Making blood immediately available in emergencies

The evolution of transfusion of blood products for resuscitation of bleeding patients over the last 30 years has largely been driven by experience on the battlefield, with increasing acceptance into the civilian community.1-43 These changes included timing and type of resuscitation fluid as well as where transfusion occurred. While substantial change has occurred, and outcomes have improved, more remains to be done. This paper will describe that evolution as well as recommending three critical changes that still need to occur to ensure widest benefit to all patients. The changes in a blood-first and balanced resuscitation in the civilian arena have been well described.9-18 It is important to note that almost all these changes occurred first on the battlefield and were then translated into the civilian world. Rather than to simply repeat the changes which have occurred, we will briefly outline the evolution of practice and describe three issues limiting wider implementation of these changes. These changes in practice did not occur sequentially, or even concurrently within the many different civilian trauma systems, (Table 1). Decreasing use of crystalloid and asanguineous colloids. Pre-positioning blood out of the BB and into the emergency department. The interventions/findings listed in Table 1 represent seismic changes in both tradition and clinical practice; they have collectively served to improve outcomes of bleeding trauma patients. Interestingly, there are no new blood products included in the described interventions. What was new is using the existing blood products in balanced ratios and predeployment of those blood products in the emergency department (ED) and prehospital areas. The process / workflow changes which enabled those improvements were new and served to quickly allow the blood products to be transfused into patients within minutes of injury or upon hospital arrival. Importantly, the workflow improvements in blood availability have also benefited other bleeding patients (non-trauma) suffering hemorrhagic shock, including those with massive GI bleeding, postpartum hemorrhage, and ectopic bleeding. In fact, prehospital agencies that have transfused blood products frequently use >50% of their inventory on non-trauma patients suffering hemorrhagic shock.44-46 While the changes described above are substantial, the three major changes described herein are required to fully implement the hard-won transfusion lessons learned over the last 30 years. These changes are critical to improving civilian survival rates from traumatic injury. The first change is adopting the walking blood back, a widely used transfusion practice on all battlefields since the United States (US) Civil War.47-53 The second change involves correcting reimbursement practices that are peculiar to US civilian practice, and which negatively impact EMS ability to provide prehospital blood product transfusion.54-59 These two issues are significantly impeding the ability of civilian clinicians to rapidly deliver blood to patients in emergency situations. Both issues will be described, and specific recommendations will be provided in this paper. The third necessary change has impact on national defense. All military (clinical) personnel working in both military and civilian trauma systems must routinely transfuse these blood products, so they are knowledgeable and ready on day one of the next military conflict to provide the best possible care.60-78 In many trauma systems, early and balanced blood product (including LTO + WB) resuscitation is now the standard of care and clear fluids (crystalloids and colloids) are minimized, resulting in improvements in patient outcomes. Recently, high-quality studies have documented that use of blood products prior to arrival at the hospital (prehospital) improves patient survival by 10% or greater.28-30 No other single intervention has this great an impact on survival. After a serious injury, truly lifesaving interventions are time dependent, with transfusion of blood no different.78-89 It is clear that transfusion of balanced blood products as soon after injury (both prehospital and in the hospital) as possible saves lives. Every minute delay in prehospital transfusion results in 2% increase in 30-day mortality.88 Given the quality of these data, and the profound results of these federally funded studies, prehospital transfusion for bleeding patients should be the standard of care. In addition to the substantial clinical efficacy, over the last 8 years, the logistics (obtaining blood products and appropriate storage and administration) and workflow for safely implementing prehospital programs have been established and can be readily replicated without significant infrastructure changes or overall cost.26 However, the reality is that only a few (approximately 1%) well-funded prehospital agencies have implemented this proven lifesaving intervention.41, 59 Unfortunately, billing and reimbursement for prehospital blood products is extremely limited via governmental or private insurers.55-59 This non-reimbursed operational and clinical cost to agencies already experiencing significant daily financial stress causes most EMS systems to avoid utilizing this life-saving intervention on their helicopters, supervisor vehicles, or ground ambulances. This clearly represents a gap in care with those least likely to afford such treatment, and a socioeconomic bias favoring the affluent. Furthermore, without a clear pathway for reimbursement for "any" blood products, industry will almost certainly avoid developing new dried blood products or performing prehospital studies.54, 79, 78 The new dried blood products under development will significantly decrease the cold chain logistical burden currently required to provide this lifesaving intervention, both on the battlefield and in the civilian sector, but will require a reasonable reimbursement strategy. Based on clinical experience and the US Department of Defense (DoD) policy, the use of prehospital blood products is widespread within the deployed DoD trauma system. Prehospital blood should likewise become standard within the civilian EMS arena. The DoD and NIH have funded prehospital studies documenting that blood products save lives; we now need our government leaders to facilitate reimbursement for all prehospital blood products. Given the experience of the military and the high-quality civilian data documenting the efficacy of prehospital transfusion, it is time that reimbursement policies are established supporting this proven lifesaving intervention.54, 56, 59 Walking blood banks have been used to deliver life-saving fresh whole blood (FWB) to combat casualties in every war the United States has conducted since 1865.47-53 However, their use in the civilian world decreased to near zero over 50 years ago. In 1993, the US military implemented the WBB during combat operations in Somalia.3, 4 However, over the last 20 years the US military routinely utilized the WBB and collected and transfused >10,000 units of fresh whole blood (FWB) primarily when blood components were not available or were considered to be inadequate.33 While FWB is not fully tested for infectious diseases, and thus not an Food and Drug Administration (FDA) approved product, outcomes of casualties receiving FWB were consistently improved compared with those receiving component therapies.35-38 Over the last several years, organizations that have traditionally collected, tested, and supplied blood have occasionally had substantial difficulty in providing adequate amounts of whole blood and blood components, resulting in canceled surgery and rationing of blood products, especially RBCs and platelets. This issue has become more obvious with more frequent announcements of national blood shortage alerts.90-92 These shortages are multifactorial, caused by supply chain issues, blood banking personnel shortages, decreasing donors and decreasing reimbursement. Compounding these issues, when a single patient suffers massive hemorrhage or when a mass casualty events happen, the already limited supplies (especially platelets) are often quickly exhausted. When these same problems occur on the battlefield, the doctrinal solution over the last 20 years of war has been to plan, train, and implement the WBB. When military units have been trained on the WBB procedures, the authors have transfused FWB within 20 minutes of calling for donors. FWB contains fresh red blood cells and 100% of all coagulation components with minimal preservatives and anticoagulants – likely making it the best transfusion product. Focusing on prescreened donors and rapid implementation of the WBB can eliminate the shortage of all blood products and their lifesaving results. While blood supply is increasingly viewed as a national strategic asset, the logistical issues of supplying blood on the battlefield are different than in civilian practice. However, from a patient centric point of view, the issue is the same: not enough blood rapidly available to save their life. Shipping blood products between cities and states may solve shortages for stable patients but is not a viable solution for patients who are actively bleeding to death.50, 51 At a minimum, the WBB should be available for the extreme, but all too common mass casualties plaguing the United States. The conundrum is obvious; the WBB solution used in every war for the last 159 years is not available today for civilian patients in the United States. The WBB delivers blood that is not as safe as FDA compliant products, but it is important to understand the risk versus benefit ratio. Mortality from hemorrhagic shock is in the range of 25%, while the risk of an infectious disease transmission in an established WBB program is in the range of 1/10,000 units.49-53 Given that 85% of massively transfused patients receive less than nine units of whole blood, the risk for an individual patient is miniscule, compared with the risk of near immediate death if blood is not available.87 Currently, several US trauma centers are working through the legal, financial, and ethical issues surrounding establishing a WBB. The United States is not leading the way in this effort. Norway and several other European countries have implemented a civilian WBB.51, 52 Recently, a new European Union Regulation has made allowances to potentially enable EU member states to incorporate WBB into their emergency plans.52 It is clear that multiple regulatory bodies are recognizing that every minute delay of transfusing blood products to a patient in hemorrhagic shock is associated with increased mortality. After discussion with hospital leaders, in addition to the legal and regulatory issues, there are financial concerns associated with routine screening of potential donors, especially in hospitals that do not routinely collect blood. However, the main barriers are the perceived legal and regulatory consequences of transfusing blood that is not completely tested. To this end, it is important to note that while the U.S. Code of Federal Regulations (CFR) does not allow for the routine use of a WBB by a licensed blood establishment (see CFR 630.1 subparts A, B, C, 630.3(a) (b)), it does allow physicians and Transfusion Services meeting certain criteria to use it without a blood establishment license during emergencies (see 607.65). One way to mitigate risk is to take another lesson learned from the DoD; implementing retrospective testing of all donated and transfused blood, and any positive result triggering an automatic notification to the donor, the recipient, the ordering clinician and public health authorities with mitigation interventions to follow.93-95 Given the positive and extensive experience of the military and international community documenting the feasibility, safety, and efficacy of implementing a WBB, it is unethical and likely legally suspect that well-developed plans to train and implement a WBB are not widely available for civilians in the United States. Establishing a citizen supported WBB which can be developed to scale in communities will represent a lasting and meaningful tenet of national resiliency and self-reliability. As described above, periods of armed conflict bring about advances in the care of combat casualties as well as civilians.60, 61 Combat medics and surgical teams hone their skills at caring for combat casualties on the battlefield. New interventions are conceptualized, developed, evaluated, and rapidly implemented. However, an important change takes place in military medicine when a war ends. The troops return home and casualty flow (and consequently clinical trauma experience and expertise) decreases. This issue was eloquently described by DeBakey in 1947 and again in 1996.60, 61 Collectively, this peacetime diminution of combat casualty care capability has been recently called the "Walker Dip," a condition well described after every war by many military physicians.60-76 Military clinicians do continue to care for patients after a war ends, but the vast majority are not trauma patients that have suffered serious injury; thus, readiness for combat casualties suffers. The human cost of the lack of trauma readiness in the military is an increase in the incidence of preventable deaths at the outset of a subsequent conflict. The most recent example of this was in the first years of the wars in Afghanistan and Iraq, where the percentage of deaths that were potentially preventable was 24%, while in the later years it dropped to 10%.77 One way to prevent the increase in mortality at the outset of a new conflict is for the US military to increase participation in the care of civilian trauma patients at current military treatment facilities. Another, complimentary and simultaneous way is to continue to increase participation in military-civilian partnerships in which military trauma teams, including prehospital combat medical personnel, work fulltime at busy and clinically outstanding Level 1 and II civilian trauma centers. Similar to the manner in which soldiers become expert with their weapon systems by routinely "going to the range", the best way to achieve excellence in trauma care is to routinely care for severely injured patients.60-76 Fortunately, the US Congress has recognized this and has directed the US military to expand the military-civilian partnership program that fosters these essential partnerships. As described above, one of the most important lessons translated directly from the battlefield to civilian trauma systems is that prehospital and hospital blood resuscitation improves outcomes. Rapid hospital-based blood product capability has been implemented in most trauma centers. However, implementation in the prehospital area is lagging because of logistic, administrative, and financial issues. As the peace interval lengthens and more and more experienced military medical personnel leave the service, these military-civilian partnerships will increase in importance. During the interwar periods when there are few combat casualties, the civilian trauma systems must maintain, study, and work to improve resuscitation strategies. The repository of trauma expertise resides in the civilian arena during peacetime, and it is necessary that the entire military medical team be expert at transfusing blood products, both prehospital and in the hospital. In conclusion, to prevent the loss of knowledge and thus the clinical outcomes gained on the battlefield, our civilian trauma systems and government officials must implement these three changes. First, our policy makers need to modify the regulations allowing EMS agencies to routinely be reimbursed for prehospital blood products. This will facilitate the spread of prehospital blood products and allow the transfusion of life saving blood as soon as possible to patients in hemorrhagic shock. Second, the WBB must become a viable option when the blood products required to save lives are not immediately available. These two interventions will save lives in the civilian world. Finally, fully implementing these two changes into the civilian trauma systems, combined with increasing military civilian partnerships, will ensure that military providers will retain these skills and knowledge when they next deploy, saving lives on the first day of the next war. All blood products should be available whenever and wherever it is needed. Unfortunately, today, prehospital blood is only available to 1%–2% of patients who could benefit. The authors believe this disparity is unacceptable. We think blood should be transfused within minutes to all injured or ill patients in hypotensive shock, wherever they are. Many will say this vision is impossible and entirely unrealistic. What would they say if their loved one was transported in an ambulance without blood, or admitted to one of the thousands of hospitals that can not provide standard therapy? More than 150,000 patients die after injury every year in the United States, and bleeding is the leading cause of potentially preventable death. Conservatively, more than 35,000 patients bleed to death in the United States every year. When viewed as a public health crisis, blood is an intervention that is proven to save lives and can be used to help address those potentially preventable deaths at every level of care. The time to make blood widely available is now. JBH conceived and drafted the manuscript and all the authors edited the manuscript. The authors reviewed, edited, and approved the manuscript prior to final submission. Dr. Holcomb is on the board of directors of Decisio Health, CCJ Medical Devices, QinFlow, Hemostatics, Zibrio, and Oxyband. He receives research grant support from the DoD, DARPA, NIH and CSL focused on hemorrhage control and resuscitation. He consults with WFIRM and Aspen Medical and is the co-inventor of the Junctional Emergency Tourniquet Tool and receives royalties from UT Health. The other authors have no conflicts.