 10.1111/anae.14184     Document Type: Article

References (49)

1. Rossaint R, Bouillon B, Cerny V, et al. The European guideline on management of major bleeding and coagulopathy following trauma: fourth edition. Critical Care (London, England) 2016; 20: 100.
2. Brohi K, Singh J, Heron M. Coats T. Acute traumatic coagulopathy. Journal of Trauma 2003; 54: 1127–30.
3. MacLeod JB, Lynn M, McKenney MG, Cohn SM, Murtha M. Early coagulopathy predicts mortality in trauma. Journal of Trauma 2003; 55: 39–44.
4. Schochl H, Voelckel W, Schlimp CJ. Management of traumatic haemorrhage – the European perspective. Anaesthesia 2015; 70(Suppl. 1): 102–7, e35-7.
5. Ker K, Kiriya J, Perel P, Edwards P, Shakur H. Roberts I Avoidable mortality from giving tranexamic acid to bleeding trauma patients: an estimation based on WHO mortality data, a systematic literature review and data from the CRASH-2 trial. BMC Emergency Medicine 2012; 12: 3.
6. Hijazi N, Abu Fanne R, Abramovitch R, et al. Endogenous plasminogen activators mediate progressive intracerebral hemorrhage after traumatic brain injury in mice. Blood 2015; 125: 2558–67.
7. Kashuk JL, Moore EE, Sawyer M, et al. Primary fibrinolysis is integral in the pathogenesis of the acute coagulopathy of trauma. Annals of Surgery 2010; 252: 434–42.
8. Cardenas JC, Matijevic N, Baer LA, Holcomb JB, Cotton BA, Wade CE. Elevated tissue plasminogen activator and reduced plasminogen activator inhibitor promote hyperfibrinolysis in trauma patients. Shock 2014; 41: 514–21.
9. Chapman MP, Moore EE, Moore HB, et al. Overwhelming tPA release, not PAI-1 degradation, is responsible for hyperfibrinolysis in severely injured trauma patients. Journal of Trauma and Acute Care Surgery 2016; 80: 16–23.
10. Theusinger OM, Wanner GA, Emmert MY, et al. Hyperfibrinolysis diagnosed by rotational thromboelastometry (ROTEM) is associated with higher mortality in patients with severe trauma. Anesthesia and Analgesia 2011; 113: 1003–12.
11. Ortmann E, Besser MW, Klein AA. Antifibrinolytic agents in current anaesthetic practice. British Journal of Anaesthesia 2013; 111: 549–63.
12. Stein P, Kaserer A, Sprengel K, et al. Change of transfusion and treatment paradigm in major trauma patients. Anaesthesia 2017; 72: 1317–26.
13. Crash-2 Collaborators IBS Effect of tranexamic acid in traumatic brain injury: a nested randomised, placebo controlled trial (CRASH-2 Intracranial Bleeding Study). British Medical Journal 2011; 343: d3795.
14. Ker K, Roberts I, Shakur H, Coats TJ. Antifibrinolytic drugs for acute traumatic injury. Cochrane Database of Systematic Reviews 2015; 5: CD004896.
15. Roberts I, Shakur H, Afolabi A, et al. The importance of early treatment with tranexamic acid in bleeding trauma patients: an exploratory analysis of the CRASH-2 randomised controlled trial. Lancet 2011; 377: 1096–101.
16. Roberts I, Edwards P, Prieto D, et al. Tranexamic acid in bleeding trauma patients: an exploration of benefits and harms. Trials 2017; 18: 48.
17. Hunt BJ. The current place of tranexamic acid in the management of bleeding. Anaesthesia 2015; 70(Suppl. 1): 50–3.
18. Morrison JJ, Dubose JJ, Rasmussen TE, Midwinter MJ. Military application of tranexamic acid in trauma emergency resuscitation (MATTERs) study. Archives of Surgery 2012; 147: 113–9.
19. Wafaisade A, Lefering R, Bouillon B, et al. Prehospital administration of tranexamic acid in trauma patients. Critical Care (London, England) 2016; 20: 143.
20. Ausset S, Glassberg E, Nadler R, et al. Tranexamic acid as part of remote damage-control resuscitation in the prehospital setting: a critical appraisal of the medical literature and available alternatives. Journal of Trauma and Acute Care Surgery 2015; 78: S70–5.
21. Dewan Y, Komolafe EO, Mejia-Mantilla JH, et al. CRASH-3 - tranexamic acid for the treatment of significant traumatic brain injury: study protocol for an international randomized, double-blind, placebo-controlled trial. Trials 2012; 13: 87.
22. Yutthakasemsunt S, Kittiwatanagul W, Piyavechvirat P, Thinkamrop B, Phuenpathom N, Lumbiganon P. Tranexamic acid for patients with traumatic brain injury: a randomized, double-blinded, placebo-controlled trial. BMC Emergency Medicine 2013; 13: 20.
23. Dowd NP, Karski JM, Cheng DC, et al. Pharmacokinetics of tranexamic acid during cardiopulmonary bypass. Anesthesiology 2002; 97: 390–9.
24. Grassin-Delyle S, Couturier R, Abe E, Alvarez JC, Devillier P, Urien S. A practical tranexamic acid dosing scheme based on population pharmacokinetics in children undergoing cardiac surgery. Anesthesiology 2013; 118: 853–62.
25. Grassin-Delyle S, Tremey B, Abe E, et al. Population pharmacokinetics of tranexamic acid in adults undergoing cardiac surgery with cardiopulmonary bypass. British Journal of Anaesthesia 2013; 111: 916–24.
26. Wesley MC, Pereira LM, Scharp LA, Emani SM, McGowan FX Jr, DiNardo JA. Pharmacokinetics of tranexamic acid in neonates, infants, and children undergoing cardiac surgery with cardiopulmonary bypass. Anesthesiology 2015; 122: 746–58.
27. Gertler R, Gruber M, Grassin-Delyle S, et al. Pharmacokinetics of tranexamic acid in neonates and infants undergoing cardiac surgery. British Journal of Clinical Pharmacology 2017; 83: 1745–57.
28. Fabresse N, Fall F, Etting I, Devillier P, Alvarez JC, Grassin-Delyle S. LC-MS/MS determination of tranexamic acid in human plasma after phospholipid clean-up. Journal of Pharmaceutical and Biomedical Analysis 2017; 141: 149–56.
29. Gehan EA, George SL. Estimation of human body surface area from height and weight. Cancer Chemotherapy Reports. Part 1 1970; 1: 225–35.
30. Brecher ME, Monk T, Goodnough LT. A standardized method for calculating blood loss. Transfusion 1997; 37: 1070–4.
31. Theusinger OM, Kind SL, Seifert B, Borgeat L, Gerber C, Spahn DR. Patient blood management in orthopaedic surgery: a four-year follow-up of transfusion requirements and blood loss from 2008 to 2011 at the Balgrist University Hospital in Zurich. Switzerland. Blood Transfusion. Trasfusione del Sangue 2014; 12: 195–203.
32. Kuhn E, Lavielle M. Maximum likelihood estimation in nonlinear mixed effects models. Computational Statistics and Data Analysis 2005; 49: 1020–38.
33. Andersson L, Nilsoon IM, Colleen S, Granstrand B, Melander B. Role of urokinase and tissue activator in sustaining bleeding and the management thereof with EACA and AMCA. Annals of the New York Academy of Sciences 1968; 146: 642–58.
34. Yee BE, Wissler RN, Zanghi CN, Feng C, Eaton MP. The effective concentration of tranexamic acid for inhibition of fibrinolysis in neonatal plasma in vitro. Anesthesia and Analgesia 2013; 117: 767–72.
35. Sigaut S, Tremey B, Ouattara A, et al. Comparison of two doses of tranexamic acid in adults undergoing cardiac surgery with cardiopulmonary bypass. Anesthesiology 2014; 120: 590–600.
36. Anderson BJ, Holford NH. Mechanism-based concepts of size and maturity in pharmacokinetics. Annual Review of Pharmacology and Toxicology 2008; 48: 303–32.
37. McCune JS, Bemer MJ, Barrett JS, Scott Baker K, Gamis AS, Holford NH. Busulfan in infant to adult hematopoietic cell transplant recipients: a population pharmacokinetic model for initial and Bayesian dose personalization. Clinical Cancer Research 2014; 20: 754–63.
38. Hoylaerts M, Lijnen HR, Collen D. Studies on the mechanism of the antifibrinolytic action of tranexamic acid. Biochimica et Biophysica Acta 1981; 673: 75–85.
39. Markus G, Priore RL, Wissler FC. The binding of tranexamic acid to native (Glu) and modified (Lys) human plasminogen and its effect on conformation. Journal of Biological Chemistry 1979; 254: 1211–6.
40. Syrovets T, Lunov O, Simmet T. Plasmin as a proinflammatory cell activator. Journal of Leukocyte Biology 2012; 92: 509–19.
41. Syrovets T, Jendrach M, Rohwedder A, Schule A, Simmet T. Plasmin-induced expression of cytokines and tissue factor in human monocytes involves AP-1 and IKKbeta-mediated NF-kappaB activation. Blood 2001; 97: 3941–50.
42. Soslau G, Horrow J, Brodsky I. Effect of tranexamic acid on platelet ADP during extracorporeal circulation. American Journal of Hematology 1991; 38: 113–9.
43. Stief TW. Tranexamic acid triggers thrombin generation. Hemostasis Laboratory 2009; 2: 73–82.
44. Lin Z, Xiaoyi Z. Tranexamic acid-associated seizures: a meta-analysis. Seizure 2016; 36: 70–3.
45. Gonzalez EA, Moore FA, Holcomb JB, et al. Fresh frozen plasma should be given earlier to patients requiring massive transfusion. Journal of Trauma 2007; 62: 112–9.
46. Kashuk JL, Moore EE, Johnson JL, et al. Postinjury life threatening coagulopathy: is 1:1 fresh frozen plasma:packed red blood cells the answer? Journal of Trauma 2008; 65: 261–70.
47. Bulutcu FS, Ozbek U, Polat B, Yalcin Y, Karaci AR, Bayindir O. Which may be effective to reduce blood loss after cardiac operations in cyanotic children: tranexamic acid, aprotinin or a combination? Pediatric Anesthesia 2005; 15: 41–6.
48. Reid RW, Zimmerman AA, Laussen PC, Mayer JE, Gorlin JB, Burrows FA. The efficacy of tranexamic acid versus placebo in decreasing blood loss in pediatric patients undergoing repeat cardiac surgery. Anesthesia and Analgesia 1997; 84: 990–6.
49. Schoemaker RC, Cohen AF. Estimating impossible curves using NONMEM. British Journal of Clinical Pharmacology 1996; 42: 283–90.