Table of Contents

 

Hemorrhagic shock is the major preventable cause of morbidity and mortality in patients who suffer trauma. Definitive hemostasis is the primary goal, but coordination of care with prehospital providers, trauma centers, and surgical teams that is based on defined institutional protocols will ensure that these patients receive optimal care.

How does hypovolemic shock differ from other types of shock: distributive, cardiogenic, and obstructive?

What are the benefits and pitfalls of the use of tourniquets and hemostatic devices in prehospital care and in the ED?

Which clinical prediction calculators for shock are most accurate and useful? ATLS® class, shock index, delta shock index, respiratory-adjusted shock index, or ABC score?

What are the benefits and limitations of eFAST when assessing for bleeding?

Serum lactate, base deficit, fibrinogen levels, coagulation testing: what are the must-do tests? Will viscoelastic clot testing replace conventional coagulation testing?

What are the factors to consider when choosing fluids, blood products, and medications? What are the dangers?

Is REBOA appropriate for use in the ED? What is the evidence on its effectiveness?

How do different societies approach the concept of massive transfusion protocol?

1. Abstract
2. Case Presentations
3. Introduction
4. Critical Appraisal of the Literature
5. Etiology and Pathophysiology
   1. The Lethal Triad
6. Differential Diagnosis
7. Prehospital Care
   1. Stabilization
      1. Tourniquet Use
      2. Hemostatic Dressings
      3. Airway and Breathing
      4. Circulation
      5. Tranexamic Acid
      6. Temperature Management
   2. Transport
8. Emergency Department Preparation
9. Emergency Department Evaluation
   1. Assessment and Recognition of the Hemorrhagic Shock State
10. Diagnostic Studies
    1. Ultrasound and Other Imaging
    2. Laboratory Testing
    3. Viscoelastic Clot Testing
11. Treatment
    1. Hemorrhage Control With In-Hospital Hemostatic Devices
    2. Resuscitative Endovascular Balloon Occlusion of the Aorta
    3. Cardiac Arrest
    4. Resuscitative Thoracotomy
    5. Airway
    6. Breathing
    7. Circulation
       1. Fluid Resuscitation
       2. Massive Transfusion
       3. Crystalloid Therapy
       4. Whole Blood and Red Blood Cells
       5. Plasma
       6. Platelets
       7. Blood Product Ratios
       8. Permissive Hypotension
    8. Hemostatic Products
       1. Tranexamic Acid
       2. Prothrombin Complex Concentrate
       3. Direct Oral Anticoagulant Reversal Agents
       4. Fibrinogen
12. Special Circumstances and Populations
    1. Central Nervous System Injury
    2. Pediatric Patients
13. Controversies and Cutting Edge
14. Disposition
15. Key Points
16. Summary
17. Time- and Cost-Effective Strategies
18. Risk Management Pitfalls for Traumatic Hemorrhagic Shock
19. Case Conclusions
20. Clinical Pathway for Management of Traumatic Hemorrhagic Shock in the Emergency Department
21. Tables and Figures
    1. Table 1. Traumatic Hemorrhagic Shock Differential
    2. Table 2. Signs and Symptoms of Hemorrhage, by Class (ATLS®)
    3. Table 3. Clinical Prediction Calculators for Shock
    4. Figure 1. Bystander Awareness Campaign Information
    5. Figure 2. Fluid in Morison Pouch on eFAST
    6. Figure 3. TEG Waveforms in Various Coagulopathic States Showing Clot Firmness Versus Time
    7. Figure 4. ER-REBOA™ PLUS Catheter
    8. Figure 5. Zones of Aortic Occlusion in Resuscitative Endovascular Balloon Occlusion of the Aorta
22. References

Abstract

The management of traumatic hemorrhagic shock has evolved, with increasing emphasis on damage control resuscitation principles. Despite these advances, hemorrhage is still the leading preventable cause of death in trauma. This issue provides evidence-based recommendations for the assessment and treatment of traumatic hemorrhagic shock. Hemostatic techniques as well as correction of hemorrhagic hypovolemia and traumatic coagulopathy are presented. The safety and efficacy of practices such as resuscitative endovascular balloon occlusion of the aorta (REBOA), viscoelastic clot testing, and whole blood resuscitation are also reviewed.

Case Presentations

Your first patient of the night is a 45-year-old man who was involved in a highway motorcycle crash. He is complaining of abdominal and pelvic pain and had a 30-minute helicopter transport time. On arrival, his vital signs are: heart rate, 130 beats/min; blood pressure, 100/60 mm Hg; respiratory rate, 26 breaths/min; temperature, 37°C; oxygen saturation, 96% on room air; and GCS, 14. You know this patient will need fluid resuscitation, but you are unsure whether you should start with crystalloid or blood…

While stabilizing the first patient, a second patient is dropped off in the ambulance bay with an inguinal gunshot wound. This 22-year-old man has a heart rate of 140 beats/min; blood pressure, 80/40 mm Hg; respiratory rate, 28 breaths/min; temperature, 36.8°C; and oxygen saturation, 98%. He has been applying his sweatshirt to the wound, which is soaked with blood. You attempt direct pressure as the team wheels him to the trauma bay and consider your options to stop this junctional bleeding...

Then you get a request for online medical command from EMS responding to a conveyor belt accident with obvious amputation and pelvic fracture. The patient is hypotensive and tachycardic, with a 10-minute transport time. You ponder whether to activate the massive transfusion protocol now and whether he is a candidate for REBOA…

And this night is just getting started.

Introduction

Hemorrhagic shock is the major preventable cause of morbidity and mortality in patients suffering major trauma.¹ Hemorrhagic shock is defined as a form of hypovolemic shock in which severe traumatic blood loss leads to inadequate oxygen delivery to tissues. While the ultimate goal is definitive bleeding control, the resuscitative decisions up to this point are complex and frequently changing, in terms of medication and fluid choice, procedural indications, and treatment goals. This issue of Emergency Medicine Practice will review the evaluation and management decisions unique to the subset of trauma patients with hemorrhagic shock.

Critical Appraisal of the Literature

A literature search was performed in PubMed, Ovid MEDLINE^®, EMBASE, multiple evidence-based medicine reviews, and the Cochrane Database of Systematic Reviews. The search terms included: traumatic hemorrhagic shock, damage control resuscitation, massive transfusion, whole blood transfusion, and pre-hospital trauma resuscitation, with a date range from 1996 to September 2020. The following organizations‘ publications were also consulted for policies related directly to the management of traumatic hemorrhagic shock: American College of Emergency Physicians (ACEP) (0), American Academy of Emergency Medicine (AAEM) (1),² Eastern Association for the Surgery of Trauma (EAST) (1),³ American College of Surgeons Committee on Trauma (ACS COT) (2),^4,5 Advanced Trauma Life Support^® (ATLS^®) guidelines,⁶ Western Trauma Association (WTA) (2),^7,8 and Committee on Tactical Combat Casualty Care (CoTCCC) (TCCC guidelines).⁹ From this search, 124 articles, guidelines, and policies were selected for further review. Most of the literature consists of review articles, editorials, and consensus guidelines. Randomized trials are few, and often utilize disparate and restrictive exclusion criteria and endpoints for resuscitation, limiting the applicability of meta-analyses and reducing the strength of recommendations in guidelines.

Risk Management Pitfalls for Traumatic Hemorrhagic Shock

2. “I thought I’d give him 2 liters of normal saline for his tachycardia.”

Overresuscitation with crystalloids causes dilutional coagulopathy and acidosis. The 10th edition of ATLS® has reduced this initial bolus recommendation.

4. “Let’s get that abdominal CT just to confirm the bullet tract.”

Not moving surgical patients in hemorrhagic shock to the OR in a timely manner is exceptionally dangerous.

6. “The wound was too high for a tourniquet, so we just gave blood.”

Achieving hemostasis is your number 1 priority. Use manual pressure, junctional tourniquets, or hemostatic dressings to temporize until surgical intervention.

Tables and Figures

References

Evidence-based medicine requires a critical appraisal of the literature based upon study methodology and number of subjects. Not all references are equally robust. The findings of a large, prospective, randomized, and blinded trial should carry more weight than a case report.

To help the reader judge the strength of each reference, pertinent information about the study, such as the type of study and the number of patients in the study is included in bold type following the references, where available. In addition, the most informative references cited in this paper, as determined by the author, are highlighted.

1. Evans JA, van Wessem KJ, McDougall D, et al. Epidemiology of traumatic deaths: comprehensive population-based assessment. World J Surg. 2010;34(1):158-163. (Retrospective; 175 patients)
2. Hayes BD, Winters ME, Rosenbaum SB, et al. What is the role of reversal agents in the management of emergency department patients with dabigatran-associated hemorrhage? J Emerg Med. 2018;54(4):571-575. (Guideline)
3. Cannon JW, Khan MA, Raja AS, et al. Damage control resuscitation in patients with severe traumatic hemorrhage: A practice management guideline from the Eastern Association for the Surgery of Trauma. J Trauma Acute Care Surg. 2017;82(3):605-617. (Guideline)
4. American College of Surgeons. ACS TQIP massive transfusion in trauma guidelines. 2014. Accessed October 10, 2020. (Guideline)
5. Bulger EM, Snyder D, Schoelles K, et al. An evidence-based prehospital guideline for external hemorrhage control: American College of Surgeons Committee on Trauma. Prehosp Emerg Care. 2014;18(2):163-173. (Guideline)
6. Henry S. ATLS 10th edition offers new insights into managing trauma patients. 2018. Available at: http://bulletin.facs.org/2018/06/atls-10th-edition-offers-new-insights-into-managing-trauma-patients Accessed October 10, 2020. (Textbook)
7. Tran TL, Brasel KJ, Karmy-Jones R, et al. Western Trauma Association Critical Decisions in Trauma: management of pelvic fracture with hemodynamic instability-2016 updates. J Trauma Acute Care Surg. 2016;81(6):1171-1174. (Algorithm)
8. Burlew CC, Moore EE, Moore FA, et al. Western Trauma Association critical decisions in trauma: resuscitative thoracotomy. J Trauma Acute Care Surg. 2012;73(6):1359-1363. (Guideline)
9. United States Army Institute of Surgical Research. Tactical Combat Casualty Care Guidelines for Medical Personnel. 1 August 2019. Accessed October 10, 2020. (Guideline)
10. Johansson PI, Ostrowski SR. Acute coagulopathy of trauma: balancing progressive catecholamine induced endothelial activation and damage by fluid phase anticoagulation. Med Hypotheses. 2010;75(6):564-567. (Review)
11. Cannon JW. Hemorrhagic shock. N Engl J Med. 2018;378(4):370-379. (Review) DOI: 10.1056/NEJMra1705649
12. D’Alessandro A, Moore HB, Moore EE, et al. Early hemorrhage triggers metabolic responses that build up during prolonged shock. Am J Physiol Regul Integr Comp Physiol. 2015;308(12):R1034-R1044. (Animal study; 7 subjects)
13. Brown JB, Rosengart MR, Forsythe RM, et al. Not all prehospital time is equal: Influence of scene time on mortality. J Trauma Acute Care Surg. 2016;81(1):93-100. (Retrospective; 164,471 patients)
14. Kauvar DS, Miller D, Walters TJ. Tourniquet use is not associated with limb loss following military lower extremity arterial trauma. J Trauma Acute Care Surg. 2018;85(3):495-499. (Retrospective; 455 patients)
15. Tjardes T, Luecking M. The Platinum 5 min in TCCC: Analysis of junctional and extremity hemorrhage scenarios with a mathematical model. Mil Med. 2018;183(5-6):e207-e215. (Mathematical model)
16. Boulton AJ, Lewis CT, Naumann DN, et al. Prehospital haemostatic dressings for trauma: a systematic review. Emerg Med J. 2018;35(7):449-457. (Systematic review; 17 studies, 809 patients)
17. Millner R, Lockhart AS, Marr R. Chitosan arrests bleeding in major hepatic injuries with clotting dysfunction: an in vivo experimental study in a model of hepatic injury in the presence of moderate systemic heparinisation. Ann R Coll Surg Engl. 2010;92(7):559-561. (Animal study; 13 subjects)
18. Hatamabadi HR, Asayesh Zarchi F, Kariman H, et al. Celox-coated gauze for the treatment of civilian penetrating trauma: a randomized clinical trial. Trauma Mon. 2015;20(1):e23862. (Randomized controlled trial, open label; 160 patients)
19. Cox JM, Rall JM. Evaluation of XSTAT(R) and QuickClot(R) Combat Gauze(R) in a swine model of lethal junctional hemorrhage in coagulopathic swine. J Spec Oper Med.17(3):64-67. (Animal study; 19 subjects)
20. Warriner Z, Lam L, Matsushima K, et al. Initial evaluation of the efficacy and safety of in-hospital expandable hemostatic minisponge use in penetrating trauma. J Trauma Acute Care Surg. 2019;86(3):424-430. (Retrospective; 10 patients)
21. Lecky F, Bryden D, Little R, et al. Emergency intubation for acutely ill and injured patients. Cochrane Database Syst Rev. 2008(2):CD001429. (Review)
22. Hudson AJ, Strandenes G, Bjerkvig CK, et al. Airway and ventilation management strategies for hemorrhagic shock. To tube, or not to tube, that is the question! J Trauma Acute Care Surg. 2018;84(6S Suppl 1):S77-S82. (Review)
23. Cotton BA, Jerome R, Collier BR, et al. Guidelines for prehospital fluid resuscitation in the injured patient. J Trauma. 2009;67(2):389-402. (Guideline)
24. Shackelford SA, Del Junco DJ, Powell-Dunford N, et al. Association of prehospital blood product transfusion during medical evacuation of combat casualties in afghanistan with acute and 30-day survival. JAMA. 2017;318(16):1581-1591. (Retrospective; 504 patients)
25. McGinity AC, Zhu CS, Greebon L, et al. Prehospital low-titer cold-stored whole blood: Philosophy for ubiquitous utilization of O-positive product for emergency use in hemorrhage due to injury. J Trauma Acute Care Surg. 2018;84(6S Suppl 1):S115-S119. (Retrospective; 124 patients)
26. Sperry JL, Guyette FX, Brown JB, et al. Prehospital plasma during air medical transport in trauma patients at risk for hemorrhagic shock. N Engl J Med. 2018;379(4):315-326. (Randomized controlled trial; 501 patients)
27. Moore HB, Moore EE, Chapman MP, et al. Plasma-first resuscitation to treat haemorrhagic shock during emergency ground transportation in an urban area: a randomised trial. Lancet. 2018;392(10144):283-291. (Randomized controlled trial; 144 patients)
28. Shlaifer A, Siman-Tov M, Radomislensky I, et al. The impact of prehospital administration of freeze-dried plasma on casualty outcome. J Trauma Acute Care Surg. 2019;86(1):108-115. (Retrospective; 96 patients)
29. Shakur H, Roberts I, Bautista R, et al. Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a randomised, placebo-controlled trial. Lancet. 2010;376(9734):23-32. (Prospective; 20,211 patients) DOI: 10.1016/S0140-6736(10)60835-5
30. The CRASH-2 Collaborators. The importance of early treatment with tranexamic acid in bleeding trauma patients: an exploratory analysis of the CRASH-2 randomised controlled trial. Lancet. Published online March 24, 2011. Accessed October 10, 2020. (Review)
31. El-Menyar A, Sathian B, Asim M, et al. Efficacy of prehospital administration of tranexamic acid in trauma patients: A meta-analysis of the randomized controlled trials. Am J Emerg Med. 2018;36(6):1079-1087. (Systematic review)
32. Lundgren P, Henriksson O, Naredi P, et al. The effect of active warming in prehospital trauma care during road and air ambulance transportation - a clinical randomized trial. Scand J Trauma Resusc Emerg Med. 2011;19:59. (Randomized trial; 48 patients)
33. Wandling MW, Nathens AB, Shapiro MB, et al. Association of prehospital mode of transport with mortality in penetrating trauma: a trauma system-level assessment of private vehicle transportation vs ground emergency medical services. JAMA Surg. 2018;153(2):107-113. (Retrospective; 103,029 patients)
34. Harmsen AM, Giannakopoulos GF, Moerbeek PR, et al. The influence of prehospital time on trauma patients outcome: a systematic review. Injury. 2015;46(4):602-609. (Systematic review)
35. Yoo Y, Mun S. The advantages of early trauma team activation in the management of major trauma patients who underwent exploratory laparotomy. Ann Surg Treat Res. 2014;87(6):319-324. (Retrospective; 27,626 patients)
36. Dowd MD, McAneney C, Lacher M, et al. Maximizing the sensitivity and specificity of pediatric trauma team activation criteria. Acad Emerg Med. 2000;7(10):1119-1125. (Observational study; 492 patients)
37. Totten A, Cheney T, O’NEil M, et al. Physiologic Predictors of Severe Injury: Systematic Review. Rockville, MD: Agency for Healthcare Research and Quality (US); 2018. (Systematic review)
38. Guly HR, Bouamra O, Little R, et al. Testing the validity of the ATLS classification of hypovolaemic shock. Resuscitation. 2010;81(9):1142-1147. (Retrospective; 107,649 patients)
39. Mutschler M, Nienaber U, Munzberg M, et al. The shock index revisited - a fast guide to transfusion requirement? A retrospective analysis on 21,853 patients derived from the TraumaRegister DGU. Crit Care. 2013;17(4):R172. (Retrospective; 21,853patients)
40. Pacagnella RC, Souza JP, Durocher J, et al. A systematic review of the relationship between blood loss and clinical signs. PLoS One. 2013;8(3):e57594. (Systematic review; 30 studies)
41. Rau CS, Wu SC, Kuo SC, et al. Prediction of massive transfusion in trauma patients with shock index, modified shock index, and age shock index. Int J Environ Res Public Health. 2016;13(7). (Retrospective; 2490 patients)
42. Schellenberg M, Strumwasser A, Grabo D, et al. Delta shock index in the emergency department predicts mortality and need for blood transfusion in trauma patients. Am Surg. 2017;83(10):1059-1062. (Retrospective; 2591 patients)
43. Caputo N, Reilly J, Kanter M, et al. A retrospective analysis of the respiratory adjusted shock index to determine the presence of occult shock in trauma patients. J Trauma Acute Care Surg. 2018;84(4):674-678. (Retrospective; 3093 patients)
44. Dunham CM, Chirichella TJ, Gruber BS, et al. In emergently ventilated trauma patients, low end-tidal CO2 and low cardiac output are associated and correlate with hemodynamic instability, hemorrhage, abnormal pupils, and death. BMC Anesthesiol. 2013;13(1):20. (Prospective; 73 patients)
45. Carter JW, Falco MH, Chopko MS, et al. Do we really rely on FAST for decision-making in the management of blunt abdominal trauma? Injury. 2015;46(5):817-821. (Prospective; 146 patients)
46. Davis JW, Parks SN, Kaups KL, et al. Admission base deficit predicts transfusion requirements and risk of complications. J Trauma. 1996;41(5):769-774. (Retrospective; 2954 patients)
47. McKinley TO, McCarroll T, Metzger C, et al. Shock volume: patient-specific cumulative hypoperfusion predicts organ dysfunction in a prospective cohort of multiply injured patients. J Trauma Acute Care Surg. 2018;85(1S Suppl 2):S84-S91. (Prospective cohort; 100 patients)
48. Thorson CM, Van Haren RM, Ryan ML, et al. Admission hematocrit and transfusion requirements after trauma. J Am Coll Surg. 2013;216(1):65-73. (Retrospective; 1492 patients)
49. Spahn DR, Bouillon B, Cerny V, et al. The European guideline on management of major bleeding and coagulopathy following trauma: fifth edition. Crit Care. 2019;23(1):98. (Guideline) DOI: 10.1186/s13054-019-2347-3
50. MacKay EJ, Stubna MD, Holena DN, et al. Abnormal calcium levels during trauma resuscitation are associated with increased mortality, increased blood product use, and greater hospital resource consumption: a pilot investigation. Anesth Analg. 2017;125(3):895-901. (Retrospective; 77 patients)
51. Giancarelli A, Birrer KL, Alban RF, et al. Hypocalcemia in trauma patients receiving massive transfusion. J Surg Res. 2016;202(1):182-187. (Retrospective; 156 patients)
52. Ditzel RM Jr, Anderson JL, Eisenhart, WJ, et al. A review of transfusion- and trauma-induced hypocalcemia: is it time to change the lethal triad to the lethal diamond? J Trauma Acute Care Surg. 2020;88(3):434-439. (Review)
53. McQuilten ZK, Bailey M, Cameron PA, et al. Fibrinogen concentration and use of fibrinogen supplementation with cryoprecipitate in patients with critical bleeding receiving massive transfusion: a bi-national cohort study. Br J Haematol. 2017;179(1):131-141. (Retrospective; 3566 patients)
54. Ishii K, Kinoshita T, Kiridume K, et al. Impact of initial coagulation and fibrinolytic markers on mortality in patients with severe blunt trauma: a multicentre retrospective observational study. Scand J Trauma Resusc Emerg Med. 2019;27(1):25. (Retrospective; 666 patients)
55. Brohi K, Cohen MJ, Ganter MT, et al. Acute coagulopathy of trauma: hypoperfusion induces systemic anticoagulation and hyperfibrinolysis. J Trauma. 2008;64(5):1211-1217. (Prospective; 208 patients)
56. Cotton BA, Harvin JA, Kostousouv V, et al. Hyperfibrinolysis at admission is an uncommon but highly lethal event associated with shock and prehospital fluid administration. J Trauma Acute Care Surg. 2012;73(2):365-370. (Retrospective; 1996 patients)
57. Gonzalez E, Moore EE, Moore HB, et al. Goal-directed hemostatic resuscitation of trauma-induced coagulopathy: a pragmatic randomized clinical trial comparing a viscoelastic assay to conventional coagulation assays. Ann Surg. 2016;263(6):1051-1059. (Prospective; 111 patients) DOI: 10.1097/SLA.0000000000001608
58. Wikkelso A, Wetterslev J, Moller AM, et al. Thromboelastography (TEG) or thromboelastometry (ROTEM) to monitor haemostatic treatment versus usual care in adults or children with bleeding. Cochrane Database Syst Rev. 2016(8):CD007871. (Systematicreview; 17 studies, 1493 patients)
59. Hancock HM, Stannard A, Burkhardt GE, et al. Hemorrhagic shock worsens neuromuscular recovery in a porcine model of hind limb vascular injury and ischemia-reperfusion. J Vasc Surg. 2011;53(4):1052-1062. (Animal study; 37 subjects)
60. Smith S, White J, Wanis KN, et al. The effectiveness of junctional tourniquets: a systematic review and meta-analysis. J Trauma Acute Care Surg. 2019;86(3):532-539. (Meta-analysis; 8 studies)
61. Bulger EM, Perina DG, Qasim Z, et al. Clinical use of resuscitative endovascular balloon occlusion of the aorta (REBOA) in civilian trauma systems in the USA, 2019: a joint statement from the American College of Surgeons Committee on Trauma, the American Collegeof Emergency Physicians, the National Association of Emergency Medical Services Physicians and the National Association of Emergency Medical Technicians. Trauma Surg Acute Care Open. 2019;4(1):e000376. (Joint statement)
62. Tibbits EM, Hoareau GL, Simon MA, et al. Location is everything: the hemodynamic effects of REBOA in zone 1 versus zone 3 of the aorta. J Trauma Acute Care Surg. 2018;85(1):101-107. (Animal study; 18 subjects)
63. Kuckelman JP, Barron M, Moe D, et al. Extending the golden hour for Zone 1 resuscitative endovascular balloon occlusion of the aorta: improved survival and reperfusion injury with intermittent versus continuous resuscitative endovascular balloon occlusion of theaorta of the aorta in a porcine severe truncal hemorrhage model. J Trauma Acute Care Surg. 2018;85(2):318-326. (Animal study; 28 subjects)
64. Matsumura Y, Matsumoto J, Kondo H, et al. Early arterial access for resuscitative endovascular balloon occlusion of the aorta is related to survival outcome in trauma. J Trauma Acute Care Surg. 2018;85(3):507-511. (Prospective; 109 patients)
65. Joseph B, Zeeshan M, Sakran JV, et al. Nationwide analysis of resuscitative endovascular balloon occlusion of the aorta in civilian trauma. JAMA Surg. 2019;154(6):500-508. (Retrospective case control; 600 patients)
66. Elkbuli A, Flores R, Dowd B, et al. Survival of trauma patients needing CPR shortly after arrival: The National Trauma Data Bank Research Data Set. Am J Emerg Med. 2018;36(12):2276-2278. (Retrospective; 9365 patients)
67. Anderson KL, Mora AG, Bloom AD, et al. Cardiac massage for trauma patients in the battlefield: an assessment for survivors. Resuscitation. 2019;138:20-27. (Retrospective; 582 patients)
68. Anderson KL, Fiala KC, Castaneda MG, et al. Left ventricular compressions improve return of spontaneous circulation and hemodynamics in a swine model of traumatic cardiopulmonary arrest. J Trauma Acute Care Surg. 2018;85(2):303-310. (Animal study; 26 subjects)
69. Seamon MJ, Haut ER, Van Arendonk K, et al. An evidence-based approach to patient selection for emergency department thoracotomy: a practice management guideline from the Eastern Association for the Surgery of Trauma. J Trauma Acute Care Surg. 2015;79(1):159-173. (Systematic review, guideline; 72 studies, 10,238 patients)
70. Inaba K, Chouliaras K, Zakaluzny S, et al. FAST ultrasound examination as a predictor of outcomes after resuscitative thoracotomy: a prospective evaluation. Ann Surg. 2015;262(3):512-518. (Prospective; 187 patients)
71. Joseph B, Khan M, Jehan F, et al. Improving survival after an emergency resuscitative thoracotomy: a 5-year review of the Trauma Quality Improvement Program. Trauma Surg Acute Care Open. 2018;3(1):e000201. (Retrospective; 2229 patients)
72. Green RS, Butler MB, Erdogan M. Increased mortality in trauma patients who develop postintubation hypotension. J Trauma Acute Care Surg. 2017;83(4):569-574. (Retrospective; 477 patients)
73. Kim WY, Kwak MK, Ko BS, et al. Factors associated with the occurrence of cardiac arrest after emergency tracheal intubation in the emergency department. PLoS One. 2014;9(11):e112779. (Case control; 2403 patients)
74. Johnson KB, Egan TD, Kern SE, et al. Influence of hemorrhagic shock followed by crystalloid resuscitation on propofol: a pharmacokinetic and pharmacodynamic analysis. Anesthesiology. 2004;101(3):647-659. (Animal study; 16 subjects)
75. Tran DT, Newton EK, Mount VA, et al. Rocuronium versus succinylcholine for rapid sequence induction intubation. Cochrane Database Syst Rev. 2015;2015(10):CD002788. (Systematic review; 50 trials, 4151 patients)
76. Heier T, Caldwell JE. Rapid tracheal intubation with large-dose rocuronium: a probability-based approach. Anesth Analg. 2000;90(1):175-179. (Randomized clinical trial; 60 patients)
77. Mayglothling J, Duane TM, Gibbs M, et al. Emergency tracheal intubation immediately following traumatic injury: an Eastern Association for the Surgery of Trauma practice management guideline. J Trauma Acute Care Surg. 2012;73(5 Suppl 4):S333-S340. (Guideline)
78. Page D, Ablordeppey E, Wessman BT, et al. Emergency department hyperoxia is associated with increased mortality in mechanically ventilated patients: a cohort study. Crit Care. 2018;22(1):9. (Prospective; 688 patients)
79. Wolthuis EK, Choi G, Dessing MC, et al. Mechanical ventilation with lower tidal volumes and positive end-expiratory pressure prevents pulmonary inflammation in patients without preexisting lung injury. Anesthesiology. 2008;108(1):46-54. (Randomized trial; 40 patients)
80. Cap AP, Pidcoke HF, Spinella P, et al. Damage control resuscitation. Mil Med. 2018;183(suppl_2):36-43. (Guideline) DOI: 10.1093/milmed/usy112
81. Riskin DJ, Tsai TC, Riskin L, et al. Massive transfusion protocols: the role of aggressive resuscitation versus product ratio in mortality reduction. J Am Coll Surg. 2009;209(2):198-205. (Prospective; 77 patients)
82. Khan S, Allard S, Weaver A, et al. A major haemorrhage protocol improves the delivery of blood component therapy and reduces waste in trauma massive transfusion. Injury. 2013;44(5):587-592. (Retrospective; 2986 patients)
83. Patil V, Shetmahajan M. Massive transfusion and massive transfusion protocol. Indian J Anaesth. 2014;58(5):590-595. (Review)
84. Cotton BA, Dossett LA, Haut ER, et al. Multicenter validation of a simplified score to predict massive transfusion in trauma. J Trauma. 2010;69 Suppl 1:S33-S39. (Prospective; 586 patients)
85. Motameni AT, Hodge RA, McKinley WI, et al. The use of ABC score in activation of massive transfusion: the yin and the yang. J Trauma Acute Care Surg. 2018;85(2):298-302. (Retrospective; 3421 patients)
86. Seheult JN, Anto V, Alarcon LH, et al. Clinical outcomes among low-titer group O whole blood recipients compared to recipients of conventional components in civilian trauma resuscitation. Transfusion. 2018;58(8):1838-1845. (Retrospective; 124 patients)
87. Maegele M, Lefering R, Yucel N, et al. Early coagulopathy in multiple injury: an analysis from the German Trauma Registry on 8724 patients. Injury. 2007;38(3):298-304. (Retrospective; 8724 patients)
88. Bulger EM, May S, Kerby JD, et al. Out-of-hospital hypertonic resuscitation after traumatic hypovolemic shock: a randomized, placebo controlled trial. Ann Surg. 2011;253(3):431-441. (Prospective; 853 patients)
89. Roberts I, Blackhall K, Alderson P, et al. Human albumin solution for resuscitation and volume expansion in critically ill patients. Cochrane Database Syst Rev. 2011(11):CD001208. (Meta-analysis; 38 patients)
90. Shafi S, Collinsworth AW, Richter KM, et al. Bundles of care for resuscitation from hemorrhagic shock and severe brain injury in trauma patients-translating knowledge into practice. J Trauma Acute Care Surg. 2016;81(4):780-794. (Review)
91. Lewis SR, Pritchard MW, Evans DJ, et al. Colloids versus crystalloids for fluid resuscitation in critically ill people. Cochrane Database Syst Rev. 2018;8(8):CD000567. (Cochrane review; 69 studies, 30,020 participants)
92. Schreiber MA. The use of normal saline for resuscitation in trauma. J Trauma. 2011;70(5 Suppl):S13-S14. (Review)
93. Young JB, Utter GH, Schermer CR, et al. Saline versus Plasma-Lyte A in initial resuscitation of trauma patients: a randomized trial. Ann Surg. 2014;259(2):255-262. (Randomized controlled trial; 43 patients)
94. Spinella PC, Perkins JG, Grathwohl KW, et al. Warm fresh whole blood is independently associated with improved survival for patients with combat-related traumatic injuries. J Trauma. 2009;66(4 Suppl):S69-S76. (Retrospective; 354 patients)
95. Rhee P, Inaba K, Pandit V, et al. Early autologous fresh whole blood transfusion leads to less allogeneic transfusions and is safe. J Trauma Acute Care Surg. 2015;78(4):729-734. (Retrospective; 272 patients)
96. Williams J, Merutka N, Meyer D, et al. Safety profile and impact of low-titer group O whole blood for emergency use in trauma. J Trauma Acute Care Surg. 2020;88(1):87-93. (Prospective; 350 patients)
97. Holcomb JB, del Junco DJ, Fox EE, et al. The prospective, observational, multicenter, major trauma transfusion (PROMMTT) study: comparative effectiveness of a time-varying treatment with competing risks. JAMA Surg. 2013;148(2):127-136. (Prospective; 1245 patients)
98. Holcomb JB, Tilley BC, Baraniuk S, 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. JAMA. 2015;313(5):471-482. (Prospective; 680 patients)
99. Owattanapanich N, Chittawatanarat K, Benyakorn T, et al. Risks and benefits of hypotensive resuscitation in patients with traumatic hemorrhagic shock: a meta-analysis. Scand J Trauma Resusc Emerg Med. 2018;26(1):107. (Meta-analysis; 30 studies)
100. Tran A, Yates J, Lau A, et al. Permissive hypotension versus conventional resuscitation strategies in adult trauma patients with hemorrhagic shock: a systematic review and meta-analysis of randomized controlled trials. J Trauma Acute Care Surg. 2018;84(5):802-808. (Meta-analysis; 5 randomized trials, 1158 patients) DOI: 10.1097/TA.0000000000001816
101. Woolley T, Thompson P, Kirkman E, et al. Trauma Hemostasis and Oxygenation Research Network position paper on the role of hypotensive resuscitation as part of remote damage control resuscitation. J Trauma Acute Care Surg. 2018;84(6S Suppl 1):S3-S13. (Review)
102. McIntyre L, Hebert PC, Wells G, et al. Is a restrictive transfusion strategy safe for resuscitated and critically ill trauma patients? J Trauma. 2004;57(3):563-568. (Retrospective; 203 patients)
103. Boutonnet M, Abback P, Le Sache F, et al. Tranexamic acid in severe trauma patients managed in a mature trauma care system. J Trauma Acute Care Surg. 2018;84(6S Suppl 1):S54-S62. (Retrospective; 684 patients)
104. Moore HB, Moore EE, Chapman MP, et al. Does tranexamic acid improve clot strength in severely injured patients who have elevated fibrin degradation products and low fibrinolytic activity, measured by thrombelastography? J Am Coll Surg. 2019;229(1):92-101. (Prospective; 630 patients)
105. Zeeshan M, Hamidi M, Feinstein AJ, et al. Four-factor prothrombin complex concentrate is associated with improved survival in trauma-related hemorrhage: a nationwide propensity-matched analysis. J Trauma Acute Care Surg. 2019;87(2):274-281. (Retrospective; 468 patients)
106. Smith MN, Deloney L, Carter C, et al. Safety, efficacy, and cost of four-factor prothrombin complex concentrate (4F-PCC) in patients with factor Xa inhibitor-related bleeding: a retrospective study. J Thromb Thrombolysis. 2019;48(2):250-255. (Retrospective; 31 patients)
107. Stinger HK, Spinella PC, Perkins JG, et al. The ratio of fibrinogen to red cells transfused affects survival in casualties receiving massive transfusions at an army combat support hospital. J Trauma. 2008;64(2 Suppl):S79-85. (Retrospective; 252 patients)
108. Nardi G, Agostini V, Rondinelli B, et al. Trauma-induced coagulopathy: impact of the early coagulation support protocol on blood product consumption, mortality and costs. Crit Care. 2015;19:83. (Prospective; 226 patients)
109. Rourke C, Curry N, Khan S, et al. Fibrinogen levels during trauma hemorrhage, response to replacement therapy, and association with patient outcomes. J Thromb Haemost. 2012;10(7):1342-1351. (Prospective; 517 patients)
110. Cardenas JC, Wade CE, Cotton BA, et al. TEG lysis shutdown represents coagulopathy in bleeding trauma patients: analysis of the PROPPR cohort. Shock. 2019;51(3):273-283. (Retrospective; 1096 patients)
111. Innerhofer P, Fries D, Mittermayr M, et al. Reversal of trauma-induced coagulopathy using first-line coagulation factor concentrates or fresh frozen plasma (RETIC): a single-centre, parallel-group, open-label, randomised trial. Lancet Haematol. 2017;4(6):e258-e271. (Randomized controlled trial; 94 patients)
112. Wade CE, Eastridge BJ, Jones JA, et al. Use of recombinant factor VIIa in US military casualties for a five-year period. J Trauma. 2010;69(2):353-359. (Retrospective; 2050 patients)
113. Shibahashi K, Sugiyama K, Okura Y, et al. Defining hypotension in patients with severe traumatic brain injury. World Neurosurg. 2018;120:e667-e674. (Retrospective; 12,537 patients)
114. Cannon JW, Johnson MA, Caskey RC, et al. High ratio plasma resuscitation does not improve survival in pediatric trauma patients. J Trauma Acute Care Surg. 2017;83(2):211-217. (Retrospective; 364 patients)
115. Leeper C. Cold stored uncrossmatched whole blood can be safely administered to pediatric trauma patients. Transfusion. 2017;57(S3):24A. (Case series; 18 patients)
116. Eckert MJ, Wertin TM, Tyner SD, et al. Tranexamic acid administration to pediatric trauma patients in a combat setting: the pediatric trauma and tranexamic acid study (PED-TRAX). J Trauma Acute Care Surg. 2014;77(6):852-858. (Retrospective; 766 patients)
117. Russell RT, Maizlin, II, Vogel AM. Viscoelastic monitoring in pediatric trauma: a survey of pediatric trauma society members. J Surg Res. 2017;214:216-220. (Survey)
118. Baksaas-Aasen K, Gall L, Eaglestone S, et al. iTACTIC - implementing Treatment Algorithms for the Correction of Trauma-Induced Coagulopathy: study protocol for a multicentre, randomised controlled trial. Trials. 2017;18(1):486. (Study protocol)
119. Williams TK, Tibbits EM, Hoareau GL, et al. Endovascular variable aortic control (EVAC) versus resuscitative endovascular balloon occlusion of the aorta (REBOA) in a swine model of hemorrhage and ischemia reperfusion injury. J Trauma Acute Care Surg. 2018;85(3):519-526. (Animal study; 12 subjects)
120. Wang C, Zhang L, Qin T, et al. Extracorporeal membrane oxygenation in trauma patients: a systematic review. World J Emerg Surg. 2020;15(1):51. (Systematic review; 58 articles, 548 patients)
121. Aoki M, Abe T, Saitoh D, et al. Use of vasopressor increases the risk of mortality in traumatic hemorrhagic shock: a nationwide cohort study in Japan. Crit Care Med. 2018;46(12):e1145-e1151. (Retrospective; 3551 patients)
122. Cohn SM, McCarthy J, Stewart RM, et al. Impact of low-dose vasopressin on trauma outcome: prospective randomized study. World J Surg. 2011;35(2):430-439. (Randomized controlled trial; 78 patients)
123. Sims CA, Holena D, Kim P, et al. Effect of low-dose supplementation of arginine vasopressin on need for blood product transfusions in patients with trauma and hemorrhagic shock: a randomized clinical trial. JAMA Surg. 2019;154(11):994-1003. (Randomized controlled trial; 100 patients)
124. Dezman ZD, Comer AC, Smith GS, et al. Failure to clear elevated lactate predicts 24-hour mortality in trauma patients. J Trauma Acute Care Surg. 2015;79(4):580-585. (Retrospective; 3887 patients)