Daniel Knoepflmacher, MD (Host): Welcome to On the Mind, the official podcast of the Weill Cornell Medicine Department of Psychiatry. I'm your host, Dr. Daniel Knoepflmacher. In each episode, I speak with experts in various aspects of psychiatry, psychotherapy, research, and other important topics on the mind.

Our topic today is delirium, an affliction of the mind that hits close to home for me. In recent years, both of my aging parents have experienced delirium. And as I record this, my 94-year-old father is still struggling with significant mental status changes that developed during a recent hospitalization. Delirium risk increases with advanced age affecting up to 50% of hospitalized older adults. More than 2.6 million of those aged 65 and older developed delirium each year in the United States, and it carries a serious prognosis with meta-analyses showing a doubling of mortality risk, significant mental and functional decline, reduced quality of life, and increased rates of hospital readmission.

We know that the longer delirium persists, the worse these outcomes become. What makes this especially troubling is how often it goes undetected. Studies show that 60% of cases go unrecognized by treating clinicians, a failure that can have severe consequences. Delirium has been targeted as a national public health concern, and yet evidence-based prevention protocols have been inconsistently implemented across the country with the majority of medical centers still lacking dedicated delirium prevention programs. As a condition occurring at the interface between psychiatry and medicine, delirium is a prime focus for consultation liaison psychiatrists working in hospitals. But I believe awareness should extend to anyone caring for older adults.

Today, I hope we can help build that awareness by exploring what delirium is, why it so often goes unrecognized, and what we can do to prevent and treat this common condition. I'm fortunate to have a gifted consultation liaison—or CL—psychiatrist with great expertise on this topic. Joining me today. Dr. Jeff Ha is the Associate Program director of Weill Cornell Medicine CL Psychiatry Fellowship Program, and someone who supervises and teaches residents rotating on the CL Psychiatry Service at Weill Cornell.

Jeff, thank you for coming on the podcast to talk about delirium with me today.

Jeff Ha, MD: Thanks for having me, Daniel. You know, delirium is such a big topic to discuss. And I'm very happy that you chose me. And I feel honored that you chose me to kind of discuss about this topic.

Host: Well, I told you it, it hits close to home for me. And you're somebody who I think of as a consummate CL psychiatrist. You're a gifted person in this field, and clearly passionate about this specialization within psychiatry. Can you share the story of how you decided to pursue a career in CL, and also specifically how you developed clinical and research interest in treating delirium?

Jeff Ha, MD: When I started psychiatry residency, I did my CL rotation. And I felt the calling.

I wanted to really fully understand all the medications that we're kind of giving our patients, and that gets into understanding the specific pharmacodynamics and understanding pharmacokinetics of these medications.

And I felt CL psychiatry, when we are giving these medications to really medically compromised patient, that we have to really understand what we are giving these medications for and why and how. So ,that kind of drew me into CL psychiatry more to kind of make me into a better psychiatrist and overall.

And the reason why I got into delirium, it is actually funny, because I went into CL Psychiatry Fellowship in Stanford right before COVID started, right? And it was 2020. I mentioned Stanford, and I was very happy about, You know, doing a lot of different projects there, but everything got shut down as soon as I started the fellowship. Thankfully enough, my mentor Dr. Jose Maldonado, he usually travels a lot because he's like the delirium guru. He's international, he travels everywhere. But because of COVID, he stayed at the hospital the whole time. So then, I got to spend a lot a time with him.

Because there were so many cOVID delirium, and like most of the ICU basically became like a COVID ICUs, and there were a lot of patients who were on ventilators, you know, with significant hyperactive delirium that were being hard to managed with the protocol that Dr. Maldonado kind of developed. So, there was a lot of experiences that I got. And it was very interesting. And I felt that the bread and butter of CL psychiatry is delirium and I get a really, really extensive training in it. Thanks to COVID, I guess. And so, that's how I came here and kind of speaking with you now.

Host: Well, it's fascinating how COVID has impacted us all. But in your case, it actually was a career inspiration for you. It kind of changed the course of what you've really focused on. And built up a lot of expertise. I want to turn to our topic, which is delirium. And, you know, it's interesting because delirious as a term, if you look it up in the dictionary and popular conversation, can also have a positive association. You know, I think of this Prince song when I was growing up, talking about being delirious because you were in love. But really, that's not the picture of delirium that we have in a medical setting. And I'm wondering if you could just provide us with a really clear definition of delirium.

Jeff Ha, MD: So, just because I'm a psychiatrist, I'll go off of the DSM-5 criteria because I feel a lot of us do have qualms with DSM, but I think it is a good place to start where everybody can speak the same language and understand what we're talking about when we're a psychiatrist, when we're talking about delirium, right?

So, the first thing is the disturbance in attention. That is the biggest and most important thing. That's why I always say our trainees or whenever, You know, speak with them in primary team is how is their attention? And we have to specifically test for the patient's attention.

Another criteria is there's an acute onset that does happen that is completely off of the patient's baseline mental status, but also with the fluctuating course. Sometimes though, it might not be fluctuating. They might actually have continuous behavior disservices services and/or confusion, right? So, this fluctuating course is there, but it is not always the case for the delirium that we see in the hospital.

Another criterion is cognitive impairment. And that could include patients with like disorientation, short-term memory deficits, as well as language or even perceptual disturbances. For example. patients are hearing hallucinations, they feel like the doctors and nurses are talking about it, or they're saying, "Oh, they were having a party the last night. And they were talking about me. And they said they're going to kill me with like a poison." There's like a paranoia there as well. But all the symptoms, there has to be an evidence that there's direct physiological consequences of a medical condition, right? So, there has to be underlying medical cause for these patients.

Having said that, sometimes these delirium symptoms will present prior to having this, you know, medical condition being diagnosed. Let's say patient with, UTI, I mean, it is like a typical example. You might not see like the foul smell of urine or pus-y urine. But then, you might actually start seeing changes in their cognition as well as attention, and like paranoia and things like that, prior to actually being diagnosed with a specific medical condition. So, delirium symptoms itself can be the initial signs.

Lastly, it is not better explained by any pre-existing neurocognitive disorder. Patients with early, you know, onset dementia or even like advanced dementia, or even patients with prior psychiatric histories. You know, let's say patients with schizophrenia or bipolar disorders. The acute symptoms that we are seeing right now cannot be fully explained by the preexisting conditions of those. Having said that, you know, as you mentioned earlier in the introduction, patients with prior psychiatric history or patients with prior neurocognitive disorder, for example, are a lot at higher risk to develop delirium.

Daniel Knoepflmacher, MD: So, that's a distinction. I mean, obviously, there's an underlying condition which puts them at higher risk, but you're this acuteness this change from baseline is really core to the diagnosis, because I've seen that sometimes with consults where it's like, "Oh, This is schizophrenia." It's like, "Well, This is not what this person who has schizophrenia looks like or looked like a week ago."

Jeff Ha, MD: That's correct. That's why it is very important for us to get a good collateral, and understanding of what the patient's baseline cognitive function is.

Daniel Knoepflmacher, MD: One question I want to ask you about is attention, because that's a very important piece. It is the first thing you mentioned. I imagine that when you're consulting for teams, attention isn't something that someone—especially someone who's not a psychiatrist, who's always paying attention to. How do you advise clinical teams to think about looking for inattention or attention changes?

Jeff Ha, MD: So, the best—I feel the best test is like the months of the year backward, because it is hard enough, but also not too easy, if that kind of makes sense, right? For example, there are multiple attention tests—months of the yea backward, days of the week backward, series of seven, things like that. But for example, days of the week backward could be pretty easy. You know, patients who might have inattention is going to be able to do that. But sometimes the arithmetic one—I have had a bad sleep, sometimes I can't do seven, negative seven sometimes, right? But months of the year backward, everybody uses it. Everybody uses the months, everybody knows the months. But then, it is hard. You'll see patients who get days of week backward really well, when you ask them to do months of the year backward, it becomes a bit difficult. And, you know, we're not using this to say that, "Oh, look, we found you, but we can also actually use this to understand what the baseline attention is." And if they're able to do, you know, months of the year backward until June yesterday, and like today, they can only do like up till October, then you know the deliriums getting a little bit worse. Or sometimes, the patients get better and they're able to do months of the year backward really fast and, you know, really good.

But having said that, all of this is just like a tool that we use to assess for attention, right? And they're not perfect because everyone's neurocognitive baseline is different. And that's also to kind of keep in mind when you're seeing the patient. Just because, if their brain is wired to be able to do really good test-oriented things and, you know, attention is easy thing to do, or counting backward is easy thing to do, then they're going to be able to do it even though they might be fully inattentive.

So overall, clinical pictures as well of when you're doing an interview with the patient. For example, if they are kind of going in and out of different topics and kind of not being able to fully be with you when you're doing an interview, then they could also be counted towards inattention. Because you'll also see a lot of times—sorry, I'm being sidetracked a little bit—but specifically about attention-wise or any type of specific tests that we're trying to do, you know, you'll see patients who know that they can't do these tasks, they will say that I don't want to do. So, that's also something to keep in mind when you're, you know, talking with or trying to assess these patients.

Daniel Knoepflmacher, MD: Well, let's look at this. You're walking into a room and you're assessing someone. I know that there's a lot of variation, but can you give us a picture? The DSM, in this case, sounds like it has a very helpful set of criteria. But what are you seeing clinically, the way that delirium is presenting in the room?

Jeff Ha, MD: Yeah. So, the way the delirium presents, just like in any psychiatric illnesses, it presents because of wide spectrum, right? Just kind of giving an example, patients who might have mild depression to moderate to severe or severe with psychotic features, they're all on the gradient, right? And the patients who are suffering from delirium are also all on the gradient.

So on the one hand, we can have a severely hypoactive delirious patient, right? The patient is withdrawn, minimal and responsive. And sometimes, you know, we get consult for these, the patients catatonic because they're so withdrawn and suffering from hypoactive delirium. On the other hand, you know, patients that when we think about delirium—because we get consults for these cases a lot—is hyperactive delirium, which you'll see. And you don't sometimes even need to go into the room to be able to tell. Because you'll also be hearing, you know, screaming, yelling. You know, patients sometimes are under restraints. You know, they are very angry and also scared. They probably are very paranoid at times as well. So, those are more of a hyperactive of cases. And I try to distinguish between them two because, as I said, we are consulted and we recognize hyperactive delirium pretty easily. We don't have to be a psychiatrist or anybody to just kind of say, "Oh, the patient is pretty hyperactive and delirious."

But studies found that actually 75% of the patients who are suffering from delirium or suffering from hypoactive delirium. And, as you mentioned, a lot of the misdiagnosis or we're missing the delirium, it comes from patients who are hypoactive. Because these patients who are hypoactive deliriants are not going to really, you know, fight, for example, when you're trying to give medications. They're not going to say mean things to the providers or try to swing at them, because, you know, they are more hypoactive deliriants, right? So, those are some of the two symptomatology that we'll see when we go see the patient. And it could be all in the gradient.

And another thing is that this could be a mixed delirium. So for example, a patient at nighttime can be super, super, you know, psychomotorally agitated. But then, during the morning and daytime, they're very subdued, they're very subtle. So, that's also another you know, phenomenonology that we'll see.

Host: And what do we understand about the underlying neurobiology? What's going on in the brain that causes all of these symptoms that you're describing and these changes in mental status?

Jeff Ha, MD: Yeah. So, the widely accepted common denominator of this neurotransmitter theory is the cholinergic deficiency. So, that's why we are recommending not to use anticholinergic medications to our, you know, medicine or primary teams like including Benadryls or even sometimes, you know, hydroxyzine, and things like that.

But I think there are other neurotransmitters that are actually involved as well, for example, excess dopamine. And that might be able to explain why the patients are having the psychotic symptoms. Patients might have excess norepinephrine drive, because they're in this flight and fight mode in a way, as well as excess glutamate within their brain, given the fact that they're in more of this excited tone, right?

And another things along with like melatonin deficiency. And this is one of the neurotransmitter that we kind of forget about, because it is really crucial, in terms of regulating circadian rhythm, that helps with the sleep-wake cycle. But important thing to note is there's no single neurotransmitter pattern that underlies. All delirium is very multimechanistic. And hence, you know, we can discuss a little bit about the symptom management of delirium a little bit later in the episode. But there isn't like a one medication that I would prefer, you know, one versus the other. It's all very clinically dependent.

Host: Although, for the anticholinergics, we definitely know. I mean, that's one that you definitely will not favor in this case.

Jeff Ha, MD: Yes, that's right, that's right. The anticholinergic medications, we would definitely try to avoid it as much as possible with medications who have significant antcholigernic property.

Host: And can you just name a few? I mean, what you mentioned, Benadryl, hydroxyzine, which are things that we sometimes use to calm people down or to help them sleep. But obviously, our own antidepressants and other medications can have anticholinergic properties. So, what are some of the ones that you always are flagging for providers?

Jeff Ha, MD: One example can be TCAs, you know, patients with—

Daniel Knoepflmacher, MD: Tricyclics.

Jeff Ha, MD: Sorry, tricylic antidepressants like amitriptyline, for example, is significantly anticholinergic. I believe Paxil is also somewhat anticholinergic as well. And I just have to kind of talk about benzodiazepines here. The reason why we try to avoid benzodiazepine is because overall it decreases the cholinergic tone of patients, within the brain. So, we want to try to avoid benzodiazepine as well.

Having said that, so there's always caveat to—that's why I never say I never use a specific medication, right? Because sometimes in the patients, for example, the patients was delirious in setting of benzo withdrawal. And we are trying to do everything to minimize benzodiazepine, but sometimes we have to use them to help the patient be out of the delirious state.

Another medication that I try to take away is benztropine. You know, a lot of patients are on benztropine. because of sometimes like a prophylaxis or for EPS and things like that. But you'll see patients who come in who have been on this benztropine forever who are on antipsychotic medications that doesn't cause too much EPS. And so, when I see that, I try to also take away the patient that's clearly delirious and kind of see for any emergence of another EPS. Now, if that's the case, then we will, you know, resume the anticholinergic medication such as benztropine. But, you know, it's always important to kind of keep in mind whenever we get consulted for delirium, we review the medication list that the patient is on to avoid worsening of anticholinergic tone the patient is already on.

 Another thing to actually think about other than neurotransmitter is there are more and more studies that are coming out that are indicating that there is a network level failure within the brain when the patients are delirious. For example, the default mode network and the salience network appears to be particularly affected.

The salience network specifically are normally acts as a switch, directing attention between the resting default mode network to task-focused states, but it seems to be disrupted in specific nodes. And, you know, when you start using the regulatory capacity, patients will start having inattention as well as fluctuating mental status.

Host: And you think that this is related to some inflammatory state or some kind of imbalance just more generally in the system?

Jeff Ha, MD: Yeah. There are studies that indicate that it could be due to inflammation within the brain as well. And so, it could be symptoms of all the delirium. It's like a chicken and the egg type of situation. Delirium itself can also cause inflammation, or it could be the inflammation markers that are causing patients to have disturbances within the brain.

Host: Well, Jeff, just to quickly—because I know you could probably talk for 45 minutes about this—but quickly give an overview of the psychopharm options that you think about when you're dealing with patients who are suffering from delirium.

Jeff Ha, MD: Yes. So as I briefly mentioned in the previous answer. So, first could be antipsychotic medications. And the patients who are showing some psychotic symptoms such as hallucinations and paranoid ideations, I would like to start with Haldol first. And Haldol has this bad rep of causing prolonged QTc out of the antipsychotics, but more and more studies are indicating that's not the case. If you are worried about QTc prolongation, you shouldn't be using any antipsychotics whatsoever. So, haloperidol is my go-to because as I mentioned before, it is one of the least anticholinergic antipsychotics. We use Zyprexa quite a bit in our setting. But Zyprexa is a very anticholinergic medication. So, I try to avoid that if we can.

Another antipsychotic that I use is quetiapine. Sometimes I also do use risperdal, especially in patients who we think that might have some type of dementia with behavior disturbances if at a baseline, we might have to think about using that as ongoing symptomatic management, even after a patient gets discharged. With the black box warning, of course, we have to say that, right? And if the patients are showing more of agitations, things like that, without too much psychotic symptoms, I do tend to use valporic acid quite often. It is to kind of reduce the hyperglutamatergic tone that we kind of discussed. And if the liver function is not doing too well, I sometimes use gabapentinoids like such as pregabalin and gabapentin. Now, it's not using GABA. It's not GABAergic medication. It actually reduces the glutamate release from the presynaptic neurons of the glutamatergic presynaptic neurons. So, you know, we shouldn't be confused with that, with the gabapentin, pregabalin versus, for example, lorazepam, right? So, I use gabapentin pregabalin quite a bit.

Another medication that I like to use is guanfacine, especially in patients who are showing more of the flight and fight type of symptoms, agitations, anxiety and things like that. We definitely use that especially in the patients who we try to come off of Precedex, for example, because they share the same mechanism of action as an alpha-2 agonist.

Daniel Knoepflmacher, MD: Well, let's turn to the impact of delirium. I mentioned some severe kind of outcomes in my introduction. Could you speak about what the morbidity and mortality is that results from delirium?

Jeff Ha, MD: Yeah. So, this is why hospital administrations and hospitals should really pay attention to patients who are suffer from delirium because, you know, in one study in 2018 showed that the hospital mortality of just 33% for hypoactive delirious patients. And sometimes 15% for hyperactive. Now, that kind of tells us, again, hypoactive delirious patients are at increased risk for mortality. And even in the ICU setting, for example, in 2021 prospective studies showed that hypoactive delirium was associated with about three times fold of increased risk of death the following day. While the hyperactive delirium was not significantly associated with that in hospital mortality. Now, having said that, that's not, you know, changing the fact that the hyperactive delirium, any patients are suffering from delirium will have a much, much higher mortality and morbidity rate, as you mentioned earlier in the podcast.

Host: So is most of that increased mortality for hypoactive because they're less obvious in the hospital, or is it because of the actual impact biologically that is, you know, represented by hypoactive delirium.

Jeff Ha, MD: I think it's both. So, patients who are more critically ill, who are really, really ill, they might not even have energy to be hyperactively delirious, right? Or it could be that, you know, they get missed and we just continue to give medications that might be making them more delirious and just be hypoactively delirious. So, it could be both.

Host: What's the time course? I mean, this is on my mind having a family member who's dealing with this. Once you've gotten, you know, to deal with the underlying problem, which we'll talk a little bit more about what those are, when do you expect people to show signs of improvement in how much over what period of time?

Jeff Ha, MD: It is a tricky question because I get asked this question a lot by both the primary team as well as our loved ones and the family members, because it's very hard to see your loved ones kind of go through this and I want to take this moment to say, you know, you're going through quite a bit, so, you know, hang in there.

Host: Thank you. And you can tell what's motivating the question. Obviously it's a selfish here. But, yeah, no, thanks.

thanks

Jeff Ha, MD: no. It is not selfish at all. It is a very, very important question because we think that, oh, once the medical condition has been resolved, the patients are going to be great. They are now going to be delirium-free, but that's not really the case. Studies found as well as, you know, my anecdotal experience and, You know, personal experience shows that that's not the case. That's just simply not true. Delirium is not simply transient. And it may not be self-limited. For example, in hospitalized patients, you know, delirium typically lasts about one week. That's just typically. However, 45% of the geriatric patients still meets criteria even at the discharge. And roughly, about 21% still have persistent symptoms at six months.

Now, in patients with underlying dementia, so patients who already have diagnosis of dementia, the outcomes are a little bit worse. Only 6% achieve full recovery, even at one month follow-up compared to 14% in those without dementia. So, you know, whenever I answer this question, I always say I hate answering this question because I say it really depends on how well the patient has been doing prior to coming in, what their functional status is, as well as how sick they were or they are, and also what the aftercare, what the prolonged course is going to look like. And so, I can't really fully give a specific timeline. But I'll say—this is like in my generic answer—the average is about one week. However, things can continue to be persistent, even the patient might be discharged from the hospital.

Host: What are the risk factors for delirium?

Jeff Ha, MD: I mean, it is very multifactorial. But as I just mentioned in part of my prior answer, the strongest and most consistent risk factor is dementia, as well as preexisting cognitive impairment. Beyond that, sometimes like advanced age; functional impairments, for example, patients with vision or hearing loss or patients who are frail or have also decreased physical mobility are at higher risk of delirium, high comorbid burden, or even patients with substance use history and prior psychiatric history that I mentioned. They're all, you know, risk factors for delirium.

Host: So beyond the risk factors, this is a condition, unlike other psychiatric conditions that we're treating as primary psychiatric conditions. This is a condition that's caused by medical problems. So, what are the medical causes that are most typical for delirium?

Jeff Ha, MD: Any medical causes that might indicate like inpatient hospitalization, for example? because patients who are hospitalized have higher risk of developing delirium itself, right? So in patients with, you know, UTI, for example can develop delirium, pneumonia can develop deliirium. Any type of acute insults to their organs, any, you know, liver issues, kidney issues, lung issues, including I just mentioned pneumonia, but patients who are in ICU settings, like for ARDS, patients who are becoming encephalopathic in the setting of hepatic encephalopathy, and uremia due to their, you know, kidney function's not working that well. They are all, you know, at high-risk for delirium.

Daniel Knoepflmacher, MD: You had mentioned earlier, you know that withdrawal is something—

Jeff Ha, MD: Oh yes. The substance withdrawals are big, big factors in patients who are suffering from delirium. Because a lot of times you'll see that the patients who are—again, this is why it's so multifactorial. Patients who are probably already going through withdrawal, they might also have a significant medical complication. And that kind of complicates things much farther in terms of how to manage delirium.

Host: When you're assessing someone for delirium during a consult, what are the other diagnoses that you keep in mind? You talked about the DSM criteria and how, you know, it can't be something else if it meets the criteria. So, are there conditions that you want to be on the lookout for that could be mistaken for delirium or even things that might be missed, because there's delirium that would hide those other conditions?

Jeff Ha, MD: Yeah, I think for hyperactive delirium, it could be obvious that like the patients might appear psychotic with a conservative primary psychosis, or patients might have like a manic episode in patients with bipolar disorder. But actually, a lot of times in the hypoactively delirious patient, we don't really get consulted for a consult for hypoactive delirium, but it's actually consult for either depression or sometimes suicidal ideation because, you know, there's a lot of data that shows the patients report suicidal ideation during their hypoactive delirious episodes, and they don't remember once they're out of that state. So, you know, those are some of the things that I always keep in mind.

Another thing I did mention is catatonia, right? The patients who are very hyperactively delirious may appear catatonic. And if you actually score Bush-Francis on this, you know, hypoactively delirious patients, it's going to be really, really high. And so, it's very important to kind of distinguish them. But sometimes, we have to understand, you know, patients who are catatonic might also be delirious as well. And that it is not just mutually exclusive things, because catatonia itself is just a constellation of symptoms, right? That you kind of see what's, you know, happening, but there's always an underlying cause of it. So, can we say patients are catatonic in setting of hypoactively delirious? Maybe. But this is always to kind of keep in mind, especially when the patient has primary psychiatric illnesses that might be indicative of developing catatonia.

Host: You brought up the suicidal ideation and how that can sometimes elicit a consult, and then you discover someone has hypoactively delirium. I'm curious how you treat that kind of SI as a consultation liaison psychiatrist. Is it just the same safety protocols and all of that as if somebody else had expressed suicidal ideation? Is it different? And is there actually, like a higher incidence of suicide associated with delirium?

Jeff Ha, MD: So, I think patients who suffer from, let's just talk about, from acutely as well as kind of chronically. So, patients who are suffering acute hypoactive delirium, and is reporting suicidal ideation. And when we go see the patient, a lot of times, they are going back and forth with the suicidality or depression. Sometimes they wax and wane. And in those cases, I would just, you know, recommend more of like a safety watch more so than like a suicide watch one-to-one and things like that because, you know, they might be more confused, they might be more impulsive and things like that.

But, you know, there will be some times where it's kind of iffy where patients do have history of depressive disorder or do have history of suicide attempts. And when you are assessing the patient, you know, they're kind of saying all the suicidal things. So sometimes they have to, you know, implement suicide watch and, you know, follow the exact same protocol that we have for patients that are at acute risk.

I don't know if there has been like a specific study that has been done in patients who had an acute hypoactive delirium with like a suicide event that happened within the hospital setting. However, there are multiple studies that shows that patients who are suffering from delirium, you know, might develop worsening of functioning once they leave from the hospital. And that could lead to increased risk of suicide in patients. So, I don't know if it's a direct like causation, but there could definitely be a correlation, if you kind of look at it more chronically, about what hypoactive delirium can cause.

But, in terms of how to treat them, again, depending on how the patient is appearing, we might implement either safety watch or suicide watch. And sometimes, we might give a little bit of like aripiprazole, like a low-dose aripiprazole to kind of help with partial dopamine agonism to see, because there has been some study that indicates that Abilify does help with hypoactive delirium or sometimes we give a little bit of a stimulant as well to kind of wake them up in the morning. And once their medical does clear up, and they're better, and when you ask them, "Hey, do you remember me?" They're like, "No, who are you?" "And you told me that you wanted to end your life." And it's like, "I'll never say that." So, most of the cases comes that way, but it's a case by case as well. Because there are some times where patients are actually suicidal and their depressed mood kind of enhances when they're, you know, hypoactively delirious. And once they're out of delirium, they're still saying they will still want to end their life because their life is miserable, their, health condition is not great, then, you know, you have to continue with suicide watch and follow the protocol.

Daniel Knoepflmacher, MD: Nuance is very important in this, obviously in everything you've discussed today. There's no one-size-fits-all. Another area of complexity when we think about all psychiatric care is cultural, cultural factors and how they play into the diagnosis and treatment. I'm curious, has there been research that looks at how healthcare disparities impact those diagnosed with delirium in the hospital?

Jeff Ha, MD: Yes. I think this are important and under-recognized issues. I think there was actually in a large 2025 study that was done, over 260,000 hospitalized older adults. And in that study, non-Hispanic black patients had about 49% higher odds of delirium present on admission and 39% higher odds of hospital-acquired delirium as well. Hispanic patient had about 31% and as well as 28% higher odds respectively.

It could be due to the fact, as we all know, that there is significant factors of socioeconomic disparities in general wellbeing and health of patients, right? So, patients could be a lot more complex when the patients are already coming into the hospital. And the increased medical complication can increase the risk of delirium as well.

Interestingly, there was a recent trauma surgery study that actually found lower documented delirium rates in Hispanic patients. But the concern is actually through lower incidences, it likely actually reflected underdiagnosis due to language barriers or implicit biases. And that distinction matters, you know, importantly clinically and research-wise.

Host: These kind of disparities impact every aspect of treatment in psychiatry and medicine. So, it's not surprising to hear how they applied in delirium as well. I want to turn to treatment. You've touched a bit on some areas of treatment, but let's dive in a little more closely into that.

You talked about how the treatment, the primary treatment is addressing effectively the underlying medical issues. What recommendations do you provide when you're consulted by a primary team to help them take care of a patient?

Jeff Ha, MD: So, I always start with making sure that our nursing colleagues are also involved in communication, especially for these patients. Because our primary team will place the order in, but then, actually, the nurses, nursing colleagues are the ones who are actually, you know, carrying them out in a way. And they are the ones who actually hands on, you know, taking care of the patients a lot of times.

So, you know, whenever there is a complex patient, I always speak directly to the nurse, who is actually taking care of the patient primarily to kind of help them guide through this. This should be done for any patients who are in the hospital, who are at even risk for delirium or who are suffering from delirium as far as we have to make sure they ask for frequent reorientation. Whenever we go in, we tell them, "This is what I always do," introduce myself, tell them the date, they're here at Weill Cornell Hospital for this specific reasons. Of course, if I want to assess for a patient orientation, things like that, then I would kind of hold that back. But for our nursing colleagues who are taking care of patients all the time, it is important for them to kind of reorient the patient all the time. Every time they go in, to speak with them.

Another thing is I would recommend to really protect the patient's sleep-wake cycle. For example, I don't know if anyone—I'm sure some folks have been in hospital setting and they were admitted, just even overnight or a day or two. It is really hard to sleep. It is so hard to sleep. And we know that sleep-wake cycle, it could be one of the symptoms of delirium. But disturbance of sleep-wake cycle can also be the precipitate of hyperactive delirious episodes and things like that. So, I always kind of speak with the primary team as well as our nursing colleagues. Like, 'Hey, do we really have to do vital sign checks on this lady overnight who is otherwise medically stable, but is having, this, you know, bouts of nocturnal behavioral agitations? Do you think maybe we should try to give medication a bit earlier during the daytime. You don't have to give atorvastatin at like 10:00 PM. You can just, you know, put it in the morning or even give it a little bit earlier or on like 7:00 PM," things like that. So, making sure that we can do everything that we can do to protect our sleep-wake cycle by minimizing unnecessary nighttime interruptions, of course, within the bounds of safe clinical treatment.

The other thing that I recommend is early mobilization. You know, get the physical therapist involved right away as soon as possible. It's sad that we can't really show a picture here, but, you know, in patients who are like on ECMO machines, for example, you know, from ICU and we get them up and we walk them around. There is no reason why if the patients are physically able to, the patients should stay in the bed, right? And I recommend them, even during the daytime, try to see if they can make the bed into more of a chair position because the patients themself, even engaging the core as they're kind of sitting up in the bed, actually activates the brain, right? And that can actually help reduce delirium. And if the patient is strong enough and is safe enough to be out of bed and in the chair, as soon as possible, that is really, really crucial, and that's really, really important.

Making sure that patients with hearing impairment or any type of sensory impairment, that they do have their glasses and the hearing aids, because that itself can actually help patients with preventing from having more episodes of delirium.

And lastly, I would review the chart and the medication list and to see if there's anything that we can reduce or eliminate any deliriogenic medications. So for example, like anticholinergic medications and I didn't really talk about too much in the prior ones, but for example, opioids can also be a significant cause of delirium. We think about anticholinergic medications and benzodiazepines, because we know that it does cause delirium and we always kind of hone in on that. But actually, studies found opioids are the most significant culprit of causing delirium. And it's kind of difficult because we know the pain itself can be precipitate of delirium, right? So, managing pain is very important, but trying to manage pain with the least amount of opioid use possible with addition of different medications to reduce the pain for patients, that is also very, very important.

Daniel Knoepflmacher, MD: When I listen to you discuss all of this, and I think about the fact, as we talked about earlier, that this is a public health issue. It's a hospital quality of care issue. Why isn't it protocolized in the way that we have protocols for sepsis or other things? I mean, these are steps that could be taken for patients both to prevent delirium and to help recover from delirium. Do you know, I mean, within CL why this hasn't been adopted more widely or what's going on in terms of these kinds of protocols?

Jeff Ha, MD: Yeah. So, I think there are a lot of implementations that has been tried in the past. And we are actually trying to do something right now as well. But when we do like a lot of implementations, for example, I think our nursing colleagues, they have so many things to click, even for like an Epic. Whenever a patient gets admitted, it becomes like an, "Oh, I think it's a screen tire" or something like that alert tiredness or something. So, you know, we want to try to come up with the most effective tool that kind of takes away burden away from, you know, folks who are caring for the patients in the front line as well. So, that's very important.

But having said that, I think we are trying to, you know, come up with a specific delirium protocol here at Cornell. And hopefully, that gets implemented better. And it's not just like a one person can say, "Oh, we're going to go with this protocol and everybody should do it," because it is buy-in from a lot of different, you know, multidisciplinary team action.

Host: You're bringing nuance to that answer to that question as well, because you're right, it's complicated and you could actually burden the nurses and the teams that are having to do this if it's not done thoughtfully. And with all that variation, one-size-fits-all protocol isn't going to work for every case of delirium. So, that makes sense. We talked earlier about how the time course for this is indeterminate. And the underlying problems for the delirium can persist. Often, there's agitation, there's things that can be harmful for the patient or for staff. How do you deal with those kinds of aspects of delirium? And just more generally, what are the ways that you treat delirium other than addressing what the underlying cause is?

Jeff Ha, MD: The answer, again is, it is going to be a nuanced answer. There's no single right answer. You know, partly because the comorbidities often limits our medication options that we have, right? For example, like the antipsychotics, you know, patients with QTc prolongations might be difficult. We work off of our neurotransmitter framework that we created that I kind of discussed before. For example, for hyperdopaminergic states, the patients who are in acute psychotic state, we do use antipsychotics. But for patients who are in excess glutamate state, you know, we can use either valporic acid or gabapentinoids or in patients who might have excess norepinephrine state that we can see and we can actually use the alpha-2 agonist, such as guanfacine or, you know, dexmedetomidine in the ICU setting.

Having said that, you know, these medications are not treatment of delirium. You know, treatment of delirium is treating the underlying medical illness. These are more used for symptomatic management. And we usually use this in the patients who are, as you mentioned in this question, our patients are agitated and can acutely harm themselves or others including nursing staff or even our medical staff.

Host: You specifically have extensive experience with delirium in the ICU. Can you speak about why the ICU is a special environment when it comes to the prevalence of delirium. And what are some of the specific ways it can be treated there?

Jeff Ha, MD: Yeah, I mean, you know, the ICU patients are like the sickest patients in the hospital, right? You don't, you know, just buy yourself way into the ICU. It is reserved for patients who are sickest of the sickest. And when patients are at increased medical comorbidity, their delirium risk goes high. And some studies report the rate as high as 83% in patients who are in ICU, right? And the consequences are significant, right? The delirium can prolong mechanical ventilation, for example, by interfering with the ability to wean sedation with the patients are on sedative drips.

And team often has like struggles to deescalate this sedative drips such as propofol or dexmedetomidine drips, when patients are delirious because they're not able to really fully follow the commands, they sometimes overbreathe the ventilator settings. So, it's kind of hard to take them out. And we know the longer the patients are intubated, the longer the patients are in the ICU, the morbidity and mortality kind of increases. So, we want to try to help bridge that gap with, you know, targeted psychotropics to facilitate extubation and shortening the ICU stays.

Host: Given that it's so prevalent in the ICU and the ICU is this intensive environment, what is the long lasting psychological impact of delirium on those who recover?

Jeff Ha, MD: So, there are multiple domains of lasting impact of delirium on patients who are trying to recover from their recent medical illness. First could be psychological impact, as well as physical impact and cognitive impact, right? I'll just kind of sum it up kind of describing the post intensive care syndrome, for example, because patients who are in the ICU settings, who have developed delirium, they are suffering from everything that we kind of mentioned with physical, cognitive and mental health sequelae that even persists after ICU discharge.

So, for example, psychiatrically, patients, you know, suffer significantly from depression, anxiety, as well as PTSD. And PTSD actually rates from about 19-22% in general ICU survivors. And about up to 44% in ARDS survivors, this acute respiratory distress syndrome and patients usually get intubated in the ICU setting. And you can imagine that could actually be very detrimental to their recovery, because the thing about PTSD is the patients who are suffering from PTSD symptoms will try to avoid anything that would remind them of their trauma. And they don't want to go into the hospital setting. They don't want to go get the treatment, because it kind of brings up the flashback memories of the delirious episodes that they might have had, or even unpleasant episodes that they had, meaning they're awake and they're intubated, and things like that.

So, these are very, very important things to consider because it affects the trajectory of the patient's overall improving healthcare, right? And so, a lot of PICS clinics are actually being established in academic centers to address this longitudinally. And this, I do believe, is where psychiatry has a specific real role in it. And there are more and more of my colleagues in CL psychiatry who are kind of more specializing in the post ICU clinics to kind of address the long lasting impact of psychological impact of delirium.

Host: Well, as a CL psychiatrist, you're helping the patient, you're really supporting the team. But I know that you interact a lot with the families of the patients. I'm curious about the conversations that you typically have with them about delirium and what are the best ways to support them through all of this.

Jeff Ha, MD: I think more so than the patients themselves, a lot of times the families are really significantly distressed because they see their loved ones suffering so much from this acute change in their mental status, whether that be, you know, having hallucinations or their, you know, loved ones are paranoid or have never been agitated at their entire life. But then, they are like throwing everything at, you know, nurses that were meant for family members. So, it's very important to kind of give support to family.

And there are three things that I always do, right? The first is education. Second is reassurance. Third is empowerment, okay? Because if we actually are able to explain what delirium is and set realistic expectation about the timeline that we actually talked about, it kind of gives them more of something to kind of hold onto, right? To kind of have an understanding of, okay, for example, this is not my parents going psychotic or things like that. It's just, you know, part of the delirium. And I always tell them about the 75% of patients who are suffering from delirium and things like that. So, it kind of helps them understand where the patient is. But also, it's very important to acknowledge the emotional toll it takes on the family members. Because a lot of times after, you know, when I kind of describe, "Hey, you guys are kind of suffering quite a bit" and, you know, most folks kind of just say that, "Oh, thank you so much for actually acknowledging that because yes, we are."

And that actually helps because, for me and for the primary team, it's very important to family to be engaged and to be involved, because a familiar face as well as voice can be much more meaningfully helpful than Haldol or Depakote or PRN of things like that because that really helps reduce the symptoms of delirium because they trust the family a lot more than doctors and nurses who were messed up coming in different times for period of time. So, it is very important to kind of address all three—education, reassurance as well as empowerment—for our family members.

Host: Thank you, Jeff. I thank you for all of what you talked about today. I want to finish with one question for you. You are a CL psychiatrist who works with all of those people we mentioned, but also residents and medical students. When you're talking to people about delirium, what are the few basic facts, the take-home points that you wish everyone knew?

Jeff Ha, MD: So, the theme of this this episode, it is very nuanced. When we think about delirium, we just think about as hyperactively delirious patients who are, you know, really, really, suffering from psychosis or even like manic symptoms. But it's not that, right? Again, 75% of the patients are suffering from mostly sometimes hypoactively delirium. And there are a lot of different ways to approach patients who are suffering from delirium and understand that this acute state that we are seeing right now can actually be a very significant burden to the patient, even though they "recover" from the medical illness, as well as to family members.

So, we're not just seeing this patient episodically to kind of give them PRN, as needed medication or like antipsychotic medication. But you have to kind of always take a step back to kind of understand and look at the whole picture of who this patient is, and to find the best ways to have the patient be back to their normal baseline, whether that would be cognitively, physically, as well as psychologically.

Host: You said it, you summed it all up well, Jeff. I really appreciate you joining me today to speak about delirium. You gave me and everybody who's listening a really detailed picture of what this condition looks like, what we need to do when we are confronting it. And I hope that it helped those who listen gain a better understanding of this topic because as we've said over and over again, this is very common. It's not always understood and it's often missed. So, I hope we've helped dispel some of that just by talking about it with each other today. So, thank you so much, Jeff.

Jeff Ha, MD: Thanks for having me.

Host: Thank you to all who listen today to Jeff and I speak about this topic here on this podcast, On The Mind. We are the official podcast of the Weill Cornell Medicine Department of Psychiatry. Our podcast is available on all of the major audio streaming platforms. And if you like what you heard, please give us a rating. I think we could use more ratings out there on Spotify, on Apple podcasts, YouTube, wherever. Wherever you're listening, please give us a rating and hopefully because you enjoyed it, you're giving us a five-star rating. And then, if you subscribe, you'll stay up-to-date with all of our latest episodes. And you can also tell your friends, so they'll come and listen as well. We'll be back again next month with another episode. Until then, wishing you good health in body and mind.

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