Latest / Behind The Knife: The Surgery Podcast / Whole Blood vs. Components: The Prehospital Debate
Transcript
- prehospital_blood === Speaker 3: [00:00:00] Welcome back to Behind the Knife. I'm Einar Li, a general surgery resident and Behind the Knife fellow at Duke Hospital. Today's gonna be awesome. I'm joined with Dr. Patrick Georgoff, trauma surgeon and trauma medical director at Duke, to discuss a , highly debated topic in trauma resuscitation, prehospital blood. This episode is inspired by a recent trial in The New England Journal of Medicine, the study of whole blood in frontline trauma, abbreviated as the SWIFT Trial. It showed no difference between whole blood or components. We'll talk about it in more detail, but first, Dr. Georgoff, can you introduce our guests? Speaker 2: Oh, man, can I ever. This is really exciting. , This is gonna be a great topic. This is an important topic in the trauma community, and we're thrilled to be joined by two heavyweights in the field, and they approach this topic from different systems and different sides of the pond, and so we're excited to have their, , viewpoints. So first is Dr. Ed Barnard. He is an as- emergency physician and a UK defense professor of emergency medicine, and an author on this trial, the SWIFT Trial, and Ed has extensive experience in [00:01:00] large-scale prehospital trials in the UK. Our other guest is Dr. Juan De Chesney, the trauma surgeon and trauma medical director and division chief at the University of Mississippi Medical Center. And he's a renowned pioneer in the use of prehospital blood and looking at the topics of balanced resuscitation and damage control resuscitation. So gentlemen, welcome. Very much, , excited to have you here on Behind the Knife. Speaker 4: Thank you for having us. Speaker 5: Yeah. Thanks very much. Looking forward to it. Speaker 2: So we can, set the groundwork, , with prehospital blood. So there are only a handful of randomized trials that compare, , prehospital blood, so products of any kind, versus some sort of standard of care, and that's oftentimes without blood. And the largest and most impactful randomized trial was the PAMPER Trial, and that compared two units of thawed plasma to, quote-unquote, "standard of care" at that time, which was non-blood-based resuscitation. And this trial showed a decrease in 30-day mortality. There [00:02:00] are, however, other relatively large trials as well, one called COMBAT, which was performed in Denver, and the other called REFILL, which was also in the UK, that did not show a difference in mortality,. Now, observational, , and registry data, on the other hand, heavily favors some sort of prehospital blood versus none when it comes to the issue of mortality. Now, what remains even less proven by the data is a more narrow question, whether whole blood beats component therapy When it comes to that pre-hospital trauma resuscitation. And the SWIFT trial is the largest, , study to date on this and the best answer that we currently have for this very specific question. And the answer was, , there was no difference between whole blood and component therapy, at least for the outcomes studied in this trial. But of course, the devil is in the details, and we're gonna get into those details today. , So, , two major questions we wanna cover. The first, whether pre-hospital whole blood is superior to component therapy. Can we know that right now? What data do we have? And the second [00:03:00] is, what are the logistical challenges associated with pre-hospital blood programs? Specifically, are we approaching the problem in the right way? So to launch us off, Armin, can you give us a few of the basics for the SWIFT trial? And Dr. Barnard, you can check his work , and correct us on some of the finer points of this really, again, , exciting study. Speaker 3: Yeah, this study asked the question of whether pre-hospital whole blood transfusion was superior to standard of care, which in the UK was component therapy. And this was done in trauma patients with severe hemorrhage. So the trial was published in March 2026 in The New England Journal of Medicine and randomized nine hundred and forty-two patients across ten air ambulance services in the UK to receive either two units of whole blood or standard of care, up to two units of red cells and plasma before hospital arrival. The primary outcome was a composite of death or massive transfusion within twenty-four hours, which was about fifty percent and statistically equivalent between groups. [00:04:00] Breaking this down a little bit, ten percent of patients in each group died within twenty-four hours. So the composite outcome was largely driven by massive transfusion. That being said, there was no statistical difference in mortality at six hours, twenty-four hours, thirty days or ninety days, nor a difference in massive transfusion alone. Speaker 2: Fantastic. Really quick, some strengths. This is the largest pre-hospital whole blood RCT to date. It's got a pragmatic real-world design, and it used physiologically complete platelet-rich whole blood, which has not always been the case with prior studies. Some areas of potential weaknesses worth mentioning is this dose ceiling of only two units of blood and powering for the trial. But Ed, correct this. What, what else-- How do you frame this discussion about your trial that, , I'm sure you put a lot of blood, sweat and tears into? Speaker 5: Yeah. Thanks very much. That's a decent summary. Thank you. , So we saw an opportunity some years ago with Equipoise in the UK for testing a new whole blood product versus component therapy in a very mature system. So our system is very different to lots of [00:05:00] parts of the world. , And that's probably important to mention and maybe expand on later. I think the other bit I'd pick up on there is what you said about in patients with severe hemorrhage. And one of the problems we have with these pre-hospital trials is identifying the right patient cohort. So undoubtedly, there'll be patients in SWIFT who did not have severe hemorrhage. And, and so what we do in that is that we dilute the potential effects. Let's say, for example, whole blood is really beneficial in patients who are actually bleeding to death compared to components. W-we're not gonna demonstrate that probably in a trial like this because you have to make decisions really early. And we know from some published research and our own experience that when you go to these patients very early, you often get it wrong. So there are hemorrhage mimics, there are other conditions. By the time you get to hospital, a bit more time has elapsed. That's a really helpful diagnostic aid. The CT scan is also a pretty good diagnostic aid, as is opening the belly or the chest and, , and seeing blood in there. So I would just, - You know, it's part of the complexity of doing these trials [00:06:00] is how do you identify the right patient cohort early. , In terms of interpreting the trial, I think we have to take it for exactly what it is, but there are some nuances around the cohort of patients who are included, , the setting, some of the timelines, and a bit about the product. So I'll just quickly talk about some of those. So, , the statistical plan is set out to try and demonstrate if there is-- if whole blood is better for these outcomes than component therapy. So it's not strictly true to say that there's no difference from the results of this study. So what we do know is that in this pretty mature pre-hospital system, with quite long timelines in this group of patients, that two units of this whole blood product, which does contain some platelets, , is not superior for these outcomes in this patient cohort. So that's a bit complicated. A complicated way, I guess, of saying we did not demonstrate that whole blood was superior. What we did show, I think that's important, is that whole blood is safe. So for the first [00:07:00] time, we have a well-controlled study that demonstrates that whole blood is a safe intervention, and that's important when we perhaps come on to discuss stuff around the logistics of how you carry product pre-hospital, how you give it quickly to patients. And, and having all the stuff in one bag is significantly easier, uh, you know, than having separate components Speaker 2: Now, , Ed, I'm gonna come back to you with the first question on, on this composite endpoint. But Juan, how did you read Ed's study? , And what does it mean for you as a trauma surgeon in the US? How did you, at first glance, take those findings? Speaker 4: You know, , f- once again, , thank you for the invitation and the, and this great panel discussion. , I'll be honest with you. We, , in New Orleans, we decided to use packed red blood cells versus whole blood just because of the finances. , It was cheaper to do it, , than just getting whole blood. And when we look at our analysis, our [00:08:00] mortality was very similar to other trauma centers, , when they-- that are actually using, , whole blood. , For example, when you look at Grady in Atlanta, when you look at the, , the team in the Virginia, the other teams in, down in the South. , So there is a little bit of correlation between whole blood outcomes and packed red blood cells outcomes. So I'm not surprised, , and I'm glad that this actually study came out, , because I felt like there, that there was some, , team members out there carrying the big flag that whole blood is so much better than packed red blood cells. But I get it. I get the potential physiological benefit when you compare side-to-side those two, , interventions. But, , in that, in the pre-hospital setting in New Orleans, at least in that fast-paced environment, we didn't really see that much of a difference. But I do believe there's a benefit of precision resuscitation, and I think that, that, that would need to be discussed further, , down the line. [00:09:00] Speaker 2: Yeah, Ed? Speaker 5: Hey, Juan, that's, , s- yeah, some great points, and I think one of them that you alluded to in the background was that we talk about whole blood, but if you look through the literature, that means a whole host of different things. Speaker 2: Yeah. Speaker 5: And there are some early whole blood studies that are actually red cells and plasma. I'd call that RCP. , And, you know, and then at the other end of the spectrum, probably there's fresh low titer O warm whole blood, which is only really given in military settings, which of course is, you know, where I come from. And I think if you're bleeding to death in front of, you know, if I was bleeding to death, I would want you to give me warm, fresh whole blood. The question here is, how much difference is there with a cold stored whole blood product that has a small dose of platelets in it compared to red cells and plasma given in an intelligent fashion? And that might give you some of the example as to why we didn't see superiority of whole blood, and that actually there's biologically very little difference between cold red and yellow together with a sprinkling of platelets [00:10:00] compared to cold stored low titer O whole blood. So actually, they're not that dissimilar in terms of what you're giving. Speaker 2: Yeah, and I think it's worth for anyone following along with this topic, , there's so many different trials and different alphabet soup with each of those trials. It's e- very easy, , to... even if you're, you know, a busy trauma surgeon, for example, to get lost into what exactly was studied within each of those trials. And so, Ed, to your point, it's really important to look at what those groups included, , and when it comes to, s- , red cells, plasma only, lyophilized plasma, leukoreduced, , whole blood, et cetera, et cetera. And, and these are all very different things. And so none of these trials, just like in, in everything else we study, are not exactly the same, so they need to be interpreted as such as well. , Let's get to this, this composite endpoint. I thought this was interesting, Ed, and maybe you can explain this for us a little bit better because, , it, it's unique. In the composite endpoint that you looked at as the primary outcome was death, makes sense, or massive transfusion. So death is a binary thing, massive transfusion a little bit [00:11:00] different, typically defined as 10 or more units in twenty-four hours. So how do you, how did you guys come up with that? And, and what do you think that means when it comes to someone opening up New England Journal of Medicine and looking at the abstract and your guys' conclusion? Speaker 5: So this is a great question, , and it's basically the reality, the harsh realities of undertaking research and getting funding. So when we set up these trials, we know we've got a certain number of patients within a certain timeframe that we might be able to include without spending billions of pounds or dollars. And so what we need to be able to do, we're always making compromise. And you might notice that the study's powered at eighty-five percent, not eighty or ninety, eighty-five percent. And that's all got to do with sample size, how quickly you can recruit to a trial and answer the question, but ultimately how much it costs to deliver that research and answer that question. So by... No-nobody wants a composite outcome. There isn't, there is, there is nothing necessarily good about [00:12:00] a composite outcome, except that it increases your... It, it, it massively reduces your sample size, , and your ability to actually deliver a trial, , within a decent timeframe, within a decent budget. So it's essentially all to do with that. Now, how we came up with that, with that composite is a bunch of consensus discussion amongst the trial group and some expert specialists, , some external specialists, but also using data to look at, ... So there's a red cells in plasma versus red cells study done in London using six-hour ambulances that's been published, , previously. And so we used data from that study to try and estimate what's called the event rate. , And actually what we ac-- found was that the event rate of these outcomes was lower in the swift cohort, and we suspect that's because we're just generally getting better at trauma care year on year. So if we use even slightly historic data to try and estimate the [00:13:00] event rate of massive transfusion and mortality from trauma hemorrhage to power a study today, we're probably gonna have underestimated the event rate. Speaker 3: Another question is about , the dosing. So in the trial, it seems like there were up to two units, and so the question for both you and Dr. Duchesney is, is that enough? Is two units of blood just too small to get an effect, especially when you're talking about this outcome? Speaker 5: So ideally, you're gonna wanna give as much of that intervention as possible, whether it's a blood trial or something else, in order to try and maximize your chances of seeing an effect, right? As in, if you wanna answer a question, you don't wanna just give a little of something, you wanna give a lot of it, assuming that you're not then moving into a toxic dose of that intervention. , We are essentially constrained by the ability of helicopter teams to carry volume, , a little bit by finance as well in terms of manufacture [00:14:00] of the novel products and also the logistics supply of that. , But we did quite a lot of work in, in surveying sites all across the UK as part of the build-up to the trial, trying to understand what volume of what products they currently carried. And, and essentially at that time, it's increased since, but at that time, the standard carriage of pre-hospital helicopter EMS in the UK is two of red and two of yellow. So it essentially mirrored the sort of pragmatic application of blood product resuscitation, , coupled with being acceptable to manufacturing, logistics supply, and overall trial cost. So I can't really answer that question for you, and part of the issue is what we're looking at is a massively heterogeneous group of patients, some of whom probably required no blood, but still got a bit, and some of whom required an awful lot of blood, and potentially may have not survived because what they needed was a much bigger volume blood [00:15:00] transfusion Speaker 3: And Dr. Chessi, I'm curious about your thoughts about this same question and e- especially when you also look at the transport time, , since in SWIFT it looked like the median transport time was about 83 minutes. So you're looking at that two units in the context of that 83-minute median transport time. And so Dr. Chessi, , what do you think about those together, , especially as it relates to in the US and the difference? Speaker 4: No, yeah, I think it's a very interesting, , question. If you look at it, , right here where I am in, , Jackson, Mississippi, our air care providers are very aggressive, and they do a lot of, , selective advanced restorative care. And one of the findings that we're seeing is that for these long transport time patients that are in that range of 67 minutes, , we are, we are-- we've transfused up to 10 units of blood en route. , So but not every, every EMS provider or air care have that capacity, right? , But you know, we've been blessed that we have a lot of blood, , that we can actually transfuse to the patients en route. [00:16:00] And, and I think that's the key here. I think, , our patients that we're seeing here in Jackson, Mississippi, at University Medical Center, we're getting a lot of patients that are one hour past injury, damage con- remote damage control resuscitation. And I think that just loading them up with all this volume, effective volume, , is making a difference because they're coming here alive. , And they're not just coding when they come here. They have signs of life, and we can actually work with those patients. So I think that's a very good question to put into context. And I just wanted to, , maybe just, , ask Ed on his thoughts about all the patients that were included that had TBIs, and was there any potential cardiac arrest patients included in the, in the system as, , in the research as well? Because that's something that us in New Orleans in our studies, we got rid of them. We got rid of, , the ones that were TBIs, , just because it can basically obscure the outcome a little bit. And we got rid of the [00:17:00] circulatory cardiac arrest on the field, , because those patients, 95% of them actually died, , regardless of any intervention. Speaker 2: And, and could you fill-- So it's roughly, what, 12% of deaths in SWIFT were from hemorrhage, right? Overall, is that correct? Speaker 5: Yeah, I think so, yeah Speaker 2: And then about 32% of deaths from TBI, roughly. Speaker 5: Yeah. Speaker 2: Okay. Speaker 5: Yeah. I can quickly also- Speaker 4: Can I, can I mention something quickly? I love that it's 11%, and let me, let me say that if you actually get rid of those TBIs, I mean, that, those numbers are gonna correlate side to side with most of the studies that actually we've done in the United States, , in a fast pace. Yeah. Speaker 2: Yeah. Speaker 5: Can we, , the, the... So in the appendix, sadly, so it's not often read, , there is, are further analyses of the, you know, checking the effects of the TBI patients within the model, and essentially there's no difference. I mean, we're, [00:18:00] we are drawn into the excitement of the PANTHER secondary analysis with almost all of the effects of PANTHER was in patients with TBI. , And we're hopefully about to start an early plasma TBI pre-hospital trial in the UK to answer that question. And of course, there are lots of reasons why giving s- blood product to patients with TBI, , certainly TBI plus extracranial injury, , is likely to be beneficial in terms of perfusion coagulopathy, , in, you know, for the TBI itself. So I think there's a lot of crossover limbically in patients who've, certainly UK with blood trauma, who have a traumatic brain injury but also have bleeding in the chest, abdomen, pelvis. But I think there's also quite a bit of crossover in terms of how we might think about managing them in the future, , but yet to be determined. Speaker 2: So going back to this, , idea of transport time, , and, and Dr. Duchesney, I wanna give you a moment if, if you'd be so kind. And I think it was 2024, , you published a trial in, , Journal of Trauma and Acute Care Surgery [00:19:00] called "Faster Refill in an Urban Emergency Medical Services System: A Prospective Preliminary Evaluation of a Prehospital Advanced Resuscitative Care Bundle" as presented at AAST in 2023. I think there were a few papers that spun off from this. Do you wanna summarize the kind of work, the work you did? We talked about it, prehospital two units of, of packed cells. Can you elaborate a little bit more on that and, , talk about how you designed or, or why you, you did that the way you did, and then we can bring this back to the Swift trial and the larger context? Speaker 4: Yeah, no problem, Patrick. , So this was, very exciting moments in New Orleans. , The-- We were able to, after a full year of working together and with the Department of Health as well, we were able to start a blood program where basically we put together, uh, together a activation model, and, and we did put together, , what kind of interventions were gonna be provided. So obviously, we were still doing our hemorrhage control for compressible bleeding, and we're doing wound packings, but we were adding advanced resuscitative [00:20:00] care. So in that bundle, what we were doing for the patients where basically if they met criteria, they receive, , every patient receives two units of packed red blood cells with a rapid infuser, handheld infuser, , two grams of calcium, and, two grams of TXA on the field. , And the, the interesting finding is that, , at first when we were putting this together, everybody was ha- had their doubts. "Oh, you're doing this in a very fast-paced environment where basically the transport time is eleven to twelve minutes. There's no need to give pre-hospital blood." But to the sur-- not to my surprise, but to the surprise of others, we were able to demonstrate that actually even in a very short transport time environment, these patients were coming in alive. Not only they were coming in alive, they, they actually were coming in with amazing shock index that were way lower than when we, , got the patient on the scene. So we were seeing a different brand of patients with non-compressible torso hemorrhoids that were able to be basically [00:21:00] resuscitated effectively. And on- and not only that, they were basically went to the OR, got their surgery done, and the mortality was cut by almost half when you compare it to the pre-hospital, , time, , where we didn't have any blood. So it worked out quite nice. , The blood is basically being carried in the satellite truck or, , transit truck, and whenever there's a nine one one call that there is active shooting, there is a activation that ha- has a high priority, , that truck will always-- was always there present, ne- side to side with the ambulance, the rescue ambulance EMS team. And, , if there was any evidence that the patient was in shock from hemorrhage, , basically the backpack that had all these, , advanced resuscitative care bundle was basically delivered to the scene, and basically the resuscitation started at that point. Speaker 2: Right. So it's a very different, very different study. , Again, these things get lumped together in terms of pre-hospital [00:22:00] blood. It's a very different trial. And I think it's worth talking about the logistics of, of pre-hospital blood and what are the difference in logistics, , between different centers, , urban, rural, transport time, penetrating, non-penetrating, US, UK. And Juan, when it comes to us thinking about real life and being actionable and going back to our jobs and thinking about the best ways to impart real change and improvement in care, w- what have you learned and, , from your work and informed by farther research like SWIFT and the upcoming randomized trials looking at whole blood versus component therapy when it comes to trying to design something? , And again, maybe for you specifically now in Jackson , Speaker 4: yeah, I, I mean, I think the, it, the will is not the problem, right? It's the, the barrier to basically supply our EMS with what they [00:23:00] need. And, , yes, there's an educational barrier in some institutions where basically they feel like there's no need to just basically press on the gas and get the patient to the hospital, , despite being proven that even a 12-minute transfer time, you will have a difference in outcomes. , So there's a lot of education that needs to be given. , There's a lot of, , legislation that still needs to be done, where basically we can tell these legislators, , up in the Whi- in the White House and Congress and tell them, "Listen, we, we are right now not providing equal care." And I think that that needs to be emphasized heavily. , There's a big disparity in resuscitation strategies, , across the United States when only 1.8% of our EMS ground transportation carry blood products. That means that the rest of United States are gonna be in a disadvantage. [00:24:00] So legislation and all these people that are in control of budgets, they need to realize that this is a big healthcare crisis where we can make a difference by just basically-- And when I say make a difference, we're gonna be bringing these patients back to workforce They're not gonna be basically deleted from the workforce. So it c- is going to create a financial income benefit at the long term by basically providing the best care to the patients on the field. So I, I think that in the se-- I, I-- The second part of your question is regarding packed red blood cells, whole blood, what do you do? Whatever you have, give it. I think that's the take-home message at this point. , I, I'm not a big advocate of either one. I think that either one will basically make a difference in the patient outcome at the long term. But I do believe that there will be-- there's a-- there will be a role, again, once again, for precision resuscitation. For long transport time, maybe whole blood, , might be a better action item for blunt [00:25:00] trauma, , versus just you can use either one, packed red blood cells or whole blood for penetrating trauma in short, , transport time. But I think that there's definitely a need to do more research. There's, , evidence that now plasma by itself is actually helping TBI patients. , TCCC just came up with their, , presentation regarding this, and I think that w- , we here in air care, we're gonna start moving forward to actually start using more plasma for TBIs. So, , there's definitely more to come, and I think that I love what Ed did in his analysis because, , we just need to create awareness that we cannot just start, , idolizing whole blood, whole blood, whole blood. I mean, at the end of the day, we're giving something that's an oxygen-carrying capacity, and I think that that's the main difference that we need to specify here. We want to provide that. Let it be whole blood, let it be packed red blood cells. Let's give something to the patient Speaker 3: And sort of similar question to you, Dr. Barratt. You know, in, in the UK- Yeah ... what are the [00:26:00] big challenges in that pre-hospital care setting and, and what's next? Speaker 2: Very different, right? In terms of the maturity and the, the resources- Yeah and the uniformity. Speaker 5: Yeah. So I think if I'm-- study that you showed earlier from New Orleans raises a really interesting point, which is that, you know, if we took a not well, a not well delivered EMS, , and we just gave them whole blood, the outcomes wouldn't have been any different to crystalloid. But what you do instead is you get people motivated and enthused about excellent trauma care. You give them education. They give a bundle of resuscitation care, which includes things like TXA, making sure the patient doesn't become hypocalcemic, a whole host of other interventions. And what you're essentially describing, I think there, is this package of care, this uplifted package of care. , I think one of the things that makes the UK potentially more challenging to demonstrate, , any differences between products that look quite similar is the maturity of the system. So [00:27:00] all patients in SWIFT were attended by a senior emergency medicine, intensive care medicine or anesthesia specialist, , together with a critical care paramedic who have years and years of experience in managing patients with severe trauma. , And, and that mature system's great, , but it does mean that we're now sort of Have a, have, have very little room for manoeuvre with improving outcomes, I feel. It's become much harder to get a one percent change in mortality now than it was a decade ago because we're better. , Don't forget, you've got Tower coming out, which is the US equivalent of SWIFT from Jason Sperry and his group, probably in the next month or two, which will be fascinating. We might even get to synthesize or harmonize those datasets. Speaker: News break, the TOWER study was actually published one day after we recorded this episode on May 19th, 2026. This is the largest US randomized trial of pre-hospital whole blood, and it's a natural [00:28:00] companion to the SWIFT trial. It was a pragmatic multi-center cluster randomized trial that involved 44 air medical bases in the United States. These were randomized two to one in one-month blocks to carry either two units of low-titer group O whole blood or standard blood components, which could include plasma, red cells, or both, and they were given to injured patients in hemorrhagic shock. The lopsided allocation was in fact deliberate. This allowed the authors to build a large enough whole blood arm to also run a pre-specified sub-study on whether blood storage age mattered. Now, the primary outcome was 30-day all-cause mortality. Secondary outcomes included earlier death time points, transfusion volumes, time to hemostasis, organ failure, and coagulation measures. Among the roughly 993 patients analyzed, the result was negative. 30-day mortality was 26% with whole blood versus 21% with [00:29:00] components, with an adjusted odds ratio of 1.24 that did not reach statistical significance. Secondary outcomes and adverse events were also similar, and a sub-study found old blood performed similar to fresher whole blood. Now, the main limitation is the possible introduction of type II error due to substantial crossover between the arms, as about a third of the whole blood group also received components. There also was low pre-hospital transfusion volumes overall, and the study was powered for a relatively large 10-point mortality difference, which could lead to underpowering. So the bottom line, like SWIFT, TOWER found that whole blood was not superior to component therapy for pre-hospital resuscitation in trauma patients, and this study also eased the concern that a 21-day shelf life meaningfully degrades the whole blood product. And with that, we'll get back to the discussion with Drs. Barnard and Duchesney. [00:30:00] Speaker 5: , I think for the future of blood products, you know, you mentioned plasma, Juan. I'm part of the UK Sovereign Dried Plasma Program. We're making a bunch of dried plasma across the road from me at the moment. , And I think probably the future for widespread blood products access to all these patients, particularly in rural communities, is dried plasma. So it's not really hit the US yet, but I reckon in the next five to ten years, two or three or four units of dried plasma with a shelf life of probably at least two years, you just reconstitute it, it takes a few minutes, and then give it. It's gonna be everywhere. It'll be on every EMS truck. It'll be at train stations. Fire crews will carry it. And I think that's massively exciting. , You know, it really gives access to, to lots of people. It won't be the answer for patients who are, who are actively exsanguinating to death in front of you. But for a large proportion of these trauma patients who, who need a bit of life-critical stabilization, something better than crystalloids, , they don't [00:31:00] necessarily need oxygen carriage unless they've lost a lot of blood. , I think it'll be a really interesting development, , in particularly more rural and remote, , pre-hospital trauma care. There's a massive program as well in, in sort of future blood technologies. There are people that can remove every antigen from a red blood cell, and there are other people who can grow red blood cells in a f- in a lab from stem cells. We're doing the first in-human study in, in Cambridge at the moment. So those technologies combined mean that blood product resuscitation is currently quite limited by finance, manufacturing, logistics. We might see all of that melt away within our lifetime, which is a massively exciting place to be for us and our patients. Speaker 2: Yeah. The, the absence of lyophilized plasma in the US is, is an interesting history and a frustrating problem. It's a little bit un- unclear why we don't have immediate access to that now. , But, , that is part of the future, I'm [00:32:00] sure. , So Ed, with this, what's gonna happen in the UK when it comes to, , pre-hospital units carrying whole blood versus component therapy in, on the tail end of this trial? Speaker 5: Yeah. I've not got the complete answer yet. We've got part of it. So we've obviously been working... While the SWIFT trial was still recruiting, we were working together with NHS Blood and Transplant, who are the, , suppliers of blood products in England, certainly, , as to what was gonna be rolled out following the SWIFT t-trial. We didn't know the results, so ob-we're obviously spinning up both the whole blood products, but also red cells and plasma. And our, our previous, , well, actually recently published work, Faster Forward Resuscitation: the Efficacy of Combined Blood Components, has demonstrated the obvious, which is it's much quicker and requires fewer people to use a combined product. So at the moment, we're planning, , to have access to red cells and plasma, which actually is, is the whole blood that Phil Spinella used in one of the RCTs that you'll [00:33:00] see on the meta-analyses in the history of whole blood versus component therapy. , And, and we suspect a great product. Now, there's further work to come from SWIFT. When you do these trials in the modern day, you can't just answer a question. You need to do a health economic analysis, and you need to do an implementation analysis in order to work out what's the cost to the country, the public, the patients, but also how implementable is the intervention that you have tested. The data on health economics and implementation, I can give you a little teaser and say that is gonna be really interesting. Look out for it. We hope to get it published in the next few months. My story anyway, you know, SWIFT is not an anti-whole blood study. , But we've got some interesting, really interesting news to give you in the next few months that expands on this story further. I should also say, as a, as a quick follow-on, there's a couple of studies we're involved in, which we are-- I've [00:34:00] mentioned, , HITPOS, which is Head Injury Prehospital Plasma Outcomes study. But within traumatic hemorrhage, we've just got three million pounds, about four million dollars in funding for a study called Cold First, which is giving cold stored platelets as the first resuscitation product in patients, , believed to have severe hemorrhagic shock in a prehospital setting. So we'll be looking to recruit a-about a thousand, eleven hundred patients in the next two or three years, , half of whom will receive cold stored platelets, which will be stored in the red cell bag or the RCP bag, , as in the, the blood carriage box, I should say, and half of whom won't receive those cold stored platelets. It's just another... You know, from a theoretical biological plausibility angle, there's a lot of early evidence which says that cold stored platelets might be really exciting and really exciting if you give them early. So there's plenty more work to do in this area. Whether we've got the way we do trials completely correct is a whole 'nother matter. Spoiler, we [00:35:00] haven't, , and there's still plenty of learning to do. Speaker 3: Yeah, that's, , quite a cliffhanger note and, and very exciting. And I, I do wanna point out, to me it's fascinating, like going through all the literature, that the whole concept of civilians getting any product at all- Yeah ... is only in the past 10, 15 years. So at least from my eyes, the system work that has been done, especially by you two, is in- incredible. . And I, I wanna ask both of you, i- what are the most important take-home points about pre-hospital whole, whole blood , , , that you want people to sort of get from this? And the other question is: What are the trials that are gonna be most important? Dr. Burn, you've answered the latter half of that question, but maybe Dr. Chesney, you can, you can answer. Speaker 2: A- and I would say pre-hospital blood products. Whole blood or red blood cells. Yeah. Speaker 4: Yeah, I think, , for the first question, I think there's gonna be, I mean, , I think, , everybody here in the United States is looking forward to the tower analysis outcomes. Also, I've heard a little bit about the outcomes already, but I'm not gonna, , s- say anything yet. , [00:36:00] But the-- what we know is that there is actually, there's going to be, , both use of packed red blood cells and, and whole blood. , And I can guarantee that that's, that's what's going to happen. That's the way we're gonna be moving forward. , There's gonna be more research regarding when to use, , pre-hospital blood in patients with traumatic circulatory arrest, , based on ultrasound, cardiac ultrasound. And I think that's gonna change a little bit of the, the timeline of resuscitation as well. And I think that, , overall, , we're gonna get to a point where precision resuscitation is going to happen. , We're gonna need to have large studies again to look into this, , where basically we're gonna be targeting TBIs with plasma. We're gonna be targeting, , patients' blunt trauma differently with whole blood or, , equipoise of other blood products. So everything is gonna change, I think, over time. And what I like is the fact that we are challenging the dogma, right? We are not [00:37:00] standing still saying, "Just bring the patient to us. Just use crystalloids." So we're changing that doctrine, , indoctrination time that you just need to press on the gas and get the patient to the hospital. So there's gonna be a need for bundle of care resuscitation. There's gonna be basically a need to, , some kind of a pre-hospital guideline that everybody can standardize their care in providing these, , resuscitative interventions. Speaker 5: And for me, I think my main message is, you know, whole blood is not dead. , Whether that, you know, how that looks in the future, I'm not quite sure. , You talk about, , precision, one, I mean, I can tell you now 'cause we carry a brain biomarker on the helicopter. I can tell you now whether you've got blood in your head within fifteen minutes of me testing you. That is how we should be selecting patients for these trials. The problem is we don't have that blood test for traumatic hemorrhage, and, and not many people are, are researching in this area. It really frustrates me. So we do lots of work in interventions. [00:38:00] We do not a lot of work in how to identify the right cohort, and then, and therefore, we can investigate precision interventions to then deliver precision medicine at the other end. My real, I guess, my academic, , closing point for me is that we are really bad at doing trials. We're really slow. They take forever. The cycle from idea to having something published and implemented is a long time, and our patients deserve more. So I'd really like to see a move towards more efficient platform-adaptive trial designs where we can inject different interventions at pace while investigating, probably using Bayesian, their effect on the outcomes, and then modify the intervention and/or add other interventions to answer multiple interrelated questions about trauma care in a much shorter period, probably for a lot less money. So I think we're likely to see an evolution of the way that we do these trials. I was lucky to meet in Farmington, Pennsylvania at a bespoke hemorrhage [00:39:00] trials think tank meeting a couple of weeks ago, and there's a lot of excitement, particularly around the U.S. and Europe, about how we can do this work better. So I think there's a lot to watch in the future. I think we're gonna get better at it, , , and hopefully get some really great answers to improve care for your patients. Speaker 2: Fantastic. , Unfortunately, that's all the time we have for this podcast. Maybe one of these days on Behind the Knife, we'll do some long-form Joe Rogan or Huberman-style stuff where we can talk for like four hours about this. Because we, we really, , we introduced some concepts. We didn't-- I don't necessarily know if we did those, all the, you know, those concepts true justice in terms of their nuance and complex-com-complexity. But I, I-- We want-- The idea of this is to get everyone thinking about these concepts and kinda where everything stands, and especially to start thinking about how this impacts you at your individual, , institutions. And we know that some type of blood product early is better than none, better than crystalloid. , We know there are specific challenges to getting, , that [00:40:00] product to patients in the field early, and that, , you can... There's a lot still to be improved, , on those side, especially in the US. , And then as you mentioned, the, the precision matters, that different products, , may be better for different patients, the best example being plasma for TBI, and that the future is now. Hopefully we'll hear about these-- we'll hear about these trials soon, these large trials, so there's interest in that space. And, , you know, this will continue to grow, and hopefully in the future, we can have more discussions about this. But again, we really appreciate y'all being on. , Ed and Lon, thank you very much, and congratulations on all the great work you guys are doing to help the trauma community. Until next time, dominate the day.