Using multivariable logistic regression analysis, we sought to identify predictors of mortality (Table 3). Adjustment was made for the following variables: age, gender, mechanism of injury, TRISS, and 24-hour transfusion of PRBC, FFP, and PLT. TEP was found to be a predictor of 30-day mortality (OR 0.26, p < 0.01, 95% CI 0.12–0.57).
Multivariate linear regression analysis was then performed to evaluate the impact of TEP on total and individual blood product utilization when controlling for age, gender, mechanism of injury, and TRISS. Implementation of TEP was associated with a decrease in 24-hour total blood products (34.36 vs. 43 U, p = 0.015) and a decrease in 24-hour platelet transfusion (4.65 vs. 11.98 U, p < 0.001). No difference was seen in 24-hour PRBC and FFP transfusion between PRE-TEP and TEP when controlling for the aforementioned confounding variables.
Despite tremendous efforts and attention directed at implementation of damage control techniques (abbreviated laparotomy, reversal of acidosis, correction of hypothermia), traumatic coagulopathy has been seriously understudied and underappreciated.2,12,15 Increasing evidence has demonstrated coagulopathy in the severely injured patient is often present in the field or upon arrival to the trauma center.14,16–18 In the absence of a predefined massive transfusion protocol, access to the appropriate volume and ratios of blood products may be significantly delayed. Failure to immediately address and treat this coagulopathy may lead to a worsening of coagulopathy from crystalloid based dilution, a hopeless “chasing” of uncorrectable labs, and an eventual exsanguination from nonsurgical hemorrhage. Our multidisciplinary group has recently designed an exsanguination protocol to address the often overlooked hematological aspects of current damage control strategies. Delivered in an early, aggressive, and predefined manner, the TEP has resulted in a 74% reduction in the odds of mortality at our institution.
Through prompt replacement of PRBC and necessary blood components, we thought that we would be able to prevent the almost inevitable coagulopathy seen in these patients. By reducing the incidence and severity of this often overwhelming process, we hoped to reduce the number of blood products consumed. Although the TEP patients received more products intraoperatively, we were able to reduce postoperative and overall 24-hour product utilization.
This reduction is not only important from a blood utilization and cost standpoint, but also for a potential reduction in morbidity among survivors. Numerous authors have demonstrated an increase in acute lung injury, acute respiratory distress syndrome, and multiple system organ failure with massive transfusion.20,24–26 By minimizing hemorrhage early and decreasing overall blood product use, the incidence and severity of these morbidities may also be reduced.
Increasing evidence has demonstrated that aggressive crystalloid-based resuscitation strategies are associated with cardiac and pulmonary complications, development of abdominal compartment syndrome, coagulation disturbances, and immunologic and inflammatory mediator dysfunction.27–30 Particular to coagulation disturbances, increasing crystalloid volumes are associated with platelet dysfunction and coagulopathy. Barak et al. demonstrated that patients who received less than 3 L of crystalloid intraoperatively had significantly less disturbances in their coagulation levels than those patients who received at least 3 L.27 This is consistent with previous investigations demonstrating the clinical significance of “dilutional” coagulopathy after excessive saline administration. In the present study, we were able to reduce the amount of intraoperative crystalloid administration by almost 2 L after controlling for appropriate confounders. Reducing crystalloid use and replacing “what is bled” is also the approach advocated by military data from Iraq using the concept of damage control resuscitation.12,14
Limitations to this study include the relatively small sample size for each cohort and the retrospective design using data collected via a trauma registry database and computerized patient chart. In addition, a notable limitation is the fact that the population is not homogenous and the cohort is not identically matched; however, these issues were addressed with the use of multivariable regression strategies. Additionally, we did not collect data on prehospital fluid and blood product administration. This may have impacted the initial physiologic presentation and triggered trauma faculty to activate the TEP. Both populations also include many individuals that died intraoperatively. Though we speculate that a fairly similar number exists between the two groups, patients who died in the OR would likely skew the data toward increased blood component utilization in the survivors. Finally, we only assessed 30-day survival on these patients and did not evaluate them with regard to long-term follow-up.
1. Acosta JA, Yang JC, Winchell RJ, et al. Lethal injuries and time to death in a level I trauma
center. J Am Coll Surg
2. Kauvar DS, Lefering R, Wade CE. Impact of hemorrhage
outcome: an overview of epidemiology, clinical presentations, and therapeutic considerations. J Trauma
3. Sauaia A, Moore FA, Moore EE, et al. Epidemiology of trauma
deaths: a reassessment. J Trauma
4. Hoyt DB, Bulger EM, Knudson MM, et al. Death in the operating room: an analysis of a multi-center experience. J Trauma
5. Farkash U, Lynn M, Scope A, et al. Does prehospital fluid administration impact core body temperature and coagulation functions in combat casualties? Injury
6. Maegele M, Lefering R, Yucel N, et al. Early coagulopathy in multiple injury: an analysis from the German Trauma
Registry on 8724 patients. Injury
7. Rugeri L, Levrat A, David JS, et al. Diagnosis of early coagulation abnormalities in trauma
patients by rotation thrombelastography. J Thromb Haemost
8. Gonzalez EA, Moore FA, Holcomb JB, et al. Fresh frozen plasma should be given earlier to patients requiring massive transfusion
. J Trauma
9. Ho AM, Karmakar MK, Dion PW. Are we giving enough coagulation factors during major trauma
resuscitation? Am J Surg
10. Ho AM, Dion PW, Cheng CA, et al. A mathematical model for fresh frozen plasma transfusion strategies during major trauma
resuscitation with ongoing hemorrhage
. Can J Surg
11. Ketchum L, Hess JR, Hiippala S. Indications for early fresh frozen plasma, cryoprecipitate, and platelet transfusion in trauma
. J Trauma
12. Holcomb JB, Jenkins D, Rhee P, et al. Damage control resuscitation: directly addressing the early coagulopathy of trauma
. J Trauma
13. Hess JR, Zimrin AB. Massive blood transfusion for trauma
. Curr Opin Hematol
14. Hess JR, Holcomb JB, Hoyt DB. Damage control resuscitation: the need for specific blood products to treat the coagulopathy of trauma
15. Hutt J, Wallis L. Blood products in trauma
resuscitation. J R Army Med Corps
16. Brohi K, Singh J, Heron M, Coats T. Acute traumatic coagulopathy. J Trauma
17. Brooks JP, Marshall JH. Early awareness of post-traumatic coagulopathy. Injury
18. Hirshberg A, Mattox KL. Planned reoperation for severe trauma
. Ann Surg
19. Wilson RF, Dulchavsky SA, Soullier G, Beckman B. Problems with 20 or more blood transfusions in 24 hours. Am Surg
20. Robinson WP III, Ahn J, Stiffler A, et al. Blood transfusion is an independent predictor of increased mortality in nonoperatively managed blunt hepatic and splenic injuries. J Trauma
21. Riska EB, Bostman O, von BH, et al. Outcome of closed injuries exceeding 20-unit blood transfusion need. Injury
22. Phillips TF, Soulier G, Wilson RF. Outcome of massive transfusion
exceeding two blood volumes in trauma
and emergency surgery. J Trauma
23. Chen RJ, Fang JF, Lin BC, Wang YD, Chen MF. Factors that influence the operative mortality after blunt hepatic injuries. Eur J Surg
24. Moore FA, Moore EE, Sauaia A. Blood transfusion. An independent risk factor for postinjury multiple organ failure. Arch Surg
25. Phillips GR III, Kauder DR, Schwab CW. Massive blood loss in trauma
patients. The benefits and dangers of transfusion therapy. Postgrad Med
26. Sauaia A, Moore FA, Moore EE, Lezotte DC. Early risk factors for postinjury multiple organ failure. World J Surg
27. Barak M, Rudin M, Vofsi O, Droyan A, Katz Y. Fluid administration during abdominal surgery influences on coagulation in the postoperative period. Curr Surg
28. Boldt J, Heesen M, Welters I, Padberg W, Martin K, Hempelmann G. Does the type of volume therapy influence endothelial-related coagulation in the critically ill? Br J Anaesth
29. Cotton BA, Guy JS, Morris JA Jr, Abumrad NN. The cellular, metabolic, and systemic consequences of aggressive fluid resuscitation strategies. Shock
30. Ng KF, Lam CC, Chan LC. In vivo effect of haemodilution with saline on coagulation: a randomized controlled trial. Br J Anaesth
Dr. Larry J. Butler (Colorado Springs, Colorado): This topic is obviously a very timely one. Over the last 48 hours we've discussed many issues related to coagulopathy in the severely-injured patient.
Gene Moore, yesterday, showed us data suggesting that the optimal FFP to packed red cell ratio was about 2.5 to 1. In the discussion of that, Dr. Lucas reminded us that over 20 years ago he similarly saw an optimal ratio in the 1 to 2 range.
Dr. Holcomb, also in the discussion of that paper, mentioned the military's experience with a 1 to 1 ratio and promised us upcoming data. In fact the next paper to be presented this afternoon deals with the civilian experience in the optimal ratio of FFP to packed red blood cells.
Factor VII's role has also been discussed in decreasing mortality in combat casualties as well as decreasing the time to operative intervention in the brain-injured patient.
So this is obviously a very pertinent topic. This study looks at the institution of a trauma exsanguination protocol. Interestingly enough, this happened just about the same time we introduced our massive transfusion protocol. And I think many of us are doing this.
Questions I have are related primarily to whether these cohorts truly related. I think there is a huge difference in the mechanism of injury, almost two to one penetrating in the study group compared to the retrospective cohort.
Several things happened then and I wondered if you looked at issues in the differences between the blunt and the penetrating in terms of prehospital time, amount of crystalloid infused, and temperature on presentation.
Also, was the operative management in these different groups of patients, the blunt and the penetrating, different, specifically the percentage use of damage control laparotomy, the use of open abdomen, or the use of embolization or other techniques?
The increase in penetrating injuries also might suggest that there was an increased ability to surgically control bleeding.
The next set of questions I have for you is in regards to the implementation of your protocol and I'd like to know how this really worked. Did you always have four units of FFP thawed?
And if you did, how much waste was there? If you didn't have that four of FFP thawed, how long did it really take you to get it?
What data or decision points did the attending trauma surgeon use to call for the next round of products? Was he getting lab work, hematocrit, INR, platelet count, fibrinogen? Or was he basing this just on clinical parameters?
Were there any breaks in your protocol? Did you have surgeons giving cryoprecipitate? Did you have them giving factor VII? If you did, were these excluded from your study? Were they included? How did you interpret this in your analysis?
Finally, I would ask if you tried to break down the data and look at penetrating versus penetrating and blunt versus blunt in your two cohorts.
Dr. Patrick Reilly (Philadelphia, Pennsylvania): Number 1, will you be very clear to the audience because it's a little unclear in your abstract and the slides, are you using stored, thawed plasma or are you using fresh frozen plasma?
Number 2, is factor VIIa formally built into your protocol or not? And if it was, was there a difference between the number of patients or timing of administration in those who received factor VIIa in your protocol versus the pre-protocol group?
And the third thing, in the conclusions you sort of hinted that the exsanguination protocol enabled more blood to be available for the injured patient quickly when you needed it. In our experience we believe that as well, but we've never been able to really document it because we can't exactly tell when the blood is transfused reviewing the operative record, only that it was transfused sometime during the operation. The only times we have are when the blood was released from the blood bank. How are you coming to the conclusion that the blood is available and it wasn't available before?
Dr. Carl J. Hauser (Boston, Massachusetts): I'd like to know whether you have looked at the incidence of the, of what we have historically called the “abdominal compartment syndrome” in these two groups but which probably should be called the “abdominal crystalloid syndrome?”
Dr. Matthew J. Wall, Jr. (Houston, Texas): These days a lot of patients are on platelet poisons. Was that one of your indications for you to institute your protocol or should it be?
Dr. Bryan A. Cotton (Nashville, Tennessee): Thank you. Dr. Butler, thank you once again for your questions. With regards to the mismatch in cohorts, there absolutely is.
We tried to pick what we thought would be the most applicable cohort, patients going straight to the OR from the trauma bay, getting at least 10 units of blood which has classically been defined as one definition of trauma, of massive transfusion.
And that was as good as we could get, at least for this part. Once this was chosen, we were actually cautioned by our statistical consultants not to “over-match” with our study group. Taking that into consideration, we did control for the discrepancies in the penetrating mechanism and the RTS differential in our multiple linear regression model.
With regards to blunt versus penetrating, we have evaluated through our PI process and I can tell you that even though the data is not here, the blunt and penetrating appeared to both benefit with regards to people that we would consider saves or not saves with regards to whether their mechanism was blunt or penetrating.
Pre-hospital variables are hit or miss. They are phenomenally collected on the aeromedical side. They are poorly collected on the ground side. So we do not include those in our database but it would probably benefit from including those.
As far as evaluating abdominal compartment syndrome, interventional radiology, implementation to mechanisms, I can tell you that we did not look at those specifically but that the overwhelming number of these are abdominal procedures not extremity procedures, although they have been activated for traumatic amputations of upper and lower extremities and some severe chest trauma.
As far as the products' availability, they are generally available within a 10 to 20 minute timeframe. And then about every 20 minutes we get a new cycle distributed to us but without much delay.
In fact, if there is one component that is delayed they will send what is ready and then send another currier with the extra components when those particular components are prepared.
As far as activation, this was 100 percent a clinical call. From the PI process we can show some times where it should have been activated earlier and it was activated in very much what we would consider a delayed fashion on some people and that was part of the learning process of clinical faculty at the second year fellowship level.
I can tell you that otherwise it was pretty much routinely activated from the trauma bay or shortly after arrival in the operating suite.
And it was pretty much a uniform activation criteria. It's all clinical acumen for the most part. We did not go based on labs or any resuscitation endpoints.
As far as cryo, factor VII, things like that, we do have cryo built into the protocol by request but it is not automatically delivered.
We have discussed that through our PI process about adding that component to one of our cycles, maybe the second or third cycle. But right now it's on a prn basis if the faculty request that.
As far as VIIa, that was initially in our protocol but no patients received it. On protocol we've had two violations. Those were removed. Factor VIIa was removed from the protocol and use by the administration for pretty much anyone unless it was part of an industry sponsored study.
And we have actually had a couple of activations on emergency general surgery patients that were in hemorrhagic shock from other sources, for intra-abdominal processes. And those two EGS patients were removed.
Blunt-blunt, penetrating-penetrating evaluation, we did not do that. With regards to Dr Reilly who recognized this protocol well as it's very similar to the one that I learned when I was at fellow at Penn, as far as FFP, it is FFP that they're thawing.
From that point it's not ready to go, unfortunately. And we've had that debate with the blood bank. They think that that would be a waste to have it already thawed.
They don't think that they go through it enough to use it as a resource, especially with the AB negative process in our population. As far as VIIa, again, it was initially built in but then removed by the administration.
And then availability, it is fairly available within about a 15-minute window once you make that phone call. And at a minimum we get all the blood. Ten units of blood is immediately available. FFP and platelets are about a 10- to 15-minute lag.
With regards to Dr. Hauser's comments, we did not evaluate the crystalloid assault of the patients and whether or not they ended up as open abdomens.
But we plan on looking at that in the future to see if by the fact that they did have a reduction in crystalloid intra-operatively and post-operatively, if this did lead to less of the abdominal crystalloid syndrome.
And then, finally, to Dr. Wall, we did not look at coagulation status pre-hospital or Plavix use, Coumadin use.
I can tell you one or two patients that may have been on Coumadin that got it but they were going to the operating suite for another process and would have had it activated most likely anyway. However, we did not evaluate that separately. And then, perhaps it should be included.