It's a privilege to be here with you today. They programmed this session several years in a row, so it's really exciting that they programmed it again. I've got some boilerplate information for you. All sessions can be evaluated through the mobile app and or the online course program. Don't forget to evaluate this session and the faculty when done. Presenter required to verbally disclose COIs. All rights are reserved. The video and audio content is exclusively the property of CHESS. Please assist CHESS staff in keeping the aisles and exits clear. Please make room for attendees to have a seat. CME claiming will be open starting on Wednesday, October 11th at noon. In terms of audio responses, I don't have any, but Akram, I think you do. Keep your phone handy and you can do that stuff. So like you say, we've got part one and two. It's a privilege to have this program again this year. Our first speaker is Akram Khan from Oregon. You may know him well from our Petal network where he's a master recruiter, but he's also a good speaker. So let's turn it over to him for non-pulmonary critical care. Thank you very much for coming. I'll warm you up for Bob and Neha's talks and start with the less day-to-day things, but things that happen frequently enough. Let's see if I can make this right. Maybe I can just press here. All right. My name is Akram Khan. I do a lot of clinical trials. These are my disclosures. Nothing related to anything we are talking about. I chose five major areas. I have a feeling with just 20 minutes, we may not hit cardiac arrest, but I have my bibliography at the end. Again, a reminder that you can poll and do sessions right through the app. So we'll start with line placement and bleeding. And I have a question for you guys. 58-year-old person presents to your ICU from the BMT floor. No active bleeding. Platelet count is 30,000. Otherwise, coagulation is completely normal. And you are doing a left IJ line with an ultrasound. And the nurse asks you, are you going to give platelets before this line placement? And we'll start with the poll. And these questions are meant more to bring things about and help you think through this. And all the questions I have put on, I really don't have an answer. All right. Around about 130 votes have been cast. Just to get us going, I will see what happens. So majority of you will not give a platelet transfusion. And in my mind also, this is probably also the correct answer. And I will go over why. This very important question was addressed in this study. And what they did was they took patients who were either in a BMT floor or in the ICU, who were going to have an ultrasound-guided line placement. And the goal was to give either one unit of platelet transfusion or not to give a platelet transfusion. And they looked for bleeding. Now, the trial showed that giving a platelet transfusion does decrease the risk of bleeding. But I want you to look at the next few slides to make your own determination. So for the primary result, they included grade 2, grade 3, and grade 4 bleeding. And I have highlighted that grade 3 and 4 bleeding, which we more commonly worry about in the ICU, as either you required some kind of an intervention or you became hemodynamically unstable. When you look at the results of the study, overall, when you included minor bleeding with grade 2 bleeding also, you showed a positive result. However, when you subset it out to the group of people who only had grade 3 or 4 bleeding, that result was not statistically significant. And going further into subgroup analysis, what they showed was that if you were doing a subclavian line on a hematology floor, probably being done by people who don't do a lot of lines, at least in the United States, you had more chances of having bleeding compared to when you were doing an IJ in an ICU. So that's why I chose that answer. Next up is nutrition. It happens every day in the ICU that you get some question from a resident or a dietician. And I'll just put this in perspective that our current guidelines from ASPEN and ESPN are to start nutrition within 48 hours in mechanically ventilated patients. They've given us a protein range of 1.2 to 2.2 grams per kilogram per day and a caloric range of approximately 20 to 25 kilocalories per kilogram per day. And at least at our system, our nutritionists are always trying to go towards a higher level. So start with another polling question. A 60-year-old male presents to the MICU. He's recently arrived, does not have very many medical problems. And your nutritionist is telling you that he has moderate malnutrition and frailty and wants to know if you want to use a high-protein diet. All right. We have around about 190, 200 votes. So we are split on this. And there may be good reason for that, and we have two articles to discuss that. The first one is looking just at protein. That was published in Lancet. And what the trial did was they took patients who had arrived relatively early, just like a case in the ICU. They were expected to be mechanically ventilated for approximately 48 hours, and they had some kind of a nutritional risk factor that would make them at risk for malnutrition. And what they did was they divided them into the two ranges of the Aspen in ESPN guideline. The usual group got 1.2 grams per kilogram per day, and the high group got the higher level of the same diet range. And what they did was that if you had a BMI more than 30, you got adjusted to a BMI of 25 kilogram per meter squared. For this particular study, they did not control the calories, although the calories were very, very similar across the two groups. And what they found out was that actually giving patients a high-protein diet, even if they have malnutrition risk factors, was not particularly helpful. The time to discharge from the ICU was very, very similar in both the groups. We'll go further and look at it in a different way what the next trial did, where they looked at not only adjusting protein intake, but also adjusting caloric intake. So a very similar patient. And this time, the question for you is, patient has just arrived in the ICU. Would you start them on the standard feeding that is recommended by Aspen and ESPN? Or would you start them on a lower calorie and protein intake and see for the first seven days? That's how the trial was designed. All right. We are around about 200 votes. I'll get us started again. And again, we seem to be split. Some people want to use standard. Some people want to use low calorie. So hopefully it will be helpful for us to go through this. And this is the Nutria 3 study that came out in Lancet Respiratory Medicine earlier during the year. And what it is doing is it is comparing these two groups that we just discussed across 61 French ICUs where you used early low calorie intake followed by early standard calorie intake. So the low calorie group got 6 kilocalories per kilogram and 0.2 to 0.4 grams per kilogram per day of protein, while the standard calorie group got what is the current recommendation. And again, they adjusted for BMI, and they looked for outcomes like extubation, withdrawal of vasoactive drugs, and mortality. And this is the primary outcome. I wanted to just give people the whole table, and I highlighted that, that using for the first seven days a low calorie, low protein diet did not lead to any significant increase in mortality. And what I was surprised to see was that you actually got discharged one day earlier from the ICU if you used a low calorie, low protein diet compared to a standard calorie, standard protein diet. And I've highlighted with stars here all the side effects, and what you notice here is that GI side effects were actually more common in patients who ended up getting the standard calorie intake. So the low calorie group gets discharged from the ICU a day earlier. Glucose control. And again, I have a polling question, and I'll again be honest, I don't have an answer for this. So you have a 66-year-old female who's admitted and currently on vasopressors, and the resident is asking you where do you want your blood sugar. You want it close to 100, 140, 180, or you're just going to let it ride and let it go up to 220? And in our ICU, our range is 140 to 180, and the reason I bring it up is that we have around about 250 wards, so we'll get going. And probably we are still split on the right answer at 140 to 180 because what is happening is that we have not clearly defined this, and Dr. Vanderberg has been working on it for many, many years, and she showed us that if you tightly controlled people, you slightly improved outcome, but you led to more hypoglycemia. So this time she came up with something slightly different, which is tight blood sugar control, giving people enteral nutrition and without early parenteral nutrition, and then using an algorithm, a computer-designed algorithm, to monitor and manage blood sugar levels. It's called the logic insulin algorithm. It's a computerized model. We use something similar in our hospital called EndoTool, but we use it for IV insulin infusions, and they wanted to study should we let blood sugar levels be around about 220 or should we try to bring them down to 80 to 110, like she had done for her previous trials. And what they found out was that once you did a tight blood sugar control or you did a liberal blood sugar control, there was no significant difference in outcomes, which was kind of surprising to me. And the other thing that is important on this slide is they are using this proprietary logic algorithm. Their incidence of hypoglycemia is slightly higher with the tighter blood sugar control, but it is not statistically different. I am not quite sure what will happen in large-scale studies, but certainly what this trial has shown us is that perhaps if we use some kind of AI or some other mechanical way of managing and monitoring insulin, we can prevent the hypoglycemia that we were causing in other studies. But on the flip side, this study has also shown that I'm not certain whether there are going to be changes in outcomes with this tighter blood sugar control. And I'm not showing you some other studies in this area that also showed, that were published in the Blue Journal, that also showed that liberal blood sugar around about 200 was not particularly harmful. Next, we'll move on to pancreatitis. And this is another polling question. A patient is admitted to the SICU with acute pancreatitis, and the SICU team is operating. So they call you to help with fluid resuscitation to determine how best to resuscitate this patient. You can give a small bolus. You can put them on some maintenance fluid. You can give them moderate or aggressive resuscitation. And the trial that we are going to discuss, discussed whether we should do moderate or aggressive resuscitation in patients with acute pancreatitis to see if it leads to changes in outcomes. All right. So most people have tended to do moderate resuscitation, which I think based on the trial that is presented here is also the right answer. And what they did was they took patients with, as I said, acute pancreatitis, very short time from admission, and they gave them either aggressive resuscitation or a moderate resuscitation. And what they found out was that, and the resuscitation parameters are the ones that I described in the introductory slide, that if you did aggressive resuscitation, you were just much more likely to cause fluid overload. But you did not have any significant difference in the risk of other complications, but fluid overload happened much more frequently. And you did not really decrease the risk of moderately severe or severe pancreatitis by doing this aggressive fluid resuscitation. So probably the right answer based on this trial is to stick with moderate resuscitation for acute pancreatitis. All right. So next, moving on to delirium and long-term outcomes. Another polling question. Essentially the gist is a patient is here with delirium, and are you going to give them some scheduled haldol? Are you going to give, which is in the trial that we discussed, are you going to give them some scheduled zeprasidone that was used in the MindUSA study? Are you going to give them 4 mg of melatonin at night that was discussed in another study? Or are you going to do redirection, maintain light and day cycle as needed, and use PRN, haloperidol, or zeprasidone as needed? All right. We have had enough people vote, so I'm going to enter our poll. And again, in my mind, this still, after these two studies that I will very, very briefly discuss, is probably the right answer. So the study we'll discuss is the use of haldol for treating delirium in the ICU. And what they did was they took people who were CAM-ICU or ICD-SC positive, gave them haldol 2.5 mg three times per day, and then as needed for a maximum of 20 mg versus placebo. And everybody who got delirious got some additional medications. Propofol, benzodiazepines, or dexmethotamidine as needed. And you stopped the treatments whenever the people stopped getting delirious or they were discharged from the ICU. So a couple of things to note. Scheduled haldol did not lead to any improvement in outcomes. So it was not helpful, as you guys very rightly pointed out. But there is another important thing to note here, which I pointed out, that nearly 60% of patients in both arms got some kind of a rescue medication, whether they needed it, you know, whether they were getting the drug or placebo. So we do end up using these rescue medications all the time, and that probably is the way to go. Now, this study also notes that the people who got haldol had a slightly lower level of mortality. The authors pointed out that they don't know why the mortality was lower. It was a pragmatic study. They did not collect a lot of other data for this group. So they don't know why the mortality is lower, and this may be something further to explore in further studies. Very briefly, earlier in the year in intensive care medicine, they came out with a pro-medic study where everybody got four milligrams of melatonin at night for three weeks while they were in the ICU. And what they found out was that it was not significantly different. How much time do I have left? None. All right. I will go ahead and stop here. No, bottom line. What's the bottom line for mobilization? Didn't work, did it? Okay. The bottom line for early mobilization is that the early mobilization did not show a difference between early mobilization versus no early mobilization. However, I will point you out to these facts from Dr. Wes Ely in his editorial. The big problem with the early mobilization study is that 81 percent of the control arm also got some form of early mobilization, and they got at least early mobilization for 10 minutes, while the study arm got 91 percent of them got early mobilization for 20 minutes. So what we have not figured out is what is the correct dose of early mobilization, and the control arm was corrupted by the fact that everybody got early mobilization there also. All right. I'll stop here. Very good. Awesome. Thank you very much, Dr. Ely. We're going to keep it moving, though. Neha Dhankaraj from Mount Sinai is our next speaker, repeat customer from last year on neurocritical care. So, like I said, kind of keep it tight. Awesome. Good morning, and thank you so much for having me again. My only disclosure is I love neurocritical care, and I love giving this kind of talk to an audience that loves evidence-based medicine as much as I do. So we are going to do a rapid fire because there's a lot of exciting things happening in neurocritical care, lots of innovations to share. So let's dive right in. First, we're going to go to the world of acute ischemic stroke. Last year, I gave you some updates. Let's do a quick refresher of how did we get here. Thrombectomy is the gold standard treatment for emergent large vessel occlusion in the anterior circulation. How did we get here? 2015, five RCTs, and then a combined meta-analysis, the ERMES meta-analysis, that showed an adjusted combined odds ratio, impressive, of 2.49. Number needed to treat to improve functional outcomes, 2.6. So this is anterior circulation. Our window expanded to 24 hours with Dawn and Diffuse 3. So what about the posterior circulation? So last year, I showed you the Bauchi and the attention trials. So yes to endovascular therapy in the posterior circulation for basilar artery occlusion right up to 24 hours. What about skipping thrombolysis because thrombectomy is so good? Hold your horses, we're not skipping thrombolysis. And that holds true because I'm going to show you some cool stuff. So just a quick refresher on what is ASPEX. ASPEX is the Alberta Stroke Program Early CT Score. All those trials for the anterior circulation had a cutoff of ASPEX of six. Cutoff of ASPEX of six or higher to prevent hemorrhagic transformation. But let's challenge that paradigm. So large core thrombectomy is the new kid on the block. There's a lot of data and controversy around this right now. So large core is equal to ASPEX less than six, but more than three. In patients presenting for more than six hours from last known normal, CT perfusion, large core, or using MRI. So we'll talk about ANGEL, ASPEX conducted in China. Very nicely conducted study looking at this large core infarct. And if you look at the functional outcomes and the shift analysis, yes, improvement in functional outcomes for the 230 patients who were randomized to endovascular therapy as compared to medical therapy alone. But a couple of caveats when you interpret the results of this study, urokinase. We don't use urokinase in the United States for acute ischemic stroke, but some patients got urokinase and patients older than 80 were excluded. When you look at the SELECT-2 trial that was conducted in the United States, when we look at that, it was terminated early, again, because of efficacy. When we look at these shift analysis, this is the modified Rankin scale, and higher is worse, lower is better, so they had better outcomes. But look at death from any cause, similar. Symptomatic hemorrhage was lesser in the SELECT-2 trial, but we're seeing more hemorrhage in ANGEL-ASPEX. So what does this mean? But not more symptomatic hemorrhage, just more hemorrhage. So in this updated meta-analysis that also includes Elon Musk's study, Tesla, he can't seem to get anything right. Nope, this Tesla has nothing to do with Elon Musk. But this Tesla did not meet its primary endpoint. But when you combine the results with SELECT-2 and ANGEL-ASPEX, there's still a benefit of thrombectomy in large-core infarct, but more hemorrhagic transformation. So here's the synopsis for thrombectomy for large vessel occlusion in anterior circulation, posterior circulation. Do not skip thrombolysis. Next year, I will talk to you about MEVO, or medium vessel occlusion trials. Patients with pre-existing disability, what should you do? Somebody comes in with a low NIH stroke scale, what should you do? Thrombolysis. Everybody knows this data. Lots of different trials that gave us this dose of 0.9 milligrams per kg, 10% as a bolus, rest as an infusion, max dose 90 milligrams, up to 4.5 hours thanks to ECAS-3. But there's a challenge to alteplase from tenecteplase. Tenecteplase has not been FDA-approved in the United States for acute ischemic stroke yet. However, this is a modified version of alteplase, larger molecule, slightly longer half-life, and can be given only as a bolus, only as a push. So definitely advantages using tenecteplase. But what does the data show when they go head-to-head? When they go head-to-head, a lot of different studies have looked at this question, 2022, three RCTs, again, showing smack in the middle, non-inferiority, alteplase versus tenecteplase, well, in my mind, there's a winner. TRACE-2, published in Lancet, looking at the outcomes, not different, but this was a non-inferiority trial, proves the non-inferiority, again, of tenecteplase. According to the European Society for Neurology, they accepted this, that yes, we're going to use tenecteplase. And a lot of centers in the United States have also moved to tenecteplase instead of alteplase, just given that there is a signal of improvement in outcomes for specific subgroups. For thrombectomy patients, if you give tenecteplase, the outcomes may be better. But TRACE-2 was not designed to answer that question. We're seeing a signal of improvement in outcomes, and also improvement in outcomes in patients who are older. Does time matter? Just like we saw in alteplase, the faster you give it, the better the outcome. Same thing, secondary analysis from the ACT study from 2022. This was just published a couple of days ago. Faster is better. What about atrial fibrillation? We know that patients who have acute ischemic strokes from atrial fibrillation have higher mortality and higher morbidity. So can we use atrial arrhythmia epiphenomena to identify these patients and put them on primary prophylaxis? Really cool, cool question. But how do you identify what these atrial epiphenomena are? So these atrial high-rate episodes were defined as episodes lasting more than 170 beats per minute for at least six minutes in patients who had any of these different devices, pacemakers, defibrillators. And these episodes occurred two months after these devices were implanted. So how about let's just put them on edoxaban. So you won't see cardioembolic stroke. You may not see systemic emboli. Not a positive study, but promising study. This one tackles a very important clinical question, timing of starting anticoagulation after acute ischemic stroke and atrial fibrillation. For me, clinically, I usually look at the size of the stroke. Is it a mild or moderate-sized stroke, or is it a large stroke? If it's a mild or moderate-sized stroke, maybe I'm going to wait at least 72 hours to prevent hemorrhagic transformation. That's probably what most of you are also doing, right? And then if it's a large stroke, we'll wait maybe up to two weeks before we start anticoagulation. So this trial was designed very nicely to stratify patients into this mild to moderate, large stroke group. However, the stroke sizes were not adjudicated in a central manner. So we don't know what or how different centers define this as. So early anticoagulation in these stratified groups, mild to moderate, let's start anticoagulation within two days. And if you have a larger stroke, maybe we'll start it at day seven or so. And the bottom line is they really did not see more hemorrhage. So for me, I'm wondering if this is going to be practice-changing. Now, are we going to see more early anticoagulation in patients with atrial fibrillation-related strokes? And this is just cool. That's why I wanted to put this here. Remote ischemic conditioning, such a nicely conducted pre-hospital. A patient is having a stroke, put in the back of the ambulance. Let's do some remote ischemic conditioning of their arm by inflating a blood pressure cuff to more than 200 millimeters of mercury. Cool idea. Lots of animal data to support this approach. However, not a positive study. Moving from acute ischemic stroke to intracerebral hemorrhage. Lots of great stuff happening here. Last year, I showed you the AHA-ICH guidelines. I'm going to talk to you about my favorite, favorite trial of this year in neurocritical care. Therapeutic targets. ICH is no longer a disease process that means poor outcome. All right? So lots of different therapeutic targets, lots of trials in the last few years. I'm going to talk about a couple of them, particularly in the minimally invasive surgical evacuation realm as well as Interact 3. So just a quick refresher on minimally invasive surgical evacuation. the MIS-T3 trial did not meet its primary outcome measure, looked at how a catheter inserted into the hematoma and dripping TPA to lyse the clot can improve outcomes. It did not meet its primary endpoint. However, it did inform the AHA-ICH guidelines that were published last year. Minimally invasive surgical evacuation is recommended to improve mortality, but can be considered to improve functional outcomes. So here's the cutting edge. This trial has not been published yet, but the findings were presented at the double ANS, the American Neurosurgical Society meeting. This is a minimally invasive paraphysicular approach to remove the hematoma, and they found an improvement in functional outcomes. So you're gonna see more minimally invasive surgical evacuation for ICH. There's more hope, there's improvement in outcomes. Blood pressure. Last year I told you who chooses odd numbers. Who chooses odd numbers for blood pressure control? But that's what's going on here. Based on Interact-2 and ATAC-2, the ICH guidelines recommended let's target SBP 130 to 150, smooth blood pressure control, get your blood pressure control in early, within two hours to prevent hematoma expansion. This is my favorite trial of the year, and I don't want you to read this figure. This is essentially a really neat step wedge cluster randomized controlled clinical trial. The implementation of a bundle, ICH care bundle, which included blood pressure control, note that their target was less than 140, coagulopathy reversal, strict glycemic control, and antipyrexia or antifever treatments. Implementing such a bundle in an international setting with low and middle income countries that did not have any protocols for providing ICH care, can that make a difference? And the simple answer is yes, it makes a difference. Better outcomes. You can see the modified rank in zero to two, much bigger than that in the control group. Seizure prophylaxis, very controversial. This trial did not change my practice, though. I do tend to put patients with low-bar ICHs on seizure prophylaxis. They ran out of funding. So they had only 50 patients. However, they did give seizure prophylaxis to patients with deeper ICHs, which we don't end up doing. But this is the peach trial. Seizure prophylaxis in ICH, particularly low-bar ICH, for about seven days, yes. Subarachnoid hemorrhage, worst headache of someone's life. This has shown up in everybody's boards. Lots of things happening in SH, right? Starting with, I was a proud co-author on these guidelines and we covered the entire spectrum, right from triage to recovery. Survival after ICH is definitely improving. So we need to focus on survivorship as well. DCI, delayed cerebral ischemia and cerebral vasospasm. How do we monitor this? How do we treat it? How do we improve outcomes? So the guidelines did a super nice job. Of course, I have a conflict of interest. I have to say that, right? But did a really nice job of providing recommendations on all the different multimodal assessments that you can use to diagnose this clinically difficult problem. And this is the number one cause of morbidity and mortality in subarachnoid hemorrhage patients. So what all can you use? The neuro exam, transcranial Doppler, CT angiogram, CT perfusion, EEG, continuous EEG monitoring, along with quantitative EEG analysis. This is looking at specific indices to be able to identify who is going into spasm. So if you thought EEG was only good for seizures and titration of anti-seizure medications and status, well, there's a lot more to that EEG story and multimodal monitoring as well. ICU survivorship, new recommendations for different multi-domain outcome measures, user screening, screening tool. And the guidelines provided this for every single domain, physical, cognitive, mental health. Fluoxetine has not had a good year. Fluoxetine in several RCTs for stroke patients, flame trial was the one that showed us maybe it's going to improve motor outcomes. And I was super excited about this. And I was putting all my stroke patients on fluoxetine. However, after these RCTs, and there is a signal of harm, fluoxetine for improving motor recovery in stroke patients, including subarachnoid hemorrhage patients is not recommended. But if your patient was on fluoxetine for depression, you can continue that. Early drain. This is the first positive RCT in more than 20 years in the subarachnoid hemorrhage world. Early drain looked at lumbar drain plus EVD, so standard of care kind of management, versus standard of care alone. So all their SAH patients who had EVDs also got lumbar drains. So comparing the two, lumbar drain versus usual care, is there an improvement outcome? Again, the shift analysis shows us, yes, there is an improvement in functional outcomes. I'm showing you the collection chambers, why this may be happening. Why an improvement in functional outcomes? Look at the collection chambers, and look at this CSF color. This is from the EVD on the left-hand side, and on the right-hand side is the collection chamber from a lumbar drain. So maybe because of gravity, you're clearing more blood and mixed with CSF, and maybe that's why it has better outcomes. Subdural hematomas, we all need to know more about subdural hematomas. With our aging population, all of us are gonna take care of these patients. But there's exciting stuff happening in the subdural world. It's not just a little bit of bleeding in the coverings of the brain, not anymore. So, first we'll start with a surgical trial. Surgical trials are always hard, right? You can't blind the patients, et cetera, but this was really nicely conducted. Looking at a subdural hematoma, randomizing them into a craniotomy, versus a hemicranial, taking a bone flap off, what is going to be better? The simple answer was that these were not different. However, there were more repeat surgeries that were required in patients who underwent craniotomy. There were more wound complications in patients who underwent hemicranial for subdural hematomas. There was obviously, like all surgical trials, there was crossover as well. Next, I'm gonna talk to you about middle meningeal artery embolization randomized controlled clinical trials. Why are we embolizing an artery for a venous bleed, right? Because subdural hematomas have these membranes that form within them, and these membranes are supplied by branches of the middle meningeal artery. There's a lot of inflammation that's happening there. So, what has been found, is when you look at this kind of subdural hematoma, this is chronic, subacute to chronic, middle meningeal artery embolization, and that chronic subdural hematoma without a craniotomy or craniectomy did not recur and also got resolved. So, this is very promising. Moving to trauma and TBI, I'm gonna highlight only a couple of things here. The PATCH trauma trial, and of course, as a neurointensivist, I love devices. We'll talk about ICP monitoring too. The PATCH trauma trial, again, very nicely conducted by the ANZICS group and looking at, in centers that take care of a lot of trauma patients, if you gave patients tranexamic acid in the pre-hospital setting, in those patients who were at a risk of developing trauma-induced coagulopathy, are you going to see an improvement in outcomes? On the right-hand side is a PATCH trauma trial. This, I just put on the left-hand side to make sure that you were awake. So, CRASH-3, which is on the left-hand side, showed an improvement in outcomes in patients with traumatic brain injury within three hours if they got tranexamic acid. However, in PATCH trauma, when patients got, including patients who had traumatic brain injury as well, when they received tranexamic acid, there was no improvement in outcomes. And the other worry is, are we causing harm? Were there more DVTs, PEs, vaso-occlusive events? The simple answer is no. They didn't have more vaso-occlusive events, but is this really gonna change our practice in light of CRASH-3? TXA, again, is not having a great decade. TXA in ICH, not recommended, and TXA in subarycnoid hemorrhage, thanks to the ULTRA trial, led to the downgrading of the recommendation of using antifibrinolytic therapy in patients with aneurysmal SAH before their aneurysm is secured. And because you were not able to cover cardiac arrest, I figured I'll do a quick rapid fire of cardiac arrest. Everyone's favorite topic, TTM. Let's do this, let's not do it. Well, the simple answer is yes to targeted temperature management. The temperature may not matter as much, but that's in my humble opinion. So, let's start with TTM and the duration, right? So, fever prevention matters, we all agree. Fever prevention matters. For how long should fever prevention be done? What about 36 hours versus 72 hours? No difference in outcomes. The BOX trial, superb. This essentially looked at a two-by-two factorial design, looking at two important questions. What should your MAP target be, and what should your oxygenation target be? Two separate studies, looking at a MAP of 73 versus 65, no difference in outcomes. And looking at O2 targets, a liberal therapy versus a more conservative therapy. So, liberal was 98 to about 105 millimeters of mercury, compared to 68 to 75 millimeters of mercury. Again, no difference in outcomes. So, the BOX trial shows us that maybe these MAP targets and the O2 targets may not matter as much, as long as you're using physiological targets. What about carbon dioxide? The TAME trial was a very well-conducted randomized controlled clinical trial. I don't expect that anyone's going to answer this question again. However, the hypothesis for this trial was hypercapnia leads to vasodilatation, so maybe mild hypercapnia can lead to better cerebral perfusion. So, let's try that. Unfortunately, that did not work. Prognostication after cardiac arrest. This is still multimodal prognosis. Prognosis in various severe acute brain injuries, including cardiac arrest, is very hard. New guidelines published by the Neurocritical Care Society. And what are the good predictors of outcomes? This paper by Claudio Sandroni's group does a nice job of summarizing all of the literature on good outcomes as well. So, how do you predict good outcomes? How do you prognosticate you still rely on multimodal prognosis? Exam, biomarkers, and imaging, EEG. Devices, let's do a quick rapid fire of ICP, portable MRI, pupillometer. ICP monitoring, the only RCT in ICP monitoring is Bestrip ICP, Bolivia, Ecuador, they don't usually use ICP monitors. Randomization, no difference in ICP monitoring versus imaging plus clinical exam guided ICP management. The Synapse ICUs, an international observational cohort study, essentially shows us the probability of your patient getting an ICP monitor depends upon where they show up in the world. Japan essentially showed that ICP monitoring guided therapy, this propensity matched cohort, improved outcomes. Well, Reactive from Europe, mostly Hungarian and Italian ICUs show that maybe it's not associated with better outcomes. The simple takeaway is ICP is just a number. And we need multimodal monitoring, multimodal assessments and TBI is a very complex disease process. Portable MRI, published in JAMA 2021, this was published just a couple of days ago. You can use a portable MRI, super low field, you don't need all that MRI safety stuff. Machine learning, artificial intelligence amplifies these images. You can diagnose ICHs at the bedside. And I'll wrap up with pupillometer. And pupillometer, the ORANGE trial, is the largest prospective study that looked at pupillometer objective readings and looking at this neurological pupillary index, yes, associated with outcomes. So I will stop here because we are running out of time. So I'm going to now show you just one last study on ICU survivorship. The APICS01 study that shows us that patients who have post-intensive care syndrome have our patients who are surviving from our ICUs and going back into the community have lots of different needs. We're going to need dedicated post-ICU clinics to help these patients get reintegrated back into society and address the unmet medication as well as unmet non-medication needs. Thank you so much. Thank you. Let's see if I can, where do you click escape here? How do you get out of here? There you go. All right, well, our first two speakers did a great job. I'm afraid mine might suck, so hopefully not. And a world tour as soon as we get loaded here. Great, so mechanical ablation and respiratory support is my topic, that's who I am. I have no relevant disclosures. And we're gonna talk about personalized non-invasive support, oxygen tolerance, something called Wean Safe, which is a survey, nutrition prior to extubation, and post-extubation support. So those of you who've attended this meeting in the last several years, I've gone through a lot of these papers related to how to keep a tube out. And some literature has shown things like, you may remember the Florale trial, where the high-flow nasal cannula had a mortality benefit over non-invasive. But then the question is, is it, what kind of non-invasive? That was face masks non-invasive. We have a helmet, and Bhakti Patel and J.P. Kress showed superiority for ARDS, but it was a small trial. And you say, well, what about the face mask? What about a bigger trial? And I think I presented to you last year in a COVID trial of face mask versus heated high-flow, where there was no superiority seen. Now, I'm old school when it comes to audience participation. How many people are using a helmet in their ICU for non-invasive ventilation? Well, there's one. So the silence is deadening, isn't it? It's interesting to me, because you could argue that we should have this available, but I'm fighting in my own institution for that availability. Now, the good news is the COVID trial, and I happen to think COVID is ARDS. It's not some particularly bizarro thing, and there was not superiority seen for the helmet, but it may be something we should offer. And so obviously, if you're gonna do it, you might as well do a bi-level, if you will, a PSV plus CPAP, not CPAP alone. And the idea here is, should we avoid wide-pressure SINGs and pleural pressure, something called patient self-inflicted lung injury? So I share with you only this, which was someone put in an algorithm, if you will, to how to make sense of all this information, really. And it's one observer's notion, not something I necessarily even agree with, but this is for acute hypoxemic respiratory failure. Over here, this is one big table. I broke into two, and you can see the left to talk about, well, you know, the PDF's not so bad. Let's start with heated high flow. All right, that's fine. And then over here, let's look at the ROCKS index. I mentioned that a couple of years ago, right? This is a simple coupling of SAT and FIO2 and respiratory to see how they're doing. And based on literature, which I shared with you years past, what are the numbers? The higher ROCKS number, the better. We had different thresholds between COVID and non-COVID with heated high flow. But you really wanna know, what about these sick people here? And this particular author said, well, it depends if they're sucking air or not. You know, less effort, give them heated high flow. More effort, maybe you ought to give them non-invasive. Now, I argue if you give them non-invasive, particularly in the context of the alveoli trial, they'd go with the helmet, right? Because there really was not superiority for face mask non-invasive alveoli. So now, if you look at the fine print here, this is talking about, and I know I'm not gonna get any hands here, looking at this PCILI notion, right? And a lot of smart people think PCILI is important, sucking air, if you will. Pleural pressure swings are bad. And you might remember in the COVID era, oh my God, they're sucking air, just tube them, right? PCILI is gonna get them. That's gonna modify their lung injury. How many people are using esophageal pressure monitoring in non-invasive ventilation? None, okay. That's what it says to do here. And so, you know, cause you're breathing fast, you're respiratory failure, let's take a balloon down your throat, right? But I think the point is conceptual and worth thinking about. And we don't have the answer. And frankly, when I look at PCILI, I keep waiting for them to show me the clinical data to say this is a bad thing. I'm not interested in people having wide pressure, pleural swings, pleural transplant pressure either, but I have yet to see a clinical outcome related to that. So when in doubt, keep the tube out, heated high flow is something to do. And I would argue, okay, if you wanna go all in there with a face mask, avoiding the large tidal volumes that might accrue, then at least give a helmet. So I have no, I don't, I'm not shilling for helmets. I don't even know who makes them, but maybe you ought to have them. Okay, moving on to oxygen saturation targets. This is the group at Vanderbilt. I think I saw Todd Rice here. They do a lot of really good implementation trials. This was a pedal trial that never got done. So thankfully we owe it to our friends, you know, Semler, Casey, Rice, and Al at Vanderbilt for doing this. And so you might remember a lot of literature, again, I've shared in the past, oxygen targets, but oxygen's a bad thing for you, right? Free radicals, you already have lung failure, hypoxic respiratory failure, might get some worsening lung injury. In the past, we saw trials that were high versus low SATs. And so, and they're kind of a, some show advantages to avoiding the high saturations, but the question was, is there sort of a Goldilocks moment here? You know, not too low, not too high. And of course, some of my colleagues at Michigan brought you information regarding saturations as they relate to African-Americans being a huge concern. So the question was, was there a U shape? Was it a sweet spot? So what these guys did was said, let's try to do it three ways, right? And based on saturation, we've got three groups. Now, it's not the saturation that injures the lung, it's the FiO2, right? So they had an experiment. The bottom line is they had three, randomized the three targets. You can see here that they achieved that. And you see over here that correspondingly, the FiO2 did differ between groups, okay? So there was an experiment, they got separation. So I think we can say that there is probably some usefulness here, except they didn't find any clinical difference, right? And in terms of ventilator-free days, which are days alive off the ventilator sensor to day 28, or other meaningful clinical outcomes like cardiac arrest, pneumothorax, what have you. So I would argue the case is now closed and I think respiratory therapists are breathing a sigh of relief everywhere, right? Because as you know and I know, they'd rather run them high and not have to worry about running in every room with the alarm. I'm not here to advocate, I'm just saying that, look, if we show low targets are superior, then for heaven's sake, do it and make your therapist do it. But you can't make a compelling argument. It's like mobility, frankly. It's hard for me to make a compelling argument for my nurses to do mobility when every trial keeps coming back negative. Okay, so let's talk about Wean Safe. There was something called Lung Safe a few years ago. It was in JAMA about ARDS, this big international survey. This is a weaning survey, comparably large in scope. About 10,000 patients, around half of them were excluded because they weren't on the vent very long. So of the subset that was on the vent for more than two days, they examined this group. This was in Lancet Respiratory Medicine earlier this year. So they had over 5,000 patients on the vent for at least two days. And this is, I think, instructive. Yes, this is observational, but I think the notion is it gives you at least a sort of a benchmark against what the rest of the, I guess you could argue Western, this is resource, not resource-limited environment, but Western medicine world does when it comes to weaning. So you got about 5,000 patients, at least 77% had at least one attempt, a separation attempt. See, we're not even calling it weaning, right? Liberation, readiness testing, what have you. And actually, a huge percentage, and this doesn't comport with, you can benchmark, of course, your own kind of population. Nearly 2 3rds had a quickie. Weaning is readiness testing. They were ready and they were off. Only 10% had a four to six day wean. You might remember the wean criteria a few years ago. I think I presented that. You know, the kind of three categories of weaning, and then only about 10%, 9.6 had a prolonged wean. 15.5 had a weaning failure, and about 20% had trachs. About 2 3rds, 65% were weaned at 90 days with about 22% dying, or 28% rather, dying on receiving ventilation. So the median time to the first attempt after meeting criteria was right away. You think that's pretty good, right? That's what you want. You don't want to be sitting around keeping people on the vent. But actually, a number of them had a delay of about five days. So that was kind of instructive to think, well, what's up with that? Why wouldn't you wean somebody who's weanable? And so here are the criteria. And I will tell you that some are not surprising, and one is really surprising, and I think really food for thought. We heard that for frailty, that's a big, important thing. Obviously, if you come to the ICU debilitated, sick, malnutrition, et cetera, it's going to be an uphill climb, so will trauma. If your head's not in the game, right? Non-trauma neuro events, or you're stealing their consciousness away with a lot of sedation and neuromuscular blockade, these are going to be barriers towards initial weaning when maybe your lung mechanics aren't particularly bad. Now, I had to do a double take with this force plot. I thought maybe I had it wrong. But having an ICU written weaning protocol was associated with delayed initial weaning. So you kind of say, that's a head scratcher, isn't it? And you say, well, that's backwards. And then you think about it a little more, and you say, well, OK, I mean, I'm old. I can change. It used to be, say, for example, you had to be off vasopressors. And so daily screening promotes weaning at my ICU. Les Ealy showed that many, many years ago. But if you wait for your ICU therapist to do weaning according to protocol, it's safe, right? You want to stretch beyond what they might do safely. But if you're waiting for that trial, maybe you're waiting a little too long. So vasopressors would be an example. I'm not talking about high dose. The literature shows, Dean Acosta, my place, I think Haley Gershengorn showed, if you're on a little piddly dose of pressures, that may not serve as a pediment of weaning. So I tried to make some sense out of this. OK, maybe I do get this. Because if the only time you're going to consider a spontaneous trial is when your respiratory therapist protocol kicks into gear, maybe you're not pushing hard enough. Now, we also had the failure to wean population as well. There's the force plot for that. Again, in this case, no real big surprises. Aging, no compromised frailty, CPR. Your head's not in the game. But that pre-existing limitation, but also deep sedation. So food for thought there, right? I mean, clearly, you can't control non-traumatic neurologic event or CPR. But you can control moderate sedation. That does seem to get in the way. We had a lot of good data on reintubation and tracheostomy, about 13.7%. As a quality kind of guy, you're never going to have zero defects when it comes to readmissions to the ICU. You're never going to have zero defects when it comes to reintubation. So there has to be some kind of acceptable, right? Because if you have a zero reintubation rate, you're probably waiting too long. So here's a benchmark for you. I mean, you can take it for what it's worth. But clearly, we're not going to have zero defects. Also, it's instructive to see a median time to trach. There was some literature. There was a data collection some years ago showing about the same thing. In interquartile range 6 to 15, there's never really been, and I think I presented some of this literature in the past. This early trach depends on definition versus late trach. No benefit to early trach. But somewhere around 10 days, right? Somewhere around a week, and then beyond. Where are you going with your patient with respiratory failure? Are they just about ready to come off? Are they unfortunately going into multiple hooking failure and likely to succumb to their illness? Or are they going to be stuck? And that's time to think about. So that does give you a reality check, too. I know that my own institution, frankly, I'm not sure we're as aggressive as we need to be on this issue. No one wants a hole in their neck. I get that. But there are reasons why tracheostomy can be a good thing. Let's move on to enteral nutrition. This is sort of a non-pulmonary issue, except it comes to extubation. Now, there was some literature, or maybe a JAMA paper years ago, trying to talk your nurses into not caring about residuals when enteral alimentation, the aphorism, if the gut works, use it. It said it didn't make any difference. We're always worried about aspiration. Aspiration, I mean, I don't want anyone to aspirate, but it's like they gurgle a little bit. Next thing you know, they're on broad-spectrum antibiotics, I swear. But there was no benefit to bird-dogging patients' residuals. Well, here's another one for you. If we talked about delays in weaning, one of the delays in weaning one could have is, well, oh, they did an SBT. Well, I'm sorry. I forgot to stop the tube feeds. All bets are off. Tomorrow's another day. Wrong. So I mean, look, for one thing, I can change. I mean, when I grew up, we're given Dobhoff tubes. What's that, right? A bowl is feeding through an NG tube. And if we didn't stop tube feeds before you wanted to pull the tube out, here's an idea. Get a syringe and suck them out. I mean, it's not that hard. But anyway, this study showed that you don't have to wait anyway. In other words, try to convince your nurses here, but it's not a freak-out. Now, I'm not talking about someone who has upper abdominal obstruction and is vomiting all the time. But for the normal population, there is no benefit to holding off extubation based on the fact that, oh, I forgot to write the order to hold the tube feeds. It just doesn't comport with an outcome of concern, like aspiration, for example. Last thing for you here is post-extubation non-invasive ventilation. Now, again, through the years I've been here with you, we've talked about all this literature. And rather than going through all of it like I did on the first slide, let me just tell you it's state-of-the-art here. And we had a paper showing that heated high-flow post-extubation was non-inferior to face-mask non-invasive ventilation, which is good. The subset of acute and chronic hypercapnic COPD patients was too small to examine. So we thought, OK, that's cool, because what? My respiratory therapists don't like to do this non-invasive face-mask post-extubation. I don't know about yours. So that kind of gets them off the hook in a way. But then a JAMA paper a couple years ago, which I shared with you, showed, hey, how about if you do both, and that's superior to heated high-flow alone? That's kind of where we're at. My respiratory therapists still hate putting people on face-mask post-extubation. So this population, though, is a rarified world. So in the study I mentioned to you, you're talking about patients who have some risk factor, at least one risk factor, puts them at high risk. And that might be age. It might be COPD. It might be heart failure, et cetera. But this study was looking at RCT people at least four, I mean, super high risk, if you will. And so this was comparing high-flow and with active fumigation with face masks non-invasive. So this is face masks. By the way, I don't know of a single helmet study post-extubation. So when I tell you I'm going to buy some helmets, don't stick them on post-extubation. All bets are off. I'd like to think that that probably would be kind of a goofy, risky situation. So we're back to face masks for post-extubation. And by the way, this is not once you're breathing 40 times a minute. This is, right, prophylactic, right? It's a number you need to treat. You're playing the odds. By doing something, maybe you get your reintubation rate lower to the acceptable range. So anyway, they had at least four of these comorbidities. These are legitimate things dating back to 1985, the Apache 2 system. Remember that one? In the public domain, obesity, secretions, clogged wounding, et cetera, et cetera. And guess what? They found that it was better to do a face mask non-invasive inhalation when you were super high risk. And again, this isn't once you're failing. This is once a tube comes out. If you wait until you're going down for the third time, and then say, oh, wait, let's try some non-invasive, then I think that's misguided. OK, so what have I told you this year? And what are my biases? Well, keeping the tube out, I'd say heated high flow is the winner. And then helmet, I would argue a COVID study is a real study, and it didn't have superiority for helmets. But we do have a CHESS guideline. We're very pleased that CHESS is supporting a guideline about non-invasive support both on the front end, keeping the tube out in post-extubation. That is ongoing. We've got eight PICO questions we've selected. I think probably too, I mean, if we're fortunate enough to get this program next year, probably too soon to have that in print. So I promise you, if we keep getting programmed, maybe two years from now we'll have that information for you. In terms of oxygen targets, really, I think we have enough information. I don't think we need to keep doing these trials anymore, in terms of having a benefit to running them low. In terms of reasons for being stuck on the ventilator, I think consciousness, right? Whether that's inherent to the patient's condition, i.e. CPR or non-neurotrauma, or alternatively, just we're sedating them too much, our delays. And sick people are more likely to be a failure to wean. And I think to a physio, I think this seems like a silly issue, except when your nurse is saying, Katie, bar the door. We're not going to extubate them, because you screwed up. You didn't write the order. And then finally, consider non-invasive ventilation to prevent reintubation. Patients at very high risk. And there may be superiority, at least in one trial, compared to heat at high flow. So that's what I have for you. I'm going to ask our speakers to hang around. We have a 15 minute gap between the next session. Please hang around for that. If not, you can sell your seat to someone else and donate it to my family center I'm trying to get money for. Thank you.

critical care

respiratory support

non-invasive ventilation

hypoxemic respiratory failure

weaning practices

ICU

oxygen therapy

enteral nutrition

extubation

high-risk patients