The Changing Landscape of Trauma Care, Part 2
Rodent studies have demonstrated large-volume crystalloid administration and breakdown or “thinning” of the endothelial glycocalyx, which leads to increased capillary leak, third-spacing, and ultimately intravascular volume depletion.14,15 This mechanism has been linked to pulmonary complications, namely acute lung injury and acute respiratory distress syndrome. Enteric edema resulting from aggressive crystalloid resuscitation has also been associated with prolonged postoperative ileus, increased risk of anastomotic leak,13 and inability to achieve primary fascial closure.16 All of the aforementioned complications are reduced when employing a restrictive fluid resuscitation strategy.17
Aggressive crystalloid administration in hemorrhagic shock also leads to dilutional coagulopathy. Multiple animal and human studies have shown an association between increased crystalloid volumes in hemorrhaging patients and increasing coagulopathy, blood loss, and mortality. In 2004, Barak et al18 demonstrated that administration of a high volume of crystalloid fluid (>3 L) or colloid (500 mL) was associated with postoperative coagulopathy; whereas in 2017, Harada et al,19 at Cedars-Sinai Medical Center in New York, demonstrated over a 10-year period that decreased high-volume (>2 L) crystalloid resuscitation paralleled a decrease in mortality.
Massive Transfusion Protocols. Many trauma centers have shifted away from high-volume crystalloid resuscitation in favor of massive transfusion protocols (MTPs) utilizing standardized ratios that more closely mimic whole blood. The MTPs center on the principle of equal transfusion ratios of blood product as opposed to packed RBCs (PRBCs) alone. This means effecting a plasma-rich resuscitation and preemptive correction of coagulopathy with FFP and platelets in addition to PRBCs.
Data from a US Army combat support hospital have demonstrated improved survival with an FFP to PRBC ratio of more than 1:1.4,20 and civilian studies have produced similar findings.21-23 All of these studies also noted improved mortality with higher (>1:2) platelet to PRBC ratios.22,23 Although, the ideal ratio remains unknown, many MTPs aim for 1:1:1 ratio (6 U FFP to 6 packed platelets to 6 U PRBC), which most closely mimics whole blood.
The Pragmatic Randomized Optimal Platelet and Plasma Ratios trial was a recent large multicenter randomized trial that compared transfusion ratios of 1:1:1 and 1:1:2. The trial was unable to demonstrate a difference in mortality at either 24 hours or 30 days, though more patients in the 1:1:1 ratio group achieved hemostasis and fewer patients in this group died from exsanguination in the first 24 hours.24Prehospital PRBC Administration. A number of studies have looked at prehospital administration of PRBCs.25-27 Holcomb et al25 showed no overall survival advantage at 24 hours, but did demonstrate a negligible blood-product wastage. In 2015 Brown et al26 found an increase probability of 24-hour survival, decreased shock, and lower 24-hour PRBC requirements with pretrauma-center PRBC transfusion. That same year Brown et al27 demonstrated that prehospital PRBC transfusion in severely injured blunt trauma patients was associated with decreased 24-hour and 30-day mortality rates, and a lower risk of coagulopathy. Currently, the Prehospital Air Medical Plasma trial is enrolling patients to evaluate the prehospital administration of plasma.28 The primary endpoint of the study is 30-day mortality; the tentative completion date for the study is January 2018.
Tranexamic Acid. Another important development in the treatment of hemorrhagic shock in recent years has been the use of TXA, an antifibrinolytic agent which inhibits the conversion of plasminogen to plasmin. It has been shown to decrease mortality in both civilian and military trauma populations.29,30
The Clinical Randomization of an Antifibrinolytic in Significant Hemorrhage 2 trial was a large multicenter randomized trial, which showed a survival benefit among those who received TXA. The generalizability of the study has been questioned in the setting of modern urban trauma centers, as most of those enrolled in the study were from hospitals with no formal MTPs and a limited availability of blood products. Additionally, no laboratory measures of fibrinolysis were available.30
Most experts currently recommend TXA use as part of an MTP if there is evidence of hyperfibrinolysis on TEG or in severe hemorrhagic shock when the time from injury has been less than 3 hours, as studies have shown increased mortality when TXA was administered longer than 3 hours after injury.30
Viscoelastic Assays
An alternative approach to standardized ratio MTPs involves goal-directed hemostatic resuscitation using viscoelastic assays to guide transfusion of blood-product components. Both TEG and rotational thromboelastometry (ROTEM) are point-of-care tools for assessment of coagulation parameters of whole blood. Although they are not new technology, their use in trauma resuscitation is a relatively new concept.
While ROTEM is more commonly used in Europe, TEG is more popular and commonly used in the United States, though not exclusively.31,32
Thromboelastography
The TEG parameters most commonly used clinically are reaction time (R-time), kinetics time, angle, maximum amplitude (MA), and lysis at 30 minutes (LY30).
