1. HEMORRHAGE RESUSCITATION AND MASSIVE TRANSFUSION PROTOCOLS CAPT William C. Brunner, MC, USN Senior Medical Officer, BSRF-2013 Assistant Professor, Department of Surgery

2. Disclosures The speaker has no relevant financial relationships with commercial interests that pertain to the content of this presentation

3. Objectives Review History of Trauma Resuscitation Discuss Coagulopathies in Trauma Discuss Integrated Damage Control Review Blood Component Preparations Discuss Individual Component Transfusion Guidelines Discuss Massive Transfusion Protocols Discuss Future Research Areas

4. History of Trauma Resuscitation World War I – Little or no systematic resuscitation after injury – Blood banking developed World War II – Widespread use of blood and albumin – Long, slow evacuation – Significant organ failure – renal, pulmonary – Late deaths from sepsis

5. History of Trauma Resuscitation Korean War – Forward Surgical Care – Rapid Care – Evacuation to Definitive Treatment – Blood and albumin as in WWII Vietnam War – Rapid evacuation – Large-volume resuscitation with blood/crystalloid – Da Nang Lung (ALI/ARDS)

6. History of Trauma Resuscitation Civilian Experience – Trauma Registries and Research – Empiric high-volume crystalloid resuscitation – Iatrogenic Coagulopathy after Trauma recognized – Directed Component Therapy Requires Laboratory evidence Empiric therapy limited – Massive Transfusion Protocols

7. History of Trauma Resuscitation Military Experience – Iraq and Afghanistan Limited Component availability Recognition of crystalloid inflammatory response Whole blood transfusion Walking Blood Bank – Simple technology – Screened donor population readily available

8. Acute Traumatic Coagulopathy Recognized in patients with significant tissue injury and hypotension Distinct from iatrogenic coagulopathy after trauma – Dilutional coagulopathy Present prior to resuscitation in rapidly evacuated severe trauma Mortality rate increased 4x Modulated through protein C activation

9. Integrated Response Damage Control Surgery – Rapid, limited, forward surgical care Control bleeding Control spillage Control contamination Restore perfusion – Avoid unnecessary interventions – Allow for resuscitation – Rapid evacuation Hemostatic Resuscitation – Limited volume – Permissive hypotension – Balanced transfusion High FFP:PRBC ratio – Colloid vs. crystalloid – Attenuate ATC – Expand resource availability Walking blood bank Freeze-dried plasma

10. Blood Components ComponentIndicationStorage TimeDisadvantage Whole BloodVolume deficit, O2 carrying capacity, massive transfusion 35 days (2°-6° C) 24 hrs fresh Short shelf life PRBCsVolume deficit, O2 carrying capacity 42 daysImmunomodulation Leukocyte-reduced PRBCs Cardiac surgery, prevent CMV infection, reduce febrile reaction and alloimmunization 42 daysCost Washed PRBCsPrevention of allergic reactions24 hrsPlasma depletion FFPCoagulopathy, warfarin reversal1 year CryoprecipitateVon Willebrand disease, Fibrinogen deficiency 1 year PlateletsMicrovascular bleeding, thrombocytopenia 5-7 daysRisk of transfusion- associated sepsis

11. Component Therapy Advantages – Wider use of limited resources 1 donated unit – multiple products – Longer storage life – Lower costs in elective use – More predictable availability Disadvantages – Multiple donor antigen exposure – Less efficacy in high volumes, Lab costs

12. Component Transfusion Guidelines Fresh Frozen Plasma – Prothrombin Time (PT) > 17 sec – Clotting Factor Deficiency (<25% of normal) – Massive Transfusion (1 unit/5units RBCs) or clinically bleeding – Severe Traumatic Brain Injury Cryoprecipitate – Fibrinogen < 100mg/dL – Hemophilia A, von Willebrand disease – Severe Traumatic Brain Injury

13. Component Transfusion Guidelines Platelets – Platelet count < 10,000/uL – Platelet count 10,000 to 20,000 with bleeding – Platelet count < 50,000 after severe trauma – Bleeding Time > 15 mins – Platelet concentrates (5.5 x 10 10 in 50ml) – Platelet apheresis (3 x 10 11 in 300ml)

14. Component Transfusion Guidelines Packed Red Blood Cells (PRBCs) – Hemoglobin < 7g/dL – Acute blood volume loss > 15% – > 20% decrease in BP, or BP <100mm Hg due to blood loss – Hemoglobin < 10g/dL with significant cardiac disease or symptoms (chest pain, dyspnea, fatigue, orthostatic hypotension) – Hemoglobin < 11g/dL in patient at risk for MOF

15. Massive Transfusion Defined as > 10 units PRBCs within 24 hrs 25-30% of trauma patients requiring massive transfusion will present with Acute Traumatic Coagulopathy (ATC) – Penetrating mechanism – Positive FAST – Arrival SBP 120 bpm – Unstable pelvic fracture – pH < 7.25, base deficit

16. Massive Transfusion Protocol Advantages – More closely replicate whole blood physiology with components – Retain shelf-life advantage of components – 25-30% reduction in PRBCs used – Predictable workload Disadvantages – Processing time limitations – Limited applicability

17. Massive Transfusion Protocol PackagePRBCs (Units)FFP (Units)Platelets (Units) Other 166 2661 apheresis 366Cryoprecipitate rFVIIa 4661 apheresis 566 666 Cryoprecipitate rFVIIa Data from O’Keeffe T, Refaai M, Tchorz K, et al: A massive transfusion protocol to decrease blood component use and costs, Arch Surg 143:686-691, 2008.

18. Massive Transfusion Protocol Typically start with 2-6 units Type O blood – Initial “emergency-release” – Subsequent units type-specific, cross-matched FFP processing time – ER prestaging thawed plasma, shelf-life 4-5 days Protocols can enhance effective use of staffing and resources

19. Special Situations Autotransfusion – Limited applicability due to capture, possible contamination Blood salvage – Intraoperative or postoperative – Labor intensive, expensive, limited utility Autologous donation, Hemodilution not applicable to trauma setting

20. Areas for Future Study Determine optimal therapeutic ratio of PRBC:FFP – PROPPR Study - 1:1:1 vs. 1:1:2 PRBC/PLT/FFP Further delineate ATC physiology and identify clinically useful modulators Delineate impact of high-ratio therapy on sub- MT trauma population Blood component substitutes Crystalloid alternatives

21. References McIntyre RC Jr., Moore FA; Blood Transfusion Therapy, Chapter 212, Current Surgical Therapy, 10 th Edition, Philadelphia, PA, 2011. Adams CA Jr., Stephen A, Cioffi WG; Surgical Critical Care, Chapter 23, Sabiston Textbook of Surgery, 19 th Edition, Philadelphia, PA 2012. Chovanes J, Cannon JW, Nunez TC; The Evolution of Damage Control Surgery, Surg Clin N Am 92 (2012) 859-875.

22. References Cohen MJ. Towards Hemostatic Resuscitation: The Changing Understanding of Acute Traumatic Biology, Massive Bleeding, and Damage-Control Resuscitation. Surg Clin N Am 92 (2012) 877-891. Committee on Trauma, American College of Surgeons. ATLS: Advanced Trauma Life Support Student Course Manual, 9 th Edition. Chcago: American College of Surgeons; 2012.