All right, well, thank you, everybody, for getting up so early in the morning in Las Vegas. Yeah, John, that doesn't count you, because you're home. All right, we're going to get going here, we're going to talk, it's a blood day, isn't it? So you guys, we're going to learn about blood all day long, and what we're going to talk about in this talk is a little bit of history, very United States-centric, and then end up with one of our favorite topics, whole blood. So I have some disclosures, none of them have anything to do with this talk. Most of what I learned about blood products is on the battlefield, honestly, and then translated back into the civilian world, back and forth. I gave my first unit a whole blood in Somalia in 1993, and as I've told several of you guys, I thought we were going to go to jail, because I thought it was illegal, and we were going to get court-martialed and all that. As it turns out, I just hadn't read history. So the first half of this whole talk is going to be about history, in case you find yourself in some God-forsaken place and worry about going to jail. You won't. I don't need to tell this group that injury is a big deal. It's the leading cause of death around the world, greater than HIV, TB, and malaria combined. And the WHO says it's by next year, actually, this is an older slide, that it was likely going to be the leading cause, the leading cause of death. So resuscitation is kind of interesting, and for those of you in the room who are a little older, like Dr. Schreiber, you've lived long enough to see pendulums swing back and forth, back and forth. So in 1864, and I'll show you this paper, whole blood was given to the United States, and up until, really, the beginning of the Vietnam War, whole blood was what was used, so for over 100 years. Then, frankly, I think we got confused with crystalloids and components for a while, and then whole blood started making a resurgence, and really spurred by this one-to-one-to-one that you guys may have heard of. And I would suggest that this year, or next year, that we'll be going back to dried plasma and whole blood, just like we did during World War II. So in 1973, this paper was published, documenting the first successful transfusion of whole blood in the United States that I can find in the literature, in June of 1864, in the Civil War, where private gross was transfused 60 milliliters from a healthy German. Dr. Bentley was the transfusionist. He was a surgeon who became the chairman and then the dean at the University of Arkansas, which coincidentally is where I went to medical school. His picture is hanging on the wall. It doesn't say he gave the first transfusion in the United States, and I certainly didn't know it when I was a medical student there at Little Rock. And then you move forward to World War I, where whole blood transfusion really started on a big scale, outside of just one-offs. Blood banks were common. Whole blood was transported in glass bottles that were refrigerated with blood banks and donor centers. And the literature from this time period talks about several really important things. We know about femur fractures. We know that laparotomy became common, but when you dive into the laparotomy literature, what it suggests is that because blood products were available, whole blood, allowed laparotomy to happen, really, on a large scale for the first time. For those of you who all like military history, and I spent 23 years in the Army, so it's something that's kind of near and dear to me, this book is absolutely fantastic, Surgeon to Soldiers, documents Colonel Pete Churchill, who escaped Boston to North Africa against the advice of his chairman, and had to deal with that when he came back, but really talks about what it means to be a surgeon on the battlefield. Now Colonel Churchill was a consultant, was able to travel around and see people, a bunch of different hospitals, not just staying in one. And what he saw was that the U.S. casualties, hundreds and hundreds of thousands of these casualties coming into hospitals with the same age men and the same injuries over and over, were not doing very well, and they were dying pale. And then right down the road a couple miles, the hospitals from the U.K., same number of casualties, same injuries, same age, and the casualties were living and they were not dying pale. And the difference was the U.K. casualties had whole blood, they had remembered the lesson of whole blood in World War I and applied it in World War II, and at the beginning of the war in this time period, the U.S. went to war, and the group of scientists that had gotten together in D.C. had decided that we didn't need whole blood, all you needed was dried plasma. So the U.S. forces went to war with dried plasma only. Dr. Churchill traveled around, saw this, and just as an aside, how many of you all have been in the military before? All right, Marty, so when you guys, when you all have written memos, right, that go up the chain, what happens to those memos? What happens to them? Circular files. Yeah, they get ignored. That hasn't changed one iota, all right? John, you might do the same thing in the civilian world, you write memos and the boss is ignored in the C-suite, right? A thousand of them. Yeah, so it's the same thing. So did Churchill accept that? He didn't. He didn't. So he found a reporter for the New York Times and told the New York Times reporter this story about the whole blood in the U.K. and the lack of whole blood in the United States hospitals and within about two months, whole blood was available in the United States hospitals based upon the report from Churchill through the reporter. It's a great example of how to use the press to the benefit of the casualties. And then he wrote this paper that was published in Annals of Surgery and presented at the American Surgical and arguably one of the most important papers to come out of World War II. It's how it's described and talks about these lessons learned and talks a lot about leaving wounds open but also about the whole blood story. So by the end of World War II, dried plasma, dried plasma and so plasma is dried in a bottle that you reconstitute it and whole blood were by far, were the normal resuscitation products to include pre-hospital in the U.S. military system. Korean War, extremely violent war, didn't receive a lot of attention but extremely violent, short-lived, rapid helicopter evacuation, whole blood again which was the transfusion resuscitation fluid of choice, forward surgery really got implemented, actually started in World War II but it got implemented really well. We all know this from the MASH TV series that people think about and there is some truth to that series. Under resuscitation, renal failure were linked and dialysis actually was developed and became widespread out of the Korean War. Now we move to Vietnam, one that the folks in this room are more familiar with, 58,000 deaths, rapid evacuation again established in Korea but also continued on and whole blood is, we started the war with whole blood just like we had at the end of World War II in Korea, started the war with whole blood and in the midst of it and I think a lot of people know this, we switched to components and crystalloid therapy. You can't find a kind of a definitive paper or a series of papers that say this is why and these are the data that support this change from whole blood to crystalloid components. At the same time that whole blood goes away, you get a rise of this thing called the denang lung. It's very interesting, right? Today we would call that ARDS, patients that survive their initial shock period, get resuscitated, go to the ICU and then develop all the complications that we're very familiar with with ARDS and multi-organ failure. It's interesting because it's a little bit of an absence of proof and clearly this is not causal, right? But there's a strong association. Hundreds of thousands of casualties are resuscitated with whole blood by the same doctors and the same injuries and the same, you know, men with the same wounds over and over again, no ARDS and then you go forward and you start getting crystalloid components and ARDS gets described by the same group of people. So it's a very interesting association, obviously not causal. We'll come back to that in a little while. People talk about the acute coagulopathy of trauma and call it different names and it's described in the UK and in San Francisco in some of the current literature, but again, much like anything else, if you go backwards and read the literature, clearly described by Simmons in Vietnam where the patients in shock have prolonged coagulation values and the ones with prolonged PT and PTT didn't do as well as the ones that didn't. Now you go kind of towards the end of the Vietnam War in 1975 and Sheldon, Lim and Blaisdell and we're going to pick up some of these papers from the real giants of resuscitation in that era and talk about the use of fresh whole blood and what they say is that, you know, for people who aren't sick, you can probably do whatever you want, give them components, you can give them crystalloid, but for the people that are really sick, you need to get your whole blood ready and see if the patients, how they do and that using fresh blood obviates the need for combining components, right, all the combining stuff and allows one transfusion unit to address the multiple needs of the patient. Really speaking to logistics and the ability and how you transfuse at the bedside, it also decreases donor exposure, right, so if you're giving a bunch of components to people, you get increased donor exposure which increase your infectious disease risk as opposed to only having one unit of whole blood which has all the good stuff in it. And then a paper that's a real favorite of mine, Carrico, Cannizzaro and Shires, 1976, Critical Care Medicines, their last kind of clinical paper, so if you're into resuscitation history, a pretty important paper to get after and speaks to this as well. Use lactated ringers, give a little bit, it's interesting, it says give lactated ringers a liter or two, the current ATLS that I taught last week says give one liter, we've come in full circle back to what, and my screen just went off up here, guys, if you can, there you go, thank you very much, and over 45 minutes, so that's a slow rate, right, a liter to two over 45 minutes in somebody in shock. See if they're a responder, non-responder, very similar, and then start giving whole blood if they're a non-responder transient and then base your further resuscitation of whole blood based on how they respond, sounds very familiar. Hypotensive resuscitation, don't pop the clot, and use whole blood resuscitation. Now this paper from Counts is a really famous blood banker at the time, but again has Carrico, Heimbach, and others, as surgeons involved with their work out of Seattle, published in Annals of Surgery in 1979, and this paper talks about, says it's unnecessary to give plasma resuscitation, and for those of us in the room who were residents just immediately after this kind of time period, this paper was used to say don't give plasma, and this paper was referenced over and over and over again, but what folks didn't realize was they were giving whole blood in this paper, and so when you give whole blood at the same time you don't need to give plasma, right, it makes sense because whole blood's got a lot of plasma in it, and then a paper I think is really interesting, Lucas and Ledgerwood, obviously Giants in Trauma Surgery, 1985, and this paper, if you go back in the ATLS manual, was referenced over and over and over for many, many iterations, 18 patients, no control group, 21 units of red cells, very little plasma, lots of crystalloid, and no platelets, and no platelets, so this paper drove massive transfusion therapy in the United States for many, many years. This paper, with all due deference to Lucas and Ledgerwood, wouldn't be published today. It's got no control group, the statistics aren't there, it just kind of says this is what we do, go and do this, because we do it, really, and I think that's kind of what happened during this era, starting in the early 70s, the switch over from whole blood to components, says this is what we do, you guys go do it, follow our lead, and then Larry Reed writes this paper, which is interesting, and I've talked about it in a small study, using modified whole blood, product no longer available, and then some post-doc exclusions of several patients, and it says, you know, don't give platelets until the patient has profound coagulopathic bleeding, is the summary of this paper. Well, today's world in transfusion, we want to keep people out of profound coagulopathy, not try to get them out, right? This kind of triage is always easier to do, keep people out of trouble rather than get them out of trouble. So the summary of the transfusion data into the 90s was 78 patients, three small studies, two-thirds without a control group, and several of them using products no longer really available at the time the paper was published, but these three papers drove transfusion therapy for 30 years. Remember, at the same time, Carrico and Shires were recommending whole blood for really sick people. So I'm going to do a little tangent here on the blood storing, I'm going to talk about crystalloid for just a second. In 1968, 1968, Moore and Shires asked for moderation in an editorial published in Anesthesia and Analgesia, their leading anesthesia journal, and says, look, we agree that we're giving too much saline. It's not meant to be a substitute for whole blood. And for those of you all who lived through the era of 20 and 30 liters of saline, it's pretty interesting that back in 1968, giving one or two, three liters of saline, the folks were causing, these guys were calling for moderation. And then you just kind of look through all this literature, all the crystalloid literature, and you can't find, I can't find a single paper that says giving more crystalloid is better for your patient than giving less. So every high-quality paper, randomized papers, less than randomized, they're still pretty good high-quality papers, giving less crystalloid is better for your patient. And as far as I can tell, we haven't found the lower limit yet when you're resuscitating patients. Kenji Inaba published a paper a couple years ago that talks about down to 500 cc's or a liter in patients in the ED. And a paper I think that Marty Schreiber gave me, the history of normal saline, there's nothing normal about normal saline. It's not normal. It has no physiologic basis. For those of you all who have done work in the cell culture, in the basic science lab, you put normal saline on cells, it kills them. So very interesting data about normal saline. Jonathan Waters did a really nice paper, Prospective and Randomized, 66 patients undergoing elective, these are open aortic aneurysms back in 2001, comparing normal saline to lactated ringers. And the normal saline increased acidosis and caused the patients to get transfused more. So a balanced electrolyte solution in these patients was better than normal saline. And of course the two papers in the New England Journal of Medicine, this is one of them last year, 15,000 patients and giving a balanced electrolyte solution ended up having less morbidity and mortality for the patients versus normal saline. So in essence, how many of you all give normal saline to your patient? You don't have to raise your hand, just answer the question yourself, you can raise your hand, but there's substantial data that says that balanced electrolyte solutions are much better for your patients than normal saline. In our system, about four years ago, we banished normal saline pre-hospital, in the ED, in the OR, in the ICU, and in the floor. It's just not available. We use plasmalite. In the old days, six or seven years ago, plasmalite was much more expensive than normal saline or lactated ringers, but now it's 90 cents a bag, it's exactly the same price. And on the bag it says you can give it with blood products. So on the bag of plasmalite it says you can give it with blood products, and the literature would suggest it improves the outcome of your patient. So back one slide, chrysolloids, bad. When people talk about what about all those inflammatory responses to blood products, right, because you have to resuscitate the patient with something. So David Meyer looked at TRALI in our system, where we've been giving a lot of blood products for a long time, transfusion-related acute lung injury, the most common fatal complication associated with blood products, and found one case out of 47,000 units transfused in our system, and that was not a trauma case. The three trauma cases out of the 15 found all got better in 24 hours. And then Bryce Robinson looked at some of our prospective and randomized data, and looked at the association, again association's not causal, of ARDS, multi-organ failure, with either blood products or chrysolloid. And the summary of this is that we described a new syndrome called CRALI, chrysolloid-related acute lung injury. The summary of the paper was that ARDS was much more strongly associated with the use of increasing amounts of chrysolloid than blood products. Remember the Vietnam War, right, where Da Nang Lung, Da Nang Lung came about when we switched from whole-blooded components and chrysolloid. Chrysolloid is used extensively in Vietnam, so I think this is kind of that pendulum swinging back again, showing the same thing. So component therapy comes in in the mid-to-early 70s, no efficacy data at all saying that it was at least as good as when we switched from whole-blooded components. Plasma was serially removed from all the components. These components were designed for extension of shelf life, not auction delivery or improved clinical outcomes. They probably work really well in patients who don't need a lot of blood products, right? The patient blood management movement, which we've been associated with at the AABB, if you're giving one or two units of blood products to people, they probably really don't need it. Well, they actually probably do pretty well, because they did need it to begin with. You can give them anything. But in the PBM world, you wouldn't transfuse those guys. This is, I think I only have two or three kind of pictures, you know, to wake you up a little bit in the morning here. This is one of my favorite slides. This is a patient I took care of in 2006. 14 new red cells, 3 of FFP, no platelets, no cryo, and 25 liters of chrysolloid. So in 2006, that was a success story, right? Guys, this is not the initial operation, obviously. It's the take-back. The bowel, this is my favorite expression here. This is your bowel on chrysolloid, kind of like that commercial, your brain on drugs, you know, sizzling in the frying pan, kind of the same thing. It was really bad for patients. 25 liters of chrysolloid. And then, kind of moving forward again to this story, you know, we started looking at this and going, well, maybe what we're doing is not right with resuscitation. And then the war starts. And we had this opportunity to see a large number of casualties coming in over and over and over again. There's nothing to do but work, eat, work out, and take care of patients over and over. And you start looking at this, and people start talking. And we started giving more balanced resuscitation in Baghdad in 2003 to 2006. And what we showed is that if you gave a more balanced resuscitation, it's the black bar on your left there, unbalanced resuscitation, the mortality was pretty high. So a more normal resuscitation at that time was 1 to 10 or 1 to 5 units of red cells to plasma. And if you gave a more balanced resuscitation approaching 1 to 1, the patients did better. Now, this is in a combat zone. There's not a lot of research nurses around. The data is a little difficult to collect. But these are U.S. casualties going all the way through their outcomes, long-term outcomes in the hospitals. And the data was pretty compelling, albeit in a combat zone. Does suffer from this problem, did they live because they got a balanced resuscitation, or did they live long enough to get a balanced resuscitation, right? At the same time, it's very interesting, and this happens in medicine and other places. And when it happens, you have to pay attention to it. Par Johansson, who's a great collaborator of ours, who works in Northern Europe, is transfusing ruptured aneurysm patients in a balanced transfusion ratio. So just like we're doing in Baghdad, unbeknownst to us, and he didn't know we were doing it either, he's doing the same thing with ruptured aneurysm patients. And the patients are doing better with a balanced resuscitation and decreasing crystalloid, publishing in 2007, the same year that we published our data. And this editorial, it's always interesting. There's no data. That's why there's a thousand authors on the editorial. But it says, give a balanced resuscitation, right? Let's do this thing called damage control resuscitation, which is, number one, stop bleeding any way you can. It doesn't matter. Do hypotensive resuscitation. Don't pop the clot. Minimize the evil, horrible crystalloid that's killing patients. Give one-to-one-to-one or whole blood. Or whole blood. Give a balanced resuscitation. Use plasma as the primary resuscitation fluid, like the guys did in World War II. If platelets are there to help stop bleeding, give platelets. Give platelets early. Don't hold on to them. Reverse hypothermia and acidosis because that messes up your coagulation proteins. And oh, by the way, stop bleeding again. Starts and stops with stop bleeding, right? Any way you can. Any way you can. Damage control resuscitation. If you kind of move forward a decade, a lot of work by a lot of people, to include some of those in the room. All kind of saying, hey, you know, this seems to be working. Let's put higher quality, bigger data sets, multi-center. Get away from the retrospective data. Do prospective observational and end up doing prospective randomized. Prospective randomized study published in JAMA several years ago now. And what we did is compared 1 to 1 to 1 to 1 to 1 to 2, and as I kind of move through this pretty quickly, there is no difference in the 24-hour and 30-day co-primary endpoints as prescribed by the FDA. But what we did see was a statistically significant decrease in exsanguination at 24 hours in the 1 to 1 to 1 group. So a therapy that was intended to help decrease bleeding and improve early survival showed that in the data. You can see these Kaplan-Meyers. They separated three hours, which is around the time to hemorrhagic death, and then are parallel on out to 30 days. You can't read this slide. This is the complication data. There was a lot of concern by the FDA and folks that by giving increased plasma and increased platelets, twice the amount of plasma and platelets in the 1 to 1 group, that we would increase ARDS and multi-organ failure, have all these inflammatory complications. And so we were very careful about collecting pre-specified complication data, especially inflammation data. And there was no difference between the groups at all. So if you move away from the randomized data, this is now retrospective data collected at our center. And this is the grade 4 and 5 liver injuries. Grade 4 and 5 liver injuries are really bad. They're infrequent. But it's not the grade 1, 2s, and 3s that kind of go home in a day or two. These are the grade 4s and 5s. You guys all know what this looks like. You get that CAT scan and the ED, and everybody kind of goes, whoa, that looks pretty bad. And the literature would suggest a lot of these people have significant and substantial complications. And so one of our fellows put this together and looked at 1,400 blunt liver injuries over five or six years, 244 grade 4 and 5. And by changing our resuscitation regimen, that's the heavy, dark line there is when we change resuscitation regimen, we decrease crystalloid and blood product use, we increase successful non-operative management, and improve survival in these patients substantially. There's no new surgery. There's no new IR person. There's no new magical treatment. Just changed our resuscitation regimen. So a retrospective series of organ-specific data. And then I just put this slide up just to kind of compare and contrast to that one from 2006. This is 2014, a much more balanced resuscitation. In 24 hours, two liters of plasma light. And you can see the bowel over there in the corner. It's not swollen. And the guy gets home day 10, all wounds closed, fascia's closed, everything's closed up after a pretty substantial injury. Now, why does this happen? Why does this happen? I think I have one or two basic science slides here. We think it's, and this is Dr. Patti's paper from the Journal of Trauma in 2010. And if you can see that little cartoon, the top left in your screen there is kind of normal arterial lect and lymphatics. And what happens is you have the glycocalyx that's lying in all of your endothelial cells. When you go into shock, right? If I shoot Dr. Schreiber right here and he falls down, and if I shoot him in the abdomen, goes into shock, every endothelial cell in his body sheds the glycocalyx. That's a mechanotransducer. Causes every endothelial cell to contract. And so you get paracellular permeability. So for eons, fluid went from the extravascular to the intravascular space and auto-resuscitates, right? But we've showed up in the last 100 years or so and put an IV in and get blood products, and then we got confused and get a crystalloid. And the crystalloid actually propagates that loss of the glycocalyx and keeps those endothelial cells contracted. But if you resuscitate with plasma or blood products, it repairs the endothelium. It helps restore the glycocalyx. The endothelial cells uncontract, that's a word. The paracellular permeability goes away and the blood products, the volume that you give to the patient stays intravascular rather than going extravascular and causing all the edema like we saw in the bowel on crystalloid earlier. So we looked at it through a microscopy and showed exactly that with this paper published by Rosemary Kosar a number of years ago. So we think that's what's going on here, right? It's kind of a mechanism. I would say that's not been completely proven, but there's been a substantial amount of data since that kind of suggests that that's what's going on. In 2016, the NICE group out of the UK said, okay, if you're injured, you need to get a one-to-one resuscitation. You know, it's interesting in the UK, they're much more relaxed and laid back than we are, but when they make a guideline, it's kind of a rule. It's not a suggestion, it's a rule. And so they really have switched over and made this their standard of care. Jeremy Cannon published in 17 that one-to-one is kind of out of the EAST guideline group, which does a lot of the guidelines for the trauma community, and says that we should give a balanced resuscitation regimen. So that's become fairly standard now around the country, and we're gonna get to this in just a minute, because a lot of you may be thinking, yeah, but it's really hard to do, right? It's kind of hard to do, get everything all together to do this one-to-one-to-one. Talking about time for just a second, Jason Sperry published what I think is probably one of the most important trauma papers ever in the New England Journal, this, a little over nine months ago now, and talks about pre-hospital, pre-hospital plasma versus crystalloid therapy, and the group that got the pre-hospital blood products plasma especially did a lot better at 30 days, significantly better than the group that didn't. So resuscitation today is largely balanced, balanced therapy, starting in a lot of places pre-hospital has become a standard, but it's hard to do. I can't do one-to-one-to-one is what you hear over and over and over again, and hopefully we can kind of get to this throughout some of the talks today, but it's really kind of interesting. Platelets can be stored cold and immediately deliverable in whole blood, but platelets only last three or four days on the shelf, four days on the shelf after the 24 hours of testing, but in whole blood, platelets will last anywhere from 21 to 25 days. Plasma, if you store it in your blood bank, is stored frozen, FFP, you have to thaw it. You can have thawed plasma that's good for five days, and you can have never frozen plasma that's good for up to 21, 25 days, but if you store it up to 35 days, if you store it in whole blood, if you think of whole blood as a way to store these products, and of course cryo, cryoprecipitate, pretty important to have fibrinogen. Every picture of a clot has this fibrinogen cross-links, right, the fibrinogen, but we don't often give it. There's some papers coming out that suggest it's probably pretty important, and cryo obviously is in the whole blood as well, but if you order it from the blood bank, they have to thaw it and mix it up in a bunch of little bags, and it's kind of painful to give to patients, so it's easier to store whole blood than all these components. Because of these storage issues, really just the logistics of blood bank supply, any blood bankers in the room? Any blood bankers in the room? So we've worked really closely with our blood bank colleagues on this, and it's pretty clear that storing whole blood is easier than storing all these different components, right, it's just easier to do, and the products, if you think about them, are easier to give. These blood banks, just like the ones in small remote surgery places in Afghanistan, Iraq, and Syria, and every place else that our U.S. forces these, there's lots of little blood banks like this, and I come from Houston, Texas. You don't have to get very far away from the 900-bed level one trauma center to get to 300-bed hospitals in Houston that don't have thawed plasma, they don't have liquid plasma, they don't have cryoprecipitate, and they don't have platelets, and they're on major highways. I tell everybody to drive very carefully when they're going past those hospitals, right? So it's pretty common, but blood bank colleagues suggest that about a third, and some even say a half, of the 5,000 hospitals in the United States can't give one-to-one-to-one immediately upon arrival. Pretty sobering thought. The other thing that's true is that in the transfusion world, massive transfusions, and if we're talking not for cancer for a minute, a lot of the massive transfusions given are to GI bleeders, right? To maternal-fetal bleeding, ectopic bleeding, non-trauma, I mean, we're all thinking about trauma here, but when I do emergency general surgery call, I take care of a lot of non-trauma bleeding people, and those same hospitals can't do that either. They can't give a balanced resuscitation right off the bat. Published a paper a couple years ago, there's a little bit of a tangent as well, thinking all this dried plasma stuff is interesting. It was available in World War II. It went away, not because of efficacy, but because a third of the survivors of dried plasma got hepatitis. Now, in the ensuing 60, 80 years, we learned a lot about hepatitis. It's actually very safe now. Nothing is 100%, but it's really, really safe, and we're relearning the efficacy part of the dried plasma, and there's dried platelets available, there's gonna be dried cryo available very soon, and people working on dried red cells. So dried products available at the point of need without the blood bank are coming rapidly down the pike. It's actually gonna be a very interesting decade for blood products. As I've suggested, and you guys can kinda see where we're going, whole blood is obviously the ultimate balanced resuscitation fluid. How many of y'all have given whole blood before? How many of y'all have transfused whole blood? All right, very good. So it'll be interesting, I think, as you guys have these meetings over the years to ask that question. How many of y'all have tourniquets and use tourniquets? So a decade ago, one person would have raised their hand. I think whole blood's gonna be the same thing. It's gonna happen pretty quickly, actually. So as I said, Bob Mabry published his paper in 2000, documenting our experience in Somalia 26 years ago, giving a lot of whole blood to casualties, and I thought we were gonna go to jail, and we were making this stuff up, and it turns out I just hadn't read the literature. This is a slide from a buddy of mine, Andy Fisher, that I borrowed, and when we came back from Somalia, he made the mistake of talking about whole blood like it was magic, and those were my words when I went and talked to blood bankers, and they didn't really, they thought I was some young, crazy surgeon who was making stuff up, but it's pretty interesting to give fresh, whole blood, fresh, whole blood on the battlefield and kind of watch the physiology of the patient improve and the coagulopathy go away. Now, the product that we're talking about in the United States, and Marty makes, Dr. Schreiber makes this point, it's not fresh, whole blood, right? It's whole blood that's been stored, tested, and in some cases, leukoreduced, which impairs platelet function, so it's a little bit different than the blood product on the battlefield, and when you read all of these papers about blood products, it's important to go to the methods section and understand exactly what product they're talking about because it changes. So this slide doesn't project really well, but what it's getting at is that if you take a unit of whole blood and then test it, it comes out to have a good hemoglobin, a good platelet count, and good coagulation function, as you might imagine, and if you take, this is John Hess's slide from a number of years ago, a blood bank colleague. If you take components and test and then put them together in a beaker, right? So if you're trying to do one-to-one-to-one and test the components with no dilution of any clear fluid at all, you come up with an anemic thrombocytopenic and coagulopathic fluid, right? So the best you can do when you do one-to-one-to-one is really a substandard from a testing point of view, hemostatic potential compared to whole blood. Other papers have been published showed exactly the same thing, and that's without diluting any of that with a single drop of clear fluid. So over 10,000 units of whole blood have been transfused on the battlefield, great experience, multiple papers documenting the outcome of the patients. The TC3 Committee, which really kind of sets the guidelines, it's kind of like the East for pre-hospital care. TC3 sets the guidelines for pre-hospital care, not only in the United States, but in most Western countries and many non-Western countries around the world. Whole blood is the preferred, is the recommended number one fluid for resuscitation, and the U.S. military is pushing whole blood as far forward as possible. Medics are carrying whole blood in their rucks in Afghanistan and Iraq and all the other places around the world. Everything else is second to that, and as you can see, the clear fluids are at distance sixth and seventh, way down there. Talked about Jason Sperry's paper where time is really critical. Minutes really do count. You know, we talk about minutes and seconds. It really does count here. This paper from the Brian Easter's group is extremely important, and what it talks about is that people are dying pre-hospital. They're dying pre-hospital. This slide shows that the peak time to hemorrhagic death, not TBI, but hemorrhagic death is within 30 minutes of injury, irrespective of mechanism, but the median time to get to the hospital in most centers by ground is 30 to 40 minutes, and by air, 78 minutes. If you think about that, our trauma systems are delivering people to hospital well after the median time of hemorrhagic death, and so that kind of speaks to Jason Sperry's paper. We need to push interventions pre-hospital to decrease truncal hemorrhagic death. We've measured time several different ways. We moved blood products from the blood bank into the ED. Exactly the same products. Nothing else changed, and by doing that, improved survival in our patients. Associations, not causality, and then David Meyer looked at some of our prospective randomized data in a secondary analysis, and we had it measured to the minute because we have people standing, you know, with clipboards and stopwatches. We were measuring what was going on, and every minute of blood product delay to the bedside increased the time to hemostasis and odds of mortality. So every minute of delay. It's pretty interesting. And then Stacey Shackelford published two years ago a very similar study to what Jason Sperry did in the New England Journal paper in the civilian world, but this is pre-hospital in the military experience, and showed exactly the same thing, is that pre-hospital blood products given within 15 minutes of injury improved survival. So timed intervention is a PI tool. Timed to blood product infusion is a PI tool I think would be very interesting because all of this data says the faster you get blood products into your patient, the better off they'll do. Whole blood shows up over and over and over again. Every single time you get into a conflict, whole blood shows up, and it's showing up in the civilian world now. We've talked about shelf life for just a second. Red cells, plasma, platelets, cryo, all have very different shelf lives, but if you put them all together, actually if you never take them apart and store whole blood, you have a shelf life of 25 to 35 days depending on the preservative that you, and anticoagulant that you draw the whole blood into. Garastranis has been pushing this pretty hard for the last five or six years, proposing Lotireol as a universal blood product in the civilian sector. Brian Cotton published a paper in 2013. It was the only prospective randomized whole blood study done so far, but many more are coming. This is a pilot study, really, just to see if it was feasible, and it is feasible to do these studies. This is a paper looking at that blood product composition, whole blood versus components, and then measuring lab values that I talked about earlier. Fresh whole blood has a superior hemostatic potential as measured by any laboratory test that you can imagine versus combining products. If you're gonna read one whole blood paper, this is probably the one to read. I think you guys all have these references, and it just goes through all of the history, a lot of things we've talked about and more with whole blood. Administrative errors, right? People are very concerned about administrative errors with blood products. 40% of the folks in this room are O positive, O positive, so if you use O positive as your universal blood product donor, you're gonna be type specific with just by closing your eyes and giving it to 40% of the recipients. Just that fact will decrease administrative errors substantially. So as we kind of close here, low titer O whole blood is what a lot of folks are using around the country now as their universal donor product, O positive, low titer O positive whole blood. This is not something crazy that you're gonna go to jail for like I thought I was gonna do in Somalia. It's an approved product. It's being published in the transfusion literature, emergency medicine, surgery and everywhere and it's coming down the pike pretty quickly. We'll talk about this in one of the sessions later on about using O positive whole blood for RH negative women and who are potentially pregnant or are pregnant. This is a paper devoted just to that subject and it speaks to the rates and the complications of alloimmunization. We'll talk about that in greater detail later. So this is a slide I used to give. I used to show that we got rid of all that crystalloid and that we use platelets and red cells and plasma as our primary resuscitation fluid. This is in the emergency department. Now I gotta X that out and this is now what we have is whole blood. Now we also still have the product still but we have whole blood pre-hospital and whole blood in the emergency department. I like this little slide. How many of y'all actually transfuse blood products or have transfused blood products at the bedside? Actually hang, Dutchess, you're not hanging products. No, you're not. So this is a real massive transfusion, right? You can see the highly organized paperwork there on the floor. The nurse is trying to keep track of is it red gold and where's the cryo and where's the platelets and is my ratio correct? All that stuff that's really hard that happens at two o'clock in the morning. And you can say, well, you know, rather than trying to keep, and then you put it into the Belmont big bucket that thing over there on the left and then what you're really trying to do is just reconstitute and make whole blood, right? So why not just give instead of six and one and one, red cells, plasma, platelets and cryo, why not just give four or five units of whole blood, right? Just four, it'd be all the same products. You have better hemostatic potential, less paperwork. I tell you, our blood bank technicians and nurses love whole blood. They love it, right? It's better and safer to do for the patients, fewer administrative errors. And it's, by the way, from a value point of view, it's cheaper than if you take, you know, John, if you go donate whole blood and they break it in the components and then your nurse, I can't remember your name, tries to give it back together again, right? It's cheaper if we just take the whole blood you donate and give the patient, right? It's cheaper. So this is not something that's crazy. This is being done now. There's actually 24 centers. I just need to update my slide. Donor centers are making it. There's no regulatory impediment. And you kind of go, well, what about your hospital? Why not do this? So it's simple. It's become, blood product transfusion becomes much more simple, actually. Most patients don't need blood product resuscitation. 90%, 90, 95% of patients coming in do not need, you can give them anything. Give them CT contrast, whatever you want. Give those patients normal saline because they'll do just fine. But the ones who do need resuscitation need blood product resuscitation. And then what we do is give whole blood and then when bleeding slows down and stops, then we switch over to components guided by lab values. How much do you need? We have two pre-hospital, four in the ED and the blood bank has 10 units. And that covers 99% of massive transfusions. If you run out of whole blood, we switch to components. So what kind? We use low titer, O positive, non-leukocyte reduced, and we can get into those questions later. So this idea of dried plasma, there's several companies making dried plasma going through the FDA. Dried plasma is easier to use than whole blood. Stored at room temperature for up to two years, reconstituted, I think we're gonna, that pendulum's gonna go right back to where we were at the end of World War II. And then components aren't gonna go either. They're gonna be used for hematopoietic stable patients that need repair of one aspect of their system, right? One aspect of their system. So whole blood's the ultimate balance resuscitation fluid. There's lots of military data. There are civilian observational studies being published and submitted to meetings right now. There are no randomized studies of whole blood other than Dr. Cotton's pilot trial from a number of years ago. There's one ongoing in Pittsburgh, single center pre-hospital and hospital whole blood pilot study funded by the NIH. And there are multiple proposals being written as we speak to do multi-center whole blood studies, kind of replicating what was done with the component therapy from a couple years ago. The Don Jenkins and I kind of put this little editorial together. When you write editorials, you gotta have a snappy title, right? So get ready, whole blood is back and it's good for patients. And it kind of speaks to some of these issues. I've talked a lot of the benefits, but change is difficult, right? It took us 18 months to change the computer system so that the computer will allow us to use whole blood because whole blood wasn't on the pick thingy on the computer, right? It wasn't an option. So before we could do it, we had to have the computer change. We'll talk about the titers. Are we gonna give O positive only? Are we gonna have O negative? Which is really difficult for the blood bank colleagues to have lots of O negative. How long are we gonna store it? And how do you recycle it from pre-hospital and the hospital after so many days? So lots of questions, but this movement is happening and I think it's gonna be good for our patients. Thank you very much. Thank you.

whole blood

balanced resuscitation fluid

trauma patients

hemostatic potential

military

improving outcomes

pre-hospital administration

logistical challenges