2. Morel-Lavallee meet Milieu intérieur

3. Claude Bernard The father of physiology Milieu intérieur: the extracellular fluid environment, and its physiological capacity to ensure protective stability for the tissues and organs of multicellular living organisms

4. “The fixity of the milieu supposes a perfection of the organism such that the external variations are at each instant compensated for and equilibrated.... All of the vital mechanisms, however varied they may be, have always one goal, to maintain the uniformity of the conditions of life in the internal environment.... The stability of the internal environment is the condition for the free and independent life. ”

5. SHOCK “the rude unhinging of the machinery of life” 1872 Gross

6. WHY? Uncontrolled bleeding is a leading cause of trauma deaths Despite advances in trauma care, the mortality rate of patients requiring large volume blood transfusion remains in excess of 30%

7. Who? 27 year old male had industrial pipes fall on him from a truck EMS and MD1 extricate, intubate, and bring him to you 90/50, 125, GCS 3T Open book pelvis, bilateral femur and ankle fractures, distended abdomen

8. Resuscitation 2014; TIC, PCC, TXA Joli Dace, PharmD, BCPS Christopher Wistrom DO Robb R Whinney DO FACOS Mercy Health System Janesville WI December 2014 No disclosures

9. 1625-Circulation described-Harvey 1667-Animal to human transfusion-Denis, Lower 1828-Human to human transfusions-Blundell 1865-Civil War- First transfusion of trauma patient 1888-Ringer ’ s solution 1909-Transfusion of trauma patient-Crile 1916-WWI- citrated glucose blood, gum saline 1930-Hemorrhagic Shock defined-Blalock 1944-WWII, Allied blood transfusions 1947-Albumin 1960-Crystalloid required 3:1-Shires 1980-Hypertonic saline in Trauma-DeFillipe 1990s Factor VIIa in trauma 1998-Hb-based blood substitute in Trauma-Gould HISTORY OF FLUID RESUSCITATION IN TRAUMA

10. 1990s Europe starts expanding use of PCC 2001 Rivers study on Goal Directed Therapy in Sepsis 2000s TEG and ROTEM to define Trauma Induced Coagulopathy 2000s PRBC: FFP 1:1 PRBC: FFP: Platlets 1:1:1 PRBC: FFP: Platlets: Fibrinogen 1:1:1:1 2008 Whole Blood in Military study 2010 CONTROL Factor VII trial (the END!!!!) 2010 CRASH-2 tranexamic acid (TXA) and trauma patients 2012 MATTERs tranexamic acid 2013 CRASH-3 TXA in head injury patients (in process) HISTORY OF FLUID RESUSCITATION IN TRAUMA

11. ATLS gives the most sage commentary: –Stop bleeding –“the amount of fluid and blood required for resuscitation is difficult to predict on initial evaluation” –Management guided by patient response

12. Prehospital Fluid Delay of aggressive fluid resuscitation until operative intervention for hypotensive patients with penetrating torso injuries improves outcomes Bickell 1994

13. Prehospital Fluid Hemorrhage induced hypotension in trauma is predictive of mortality and morbidity Requirements for large volume of crystalloid resuscitation is associated with increased mortality –Heckbert presented a retrospective review at EAST (published in J Trauma):

14. Prehospital Fluid Prehospital fluid administration is associated with higher mortality in trauma patients: a National Trauma Data Bank analysis. Patients receiving IV fluids were significantly more likely to die in nearly all subsets of trauma patients. Routine use of prehospital IV fluid for all trauma patients should be discouraged. –Ann Surg. 2011, Haut ER, et al. The Johns Hopkins Hospital

15. Colloid vs Crystalloid The debate will never end… over 50 studies over 50+ years with no winner 2011 South Africa Colloid vs crystalloid in trauma patients Colloid: – Superior initial resuscitation using colloid – Decreased lactate levels – Less renal injury after penetrating trauma

16. Hypertonic Saline Provides smaller volume resuscitation Rapid restoration of hemodynamics with laboratory evidence of improved microcirculatory hemodynamics The role of hypertonic saline in trauma resuscitation is still being defined

17. Blood substitutes Despite many years of research, the ideal blood substitute continues to elude researchers….

18. Cryoprecipitate A cryoprecipitate:RBC ratio of 1:1 has been shown to reduce 24-hour and 30-day mortality in civilian trauma. Rx: One 10-unit bag of cryoprecipitate for every 10 units of red cells transfused.

19. Goal Directed Therapy Early Goal-Directed Therapy in the Treatment of Severe Sepsis and Septic Shock. Emanuel Rivers, et al. Engl J Med 2001 Prospective randomized trial

20. Massive transfusion Multicenter prospective cohort 415 blunt injured adults required >/=8 units PRBCs within the first 12 hours FFP:PRBC transfusion ratio >/=1:1.5 is associated with a lower risk of mortality after massive transfusion. Sperry JL, et al. J Trauma. 2008 University of Pittsburgh Medical Center Sperry JL

21. Massive transfusion A greater than 1:1 FFP:PRBC ratio has –Decreases mortality –Not associated with a higher organ failure –Not associated nosocomial infection –Twofold higher risk of ARDS

22. Blood as a Therapy/Drug GOAL To increase Oxygen delivery to hypoxic tissues while minimizing side effects To increase Oxygen delivery to hypoxic tissues while minimizing side effects

23. PRBC Ingredients Red blood cellsRed blood cells White blood cellsWhite blood cells ProteinsProteins IonsIons

24. Blood Complications May transmit diseasesMay transmit diseases Transfusion reactionsTransfusion reactions Spoils: stored blood is not “Normal Blood”Spoils: stored blood is not “Normal Blood”

25. Old Blood is bad blood!!! Fitzgerald et alFitzgerald et al –Sepsis model showed 28 day old RBC transfusion decreased systemic O2 uptake Marik et alMarik et al –Transfusion of 3u of PRBC to a Hg of 9-11 G/dl in septic mechanically ventilated patients had no improvement in O2 uptake –in fact patients receiving blood >15 days old had splanchnic ischemia Fitzgerald RD, et al. Crit Care Med 1997;25:726-732 Marik PE, et al. JAMA 1993;269:3024-3029

26. Old Blood is bad blood!!! Older blood = less O2 delivery Older blood = More cytokines More cytokines = More reactions

27. Old Blood is bad blood!!! Macrophage function alteredMacrophage function altered Decreased Lymphocyte antigen responseDecreased Lymphocyte antigen response Decreased Helper cell activityDecreased Helper cell activity Increased Suppressor cell activityIncreased Suppressor cell activity There is a dose response relationship!!

28. Recommendations Stop BleedingStop Bleeding Acute hypovolemic anemia needs bloodAcute hypovolemic anemia needs blood Maintain euvolemia with crystalloidsMaintain euvolemia with crystalloids Use leukocyte deplete bloodUse leukocyte deplete blood Newer blood is more effectiveNewer blood is more effective

29. Recommendations Hgb 6 - Healthy pt without heart diseaseHgb 6 - Healthy pt without heart disease Hgb 10- patients with symptomatic CADHgb 10- patients with symptomatic CAD Transfusions should be based on symptoms, not on absolute numbersTransfusions should be based on symptoms, not on absolute numbers

30. Trauma Induced Coagulopathy

31. 20 years ago… Traumatic coagulopathy from major hemorrhage was believed to be a late consequence of – hemodilution – acidosis – Hypothermia – loss of coagulation proteins through bleeding and consumption

32. Old Standard Prothrombin time (PT) Activated partial thromboplastin time (aPTT) Plasma fibrinogen concentration PT and aPTT- – very initiation of clot formation – only 5% of the entire thrombin is generated – unhelpful for distinguishing between lack of coagulation factors and substrate. Tests were not developed to assess coagulopathy in acute bleeding situations such as trauma They don’t assess clot quality and stability, which are important determinants of TIC

33. 20 years ago… Trauma Hemorrhage Coagulopathy

41. THE END OF VIIa J Trauma. 2010 Sep;69(3):489-500. doi: 10.1097/TA.0b013e3181edf36e.Results of the CONTROL trial: efficacy and safety of recombinant activated Factor VII in the management of refractory traumatic hemorrhage.Hauser CJ1, Boffard K, Dutton R, Bernard GR, Croce MA, Holcomb JB, Leppaniemi A, Parr M, Vincent JL, Tortella BJ, Dimsits J, Bouillon B; CONTROL Study Group.Author informationAbstractBACKGROUND:Traumatic coagulopathy contributes to early death by exsanguination and late death in multiple organ failure. Recombinant Factor VIIa (rFVIIa, NovoSeven) is a procoagulant that might limit bleeding and improve trauma outcomes.METHODS:We performed a phase 3 randomized clinical trial evaluating efficacy and safety of rFVIIa as an adjunct to direct hemostasis in major trauma. We studied 573 patients (481 blunt and 92 penetrating) who bled 4 to 8 red blood cell (RBC) units within 12 hours of injury and were still bleeding despite strict damage control resuscitation and operative management. Patients were assigned to rFVIIa (200 μg/kg initially; 100 μg/kg at 1 hour and 3 hours) or placebo. Intensive care unit management was standardized using evidence-based trauma "bundles" with formal oversight of compliance. Primary outcome was 30-day mortality. Predefined secondary outcomes included blood products used. Safety was assessed through 90 days. Study powering was based on prior randomized controlled trials and large trauma center databases.RESULTS:Enrollment was terminated at 573 of 1502 planned patients because of unexpected low mortality prompted by futility analysis (10.8% vs. 27.5% planned/predicted) and difficulties consenting and enrolling sicker patients. Mortality was 11.0% (rFVIIa) versus 10.7% (placebo) (p = 0.93, blunt) and 18.2% (rFVIIa) versus 13.2% (placebo) (p = 0.40, penetrating). Blunt trauma rFVIIa patients received (mean ± SD) 7.8 ± 10.6 RBC units and 19.0 ± 27.1 total allogeneic units through 48 hours, and placebo patients received 9.1 ± 11.3 RBC units (p = 0.04) and 23.5 ± 28.0 total allogeneic units (p = 0.04). Thrombotic adverse events were similar across study cohorts.CONCLUSIONS:rFVIIa reduced blood product use but did not affect mortality compared with placebo. Modern evidence-based trauma lowers mortality, paradoxically making outcomes studies increasingly difficult.Hauser CJ1, Boffard K, Dutton R, Bernard GR, Croce MA, Holcomb JB, Leppaniemi A, Parr M, Vincent JL, Tortella BJ, Dimsits J, Bouillon B; CONTROL Study Group.Author informationAbstractBACKGROUND:Traumatic coagulopathy contributes to early death by exsanguination and late death in multiple organ failure. Recombinant Factor VIIa (rFVIIa, NovoSeven) is a procoagulant that might limit bleeding and improve trauma outcomes.METHODS:We performed a phase 3 randomized clinical trial evaluating efficacy and safety of rFVIIa as an adjunct to direct hemostasis in major trauma. We studied 573 patients (481 blunt and 92 penetrating) who bled 4 to 8 red blood cell (RBC) units within 12 hours of injury and were still bleeding despite strict damage control resuscitation and operative management. Patients were assigned to rFVIIa (200 μg/kg initially; 100 μg/kg at 1 hour and 3 hours) or placebo. Intensive care unit management was standardized using evidence-based trauma "bundles" with formal oversight of compliance. Primary outcome was 30-day mortality. Predefined secondary outcomes included blood products used. Safety was assessed through 90 days. Study powering was based on prior randomized controlled trials and large trauma center databases.RESULTS:Enrollment was terminated at 573 of 1502 planned patients because of unexpected low mortality prompted by futility analysis (10.8% vs. 27.5% planned/predicted) and difficulties consenting and enrolling sicker patients. Mortality was 11.0% (rFVIIa) versus 10.7% (placebo) (p = 0.93, blunt) and 18.2% (rFVIIa) versus 13.2% (placebo) (p = 0.40, penetrating). Blunt trauma rFVIIa patients received (mean ± SD) 7.8 ± 10.6 RBC units and 19.0 ± 27.1 total allogeneic units through 48 hours, and placebo patients received 9.1 ± 11.3 RBC units (p = 0.04) and 23.5 ± 28.0 total allogeneic units (p = 0.04). Thrombotic adverse events were similar across study cohorts.CONCLUSIONS:rFVIIa reduced blood product use but did not affect mortality compared with placebo. Modern evidence-based trauma lowers mortality, paradoxically making outcomes studies increasingly difficult.

51. Now…

52. Evolving plan…

53. Viscoelastic testing TEG or ROTEM provide a real-time graphic representation of clot formation enabling clinicians to individualize correction of coagulopathy more accurately and substantially faster than standard coagulation tests

54. Viscoelastic Testing Excellent to assess coagulopathy in trauma. Performed at the bedside using whole blood (not plasma) samples so the contribution of platelets and fibrinogen to the clot kinetics can be assessed. Provide a timely assessment of the initiation of coagulation AND of the clot formation process and the maximal clot strength Considered the gold standard for diagnosing premature dissolution of the clot, which has been identified as an important contributor to mortality

58. Trauma-induced coagulopathy (TIC) Multifactorial etiology: – Blood loss – Hypothermia – Acidosis – Loss coagulopathy – Dilutional coagulopathy – Consumption coagulopathy – Hyperfibrinolysis – Metabolic changes

60. Recommendations Stop surgical bleeding Warm fresh whole blood or best practice component therapy in a ratio of 1:1:1:1 (plasma:platelets:cryoprecipitate:RBCs) TXA PCC Fibrinogen concentrate Point of care TEG directed care

63. Management of Trauma Hemorrhage: Possible Role of Kcentra, a 4-factor Prothrombin Complex Concentrate Joli Dace, PharmD, BCPS Mercy Hospital and Trauma Center

64. 64 Objectives Define PCC and availability in US Compare Kcentra with plasma Brief overview of coagulation cascade Review possible Kcentra use in trauma: Emergent reversal of oral anticoagulants Management of trauma hemorrhage Discuss Kcentra nursing considerations

65. 65 What are PCCs? “Prothrombin complex concentrates” Concentrated clotting factors Derived from pooled human plasma PCC Products Available in US Therapeutic Clotting Factors Alternative Names Profilnine SD ® II, IX, X 3f-PCC Kcentra ® II, IX, X, VII 4f-PCC BeriPlex ® P/N (outside US) Feiba ® NFII, IX, X, aVII Activated 4f-PCC Factor VIII Inhibitor Bypassing Activity

66. Comparison: Kcentra and FFP 3-6,18 Kcentra ® FFP Clotting Factors II, VII, IX, XII, V, VII – XIII; fibrinogen Anticoagulants AT, heparin, protein C & Sprotein C & S Preparation Dilute each 500mg vial with 20mLThaw; ABO match Volume Average 40 -100 mL/doseAverage 30 mL/kg Administration Rate Weight-based (~8- 20min) 7x faster than FFP 3 Each unit over 30-60 min Considerations Less volume and faster administration = faster restoration of factor levels 3 Dilutional coagulopathy Risk of transfusion- related acute lung injury

67. Coagulation Cascade Image borrowed from AnaesthesiaUK at http://www.frca.co.uk/images/clotting_cascade.gif Action of oral anticoagulants: Warfarin inhibits factors II, VII, IX, and X (vitamin K dependent clotting factors). Novel oral anticoagulants (NOACs) inhibit either factor Xa or IIa.

68. 68 Emergent Warfarin Reversal 1-4,7 Warfarin prevalent; worse trauma outcomes 1 Kcentra approved for warfarin reversal in either: Acute major bleed (head, spine, uncontrolled GI, extremity/compartment syndrome) Urgent surgery or invasive procedure within 6h 2 INRReversal ≤ 1.5vitamin K 5 - 10 mg IV STAT 1.6 – 1.9 vitamin K + FFP 2.0 – 3.9 Kcentra 25 un/kg (max 2500 un) ± vitamin K IV 4.0 – 6.0 Kcentra 35 un/kg (max 3500 un) ± vitamin K IV > 6.0 Kcentra 50 un/kg (max 5000 un) ± vitamin K IV For vitamin K administration in non-emergent warfarin reversal, see 2012 Chest Guideline 7.

69. 69 Emergent NOAC (Novel Oral Anticoagulant) Reversal Strategies 8-12 NOAC Drug Class Factor Xa Inhibitors Direct Thrombin (IIa) Inhibitor NOAC Agents apixaban (Eliquis) rivaroxaban (Xarelto) dabigatran (Pradaxa) Coagulation Testsanti-Xa, PT, aPTTECT, dilute TT, aPTT Activated Charcoal?Yes, if last dose < 2h ago. Hemodialysis?Not useful.Yes – prolonged (2h+) PCC to reverse? Kcentra 25 – 50 un/kg Alternative Reversals? ? FEIBA 25 un/kg 10 aDabi-Fab (future) 11

70. 70 Management of Trauma Hemorrhage – Standards of Care 16 Consider TXA early (bleeding or at risk) Correct hypothermia, acidosis, hypotension Maintain Hgb (7-9 g/dL), platelets (50-100k) Fibrinogen – maintain > 1.5 – 2 mg/dL 19 Depleted earlier than blood factors at 142% blood loss vs. 200-240% before fII, fVII critically low 13 Risk factors for low fibrinogen level on admission 14 : injury severity score, shock, SBP<90, prehospital fluid needs Calcium – maintain iCa > 0.9 20

71. 71 PCC in Trauma Hemorrhage Evidence of benefit – evolving. Lack of prospective trials demonstrating mortality benefit Retrospective reports demonstrate decreased INR, bleeding, need for PRBCs, stabilized blood pressure 22-25 Guidelines differ 16,17 ; local use positive Thrombosis risk: low (0-1.4% for current 4fPCCs) Exclusion criteria: DIC, HIT optimal Kcentra dose: uncertain. (?25-50 un/kg; max 100kg) Possible role of PCC in: Massive hemorrhage unresponsive to conventional tx TEG-guided: ongoing bleed with CT > 90s 15 Hgb-driven “Coagulation Box” model: Hgb < 5.5 26

72. 72 Kcentra – Nursing Considerations Verbal orders Clarify which “PCC”, what un (fIX)/kg dose, indication Contact blood bank or pharmacy to alert of STAT order Administration Weight-based dose; rate variable (~10-20 min) Emergent reversal. Give ASAP (expires 4hrs after mixed) Document lot numbers (blood product) Monitor for allergic reactions and thrombosis (0.9- 1.4%) Cost

73. 73 References 1.Dossett LA, Riesel JN, Griffin MR, Cotton BA. Prevalence and implications of preinjury warfarin use: an analysis of the National Trauma Database. Archives of Surgery. 2011. 2.National Advisory Committee on Blood and Blood Products. Recommendations for use of prothrombin complex concentrates in Canada. Accessed on 11/7/2014. http://www.nacblood.ca/guidelines/PCC-Recommendations-Final-2014-05-16.pdf. 3.Kcentra website: www.Kcentra.com. Maintained by CSL Behring. Accessed on 11/7/14.www.Kcentra.com 4.Lexi-Comp, Inc. (Lexi-Drugs). Lexi-Comp, Inc.;January 29, 2015. 5.Tanaka KA, Szlam F. Treatment of massive bleeding with prothrombin complex concentrate: argument for. J Thromb Haemost. 2010;8:2589-91. 6.Godier A, Susen S, Samama C-M. Tanaka KA, Szlam F. Treatment of massive bleeding with prothrombin complex concentrate: argument against. J Thromb Haemost. 2010;8:2592-95 7.Holbrook A, Schulman S, Witt DM, et al. Evidence-Based Management of Anticoagulant Therapy. Antithrombotic Therapy and Prevention of Thrombosis, 9 th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2)(Suppl):e152S-e184S. 8.Nutescu EA, Dager WE, Kalus JS, Lewin JJ, Cipolle MD. Management of bleeding and reversal strategies for oral anticoagulants: Clinical Practice Considerations. Am J Health-Syst Pharm. 2013;70:1914-1929. 9.Tran H, et al. New oral anticoagulants: a practical guide on prescription, laboratory testing and peri-procedural/ bleeding management. Int Med J. 2014;44:525-536. 10.Dager WE, Gosselin RC, Roberts AJ. Reversing dabigatran in life-threatening bleeding occurring during cardiac ablation with factor eight bypassing activity. Crit Care Med. 2013; 41(1):e42-46. 11.Grottke O, van Ryn J, Sprink HMH, Rossaint R. Prothrombin complex concentrates and a specific antidose to dabigatran are effective ex-vivo in reversing the effects of dabigatran in an anticoagulation/liver trauma experimental model. Crit Care. 2014;18:R27. 12.Dickneite G. Prothrombin Complex Concentrates as Reversal Agents for New Oral Anticoagulants: lessons from preclinical studies with Beriplex. Clin Lab Med. 2014;34:623-635.

74. 74 References, cont. 13.Hiippala ST, Mllyla GJ, Vahtera EM. Hemostatic Factors and Replacement of Major Blood Loss with Plasma-Poor Red Cell Concentrates. Anesth Analg. 1995;81:360-5. 14.Rourke C, et al. Fibrinogen levels during trauma hemorrhage, response to replacement therapy, and association with patient outcomes. J Thromb Haemost. 2012;10:1342-51. 15.Sorensen B, Fries D. Emerging treatment strategies for trauma-induced coagulopathy. Brit J Surg. 2012;99(Suppl1): 40-50. 16.Spahn DR, et al. Management of bleeding and coagulopathy following major trauma: an updated European guideline. Crit Care. 2013;17:R76. 17.Kozek-Langenecker SA, et al. Management of severe perioperative bleeding. Guidelines from the European Society of Anaesthesiology. Eur J Anaesthesiol. 2013;30:270-382. 18.Fries D. The early use of fibrinogen, prothrombin complex concentrate, and recombinant-activated factor VIIa in massive bleeding. Transfusion. 2013;53(s):91s-95s. 19.Tanaka KA, Esper S, Bolliger D. Perioperative factor concentrate therapy. Brit J Anaesth. 2013;111(S1): i35-i49. 20.Schochl H, Grassetto A, Schlimp CJ. Management of Hemorrhage in Trauma. J Cardiothor Vasc Anesth. 2013;27(4): S35-S43. 21.Franchini M, Lippi G. Prothrombin complex concentrates: an update. Blood Transfus. 2010;8:149-54. 22.Joseph B, et al. Factor IX complex for the correction of traumatic coagulopathy. J Trauma. 2010;72(4):828-834. 23.Schick KS, Fertmann JM, Jauch KW, Hoffmann JN. Prothrombin complex concentrates in surgical patients: retrospective evaluation of vitamin K antagonist reversal and treatment of severe bleeding. Crit Care. 2009;13:R191. 24.Carvalho MC, Rodrigues AG, Conceicao LM, Galvao ML, Ribeiro LC. Prothrombin complex concentrate (Octaplex): a Portuguese experience in 1152 patients. Blood Coag Fibrin. 2012;23:222-228. 25.Lorenz R, et al. Efficacy and safety of a prothrombin complex concentrate [Beriplex] with two virus-inactivation steps in patients with severe liver damage. Eur J Gastroenterol Hepatol. 2003;15:15-20. 26.Hilbert P, et al. The “Coagulation Box” and a New Hemoglobin-Driven Algorithm for Bleeding Control in Patients with Severe Multiple Traumas. Arch Trauma Res. 2013;2(1):1-10. 27.Majeed A, Eelde A, Agren A, et al. Thromboembolic safety and efficacy of prothrombin complex concentrates in the emergent reversal of warfarin coagulopathy. Thromb Res. 2012;129:146-51. 28.Innerhofer P, et al. The exclusive use of coagulation factor concentrates enables reversal of coagulopathy and decreases transfusion rates in patients with major blunt trauma. Injury, Int J Care Injured. 2013;44:209-216.

75. Thank you Questions? jdace@mhsjvl.org

77. TXA (tranexamic acid) Christopher Wistrom DO Associate EMS Medical Director Mercy Health Systems 12/4/2014

78. What Is It? TXA is a lysine derivative compound. That blocks fibrin receptor site on plasminogen therefore doesn’t allow fibrin to bind and secures the integrity of the already existing clot

79. In the Literature CRASH-2 MATTERS MATTERS 2 CRASH-3

80. CRASH-2 20,211 patients 274 hospitals 40 countries 10,096 with TXA 10,115 placebo Results – Treatment within 1 hour of injury Mortality TXA group 5.3% v. Placebo 7.7% – Treatment within 3 hours of injury Mortality TXA group 4.8% v. Placebo 6.1% – No effect on Vascular occlusive events

81. MATTERs Retrospective study with 900 NATO casualties TXA reserved for more severely injured Results No difference in mortality at 24 hours 28 days TXA group with half the mortality of non TXA group

82. MATTERs-2 Retrospective observational study 1332 patients from Trauma Registry 4 groups with endpoint of mortality at discharge – TXA 18.2% – Cryoprecipitates 21.4% – TXA and Cryo 11.6% – Neither 23.6%

83. CRASH3 Currently underway Seeing to answer question of TXAs utility in isolated head trauma Goal to enroll 10,000 patients No answers on this yet At this time NO indication for TXA in isolated head trauma

84. Dosing 10mg/kg bolus given over 10 min – Standard adult dose is 1 G 10mg/kg infusion over 8 hours

85. In the hospital Has a history of use in orthopedic surgery Also has been used by some OB-GYNs Dentists and oral surgeons have used the product for decades

86. In the streets Is being used by progressive EMS systems throughout the country Several Helicopter services Ground based crews Using standard CRASH-2 Criteria for patient selection (hx of trauma and either tachycardia or hypotension)-contraindicated for isolated head trauma at this time

87. On the battlefield Standard of care In conjunction with tourniquet use has saved countless lives and dramatically decreased all cause mortality Since CRASH-2 the WHO has added TXA to list of essential drugs

88. Over the counter Japan and UK sold OTC for Menorrhagia

89. Why is this important? All indicators at this time point to TXA being a highly useful therapy for those with trauma associated life threatening bleeding Best results are if given within the first hour No signs at this time of any increase in DVT/PE Cheap. Easy. Safe

90. TAKE HOME POINTS TXA decreases mortality if given early (earlier the better) TXA does not increase risk for DVT/PE TXA not currently indicated for isolated head trauma It will be showing up in an ED near you, and needs to be followed up with infusion in ICU/OR

91. Works cited TXA http://www.nytimes.com/2012/03/21/health/tranexamic- acid-cheap-drug-is-found-to-staunch-bleeding.html?_r=0 http://www.nytimes.com/2012/03/21/health/tranexamic- acid-cheap-drug-is-found-to-staunch-bleeding.html?_r=0 The CRASH-2 Collaborators. Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant hemorrhage(CRASH-2): a randomised, placebo-controlled trial. Lancet 2010; 376:23- 32.. Morrison JJ, Dubose JJ,Rasmussen TE,Midwinter, MJ. Military Application of Tranexamic Acid in Trauma Emergency Resuscitation(MATTERs) Study. Arch Surg 2012; 147:113-9. JAMA Surg. 2013 Mar;148(3):218-25. doi: 10.1001/jamasurg.2013.764. JAMA Surg.

94. Source: CDC.gov and bls.gov

95. The Casualty Care in the Classroom task force was formed in January in response to an active shooter tabletop drill mediated by the FBI last winter with participants from all city services and other local agencies.

96. Why Leading cause of preventable death in trauma? How has the military approached this? Global war on terror medical studies. Application to civilian setting

97. Others Attempts Not a truly novel idea-it has been tried Others have tried expensive, invasive kits with a large training burden Also have tried simple kits with poor education and implementation plans

98. Development Multidisciplinary team effort Law Enforcement EMS/FD Medical Professionals Educators

99. Our Program Cost effective Local approach Local teachers School specific implementation Plan for sustainability Blanket type distribution and training

100. For More Information E-mail- mhsCCC@mhsjvl.orgmhsCCC@mhsjvl.org Or visit our website at – http://onlinemercy.com/casualtycarekits/ http://onlinemercy.com/casualtycarekits/