Good morning to everyone, and thank you for joining us for this faculty session for Current Concepts in Critical Care Pediatrics for 2022. I'm Sharon Irving, and I'm the chair of Current Concepts Pediatrics for Society of Critical Care Medicine. I'm joined this morning by my co-chair, Dr. Kyle Reiter, and the past chair, Dr. Nicholas Ettinger. And, Kyle, with that, I'm just going to do a little bit of housekeeping. You all, as attendees, are in a listen mode. Should you have questions for us, if you look in the operator panel, you'll see a section that says questions. Please type them in there, and we can all see them. And between myself, Kyle, and Nick, we will make sure that the panelists get the right question for their talk. And then, if you have other things, please type it in there. We do have IT help in the background, so if you're having challenges with hearing or seeing something, please type it in, and they will help you individually. So, with that, I'm going to turn it over to my co-chair, Kyle Reiter. Welcome. So, welcome, everyone, again. Very glad to have you all join us today, and thank you very much to our faculty for being here to field questions. So, I'm Kyle Reiter. I am a pediatric intensivist at Duke Children's, and we're just going to have each of the faculty who are joining us today introduce themselves. So, we'll start off with Tom. Morning, everyone. I'm Tom Nakagawa. I am a pediatric intensivist. I'm with the University of Florida Healthcare in Jacksonville. I'm also your SCCM council representative. Great. Thank you, Tom. Atpal. Hi. Good morning, everyone. I'm Dr. Balala. I'm a pediatric intensivist at Driscoll Children's Hospital, Texas A&M University, and also the research advisor for the Driscoll Health System, and I have been past chair of this committee and deeply involved with SCCM since many years. Thank you. Christopher. Hi. Good morning, everyone. Welcome to our session today. My name is Chris Watson. I'm a pediatric intensivist at the Medical College of Georgia and also a committee member of the Current Concepts Committee. I'm excited to be with you all today and have the chance to join this conversation. And last but not least, we have Phil Spinella, who's joining audio, and hopefully is here as well. Hi. Good morning. Phil Spinella, a professor of surgery and also critical care medicine at the University of Pittsburgh, and I co-direct our Trauma and Transfusion Medicine Research Center, in addition to being the associate medical director for the Center for Military Medicine Research here. And then finally, I realized just to introduce yourself, Nick, as the past chair of this committee, but one of our moderators today. Good morning, everybody. It's great to be here. I'm Nick Ettinger. I'm a pediatric intensivist at Texas Children's Hospital, and glad we're all together. Excellent. So, again, thanks to our faculty for being here, and thanks to you all for attending. So, with that, are there questions from the attendees who are here with us? I see we have a few. Are there specific questions that you have for us? Okay. Hearing none at the moment, and not seeing any typed in, and if I miss questions, please let me know that I've missed them in the chat. Hearing none, I'm going to start with you, Tom. These are some very interesting, you know, with all that's going on in terms of pediatric pain, brain death, excuse me. Can you just give us a little bit in terms of how has the pediatric critical care community accepted and begun to utilize and educate on these? Because in my experience, I'm a pediatric critical care nurse practitioner, this is one of the tougher things that providers, both at the physician level and nursing level, have to deal with, and understanding this definition. So, how have you been able, or how have you heard that providers have accepted? So, great question, Sharon. When we put together the original revised guidelines, we really wanted to try and standardize those guidelines as much as possible so that everybody would be performing a brain death examination and apnea test the same way. And your question is timely, because just this week, we had a publication that came out in the Journal of Child Neurology that looked at a comparison survey through SCCM, looking at the SCCM membership specifically in pediatric critical care. There was a survey done in 2013, some of you may have participated in that, and that was 18 months after the revised guidelines had come out in 2011. And then we did another survey in 2019. Dr. Krawick took the lead on this, and what we found in the survey results is that the 2011 revised Pediatric Brain Death Guidelines have been readily adopted by most of the survey participants. It has standardized how we make a determination of death. People are utilizing the guidelines in the electronic form, using the checklist, but more importantly, we've actually reduced the amount of diagnostic error that occurred. The diagnostic error that we were seeing in 2011, prior to 2011, with the 2013 survey, included everything from 1987 forward. And those guidelines, while they, I think, were well-intended, left a lot of latitude for clinicians to perform the examination in a number of different ways, and we were much more specific in the 2011 guidelines. What we did find is that reduction in diagnostic error was not necessarily on the clinical examination side. Diagnostic error actually was occurring with our ancillary studies, and interpretation of those ancillary studies. And again, we emphasized in those 2011 guidelines that the determination of neurologic death in children, as it is in adults as well, is a clinical diagnosis. There is no requirement to do an ancillary study unless you can't complete the examination and the apnea test. Great question. And I would refer any of the participants out there today to that journal about neurology. It is online. It just came out this week. Great. Thank you. Thank you. That's very, very helpful. So, in talking about brain death, right, before we get there, we always talk about neurological and brain protective measures. So, I'm going to switch to you, Dr. Uptal, I'm so used to calling you Paul, that I always trip over how to say your name correctly. So, I'm going to switch over to you and talk about neuroprotective strategies. And at what point, in terms of those neuroprotective strategies, do you see that providers should say, now we really need that better neurological exam to determine where we are on that scale? Yeah. So, again, very good question. I think whenever a patient has a significant brain injury, whether traumatic or post arrest, I think first 24 to 48 hours, I would suggest that neuroprotective strategies are continued for that duration, including sedation and paralysis, if needed, in order to gain maximum benefit. And I think at some point, when there is a need for coming off of the sedation and paralysis based on the patient's stability, at that point, one should start looking at a neuro exam. Also, I think the neurologic exam depends a lot on what temperature strategies are being followed. So, again, there are center-specific targeted temperature management strategies. Because the TAPCA trial showed no significant benefit of therapeutic hypothermia versus normothermia, some centers have adopted a normothermia strategy versus some other where they have hypothermia strategy. And some centers do not have a specific strategy. And it is, you know, individual intensive is driven. So if there is a hypothermia strategy followed at a particular center, then first 48 hours is the hypothermia range. And then there is slow re-warming. I think that potentially can allow the brain death exam when you reach the target temperature, which, you know, based on brain death exam guidelines, you should be able to do the exam beyond 34 degrees centigrade. So I think if the center is following hypothermia guideline, then ideally, they should look at 24 to 48 hour hypothermia followed by slow re-warming to reach the temperature which will allow brain death exam or a neurologic exam. I hope that answers the question. So it's a... Sorry, go ahead. Nick has a question. I was going to follow that up with just to talk about, can you talk a little bit about your personal practice of who do you not cool, who do you cool at admission, and how do you make that decision? Yeah, that's exactly the question I was going to go with, because I think, you know, is there a set of population where we think there might be a real benefit? Yeah, that's again a very good question. So I think knowing from the neonatal world that hypothermia has shown at least short-term significant benefits, Dr. Shankaran's landmark paper, I think there is some value to adopting hypothermia strategy in the neonatal period. I mean, the mechanism of injury may not be same as what we had in Dr. Shankaran's paper, which was perinatal hypoxemia, right, birth asphyxia. So it's always going to be hard to generalize, but at least the post-cardiac arrest population, if it's neonatal, then in my personal opinion, hypothermia or low normothermia might have benefit. And another population where hypothermia or low normothermia might be of benefit is the teenagers with primarily ventricular tachycardia or ventricular fibrillation cardiac arrest. So these are the two extremes of population in pediatric world. It would be okay to consider hypothermia or low normothermia strategy. And for the rest of the population, our protocol follows mostly normothermia guidelines, just so that there is easy nursing care to control the temperature, there is less risk of rapid re-warming, and brain death exam can be done practically any time. So because of these three potential benefits, for most of the pediatric population, we have normothermia guidelines, and the key is avoiding fever at all costs. I hope this answers the question. Yeah. I'm just curious, for traumatic brain injury, if you have uncontrollable intracranial hypertension, despite maximum medical therapy, putting a kid in a barbed comb, and you're still having ICP issues, I'm curious, for my colleagues, how many of you at that point would consider cooling that patient? That's a great question. Maybe I can go first. We have adopted a cooling option in those extreme cases, when you have run out of all the options. Again, in my anecdotal few cases where we adopted cooling in TBI patients, overall outcome was this small. Again, not necessarily related to cooling, but it was just a pathophysiology. But yeah, I would like to also know from other experts here. Yeah, I will say that we've, after the Cool Kids trial that was done several years ago, specifically on that population, we generally do not cool those patients, even in the setting of refractory increased intracranial pressure, with the general thought of, yes, it will lower the number and make us feel better, but the data that we at least have suggests that it won't change that outcome. We generally do not cool at that point, but completely agree with the point that was made earlier, all of our focus is on avoiding hyperthermia, avoiding fever. Yeah, Phil Finnella here. I agree with the previous comments. When we rarely use hypothermia, it was often very late, and as a result, very likely not going to be helpful, right? If we wait that long, the cat's out of the bag already, so to speak. And I'll jump in from a nursing perspective as well, and then Chris, I want to hear your thoughts on this as well. But I will say that from a nursing perspective and thinking about the labor intensity that it takes to cool a patient and keep them cool, particularly when that trial was happening and we didn't have all of the fancy equipment, and literally it was getting ice and cooling in some very rudimentary kinds of, pal, you remember those days, right, in some rudimentary measures, it's a lot of nursing power, okay, and can be very labor-intensive. And so the quandary that we and my nursing colleagues would find themselves in is that the decision is made, but then there's a time lag. And so it's sometimes difficult to keep the patient cool, but it's a lot of work. And so it's sometimes difficult to get them to that place because of the time lag just by the sheer work that it takes to cool a patient. So I think all of those things have to come into play when we're talking about this. But Chris, what's your experience with this? Yeah, absolutely. That's, I think, very much the key, the labor-intensive nature of this. As Kyle alluded to, and Pal mentioned, the use of TTM and the importance of normal thermia from the outset is itself fairly labor-intensive. Sometimes that still requires active aggressive cooling just to maintain the normal thermia. And I think that's our original question was about cooling, as Tom mentioned, and refractory intracranial hypertension. And I think that we do cool to normal thermia very aggressively. The use of therapeutic hypothermia, I think, has taken a little bit of a back burner position, as was mentioned, just because of the outcomes associated with that. But that still needs to be highlighted as to how important and how resource-intense that can be just to maintain normal thermia in the midst of minimize hypertension. Agreed. Any last comments on that? Or else we'll shift a little bit and go into some trauma and massive bleeding. I was going to just ask the group, we've mostly been talking about out-of-hospital situations. What about the in-hospital arrest? Does that change people's approach? The in-hospital witness arrest? It should. I mean, in my experience, and based on the literature, I think the normal thermia or low normal thermia would be applicable to both in-hospital and out-of-hospital cardiac arrest population. And just a quick comment to kind of a counter comment to the nursing component. Yes, I totally agree that there is a need for nursing education and also a lot of bedside nursing efforts. But some of the devices which allow automatic mode, whereby you put the internal probe, esophageal and or a bladder probe and connect it to the device and set a range, it does a fairly good job in keeping it in the normal thermia range. The key is having a TTM protocol for the institution. If you do not have a protocol and if you do not have buy-in from physicians and nurses to control the temperature, whether it's low normal thermia, normal thermia, hypothermia, you will see wide temperature fluctuations, including fever. So for both in-hospital, out-of-hospital, the simplest approach would be having a normal thermia TTM protocol and some nursing training and education and bedside checklist to make sure that there is no room for fever. That's the key. I'm going to add one thing to that, Paul, is in addition to those checklists is to have key players that know from a nursing standpoint where equipment is located, know that policy, know that protocol, and are the lead people. That's a key component in terms of the group effort, if you will, of all providers to get everything done. You need the people putting in the orders, but you also need the people gathering the equipment who know exactly where it is, who know what the protocol is, who know how to start. And that is what helps in terms of bedside education, because the other people that we haven't talked about here is the family, right? Because someone needs to be explaining to them at the same time what is happening. And oftentimes there's the urgency to get the patient cooled, but there's also the urgency to keep the family involved in the care. And so some of that responsibility comes to both our bedside nurse colleagues and the advanced practice colleagues, because sometimes we're the ones kind of right in the middle, right, doing various kinds of tasks with that. So I think everything that everyone has said is very, very pertinent. And for us to remember that that other component is making sure the family is well-informed as to what we're doing and the reasons why. So the education component of this is extremely important. And Tom, back to what you were saying in terms of making sure that all players are updated as much as possible, because if our cooling and all of these things are not successful and we do have to get to that point, again, it's helpful to have as many people as possible educated on the processes that we're doing so that we can communicate well with each other and with families. And that's such a key principle that holds true for so much of what we do in critical care, certainly not just, you know, our hypothermic protocols, but we'll carry over to the other topics today as well. Yeah, standardization is so important. And just going back to, you know, the brain neck guidelines specifically, the mechanism of neurologic injury is different in children. And it changes with age too, which has to be taken into consideration. And we were very specific about that, that you really need to wait 24 hours or more following cardiac arrest or severe brain injury before you begin to think about neuroprognostication and even walk down that path of doing brain death testing. Because I think that we've all been there before. You see these anoxic injuries come in and over 24, 36 hours, they develop agonal respirations, they start to move a little bit, and then they progress over the course of the next 72 hours. And they either get to a point where they do herniate and you can do brain death testing or they're left vegetative because they don't herniate. Exactly, exactly. All right. Thank you so much. That was, that was excellent. So let's shift a little bit. And I'm going to pull Chris into this conversation and you as well. So and talk about transfusion thresholds. I think we see these kids come in and, you know, like, what is that answer? And how do we, again, I think the one component that keeps coming up here for me, at least, is the education and standardization that's necessary. So, Chris, I'm going to ask you to talk about that just a little, a little bit. Yeah, thank you. I think this is such a very cool and kind of evolving field that it's just great to kind of see the research that's been coming out of the different communities and still very much is plugged into that with the Polisi Blood Net group, and some of the great publications that have come out of there. The TAXII study recently gave us, you know, a more standardized approach to how we can transfusion thresholds. And now TAXICAB coming out this year gives us that much more kind of evidence-based approach to transfusion guidelines in pediatric patients, not just from the RBC standpoint, but also from plasma and platelets perspectives. I mean, I think the thing that's very unique about this is that, much like the rest of critical care, right, this is becoming a very patient-centric algorithm where patient factors and disease factors, very specifically in the interplay between them, are leading to an individualized approach to this. And thinking about your Choosing Wisely campaign and restrictive strategies to try and minimize any iatrogenic injury as part of this is weighed against the benefits. So the risk-benefits analysis is something that is very specific and dynamic in time. You know, sepsis at the outset versus kind of indolent and ongoing sepsis and kind of the inflammatory cascades that are involved in that may have different implications for transfusion strategies. And I think those are the things that are very unique and very interesting about where we're at with this, and as the research continues to evolve, kind of the immunomodulation and the impacts of transfusion strategies, I think, is something where we'll continue to see a much greater depth and kind of exploration of what that looks like. And these guidelines have been extremely helpful to give us a standard practice and to help us minimize any further injury. But I'm very excited about where this is continuing to go in the future. Yeah, no, good comments, and I agree. The major problem, though, right, with using hemoglobin as the threshold to trigger red cells is that the evidence is pretty clear that the hemoglobin itself is very suboptimal when it comes to identifying the need for a red cell transfusion or not. But that's unfortunately kind of the place that we're currently in. We don't have adequate physiologic measures to determine who needs a red cell transfusion or not. And there are a few, you know, current studies. Jen Mazinski has R01 funding to try to start to get some data on this topic in patients with septic shock. Alan Docter and I are working on artificial intelligence algorithms to try to help inform, you know, what patient would benefit from a red cell transfusion versus who would be harmed by a red cell transfusion. So until that all gets figured out, we are still kind of stuck with basically having a hemoglobin trigger in general, although, of course, we could all, you know, try to figure out if the patient does need a red cell transfusion despite, you know, an actual hemoglobin threshold. But that's still what most people rely on. So, you know, I'm presuming this conversation started with specifically talking about either post-arrest or TBI patients. If we're talking about, you know, all critically ill patients, I think it's real important to separate patients with life-threatening hemorrhage versus those that don't have life-threatening hemorrhage. And those with life-threatening hemorrhage, we really shouldn't be using in the beginning any laboratory measures to indicate the need for transfusion and should be trying to target a balanced approach to their resuscitation, whether it's giving a balanced amount of red cells, plasma, and platelets, or using low-titer group O whole blood, which is becoming more and more very common, actually, in the adult world and becoming relatively common in the pediatric community. And we can pull the string on that if people want to or not. Following up that comment, Dr. Spinelli and Dr. Watson, what are your thoughts on the use of Rotems to guide transfusion strategies versus traditional, more traditional measures of coagulation? Are we all, you know, is Rotem going to be the new standard of how we determine things? Can you talk a little bit more about that? Sure. I definitely think it's better than using classic coagulation tests for multiple reasons, but it's not perfect. So I do use it to basically, you know, provide goal-directed hemostatic resuscitation once I've gotten over the initial life-threatening hemorrhage with whole blood. So I do think it's valuable. I do think it should replace waiting for a platelet count, so to speak, or waiting for an INR or even a fibrinogen concentration. But it's been difficult for the health systems to implement it without randomized control trial data to support it. But it's interesting, in the systems that have implemented, it does seem that, in general, you decrease the amount of total blood products used over time because you wind up using the right product at the right time. So I'm in favor of it, but we have to recognize it's not perfect because it doesn't include, the assay doesn't include flow, right, and it doesn't include biologic surfaces. But it is, I think, better than what we've been doing. Chris? Yeah, I would just add on to that, as well, that I think there's an experiential component to that, right, this is not, it does require education and experience and is not uniform, probably, in practice across our different ICUs and kind of PICUs nationally and internationally because of that. And that's not something that can't be overcome, but I think that, perhaps, is a bit of a limiting factor in the dissemination of that as a tool. I think, as Bill mentioned, it absolutely has a place and provides much greater depth of information in thinking about the chronology of a critically ill patient and how that changes through their illness, as well. Helps to give information about that that's dynamic, as the patients are. And the guidelines absolutely aren't meant to be strict thresholds and very much adapt to patients and their illness and where they're at in that. But further information, as Bill had mentioned, kind of thinking about biological and physiological markers and what we do have available to us until there's greater depth of what those markers are and tools that we have. This, most certainly, is something else that we should use as a tool and build our experience and our knowledge in the use of that. So, I was gonna pull back, again, to that idea of a hemoglobin cutoff and should there be a set hemoglobin cutoff or not. And obviously, we're left with the TAXI guidelines, which I think have been incredibly useful. That being said, when you have that patient who's between five and seven, it is still clinical judgment required. And what I have seen is there's still a lot of discomfort in allowing someone to sit at 5.2, even though they're clinically stable in many ways. And so, would love to hear from you, Chris and Phil, what are the clinical signs that we really should be pushing and how do you communicate to our folks, not only our physicians, but also our nursing staff, who have sometimes been doing this for a long time, about that 5.5 is okay in this patient? So, it's a great question and definitely a space where that requires kind of reflective practice and growth of ourselves and our community to push ourselves to recognize what Phil mentioned earlier, is that transfusion is not necessarily a benign intervention. There's risks absolutely associated with that. And I'm thinking about that and looking at the individual patient and identifying where they're at. Are they in the plateau phase of their illness or in the recovery phase or are they still in the acute worsening phase of things? It's very much a patient centric evaluation that we have to do at the bedside. And I don't think there's necessarily a set answer there, but there are patients perhaps where that 5.5 is okay. And then there are patients where clearly six may not be adequate or require intervention earlier. And so I think that's a great space to ask ourselves, what our outcomes are and what our metrics are for measuring success and improvement in that clinical critically ill patient. Yeah, I mean, a very good question and difficult one to answer specifically, but it's basically how much is the patient compensating for that degree of illness? And do you think the red cell transfusion will benefit you more than the risks that it also brings you? And are there other ways to reduce the compensation for the anemia than the red cell transfusion itself? Right, again, so it's very patient specific, but there could be other ways to improve preload, to improve cardiac output, to improve O2 delivery, for example, but every intervention comes with the risk. But I think what the problem is, most physicians don't truly understand the risks with red cell transfusions or all transfusions, specifically the immunomodulatory aspects. Yeah, I think that most people don't realize that in the 70s, before immunosuppressives were developed, red cell transfusions were specifically used in kidney transplants to cause immune suppression to improve allograft survival. Okay, that's a holy shit statement, right? Think about that, think about that. Oh, kidney transplant, give them red cells to improve graft survival because that's how immunosuppressive it is. It's crazy, but that's what we were doing, that they were doing in the 70s. But most people don't realize it. Oh, we're just gonna increase the hemoglobin, increase the boxcars, yeah, but the unintended consequences are not truly appreciated. And it's hard to publish that and to prove it because critically ill patients have so many other factors that are affecting their outcomes. This is a hard area to provide concrete data, but you look at all of the observational data and then clearly it's biased, but there's such a strong adverse effect of red cell transfusions in most large studies. At the very least, it should at least make you wonder, right, and be a little bit careful and not cavalier about transfusing red cells. And we've come a long way. I mean, when I was a fellow in 2000, 2003, we were using hemoglobin triggers of 12 or 14, right? I mean, so we've, you're talking about five to seven. So it's gotten better, but there are still plenty of people transfusing at 10 ECMO, right, when they have full cardiac support. Anyway. Hal, please. Sorry, so I completely agree, all amazing comments, but I think we all probably, most of us have a practical difficulty that we are not just us. We deal with surgeons, cardiac surgeons. And so my question to the experts here is, when you have these guidelines, how do you translate to the bedside, especially in a specific population like congenital heart? Because, I mean, even today, the surgeons swear on hemoglobin, especially single ventricle, oh, push the hemoglobin to 14 plus. So how do you deal with that? How do you have institutional protocols buying from everyone? Can you please help us? Yeah, I wish I had a magic wand to improve logic in some of our surgical colleagues, but we haven't made that yet either. But honestly, it takes effort, effort and education and sitting with your surgeons. I mean, they are, they're smart people, right? They wanna do what's best for their patients, but they're doing what they're taught. And until someone else spends the time and sits with them and goes through the literature, that's the only way we're gonna help change people's minds. It just takes effort. And honestly, most people don't have the time or energy, right, to do it. But when you do, I've been able to help change minds to a certain degree. It just, it takes effort on our part. And of course, they need to be willing to listen, but many are. It's just getting together, right, and having that conversation. Yeah, I would agree as well. I think that this is a great space for the importance of these kind of novel studies and research that's coming out in pediatric critical care, right? This has been a place where there's been a paucity or a gap in our evidence base for a long time, extrapolating from adult research. And now there's a great evidence base coming out, and this is just kind of scratching the surface of that. And I think in the years that come, we'll continue to see that evolve and thinking about our shared interests of having good outcomes for our patients and their families is the common place to start that conversation. And with the evidence to show as to what strategies will actually improve those outcomes, I think is where we can find that olive branch to help move our practice forward as a multidisciplinary team. Yeah, I think to answer your question, it's with difficulty that we manage that. But I really wanna point to what Tom brought up earlier about the importance of standardization and coming up with those protocols. And it's coming up with those protocols in advance. So new guidelines come out, sit down, look at the protocols and talk about them in a way when you don't have that actual patient in front of you, as opposed to waiting until, oh, we're trying to make a decision for this individual patient. I think the conversations go differently when you're in the room talking about patients in masks, as opposed to Johnny, who's right here, who I wanna do everything for. I'm gonna jump on that as well, Kyle. And as you're doing those protocols, include your senior bedside nursing colleagues, right? Because they're gonna be the ones that can tell you, you know, you can tell, right? I'm the nurse in the group with my esteemed panel here, but I was a bedside nurse for a long time. And then I've been a nurse practitioner for a long time. And having helped educate colleagues on particular guidelines related to early feeding, right? It takes exactly as you said, Dr. Spinella, it takes being the squeaky wheel and asking the questions. You know, so I would encourage you, Kyle, I agree with you 100%. It's not waiting until that point in time. The other thing I go back to is in terms of bringing the nursing lens to all of this, when we talk about all of this, is the just-in-time education, right? And so if you have that patient that you're holding off for whatever reasons, and you're comfortable with their hemoglobin being at that six range or even at the five range, taking a couple of minutes and educating and discussing, because it's not always educating, but it might be discussing with that bedside nurse why you're comfortable with that and what things to look for that would make you uncomfortable with where they are, right, goes a long way, because they're gonna pass that on and they are also learning at the same time. You know, just like in every other profession, the nursing staff at the bedside is a little bit younger in terms of nursing years, right? And so taking that few minutes and saying to them, I know that what you learned or what you saw or what was in the orders was hemoglobin less than seven, we're gonna transfuse. But let's look at this patient. What kinds of clinical markers am I comfortable with and what kinds of clinical markers am I not comfortable with so that we would pull that trigger to go ahead and transfuse versus holding on? That few minutes goes a long way. And Sharon, and then we'll turn it over to Tom. I just wanna say thank you for keeping us honest around that. I mean, there's nowhere, it's hard to find other places where we practice team-based care like we do in the ICU. And it's so important to include the expertise of all those folks at the bedside and the buy-in of all those folks. So thank you for keeping us honest on that. Those that know me know I'm always that, like, wait a minute, wait a minute, wait a minute. You know, I think, and I so agree with what Phil said, you know, we work to treat a number because we think it's going to make the patient better. We're going to give more boxcars. We can improve content. We can improve capacity and tissue oxygenation, all those things. I think the one thing we don't focus on though are the adverse effects from transfusion. And I don't think people are aware enough of the adverse effects from transfusion. You know, if we go back to the brain death guidelines, the classic question I always get is why do we have to wait 12 hours for this group or 24 hours for this group? Why can't we just do two examinations? You can, you can do them back to back if you want to, but the unintended consequences, if you make a mistake and you declare a patient dead and you didn't follow the guidelines, then you've got a bigger problem on your hand. And I don't think people really understand the consequences and have seen some of the reactions that you get from transfusions. I think we need to make our colleagues more aware of some of those adverse effects that can clearly hurt our patients. And I think also the courage to not do something because you have that family at the bedside. You have folks who just want to help. And so that there's that natural reflex of doing something else. And it sometimes takes a lot to be patient and wait. And that's if one of the things is I've worked with trainees over the years that's come up again and again is that comment of you see people with experience. One of the things they gain is the ability to sit back and wait, to wait for an intervention to take effect or to know when to not do something. Yeah, sometimes less is more. Yeah, absolutely. Exactly, exactly. And that's where the education for all the participants comes into play. Even, you know, the residents that are coming through the ICU these days, like that few minutes of education makes a huge difference to them because they too, you know, they want to do well. They want to impress those of you, you know, like they're attending, that they stayed on top of their patient and they did everything right. And that number hit like seven. And we talked about we're going to transfuse at seven. So it's like 6.9. So they're writing for that transfusion. And it just takes a little bit of time to say, as I tell my students all the time, no one thing by itself, right? Put your whole picture together, pull everything together and then make a decision about how you're going to do and what you're going to do and talk to the available people. But it's no one thing by itself. So I agree 100%. Other thoughts? This has been like excellent. I do have another question for you, Dr. Spinella, in terms of the massive bleeding and such. And you brought up a good point to look at the different populations in which we may experience massive bleeding. We recently in our institution had a situation that occurred down in our CT scanner and this patient ended up massively bleeding and was all kinds of resuscitative efforts that came into play. Can you talk about how that looks or if it even looks different from a outside of the ICU and outside of the hospital and how we can direct colleagues to kind of help begin to think about those things? Right now, really good question. And it's another difficult one to answer. I think on the surface, I would think, right, that any patient who is massively bleeding, whether it's trauma from a post-surgical or even from massive bleeding from a medical illness, would need to at least start with a balanced resuscitation, whether it's red cells, plasma, and platelets or just whole blood itself, right? And even when I was a fellow, we would say, if you're bleeding whole blood, replace whole blood, right? And it kind of makes sense. But we just published, well, we just published data in the trauma population showing that a balanced resuscitation is likely helpful, but we're in the process of publishing the medical and surgical populations in that large study that we did. And interestingly, it doesn't seem to be panning out that in medical and surgical bleeding, that a balanced resuscitation is at least associated with improved survival. Now, again, it's an observational study. Numbers aren't that big. Maybe it's just an artifact, so to speak. But what I'm trying to say is, maybe there are different ways that we need to treat massively bleeding children according to the etiology of the bleeding, but we just don't know it yet. And I would defer on the side of using a balanced resuscitation, no matter what the etiology of the massive bleeding was. But then when appropriate, which I can define, then switch to a Tega Rotem-directed resuscitation, as long as the team knew how to interpret the results, et cetera. So I don't know if that answers your question exactly, but the literature in the trauma world is, I think, clearly showing even in children that group O whole blood appears to be superior to individual components. And the non-trauma population, it's still harder to tell, but if it was me or my child, I'd want to give them a balanced resuscitation, too. And with the increasing use, and I suspect we'll see more and more of folks using Tegs and Rotems to help understand the gaps, do you see that we're gonna be using more of things like our prothormin complexes, like our fibrinogen concentrates? Is that, you know, I know right now, the data, it still needs a lot more work, so I'm asking you to read the tea leaves, but do you think that the presence of Rotems are really gonna start to drive those complex uses? I definitely think it will improve, increase the use of either cryoprecipitate or fibrinogen concentrates. I would err on the side of using cryo versus fibrinogen. There are some logistic hurdles with cryo, but there was just a new product with cryo that just got licensed that allows it to be stored for five days, so it can be immediately available. You don't have to have to thaw it, and it's much cheaper than fibrinogen. So I think you'll see an uptick in either cryo or fibrinogen with Rotem or Teg use. Tretazamic acid, I think, will also potentially increase. It's interesting, only 15% of massively bleeding children give either TXA or Amicar these days. It's quite interesting. While people are still using Factor VIIa at 15%, despite all of the adult data indicating its potential harm. So yes, I do think it'll shift and increase some of the hemostatic adjuncts. PCCs, I'm not so sure. Again, PCCs, Factor II, VII, IX, X, Protein C, Protein S, and K-centra, really are not the specific factors needed in patients with trauma-induced coagulopathy. It's made for a coumadin reversal. And thrombin generation is normally not the issue in these children that are massively bleeding, at least early. So I don't think PCCs will really increase much, but cryo or fibrinogen and TXA, yes. And of course, you all know, I think you know, there's a TXA trial called the Tick-Tock trial that looks like it's probably gonna get funded. So we will hopefully have some evidence regarding transemic acid use in the trauma population soon. And I'm working on getting funding for a whole blood trial where we would co-enroll with the TXA trial. And so hopefully, four to five years from now, we'll have some higher level evidence. But until then, we have to continue to do our best. Excellent, thank you. Yeah, thank you very much. Thank you. I think your point, though, is very well taken in terms of really thinking about the etiology of the massive bleeding and being sure that we don't just group massive bleeding into a trauma bucket, you know, because it does happen. And that is outside of the trauma population, for sure. And people, what I've seen over the years in various institutions is when that occurs, people just kind of stand there for a minute, like, wait, what's happening? Surgical, they get that. But the medical bleeding that spontaneously happens that can be massive for whatever reasons, post-procedural or whatever, that's the one that I think stumps people. And with the work that you do, Chris, in terms of transfusion threshold, it really stumps people, is what I've seen, practically, at the bedside. And when do you enact the massive bleeding protocols in the various institutions, if you have one, right? And you should. But those are the things that I have seen as a bedside provider that stumps people. Coming back to the question of standardization and protocolizing things, maybe, Dr. Watson and Dr. Simele, can you talk about what are, for institutions who are trying to improve their massive transfusion protocol process, can you talk about any potholes to avoid or goals to look towards in terms of improving that and standardizing that process? Or sort of QI question, then, medical question. That's an important one. And honestly, we've just recently endeavored on it. We've just recently endeavored on revising and updating our own pediatric massive transfusion protocol. And I definitely think there's some experiential component to that, and certainly in standalone, large pediatric institutions, versus other, perhaps, community-based, or thinking about in other resource-limited settings, thinking about what that looks like is important. Some extent, some part of that is certainly extrapolated from kind of adult experience previously. And building on that, I think, is the important part. So from a QI standpoint, having a multidisciplinary team evaluate that process, walk through it, and identify the potholes along the way, I think has been key for us to make sure that we thoughtfully build out a pathway that made sense with coolers and matched packets of product to be able to do it for children across the spectrum is something that required a frame shift from kind of an adult mindset in a mixed adult pediatric clinical setting like I practice in. So I think that's one of the things to think through. I'm also interested in Phil's additional thoughts, as he kind of mentioned earlier, about the immunomodulatory effects of blood products and thinking about what the future of storage and blood preservation has in store for us as we kind of think about MTP protocols for pediatric patients and how that is changing going into the future as well. And earlier, we talked about that. Go ahead, Phil. Yeah, I was just gonna say, for a common pitfall that's under-recognized, and that's hypocalcemia, that occurs with massive transfusion. The citrate in each of the products, right, causes, and of course, consumption, leads to hypocalcemia quickly. And if it's not treated, you're gonna have worsened bleeding because calcium's a cofactor for coagulation, and you're gonna have reduced cardiac output because it's also important for myocardial contractility as well. So I'm pushing hard now for people to be checking calciums very frequently during massive transfusion protocol activation almost every half hour, if possible, because if you're giving a lot of products and a lot of citrate, you're gonna continue to get hypocalcemia versus just giving empiric calcium, which is maybe in the pre-hospital setting is reasonable. But if we have ISATs and calcium in the ICU in two minutes, we should be measuring it often and correcting it. So that's a big pitfall that most MPP protocols don't include that they should. The future of blood product manufacturing to reduce immune modulation. There are a few products in development that can reduce the immune suppression or inactivate white cells through either pathogen reduction technologies or even storing red cells in hypoxic conditions, interestingly. When you do that, you reduce the oxidative injury to the red cells and there's less immune suppression as a result of less microparticle generation. So there are products in development that may help mitigate it, but they're not here yet. And I'm sorry, with that, if it's okay, I'm gonna sign off. I'm giving my own lecture in a minute now and I need to get off. But this has been great. I appreciate the opportunity and take care. Thanks, Phil, good luck. Thank you, thank you. Good luck with your talk as well. And I was just gonna say that I'm gonna pull you right in here, Tom, that we're close to time, but please go ahead, Tom. Yeah, you know, back to what you were talking about earlier, Sharon, and that's really making sure that everybody's aware of your protocols, massive transfusion protocols. But the other thing is, you've gotta get your rapid infuser set up. And I gotta tell you, if you're using it once a year or once every other year, make sure that people are comfortable setting up the rapid transfuser. Make sure you got all the parts and pieces because the situation's already chaotic and now you're trying to do a massive transfusion protocol and you need the machine to help you do that, right? Yeah, I was gonna put a plug that massive transfusion protocol is a great SIM scenario to run with your team. If you think about SIMs, they're used to train people on things that don't happen that often clinically, but they need to know. And to actually have people go and get the blood and have people set things up is a great scenario to run. So I'll throw that as a plug. I'm a strong- And with that. I need to step out. Thank you so much, everyone. It's an amazing discussion. Thank you. With that, we are gonna end this session. I appreciate all of our panelists. It's been a very, very exciting and great discussion on topics that are pertinent in our ICUs these days. So thank you all very, very much. Thanks to all our faculty and to our attendees. And tune in at 3 p.m. today for session number two with Dr. Fitzgerald, Dr. Randolph, Dr. Watson again, and also Maureen Madden, Dr. Madden from Northwestern. Great, thank you, everyone. Take care. We'll see you this afternoon at four o'clock Eastern time. Yes, right. Thanks.

critical care pediatrics

brain death examination

neuroprotective strategies

transfusion thresholds

massive bleeding management

standardization

ROTEM

cryoprecipitate

multidisciplinary collaboration