PAMPer Trial

Three This is the East Drama Cast Drama Cast with your moderators. Dave Morris from Intermountain Medical. Carrie Valdez from Covenant Hospital in Saginaw, Michigan. And Matt Martin from Madaganar. Center. This program brought to you by the Online Education Committee of the Eastern Association for the Surgery of Advancing science, fostering relationships.

Well welcome to another edition of the East Trauma Cast. Uh I'm very excited about the topic today. Uh this is something that has made headlines uh across the uh field of medicine. I've had a lot of questions about this topic from colleagues of mine outside of trauma surgery, uh in critical care and in other areas. So uh this should be very exciting. Uh joining me today are uh doctors Jason Sperry and Mark Yezer, uh who are uh lead author and co author of the uh

uh pre hospital plasma during air medical transport in trauma patients at risk for hamer hemorrhagic shock. Uh article published in the New England Journal in on july twenty sixth of twenty eighteen. Known as the Pamper trial. You may have seen it advertised. Um first off let me welcome uh Dr. Jason Sperry. Uh Jason's an assistant professor of surgery and critical care at the University of Pittsburgh Medical Center. Jason, thanks for joining us. Happy to be here.

And also joining us is uh Dr. Mark Yezer, who's Professor of Pathology in the Division of Transfusion Medicine at the University of uh Pittsburgh Medical Center. Mark, thanks for joining us as well. Well, thanks for inviting me. Uh I wanted to just kinda give a brief uh mention. Uh we initially heard this day to those of us uh who were at the Thor meeting. Uh Jason presented this at the Thor meeting in Norway this uh

last June and it was uh great to see the data already coming out. Uh congratulations to both of you on uh the study and getting it published in the New England Journal and uh it's really uh it's really impressive uh that this was able to be done. and and published in such a prominent location. So cong congratulations to you both.

Um if you are one of the few listeners who may have not read the paper yet, I'll just highlight real quick what the findings were. Uh this was a prospective uh randomized trial, cluster randomized uh trial.

looking at the use of pre hospital plasma in injured uh trauma patients and compared that to standard care resuscitation. Uh they were able to randomize a total of five hundred and one patients and um basically showed a mortality benefit of uh it was uh let's see mortality in the plasma group was twenty three point two percent and in the standard care group was thirty three percent.

uh for a p value of point zero three, so definitely mortality benefit and also did not show any increased risks of uh complications such as acute lung injury, multi organ failure or uh things of that. So uh if you haven't read the paper again it's in the july twenty sixth, twenty eighteen edition of the New England Journal. Uh first question, uh let me just jump right in uh Jason and just uh ask you real quick, uh is this study the nail in the coffin for saline for trauma patients?

Um well I think that's uh it depends on what's available, uh, in the pre hospital environment and uh if uh Plasma is uh available that may be a better resuscitation fluid in patients that are critically injured. Uh it may if you are less than uh severely injured, um that uh crystalloid may be just fine. If your hypotensor are in shock Um this evidence uh suggests that plasma may be um m uh significantly better than uh crystalloid uh uh types of resuscitation.

And let me just uh again for people who may not have read the paper that what's interesting and maybe I'll have you uh will you describe a little bit the difference between standard care and the uh interventional arm? Because I thought it was uh one of the key subtleties of this of this paper that was very interesting.

Um so st standard uh care arm was um it varied a little bit across the sites we had uh um six different universities with uh uh uh nine different hospitals and uh twenty seven different air bases and um Standard care consisted of crystalloid primarily in in the pre hospital uh environment, but about half our helicopter bases that were used for the trial also carried pack red blood cells.

Um, so and they all had similar uh transfusion guidelines. Uh you had to be hypotensive and at risk of bleeding and then they would get one to two units of pacquet blood cells and then crystalloid. Um Yeah, that would follow uh in patients that required resuscitation or had persistent hypotension.

Um so again the standard of care arm was uh for some helicopter bases it was packard blood cells followed by crystalloid and other helicopter bases it was just crystalloid. The interventional arm Again was uh once that patient met inclusion criteria, which was hypotension with tachycardia or just severe hypotension less than a systolic of seven. then those patients were to receive plasma first, two units.

And then they would follow their standard resuscitation guidelines. If they had pacquet blood cells and they were still hypotensive, they would receive and then blood. And if they continued to need resuscitation, then they would receive crystalline. Patients uh in the plasma arm that didn't have mm-cre blood cells, then it would go plasma and then crystalloid, depending on if the patient remained uh hypotensive and required resuscitation.

And so really this uh there was uh if I remember from the paper of something like forty percent of the standard care patients did get red blood cells and and so This is really uh fascinating because the um this isn't just a question of blood vers or blood products versus no blood products. This is specific to the benefit was specific to plasma. Am I correct in making that?

Yes. So we were able to um do some subgroup analysis. So s so a certain number of patients received pre hospital uh blood, about one hundred and seventy two out of the one of five hundred and one.

and um received uh packard blood cells in the pre hospital environment, irrespective of uh of arm. Um so about a little over a third received Packard blood cells. Um But um we were able to show in subgroup analysis that there was a signal, um, whether irrespective in those that didn't receive packly blood cells, plasma

uh was uh strongly um associated with thirty day mortality benefit and it was uh also associated with a mortality benefit. Um it didn't uh maintain its statistical significance in those with pachler blood cells. But the signal uh is uh there in both subgroups and uh at least the results of the primary analysis would suggest and that there was no um that Pacquiao blood cells uh um maybe important but the driving force in this study was the the plasma was the beneficial factor.

And so Mark, as a as a transfusion medicine specialist, what's your take on this? What what what is uh w y w ha you know, how do you interpret the the plasma benefit um or the signal that's there even in the patients that got their red blood cells? You know, I think it speaks to the uh the need to address the coagulopathy of trauma early, uh w when it occurs.

Um and there are a lot of logistical issues with getting plasma in these patients on time, issues with um recycling the plasma so you don't waste it, uh and how do you get the plasma to the bases and back? Um And and and and I think what what what what Pamper does is a really nice complement to what the group in um what Gene Moore's group did in in Denver in their um ambulance resuscitation study.

where they showed that uh basically patients who are who can get to the hospital quickly in in sixteen or seventeen minutes don't see the benefit of of of of plasma. But in our study, which was had an almost double the uh the um transit time to the hospital we showed there was a benefit. So I think uh I think addressing the coagulopathy early is important, although gene study shows it doesn't have to be immediately.

It may take some time for the acute traumatic coagulopathy to maybe set in and that's the The mechanism perhaps. Yeah, I wonder, you know, I mean if y if you look at the uh at the time difference, I wonder if if it starts at minute seventeen or eighteen, just after Jean's patients got to the hospital and sometime while while our patients were still in the air.

Because they received red cells and unlike the uh the the the Shockover data from from uh her study from Jamma that looked at military transport pictures. Getting something was better than getting nothing, which I think makes sense. But in our case, refine it a little bit more and say that that of these components, maybe plasma is the most important.

Obviously it'll be interesting to do this again with whole blood and see um i i if if we get the same findings or something different between whole blood and and plasma. Even more bang for your buck. Yeah. In the same in the same bag, exactly. Um w while you're talking about uh plasma, Mark, t tell me y I mean, in your study you guys used thawed plasma. Um Is there any uh you know, any way that it would be different if this was F F P versus liquid plasma never f uh never frozen or even uh

Freeze dried plasma. I mean Jeremy Cannon in the same issue of the uh of the uh New England Journal wrote an editorial that was commenting on this paper really in sort of ideal resuscitation and mentioned freeze dried plasma as maybe another aspect that will come out in the future. What are your thoughts about those different types of plasma products, Mark?

Uh y you know, we we we've never done and probably will never do uh a head to head study of F F P which means plasma that was frozen within eight hours of collection, F P twenty four, which is plasma frozen within twenty four hours of collection.

And then thawed plasma prepared on day one from FFP, from F twenty four, etcetera. There's so many permutations of this that that to enroll enough patients to show us any benefit is gonna take uh somebody who wins the lottery giving us all their money and that's just not gonna happen. Yeah. So uh so I think I'm still playing though, just so you know, I'm still playing the lottery, just in case. I'd love to fund it.

You know, um I think that I think that, you know, the in vitro stuff shows that that this is all basically very similar. Uh and there was a study of plasma transfusion that was actually able to break out some of the um some of the different components patients who got F F P versus F P twenty four and there was no no coagulation difference. Uh

Uh so I think the assumption that these are all basically equivalent products is reasonable. Um w with with respect to the different plasma products. Uh in terms of liquid plasma, it's just it's not really a product that's very commonly available in USA.

And it's something that that warrants study. Than than liquid plasma or frozen plasma and so it needs to be studied by itself as well. I think that the freeze dried plasma would have obvious logistical Um uh it would simplify the logistics even more, uh because it doesn't have a five day shelf life or

even a thirty day shop life or or whatever it is for for for liquid plasma. So I think there's some very attractive features to to the freeze dried um product. We just need to know if it works as well.

And uh I guess sort of on the same same vein. Um what are your thoughts about uh Prothrom and complex concentrate? Um do you think it would have a similar effect or is there something about the volume or the sort of the rheology of the fluid that you're giving? your opinion. I know it's a speculation, but what are your thoughts on that? Well yeah, I I think that's a that's an interesting question. And I think I think the beauty of plasma is is that it's got everything in there

It's got the pro and anticoagulant factors. It's got everything else that's that's flowing in the donor uh in that plasma. It's not just a couple of factors and two uh anticoagulant factors if you're using the four factors. So I think there's a lot of stuff that's in plasma that can be helpful uh in the resuscitation. I don't know what exactly that that that is.

Uh but I think that that that the coagulopathy of trauma is very complex. I think the uh the damage to the endothelium is complex. And I think assuming that a product that's got two seven nine and ten and protein C and protein S Um and that's it. I think assuming that that thing that product is gonna deal with this complex coagulopathy is is a limited view, right? I think I think uh I think that these factors do what they do and that's it. But the plasma itself provides volume, provides

other things that aren't just coagulation factors that that might be useful in reversing this coagulopathy. So, you know, uh uh I I I I think that that that's basically the the reason why we we like plasma and the mystery of using the plasma. Though PCC is thought to maybe have not just more than just coagulation factor, but may have some of the other components, then there might be some preliminary evidence that it's bene that it's beneficial.

But uh that would probably need to be tested and uh obviously it has a an expense associated with it too,'cause it's a um marketable product.

Um in your study while we're on the subject of coagulopathy, I mean um the the I guess the standard INR um for the intervention or the plasma patients was one point two and then the standard care was uh one point three. Um that did reach statistical significance d and

a as you were, you know, sort of on the ground taking care of the pa the patients, is this sort of the fact that it's only point one different, is that what are we to make of that difference? Is that just a statistical sort of artifact or i were they actually different in their coagulation when they arrived to the hospital, do you think?

If you look at the the s the subgroups, we haven't uh delved into the deeper questions of whether you know, mass mass the transfusion and the and the percentages, but there was not an extreme difference of why people died from from hemorrhage. There was not a um there was lower packlar blood cell transfusion uh um in the plasma group. Um it did not uh remain statistically significant after uh controlling for multiple comparisons, which was required by the New England Journal.

Um so it had a statistically significant P value, but when you adjusted for all the other secondary outcomes that we looked at, it didn't uh hold up to multiple comparisons. Um so there was a lower um blood transfusion volume overall and for pacroid blood cells. Um in uh in addition, those those p values are listed but they didn't they didn't hold after multiple comparisons in the paper and in the manuscript.

Um the the massive trans causes of h of death are were similar and w haven't delved into that via secondary analysis quite yet. But we'll be looking at and characterizing how whether plasma had a m more major effect than those that uh you know had coagulopathy and required larger volumes of transfusion. Um but um Th there was a strong signal in those that received less than four units of Pacra blood cells. Some of these patients didn't receive any of Pacquiao blood cells.

Um and there was a strong effect in the majority of all the subgroups when they when we analyzed them, irrespective of uh whether they received Packard Blood Cells Pre hospital, whether they had traumatic brain injury, whether they had uh um short or prolonged uh on pre hospital t transport times.

I want to talk a little bit about the uh the complications after these patients were resuscitated. There was no real difference between the group One of the things that I get thrown back at me a lot as I talk about whole blood and uh sort of aggressive use of plasma is well, we've got to worry about acute lung injury and trolley. Mark, is that a real thing? Oh absolutely. Trolley is a a bona fide transfusion reaction. Uh typically it happens when the the donor has been multiparous.

uh and uh and has made uh HLA antibodies, although antibodies to other um blood cells can can cause trolley. Um and ediconchite can be a very serious uh reaction. Patients can die from it if they're not recognized and treated uh appropriately. and quickly. But luckily the the transfusion community has recognized that trolley is a real problem and we recognize a pretty straightforward way to mitigate it, which is to make sure that our donors don't have these these HLA antibodies.

Uh and so some some blood centers will not collect transfusible plasma from women who have ever been pregnant because there's a stepwise increase in the uh incidence of uh uh of producing an HLA antibody um with increase in pregnancies. So some find it easy to just say, all right, no, no women with any pregnancies.

Some women as some centers will say, no no women can can donate just because women might not know they've been pregnant or admit they've been pregnant or forget or something. So they don't want to test for the antibodies and they just want to make a very broad uh and safe uh policy.

So I wasn't surprised that there wasn't uh any trolley in this study because um you know the incidents that that that we quote in in the tri in in the Transhusion community of trolley is about one in twelve thousand. So we didn't quite have twelve thousand patients for the night. Um and and so I wasn't surprised at all, uh, because the numbers were small.

And because the incidents are small because the products are safer. So it's definitely a real thing to worry about. Um but like I said we we've taken some important steps to to really get that risk down. Yeah, in fact I think uh the blood bankers have done such a good job and that's really the root of my question, is like I don't I don't I have not seen a true in s you know, a full blown trolley case in a really long time and so it's sort of like the uh

the princess bride bride scene with the rodents of unusual size, you know, I don't think they really exist. You know, obviously they do, but it just seems like uh we're so protected from them by the uh by the blood bank community, so um very Yeah, I think it's an important safety innovation and it and and it's led to some interesting consequences. One of them is um and we we encounter this in in Dooming Pamper as well, was we just don't have a lot of A B plasma to go around anymore.

Because it's a low incidence um blood group to begin with, three to five percent of of the donors are are A B. And then you take out the multiparous women or those with antibodies and and it really you know, really puts a a strain on the A B plasma inventory and so we've switched to using well not switched, but we've augmented our A B plasma with group A plasma. And at our center in in Pittsburgh we titer the the anti B in in the A plasma and we use a low titer.

Uh but but as we saw in a in a survey that that that Nancy Dunbar did a few years ago, um I think it was almost uh seventy nine percent, eighty percent of the centers in USA that use Group A plasma don't even tighter it. They just take the A plasma

and uh assume that that that the recipient is either going to be group O or group A, which is right about eighty five percent of the time. And if they happen to be B or A B, well they're getting resuscitated, there's all kinds of other fluid that's going in, there's all kinds of reasons why they won't humolize.

Uh and so it's really uh the the this sort of trolley pressure on us has led us to innovate and has led us to um to come up with ways around it that are safe and effective for the patients. So we started using group A plasma probably midway through the study.

Well, um based on this study then, have you guys moved to putting plasma into all of the helicopters? Uh or there are still some that are only uh red blood cells, and do you think that we have enough evidence to sort of make that push? I think I uh think we have the evidence but we don't have the appropriate product. As was alluded to earlier, uh liquid plasma versus freeze dried plasma versus thaw plasma.

W sod plasma is not the it's a very difficult situation. We had to courier it out for the study. We had to courier it every five days or when it was used on the on the helicopter base. And then uh we attempted to recycle uh most of the plasma and we tried to bring it back before it expired and allowed the blood bank to use it about fifty percent of the time. We were

um assuming all the temperature regula regulations were followed um for each of those. But um W as of right now we are not have not implemented it on our helicopters ba even based upon uh um our study. Um and we'll probably be waiting for uh the use of either liquid plasma or freeze dried plasma because the five day shelf life is is uh inhibitive, prohibitive.

Um and may be prohibitive across the country. Um unless those helicopter bases are that are actually staffed right at the hospital or right at the blood bank where they can they can get it. um uh relatively with ease with such a short shelf life. So it's uh the the result of these s this study I believe should promote the F D A approval for freeze dried plasma. Um it should be a big uh uh uh initiator of that and hopefully that will be coming in the next uh uh year or so.

And I think that's the the w one of the beauties of whole blood is that you've got a four times longer at least um shelf life. Uh you could potentially keep your whole blood for twenty one or thirty five days depending on how you collect it. Uh and it's got a dose of plasma and a dose of red cells in it. And so we know from from the the military and from our data that plasma's good for longer transport time, so a unit of whole blood ought to be uh

you know, an important fluid for for pre hospital resuscitation. I couldn't agree more. Um Um uh regarding that and that gives you a thirty day shelf life similar to what the pack red blood cells which uh more and more helicopter uh uh EMS services are carrying. Um uh across the country. Um but whole blood, cold stored would be uh um uh very be the other thing that is driven by the results of this uh study.

Just out of curiosity, you mentioned it earlier, both of you had uh touched on it. Um how what was the wastage like in this study where you were so constrained because of the thawed plasma shuffling? We we had multiple sites uh and um we attempted to retrieve that data. We got it from about eighty five eighty to eighty five percent.

Um and particularly we have the best data from the University of Pittsburgh. And I was just looking at that data mm yesterday. Um And w uh, I believe there was about a fifty percent actual use, about around seventy five to eighty percent were brought back and re re recycled and met temperature criteria.

and fifty percent of those that were brought back to the blood bank approximately were used um and given to a patient um successfully which we would consider as fully recycled Um and you can correct me if I'm wrong, Mark, regarding those numbers. Yeah, I think it was a little higher. I think it was about fifty eight percent um were were retrieved and were transfused.

But it depends on how you s how you set up your recycling, right? Like we we did the recycling um on late uh late on the fourth day or early on the fifth day. Which created a very short period of time for us to use that plasma. But if you have more couriers or you want to send them more frequently and you get the plasma back on the third day, for example, then you've got a bit longer to to actually get'em into somebody who needs it in the hospital.

So th there are ways to tweak it but they have their costs. Um you know, if you have more couriers, an unlimited number of couriers, a lottery winner funds a courier, you know, you can you can bring your plasma back uh whenever you want. But if you don't happen to have a uh a a rich benefactor, then you know, you have to decide what the cut point's gonna be. We pick the we we were biased towards leaving the plasma at the base as long as possible so we could use it.

Uh and so that's why our fifty eight percent utilization was um the way it is. Had we brought it back earlier, you know, it could have been a bit higher I think. So that's up to each center.

to uh to figure out how they're gonna do it. And there are centers that are using liquid plasma. Um I think there are relatively few. Mm University of Texas at Houston I believe was, if if not still is using liquid plasma which has similar I've got thirty, twenty eight day to thirty day shelf life and um similar to pack for blood cells and uh

Which uh it depends upon each transfusion center's uh capabilities um for uh liquid plasma, which is also relatively precious of the A light low titer B or A B variety. Mark, in terms of production, is it is it more work to make liquid plasma? And I guess the follow up question is is if we were to say make a push for liquid plasma, is that something that the blood banking community could support more hospital uh or or uh health transport.

You know, I that's a good question. A and I'm not really sure what the limitation is on on lithoplasma right now, why it's not being used uh more frequently. And and I suspect there just isn't a lot of demand for it. I suspect that if uh if a lot of noise was made about liquid plasma, uh then the blood centers would produce it. I imagine it's a very similar thing to to whole blood. Where a few years ago there wasn't really a lot of demand for it.

So there wasn't much produced, although it could have been produced. Now there's more demand and the blood centers are swinging on to this product and and and opportunity to to provide it. So I think if uh I think if if if the trauma community um wants it, then they ought to uh ought to make a point of of of asking for it. And the more the blood center hears it, the more they'll be inclined to to satisfy the customer's uh wishes with it.

So the demand will help drive the supply a little bit in this case. Yeah, I think so. You know, because I I I I I don't think that the blood centers are really aware of of um the benefits of using uh uh the liquid plasma in this setting. But if they were, if their eyes were open to it, then uh I think they'd be they'd be quite willing to to produce it.

Um one other question, as long as we're talking about sort of rolling it out in the pre hospital environment and and y Jason, you mentioned this as well. Um The the Denver group when they published that you know the pre hospital plasma didn't seem to make a huge difference but they had such short Transport times. Do either of you ever see a roll of plasma in ground?

Transport crews or is that just sort of do we have the evidence to say that that's not necessary because the transport times are short. Sure. I mean the the Denver st combat study was an excellent well run study. Um it they had shorter hospital times and they also had a higher percentage of penetrating trauma. Um and uh we had fifteen percent and they approached uh fifty percent by not looking at the article uh myself but from my remembrance of reading it and and knowing it. Um

And so th there are there are differences in our cohort. They their overall mortality was ten percent and our overall mortality uh ten to twelve percent and our overall mortality was uh thirty percent. And so the cohorts are different and they're there's two d there are two different patient cohorts and the use of plasma in those separate but in different and uh unique cohorts are are different. The res the response is different. So

just need to be careful in attributing one or the other but th the the study cohorts were totally different. When we look at time there are uh differences and w um and um They have uh w vast majority are less than twenty minutes and and pretty much the vast majority of ours are greater than twenty minutes. There's a little bit of overlap between the Um cohort.

And those with longer pre hospital times have a higher rate of mortality and those with lower pre hospital uh times have a lower rate of mortality and that can be due th that's m not be that may not be just due to time, that may be due to differences in the in the cohorts. So any comparison of whether th that study shows plasma is not beneficial or is beneficial, depending on time it's it's really specific for the uh uh the the cohort uh study.

And I and that's the best, yeah. And they're both unique. Mark, any thoughts? Yeah, that makes a lot of sense to me as well. Um but I wonder even if the um quite a lot of the trauma takes some time to develop, if trying to sort of get ahead of it early

uh might might still make some sense. And that gets back to Jason's point about the the the two cohorts being being somewhat different. It would have been interesting to see what would have happened in in our cohort if we'd had shorter times of plasma would still have had uh an effect

But again I think whole blood is is really the the ideal resuscitation fluid in this setting because the patient needs both and if he can get started with a plasma and a red cell at the same time while they're on root Then there'll be that much more ahead when they actually get to the hospital. But again, it it really does come down to the uh the types of patients that that that are become.

And we also have to be careful'cause in penetrating trauma there may be some there was no harm shown in in our penetrating uh uh percentage. It's a small group, but there wasn't a strong signal in our penetrating uh patient. And so that it may be though that it doesn't it's not causing harm, but uh it may um

you know, hypo resuscitation, uh, which is another management algorithm, may be more beneficial with short transport times and penetrating. So there may be you know, a specific subgroup of of both combat patients and pamper patients where plasma is beneficial and then there may be a smaller subgroup where you know it may not be and it it could be We're gonna try to tease those things out uh over time. Talk about personalized medicine. I mean does it get any more personalized than this? Yeah.

Yeah, that's uh one of the things that I think keeps becoming more and more clear as these studies come out is that um you know, we we tend to lump all bleeding patients kind of together into one category and there's clearly different phenotypes of exanguinating hemorrhage or different uh I'd also like to state that these all these patients weren't weren't bleeding. Um there was some bleeding and there was patients that required massive transfusion um

But um there was multi you know, polytrauma patients with both T BI and uh and moderate injury. Um And um the you know, plasma may benefit more than just from a coagulopathy standpoint. Um, it may benefit from an endothelial cell protection standpoint, which

Um, you know, we're looking into as from secondary analysis standpoint uh from samples that were obtained and measuring endothelial cell markers uh across the groups to see if we can find an underlying mechanism. But maybe why there's a significantly significant subgroup for traumatic brain injury um which demonstrated a twenty one percent mortality difference than a Right. Um, which was even greater than the the overall uh uh ten percent mortality benefit associated with uh plasma.

Um so there there may be some things that we uh we may may be able to attribute to plasma that as of yet has only been hypothesized in the basic science laboratory and uh it'd be nice to show it in

in this uh randomized trial that maybe it's protecting the endothelium and that maybe irrespective of blood loss. Now What drives the endothelium to be sick is is shock and is in hemorrhage but it may not be may be uh protective via different mechanisms other than just uh uh uh preventing further blood. You know, I at Thor this year we talked a lot about um plasma as a volume expander, which would clearly be something uh

useful to patients who are bleeding. But it's still quite controversial as to whether we should be using it just for that rule as well. So I think there's a lot we still don't know about plasma and and what it can and can do for for for trauma patients.

Well again it's a it's a monumental study and and I can only imagine the logistics it took to to to get it off the ground. In fact we we ha a fair number of our listeners are sort of uh researchers at the earlier stages of their career w what was it like to get a study like this off the ground? Um there was a large multi year process of uh this type of study which is called exception from informed consent or efic trial.

'Cause we did it to patients before the without their ability to consent and we did it in an emergency setting. Um so first uh required um uh applying for an I and D to from the FDA. And that took uh six to n six months to a year with multiple revisions and they had to approve our protocol. Then we had another six months or so of getting IRB approval and then doing community consultation.

and uh community notification, allowing patients the potential to opt out from the trial and then finally getting it executed and getting plasma on the helicopters, organizing the couriers, getting University of Pittsburgh with Doctor Yezer's help um significantly and Doctor Trelozzi, um, both from our blood banking colleagues. um getting us running at Pittsburgh and then we took it after we did that, we did the same thing at six uh uh six other sites.

Um it had to do community consultation in each of those places. And so it took approximately a little under two years at the University of Pittsburgh before we could be enrolling and then another six months uh or longer to get the sites up and running. And so it took a two and a half year up front time to get all cylinders firing and enrolling. And then we took three and a half years to enroll. Um

It was difficult to say and then executing a multi center trial is uh you know, a difficult in general. Um doing it under e exception from informed consent conditions are uh also makes it uh challenging. But but very fun to do and uh exciting and complex.

Yeah, and and kudos honestly, I as you're talking about this and reading through the methods I can just only imagine um the logistical headaches and I'm sure it it probably felt like it was never gonna happen at multiple points along the way. So Uh you know, congratulations for for having the intestinal fortitude to carry it through you and all of your co authors. I know it takes a village of people to d to do something uh as involved as this.

So strong work and thank you for all of those efforts and in uh helping advance the science.

Well I think uh that's uh sort of a nice overview. I I recommend to all the listeners if you haven't had a chance again go find the article and read through it and I'd also recommend the editorial by uh Jeremy Cannon that's in the same article as they kinda go together.

Um this is an interesting and exciting area of uh trauma surgery and resuscitation and it crosses this is kinda what I like about the Thor meeting and what I like about resuscitation is it crosses through a bunch of different disciplines trauma surgery, anesthesia, emergency medicine, blood banking I mean there's uh pre hospital, in hospital, post I mean e everything kinda comes together in this issue and it's uh very complex and uh

and interesting. So uh I want to thank both of my guests Doctor uh Jason Sperry from the University of Pittsburgh and Doctor uh Mark Yezer also from the University of Pittsburgh. Thanks for your time today in discussing this. No, it's our my pleasure. Yeah, our pleasure. That's that's for sure. We will uh put a link to the article, uh at least to the PubMed version of the article, up on the East website uh to protect copyright laws, of course.

But you can go find it there. And um hopefully we'll hear more from this uh data as you continue to uh analyze it and find other important lessons. Thank you both. Thank you, have a great day. Thanks again. Bye. And that wraps up another edition of TraumaCast brought to you by the East Online Education. You can check out all the great educational and career development resources available on the Eastworth. So if you're searching for a little bit of a little bit of a little

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