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Initiation and Termination of Massive Transfusion Protocols: Current Strategies and Future Prospects

Foster, John C. MD*; Sappenfield, Joshua W. MD; Smith, Robert S. MD; Kiley, Sean P. MD

doi: 10.1213/ANE.0000000000002436
Blood Management
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The advent of massive transfusion protocols (MTP) has had a significant positive impact on hemorrhaging trauma patient morbidity and mortality. Nevertheless, societal MTP guidelines and individual MTPs at academic institutions continue to circulate opposing recommendations on topics critical to MTPs. This narrative review discusses up-to-date information on 2 such topics, the initiation and termination of an MTP. The discussion for each begins with a review of the recommendations and supporting literature presented by MTP guidelines from 3 prominent societies, the American Society of Anesthesiologists, the American College of Surgeons, and the task force for Advanced Bleeding Care in Trauma. This is followed by an in-depth analysis of the main components within those recommendations. Societal recommendations on MTP initiation in hemorrhaging trauma patients emphasize the use of retrospectively validated massive transfusion (MT) prediction score, specifically, the Assessment of Blood Consumption and Trauma-Associated Severe Hemorrhage scores. Validation studies have shown that both scoring systems perform similarly. Both scores reliably identify patients that will not require an MT, while simultaneously overpredicting MT requirements. However, each scoring system has its unique advantages and disadvantages, and this review discusses how specific aspects of each scoring system can affect widespread applicability and statistical performance. In addition, we discuss the often overlooked topic of initiating MT in nontrauma patients and the specific tools physicians have to guide the MT initiation decision in this unique setting. Despite the serious complications that can arise with transfusion of large volumes of blood products, there is considerably less research pertinent to the topic of MTP termination. Societal recommendations on MTP termination emphasize applying clinical reasoning to identify patients who have bleeding source control and are adequately resuscitated. This review, however, focuses primarily on the recommendations presented by the Advanced Bleeding Care in Trauma’s MTP guidelines that call for prompt termination of the algorithm-guided model of resuscitation and rapidly transitioning into a resuscitation model guided by laboratory test results. We also discuss the evidence in support of laboratory result–guided resuscitation and how recent literature on viscoelastic hemostatic assays, although limited, highlights the potential to achieve additional benefits from this method of resuscitation.

Published ahead of print August 29, 2017.

From the *University of Florida College of Medicine, Gainesville, Florida

Department of Anesthesiology, University of Florida College of Medicine, Gainesville, Florida

Division of Acute Care Surgery, Department of Surgery, University of Florida College of Medicine, Gainesville, Florida.

Published ahead of print August 29, 2017.

Accepted for publication July 17, 2017.

Funding: None.

The authors declare no conflicts of interest.

Reprints will not be available from the authors.

Address correspondence to Joshua W. Sappenfield, MD, Department of Anesthesiology, University of Florida College of Medicine, 1600 SW Archer Rd, PO Box 100254, Gainesville, FL 32610. Address e-mail to jsappenfield@anest.ufl.edu.

Concerns regarding improper administration of massive transfusions (MTs) led to the development and implementation of massive transfusion protocols (MTPs) in the mid to late 2000s.1–6 These protocols were designed to establish a method for the timely and coordinated delivery of blood products throughout the hospital and to develop evidence-based guidelines for the delivery of blood products and adjunctive therapies.1,7–9 In support of their overall efficacy, data have since shown that, compared with MT events in hospitals without an MTP, MTP-guided resuscitation is associated with significant improvement in overall patient survival, as well as reductions in blood product utilization, blood product waste, and incidence of complications associated with blood product transfusions.10–13

As of 2017, MTPs have been widely adopted by academic institutions within the United States.14 Despite this, a comparison of interhospital MTPs revealed that they vary extensively with regard to the criteria for initiation, the role of point-of-care-testing (POCT), the end points for termination, and the indications for therapeutic adjuncts to blood products such as crystalloid fluids, calcium, tranexamic acid, and prothrombin complex concentrates.14,15 This lack of MTP uniformity is concerning, especially given the literature demonstrating the benefits provided by evidence-based MTPs and the consequences of inappropriate MTP utilization.9–13,16–19 It also raises some questions, including whether there is sufficient evidence to permit the development of a standardized MTP, and whether geographic differences in trauma patient demographics would affect the efficacy of a standardized MTP at individual trauma centers.

With these questions in mind, the goal of this article is to provide a narrative review on 2 contended topics that are invaluable to MTP guidelines: the decision to initiate an MTP and the decision to terminate 1. Through an analysis of the evidence-based methods available for guiding the decision to initiate and terminate an MTP, this article aims to discuss the following: the comparative strengths and weaknesses of validated approaches to guiding MTP initiation and termination, the potential for integrating these methods into a standardized MTP, and any additional research topics that would fill gaps in the existing literature.

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METHODS

Recommendations on the initiation and termination of MTPs and their supporting references were sourced from respective MTP guidelines published by the American Society of Anesthesiologists (ASA), the American College of Surgeons (ACS), and the European Society for Advanced Bleeding Care in Trauma (ABC-Trauma).20–22 Additional evidence not referenced in these papers was obtained through literature searches in PubMed from December 2006 to January 2017 using the keyword “massive transfusion protocol” and MeSH terms “shock, hemorrhagic/blood,” “shock, hemorrhagic/diagnosis,” “wounds, stab/mortality,” and “wounds, gunshot/mortality.” Search results were limited to randomized control trials (RCTs), non-RCT studies, and systematic reviews with human subjects and in the English language. Whole articles were screened for their relevance to the subject of initiation and termination of MTPs, and then incorporated into the narrative review if they were determined to contain new and relevant information regarding this topic.

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INITIATION OF MASSIVE TRANSFUSION PROTOCOLS

Patient survival during massive hemorrhage is critically dependent on rapid identification and control of the bleeding source(s). This is evident from 1 institution’s observations of a significant reduction in overall and hemorrhage-related mortality after the simultaneous application of several hemorrhage control interventions, termed the “bleeding control bundle.”23 An additional component of the bleeding control bundle that assists in hemostasis and delaying death from exsanguination is the early initiation of an MTP.23–25 This statement is supported by observations that patient mortality after massive hemorrhage significantly improves with decreased time between patient presentation and MTP activation, and with decreased delays between MTP activation and the initiation of an MTP.13,17,26–28 Evidence-based guidelines for the prompt identification and early resuscitation of patients requiring an MT is therefore a crucial topic within MTPs.

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Societal Guidelines

Despite evidence of mortality benefits with early MTP initiation, the enduring question remains how a physician can quickly and accurately determine whether a hemorrhaging patient requires an MT.29 Within the trauma literature, there are numerous publications outlining the various imaging modalities, MT prediction tools, estimated blood loss guidelines, laboratory markers of tissue perfusion, and components of the patient’s history and examination that are meant to supplement clinical reasoning and aid in the decision to initiate an MTP.29–48 Conveniently, the MT literature has been compiled and analyzed by several prominent medical societies, including the ASA, ACS, and ABC-Trauma, for the purpose of providing physicians with evidence-based recommendations regarding MT and MTPs.20–22 These up-to-date MTP guidelines have all been completed or updated within the past 5 years and, because of their recognition and reach, have significant potential to influence the practice of anesthesiologists, surgeons, and emergency medicine physicians involved in the initial evaluation and management of trauma patients.14,49 Given the significant influence of the ACS, ASA, and ABC-Trauma societies and their in-depth analysis of the MT literature, it is prudent to use their guidelines as an initial tool to identify evidence-based modalities for guiding the decision to initiate and terminate an MTP after traumatic injury.

Table 1.

Table 1.

The recommendations from the ASA, ACS, and ABC-Trauma on MTP initiation after traumatic injury are presented in Table 1.20–22 Each guideline similarly recommends a systematic approach to MTP initiation that combines the clinical assessment of tissue perfusion and estimated blood loss with a validated MT prediction score.20–22 Utilizing clinical reasoning when guiding MTP initiation is essential, as was established by studies demonstrating clinical reasoning to be 65.6% sensitive and 63.8% specific for predicting MT requirements.39 The positive predictive value (PPV) and negative predictive value (NPV) of clinical reasoning were 34.9% and 86.2%, respectively.39 While these values would suggest that clinical reasoning alone is insufficient to independently guide the initiation of an MTP, it remains a valuable decision-making tool, especially when laboratory values or imaging are still pending or altogether unavailable. The MT prediction score components of MTP recommendations will be discussed individually subsequently.

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MT Prediction Scores for Guiding MTP Initiation

The US-based societies, the ASA and ACS, both recommend the Assessment of Blood Consumption (ABC) score (Table 2) as a simple, 4-variable scoring system for rapidly predicting MT risk in trauma patients and aiding in the decision to initiate an MTP.20,21 The initial validation of the ABC score was conducted using trauma patient data sets recorded at the Vanderbilt University Medical Center between 2005 and 2006.30 The ABC score correctly predicted the retrospective need for MT in 84% of cases, with a sensitivity of 75% and specificity of 86%.30 Revalidation of the ABC score was conducted using trauma patient data sets recorded at 3 large level 1 trauma centers in the United States (Parkland Memorial, Johns Hopkins, and Vanderbilt University Medical Center) between 2006 and 2007.16 The revalidation data concluded that the ABC score was 75-90% sensitive and 67%-88% specific with regard to its ability to retrospectively predict MT requirements within 24 hours of trauma.16 The PPV and NPV were 55% and 97%, respectively.16

Table 2.

Table 2.

The major advantages of the ABC score are that the 4-scoring variables and cutoff values are easy to recall, that all variables can be rapidly obtained in the prehospital setting and at initial presentation, and that the unweighted scoring system can be immediately calculated and interpreted once all variables are obtained. In addition, the 97% NPV indicates that a negative ABC score is highly successful in correctly identifying patients who will not require an MT, which is arguably the most important feature of an MT prediction score. However, as this scoring system is used as an early predictive tool for identifying patients at risk for requiring an MT, the 55% PPV is concerning. It indicates a tendency for a positive ABC score to overtriage patients into receiving an unnecessary MT. If used independently, this would lead to an increased likelihood of blood product wastage and complications associated with blood product transfusions. An additional limiting feature of the ABC score is that it is not sensitive for other sources of major bleeding, including severe injuries to extremities, retroperitoneal vasculature, and pelvic vasculature.16,30

In place of the ABC score, the ABC-Trauma guidelines recommend utilizing the Trauma-Associated Severe Hemorrhage (TASH) score (Table 2) for predicting MT risk in trauma patients and aiding in the decision to initiate an MTP.22 In comparison to the simplistic ABC score, the TASH score is a 7-variable, 28-point, weighted scoring system that was developed through multivariate analysis of trauma patient data sets recorded between 1993 and 2003 in the multicenter Trauma Registry of the German Trauma Society (TR-DGU).48 Retrospective validation of the score within the same registry demonstrated that the TASH score was able to correctly classify 88.8% of patients with regard to their MT requirements.48 The retrospective revalidation of the TASH score was conducted using patient data sets recorded from 2004 to 2007 in the TR-DGU database.31 This study concluded that the TASH score was 31% sensitive and 98% specific for correctly predicting MT requirements after trauma.31 Although the PPV and NPV were not provided, using the provided values for sensitivity, specificity, and the 2004–2007 TR-DGU MT incidence of 8.4%, we were able to calculate a PPV of 58.7% and NPV of 93.9%.31

The validation and revalidation data on the TASH score suggests that it is very similar to the ABC score in that a negative score accurately identifies patients who will not require an MT, but that a positive score will often incorrectly predict MT requirements in patients who do not require an MT. Despite the similarities, there is 1 notable feature of the TASH score that favors its potential for widespread implementation within a standardized MTP. This feature is the ability for users to modify several score parameters, including the values and points for each TASH score variable, the positive cutoff threshold on the 0- to 28-point scale, and the TASH score algorithm for predicting individual patient MT risk, thereby altering the statistical performance of the scoring system.31 This feature could be of significant value as it presents physicians with the ability to internally validate and fine-tune the TASH score and MT prediction algorithm within each institution—as was done by the authors in the revalidation study—and thereby fit the scoring system to better predict MT requirements specific to the local trauma patient population.

There are, however, several concerns with the TASH score that may limit its widespread applicability, especially in the time-sensitive setting of a massive hemorrhage. Unlike the ABC score, the TASH score requires 2 laboratory results, hemoglobin and base excess, to result before completing the score calculation. If these values are obtained by POCT, the complete TASH score has been shown to require on average 7:56 minutes to calculate.50 In comparison, the ABC score’s variables can be calculated in 5:02 minutes; it should be noted that this does not consider use of prehospital data for ABC score calculation which would reduce this time by several minutes.50 While the specific laboratory variables necessary for the TASH are relatively quick to acquire with use of POCT, they still present an additional obstacle that delays the decision to initiate an MTP, particularly at hospitals with limited staff and resources. The calculation of the TASH score, with its weighted scoring system, multiple variables, and array of possible results, is also much more complicated than the ABC score. This complexity could present a barrier that reduces physician compliance with the scoring system and increases the potential for errors in scoring and interpretation, altogether leading to further delays in the initiation of an MTP.

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Directly Comparing the MT Prediction Scores

During the initial development of the ABC score at the Vanderbilt University Medical Center, the authors also calculated the TASH score for each patient to directly compare the 2 scoring systems. The area under the receiver operating characteristic (AUROC) of the TASH and ABC scores were 0.842 and 0.859, respectively, with a difference that was found to be statistically insignificant.30 These results showed that the TASH score’s ability to retrospectively predict MT requirements for trauma patients in the urban United States was very similar to that of the ABC score. However, in 2012, a European study retrospectively calculated 6 unique MT scoring methods, including both the ABC and TASH scores, using trauma patient data sets from the TR-DGU database.32 The TASH score had an AUROC of 0.889, which was significantly greater than the ABC score’s surprisingly low AUROC of 0.763.32 Mitra et al51 also directly compared the TASH and ABC scores using trauma patient data sets from the Australian Royal Prince Alfred trauma registry. Mitra et al51 found the TASH score to have an AUROC of 0.90, again significantly greater than the ABC score’s AUROC of 0.78. The ABC score’s reduced statistical performance measures when calculated with data from outside the urban United States raises concerns regarding its widespread applicability within a standardized MTP.

An explanation for the significant reduction in the ABC score’s ability to retrospectively predict MT, and the TASH’s consistent ability to predict MT, when tested across dissimilar trauma databases may lie in the differences between trauma demographics. Data on patient demographics from the United States, European, and Australian trauma registries utilized during the validation of the ABC and/or TASH scores are shown in Table 3.16,30–32,48 There are several disparities between the trauma registries that are evident from this table, including differences in the Injury Severity Scores, mean patient age, prevalence of MT, and relative percentage of penetrating mechanisms of injury. Of these epidemiological variables, the relative percentage of penetrating injury is the only 1 that is not only predictive of MT risk but also an important MT prediction score variable (Figure) and whose value may affect a scoring system’s AUROC (AUROC is independent of disease prevalence, which in this scenario is the prevalence of MT).30,48,52 As the prevalence of penetrating injury has the potential to directly affect the statistical performance of the ABC score, understanding the epidemiological differences in injury patterns between the United States and other countries is imperative.

Table 3.

Table 3.

Figure.

Figure.

Epidemiological data from the TR-DGU report the percentage of traumatic injuries with a penetrating mechanism as ranging from 4.8% to 5.3%.29,30,46 Of the penetrating injuries encountered in an urban European setting, approximately 80% are stab wounds (overall incidence of 4.7%) and 20% are gunshot wounds (overall incidence of 1.1%).53 The Royal Prince Alfred Hospital in Australia presents similar statistics, with 5.7% of all traumatic injuries having a penetrating mechanism and with <1% attributable to gunshot and stab wounds.54 These numbers differ from those observed in the urban Unites States, where the percentage of traumatic injuries with penetrating mechanism ranges from 18% to 59%.27,48 In addition, the urban United States encounters a higher percentage of gunshot and stab wounds, with 1 urban trauma center observing that 5.8% of all traumatic injuries encountered were from gunshot wounds and 6.3% from stab wounds.55–57

These observations are noteworthy as the mechanism of injury has a significant effect on patient morbidity and mortality. Epidemiological studies have observed that, in comparison to blunt mechanisms of injury, patients with penetrating trauma are significantly more likely to die at the scene of injury, to die within the first 6 hours after trauma, and to require emergency intervention for hemorrhage control.56,58 Moreover, gunshot wounds have case-fatality rates that are higher than any other mechanism of injury.55–57 This epidemiological data highlight the substantial risk for massive endothelial damage that occurs with penetrating mechanisms of injury, especially gunshot wounds, thereby placing patients at increased risk for hypovolemia, decreased tissue perfusion, and the lethal combination of the hypothermia, metabolic acidosis, and coagulopathy.59 In addition, these data likely explain the observation made during the ABC validation study of an association between penetrating mechanisms of injury and MT risk in the United States, and why the ABC score’s ability to identify patients requiring a MT would be diminished when applied to patient data from European and Australian trauma registries.

With variations in trauma patient demographics as a likely explanation for the ABC score’s relatively poor performance when applied to trauma registries outside the urban United States, one would also expect that the ABC score’s performance in the rural United States, where the prevalence of both penetrating trauma and gunshot wounds is reduced relative to urban areas, to also decline.60 This concern was addressed in a small retrospective study that compared the ABC and TASH scores for their ability to predict MT requirements in a rural United States trauma setting. The authors observed that the ABC score’s performance, with an AUROC of 0.81, was similar to that observed in its validation and revalidation studies.47 The results of this study would suggest that the effects rural trauma demographics have on the statistical performance of the ABC score is minimal, and would support the application of the ABC score in the rural setting. However, as trauma demographics are variable across the United States, trauma centers that observe patient characteristics differing from those presented in this rural ABC validation study should consider revalidation or coapplication of both the TASH and ABC scores to reduce the likelihood of false-negative MT predictions.

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Initiating MT in the Nontrauma Patient

Although the field of acute care surgery is the foundation for research on MT and MTPs, massive hemorrhage after traumatic injury is not the only reason for initiating an MTP.61 The percentage of overall MTP activations that occur in nontrauma patients is extremely variable and hospital specific, ranging from 8% to as high as 50%.62–64 Despite the high prevalence of MTs that occur in nontrauma patients, literature discussing the role of MTPs outside of trauma is limited and MTP guidelines often overlook MTP initiation in nontrauma patients.20–22,64,65 In addition, although the use of MTPs to guide resuscitation in massively hemorrhaging nontrauma patients is associated with significantly decreased time to delivery of blood products and a significant increase in the percentage of transfusions delivering balanced ratios of blood products, MTPs have not been shown to improve patient outcome in this setting.66,67 One possible explanation for the lack of observed mortality benefit may relate to the abundance of MTP “overactivations” that occurs outside of trauma.62,63 These overactivations, which are defined as MTP activations in which patients do not receive sufficient blood products to meet the classic definition of an MT, indicate that hemorrhage outside of trauma is characterized by considerably fewer cases of truly massive hemorrhage for which MT has been proven to be beneficial.17

Due to the high percentage of MTPs occurring in nontrauma patients, the high prevalence of MTP overactivations in the nontrauma setting, and the lack of objective data to suggest mortality benefits, precise guidelines for guiding MTP initiation in nontrauma patients are imperative. Unfortunately, the decision to initiate an MTP in the hemorrhaging nontrauma patient does not benefit from the ability to apply validated scoring systems, such as those utilized in trauma. However, the success of risk prediction scores for guiding intervention in patients with gastrointestinal bleeding, most notably the Glasgow-Blatchford score, would suggest that new MT prediction scores specific to nontrauma hemorrhage could be developed.68 In addition, the Glasgow-Blatchford score shares multiple variables with both the TASH and ABC scores, implying that development of an MT prediction score for use in nontrauma patients would likely benefit from using the existing MT prediction scores as templates.30,48,68

In cases where blood loss can be measured or estimated, the decision to initiate an MTP in all hemorrhaging patients could be supported by whether or not the patients meet criteria for “massive hemorrhage.”1,5,6,8,69–72 However, due to the lack of validated criteria for defining massive hemorrhage and concerns regarding the inaccuracy of blood loss estimates, new literature has proposed utilizing the “intensity of resuscitation” as a surrogate marker for hemorrhage severity.69,73,74 The authors who proposed the idea of resuscitation intensity observed that trauma patients who received 4 or more units of any fluid, including crystalloid or various blood products, within 30 minutes of arrival had significant increases in 6- and 24-hour mortality rates.74

Interestingly, newer definitions of MT that define it as a threshold transfusion rate of at least 3–4 units of packed red blood cells (RBCs) per hour also mirror the idea of resuscitation intensity.75,76 In addition, the transfusion rates of 3–4 RBCs per hour are notable as they are the transfusion rates at which patient mortality begins to increase, again paralleling the observations of resuscitation intensity.75,76 Therefore, through prospective monitoring of “resuscitation intensity” using evidence-based blood and crystalloid threshold transfusion rates as surrogates for massive hemorrhage, physicians have methods for identifying hemorrhaging nontrauma patients at significant risk for higher mortality rates that would potentially benefit from a formal MTP initiation. In the absence of MT prediction scores, resuscitation intensity offers a valuable objective method for aiding in the decision to initiate an MTP in the nontrauma setting.

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Hemostatic Resuscitation in the Prehospital Setting

Given the negative effect that time delays before MT initiation have on patient outcomes and the high hemorrhage-related mortality rates that occur within the first hour after trauma, the prolonged transport times reported in both rural and urban settings are alarming.13,17,26,27,56,77–81 These prolonged prehospital transport times are likely responsible for increased patient mortality, and in the setting of massive hemorrhage this effect is likely even greater.82–84 In addition to existing protocols that successfully reduce prehospital transport time and transfer delays, implementing guidelines for hemostatic resuscitation of hemorrhaging trauma patients in the prehospital setting has significant potential to improve patient survival.

Several hospital systems around the world have researched the use of blood products during prehospital transport.85 Although the current level of evidence is low and the results are variable, prehospital transfusion of plasma is associated with improved neurological outcomes, reduced blood product requirements, and improved early mortality.86–91 Whole blood has also shown mortality benefit in the prehospital setting. Whole blood transfusions have been used during military special operations with great success, and programs in the United States have successfully implemented methods for acquisition, banking, and transfusion of whole blood.92 In the military trauma setting, whole blood was shown to decrease mortality, reduce transfusion volumes, and better correct coagulation parameters compared to individual components of whole blood.93–96 Despite these accomplishments, at this time the greatest benefit whole blood is limited to resuscitation in the prehospital setting where whole blood provides several critical components necessary to support hemostasis in a compact package.97–99

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TERMINATION OF MASSIVE TRANSFUSION PROTOCOLS

Prolonged resuscitation with large volumes of blood products puts patients at risk for developing numerous physiologic disturbances and severe complications.18 However, while physicians must be cautious to avoid prolonged and unnecessary MTs, the decision to terminate an MTP should not be premature. Failure to adequately resuscitate the patient can lead to protracted tissue ischemia, increased bleeding risk, and increased patient mortality.100 These opposing issues detail the importance of evidence-based guidelines for the termination of MTPs.

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Societal Guidelines

Table 4.

Table 4.

The MTP guidelines presented by the ASA, ACS, and ABC-Trauma regarding MTP termination are presented in Table 4. These societies similarly recommend guiding MTP termination with clinical judgment and the fulfillment of 3 broad criteria. These include bleeding source control or a decelerating rate of blood loss, stable or improving hemodynamic vital signs, and decreasing or absent vasopressor requirements.20–22 As MT is designed to provide hemostatic resuscitation during periods of massive hemorrhage, evidence of slowing blood loss and adequate resuscitation is judicious, evidence-based criteria for guiding the termination of an MTP.100 The ABC-Trauma guidelines, however, are unique in their recommendation for prompt termination of the algorithm-guided model of resuscitation that delivers fixed ratios of blood products and rapidly transitioning into a resuscitation model guided by laboratory test results, even when patients do not meet the previously stated MTP termination criteria.22

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Laboratory Testing for Guiding MTP Termination

The information presented in this article has thus far illustrated the importance of MTPs during the resuscitation of hemorrhaging trauma patients in whom survival is dependent on rapidly restoring circulating blood volume while simultaneously correcting anticipated trauma-associated coagulopathies. However, in patients requiring prolonged resuscitation with blood products due to persistent hemorrhage, the algorithm-guided method of resuscitation used during an MT would theoretically benefit from supplementation with a model that utilizes laboratory results to guide further resuscitation. A laboratory result–guided method would allow for accurate correction of specific abnormalities of hemostasis and oxygen-carrying capacity, while simultaneously reducing unnecessary blood product transfusions. This approach to resuscitation is supported by MT literature demonstrating that when laboratory result–guided resuscitation is used in conjunction with algorithm-guided resuscitation, patients require fewer blood products, patient morbidity is reduced, and there is an improvement of objective hemostatic markers.101–104 Furthermore, increasing uncertainty regarding the efficacy and safety of an extended algorithm-guided MT with fixed ratios of plasma to RBCs and platelets to RBCs has fostered the notion of transitioning to a laboratory result–guided resuscitation at the earliest opportunity.73,105–110 This model of laboratory result–guided resuscitation has been successfully used at select hospitals in Denmark, where it is termed the “Copenhagen Concept.”111 It is also being intermittently applied in select hospitals in the United States when the results of laboratory tests can be obtained in a clinically relevant timeframe.111

The majority of the ABC-Trauma’s recommendations regarding laboratory result–guided resuscitation specifically pertain to the use of conventional coagulation assays (CCAs). However, increasing focus is now being directed toward viscoelastic hemostatic assays (VHAs) as a method to guided resuscitation in hemorrhaging trauma patients. Given that a critical aspect of MT is supporting hemostasis, VHAs have significant potential as they can further elucidate trauma-associated coagulopathy by identifying disruptions at specific intervals in the cell-based model of hemostasis, including impaired thrombin generation, impaired clot strength, and aberrant fibrinolysis.112 This information is also capable of being presented rapidly and in real time, with early rapid thromboelastography values available within 5 minutes and all data within 15 minutes of running the test; in comparison, CCA results can take up to 48 minutes to return.113,114 Fast turnaround times are critical during MT as they not only allow for rapid identification and treatment of coagulopathies but they also lessen the physiological changes that may occur between drawing the laboratory test and treating the abnormal result. The benefits of VHAs over CCAs were shown in a RCT that compared CCA- and VHA-guided resuscitation of trauma patients after MTP activation.115 The authors observed that mortality was significantly lower and fewer patients died due to hemorrhage in the VHA group.115 Additionally, VHA-guided resuscitation was associated with decreased transfusion of platelets and plasma during the first 2 hours of resuscitation.115 These results would suggest that VHA-guided resuscitation is superior to CCA-guided resuscitation in hemorrhaging trauma patients.

Despite the potential for VHAs to guide laboratory result-based resuscitation in trauma patients, as well as historical data on the success of VHA-guided resuscitation during cardiac surgery and liver transplantation, research evaluating the morbidity and mortality outcomes of VHA-guided resuscitation after trauma has yielded limited results.67,116–120 A 2014 systematic review evaluated 55 observational studies on the use of VHAs to diagnose coagulopathy and guide blood product transfusions after trauma.116 The findings were overall inconclusive, and only 1 of these observational studies directly compared the results of VHA-guided resuscitation to the traditional algorithm-guided resuscitation in hemorrhaging trauma patients. The results from this study showed no overall difference in volume of blood product transfused, ventilator days, intensive care unit days, or overall patient mortality between the 2 treatment groups.121 The authors did, however, observe that VHA-guided resuscitation significantly improved mortality in a cohort of penetrating trauma patients that received more than 10 units of RBCs (54.1% mortality for MTP versus 33.3% mortality for VHA).121 What is most evident from this systematic review is the lack of RCT data directly comparing MT with algorithm- and VHA-guided resuscitation. Nevertheless, the available data would suggest that VHA-guided resuscitation after trauma may have a beneficial role in supplementing the algorithm-guided approach to resuscitation within the early rounds of an MT, especially in patients who continue to massively hemorrhage and are thus persistently at high risk for tissue hypoperfusion and trauma-associated coagulopathy.59

Finally, when considering laboratory result–guided resuscitation during massive hemorrhage, it should be noted that 1 of the primary benefits of an MTP that may be lost is the rapid delivery of a balanced ratio of blood products to the patient’s bedside.3,13,67 Therefore, if the decision to transition from an algorithm-guided approach to a laboratory result–guided resuscitation protocol is made, physicians should continue the official MTP to benefit from a continuous and timely delivery of blood products.

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CONCLUSIONS

The advent of MTPs in the past 10 years has had a significant positive impact on hemorrhaging trauma patient morbidity and mortality. However, despite years of ongoing research, academic institutions and societal guidelines on MTPs are still unable to reach agreements on the best methods for guiding the initiation and termination of MTPs. The lack of consensus regarding these critical MTP components warrants an analysis and comparison of the current MTP initiation and termination guidelines as well as the relevant literature.

The ABC and TASH scores are validated MT prediction scores recommended by several MTP guidelines for aiding in the decision to initiate an MTP in hemorrhaging trauma patients. Both scoring systems reliably identify patients who do not require an MTP after trauma while demonstrating a tendency to incorrectly overpredict MT requirements. The ABC score’s uniquely simplistic scoring system, easy-to-remember variables, and rapid calculation have made it a prominent component of MTPs in the United States. Still, the effect that local trauma demographics, specifically, the prevalence of penetrating trauma, may have on the statistical performance of the ABC score highlights an area for additional research.

The decision to initiate an MTP outside of the trauma setting does not benefit from the ability to apply validated MT prediction scores. However, risk prediction scores for guiding the decision to intervene in cases of gastrointestinal hemorrhage are supportive, and they evaluate variables similar to those found in MT prediction scores. This highlights the potential for developing effective MT prediction scores for use in hemorrhaging nontrauma patients and for using current trauma MT prediction scores as templates. Also of considerable value in the setting of massive hemorrhage in nontrauma patients is the concept of resuscitation intensity, which is considered a surrogate marker for hemorrhage severity. This concept allows physicians to identify hemorrhaging patients with an elevated mortality risk through their RBC and fluid transfusion rates, and thereby identify high-risk patients who may benefit from an MTP initiation. Further research to determine the ability of resuscitation intensity to guide MTP initiation in the setting of nontrauma hemorrhage is required.

Last, despite the serious complications that can arise with transfusion of large volumes of blood product, the topic of MTP termination has considerably less relevant research compared to MTP initiation. Current societal recommendations regarding MTP termination emphasize clinical reasoning to identify patients with bleeding source control and adequate resuscitation. The ABC-Trauma’s guidelines present an additional recommendation for prompt termination of the algorithm-guided model of resuscitation and rapidly transitioning into a resuscitation model guided by laboratory test results. Literature has shown that CCA-guided resuscitation during massive hemorrhage leads to fewer blood product transfusions and improved patient mortality. Furthermore, the encouraging literature on VHAs and their ability to surpass CCAs with regard to identifying and treating coagulopathies emphasizes the potential of these tests to further enhance the benefits obtained through utilization of laboratory result–guided resuscitations during the termination of MTPs. RCTs directly comparing algorithm-guided and laboratory result–guided resuscitation methods are needed before further recommendations can be made regarding the functional role for this approach to guide MTP termination.

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DISCLOSURES

Name: John C. Foster, MD.

Contribution: This author helped with the conception of the work, drafting of the manuscript, critical revision of the manuscript, and approval of the final manuscript.

Name: Joshua W. Sappenfield, MD.

Contribution: This author helped with the conception of the work, drafting of the manuscript, critical revision of the manuscript, and approval of the final manuscript.

Name: Robert S. Smith, MD.

Contribution: This author helped with the conception of the work, drafting of the manuscript, critical revision of the manuscript, and approval of the final manuscript.

Name: Sean P. Kiley, MD.

Contribution: This author helped with the conception of the work, drafting of the manuscript, critical revision of the manuscript, and approval of the final manuscript.

This manuscript was handled by: Marisa B. Marques, MD.

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