Safety of intravenous tranexamic acid in patients undergoing supratentorial meningiomas resection: protocol for a randomised, parallel-group, placebo control, non-inferiority trial

Shu Li, Xiang Yan, Ruowen Li, Xingyue Zhang, Tingting Ma, Min Zeng, Jia Dong, Juan Wang, Xiaoyuan Liu, Yuming Peng, Shu Li, Xiang Yan, Ruowen Li, Xingyue Zhang, Tingting Ma, Min Zeng, Jia Dong, Juan Wang, Xiaoyuan Liu, Yuming Peng

Abstract

Introduction: Growing evidence recommends antifibrinolytic agent tranexamic acid (TXA) to reduce blood loss and transfusions rate in various surgical settings. However, postoperative seizure, as one of the major adverse effects of TXA infusion, has been a concern that restricts its utility in neurosurgery.

Methods and analysis: This is a randomised, placebo-controlled, non-inferiority trial. Patients with supratentorial meningiomas and deemed suitable for surgical resection will be recruited in the trial. Patients will be randomised to receive either a single administration of 20 mg/kg TXA or a placebo of the same volume with a 1:1 allocation ratio after anaesthesia induction. The primary endpoint is the cumulative incidence of early postoperative seizures within 7 days after craniotomy. Secondary outcomes include the incidence of non-seizure complications, changes of haemoglobin level from baseline, intraoperative blood loss, erythrocyte transfusion volume, Karnofsky Performance Status, all-cause mortality, and length of stay, and total hospitalisation cost.

Ethics and dissemination: This trial is registered at ClinicalTrial.gov and approved by the Chinese Ethics Committee of Registering Clinical Trials (ChiECRCT20200224). The findings will be disseminated in peer-reviewed journals and presented at national or international conferences relevant to subject fields.

Trial registration number: NCT04595786.

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

Conflict of interest statement

Competing interests: None declared.

© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
Consolidated Standards of Reporting Trials flow diagram. EPS, early postoperative seizure; KPS, Karnofsky Performance Status; TXA, tranexamic acid.

References

    1. Walsh KM. Epidemiology of meningiomas. Handb Clin Neurol 2020;169:3–15. 10.1016/B978-0-12-804280-9.00001-9
    1. Buerki RA, Horbinski CM, Kruser T, et al. . An overview of meningiomas. Future Oncol 2018;14:2161–77. 10.2217/fon-2018-0006
    1. Hooda B, Chouhan RS, Rath GP, et al. . Effect of tranexamic acid on intraoperative blood loss and transfusion requirements in patients undergoing excision of intracranial meningioma. J Clin Neurosci 2017;41:132–8. 10.1016/j.jocn.2017.02.053
    1. Brandel MG, Rennert RC, Wali AR, et al. . Impact of preoperative endovascular embolization on immediate meningioma resection outcomes. Neurosurg Focus 2018;44:E6. 10.3171/2018.1.FOCUS17751
    1. Alan N, Seicean A, Seicean S, et al. . Impact of preoperative anemia on outcomes in patients undergoing elective cranial surgery. J Neurosurg 2014;120:764–72. 10.3171/2013.10.JNS131028
    1. Rajagopalan V, Chouhan RS, Pandia MP, et al. . Effect of intraoperative blood loss on perioperative complications and neurological outcome in adult patients undergoing elective brain tumor surgery. J Neurosci Rural Pract 2019;10:631–40. 10.1055/s-0039-3399487
    1. Levy JH, Koster A, Quinones QJ, et al. . Antifibrinolytic therapy and perioperative considerations. Anesthesiology 2018;128:657–70. 10.1097/ALN.0000000000001997
    1. Mebel D, Akagami R, Flexman AM. Use of tranexamic acid is associated with reduced blood product transfusion in complex skull base neurosurgical procedures: a retrospective cohort study. Anesth Analg 2016;122:503–8. 10.1213/ANE.0000000000001065
    1. Vel R, Udupi BP, Satya Prakash MVS, et al. . Effect of low dose tranexamic acid on intra-operative blood loss in neurosurgical patients. Saudi J Anaesth 2015;9:42–8. 10.4103/1658-354X.146304
    1. Goobie SM, Staffa SJ, Meara JG, et al. . High-Dose versus low-dose tranexamic acid for paediatric craniosynostosis surgery: a double-blind randomised controlled non-inferiority trial. Br J Anaesth 2020;125:336–45. 10.1016/j.bja.2020.05.054
    1. Zhao Y, Xi C, Xu W, et al. . Role of tranexamic acid in blood loss control and blood transfusion management of patients undergoing multilevel spine surgery: a meta-analysis. Medicine 2021;100:e24678. 10.1097/MD.0000000000024678
    1. Almuwallad A, Cole E, Ross J, et al. . The impact of prehospital TXA on mortality among bleeding trauma patients: a systematic review and meta-analysis. J Trauma Acute Care Surg 2021;90:901–7. 10.1097/TA.0000000000003120
    1. Hemapriya L, More G, Kumar A. Efficacy of tranexamic acid in reducing blood loss in lower segment Cesearean section: a randomised controlled study. J Obstet Gynaecol India 2020;70:479–84. 10.1007/s13224-020-01351-3
    1. Nikolaou VS, Masouros P, Floros T, et al. . Single dose of tranexamic acid effectively reduces blood loss and transfusion rates in elderly patients undergoing surgery for hip fracture: a randomized controlled trial. Bone Joint J 2021;103-B:442–8. 10.1302/0301-620X.103B3.BJJ-2020-1288.R1
    1. Lecker I, Wang D-S, Whissell PD, et al. . Tranexamic acid-associated seizures: causes and treatment. Ann Neurol 2016;79:18–26. 10.1002/ana.24558
    1. Lecker I, Wang D-S, Kaneshwaran K, et al. . High concentrations of tranexamic acid inhibit ionotropic glutamate receptors. Anesthesiology 2017;127:89–97. 10.1097/ALN.0000000000001665
    1. Furtmüller R, Schlag MG, Berger M, et al. . Tranexamic acid, a widely used antifibrinolytic agent, causes convulsions by a gamma-aminobutyric acid(A) receptor antagonistic effect. J Pharmacol Exp Ther 2002;301:168–73. 10.1124/jpet.301.1.168
    1. Schwinn DA, Mackensen GB, Brown EN. Understanding the TXA seizure connection. J Clin Invest 2012;122:4339–41. 10.1172/JCI66724
    1. Li X, Wang C, Lin Z, et al. . Risk factors and control of seizures in 778 Chinese patients undergoing initial resection of supratentorial meningiomas. Neurosurg Rev 2020;43:597–608. 10.1007/s10143-019-01085-5
    1. Wirsching H-G, Morel C, Gmür C, et al. . Predicting outcome of epilepsy after meningioma resection. Neuro Oncol 2016;18:1002–10. 10.1093/neuonc/nov303
    1. Ersoy TF, Ridwan S, Grote A, et al. . Early postoperative seizures (EPS) in patients undergoing brain tumour surgery. Sci Rep 2020;10:13674. 10.1038/s41598-020-70754-z
    1. Chen WC, Magill ST, Englot DJ, et al. . Factors associated with pre- and postoperative seizures in 1033 patients undergoing supratentorial meningioma resection. Neurosurgery 2017;81:297–306. 10.1093/neuros/nyx001
    1. Lu VM, Wahood W, Akinduro OO, et al. . Four independent predictors of postoperative seizures after meningioma surgery: a meta-analysis. World Neurosurg 2019;130:537–45. 10.1016/j.wneu.2019.06.063
    1. Houston BL, Uminski K, Mutter T, et al. . Efficacy and safety of tranexamic acid in major non-cardiac surgeries at high risk for transfusion: a systematic review and meta-analysis. Transfus Med Rev 2020;34:51–62. 10.1016/j.tmrv.2019.10.001
    1. Yates J, Perelman I, Khair S, et al. . Exclusion criteria and adverse events in perioperative trials of tranexamic acid: a systematic review and meta-analysis. Transfusion 2019;59:806–24. 10.1111/trf.15030
    1. Dadure C, Sauter M, Bringuier S, et al. . Intraoperative tranexamic acid reduces blood transfusion in children undergoing craniosynostosis surgery: a randomized double-blind study. Anesthesiology 2011;114:856–61. 10.1097/ALN.0b013e318210f9e3
    1. Chan A-W, Tetzlaff JM, Altman DG, et al. . Spirit 2013 statement: defining standard protocol items for clinical trials. Ann Intern Med 2013;158:200–7. 10.7326/0003-4819-158-3-201302050-00583
    1. Stevens PE, Levin A, Kidney Disease: Improving Global Outcomes Chronic Kidney Disease Guideline Development Work Group Members . Evaluation and management of chronic kidney disease: synopsis of the kidney disease: improving global outcomes 2012 clinical practice guideline. Ann Intern Med 2013;158:825–30. 10.7326/0003-4819-158-11-201306040-00007
    1. Klein AA, Bailey CR, Charlton AJ, et al. . Association of anaesthetists guidelines: cell salvage for peri-operative blood conservation 2018. Anaesthesia 2018;73:1141–50. 10.1111/anae.14331
    1. Mueller MM, Van Remoortel H, Meybohm P, et al. . Patient blood management: recommendations from the 2018 Frankfurt consensus conference. JAMA 2019;321:983–97. 10.1001/jama.2019.0554
    1. NICE . Blood transfusion guideline. [18 Nov 2015], 2015. Available: [Accessed 27 Jan 2021].
    1. Fisher RS, Cross JH, D'Souza C, et al. . Instruction manual for the ILAE 2017 operational classification of seizure types. Epilepsia 2017;58:531–42. 10.1111/epi.13671
    1. Swanson TH, Garrett PJB, Burdette LJ, et al. . Outcome of patients with early postoperative seizures following anterior temporal lobectomy. J Epilepsy 1991;4:199–203. 10.1016/0896-6974(91)90076-U
    1. Mauro AM, Bomprezzi C, Morresi S, et al. . Prevention of early postoperative seizures in patients with primary brain tumors: preliminary experience with oxcarbazepine. J Neurooncol 2007;81:279–85. 10.1007/s11060-006-9229-7
    1. Simpson D. The recurrence of intracranial meningiomas after surgical treatment. J Neurol Neurosurg Psychiatry 1957;20:22–39. 10.1136/jnnp.20.1.22
    1. Fisher RS, Cross JH, French JA, et al. . Operational classification of seizure types by the International League against epilepsy: position paper of the ILAE Commission for classification and terminology. Epilepsia 2017;58:522–30. 10.1111/epi.13670
    1. Landriel Ibañez FA, Hem S, Ajler P, et al. . A new classification of complications in neurosurgery. World Neurosurg 2011;75:709–15. 10.1016/j.wneu.2010.11.010
    1. Jaramillo S, Montane-Muntane M, Gambus PL, et al. . Perioperative blood loss: estimation of blood volume loss or haemoglobin mass loss? Blood Transfus 2020;18:20–9. 10.2450/2019.0204-19
    1. Lin Z, Xiaoyi Z. Tranexamic acid-associated seizures: a meta-analysis. Seizure 2016;36:70–3. 10.1016/j.seizure.2016.02.011
    1. Zufferey PJ, Lanoiselée J, Graouch B, et al. . Exposure-Response relationship of tranexamic acid in cardiac surgery. Anesthesiology 2021;134:165–78. 10.1097/ALN.0000000000003633
    1. Heyns M, Knight P, Steve AK, et al. . A single preoperative dose of tranexamic acid reduces perioperative blood loss: a meta-analysis. Ann Surg 2021;273:75–81. 10.1097/SLA.0000000000003793
    1. Kurzwelly D, Herrlinger U, Simon M. Seizures in patients with low-grade gliomas--incidence, pathogenesis, surgical management, and pharmacotherapy. Adv Tech Stand Neurosurg 2010;35:81–111. 10.1007/978-3-211-99481-8_4
    1. Skardelly M, Rother C, Noell S, et al. . Risk factors of preoperative and early postoperative seizures in patients with meningioma: a retrospective single-center cohort study. World Neurosurg 2017;97:538–46. 10.1016/j.wneu.2016.10.062

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