U.S. Army Institute of Surgical Research

1. Far-forward Resuscitation of Combat Trauma Without RBCs or Whole Blood? U.S. Army Institute of Surgical Research LTC(P) Andrew P. Cap, MS, MD, PhD, FACP Chief, Coagulation and Blood Research Program, USAISR Program Director, SAMMC Clinical Research Fellowship Associate Professor of Medicine, Uniformed Services University Adjunct Associate Professor, University of Texas Medical Director, Akeroyd Blood Donor Center

2. Disclaimer: The opinions or assertions contained herein are the private views of the author and are not to be construed as official or as reflecting the views of the Department of the Army or the Department of Defense.

3. Unmet Military Need for Resuscitation of Hemorrhage BLUF • Optimal trauma/hemorrhagic shock treatment • Bleeding = #1 cause of preventable death • Hemorrhage control • Resuscitation that delivers oxygen, mitigates coagulopathy • EARLY TREATMENT CRITICAL TO SUCCESS • Blood-based resuscitation is best… • Functionality of whole blood delivered ASAP (WB or 1:1:1)  but may not be available • We need better options than crystalloid/ colloid (oxygen delivery w/o worsening coagulopathy).

4. US Military Death Distribution 4,596 Combat Deaths (2001-11) DOW Died of Wounds (Level II and above) 506 deaths Killed in Action (Level I) 4,090 deaths Total Pre-MTF Combat Deaths 4,090 Potentially Survivable Deaths 1,075 (26%) Hemorrhage 984 (91.5) Airway 69 (6.4) Other 22 (2.0) Potentially Survivable Hemorrhage 984 (24%) Truncal 675 (17%) Junctional 170 (4%) Extremity 139 (3%) KIA Eastridge et al. J Trauma 2013.

5. 10% of Combat Casualties: high risk of bleeding to death • Numbers to keep in mind: • 58,831 = dead + wounded in IRQ & AFG • 53,724 = survivors + potential survivors • 8,836 transfused, ≈50% MT, avg. 12.3 • ≈1,500 bled to death w/o transfusion • before reaching hospital (failed current pre-hospital therapy) • At least 10% of injured soldiers are at very high risk of death due to hemorrhage. • NB: assuming current levels of battlefield lethality – could get worse… http://www.defense.gov/news/casualty.pdf ASBPO Blood Transfusion update

6. Twin Challenges of Resuscitation • Maintain Oxygen Delivery (DO2)/ pay Oxygen Debt • Dependent on Cardiac Output (CO) and Hemoglobin (Hgb) • Improving delivery: more red blood cells in tank (transfusion) or increase pumping • Below “DO2crit”, oxygen consumption becomes directly dependent on DO2 • This is unsustainable! Oxygen debt must be repaid! • Avoid/ treat coagulopathy: • Dysfunction of coagulation system, endothelium and platelets following tissue injury and hypoxia • Worsened by hemodilution, acidosis, hypothermia (contribution of crystalloid/colloid resuscitation) • Compromised hemostasis worsens bleeding: bloody vicious cycle

7. How do we meet these challenges? • Early hemorrhage control • Tourniquets, hemostatic dressings • Blood-based resuscitation • Functionality of whole blood delivered ASAP (WB or 1:1:1) • Rapid delivery to surgical care • US goal is <1 hour

8. Time to Death: KIA/DOWGolden Hour is too late… JTS 2016.

9. Pre-Hospital Transfusion Saves! Transfused on US MEDEVAC or not within 30-35 min of injury Shackelford, Del Junco MHSRS 2016.

10. Pre-Hospital Transfusion Saves!This should not be surprising… This matters even during short evacuations! Relevant to civilian medicine! Shackelford, Del Junco MHSRS 2016.

11. Timing is everything. *34 min from injury Increasing duration of shock is not helpful! Think BLS. Shackelford, Del Junco MHSRS 2016.

12. Golden Hour is too late…NEED BLOOD at POI JTS 2016.

13. Challenges of our current approach… Depends on rapid helicopter evacuation to surgical care (<1 hour) Massive logistical challenge including cold chain to supply blood products from US In-theater collection of WB & platelets possible but donor pools may be limited in some circumstances

14. The Good Old Days… Ahh, good old Bagram…

15. Brave New World…

16. Evac & “first MTF” considerations • Assume CASEVAC, not MEDEVAC (> 1hr) • Assume “first MTF” is, at best, Role 2

17. STRATEVAC considerations • May have to use smaller platforms • In-flight critical care constraints

18. This is going to be more complicated, but even more important! • Reduced logistical footprint, reduced medical support • Tyranny of distance = long evac • Endemic disease VS.

19. And then there’s this problem:A2AD No helicopters = No timely evac No blood resupply What to do if you can’t you can’t patient to blood or blood to patient?

20. TCCC Risk Mitigation • Walking Blood Bank (e.g., 75th Ranger Regiment ROLO) • Best overall solution, but: • Optimal for platoon or larger elements • For small SOF teams, quantities highly constrained • Need highly trained personnel, equipment • Requires pre-deployment TTD testing/ anti-A/B titers • Type-specific WB availability is slow (type donor & recipient) • Dried plasma • Volume expansion • Avoidance or treatment of coagulopathy • Endothelial benefits • No oxygen carrying • Worst case: crystalloid/colloid. Can we do better??

21. Things to avoid (doing harm) • Crystalloid • WT/volume for medic • Minimal intravascular resuscitation • Tissue edema • Acidosis with saline; all cause hemodilution (coagulopathy) • Starch (Hextend, etc.) • Hemodilution • Acquired vWD/FVIII deficiency & platelet dysfunction  worsens bleeding • All other colloids: hemodilution, no oxygen carrying • We need relatively stable products that: • Carry oxygen • Without aggravating coagulopathy (give w/ plasma or fibrinogen+ TXA?)

22. Future ROLO protocol? 75th Rangers ROLO Protocol Insert “Product X” here if FWB unavailable?

23. Questions?