All right, let's go ahead and get started. I want to welcome everybody to AAP Virtual Didactics today. My name is Sterling Herring. I'm a PGY3 at Vanderbilt. First as always, I want to recognize and appreciate those who have been most affected by the COVID-19 pandemic. We recognize that the burden of this pandemic has not been distributed equitably, so we appreciate those of you for whom this has been particularly professionally or personally difficult. Also want to appreciate Amos Song, who covered for me on Thursday and Friday of last week as I was out. Goals of this, as always, are to augment didactic curricula ongoing at your home institutions, to offload stretched faculty due to the logistical difficulties presented by this pandemic, to provide additional learning opportunities for off-schedule residents, again, due to some of the scheduling difficulties presented by COVID-19, and then further to develop more digital learning resources and support physiatrists in general during COVID-19. Same housekeeping rules, as always, we're going to keep everybody video and audio muted. If you have any questions, if you'll click on your participants list and see, you should see my name up near the top somewhere, Sterling Herring, if you double-click my name, it'll open a chat box and you can send me any content-related questions. If you have any general questions about the series or you have someone that's interested in presenting or something like that, please reach out to Candice Street, her email is there on the screen, or you can track us down on Twitter. So without further ado, we're excited for today's presenter. Welcome Dr. Seema Desai from Carolinas Rehab. Thank you for joining us today. Thanks for having me. All right. Let's get started here. All right, so my name is Dr. Seema Desai. I am one of the traumatic brain injury attendings here at Carolinas Rehab in Charlotte, North Carolina. I'm also one of the assistant professors of our Physical Medicine and Rehabilitation Department. I don't have any disclosures today. The objectives, we're gonna keep them relatively simple. Just want you guys to be able to describe what normal sleep-wake cycle looks like, which actually is more complex than most of us think. Describe just the main neurotransmitters that are involved in what I call our sleep-wake on and off switch and what their purposes are. And then just explain the most common mechanisms of the drugs that we do use in our TBI population for sleep. I will be using Poll Everywhere pretty extensively throughout this presentation, just to make it as interactive as possible. So you can either download the app or you can respond on your phones by going to www.pollev.com forward slash my name's Sima Desai 890. So I just wanna know where everybody's from today, just given that everyone is coming from different parts of the nation and see what's going on. All right, we look like we got Nevada, Pennsylvania, Texas, a couple in Texas, Washington, Minnesota, Tennessee, great. That's my home state where I grew up. California, awesome, Illinois. It sometimes takes folks a little bit to get all logged in to. I figured as much. And over in the chat, we're seeing Puerto Rico, Dominican Republic, Peru, Chicago. Awesome, I wish I could have put a world map on here. That would have probably been a little more useful. Singapore. Wow, Singapore. Well, thank you everyone for joining in today. I really appreciate all the time and effort everyone is putting in during this pandemic, even just to listen in on lectures and learn a little bit. So I hope everyone takes away at least something from this lecture. All right, so this is just a basic little figure to show you that the relationship between TBI and sleep and how it's really multiple factors involved that contribute to sleep disturbances, including psychiatric disturbances and fatigue. So it's important just to keep in mind that these are all factors that play a role in our TBI population. So the way I'm gonna break down sleep disturbances today is into three main categories. By no means is this extensive, but it's kind of the best way to think about it when you're seeing patients. So insomnia, which is defined as the difficulty in initiating or maintaining sleep, a lot of times associated with daytime fatigue or impaired functioning. We see this most commonly in our acute TBI population. So patients who are coming to us on the acute side of rehab. And then you have hypersomnia. This is that excessive daytime sleepiness. We see this a little more in our chronic TBI population once you're following them in clinic for several months or even years. And then the last one, which is not as common, but you will still see, are sleep-wake alterations. You can also call this a circadian rhythm disorder. This is the inability to go to sleep or stay awake at a desired clock time. But it's really important to keep in mind that the sleep-wake cycle alterations, their duration and pattern of sleep, are actually normal once they're able to fall asleep, which is why it's very important to get your sleep docs involved in this population early on, if possible. And if at any point people have questions, I'm happy to stop and try to answer them as well. So this is just a table of REM and non-REM, or rapid eye movement and non-rapid eye movement. So our sleep-wake cycle in general is regulated by the interaction of our internal biological clocks and the environment. So the sleep cycle itself is just divided into two basic states. You're either in REM or you're in non-REM sleep. Your REM cycle occurs every 90 to 100 minutes, and lasts about 10 to 40 minutes. During your REM cycle, you have actually increased or high levels of brain activity as well as your physiologic status is similar to that of when you're awake. So high blood pressure, increase in blood pressure, increase in heart rate, increase in respiratory rate. Whereas your non-REM sleep is more of a peaceful state, and there are actually four stages of non-REM, which we'll go through in the next slide. But just keep in mind that a majority of your sleep is actually in that non-REM phase. So these are just the four stages of non-REM. The way I'll just break them down is, you don't need to ever memorize this whole slide. You just need to keep in mind that non-REM is four stages. The first stage is just mixed frequency waves. The second stage is characterized more by spindle-shaped tracings, as well as K-complexes. And the third and fourth stage are just delta waves. These are some things that have come up on old SAEs, so could be helpful during a test if you really need it. But just keep in mind, again, that even the stage four, that occupies more than 50% of your sleep. So that's kind of just a good way to differentiate your REM from your non-REM. So let's kind of dive into some studies. I do want to point out that there is not a lot of great evidence in our blood test and there is not a lot of great evidence in our brain injury population regarding sleep. So a lot of the studies that I'm showing you are very old and not as up-to-date. So if you enjoy research, this would be a great place to get involved, either with your own institution or even trying to do a fancier multi-site study. So what we've found is that the prevalence of sleep disturbances in the acute phase is pretty high. So there were two studies done by Mackley and they were looking at the prevalence of sleep issues in the moderate to severe TBI patients once they were admitted to an acute inpatient unit. And what they found in the first chart here is that the affected patients had significantly longer length of stays, whether it be in acute care or the rehab, if they had sleep disturbances. And in that first study, he had about 31 patients. And of those 31 patients, about 70% of patients that had moderate to severe TBI had sleep issues. So it's important to keep in mind when you're either seeing consults in acute care or even admitting them to your service that them not getting good sleep is gonna actually prolong their length of stay. And then the second study that he did was actually an even smaller study, but had some very relevant findings. What he looked at was sleep efficiency, which is the ratio of the time you spend asleep compared to the total time you spend in your bed. And so in this pretty small study, I think it was only about 14 patients, he found that as patients cleared PTA, which they use the O log for that, their sleep efficiency scores actually improved. For you or me, our sleep efficiency scores are probably around 85 to 90%. So it's very important that either if you're doing the GOAT at your institution or you're doing the O log, the O log is just nice because it's quick and it's a quantitative measure of the orientation status. But keep in mind to clear PTA, you do need a score of 25 or better on the O log. And if you're using the GOAT, about 75 or better consecutively for two days. So just something that you want to pay attention as your patients are clearing PTA when they come to you. So then what about the prevalence of sleep issues in the chronic phase? And by chronic phase, I mean your TBI patients that are coming to you several months after they've been discharged or your super chronic ones who've been seeing you for several years. So one of these very old studies from Cohen suggested that the sleep complaints really vary temporally. So insomnia occurs pretty much very soon after injury. And then the hypersomnia, which is that excessive daytime sleepiness occurs months to years after the injury. What that study found was that in their acute patients, patients who had had their injury just three to four months post-injury, a majority of them, about 80%, had either difficulty initiating sleep, that early insomnia or maintaining sleep, that middle insomnia. And just a small percentage had that hyperinsomnia. However, when they looked at their outpatient population for patients who had TBIs from two to three years prior, a majority of those patients, 70%, were complaining of this hypersomnia. However, a more recent study from VIRMA showed that chronic TBI patients really actually have this spectrum of sleep disturbances, which is something from anecdotally speaking, I see more in my population. Fall into the 80, 14, or the 70% range. They fall kind of a little more in this range. About 50% of the patients were complaining of hypersomnia, either due to narcolepsy, sleep apnea, or some sort of periodic leg movement. 25% had insomnia, either related to high anxiety or depression. And then another 25%, which is that smaller population, had these REM behavior disorders. REM behavior disorders are the most common type of parasomnia. I didn't put parasomnias as a part of those slides a couple minutes ago, but basically what parasomnias are, are they're just a category of sleep disorders that involve any sort of abnormal movement or behavior or emotion, or even dreams that occur while falling asleep, sleeping in between your sleep stages, or when you're waking up from sleep. What we do know is that there are pathophysiological changes that occur in the brain during the recovery process, and the severity of injury has been postulated to be some factors responsible for this change. But we really don't know. This is just based on some of the basic research that's been done out there. So I'm gonna start talking, I'm gonna break the three different types of sleep disorders down that we see the most. So insomnia, which we already talked about, is that inability or difficulty in initiating or maintaining sleep, a lot of times associated with daytime fatigue. I'm sure as residents, and I know when I was a resident or a fellow, you obviously can sometimes feel that way. In a mild TBI population, we do see a pretty significant relationship between insomnia and depression. So I personally in my clinic will actually administer the PHQ-9 to all my TBI patients, just because I do see depression so commonly, especially in my mild TBI population. And the sooner we can treat that, usually the better outcomes we tend to have. Also, it's just very important in general that you're screening your TBI population for depression. Is the severity of TBI related to insomnia? We're really not sure. There's a lot of conflicting data. Some says yes, some says no. But we do know that severe TBI patients may be under-reporting their insomnia compared to our mild TBI patients who are actually able to verbalize that information to you. So if you have a caregiver who is taking care of your patient, it's very important to just get a very detailed history from them as well. And is pain after TBI related to insomnia? Again, there's lots of conflicting data. It could or it could not be, but always something to kind of just keep on your differential. So hypersomnia. Hypersomnia is that excessive daytime sleepiness. We do tend to see this more so in our chronic TBI population and so a relatively older study that was done, it was actually done in a residential rehab facility. So these tend to be patients who have had a traumatic brain injury or even a non-traumatic brain injury many months ago. And so they're kind of more leaning towards that chronic TBI direction. And what they found is that 47% of their patients actually had hypersomnia, but they weren't able to find any differences between their hypersomnolent patients and their non-hypersomnolent patients in their GCS scores, their length of coma, their time since their brain injury, the nature of their injury, gender or medications. But what they were able to find is that subjects with hypersomnia were typically unable to perceive their hypersomnolence. So again, very important if you have caregivers or your nurses, your therapists to really get a good history from them as to what's going on. But if the patient comes into your clinic or even on the acute care side, they're complaining of this excessive daytime sleepiness, it's really important that you do evaluate that with sleep studies, either looking at sleep apnea, OSA, or narcolepsy as well, because that could be something that's happening. And then the third type are what we call these sleep-wake cycle alterations, or you can call them circadian rhythm disorders. It's really just defined by the inability to go to sleep or stay awake at that desired clock time. And just remember, these patients, their pattern of sleep is still normal, unlike the insomnia and hypersomnia patients. The pathogenesis, we're really just not sure, but what we can say is that there's some thought that it's a dysfunction from the suprachiasmatic nucleus. If you quickly look at this, you'll see that the extrinsic type is that shift-work sleep disorder. So these are obviously patients who have been working that third shift their whole life. It's very hard to get their sleep back on a regular sleep cycle, just because they've been living that way for so long. And then if they have the TBI on top of that, it makes it even harder. But another thing to keep in mind is that the delayed sleep phase disorder, that's something that we actually see pretty commonly in our mild TBI population. So something to be asking when you see your mild TBIs in clinic. So then we're just gonna quickly talk about TBIs and disordered sleep patterns. So these are kind of just the most common things and things that I pay attention to when I'm evaluating patients, whether it be on consults or if I'm seeing them in clinic or if I'm seeing them on the inpatient side. So obese patients, we all know, are just more likely to develop sleep disordered breathing, particularly OSA. So I know in our hospital, we're actually able to do overnight pulse oximetries, but we're not actually able to do a sleep study. So even if the overnight pulse ox gives us some information, that usually triggers me to then send that patient to a sleep specialist, so that way they can get that done as soon as they get home. Patients with TBI are actually more likely to even develop these upper airway musculature disorders, and that's really due to cranial nerve lesions. So when you're doing that neurological exam on our patients and they have a cranial nerve palsy, just keep this in the back of your mind that they may also end up having upper airway disorders or abnormal sleep patterns. You can also get hypoventilation syndromes. These are manifested by these decreased breath sounds at the lung bases, and that worsens at night. So again, asking your nurses, your respiratory therapist, what's going on with some of your patients at night when you see them in the morning. And then you can get this combination of what we call a central sleep apnea plus a REM parasomnia. These you could see, I've only seen a handful of these, but these you can see with brainstem injuries. So any patient that's coming in, and you know that they've had some sort of brainstem dysfunction, this is something just to keep in mind. And it's because your midbrain and your pons are your primary generator of the REM adonia, and your medulla is part of your respiratory control center. So that's why you get this combination of a central sleep apnea plus a REM parasomnia. All right, sorry. So this is just a really detailed chart to kind of just show you, it's just important to determine if the symptoms are occurring in isolation or are they occurring secondary to some sort of neuropsychiatric disturbance, like a mood disorder. Medical illnesses like idiopathic sleep disorders, viral illnesses, medication side effects, all of these things should be ruled out, obviously, when you're taking a good history and physical. The key elements to obtaining this detailed history is getting a history if you can from your patient, but if not, getting that collateral information from the family is very, very important. We're trying to review old records if you can, and just performing just a really good physical exam, getting that medical, neuro, and psychiatric exam if possible. And then if the sleep disturbance is not considered to be secondary to any sort of clinical syndrome, you really should be looking at getting some sleep studies. They usually cannot be done on an inpatient basis, but if you can, if your institution does that, then that's great. But a lot of times, these studies are really helpful in identifying the type of sleep disturbance as well as help differentiate what type of fatigue they're really having. So the evaluation. How do you actually evaluate these TBI patients who have sleep disturbances? The best way to really do it is to break it down. I like this chart just because it kind of focuses on figuring out who the patient is, what do they look like pre-injury, what do they look like post-injury, what were their behaviors before, what are their behaviors now, and kind of what's their life story, what were any sort of environmental factors, social factors, did they work the third shift? All those questions are really pertinent and part of what I kind of tell our residents, our functional history. So I'm just gonna talk about just three tests. I personally don't do these tests, obviously, because I'm not a sleep specialist, but just good to know what you're looking at when you do get that report from the sleep medicine docs. So this is a PSG or a polysomnography. It's really the gold standard for measuring sleep disturbances. It's great because it assesses breathing, respiratory muscle effort, the muscle tone, their REM cycle, their non-REM cycle. It actually has an EEG hooked up to it, an EKG, some of them even have these EMGs, and you can look at the eye movements as well. They can be modified to actually look for very specific things. If you know what you're looking for, it can look for very specific breathing problems, parasomnias, GERD, and even some erectile dysfunction. It's great because it actually looks for the disruption of sleep architecture, looks at motor activity, as well as cardiopulmonary irregularities. The PSG is most useful in kind of diagnosing that OSA, the central sleep apnea, the upper airway resistance syndrome, even nocturnal seizures, since you can connect that EEG, as well as those periodic limb movements. This one is probably one most of you guys may not have heard of. We don't do these, I don't actually see these a ton, but it's important to at least be able to recognize what type of test it is. It's called a multiple sleep latency test. It's a very well-validated measure of physiologic sleep and provides an objective measure of that sleepiness that our patients may be saying, I feel sleepy, I feel sleepy, and figuring out what it is. It helps differentiate from that subjective complaint of sleepiness and fatigue. And it's basically a four to five, 20 minute nap at two hour intervals. And then they measure how quickly you fall asleep. This is a great test that we use for narcolepsy or hypersomnia. And basically it can also identify if you're going into REM during a nap, which you shouldn't be. So that would be very abnormal. A mean sleep latency of five minutes or less would indicate an abnormality. So this is something to kind of look out for when you're getting these reports back from your sleep medicine doctors and trying to decipher what it means. All right. So then there's also actinography. This is what you'll see a little more in research. It's a small wrist kind of watch and it records your movement continuously up to 22 days. It's kind of like a Holter monitor. It differentiates between sleep and wakefulness based on your movement. They use these a lot more in the dementia population, children, and even your agitated TBI patients. It's great because you can use this both in the acute TBI patients and your chronic TBIs. And it looks at a variety of things. It looks at your circadian rhythm, your sleep efficiency, just your general activity. So this is used a lot more in research because it can kind of answer a lot of questions as opposed to having patients come in for either PSGs or those multiple sleep latency tests. All right. I'm gonna stop here for now before we start talking about the circuits. Are there any questions or concerns? None have come through yet. I have a question or two, but we can wait till the end. I wanna make sure you get through all your content. Okay. All right. So this, we're gonna start talking about the sleep circuits. And so this might get a little bit confusing. So if it does, what I'll do is I'll stop at the end of these next couple of slides. And if I need to delve into them more, I will. So basically, if you're looking at the center of the screen, I didn't get my mouse, this guy right here, he's an awake, alert, problem-solving individual, like all of you guys out there that has the right balance of too much or too little arousal. So that's where we all want to be, ideally, at least when we're rounding in the morning, and as that arousal increases beyond normal, we call this hypervigilance. That's right here. And if this is increased at night, we call this insomnia. So from a treatment perspective, we say insomnia is characterized by this hyperarousal at night, and we treat it using sedatives or hypnotics so that we can actually move the patient from having insomnia to hopefully falling asleep. But just keep in mind, it's really important that you can get cognitive dysfunction with even being under stimulated as well as being over stimulated. So when you're assessing your patients in the morning, that's something to keep in mind. So then we're still going to talk about, I call this now the game of sleep. It's just really important to understand who the main players are, and these are just your main neurotransmitters. So they're histamine, dopamine, norepinephrine, serotonin, and acetylcholine. Most of the drugs that we use in our TBI patients work by blocking one or more of these sites. So that's why I said it's very important to kind of know who these five players are. So the best way to kind of think about the sleep-wake cycle is thinking about it as a multi-circuit system. So I'm going to try and break this down. So the brainstem actually regulates your cortical arousal system, and you should think of it kind of like a volume button on the radio. And then there's this other set of circuits in the hypothalamus. That's actually what regulates sleep and wakefulness, like an on-off switch, like you see in the picture. So the on switch is known as a wake promoter, and that's actually localized in your TMN, or the tuberomammillary nucleus of the hypothalamus. The off switch, which is in the blue, is known as your sleep promoter, and that is localized in your VLPO nucleus, or the ventrolateral preoptic nucleus of the hypothalamus. Then you actually have two neurotransmitters that are involved in the switch. So histamine from the TMN and GABA from the VLPO. So hopefully we have all that down. Once the switch is actually turned on, the wake promoter TMN is active, and now histamine is released into your cortex, and it's also released to the VLPO. So the wake promoter is now on, and the sleep promoter is now inhibited. So this is what happens when our sleep switch is on. So as the day progresses, another circuit comes into play, our circadian wake drive. So that, our circadian wake drive diminishes, we eventually get sleepy, and then once that tipping point is reached, the VLPO, which is in purple, is now active, and the sleep switch is turned off. As a result of that, GABA is now released to the TMN, and now the wake promoter is inhibited. So what you'll see on the screen here is there's an LAT and an SCN. So these are two other sets of neurons that are also involved in this process, and one of them is called orexin, and that's localized in your lateral hypothalamus, which is where it says lat at the top in purple. And that actually stabilizes wakefulness, helps you stay awake. And then you also have melatonin-sensitive neurons, and those are located in the suprachiasmatic nucleus. That's the SCN. The SCN is the brain's internal clock, and it helps regulate the circadian input to the sleep-wake switch, and it's programmed by hormones, light, activity, to either promote wakefulness or it helps promote sleep. So I'm going to stop at these slides before I move on to see if there's any questions about the switch and the circuits in general, because it can get complicated. Briefly, I had read something maybe a year or two ago about these sleep masks that people are sometimes using on planes that are electronic and somehow manipulate the, I assume, suprachiasmatic nucleus. Is there any evidence for use of anything like that in TBI patients? Not at the moment there isn't, but I wouldn't be surprised if that is a target for even medications going forward, just because they're honestly all the medications that we use in our TBI population are off-label use. So we actually don't have anything that's truly on-label for our patients, and if it's something that they don't have to take orally, that they can just put on, that would be a great alternative, but something that I would need to look into a little more. Okay, thank you. And another question came through is, when you're saying that the switch is on, does that mean promoting wakefulness or promoting sleep? You're promoting wakefulness. So I always think of the on switch, sunny outside, you need to wake up, and so you need to get your day going, so that's when histamine gets released. Okay, perfect, thank you. Yeah, all right, so now we're going to talk about the fun stuff, or at least for me this is the fun stuff, kind of what drugs to use, what drug not to use. Just so you guys know, this isn't an extensive list of every single drug you can use, but these are the most common ones that we use in our TBI patients, and most of these, if not all of these, are off-label use, so just so you guys all know. So Haldol and benzodiazepines are what we all call the big no-no drugs in TBI. Haldol, because it's a D2 antagonist, and benzos are actually GABA modulators. The reason why we don't give these drugs is because there was actually great research that was done that showed us this is actually very detrimental to cognitive recovery. It's very important that, although this seems obvious to us as a psychiatrist, this isn't always obvious in your consult population, especially when you're rotating on the neurosurgical unit or your trauma unit. This is something that even our institution has, we've educated our trauma surgeons and our neurosurgeons to really avoid giving these medications, if possible, because it is so detrimental to their cognitive recovery. So we can't use Haldol, we shouldn't be using benzos, so why don't we just give our patients some Benadryl? Well, Benadryl is great for some things, but not in our TBI population because it has a lot of antihistamine activity, but the negative part of this is actually it's anticholinergic activity, so that blurry vision, the constipation, the memory problems, the dry mouth. A lot of our TBI patients already have memory issues, they even may have visual issues from, depending if they already have a cranial nerve palsy, constipation, things we don't want in our patients in general. Trazodone, this is probably the most common one, at least that I had used when I was first in residency. At high doses, this is an older drug that was used to actually block the reuptake of serotonin, which is why it was used for depression, but at low doses, it works as a alpha-1 antagonist and also has some antihistamine activity at very low doses. So anywhere from that, and I put 50 here, but we even use 25, so anywhere from 25 to 200 milligrams, you're really only going to be targeting sleep. So if you're trying to target depression, there are other medications you can use out there for that. But this is actually a really great drug because it helps with sleep initiation, sleep maintenance, and chronic sleep issues. Some other drugs, I call them the Z-drugs, or you may have been, you may have been told about them being labeled as Z-drugs. So these are GABA-A modulators. Ambien is probably the most common one you guys have heard of, Zolpidem or Lunasta, which is estopaclone. These were used initially to help initiate sleep or help with chronic sleep issues. The issue with these Z-drugs is that they do cause daytime sleepiness, amnesia, and anticonvulsant activity. So in my TBI patients, I really avoid the Z-drugs as much as possible, but sometimes patients will come in on these medications already, and they're like, this is the only medication that works, and they really don't want to try anything else. So it's just important to keep in mind that their brain has changed since their TBI, and so the effects may also be different. It's also important to keep in mind the Z-drugs bind to GABA-A, and so that's why Ambien was touted as such a great drug is because it binds to the GABA-A receptor, so it doesn't cause a high degree of tolerance as compared to benzodiazepines that actually cause a conformational change, which is why benzos do cause that tolerance. You also have martazapine, so this is an alpha-2 agonist. It also blocks your 5-HT receptors, and it also has some antihistamine activity. If you're using it exclusively for sleep, then you really just want to use the 7.5 milligram dose, but let's say you want to use it for mood, sleep, and their appetite because they're not eating well, then 15 milligrams or more is actually when where you're going to actually start affecting your appetite and your mood and being able to get a little more what I call a two-for-one or a three-for-one result. There's also hydroxyzine. This is an H1 antagonist, so I call it Benadryl's cousin, but it has a lot less anticholinergic properties than all the other antihistamines out there. So this is a medication that can be used in our patients, and it usually is pretty well tolerated. And then you have your melatonergic hypnotics. So melatonin, which is just over-the-counter, acts at three different receptor sites. It works at MT1, MT2, and MT3. If you're going to use a prescription version, which is remeltion, that starting dose is eight milligrams, and it's just an MT1 and an MT2 agonist, and it only helps with sleep initiation. Melatonin in general is not going to help with sleep maintenance. So if your patients are telling you, I'm able to fall asleep, I'm just not able to stay asleep, melatonin is probably not going to do very much. So then what about sleep in the agitated patient? When you get that phone call at one o'clock in the morning when you're on call, and the nurse tells you she needs something for sleep because this patient's really agitated. So there are some options. You can use these atypical dopamine antagonists, but it's important to keep in mind these don't come without side effects. So Seroquel or Cotiapine can be used, but it's very sedating, and it actually has a very large amount of histamine activity. So you might want to be wary about using that because it can cause your patients to just feel a little groggy in the morning, and then cognitively they may not perform as well. Zipraxidone is always an option, but this has the highest QT prolongation out of all the atypicals. So before I even start an atypical, or someone comes over to me on an atypical, I always get an EKG to check that QTC interval. Olanzapine can be used. This is what we use a little more in the acute care setting, and Risperidone. Just keep in mind with Risperidone, the side effect of gynecomastia is real, and so you just want to be careful with the dosing. And then there's a lot of novel agents, or I just call them expensive agents. One of them is called suvorexin. Its brand name is called balsamra. These are actually orexin blockers. So if you remember back a couple of slides ago, I talked to you a little bit about the circuit and how there's another set of neurons involved, one of them being orexin. So some scientists got together and figured if you block orexin, you'll actually be able to sleep. So that was actually found to be true. So this is a good drug, and it helps with initiation and maintenance of sleep, but it's extremely expensive. I think it's about $400 a month for a 30-day supply. So not really realistic from a monetary perspective for our patients. All right. So we're going to start with a case, and this is where we're going to need everyone to be a little more interactive. So this is where we'll use Poll Everywhere pretty extensively. So how much sleep did everyone get last night? I can tell you, I got seven to eight hours. Okay. Some of you aren't getting much sleep at all, the four to five-hour range. Some of you, looks like a majority of you are getting seven to eight hours. That's pretty good. All right. And some of you got eight to nine. That's amazing. I'm a little jealous. All right. Okay. Well, thanks for that. All right. So we're going to get started with a case. This was a case I actually encountered in fellowship, and it was probably one of the more challenging cases in terms of having a brain injury patient with sleep issues. That's pretty much what we spent almost a majority of the admission trying to figure out. So this is a 62-year-old male. He has a past medical history of Parkinson's, status was a deep brain stimulator in 2015, diabetes, BPH, hyperlipidemia, and also has already existing OSA and was using a CPAP regularly at nighttime. He unfortunately experienced a TBI after a fall with bilateral subarachnoids. He ended up presenting to us with kind of deconditioning more so, and the family's health was a little bit more so. And the family's number one complaint was that he had not slept in days and that they really just felt if he could get a good night of rest, he'd be able to function better. So given that we didn't know too much more about him, we just decided, well, we'll just give melatonin since the family says he's just been having trouble falling asleep. So we started with six milligrams at bedtime to just kind of observe the overall effects over the next couple of days. And the melatonin didn't really appear to be working to help facilitate this better sleep when we first started it. So what are some, I guess, non-pharmacologic approaches for helping our patients with sleep disturbances? And there's no wrong answer for this. Dark room. Good. Sleep hygiene. Yep. Stimulus regulation. So light, TV, sound, turning off the lights at bedtime, limiting electronic exposures. Yep. Optimizing the sleep environment. Ballerine. Exposing them to light during the day. Yep. All these things are great. Yep. Limiting daytime naps. Absolutely. Adequate nutrition and hydration. Yes. Very important. And good sleep hygiene. I've seen that a couple of times. A regular schedule. Absolutely. A regular schedule. Absolutely. Limiting overnight disturbances. Exercise. Very good. Yep. Physical activity during the day. Great. Limiting the time you spend in bed. Absolutely. All these things are very important. This little table here kind of hits all the points you guys all just said. So kind of having that good sleep hygiene of going to bed at the same time, trying to wake up around the same time. I tell this more for my mild TBI patients. Avoiding those daytime naps. And if they do feel sleepy, try to keep the naps short. Obviously, in our TBI population, we don't want them consuming alcohol. But I especially tell this to our mild TBI patients who come to me in clinic. Avoiding sort of stimulating activities before bedtime. And avoiding all the bright noise, lights, electronics, all that stuff. So great. So since the melatonin didn't work, what would you guys like to try next? And like I said, there's really no wrong answers in this. Trazodone. Okay. Great option. Trazodone again. Zolpidem. Okay. Someone wants to try Z-drug. Seroquel. Okay. Trazodone. Atarax. Yep. Atarax is also hydroxylene. So yeah, that's also an option. Change the timing of the melatonin. Yes. You can always change the timing of the melatonin. Trazodone. Yeah. So changing the timing of the melatonin is a great option. We had already actually done that. Increasing the dose of melatonin. Correct. You could. We tend to not increase more than six to nine milligrams just because there have been research studies that show that after you get past that six milligram dose, you're really not getting a great effect. So I usually don't go past the six milligram mark personally. Someone said Trazodone or low dose mirtazapine if they had mood symptoms. Yep. Absolutely. Those are all great options. Seroquel. He didn't have any agitation. And it's important to keep in mind that this patient is Parkinson's. So he's already dopamine depleted. So by adding a dopamine agent on top or anti-dopamine agent on top, you may be depleting him even further. So I'll just let you guys know what we did. We decided to pursue Trazodone like a lot of you guys mentioned. We started at 50 milligrams. He pretty much got minimal sleep on that 50 milligram dose. So we were like, all right, well, let's go up. So we went up to 75 milligrams and then he got about four to five hours of sleep. And we were like, okay, well, that's better than the two that he was getting before. But obviously four to five hours is just not enough. So then we actually went up even further. We went to a hundred milligrams. And by that time, our nurses and therapists were telling us, wow, he's really becoming very restless during the day. And then we had also increased his Ritalin. So there were a number of things kind of contributing to what we thought could be preventing him from getting a good night of rest. So what class of drugs are you guys going to want to avoid in him as a result of knowing all this? Benzos. Yep. Very good. We want to avoid Benzos. Haldol. Yep. No antipsychotics. Yep. Yeah. So even those atypical, any sort of dopamine antagonist, like you guys are saying, the typical antipsychotics, as well as the atypical antipsychotics are what you would really just not want to have in this patient. And EQT prolonging medications, exactly. So that's just something to keep in mind, especially when you have a Parkinson's patient who has sleep issues. So want to definitely avoid those dopamine, antidopamine agents. So we decided at that point, and someone had mentioned Atarax on one of the previous slides, that we would try Atarax since the trazodone didn't seem to be doing the trick. So we actually discontinued the trazodone and we actually reduced his Ritalin. And we also reduced his dopamine. So we actually didn't seem to be doing the trick. So we actually discontinued the trazodone. And we actually reduced his Ritalin dose because we also thought that that may have been contributing. We didn't do these at the exact same time. As a lot of you know, in the TBI population, we try to do things one at a time because you may not know what may be contributing if you remove things all at the same time. So what we found is he actually did fall asleep with the lower dose of hydroxyzine, which was 25 milligrams, but he didn't really stay asleep. We were just able to get him to fall asleep for a couple hours. So what do you guys want to do next? Ramelteon, okay. So Ramelteon is one of the melatonin hypnotics we talked about, which is prescription only. Mirtazapine, yep, that's definitely an option too. Anything else anyone wants to do? Someone really wants us to start Z-Drugs. Reviewing his medication, including over-the-counter, correct. You should always be doing that when you start to, or if you have any sort of bump in the road and you're not really sure why you're not getting any results. It's always a great idea to go back through all their medications and see if there's anything that's causing any sort of changes. Someone said, I think Z-Drugs are only approved for sleep maintenance. Oh, thank you. Okay. All right. So I'll tell you guys what we did. And like I said, I just want to reiterate, there's no necessarily wrong answer. It's just everyone has a different way of pursuing this. And so this is just how we went about it. So we decided since 25 didn't do the trick, we thought maybe just giving this patient a higher dose of the hydroxyzine, 50 milligrams scheduled as well as PRN, if that would make a difference. So that actually made things worse. And so the patient didn't sleep very well at all. So we ended up just discontinuing the hydroxyzine since he tolerated the 25 milligram dose. Someone had mentioned, try to give remeltion. So that's exactly what we did. We actually did a combo. So we did a combination of the hydroxyzine plus the remeltion. And he got an amazing night of rest with that. But something we were trying to get him home to his wife. And so what is a non-clinical factor to actually consider when prescribing remeltion for patients that you definitely know are going to be going home? Pricey, yes, someone put pricey, question mark. Yes, it's actually cost. Yes, cost. So something that we don't always think about is what is the cost of our medications that we're prescribing to our patients? And so, yes, remeltion is actually extremely expensive. It's about $100 for a 30-day supply. I can tell you a majority of my patients cannot afford that. So something that's very important is that our patient, we actually had sent the prescription to the pharmacy to see if the wife would be able to get any sort of discount or something for remeltion, but we weren't actually able to lower that cost. So that really wasn't an option for the patient. So then we were kind of back to, okay, now what do we do? So hydroxyzine plus remeltion worked, but we can't send the patient home on remeltion. So what other options can we do? And this one really is, there's no right answer. Melatonin plus hydroxyzine. Okay, that's an option. Add back the melatonin. Ascirotendin, that's an option. Linesta is now affordable, okay. Atarax plus the PRN dose plus environmental modification. That's an option. Yeah, these are all great options. What we ended up doing is, we ended up, since the higher dose of hydroxyzine made the patient too restless, and remeltion was not an option, we actually decided to go in a completely separate direction. And we decided to just start gabapentin, just given the patient was having some pain. And we just wanted to kind of leverage that side effect of sedation of gabapentin to see if that would help the patient with sleep. And so this actually is ultimately what worked for the patient, is just a very low dose of gabapentin at bedtime only seemed to do the trick. So what does this tell you about TBI and sleep? Basically what this tells you is that there really is no algorithm out there for treating insomnia and TBI. So some of it is trial and error, but some of it is also going back and talking to your patient, talking to your nurses, talking to your therapist, and figuring out what the patient's sleep habits are, and what are you really targeting? Are you trying to target initiation of sleep? Are you trying to target maintenance of sleep? And then the mechanisms of all your drugs. It's very important, again, that you keep in mind, you know, your atypical dopamine agents are not gonna be good for a Parkinson's patient. And that you also keep in mind these non-clinical factors, such as cost for your patients. Because a lot of times patients will come back to you and say, I stopped taking that medicine because I couldn't afford it. And so we don't wanna be sending our patients home on medications that they can't afford. So you wanna be able to work with them and their families to find really what best works for them. Those are some of my references. If you guys have any questions, please don't hesitate to email me. My email is attached here, sima.desaih.health.org. You can also send me a tweet on Twitter. My handle is at sima, A-Desi-M-D. And I'll take any questions that you guys have at the moment. Thank you so much. This is really helpful. I'm gonna wanna go back and review some of this in the future. Kind of the drug mechanisms, like you said, are super important, but need reviewing, we'll say. Quick question. Sometimes I've found it difficult, especially in an inpatient setting, to draw a line between pathological sleep disturbances associated with the TBI itself versus just difficulty sleeping due to being in the hospital or just trauma-related stress and dealing with all the difficulties that come with new trauma and then new difficulties with life or bills I've got to pay at home and those sorts of things. How do you kind of flesh those things out? So it is hard to flesh those things out. What I do is we actually have, personally, we have a great psychologist in our system who will help us with pretty much any of our patients and kind of helping us figure out, is this more mood-related and that's why they're not sleeping? Or are they just very anxious since they're injury and that's why they're not sleeping? So it is, it's hard to flesh out. And so it takes a lot of time and usually it takes a good 45 minutes to an hour of really sitting with your patient and trying to figure out, okay, are you not sleeping because you have all these stressors going on or are you not sleeping? And a lot of times your nurses can tell you some of this information, the night nurses, because by the time you switch shift and the morning nurses come on, they don't always get all that information. So it's really important to really talk to those night nurses too and ask them, were they up all night? Were they up all night because they were rolling around in the bed or was the TV on all night? Or was their door shut? We have something here at our hospital called Cluster Care. And what it is, is they basically, my patients will not get disturbed from 10 p.m. to about 6 a.m. So for my patients who are telling me, you know, I just hate that people keep coming in and out of my room every hour on the hour and that's why I can't sleep. So then we try something as simple as what we call a cluster care. And that way, the nurse may look in the room and make sure the patient looks okay, but won't go in and get a full set of vitals. And so that sometimes is just easiest thing. And then the next morning, the patient tells you, oh, I got great sleep. So it's a little hard to decipher, but it takes a lot of kind of deep digging with your patients to figure out what it really is. And a little bit of investigative work in terms of talking to your nurses, your therapists, and anyone else who is on the unit with your acute care patients. I don't know if that answered the question well, but. It does, I appreciate it. That's really helpful. Thank you. Another question that came through was, how does this list of medications or how does your pharmacological approach change if it's a pediatric patient? So pediatric patients, everything changes. Their dosing, their medications, it's just a lot more complicated. I haven't done pediatrics in several years, so you wouldn't probably want me managing that. But what I can tell you is pediatric dosing is very different as well as management in terms of what types of dosing you would use. But the youngest patients that I get currently are 18. And so I still, I dose everything for them like a regular adult, but melatonin is still a very safe drug in terms of pediatric population-wide. But outside of that, I'm not really able to answer that question. Okay. Thank you very much. I appreciate it. That's all the questions we have right now. But we have your information up there and I think we have it here as well. Yep. Perfect. On Twitter there. So again, thank you so much. This is a fantastic lecture. For anybody who didn't get to watch the whole thing, I know I get regular comments that, I got paged and whatnot. Where do I find this? That is the website right there. Physiatry.org slash webinars. You'll find links to all of this. If you click up near the top, there's a link to all the recorded lectures. If you have any questions that came up after this, you want to reach out to Dr. Desai directly. That is her Twitter handle and then mine and AAP as well. So anything that comes up, please reach out. Dr. Desai, thank you so much. This has been fantastic. We appreciate you joining us today. Thank you so much. Like I said, if you guys have any questions, don't hesitate to reach out.

sleep disturbances

traumatic brain injuries

insomnia

hypersomnia

sleep-wake alterations

sleep-wake cycle

circuits

neurotransmitters

medications