Tranexamic Acid (TXA)

1. Tranexamic Acid (TXA) Training requirements for State EMS Authority approved Local Optional Scope of Practice Please see updated protocols in general updates Procedure #706 – Hemorrhage Control Protocol #660 – General Trauma Protocol #661 - Traumatic Cardiac Arrest

2. Recognition of hemorrhagic shock • Review Tranexamic Acid (TXA) • Indications for use • Action • Contraindications • Dosing • Adverse reactions • Discuss communication/documentation needed for hospital handoff report Objectives

3. Hemorrhagic Shock

4. Systemic reduction in tissue perfusion below that which is necessary to meet metabolic needs of tissues and organs • Hypoperfusion results in oxygen debt • Hypoperfusion is a time dependent event Definition: Hemorrhagic SHOCK

5. Change in mentation • Tachycardia • Hypotension • Cool, Clammy skin • Prolonged capillary refill • Narrowed pulse pressure Classic signs of shock

6. Signs can be difficult to appreciate in early shock and can be missed until the patient is in trouble • Compensatory mechanisms allow significant reductions in circulating blood volume, stroke volume, and cardiac output to occur well before changes in systolic BP Patients don’t suddenly deteriorate, rather we suddenly notice…

7. Maintain a high-index of suspicion for occult hemorrhage: • Internal bleeding • Ongoing venous oozing • Open fractures • Bleeding covered by bandages • Epistaxis, vaginal bleeding, GI bleeding • Anticoagulated patients Patients don’t suddenly deteriorate, rather we suddenly notice…

8. Systolic BP drop is a late sign • Systolic BP does not fall until: • Adults 30% blood loss • Pediatrics 40-45% blood loss • SBP < 90 mm Hg: mortality approaches 65% Blood Pressure

9. Humerus 750ml • Tibia 750ml • Femur 1500ml • Pelvis > 3L • Soft tissue trauma can increase fluid loss with the activation of inflammatory response that increase vascular permeability Fracture-associated blood loss

10. Injury to blood vessel attracts • Clotting factors • Platelets • Activated platelets begin to trap blood cells TXA Mechanism of Action

11. Platelet plug is unstable and may not stop all bleeding Strands of fibrin begin to wind into platelet plug Fibrin stabilizes plug Plasmin Plasmin is present in blood in its inactive form (plasminogen) Degraded Fibrin • Activated Plasmin degrades Fibrin • Fibrinolysis • Inhibits formation of a stable clot TXA Mechanism of Action

12. TXA blocks Plasminogen from being converted into activated Plasmin Plasmin • Reduction of circulating Plasmin: • Less fibrinolysis • Clots are not broken down • More rapid formation of stable clots Degraded Fibrin TXA Mechanism of Action

13. Classification: • Plasminogen inactivator • Anti-fibrinolytic • Action: • Inhibits conversion of plasminogen to plasmin • Reduces fibrinolysis and clot breakdown • Stabilizes clot formation Classification & Action

14. Blunt or penetrating traumatic injury with SBP ≤90 • Significant blood loss with ongoing bleeding not controlled by direct pressure, hemostatic agents, or tourniquet application • External bleeding should be managed with the methods listed above • TXA is given only if these measures are not successful • Base hospital consultation and orders • Unclear on indications • Other causes of life-threatening hemorrhage • i.e. GI bleeding, vaginal bleeding, ENT post-op, etc Indications

15. Patients less than 15 years old • Greater than 3 hours post injury • Isolated Traumatic Brain Injury • Isolated spinal shock • Spinal injury with motor signs and hypotension • Isolated extremity hemorrhage when bleeding has been controlled • TXA should not be used in trauma patients with these isolated injuries • TXA is NOT contraindicated in a trauma patient with hemorrhagic shock AND associated TBI/spinal injuries/ extremity injuries Contraindications

16. Hypotension with rapid IV infusion • Chest tightness • Difficulty breathing • Facial flushing • Blurred vision • Nausea/Diarrhea Adverse Reactions

17. Base contact, consultations, and destination for patients receiving TXA should be a trauma center • SVRMC or MRMC • SLO County Policy #121 • Patient will likely require: • Massive Transfusion Protocols (MTP) • Repeat doses of TXA • Surgical interventions • Other interventions Transport to a Trauma Center

18. CRASH2 trial (2010): • If given within three hours of injury, TXA reduces the risk of death due to bleeding by about a third • http://www.crash2.lshtm.ac.uk/ MATTERS trial (2011): • Marked improvement in survival in most severely injured compared to those who did not receive it • https://jamanetwork.com/journals/jamasurgery/fullarticle/1107351 CalPAT Trial (2017) California Prehospital Antithrombolytic Trial: • TXA reduced 30-day mortality from 8.3% to 3.6% • Mortality benefit greater in more seriously injured patients References, Clinical Trials

19. Mixing instructions: • 1gm of TXA into 100mLNormal Saline (NS) • Inject through injection port • Use full 100 mL bag of NS, or • Burette filled with 100 mL of NS • Label the bag/burette with the drug name and final concentration • “TXA 1gm in 100mL” Dosage and Administration

20. Administer 1 gm in 100mLNS IV/IO over 10 min • No repeat • Delivery of a highly specific concentration is not necessary • Dilution and infusion rate are safety measures to mitigate adverse reactions • Use Macrodrip tubing • Infuse >10 min • 10 gtts tubing <100 drops/min • 15 gtts tubing <150 drops/min Dosage and Administration

21. TXA may be infused while fluid bolus is being administered for hypotension • Protocol #660 – titrated bolus UP TO 500 mL • Goal is to limit total IV fluids administered while maintaining perfusion • Target is to treat with permissive hypotension • Count TXA volume in total volume of fluids • TXA may be infused through a second IV while titrated fluid bolus is being rapidly administered through primary IV • Use a saline extension so that TXA may be removed once infusion is completed • TXA may be piggybacked on primary line of NS • Piggybacked TXA should be hung higher then the NS so that the TXA infuses first • This will slightly limit the rate of the fluid bolus Dosage and Administration

22. TXA Local Optional Scope of Practice is approved by the State EMS Authority. Special reporting requirements on TXA use. Required prehospital documentation: • ePCR • During hospital verbal report/handoff Document: • Time of injury - confirm <3 hours • Time of administration of TXA • Any adverse reactions Communication/Documentation

23. TXA works to prevent clot breakdown • Administer to trauma patients, age ≥15 with: • Blunt or penetrating injury with SBP ≤90 • Significant blood loss/bleeding not controlled by BLS measures • Use base physician orders for other life-threatening bleeding • Must be started within 3 hours of injury • Receiving hospital must be informed of the injury time and time of 1st dose TXA Summary

24. End of Presentation Please Review: 2019 General Updates Pain Management and Fentanyl Vasopressor Doses of Epinephrine