The impact of early thromboelastography directed therapy in trauma resuscitation

Severe blood loss leading to hemorrhagic shock represents a major factor in trauma related deaths. An intrinsic dysregulation of the coagulation cascade known as trauma induced coagulopathy (TIC) [1] – contributes to the ongoing hemorrhage. One in every four trauma patients presents to the hospital with established TIC that may lead to a sequence of deleterious events [2‐4]. Effects of TIC include uncontrolled bleeding, massive transfusion, and multi-organ failure. Further, TIC corresponds to having longer intensive care unit (ICU) and hospital length of stay (LOS), as well as a fourfold increase in mortality [5]. Conventional coagulation tests (CCTs) offer valuable information in monitoring the different aspects of coagulation. However, CCTs have several limitations: (1) they fail to delineate the complex nature of TIC, (2) they are time consuming, and (3) they have questionable value in guiding transfusion requirements [6, 7]. A systematic review in 2011 suggested that CCTs are insufficient to diagnose TIC [8, 9]. Thrombelastography (TEG - Heamonetics Corp, Braintree, MA USA) or rotational thromboelastometry (ROTEM - TEM international; GmbH, Munich, Germany) provides an alternative diagnostic modality for TIC that overcomes the aforementioned limitations. And ROTEM are visco-elastic tests offering a prompt global overview of all dynamic sequential aspects of the TIC process by providing data on the speed of coagulation initiation, kinetics of clot growth, clot strength, and its breakdown [6, 10]. Clinicians have developed massive transfusion protocols (MTP) to prioritize the correction of coagulopathy by delivering blood products in a systematic and coordinated fashion. Moreover, by using visco-elastic tests, physicians can obtain a more detailed assessment of all stages of hemostasis that allows developing a patient specific goal directed therapy [6, 11].

In trauma patients with TIC, evidence exists that visco-elastic tests supersede CCTs in delineating the process of the clotting cascade and therefore are useful in guiding blood products transfusion [7]. Recent guidelines on the management of TIC encourages a treatment strategy focused on goal directed resuscitation with more restriction in the use of intravenous fluids during initial resuscitation [10]. Indiscriminate administration of crystalloids, albumin, or even packed red blood cells (PRBCs) may cause cardiac and pulmonary complications, gastrointestinal dysmotility, and coagulation disturbances. Hence, visco-elastic tests can provide detailed information on which blood products would prove most efficacious to the hemorrhaging trauma patient and accordingly help guide transfusion therapy in appropriate quantities [5, 12]. Since the bleeding trauma patient often requires a significant amount of resources, goal directed restriction in blood products may also help with reducing the economic burden of caring for these patients [10].

There is a paucity in the literature on studies that attempt to evaluate relationships between the use of visco-elastic tests and resuscitation outcomes and costs in trauma patients [13]. The aim of this study was to evaluate the impact of using TEG on 4 main outcomes: (1) Blood products utilization; (2) crystalloids utilization; (3) hospital LOS and ICU LOS; and (4) the cost of utilized blood products and length of stay.

Table 2 contains basic patient demographics for the 134 patients (87 in the preTEG group and 47 in the postTEG group) who met the inclusion criteria. No significant differences were appreciated between the preTEG and postTEG groups. A higher rate of TXA administration was noted in the postTEG group (5.8% preTEG and 14.9% postTEG) yet the difference was not statistically significant (p = 0.0757.)

TEG is a dynamic, visco-elastic test that monitors the thrombodynamic properties of blood as a clot is induced. Prior studies have established that visco-elastic tests are superior to CCTs in recognizing TIC resulting in earlier and more accurate intervention [11]. By providing a more comprehensive description of global hemostatic functional aspects, visco-elastic tests produce tracings that correspond to coagulation disturbances allowing a more ‘targeted’ blood component replacement approach. By directing blood transfusion therapy in trauma patients, visco-elastic tests may serve as a useful and cost-effective tool in patients with TIC or those requiring massive blood transfusion. In addition, using visco-elastic tests can potentially help avoid complications associated with MTP. Holocomb et al. demonstrated that using visco-elastic tests provide results faster and cheaper than CCTs, and are strongly associated with clinical outcomes of interest for severely injured trauma patients [15].

The notion of using visco-elastic tests to ‘guide’ blood transfusion was derived after the study by Kang et al. where a TEG-based transfusion algorithm was used during treatment of liver transplant patients [16]. In that study, the TEG based approach resulted in less blood products usage than transfusion guided by the CCTs [16]. Thereafter, interests developed for using visco-elastic test guided transfusion algorithms in cardiovascular surgery and trauma [17]. Tapia et al. demonstrated that TEG-guided resuscitation was superior to standard MTP in patients with penetrating injury that received more than 10 units of blood [14]. The study by Tauber et al. further adds to the evidence that rotational thromboelastometry assays are useful in managing trauma patients [18].

Our study results demonstrate that after TEG implementation, despite an initial increase in the use of FFP and PL during the first 4 h of trauma resuscitation, an overall reduction in the use of PRBCs and FFP was observed during the first 24 h similar to other studies [11, 19, 20]. In the study by Gonzales et al. [11], patients randomized to either MTP goal directed by visco-elastic test or by CCTs. The volumes of PRBCs, FFP, PLs, CRYO and crystalloids were compared at 2, 4, 6, and 12 h [11]. Similar to our results, they revealed significantly higher volumes of FFP and platelets in the first 2 h of resuscitation in the visco-elastic test directed MTP group compared to the CCT group [11]. However, contrary to our results, no difference in the use of PRBCs across all times was observed in their study. We explain this difference by our ‘hemostatic resuscitation’ strategy – early blood products administration and less crystalloids during initial resuscitation – adopted around the same time TEG use was implemented at our center. Nonetheless, the effect of TEG implementation during initial resuscitation was evident by the utilization of lower volumes of PRBCs and FFP when assessed over the first 24 h period. Schochl et al. [19] similarly demonstrated a reduction in PRBCs as well as PLs in TEG directed resuscitation with fibrinogen concentrate and prothrombin concentrate complex. More recently, Stein et al. [20] also demonstrated a reduction in PRBCs and FFP during the period after TEG implementation, and noted a significantly higher rate in use of TXA (similar to our study) and coagulation factor XIII during that period. With regards to the higher use of PLs in our study, we experienced difficulty in extracting data pertinent to the history of antiplatelet use prior to trauma from patients’ charts. However, clinically significant platelet dysfunction following trauma has been previously documented [21].

Studies have shown that using red blood cell transfusion by itself is associated with greater risk of infection, increased hospital stay, costs and mortality [7]. Significant evidence exists of increased morbidity and mortality in patients receiving excessive transfusions, resulting in continued efforts to safely reduce the use of blood products in severely injured or hemorrhagic patients [5]. The 2016 European guidelines on management of major bleeding and coagulopathy following trauma encourages restriction in volume replacement during resuscitation and guidance by goal-directed strategies [10]. Several authors advocate the use of visco-elastic tests to guide and reduce blood product requirements during resuscitation by transfusing on the basis of specific component requirements [19, 22‐24]. In a recent single-center, parallel-group, open-label, randomized trial, the use of fibrinogen supplementation for severe clotting failure in multiple trauma demonstrated superiority over FFP [25]. This evolving visco-elastic test based strategy does not require adhering to the fixed-ratio approach used in most MTP. Although a fixed-ratio strategy attempts to mimic whole blood concentrations and improves survival, it tends not to occur without complications (described earlier) in those who receive excessive transfusions [5]. Thus, implementation of strategies that both avoid (a) excessive transfusion and (b) provide appropriate and adequate replacement while preserving these ratios, seem sensible. Our study demonstrates that using TEG, generates these types of results. We observed reductions in the volume of PRBCs and FFP utilized in the first 24 h of resuscitation with reductions being more pronounced in patients with penetrating injuries – who often require massive transfusion – while maintaining our PRBCs:FFP ratio at 1:1 (observed from our monthly performance improvement metrics).

Similarly, Tapia et al. demonstrated comparable transfusion ratios before and after implementation of an MTP [14]. In their study, visco-elastic tests were used only during the pre-MTP period and provided appropriate ratios on the basis of laboratory data (visco-elastic tests) rather than predefined ratios [14]. Studies have shown that following a rigid 1:1:1 (PRBCs:FFP:PLs) transfusion protocol, may lead to excessive administration and unnecessary exposure to blood components, and increase the risk of inflammation, acute respiratory distress syndrome (ARDS), sepsis, multiple organ failure, and mortality [10, 26, 27]. Protocols that include early and individualized goal-directed coagulation therapy are rapidly evolving and continue to replace the predefined ratio-driven protocols [6].

In a RCT by Gonzalez et al., no significant difference in the amounts of crystalloids transfused in the first 24 h in conjunction with a visco-elastic test based protocol was observed [11]. To the contrary, our results demonstrate a significant increase in the volume of crystalloids transfused in patients with penetrating injuries during the first 4 and 24 h. We hypothesize this may have resulted from a tendency by our anesthesiologists to inadvertently increase the volume of crystalloids transfused in patients that required operative intervention during the perioperative period. Similar to our results, the study by Tapia et al. revealed that using visco-elastic tests on patients with either blunt or penetrating mechanisms of injury resulted in a significantly higher amount of transfused crystalloids [14].

The overall mortality rates were virtually identical before and after TEG implementation. Even though an adjusted mortality benefit was observed in the postTEG group, the application of our model may not be relevant in the clinical setting.

Upon review of literature, studies that attempted to evaluate the impact of visco-elastic test usage in the trauma setting on hospital and ICU LOS, are scarce. This makes our evaluation of hospital and ICU LOS one of the unique features of this study. Our results demonstrate a significant reduction in both hospital and ICU length of stay in the postTEG group. This was true for both patients with blunt or penetrating injuries. While these reductions are astonishing, it is intuitive to assume that in addition to TEG, several cofounding factors probably contributed to these results. Interestingly, similar to our results, the recent RCT by Gonzalez et al. demonstrated a 7.5 days increase in ICU-free days in the TEG group, however, this result was not statistically significant [11]. When exploring ways to drive down healthcare costs evaluation of length of stay becomes important. In the United States, the ICU represents one of the largest cost drivers in the hospital setting [28].

A systematic review and cost effectiveness analysis by Whiting et al., indicated that viscoelastic testing is both lower in cost and more effective than standard laboratory tests in patients undergoing cardiac surgery and in trauma patients [7]. In 2005, Dasta et al. conducted a study to investigate the daily costs of ICU care and mechanical ventilation across a large and diverse sample of U.S. hospitals [28]. This retrospective analysis of the NDCHealth Hospital Patient Level Database (data from approximately 300 U.S. general medical/surgical hospitals) demonstrated a stable unadjusted daily cost for the first 3 days in the surgical ICU of approximately $3500/day [28]. In trauma patients, the mean daily costs for the first three ICU days were $10,299, $4887, and $3876 for patients requiring mechanical ventilation, and $5973, $3275, and $3059 for patients not requiring mechanical ventilation. Using these figures as a standard we can estimate the range of cost savings associated with the 7 day reduction in ICU length of stay observed in this study. On the low end, by using the $3500/day cost, a 7 day decrease in ICU length of stay would correspond to savings of $24,500. On the high end, a 7 day reduction in ICU length of stay in patients that required mechanical ventilation would correspond to savings of $19,062 for the first 3 days (by adding up the mean costs for days 1–3), and $14,000 for the remaining 4 days (by multiplying $3500 by 4 days), a combined cost savings of $33,062. Besides these ongoing cost savings, it is important to note though that the initial cost incurred by our institution to purchase the TEG analyzer was $53,625. It is estimated that the cost of materials per test is approximately $17.33 [7].

Apart from its retrospective nature, we recognize other limitations to this study. Although we think that reductions in blood products usage would correspond to a decrease in bleeding, we could not assess nor quantify encountered bleeding due to inconsistencies in documentation. Repeat TEGs were performed only on some patients as they were not part of the protocol. This did not enable a more comprehensive analysis on the impact of TEG after initial resuscitation. Due to the small sample size, we could not further explain the increased utilization of blood products in the patients that received repeat TEGs compared to those that received the initial TEG only. Despite the higher mortality rate observed in patients who received the initial TEG only – which may overall represent less volumes of blood products transfusion because of death – relative to patients who received repeat TEGs, the difference was not statistically significant. Another limitation is that we did not collect data on platelet mappings that may have been performed and which may have enabled better assessment of the differences observed in PLs transfusion. Additionally, it is well known that fibrinogen reaches critical low levels early in trauma [29‐31]. Measurement of functional fibrinogen was not part of our TEG protocol and was only obtained based on physician discretion. Thus, we did not collect data on fibrinogen levels. We also experienced difficulty exporting data on TEG parameters from the manufacturer’s software for analysis. Although, we did have documentation of a few TEG parameters in electronic medical records, this data was not consistently available for the entirety of the TEG implementation period. Thus, though important, we were unable to report this data. Lastly, our TEG-based transfusion algorithm did not specify the type and amount of transfused blood products based on TEG parameters. Fortunately, several transfusion algorithms that describe both the type and volumes required are recognized and have been well described in previous literature [6]. Trauma surgeons at our institution recognize and utilize these algorithms during practice.

Our study results demonstrate that using technologies such as TEG to direct trauma resuscitation appears to achieve an overall reduction in utilization of PRBCs and FFP with an increase in the use of PLs in the first 24 h of resuscitation, while maintaining a PRBCs:FFP ratio at 1:1. TEG use was associated with reductions in hospital and ICU length of stay of 10.2 and 7 days for all patients with either blunt or penetrating injury. Estimation of associated costs revealed cost savings of $1632 per patient in blood products utilization during the first 24 h for patients with penetrating mechanism of injury, and an overall cost savings of $24,500 – $33,062 for a 7 day reduction in ICU length of stay.