Uncontrolled hemorrhage requiring emergent surgery after major trauma continues to be a contributor to perioperative death (Intensive Care Med 2019;45:709-11). While most hemorrhage deaths occur before injured patients reach the hospital, advancement in medical management has improved survival for those who make it to our ORs. Often, the resuscitation of these patients is complicated by an acquired coagulopathy that requires a “hemostatic resuscitation,” which is the restoration of tissue perfusion with components that improve clot effectiveness (Br J Anaesth 2012;109:i39-i46). The concept of fixed ratio transfusions (such as 1:1:1; 1 U of packed red blood cells: 1 U fresh frozen plasma: 1 donor’s worth of platelets) was developed following the recognition that some seriously injured patients benefit when hemostatic resuscitation was started immediately and continued aggressively. Due to the inability to assess for specific coagulation defects in a timely fashion during resuscitation of the patient in hemorrhagic shock, it can be difficult or impossible to identify which patients would benefit from fixed ratio algorithms and which would not. It is therefore inevitable that some patients will receive empiric blood products that they did not need and would not benefit from. Some may be harmed by transfusion reactions. While there is little question that the use of blood products will be required not only to restore volume but also to address the trauma-induced coagulopathy (TIC), the best approaches to assessing and treating this coagulopathy continues to be a focus of significant research.
A popular concept in resuscitation research is the role of point-of-care viscoelastic hemostatic assays (VHAs) as adjuncts to conventional coagulation tests (CCTs; prothrombin time, partial thromboplastin time, platelet count, fibrinogen level, etc.) or as a complete replacement for them. VHAs encompass a range of platforms, such as thromboelastography (TEG) or rotational thromboelastometry (ROTEM), that universally incorporate a whole blood testing approach to provide a functional measure of clot formation and degradation to supplement existing CCTs. Proponents of goal-directed transfusions believe that the ability to assess whole blood clotting with the use of a VHA could allow for more directed, timely therapy and minimization of unnecessary blood product transfusion. Recent guidelines addressing bleeding in the trauma patient have begun to incorporate VHAs with goal-directed transfusion and resuscitation recommendations. The European Guideline on Management of Major Bleeding and Coagulopathy Following Trauma, updated in 2019, recommends coagulation monitoring with CCTs or VHAs (Grade 1C), while resuscitation measures should be continued using a goal-directed strategy guided by CCTs and/or VHAs (Grade 1B) (Crit Care 2019;23:98).
Which approach is better?
In a recently published “pro-con” discussion on whether VHAs should replace the use of fixed ratio transfusion protocols in trauma, the authors review the current literature examining the use of a more goal-directed resuscitation approach (Anesth Analg 2022;134:21-31). They point out that VHAs in other surgical procedures, most notably cardiac surgery, have been associated with a reduction in plasma and platelet administration but had little or no impact on mortality. The most recent systematic review in 2017 examining the role of VHAs in bleeding patients found insufficient data at that time to make any recommendations regarding their efficacy in improving outcomes in trauma patients when compared to usual care (Anaesthesia 2017;72:519-31).
The Implementing Treatment Algorithms for the Correction of Trauma-Induced Coagulopathy (iTACTIC) trial published in 2021 attempted to address this controversy directly. In this most recent multicenter trial, trauma patients triggering a local massive transfusion protocol were randomized within three hours of injury and a maximum of one hour after admission to either a CCT- or VHA-guided resuscitation using TEG or ROTEM (Figure) (Intensive Care Med 2021;47:49-59). In their intention to treat analysis, the investigators found no difference in 24-hour or 28-day mortality nor for total blood components administered. The limitations noted in this study, however, are significant, and the role of VHAs in guiding resuscitation continue to be debated (J Clin Med 2021;10:320). The small number of patients requiring a massive transfusion, a low incidence of TIC, and a confluence of patients with traumatic brain injury (TBI) and death due to hemorrhage all suggest that further work needs to be done to identify those patients most likely to benefit from VHA goal-directed therapy.
It is also clear that there is a geographic variation in practice. In the United States, the most recent emphasis in trauma resuscitation is a shift toward the use of cold whole blood (WB) as an evolution of the 1:1:1 strategy for initial resuscitation, with less availability and usage of VHAs. In the European clinical arena, use of VHA-guided therapy has been more extensively employed with several studies showing improvements in outcomes leading to greater incorporation in guidelines for hemorrhage management (Br J Haematol 2018;182:789-806). One significant difference, however, is the proportion of penetrating trauma, which is much higher in North America, as the management of these patients requires rapid surgical intervention to control hemorrhage.
Where are we going in the future?
The increasing reliance on VHA-guided therapy has resulted in two major benefits: 1) improvements in VHA technology, and 2) more focused trials. VHAs in the past required pipetting and were very sensitive to environmental factors such as vibrations and table slope. More recent devices have incorporated a cartridge-based approach, making them more accessible and consistent. They are also becoming increasingly more portable and can now be used in a point-of-care approach to assess coagulation defects during resuscitation. A detailed review of current and emerging VHA technology was published in 2020 (Diagnostics (Basel) 2020;10:118).
The future role of VHAs in trauma resuscitation will likely be guided by ongoing studies. The Pragmatic Prehospital Group O, Whole Blood Early Resuscitation Trial (PPOWER) will look at a strategy of early WB (up to 6 U) followed by transition to a TEG-guided goal-directed resuscitation (asamonitor.pub/3K6j5M3). The hypothesis of this study is that WB will lead to better outcomes when combined with TEG-guided therapy. The Sang Total pOur la Reanimation des Hemorragies Massives (STORHM) trial in France, while not focused on VHAs, will compare WB to a 1:1:1 fixed resuscitation (Transfus Clin Biol 2019;26:198-201). Finally, the Shock, Whole Blood, and Assessment of TBI (SWAT) trial will also compare WB to standard blood component therapy in patients with and without TBI using multiple sites in the Linking Investigations in Trauma and Emergency Services (LITES) Network (asamonitor.pub/3raMmwF). This may help address the issue of concurrent TBI and severe hemorrhagic shock to better understand the linkages.
Regardless of the initial approach to trauma resuscitation, the use of VHAs would appear to offer the benefit of better targeted therapy and avoidance of excessive blood product administration in many clinical settings. As the technology improves, ongoing studies should allow us to improve the overlying algorithms that VHA-derived data provides us during the perioperative management of our bleeding trauma patients.