Comparing Two Tranexamic Acid Dosing Regimens for Blood Loss Reduction in Supratentorial Brain Tumor Surgery: A Multicenter, Double-Blind, Randomized Trial
-
Sohrab Salimi
,
Sara Salarian
,
Noor Mohammad Arefian
,
Hamidreza Khayat Kashani
,
Niloofar Abdous
,
Dariush Abtahi
Abstract
Background: The optimal dosing regimen of tranexamic acid (TXA) for minimizing blood loss during supratentorial brain tumor resection remains undefined. This study compared two dosing protocols to evaluate efficacy and safety.
Methods: In this double-blind, randomized trial (September 2020–September 2021), 60 patients aged 18–60 years undergoing supratentorial tumor surgery were allocated to receive either TXA1 (20 mg/kg bolus + 1 mg/kg/h infusion) or TXA3 (20 mg/kg bolus + 3 mg/kg/h infusion). Primary outcomes included intraoperative blood loss; secondary outcomes encompassed transfusion needs, surgical duration, hospitalization length, and thromboembolic complications.
Results: The TXA3 group demonstrated an 18% reduction in mean intraoperative blood loss compared to TXA1 (402.93 mL vs. 470.61 mL; mean difference −67.68 mL, 95% CI −139.4 to 3.9; p = 0.053). Transfusion requirements were lower in the TXA3 cohort (0.43 ± 0.9 vs. 0.64 ± 1.2 units; p = 0.34), though not statistically significant. Surgical duration was prolonged in the TXA3 group (p = 0.047), but hospitalization was shorter (p = 0.049). Thromboembolic event rates were comparable between groups (p > 0.05).
Conclusion: Higher intraoperative TXA infusion rates were associated with reduced blood loss and shorter hospital stays without elevating thromboembolic risk. These findings support TXA’s utility in improving perioperative outcomes and resource efficiency for supratentorial tumor resection.
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[3] Hoz SS, Al-Jehani H, Al-Sharshahi ZF, Matti WE, Al-Dhahir MA, Kadhum HJ. Supratentorial brain tumors: Are there indications for urgent resection? Surg Neurol Int. 2021; 12:194.
[4] Wang C, Li P. Risk factors for intraoperative blood loss in resection of intracranial meningioma: Analysis of 530 cases. PLoS One. 2023;18(9):e0291171.
[5] Delawan M, Sharma M, Ismail M, Algabri MH, Abdalridha RH, Alawadi MN, et al. Methods of Hemostasis in Cranial Neurosurgery: An Anatomy-Based Stepwise Review. World Neurosurg. 2023; 178:241-259.e3.
[6] Cai J, Ribkoff J, Olson S, Raghunathan V, Al-Samkari H, DeLoughery TG, Shatzel JJ. The many roles of tranexamic acid: An overview of the clinical indications for TXA in medical and surgical patients. Eur J Haematol. 2020; 104(2):79-87.
[7] Tranexamic acid: uses, interactions, mechanism of action | DrugBank Online [Internet]. [cited 2024 Dec 27]. Available from: https://go.drugbank.com/drugs/DB00302
[8] Perel P, Al-Shahi Salman R, Kawahara T, Morris Z, Prieto-Merino D, Roberts I, 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(13):iii-xii, 1-54.
[9] Delawan M, Sharma M, Ismail M, Algabri MH, Abdalridha RH, Alawadi MN, et al. Methods of Hemostasis in Cranial Neurosurgery: An Anatomy-Based Stepwise Review. World Neurosurg. 2023; 178:241-259.e3.
[10] Nguyen A, Brown NJ, Gendreau J, Nguyen BA, Pennington Z, Zhang A, et al. The association of thromboembolic complications and the use of tranexamic acid during resection of intracranial meningiomas: systematic review and meta-analysis of randomized controlled trials. J Neurosurg. 2023; 140(4):1008-1018.
[11] Mullin JP, Soliman MAR, Smith JS, Kelly MP, Buell TJ, Diebo B, et al. Analysis of tranexamic acid usage in adult spinal deformity patients with relative contraindications: does it increase the risk of complications? J Neurosurg Spine. 2024; 40(6):684-691
[12] Yoo JS, Ahn J, Karmarkar SS, Lamoutte EH, Singh K. The use of tranexamic acid in spine surgery. Ann Transl Med. 2019; 7(Suppl 5):S172.
[13] O’Donnell DB, Vazquez S, Greisman JD, Uddin A, Graifman G, Dominguez JF, et al. Tranexamic Acid Dosing in Craniosynostosis Surgery: A Systematic Review with Meta-analysis. Plast Reconstr Surg Glob Open. 2022; 10(10):e4526.
[14] Shafique N, Akbar UA, Umer AM, Kumar B, Muhibullah F, Siddiqui F, et al. Tranexamic Acid for Trauma Care: An Updated Meta-Analysis of Mortality and Thromboembolic Events in Severely Injured Patients. Blood. 2023;142(Supplement 1):5570–5570.
[15] Fouche PF, Stein C, Nichols M, Meadley B, Bendall JC, Smith K, et al. Tranexamic Acid for Traumatic Injury in the Emergency Setting: A Systematic Review and Bias-Adjusted Meta-Analysis of Randomized Controlled Trials. Ann Emerg Med. 2024;83(5):435–45.
[16] Chauhan MS, Mahmood ST, Chaterjii G, Shakya M, Pal V, Siddhartha P V. Role of Tranexamic Acid in Controlling Blood Loss in Total Hip Arthroplasty. Int J Curr Pharm Res. 2024;84–7.
[17] Vychopen M, Arlt F, Güresir E, Wach J. Intraoperative tranexamic acid administration in cranial meningioma surgery: a meta-analysis of prospective randomized, double-blinded, and placebo-controlled trials. Front Oncol. 2024; 14:1464671.
[18] Khalid A, Nazir U, Raza N, Aslam S, Majeed MN, Hassan Z, et al. A Comparison of the Use of Tranexamic Acid versus Placebo in Patients Undergoing Excision of Intracranial Meningioma. Pakistan J Neurological Surgery. 2022; 26(4):654–66.
[19] Hollingworth M, Woodhouse LJ, Law ZK, Ali A, Krishnan K, Dineen RA, et al. The Effect of Tranexamic Acid on Neurosurgical Intervention in Spontaneous Intracerebral Hematoma: Data from 121 Surgically Treated Participants from the Tranexamic Acid in IntraCerebral Hemorrhage-2 Randomized Controlled Trial. Neurosurgery. 2024;95(3):605–16.
[20] Luo H, Zhang X, Xie C, Wu L, Cai G, Ren Y. Efficacy and safety of topical tranexamic acid in spinal surgery: a systematic review and meta-analysis. EFORT Open Rev. 2024;9(8):796–805.
[21] Stejskal P, Trnka, Hrabálek L, Wanek T, Jablonský J, Novák V. Effects of Tranexamic Acid on Perioperative Blood Loss and Wound Hematoma Development in Lumbar Spine Surgery: a Prospective Randomized Study. Acta Chir Orthop Traumatol Cech. 2023;90(3):176–80.
[22] de Faria JL, da Silva Brito J, Costa e Silva LT, Kilesse CTSM, de Souza NB, Pereira CU, et al. Tranexamic acid in Neurosurgery: a controversy indication—review. Neurosurg Rev. 2021; 44(3):1287–98.
[23] Roberts I, Shakur-Still H, Aeron-Thomas A, Belli A, Brenner A, Chaudary MA, et al. 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(10210):1713–23.
[24] Chakroun-Walha O, Samet A, Jerbi M, Nasri A, Talbi A, Kanoun H, et al. Benefits of the tranexamic acid in head trauma with no extracranial bleeding: a prospective follow-up of 180 patients. Eur J Trauma Emerg Surg. 2019; 45(4):719–26.
[25] 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 Emerg Med. 2013;13(1):20.
[2] Vandse R, Lien D, Pillai P. Management of patient with supratentorial tumor. In: Problem based learning discussions in neuroanesthesia and neurocritical care [Internet]. 2020 Mar 10 [cited 2024 Dec 27];209–34. Available from: https://link.springer.com/chapter/10.1007/978-981-15-0458-7_17
[3] Hoz SS, Al-Jehani H, Al-Sharshahi ZF, Matti WE, Al-Dhahir MA, Kadhum HJ. Supratentorial brain tumors: Are there indications for urgent resection? Surg Neurol Int. 2021; 12:194.
[4] Wang C, Li P. Risk factors for intraoperative blood loss in resection of intracranial meningioma: Analysis of 530 cases. PLoS One. 2023;18(9):e0291171.
[5] Delawan M, Sharma M, Ismail M, Algabri MH, Abdalridha RH, Alawadi MN, et al. Methods of Hemostasis in Cranial Neurosurgery: An Anatomy-Based Stepwise Review. World Neurosurg. 2023; 178:241-259.e3.
[6] Cai J, Ribkoff J, Olson S, Raghunathan V, Al-Samkari H, DeLoughery TG, Shatzel JJ. The many roles of tranexamic acid: An overview of the clinical indications for TXA in medical and surgical patients. Eur J Haematol. 2020; 104(2):79-87.
[7] Tranexamic acid: uses, interactions, mechanism of action | DrugBank Online [Internet]. [cited 2024 Dec 27]. Available from: https://go.drugbank.com/drugs/DB00302
[8] Perel P, Al-Shahi Salman R, Kawahara T, Morris Z, Prieto-Merino D, Roberts I, 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(13):iii-xii, 1-54.
[9] Delawan M, Sharma M, Ismail M, Algabri MH, Abdalridha RH, Alawadi MN, et al. Methods of Hemostasis in Cranial Neurosurgery: An Anatomy-Based Stepwise Review. World Neurosurg. 2023; 178:241-259.e3.
[10] Nguyen A, Brown NJ, Gendreau J, Nguyen BA, Pennington Z, Zhang A, et al. The association of thromboembolic complications and the use of tranexamic acid during resection of intracranial meningiomas: systematic review and meta-analysis of randomized controlled trials. J Neurosurg. 2023; 140(4):1008-1018.
[11] Mullin JP, Soliman MAR, Smith JS, Kelly MP, Buell TJ, Diebo B, et al. Analysis of tranexamic acid usage in adult spinal deformity patients with relative contraindications: does it increase the risk of complications? J Neurosurg Spine. 2024; 40(6):684-691
[12] Yoo JS, Ahn J, Karmarkar SS, Lamoutte EH, Singh K. The use of tranexamic acid in spine surgery. Ann Transl Med. 2019; 7(Suppl 5):S172.
[13] O’Donnell DB, Vazquez S, Greisman JD, Uddin A, Graifman G, Dominguez JF, et al. Tranexamic Acid Dosing in Craniosynostosis Surgery: A Systematic Review with Meta-analysis. Plast Reconstr Surg Glob Open. 2022; 10(10):e4526.
[14] Shafique N, Akbar UA, Umer AM, Kumar B, Muhibullah F, Siddiqui F, et al. Tranexamic Acid for Trauma Care: An Updated Meta-Analysis of Mortality and Thromboembolic Events in Severely Injured Patients. Blood. 2023;142(Supplement 1):5570–5570.
[15] Fouche PF, Stein C, Nichols M, Meadley B, Bendall JC, Smith K, et al. Tranexamic Acid for Traumatic Injury in the Emergency Setting: A Systematic Review and Bias-Adjusted Meta-Analysis of Randomized Controlled Trials. Ann Emerg Med. 2024;83(5):435–45.
[16] Chauhan MS, Mahmood ST, Chaterjii G, Shakya M, Pal V, Siddhartha P V. Role of Tranexamic Acid in Controlling Blood Loss in Total Hip Arthroplasty. Int J Curr Pharm Res. 2024;84–7.
[17] Vychopen M, Arlt F, Güresir E, Wach J. Intraoperative tranexamic acid administration in cranial meningioma surgery: a meta-analysis of prospective randomized, double-blinded, and placebo-controlled trials. Front Oncol. 2024; 14:1464671.
[18] Khalid A, Nazir U, Raza N, Aslam S, Majeed MN, Hassan Z, et al. A Comparison of the Use of Tranexamic Acid versus Placebo in Patients Undergoing Excision of Intracranial Meningioma. Pakistan J Neurological Surgery. 2022; 26(4):654–66.
[19] Hollingworth M, Woodhouse LJ, Law ZK, Ali A, Krishnan K, Dineen RA, et al. The Effect of Tranexamic Acid on Neurosurgical Intervention in Spontaneous Intracerebral Hematoma: Data from 121 Surgically Treated Participants from the Tranexamic Acid in IntraCerebral Hemorrhage-2 Randomized Controlled Trial. Neurosurgery. 2024;95(3):605–16.
[20] Luo H, Zhang X, Xie C, Wu L, Cai G, Ren Y. Efficacy and safety of topical tranexamic acid in spinal surgery: a systematic review and meta-analysis. EFORT Open Rev. 2024;9(8):796–805.
[21] Stejskal P, Trnka, Hrabálek L, Wanek T, Jablonský J, Novák V. Effects of Tranexamic Acid on Perioperative Blood Loss and Wound Hematoma Development in Lumbar Spine Surgery: a Prospective Randomized Study. Acta Chir Orthop Traumatol Cech. 2023;90(3):176–80.
[22] de Faria JL, da Silva Brito J, Costa e Silva LT, Kilesse CTSM, de Souza NB, Pereira CU, et al. Tranexamic acid in Neurosurgery: a controversy indication—review. Neurosurg Rev. 2021; 44(3):1287–98.
[23] Roberts I, Shakur-Still H, Aeron-Thomas A, Belli A, Brenner A, Chaudary MA, et al. 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(10210):1713–23.
[24] Chakroun-Walha O, Samet A, Jerbi M, Nasri A, Talbi A, Kanoun H, et al. Benefits of the tranexamic acid in head trauma with no extracranial bleeding: a prospective follow-up of 180 patients. Eur J Trauma Emerg Surg. 2019; 45(4):719–26.
[25] 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 Emerg Med. 2013;13(1):20.
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How to Cite
1.
Salimi S, Salarian S, Arefian NM, Khayat Kashani H, Abdous N, Abtahi D. Comparing Two Tranexamic Acid Dosing Regimens for Blood Loss Reduction in Supratentorial Brain Tumor Surgery: A Multicenter, Double-Blind, Randomized Trial. Arch Anesth & Crit Care. 2025;.
