Improving Outcomes After Severe Truncal Injury

Transport Time and Preoperating Room Hemostatic Interventions Are Important: Improving Outcomes After Severe Truncal Injury

John B. Holcomb, MD, FACS

Objectives: Experience in the ongoing wars in Iraq and Afghanistan t is widely accepted that injury is a global public health cri- confirm that faster transport combined with effective prehospital sis with death rates increasing worldwide (1). In the United interventions improves the outcomes of patients suffering hemor- IStates, injury is the leading cause of life years lost, outstrip- rhagic shock. Outcomes of patients with hemorrhagic shock and ping cancer and heart disease (2). In 1983, Trunkey (3) described extremity bleeding have improved with widespread use of tourni- the classic trimodal pattern of death after injury, emphasizing quets and early balanced transfusion therapy. Conversely, civil- that the largest opportunity to save lives was very early after ian patients suffering truncal bleeding and shock have the same injury. With years of research and trauma system development, mortality (46%) over the last 20 years. To understand how to multiple authors have demonstrated that this pattern is now uni- decrease this substantial mortality, one must first critically evalu- modal (4). It is clear that patients dying from hemorrhagic shock ate all phases of care from point of injury to definitive hemorrhage after severe truncal injury represent the single largest opportu- control in the operating room. nity to improve care in both the civilian and military arena (5, 6). Data Sources: Limited literature review. The lessons learned from many battlefields have always informed Data Synthesis: The peak time to death after severe truncal injury civilian trauma care, and the ongoing war in Southwest Asia is is within 30 minutes of injury. However, when adding prehospital no exception (7–9). Interventions like improved training, tour- transport time, time spent in the emergency department, followed by niquets and whole blood product resuscitation have lead the way the time in the operating room, it currently takes 2.1 hours to achieve toward increased survival on the battlefield. As described in the definitive truncal hemorrhage control. This disparity in uncontrolled recent National Academies of Medicine trauma report and the truncal bleeding and time to hemorrhage control needs to be recon- Stop the Bleed initiative, it is imperative that these military les- ciled. Prehospital and emergency department whole blood transfu- sons learned translate widely to the civilian sector (10–14). Sim- sion and temporary truncal hemorrhage control are now possible. ilarly, innovative interventions found useful in civilian trauma Conclusions: The importance of rapid transport, early truncal should translate rapidly to the battlefield. hemorrhage control and whole blood transfusion is now widely Simultaneous with multiple clinical changes on the battle- recognized. Prehospital temporary truncal hemorrhage control field, a deployed trauma system was created that collected data and whole blood transfusion should offer the best possibility of for a comprehensive registry. The system of care also included improving patient outcomes after severe truncal injury. (Crit Care deployed research teams at multiple key locations. The sys- Med 2018; 46:447–453) tem allowed leaders to understand the outcome of casualties, Key Words: injury; prehospital time; truncal hemorrhage control and conducted robust performance improvement initiatives, ensuring that unanticipated outcomes did not go unnoticed (15). Since the largest percentage of potentially survivable Department of Surgery, Center for Translational Injury Research, McGovern deaths occur prehospital, a central focus of the system efforts Medical School, UT Health, Houston TX. was on decreasing the killed in action (KIA) rate by improv- Supported, in part, by The Center for Translational Injury Research. ing care on the battlefield, especially by first responders and Dr. Holcomb is the Chief Medical Officer of Prytime Medical, is on the medical advisory board of Arsenal Medical, a founder, and on the board medics at the point of injury. Kotwal et al (16, 17) have elo- of directors of Decisio Health and receives royalties from the University quently described the beneficial effect of faster transport com- of Texas for coinventing the Junctional Emergency Tourniquet Tool. He bined with improved prehospital care on the battlefield. Butler received funding from Prytime Medical, Decisio Health, Terumo BCT, and the University of Texas. (18, 19) recently summarized the issues surrounding improv- For information regarding this article, E-mail: [email protected] ing prehospital care, emphasizing the importance of strong Copyright © 2018 by the Society of Critical Care Medicine and Wolters leadership willing to challenge tradition. Decreasing the KIA Kluwer Health, Inc. All Rights Reserved. rate results in sicker patients arriving alive to hospitals, plac- DOI: 10.1097/CCM.0000000000002915 ing increased stress on the ICUs in those facilities. There was

Critical Care Medicine www.ccmjournal.org 447 Copyright © 2018 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved. Holcomb concern that this would result in an increased died of wounds many have, that the time to death in trauma centers today (DOW) rate. During the war, dedicated ICU teams were is no longer trimodal but rather unimodal (Fig. 1) and that implemented, emulating the civilian evolution of ICU care. patients dying from hemorrhage do so quickly, 1.65 hours after Fortunately, the increase in DOW did not happen (17). admission. The overriding lesson learned from the last 16 years of Fox et al (22) have described the highly reproducible time war is that timely, effective interventions must occur as soon to death from injury after hospital admission in five high-qual- as possible after injury in order to improve outcomes. To ity prospective studies (n = 4,064). They show that bleeding be maximally effective, hemorrhage control interventions patients die rapidly and in a consistent pattern. Early trauma must move out of the operating room (OR), interventional deaths are largely due to hemorrhage, and the median time to radiology (IR), or ICU and into the emergency department hemorrhagic death from admission is around 2 hours (Fig. 2). (ED) or preferably prehospital arena. Although this seems The hourly death rate decreases rapidly after admission from obvious and simplistic, this lesson has not been applied to 4.6% per hour to 1% per hour at 6 hours and less than 0.1% its fullest potential, both on the battlefield and in the civilian per hour by 9 hours after admission. sector. During the last 40 years, the civilian trauma system Champion et al (23) published an analysis of motor mantra has been for emergency medical services (EMSs) vehicle crash mortality from 2001 to 2005 (n = 55,537). The not to “stay and play” but to “scoop and run” and then drive Fatality Analysis Reporting System database includes both or fly faster to the hospital. Once in the trauma center, clini- prehospital and hospital deaths and showed that while hos- cians have worked to minimize patient time in the ED and pital deaths have declined significantly, prehospital deaths run faster to the OR, where definitive truncal hemorrhage have risen. The rate of death curve (Fig. 3) is strikingly simi- control finally occurs. This approach has served its purpose lar to that from Oyeniyi et al (4) and Fox et al (22), (Figs. 1 for a large number of patients but has likely reached the and 2). They concluded that an increase focus on prehospital point of diminishing returns. For example, in hypotensive intervention is warranted. patients with severe abdominal bleeding, mortality after Harvin et al (20) recently described the outcome of 1,706 emergent trauma laparotomy has not changed (≈ 45%) in patients requiring trauma laparotomy within 90 minutes of over 20 years (20, 21). Is this because control of truncal hospital arrival at 12 level 1 trauma centers. Patients who hemorrhage is still delayed until patients arrive in the OR? arrived with a systolic blood pressure greater than 90 mm Hg To modify and improve the existing system in a data-driven had a mortality of 11%, whereas hypotensive patients (sys- fashion, it is instructive to evaluate and optimize every step tolic blood pressure ≤ 90 mm Hg) died 46% of the time. This of the process from injury to finally achieving definitive rate is essentially unchanged from that reported by Clarke hemorrhage control in the OR or IR suite. Based on this et al (21) 2 decades ago. Importantly, this group described concept, I will use several different data sources and outline the median time in ED was 24 minutes, and time from ED the logic on how one might potentially realize the aspira- admission to surgical start was 42 minutes. There was sig- tional goal of the National Academies of Science report of nificant mortality variation between sites. Published articles “Zero Preventable Trauma Deaths.” (10) usually “count” hemorrhage control occurring immediately upon arrival to the hospital or OR, but that is not the case. DATA SOURCES They suggest that novel interventions in the field or ED may Multiple civilian and military papers have described various be critical adjuncts to allow greater time to operative hemor- elements (time, hemorrhage control, and resuscitation) of rhage control. the entire injury to definitive hemorrhage control process. Chang et al (unpublished observations, 2017) reported The following is by no means an exhaustive review, and I on data from the Pragmatic Randomized Optimal Platelet only describe the highlights of each article relevant to this and Plasma Ratio study (n = 680), focused on time to hemo- discussion. stasis after arrival in the OR or IR suite. Time to hemostasis In an extremely important article, Alarhayem et al (6) has rarely been reported, although most clinicians agree that recently published data from the National Trauma Data Base earlier is better. They found that patients achieving hemor- (n ≥ 2.5 million patients) showing that mortality after severe rhage control went to the OR/IR faster and had fewer trans- truncal hemorrhage increased significantly within 30 minutes fusions. While time from ED to OR was consistent between of injury and then decreased. The median transport time in sites (median 23 min), the time to hemostasis after arrival in their study was 37 minutes, longer than the peak time of death. the OR was highly variable between sites (median 67 min) They concluded that current trauma system design is centered and was associated with outcome. After adjusting for multiple on the often quoted “golden hour” resulting in prehospital variables, they conclude that earlier time to hemostasis was transport times greater than the peak in truncal injury–related independently associated with reduced 30-day mortality in death. They suggest that future efforts should be focused on bleeding trauma patients. prehospital interventions that will support these patients until Kotwal et al (17) described the effect of decreasing the pre- reaching definitive care in trauma centers. hospital transport time from 90 to 43 minutes in greater than Oyeniyi et al (4) reviewed 15,874 admissions and 1,029 4,500 severely injured combat casualties, combined with blood death in their single-center 4-year study. They document, as product resuscitation. KIA deaths decreased while avoiding a

Figure 1. A, Time to death during 72 hours (unimodal) after admission at a single trauma center. B, Time to death during 40 days (unimodal) after admission in 1,029 patients at a single trauma center. Modified from Oyeniyi et al (4). Hem = hemorrhage, TBI = traumatic brain injury. trauma centers, whereas more severely injured helicopter patients required 76 minutes. An adjusted analysis showed no difference in mortality between the groups. Brown et al (25) have stud- ied prehospital transfusion in civilian trauma patients and concluded that blood product resuscitation improves outcome of severely injured patients. Similarly, O’Reilly et al (26) in a matched group of military casualties associ- ate improved outcome with prehospital transfusion. In an extremely important Figure 2. After admission, PRospective Observational Multicenter Major Trauma Transfusion (PROMMTT) article, Shackelford et al (27) and Pragmatic Randomized Optimal Platelet and Plasma Ratio (PROPPR) patients die early and at a very describe the significant effect reproducible rate, n = 1,925. Modified from Fox et al (22). of prehospital transfusion in concomitant increase in DOW. Overall battlefield survival was combat casualties. They showed that transfusion within 36 improved. minutes of injury was associated with improved survival. Newgard et al (24) described time to transport across 112 In civilian patients, Meyer et al (28) described the relation- EMS agencies in North America (n = 2,049), with 34% trans- ship between delivery of coolers of blood products from ported by air. Ground patients took 43.5 minutes to arrive at the blood bank to the bedside and survival of massively

Finally and perhaps the most dramatic example of how pre- OR hemorrhage control can save lives has been the widespread deployment of tourniquets, first on the battlefield and now across the civilian environment. In 2006, Kragh et al (46) docu- mented the significant improvement in survival after combat injury over 7 months in 232 patients with prehospital applica- tion versus waiting until hospital arrival. Although this change did not happen overnight, by the end of 2011, tourniquets were widespread, and preventable combat deaths from extremity hemorrhage had significantly dropped from 7.8% to 2.6% (18). In a similar fashion, Scerbo et al (47) showed in an 8-year, single-center study of 306 civilian patients that prehospital use of tourniquets increased over time was safe and significantly improved survival (48). Figure 3. Death versus time: U.S. vehicle-related fatalities from 2003 Summarizing the articles described above reveals that faster to 2005. n = 55,537. Modified from Champion et al (23). Prehospital transport is usually better, most prehospital times are longer intervention, emergency department intervention, operating room than 30 minutes, and earlier effective intervention aimed at definitive hemostasis. hemorrhage control and blood product resuscitation improve outcomes. It appears that combining these interventions, rapid bleeding patients. Every minute of blood product delay to transport with effective hemostatic resuscitation and hemor- the bedside increased the time to hemostasis (p < 0.001) rhage control, is particularly useful. and odds of mortality by 5%. van Oostendorp et al (29) describe the importance of earlier truncal hemorrhage control and reviewed the vari- DISCUSSION ous methods available today and those under development. Transport time and early intervention has long been the Temporary truncal hemorrhage control outside the OR (pre- essence of trauma care. Cowley created the sound bite, “The hospital, ED and ICU) is achieved around the world via the Golden Hour” around 1976, and it has become ensconced transfemoral artery resuscitative endovascular balloon occlu- in trauma tradition, resulting in 60-minute transport times sion of the aorta (REBOA) approach (30–39). There are mul- for many trauma systems (49). However, recent military tiple different approved catheters of various sizes being used and civilian data support the more obvious solution that for this minimally invasive approach, with early human use there is no hard and fast cutoff for patients who are criti- ranging from trauma, vascular and emergency general surgery cally injured and rapidly bleeding (6, 17). Faster is better, to postpartum hemorrhage (29). Current studies are all small especially when combined with hemorrhage control and and retrospective, with their attendant biases. It appears that blood product resuscitation (17, 50). During the last 40 smaller size catheters are associated with fewer complications, years, the civilian trauma system mantra has been for EMS while prolonged balloon inflation is associated with increasing to “scoop and run” and drive or fly faster to the hospital, ischemic injury, although true risk to benefit in these critically minimize time in the ED and run as fast as possible to the ill patients remains to be seen (32). To understand how best to OR, where definitive truncal hemorrhage control finally use these new devices, the U.S. Department of Defense (DoD) occurs. It is important to measure the time required for is funding a multicenter observational trial of the REBOA each step and realize that uncontrolled truncal hemor- approach, whereas the U.K. National Health Service (NHS) is rhage is continuing while this sequence unfolds. Prehospi- funding a randomized trial, with both studies starting in the tal transport is variable, and in multicenter studies, ranges ED (40, 41). Both studies are currently enrolling (33, 34). These from 37 to 76 minutes (6, 24). Hospital process improve- prospective studies will allow a data-driven discussion regard- ment has resulted in ED times of 24 minutes before moving ing safety, indications, and outcomes. Last, Rago et al (42, 43) to an OR (14). Finally, hemostasis does not occur imme- and Mesar et al (44) are using a different approach, with a peri- diately upon arrival in the OR. There is the prep, drape, toneal space-filling self-expanding foam. They have completed anesthesia, and operating time, resulting in a total time to an extensive preclinical program, successfully describing iliac hemostasis of 67 minutes after arrival in the OR (R. Chang artery and liver injury hemorrhage control, for up to 3 hours et al, unpublished observations, 2017). Some may argue after injury. They also completed a novel “recently dead” study, with these times, but as with all opinions, it is always best confirming the correct foam dose for their upcoming DoD- to actually measure the variable under discussion. When sponsored U.S. Food and Drug Administration-regulated trial actual times are measured, they are almost always longer. (44). The ResQue Foam study should start enrolling in late Adding these times together is sobering: 37 (prehospital) + 2018 for ED control of severe abdominal bleeding (45). It is 24 (ED) + 67 (OR) = 128 minutes (2.1 hr) from injury to encouraging that the NHS and the DoD are funding multi- definitive hemostasis. During these 128 minutes, patients center studies of these novel devices. are dying from uncontrolled truncal hemorrhage.

Over the last 40 years, trauma systems have proliferated and matured. We have implemented systems that find and transport patients to trauma centers and for the large majority of patients, this is more than adequate. However there is a group, the rapidly bleeding patient, which consistently die before achieving definitive hemostasis. Alarhayem et al (6) showed that mortality after severe truncal hemorrhage increased significantly within 30 minutes of injury and then decreased. The median transport time in their study was 37 minutes, longer than the time to peak truncal death rates. Is this disconnect why the recent article by Harvin et al (20) showed at 12 lead- Figure 4. Timeline of truncal hemorrhage control. ED = emergency department, OR = operating room. ing trauma centers, patients requiring emergent trauma laparotomy have a substantial mortality (46%) that is unchanged This is simply too long. Looking to the near future, two new over the last 20 years? The physiology of bleeding to death situations can be constructed (Fig. 4): in the hospital (median of 2 hr) occurs faster than our current systems provide temporary or definitive hemostasis. It is 1) Moving temporary truncal hemorrhage control from likely that the total prehospital transport time versus bleeding the OR to the ED would result in 37 (prehospital) + 18 to death issue is even greater in more austere settings (rural (ED) = 55 minutes, assuming that the intervention occurred and many deployed military units). Patients consistently bleed ¾ of the way through the ED stay. This would result in a 57% to death before our trauma systems can deliver patients to decrease in the time of uncontrolled truncal hemorrhage. the hospital, much less the OR. What will we do about this 2) Moving temporary hemorrhage control from the OR or ED conundrum? to prehospital setting would result in the largest potential improvement, assuming that the intervention occurred ¾ of the way through transport, at 28 minutes or a 78% PROPOSED SOLUTIONS decrease in the time of uncontrolled hemorrhage. The time required to locate and move patients from the injury scene to hospital and into the OR will be hard to sig- Although clearly these calculations are open to interpreta- nificantly change. While minutes can still be shaved from the tion and not exact, the point is that, current system design, we have likely reached the limit that 1) the death curve after injury is highly reproducible. would result in substantial improvements in patient out- 2) the median time to hemorrhagic death after admission is 2 comes. Time to arrival at high-volume levels 1 and 2 trauma hours. centers could be decreased by creating more centers, but 3) the current time to definitive hemorrhage control from that has its own issues, not the least of which are economic, injury is 2.1 hours. political, and volume related. The reproducible physiology 4) the mortality after severe truncal hemorrhage increases of bleeding to death (Figs. 1, 2, and 3) is also hard to modify significantly within 30 minutes of injury and decreases with current treatment paradigms that limit truncal hem- thereafter. orrhage control to the OR or IR suites. The lesson learned 5) pre-OR temporary hemorrhage control is possible. with extremity tourniquet hemorrhage control was to apply them as early as possible (prehospital vs hospital). Similarly, By moving the temporary truncal hemorrhage control blood product resuscitation improves outcome, especially time line up and to the left (Fig. 4), it is likely that substantial when started prehospital (27). Blood product resuscitation improvements in outcome could be achieved. In my mind, this is better than crystalloid, and balanced blood product resus- is the major lesson learned from the ongoing war. Blood prod- citation is superior to unbalanced (51). With greater than uct transfusion has moved out of the OR to the ED over the last 10,300 units transfused in the ongoing war, it is clear that decade and is now prehospital in multiple civilian systems. Use whole blood is the optimal balanced resuscitation product of prehospital whole blood is being used routinely in current (52, 53). It appears that the best way to improve outcomes combat operations and in several locations across the United in bleeding trauma patients is to stop bleeding earlier, resus- States. Prehospital hemorrhage controls with tourniquets were citate them with blood products “while” moving rapidly to never used a decade ago and are now common place. Perhaps the hospital. Much like the military lessons learned concern- more important than these is the life-saving potential of earlier ing prehospital tourniquets and blood products, to signifi- (pre-OR) temporary truncal hemorrhage control. To accom- cantly improve outcomes in patients suffering hemorrhagic plish these changes, surgeons must work collaboratively with shock from truncal injury, we need to implement interven- multiple members of the extended trauma team (emergency tions that facilitate temporary truncal hemorrhage control medicine, anesthesia, physician assistants, nurses, and medics), as close as possible to the point of injury. and implement new training and intervention paradigms. Using the data described above, it currently takes 37 (pre- With appropriate training, I am confident that these inter- hospital) + 24 (ED) + 67 (OR) = 128 minutes or 2.1 hours ventions can safely occur outside the OR. Our existing trauma from injury until truncal bleeding is definitively controlled. systems provide the framework within which to implement

Critical Care Medicine www.ccmjournal.org 451 Copyright © 2018 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved. Holcomb pre-OR truncal hemorrhage control interventions combined ventable Deaths After Injury. 2016. Washington, DC, The National with whole blood resuscitation paradigms. To fully realize the Academies Press. Available at: http://www.nationalacademies.org/hmd/ Reports/2016/A-National-Trauma-Care-System-Integrating-Military-and- benefits, these interventions need to occur either before or Civilian-Trauma-Systems.aspx. Accessed September 26, 2017 during transport. At the minimum, they should occur in the 11. Levy MJ, Jacobs LM: A call to action to develop programs for bystand- ED before moving to the OR or IR suite. Finally, it is extremely ers to control severe bleeding. JAMA Surg 2016; 151:1103–1104 important that the military and civilian research community 12. 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