1. Damage Control Resuscitation Mazen Kherallah, MD, FCCP Executive Director of Quality Assurance SEHA: Abu Dhabi Infectious Disease & Critical Care Medicine Consultant Sheikh Khalifa Medical City 1
2. Outline Introduction Damage Control Resuscitation Data from the Battlefield Plasma Platelets Fresh Whole Blood Conclusion
3. Definition of Massive Transfusion Replacement of a blood volume equivalent within 24hr >10 unit within 24 hr Transfusion > 4 units in 1 hr Replacement of 50% of blood volume in 3hrs A rate of loss >150ml/hr
4. Hemorrhaging Trauma Patient:Case Report* 24 y/o Iraqi special forces soldier Multiple high-velocity GSW through-and-through flanks and pelvis. Arrived via helicopter. Unknown pre-hospital time. Arrival SBP ~50 *courtesy of Dr. Al Beekley
5. Injuries Left lobe of liver laceration Through-and-through distal esophagus 6 gastrotomies Splenic rupture Proximal splenic artery injury Distal pancreas laceration Left kidney laceration Multiple small bowel enterotomies Evisceration of omentum through left flank Bladder injury Extra-peritoneal rectal injury Pelvic fracture Internal iliac artery and vein lacerations Left open tibia/fibula fracture
10. Introduction: Trauma/Coagulopathy Hemorrhage is the leading preventable cause of death from trauma Resuscitating these casualties requires some understanding of why they are bleeding …and continue to bleed despite getting transfused
11.
12. Coagulopathy of Trauma “trauma triad” of hemorrhage, acidosis, hypothermia Dilutionalcoagulopathy Excessive use of crystalloid, RBCs Consumptive coagulopathy Hyperfibrinolysis 20% on admission with ISS>15 Acute coagulopathy of trauma
16. Thermal Coagulopathy The coagulation cascade is an enzymatic pathway that degrades with temperature and ceases at 92 F Hypothermia slows the enzymatic reactions of the coagulation cascade Hypothermia prevents the activation of platelets by traction on the glycoprotein 1b, IX, V complex by von Willebrandfactor (VWF) A temperature < 96°F or 35°C is associated with an increase in mortality.
17.
18. Critical requirements for fluid, volume, red cells, albuminCritical dilution for coagulation factors occur after loss of 1.2 blood volumes and for platelets at 2 blood volumes
19. Acidotic Coagulopathy Acidosis – interferes with the assembly of coagulation factor complexes Acidosis contributes more to coagulopathy more than hypothermia (not reversible)
20. Consumption Coagulopathy Consumption of coagulation factors and platelets – highly localized at site of injury Nanomolecule of TF present in every square meter of fibroblasts or smooth-muscle cell – all of FVII could be removed from the circulation by 3-30m2 of endothelial disruption Schester, Glesen Taby, et al 1997 Dietzen, Page Tetzloff, 1997 FVII TF TF TF Subendothelial smooth-muscle cells, Fibrobasts
21. Increased fibrinolysis Generation of thrombin at injury sites leads to its binding to thrombomodulin on normal endothelium with activation of protein C Reduced local thrombin concentrations lead to thin fibrin strands with high surface-to-volume ratios and prevent the activation of TAFI (thrombin-activated fibrinolysis inhibitor) Low vascular flow leads to release of tissue plasminogen activator (tPA) from intact endothelial cells
22. Acute Coagulopathy of Trauma Very early within 10 min of arrival Hypoperfusion and shock (oxygen debt) Anti-coagulation and hyperfibrinolysis Increased soluble thrombomodulin Increased activated protein C Decreased utilization of fibrinogen Decreased plasminogen activator inhibitor No coagulation factor deficiency or dysfunction at this early time. Brohi K. Acute Coagulopathy of Trauma. J Trauma. 2008:64(5);1211-1217
23. New Diagnostic criteriaAvoids 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
24. Patients At Risk for Massive Transfusion: MT Hypothermia < 96.5 23
25. Acidosis 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 massive transfusion and mortality in both civilian and military trauma. Patients have an elevated BD before their blood pressure drops to classic “hypotension” levels.
26. 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 et al., 2003)
27. Limiting effects of coagulopathy Hypotensive resuscitation – reducing the therapeutic goal for mean blood pressure = less fluid, less blood Local modalities Fibrin glue Hemostatic bandages Argon lasers
28. Limiting effects of coagulopathy Antifibrinolytics Fresh whole blood Increase early availability of plasma using thawed but type-specific 5-day plasma Recombinant activated factor VIIA (rVIIa) or combinations of fibrinogen and prothrombin complex concentrates
29. Limiting effects of coagulopathy 7. Combination of all approaches with rapid identification of coagulopathic patients, prompt initiation of 1:1:1 resuscitation ratios with RBCs, prethawed universal donor AB plasma and pheresis patients, conversion to FWB, frequent use of rVIIa in conjunction with attention to avoiding hypothermia and treatment of acidosis.
30. Identify Patients in Trouble 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
31. Outline Introduction Damage Control Resuscitation Data from the Battlefield Plasma Platelets Fresh Whole Blood Conclusion
33. How to Resuscitate these PatientsDamage Control Resuscitation First “patching up the holes,” and delaying definitive care Early surgical control of bleeding Hypotensive resuscitation Hemostatic resuscitation Bleeding Control Prevent/treat: acidosis, hypothermia, hypocalcemia, coagulopathy Permissive hypotension: Minimize rebleed: avoid “popping the clot”
34. 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.
36. 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
38. Outline Introduction Damage Control Resuscitation Data from the Battlefield Plasma Platelets Fresh Whole Blood Conclusion
39. Data from the Battlefield Recent conflicts in Iraq and Afghanistan have provided means for the study large numbers of severely injured patients Military medicine has made an effort to be data driven Joint Theater Trauma Registry We’ll look at three studies: FFP:RBC ratio Platelet:RBC ratio Warm Fresh Whole Blood
40. FFP:RBC Ratio study 246 massively transfused patients at a Combat Support Hospital Divided into 3 FFP:RBC ratio groups <1:4, 1:2 - 1:4, >1:2 Compared baseline demographics and outcomes Performed multivariate regression analysis for overall mortality Borgman, MA, Spinella, PC, et al. “Ratio of blood products affects mortality in trauma,” J Trauma 2007:63(4); 805-813
41. Effect of FFP:RBC ratio on overall mortality Chi Square Low to Med: p=0.01 Med to High: p=0.02 Mortality n=31 n=56 n=165 FFP:RBC Ratio Borgman, MA, Spinella, PC, et al. “Ratio of blood products affects mortality in trauma,” J Trauma 2007:63(4); 805-813
42. FFP:RBC ratio Mortality % n=31 n=56 n=165 Borgman, MA, Spinella, PC, et al. “Ratio of blood products affects mortality in trauma,” J Trauma 2007:63(4); 805-813 Data: median (IQR)
44. Cause of death by ratio group 95% 70% Mortality % 39% Borgman, MA, Spinella, PC, et al. “Ratio of blood products affects mortality in trauma,” J Trauma 2007:63(4); 805-813
46. Limitations of 1:1 study Retrospective Regression analysis may not include all confounders Survivorship bias, in that those that died early died before they could receive plasma. 24 hour totals of FFP and RBC “catch-up” bias: where the survivors, who survive to 24 hours get transfused plasma later in the day to correct their coagulopathy and our numbers are simply a reflection of this.
47. Applying Hemostatic Resuscitation Must identify who is at risk EARLY Death from hemorrhage typically occurs in the first 6 hours Applying hemostatic resuscitation liberally places patients at unnecessary risk for multiorgan failure, respiratory compromise, and thromboembolic events Several predictive scores TASH score ABC score
48. TASH: Trauma-associated Severe Hemorrhage Score Systolic blood pressure (<100 mm Hg=4 pts, <120 mm Hg=1 pt) Hemoglobin (<7 g/dL=8 pts, <9 g/dL=6 pts, <10 g/dL=4 pts, <11 g/dL=3 pts, and <12 g/dL=2 pts) Intra-abdominal fluid (3 pts) Complex long bone and/or pelvic fractures (AIS 3/4=3 pts and AIS 5=6 pts) Heart rate (>120=2 pts) Base excess (<-10 mmol/L=4 pts, <-6 mmol/L=3 pts, and <-2 mmol/L=1 pt), Gender (male=1 pt).
49. Mortality based on TASH score TASH: Trauma-associated Severe Hemorrhage Score Borgman, MA Unpublished data
50. Potential Plasma Mechanisms Activates human endothelial cell kinase pathways Protective for endothelial cell injury Restores endothelial glycocalyx Needed for cell integrity and function Decreased pulmonary and lymphatic endothelial cell permeability Increased Syndecan-1 expression Endothelial cell glycocalyx membrane protein involved in cell function and integrity JB Holcomb. Presented at 2009 Shock Society Conference
52. 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.
53. Apheresis Platelets Evaluated 462 casualties in Iraq who received a massive transfusion Three groups based on aPLT:RBC ratio >1:16, 1:8-16, <1:8 Evaluated 24hr, 30 day survival Perkins, JG, Cap, AP, Spinella, PC, et al. “Evaluation of the impact of Apheresis Platelets.” J Trauma. 2009; 66: S77-S85
54. Mortality at 30 daysCox Hazard Regression VariableHazard Ratio p Value ISS 1.06 <0.001 INR 1.16 0.03 Plasma Ratio 0.98 0.01 aPLT ratio 0.91 <0.001 Base deficit 1.04 0.07 Stored RBC units 1.03 0.08 Perkins, JG, Cap, AP, Spinella, PC, et al. “Evaluation of the impact of Apheresis Platelets.” J Trauma. 2009; 66: S77-S85
55. Survival to 24hrs and 30 days Perkins, JG, Cap, AP, Spinella, PC, et al. “Evaluation of the impact of Apheresis Platelets.” J Trauma. 2009; 66: S77-S85
56. Warm Fresh Whole Blood Retrospective, 354 pts transfused ≥1U of RBCs Compared patients transfused Fresh Whole Blood + (PRBC, FFP) Stored components (PRBC, FFP, aPLTs) Groups compared equal in: Age, severity of injury Admission vital signs and labs, RBC amount Average patient was in hemorrhagic shock Base deficit of 6 and INR of 1.4 Spinella, PC, Perkins, JG, et al “Association of Warm Fresh Whole Blood with Survival” J Trauma. 2009; 66;S69-S76
62. Discussion Potential mechanisms for WFWB association with improved survival Improved function of RBCs, plasma, platelets in WFWB Thoroughly documented - Increased storage time for all blood products leads to decreased function 1-4 WFWB use minimizes use of old RBCs Old RBCs: hyperinflammatory, immunomodulatory, impair vasoregulation, poor O2 delivery Increased anti-coagulants and preservatives in stored components 1 Spinella PC, Crit Care Med, 2007 2 Napolitano LM, Crit Care Clinics, 2004 3 Lavee J, J Thor CardiovSurg, 1989 4 Mohr R, J Thor CardiovSurg, 1988
63. Discussion WFWB patients - Increased incidence of Renal failure ARDS, DVT – approached significance Since survival increased in WFWB group May be result of these patients living long enough to develop these complications Univariate analysis only and not adjusted with multivariate analysis
68. Fresh Whole Blood 2831 FWB donor units 3 (0.11% +HCV) 2 +HTLV 0 (HBV, HIV) Baghdad Combat Support Hospital Biokit (Madrid, Spain) 408 screened 2 positive HCV (units discarded) Spinella, PC., et al “Risks associated with Fresh Whole Blood and Red Blood Cell Transfusions at a Combat Support Hospital.” Crit Care Med. 2007; 35:2576-2581
69. 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.
70. Limitations Retrospective Hypothesis generating not hypothesis testing WFWB group had mix of WFWB, RBC, plasma Not available in database Crystalloid and colloid amounts AIS scores Cause of death
71. Military vs. Civilian data There are significant differences in military trauma More often blast and penetrating trauma vs. blunt trauma However, civilian studies have generally corroborated military findings Two studies: (of 7 civilian) German Trauma Registry US Multicenter Study
72. German Trauma Study 713 patients transfused >10 units Divided into 3 RBC:FFP ratio groups: <0.9, 0.9 – 1.1, >1.1 Excluded deaths in the ED Minimizes survivorship bias Counted transfusions in ED and OR (not ICU) Average 4 hours Minimizes catch-up bias Maegele, M. et al. “Red blood cell to plasma ratios transfused during massive transfusion are associated with mortality in severe multiply injury.” Vox Sanguinis, 2008.
74. US Multicenter Review 16 centers, 467 patients Excluded deaths within 30 min 4 groups based on 1:2 ratio cut-off of plasma or plt to RBCs: 24hr survival High plasma, high platelets 87% High plasma, low platelets 86% Low plasma, high platelets 83% Low plasma, low platelets 58% Holcomb, et al. “Increased plasma and platelets to RBC ratios improves outcome in 466 massively Transfused Civilian Trauma patients.” Annals of Surgery. 248 (3) 2008. 447-458
75. Survival to 30 days High FFP and Plt Low FFP and high Plt High FFP and low Plt Low FFP and Plt
76. Massive Transfusion Protocol Implemented “trauma exsanguination protocol” Before/after cohort study 10 pRBC + 6 FFP + 2 PLT Then 6 pRBC + 4 FFP + 2 PLT Mortality 65.8% to 51.1% Showed decreased RBC and FFP and PLT utilization Cotton, et al. “Damage Control Hematology” J Trauma May 2008
78. Current Army Policy Transfuse to a ratio of 1:1:1 of FFP:RBC:PLT for those patients presenting with severe life threatening trauma/hemorrhage at risk for massive transfusion Use of fresh whole blood is authorized for patients with life-threatening injuries (at discretion of MD)
80. 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.
81. 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 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.
82. 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
85. Suspected active haemorrhageIf so activate MMT (match 3 of the ocriteria) MMT ACTIVATION For Trauma PATIENT ARRIVAL Take bloods (FBC, U&E, Clotting, fibrinogen and X-match and ABG) Send pink bottle with X-match form to blood bank urgently ( please obtain 2 samples for x-match at different time if possible) HAEMOSTASIS THERAPY TARGET end point: Hb: 8-10 g/dl Platelets > 100 PT&APTT (INR)< 1.5 Fibrinogen > 1.0 g/l Ca²⁺ > 1 mmol/l pH: 7.35-7.45 BE: ± 2 Tª > 36 °C MMT PACK 1 4 x O –ve RBC ( female) or O+ve(Male) 4 x AB FFP (or Group specific if possible) HAEMORRHAGECONTROL: Surgery Stabilize fractures Pelvic brace PREVENT HYPOTHERMIA Fail to reach targets RE-ASSESSMENT ABCDE If haemorrhage continue HAEMOSTATIC DRUGS: Consider the following if bleeding persist despite surgical interventions: Activated factor VII Beriplex (consider when patient who is on anti-coagulant) Antifibrinolitic agents Please discuss any of these therapeutic measures with Haematologist on call) Activate MMT PACK 2 Please, specify location of patient 2 x packs of Cryoprecipitate if Fibrinogen is < 1.0 g/l MMT PACK 2 INTRA-OPERATIVE CELL SALVAGE: Transfuse 1 x FFP every 250 ml of blood Transfuse 1 x ATD platelets every 1000 ml of blood Once administered check: FBC, Clotting, fibrinogen and ABG 4 X RBC 4 X FFP 1 X ATD Platelets When MMT stops Notify blood bank Return any unused products Resume standard ordering practices
88. Suspected active haemorrhageIf so activate MMT (match 3 of the ocriteria) MMT ACTIVATION For Trauma PATIENT ARRIVAL Take bloods (FBC, U&E, Clotting, fibrinogen and X-match and ABG) Send pink bottle with X-match form to blood bank urgently ( please obtain 2 samples for x-match at different time if possible) HAEMOSTASIS THERAPY TARGET end point: Hb: 8-10 g/dl Platelets > 100 PT&APTT (INR)< 1.5 Fibrinogen > 1.0 g/l Ca²⁺ > 1 mmol/l pH: 7.35-7.45 BE: ± 2 Tª > 36 °C MMT PACK 1 4 x O –ve RBC ( female) or O+ve(Male) 4 x AB FFP (or Group specific if possible) HAEMORRHAGECONTROL: Surgery Stabilize fractures Pelvic brace PREVENT HYPOTHERMIA Fail to reach targets RE-ASSESSMENT ABCDE If haemorrhage continue HAEMOSTATIC DRUGS: Consider the following if bleeding persist despite surgical interventions: Activated factor VII Beriplex (consider when patient who is on anti-coagulant) Antifibrinolitic agents Please discuss any of these therapeutic measures with Haematologist on call) Activate MMT PACK 2 Please, specify location of patient 2 x packs of Cryoprecipitate if Fibrinogen is < 1.0 g/l MMT PACK 2 INTRA-OPERATIVE CELL SALVAGE: Transfuse 1 x FFP every 250 ml of blood Transfuse 1 x ATD platelets every 1000 ml of blood Once administered check: FBC, Clotting, fibrinogen and ABG 4 X RBC 4 X FFP 1 X ATD Platelets When MMT stops Notify blood bank Return any unused products Resume standard ordering practices
89. 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: Early FFP and Plt Minimize crystalloid Stop the bleeding Stay out of trouble Thawed or liquid plasma Whole Blood Consider use of rFVIIa
