Effect of tranexamic acid on the prognosis of patients with traumatic brain injury undergoing craniotomy: study protocol for a randomised controlled trial

Bei Wu, Yu Lu, Yun Yu, Hongli Yue, Jie Wang, Yingzi Chong, Weihua Cui, Bei Wu, Yu Lu, Yun Yu, Hongli Yue, Jie Wang, Yingzi Chong, Weihua Cui

Abstract

Introduction: Abnormal coagulation function aggravates the prognosis of patients with traumatic brain injury (TBI). It was reported that the antifibrinolytic drug tranexamic acid (TXA) could reduce intracranial haemorrhage and mortality in non-operative patients with TBI. However, there is a lack of evaluation of TXA in patients with TBI undergoing craniotomy.

Methods and analysis: This is a single-centre randomised controlled, double-blind, parallel study aiming to investigate the effectiveness and safety of TXA in patients with TBI during the perioperative period. Blood loss and transfusion, neurological function, adverse events, mortality and serum immune-inflammatory cytokines will be collected and analysed.

Ethics and dissemination: Ethical approval has been granted by the Medical Ethics Committee of Beijing Tian Tan Hospital, Capital Medical University (reference number KY 2020-136-03). The results of this study will be disseminated through presentations at scientific conferences and publication in peer-reviewed journals.

Trial registration number: ChiCTR2100041911.

Keywords: anaesthesia in neurology; bleeding disorders & coagulopathies; neurological injury; neurosurgery.

Conflict of interest statement

Competing interests: None declared.

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

References

    1. Talving P, Benfield R, Hadjizacharia P, et al. . Coagulopathy in severe traumatic brain injury: a prospective study. J Trauma 2009;66:55–62. 10.1097/TA.0b013e318190c3c0
    1. Abdelmalik PA, Boorman DW, Tracy J, et al. . Acute traumatic coagulopathy accompanying isolated traumatic brain injury is associated with worse long-term functional and cognitive outcomes. Neurocrit Care 2016;24:361–70. 10.1007/s12028-015-0191-0
    1. Frontera JA, Lewin JJ, Rabinstein AA, et al. . Guideline for reversal of antithrombotics in intracranial hemorrhage: a statement for healthcare professionals from the neurocritical care Society and society of critical care medicine. Neurocrit Care 2016;24:6–46. 10.1007/s12028-015-0222-x
    1. de Oliveira Manoel AL, Neto AC, Veigas PV, et al. . Traumatic brain injury associated coagulopathy. Neurocrit Care 2015;22:34–44. 10.1007/s12028-014-0026-4
    1. Albert V, Arulselvi S, Agrawal D, et al. . Early posttraumatic changes in coagulation and fibrinolysis systems in isolated severe traumatic brain injury patients and its influence on immediate outcome. Hematol Oncol Stem Cell Ther 2019;12:32–43. 10.1016/j.hemonc.2018.09.005
    1. Ker K, Roberts I, Shakur H. Antifibrinolytic drugs for acute traumatic injury. Cochrane Database Syst Rev 2015;5:CD004896. 10.1002/14651858.CD004896.pub4
    1. CRASH-2 collaborators, Roberts I, Shakur H, 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:e1–2. 10.1016/S0140-6736(11)60278-X
    1. CRASH-2 trial collaborators, Shakur H, Roberts I, et al. . Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a randomised, placebo-controlled trial. Lancet 2010;376:23–32. 10.1016/S0140-6736(10)60835-5
    1. Yokobori S, Yatabe T, Kondo Y, et al. . Efficacy and safety of tranexamic acid administration in traumatic brain injury patients: a systematic review and meta-analysis. J Intensive Care 2020;8:46. 10.1186/s40560-020-00460-5
    1. Perel P, Al-Shahi Salman R, Kawahara T, et al. . CRASH-2 (Clinical Randomisation of an Antifibrinolytic in Significant Haemorrhage) intracranial bleeding study: the effect of tranexamic acid in traumatic brain injury--a nested randomised, placebo-controlled trial. Health Technol Assess 2012;16:1–54. 10.3310/hta16130
    1. Yutthakasemsunt S, Kittiwatanagul W, Piyavechvirat P, et al. . Tranexamic acid for patients with traumatic brain injury: a randomized, double-blinded, placebo-controlled trial. BMC Emerg Med 2013;13:20. 10.1186/1471-227X-13-20
    1. CRASH-3 trial collaborators . Effects of tranexamic acid on death, disability, vascular occlusive events and other morbidities in patients with acute traumatic brain injury (CRASH-3): a randomised, placebo-controlled trial. Lancet 2019;394:1713–23. 10.1016/S0140-6736(19)32233-0
    1. Maegele M, Schöchl H, Menovsky T, et al. . Coagulopathy and haemorrhagic progression in traumatic brain injury: advances in mechanisms, diagnosis, and management. Lancet Neurol 2017;16:630–47. 10.1016/S1474-4422(17)30197-7
    1. Kearney TJ, Bentt L, Grode M, et al. . Coagulopathy and catecholamines in severe head injury. J Trauma 1992;32:608–12. 10.1097/00005373-199205000-00012
    1. Carney N, Totten AM, O'Reilly C, et al. . Guidelines for the management of severe traumatic brain injury, fourth edition. Neurosurgery 2017;80:6–15. 10.1227/NEU.0000000000001432
    1. Abdelmalik PA, Draghic N, Ling GSF. Management of moderate and severe traumatic brain injury. Transfusion 2019;59:1529–38. 10.1111/trf.15171
    1. Capizzi A, Woo J, Verduzco-Gutierrez M. Traumatic brain injury: an overview of epidemiology, pathophysiology, and medical management. Med Clin North Am 2020;104:213–38. 10.1016/j.mcna.2019.11.001
    1. Seule M, Brunner T, Mack A, et al. . Neurosurgical and intensive care management of traumatic brain injury. Facial Plast Surg 2015;31:325–31. 10.1055/s-0035-1562884
    1. Galgano M, Toshkezi G, Qiu X, et al. . Traumatic brain injury: current treatment strategies and future Endeavors. Cell Transplant 2017;26:1118–30. 10.1177/0963689717714102
    1. Yeatts SD, Martin RH, Meurer W, et al. . Sliding scoring of the Glasgow outcome Scale-Extended as primary outcome in traumatic brain injury trials. J Neurotrauma 2020;37:2674–9. 10.1089/neu.2019.6969
    1. Nichol AD, Higgins AM, Gabbe BJ, et al. . Measuring functional and quality of life outcomes following major head injury: common scales and checklists. Injury 2011;42:281–7. 10.1016/j.injury.2010.11.047
    1. Bagiella E, Novack TA, Ansel B, et al. . Measuring outcome in traumatic brain injury treatment trials: recommendations from the traumatic brain injury clinical trials network. J Head Trauma Rehabil 2010;25:375–82. 10.1097/HTR.0b013e3181d27fe3
    1. Ardolino A, Sleat G, Willett K. Outcome measurements in major trauma--results of a consensus meeting. Injury 2012;43:1662–6. 10.1016/j.injury.2012.05.008
    1. McMillan T, Wilson L, Ponsford J, et al. . The Glasgow Outcome Scale - 40 years of application and refinement. Nat Rev Neurol 2016;12:477–85. 10.1038/nrneurol.2016.89
    1. Jaramillo S, Montane-Muntane M, Capitan D, et al. . Agreement of surgical blood loss estimation methods. Transfusion 2019;59:508–15. 10.1111/trf.15052
    1. Sattin D, Minati L, Rossi D, et al. . The coma recovery scale modified score: a new scoring system for the coma recovery Scale-revised for assessment of patients with disorders of consciousness. Int J Rehabil Res 2015;38:350–6. 10.1097/MRR.0000000000000135
    1. Bodien YG, Carlowicz CA, Chatelle C, et al. . Sensitivity and Specificity of the Coma Recovery Scale--Revised Total Score in Detection of Conscious Awareness. Arch Phys Med Rehabil 2016;97:490–2. 10.1016/j.apmr.2015.08.422
    1. Barthélemy EJ, Melis M, Gordon E, et al. . Decompressive craniectomy for severe traumatic brain injury: a systematic review. World Neurosurg 2016;88:411–20. 10.1016/j.wneu.2015.12.044
    1. Bonow RH, Barber J, Temkin NR, et al. . The outcome of severe traumatic brain injury in Latin America. World Neurosurg 2018;111:e82–90. 10.1016/j.wneu.2017.11.171
    1. Cooper DJ, Rosenfeld JV, Murray L, et al. . Patient outcomes at twelve months after early decompressive craniectomy for diffuse traumatic brain injury in the randomized DECRA clinical trial. J Neurotrauma 2020;37:810–6. 10.1089/neu.2019.6869
    1. Hyder AA, Wunderlich CA, Puvanachandra P, et al. . The impact of traumatic brain injuries: a global perspective. NeuroRehabilitation 2007;22:341–53. 10.3233/NRE-2007-22502
    1. Epstein DS, Mitra B, O'Reilly G, et al. . Acute traumatic coagulopathy in the setting of isolated traumatic brain injury: a systematic review and meta-analysis. Injury 2014;45:819–24. 10.1016/j.injury.2014.01.011
    1. Brain Trauma Foundation, American Association of Neurological Surgeons, Congress of Neurological Surgeons, et al. . Guidelines for the management of severe traumatic brain injury. IX. cerebral perfusion thresholds. J Neurotrauma 2007;24 Suppl 1:S59–64. 10.1089/neu.2007.9987
    1. Nakae R, Takayama Y, Kuwamoto K, et al. . Time course of coagulation and fibrinolytic parameters in patients with traumatic brain injury. J Neurotrauma 2016;33:688–95. 10.1089/neu.2015.4039
    1. Wada T, Gando S, Maekaw K, et al. . Disseminated intravascular coagulation with increased fibrinolysis during the early phase of isolated traumatic brain injury. Crit Care 2017;21:219. 10.1186/s13054-017-1808-9
    1. Walker PF, Foster AD, Rothberg PA, et al. . Tranexamic acid decreases rodent hemorrhagic shock-induced inflammation with mixed end-organ effects. PLoS One 2018;13:e0208249. 10.1371/journal.pone.0208249
    1. Solomon C, Traintinger S, Ziegler B, et al. . Platelet function following trauma. A multiple electrode aggregometry study. Thromb Haemost 2011;106:322–30. 10.1160/TH11-03-0175
    1. Albert V, Subramanian A, Agrawal D, et al. . Acute traumatic Endotheliopathy in isolated severe brain injury and its impact on clinical outcome. Med Sci 2018;6. 10.3390/medsci6010005. [Epub ahead of print: 16 Jan 2018].
    1. Ziliotto N, Bernardi F, Jakimovski D, et al. . Coagulation pathways in neurological diseases: multiple sclerosis. Front Neurol 2019;10:409. 10.3389/fneur.2019.00409
    1. Singleton Q, Vaibhav K, Braun M, et al. . Bone marrow derived extracellular vesicles activate osteoclast differentiation in traumatic brain injury induced bone loss. Cells 2019;8. 10.3390/cells8010063. [Epub ahead of print: 17 01 2019].
    1. Wang D, Yang Y, He C, et al. . Effect of multiple doses of oral tranexamic acid on haemostasis and inflammatory reaction in total hip arthroplasty: a randomized controlled trial. Thromb Haemost 2019;119:092–103. 10.1055/s-0038-1676625
    1. Gando S, Sawamura A, Hayakawa M, Trauma HM. Trauma, shock, and disseminated intravascular coagulation: lessons from the classical literature. Ann Surg 2011;254:10–19. 10.1097/SLA.0b013e31821221b1
    1. Mazzeo AT, Kunene NK, Choi S, et al. . Quantitation of ischemic events after severe traumatic brain injury in humans: a simple scoring system. J Neurosurg Anesthesiol 2006;18:170–8. 10.1097/01.ana.0000210999.18033.f6
    1. Hulka F, Mullins RJ, Frank EH. Blunt brain injury activates the coagulation process. Arch Surg 1996;131:923–7. 10.1001/archsurg.1996.01430210021004
    1. Burke JF, Stulc JL, Skolarus LE, et al. . Traumatic brain injury may be an independent risk factor for stroke. Neurology 2013;81:33–9. 10.1212/WNL.0b013e318297eecf
    1. Baharoglu MI, Germans MR, Rinkel GJE, et al. . Antifibrinolytic therapy for aneurysmal subarachnoid haemorrhage. Cochrane Database Syst Rev 2013;8:CD001245. 10.1002/14651858.CD001245.pub2
    1. Kaufman HH, Hui KS, Mattson JC, et al. . Clinicopathological correlations of disseminated intravascular coagulation in patients with head injury. Neurosurgery 1984;15:34–42. 10.1227/00006123-198407000-00008
    1. Lawati KA, Sharif S, Maqbali SA, et al. . Efficacy and safety of tranexamic acid in acute traumatic brain injury: a systematic review and meta-analysis of randomized-controlled trials. Intensive Care Med 2021;47:14–27. 10.1007/s00134-020-06279-w

Source: PubMed

Sponsoren und Mitarbeiter

Krankheiten

Drogeninterventionen

3
Abonnieren