Evaluation of Prehospital Blood Products to Attenuate Acute Coagulopathy of Trauma in a Model of Severe Injury and Shock in Anesthetized Pigs

ABSTRACT Acute trauma coagulopathy (ATC) is seen in 30% to 40% of severely injured casualties. Early use of blood products attenuates ATC, but the timing for optimal effect is unknown. Emergent clinical practice has started prehospital deployment of blood products (combined packed red blood cells and fresh frozen plasma [PRBCs:FFP], and alternatively PRBCs alone), but this is associated with significant logistical burden and some clinical risk. It is therefore imperative to establish whether prehospital use of blood products is likely to confer benefit. This study compared the potential impact of prehospital resuscitation with (PRBCs:FFP 1:1 ratio) versus PRBCs alone versus 0.9% saline (standard of care) in a model of severe injury. Twenty-four terminally anesthetised Large White pigs received controlled soft tissue injury and controlled hemorrhage (35% blood volume) followed by a 30-min shock phase. The animals were allocated randomly to one of three treatment groups during a 60-min prehospital evacuation phase: hypotensive resuscitation (target systolic arterial pressure 80 mmHg) using either 0.9% saline (group 1, n = 9), PRBCs:FFP (group 2, n = 9), or PRBCs alone (group 3, n = 6). Following this phase, an in-hospital phase involving resuscitation to a normotensive target (110 mmHg systolic arterial blood pressure) using PRBCs:FFP was performed in all groups. There was no mortality in any group. A coagulopathy developed in group 1 (significant increase in clot initiation and dynamics shown by TEG [thromboelastography] R and K times) that persisted for 60 to 90 min into the in-hospital phase. The coagulopathy was significantly attenuated in groups 2 and 3 (P = 0.025 R time and P = 0.035 K time), which were not significantly different from each other. Finally, the volumes of resuscitation fluid required was significantly greater in group 1 compared with groups 2 and 3 (P = 0.0067) (2.8 ± 0.3 vs. 1.9 ± 0.2 and 1.8 ± 0.3 L, respectively). This difference was principally due to a greater volume of saline used in group 1 (P = 0.001). Prehospital PRBCs:FFP or PRBCs alone may therefore attenuate ATC. Furthermore, the amount of crystalloid may be reduced with potential benefit of reducing the extravasation effect and later tissue edema.

[1]  David B Hoyt,et al.  Transfusion of plasma, platelets, and red blood cells in a 1:1:1 vs a 1:1:2 ratio and mortality in patients with severe trauma: the PROPPR randomized clinical trial. , 2015, JAMA.

[2]  C. Wade,et al.  Prehospital Transfusion of Plasma and Red Blood Cells in Trauma Patients , 2015, Prehospital emergency care : official journal of the National Association of EMS Physicians and the National Association of State EMS Directors.

[3]  A. Cap,et al.  The pathogenesis of traumatic coagulopathy , 2015, Anaesthesia.

[4]  M. Dubick,et al.  Systemic and microvascular effects of resuscitation with blood products after severe hemorrhage in rats , 2014, The journal of trauma and acute care surgery.

[5]  K. Asehnoune,et al.  What’s new in management of traumatic coagulopathy? , 2014, Intensive Care Medicine.

[6]  J. Dixon Hemostatic Resuscitation is Neither Hemostatic Nor Resuscitative in Trauma Hemorrhage , 2014 .

[7]  M. Cohen,et al.  An Update on the Coagulopathy of Trauma , 2014, Shock.

[8]  A. Sauaia,et al.  Plasma First in the Field for Postinjury Hemorrhagic Shock , 2014, Shock.

[9]  E. Kirkman,et al.  Deployed research , 2014, Journal of the Royal Army Medical Corps.

[10]  R. Gerhardt,et al.  Freeze-Dried Plasma at the Point of Injury: From Concept to Doctrine , 2013, Shock.

[11]  M. Dubick,et al.  Evaluation of resuscitation fluids on endothelial glycocalyx, venular blood flow, and coagulation function after hemorrhagic shock in rats , 2013, Journal of Trauma and Acute Care Surgery.

[12]  J. Holcomb,et al.  Fresh Frozen Plasma Lessens Pulmonary Endothelial Inflammation and Hyperpermeability After Hemorrhagic Shock and Is Associated With Loss of Syndecan 1 , 2013, Shock.

[13]  M. Hayakawa,et al.  Massive Amounts of Tissue Factor Induce Fibrinogenolysis Without Tissue Hypoperfusion in Rats , 2013, Shock.

[14]  M. Midwinter,et al.  Utility of interim ROTEM(®) values of clot strength, A5 and A10, in predicting final assessment of coagulation status in severely injured battle patients. , 2013, Injury.

[15]  L. Blackbourne,et al.  En-Route Care Capability From Point of Injury Impacts Mortality After Severe Wartime Injury , 2013, Annals of surgery.

[16]  S. Ausset,et al.  The evolving role of lyophilized plasma in remote damage control resuscitation in the French Armed Forces Health Service , 2013, Transfusion.

[17]  J. Differding,et al.  The use of lyophilized plasma in a severe multi‐injury pig model , 2013, Transfusion.

[18]  L. Blackbourne,et al.  Ten-year analysis of transfusion in Operation Iraqi Freedom and Operation Enduring Freedom: Increased plasma and platelet use correlates with improved survival , 2012, The journal of trauma and acute care surgery.

[19]  R. Branson,et al.  Lessons From the Tip of the Spear: Medical Advancements From Iraq and Afghanistan , 2012, Respiratory Care.

[20]  M. Cohen,et al.  Animal models of trauma-induced coagulopathy. , 2012, Thrombosis research.

[21]  K. Brohi,et al.  Acute traumatic coagulopathy , 2012, Current opinion in anaesthesiology.

[22]  S. Ausset,et al.  Use of freeze-dried plasma in French intensive care unit in Afghanistan. , 2011, The Journal of trauma.

[23]  C. Wade,et al.  Initial resuscitation with plasma and other blood components reduced bleeding compared to hetastarch in anesthetized swine with uncontrolled splenic hemorrhage , 2011, Transfusion.

[24]  E. Kirkman,et al.  Blast injury research models , 2011, Philosophical Transactions of the Royal Society B: Biological Sciences.

[25]  Jodie L. Conyers,et al.  Protective effects of fresh frozen plasma on vascular endothelial permeability, coagulation, and resuscitation after hemorrhagic shock are time dependent and diminish between days 0 and 5 after thaw. , 2010, The Journal of trauma.

[26]  Sarah Watts,et al.  Prolonged Permissive Hypotensive Resuscitation Is Associated With Poor Outcome in Primary Blast Injury With Controlled Hemorrhage , 2010, Annals of surgery.

[27]  J. Ingerslev,et al.  Evaluation of coagulation kinetics using thromboelastometry—methodologic influence of activator and test medium , 2010, Annals of Hematology.

[28]  Michael J. Duggan,et al.  REPRODUCIBILITY OF AN ANIMAL MODEL SIMULATING COMPLEX COMBAT-RELATED INJURY IN A MULTIPLE-INSTITUTION FORMAT , 2009, Shock.

[29]  M. Dubick,et al.  Thrombelastography is better than PT, aPTT, and activated clotting time in detecting clinically relevant clotting abnormalities after hypothermia, hemorrhagic shock and resuscitation in pigs. , 2008, The Journal of trauma.

[30]  C. Wade,et al.  Increased mortality associated with the early coagulopathy of trauma in combat casualties. , 2008, The Journal of trauma.

[31]  M. Cohen,et al.  Acute coagulopathy of trauma: hypoperfusion induces systemic anticoagulation and hyperfibrinolysis. , 2008, The Journal of trauma.

[32]  S. Sarwar,et al.  National Confidential Enquiry into Patient Outcome and Death , 2007 .

[33]  Charles E. Wade,et al.  Causes of Death in U.S. Special Operations Forces in the Global War on Terrorism: 2001–2004 , 2007, Annals of surgery.

[34]  M. Cohen,et al.  Acute Traumatic Coagulopathy: Initiated by Hypoperfusion: Modulated Through the Protein C Pathway? , 2007, Annals of surgery.

[35]  R. Lefering,et al.  Early coagulopathy in multiple injury: an analysis from the German Trauma Registry on 8724 patients. , 2007, Injury.

[36]  P. Mahoney,et al.  ABC to ABC: redefining the military trauma paradigm , 2006, Emergency Medicine Journal.

[37]  S. Cimbanassi,et al.  Organized trauma care: does volume matter and do trauma centers save lives? , 2003, Current opinion in critical care.

[38]  Mauricio Lynn,et al.  Early coagulopathy predicts mortality in trauma. , 2003, The Journal of trauma.

[39]  Ari Leppaniemi,et al.  A profile of combat injury. , 2003, The Journal of trauma.

[40]  A. Sauaia,et al.  Epidemiology of trauma deaths: a reassessment. , 1993, The Journal of trauma.

[41]  S. Stern,et al.  Effect of blood pressure on hemorrhage volume and survival in a near-fatal hemorrhage model incorporating a vascular injury. , 1993, Annals of emergency medicine.

[42]  Harris Js,et al.  National Association of Emergency Medical Technicians. , 1975 .