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Antipsychotics have been a hot topic in the ICU. Do they treat delirium? Can they be used to replace continuous sedation? When and how can we utilize antipsychotics to optimize care and outcomes? Dr. Marie Rueve from episode 160 joins us again to clear the air on antipsychotics in the ICU.

 

Episode Transcription

Kali Dayton 0:05
This episode I’m bringing Dr. Rueve from Episode 160 to talk about the big controversy over anti-psychotics in the ICU. Dr. Rueve, thank you so much for coming back on the podcast. You were on our podcast a couple of episodes ago. And there was just so much more to talk about, especially to learn from with you. Do you mind introducing yourself again to us?

Dr. Marie Rueve 2:31
Yes, happy to thank you for having me back. So my name is Marie revie and I’m a consults psychiatrist at a hospital in Ohio. We have about a 24 bed, medical ICU as well as about a 12 bed surgical ICU that we cover. And I try to help the ICU team as much as possible with everything ICU, collaborative, liberation implemention.

Kali Dayton 2:57
And I wanted to ask a little bit of a follow up from our last episode because we talked about psychiatrists in the ICU. I have been working with a trauma ICU that has a lot of need for site inpatient psych support. And they just have said that they do not have it that psychiatrists will come by and say, Well, let me know when they’re extubated. And and walk away. What advice before we move on to our next topic, but what advice would you give to an ICU that’s not feeling like they have a good psych support?

Dr. Marie Rueve 3:33
Yeah, that’s really a tough one. And I’m sure that’s the case. And a lot of places, like I said, we’re trying to educate psychiatrists actually, about how they can be more helpful in the ICU, even you know, whether or not the patient can talk and trying to put out some educational materials for psychiatrists in that regard. That’s a, that’s a tough one, they would have to, you know, we could consider maybe linking to this episode or something, some basic resources on psychopharmacology, things like that I can refer to, you know, we could give it I’m expecting an article to come out in psychiatric times.

Pretty soon that I was an author of several authors on that’s describing how psychiatrists can be helpful in the ICU for a psychiatry readership. Maybe they could pass that along to their psychiatry colleagues. Something like that. Yeah, to try to get the word out more than that psychiatrists can be helpful because that is a barrier.

Maybe also kind of like trying to be real specific about the question that they want answered, maybe acknowledging that to the psychiatrists that they’re asking to help them, you know, like, yeah, no, I, I know they can’t talk and all that, but can you at least sort of take a look at their medications and see if, if you could be helpful with agitation or they’re withdrawing from this substance? You know, maybe trying to be as specific as possible would help the psychiatrist, see if there’s something they could do, despite not being able to do like a standard interview, okay, perfect. And

Kali Dayton 5:03
We’ll link into the past episode with you into this episode, all citations that you’re willing to share that they could pass on to their psychiatrist. Okay. Now this episode, I wanted to really pick your brain about your thoughts and the research behind anti-psychotics in the ICU because this has been a hot topic. I’ve used them sparsely. I think they do have a place in the ICU. I’ve also seen teams using them almost to replace continuous sedation.

I’ve heard I’ve seen off Seroquel, 200, BID, TID, with the objective to keep them comatose. So we’ve had conflicting research come out about anti-psychotics. And so there’s been a lot in the delirium world in the critical care world about don’t use them use them. Let’s clear the air. What are your thoughts?

Dr. Marie Rueve 5:56
So I think anti-psychotics are vastly misunderstood. And you know, the intensivist that I work with will actually say that they really appreciate my help, because they don’t know a whole lot about antipsychotics. And that’s a little bit like what we talked about last time that everything’s so siloed anymore. You know, I could say to the intensivist, well, I know a little bit about breathing treatments, like albuterol is one of them. Right. But I certainly don’t know, the panoply of different things we give, we give people to help their lungs out.

And similarly, I think it’s helpful, like we were just discussing to have somebody a little more familiar with antipsychotics, because they do you have some differences between all of them, they do have some different roles, we do have to watch out for some side effects and things like that. So it can, they can be a little tricky, but overall, especially when we’re comparing them to, you know, continuous sedative infusion, like we talked about last time, their side effect profile is just much, much preferred.

And I find in talking to nurses, other physicians, and of course, patients who take them that a lot of their fears about antipsychotics are really coming from their own beliefs, or myths, or something along those lines, and not from the actual understanding of the pharmacology of the medicines themselves. So anti psychotics have been around for a long, long time held all is the prototypical anti psychotic, it’s been around since like 1954, or something like that.

So we have a ton of experience with Haldol, in all kinds of settings, including it being the most common one used for delirium. And I think a lot of that has to do with how doll being really the only one available in IV formulation. And so that makes it extremely convenient to use in this population, right. But they’re, again, like hell doll and some of it is has to do with the field of psychiatry itself. It has to do with the whole market for anti-psychotics being very influenced by drug companies for a long period of time when the newer second generation ones came out, held off can be vilified somewhat related to those things.

And so we really have to get back to the truth about how though, there was a very helpful review paper published in Psychosomatics. In 2020, on IV held all by the console psychiatry group at Mass General headed by Dr. Scott beach, and it’s a great review about everything you ever wanted to know about IV Haldol, really pulls apart, like the myths and beliefs versus the fact like the fact and fiction type difference there. And so we could link that when I find that paper to be extremely helpful for anybody who uses IV Haldol to understand really, what are the risks? Really, what are the benefits? And then the second one is to to understand.

Kali Dayton 8:44
What are the indications so when you say it’s been used for delirium? I think there was belief in the past that and I psychotics could help treat delirium. But does it? are we managing the condition or the symptoms? What are your thoughts?

Dr. Marie Rueve 9:01
Correct. So we don’t have any evidence that Haldol or any other anti psychotic treats delirium, at least a preponderance of evidence, delirium itself as an entity. Like we have some evidence that physical and occupational therapy sessions can can cut delirium rates in half, like family presence can cut delirium rates in half like the eight s bundle overall can cut delirium rates in half. So when we’re talking about anti psychotics, we have to be sure we’re using them for the right indication and the mountain of evidence that we have related to antipsychotics like haldol and the newer ones that I was referencing before. It talks about it treating perceptual disturbances which we know are very common in delirium, right.

So hallucinations, delusions, paranoia, specifically, all the anxiety and agitation and kind of combativeness even that can come from having those symptoms and just agitation in general agitation from all cause the If you look at traumatic brain injury literature, if you look at other neurologic literature, both acute and chronic psychiatric disorders and delirium, it can definitely, you know, the research on delirium, the antipsychotics definitely help agitation. And so we’re looking at treating those specific symptoms that a patient who has delirium is suffering from. And then we would have reason to use the antipsychotics and believe that they would help the situation.

Kali Dayton 10:28
So more specifically hyperactive delirium.

Dr. Marie Rueve 10:31
Yeah, so things would most commonly occur in hyperactive delirium. You could have delusions, paranoia, hallucinations, in hypoactive delirium, and the patient does not really acting out on that too much, that can be difficult to parse out, you know, sometimes we can look for subtle things on mental status exam that might suggest that they’re responding to internal stimuli as we say things like that. But that’s definitely a harder call hypoactive or I’m sorry, hyperactive delirium, which have a lot more clear indication for anti-psychotic.

Kali Dayton 11:05
We’re using it to manage their their agitation, but also help them really be more comfortable, because we’re addressing the root cause of their agitation, which is the hallucinations, the delusions, things like that. But at the same time, it’s from a bedside provider perspective, you know, as a nurse, I like that it’s going to take them maybe from uracil plus three down to RASS of plus one or zero, right? We’re having, we’re getting a little bit of a chemical restraint benefit, right, helping them stay safer and not trying to climb out of bed be combative, things like that.

And I think that’s, we use a respond to the hyperactive delirium, that kind of agitation with more sedation. And we’re using sometimes out of and pushes that they’re not intubated. And so the risk versus benefit is drastically different. So not that anti psychotics are going to treat and resolve the delirium, but it’s going to really address some of the some of the symptoms, but come with a lower rate of adverse events, right, or consequences.

Dr. Marie Rueve 12:09
Yes, that’s what I would say. So especially when compared with those other choices like sedatives and such that are delirio genic. So held all in the antipsychotics are not sedatives. I always give the example you know, working on an inpatient psychiatry unit, where we don’t have delirious patients if we can help it. We do have psychotic agitated patients and such you need medications to help them with those symptoms at times.

We almost always combine the anti psychotic with a benzo because the antipsychotics are not very sedating in and of themselves. And we need actually on inpatient psychiatry, the extra sedation of the of the benzo in combination with it, or in the emergency room sometimes. So especially certain ones like how old all hell Peridot Risperidone, those really do not have a whole lot of sedation associated with it. They’re described as being calming, but not sedating. So that’s one benefit of the side effects and kind of how they’re different from sedatives.

The other major benefits to using antipsychotics for those symptoms that you described, you know, how we look at agitation, right people trying to exit the bed falling out of bed hitting people pulling out lines in tubes, dislodging devices generally, not able to like participate in care, they’re not taking their medications or not allowing lab draws, they’re not, you know, they’re just generally interfering with what we’re trying to do to help them. The antipsychotics do not cause respiratory depression.

They do not, in general, affect vital signs. So like all the concerns with bradycardia, and hypotension and things like that, that we have with sedatives, those are just not going to happen, especially with particular choices of antipsychotics. And they don’t cause delirium. And so, you know, they they aren’t going to make the brain worse. In that regard. The side effects of antipsychotics that we worry about in the world of psychiatry are actually longer term ones for the most part. And so we’re looking at short term, very temporary use of the anti psychotics for these specific symptoms in delirious patients.

The side effects that we worry about with antipsychotics, those are generally with longer term use, like schizophrenic patients who need to be on antipsychotics for their lifetime. That’s where we get into looking at you know, waking blood sugar, dis control, other elements of metabolic syndrome, those aren’t going to happen short term in the ICU. And similarly with extra pyramidal symptoms or movement disorders. Those especially the most feared one, you know, tardive dyskinesia tardive means delayed, it means longer term use.

So that’s not something we worry about in law in the short term. You can have a few of the EPS syndromes like just Tonia which is like a acute muscle contraction in different parts of the body that can be a little bit painful. You can look at Parkinsonian type symptoms, those could occur. These are all extremely rare, though, in my experience treating delirious patients with antipsychotics every day, or I should say agitated, Delirious patients within psychotics every day. Read into those things maybe a handful of times. It’s it’s very rare to have those. So really, the short term side effects that we would worry about are are very minimal.

The critical care literature would agree with that, I think because they generally point out that the main problem with antipsychotic use in delirium is that people get started on them and then not taken back off of them. Right. And so they leave the hospital on antipsychotics that they probably don’t need over the long term. And you might have longer term side effect risk associated with that.

Kali Dayton 15:54
Things like though they’re not necessarily sedatives, that sometimes they’re prescribed at such high rates, because they’re trying to replace the sedatives. They’re trying to bridge from IV sedation to like I said, high dose, Seroquel, for example. So they just get them to LTACH.

Dr. Marie Rueve 16:12
Yeah.

Kali Dayton 16:12
And so it’s looking at what are the goals of our care? Is this to help them be more calm and compliant so that they can participate in occupational, physical therapy? So they can mobilize? So that they can communicate? So we can actually treat their delirium? Or is it to try to get them to stay comatose? Not moving, not arousing? What are the goals?

Dr. Marie Rueve 16:34
Right. So we always want to keep those goals in mind like SCCM laid out in its ICU collaboration literature, right for the awake, communicative, participatory patient who can verbalize needs to us. You know, that’s always the goal. And a lot of times I have to remind patients and families that that’s the goal, some of them get a little freaked out when the psychiatrist walks into the room, and I have to explain to him therfore. Exactly. And review of those goals.

So we’re, you know, we’re all on the same page. It’s very important. So yeah, I don’t I definitely do not recommend antipsychotics as a replacement for sedatives. I do often get consulted, or like I mentioned last time will sometimes consult myself for my own team, for patients who are cam positive, and are on various sedative infusions. And maybe we’re trying you know what the report usually is from the nurses that we’re trying to have a spontaneous awakening trial, or we’re trying to taper off the sedatives and we’re running into agitation. However, we’re going to define that right plus three plus four is is what we normally but sometimes we’re really just meaning they’re kind of restless and weakly in bed.

And so we do have to differentiate there. But, you know, given the difference in the side effect and risk profiles of continuing for days on these IV sedatives versus doses of the anti psychotic if the nurse is reporting that there’s been agitation in the last few hours when I’ve tried to turn down the sedatives and he or she can describe some version of that being, you know, exiting from the bed taking a swing of things, calling it stuff going for their tube or something like that. Then I feel justified that yes, toward the goal of of getting the sedatives let’s cover for that agitation symptom that we saw.

Because delirium is tricky, it fluctuates, right? It’s like delirious patients can look one way at an 8am says assessment for a nurse and then when I come around to like 10, they’re like, Ras, negative four, and I’m trying to believe the nurse that they were agitated a few you know, it’s like, we all see a different picture. Depending on when we pop in to see these delirious patients to some taking the report into account. We may choose to start like an IV how dal PRN push order, if there’s been a report of agitation with trying to remove the sedative, as long as their QTC is okay, which is the other major, you know, side effect or sort of like, parameter that we worry about related to anti psychotic. So we can get into that, you know, specifically a little bit too, if you’d like.

But, yeah, it’s a little bit for the complaint of whatever form of agitation that was verbalized at rounds. What happened when I tried to turn the sedative down. And it is a little bit like we talked about last time for almost for the staff benefit, right, that there’s something else there. So I can go ahead and get these Saturday’s off because there are other ways to treat. They’re giving me other ways to treat the symptoms that I was reporting to them earlier. So that helps I find that helps staff like Turn, turn down the Satish a bit more rapidly if we have something else available. Yeah,

Kali Dayton 19:53
Absolutely. I think there’s something really vulnerable and scary about saying just turn it off. As a provider just to jump in and say, turn it off, and then we walk away. And then they’re left with this patient that’s going to suddenly emerge really agitated and thrashing. I appreciate that you, you mentioned the variation and definitions of agitation. I also see agitation as a brasa plus three or plus four. But I also appreciate that we oftentimes use the word agitation to describe a RASS plus one or plus two. And I think intervention is absolutely needed when there’s a plus three or plus four, it’s a risk, it’s a danger, you have to have something on hand to avoid the risks of harm to the staff or harm to the patient.

So I liked that idea of having something IV quick acting, but also not continuous. Not a long term plan, but to say, how are we going to mitigate the risks while we figure out what they need, and utilize all the other tools that we have communication and family and mobility? But when right now, when we just resume sedation, we take away all those tools? Yes, if the real cause of that agitation was delirium. Now, we’ve resumed the very thing that caused it. One of the main things that to cause it. So that makes a lot more sense to give something that would manage the symptoms without exacerbating the condition.

Dr. Marie Rueve 21:20
Right. And without doing anything possible, related to their respiratory status, either, which is usually you know, like, the most common thing that people are in the ICUs.

Kali Dayton 21:31
The main cause of failed the breathing trials is sedation.

Dr. Marie Rueve 21:36
Exactly. For sure. Yeah. I have asked our nurses and I haven’t really gotten a clear answer of like, which I also don’t see in the collaboration literature about like, when you do a spontaneous awakening trial, you know, or you try to turn down the sedative, like how long are you supposed to try to help the patient through it before you resort to either turning the sedation back on at half dose of the case of spontaneous awakening trial or giving an another medication.

I have a much lower threshold for going out and giving another medication like IV holdall if they’re QTC is okay in that scenario, because it’s we’re still kind of going, it’s helping us kind of go toward our goal of getting the sedation offs. But it’s hard. It varies with nurses like I’ve heard you describe the spontaneous awakening trial like watch for their arm to move and then turn it back on.

Kali Dayton 22:29
Yeah, another nurse is on here talking about when she was training into the ICU. She didn’t even realize they were doing an awakening trial. So when she asked the nurse, what are we doing the SATs? She said, “Oh, we already did it. Remember he breathed five times above the vent?” And that was it.

Dr. Marie Rueve 22:45
Right.

Kali Dayton 22:46
But that also it’s hard. Because if you have another patient that you’re managing, you turn sedation off, you don’t know necessarily depending on the type of sedation and the body habitus and how long they’ve been sedated. You don’t know when they’re actually going to be de sedated? Exactly. And so it’s hard as a nurse to turn it off, and maybe their bariatric patient patient has been a proper fall. Are they going to suddenly be on the ceiling in 30 seconds? Or in two weeks? You just don’t know?

Dr. Marie Rueve 23:13
yeah. So it’s right. The longer the longer they’re on it. That’s what I tried to emphasize to the team here. You know, we, we will have a lot more luck getting this off if we follow. Dr. Ely’s advice of like, “Every time the sun rises, we have to be asking these questions of does the patient still need all these things?” Not five to seven days later, because then we’re we are full of it. All of it. The fentanyl the propofol, we have a huge reservoir of it in our system. And it’s completely all bets are off as far as when we’re going to see this actually exit their system.

Kali Dayton 23:45
Right. And just because you’re giving an IV push of Haldol doesn’t mean that you’re resuming sedation. You’re still progressing forward. You’re still allowing the body to metabolize all those other things out without prolonging time on the ventilator.

Dr. Marie Rueve 24:02
Yeah, and so that’s, I think, an important differentiation with antipsychotics is I really tried to be careful about my language with the team that these are not sedatives, right? These are medications that can cause agitation, and treat perceptual disturbances. And those are very uncomfortable for the patient. So we give this medication to help them through that, but we’re still proceeding with our goal of removing the sedation and progressing toward extubation. You know, like I said, last time, we try to get the brain and the lungs to the point of being able to activate this patient at the same time. And yeah, the the anti-psychotics will not adversely affect spontaneous breathing trials for sure.

Kali Dayton 24:44
I’ve asked to I interviewed Dr. Paul Wischmeyer who himself had been patient, and he had delirium. At one point, I mean many points actually. But one time when he was young, he received how though he said it was like being pushed If he experienced being pushed off a higher level and falling into glass and shattering glass. How common is that experience with how dull because that made me hesitate that made me worried that we were exacerbating delirium or delusions or giving them worse experiences.

Dr. Marie Rueve 26:27
Yeah. So I listened to that episode is very fascinating. And I’ve heard some other folks on different various podcasts in this realm kind of either lump held all in with other sedatives or explain this whole complicated situation with all these different medications on board and then say, but I think it was the hell doll that did that. Right? Are you differentiating from all this other stuff that was going on at the same time. So what I usually tell patients because I hear it and see that a lot.

This is one of those situations like if I had a nickel for every time this came up. And it’s not that this is a common reaction. It’s it’s a common misunderstanding, and in my opinion of what’s going on at the time. So we said that the anti psychotics don’t treat delirium, right, they treat some of the symptoms of delirium. So when we give a delirious patient a dose of an anti psychotic for whatever indication, we have to do that the delirium is still going on. And so what they’re symptoms that they’re experiencing, in the wake of giving that anti psychotic that are basically pharmacologically impossible to have been caused by that anti psychotic.

We that’s from the delirium itself, ongoing. So I have patients all the time, I was just talking today. I mean, this happens every day, I was just talking today to a wife of a patient cancer patient who has been struggling with delirium for a long time, he’s not in the ICU, thankfully. But the same principle applies, you know, and he’s experiencing a lot of what in dementia we call sundowning, which is where their sleep wake cycle is reversed. And they suddenly get restless and energized, and kind of all over the place in the evening into the into the nighttime, right? And he gets his age, his bedtime, Risperdal dose right in the middle of that happening to extremely low ginger dose response. And the, you know, the wife is interpreting that the “Risperdal is causing this, because he gets the Risperdal dose, and then this is happening.”

And it’s like, but actually, this would be happening if we didn’t give the Risperdal dose too, right, because this is his delirium. And it kicks up around night, you know, evening into nighttime for a lot of people. And so it’s temporarily connected. Yes, he got the risk for at all dose, he probably got. So got like six other medications at bedtime, that we’re not pinpointing is the one that causes him, you know, to be restless after that.

So that’s a little bit of an example of our beliefs about the medication, not and maybe it’s not enough medicine to treat his agitation that’s happening in the evening and actually need to increase the dose a bit a little bit. But I can be pretty pharmacologically confident that the Risperdal is not causing that to happen. That’s the delirium ongoing, and similarly for Dr. wishmaker. That’s what I probably would respond to him is that he may have temporarily around there gotten a dose of hell doll, and then had that experience afterwards.

I don’t question that. That’s what he what he experienced. But I would question that that effect was directly from the hell doll versus the ongoing delirium itself that, like we said, comes and goes, fluctuates up and down different times of day, are to really pinpoint that so I don’t see it from a cause effect standpoint, it’s usually the ongoing delirium. The other thing that we’re this exemplifies itself is, you know, delirium can fluctuate also between hyperactive and hypo active, right? And so patients can be agitated, agitated, agitated, or All night I come in in the morning they’re somnolent.

And the nurse will have held the morning Risperdal dose, because or the nurse gave the morning Risperdal dose now the patient’s somnolent. And so they’ve held it and they’re not gonna give any more antipsychotic because it knocked them out. And it’s like, it doesn’t knock people out, though, any more than the antibiotic that you gave them, knocks people out, because you also gave that at nine o’clock this morning, but we don’t think that caused them to be knocked out, you know. So this is the fluctuating delirium. It can fluctuate down into hypoactive delirium, which can actually for some people be basically unresponsiveness and coma.

That just means that their delirium fluctuated down there, it doesn’t mean that the Risperdal sent them down there. And so we were seeing the ongoing delirium, we need to continue to provide treatment for the delirium itself in the forms of debt that we’ve, you know, described and also, if they continue to have some agitation medication for that, too.

Kali Dayton 31:02
And how do you navigate when to give by practicing versus Risperidone versus Seroquel?

Dr. Marie Rueve 31:07
Yeah, lots of lots thoughts. I will say that when I’m rounding with the ICU, and I have a patient where the nurse is giving a report of agitation and we’re trying to get sedatives off or whatever. The first thing I do is look at their QTC. And if it is less than 500, and they have IV access, then I will give IV held out for sure, because it is the best tolerated medication, it’s purely dopamine blocking, so it doesn’t have anticholinergic effects. It’s actually IV held all interestingly enough, really doesn’t have EPS associated with it. So it really doesn’t have that side effect in that formulation. It’s safe in any kind of organ failure.

So there’s no dose adjustment based on whether the kidneys or liver functioning or not. And it’s not going to do anything to their respiratory drive. So it’s extremely safe in an unknown patient, as long as that Q TC is below 500. It’s not very sedating, though. So if I have a patient who is almost like purely hyperactive delirium or in other scenarios, if we have a agitated, anxious patient who’s trying to tolerate BiPAP, and things like that, and I actually want a little bit more sedation without having to give benzos that I will go to in the ICU, then I will go to either Seroquel or Zyprexa, usually, and the difference there is that a couple of things so

Seroquel has a little bit more QTC prolongation risk with it. Zyprexa really doesn’t have a whole lot of QTC prolongation risk. So that may be a differentiator. They both have a fair amount of anti histamine and anticholinergic effect to them. So that’s what’s going to cause the sedation effect like this, the somnolence sort of effect. And that sometimes is a good thing in some of these agitated situations where we’re trying to hurt people, right? Like that might be why we’re we would give somebody a benzo in that scenario, dose, a dose not an infusion.

To me though a benzo compared to the anti psychotics for that scenario, patients trying to tolerate BiPAP and as anxious, the anti psychotic doesn’t have any respiratory depression risk. And it doesn’t have any literature that says, you know, every milligram of Ativan that you give you have a 20% risk that your patient is going to be delirious the following day. So to me, it’s a lot safer and most likely to be better tolerated to use some a little bit of Seroquel or Zyprexa in that scenario. The other time that I use the apraxia or Seroquel again, mostly depending on the QTC, which one I’m going to pick is at nighttime.

So trying if I have if I have an agitated person, like I had a patient in the emergency, or I’m sorry, in the ICU earlier this week, who is like calling 911 At night, I don’t even know how he was actually getting his phone to do that was delirious day. But that was the report. So there was agitation and all this overnight. And so given that his cue Tec was a little prolonged, we chose Zyprexa or olanzapine and we give like five or 10 milligrams of that at night time to treat the agitation pattern overnight that we’re seeing that’s very common with delirium, but it’s a little bit more sedating than something like held also, it’s going to promote sleep at the same time without having to give other agents for sleep.

So we’re kind of accomplishing both of those things in one pill. So that’s a little bit how I choose between the different ones. The other things that come in the ICU right or like if they have enteral access or not. So if you if I have a patient, like a common corner I’ll get into is I have a patient too. Who is having some agitation in their QTC is 600. And they don’t have any enteral access. And it’s like, okay, so now what are we going to do with this person? And that’s where I usually will go to intramuscular antipsychotic Yep. So you have intramuscular held all same, you know, reasons, I would pick that as, as we already discussed.

And then you have intramuscular, olanzapine or Zyprexa in five or 10 milligram doses. So again, I can give that patient 10 milligrams of Zyprexa at bedtime, to help with sleep and overnight agitation in an im formulation. So that that helps a lot to them whenever they can take po again, then we you know, switch to pills, because I don’t really like sticking people like that if I can help it. But sometimes it’s the only way.

Kali Dayton 35:51
Right, especially if you’re in a crisis, right. So that’s a difficult situation, even on the medical floor. It’s not just in the ICU, but you have patients with actual agitation, the nurses have five other patients. And yet when we give Ativan or just igniting this whole domino effect, that that really is not beneficial to anybody who has really good experiences with the PEXA. Or circle at night. For the hyperactive delirious patients, the ones that are just constantly going, going, going, going, going. But my. But I was wondered, I mean, it makes us feel better. It’s definitely easier for the nurse. But is that real restorative sleep?

Dr. Marie Rueve 36:35
Yeah, so the anti psychotics do not they do promote sleep, real restorative sleep. So it’s not going to be sleep disrupting, like, benzodiazepines or alcohol is, for example, because it works that same way as benzodiazepines or some of the other sedatives that we know, disrupt sleep precedents being the the exception to that, right. So precedents does promote restorative sleep or pretty natural sleep overnight.

And so that’s a that’s a fair choice that sometimes I leave to the, uh, you know, ICU team in general, like, we can use precedents here, or we could use one of these anti-psychotics here to help lessly tell both, or to help with agitation, they will both preserve sleep. I like the, you know, studies that look at cycling precedents overnight and then turning it down or off during the day, I haven’t gotten my team here to really experiment with that one too much. And, of course, the other tie. The other thing that precedent says is tied to the ICU.

So sometimes we will opt for the antipsychotic choice, because those can be used anywhere in the hospital least in our hospital. But pressing X is in the ICU. And so if they’re trying to get them out of the ICU, and we’re almost there, but we’re having this agitation, and that’s another nice place to use antipsychotics. And I do really see it as my responsibility as the consultant or the member of the team who’s kind of suggesting their use in these appropriate scenarios and for these appropriate symptoms to follow the patient, and be sure that I’m tapering them off the antipsychotic when they don’t need it anymore either.

Just like I would just like we kind of promote, you know, to like, let’s not use a sedative anymore when we need it. Right. The same rule applies to anti-psychotics being that hospitalization is so short, and patients aren’t given really a whole lot of time and a lot of cases in the hospital to totally convalesce from their illness, you know, they’re sent to an acute rehab, they’re sent to a nursing facility, they’re sent home health. We sometimes give a taper we write for a taper of the antipsychotic for after discharge.

So don’t generally do not just say, “okay, they’re on, you know, haldol five milligrams twice a day. Goodbye, like discharge on that.” I will write like, “we can keep with the haldol twice a day for a week, let them settle back in at home. Then we can go down to five milligrams at bedtime for two weeks and stop”– something like that. So there’s like a direction for how this is going to end even if I’m not personally there at the time to make sure it ends.

Kali Dayton 39:17
No, that’s great. I think sometimes especially during COVID We had such large volumes leaving the hospital to these LTACHs. They were so inundated with so many of these patients that were having to anti-psychotics us as a transition think especially Seroquel because it is sedating.

Dr. Marie Rueve 39:32
Yeah,

Kali Dayton 39:32
I just as a Seroquel were being given, they’re sent to the LTACH, and they would say all those doses for a long time. It just seemed like there was so much to manage and the LTACH that there wasn’t a strong, reliable system to make sure that these medications were being reviewed, tapered, discontinued, reassessed, and that that can really harm patients and they continue to be comatose. obtunded or lethargic and the Eltech where they’re supposed To be rehabilitating. Yes, and they’re really do them a disservice in the long run as well.

Dr. Marie Rueve 40:05
Yeah, Seroquel, I think came into a lot of favor as an anti psychotic based on John Devlin’s study of it in 2010 that was published in critical care medicine, which he will describe or I’ve heard him describe on I haven’t talked to myself, but I’ve heard him describe on podcasts that he will he will say that well, that was a pilot study that was only 36 patients that was adding Seroquel up to 200 milligrams twice a day, to patients who are receiving Halldor for whatever hyperactive symptoms of delirium they were having at the time.

And it did show that pilot study did show benefit, including in reduction in severity and length of delirium course. So that really hasn’t been reproduced in the way they have studied anti-psychotics in the ICU for delirium as far as RCT goes since then, but his study did give some basis for that use and I did you know, when that came out in 2010, we did kind of adapt to that to a little protocol of sorts of like this combination of Haldol and Seroquel, because those are very interesting.

Opposite anti-psychotics, really, they’re both anti-psychotics They’re both labeled as dopamine blockers, how they’ll pretty much only blocks dopamine. Seroquel is very light on the dopamine receptor. Actually, it doesn’t do a whole lot of dopamine blocking. It has a lot of anti histamine. A lot of anticholinergic, a lot of serotonin action. It’s a very mixed low potency drug, which is where the high number of milligrams comes from. So we would do like, kind of riffing off his study. We would do you know, like some Haldol dosing during the day because of course, it’s calming but not sedating.

And then we would maybe you Seroquel, a bedtime dose of Seroquel plus maybe one other rescue dose of Seroquel available during the day for high anxiety or agitation. So that combination even though in the rest of psychiatry like treating schizophrenic patients, I tend to not use combinations of antipsychotics like that we tried to do mono therapy. Sometimes these very opposite anti-psychotics can help can work in a combination.

And so I think that’s where Seroquel got a lot of traction for use in the ICU was from that 2010 study. In my experience, though, it’s not a it’s not the most ideal one to pick, it’s better than say President so if we talk about the mind USA study from 2018 We can talk about zyprasidone a little bit because that’s at the bottom of the list as far as helpful anti-psychotics.

Seroquel does have that a little bit more que QTC prolongation. It is less dopamine blocking and has all those other kind of messy receptor interactions that cause a lot of side effects with it. And so I find it hard to use as monotherapy to help with delirium, because I’m not really getting that dopamine blockade. I do like it combined with a strong dopamine blocker. To help with that, you know, I guess you’d have to say sedating, or sometimes we use the term soporific sort of effect, like helping with sleep at night, but in my mind, less dangerous or egregious than like giving a patient you know, Benadryl or a benzo or something to help us sleep at night.

Kali Dayton 43:28
I guess you’re looking at it from an A to F bundle perspective, where you’re watching patients to be awake, communicative mobile. I think sometimes we’re giving these medications with the perspective of the more traditional approach to have them more comatose, lifeless, just laying in bed, not bothering anybody. So I think management depends on what our goals of care are. And then the benefit is gauged accordingly. Because I think people will have really liked high doses of Seroquel because it is sedating. But is that our goal to sedate them?

Dr. Marie Rueve 44:03
Yes, correct. And I would never give I don’t recommend antipsychotics just for delirium right across the board, like we’re giving it for those specific symptoms that we talked about. And I will take a nurse report in recent hours, even if I’m not seeing it myself when I go to look at the patient because delirium does fluctuate like that. And so I think that’s important to take everybody’s experiences with the patient into consideration, but we are doing it for those specific symptoms not for delirium itself.

And so in general, a hypoactive delirious patient is not going to receive anti-psychotics Because there’s no reason to think that it’s going to do anything unless you have that kind of rare hypo active delirium patient who is either able to report to you that they’re having some paranoia that they’re seeing, you know, blood come down the walls or snakes on On the floor or something like that, or they’re awake 24/7. And having a lot of trouble sleeping, you know, there are some other choices for sleep that we could consider that aren’t anti psychotics, but something like that, you know, otherwise hypoactive delirium by itself, it’s not really going to be benefited very much by a by an anti psychotic,

Kali Dayton 45:19
Excellent. And I just love the idea of having more things to help keep patients and clinicians safe, but not take away the opportunity to actually treat the delirium with sleep, family mobility. And so I think that that is our goal to help patients access those tools, then we see these kind of interventions as part of giving them access, instead of depriving them with sedation, but also a patient’s rasa plus three or plus four, you also can’t communicate with them, mobilize them, they can’t really connect with their families because they’re just levitating off the bed.

So finding the middle ground, I think we, maybe some people that have heard me talk think that this is a no sedation, non pharmacological 100%, all the way approach, and an absolutely is not it’s figuring out what tools we have accessible. What are the pros and cons? What are the risks associated with these interventions? And how do we safely utilize them to optimize outcomes of our patients? I love that we’re looking at Anna psychotics as a very temporary, useful tool, but also making sure that we have a way to get them off down the road, too. Right?

Dr. Marie Rueve 46:29
Yes, so they’re definitely a tool in our toolbox. And they serve a purpose. And they have a very long, well established history of treating certain symptoms that do happen in in delirium, and in ICU patients across the board. And we do use them in psychiatry, I would say, you know, off label a lot for anxiety, anxiety is a very frequent, I say phenotype of delirium, right? If you’re confused, if you’re having some paranoid thoughts that maybe you’re not directly verbalizing to people, or whatever we’re going to see anxiety as a result of that.

And antipsychotics are very, you know, very effective at calming that down, again, without a lot of the other side effects that come along with the other choices of medications, when we actually really look at the pharmacology of these different agent choices.

Kali Dayton 47:22
This has been so helpful to have another perspective on how to manage delirium, even though this isn’t treat delirium, it can help us manage it and allow us to treat it, anything else you would add?

Dr. Marie Rueve 47:33
I just was like what you were saying before about, you know, that we’re not we’re not all one or the other, right? We’re not like, I’m a psychiatrist, I’m not all medication. And you’re not anti medication. I always start my notes, which the folks around here seem to appreciate. But when I get to the recommendation sections of my notes, you’re probably a little worn here than they have to be. I do start out with like wanting to avoid benzos, Anticholinergics, and unnecessary opiates.

We need to do all these non pharmacologic interventions that have been proven to decrease delirium like Sharon anyways, work from 1999. And I list them all out about the blinds, the eyeglasses, you know, early mobility, the catheters, the everything, constipation, cetera, et cetera, like all those other things that we need to fix to be sure the patient’s comfortable. And I do also have a little bit of homage to Dr. Ely, Dr. Dre pneumonic, you know, about, like, have we removed the drugs? Like I mentioned, you know, are we working towards disease removal? And are we doing these things in the environment, those are the important things for treating delirium.

If there’s no contraindication, to it, is this patient working with PT OT, because that’s been demonstrated in the literature to cut delirium in house. And I always personally, when I’m seeing these patients and their families, if there’s family at the bedside of a delirious patient in the ICU, or anywhere in the hospital, I always personally say to the family, thank you for being here, because you are a treatment. I think a lot of families have a lot of anxiety, they’re in the way, you know, they’re kind of, you know, hanging out, and they don’t really need to be there, whatever. I tell them that, you know, obviously, you can’t be here 24/7.

You have other things in life, but when you are here, it’s very helpful for treating this scary condition of delirium. Because they’re loved our medicine. Yes, they are. their loved one looks totally different. A lot of times, they’re worried it’s a permanent state, and they’re going to be there forever. So just those few minutes of chatting with the family and saying, you know, thank you for being here. It’s really helping we know from the science that this really helps get their brain back online.

And then I go into some of the pharmacology recommendations, a lot of which can be you know, stop this, stop that stop. Then we’ll add a little bit of this, you know, on for sleep or for calming during the day or whatever I do. recommend a lot of melatonin. There is some studies out there pointing to its potential helpfulness and cutting down delirium, although a that hasn’t been well replicated, and there isn’t a specific mechanism of action that’s been identified for that.

The 2018 PADIS guidelines were mentioned that, but they didn’t put that in there as like a across the board recommendation that everybody should have. If it’s appropriate for the patient, and they’re having trouble with that sleep wake cycle, I will suggest that Trazodone is another medicine. That is an old old antidepressant that helps with sleep in small doses, and is quite benign, as far as sleep medicines go, has, doesn’t have like the EPS risk and things like that, that antipsychotics do.

So sometimes if we’re really only having sleep trouble, I might recommend small doses of Trazodone to see if that helps. So there are some very that I also also almost always try to mention in there, like multimodal pain control, right? Do we have this patient on Tylenol? If it’s appropriate? Are they supposed to be on Gabapentin at home, and we’re not giving it to them here and their kidney function is fine. So can we restart that, you know, these these other types of coming at it from all directions? So my notes, I feel like really try to emphasize this well rounded approach.

The antipsychotic is kind of like one line in there if it’s going to be helpful. But all these things are required for treating delirium, which is why I find myself talking about ICU liberation all the time, right? Because antipsychotics are such a small piece of it, they can be extremely helpful in the right, setting the right patient for the right reason, but I’m not going to treat delirium with antipsychotics. I’m not going to resolve all these delirium cases we have to be coming up these patients to help them from the ICU liberation collaborative, ABCDEF bundle viewpoint on how to get this done for this person, brain and body.

Kali Dayton 52:01
This has been so helpful I think people are gonna love this really resonate with this because I think there’s been as we can both appreciate a lot of misunderstanding about anti-psychotics About delirium in general. I think you’ve done such a great job of clearing the air. All your citations that you’ve mentioned, I will include in the episode transcript, and anything else you want to share with everyone will include on the website. Okay, perfect. Thank you so much.

Dr. Marie Rueve 52:26
Thank you.

Transcribed by https://otter.ai

 

Citations

IV Haldol – Beach et al 2020 review in psychosomatics.

PO Seroquel  – Devlin 2010 critical care medicine.

QTc prolongation – Beach et al, Psychosomatics 2018 review.

AID ICU Oct 2022 NEJM

 

Detailed Summary

Some of the basic attributes of key antipsychotics for use in the ICU:

• IV Haldol – Beach et al 2020 review in psychosomatics – everything you ever wanted to know about IV Haldol
• PO Haldol
• PO Seroquel – Devlin 2010 critical care medicine – up to 200mg BID Seroquel in ICU delirium patients with free use of rescue Haldol was more effective in reducing length and severity of delirium. Onset 1-2 hours
• PO Risperdal
• IM and PO Zyprexa IM up to 45 min, oral about 6 hours

Scheduling vs PRN, alternating around the clock

Appropriate dosing. I start at 5mg Haldol, 100mg Seroquel, 5-10mg Zyprexa, 1-2mg Risperdal

 

Other adjuncts for treatment of agitation, anxiety, insomnia in the ICU:

• Precedex/oral clonidine
• Melatonin
• trazodone, remeron
• Valproic acid (oral or IV)

 

So enteral access is extremely important, also extremely important for nondeliriogenic multimodal pain control:

• Tylenol (also IV)
• Gabapentinoids
• IV ketamine at pain dose range 2.5-20 mcg/kg/min
• Bolus opioids – scheduled oxy, PRN oxy, PRN IV if unable to use oxy or for immediate procedure

Noting that IV opioids are extremely short acting, so we have to overshoot dose to toxic range to make it last even an hour (looking at fentanyl kinetics for example), whereas appropriately dosed oral oxy if pt is absorbing through the gut (Tylenol test)

 

It is pharmacologically impossible for Haldol to cause hallucinations or delusions – it is no more possible than an antibiotic causing an infection. Haldol blocks dopamine. Psychotic symptoms are from excess dopamine. If there are delusions or hallucinations after antipsychotic is given that is purely temporally connected and NOT cause-effect.

 

Antipsychotics are ideal for treating agitation because they:

• DO NOT cause respiratory depression
• DO NOT cause hemodynamic instability or any change in VS
• DO NOT cause really sedation at all especially Haldol and Risperdal
• Especially haldol is safe in any organ failure, others require minimal adjustment in kidney failure like 30% dose decrease
• DO NOT cause delirium or psychosis or cognitive impairment in the short term

 

Antipsychotics rarely cause acute EPS:

• Dystonia
• Parkinsonism
• Akathesia

 

Rates:

• Metabolic syndrome is a long term effect with months of use in some patients, ie schizophrenia
• TD is also be definition a DELAYED syndrome with extensive long term use of older agents

 

QTc prolongation: Beach et al, Psychosomatics 2018 review.

• Haldol IV – 2020 review – likely overblown, recommend following if >20mg daily and other RFs if IV, likely “excessively low” and skewed by other RFs in populations reported (older, sicker, other meds, etc)
• Haldol PO/IM – no increased risk
• Seroquel – 1 to 10msec with 100mg dose, 2.6% in >30msec change
• Risperdal – 8msec
• Zyprexa – few msec if that, fewer QTc prolongation than placebo in one study with IM, and one study of psych pt’s receiving 40-160mg a day of olanzapine resulted in 1% of patients with “significant QTc prolongation.

 

Biggest risk per SCCM with antipsychotics is people leaving the ICU on them and ending up on them long term, 20-30% of ICU discharges.

 

Critiques of MIND USA:

• No psychiatrists were involved in the design of the study. Two psychiatrists are mentioned to have communicated with the research team about antipsychotics, I presume whose experience is in treating schizophrenia and bipolar, not delirium and not full-time C/L psychiatrist.
• 89% hypoactive delirium
• Ziprasidone is extremely poor antipsychotic with lots of QTc prolongation, no routine IV use, no role in medical patients
• All of the patients in all groups were on gobs of propofol, fentanyl, and bnz according to the supplementary charts, so there was no separation of groups – the same phenomenon I heard discussed on this podcast as the primary criticism for the TEAMS study and why there looked to be no benefit from increased mobility, even though we all know it is beneficial, just like we all know antipsychotics are helpful in certain situations.

MIND USA did prove that these antipsychotics are extremely safe to use in critically ill patients.

 

An ideal study in the ICU would compare IV Haldol to fentanyl or propofol (even with IV Zyprexa with equivalent dosing) with no other sedatives on board. Pts would be managed either with the antipsychotic or with the sedative, not with the antipsychotic on top of the sedative, because I could have already told you from long ago that Haldol cannot fight against the tsunami of delirium and coma that these sedatives bring forth. Short term outcomes would include measurements of agitation resolution with scales, patient and nurse report, and then could also look at survivability and cognitive outcomes including longer term. The antipsychotic is going to do nothing with all that sedative being infused. The antipsychotics offer an alternative to managing agitation in the ICU with MUCH better physical and cognitive outcomes and effects that sedative infusions.

AID ICU Oct 2022 NEJM

 

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