22 Dec Prehospital Blood Products Resuscitation
Blood and blood products are used in different ways by EMS around Europe and beyond. The review by Dr. Pietro Fransvea (Department of Emergency Surgery, Catholic University, Policlinico Gemelli of Rome) on this topic was performed on behalf of Work Package 3. “Blood and blood products use in the pre-hospital setting”, identifies gaps and needs of these procedures. It is a basis to stimulate discussion and collaboration between academia and practitioners to foster innovation on this topic.
Haemorrhage remains one of the principal causes of death in both civilian and military (battlefield) trauma. Haemostasis is, therefore, a key determinant for a patient survival both immediately after the trauma and over the ensuing hours. Unfortunately, a patient haemostatic potential is impaired by the rapid development of a coagulopathy associated with trauma.(1;5)
In the context of major trauma, in-hospital blood product has been shown to be superior to crystalloid in haemorrhagic shock, and the administration of high ratios of plasma to packed red blood cells is a routine practice for in-hospital trauma resuscitation. The early phase of trauma-induced coagulopathy is associated with tissue hypoperfusion and traumatic shock, and it is referred to as Acute Trauma Coagulopathy (ATC). Several studies have shown that the presence of ATC is independently associated with increased mortality, morbidity, Length of hOspital Stays (LOS), duration of stay in the intensive care unit, and transfusion requirement. Current therapy centres on early and aggressive use of blood products such as plasma and fibrinogen, as well as red blood cells, with an emphasis on a high ratio of plasma to red blood cells, whereas the use of colloids and crystalloids is limited. (6-9)
Military and civilian emergency teams are increasingly carrying PreHospital Blood Products (PHBP) for trauma resuscitation. However, the literature reporting PHBP for trauma resuscitation is contradictory and provides only poor-quality evidence. (10-14). The current available most common blood products are reported in table 1. The U.S. Army Ranger Regiment was an early adopter of prehospital blood transfusion and uses the following criteria for transfusion: signs and symptoms of haemorrhagic shock; OR 1+plus amputation; OR blunt/penetrating trauma (junctional/abdominal/thoracic); OR pelvic fracture; OR SBP (systolic blood pressure) = 50; pulse >100. (20).
In Australia, the Greater Sydney Area Helicopter Emergency Medical Services (GSAHEMS) is an intensivist-based prehospital critical care service that has extensive experience in prehospital blood transfusion. In the prehospital environment, they transfuse blood if there is “persistent haemorrhagic shock despite haemorrhage control measures after crystalloid infusion.” The Australian Queensland Ambulance Service Trauma Response Team administers blood products in the prehospital environment, and a retrospective review of cases was published in 2014 demonstrating benefit in appropriate clinical situations.
In 2014, proposed criteria for prehospital blood products in combat casualties were refined based on data from Afghanistan and updated in 2020 using a larger data set from the entire DoD Trauma Registry (DoDTR). A case series reviewing the benefits of early whole blood administration in combat casualties was published in 2016.
The UK MERT (Medical Emergency Response Teams, UK military helicopter retrieval in Afghanistan) was able to project FFP (Fresh Frozen Plasma) and PRBCs (Packed Red Blood Cells) into the prehospital arena. By contrast, civilian helicopter ambulance services in the United Kingdom project PRBCs but no plasma in the context of pre-hospital trauma support
However, while permissive hypotension has become an established prehospital resuscitation strategy, there is no clear evidence to guide the type and volume of fluid that should be used. (15-17) Several studies in animal models showed that plasma is a superior resuscitation fluid to crystalloid in a prehospital model of severe haemorrhagic shock as it attenuates hyperfibrinolysis and improves systemic perfusion. (18). Borgman et al., in a retrospective cohort with war injuries, were the first to report a sharp decrease in death rate after traumatic shock when a 1:1 plasma/packed red blood cells (RBC) ratio was initiated within 4 h after trauma occurrence. (19)
Gaps and needs
The initial management of ATC focuses on preventing progression to haemorrhagic shock by arresting the bleeding and restoring circulating blood volume. Since the prehospital projection of PRBCs and FFP does have significant logistical implications (e.g., ensuring appropriate storage conditions and traceability) and some clinical hazards (e.g., possible transfusion reactions and infection), especially in austere circumstances, it is important to determine whether earlier (prehospital) administration confers advantage compared with immediate in-hospital administration. (20). The fluids administered in the pre-hospital setting can help but also potentially harm the patient. Resuscitation using large volumes of crystalloids can increase blood pressure but may also exacerbate coagulopathy and burst the forming clots if blood pressure is raised too rapidly. High-volume crystalloid resuscitation has been associated with hyperfibrinolysis upon presentation to the hospital, partially through dilution of circulating antifibrinolytic proteins, and is independently associated with morbidity.
Permissive hypotension with low-volume crystalloid administration was demonstrated to be effective for the management of patients with traumatic injury in a landmark study in the pre-hospital setting, in particular, subsequent subgroup analysis indicated the benefit was greater for patients with pericardial tamponade. (20-31). According to Advanced Trauma Life Support (ATLS®), permissive hypotension is the main strategy of fluid resuscitation, and it consists in balancing the objective of organ perfusion with the risks of further bleeding, accepting blood pressure lower than normal, however, it is necessary to carefully evaluate the patient’s response, basing on evidence of adequate perfusion and oxygenation of vital organs, controlling diuresis, level of consciousness and peripheral perfusion. This resuscitation strategy can be adopted as a “bridge” solution but does not replace absolutely the need for surgical control definitive of the bleeding. (32)
Furthermore, to aid in the translation of military lessons learned into the civilian setting, it is important to compare the military (prehospital PRBCs:FFP) and civilian (prehospital PRBCs alone) putative best practices to the original (often current) standard of care (limited use of asanguineous fluid). Military data often lacks initial vital signs such as SBP, HR, RR prior to blood product initiation (33). Moreover, in a study by Moore H. B. et al. pre-hospital plasma resuscitation in an urban setting with short transportation times did not reduce mortality and was associated with a prolonged INR. In a post hoc analysis of two clinical trials of pre-hospital plasma transfusion, the benefit of this measure seemed to be limited to those with a blunt injury and transport times >20 minutes (18). Ongoing work is evaluating the potential role of lyophilized plasma in the pre-hospital setting (as it overcomes the logistical challenges of thawing plasma in the mobile setting) and of whole blood as a pre-hospital resuscitation strategy (which has been proven to be feasible, but its effect on coagulopathy remains to be determined. (11-13)
Regarding the use of TraneXamic Acid (TXA) two recent randomized controlled trials showed that pre-hospital TXA administered during air medical or ground transport of severely injured patients without Traumatic Brain Injury (TBI) does not indicate improved survival, but shows that it is safe and improves survival in patients in severe shock and that TXA for TBI does not indicate improved neurological recovery, although a subgroup receiving a dose of 2g appeared to have improved survival. (21,22) Moreover, the use of fibrinogen and other products that do not require refrigeration needs to be examined to reduce the logistical burden associated with the prehospital deployment of these important products. (21)
Due to different national guidelines and regulations of blood component therapies, there is wide heterogeneity in concepts of prehospital damage control resuscitation. Tranexamic acid administration is widely accepted, whereas the transfusion of whole blood, blood components, or coagulation factors needs further examination in the civilian setting. Moreover, several storage and availability and transportation gaps are far to be resolved.
- Assurance that blood centres will have products available in a timely manner
- variable expiration dates between products (range from 5 up to 25+ days)
- Pre-hospital units may not use enough blood to make it worth the hassle.
- Blood needs to be stored at proper temperatures both at the station and while transport
- The expense of regulated coolers, refrigerators, and thermoregulators
- Loss or waste of products due to misuse or lack of use prior to the expiration
Moreover, transfusion reactions are still a matter of debate. Various products pose a risk for different reactions: Anaphylaxis – Circulatory overload – Lung injury. For example, PRBC transfusion is associated with the highest rates of Transfusion Related Acute Lung Injuries (TRALI) and Plasma can cause significant Transfusion-Associated Circulatory Overload (TACO) – Hydrostatic edema – acute respiratory distress, hypoxia, pulmonary edema, increased SBP. This suggests a context-specific balance of risks and benefits.
However, very few patients had reported complications from blood product administration, including anaphylaxis, TRALI, or TACO (34). Reported transfusion reactions were minimal, mostly mild, and easily treated (14).
For example to date, FFP requires either a thawing phase of 30 min and then transport to the scene or storage at 4 °C after thawing, with a high risk of wastage. Regarding this, in the literature, some studies are addressing the use of French Lyophilized Plasma (FLYP). FLYP initially developed by the French Military Blood Institute has shown effectiveness in the management of patients at risk for haemorrhagic shock in the military setting. FLYP has practical advantages that include storage at room temperature, easy reconstitution in less than 6 min, and compatibility with all blood groups. These features suggest possibilities for FLYP use in the prehospital setting for the management of severe traumatic bleeding (23). Moreover, in 2016, US military special operations teams began receiving Low Titer Group O Whole Blood (LTOWB) for use at the Point Of Injury (POI) with the results that the use of cold-stored LTOWB at POI is feasible during combat operations. Furthermore, data are needed to validate and inform best practices for POI transfusion (24). In the civilian setting, Bohaval et al. showed that severely injured patients received LTOWB and more overall product units but had similar 24 h mortality when compared with the only LTOWB or control groups. No increase in transfusion-related complications was seen after LTOWB transfusion, and they concluded that LTOWB should be strongly considered in the resuscitation of trauma patients at civilian centers (25).
In addition, widespread implementation of blood production in pre-hospital resuscitation (especially plasma) in civilian practice is challenging. To address these issues, several prehospital programs have been successfully performed in collaborative agreements with local blood banks to facilitate blood administration:
- Blood not utilized in prehospital administration can be recirculated into blood Bank supply for use before expiration. (Recommended life span for PRBCs is 35 days; Recommended life span for LP is 26 days; Recommended life span for WB is 10-21 days; Recommended life span for thawed FFP is 5 days).
- Multiple options for storage are available based on the prehospital environment.
Target storage temperature is 35.0 – 39.0 degrees Fahrenheit (28). Electronic data collection can be easily documented and monitored with digital thermometer systems (29). With all these measures a minimal wastage of blood products are reported across studies (< 1.9%) (31)
In conclusion, pre-hospital blood products are yet to be shown to be of any clinical benefit, there are still major logistic and financial open questions and a lack of randomized adequate clinical data. A Cochrane review of plasma in massive transfusion is yet to be published (26), whereas a review of plasma transfusion in the critically ill failed to identify any relevant randomized studies (27). A recent observational study (29) showed that early plasma administration is associated with improved 30-day survival (30). However, the PROPPR trial found that despite achieving earlier haemostasis, resuscitation with plasma, platelets and PRBC in 1:1:1 ratios did not improve overall survival compared with 1:1:1 (31). If the use of blood production for pre-hospital resuscitation is achievable with minimal wastage of universal donor components and with short-term safety, no more than low-quality evidence supports this as a “standard of care.” However, the available data is promising and makes physiologic sense.
NO-FEAR project aims to analyze and innovate the field of emergency medicine. We kindly invite you to take part in our survey, which is dedicated to investigating the use of blood and blood products in the context of pre-hospital life support.
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- Cohen MJ, Christie SA. Coagulopathy of Trauma. Crit Care Clin. 2017;33(1):101-118.
- Moore HB, Moore EE, Morton AP, et al. Shock-induced systemic hyperfibrinolysis is attenuated by plasma-first resuscitation. J Trauma Acute Care Surg. 2015;79(6):897-904.
- Jennings LK, Watson S. Massive Transfusion. In: StatPearls. Treasure Island (FL): StatPearls Publishing; August 30, 2021.
- Savioli G, Ceresa IF, Caneva L, Gerosa S, Ricevuti G. Trauma-Induced Coagulopathy: Overview of an Emerging Medical Problem from Pathophysiology to Outcomes. Medicines (Basel). 2021;8(4):16. Published 2021 Mar 24.
- Hashmi ZG, Chehab M, Nathens AB, et al. Whole truths but half the blood: Addressing the gap between the evidence and practice of pre-hospital and in-hospital blood product use for trauma resuscitation. Transfusion. 2021;61 Suppl 1:S348-S353. doi:10.1111/trf.16515
- Fecher A, Stimpson A, Ferrigno L, Pohlman TH. The Pathophysiology and Management of Hemorrhagic Shock in the Polytrauma Patient. J Clin Med. 2021;10(20):4793. Published 2021 Oct 19. doi:10.3390/jcm10204793
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- Quintero L, Meléndez-Lugo JJ, Palacios-Rodríguez HE, et al. Damage control in the emergency department, a bridge to life. Colomb Med (Cali). 2021;52(2):e4004801. Published 2021 May 30. doi:10.25100/cm.v52i2.4801
- Moore, H. B. et al. Plasma-first resuscitation to treat haemorrhagic shock during emergency ground transportation in an urban area: a randomised trial. Lancet 392, 283–291 (2018). This randomized controlled trial shows that prehospital plasma in a ground ambulance system does not improve survival in seriously injured patients.
- Pusateri, A. E. et al. Association of prehospital plasma transfusion with survival in trauma patients with hemorrhagic shock when transport times are longer than 20 minutes: a post hoc analysis of the PAMPer and COMBAT clinical trials. JAMA Surg. 155, e195085 (2019).
- Nadler, R. et al. Early experience with transfusing low titer group O whole blood in the pre-hospital setting in Israel. Transfusion 60, S10–S16 (2020)
- Leeper, C. M., Yazer, M. H. & Neal, M. D. Whole-blood resuscitation of injured patients: innovating from the past. JAMA Surg. 155, 771–772 (2020).
- Smith IM, James RH, Dretzke J, Midwinter MJ. Prehospital Blood Product Resuscitation for Trauma: A Systematic Review. Shock. 2016;46(1):3-16. doi:10.1097/SHK.0000000000000569
- Woodward L, Alsabri M. Permissive Hypotension vs. Conventional Resuscitation in Patients With Trauma or Hemorrhagic Shock: A Review. Cureus. 2021;13(7):e16487. Published 2021 Jul 19. doi:10.7759/cureus.16487
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