TXA. Things Change. Tranexamic Acid TXA. Resuscitation 2017 TXA In The ED March 31, MAST Trousers. High Flow IV Fluids.

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1 Resuscitation 2017 In The ED March 31, 2017 Corey M. Slovis, M.D. Vanderbilt University Medical Center Metro Nashville Fire Department Nashville International Airport Nashville, TN SECURE THE ABC S MAST Trousers Things Change High Flow IV Fluids High Dose Epi Atropine Use High Flow O 2 Tranexamic Acid An anti-fibrinolytic Blocks fibrin clot dissolution binds to plasminogen Blocks plasminogen fibrin interaction FDA approved in 1989 for hemophilia 1

2 TPA Plasminogen Plasmin Fibrin Clot Dissolution Fibrin Split Products Decreasing Blood Loss Tooth extractions in hemophilia Refractory nose bleeds Decrease surgical blood loss (orthopedics: spine and hip; ob/gyn: hysterectomy) During cardiopulmonary bypass Post major trauma? Hyperfibrinolysis Acute Coagulopathy of Trauma Seen in 25-40% of severe trauma patients Hypoperfusion Acidosis Hypothermia Hyperfibrinolysis (HF) in patients with severe trauma = % mortality LY30 > 3% Activation of protein C LY30 > 3% fibrinolysis Lancet 2010; Does work in severe hemorrhage? 20,211 patients with major trauma 10,046 patients got within 8 hours Hospitals in Africa, Asia, Eastern Europe Lancet 2010; hospitals in 40 countries 1 gram of in 10 minutes 1 gram over next 8 hours Death in hospital including: AMI, CVA, PE, MOSF, CHI 2

3 30d All Cause Mortality Crash-2 Lancet 2010;376:23-32 Death from Bleeding Lancet 2010;376: % 4.9% Death (%) % 14.5% p= p= RR= Placebo Placebo Problems with CRASH - 2 Only 5% of patients had bleeding as a cause of death Selection bias No lactate or base deficit Only 31.5% had a SBP < 90 TBI was #1 cause of death More Problems with CRASH % patient follow up hard to believe Only a 0.8% absolute reduction in death by bleeding No transfusion reductions Only 48% had HR > 107 Lancet 2011;377: Reanalyzes prior CRASH-2 data 20,211 trauma patients Randomized to or placebo Administered up to 8 hours post trauma Does time to matter? 3

4 Bleeding Death with vs Placebo Lancet 2011;377: Crash- 2 RR reduces trauma mortality from bleeding by about 1/3 if given within 3 hours <1 hr 1-3 hr 3 hr Bleeding Death with by Time Lancet 2011;377: Crash- 2 Lancet 2011;377: % % p=0.004 RR=1.44 given after three hours increases the 3 2 risk of death by bleeding by about 40% 1 0 <3 hr >3 hr Potential Benefits (if given within 3 hours) Crash-2 showed early reduced mortality from traumatic bleeding Could it really affect worldwide mortality? Should only be used in third world countries? BMC Emerg Med 2012;12: 1-7 BMC Emerg Med 2012;12: 1-7 4

5 Use At the present time both the US and British Armies include in trauma protocol UK National Health Service recommends for all major trauma victims Authors Conclude BMC Emerg Med 2012;12: 1-7 has the potential to save between 112, ,000 lives per year worldwide if given within 1-3 hours of trauma is now a WHO Essential Medication What about a study that directly applies to trauma in the US Arch Surg 2012;147: vs. no- US Troops in Afghanistan All pts required >1 unit blood Subgroup got > 10 units PRBC Retrospective study, 896 pts in US Military Arch Surg 2012;147: in Massive Transfusion Arch Surg 2012;147: % Mortality % ISS % 17.4% ISS 25.2 p = % Mortality % % p = % 5 5 No No N=603 N=293 N=196 N=125 5

6 Conclusions in the Military dramatically decreased mortality Benefits greatest in those requiring massive transfusion increased survival by factor of for those requiring massive transfusion decreased coagulopathy Only administer within 3 hours Only for severe hemorrhagic shock (SBP < 75) With predictor of fibrinolysis or LY30 > 3% J Trauma 2013;74: J Trauma 2013;74: Still Not Known Is of benefit if: MTP used and/or Damage control resuscitation used Whether fibrinolysis testing should be done before administered BMC Emerg Med 2013;13:20 Can decrease intracranial bleeding s/p TBI? Double-blind, placebo controlled, randomized 238 patients > 16 years old GCS 4-12 s/p TBI 2 Gm : 1G in 30 min, 1G in 8 hr Progressive Intracranial Hemorrhage BMC Emerg Med 2013;13:20 27% 18% RR = 0.65 CI = 1.05 Was there a ICH on 2 nd CT not seen on first? Did initial bleed increase by 25% hrs post injury STD Rx 6

7 Improved Motor and Risk of Death P = NS 31% 31% for ICH Take Homes Trend toward decreased bleeding 10% 14% But no true significant difference in ICH, ICH size, improved motor GCS or risk of death STD Improved Motor STD Death not of proven efficacy for traumatic ICH Does have a role in a US Level 1 Trauma Center J Trauma and Acute Care 2014;76: Level 1 trauma patients - Miami FL All required immediate OR or blood 1 gram IV then 1 G over 8 hours 54% penetrating trauma, 25% TBI 150 pts and 150 matched controls Mortality vs Standard Care J Trauma and Acute Care 2014;76: % J Trauma and Acute Care 2014;76:1373 August 2009 January % SBP < 120 mm Hg 30% SBP < 70mm Hg ¾ required surgery and transfusion Evaluated mortality in 150 matched pts 17% No P = % 7

8 Use new drugs as soon as possible Before they develop side effects or loose efficacy J Trauma and Acute Care 2014;76:1373 Authors state groups perfectly matched group received more fluids, RBCs and FFP in OR If the death within 2 hours patients excluded then: Changes 81 deaths to 61 total deaths vs No Deaths in 2 hrs excluded J Trauma and Acute Care 2014;76: % No 17% P = J Trauma 2014;77:852-8 Is effective in Pediatric Trauma? 37% 766 pediatric trauma pts < 18 yo NATO hospital in Afghanistan 9% (66 pts) received 73% had penetrating injuries Patients J Trauma 2014;77:852-8 J Trauma 2014;77:852-8 Average age 11 yo ± 5 Not randomized study; retrospective review Used matched controls in 3:1 ratio at 1 gram within 3 hours More severely injured (ISS 18 vs 10) Lower GCS (8 vs 13) More required transfusions (85% vs 30%) Higher unadjusted mortality (15% vs 9%) 8

9 Propensity Adjusted Analysis 100% 75% Neurologic Status GCS % J Trauma 2014;77: % P= % 50% 25% J Trauma 2014;77: % No in Children Take Homes Similar to the adult military experience it seems to work! 2017 Where Are We? A tale of 2 dissimilar studies Mortality in Hyperfibrinolysis J Trauma Acute Care Surg 2015;78:905-9 J Trauma Acute Care Surg 2015;78:905-9 Does decrease mortality in trauma patients with proven fibrinolysis? 98 Level 1 trauma patients, retrospective study Herman Hospital Houston TX Compared to 934 non- patients All pts had LY30 3% 50% 40% 30% 20% 10% 0% 17% No 40% 9

10 J Trauma Acute Care Surg 2015;78:905-9 Comments and Results group lower BP (103 vs 125 sys BP) Much more likely to be transfused Twice as likely to go to OR (27% vs 13%) No increase DVTs or PE with Using multivariate analysis had no positive or negative impact on survival Critical Care 2016;20: Does Prehospital Decrease mortality? 258 pt matched EMS- vs no German Automobile Air Rescue Services Mean ISS of 24 for both groups Average scene SBP: for both 75% required intubation in each group Early vs Late Mortality Critical Care 2016;20: % 16.3% 16% 14% 12% 10% 8% u d eds 18% 12.4% 5.8% p=ns Guidelines For Use % 4% 2% 0% No No 24 Hours Late best if within 1 hour Prehosp Emerg Care 2016;20:557-9 Suggested criteria for use: Prehosp Emerg Care 2016;20:557-9 EMS and trauma receiving faculty should have jointly-developed protocols Clear handoff and documentation of administration essential Internal hemorrhage with HR SBP 90 Pediatric use is currently not recommended due to increased incidence of seizures (in cardiac patients) 10

11 Use Going Forward Emerg Med Australia 2014;26:194-7 Prehospital antifibinolytic coagulopathy and hemorrhage study PATCH Study Australian study Currently underway Evaluates for EMS use A randomized study in high morbidity high mortality Australian and New Zealand patients Prehosp Emerg Care 2015;19:79-86 STAAMP Trial During Air Medical Prehospital Transport US Department of Defense trial Using during air evacuations Placebo-controlled, randomized Rochester NY, Pittsburg, Utah and San Antonio < 2 hrs of injury, < 90 SBP, HR > dosing regiments Summary Proven on battlefield Proven in 3 rd world countries Role is soon to be clarified SECURE THE ABC S Data appears somewhat confusing Don t be too sure either way 11

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