New Strategies for Massive Transfusion in the Bleeding Trauma Patient

Abstract

Trauma continues to be the leading cause of death among those younger than 40 years. A major cause of death within the first 24 hours is hemorrhage. Many of these patients present with severe coagulopathy and require massive transfusion. Earlier control of coagulopathy has been shown to improve survival. To address coagulopathy sooner, changes in the way we identify and resuscitate the exsanguinating trauma patient have evolved. These changes include early identification of at-risk patients and early, aggressive transfusion of plasma and platelets. This article reviews the key massive transfusion triggers and resuscitation strategy of damage control resuscitation.

Acute care nurse practitioners (ACNPs) are expanding their roles and responsibilities in emergency departments (EDs) and intensive care units (ICUs). In 2005, Kleinpell 1 reported that 5% to 8% of ACNPs worked in trauma ICUs and 9% to 12% in EDs. Of the ACNPs surveyed, more than 50% were responsible for the management of resuscitation efforts, vasoactive infusions, and initiation of blood component therapy.1 Because of the Accreditation Council for Graduate Medical Education-mandated resident work hour reforms, the demand for ACNPs in critical care areas has increased as well.2

One of the most challenging patients encountered by an ACNP is the hemorrhaging trauma victim. Patients who are actively hemorrhaging represent less than 10% of trauma patients seen in EDs, but they are at the highest risk of death within the first hours of admission. Consequently, immediate decision making and precise actions are necessary to avert death by uncontrolled hemorrhage. The cause of death is generally not due to the lack of surgical hemostasis but a result of the multifaceted roles played by the "lethal triad" of acidosis, hypothermia, and coagulopathy (Figure 1).3-8 Recent literature has focused on recognition and treatment of coagulopathy, as this component is the most difficult to manage if not aggressively treated.3,4 Tailored resuscitation efforts in this select group of patients attempt to mitigate this deadly spiral. Acute care nurse practitioners working in the trauma setting must be able to rapidly identify patients in need of massive transfusion and immediately initiate resuscitation efforts to improve patient outcomes.

Figure 1 - Click to enlarge in new window

Figure 1. The "lethal triad" of death from traumatic injury.

BACKGROUND

Hemorrhagic shock accounts for nearly 50% of traumatic deaths within the first 24 hours after injury.3 Often, death occurs within 6 to 12 hours of admission to the hospital.5 Traditional resuscitation efforts have focused on the treatment of 2 components of the "lethal triad": hypothermia and acidosis. We have learned that coagulopathy begins at the time of injury, can be lethal, and must be addressed early in resuscitation efforts.3,4 In recent military conflicts, surgeons treating soldiers recognized the negative impact of coagulopathy on patient outcomes and challenged the dogma of crystalloid-based resuscitation strategies. This led to modification of the onset and ratio of blood products delivered to the exsanguinating patient.3,6-11 Over the last decade, increasing research has shown that early administration of high ratios of plasma to red blood cell transfusion to treat postinjury coagulopathy improves mortality.4,6-8,10,12-15 This concept is known as "damage control resuscitation" (DCR) and focuses on the early recognition and rapid control of coagulopathy through aggressive transfusion of plasma.3,6-11 Ongoing research continues to explore criteria that will rapidly and accurately predict the need for massive transfusion within minutes of a patient's arrival. This article reviews current massive transfusion triggers to identify patients at risk for hemorrhage as well as the implementation of DCR to stop bleeding and mitigate the lethal triad.

EARLY IDENTIFICATION OF PATIENTS NEEDING MASSIVE TRANSFUSION

Significance of Early Initiation of Massive Transfusion on Coagulopathy

Early recognition of the injured patient requiring a massive transfusion is essential to treat coagulopathy before he or she spirals into acute coagulopathy of trauma shock. The exsanguinating patient requiring massive transfusion, defined as more than 10 units of packed red blood cells (PRBCs) within 24 hours, is at significant risk of death from uncontrolled bleeding and persistent coagulopathy.9 Although trauma patients requiring massive transfusion are relatively rare, they are at the highest risk of death from uncontrolled bleeding.5 Adding to the challenge of identifying patients before they reach circulatory collapse is the trauma patient's ability to compensate for severe hemorrhage. These compensatory mechanisms may allow for "normal" vital signs despite hemorrhage, which can mask the true severity of their injuries.16

Using trigger points to predict the need for massive transfusion allows for earlier initiation of interventions, aggressive replacement of blood and coagulation factors, and ultimately improvement in survival. In addition, achieving hemostasis sooner could potentially lead to a decrease in the overall use of blood products, thereby preventing the subsequent undesirable effects of massive transfusion. Although massive transfusion is necessary to prevent death in this patient population, it can be harmful when inappropriately used. Known sequelae from massive transfusion include increased incidence of nosocomial infections, acute respiratory distress syndrome, transfusion-related acute lung injury, multisystem organ failure, and death.5,9

Scoring Systems

There are numerous trauma-scoring systems available to categorize severity of injury but no universal guidelines to predict need for massive transfusion. An Injury Severity Scale (ISS) score is a calculation of anatomical injury and can be assigned to all injured patients. A score greater than 15 is considered severe. The ISS score of patients requiring massive transfusion often ranges from 25 to 50.5,6,10-11,14 As the score increases, there is correlation between the need for blood transfusions and increased mortality.17 In association with the increased rate of transfusion, Brohi et al18 first described the direct correlation between an ISS score over 15 and the increased number of patients with already-present coagulopathy presenting to the ED. Despite the increase in the ISS score, it is the presence of coagulopathy that is independently associated with a higher mortality rate above and beyond the severity of injury.18 While the ISS score is useful in categorizing trauma patients, it is mostly used for research purposes and can only be calculated once the extent of all injuries have been classified, making it impractical as a predictor of massive transfusion. Deciding when a patient needs a massive transfusion depends on many factors, but early recognition of coagulopathy is the most important factor because it is the most difficult to treat.3,4

In recent years, emphasis has been placed on identifying trigger points that are easily obtainable, rapidly available, and accurate in predicting the need for massive transfusions. In 2007, Schreiber et al 17 reported the number 1 predictive value for massive transfusion was a hemoglobin of 11 g/dL or less, along with an international normalized ratio (INR) of more than 1.5, and the presence of a penetrating injury. McLaughlin et al5 followed in 2008 with the development of the McLaughlin score. This score identified additional transfusion triggers to be as follows: systolic blood pressure (SBP), less than 110 mm Hg; heart rate, more than 105 beats per minute; pH, less than 7.25; and hematocrit, less than 32%.5 In 2010, Cotton et al19 demonstrated that an Assessment of Blood Consumption score of 2 or more points would accurately predict the need for massive transfusion.19 This score incorporated the use of FAST (focused assessment with sonography for trauma) along with SBP, heart rate, and mechanism of injury to evaluate the patient.19 Although this scoring system is simple to use and the variables are readily attainable, expertise is required in the use of FAST and it does not specifically identify coagulopathy. As recently as 2011, Callcut and colleagues20 looked at 5 triggers for massive transfusion including SBP less than 90 mm Hg, Hgb less than 11 g/dL, temperature less than 35.5[degrees]C, an INR more than 1.5, and base deficit 6 or more.20 By itself, an INR of more than 1.5 was the most predictive of the need for massive transfusion.20 However, when the criteria were met for both INR and SBP, an even higher likelihood of transfusion occurred.20 Overall, when 3 or more criteria were met, the probability of transfusion increased.20 Many transfusion triggers have been identified and used in various combinations to predict massive transfusion. A summary of these scoring systems is presented in the Table.

TABLE Summary of Mas... - Click to enlarge in new window

TABLE Summary of Massive Transfusion Predictive Values

Massive Transfusion Triggers

Because of the interrelationship of coagulopathy and acidosis within the "lethal triad," identifying the severity of acidosis as a trigger for requiring massive transfusion is necessary. Acidosis contributes to worsening coagulopathy by causing further tissue hypoperfusion, impairing platelet aggregation, and disrupting the clotting cascade. Traditionally, blood pressure and urine output were markers of acidosis and perfusion in hemorrhagic shock.7 Although these are important and must be monitored closely, blood pressure and urine output may normalize while tissue hypoxia persists. Niles and colleagues4 demonstrated that an increased base deficit 6 or more directly correlated with severity of coagulopathy and the need for massive transfusion. A progressively higher base deficit correlated with a higher mortality rate, occurred prior to a drop in blood pressure, and was a better overall indicator of tissue hypoperfusion.4,21,22 If acidosis persists, coagulopathy will not resolve.

Coagulopathy and acidosis make up 2 sides of the "lethal triad." Hypothermia completes the triangle. Of the 3 components, hypothermia is the easiest to combat and predicts mortality but is least predictive of the need for massive transfusion.4,20,23 However, in the presence of coagulopathy and acidosis, hypothermia does predict the need for massive transfusion.20 Hypothermia contributes to bleeding through induction of thrombocytopenia and inactivation of coagulation enzyme factor function.24 Because of this relationship, a temperature of less than 36[degrees]C or 96[degrees]F in the trauma patient should be one of the potential triggers for massive transfusion.10,12,14,20,23

Hypotension in the trauma patient has also been directly linked to the need for massive transfusion and increased mortality. Although defined in the literature as an SBP of 90 mm Hg or less, the data to support this number are scarce.25-27 According to recent research by Eastridge and colleagues,27 once the patient's SBP falls to 90 mm Hg, a state of hypoperfusion and shock will follow. Mortality was shown to increase by 6% for every 10 mm Hg drop in SBP below 115 mm Hg. Furthermore, when the SBP dropped to 110 mm Hg, a progressive increase in base deficit occurred, indicating worsening of acidosis.27 Overall, trauma patients presenting to the ED with an SBP between 90 and 109 mm Hg have an increased mortality rate.25-27 Therefore, a more liberal SBP parameter of 110 mm Hg or less may be a better predictor of the need for massive transfusion.

Five key values have been shown to be the most predictive of the need for massive transfusion and are presented in Figure 2. Additional non-laboratory-based factors that may predict the need for massive transfusion are age 55 years or older, decreased mental status, and weak or absent radial pulse.5,10,15,23,28,29

Figure 2 - Click to enlarge in new window

Figure 2. Five key triggers for massive transfusion. Hgb, hemoglobin, INR, international normalized ratio; SBP, systolic blood pressure.

HOW TO RESUSCITATE?

Traditional Versus Modern Strategies

Once the patient has been appropriately identified as requiring massive transfusion, immediate resuscitation should begin. Traditional fluid resuscitation in the majority of trauma patients consists of immediate placement of large-bore intravenous catheters, crystalloid replacement of 3 mL to every 1 mL of blood loss up to 6 to 10 units PRBCs, followed by fresh frozen plasma (FFP), platelets (PLTs), and/or cryoprecipitate per Advanced Trauma Life Support guidelines.30 However, for the exsanguinating patient, resuscitating in this fashion can lead to unnecessarily high volumes of crystalloid and PRBCs without administration of plasma, resulting in adverse outcomes.11-12,26,31 Excessive crystalloid resuscitation may result in hemodilution, depletion of coagulation factors with exacerbation of coagulopathy, worsening acidosis, acute respiratory distress syndrome and abdominal compartment syndrome, and ultimately increased mortality.9,11-12,26,31 Therefore, the use of crystalloids, which are inherently acidic and proinflammatory, should be minimized to primarily maintain intravenous access and flush between blood products.7,11-13 This change in the crystalloid usage during resuscitation has been widely successful in the treatment of combat injuries during recent conflicts.6,7,11 Consequently, this new strategy of DCR has been developed and is now an integral part of resuscitation in many civilian settings. Central tenets of DCR are the achievement of permissive hypotension and early diagnosis of coagulopathy with aggressive management via predefined ratios of plasma to PRBCs.3,6-11

Permissive Hypotension

The first goal of DCR is to maintain circulation with minimal crystalloid. This is achieved through permissive hypotension, as defined by achieving, but not exceeding, an SBP of 90 mm Hg.7,12 Success of permissive hypotension in penetrating trauma was first described by Cannon in 1918.32 Cannon's research has been widely supported in the literature for all trauma patients except those with traumatic brain injuries.9,26,32 In 1994, the landmark study by Bickell et al26 demonstrated that delayed pre-hospital and ED fluid resuscitation improved mortality. Patients included in this study had penetrating torso injuries and an SBP of 90 mm Hg or less when emergency medical services arrived on the scene.26 They were given either standard fluid resuscitation or no fluids in the field or in the ED. Patients in the delayed resuscitation group demonstrated less intraoperative bleeding and significant decrease in mortality.26 Outcomes in the immediate fluid resuscitation group were increased SBP, decreased hemoglobin and platelet count, as well as prolonged PT and PTT.26 Results of this study demonstrate that overcorrection of SBP levels to "normal" limits with crystalloid can accelerate hemorrhage by worsening coagulopathy and disrupting already formed thrombi. Rebleeding after correction of low blood pressure levels has been coined "popping the clot."7,9,12,26,32 To avoid this phenomenon, plasma and blood products should be the primary intravenous fluids administered to achieve correction of anemia and replacement of coagulation deficits. All other intravenous fluid rates should be monitored closely, dialed down to keep the vein open, and turned off when not absolutely necessary. This strategy can allow tamponade of bleeding to occur, even if major vascular structures are injured (Figure 3).

Figure 3 - Click to enlarge in new window

Figure 3. Intraoperative photograph of patient suffering a gun shot wound to the inferior venal cava (IVC). The patient was treated with permissive hypotension. The wound (circle) is visible and was not actively bleeding at the time of surgical exposure. GB, gall bladder.

Control of Postinjury Coagulopathy

The second goal of DCR is to be proactive in controlling bleeding through early recognition of coagulopathy and transfusion of plasma.3,6-9,13 Initial recognition of coagulopathy can be achieved through the use of the aforementioned trigger points of massive transfusion. Once identified, the blood bank should be notified of the need to initiate massive transfusion and DCR should begin immediately. Damage control resuscitation was first described in the military setting advocating predefined FFP:PRBC transfusion ratios of 1:1 in actively hemorrhaging patients to achieve hemostasis and decrease mortality.3,6-9,11 Duchesne et al13 and Gonzalez et al10 echoed similar findings of improved survival in the civilian setting, using a predefined FFP:PRBC ratio of near 1:1 during massive transfusion. However, additional studies by Kashuk et al14 and Teixeira et al15 demonstrated that lower FFP:PRBC ratios of 1:2 to 1:3 were associated with improved survival. Despite the lack of consensus on the optimal ratio of FFP:PRBC, plasma transfusion must be considered early in the resuscitation algorithm to avoid falling behind in correction of coagulopathy.8 Research is ongoing to gain consensus on this matter.33,34 Most recently, the US Department of Defense approved 10 major trauma centers to be participants in the prospective, observational study of trauma transfusion practices (PROMMTT study).33,34 Data from this study will attempt to clarify the optimal ratio of blood products to be transfused and the subsequent effect on patient outcomes.33,34

Optimal timing and ratio of platelet transfusion also continue to be an area of ongoing research. When a patient is hemorrhaging and receiving massive transfusions, the process of platelet depletion, dilution, and dysfunction occurs in a similar fashion to destruction of coagulation factors. Inevitably, this process leads to worsening coagulopathy. Traditionally, the threshold for platelet transfusion has been 50 000/[mu]L, but newer research indicates that a higher platelet count of 100 000/[mu]L in the bleeding patient improves survival.11,34 Along with maintaining a higher platelet count, higher ratios of FFP:PRBC:PLT transfusion have shown to decrease mortality.11,30,36 Holcomb et al11 demonstrated improved survival when FFP:PRBC:PLT ratios were increased to 1:1:1. However, Gunter and colleagues36 found that a lower PRBC:PLT ratio of 1:5 significantly reduced mortality. The number of platelets transfused within the first 24 hours postoperatively also improved outcomes.36 These findings, although different in ratio, support early platelet transfusion along with plasma and red blood cells to manage coagulopathy. With this type of strategy, all blood products serve a purpose to restore volume while correcting anemia, replenishing fibrinogen and clotting factors, and replacing lost or damaged platelets. Additional adjuncts to plasma and PRBC transfusion to correct ongoing coagulopathy are cryoprecipitate and recombinant factor VIIa (rFVIIa). Research regarding the use of these products in massive transfusion is ongoing.3,37-40

Role of Massive Transfusion Protocols

As a result of changes in the resuscitation paradigm, current massive transfusion protocols (MTP) may be inadequate and in need of revision. Without immediate availability of appropriate ratios of blood products, a predominantly crystalloid-based resuscitation may occur, leading to worsening coagulopathy and uncontrollable bleeding.9,41 Newer protocols are being implemented that reflect the strategy that FFP:PRBC:PLT ratio be 1:1:1.10,42 In 2008, Cotton et al41 demonstrated that the benefits of using a predefined MTP were decreased delay in early plasma transfusion and improved mortality. Gonzalez et al10 in Houston revised their protocol to emphasize early transfusion of FFP after finding that their patients arrived to the ICU inadequately resuscitated under their former MTP. Trauma surgeons at the University of Cincinnati Division of Trauma and Critical Care recently revised their MTP to include immediate access to liquid plasma in the ED, in addition to increasing the number of PRBCs, FFP, and PLTs available upon activation of protocol.33,42 Development and use of an MTP in this patient population grant immediate access to blood products, resulting in early transfusion of plasma.