Hello, everyone. Thank you for joining the webinar today titled Moderate and Severe Traumatic Brain Injury, ICU Complications and Early Prognostication. This is part of the TCAA's TBI webinar series, and we hope that you will take the time to experience the entire series. I'm Kim Berry. I am the past chair for the TCAA's Education Committee, and I will be the moderator for this webinar. It is my pleasure to introduce Dr. Stephanie Capucci. Dr. Stephanie Capucci is a critical care neurologist and an assistant professor of neurocritical care at Yale School of Medicine in Connecticut. She completed her neurology residency at Beth Israel Deaconess Medical Center in Boston, followed by a fellowship in neurocritical care at Yale. Stephanie's academic pursuits focus on educational innovations in neurologic emergencies and addressing ethical ambiguities in critical care. She is passionate about improving the care of neurocritically ill patients and reducing rates of moral injury among ICU practitioners. So thank you, Dr. Capucci, for taking the time today to share your expertise with our attendees, and I will pass the webinar over to you. Thank you guys so much for having me. As Kim said, my name is Stephanie Capucci. I'm going to talk to you today about moderate and severe traumatic brain injury, and we're really going to focus on ICU complications and early prognostication. You'll have the opportunity, if you haven't already, to hear from one of my colleagues, Dr. O'Keefe, about some of the hyperacute management of brain injury and sort of that first golden 72 hours, and so we're going to focus here more so on the ICU course. This is the TCCA educational statement. I have no disclosures. Here are some learning objectives for our talk today. I'll let you guys take a second to read those, but as I already mentioned, we're going to really focus on some of the systemic and neurologic complications that occur during the ICU course, and we're going to spend the latter half of the talk focusing really on prognostication and prognostication science for these patients. I want to start off by acknowledging that the ICU course for these patients is really only a fraction of their journey, right? While I firmly believe that a patient's recovery is dependent on good critical care, I also want to acknowledge that many of you may encounter these patients at different points in their recovery, and this is really only a fraction of that. We're going to start today with a clinical case, so this is a 22-year-old, status post motorcycle crash. Her initial GCS in the field was 6. She was intubated, arrived at our hospital with a GCS of 5T, off sedation. Her pupils were 5 millimeters and sluggish. We use pupilometry at my shop, and so her NPIs were 1.2, which is very sluggish. The remainder of her brainstem reflexes were initially absent. She had flexion posturing in her extremities, though her exam did improve to a GCS of 7T after 23.4% or hyperosmolar therapy. I'll show you her CT scan here. What you're seeing is a holohemispheric right-sided subdural, some scattered subarachnoid hemorrhage, especially on the right side. She has multiple contusions, one in the left high frontal lobe, some in the right temporal lobe, and global cerebral edema. She also had a CTA, which I don't have for you here, but she did have some blunt cerebral vascular injury to her carotid arteries, and she was actually taken to the operating room for a right-sided decompressive hemicrania on presentation. Her other injuries that she suffered during her accident are included below. And so when we talk about the ICU care of severely brain injured patients, our goal is really to prevent secondary injury. You know, traumatic brain injury is really a heterogeneous disease, and this just means that, you know, our subdural patients and our patients that have diffuse axonal injury or that have multiple contusions, the pathophysiology underlying those things is quite different. Mechanism of injury matters, and the complications patients are at risk for differ based on that initial pathology. And this will have implications not only for the way that we care for our patients in the ICU, but the way that we help prognosticate for them in the future. You know, when we're talking about preventing secondary brain injury, we typically have some basic brain-centered resuscitation goals, and really the goal here is that you want to avoid the extremes of physiology. And so at the risk of being sort of similar to the nephrologist and saying avoid nephrotoxins at the bottom of every one of our notes, you know, it's really important that we are kind of following these guidelines. And so you want to avoid hyponatremia, and so to do that, we often will set a sodium goal, even if it's just a normal sodium goal, and this helps us avoid big fluctuations even within the realms of normal. You want to ensure like normal oxia, so a PaO2 goal of 80 to 180, PCO2 goal of 35 to 40, avoiding both hypo and hypercapnia. You want to make sure that you're achieving euglycemia and not be afraid to use an insulin drip if you're having trouble getting a patient's blood sugar below 200. And then when it comes to blood pressure goals, you know, there's a lot of data coming out in sort of this trend towards moving a bit more in the individualized direction, but the Brain Trauma Foundation still has systolic blood pressure goals for us, and so typically we're talking about systolic blood pressure above 100 for all comers, or systolic blood pressure above 110 for those that fit into that 15 to 50 age range. And so we really want to think about, when we think about systemic complications, we really want to think about how other systems affect brain health and recovery after TBI, and so we're not going to spend a lot of time in this talk talking about intracranial hypertension because it's a little bit outside what we're going to cover today, but we're really going to talk about some of that crosstalk between other organ systems and the brain. So when we're talking about oxygenation and lung health, you know, what we do know is that systemic hypoxemia is bad. It's associated with worse outcome, higher rates of mortality. There's an ongoing trial right now, BOOST-3, that's looking to see whether or not brain tissue oxygenation is actually going to be a target for our treatments moving forward, but in the interim, you know, we're just trying to avoid systemic hypoxemia, right? And so one way that we can do that is talking a little bit about ventilator-associated pneumonia. So, you know, this trial recently came out just this past year called PROFI-BAP, and it was looking at a heterogeneous severe acute brain injury patients, so not just those with TBI, and what they did was they looked to see if two grams of ceftriaxone given within the first 12 hours of intubation decreased the risk of early ventilator- associated pneumonia. It was a statistically significant trial, so they did find a significant difference in early ventilator-associated pneumonias, and they also found in their kind of secondary outcomes reduced ICU and hospital stay and total exposure to antibiotics. We know that about 20% of comatose TBI patients get an early VAP within that first seven days of hospitalization, and so that figure comes from the center TBI trial, and so, you know, we have started to include this in our kind of trauma bundle when patients come into the emergency department, and it's something to kind of think about. When we talk about acute lung injury, we know that those patients have higher mortality. We know that their neurologic outcomes are actually worse, and part of this may be because there's some conflict, right, between the optimal treatment of acute lung injury and severe acute brain injury. So, for example, with an ARDS patient, kind of run-of-the-mill ARDS patient in the medical ICU, we might be allowing for some permissive hypercapnia in those patients, allowing their PCO2s to go as high as 50, even higher, and that is not something that we're necessarily going to tolerate in someone who just had a severe TBI. You know, similarly, some of the maneuvers that we can use on the vent, increasing the PEEP, you know, doing a recruitment maneuver, those types of things might not be safe in somebody who's at risk for increased ICP, and so, you know, I think sort of historically, we had assumed that prone positioning was not something that we could do in these patients because of the, just kind of the challenge of it, patients needing, patients with EVDs, those types of things being hard to position prone, and then the increased risk for some compression on the abdomen causing increased ICP, but one thing the COVID pandemic did teach us was that, you know, there were a number of cases that were published that did demonstrate this was safe and led to, you know, some better outcomes from a hypoxemia perspective and a brain health perspective, and so, you know, that is something that can be considered, especially with some, like, wedges and pillows and those types of things used to kind of offload the abdomen. The other thing that can be really helpful in these patients, and it's probably underutilized, is, you know, process cyclines and pulmonary vasodilators in general. There are a number of small case reports that demonstrate this actually can improve ICP and cerebral oxygenation. There are, you know, side effects to process cyclines, thrombocytopenia being one of them, which could be consequential in our patients and would be something to watch out for. You know, if you're considering some of these more advanced treatments, you would want to definitely have an ICP monitor, and part of that is because, right, you know, some of our patients that have severe ARDS, we are paralyzing them. They're on high amounts of sedation, so you're not necessarily getting your best neurologic exam, and similarly, like, the maneuvers that we just discussed, those can be kind of high risk, and you would want to see what is actually happening to your brain physiology in that setting. Also going to touch here a little bit on some of the systemic kind of circulatory complications that can affect brain recovery and brain health, and so, you know, in general, just like hypoxemia is associated with worse outcomes, hypotension similarly as well, and so, you know, I kind of making a particular point here to not go into great detail about what the blood pressure target should be in these patients, and part of the reason for that is because I think, you know, there has been a bit of a trend towards more individualized blood pressure goals as more and more institutions start to use multimolar monitoring to determine some kind of parameters of auto-regulation, so I'm not going to dive too much into that, but because I know that not everybody has access to that at their institution, but what we do know is that frank hypotension is bad, right, and if there are times when your ICP is higher, then you may need to consider increasing those blood pressure goals to optimize your cerebral perfusion pressure, right, so there's this equation that we talk about, you know, cerebral perfusion pressure, you know, the pressure that your brain is seeing is equivalent to the MAP minus your ICP, right, and so, you know, in times when there's a systemic hypotension, we may need to artificially have a higher MAP goal. Similarly, if there are times when the ICP is high, you may have to push up that MAP goal, and so, really, when it comes to shock, the moral is aggressive resuscitation and early recognition, so making sure that we are on the lookout for signs of SERS and sepsis and treating septic shock early with fluid resuscitation and vasopressors and antibiotics where appropriate. It's also worth mentioning that, you know, stress cardiomyopathy is probably somewhat underreported in TBI cohorts, you know, we tend to think of stress cardiomyopathy being seen in our subarachnoid hemorrhage patients, but these mixed neurologic, there was a good study a couple of years ago that looked at rates of stress cardiomyopathy in a large cohort, and there was a number of different types of neurologic injury in about, so all of the patients in that cohort had stress cardiomyopathy, and about 13% were in the setting of TBI, so it's not entirely rare, and it's probably worth kind of having on our radar because it may affect the way that we, you know, treat a patient's hemodynamics or the type of fluid resuscitation we give them. And then lastly, when it comes to circulation, I want to talk a bit about anemia, because there were two big trials that just came out in the last year, one was titled HEMOTION and the other was titled TRAIN, and both looked at basically a liberal versus a more standard transfusion threshold, and so, you know, historically we use transfusion thresholds of 0.7, and so HEMOTION was looking at a brain, severe traumatic brain injury cohort, and their primary outcome was the rate of unfavorable neurologic outcome by GOSS-E, and they did see lower rates of unfavorable neurologic outcome, but the study was powered to only detect a 10% difference between groups, and so they had their kind of liberal transfusion group, which targeted a hemoglobin less than 10, and their standard transfusion group, which targeted a hemoglobin above 7, and they detected about a 5.5% difference between groups, which wasn't statistically significant in this setting, but it may have been clinically significant, you know, 5.5% in a traumatic brain injury cohort is not small. Shortly after the HEMOTION study was published, TRAIN was also published, and this was a mixed cohort of severe acute brain injury, so not just TBI, and again that looked at a liberal transfusion threshold, so they used hemoglobin less than 9 versus the standard threshold of 7, and they did see a statistically significant difference, a lower rate of unfavorable neurologic outcome in the liberal transfusion group, and so taken together, you know, there might be some equipoise there to be a bit more liberal about our transfusion thresholds in these patients. You know, I don't think either study was a slam dunk to the extent that you're, that we're maybe going to change across the board our transfusion threshold to 9, for example, but, you know, certainly in a patient who has had a significant drop in their hemoglobin or is hypovolemic, you may be a bit less concerned about being liberal with your transfusion threshold. So let's get back a bit to our clinical case. It's now post-op day five. Her early course has been complicated by multifactorial shock. Her EF was found to be 45%. She had apical akinesis and a ventilator-associated pneumonia. Her exam post-operatively was stable, had some minimal improvements. She had an intact brain stem. She did not eye open or follow commands. She had a left-sided hemiplegia, and she would withdraw tenoxious stimuli on the right. Her MRI revealed grade 2 DAI, and I was having some issues with file size today, so I will spare you going through her MRI. So I want you to stop for a second and ask yourself, how do you think she's going to do? What is diffuse axonal injury? So diffuse axonal injury refers to the shearing injury that occurs primarily to the white matter tracts in the brain. Historically, this was defined based on post-mortem studies of histopathology, but we now use MRI studies to look for these changes. The SWI sequences on an MRI, which look at blood and flare imaging, are the most sensitive for these, and we classify them into three grades. So the first grade is supersentorial, and that basically involves microhemorrhage and shearing injury to the bilateral cerebral hemispheres, but sparing the corpus callosum. Grade 2 has a focal lesion in the corpus callosum, and then grade 3 involves the brain stem. Historically, it was thought that grade 3 DAI was a poor prognostic indicator, although what we've been learning more recently is that it has less to do with the grade of DAI and more to do potentially with the location of that injury. And so there was this great study a number of years ago, Izzy Seif's group at MGH Brigham, they looked to see in a cohort of brain-injured patients where in the brain stem, whether or not location in the brain stem correlated with outcome. And so the brain stem, it's this area where there's really high traffic. There's lots of these tracks that are really important for some of our really basic functions all kind of packed next to each other. And what they found was that when there was injury, regardless of the size or the quantity of the DAI or the microhemorrhage, what they found was that the location actually in the dorsal brain stem was more important than kind of the amount of microhemorrhages that they had or the grade itself. And so this makes some sense, the dorsal brain stem is an area where there's a lot of kind of the ascending arousal network, which helps control consciousness. And so it does make some intuitive sense as well that those patients would, you know, not have as good of a neurologic outcome. The sheer like number of micro hemorrhages and shearing injury doesn't seem in the more severe TBI patients to really correlate with their cognitive outcomes, but in more mild injury, you know, patients that do fairly well from a functional perspective, that burden might be more important. Okay, so to get back to our case a bit, you know, it's now post-op day 10, and she actually had started to have some improvement over the last couple of days. She had started to eye open, she was tracking regarding, she was still not following commands and she was still hemiplegic on the left. But today, you know, you hear that she's more lethargic, she's no longer eye opening, she's not tracking, she's started to spike fever over the last 48 hours. She's completed a course for antibiotics for her ventilator associated pneumonia and has since been pan cultured, which was negative. She now is hypertensive and tachycardic and the team diagnoses her with Paroxysmal sympathetic hyperactivity. So what is Paroxysmal sympathetic hyperactivity? You know, we tend to refer to this as PSH, but some folks may have heard it referred to as storming, and this may seem silly, but it's important. You know, by definition, it must be Paroxysmal, which means that it must have an onset and an offset, right? So if your patient has sustained tachycardia or sustained fever, you know, that is not PSH. You know, PSH is characterized by really this sympathetic overflow, right? It's due to the inhibitory neurons of the sympathetic nervous system no longer functioning. And so you just kind of get this unchecked sympathetic activity and these patients get tachycardic and hypertensive and hyperthermic. They often have rigidity or posturing and those symptoms tend to cluster together, although you don't need all of them to be classified as PSH. You know, the treatment for PSH kind of falls into two major categories. One would be abortive. And so typically we think of IV opioids as being the most effective in this case. You know, we use fentanyl a lot in the ICU and that does have some efficacy, but morphine actually has the best evidence here. And so you can consider switching to morphine or Dilaudid if that's appropriate for your patient. We can also use IV benzodiazepines like Versed or Diazepam. And then we have our kind of preventative medications. And so, you know, there are a couple of classes of meds that we think about here. Beta blockers like propranolol, which can be given several times a day, adding an additional kind of standing enteral opioid. Gabapentin can be helpful. Clonidine can be helpful. And then if patient is having significant hyperthermia, bromocriptine can be used as well. I've seen Dantrolene used a number of times more in the outpatient setting. It's not something that I'm particularly familiar with using in the ICU, but it's another option as well. And really in these patients, you want to start to think about some of the triggers of PSH. And, you know, are their secretions bad? Would increasing their pulmonary hygiene, would those types of things be helpful for them? Is there a new infection brewing? Are they constipated? Do they have diarrhea? Is there something you can do about those things? And is there pain that's underlying some of this that you need to treat? And so kind of being aware of all of those triggers and doing what you can to treat them when possible. So having talked about all of that, let's look back at our case for a second, right? You know, we're talking about this patient, she's being more, she's more lethargic. She's no longer eye-opening or tracking. You know, this is a regression in her neurologic exam. This is an exam change, right? Paroxysmal sympathetic hyperactivity doesn't cause that, right, we may give medications that cause people to be more lethargic, but for the most part, you know, that should have no, you know, PSH does not affect your neurologic exam. And so we need to take a step back and we need to reevaluate and start to develop a differential diagnosis for delayed neurologic worsening. This is a framework that I use, but I think it can be helpful. You know, I think starting with your, just a dry head CT, right? Is there any concern for new mass effect? Is the previous subdural hemorrhage any larger? Is there a new cerebral edema? Do we have to be worried about hydrocephalus or is there a new hypodensity that would make us concerned for CT evidence of infarct, right? I think it's important when we have a high suspicion for a clinical exam change that, you know, we don't want to fall into the last CT fallacy, right? Where we get a new head CT and we're comparing it to the one that was done maybe 48 hours ago. And we don't really see too many differences, but sometimes when you compare it to the one that was done a week ago or 10 days ago, small changes that can be clinically significant for a patient become more apparent, right? You realize that, oh, really, actually the perihemotomal edema around their contusion is a lot worse, or the subdural actually went from six to seven to now nine millimeters and that's making a difference. This can be a great time to sort of get on the phone with your friendly neighborhood radiologist and, you know, explain what your concern is. I know many of us get frustrated by the whole concept of a clinical correlation is advised, but this can be a time when that can be really helpful to tell your radiologist, this is actually what I'm really worried about. Are you sure you don't see anything that would explain that? You know, and then there's a few other questions you can start to ask yourself, you know, is this patient at risk for vasospasm? Did they have significant subarachnoid hemorrhage, you know, that would put them at higher risk? Did they have blunt cerebrovascular injury when they came in, and now they have more stenosis of that ICA? And transcranial Doppler or TCDs can be like really helpful in this situation if you have them available at your shop. They are bedside tests, they're ultrasounds and they're non-invasive, and they can help you evaluate, you know, changes to velocities that would be indicative of vasospasm. It's not perfect and really the trend is what can be most helpful. And so if you think that you might be using TCDs, it's really helpful if you have the forethought to get a kind of a baseline test when the patient comes to the hospital soon after their injury. If you don't have TCDs available, you know, repeating the CTA from when they came in can be helpful to kind of answer that question of vasospasm or new stenosis. You know, you want to start to ask yourself, have I, has this patient ever been connected to EEG? If yes, then has it been recently? And do you need to consider repeating an evaluation for non-convulsive seizures? Again, not everybody has access to continuous EEG monitoring, but repeating a routine over a couple, at a couple of different time points can be really helpful. And then one that I think gets lost sometimes is, you know, is this patient at risk for CNS infection? Did they have a cranial surgery? Did they have a depressed skull fracture that wasn't operated on? You know, did they have an EVD that puts them at risk for ventriculitis? Did their initial injury make, raise concerns for a CSF leak? And maybe they have seeded the CSF space from that perspective. And really, if you get concerned about a CNS infection, the way to answer that is to obtain CSF. And usually this is by LP, but we do have to acknowledge that that's not always safe in all of our patients. And so some of these patients might still have an EVD, you can get a proximal CSF sample. But if it's not safe to obtain CSF, really the test then would be to do an MRI with and without contrast, and to consider actually putting those patients on empiric coverage, if you're not gonna be able to get the needed microbiology. And, you know, if all of that is negative, right, you wanna take a step back and also reconsider systemic factors. You know, is there a new medication we started? Is there an infection? Did, do they have a new liver injury that's causing them to have elevated ammonia, something like that? You can consider repeating an MRI, acknowledging that, you know, leaving the ICU to lay flat for 45 minutes is not a small thing in a lot of these patients. And you wanna make sure that they can tolerate from a respiratory and neurologic standpoint laying flat for that period of time. You know, I think there are some, you know, red flags that really make you worried about kind of missing something that's sinister. And the biggest one of that would be increasing hypertension. So is there a reason this patient needs a higher blood pressure, like increased ICP or new vasospasm? And then the acuity of the exam change as well can make you worried. And so kind of weighing those things and when you're kind of following this type of evaluation. So in our case, you know, she had another MRI, which was concerning for right temporal, like early abscess. Her CSF was inflammatory, but somewhat equivocal. Although her CSF lactate was four, she was treated empirically for a CNS infection, though the CSF remained negative. Clinically, she improved. She started eye opening, tracking and regarding, basically back to how she was prior to her setback. She still was not following commands and she was still only moving the right side to noxious, not purposefully. He remained hemiplegic on the left. You know, her family was in agreement with tracheostomy and gastrostomy tube once her acute illness had subsided. But they ask you in that setting, you know, when will she wake up? How is she gonna be? What is her life gonna be like? And so I want you to take another second and ask yourself, how is she gonna do? What do you tell this family? You know, we're gonna spend the next 20 minutes or so kind of going through the sort of illness trajectory and prognostic discussions, right? I mean, I think it can be really helpful to have a broad sense of what that illness trajectory might look like after really any kind of severe acute brain injury, but especially the moderate and severe TBI folks. When we're talking about this type of illness, you know, it's very different than other types of chronic illness, right? You know, these patients, they were very high functioning before they came into the hospital. And they, rarely any of this is accounted for in their advanced directives, right? And so something that was happened very acutely, you know, we've all kind of seen the boilerplate advanced directive that say, if I'm deemed to be in a terminal state and there's no chance of recovery, I would not want X, Y, Z. And to be honest, that's usually not the situation that we're in, right? Usually there's some degree of uncertainty. And so it's hard for those advanced directives to really apply to a lot of our patients. I think it's important to have sort of this 50,000 foot view of when you're gonna have natural time points to be discussing values with these patients. You know, I think there's an opportunity early on, right? When you're offering a lifesaving intervention like surgery or EVD, just to start to elicit some of those values. It doesn't mean that you don't have to offer those things, but just using that opportunity to get to know the patient and what was important to them. Probably the biggest time point where we are having these discussions is around tracheostomy and feeding tube. You know, this tends to be around the two week mark when, you know, it's, we've started to gather a little bit of data about how the patient has been doing over time and putting patients through surgeries, even if they're ones that we do fairly frequently, it's a big deal. And so sitting down to have discussions about values during that period of time is important. I think, you know, another time when we're doing, when we're discharging patients from the ICU to a different level of care, it's important to start to lay out what that trajectory might look like for patient surrogates. And again, at hospital discharge, you know, this is not a time point that I am typically involved in, but I think it is part of our really duty to these patients to make sure that they have a sense of what the next several months is gonna look like and what opportunities they will have to re-engage with the healthcare system and to re-engage about goals of care. I find, you know, making sure that you have a conversation in that first one to three days with the patient's family and patient surrogate decision-makers about how much of a marathon this journey is going to be is really important because we know that caretakers experience a lot of anxiety and a lot of mood symptoms themselves and kind of allowing space for them to be taking care of themselves is important. And then I think, you know, one of the things that we wanna start talking about is, you know, for these patients that we are giving prolonged time to see how they will do, introducing the concept of a time-limited trial, right? You know, when are we gonna re-evaluate goals of care? When are we gonna make sure that what we're doing is values concordant, right? Is it gonna be at six months or 12 months? Will there be opportunities if the patient gets re-hospitalized to discuss that? And is there a time in clinic follow-ups to be able to address that? I think, you know, as practitioners who have some of these conversations, it's important for us to be aware of the disability paradox. This is something that has not been particularly well-studied in TBI, but is well-studied in other groups. And we know that patients, you know, may say sort of that they are, that a certain level of disability would be unacceptable to them. But once they actually arrive at that level of disability, they report a good quality of life. And so this just sort of highlights that the job that we are asking of the surrogate decision-makers is a challenging one, asking them to tell us what their loved ones would want and how much they would be willing to go through is hard. And so we need to be able to give some leniency there. So how do you formulate a prognosis? And like, why is this so hard, right? Part of this has to do with the heterogeneity of the pathophysiology, right? We talked about this at the very beginning. Like a patient that comes in with multiple contusions is not the same as a patient that has diffuse axonal injury. You know, the motor vehicle accident in a 25-year-old is not gonna be the same as the 65-year-old with a long list of comorbidities that falls off a ladder, right? And we also have to acknowledge that our data does not do a great job about deciphering between the different types of pathophysiology and deciphering between kind of those age groups, right? So we need to be aware of the rates of withdrawal of life-sustaining therapy, right? So, and this withdrawal of life-sustaining therapy really just refers to this time when, you know, for example, patients are palliatively extubated and the rates of withdrawal of life-sustaining therapy are incredibly high. Most patients that die of TBI die from withdrawal of life-sustaining therapy in our ICUs. And so recently NCS came up with a guideline that recommends against any prognostication discussions for the first 72 hours, and really a strong recommendation for a two-week trial of critical care prior to prognostication discussions. You know, in the NCS guidelines, they looked at a number of clinical variables that I put on this slide. They looked at them in isolation, so as an isolated predictor, not in like a multivariate sense for neurologic recovery. And you can see that essentially all of these clinical variables are in this red as being deemed not to be reliable for predictors of mortality or functional outcome with the exception of bilateral pupillary unreactivity. And one, to go one step further, you know, a lot of the data that we had up until recently really was just evaluating outcomes at six months post-injury. The TRACT-TBI data, which I'll look at shortly, suggests that there is some penchant for continued improvement up to 12 months out. And so, you know, maybe even evaluating six months, outcome at six months really isn't the right variable that we should be asking ourselves about. So then what do we do, right? We individualize care. We gather as much data as possible. We take together the clinical diagnosis. We take the patient's exam, their trajectory, their hospital complications, their level of functioning before the hospital, their neuroimaging, their neurophysiology studies, right? And we take all of those together and we discuss them with patient surrogates and patient family members in the context of patient values, right? You know, the question I think that we really need to be asking ourselves and our patients is, you know, how much are they willing to go through for the chance of recovery? And sometimes when you have that discussion, you know, family members say, you know, he would be mad at me for having kept him alive for this two weeks in the ICU, right? And then that becomes, you know, that's not the patient that you probably advocate for doing a year long time limited trial in, right? because it wasn't within his values. So this is the track TBI data that I was just talking about that was published in 2021. And I think if you look at this last column on the this first graph here, what you see is that greater than 50% of the severe TBI group was able to function at home independently for eight hours a day. And that's like a really meaningful qualitative outcome, right? Like being home at eight hours alone, you know, allows your spouse to have a job. It allows you to be taking care of some of your activities of daily living to feel independent, right? And so why can't we just say to our family members then, you know, 50% of the patients that come in like your loved one are able to function independently and then 50% of them have, you know, severe, are dependent on care. And part of that is because of withdrawal of life-sustaining therapy. So in this study, for example, 75% of all death that occurred in this cohort of patients occurred in the first few weeks. That means that 75% of the people that died from their TBI died in RICs. And so this data really reflects a cohort who well-meaning physicians at level one trauma centers sat down with families and said, give them time, or were told by their family members, please, who asked for time, right? And this is then their outcomes. And so, you know, the self-fulfilling prophecy may be at play here. And we just need to be aware of that when we are having these discussions, because, you know, the patients that we don't think will do well, they go on to have withdrawal of life-sustaining therapy. And so, you know, we have to be cautious about giving kind of some of these hard numbers when we talk to families, although, you know, that is sort of what they want. When we look back at data for what families want from critical illness communications, they're usually asking for specific numbers. I do think it's worth talking for just a couple of minutes here about something called cognitive motor dissociation. So you guys may or may not have heard of this. It's something that's sort of coming out of the zeitgeist and into the community a bit. Lay people are starting to ask more about it, I think, especially with the new New England Journal article. So cognitive motor dissociation is this idea that there's a subset of patients who, when you go to the bedside and perform behavioral tests, don't follow commands reliably. But when you do fMRI or EEG studies and ask them to perform tasks, there's a sort of a biological signature that's indicative of awareness that they have that the fMRI or the EEG is demonstrating that there's, you know, a neural chain when you ask them to perform a task, which is suggestive that potentially, despite them not following commands at bedside, they actually have a degree of retained awareness. So what does that mean now for prognosis and for what we tell families? I think there's a lot of caveats with this data, right? So it's really early. You know, Jan Klassen out of Columbia has done a lot of really great work with CMD and is sort of the champion in our field for this. You know, there are small data sets that have been published that suggest that CMD might help us, like identifying that a patient has CMD might help us predict that they will go on to have an improved functional recovery, that these are patients who seem to be in a vegetative state at bedside but actually have CMD and then they will have a better neurologic recovery than some of the other folks who don't have CMD. And so the sort of the big promise here or the idea here is that, you know, maybe this is a group that could benefit from new treatments. Maybe this is a group who we could use that information to have conversations with their families to give them more time to advocate for these time-limited trials. The more recent study that just came out in the New England Journal, Bodian wrote about this. It was a small cohort as well, but his was very, very young. So this was the median age in the paper that was just published. It was 38. And so this is not generalizable to our general population, right? And they also really looked at delayed time points. So they were looking at cognitive motor dissociation. I think the median time that they were evaluating in that study was about eight months, which I think then really begs the question of exactly how surrogate decision makers will use this information, right? Right now, there aren't treatments that we have where that we can identify these patients that have CMD and give them a medication that will allow them to, you know, become interactive in a certain number of months. So, you know, I think there's a real concern that identifying CMD, especially at the later time points, may actually increase withdrawal of life-sustaining therapy, right? If you go to a family and say, actually, they have some retained awareness at seven or eight months past their injury, you know, that in some ways is horrifying. I think, you know, that they have been sort of in this functionally locked in states during that entire time. I think there are also, you know, real concerns about distributive justice with this type of technology. You know, we're not using fMRI or EEG in this way in a clinical context. And so who has access to these tools and who is able to sort of get evaluated for CMD? And is there a way that we can make this a tool that's able to be distributed to lower resource settings? And can we do that in a way that does not worsen inequity, right? I think, you know, these are all just questions that I have ethical considerations, I think, but I think, you know, there needs to be kind of more information about that. And then I think the last thing to just remember is that these are patients who have been hospitalized or in an institution for months, three, six, 10 months a year, right? How many times did someone go into that patient's room and do something to that patient without explaining what they were doing, right? How many times did we go into that patient's room and have a conversation about the patient without addressing them at all? And so, you know, I think if anything, these studies just really emphasize that the way that we treat our patients at the bedside really matters. You know, I perhaps should have talked about this a bit earlier because I think it's super important and really is something that happens early on. But, you know, when we talk about values elicitation, it's so imperative that we're asking about the patient, that we're getting to know who they were and what was important to them. Did they have loved ones who were critically ill in the past or dependent on care? And how did they react to those things, right? When we're dealing with so much uncertainty, getting a sense of who the patient was and how they would want to move forward and how long they would want to wait for a good recovery is really the question that we need to be asking. And then, you know, what does a good recovery look like for them and is that really possible? You know, I still think that using a framework where we present best case and worst case scenario and perhaps the most likely outcome is really helpful for families. And I think, you know, presenting it in that way really allows for this nuance where we can emphasize the prolonged hospitalization and kind of the multiple setbacks that we expect, especially in older adults. It's important to realize, right, that when you get a readmission into your ICU on hospital day 240 that, you know, that paradigm of best and worst case may have changed and being willing and able to reevaluate to make sure that you're still providing values concordant care. And then last, like, what we do know when we have looked at how patient families, you know, respond to critical illness communications, they want us to be honest about uncertainty. And it's okay to do that and also make a recommendation, right? So, you know, saying, hey, you know, I'm worried that they're not going to recover as well as we hope. Like, well, if that was going to happen, how would they feel? And further evaluating, you know, it sounds like being at home was really important to them. At this point, we're not sure if that's possible, right? Using I wish and I worry statements can be really helpful in these patients. I apologize for just having one slide on this, because I do think it's really important. But just to kind of wrap up here, you know, the cognitive outcomes that impact quality of life aren't always captured in our outcomes research, right? We are very focused on functional neurologic activity and don't always spend as much time with the attentional deficits and the mood symptoms that really impact quality of life. And we know from some of the later data that came out of the TRACK-TBI study that post-TBI symptoms and health-related quality of life remain fairly static between one and five years. And so, there's really probably work to be done here, right? We would hope potentially that the quality of life would get better the farther they were out of their injury, but that doesn't seem to be the case. So, I'm just going to wrap up here with our case. You know, she was in our inpatient hospital for 64 days. On hospital day 50, she intermittently started following some commands. She goes to acute inpatient rehab where she's decannulated. She passes for a diet. She starts to ambulate with assistance. She's now almost two years out from her injury. She's ambulatory without assistance. She hasn't been able to She has traced left-sided weakness and well-controlled post-traumatic epilepsy despite not having seizures in the hospital. She's now living alone with her three-year-old daughter as her primary caretaker, and she just started working last month. Major symptoms that she still suffers from include fatigue, cognitive slowing, attentional difficulties, and pain. So, with all that in mind, here are a few of my conclusions when I was putting this presentation together. You know, systemic and neurologic complications should be expected in many of our moderate and severe TBI patients. Our goal should be the avoidance and minimization of secondary injury. Data is limited in many aspects of our care in the severely brain-injured patient, but especially for older adults. We need to be cautious about generalizing population-based data to these patients, especially when they have significant comorbidities. A lot of our data reflects the younger population. And then prognostication is challenging. If it is within a patient's values to be given time, we should acknowledge uncertainty, contingency plan for the future, and err on the side of allowing time for definitive prognostication. So, we need to be careful about that. Thank you guys so much for listening. I'm happy to take any questions. First of all, thank you very much for this case study method of teaching. Most of our audience, I'm sure, will appreciate the application of theory to an actual patient. A couple of questions. When you were discussing the VAP and ARDS, do you involve pulmonology early in that given the importance of managing that? We typically don't involve them right at the beginning. I think in a patient who does have severe ARDS, they can be really helpful. And so, if you're considering some of the advanced therapies where you're having really refractory hypoxemia and you're talking about proning a patient or putting them on fosacyclines, other vasodilators, I think that that would be a really great time to involve them. You know, we do see ARDS in our ICUs and so are fairly comfortable managing some of the more moderate injury. But I think what we know in these patients, right, is that they are incredibly complicated and that typically, you know, having excellent interdisciplinary care is important. And so, certainly for patients who are refractory and are on that more severe side of the spectrum, they can be really helpful. Great. So, when you're talking about being collaborative and that interprofessional, when you're talking about managing shock, how collaborative and how challenging is it to be collaborative when you have a multiply injured patient and you're managing more than one injury at a time? Yeah, I think it can be really challenging, right? I think, right, this particular patient that we talked about in some ways was easy because they didn't have a significant injury or those types of things. They didn't need to go to the operating room, you know. I think a lot of those discussions need to be held in real time. They need to be held oftentimes in person where you're discussing, you know, what is the most life-threatening thing for this patient right now? You know, if the patient is not going to survive without going to the operating room on the first day for like an abdominal injury, for example, then we as the neurologists that are helping these patients need to be able to give you guys some guidelines maybe for the operating room and do what we can to optimize things. But I think that, again, is a time when just like open and honest communication is super important and doing what we can to optimize care. Great, yeah. So a little more of a focus question, how common is PHS or storming? How common is that? Yeah, it's really, it's pretty common. So in the, you know, in the severe, moderate and severe traumatic brain injury group, figures vary a bit, but in the 20 to 40 percent range. So it's something that we see pretty often and it used to be thought of, I think as many of our markers, it used to be thought of as sort of a poor prognostic indicator, but that hasn't been borne out in more recent data sets. And so, you know, I think it's something that can lead to a lot of hypovolemia, can lead to a lot of muscle injury, those types of things. And so that we want to kind of treat earlier on. Very good. Last question, I think. During the presentation, you referred to values and goals. And I think that the way you approach this has been a fantastic sort of overview and a good way to approach it. But in your experience with those health care discussions, which providers do you think should be part of that conversation when you're having those discussions with the family? Yeah, so I, at my core, I'm a teacher. And so I do believe that a lot of our trainees should be involved in these discussions. I think our bedside nurses bring so much value. And so when they are able to come to these conversations, you know, they spend time with the patients and the families much more than we do as physicians. And I think can really shed a lot of light on the patient and the family and the types of things that were important to them. And so I think ideally, these situations are, these conversations are ones that involve multiple members of the team, including the bedside nurse, any trainee or APP that might be taking care of the patient directly. But I also think that, you know, these are typically our life and death discussions that we're having, right? We just talked about sort of the rates of withdrawal of life-sustaining therapy and how that's the sort of major cause of death in these patients. And so you want to make sure that your team, whoever is leading that discussion, you're treating critical illness communication like a procedure. So it should be something where whoever's leading the discussion has experience with it, that you guys have a plan going into whatever family meeting you're going into and that you leave the family meeting and are able to have a debrief, right? And so I fully believe in giving the autonomy to some of the providers in terms of our APRNs and our residents and fellows, but also doing so under supervision and making sure that those are conversations that are had again with collaboration, right? So last thing you want to do is go into a meeting like that, where I, as the neurocritical care doc, am having one opinion and it turns out that the, you know, the trauma attending came by and spoke to the family half an hour earlier and said something completely different. So making sure that everybody is on the same page as we approach those discussions. Fantastic. Thank you. Well, that ends my list of questions for you. Before we sign off, do you have any parting thoughts or comments that you would like to leave with our audience today? No, I just really appreciate having the opportunity to chat with you all. I think hopefully this was helpful and please feel free to involve us as your neurocritical care colleagues in the care of these patients. Fantastic. Thank you very much, Dr. Kouchi. I appreciate your time and your expertise. I think that we've learned a lot of valuable information today. So on behalf of the TCA, I want to thank you for joining us and again, extend my thanks to Dr. Kouchi. Thank you very much. Have a great day. Thank you.

traumatic brain injury

ICU complications

secondary injuries

ventilator-associated pneumonia

paroxysmal sympathetic hyperactivity

prognostication

cognitive motor dissociation

interdisciplinary collaboration

individualized care