1. Damage Control Resuscitation Gregory W. Jones M.D. CDR MC USN Naval Hospital Camp Pendleton

2. “Damage Control Resuscitation represents the most important advance in trauma care for hospitalized civilian and military casualties from this war.” Cordts, Brosch and Holcomb, J Trauma, 2008

3. Acknowledgment Thanks to COL Jay Johannigman, MC, USAF, for his significant contributions to this presentation.

4. Case Data 25 year old SGT involved in IED blast Tourniquet applied at scene one hour ago Systolic BP 90 Mental Status: Awake, confused Blood oozing from superficial wounds Temp 96 F

5. Patient Assessment Sick or Not Sick What are reliable criteria for initial assessment? Which criteria can predict outcomes and direct therapy?

6. New Diagnostic criteria Avoids the “but he looked good” phenomenon Within the first five minutes in the ED –Identify patients in trouble –Identify patients with increased mortality –Identify patients with increased probability of massive transfusion

7. The Lethal Triad Acidosis Hypothermia Coagulopathy Death Brohi, K, et al. J Trauma, 2003.

8. Damage Control Resuscitation Acidosis- Base Deficit > - 6 Coagulopathy – INR > 1.5 Hypotension – Systolic B/P < 90 Hemoglobin - < 11 Temperature - < 96. 5 Pattern recognition Weak or absent radial pulse Abnormal mental status Severe Traumatic Injury

9. Challenges Requires robust Medical setting Need system approach to deliver casualties to most capable facilities Isolated and far forward facilities can still benefit from these principles

10. AcidosisAcidosis Base deficit (BD) ≥ 6 identifies patients that –require early transfusion, –increased ICU days and –risk for ARDS and MOF BD of ≥ 6 is strongly associated with the need for MT and mortality in both civilian and military trauma. Patients have an elevated BD before their blood pressure drops to classic “hypotension” levels. Acidosis contributes more to coagulopathy more than hypothermia (not reversible) Base deficit (BD) ≥ 6 identifies patients that –require early transfusion, –increased ICU days and –risk for ARDS and MOF BD of ≥ 6 is strongly associated with the need for MT and mortality in both civilian and military trauma. Patients have an elevated BD before their blood pressure drops to classic “hypotension” levels. Acidosis contributes more to coagulopathy more than hypothermia (not reversible)

11. Coagulopathy on Presentation An initial INR ≥ 1.5 reliably predicts those military casualties who will require MT. Pts who have a significant injury present with a coagulopathy. Severity of injury and mortality is linearly associated with the degree of the initial coagulopathy. An initial INR ≥ 1.5 reliably predicts those military casualties who will require MT. Pts who have a significant injury present with a coagulopathy. Severity of injury and mortality is linearly associated with the degree of the initial coagulopathy.

12. Coagulopathy and Trauma Derangements in coagulation occur rapidly after trauma By the time of arrival at the ED, 28% (2,994 of 10,790) of trauma patients had a detectable coagulopathy that was associated with poor outcome Brohi Graph Here (Brohi et al., 2003)

13. HypotensionHypotension A systolic blood pressure of 90 mm Hg or less is indicative casualties that have lost over 40% of their blood volume –(~2000 ml in an adult) –They have impending cardiovascular collapse and have significantly increased mortality. A systolic blood pressure of 90 mm Hg or less is indicative casualties that have lost over 40% of their blood volume –(~2000 ml in an adult) –They have impending cardiovascular collapse and have significantly increased mortality.

14. HemoglobinHemoglobin Otherwise young healthy soldiers with a Hgb of < 11 have only one reason for their anemia, namely acute blood loss.

15. TemperatureTemperature A temperature < 96°F or 35°C is associated with an increase in mortality. Trauma patients that are hypothermic are not perfusing their tissue The coagulation cascade is an enzymatic pathway that degrades with temperature and ceases at 92 F A temperature < 96°F or 35°C is associated with an increase in mortality. Trauma patients that are hypothermic are not perfusing their tissue The coagulation cascade is an enzymatic pathway that degrades with temperature and ceases at 92 F

16. Diagnosis done Diagnosis Done –How to resuscitate these casualties? Diagnosis Done –How to resuscitate these casualties? Damage Control Resuscitation 1. Hypotensive resuscitation 2. Hemostatic resuscitation

17. Hypotensive Resuscitation Time Honored technique developed by Military physicians during WWI and WWII Maximizing the resuscitation benefit to the mitochondria while minimizing rebleeding by avoiding “popping the clot” Supported by a significant body of scientific data. This approach preserves the resuscitation fluid within the vascular system Logistically sound by preventing needless waste of blood and fluids. Time Honored technique developed by Military physicians during WWI and WWII Maximizing the resuscitation benefit to the mitochondria while minimizing rebleeding by avoiding “popping the clot” Supported by a significant body of scientific data. This approach preserves the resuscitation fluid within the vascular system Logistically sound by preventing needless waste of blood and fluids.

18. Hemostatic Resuscitation Damage control philosophy can be extended to hemostatic resuscitation restoring normal coagulation minimizing crystalloid Traditional resuscitation strategies dilute the already deficient coagulation factors and increase multiple organ failure The aggressive hemostatic resuscitation should be combined with equally aggressive control of bleeding Damage control philosophy can be extended to hemostatic resuscitation restoring normal coagulation minimizing crystalloid Traditional resuscitation strategies dilute the already deficient coagulation factors and increase multiple organ failure The aggressive hemostatic resuscitation should be combined with equally aggressive control of bleeding

19. Standard Resuscitation Paradigm Crystalloid 3:1 Ratio Blood FFP Transient or no response 6-10 u PRBC Crystalloid Oh- By the way: show me the data

20. Hemostatic Resuscitation 1. Early Dx in ED 2. 1:1 ratio (PRBC to FFP) 3. ED use of rFVIIa 4. Call for FWB from the ED 5. Frequent cryo and platelets 6. Repeated doses of rFVIIa in OR and ICU as required 7. Minimal crystalloid 1. Early Dx in ED 2. 1:1 ratio (PRBC to FFP) 3. ED use of rFVIIa 4. Call for FWB from the ED 5. Frequent cryo and platelets 6. Repeated doses of rFVIIa in OR and ICU as required 7. Minimal crystalloid

21. Thawed Plasma Thawed plasma should be used as a primary resuscitative fluid. This product should be present upon arrival of the casualty in the ED This approach not only addresses the metabolic abnormality of shock, but initiates reversal of the coagulopathy present in the. Thawed plasma should be used as a primary resuscitative fluid. This product should be present upon arrival of the casualty in the ED This approach not only addresses the metabolic abnormality of shock, but initiates reversal of the coagulopathy present in the.

22. Electrolytes (mmol/L) average unit of FFP ~ 300cc Na 165 (48mmol/unit) K 3.3 (1.0mmol/unit) Glucose20 Calcium1.8 Citrate20 Lactate3 pH 7.2-7.4 (LR 6.5, NS 5.0) Phosphate3.63 Plasma Composition

23. 1:1 Ratio of PRBC to Plasma Increased FFP transfusions within first 24 hrs of admission were independently associated with increased survival. Median ratio of FFP: RBC was 1:1.7 in survivors compared to 1:3 in non-survivors (p<0.001). Increased FFP transfusions within first 24 hrs of admission were independently associated with increased survival. Median ratio of FFP: RBC was 1:1.7 in survivors compared to 1:3 in non-survivors (p<0.001).

24. Mortality PRBC:FFP

26. Fresh Whole Blood Fresh whole blood (FWB) must be called for early after ED arrival, takes 60 minutes –Injury Pattern recognition FWB is the optimal resuscitation fluid for severely injured casualties. FWB is the best fluid for hypotensive resuscitation for hemorrhagic shock.

27. Component Therapy vs Fresh Whole Blood PRBC Hct 55% 335 mL Plt 5.5x10 10 50 mL FFP 80% 275 mL So Component Therapy Gives You 1U PRBC + 1U PLT + 1U FFP + 10 pk Cryo = COLD 660 COLD mL Hct 29% Plt 87K Coag activity 65% 750 mg fibrinogen 500 mL Warm Hct: 38-50% Plt: 150-400K Coags: 100% Armand & Hess, Transfusion Med. Rev., 2003 1500 mg Fibrinogen

28. Scoring System SBP < 110 HR > 105 Hct < 32 pH < 7.25 n=180 n=153 n=203 n=115 n=57

29. rFVIIa In military casualties requiring massive transfusion, early administration of rFVIIa decreased pRBC use by 23% rFVIIa increases the SBP at which arterial rebleeding occurs –suggesting the formation of a tighter, stronger fibrin plug in the presence of high concentrations of rFVIIa Seven prospective, randomized surgical trials have documented the safety of this drug. The clinical goal is a subnormal PT or INR, ensuring that if bleeding is still occurring then surgical intervention is required. In military casualties requiring massive transfusion, early administration of rFVIIa decreased pRBC use by 23% rFVIIa increases the SBP at which arterial rebleeding occurs –suggesting the formation of a tighter, stronger fibrin plug in the presence of high concentrations of rFVIIa Seven prospective, randomized surgical trials have documented the safety of this drug. The clinical goal is a subnormal PT or INR, ensuring that if bleeding is still occurring then surgical intervention is required.

30. When comparing rFVIIa (+) to rFVIIa (-) patients –24 hour mortality was 7/49 (14%) and 26/75 (35%), (p=0.01) –30 day mortality was 15/49 (31%) and 38/75 (51%), (p=.03). SBP was higher in the rFVIIa (+) group The use of rFVIIa was associated with improved early and late survival after severe trauma and massive transfusion. rFVIIa was not associated with increased risk of thrombotic events. The Effect of Recombinant Activated Factor VII on Mortality in Combat-Related Casualties With Severe Trauma and Massive Transfusion Philip C. Spinella, MD, Jeremy G. Perkins, MD, Daniel F. McLaughlin, MD, Sarah E. Niles, MD, MPH,Kurt W. Grathwohl, MD, Alec C. Beekley, MD, Jose Salinas, PhD, Sumeru Mehta, MD, Charles E. Wade, PhD,and John B. Holcomb, MD J of Trauma- Feb 2008

31. Retrospective Study of Combat Casualties Who did and did not Receive rFVIIa Jan 2004 - Oct 2006 n = 615 329 US casualties did not receive rFVIIa ISS = 21 ± 14 Complications = 17% –Thrombotic = 11% ICU days = 6 ± 24 Hospital days = 27 ± 40 PRBCs = 8 ± 7 Mortality = 19% 286 US Casualties did receive rFVIIa ISS = 24 ± 13* Complications = 23%* –Thrombotic = 14% ICU days = 10 ± 15* Hospital days = 37 ± 35* PRBCs = 18 ± 22* Mortality = 21% * P < 0.05

32. Summary Recognize Shock –Five Critical Criterion –Identify the critical 10 % Resuscitate Immediately –Devote attention to Hemostatic resuscitation Provide volume that also restores the hemostatic cascade Minimize crystalloid Stop the bleeding Stay out of trouble Thawed or liquid plasma –Whole Blood