Good morning. Okay. There we go. Don't judge. My feet are killing me. I'm Dee Bender. I am the Professional Development Committee Chair. And a couple of reminders that you have heard day after day after day, but I'm going to remind you again this morning, download the AANACE app so you can download it for free. Okay. So, let's get started. and claim your CE. It's actually not the CE app. Download the AANA Meetings app. You can find bios in there. There are slides to presentations in there, but that's also the easiest way to claim your CE. You have until September 9th, noon Pacific time to do it. That's enough, because I know that you've heard that. So I'm gonna move along to the thing that's important here, okay. It's my pleasure. To introduce some of my favorite colleagues, actually. Dr. Brett Morgan. Dr. Zahn, Sentamal, and Ms. Rhea Timmerman. I'm gonna let them tell you their positions, because when I read it, I don't think it has the humanizing effect. It doesn't. I can tell you this, and I'm just reading it. I would like you to say it, because you're talking to your audience, and you don't want to hear me talk. So you guys welcome them. Thank you. OK, make sure everything goes up on the screen as it's supposed to. Good morning, everybody. Thank you for joining us this morning for what we hope will be a very interesting talk on an issue that we know all of you as anesthesia professionals are very interested in and interact with pretty frequently. My name is Brett Morgan. I am the senior director of education and practice here at the ANA and one of the CRNAs on staff. And I have the privilege of working with subject matter experts from around the country to explore how the ANA can better educate and expose our members to contemporary topics related to nurse anesthesiology and connect you with those subject matter experts. So today, I'm really honored to be joined on the stage with two of our nation's leading thought leaders and nurse scientists studying the relationship between anesthesia and brain health, particularly in our most frail and vulnerable population. So that's what we're going to be talking to you about today. I will introduce Dr. Zahn Sentamol, who will provide his expertise, having done original research in this area, and then Rhea Timmerman, who is also currently completing a PhD in this area of science and has really developed quite an expertise in this area. So thank you for joining us today. Hoping I'm going to hit the right buttons here. We do not have any conflicts of interest related to this topic to disclose, and we will not be discussing any off-label uses of monitors or drugs during our talk. By the end of today's talk, we do hope to have made a bit of an impact with you on exposing you to what the current research is in the area of anesthesia and post-operative brain health, particularly in our frail patient populations. The term elderly is often used, but we are going to use the term frail patient a lot today, meaning those who biologically have reached advanced ages, even if their chronological age doesn't reflect that. We're going to discuss brain monitoring in particular in that frail population, and then we're going to hopefully give some clinical applications and tools for how you might want to incorporate monitoring and process EEG into the care of those patients. I want to stop and just let you guys know that this team, we authored a manuscript that was published in the most recent journal of the AANA Journal, and that is the crux or the premise for this talk that you're hearing today. If you have not read that article, I would encourage you to take a look. You can scan this QR code, and that will take you to the article. And that'll give you a little bit more detail on some of the stuff we're going to talk about today. All right. So as our population continues to grow older, the demand for surgery in our frail population will continue to steadily rise. It is expected by 2050, 22% of the population will be 65 or older. We know that aging leads to anatomic and physiologic changes to the brain that makes our frail patients more sensitive to the depressant effects of anesthetic medications, and places them at an increased risk of developing post-operative neurocognitive complications, such as post-operative delirium and post-operative cognitive dysfunction. This morning, we are going to discuss how you, as an anesthesia professional, can decrease the impact of your anesthetic on our more frail patients. And the role that we as CRNAs play in decreasing post-operative cognitive dysfunction. I was going to say I'm going to invite, but they're already here. I'm going to be joined today by my esteemed colleagues, who will provide you with an overview of some of the common terminology and theory related to this topic. And these two experts will provide answers to some of the more common questions about monitoring brain health and anesthesia in our elderly patients. We will save some time at the end for questions, and we hope that you'll have some great conversation with us. So without further ado, I welcome my colleagues, and we'll get started. All right, good morning, everyone. So who here has taken care of somebody that has developed post-operative delirium or post-operative cognitive dysfunction? Raise your hand. It should be a lot of you, because this is actually two pretty prevalent anesthesia related neurological disorders. So first, we're going to go over some definitions of these two disorders, and also throw in a little bit about dementia and Alzheimer's disease as well. Because the signs and symptoms of dementia and Alzheimer's disease seem very similar to these neurological diseases, but the disease process and the pathology for dementia and Alzheimer's is a lot different. So for post-operative delirium, so post-op delirium is this acute fluctuating disturbance in attention. And it develops fairly short term, so within hours after anesthesia or maybe even days after anesthesia. This is very different from emergence delirium. So emergence delirium is when you're coming out of anesthesia. This develops several hours after anesthesia. These patients are disoriented, they have memory impairment, and they have changes in their behavior. And what's interesting about developing post-operative delirium is that it greatly increases your mortality rate. So if a patient has developed post-operative delirium, their mortality rate goes up to about 8% to 10% within 30 days of developing it. So it is a serious disorder. And I think a lot of times as anesthesia providers, because we only see patients in that acute period, sometimes we don't realize how many of our patients actually develop it after our anesthetic care. People that have certain surgeries, like cardiac or orthopedic surgeries, they're also more likely to develop post-operative delirium than other types of surgeries. Other impacts, so besides increased mortality, they can have increased hospital stay, increased risk of complications like infections, falls, or ulcers. And they have a really high rate of discharge to long-term care facilities rather than going to their home. So a pretty serious condition. So post-op cognitive dysfunction is a little bit different. And I think sometimes as providers and researchers, we use these terms interchangeably, but they are two distinct disorders. So while post-op delirium is more acute, happens in that more acute period, post-op cognitive dysfunction is a little more subtle and takes a little bit longer to develop. So post-op cognitive dysfunction, it sometimes takes a couple of days to a couple of weeks to a couple of months to develop. And this is, like I said, more subtle. And you're going to see more problems in memory, executive function, and other types of cognitive abilities. And the percentage rate of people that develop post-op cognitive dysfunction ranges in research, but it's anywhere up to 30% of our patients, so a big portion of our patients. And post-op cognitive dysfunction also increases mortality rate. So these patients are about two to three times higher, having a higher mortality rate than the general population who do not develop post-op cognitive dysfunction. And they have the same impact as well. Longer hospital stay, increased time to, increased incidence of going to long-term care facilities. Some of these patients, especially some of the younger patients, can't return back to work, which is a big deal, right? So they're not able to resume their activities of daily living. Now, dementia and Alzheimer's is a different disease. Now, dementia and Alzheimer's is a disease that takes literally decades to develop, upwards of two decades. A lot of times people have pathological changes to their brain that's happening before you see any clinical signs at all. And that's why research in biomarkers, plasma and CSF biomarkers, is starting to increase for this population. So dementia is kind of this umbrella term. It encompasses a lot of different diseases. Perhaps the most common that we know, it accounts for about 60 to 80% of the diseases is Alzheimer's disease. It's progressive. While POD and POCD is reversible, dementia and Alzheimer's is not reversible. And some key differences besides that, between POD and POCD and dementia, is the cause, the onset, the duration, and the age of onset as well. So while POD, POCD can happen in usually elderly population, it can happen at any age, whereas dementia and Alzheimer's is usually in an elderly population. There are some early onset Alzheimer's diseases, but for the most part, it's in a much older population. So over the last 30 years, studies in postoperative cognitive dysfunction and delirium have really taken off. It was initially written about in older studies where an individual couldn't do their shopping, or an individual was confused, or they're not just the same self after the anesthetic. But in the 90s, a group of Scandinavian researchers, they initiated something called the International Study of Postoperative Cognitive Dysfunction. And there they really started to set the objective criteria to how we're gonna measure postoperative cognitive dysfunction and fit it into cognitive domains. But because this was studied really in an anesthesia silo, we didn't, it wasn't included psychologist, neurologist, gerontologist. We studied it as an anesthesia phenomena. But in the early 2000s, as the body of research increased and more understanding of the cognitive domains, excuse me, that the dysfunction incorporated, they were able to start to find similarities between postoperative cognitive dysfunction and the other dementias. So delirium, as Rhea just mentioned, is really the first stage. In 2010, a anesthesia physician from Australia named Liz Everett, she got together a group of international experts, so about 40 international experts, and they came together to find consensus. And in that consensus, they were able to create a new definition where delirium and postoperative cognitive dysfunction were incorporated into a spectrum. And this spectrum you can see on this illustration above. So delirium is a phenomena. Again, it can start in the recovery room, and it can extend up to about seven days. And postoperative cognitive dysfunction really takes five to seven days to establish, and then can last up to a year. But really, incorporating the larger group of the scientific specialist community, gerontologist, psychologist, pharmacist, even surgeons, we were able to realize that these cognitive domains could fit into this larger umbrella called perioperative neurocognitive disorders. And from that, it was then included in the 2013 revision of the DSM-5 from the American Psychological Association. Before that, postoperative cognitive dysfunction wasn't included. Delirium was included, but not really emergence delirium. It was maybe a subset of delirium, but not really this clear anesthesia-focused psychological disorder. And from that, you can see how there are different graduates of neurocognitive disorders and postoperative cognitive dysfunction. And this is where the involvement of psychologists and the greater community has helped us in this evolving terminology. When you do neurocognitive testing, it is either from an individual against a normative group, a larger normative group, or it is against the individual over time. So they have a baseline standard neurocognitive exam. They're evaluated a year later. And so how the individual does, compared against himself, compared against the normative group, it is how, if they do worse, it's considered in terms of standard deviations. Are you one standard deviation worse? Are you two standard deviations worse? So mild neurocognitive disorder from postoperative cognitive dysfunction is akin to mild cognitive impairment. And just like Rhea mentioned, there is a subtle increase in symptomology, a prodromal phase of the dementias, where you may have word-finding difficulties. And it's not when I have trouble finding a word in class. Or you may have, when you drive in your car, but you can't find your way back home, that executive function domain problems. These start to be elucidated. And they're very fine changes. A lot of people have very, they can compensate for their problems that they have in dementia. They can laugh through their word-finding problems. Or they can just quit driving. Or multiple different mechanisms to conceal this. But after about a year, as if individuals don't improve, there is a small subset of individuals that don't get better after postoperative cognitive dysfunction. And that will then transition into a more of a psychology neurocognitive decline phenomena. So what are the patient factors? I apologize if I don't speak extemporaneously about things, because details matter, and I like details. So the leading factor, the leading cause of having a perioperative neurocognitive decline is gonna be advanced age. So at age greater than 65 years, what gives you about a 21% increased risk of delirium and postoperative cognitive disorders. And at age of 80, will lead to a 36% increased risk. A preexisting cognitive decline. So if you have baseline cognitive dysfunction, then you will have a 12 times increased risk of delirium. If you have cognitive decline, then you have a 22% postoperative cognitive dysfunction risk. So if you do poorly at your initial neurocognitive exam, and then you do, that is very predictive of having cognitive decline and experiences delirium and postoperative cognitive dysfunction. Frailty, frailty is multifactorial. It's a hot topic right now with ERAS. Nutritional problems, hypoalbuminemia, less than 3.7. Environmental toxins, being exposed to chronic environmental toxins. Did you smell gasoline when you were a little kid? That has benzene in it. Benzene is a neurocognitive toxin. Have you bought a new car? Did it have the new car smell? That's plastic off venting, that's benzene. And that can be associated with neurocognitive decline. Did you have typing class in high school? Did you smell correction fluid? That's trichloroethylene. Again, that's a neurotoxin. Not that I did any of those things. So and then the male gender. So the male gender has odds ratio of 1.87. You have an increased risk of having delirium, postoperative cognitive dysfunction situation. Low education or a lower cognitive reserve is what is the concept. So individuals that have a lower education have increased risk of delirium and postoperative cognitive dysfunction. That's why you must read your AANA journal every two months so you can protect yourself from delirium and postoperative cognitive dysfunction when you're older. If you read nurse anesthesia, then you will reduce your risk of delirium and postoperative cognitive dysfunction when you're older. It's effective. As far as anesthesia related factors, so fluid fasting, fluid flasting, greater than six hours, it has a 10 times increased risk of having delirium. Put these individuals at the first case. I see a lot of times we have E-RAS and I work with a colorectal surgeon and that individual, they're asking me, how much fluid have you given? And I've given enough. And I ask, did you make sure that they drank their carbohydrate low the night before? And they're like, no. And I'm like, we can't do E-RAS a la carte, right? We have to make sure when they hydrate these patients. Individuals over 65, individuals that are frail, individuals at risk, they don't need to be fluid fasting over six hours. Hypotensive episodes, cumulative hypotensive time. I went to a presentation a couple days ago, fascinating new research coming out about hypotensive episodes and how that can be associated with postoperative cognitive dysfunction. We know benzodiazepines, tertiary anticholinergics, dopaminergic agents. I think we already know we avoid those things in the elderly. Anesthesia choice. So a large meta-analysis with Cochran methodology from 1985 to 2023, they looked at every study that compared propofol versus volatile anesthetics. 317 randomized controlled trials, over 50,000 individual patients. Propofol odds ratio was 0.63 compared with volatile anesthetics as far as the risk for delirium. And then birth suppression. So probably the biggest thing that has really come out lately is avoiding birth suppression, avoiding isoelectric EEG. That changes the neuronal, intracellular and intercellular environment. Birth suppression in the elderly leads to a blockage of the potassium ATPase pumps. It also leads to increased levels of intercellular calcium and leads to a toxic environment. And this is okay for individuals that are young. Did you ever take care of a patient with increased ICP in the trauma ICU or maybe in the neuro ICU? Did you ever put, I put people in a pentobarb coma but that tells my age, but did you put somebody into a drug-induced coma in order to give them a quiet brain? Did you decrease the amount of oxygen utilization? Individuals that are young tolerate this much better than individuals that are old. And then surgical considerations. So the biggest thing is going to be the inflammatory impact that a surgery has. Intra-abdominal surgery, intra-thoracic surgery, aortic clamp time, all those things are high inflammatory burdens. They increase your risk. And then the length of surgery and at-risk individuals. So for every extra 30 minutes of OR time or anesthetic time, that is, you have an increased 6% risk of delirium. So maybe these people aren't teaching cases for the surgeon. And then I'm just curious, Dr. Sensible, when you said the odds ratio of purple fall, maybe there are some non-researchers or residents out here that maybe want some clarification on what you meant by that? Right. So odds ratio, it's hard to, it's hard to describe and hard to determine. You don't want to say that this is 1.8 times. So odds ratio of 1 is really an equivocal study. That means we didn't really find anything. If you have an odds ratio of 1.87, then that individual had a, has a higher incidence, a higher risk of whatever phenomenon that you're looking at. Similarly, if you have an odds ratio of 0.6, the female gender has a lower odds ratio compared with males. If you have a number below 1, a lower odds ratio that's associated with a decreased incidence. But remember, you have to be careful about where you put your variables, right? And you have to really read in and understand what you're comparing to another thing and making sure that you have the odds ratio on the right side. Okay, I'm a little bit more concerned about the new car smell. I like that smell. I like that smell. Now I'm worried about that. Sorry. So as far as the mechanisms, the actual cellular mechanisms of post-op cognitive dysfunction and post-op delirium, of course it's multifactorial. But what it comes down to is your immune system. So what's happening with the development of POCD and POD is that there's neuro inflammation that's happening into your, in your brain and microglial activation. Microglia are the macrophages of the CNS. What's happening is, now it's not just anesthesia itself. If you expose humans or animals to just anesthesia, this process doesn't develop. It's anesthesia plus surgery. So you have the surgical process, you have tissue injury. That tissue injury is going to stimulate this neuroinflammatory cascade to occur. So when you have tissue injury, you're activating the peripheral immune cells, which is going to release these pro-inflammatory cytokines and mediators. Mediators like IL-1, IL-1 beta, IL-6, and TNF-alpha, which is tumor necrosis factor alpha. These factors then cross into the blood-brain barrier and activate the microglia. And you can see in the image on the left side, you see the phenotype, the shape of the microglia is changing when it becomes activated. So when it's in its inactive state, it's looking a little bit more spidery with these little processes. But when it becomes activated, it changes its phenotype to be more amoeboid to these, this rounded shape here. And it does a lot of these different pathways that you see around the circle here. So I won't go through every single one of them, but let's go through like oxidative stress, for example. So what this activated microglia do is then release factors around neurons and astrocytes. And with oxidative stress, so it's going to increase the amount of reactive oxygen species. Reactive oxygen species then go damage DNA proteins and lipids, and that causes neuronal death. You can see autophagy disorder. So autophagy is a normal process. Autophagy is when the cells clean up the cellular debris, get rid of that waste. But in this process, that is disrupted. Other things we see during this process is actually blood-brain barrier dysfunction. So we have tight junctions. It's one of the components of the blood-brain barrier. It keeps toxins from going into the brain. But when you undergo this surgical process and this inflammatory process begins, and also when you give very, very deep anesthesia, the blood-brain barrier integrity starts to break down. So it's more likely for these inflammatory mediators to cross through and do this microglial activation. And the last one I'm going to talk about is the topic that I'm pretty fascinated about, which is the gut-brain axis. You've heard of a lot of stuff coming out about the microbiota, right, and how dysfunction in the microbiota is, you know, does lead to a lot of the different neurological diseases that we see in people. And this is still, you know, ongoing research right now. When the gut, you know, the microbiota and the gut, when the gut integrity starts to break down, this bacteria will translocate into the bloodstream and release toxins, endotoxins, that also go on through the blood-brain barrier and cause this dysfunction as well. So like I said, multifactorial, lots and lots of things going on to cause this issue. A little bit more of a detailed schematic to demonstrate what I'd already discussed. So in the top left-hand corner, you can see that surgical process occurring and the tissue damage that's occurring in order to perform that surgery. What it's going to release is these damage-associated molecular patterns, or these DAMPs. And these DAMPs go in to stimulate these peripheral immune cells that are always floating around in the blood. The peripheral immune cells are going to release those inflammatory mediators, so like I said, that IL-1 beta, IL-6, and tumor necrosis factor, and that's going to go through the blood-brain barrier. And especially if the integrity of the blood-brain barrier is damaged, these mediators are going to go through more readily. Within, you know, once it crosses the blood-brain barrier, it's going to activate that microglia, which is then going to release lots of different factors that ultimately damage neurons within the brain. I do want to make a note real quick about the type of anesthesia. So Dr. Sentamol did talk a little bit about TEVA versus GA, and you'll read lots of studies that are seemingly contradictory to one another, and we'll get into that in a little bit when we talk about why these studies differ so much because of the methodology. You'll see some studies that will say that TEVA is a little bit better for patients than volatile agents. They, you know, see that volatile agents are a little bit more damaging to patients. You'll see other studies that say that it makes no difference, that you'll see cognitive dysfunction with either one. There'll also be studies that you'll see that look at GA versus regional, and I think intuitively we think that with regional, we would have better outcomes for these patients, right, because they're not getting that systemic general anesthesia. But the research shows that even with regional anesthesia, patients can still develop post-operative cognitive dysfunction and post-op delirium. What seems to be consistent in the research, though, is that if you do choose to give general anesthesia, the depth does matter. If you have long periods of, or increased periods of, birth suppression within these patients, it's going to increase this molecular process. It's going to make this molecular process worse, and there have been some studies to support certain medications. We're going to get through this and get to this in a little bit, supporting certain neuroprotective medications like dexmedetomidine for these patients. Thank you both for providing a nice foundation for the discussion we're going to have, and I hope that you guys are as impressed as I am with both of their knowledge on this subject. Sort of going out to the two of you, as CRNAs, how can we be proactive in assessing neurocognitive disorders across the perioperative setting, and are there certain screenings or questions we could be asking our patients? Yeah, can I take this one? Yeah. So I talked about the International Study of Post-operative Cognitive Dysfunction, that Scandinavian study from the mid-90s, where they really set the objective measurement, what cognitive domains that post-operative cognitive dysfunction utilized. Well, they used a comprehensive neurocognitive battery delivered by a neuropsychologist, and this was, and they borrowed this concept from Alzheimer's disease research. They used very fine tools, but if you can imagine how much it costs to do an anesthesia research study with a pre-anesthetic, a one-week post-anesthetic, and a three to five month post-anesthetic neurocognitive assessment by a neuropsychologist, it's going to be expensive study. So that's really set, that's really set the baseline for how we look at anesthesia studies for post-operative cognitive dysfunction. But the gold standard is the benchmark for studying the dementias is the NIH Alzheimer's Disease Centers. So there's 35 of these Alzheimer's Disease Centers. The one in Kentucky is in Lexington, Kentucky, at the University of Kentucky. They administer the uniform data set, and it is administered again by a neuropsychologist. It takes 40 minutes. It can find very fine fluctuations. It can detect mild cognitive impairment, but again, very expensive. But when I did a research study in 2016-2017, we used a different neurocognitive battery, and it's called the Cambridge Cognition, will you switch it one more time? I'm sorry about that. We did use the Cambridge Cognition CANTAB MCI, and so this is a tablet-based cognitive exam where you look at a picture, an image, a shape, right, and then you memorize it. It will go away for a certain length of time. Memorize the picture. Now in just a second it's going to show you four of images. Which one was it? You missed it. So, so our cognitive exam was the CANTAB MCI. It was engineered and validated and normalized to detect mild cognitive impairment. It's actually used at the NHS, England's National Health Service. So at 65 years old, you can go into any general practitioner, any internal medicine physician's office, and at 65 years old you'll get a baseline CANTAB. And then from there, if you showed deviations, if you showed changes in your cognition, if you have subjective comments by your family members that you've changed a little bit, we can do another CANTAB MCI and we can see if your standard deviations have changed, right, if you're doing poorly. And then from there we can try to get you to the right providers, the right medicines. We can put you in the right living situations. But that was expensive too. Now it didn't require a neuropsychologist. I mean, I could have done it. So it was very difficult to find funding to do this, even though it didn't require a neuropsychologist. Can you go back to the one before? That was terrible to do you. I'm sorry. So, but what are simpler tests that we can do? The Montreal Cognitive Assessment. Have you heard of the MOCA before? So this is a paper test that's free online to any health care provider and it is sensitive enough to detect mild cognitive impairment. But in this, I think you can see that there is a number counting test where you draw across from 1, 2, 3, 4, 5, 6, 7, 8, 9, 10. There's also a clock drawing test, if you remember that from the many mental status exam, the clock drawing test. But this requires an individual to be able to have the dexterity to write. And I know my mother-in-law has a tremor. This would be very difficult for her to do. But she could count 1, 2, 3, 4, 5, 6. She knows what time it is. If MSNBC is on, she knows exactly what time it is. And then in 2022, one study I'd like to bring to your attention. It was done by the folks at Washington University in St. Louis. They used a cognitive screening and in a questionnaire. The cognitive screening was called the short blessed test. And it was a group of about six questions. And from that, you could screen for cognitive dysfunction. And then there was more of a subjective that something called the 88, the Alzheimer's disease 8 questionnaire. And that could involve the family members. This questionnaire battery, it literally takes about four minutes to do. And I did it on my wife. And she didn't appreciate that very much. But she did really well, by the way. But they evaluated this. From 2013 to 2018, they utilized the short blessed test and the 88 in all preoperative clinics for anybody over the age of 65. So over 22,000 patients over 65 from 2013 to 2018, they found that 23.5% of patients had signs of cognitive impairment. And this was generalized screening. This is not at risk individuals, anybody over 65, a 23.5% increased risk or 23.5% incidence of a cognitive decline. And that matches what the greater research tells us that about 20% of the population that are over age 65 have a cognitive problem. Now, again, these tests are free to health care providers, you can download the test online. This is something that's very practical that you can use in any preoperative clinic, it literally takes three to four minutes to do right. And if you have a positive screening, that's like having st changes on a 12 EDKG. I mean, to me, that's an ASA for patient, you have cognitive decline, right? I need to stop, I need to send you to a gerontologist, I need to have your medication, your your medications that you take at home evaluated, I need to make sure that there's no problems with your cardiovascular system, right? I need to search for problems. If I can manipulate the schedule, I'll put you first case, I'm going to make sure you drink your carbohydrate drink. And then we'll do some other interventions that we'll talk about a little bit later. Yeah, so, you know, what can we do as providers in the perioperative period to, you know, if we identify a patient that is high risk, is there anything we can do to maybe decrease the incidence of POD and POCD? So preoperatively, I know that, you know, we don't see patients oftentimes, months before surgery, but if they're, you know, pre pre admission testing process, or maybe the surgical schedulers or whatnot, can lead patients to do what we call pre habilitation. Now, this is a process that is still undergoing a lot of research. So we can't definitively say that pre habilitation leads to decreased risk, but we're still because we're still studying this. So this is when patients about six to eight weeks before surgery, go through this pre habilitation process. And it looks at all of these different factors that Dr. Sentamal was talking about some basic things like nutritional support, making sure they get enough sleep, making sure that we treat any physical or mental conditions. So if we have uncontrolled, maybe diabetes, getting that under control, uncontrolled mental disorders like depression, all of these things matter leading up to surgery. And we can increase their cognitive training, which increases their cognitive reserve before they go into surgery. Physical training that's going to reduce inflammation, increase cardiovascular function, improve overall health. And then also, you know, something I think that we often overlook is engagement and education of our patients. So this decreases anxiety for our patients knowing what their surgical process is going to be, gets them more involved in their care and more likely to follow through with their postoperative care. For ERAS, a lot of us are pretty familiar with the ERAS process, and it definitely applies to these types of patients. So making sure that our patients mobilize early, we talked about the fluid status, so making sure that they don't become dehydrated, optimizing their pain management, right, not giving them long term opioids like morphine, some of the other things, you know, using more of our multimodal techniques to minimize the amount of opioids, but making sure that they stay comfortable. Avoiding certain medications that are long term, mind altering medications like not giving our benzodiazepines, avoiding anticholinergics, avoiding things that are going to linger in a patient's body, pharmacology wise, that is going to increase their cognitive dysfunction. Making sure that we don't put in drains and catheters, it's all part of the ERAS protocol, minimize infections, right, not leaving those indwelling catheters in. So, you know, we're familiar with the ERAS protocol, making sure we're using a lot of these different components to optimize the patient's care. So, so benzodiazepines, of course. So what crosses the blood brain barrier? Is it tertiary or quaternary amines? I can't remember. It is tertiary. So it's too early for that. So anyways, so, but so tertiary amine or quaternary amines don't cross the blood brain barrier because they're ionized, right? But what if you have an impaired blood brain barrier, right? That glycopyrrolate that you thought was going to be okay can cross the blood brain barrier. If you have an inflammatory deficit, if you're at risk, right? So staying away from those, avoiding any anticholinergic or dopaminergic drug, that's super important. And then there is the concept of deep cumulative hypnotic time, right? This values are other process EEG values that are less than the range. Those studies go backwards and forwards. You know, it seems like there's a different one every year, but just like you said, Rhea, you know, isoelectric EEG and burst suppression are bad. And then dexmedetomidine. So dexmedetomidine, it has had some equivocal studies backwards and forwards, but I think it is going to be very, very useful and especially avoiding delirium. And then last year at Vanderbilt, there was a study by the anesthesia physician named Jelly, but it was in cardiothoracic patients. They looked at acetaminophen, gabapentin, ketamine, lidocaine, dexmedetomidine, but only 48 hours of IV acetaminophen was significant and had an association with decreased risk of delirium. As far as surgical factors, we want to avoid hypotension, right? We talked about that a little bit earlier, but we also want to avoid hypo or hyperthermia. Hypothermia can precipitate burst suppression in isoelectric EEG. So letting somebody get cold in the operating room is that is going to make it easier for you at a increased depth of anesthesia to cause burst suppression. A dose that usually doesn't cause burst suppression, but if they're 34 centigrade, you can induce burst suppression with that. And then hypoxemia, right? Hypoxic episodes, we all know to avoid those. Yeah, as far as monitoring goes, and Dr. Stentzmal already alluded to this, so the, and we keep saying this over and over about the depth of anesthesia, right, and how that matters. Process EEG is a monitor that can help you give less anesthesia, making sure that patients are being anesthetized properly, but not going into these periods of burst suppression. Using a process EEG, it has been shown to improve the recovery time and the orientation time. So studies have shown that patients become, are awake 30 to 50 percent faster. Shows that, you know, there are studies that have divided groups into two, where one provider was using a process EEG monitor to guide the anesthetic and titrate the anesthetic, whereas the other group had the process EEG applied, but the provider, it was blinded to the provider, and the provider was giving routine care. These studies have shown that providers that are using the process EEG to guide their care do give less anesthesia. Those patients wake up faster, they recover faster, and they get to a fully oriented status in the PACU a lot faster. So, of course, there are several process EEG monitors that are on the market. Perhaps the one that is most widely available is the BIZ Monitor. So we'll talk about the BIZ Monitor for the rest of this presentation. The BIZ Monitor is a tool that looks at the EEG data, all the different waveforms, puts it through an algorithm to give you a number, a quantitative number that's going to range from zero to 100. We'll talk about what the different, and a lot of you are familiar with what the different numbers mean, but we usually say that between 40 and 60 is the optimal anesthesia range. So anything above 60 is getting on the lighter side or more of the sedation side, and then getting below 40 we would consider deep anesthesia. The BIZ Monitor can, like I said, just like other process EEG monitors, it's going to improve the amount of titration that we do. So we can titrate our anesthetics a little bit more accurately. It's going to decrease the amount of anesthesia that we give. And it has, there are a research that does support that using some kind of process EE monitor does decrease the incidence of post-op delirium and post-operative cognitive dysfunction. And patients do recover faster using a process EEG monitor. I do want to talk a little bit about the limitations and the considerations of using a process EEG monitor, and I'm sure a lot of you in the crowd have your opinions about process EEG monitors as well. But I do want to point out that using a process EEG monitor is an adjunct to your other, you know, patient factors and monitors, right? We're still using our minimal alveolar concentration. We're still looking at vital signs and hemodynamic status and other patient signs and symptoms in looking at the, you know, using your clinical judgment to look at the entire picture of whether a patient is properly anesthetized versus deeply anesthetized versus light, right? We're not just looking at this one singular number and making our clinical decisions solely on that number, right? We have to take this into consideration as an adjunct with all of the other things that we use in the operating room and all the other patient factors. So just keep that in mind. Just to add to that, you know, it measures the power of EEG waveforms. So when you go into steep Trendelenburg position, the brain is going to be closer to the skull, and that's going to change the amplitude of detection of the little sticker. Now, as you raise the patient up, right, the bis value will go up. So in an individual that is elderly, we all know that the brain atrophies with age, right? And so in the elderly, this Trendelenburg and reverse Trendelenburg is even more dramatic. So keep that in mind. So this is just a schematic that shows that as you go through, as you deepen the anesthetic, the brain waves actually change. The first, this awake brain wave, they're called beta waves. They have a very fine, high frequency, low amplitude presentation in that 100 range. As you get into a sedated, we get more into what we call a sedated brain wave. So this is a in that 100 range. As you get into a sedated, we get more into what we call an alpha, an alpha category that is a slow frequency and a greater amplitude. And then as you move down into the theta and delta waves, they get to be a long, a much longer wave, a larger amplitude. So when we look at this, we really look at beta, alpha, theta, and delta waves. Um, what do we make in Louisville, Kentucky? Bourbon. The Louisville slugger, the Louisville slugger. And so the way I remember this is, is batted B-A-T-D, right? Beta, alpha, theta, uh, delta. Um, if that helps you remember that. And then we can see the isoelectric and burst suppression. Yeah. I mean, going back to that last slide there. So what, when the bismutter was created, it's a correlation, right? They correlated what, you know, this process EEG looks like with a number, with a clinical, uh, you know, presentation, right? This is a correlation. And so when you do the studies for it, you're looking at patients that are, uh, you know, you know, patients that are, that don't have, um, severe neuropathology. So there are certain, you know, cohorts of patients or conditions where you can't interpret the, the biz value as readily. So people that are on different psychotropic medications, patients that have, um, severe neuropathology or patients that have high EMG activity, right? So if the patient is not paralyzed and sedated, then the number is not going to be as accurate, right? We sometimes use the biz monitor for patients that are, you know, undergoing Mac sedation, but really it is the most accurate when the patients are paralyzed and sedated. That's when you're going to get the best value. That's a really good point. Thank you for sharing that. So, um, we've talked about this, the studies of, of, uh, deep, uh, cumulative deep hypnotic time are back and forth. Um, but you may have read about the balance trial. It was kind of equivocal. We found we, you may have read about the engages trial, the trial that was done at Washington universe, uh, in St. Louis. Um, that trial, um, showed that, that there, that, that EEG guided anesthesia had an increased risk of delirium, um, when compared with non EEG guided, uh, anesthesia. But if you're a real, if you're very critical in reading the research, uh, they mentioned in there that 23% of the individuals in the process EEG guided group moved during the surgery. So that tells me they weren't chemically paralyzed effectively. Right. Um, and then, so I think if you're not chemically paralyzed that affects the EMG, that will affect the SQI. If you've seen the system quality index on the best monitor, and then, so you're flying through the clouds. I've never flown before. Like I've never flown the airplane, but I think it would be like flying through the clouds. You don't really see what you're seeing. So, so you've mentioned several studies and they're quite a bit of variation on the outcomes. Can you give some insight into why we may see such variation across the evidence? So I see, uh, over the last 20 years of studying this phenomena, it, the quality of the neuropsychological battery that is implemented, right? Um, has that neuropsychological battery, the combinations of tests that you use to look to find these things, has it been established? Has it been normalized in the patient group? Uh, are you, do they follow the, the steps of the test very closely? That's very important. Um, another thing is the ability of the study to find a big difference. Is there a large difference between the process EEG group? You know, are they more toward the 55 to 60 range? And then the standard care group, are they down in the, in the, uh, in the low forties, um, or excuse me, the low thirties. You know, if there's a big gradient between the two, then you're going to see significance. If there's not a big gradient, you don't see significance. And then confounders. If you use, if you allow the providers to use multiple different anesthetic modalities, they're in the process, the EGE group, but you allow them to use benzodiazepines and you allow them to use anticholinergics. Are there in the, uh, they're in the, uh, uh, the, the, the standard care of the non guided group, but you allow them to use ativa, right? Um, methodology and studies matters. That's why you have to read the methods. Um, I love the opportunity. When you read a study, it should be fun. And I'm, that may seem crazy, but you're trying, you're trying to shoot holes in the study. You know, um, when we do journal review, I always like to see if they, you know, they get their six shooter out and twirl it and shoot holes in the study. That makes me happy. I think for the residents in the audience, uh, I, I appreciate that you, you mentioned that because the methodology is really the crux of where we're seeing all the variation and it's important as you're learning all those courses that, you know, are giving you a hard time that there really is true value. Um, so for both of you, how does running anesthesia, what we would refer to in clinical practice on the deeper side, uh, actually negative or potentially negative, negatively impact our patient? I think we alluded to this already when we talked about the mechanism of action of this, these disorders and running anesthetics on the deeper side does disrupt the integrity of the blood brain barrier. So it's going to increase this neuroinflammatory process, all these inflammatory mediators that are going to move in and activate this neuroinflammation. And we talked a little bit about oxidative stress. So it increases the amount of reactive oxygen species, um, especially in these birth suppression periods. And that's going to damage certain cellular components, like, especially DNA. Um, and then also, you know, disrupting the neurotransmitters within our brain, the balance of neurotransmitters like glutamate and GABA, and that's also going to lead to negative effects and neuronal death. Um, some mentioned earlier a little bit about sodium potassium pumps, right? And, and calcium going into the cell and, uh, calcium, you know, we, we think of calcium sometimes as this benign thing, right? Because we talk about calcium all the time, but calcium in the brain leads to a lot of like cytotoxic damage within the brain. If you have too much calcium that enters the neuron, this actually turns on cell death pathways, death pathways like apoptosis, pyroptosis, and these cell death pathways eventually kill neurons and lead to these disorders. So, um, this is a tool that I like to use. Um, I've used the BIS system throughout my research, and this is the, the process EEG system that I'm most familiar with. Uh, but the new platforms have something called density spectral ray. And I don't know if you've seen this, um, but this requires the batted concept that I mentioned earlier. Um, if you notice here, there is a range of EEG. If you look below, these are both 30 minute-ish anesthetics. And if you can look up above there on the left side below the DSA, there, there is a 30 hertz, a 13 hertz, an eight hertz, a four hertz, and then zero, right? And that's that frequency. So, um, in that 13 to 30 hertz range, that's beta, right? That's awake, right? And then when you get to the alpha range at seven to 13, it's eight to 13 on this particular monitor. That's resting, that's relaxed, that's stage one of sleep. Um, that is where we start getting into that general anesthetic realm. Uh, and then theta, which is in that four to eight, and then there's delta in the 0.5 to, to 3.5 range. And that's real slow, deep anesthesia. Um, individual anesthetics have their own signature. So, in this individual right here, in both of these anesthetics, to me, it looks like that they have, what was it? It was beta, and then alpha's below that. So, they have alpha waveforms, and then below that, they have beta, and then delta. So, hot, warm colors are where you have the most power. So, in both of these images right here, we have warm colors that are in the alpha and in the delta range. This is a signature of propofol anesthetic. If it was sevoflurane, you would have something called fill-in between the alpha and the delta in the theta range, and then it's going to look like a, a hot, uh, just the bottom of the, of the graph is hot. Notice in this individual right here, they have something called the, uh, you see the SR right there, and it has five percent, and that is called the suppression ratio. So, for the last 63 percent, or 63 seconds, five percent of that time was in burst suppression, and there is also the ST, which is the, um, the suppression time. So, over the 30 minutes, you've all, you've had 57 seconds of isoelectric EEG. Um, there's also spectral edge frequency, which is a fine white line that tells you at any given time what your maximum amplitude was, um, and, uh, I think this is brilliant. Um, this will allow us, uh, to, to finally, uh, analyze our anesthetics. All right. So, we'll end with a, a, a question for you, Rhea. You mentioned in the very beginning of this presentation that we were, we're not going to, um, focus on dementia or Alzheimer's, but I think the audience might be interested in, in what your thoughts are on this particular subject. So, earlier, Dr. Sentamul had talked about how if you have pre-existing, uh, neurocognitive disorders, that it increases, at baseline, it's going to increase your chance of developing more severe post-op cognitive dysfunction and delirium. So, we're going from pre-existing to then developing POD and POCD. I think this question really more alludes to if you don't have any pre-existing pathology at all, neurological pathology, and you experience POD and POCD, does that increase your risk of developing dementia later on in life? And when all of this first came out, it was actually during a, uh, 1955 study by Dr. Bedford that started talking about these types of disorders, POD and POCD, after anesthesia, and that's the first thing that the public said. They kind of got freaked out about that. They're like, oh, wait, is, if I develop this, am I going to develop dementia and Alzheimer's disease? So, it was a pretty big scare amongst the public. And since there have been lots and lots of studies looking at to see if there's some kind of connection, um, just like with the research with POD and POCD, it's still inconclusive. There isn't a strong connection, but I'll talk about two or three main studies that we have so far. Uh, there are, there's a study in Sweden that looked at patients for about 11 to 12 years, so patients that developed POD and POCD, and then subsequently went on to, uh, develop dementia and really didn't see any, um, significant link between the two. Uh, you know, dementia takes, like I said, decades to develop. So, for me personally, I just don't think this is a long enough period of time, you know, looking at patients. And personally, you know, because dementia, the pathology of the dementia develops so far in advance before you see clinical signs. Uh, it seems to me that patients that develop POCD, POD, POCD, and then develop dementia, they were probably already going to develop dementia, um, anyway. Um, Taiwan also did a series of studies. So, they did a retrospective study where they looked at, uh, more of a database study. They looked at it over, you know, anywhere from 130,000, 150,000, um, charts looked at them, um, over the course and seemed to have found some kind of link. Of course, retrospective database studies take it for what it's worth, right? That's not really a rigorous scientific study. So, they then went and did a prospective study of about 4,000 patients and looked at them over a long period of time and still didn't find any link between developing POD, POCD, and then developing dementia. So, I will say that the research, you know, is really inconclusive, um, really doesn't have any link, thank goodness, between the two diseases. So, um, yeah, I guess we'll do a Q&A session. So, we started just a couple minutes later than we were supposed to. So, I think we have time for one or two questions and then we'll stick around in the front if you have additional questions. Absolutely, yeah. So, thank you so much, guys. Hello. Thank you so much for that discussion. Um, you had mentioned earlier in the lecture about dexmedetomidine being a neuroprotective. At what doses? Is that a single dose or an infusion? What kind of data do you have on that? Yeah, the data is on infusions and the normal infusions that we would, we would give the 0.4, 0.7 doses. So, yeah, so it would be, uh, there are many, many studies that have supported the, uh, the use of dexmedetomidine. We still don't know exact mechanism of action of how it's neuroprotective. Um, that could, because we know how it works, right? We know what the mechanism, but we don't know how it's neuroprotective for patients. But we do see there's a correlation between giving the infusion and decrease of incidence of POD, POCD. And actually, when I designed my study, I made sure that that was one of the groups that got dexmedetomidine. Yeah, but I'm happy to forward the studies to you. Thank you so much. So, we talked about, uh, using the BIS monitor quite a bit and, uh, Don did a little bit of EEG monitoring. I know all the markets, all the monitors on the market right now allow viewing the live data. What are your thoughts on starting to teach, uh, interpretation of raw EEG data? Is that something we should be moving towards as a profession and, and making that sort of a standard of, of our education? Processed EEG is not an awareness monitor, but it's so much more. It's so much more. And, and it's so much more for an individual over 65, or it's so much more for an individual that it has a, you know, a 60 pack year smoking history at 50 years old, right? My understanding, and correct me if I'm wrong, is that the monitors allow you to see the raw waveform and what's processed is the, the number that they're giving you. So, uh, I know there is education out there on looking at those waveforms and, uh, sort of interpreting that and kind of like, uh, Zahn did, you know, looking at, okay, this is isoelectric, this is beta. Yeah. I think having a basic understanding of that is, is totally reasonable and definitely, I think would put us ahead of our, uh, peers. Colleagues. Yeah. I don't know. Colleagues. 32 different points of, of EEG. Right. I guess that's what I was getting. Valuable interoperatively. But I think knowing a beta wave from an alpha wave from a theta wave and a delta wave and seeing them transposed on top of each other, right. And, and to see the beta ratio, which is what that calculation is actually calculating, you know, is valuable. Right. Exactly. That was kind of my reading. The DSA is also, I think, a great skill to have, um, looking at those color patterns, you know, Dr. Sentinel was talking about, this looks like a propofol signature because you saw those two red hot bands, as opposed to a volatile anesthetic showing that one, uh, red band, but those colors are correlated to the waveforms, you know, so that's just another way of looking kind of like an easier way of getting a visual kind of overview as to what the waveforms are doing. So I think that's also a good skill to have as well. Well, I'm going to stop everybody here. Thank you both for joining us today and thank you audience for your participation. Uh, if you're interested in the article that was, um, that this conversation was based off of, there will be copies of it at the, um, Medtronic, uh, uh, booth in the exhibit hall and you can always use that QR code too. So thank you everybody.

neurocognitive disorders

anesthesia

frail patients

elderly patients

postoperative delirium

postoperative cognitive dysfunction

neuroinflammation

BIS Monitor

dexmedetomidine

anesthesia depth