Again, I'm Brenda Punn. I work at Vanderbilt University Medical Center with the Critical Illness and Brain Dysfunction Survivorship Group, the SIB Center. And most of the work that I do has focused on research with delirium and sedation in the ICU and long-term cognitive outcomes. And I have not done any sleep research. I've partnered with some sleep researchers. And my part of the lecture today is gonna be focusing on the effects of sleep, poor sleep for the ICU patient. Here's some disclosures. And if I talk about treating delirium, it's gonna come up a few times. I joke of anything from the PAT-IS guidelines. If you talk about one, you sort of have to mention all of them. It's a package deal. And so if I mention anything about delirium, it's off-label. There's nothing to treat on, there's no label indication for any drug for delirium. And so sleep, we all do it. We all experience at one time or another in our lives some disruption in it. Whether you have something wake you up in the middle of the night, whether you at certain times of your life push yourself through, that you stay up late or get up early than what a full night's sleep would be for you, or whether there are external factors that are disrupting our sleep, but we all do it. And we all know, I think this is one of those duh things that we sometimes try to research, we all know that poor sleep is not good for us. And we all feel the effects of that, right? But we often don't appreciate it in other people, even our family members. People, like if they have a bad night's sleep and they feel a little off, we don't always appreciate how crummy that feels until we have a bad night's sleep, and we feel really crummy the day or the next day. Sometimes it's not always the first day after losing some sleep, but it's the next day that you feel the crash, or our shift work, we often can see that too. And for all of you that, do you ever have trouble sleeping somewhere that's not your bedroom? Like a hotel room, being in someone's guest room, sleeping somewhere that isn't your bedroom. Keep that in mind when we talk about everything that we have for today, because it really, we have all these patients that are not in their bedrooms. We've created a bedroom for them, and they are there in that room, and it's not their usual room. And there's all kinds of stuff going on with them that doesn't usually happen. So you can imagine the challenges there. So I wanted to start, since all the lectures in this session are gonna be about sleep, is to do just a primer on sleep. And that I am positive there are probably experts in the room that know way more about this than I do, but I'm guessing we can find some common ground here with these different definitions. So we've got three stages of non-REM sleep. Stage one, stage two, and stage three. Stage three is really that we often hear deep sleep. That's stage three. And then we have REM sleep. If we were, they can be categorized by their EEG patterns if we would do polysomnography on patients. And we'll, I think a couple important components, and you'll see this come up when we talk about different studies, is the different types of waves. Specifically, when we see that stage two sleep, we start to see something called spindles and K-complexes. And those really, we think, are associated with memory. So when we see those, we think the brain is doing some things with memory consolidation and information processing. And then we see those delta waves, those slower waves. As we move through N1 to N3, the waves get bigger and slower. And that's where the body, it's really that restorative sleep, physiologic restorative sleep. And then in REM sleep, we see this fast random waves, that rapid eye movement. And we think that during that stage, what's happening is memory consolidation, long-term memory implanting or imprinting, and immune function and tissue repairs happening in those stages. No one's 100% sure about all of these stages and exactly what's really being imprinted in each one of these stages. But that's generally the best guess. What we really want to pay attention to is that this deep sleep, or non-REM stage three, and REM sleep are really important for restoring the body. So our sleep is designed in a way that gets us to those two places and elongates our time in those two places. We're gonna look at how we cycle through them in a second. But those are really important. So when those are lost, the effects of the restorative sleep are lost. And I think that's a really big take-home as you interpret all the research that'll be shared. So I really like this schematic here. And you can see that there's the light sleep and the deep sleep, that's N1, 2, and 3. Then the REM sleep is a lighter sleep. It's not a deeper sleep, but it's a lighter sleep, but it's that dreaming sleep that we have. And you can see that as you go through the night, you have these about 90-minute cycles. Did anybody ever have a child who had night terrors? So I had a daughter till she was about seven regularly had night terrors. If she was sick or anxious when she went to bed, we could predict strep a day before we had any other symptoms because she would have a night terror. For her, it was 65 minutes after she went to bed. So it was the end of her first sleep cycle. It's right when she came up in that first sleep cycle, she would start screaming in terror. And so you can see that for most of us adults, we have several cycles through the night and that those cycles are about 90 minutes long, give or take, on average for us. And the thing that I'd like to highlight here is that deep sleep, we start out the first cycle, we get the most deep sleep. So you get into deep sleep early in the course of your night. In your early cycles, you have more deep sleep. And then as you progress through the rest of your cycles, it switches to more REM sleep. So if you start interrupting the sleep in these cycles, you can see how you disrupt that transition. You disrupt the amount of time that would be in each one of those different stages. The early part of sleep for the night for most of us and the later part of sleep in the night. Really, we see the deep sleep in the early and the REM sleep elongate in the later part of sleep. And that's really important because when we think of sleep deprivation, we can kind of categorize it into three buckets. You get an inadequate amount, so your total sleep time or your TST, you're gonna see that on many slides. You have a poor quality that's objective that we can look at polyscenography or actigraphy and we can see that you didn't get a lot of the stages that you needed. You didn't get the right amount of the stages, that you didn't cycle through, you had a lot of fragmentation, a lot of waking up. So we can objectively measure the quality. And we also can subjectively measure poor sleep quality by asking patients and saying, how did you sleep? How was it for you? Do you feel restored? Do you feel like you got a good night's sleep? And that can be the subject. So we can really measure sleep deprivation in three different buckets, total time, objective quality and subjective quality. And when we look at ICU sleep versus healthy adults, and it's important, I think something like 30% of the adult population in the United States has sleep deprivation in some way or another. So I'm not sure who the healthy adults are, they're comparing here. But when we look at sleep in the ICU and sleep in healthy adults, the total sleep time, so that first bucket that we talked about, it's usually about the same. The patients are sleeping, they're getting into some stage of sleep for about the same amount of time as a healthy individual would have had total sleep time. However, the sleep that they have, those other two buckets, the quality of sleep, subjectively and objectively, is screwed up. There's more sleep fragmentation, so a lot more awakening, so staying up in those lighter levels and peaking all the way up. There's more light sleep, so that's stage one and stage two of non-REM sleep. There's more sleeping during the day versus sleeping during the night, so the sleep is happening in different times of the day. There's less of that deep sleep, and there's less of that REM sleep that we talked about. And if you lose that, we've already talked about, that you miss out on the restorative parts of those sleeps, the benefits of that. And it's a common complaint of our ICU patients. They feel like they didn't sleep at all. They have very poor sleep, they have a lot of memories of nightmares, they have a lot of feeling not rested, mind fog that they're attributing to poor sleep. So you can see that even the total sleep time is the same, that the quality in both the objective and subjective is poor. General effects of inadequate sleep, and really, I think this is more of one of those does, we all know this, that immune system compromise, and when we don't get enough sleep, there's cognitive problems, muscular complications, floor, glycemic control, increased perception of pain that you feel things hurt more. And if you've ever had a surgery, and you're in pain overnight, you can't fall asleep, you know, it seems like the worst pain in the world is when everyone else in your house is asleep, and you're awake feeling this pain. But when noise and distraction starts happening in the days going on, the pain is not as intense. Emotional distress, depression, and we can all, in some way or another, relate to that. And cardiovascular disease, especially with sleep apnea. So when we look at sleep derangements and ICU outcomes specifically, I wanna look in three specific buckets. Those points that I shared earlier is mostly, we get that from the non-ICU population that really has looked at all those different outcomes associated with sleep. And when we think of ICU outcomes and sleep derangements or deprivation relatedness, we can put that into three buckets. So we're gonna talk about delirium, told you we'd mention it. And then those common ICU outcomes like length of stay, time on the vent, mortality, and then post-ICU outcomes. And what is life like after the ICU related to poor sleep that you had in the ICU, which for many of your patients, if you've never, everybody should, this is one of my biggest take-homes of my career is, you need to talk to ICU survivors about what the ICU was like. You should find as many of them as you can and talk to as many of them as you can and ask them, tell me about it, what was it like? Tell me about it. One of their frequent complaints, like what they remember the most was being awake or not being able to fall asleep or not getting the right sleep or being woken up a lot. My dad used to joke that the hospital's the only place you go where they wake you up to give you a sleeping pill. And I think he had some truth to what he was saying. So let's look at these three outcomes. So delirium, when we, it's a real chicken and egg situation. There's a consistent relationship. The studies that look at delirium and sleep, whether sleep is the outcome or delirium is the outcome of the sleep study or whether sleep is the outcome of the delirium study, we can see that there's severe REM reduction is associated with delirium and daily lorazepam dose. So patients that have more delirium and more lorazepam have more REM dysfunction. We also see studies that look at multi-component strategies to reduce sleep, reduce delirium. And so, but not all of them improve sleep. So we see this relationship of these strategies that we might target, not all of them in the way that they measured sleep, objectively, they didn't all improve sleep, but most of them improved delirium in some way. So which came first? Is it the delirium that really drives poor sleep or is it poor sleep that's driving delirium? And the answer is, we don't know. We don't really understand this. I lean towards, if I'm having poor sleep, I'm gonna be delirious. I'm gonna be really confused. I was just on the phone talking to my daughter about some wacky dream that I had right before I woke up this morning that was really a mixture of the noises that were going on in the street and something that had recently happened to us and I woke up and thought it was kind of real and I was still a little bit sad or emotional about it. And then I realized, oh my goodness, that was the silliest thing ever. That was my dream. And here I'm having this reaction to it. And so we don't really know which is driving which, but we see a consistent relationship that poor sleep and delirium seem to show up together all the time. I love this image that this was in a paper by Paula Watson, one of my colleagues at Vanderbilt, and I love it. It just shows, like we don't, I mean, they all, there's such synergism here related to this that we're just really not sure what might be causing what because the arrows are going in every direction and they're really feeding each other in a way. And I just really have, I appreciate this because it just reminds us of how multifactorial that it really is. It's not clear-cut that one is causing the other. But we do know they go together. And that's one of the reasons that as we think of the A to F bundle, there's always a campaign of will there be a G for good sleep? And then there's a group of people that says no, it falls under the delirium. And others that say no, it falls under G for good sleep. And so who knows if we'll get a G or not. But that's why is that we really can't separate those two very clearly. What about those classic ICU outcomes with time on the vent, length of stay, and mortality? So when we look at this study with hypercapnic patients with abnormal sleep, they had increased daytime sleep and reduced REM sleep, which we already know is a problem. They were more likely to fail their non-invasive ventilation and required intubation. Their ICU stays were longer, and both their ICU and hospital mortality rates were greater. When we look at another study, the better rest activity cycle consolidation, so making day, day, and night, night, and really getting 80% of their sleep, greater than 80% of daytime activity happen instead of sleep happening, napping all the whole time through the day, was associated with shorter ICU. So better sleep was associated with shorter ICU in hospital stays in traumatic brain injury patients. And then when we look at this third study, studies that looked at quality improvement initiatives to improve sleep, improvement of both nighttime noise, so less noise at night, and was related to, in these multi-component strategies, they did improve nighttime noise, so lowering the noise at night, and delirium and coma were improved. They have fewer days in delirium and coma. But there was no improvement in perceived sleep. So we look at these usual outcomes that we talked about, and these might be three of our best studies that we have to look at for these things, and we can see all three of them use different measurements, objective measurements for sleep, or measurements for sleep. The first study looked at polysomnography, which is really hard to do in a mass way on hundreds of patients. You need a lot of equipment, you need a lot of people that can read and interpret and manage, and you need patients that will cooperate with having this on. And frankly, you need ICU nurses that will cooperate with having that on their patients and families that will cooperate. So polysomnography research is really difficult to do. And the second study looked at measuring actigraphy levels. That's easier, right? So you can put watches and wrist anklets on and measure activity in the patient and make some assumptions that that correlates to sleep. And then the third study looked at subjective questioning of the patients. So did it matter? Did you feel like you had more sleep? So when we look at these, the challenge is that's the heterogeneity that we get in these studies is that they're all using different measurements to measure sleep. And so in the end is that there's some signal on these outcomes, these really important ICU outcomes, but way more research is needed and consistent research that's looking at using the same measurements over and over in populations. And then the last area, so we looked at delirium, we looked at those common outcomes that we think about in the ICU, and the last one is what about the post-ICU period? And really we have little to no research there that we don't know. And this is one of those driving areas where we need more research. Factors associated with poor sleep is if you've got preexisting sleep condition, you have illness severity, your delirium, again, chicken and egg, not sure there. Medication effects, so some of our medications, benzodiazepines, propofol, most of our sedatives, opioids. We see reduction of sleep with those medicines. Patient vent dyssynchrony causes some sleep disruption. Light at night, frequent care activities, noise, all of those are disrupting of sleep. Pain, and then worry, anxiety, loneliness. Those all mess with sleep. So you can look through these, and when we get to the part in the talks today that we will discuss factors to strategies to improve sleep, we can think of what of these are modifiable? What can we do? Well, we're not gonna really be able to fix their preexisting sleep condition. If they came in with insomnia, we're probably not gonna be able to help fix that and cure them, but we can certainly make strategies of light reduction during night, increase daytime activities, decrease the noise at night, bundling our care so that we're not coming in and waking our patients up four or five times at night, doing those things. So really being thoughtful about the factors that are modifiable versus those that we don't have much control over. So in summary, sleep disruption, we see the two major areas that we think that is really affecting our ICU patients is this decreased deep sleep and decreased REM sleep. And so thinking of things that we do that can really improve those two buckets and also knowing that it's not benign, that sleep disruption, whether that results in your subjective quality or your objective quality or your total time that you were sleeping and all those areas, it's not benign. That's linked to long-term outcomes for our patients and that there are modifiable risk factors. When we think of that, there are things that we can do. Several of those multimodal or several strategies are looked at bundling care things, whether it's eye mask or earplugs to noise reduction strategies of having a kind of a bundled approach of changing the culture in your ICU to help improve sleep. And we see that we can see benefits there, maybe not always in the sleep that we're measuring, if we're measuring in the right way, but we see other outcomes improve as well. So with that, I'm gonna wrap up and we're gonna take questions at the end.

sleep disruption

ICU patients

overall health

cognitive function

deep sleep

modifiable risk factors