Vasopressin in Hemorrhage Resuscitation

Three This is the East Drama Cast. With your moderators. Jacksonville. Dave Morris from Intermountain Medical Center in Salt Lake City, Utah. Carrie Valdez from Spectrum Health in Grand Rapids, Michigan. You by the Online Education Committee of the Eastern Association for the Surgery of Trauma. Advancing Science.

Well, hello and welcome to this edition of the Trauma Cast. In trauma, there is a lot of dogma or inherited wisdom. One of the absolutes in trauma resuscitation is the strict avoidance of vasoactive medications in the resuscitation of hemorrhage. This dictum was backed up by several clinical studies over the past few decades, but there have been several animal studies that seem to contradict the clinical outcome.

in August of twenty nineteen, and the edition of the uh JAMA Surgery, my guest today, Doctor Carrie Sims, was uh coordinator and lead author of a study titled Uh effect of low dose supplementation of arginine basopressin on need for blood product transfusion in patients with trauma and hemorrhagic shock. uh this uh study uh cause caused quite a stir on the uh social media world and I am fortunate enough today to have Dr. Carrie Sims with me today. Carrie, welcome to the podcast. Thank you.

And um for those who may not be uh uh acquainted with you, would you mind just giving us a short introduction of yourself and where you're at, where you're headed and all those kinds of things? Sure. So I'm uh Carrie Sims, I'm one of the trauma critical care attendees at the University of Pennsylvania.

Uh and I'm the research director for the Panacute Research Collaboration, which uh helped us with the study. Um I'm actually heading towards uh Columbus to be the chief of trauma at the Ohio State University starting in January. Um and thank you, Dave, for the opportunity to talk about our study. Yeah. And I think for full transparency I have to um

mention the fact that Carrie kind of brought me into my uh research maturity, I would say. She kinda dragged me kicking and screaming against my better efforts. And so I I owe her a a a career debt uh for for helping me to get to where I am at today. So thank you, Carrie. Yeah, I think I...

Um oh well let's dive right in. So um Again, as I said, this uh this paper did cause uh a little bit of a stir. It got quite a bit of uh mention on social media, there was a lot of people kind of debating. Um I have been approached by my own um emergency medicine colleagues who are watching this uh with uh a lot of interest.

And um uh and so I think there's a lot of interest in this topic out there. So would you mind just tell me um tell me a little bit of the background and sort of the lead up? How did you come up with the idea for the study and what was really the the the basis for for trying to get this study done? So the uh the study um really was um born out of a um ob observation when I was a fellow.

So um I was a fellow at the University of Pennsylvania just like you were back in the day and um I admitted a patient uh to the ICU who had A major liver trauma. He had been a motorcycle crash. Um had gone to the operating room with an X Lab, was very unstable, um large volume of suscitation. uh came to the ICU and just wasn't doing well and uh you know was on pressers, we were transfusing, uh he just, you know, was not going in the correct direction. We actually brought him back down to

interventional radiology to make sure that he wasn't bleeding. He didn't appear to be bleeding. Came back from uh that to the ICU and and continued to be very unstable. And uh we had just had a journal club probably a couple of weeks before about uh vasopressin and uh vasopressin deficiency in septic shock.

And I sort of wondered whether or not this was early sepsis. Was there somehow some bacterial overload, something that happened? Maybe he was really vasoplegic from being vasopressin deficient because he was in early sepsis or in profound in inflammatory state. So I put in a swan back in the day when we actually used swan catheters, and he was in fact profoundly vasoplegic. So I thought, oh, I'll just put it on some vasopressin and

See what happens. And lo and behold, we put on vasopressin, the pressor the the blood pressure improved substantially. I was able to wean down the norepinephrine and epinephrine. he started to make urine. He really looked fantastic by the time we rounded the next morning. And I was so as as all fellows out there will know, uh after you've taken care of a really sick patient overnight, I was so proud of myself for having like

turned the chip around that I was really feeling in the world. Yeah. Yeah. Like I was really like very, you know, very proud of myself that I was really coming into my own as a as a critical care provider and Um, let me tell you that my attending was not happy. Uh and so um, you know, um basically read me the Riot Act about how vasopressors are should not be used in trauma, despite the fact the patient had been on vasopressors, you know, when I received him.

um that I should have just been using fluid and and blood products to resuscitate him. And he made a very public show of how I was wrong. Um and for anybody who knows me, um, that just does not fly with my personality at all. Um and so I set out to show him that that that he that he was wrong. Um and so I, you know, did a lit search uh and found that there really wasn't very much out there in terms of vasoplegia in hemorrhagic shock.

There was a couple of animal studies looking at the Brattleboro rat, which is an animal that doesn't make vasopressin but has vasopressin receptors. uh and how hemorrhagic shock in that animal model uh was, you know, profoundly lethal. Um, despite uh, you know,

other animals uh you know not dying as quickly. Um and and there really wasn't a lot out there. There was one study out there by Lan Landry, who was the author of the Vasopressin Deficiency in Septic Shock, in which they looked at two patients um as well as uh an animal model of ten uh dogs and looked at vasoplasia and vasopressin deficiency and that was really the basis

for um uh the d the idea that the notion that vasopressin deficiency exists in hemorrhagic shock. So then I um You know, it's it wasn't clearly was not uh demonstrated in humans at this point. So I then did a study in which, as a young faculty member, I looked at blood samples in patients who were undergoing massive transfusion. And I took a blood sample on arrival, and then after every fifth unit of blood product,

um throughout the course of the resuscitation. And so you know patients who got, you know, 20 plus volumes or 20 plus units of blood product. Um, if you look at their vasopressin levels, they actually start off very high in our trauma bay, primarily because our transport time for our patient population is very uh short. Um, but with the uh active uh resuscitation and blood loss and and massive exsanguination, massive resuscitation.

those vasopressin levels are cut in half by the fifth unit of blood product. So it really did look like, just like Landry's dog study, that our our patients were exhibiting um vasopression deficiency, are losing vasopressin levels. um with active resuscitation. Um So that was sort of the the um the impetus um for suggesting that vasopressin deficiency existed in humans.

Um we then went to the lab where we uh investigated the use of vasopressin in an uh a rat model and were able to show that giving vasopressin with resuscitation improved uh renal So with all of this information about the human data and the um animal data Uh we went to the uh FDA and the uh and got permission to do an exception from inform consent trial uh to look at giving patients vasopressin early during the course of the resuscitation.

Um while we were getting that set up, there was an another study with um uh Doctor Cohen did looking at uh vasopressin in uh trauma patients. Their protocol was slightly different than ours, but what it did show was that it was safe to give and that it did decrease the amount of uh crystalloid resuscitation that patients required if you give it early.

So with that um we were able to then conduct our trial uh at So um I you've you've done a um a great job summarizing some of this stuff, but when you go now it's interesting when you go and search uh lit search for vasopressin in in trauma, what you find or in shock, what you find is kind of mixed

you find um clinical studies from, you know, fifteen, twenty years ago that kind of say uniformly bad, but there's a lot of uh animal studies, as you mentioned, that really kind of support it. What's interesting I thought from some of the clinical studies um is that um

Norepinephrine and epinephrine, phenyphrine were kind of unifor uniformly um unhelpful for patients, but there seemed to be this sweet spot where vasopressin didn't have the same effect. I'm thinking specifically of uh study by Jason Sperry and I think uh senior author was Gene Moore that had that, you know, basopressin did not show the same

deleterious effect is uh norepinephrine and epinephrine. Right. I yeah, exactly. And I I think that that you mean to mention that those studies, both of those trials uh that you mentioned, were actually retrospective reviews. Um so retrospective clinical trials uh as opposed to prospective trials. So I think that it it sort of calls into question which patients were getting vasopressin in the beginning. Was it uh that there was somehow

that those patients were sicker, that it was given late in the game. It's not really clear. So I think that our study um really helps define the role of where vasopressin might be helpful and does show that it actually is beneficial.

Well so um let's get into the methods a little bit. I think um I uh there's uh there's a lot of interest in the idea of the exception from informed consent or ethics studies, uh sp particularly in trauma.

Can you talk a little bit about the challenges that you faced? I um having you know practiced myself for a little while in Philadelphia, I know that there's not always the best relationship between uh healthcare and the community and so uh I think it's probably particularly challenging to do an ethics study in this in this part of the world. Can you talk a little bit about what how you how you accomplished this and what you did to kind of build the bridges to the community?

So in order to really advance uh the care of the injured patient, uh exception from informed consent trials are absolutely essential. There is no way that we're gonna be able to really advance care and improve care if we don't do these kind of trials. And the FDA has recognized that as well. Um, so in order to do uh an exception from informed consent trial, you really need to fulfill multiple criteria. This the trial itself. It has to be based on

very good preclinical or clinical data. There has to be equipoise. Um, there has to be um benefit to the potential patients themselves. There has to be no real alternative or really poor alternatives to the uh proposed therapy. Um and then the one that everyone really remembers is this the concept of um Community consultation. So as as you mentioned, you know, communities uh um particularly patients who are um at risk for urban violence are also uh communities that have been in the past

um sort of taken advantage of in terms of research. Uh you know, if you think about Tuskegee and also some of the the trials for that have been conducted at Penn in terms of um dermatology and uh skin issues. You know, there there's a history of not treating underserved populations. very uh well. Uh and so it was really important for us that if we were gonna do this exception from ins informed consent trial that we actually had buy in from the community.

Um we think that it was uh we thought that the the trial would be beneficial to the patients and it met all of the strict criteria for the FDA, including uh a very limited uh time uh to enroll. Um, but you know, whether it's correct on paper or it's correct in the community, you're absolutely right. There's a you know, that's a very big important difference.

So in order to do this trial, we actually did two things. Exception from informed consent requires that you consult the community that will be impacted by the research. And traditionally that's been thought of as a geographic community, so the people around the um the uh place that you're gonna be doing the study. Um That may or may not actually capture our our patient population. So what we thought would be better would be to actually interview patients and their families who had experienced

Trauma. Um and do A qualitative study about what their thoughts were about exception from informed consent in general, but also our study in particular. And what we found was that there was an overwhelming support for the trial.

We also then went out to the community at large and held the focus groups um which ranged from um you know community uh centers um the mayor's groups uh the block uh uh neighborhood block groups um a mosque, a a church, uh and try to get a whole spectrum of people in the community who might have an interest.

in uh this type of research. Um and again, what we found was that there was an overwhelming uh response that this was an important study to be done in this community because they were so impacted by gun violence and so many of them were dying that the community really felt that if there was a way to save their lives that we should be doing the study. And and then they gave us great suggestions on how to get it done. It was really remarkable actually. Well and um

You know, obviously this sounds like a very involved thing. I think you were working on this lead up to the study even when I was there as a fellow, which was uh I you know, a year or two before you actually started enrolling. So the the amount of work it it it takes is just tremendous, which explains why It's so hard to do. But uh congratulations on getting all that done and it sounds like it was

Um sounds like it was very beneficial for uh for both the study and for the for the community. So that's that's fantastic.

Yeah, you're you're not kidding. When it when you think about the time from the time of conception of the concept uh to the actual publication of the paper, it was over ten years. Yeah. Well let's uh let's dive into the nitty gritty of the study then. Uh why don't you tell me a little bit about um kind of how you designed it, what the protocol was and kind of how you um you know what the what the intervention group and the comparator group w were defined and and and how that went about.

So uh based on our our finding, our previous finding that uh patients who receive more than five units of blood product start to develop vasopressin deficiency. We uh included uh patients who were in exsanguinatine hemorrhage who received six units of blood product. So then we would know uh that that they were in fact uh potentially at risk for vasopressin. Um, so folks would come in uh and they would be blindly randomized to either receiving

um the the vasopressin as a bolus followed by an infusion or a saline placebo. There were a number of exclusion criteria. just because of safety issues. So for example, patients who were already in renal failure or who had um evidence of coronary artery disease were excluded. Patients over the age of 65 were excluded for the risk of coronary artery disease. Um and then, you know, the this typical players, the pregnant patients and the those who were prisoners uh for

uh ethical reasons um were excluded. We also excluded patients who had um CPR in the field because of their low likelihood of survival, as well as patients who received an ED thorocotomy because of the low chance that they would survive as well, with only a h uh with the goal of an

enrolling a hundred patients to see a decrease in blood product uh transfusion, if we included a lot of people who were going to die, um, we would we would not be able to see any difference. Yeah, so we were very specific about our inclusion and exclusion criteria. based on um a power analysis to look at uh a decrease in blood product transfusion.

Um so patients would come in. We had uh this took a lot of effort. We had a people who uh were uh researchers who would come down to every trauma and and they would evaluate how much uh blood products they were getting and as soon as the uh um six unit of blood product uh wasn't given, uh they immediately enrolled the patient. So it took coordination between the researchers, um, the trauma team, anesthesia, um, and all of those uh

um communications and uh bridges needed to be built before the study could actually be implemented. Because you can imagine at a teaching university if you show up to the uh operating room and say this guy is enrolled in study and you need to give them this medication, people will be like, what are you insane? Uh and so you know we needed to get buy-in from all uh the nurses, from the trauma team, from the medicine emergency medicine team.

like everyone needed to be on board with actually doing this trial and then we needed people to be there uh watching uh in real time so that the the drug could be given. There were some uh caveats as well, like we had originally planned for the vasopressum to be

stored in pharmacy and then, you know, after a couple of enrollments realized that that was the delay there was too much of a delay in getting the medication. So we then got a, you know, r uh a research refrigerator in the trauma bay and so we're able to make up the medication uh or the or the placebo uh in in real time and not have to depend on promise you to bring it down to us. So that was actually another little hurdle that we got over.

Um it really was a it was a you know a a challenging trial in a number of those respects. Uh and then post uh uh surgical or post IR Um we follow these patients out for 48 hours, which also included uh the research assistant taking um down every uh uh you know CC of of fluid people got, how much urine they made, how much blood products they got in real time.

Keeping track of all of that. Wow. So I mean it it just sounds like a Herculean amount of effort and and and I I'm willing to bet a lot of this occurred in the hours between seven PM and seven AM as well. Correct. Yeah, correct. Well um let's talk a little bit now about some of the some of the criteria. So um just to reemphasize you you randomized people after they had already received

um five units, right? So this maybe the sixth unit was infusing when they were randomized and started receiving the presser. Uh so they were they were randomized as the sixth unit was going in um and they then got the bullis as soon as the sixth unit of blood profile. Okay. And the bolus was the bolus was four units of vasopressin, so it's one tenth of the old uh ACLS dose. Mm-hmm.

Drips that we typically would run in a septic patient in the ICU, which is point oh four, so it's kind of in that sweet spot. Correct. Yes, and that was actually recommended by Dr. Landry. Um, we consulted with him and he felt that that would that amount of bolus would get you to an appropriate level of a hundred, at least a hundred picograms per deciliter.

And then following the bolus then the the point oh four unit drip was run um basically continuously and you titrated based on a map goal of sixty five according to the paper. Yes, so the the drip was run continuously in the operating room. Um and so it only became we only started titrating it when the patient uh uh had determined. Yeah, it had to go out of control.

And so there was it sounds like there was still sort of uh an attempt to kind of do permissive hypotension or not reg you know, normalizing the blood pressure until definitive hemorrhage control was there. So the point oh four was going in and even if it wasn't bringing the pressure up to quote unquote normal, it was just left where it was. So that I think that's a critical point to to understand as well.

Well, so the so the the map goal was sixty-five. So if you once you were enrolled, if you were not making a map goal of sixty-five after definitive hemorrhage control, you were given other pressers to make it. sixty five. Right, right. After after surgical control or depending on control correct. Okay. Um and then it was and and you terminated data collection at forty eight hours. Why why pick forty eight hours?

Uh, because when we re observed the um other uh patients with the the vasopressin deficiency. We found that most people had recovery of their vasopressin levels or were no longer requiring pressors at 48 hours. And it gives you a certain amount of time for your pituitary to create vasopressin and start to secrete it at a normal rate. Okay. Okay. Uh so forty eight hours was

And um so let's go into some of what you found then, some of the some of the findings and differences between the groups. Oh, okay. So what we found was that the vasopressin group Um did require less blood product uh uh transfusion over the 48 hours. We also, so that was our major finding. The sort of surprising finding was that we found that the vasopressant group actually required actually developed fewer DVTs as well.

Um, and then finally, we weren't really powered to look at differences in either mortality or many of the major complications. But there was a trend toward uh decreased length of stay, decreased uh uh renal failure, and decreased um ventilatory requirements. So not really powered to look at that, but there were trends toward the toward

And and it looks like I mean the y you say significantly fewer blood products, but it was it was about twice, right? I mean the median I think was about one point five for the vasopressin group or one point four, I'm looking at it now. and two point nine for the non vasopressant group. So it wasn't it wasn't just a uh you know, a small amount here. There was a substantial decrease. Correct.

over the course of a massive transfusion, right? Mm-hmm. Yeah. Yeah. Um so um With those results, um, let's talk a little bit about um well real briefly let's talk about kind of if this has changed your practice and if you're doing this routinely now, um and then I will I'll I will ask you to sort of speculate about some of the some of the other theoretical questions that the the the study raises. So but but first off, has ha have you started doing this now with all of your bleeding patients?

Yes, I have. And um A have you seen similar improvements um or any other sort of anecdotal, you know, not not studied, but have you seen improvements of those other outcomes that weren't uh powered for in this study? Oh well I think it's it's very I mean it's very hard to to uh

d do though uh it's very hard to tell in that kind of thing. You know what I mean? Because um i it you uh you give it and you you have good outcomes or you know it's it's unless you actually do a controlled trial or you actually do a very uh deep dive into whether or not it's beneficial or not Yeah, yeah, but you certainly haven't seen any downsides of it. No, I would I have not seen any downsides.

Yeah. Um so um let's let's speculate a little bit here. Do you think um Uh you know, most of your patients were men, uh most of them were penetrating trauma just being uh West Philadelphia. Do you think the similar effect would hold up for blunt trauma or is that is there any reason that blunt trauma would behave differently than penetrating trauma?

I I don't think that there would be any difference and we did have some blunt trauma patients. I can't think of a a mechanism about why penetrating versus non penetrating trauma may um benefit from vasopressin more preferentially. I I think it more has to do with uh uh either prolonged shock states in which vasopressin levels decrease, uh and that's certainly been borne out in animal studies.

or um, you know, the amount of blood product that we give you uh in in transfuse. So if you're getting a massive exanation protocol, then you are gonna have decreased vasopressin levels. So I I I can't imagine the mechanism necessarily

a significant impact unless maybe blunt mechanism may actually benefit more because it's also a a more pro inflammatory state. Uh I I just I don't know. It's very spectacular. Interesting. And is there any reason to think there would be sex differences between male and female? I don't think so.

Uh I do think, you know, the data would suggest that women uh tolerate uh uh trauma better than men. Uh so I I don't know if we would see as much benefit with women, but it's hard to it's hard to imagine that there's terms of um vasopressin. In uh the post um sort of OR phase in the definitive hemorrhage control, after that's been accomplished. Um you did also allow other pressors to be used.

Um one question I've had is um how were you sure that they still had definitive hemorrhage cr control? Um were you able to kind of distinguish between maybe people who had another source of bleeding or ongoing hemorrhage as the cause of their hypotension versus The vasoplegia or sort of the post resuscitation uh hypotension sort of phase. How d how did you suss that out? So I I think first of all we didn't have a lot of patients, if any that I recall who were had ongoing bleeding.

Um, I think we did definitive control was actually pretty definitive. And of those people who did have ongoing bleeding, their lactic acid just didn't clear. So they were hypotensive, requiring pressors with a and their lactic acid me remained elevated. So we followed that as well. Um So I think that if you're resuscitating with fluids and um vasopressin uh and vasopressin is on board, if your lactic acid isn't clearing, that that there's a problem.

Um in terms of why we chose a math of sixty five, uh my concern was that um You know, it it's it's now almost taken for granted that vasopressin deficiency, if you add vasopressin on, you get a a blood pressure benefit. Um but I think what our your uh readers or your listeners may want to know is that if I give healthy volunteers vasopressin at the point oh four level, it doesn't change your blood pressure.

So so this is it's important to think about this as um not necessarily as a vasopressor that we're adding on per se, but more that we're adding back hormonal supplementation. Um that happens to have a presser effect in patients who are vasopressant. So if I if I give it to healthy people, it's not gonna change their blood pressure. Um, but if people are deficient, which we had

uh sort of hypothesized that they would, giving vasopressin will improve their blood pressure. So clearly having different blood pressures and two different groups can have different impact. So in order to control for the the uh impact of blood pressure on uh outcomes, we had to have a group we had to ha keep the blood pressure at a at a controlled value. Does that make sense? Yeah, yeah.

Um otherwise the impact that we would have seen um if there was a difference in blood pressure, people would say, Oh, well, because it was a difference in blood pressure, that's why you're seeing the um the the benefit of vasopressin or the uh the lack of benefit in if if we So it was really important to control for that aspect to have a blessing. Now and other people will say, Well, you know, why did you choose sixty five? You know, sixty five is amino arterial blood pressure and and that

Um, you know, that's a that's a tricky thing. People really don't know what the the best amino arterial blood pressure uh for patients really And so 65 has been chosen for sepsis. And so we chose it for um somewhat arbitrarily for this study as well, because there had to be controlled blood pressure since that that variable would be changing in patients who were vasoproussible.

Right. And presumably somebody with less than sixty five in the non vasopressin arm could conceivably get more blood products just because of having a lower map. So so that's why you had to equalize between the two groups. Exactly. Precisely. Um There's um there's been some interest um in the um especially in the EMS world about um you know avoiding intubation in the critically ill or or bleeding patient as in order to avoid sort of precipitating

um codes and and things like that. And so there's been some interest in push dose dazopressin under those circumstances. Um And so I my question for you is do you think um you waited in this study until after five units of blood, do you think there would be any benefit to sort of doing earlier dosing of that of that bolus dose of vasopressin? I think that there may be benefit.

But I don't know uh whether there will be. Um, it's certainly if you have to do some procedure uh that you know is going to drop the blood pressure. Um giving vasopressin for that is is a fine idea in my opinion because our patients uh in those circumstances are already profoundly acidotic.

And we know that pressors, uh traditional pressers like epinephrine and norepinephrine don't work as well in an acidic environment. So giving patients vasopressin may actually which doesn't uh which works very well uh in an acidic environment, uh maybe the presser of choice. Um that being said, um I don't think we should be using vasopressin uh to treat um hypovolemia.

Um so vasopressin in this study um was really to treat the vasoplasia that develops in prolonged shock or in um a vasopressin deficient state where you've washed out or used your vasopressin. Um, it's n it was not designed to treat hypovolemia um from blood loss with vasopressin. I'm not sure that's a great idea. Um the studies, the animal studies that have looked at vasopressin, high dose vasopressin in um severe hemorrhagic shock, those are all um

Done in a late stage shock setting as well. And they, while they do prolong survival, there's really not good long-term follow-up. uh in terms of uh you know whether or not there's more multi-organ failure or what have you. So I I would not take from this paper um that you should be giving vasopressin to treat hypovalina. I would take from this paper uh that you should be using vasopressin to prevent Shock induced vasoplegia while resuscitating the

Does that make sense? Absolutely. And and that was one of my thoughts about this is that I could see, you know, if I was in a a small hospital, maybe maybe a more resource restricted environment that didn't have a bunch of blood products.

I could see the light bulb going on and saying, Oh, what I'm gonna do then is I'm gonna give vasopressin and then you could see it's a short uh jump from there to not giving blood products, you know, giving push dose vaso and then sending the patient on the helicopter or ambulance or whatever to uh transfer out of your uh out of your correct correct yeah so so I I think that that would be um you know um

We don't have a study to show that that that's safe. Um, and I'm not sure that this study actually supports that because this really was Looking at patients who are at risk for vasopressin deficiency. And to remind our our your listeners that vasopressin deficiency leads to both arterial vasoplasia but also venous vasoplasia. So in that setting the venous tank is getting larger.

So it can certainly be used at um to close down the tank if you believe that you are getting uh uh vasopressin deficient, but it should not be used to treat um hypovolemia per se.

Well, if you had unlimited resources and time and volunteers, uh what would your future directions of inquiry and along this line be? So I I think the study is now begging for a uh multicenter randomized control trial uh so that we can look at giving um vasopressin um uh earlier um and look at the impact on um mortality and morbidity.

So so for example, I think in patients who are at risk for developing vasopressin deficiency, those that require large volume resuscitation, I think that it is uh it would be nice to know that it were safe to give as you start to resuscitate the patient, not foregoing resuscitation, but initiating it sooner. Um and then also looking at what are its uh uh implications in terms of survival and uh you know, the development of renal failure.

Okay, well uh for those listening I will put links to the uh articles that we've mentioned during this podcast, specifically the Dr. Sims paper here from JAMA Surgery in twenty nineteen, August twenty nineteen edition. Um thanks so much for spending time with me today, Carrie, and uh for uh elaborating on this. I think uh I I think there's a lot of people that are interested in this concept and I think uh this may be one of those papers that we see has

Uh it shows up in a lot of those uh papers that you should know or papers that should change your practice kind of discussions at different trauma conferences. So congratulations on getting it done. It sounds like it was a a tremendous amount of work and uh labor of love to get it uh to get it all the way through the process. Thanks so much, David. I really appreciate your time. And that wraps up another edition of TraumaCast brought to you by the East Online Education.

Association for the Surgery of Trauma. You can check out all the great educational and career development resources available on the East website. Trauma cast series. Networking and building relationships and career development, remember that all you need to do is look to the east.