Transfusion therapy has come full cycle in Iraq and Afghanistan as fresh whole blood (FWB) use has again found a place in the resuscitation of military casualties. The use of equal ratios of packed red blood cells, plasma and platelets (so called 1:1:1 therapy) to effectively reconstitute whole blood is gaining ground in civilian trauma centers to attempt to replicate the approach of military trauma teams. While this is an exciting and potential live saving therapy, have we considered the “collateral damage” of these trauma resuscitation protocols and does the current evidence support this approach?
The first point to be made is that blood is not a benign substance and has a number of adverse effects that can mitigate or even eliminate clinical benefits. While the most common causes of death for trauma patients within the first 48 hours is either exanguination or massive head injury, after 48 hours the leading causes of death are sepsis, multisystem organ failure and ARDS, all linked causally to blood transfusions in a dose-dependent manner. The great paradox of trauma resuscitation protocols is that the physicians who use them are typically boarded in critical care medicine, a specialty that helped define modern blood component therapy and coined the phrase “less is more” to describe the clinical benefits of conservative transfusion triggers. Even in trauma patients, transfusions should always be used in a cautious and thoughtful manner, giving no more or no less blood than the patient needs based upon the best available evidence.
While much has been made of the experience in Iraq demonstrating the efficacy of “high ratio” FFP:RBC protocols (approaching 1:1), can we extrapolate this data to civilian trauma patients? Beyond the fact that combat injuries are not easily replicated in civilian trauma centers (thankfully) since these patients often have multiple penetrating wounds and massive orthopedic blast injuries, there also has been intermingling of fresh whole blood along with the use of recombinant factor VIIa in military casualties. Further, the most cited military study by Borgman1 retrospectively reviewed combat injuries from 2003- 2005 in Iraq, during which time there were a number of logistic changes to the military trauma system as well as alterations in the medical management of trauma patients. Beyond the military data, there are precautions in interpreting the growing number of papers citing the civilian trauma experience. All civilian studies to date are either retrospective studies or prospective cohorts using retrospective “controls”, again raising the issue of changes in patient care beyond these resuscitation protocols over time. There is also a significant issue in that trauma patients are a tremendously heterogenous group (as opposed to say hip replacement patients) making comparisons across patient groups challenging at best. This particular issue has likely contributed to the undoing of blood substitute studies in trauma thus far. Other issues include a subjective and after-the-fact segmenting of trauma patients into “buckets” of ratio groupings introducing the possibility of bias, particularly since there at times seems to be an overt push to validate reconstituted whole blood (1:1:1 therapy). Most concerning is an issue that has often been overlooked in the discussion section of these papers, the thorny issue of “survivor bias”. The concern here is that only patients who survive long enough to receive treatment get the additional plasma therapy, which then effectively labels nonsurvivable injuries in the lower plasma ratio groups as treatment failures. Best described in a recent paper by Snyder et al, “Therefore, it could be concluded that the nonsurvivors in our study population did not die because they got a lower FFP:PRBC ratio; they got a lower ratio because they died.”3
The final issue to discuss is recently published data from civilian trauma centers that is somewhat at odds with the military data. A review of FFP:RBC ratios and outcomes at two trauma centers (LA County/USC and Grady Memorial) showed no further survival benefit in patients given ratios of FFP:RBC beyond 1:3, suggesting that plasma use in higher ratio protocols might be excessive and wasteful.4,5 The most concerning data comes out of Denver Health where an analysis of their data demonstrated a “U” shaped curve, with a decline in mortality as FFP:RBC ratios increased to 1:3, but as the ratio climbed further to 1:1 mortality rates also increased.6 As the authors discussed, once the therapeutic effect of the plasma has peaked, the adverse effects such as transfusion related lung injury (TRALI) and transfusion associated circulatory overload (TACO) may predominate. Once again we come to appreciate the fact that blood has a very narrow therapeutic window, so the optimal ratio of FFP:RBC in these trauma protocols is much more than an academic question.
I hope that you can join me for a webinar on January 25th at 1 PM EST entitled “Trauma Blood Management: Damage Control Resuscitation and Massive Transfusion Protocols”. In addition to discussing the literature on trauma resuscitation protocols in much greater detail, we’ll review damage control resuscitation including pre-hospital care, adjuncts to trauma resuscitation such as recombinant factor VIIa, and the physiology of Acute Coagulopathy of Trauma Shock (ACoTS). We’ll also discuss strategies to minimize the collateral damage of trauma resuscitation, such as using best-practice massive transfusion protocols, designating a limited number of gatekeepers who can initiate the protocol, incorporating active check points for the continuation of the protocol, and using point-of-care/ near patient testing to convert the approach from empiric to goal-directed therapy at the earliest possible time.
Submitted by: Timothy Hannon, MD, MBA | Founder & President, Strategic Healthcare Group, LLC
Selected References:
- O’Keeffe T, et al. A massive transfusion protocol to decrease blood component use and costs. Arch Surg 2008;143(7):686-91
- Borgman MA, et al. The ratio of blood products transfused affects mortality in patients receiving massive transfusions at a combat support hospital. JTrauma 2007;63:805-13
- Snyder CW, et al. The relationship of blood product ratio to mortality: survival benefit or survival bias? JTrauma 2009;66:358-64
- Teixeira PGR,et al. The impact of plasma transfusion in massively transfused trauma patients. JTrauma 2009;66:693-97
- Dente CJ, et al. Improvements in early mortality and coagulopathy are sustained better in patients with blunt trauma after institution of a massive transfusion protocol in a civilian level I trauma center. JTrauma 2009;66:1616-24
- Kashuk JL,et al. Postinjury life threatening coagulopathy: is 1:1 fresh frozen plasma: packed red blood cells the answer? JTrauma2008;65:261-71
