The effects of timing of prehospital tranexamic acid on outcomes after traumatic brain injury: Subanalysis of a randomized controlled trial

In this study we examine the effect of early versus delayed prehospital administration of tranexamic acid in patients with traumatic brain injury. Outcomes were not significantly different but select complications were lower with early administration. BACKGROUND Tranexamic acid (TXA) is an antifibrinolytic that has shown some promise in improving outcomes in traumatic brain injury (TBI), but only when given early after injury. We examined the association between timing of prehospital TXA administration and outcomes in patients with moderate to severe TBI. METHODS Patients enrolled in the multi-institutional, double-blind randomized prehospital TXA for TBI trial with blunt or penetrating injury and suspected TBI (Glasgow Coma Scale score ≤ 12, SBP ≥90) who received either a 2-g TXA bolus or a 1-g bolus plus 1 g 8 hour infusion within 2 hours of injury were analyzed. Outcomes were compared between early administration (<45 minutes from injury) and late administration ≥45 minutes from injury) using a χ2, Fischer's exact test, t test, or Mann-Whitney U test as indicated. Logistic regression examined time to drug as an independent variable. A p value less than 0.05 was considered significant. RESULTS Six hundred forty-nine patients met inclusion criteria (354 early and 259 late). Twenty-eight-day and 6-month mortalities, 6-month Glasgow Outcome Scale–Extended, and disability rating scale scores were not different between early and late administration. Late administration was associated with higher rates of deep venous thrombosis (0.8 vs. 3.4%, p = 0.02), cerebral vasospasm (0% vs. 2%, p = 0.01), as well as prolonged EMS transport and need for a prehospital airway (p < 0.01). CONCLUSION In patients with moderate or severe TBI who received TXA within 2 hours of injury, no mortality benefit was observed in those who received treatment within 45 minutes of injury, although lower rates of select complications were seen. These results support protocols that recommend TXA administration within 45 minutes of injury for patients with suspected TBI. LEVEL OF EVIDENCE Therapeutic/Care Management; Level II.

[1]  James G. Chandler,et al.  Traumatic brain injury provokes low fibrinolytic activity in severely injured patients , 2022, The journal of trauma and acute care surgery.

[2]  F. Guyette,et al.  Early Prehospital Tranexamic Acid Following Injury Is Associated With a 30-day Survival Benefit , 2021, Annals of surgery.

[3]  C. Callaway,et al.  Tranexamic Acid During Prehospital Transport in Patients at Risk for Hemorrhage After Injury: A Double-blind, Placebo-Controlled, Randomized Clinical Trial. , 2020, JAMA surgery.

[4]  L. Morrison,et al.  Effect of Out-of-Hospital Tranexamic Acid vs Placebo on 6-Month Functional Neurologic Outcomes in Patients With Moderate or Severe Traumatic Brain Injury. , 2020, JAMA.

[5]  D. Morris,et al.  The Use of Tranexamic Acid (TXA) for the Management of Hemorrhage in Trauma Patients in the Prehospital Environment: Literature Review and Descriptive Analysis of Principal Themes. , 2020 .

[6]  F. Althabe,et al.  WHO essential medicines for reproductive health , 2019, BMJ Global Health.

[7]  R. Matthews,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 , 2019, The Lancet.

[8]  S. Urien,et al.  Optimisation of the dosage of tranexamic acid in trauma patients with population pharmacokinetic analysis , 2018, Anaesthesia.

[9]  W. Dorlac,et al.  Tranexamic Acid Use in Prehospital Uncontrolled Hemorrhage , 2017, Wilderness & environmental medicine.

[10]  I. Chalmers,et al.  Effect of early tranexamic acid administration on mortality, hysterectomy, and other morbidities in women with post-partum haemorrhage (WOMAN): an international, randomised, double-blind, placebo-controlled trial , 2017, The Lancet.

[11]  P. Edwards,et al.  Tranexamic acid in bleeding trauma patients: an exploration of benefits and harms , 2017, Trials.

[12]  V. Rahimi-Movaghar,et al.  The effect of tranexamic acid in traumatic brain injury: A randomized controlled trial , 2017, Chinese journal of traumatology = Zhonghua chuang shang za zhi.

[13]  Xiaoyi Zou,et al.  Tranexamic acid-associated seizures: A meta-analysis , 2016, Seizure.

[14]  E. Kochs,et al.  Tranexamic Acid Impairs.-Aminobutyric Acid Receptor Type A-mediated Synaptic Transmission in the Murine Amygdala , 2014 .

[15]  E. Kochs,et al.  Tranexamic Acid Impairs &ggr;-Aminobutyric Acid Receptor Type A–mediated Synaptic Transmission in the Murine Amygdala: A Potential Mechanism for Drug-induced Seizures? , 2014, Anesthesiology.

[16]  C. Guerriero,et al.  The CRASH-2 trial: a randomised controlled trial and economic evaluation of the effects of tranexamic acid on death, vascular occlusive events and transfusion requirement in bleeding trauma patients. , 2013, Health technology assessment.

[17]  M. Midwinter,et al.  Military Application of Tranexamic Acid in Trauma Emergency Resuscitation (MATTERs) Study. , 2012, Archives of surgery.

[18]  P. Sandercock,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. , 2012, Health technology assessment.

[19]  The Lancet.  Bringing women to the forefront of science and medicine. , 2012, The Lancet.

[20]  A. Sauaia,et al.  Primary Fibrinolysis Is Integral in the Pathogenesis of the Acute Coagulopathy of Trauma , 2010, Annals of surgery.

[21]  J. Murkin,et al.  High-Dose Tranexamic Acid Is Associated with Nonischemic Clinical Seizures in Cardiac Surgical Patients , 2010, Anesthesia and analgesia.