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SNI Digital, Innovations in Learning,
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in association with SNI, Surgical Neurology, International,
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are pleased to present in association with UCLA neurosurgery, Lyndon Liao, chairwoman, and its faculty,
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the UCLA Department of Neurosurgery 101 lecture series on neurosurgery in Clinical and Basic Neuroscience.
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This series of lectures are provided free to bring the advances in clinical and basic neuroscience to physicians and patients everywhere. One out of every five people in the world suffers from a
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neurologic related disease.
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A topic of this lecture and discussion will be new advances in pediatric neurocritical care. improving patient survivals.
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It'll be given by Jose A. Paneda Soto, who's the Director of Pediatric Neurocritical Care, and is a Health Sciences Clinical Professor in Pediatrics in the Division of Pediatric Critical Care at
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the David Geffen School of Medicine at UCLA in Los Angeles, California.
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The references in this talk were given with the presentation.
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All right, let's get started. Thank you. I wanted to say a special thank you to Dr. Pineda for coming to speak with us today.
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He joins us from Washington University in St. Louis and is the pediatric neurocritical care specialist here. And so hopefully we'll be spending a lot more time working together and you guys will
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become pretty familiar working with them. Thank you. It's wonderful to be here. I was sharing with Dr. Wang that we interact with you as every day, pretty much. So it's a very important
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relationship, a very important collaboration. And hopefully we can
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work together and make your life easier and make our kids better So together. So an introduction to neurocritical care and then at the end, a very brief introduction about how we are approaching it
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here at UCLA. So neurocritical care in pediatrics is a different breed, let's say, compared to adults. As many other specialties or self-specialties in medicine, we follow the tracks of
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adult medicine. Critical care, of course, started in adults Pediatric critical care follow in the '60s. Adult neurocritical care has been around for a few years. This is an outdated map already.
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But we're talking about over 100 freestanding adult neurocritical care units. And the last time I count is actually over 60 adult neurocritical care fellowship programs. They have more certification
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for that self-specialty now
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Our field is a lot. smaller, right? We're not going to grow to that magnitude, I think, because there is much less children who need neurocritical care than there is adults. But as pediatric
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critical care evolves, there has been an increase in the relative contribution of neurological disease to both mortality and long-term morbidity. Whether it be because children who will die at the
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scene and now arriving to the hospital and have a chance to try to survive their illness or their injury, or because of new technologies like ECMO,
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the number one cause of mortality and morbidity for children on ECMO support is brain injury. And then just in general, right, regardless of the primary diagnosis, neurological outcome has the
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largest impact on quality of life. I think we will agree on that, especially in a child, right, and children have a very high bar for where they define good quality of life for them. For example,
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social life being able to reintegrate into school, ride a bike with their friends is incredibly important.
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And we also measure our outcomes differently, right? We're looking at the next 10, 20, 30, 40 years of life, right? So sometimes when children are in the ICU or leave the hospital, they don't
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look very well. But one thing that we have learned as part of what we do, we follow children long-term after the ICU now, as much as we can, is that they always succeed our expectations, right?
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This child was suffered an episode of drowning, for example, cardiac arrest, and he didn't look good even a few weeks or a couple of months after leaving the hospital, but here is him on his first
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day of kindergarten, and he continued to progress.
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Now, if we focus now on the ICU environment, incredibly complex, right? And these children, they don't have a sense of humor. The brain doesn't have a sense of humor, as you know, it's very
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time sensitive, right? And on the, this panel on the, on the left of the slide, we have the, one day the ICU, right? That's the integrated ICU workflow. And on the right panel, we have the
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internal workflow of an ICU attending, right? 17 to 24 patients, usually all of them critically ill, and your attention is being pulled to all those patients. And I guess those of her who are
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biased towards the brain believe that children with acute neurological injury or illness need a special kind of attention to optimize outcome in the ICU. So that's where this comes from, right? A
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few years ago, 2018, There was a national survey of what a neurocritical care pro or who had neurocritical care problems, and what they look like, right? And it turns out that there was about 45
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children's hospitals who responded that they had a neurocritical care problem. 82 of them, though, was a neurology team who will consult in the ICU, right? That's what they call the problem. And
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when I asked the senior author, Robert Tasker, I think I wrote an editorial on this paper, or one of those back and forth with the authors. But I ask him, when you ask people if they had a
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program, did you tell them what you meant by do you have a neurocritical care problem? And he said, no, we didn't, because we don't really know. And that was kind of like a fair answer in 2018.
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But there also got my attention and the attention of others regarding, you know, we need to do a better job defining what pediatric neurocritical care is. So some of us started by asking, well,
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what is the population that we are dealing with? And this is interesting, and it's relevant to you.
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We look at
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130, 000 PQ patients from 123 PQs nationally, and roughly about 24 were there mainly for a brain reason. One limitation of this paper was that we only look at the primary diagnosis. If we had
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looked at secondary diagnosis, we probably will be even higher, but roughly it's about one out of three patients in the ICU are there because of a brain reason, right? They represented 30 of them
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were scheduled and missions to the ICU, mainly from the OR. That sounds very familiar. That's basically your patients, right? So post-op, the pediatric neurosurgery patients are an important
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component of this population, and usually they are in the ICU, or close monitoring observation. Usually there is not a lot to do, but when there is, there is, right? Post-op diabetes, incipus,
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seizures, all kinds of things. That's why these children come to us. In general, not so much the plan and missions from the OR, but in general, to the African neurocritical care patients have a
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higher mortality and more disability than general ICU patients in pediatrics. There was an editorial also written about this paper by our colleagues at Children's of Philadelphia. And it pointed out
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again some good opportunities. How can we, who are the high risk and low risk patients within this pediatric neurocritical care population? In other words, who are the ones that we should really
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give be putting our resources in and our attention too? And how can resources, resource utilization be optimized? Neuroimaging is
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one, right? sending a child on the night of. surgery to MRI when they're still recovering from general anesthesia with a nurse from the ICU is not a simple task, right? So are there opportunities
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for innovation with, for example, portable imaging that will answer our questions and keep us from having to move children in the middle of the night? So we're working on all that. This is a rough
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list of the main diagnosis that we deal with otherwise. These are not post-op patients, but you will commonly get consulted in these patients or in these situations. So that's what I bring them up.
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Trauma, of course, we're gonna talk about that. Very briefly, stereosepilepticus,
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that is not something that you usually engage with, but it's in
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2023, within neurocritical care diagnosis, stereosepil, refractory stereosepilepticus was the number one diagnosis in our
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ICU here.
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common. And then we have the post-op epilepsy surgery patient population who usually of course they are not in the status but they are also part of this population. This is just a status epilepticus,
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right? So something that is getting a lot of attention in terms of what is the optimal pharmacological treatment revisiting the toxicity of the medications that we use and then using innovative
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treatments for the super refractory cases, hypothermia for example, has been used in adults and we have some occasional good experiences with children that don't respond to anything else. I'm going
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to skip over the EEG monitoring approaches. Stroke is more as closer to
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what you get called for in the ICU.
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It's a big challenge in pediatrics, Right? Imagine detecting sorrow. neurological deficits in a two year old, right? So it's no surprise that the average time between onset and presentation is
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more than a day, which basically takes out the possibility of pharmacological intervention with TPA or any of the new medications. The most common causes are arteriopathies, infection, cardiac
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disease, and of course, sickle cell disease In sickle cell disease, in particular, the incidence of stroke is 20 times that of children without the disease. So in that patient population is very,
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very
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common, actually. And the question of when you have a severe case, right, with brain edema, concerns with intrachenal hypertension, decompressive connective as after a massive stroke, right, I
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would say it's as controversial, if not more controversial than in the adult world, right? And it's basically a case by case conversation between everybody involved, but it's not something that we
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have evidence for.
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Any questions so far, feel free to interrupt, ask questions.
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Several business from Boses, much more common, right? The mortality is only about 3 And
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the recurrence is about 6, but that is with treatment, right? If left undetected or left untreated, it's an entity that can have horrendous complications and high mortality, right? And of course,
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there are recommendations on how you treat this. What those recommendations don't
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include is, what do you do with the really difficult, unique cases? of which we had one last week, right? A child who was playing soccer, fell, developed, you can see the right-sided
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sandestrombosis.
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And he also had this infra-tentorial epidural hematoma, right? You are not gonna fight guidance for how to handle this on any guidelines, right? And it was basically a daily conversation with Dr.
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Wang and the ICU and the neurosurgery team and neurology about how do we approach this? How do we time anticoagulation? What are we looking for? So that's basically how
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we handle those cases.
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You know, we have to go as the patient dictates in a multidisciplinary approach.
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Cerebral vascular abnormalities are common? Yes, question
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Yeah, it was fine.
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Yeah, it's in children as cerebral venous robust is most common causes are dehydration, infection, trauma, and I think with trauma it's more common than we wish, it's relatively common. The most
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common presenting symptom is seizures, which he had, right? He was he's having a little fracture, but he actually didn't even seek medical attention initially with the anesthesia and and that's
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those along with the literature.
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You know, certainly with many conversations over the weekend about this patient, yes.
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Vascular abnormalities, you know, AB malformations, aneurysms, also more common than we think, and a place that like UCLA, my sense is we see even more than other places because of the
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reputation And the fact that, you know, if it was my child with an almighty in the brain, I will bring them here, right? Do you want that expertise from the adult world to be spilled over to
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these cases because we don't see them every day. Like you see an adult almost every day, right? Couple of things about it. Basal spasm is as common as it is. In as common in children as it is in
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adults after certain types of superino hemorrhage.
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We don't have a magic bullet for it, but there are some serious that have reported success using millerinon in children, which is also using adults, right? Not, I wouldn't say the most popular
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treatment or the most effective in adults, but in children are very limited experiences is mainly with millerinon. Nymodipin, extremely difficult to those in children. It's all, or also the
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absorption is erratic and for babies under six months of age or so, the kinetics are quite tricky.
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But basis pass does happen. This is a picture of a patient of ours who had an aneurysm exploit when he was playing soccer in St. Louis. That's David Limbrek who used to be there. And, you know,
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he had a good outcome, as you can tell. And you look at the MRI, right? But he did have some basis pass that led to secondary insults and some ischemia that we wish we had been able to prevent.
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So it's as much as a big deal in children as it is in adults. We use transcranial Doppler to screen. The
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gold standard, of course, is neuroimaging to diagnose it. One caveat about TCD in children is that the solvable velocities, all the parameters that we get are age and gender dependent. We're
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gonna talk a little bit about that, more about that. Extra-course, boreal support. I mentioned briefly that the number one cause of death and disability in children on ECMO
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And it's a combination of thrombotic or hemorrhagic injury. And you're gonna get called about these cases. And because it's really, we understand that 999 of the time there is nothing to do, but
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it's just very frustrating. So out of desperation, you're gonna get that call, is there anything we can do? The implications are huge. That child is gonna have to come off ECMO and likely is not
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gonna survive if there is a catastrophic or a significant brain injury. Needless to say ECMO requires anti-equagulation, although that's changing, but able to do a lot of extracurricular poreal
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support now without anti-equagulation. So asking that question, can you stop the heparin? The answer most of the time these days is likely gonna be, we already did. And then we try to go as long
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as we can without it It's an area of active research, as you can see here. This is a baby who was on ECMO for adenovirus sepsis and he ended up having a big stroke, but likely related to his
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adenovirus more than anything else. But as you can see, the kidneys, we can monitor closely or replace with the machine. Same thing for the lungs and the heart. The brain is an ex-frontier with
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this type of approach. So we're actively working on that from the research side
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This is a
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cerebral vascular study on the baby, three months old with meningitis, right? A big challenge, right? You're also gonna get asked, you know, is there anything we can do? There are signs of
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intracranial hypertension. We used to call it basis plasma, but it appears that it's more arthritis, right? Information of the blood vessels. And as you can tell, it can lead to catastrophic
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vascular disease and brain ischemia.
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Um, with a lot, a lot, uh, very little to do, uh, monitoring ICP in meningitis is controversial. Um, it's not something that we even do routinely that I don't think we will do it. Maybe on an
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exceptional circumstance, but in general, um, it's not a, a process that is reversible enough, right? Uh, there are also concerns about, uh, the type of therapies that we use to control
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intercranial hypertension, like hyper-smaller therapy, when you have a lot of vascularopathy or, uh,
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vasogenic edema, will we make, be making things worse by giving those therapies, uh, instead of helping? Um, we do think about steroids. Sometimes we see these cases early to try to decrease,
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decrease inflammation, but there is not evidence to support that, uh, in the classic sense of what we mean by clinical evidence. Um, neuromuscular disorders is I guess less, less relevant for
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what we are, uh, talking about, but I bring it up in the sense that children with, for example, neuromuscular disease who would not survive past a couple of years of age in the past, now are
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surviving into the teenager years. So in an effort to improve their quality of life, spinal fusion cases, for example, are gonna be done these days in some very vulnerable patients, right? There
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is spine vasculature when you look at it, is different, is abnormal. It looks like a spider web sometimes. So those children are gonna come to the ICU and based on what was observed in the OR,
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with let's say, with no spinal monitoring, we will agree on a target for perfusion pressure, right? So it's data-driven. That type of collaboration between the OR and the ICU makes a big
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difference for these patients. And then we have trauma, right?
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It's like this silent enemy is always there. We don't get cases every week. We're not a very active trauma center. But when we get them, we have to be ready to act as if we saw a case every day,
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right? Because those kids need, there is certain approaches to their care that is gonna make a big difference in their outcome.
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And then these are just some statistics, a couple of cases. I used to have this contest in St. Louis with an neurosurgery residence as to who could guess what kind of card that was. And then I
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will offer a bottle of wine, only one time somebody guessed correctly.
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Now, on top. No, please. It's a key.
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That was a 4F
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150 versus a 3.
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I don't even recognize. So this was one of our severe head in your patients. We're going to talk more about him. In a nutshell, you deal with this all the time, right? You know, about the
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guidelines and management of severe TV. So we're not going to spend a lot of time on those details, but more like from the big picture kind of perspective. We've been looking for the magic not a
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protective drug for 57 years old longer than that. It seems before I was born, and we still don't have it
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But what we do have is ICU care that leads to better environmental and physiological support right to prevent secondary insults And if you look at outcomes. from the 60s when mortality for severe
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head injury was 60, right? Now
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mortality for pediatric severe TBI in a center that is dedicated to it is less than 5, right? Not because of a drug, but because of the care, much of which actually the original adult guidelines
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and everything came out of here, right? There was a lot of big TBI tradition here as you know.
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So the basics, right, what we mean by secondary insults, when you have head trauma, there is going to be primary injury and secondary injury. Primary injury is going to happen at the scene,
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right? Prevention is the only solution for that. Not much we can do a couple of caveats, right? In the baby, and well, maybe I should say an infant, child less than two years of age, the scalp,
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the scalp, out represents. a lot of body surface area, right? And it's very well-perfused. So it's important to remember when you arrive in the ER and say, well, this baby was kicked by a horse,
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right? Maybe their brain injury is not the worst, although it can be pretty bad in those circumstances, but they can exangulate from a scalp laceration, right? Or experience a hypotensive episode
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because of bleeding that is gonna make their brain injury worse. So it's just something to keep in mind And obviously, hematomas, right, epideral hematomas, I used to remember what the record was
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for this child. It was minutes from arrival to the OR and evacuation of this hematoma and she left the ICU in three days a week. And that's what we could tell without deficit. So that type of
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primary injury is can deal with very effectively, right? Secondary injury, I have a different perspective on that, Everything that happens at the scene, the original trauma, we're gonna be
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treating after the injury with a therapeutic window that is closing by the minute. And that in some cases, it's extremely short. Secondary injury, right, as we think of it as injury, is
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happening in the ICU, sometimes in the future, right? So it's a very different therapeutic window. We can even get ahead of it, or we can treat it immediately, or we can prevent it, right? So
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the focus and the progress that has been made in treating severe TBI is from treating or preventing secondary insults. And we're hoping now that pharmacological approaches, maybe we're not as
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effective in treating a brain that has been mechanically injured, but we may be able to protect patients pharmacologically. against secondary insults, which even in the best hands, there is gonna
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be always a degree of exposure to those. I'm talking about hypotension, increase intracranial pressure, seizures, hyponatremia, for example, hypercabnea with hyperventilation. Those are the
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main ones, hypoxia, of course. So we're gonna get a little bit into that. This is a paper that we published in 2013.
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When I got to St. Louis, before I was there, I had a basic science lab. And I was hitting little rats in the head to study brain injury. And the chair there told me, you know, to say everything
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that you find out in the
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lab in
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rats, you don't have to ask if it's true in children, right? And he was very persuaded, you can tell. So why not just study children? right, and let the good people in the lab do their thing,
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but you focus on clinical research, I will support that. And I said, well, if my lab is gonna be the ICU, I need to decrease the noise, right? That I had learned in the lab, if there is too
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much noise in your model, you're not gonna find a signal, I said, right? So we did that for a few years. And one day my division chief said, You know, we've been doing this for a while. Why
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don't you see if it made a difference in outcomes? Right, and that was this paper It turns out that standardizing care, having a multidisciplinary approach that focus on the published guidelines at
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the time, decreased mortality by 70, but more importantly, improve outcome in survivors at discharge, right? And the effect size of that approach was basically as large as we would dream of with
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any neuroprotective drug in a lab So my chair was right, right? paper, shake things a little bit, got some attention. And since then, many places have reproduced this, which is reassuring.
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Actually had a slide about that, but moving on to, so what was this, right? This, I meant to mention this graph here. One of the things that we observed was, children in this cohort got ICP
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monitoring earlier and for longer And when we quantified their ICP-directed therapies, there is a scale for that called the pilot scale. They also received more intense ICP-directed therapies,
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right? We didn't completely raise their exposure to intracranial hypertension, but we were very focused on that. And the longer monitoring, we think it was because we had a consensus approach and
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went to back off and instead of having it arbitrary. So that was that. Secondary insults that we focused on many years ago, And this is 1997.
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And this was a very important study that answered a few questions. This was done by Dave Adelson, a pediatric neurosurgeon and also a good friend.
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Children are a hyperimic when they are young, right? Sure, I cannot have said Dave Adelson, good friend.
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Oh, we're trying to bring him over to give him round rounds one day Yeah, wonderful. So he pointed out that children were hyperimic, that's normal, right? But that information led to the
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approach of hyperventilating children, especially many years ago, right, to decrease their intracranial pressure, right? Turns out that it was not a good idea because they were not hyper, they
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were not hyperimic because of the injury, they were hyperimic because of their age and gender, right? So this isn't the study in Germany. Classic scenario, your ICP is 44. You gotta do something,
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right? CO2 is 45, CPP not too bad, 54. Cervival flow, this is seen on CT, right? 59, which is slow, but sort of decent, right? That's global perfusion. The patient was hyperventilated,
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and then they repeat the scan, right? PCO2 is now 30, ICP is 15, right? The CPP is luxurious, 82 But look at cerebral blow flow, right? 14, that's the level that we see in an area that has a
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stroke, right? Or is it a penumbra area? And the fact that that second picture is black is not that it's a black, bad picture, is there is no cerebral blow flow, right? Very hard to see. So
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that's what hyperventilation can do to children with severe TBI. Going in reverse translation, many years later, or a few years later, there was this study in rats that if you control everything
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and hyperventilate, you kill cells in the hippocampus, right? Actually, two studies, Dave's and this study were pretty close, but we kept hyperventilating for many years. This is an example,
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fast forward 10 years, 2008, Monica Babylala in Seattle. She showed that hyperventilation was still happening, right? And it correlated with mortality, not even worse outcome, mortality in
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children with severe TBI. And one interesting finding is that most, if not all of these hyperventilation episodes were unintentional, right? So the guidelines will tell you, if a patient is
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herniating 100 oxygen transient hyperventilation until you do something else, right? And then you back off. But that was not the case here. They were just the ventilator change Somebody was not
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paying enough attention, CO2 was 30, that's what we're talking about. So that's something that we should be able to fix in the ICU, right? So if you see an entire lot of 25 in a severe TBI
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patient in the PQ, ask what's going on. It may make a big difference. Hypoxia, right? Hypotension is pretty obvious, right? If you don't refuse the brain, you cannot preserve it. But hypoxia
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is kind of freaky because it sneaks by under the radar, right? The reaction to a saturation of 88 in a patient with severe TBI is not the same as the reaction to a systolic blood pressure of 80 or
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75, right? One is an emergency, the other one, well, let's fix it. Turns out that the impact of a secondary insult of hypoxia is as bad or worse than hypotension in these patients We do this
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study where we look at a group of patients and try to understand under which circumstances they were hypoxic. And then we simulated that in mice. And what we found was that hypoxia, when everything
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else is controlled, was producing a lot of axonal injury.
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Acceleration is a 90.
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And then hypotension, right? Just to make a very long, long, long story short, is the story of hypothermia and severe TBI You can cover this wall with preclinical studies showing that hypothermia
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works as an neuro-protective strategy, right? And there were some early studies in humans that suggested the same thing. So there was these big trials, right? And they didn't work.
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So in adults, depending on where you went, right? Hypothermia could be harmful or beneficial to outcome.
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This is in adults, The general happening is the centers that had an approach where they will restrict fluid in the management of severe TVI, keep the patients really dry, they had a higher
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incidence of hypotension. And that erased the beneficial effect of hypothermia probably in those patients. During rewarming, you also dilate so hypotension can even get even worse. The story is
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not that much different in children. There was a huge trial in Canada of hypothermia for severe TVI, same story. The incidence of hypotension was higher in the hypothermia group. And we believe
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that that erased the beneficial effect of hypothermia and TVI in children. Then there was in 2000, a
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study in rats, right? The same story that was observed in hyperventilation. If you induce hypothermia after severe TVI in rats, And then.
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and give hypotension to one group but not the other, you erase the effect of hypothermia, even in an animal model. So very powerful
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effect of
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secondary insults on severe TBI to the point that it changed my career, right? I was very focused on finding that neuro-protective drug and I was like, I'm gonna be doing what everybody did before,
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throwing this little dog to fight a bunch of wrecks, dinosaurs in the jungle, right? We really need to create a better environment than the ICU with that minimizes the secondary insults to give any
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of those drugs a chance to work, right?
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So that's basically a story of how pediatric neurocritical care can improve outcomes focused on TBI. Obviously, a problem is more than just patients improving outcomes as the main reason we will
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have it, but there is more to it, right? So this is the effect immortality that I talk about, right? And the paper was published around here. And what was nice to see is with the exception of
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this year that effect on outcome and mortality persisted, right? It was sustained. And this is just the research that has been going on, right? When we asked our senior mentors, you know, how
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do you develop a new field like pediatric neurocritical care 10, 15 years ago? They said, you do it by doing something else that nobody else does, right? Something different. How do you find out
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what is different, what is innovative through research, right? So, a pediatric neurocritical care problem is not such a thing unless you have any, you're doing research on these patients and
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trying to do more unique things. That's the slide that I was looking for, how these findings were reproduced by others. This is Jay Welland said, at Vanderbilt, and they basically call and say,
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Give us your protocol, we want to see if it works. in classic J. Wellens fashion. And then they implemented it, the same effect in mortality and the same effect in outcomes in survivors in
37:04
Vanderbilt. So that was very reassuring to see. Big picture, right? This is a bunch of pediatric trauma centers and going from the left to the right
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centers that are
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American College of Surgeons certified and monitor ICP in children with severe TBI routinely have better outcomes in terms of mortality, right? Predicted versus observed mortality are supposed to
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match, right? You see that here towards
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the right side of this graph. One important caveat, what about babies with an open fontanelle, right? Can they experience increased intracranial pressure? That's something that has persisted over
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the years to believe that they don't, but they do, right? up in sutures and up in font and there's My bias sometime, right? But if swelling is enough and the young brain swells more, the dura
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doesn't expand, right? So it's not uncommon that in little babies, when you put the monitor and the ICPs and the thirties with a wide open fontanel, that can be misleading, right? Sometimes it's
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just full, it's not bulging, it's not pulsatile, but well, the pressure is really high.
38:18
Challenge for that is, this is, you
38:22
do brain oxygen monitoring in adults here with severe TBI or used to, right? So we did it for a while in children in St. Louis. If you were at the nature, it was fine, but can you imagine trying
38:34
to do that in a tumor tool, impossible, right? Even a chameleon monitor, that single fiber optic, is a big deal in a baby. And the challenge there is that the technology that we have was
38:46
developed for adults, right? There is no, there is not such a thing as an infant. intra-perinkeeper ICP monitor, right? That makes a challenge and may explain why only 50 of infants who meet
39:02
criteria for ICP monitor in actually get a monitor, right? And needless to say, they have worse outcomes and they have higher mortality. But there are technological challenges.
39:16
So what about non-invasive monitoring of brain perfusion? We're working on that. Hopefully by next year, we're gonna be testing new technology and collaboration with Caltech. But what we have now
39:25
is really not very helpful. Meers is very popular. I'm sure you have seen that at the bad side. It only penetrates about a centimeter and a half, right? So if you have a patient on ECMO who is
39:35
very swollen or a trauma patient with scalp swelling, that infrared light is probably measuring something in the skull, right? So we don't really have anything non-invasive that is reliable, that
39:51
we will really. be confident using these days,
39:55
but it's being developed. This is just an example of patient on ECMO. I noticed the ECMO pump caught at some point because of technical challenges, and the nearest didn't change. Had blood
40:06
pressure, of course, dropped. So we don't really have good non-invasive technology for children these days.
40:13
Another caveat, this is
40:18
the classic picture that you see on your textbooks of cerebral blood pressure out of regulation. And this is the normal range of blood pressure where you can maintain your cerebral flow. Most people,
40:32
when you reach about 160, that's when you lose cerebral blood pressure out of regulation and flow becomes passive. And you know, the implications of all that. And then you have the same inflection
40:43
point on the other side where you can no longer maintain cerebral blood flow with a certain blood pressure and then it starts dropping. That's a smoother line that looks really nice on textbooks,
40:53
right? This is the original data that led to that figure, right? And as you can see, there is a lot of individual variability. So 160 works for most people, but not for everyone. Same thing on
41:08
the other side of the curve, right? Most people probably can maintain cerebral flow with a map of 50, 55, 45, but not everyone, right? That's why we need better technology to actually measure
41:21
cerebral flow or brain oxygenation in these patients. The Lycocs, which you're very familiar with, has been used in children. There are a few published papers and it's basically the same dress
41:32
holes as in adults, right? Anything less than 25 is concerning. Every minute you spend below 10 is gonna worsen your outcome or your chances of good outcome.
41:43
This is some studies that we deal with MRI, measuring the oxygen extraction fraction. in the brain after severe TBI. And basically the brain shuts down, or oxygen extraction fraction shuts down
41:57
after severe TBI. But the lower it is, the worse the outcome, right? And it's not due to hyperimia. So something is going there. And what I mean by that is simply maintaining perfusion to the
42:10
brain is not gonna fix everything, right? So that's why we need to continue to do research about this. I have these pictures of my daughter She's now 24, I think even the last picture is outdated.
42:22
But one challenge that we have is ICP dress holes, for example, serial oxygenation, the dress holes, the numbers that we use are the same when she was this young than when she's this old, right?
42:36
Her brain has changed a lot in that period of time. So we need to better understand the developmental implications on brain physiology when we treat these patients in the ICU.
42:51
This is a study from 2015 in Cambridge in England, right? What did the number 20 come from? Does anybody know? How did we decide that 20 was the dressful for intracranial pressure?
43:08
Exactly, right?
43:12
Yeah, it was epidemiological data, right? And I have to say it was quite good, right? Because when you pass forward to 2015 and you look at super high resolution data, various sophisticated
43:26
analysis, right? This is adults on the left, children on the right, and they look at, they actually measured the number of minutes you spend about any dressful. They didn't pick a dressful.
43:39
They said, let the data give us a dressful, right? And outcomes, right? Controlling for relevant confounders, of course. And the number was 20, right? time that you can spend about 20 if
43:52
you're a child or a adult is very limited. And then they went one step forward, right? And said, what about auto regulation, right? If your blood pressure auto regulation is disrupted, right?
44:08
The amount of time you can spend over 20 or below 50 for CPP is about zero minutes, right? You just don't tolerate it. And that may be because there's the the the stressful for cerebral perfusion
44:21
pressure that maintains the level of flow, if your auto regulation has changed, it's different, right? I have a patient many years ago, T bone accident, and her brain oxygen tension was like
44:33
five, right? And her CPP was 55. ICP was well-controlled. What's going on here, right? So we increase her CPP by five points from 55 to 60, Your brain oxygen tension normalized, right?
44:48
Whether it makes a difference, that's the boost trial, right? That we are part of and in adults and it's going on, we'll see what it shows. It's probably not gonna help every single patient, but
44:57
the patient with disrupted out the regulation in when you can improve cerebral perfusion might be the one who benefits from that technology, right? She went on to become an occupational therapist.
45:10
Spinal cringery, right? Another example of something that we don't see every day that we actually rarely see, but we're expected to be prepared to perform as we saw it every day, right? 'Cause
45:24
that kid also has one chance to have an optimal outcome. Early surgical decompression steroids, you name it, right? A lot of things have been tried and we don't have a lot to offer, but good
45:38
supportive care hopefully will continue to improve outcomes. This is one of our patients actually, you might be familiar with him horrible injury One thing that we do know. It's one of those cases,
45:49
steroids, right?
45:51
The effect shown in the initial clinical trial, it was one, was actually weaker than we believe, right?
46:00
And it's not being reproduced. What has been reproduced is a lot of side effects from using steroids. So this is a paper that I commend our colleagues in Cincinnati at Cincinnati Children's
46:13
orthopedic surgery, neurosurgery,
46:18
where they look at their experience using steroids for spinal cord injury in children. And it was so, let's see, the word disappointing to them that they took it off formulary, so that nobody can
46:31
do it, right? High, higher incidence of side effects and a bunch of children who didn't have injury and met enough to meet criteria to get steroids, got them too, and got side effects, right?
46:44
basically the pediatric approach this day is consistent with the adult ganglant recommendations that steroids are not indicated after spinal cord injury and it thoughts on that any different
46:55
perspectives
46:58
but it still comes up right and I think it's out of desperation people will call me and say can we give steroids right it it comes up uh this is probably just what I mentioned right idiopatic
47:09
scoliosis even but uh these patients depending on the patients sometimes do need ICU monitoring um to avoid complications uh revisiting sedation right um we don't like keeping your kids in a medical
47:23
induced coma right but um try to keep a six-year-old in the bed with endoc - an endotracheal tube a bolt an angi tube etc etc and they may be in pain uh so sedation and analgesia are inevitable in the
47:38
ICU but we are rethinking it right because these medications are right, to the normal brain, to the healthy brain. We know even less about what they do to the injured brain, right, so we are
47:52
trying to optimize our approach to sedation. Every drug is basically a poison to the brain in children, propofol, right? This is in newborn monkeys, and all those little black dots are dead cells
48:06
from one dose of propofol, right? So giving these drugs to the immature brain at the wrong time can have significant implications.
48:16
Just going back into, so what can we do? What do we have to offer, right? High-grade resolution monitoring the ICU and, the ability to look at trends.
48:26
This is one of our TBI patients. When we plotted the ICP every 60 seconds and then somebody, God bless them, manually overlapped every single therapy that we gave, right? To see what happened,
48:39
right? And we learn things like, for example, If you give money to the same child or the same education. seven times the response is different each time to the same dose of mannequin, right? So
48:50
we cannot just give it and walk away because it worked the last time. Same thing for sedation. This is a paper that we published almost 10 years ago now. Our nurses said one day, you know, those
49:00
boluses of midacetam and fentanyl that you ask us to give all the time is so frustrating, they don't do anything. Like what do you mean they don't do anything? Well, the ICP doesn't change or it
49:11
goes up. So we did a study, right? We were very careful for controlling for other interventions and our nurses were right, right? Medasolum and fentanyl increase ICP exposure in this cohort by 37,
49:26
right? And then I look at the literature in adults and there is a few reports, especially with fentanyl. And the thinking is that when you have decreased compliance in the brain and you give a big
49:36
dose of fentanyl, you have systemic vasodilation, blood pressure goes down, CD-RO Basal Dilation, right? increase the river below volume, increase ICP.
49:47
So the moral of the story here is, if you give a bolus of pentaneer adenylasin when it doesn't work, right? Based on data, chances are, it's not gonna work the next time, or the next time, or
49:58
the next time. Think about what else could we do? This patient probably is already saturated with sedation too. This
50:05
is just an example of this approach. We had an NIH-funded grant recently. You just finished, so we're going to the next phase, but the way that you display data is important, right? And you have
50:16
seen this in the adult neuro ICU here. One thing is to see how the patient is doing, right, in rounds in the morning. Oh, it's going well. All your data is in your head, right? And that has
50:29
limitations. So what about rounding in the morning and say, how are things going? Well, here is the trend, right, of ICP or CPP. Take it one step further. This is the percent of time in the
50:40
last shift we spent about the rest of all. or below the threshold, right, as a graph. People get that a lot
50:48
more, right? And there is more literature coming, showing that this approach actually improves outcomes. They call it, I don't know. It's not the word that I will have chosen, but supervised
50:59
physiological management. Like for somebody is watching and saying, your ICP exposure double in the last 12 hours, what's going on, right? Is it the patient or is an opportunity that we have to
51:11
do something?
51:13
Talk about the research. And then part of our research now is includes implementation science, right? Many times we say that we start a program, but it doesn't make a difference, right? We lose
51:27
momentum. But if we take an implementation science approach from the get-go, we need to have the metrics to first objectively demonstrate whether it's making a difference or not.
51:41
ask ourselves if it doesn't, why, right? What is the opportunity to make this well-intentioned approach at X or Y institution work better? So we're focusing a lot on that. So in summary, right,
51:58
pediatric neurocritical care is a quote unquote to small population, but it's 30 of our ICU population, probably more. We measure outcomes differently because we need to track them for a long time
52:10
over development. As we build this workforce for pediatric neurocritical care, the approach is going to be different than adults, right? We don't have the volume, it's different. There are,
52:21
however, already 14 problems in the country where as a pediatric intensive is sort of a pediatric neurologist, you can decide to focus on neurocritical care and get some extra training. But it's
52:34
going to be very different from the from the adult world
52:39
But hopefully we'll have more. brain bias people in the ICUs for you to work with in the future.
52:48
And it has to be a multi-disciplinary approach. When people ask me, what is a pediatric neural intensivist that said, I don't know, it doesn't exist, right? It's a good intensivist who knows how
53:00
to work with a neurologist and they're not a surgeon because that's what these children really need, right?
53:10
And then this is just what we mean by outcomes. I think that's my last slide.
53:17
Yeah, this is just more basically what our goals are. So what we're doing here,
53:23
we did over 30 interviews, some of you participated in those interviews. We're actually doing it at three institutions, trying to find out from the system dynamics point of view what is a good fit
53:36
for a given institution, right? And we had in that Study, we have UCLA. CHLA and Mercy Children's Hospital in Kansas City. They're very, very different, right? Through this approach, we're
53:48
trying to identify common factors that every neurocritical care program will benefit from. And we're also trying to find things that are unique to each institution. So you have to approach them that
53:59
way for things to work. So for now, right, what the conclusion was that at UCLA because of our volume and use our environment in general, well, we need this collaboration from a consult with a
54:13
pediatric neurocritical care consult service, right? We chose five diagnosis. You can probably guess which one those are. TBI is one of them stroke or any intra-cannial hemorrhage, post cardiac
54:25
arrest care, which I didn't talk about, severe spinal cord injury. So is those or any case that is
54:35
challenging and you know, you would like to discuss but basically when we. decided to go that way, we had an implementation team that included Dr. Fala and Dr. Giza, and we have an operational
54:47
team that includes you, right? So the expectation here is that I will be there to support you in the management of these patients, not to detect what to do, but to make sure that what we intend to
55:04
do actually happens, right? That's called the therapeutic gap, right? And one of our goals is to close that therapeutic gap, right? It's never gonna be perfect, but we wanna make it better
55:16
because we think it's impactful. And, you know, it cannot be a one-man game, it would not be sustainable, right? I love it, you know, I get calls from here and from other places all the time
55:24
and I don't mind, but we wanna have a real team, it's more than one person. So we're training two of our junior faculty who already have a background in neurocritical care from DC children to,
55:25
yeah.
55:40
grow the team so that somebody is available
55:45
247 to follow those high risk patients as a consult
55:52
service approach. So that's kind of like where we are.
55:57
Communication is still through the ICU, right? I might reach out to you or like with - I had conversations with Anthony over the weekend about this very challenging patient, right? But one of the
56:10
important things here is I don't want to get in the way of communication between you and the ICU. That hasn't changed. It's like a supportive role. And if I reach out because something is not clear
56:21
or because we have a real challenging patient, I make sure I communicate that with the ICU and preserve those lines of communication between you
56:33
We hope to grow it too with more educational opportunities and maybe, you know, how they have leave it rounds in the PQ, why not have neurocritical care rounds once a week when they talk about our
56:43
patients there.
56:46
All right, that's all I have.
56:54
Have a good day. Have a good day.
57:01
What's the age cut off officially for maybe 18 year old, 20, 19 year old, has a bad TBI, so which ICU units they should go and kind of the interplay of the neuro ICU, the daughter ICU versus her
57:16
team. So the question is, what's the cut off for neural trauma, adult ICU versus piggy, right? One hard cut off is 14 years of age, is piggy and that's dictated by national trauma guidance and
57:35
giving it a little bit for that, right? We have a bunch of 10 year olds and your adult ICU that's not consistent with national practice. 14 to 21, this is still a child, it's a little bit more
57:49
vague, right? but there are some studies at least two or three showing that. adolescents who go to a pediatric trauma center with the BMTBI do better right not sure they didn't that's you know
58:07
explaining why so he's a is a little bit arbitrary you know if you're 17 and you have a good T and that's it too you're gonna end up in the adult I see you and that's fine right if you are 17 and you
58:20
look at your 12 which some children do you're gonna end up in the PQ right and one day I look I wanted to expand my research with treatment so I look at bars you wish right and see well how many
58:32
teenagers are going there that I could recruit and it was about 17 upper pediatric semi - TBI population so I started working with with Bauquic here they have a trauma there to work together at least
58:46
in the research part but so to answer your question officially 14 we went 14 and 21 is a little bit big. Yeah.
58:57
I think you have, Sergeant.
59:01
I have the opinion. There are children born from the addicted mother and they go with seizures. You're admitted, because I know at Children Hospital they see these seizures. Do you take care of
59:14
these case babies with a drug addiction's mother? And how long do you observe them? Because they go to seizures. That's my understanding is Yeah, like the mother. The mother is the drug addict.
59:29
You're on pain or something. Right. Those babies usually go to the NICU. The neonatal intensive care unit. OK. Yeah, so we don't see them. We see around withdrawal and abstinence in the PQ,
59:41
but that's from our own sedation approaches. But babies who were born and exposed to narcotics or something else in utero is in the neonatal intensive care unit. Yeah. And can you comment on that?
59:55
things goes because from time to time I have. and I know they come from hospital. Yeah, yeah. Children in hospital, what's the big take care of that? Yeah, no, I wish I could comment more on
1:00:07
that, but I know that there are neurologists who specialize in immunonorrology these days. And it's also an evolving and growing field, but do we have something groundbreaking that is being spoken
1:00:22
in the pediatric community about that problem, not that I'm aware of, but it's having work at that age? Yeah.
1:00:31
Are there kind of key differences in the management of intracranial hypertension that we should all be aware of? I'm thinking specifically of stuff like what defines intracranial hypertension,
1:00:42
what are cut offs or that sort of thing for treatment? And then also kind of differences in management, a hypertonic saline and manatol. You know, five years ago there was some literature that was
1:00:53
just coming out.
1:00:56
Are there any key differences that we should be aware of? Yeah, you know, I'm ready, brother. So there was this huge perspective, a study called ADAP, and we were part of an umbrella with 1,
1:01:05
000 children with severe TBI.
1:01:08
And based on that, we learned that hypertonic sailing, if your goal is to go ICP where appears to be more effective than manito in children. So it's basically probably going to be coming the first
1:01:22
line therapy. We still use manito occasionally, but it's 3, which, by the way, works in two ways, right? And you give the volus of 3, usually 5 per kilo of the 10 per kilo of children.
1:01:37
There is an increase in cerebral bone pro. There is vasoconstriction and ICP comes down that way. Does he acute the pain, right? But if a child has persistent either kind of hypertension and you
1:01:47
want to create a small ingredient to decrease it, that requires to soluble in the high 150s, right?
1:01:56
time. But what has been shown is that once you reach that the smaller gradient, the height of the peaks of ICP and the frequency is less, right? So it's effective and appears to be more effective
1:02:08
than magnitude. The other thing is CSF, you know, and I was a co-author on that paper, but I was a little bit,
1:02:16
not 100 happy with it. So we showed that the brain seeks that the person is not in children with CVI didn't make a difference in outcomes, right? It lowered ICP a little bit, right? And my thing
1:02:32
on that is if you look and as you are a patient with severe TVI and an EVV, right, they are open to the brain and there is nothing coming out, right? So having an EVV or an EVV open to the brain
1:02:48
doesn't equal CSF damage, right? If it's not happening, it's not going to impact outcomes. So that's, I You know, putting a DVD in a child is more challenging than doing it in an adult. There
1:03:03
is that paper that says that it doesn't make a difference. But I think if you have the expert he is, which I think we got here. And then you see a safe to drain. It may help help, you know, have
1:03:14
to escalate other therapies as much. Besides that, you know, the dress will is 20 people talk about a dress full of 18 But I don't think that's, that's well supported. Very different is this a
1:03:27
liberal population pressure dress, because his age, the pen, right.
1:03:33
CPP of 40 or less is really bad regardless of age, whether you're three or 15, a CPP of 40, you're getting a secondary insult Whether 55 or 60 is what a 12 year old needs, we have arbitrary
1:03:51
recommendations by age, right. But I don't think we know for sure. out of regulation with nothing else, right? So I think there's a conversation that we need to continue to have. We pick these
1:04:03
arbitrary address holes by age, but we need to keep an eye and keep looking for better ways to ask is this the right CPP for this child at this age, right? For one, I think we need, we have the
1:04:16
capacity. I wish we could implement and we will, real-time assessment about the regulation, right? Just as a mathematical rolling average, so that you need later every 15 minutes so that we can
1:04:29
pick better, more educated, age-dependent rescuers.
1:04:34
Besides that,
1:04:37
you know, I think some children actually expectations when you see their injuries, I actually had a couple of pictures that you saw the bullet, right? They went through the brain, didn't destroy
1:04:48
anything bad, you know, the triangle of death that they talk about in the military. That child, the last call that I got from his mother, she was really worried because he wanted to get his
1:04:57
driver's license. But we managed his high speed for like 14 days, right? That the bullet creates this expansion and compression. Horrible, but he did really well. And the other kid with the
1:05:10
F-150, he had a
1:05:14
chasm in the trauma bay, couldn't get their hair away. He became oppressed, right? And he's doing really well So yeah, they, subjectively, I was saying that we pulled them out of the hole in
1:05:27
this whole life that can be ready for probably 30 years, right? That's another difference, David.
1:05:37
Wow, one final question, kind of fine. I think what's being done is really great. I think we've had some experiences where you have some bad TVIs or Apple, since we've shown you have big Q kind
1:05:48
of the role of, like, the neuro ICU. Thank you, which is us. not always disconnect, but it's hard to be, pick you a lot of times from kind of the further, certainly for to, like the neuro ICU.
1:06:00
Do you see the role for the neuro ICU on some of these animals and child children that may be in pick you? They're not quite young children, but they're not quite adults. And kind of what role the
1:06:14
operations role or something like that? Yeah, yes, they have a role. So if you look at the studies that I show you including my own studies, most of those patients were adolescents, right?
1:06:25
What's up, when I say I manage TBI, I'm speaking mainly about adolescents, right? So we do have the expertise, right? If you call Paul Bespin and I talk frequently, obviously, right, and
1:06:40
money, money blanco, right? Our approach now is, if you call them a lot of fake you patient, they're gonna say call the said, that's the agreement that we have, right? If I am in the people.
1:06:53
this kid that we had, you know, with self-titorial epideral tingatoma and Alzheimer's diagnosis at the same time, you know, I just wanted to make sure I was telling Anthony the right things. So I
1:07:04
called Paul myself and I discussed the case with him. So when you guys talk to me, you're not excluding them, right? What a team. And I'm the kind of person that you, if I tell you something and
1:07:17
say, you know, will you run this by Dr. Bespin and this teenager? I will absolutely do it anytime. Right, so that's kind of our approach now. Before I came, I think they have, they were more
1:07:28
engaged with picking patients. As far as you guys and they pick you and everything, you know, that's such an important relationship. I think those outcomes in DDI that we had in St. Louis were
1:07:40
because of the relationship with neurosurgery. In fact, this was a little unconventional. What I did is the bad way that we have the bad side, one page,
1:07:50
was written by of the surgery residents, right? and edited by the PQ and endorsed by the PQ, but it was written by you guys, and then included the section there, when do we call neurosurgery,
1:08:01
right? So when we revise our severe TBI pathway here, I would like to get you involved at any level that you want. So just let me know if you would like to engage if you'd like to meet it, you
1:08:15
know, like we have done right now, it's like a couple of pages long, it's good, but you know, I think we did something more practical at the bedside, but yeah, with your input, indication is
1:08:28
this key, sure, awesome.
1:08:38
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