The Trauma-Science Intersection and Prehospital Care

A simulated injured gunshot victim being taken to a Fire and Emergency Medical Services paramedic unit for transport to a trauma center during a simulated active shooter training scenario at Joint Base Anacostia-Bolling. (Photo by Shay Seaborne.)

By Mary Jane Dittmar

“Over the last 20 years, care for injured patients has undergone a revolution,” states J. B. Holcomb in “Major scientific lessons learned in the trauma field over the last two decades.”¹ Holcomb cites some of the “amazing changes in care in the combat theater that have transitioned into the civilian world,” including the following.   

Training. Holcomb says that prehospital and hospital team training, simulation centers, an the training and equipment designed for the military environment have become commonplace as Tactical Combat Casualty Care (TCCC) spreads worldwide² and have transitioned into clinical practice in the civilian world, where mass-casualty and terrorist events are increasing.

Bleeding. Twenty years ago, bleeding patients were largely on resuscitation to various oxygen or cardia output-based outpoints. Today, Holcomb says that a variety of interventions are needed to save lives. Among them are the “Multitude of hemorrhage-control devices [truncal junctional, extremity, intravascular, and intraperitoneal] combined with hemostatic resuscitation and rapid operative intervention” critical for survival. This “bundled approach to hemorrhage control” has resulted in a decrease in hemorrhagic deaths and edema-related complications for patients.³

Transfusion. Holcomb points out that exsanguination is the leading cause of potentially preventable death for those who die after injury, and bleeding to death occurs within six hours of admission. He cites the concepts that have come into use over the past 20 years, which are the current treatment for traumatic hemorrhagic shock and the simultaneous mechanic hemorrhage control coupled with damage control resuscitation with an emphasis on using plasma as the primary resuscitative fluid.⁴ “Optimal resuscitation now starts in the prehospital area with blood products,” Holcomb says. He notes that the current paradigm is changing, saying, “The TCCC guidelines recommend a move from balanced component transfusion to whole blood.”⁵

Although he says it is impossible to predict with certainty what will occur in the future, Holcomb is expecting that advances in prehospital resuscitation and hemorrhage control will continue, extending the survivable prehospital time to operative intervention. He adds that there is a need to decrease mortality and morbidity from sepsis and all types of traumatic brain injury (TBI) and to improve pain control. Cellular therapy, he suggests, will become an important early intervention to appropriately modulate the inflammatory system, decreasing multiple organ failure and rebuilding or replacing damaged organs.⁶

“Bleeding: The Number-One Cause of Preventable Deaths”

In “Trauma care: Finding a better way,” ⁷ Hasan B. Alamconcurs that revolutionary changes have been occurring in trauma care. However, he stresses that improvement is needed in the period immediately following the injury, including the prehospital phase. He explains that patients with massive bleeding sans head injuries have mortality beyond the first 24 hours of under 10 percent⁸, but there has been no difference in the period immediately following the injury, including the prehospital phase. The majority of deaths in this period are attributable to hemorrhage and/or TBI. Alam says that since bleeding is the more treatable of these two causes of death, it is the number-one cause of preventable deaths.

Alam points to a multinational trial of more than 20,000 patients that showed that most of the deaths occurred within a few hours of injury with fewer than 2.5 percent of the injured succumbing to multiple organ failure.⁹ He also points out that in combat, 87 percent of battlefield deaths occur before the patient reaches a medical facility¹⁰ and around 91 percent of these deaths are attributable to bleeding. Therefore, he says, “The current goal of early care is to keep patients alive long enough to be evacuated to higher echelons of care for definitive treatment.”

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Alam says that in the not-too-distant future, trauma care will differ in the following areas:

• Early hemorrhage control and damage control resuscitation.
• Use of specific prosurvival drugs that can be given in the prehospital setting to keep injured people alive long enough to be transferred to higher levels of care.
• Prehospital use of preserved plasma products, platelets, and red blood cells.
• Safe and effective nonblood oxygen-carrying fluids that can be easily administered.
• Temporary use of hypothermia or hibernation strategies for patients with potentially survivable injuries who need more time for surgery or transfer.
• Individualized therapy (precision medicine) with administration of agents based on the individual’s specific needs.
• Monitoring of response to therapy beyond the measurement of basic physiology by looking at key molecular and cellular disturbances.

Alam sees two of these predictions—pharmacological treatment to create a prosurvival phenotype and therapeutic hypothermia—as being “at the cusp of clinical reality.” In the first case, he points to valproic acid (VPA), a commonly used anti-seizure medicine that, when given in larger doses, can create an anti-inflammatory and prosurvival phenotype.^{11, 12} VPA, he explains, even the absence of conventional resuscitation strategies, has been shown to improve survival and mitigate organ damage in models of lethal hemorrhage¹³ poly-trauma,^14-15 septic shock,¹⁶ ischemia-reperfusion injury,¹⁷ and TBI.¹⁸ A Phase 1 clinical trial of VPA for treating hemorrhage has been conducted; Phase II and III clinical trials are expected to follow. This pharmacological approach, he adds, is equally effective when hemorrhage is complicated by severe TBI.

In therapeutic hypothermia, the focus is on “rapid total body preservation, repair of injuries during metabolic arrest, and controlled resuscitation—a process termed “emergency preservation and resuscitation.” Research with canine models have clearly shown that rapid induction of deep/profound hypothermia (15°C) can improve an otherwise dismal outcome after exsanguinating cardiac arrest.^19-20 A prospective multiinstitutional trial is underway to establish its feasibility.²¹

References

1. Holcomb JB. (2017) “Major scientific lessons learned in the trauma field over the last two decades.” PLoS Med; 14(7):e1002339. https://doi.org/10.1371/journal.pmed.10002339.
2. Butler FK. Two Decades of Saving Lives on the Battlefield: Tactical Combat Casualty Care Turns 20. Mil Med 2017 Mar; 182(3):e1563-e1568. pmid:28290925.
3. Oyeniyi BT, Fox EE, Scerbo M, Tomasek JS, Wade CE, Holcomb JB. Trends in 1029 trauma deaths at a level 1 trauma center: Impact of a bleeding control bundle of care. Injury. 2017 Jan; 48(1):5-12. pmid:27847192.
4. Holcomb, JB, Jenkins D, Rhee P, Johannigman J. Mahoney P, Mehta S, et al. Damage control resuscitation: directly addressing the early coagulopathy of trauma. J Trauma 2007 Feb; 62(2):307-10. pmid:17297317.
5. Butler FK, Holcomb JB, Schreiber MA, Kotwal RS, Jenkins DA, Champion HR, et al. Fluid Resuscitation for Hemorrhagic Shock in Tactical Combat Casualty Care: TCCC Guidelines Change 14-01—June 2, 2014. J Spec Oper Med 2014; 14(3):13-38. pmid:25344706.
6. Pati S, Pilia M, Grimsley JM, Karanikas AT, Oyeniyi B, Holcomb JB, et al. Cellular Therapies in Trauma and Critical Care Medicine: Forging New Frontiers. Shock. 2015 Dec; 44(6):505-23. pmid:26428845.
7. Hasan B. Alam. 2017 Trauma care: Finding a better way. PLoS Med 14(7): e1002350. https://doi.org/10.1371/journal. pmid:1002350
8. Shackford SR, Mackersie RC, Holbrook TL, Davis JW, Hollingsworth-Fridlund P, Hoyt DB, et al. The epidemiology of trauma death: a population based analysis. Arch Surg. 1993; 128:571-5. pmid:8489391.
9. CRASH-2 trial collaborators. 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; 376:23-32. pmid:20554319.
10. Eastridge BJ, Mabry RL, Seguin P, Cantrell J, Tops T, Uribe P, et al. Death on the battlefield (2001-2011): implications for the future of combat casualty care. J Trauma Acute Care Surg. 2012;73(6 suppl 5):S431-S437. pmid: 23192066.
11. Li Y, Alam HB. Creating a pro-survival and anti-inflammatory phenotype by modulation of acetylation in models of hemorrhagic and septic shock. Adv Exp Med Biol. 2012; 710:107-33. pmid:22127890.
12. Halaweish I, Nikolian V, Georgoff P, Li Y, Alam HB. Creating a “Prosurvival Phenotype” Through Histone Deacetylase Inhibition: Past, Present, and Future. Shock. 2015; 44 Suppl 1:6-16.
13. Shults C, Sailhamer EA, Liu Y, LIu B, Tabbara M, Butt MU, et al. Surviving blood loss without fluid resuscitation. J Trauma. 2008;64:629-38. pmid: 18332802.
14. Alam HB, Shuja F, Butt MU, Duggan M, Li Y, Zacharias N, et al. Surviving blood loss without blood transfusion in a swine poly-trauma model. Surgery. 2009; 146:325-33. pmid:19628092.
15. Liu Z, Li Y, Chong W. Deperalta DK, Duan X, Liu B, et al. Creating a prosurvival phenotype through a histone deacetylase inhibitor in a lethal two-hit model. Shock. 2014;41:104-8. pmid:24430491.
16. Kim K, Li Y, Jin G, Chong W, Liu B, Lu J, et al. Effect of valproic acid on acute lung injury in a rodent model of intestinal ischemia reperfusion. Resuscitation. 2012;83:243-8. pmid:21824465.
17. Jepsen CH, deMoya MA, Perner A, Sillesen M, Ostrowski SR, Alam HB, et al. Effect of valproic acid and injury on lesion size and endothelial glycocalyx shedding in a rodent model of isolated traumatic brain injury. J Trauma Acute Care Surg. 2014;77:292-7. pmid:25058256.
18. Alam HB, Pusateri AE, Kindzelski A, Egan D, Hoots K, Andrews MT, et al. HYPOSTAT workshop participants. Hypothermia and hemostasis in severe trauma: A new crossroads workshop report. J Trauma Acute Care Surg. 2012 oct; 73(4):809-17. pmid: 23026915.
19. Behringer W, Safar P, Wu X, Kentner R, Radovsky A, Kochanek PM, et al. Survival without brain damage after clinical death of 60-120 minutes in dogs using suspended animation by profound hypothermia. Crit Care Med. 2003;31:1523-31. pmid:12771628.
20. Taylor MJ, Bailes JE, Elrifai AM, Shih SR, Teeple E, Leavitt ML, et al. A new solution for life without blood: asanguineous low-flow perfusion of a whole body perfusate during 3 hours of cardiac arrest and profound hypothermia. Circulation. 1995;91:431-44. pmid:7805248.
21. Tisherman SA, Alam HB, Rhee PM, Scalea TM, Drabek T, Forsythe RM, et al. Development of the Emergency Preservation and Resuscitation for Cardiac Arrest from Trauma (EPR-CAT) Clinical Trial. J Trauma Acute Care Surg. 2017, May 22. pmid:28538639.

Mary Jane Dittmar is the senior associate editor of Fire Engineering and a conference manager of FDIC International. Before joining the magazine in January 1991, she served as editor of a trade magazine in the health/nutrition market and held various positions in the educational and medical advertising fields. She has a bachelor’s degree in English/journalism and a master’s degree in communication arts.