Prehospital Plasma for Trauma Saves Lives for Long Transport

Ricki Lewis, PhD

December 20, 2019

For patients with severe injuries, plasma transfusion during transport to a hospital is associated with greater survival at 28 days if the transport takes more than 20 minutes, according to a comparison of two recent studies. The comparison was published online December 18 in JAMA Surgery.

Civilian and military clinical practice guidelines call for early transfusion of plasma in cases of severe trauma and hemorrhagic shock so as to achieve a plasma-to-red-blood-cell ratio of 1:1 to 1:2. The seemingly contradictory findings of two recent randomized clinical trials prompted Anthony E. Pusateri, PhD, of the US Army Institute of Surgical Research, and colleagues to hypothesize that duration of prehospital plasma delivery affects 28-day mortality.

The Prehospital Air Medical Plasma (PAMPer) multicenter clinical trial followed 501 trauma patients who were transported via helicopter to a level I trauma center. Patients received either plasma and then standard care or only standard care. Prehospital administration of plasma resulted in a significantly lower 30-day mortality of 23.2%, vs 33.0% (P = .03) for patients who did not receive plasma en route to the hospital.

The second investigation, the single-center Control of Major Bleeding After Trauma (COMBAT) clinical trial, found that there was no survival advantage for 125 patients in an urban area who were driven to a nearby hospital and who had immediate access to blood components upon arrival. These patients received prehospital plasma and then standard care or standard care with crystalloid.

In both studies, 2 units of thawed plasma were delivered. Median time to the hospital was longer in the PAMPer helicopter study (41 min; range, 33 – 52 min) compared to COMBAT (18 min; range, 15 – 22 min). Perhaps the shorter time to the hospital of ground transport was insufficient for the plasma to have an effect.

The studies were developed with the aim of ad hoc comparison. The same design parameters and data elements were used, and samples and data were shared. For example, the investigations used the same inclusion and exclusion criteria, blood draw timings, adverse event monitoring, methods to assess transport time, and data collection.

"It was not possible to determine a time effect within either study independently, but analysis of the combined data from both studies offers the opportunity to examine this question," the researchers write.

The planners, from the Trans-Agency Consortium for Trauma-Induced Coagulopathy (TACTIC), which included researchers from the Department of Defense and the National Institutes of Health, intended for the studies to be compared. "This was proactive and smart, and it saved money that would have been requested for an additional clinical study to answer lingering questions after each of the COMBAT and PAMPer trials," write Todd E. Rasmussen, MD, and Laura R, Brosch, RN, PhD, of Edward Hébert School of Medicine at the Uniformed Services University, Bethesda, Maryland, in an invited commentary.

The post hoc analysis of 626 patients revealed "a significant overall survival benefit for plasma." The 28-day mortality was lower in the plasma group (61 of 297 patients; 20.5%) compared with the standard care group (94 of 329 patients; 28.6%; P = .02;), with a hazard ratio (HR) of 0.65 (P = .01) after adjustment for age, injury severity, and whether the patient was enrolled in PAMPer or COMBAT.

Combining the studies, patients in the standard care group had slightly more than double increased mortality risk when prehospital transport was longer than 20 minutes (HR, 2.12; P = .04), but this was not the case for the patients who received plasma on the ride to the hospital (HR, 0.78; P = .46).

Patients who received prehospital plasma were 47% less likely to arrive at the emergency department with coagulopathy than those who had not received plasma (OR, 0.53; P = .002). This association held only for patients who were in transport for longer than 20 minutes.

The observation that for the standard care group, transport times longer than 20 minutes were associated with increased mortality "emphasizes the importance of minimizing time to definitive care," the researchers write, as well as the importance of rapid hemostasis.

"The present findings have important implications for the treatment of patients with traumatic hemorrhage when surgical care and in-hospital transfusion may be delayed, such as in military settings, in rural and remote trauma, and in civilian disaster scenarios," the researchers conclude.

The commentators write that the coordinated studies approach validates registry-based studies, which have been criticized for nonrandomization, poor quality of data, and selection bias. "However, an often overlooked benefit of registry-based studies is their ability to improve the efficiency of subsequent prospective, controlled trials, such as in this sequence of studies," they write. They also applaud the collaboration of the Department of Defense and the National Institutes of Health, because the finding regarding the value of transfusing thawed plasma for more than 20 minutes is applicable to both combat and civilian settings for traumatic injuries with hemorrhagic shock.

Limitations of the study are the different modes of transport in the two investigations and the lack of information on the time from injury to plasma transfusion.

The authors and commentators have disclosed no relevant financial relationships.

JAMA Surg. Published online December 18, 2019. Abstract, Commentary

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