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Hemorrhage and Transfusion Adjuncts in the Setting of Damage Control Joseph Cuschieri, MD FACS Professor of Surgery, University of Washington Adjunct Professor of Orthopedics and Neurosurgery, University of Washington Program Director Surgical Critical Care, University of Washington Director of Surgical Critical Care, Harborview Medical Center Financial Disclosure No financial support Objectives Understand the role of damage control principles in minimizing transfusion 1

Damage Control in Trauma Goal of Damage Control To preserve life Control hemorrhage Prevent/control contamination Reverse coagulopathy Prevent further injury Bloody Vicious Cycle or Lethal Triad Coagulopathy Hemorrhage Acidosis Tissue Hypoxia Hypothermia Coagulopathy Kashuk, J.L., et al., Major abdominal vascular trauma--a unified approach. J Trauma, 1982. 22(8): p. 672-9. 2

Hypothermia Clinically significant at temp < 35 Prolongs clotting times, increases fibrinolysis, causes platelet dysfunction Increase in sympathetic drive Peripheral vasoconstriction End-organ hypoperfusion Metabolic acidosis 100% mortality in trauma patients undergoing laparotomy with temp < 32 Jurkovich, G.J., et al., Hypothermia in trauma victims: an ominous predictor of survival. J Trauma, 1987. 27(9): p. 1019-24. Hypothermia effect on blood loss Reynolds B. Journal of Trauma and Acute Care Surgery. 2012:73(2):486-491. Hypothermia induced Coagulopathy Kutcher M, et al. Journal of Trauma and Acute Care Surgery. 2015:78(3):516-523. 3

Damage Control Resuscitation Effect of early resuscitation on hypothermia induced coagulopathy Reynolds B. Journal of Trauma and Acute Care Surgery. 2012:73(2):486-491. Acidosis Anaerobic metabolism resulting from tissue hypoperfusion Cardiac depressant effects Exacerbation of coagulopathy 4

Coagulopathy Exacerbated by acidosis and hypothermia Consumption and dilution of factors Acute coagulopathy of trauma Hypoperfusion driven Hyperfibrinolysis and activation of protein C Gubler KD, Gentilello LM, Hassantash SA, et al. The impact of hypothermia on dilutional coagulopathy. J Trauma 1994;36(6):847 51 Brohi, K., et al., Acute coagulopathy of trauma: hypoperfusion induces systemic anticoagulation and hyperfibrinolysis. J Trauma, 2008. 64(5): p. 1211-7; discussion 1217 Damage Control Sequence Traditional Model Damage Control Model Case Presentation 70 year old struck by a garbage truck. Mangled left lower extremity, right lower extremity deformity Field vitals: HR 127, RR 28, BP 101/80 5

Rapid transport Damage Control Prehospital/ED Tourniquets/Pelvic binding Permissive hypotension Damage control resuscitation Case Presentation: Field Patient intubated in field. Tourniquet applied in field to stop ongoing hemorrhage from left lower extremity. HR 129, BP 92/78, RR 22 Tourniquet Phobia But-I learned that tourniquets are dangerous and should only be used as a last resort! www.specialmedics.com 6

152 patient transferred to five Level I Trauma Centers. 66 extremity injuries-27 tourniquets applied prehospital-all improvised. Eight limbs presented to the ED with life threatening exsanguination and had no prehospital tourniquet in place on arrival. At one collaborative hospital with detailed ED records and photos available, all six improvised tourniquets encountered were venous tourniquets and required replacement with a CAT tourniquet to prevent ongoing extremity exsanguination and effect hemostasis upon arrival in the ED. Case Presentation Outside Hospital Upon presentation to outside hospital, HR 130, BP 90/80, RR 24, Temp 35.5 C Airway verified, ETCO2 detected and recorded 18 Active bleeding from left upper thigh, combat gauze applied. 7

Case Presentation: Outside Hospital 2 units P RBCs administered Pelvic fracture sheeted TXA administered 8

9

Case Presentation: Outside Hospital Hemorrhage from lower extremity improved with combat gauze and tourniquet. Vital signs stabilized (HR 120, BP 101/84, RR 18) following 4 units of P RBCs and 1 FFP. BD 11, and lactate 6.8 Underwent CT scan of head/chest/abd/pelvis and CTA of left lower extremity Case Presentation: Outside Hospital CTA Left Lower Extremity Case Presentation: Transfer Transferred to HMC for possible salvage of left lower extremity. Required 2 additional units of P RBCs to maintain SBP > 90 mmhg 10

Case Presentation: Arrival to HMC HR 119, BP 105/87, RR 16 Patient on Pradaxa for atrial fibrillation, which was reversed with Praxabind. Massive transfusion activated. Taken emergently to OR for control of bleeding from left lower extremity, and external fixation of pelvis Direct Oral Anticoagulant Mechanism of Action Direct Oral Anticoagulants Effect on Coagulation Tests Rivaroxaban (Xarelto) Dabigatran (Pradaxa) Apixaban (Eliquis) aptt or or PT/INR or or or Thrombin Time Minimal effect Minimal effect Hemoclot thombin inhibitor assay No effect No effect Anti Factor Xa Minimal effect 1. Xarelto PM, July 18, 2012 ; 2. Pradaxa PM November 12, 2012; 3. Eliquis PM November 27, 2012; 4. Goette Trends Cardiovasc Med. 2013 [Epub ahead of print] 11

Reversal of DOAC anticoagulant effect Prothrombin Complex Concentrate (PCC) -3 factor PCC (factors II, IX, X) -4 factor PCC (factors II, VII, IX, X) No high-quality evidence efficacy and safety of PCC in the bleeding patient PCC associated with 1.4% risk of thrombosis when administered to bleeding patients on warfarin Risk of Thromboembolism Mechanical Heart Valve Atrial Fibrillation VTE High Risk (>10%) Any mitral valve prosthesis Older aortic valve prosthesis Recent stroke or TIA (within 6 months) CHADS 5-6 Recent stroke or TIA (within 3 months) Rheumatic valve disease Recent VTE (within 3 months) Severe thrombophilia Moderate Risk (5-10%) Bileaflet aortic valve prosthesis + 1 additional risk factor (CHADS) CHADS 3-4 VTE within 3-12 months Nonsevere thrombophilia Low Risk (<5%) Bileaflet aortic valve prosthesis with no additional risk factors or atrial fibrillation CHADS 0-2 with no previous TIA or stroke Single VTE >12 months and no other risk factors 12

Case Presentation: OR Underwent mid-femur amputation and debridement of devitalized soft tissue and muscle, external fixation of right tibia, and packing of his open left flank/pelvic wound. Received 6 units P RBCs and 6 units FFP Upon completion patient HR 92, BP 117/69, RR 18. Taken to TSICU Re-warm ICU Phase of Damage Control Aim for 37 degrees External/internal/extracorporeal Correct coagulopathy INR < 1.2, fibrinogen > 100mg/dL, platelets > 100,000/mm3 Correct acidosis Resuscitation Beware of excessive chloride administration Hypothermia effect on the inflammatory response Antigen presentation and cell adhesion pathways down regulated. Cytokine signaling pathways upregulated 13

Affect of rewarming of hypothermia Standard Rewarming (n=46) Active Rewarming (n=14) P value Rewarming rate 1.0 (0.8-1.2) 1.8 (1.6-2.3) <0.001 Nosocomial Infection 31 (67.4) 5 (35.7) 0.03 Mortality 9 (19.6) 2 (14.2) 0.21 Complicated Outcome 36 (78.3) 4 (28.6) <0.001 Case Presentation: ICU Arrival vital signs: HR 98, BP 111/78, RR 18, Temp 34 C Warm fluid administered, rewarming catheter considered as patient dropped SBP to 90 mmhg. Due to hypotension patient underwent further blood product resuscitation, and went for potential angiographic embolization of pelvis. 14

Patient Case: Pelvic Angiography 15

Patient Case: ICU Patient received 3 units P RBCs and 3 units FFP while undergoing angiographic evaluation. Upon return to ICU, the patient demonstrated further improvement in shock state with BD reduced to 3.2, and vital signs of HR 93, BP 131/68 and temperature of 36.2 C. 16

Case Presentation Hospital Course Patient extubated with minimal signs of delirium. Underwent definitive repair of tibia fracture. Multiple debridements of right thigh and left flank, requiring skin grafting. Working with rehab psychiatry, physical therapy, and occupational therapy. Conclusion Damage control principles are a vital tool in the resuscitation of severely injured patients. Important to apply the principles in the appropriate patient, and to work on both hemorrhage control, resuscitation, and correction of coagulopathy. Principles should be focused selectively on individual patients, with knowledge of both risk and benefits. Thank You 17