Great. Thank you for the wonderful talks. So the case presented in the case prologue strikes personal accord because we consult on all the other ICU services. And just last month, I have consulted on two patients with the same identical clinical scenario. So they come in for completely unrelated surgical reasons. Does not wake up with daily spontaneous awakening trials. A few days later, they get a CAT scan and malignant MCA stroke, which led to ultimate withdrawal of care and death. So this raises the question that not, perhaps outside of the neural population, we almost never do multimodal neuromonitoring on patients who are comatose for a variety of reasons. Should we be? And if so, with which modalities? Excellent question. So one of the messages I hope we were able to convey that all of us who are in critical care, we all need to have certain fundamental skills no matter what kind of patient population we're seeing. Because a lot of our patients are going to come in with different comorbidities. They're going to have a higher risk of developing, for example, neurological complications. We highlighted that. Your patients came in with unrelated surgical procedures and then developed these malignant MCA syndromes right underneath our noses. So how is that happening? So one, while we are delivering subspecialty care, we do tend to get very narrow in our perspective. And we take care of patients with that focus, with that organ-specific focus, whether it's cardiac, whether it's neuro, whether it's the abdominal sepsis and the SICU, et cetera. We've got to take one step back and make sure that we apply a certain standard for monitoring our patients, irrespective of the underlying pathology. So I cannot emphasize this enough. In your sedated paralyzed patient, if you can't do a neuro exam, the least you should do and ask your nurses to do is check the pupils. And when you walk into the room for a patient who is on the ventilator, the very tenet of having that A2F bundle, your ICU liberation bundle, the SAT, the SPT, talk to your patient, look for asymmetry, all of that can be accomplished very quickly when you synthesize that with your focus bedside assessment for that patient. I wonder if in those two patients, if we had taken that step back and continued to monitor at least their pupils or look for this kind of asymmetry, would we have captured that acute ischemic stroke much earlier and send them to thrombectomy? That's one piece that comes to mind. The other issue with how we, in terms of the timing, often when we get consults from other ICU settings and we find a patient's not waking up, their ARDS is all better and you've dialed everything back, sedation paralysis is off and now the patient's not waking up, and then we go ahead and do a CT head. There are good papers now, particularly in patients on VA, VV ECMO, great group out of Hopkins that's doing a lot of these multimodal, non-invasive neuromonitoring in patients who are at a higher risk of developing neurological complications. And then we have so much in that toolkit, including, of course, that clinical assessment. You have your point of care ultrasound. Right next door, just a couple of doors down, there's a whole neuromonitoring skill station right now that's talking about continuous EEG monitoring, which is surface EEG monitoring. And EEG is not just for seizures. EEG gives us so much more rich data. In a lot of ways, an EEG is like your telemetry strip. It's continuous, it's physiological, it gives you so much data. So the problem is access to those modalities. So non-invasive, you've got electrophysiological, you've got the point of care ultrasound. Transcranial Doppler, we underutilize this modality. And not all of us as intensivists learn how to do this, but when we are doing our cardiac Dopplers, we're very facile in doing this. So it really makes us wonder how much we learn from each other, and then creating these protocols. For instance, at our institution, this multidisciplinary team put together a monitoring protocol, non-invasive neuromonitoring protocol for patients with fulminant hepatic failure. And it's been implemented with the liver transplant team, our surgical and transplant intensivists. And I see Adele in the audience. But it takes that kind of crosstalk and collaboration to one, critically evaluate whether you as a group, not just one critical care team, you as a group agree that there is utility in monitoring these patients. And then coming up with your internal thresholds based upon what has already been described in literature. There is literature on transcranial Doppler, in fulminant hepatic failure, cerebral edema patients. There is literature on serial CTs in patients who are at a risk of developing malignant MCA syndrome. The utility of EEG monitoring, right? And biomarkers. So there's a lot that can be done outside of the realm of that invasive multimodal monitoring. So I hope that with the group we've been able to share, that there is so much more. When we think of traditional multimodal monitoring, we're all thinking invasive. But multimodal monitoring is what we're doing every single day in the ICU anyway for the body, then why not integrate that with how we monitor the brain as well? Thank you. You wanted to add something? Oh, I was saying there's a lot of promising data for NEARS, which is essentially like pulse oximetry, but it's what near infrared spectroscopy. And it's particularly with MCA. And this is both true for looking at vasospasm and aneurysmal subarachnoid, but also there's some data for stroke. If you're looking for MCA syndromes in patients that you can, and this is something else non-invasive. It's as simple as putting some stickers on a forehead. Thank you for the presentations. Again, my name is Agit Katan. I'm from Santa Rosa, California. For those of us that are in centers that don't have neurointerventional capabilities, should we be thinking of ICH and large intraparenchymal hemorrhages similar to acute ischemic strokes with LVO and trying to get these patients out to larger centers that have that capability? Typically the way that it's been working for us is we've been admitting all those patients, but it seems like there's some decent data that the outcomes are better if they do get a minimally invasive surgery. So should I be pushing the ED docs to consider transferring these people out? And if so, is there a subgroup of patients that I should really push for? That's an awesome question. So this goes back to that systems of care you know, paradigm. Knowing the strengths of your hospital health system and then what is available in your region. Whether your hospital is part of a network of hospitals, one or two of which may have these resource intensive therapies available or not. So speaks to that regionalization of care and moving patients from one hospital to another. So one is case selection. So the same kind of things that you're probably thinking of when you're trying to refer a patient for ECMO. Not every hospital is going to have access to ECMO. Not every hospital is going to have a PERT team. Not every hospital is going to have a shock team. So using that same kind of paradigm, when we apply that to neuroemergencies and knowing that we've got to walk lockstep in terms of the evolution of evidence, one possible strategy would be this awareness of what is available. Is it within your health system? If not, what is available in your region? Can you a priori, and not when the patient arrives, I'm talking about getting your administration involved a priori, having these discussions about transfer agreements, that if the patients with these criteria arrive, we're going to be transferring them. And then who sets up the transfer and you follow the EMTALA rules, et cetera for that. But referral early and having that kind of pathway in place because time is brain and millions of neurons are going to die as we continue waiting and trying to figure out how this is going to happen. So one, knowing that knowledge, two, from a legal perspective, having that transfer agreement in place and care should not wait. What I mean by that is once you have identified a patient potentially, or you're thinking of referring a patient, although that bundle of care, your ABC, your coagulopathy, your blood pressure management, whether this patient needs their airway secured, your hyperventilation, your hyperosmotic therapy, you've got to start care delivery as a continuum so that the team that's going to receive this patient is not going to play catch up. But having those kinds of agreements in place makes a difference. What MIS technique is going to prove to be like that gold standard, that thrombectomy stent retrievers was the technology that changed the landscape for thrombectomy. Right now in the MIS world, there are some promising techniques. One trial, the results of which were presented at the AANS, the Neurosurgical Society meeting last year, but the paper has not been published yet, EnRICH, looked at paraphysicular clot evacuation developed by this company called NICO Corporation. But it's a different technique as compared to what we use, for example, at our health system, which is SCUBA, which is underwater evacuation of an ICH. So the purpose of sharing this is there isn't full agreement on what kind of technology or technique should be the gold standard, but there is agreement that in appropriately selected patients, MIS can improve mortality. So with that in mind, getting your systems of care that ball rolling will be appropriate. So how do you select which patient? So, you know, knowing that kind of volume, whether it's about 20 to 30 CCs, that's what's recommended in the AHA guideline statement based on the literature up till that point, but that is also going to change. So you don't want to send a patient with a very small ICH for evacuation because you can end up causing more damage. You won't be sending, and most of these trials are going to exclude, there are RCTs, randomized controlled clinical trials that are ongoing, that are going to exclude patients with thalamic hemorrhages or dominant thalamic hemorrhages because those patients can also not improve and they may slip into a coma. CKD patients are also being excluded from those trials because it's very hard to get inappropriate hemostasis so that hematoma will still expand. So just looking at some of these trials, come up with your multidisciplinary inclusion criteria, speak to your endovascular team, your neurosurgery team, are you going to be willing to do one, two, three? From a low bar hemorrhage perspective, 100 CCs, there's more than a centimeter midline shift, it's a 45 year old with an underlying AVM, that's not the kind of patient who's going to undergo MIS. That's the kind of patient who's gonna need their skull off, go to endovascular, take care of that AVM, embolize an aneurysm associated with that AVM, et cetera. So that care paradigm and appropriate case selection, that needle will move once we see some of these RCTs that are going to be published. But till such time, engage your stroke team, your neurosurgery team, your endovascular team, neurocritical care if you have that available. Talk together, come up with your criteria and sign these transfer agreements. That would be my recommendation. I'm Rob Planbeck from Creighton. One question I had, you touched briefly on hyperosmolar therapy specifically and malignant edema from MCA infarctions. What's the role of continuous infusions of hypertonic saline to target sodium goals? I know a lot of centers do it, but I don't see a lot of good data. So what is your interpretation of the data that's out there? No, you nailed it, right? There isn't a lot of good data, but we'll take a leaf from the TBI world. COBE, the COBE trial, French study, really well conducted, multiplies use. So looking at these continuous infusions for targeting a particular sodium, is that better than doing bolus osmotherapy? A lot of these observational cohort studies, retrospective studies in patients with malignant MCA syndrome have also shown us that bolus osmotherapy is potentially better than doing continuous infusions. Physiologically, why that makes sense? The whole idea is to use it as a bullet. You want to create that gradient. If your plasma sodium and your brain's sodium is equilibrated, it takes a few hours to do that, then you're not going to be able to diurest the brain, essentially that. But when you create that rapid gradient, you give that 23.4%, your plasma sodium is much higher than your brain sodium, you're going to be able to literally diurest your brain and reduce some of that edema. So current recommendation from the Neurocritical Care Society is also to use bolus osmotherapy as compared to continuous infusions. The other problem with continuous infusions, so the first principle of medicine, first do no harm. Using those continuous infusions, increasing the amount of time your patient is going to spend on mechanical ventilation, pulmonary edema, AKI, magma, non-anion gap, metabolic acidosis, like there's a lot of other problems our patients will run into when we use these continuous infusions. And when we really need it, it's not going to work. So that's why our practice has become bolus osmotherapy. Neurocritical Care Society guidelines also recommend bolus osmotherapy. I agree with you, there isn't phenomenal data to say absolutely this is the only thing that works, but common sense and physiology tells us yes, that might be the right thing to do. Thank you. Thank you. I have a question about your status epilepticus dosing based on ESET. Now for patients who weigh more than 75 kilograms, do you follow the ESET max dose? Levator Acetam? What? Are you talking about Levator Acetam or for all the? All three, like do you follow the max dose, especially Levator Acetam and you know, the side effect is drowsiness. Do you follow those max doses in overweight patients? I would say yes, it's a very weighted question. Pun unintended. Essentially, what weight do you use? You know, ideal body weight versus your dry weight. What is the right weight to use? That's a little bit tricky. And then for certain medications, we have better data as compared to others. Again, going back to first do no harm. I don't want to overdose a patient, nor do I want to underdose, but I do end up at least, I'm gonna speak for myself, not for my entire group, because we don't all agree. But essentially, yes, we do end up using, you know, that max dose for Keppra. Like for example, we'll do the 4.5 and not beyond that. Hi, Steven from MD Anderson again. So thanks to Diane, especially time is important, but time is money. So that's a tough one. So recently I had a case where the patient came in for looking for a miracle treatment to his cancer, but end up in cardiac arrest and near brain death. And Texas is not a very friendly state. It's very pro-life. So even if we declare brain death, they have 10 and recently changed the 25 days to appeal to find another place to go. And the family didn't even allow us to do any apnea tests. So, and the institution does not support futility by two PC providers. And so with all of those restrictions, there is certainly moral, financial, and a lot of distress from both and tensions between the teams. So in those, now we already give enough treatment, support and time. So how do you tackle those situations? Especially there's a right to life group that's waiting out there, joining your goals of care discussion on top of all this. So I think there's actually a niche that has not been adequately carved out yet in critical care that allows for continued aggressive care without being in the ICU. And so these patients that you're allowing for delayed awakening to not be necessarily taking up space that you can still provide the type of support they need. But the truth is this doesn't exist yet. But as we're getting more and more data that patients do better with time, it's telling us that there needs to be a place to allow for that to happen. In terms of if your institution is going to allow two physicians to withdraw on a patient, some places they do, some places they don't, that's a hotbed I want nothing to do with. And it does create a lot of distress on both sides, but there have to be some type of options for patients that there is hope that exists. And I don't think there's a place like that yet. I'm just curious about the funding part, but I don't think we have a solution to that. Just something to think about. You're in a very unenvious position. Yeah. So are you guys going to not withdraw tomorrow? That's convincing. Yeah, that's great. So the tincture of time. And then going back to how long is enough. So there is a joint professional standard statement endorsed by a couple of different societies. The longer you can wait, the better it is. But if you are in a resource-limited setting, how do you wait long enough, right? And then the moral burden. Now that you know that there is a self-fulfilling prophecy, but you don't have the resources or the capacity to wait, what do you do? I think that's a difficult one. That's a truly difficult one as we grapple with the, what we learned from Diane's talk was this prognostic humility. Like the more we know, the less we realize the, the more we realize, the less we know. So essentially, the longer you practice, the more humility you end up having because you realize that there is so much uncertainty. But unfortunately, our care always needs to be patient-centered, but we don't always have the luxury of doing that. I don't think right now we have a good solution for that. All we know, yes, we need to give more time in every kind of severe acute brain injury. 72 is what is recommended, but when you look at a lot of the other papers that are looking at the primary cause of death in a lot of patients with severe acute brain injuries, stroke, TBI, post-cardiac arrest, the longer you can wait, the better it is. But it's a hard one. Enjoyed the talks. The track TBI, meaning age was mid-30s. What do I do with a 70-year-old? Yeah. He was mentioning in a lot of the trauma studies that these are patients that didn't have significant comorbidities. Some of them did have polytrauma that could have affected, but it was a lot different than patients that come in that are 80 with a lot of other medical comorbidities and have lived a long life. It's all of those factors combined. So again, not looking at one organ system or one thing. Oh, I should say, the older I get, the bar for what is old also keeps moving, right? So that's number one. Two, age is just a number, right? So there's the physiological reserve, there's frailty. So you can have a patient in their 30s and 40s being really frail, but a 70-year-old may be really robust. So our ability to understand what our patients are coming with with respect to their reserve. So their comorbidity burden, their frailty, their physiological reserve, cognitive reserve, what are they coming in with? Our ability to assess that and taking the time to assess that and then looking at what happens to them as part of that primary disease process, irrespective of what brought them to the ICU, we know they're going to develop a whole bunch of other things. That cumulative prognosis, moving the needle there, whether we lean on certain objective measures, imaging measures, biomarkers, getting a better psychosocial reserve-related history, so we can factor all that in. But what's even more important is once you save someone's life, what kind of resources do they have the, what can they avail of? What kind of rehab settings are they going to go to? And there are lots of patients who are not going to have any psychosocial support, are not going to be able to go to any rehab facilities or long-term acute care hospitals, and despite all of the hard work of the multidisciplinary teams in the ICUs, they're still going to be committed to a bad outcome. So that systems of care approach, and one of the reasons why I said our work, while we do most of our work in the ICU doesn't stop there, the SCCM has done a phenomenal job of really bringing post-intensive care syndrome, the physical, cognitive, mental health problems that these patients suffer from, their caregivers suffer from, to the forefront, but we as a community really need to band together to figure out what kinds of resources are needed eventually from guidelines to policy, from policy to making sure that health systems are incentivized to provide that kind of care. That's going to take time, but we need to again start moving the needle there. That's why that 70-year-old, I don't know, man, we got to find out more about that guy. Yes. Any other questions? All right, so I just wanted to take the opportunity to thank all these outstanding speakers, and thank you, Dr. Morali, for conducting all the clinical cases. Thank you. Each and every one of you should have access to the e-book, so the chapters are there, and if other questions come out, feel free to reach out, and I'm sure authors will be happy to answer any questions they have, and I hope you enjoy the current concepts course, and thanks for coming.

multimodal neuromonitoring

intraparenchymal hemorrhages

osmotherapy

status epilepticus dosing

ethical dilemmas

psychosocial support post-ICU care