Tranexamic Acid in Trauma

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Tranexamic Acid in Trauma Kids Too? Developing EM 2014 Salvador da Bahia, Brazil Suzanne Beno MD FRCPC Trauma Co-Director The Hospital for Sick Children Toronto, Ontario


ObjectivesReview the evidence for tranexamic acid (TXA) in trauma Identify current knowledge gaps for TXA in trauma Discuss the use of TXA in pediatric trauma


Scenario 1A young male presents to a trauma center extremely short of breath with stab wounds to his left flank. A chest tube is placed with return of a large volume of blood. He is stabilized but remains tachycardic, pale and agitated.


Scenario 2A 5 year old girl on her bicycle is hit by a car. She presents with mild tenderness in her upper abdomen and tachycardia. Her FAST is grossly positive and an abdominal CT scan reveals a Grade 5 liver laceration. She is admitted to the ICU for observation.


TraumaLeading cause of death in North Americans 1-44 years of age Hemorrhage most preventable cause of death after trauma in both adults and children Hemostatic resuscitation and recognition of acute traumatic coagulopathy (ATC) and specifically hyperfibrinolysis No medical therapy has proven survival benefit in children, but evidence DOES exist in adults


Tranexamic AcidPrevents the breakdown of existing clots Mitigates the systemic anti-inflammatory response to massive hemorrhageFibrinFibrinolysisTXA


Tranexamic AcidFirst clinical trial using oral TXA published in 1968 - heavy menstrual bleeding - FDA 2009 Dental extractions with hemophilia reported in 1972 - FDA approval 1986 TXA now widely used in many conditions Extensive safety and efficacy profile in reducing the need for blood transfusions in elective surgery both adults and childrenCap AP et al. J Trauma 2011


TXA in Trauma What’s the evidence?


prospective randomized placebo-controlled trial of 20,211 patients, 274 hospitals, 40 countries Inclusion criteria: adults (16 years and up) with unstable vital signs or high clinical suspicion for hemorrhage within 8 hours of injury Randomized to TXA versus placebo One gram over 10 minutes followed by a second one gram infusion over 8 hours


CRASH 2 Analyses Summary ResultsDecreased all-cause mortality 16.0% to 14.5%, NNT 67 Decreased risk due to bleeding 5.7% to 4.9%, NNT 121 Greatest reduction in deaths due to bleeding: Severe shock (≤ 75 mmHg) 14.9% vs 18.4% Within first hour - benefit seen within 3h of injury Increased risk of death if administered after 3 hours TXA not associated with ↑ vascular occlusive events TXA safe and effective across all mortality groups


Retrospective, observational Military environment Overall: AR 7.6%, 6.5% MT: AR 13.7%, RR 49% OR for survival 7.228 [95% CI 3.0 to 17.3]


TXA Is Cost Effective


One dose TXA costs ~ $5.40 - $65 One dose Factor VIIa costs ~ $8500


Adverse EffectsSeizures (perioperative - high dose) Rapid infusion hypotension Thromboembolism no difference between groups in CRASH 2 not seen in pediatric surgery (high doses) systematic reviews have not found a concernHenry et al Cochrane Review 2011 Ker et al BMJ 2012, Faraoni D, Goobie SM Anesth Analg 2014


Ideal hemostatic AgentEasy to store and use Stops inappropriate hemorrhage Does not clot working vessels No side effects (minimal) Free (cheap)Richard Dutton EMCrit Conference 2011


Knowledge GapsUse in significant traumatic brain injury? (CRASH 3) Optimal dosing? Mortality benefit in advanced trauma systems (PATCH) Emerg Med Aust 2014, J Trauma Acute Care Surg 2014 “True” risk of thromboembolism? Role of fibrinolysis testing prior to giving TXA? Indications in pediatric trauma?


Pediatric Trauma Differences & Similarities Broad anatomic, physiologic, developmental age spectrum Different hemodynamic response Blunt >> penetrating Low operative rates TBI common in bothBeno et al. Crit Care 2014


Pediatric Trauma Coagulopathy ATC is prevalent in pediatric trauma (27, 38, 77%) ATC strongly associated with ↑ mortality in children (civilian and in combat support hospitals) OR 2.2 TBI and early coagulopathy significantly ↑ mortality (fourfold)Hendrickson et al. J Pediatr Surg 2012 Patregnani et al. Pediatr Crit Care Med 2012 Whittaker et al. Shock 2013


Pediatric Trauma Hyperfibrinolysisnot clearly described Fibrinogen levels low in 52% of children needing transfusion [20% < 100 mg/dL] rTEG in pediatric trauma Hendrickson et al. J Pediatr Surg 2012 Vogel etal. J Pediatr Surg 2013


Pediatric Trauma TXA makes sense! Hemorrhage, like in adults, is the second leading and main preventable cause of traumatic death Trauma-associated coagulopathy exists in kids Hyperfibrinolysis - very likely Track record of safety and efficacy when used in HIGH doses in pediatric surgery Healthier vascular systems


Pediatric Trauma Practical ConsiderationsIntraosseous route (no data) Pre-hospital administration (by age?) Adolescents and children (different) Careful prospective monitoring


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Last Updated: 8th March 2018

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