Discussion
Among injured patients presenting with hemorrhagic shock to an adult level 1 trauma center, times to blood component transfusion were short and were not associated with hospital mortality. The volume of blood component therapy was associated with mortality and is potentially a modifiable risk factor. This study suggests that implementation and evaluation of strategies to reduce bleeding and the need for blood component transfusion during trauma resuscitation could improve outcomes.
The setting of this study and restrictions to the included population must be considered when interpreting these results. Mature trauma systems have achieved substantial improvements in outcomes through a system-based approach, resuscitation using trauma teams, and inpatient management using dedicated trauma services.9–12 In this mature adult trauma center, despite blood components requiring transport from the blood bank, times to transfusion were relatively short. This is likely associated with an established prehospital notification, an MHP that is frequently activated and audited, and a pneumatic tube that transports blood components directly to the trauma center. In such a setting, further incremental improvements in time to transfusion are unlikely to significantly improve patient outcomes.
A modifiable risk factor identified in this study was the volume of blood components transfused, with 8% higher odds of death for every unit of blood component transfused in our study. Although transfusion of blood components remains essential for trauma resuscitation, there appears to be a need to implement and assess innovative strategies to reduce blood component transfusion. During trauma reception and resuscitation, such strategies can be broadly categorized to direct control of bleeding using surgical and/or angioembolisation techniques and reduction in blood component requirement through optimization of physiology and coagulation (figure 2). The evaluation of such strategies is therefore a priority target for further research, particularly among discrete subgroups of patients such as those with TBI or penetrating trauma.
Figure 2Research priorities to achieve earlier in-hospital hemostasis.
Reducing the time to definitive hemorrhage control is another modifiable risk factor. The median time to transfer was 2.38 hours (IQR 1.5–3.7). This was substantially longer than recommended. For example, the Royal Australasian College of Surgeons guideline for emergency operative intervention is 30 minutes and for interventional radiology 60 minutes, to effect hemorrhage control.13 There are multiple confounders in the association of time to hemorrhage control and outcomes that include detection and characterization of hemorrhage, availability of theater and staff. Therefore, rather than promoting a linear association of time to theater with outcomes, in some cases, it is prudent to accept some delays to surgery to achieve greater understanding on the pathophysiology of bleeding. But recognition of delays to definitive hemorrhage control demands investigations into strategies to enable earlier therapy.
Hybrid trauma resuscitation bays and operating rooms reduce the time to hemorrhage control by enabling earlier surgery and angiography, while concurrently providing capacity for assessment using imaging and ongoing hemotherapy.14 Management in hybrid resuscitation bays has been associated with reduced blood component transfusion and lower mortality.15 16 However, trials are required for definitive evidence on benefits towards patient outcomes and cost-effectiveness. During surgical management, the role of cell salvage during trauma resuscitation remains unknown and requires further assessment.17 18
There is substantial potential for adjunct products to reduce blood component transfusion. Early administration of tranexamic acid has been consistently associated with lower mortality, without higher thromboembolic complications.8 19 Dosing and the effect of tranexamic acid on functional outcomes of patients require further assessment. Similarly, there is some uncertainty regarding the role of prothrombin complex concentrates, with potential benefits unknown, and there have been suggestions of thromboembolic events.20 Further trials are indicated and are currently enrolling patients. Pre-emptive fibrinogen replacement may also reduce other blood component requirements and although a recent trial did not demonstrate a benefit, further trials are underway.21
This study is limited in being conducted in a single adult trauma center. The results, therefore, may not be generalizable to other centers. In particular, the results should not be extrapolated to prehospital care, where early access to blood components may be life-saving. In our center, a ratio-based MHP was used and this practice differs from settings using viscoelastic hemostatic assay (VHA)-based MHPs. However, whether VHA-based resuscitation results in lower blood component transfusions or improved mortality remains unknown.22 Transfer times to the operating room or angiography suite may be significantly lower at other centers. We did not consider the effect of survival bias in the analyses. The concept of survival bias would posit that some patients would have died prior to the opportunity to be transfused large volumes of blood products. This bias, if present, would shift the association between blood products and mortality towards null, and hence, consolidates the findings of this study. Our study only included patients with hypotension on arrival, and therefore would have excluded patients who may have had occult hemorrhage and presented with a higher blood pressure. Investigations into diagnosis of occult hemorrhagic shock remain a target for future research. We also excluded patients who did not receive a blood transfusion, with the possibility that death could have resulted due to delays in initiation of transfusion, However, our assessment of the subgroup of patients who died without being transfused suggests that death was associated with severe TBI and multitrauma in older patients, and not due to inability to transfuse blood components. Finally, it is acknowledged that in severely injured patients, a massive transfusion is sometimes essential therapy, and a reflection of tissue injury and shock.
As a retrospective analysis, it is possible that unknown confounders were unaccounted for. However, we adjusted for the common variables associated with mortality after major trauma, age, shock severity and injury severity. Finally, in our discussion, we have not considered the potential for prehospital management to improve outcomes. This is an evolving field and contains many more targets for urgent research.