#296 - Understanding Delirium in the NICU

Hello Friends 👋

Delirium in the NICU is an under-recognized and under-assessed challenge. In this episode of The Incubator Podcast, Ben and Daphna sit down with Dr. Karishma Rao and clinical pharmacist Alex Oschman from Children’s Mercy Hospital to explore the complexities of neonatal delirium. Drawing on their collaborative work and recent publication in Frontiers in Pharmacology, they unpack the nuances of distinguishing delirium from pain, agitation, withdrawal, and sedation—particularly in medically complex, long-stay infants.

The conversation highlights the limitations of current assessment tools, such as the CAPD (Cornell Assessment of Pediatric Delirium), and the barriers to implementation in the NICU setting. The team shares practical strategies, including modifying pain and withdrawal protocols, minimizing deliriogenic medications like benzodiazepines and opioids, and emphasizing non-pharmacological interventions like early mobility, sleep hygiene, and environmental optimization.

They also discuss pharmacologic options when needed, such as the selective use of atypical antipsychotics like quetiapine or risperidone, and raise critical questions about how developmental care might reduce the need for sedation altogether. This episode is a call to action for NICU teams to better understand, assess, and address delirium in our most vulnerable patients through collaborative, multidisciplinary care. 

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The articles covered on today’s episode of the podcast can be found here 👇

2022 Society of Critical Care Medicine Clinical Practice Guidelines on Prevention and Management of Pain, Agitation, Neuromuscular Blockade, and Delirium in Critically Ill Pediatric Patients With Consideration of the ICU Environment and Early Mobility.

Smith HAB, Besunder JB, Betters KA, Johnson PN, Srinivasan V, Stormorken A, Farrington E, Golianu B, Godshall AJ, Acinelli L, Almgren C, Bailey CH, Boyd JM, Cisco MJ, Damian M, deAlmeida ML, Fehr J, Fenton KE, Gilliland F, Grant MJC, Howell J, Ruggles CA, Simone S, Su F, Sullivan JE, Tegtmeyer K, Traube C, Williams S, Berkenbosch JW.Pediatr Crit Care Med. 2022 Feb 1;23(2):e74-e110. doi: 10.1097/PCC.0000000000002873.PMID: 35119438

Detection and Management of Delirium in the Neonatal Unit: A Case Series.

Groves A, Traube C, Silver G.Pediatrics. 2016 Mar;137(3):e20153369. doi: 10.1542/peds.2015-3369. Epub 2016 Feb 2.PMID: 26908706

Challenges in management of refractory pain and sedation in infants.

Oschman A, Rao K.Front Pharmacol. 2024 Jan 3;14:1259064. doi: 10.3389/fphar.2023.1259064. eCollection 2023.PMID: 38235119 Free PMC article. Review.

Delirium in the NICU.

Tarrell A, Giles L, Smith B, Traube C, Watt K.J Perinatol. 2024 Feb;44(2):157-163. doi: 10.1038/s41372-023-01767-5. Epub 2023 Sep 8.PMID: 37684547 Review.

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The transcript of today's episode can be found below 👇

Ben Courchia (00:00.792)

Hello everybody, welcome back to the Incubator podcast. We're back this Sunday with a special interview. Daphne, how are you doing this morning?

Daphna Yasova Barbeau (00:08.767)

I'm doing really well. I've really been looking forward to this interview. I was telling our guests offline that this is both kind of an area of interest for us. So we're really glad to bring it to the community for sure.

Ben Courchia (00:21.698)

Yeah, we are joined today by Dr. Karishma Rao and Alex Oshman. Karishma, you're a neonatologist at the Children's Mercy Hospital in Kansas City, Missouri. Alex, you're a pharmacist in the same institution. Welcome to you both on the Incubator podcast.

Karishma Rao (00:43.478)

Thanks for having us. I've been looking forward to this for a while.

Ben Courchia (00:47.33)

You

Alex Oschman (00:48.269)

Yeah, thanks for having us. It's been really exciting to talk about this. I've talked about this at a couple of conferences, primarily pharmacy conferences. I think it's a really complex question that I think it's glad that Nick user be more aware about.

Ben Courchia (01:02.54)

Yeah, today we're talking about delirium. Specifically, obviously, we want to talk about delirium in the neonatal ICU. And I think this is something that is becoming a little bit more recognized in recent years. And it's also being recognized that we don't know very much about delirium in the NICU. You two have authored a very interesting paper in Frontiers in pharmacology. It's an open access.

Daphna Yasova Barbeau (01:22.035)

That's right.

Ben Courchia (01:32.268)

paper called Challenges in Management of Refractory Pain and Sedation in Infants. There is a very interesting section there on delirium. There are some other interesting papers that you referenced that have been published. And I think that the best place to start is sort of with the definition. I know that in this particular paper, you talk about delirium being the behavioral manifestation of acute cerebral dysfunction.

And I think that's a great place to start. It sort of defines delirium pretty well, but it doesn't tell us much about what that behavioral manifestation really looks like. Alex, I'm going to start with you. Can you tell us a little bit about what delirium presents as, and is it something that we should be concerned for in every baby in our NICU, or is this something that a certain maybe group of infants is at higher risk of?

based on their either inherent or extrinsic parameters or comorbidities.

Alex Oschman (02:39.609)

Great question, you went straight for the hard one right off. There's a whole lot of answers in that. I'm going to start first with, you know, what are the signs and symptoms you should look for? I'm going to say this a lot, Christmas probably going to this a lot too. It's hard to know, right? We're talking about NICU babies. And when you look at a lot of our NICUs nowadays, right? We have preterm neonates, we have...

former pre-menu neonates, and then we have up to, depending on your NICU setup, 18 to 24 month olds. So what that's going to look like, I think it's kind of hard. Those patients range a broad range. When we look at delirium for the adult population, there's three major subtypes. There's this like hyperotonic, hyperalgesic, hypertonic, and a mixed. And so I don't think we know enough necessarily. I think we generally think of

you know, this inattention, inattention, unawareness of surroundings, hyper agitation is what I kind of like to call it, is what we see. But it doesn't necessarily mean that, you know, maybe some of those babies that are really sedate and are like, wow, look, like they're really like quiet over there. Does it mean that maybe they have to learn? I think those are the ones we probably know less about because they're not really on our rate.

Ben Courchia (04:01.87)

Absolutely. There's a very interesting case series that was published in Pediatrics by Alan Groves in 2016, I believe. And I think that as I took some notes on some of the papers that I was reading preparing for this interview, I really liked the representation of, based on the different types that we mentioned, a representation of a baby with delirium, especially in the

Alex Oschman (04:08.321)

Mm-hmm.

Ben Courchia (04:31.04)

hyperactive subtype as the baby that's impossible to sedate, quote unquote. I think that this is something that might resonate with a lot of people where, and that's something that is quite well described in that case series where it seems like all three babies that were presented there seem to be these babies that despite appropriate sedation that should have been OK for a baby intubated and pre-op post-operatively, turns out not to be OK. And so, Karishma, I wanted to maybe turn to you and maybe get your thoughts on this.

It seems that the discussion about delirium really shines a light on pain assessment and pain management. So can you tell us a little bit about how these two are tied together?

Karishma Rao (05:14.582)

So neonatal pain is my other, I think, area that interests me and management of pain in the neonate. So I think one of the ways that I actually kind of got interested in it and leveraged Alex's brain power to better understand this over the years was that it was first, think, the fact that until the 1980s that

pain in neonates itself was so under recognized and under treated and under appreciated. And since then we've evolved into trying to better assess this, trying to have better scales, but we all still admit that we're not the best at assessing neonatal pain. And we also find that there is sometimes discrepancies between the bedside staff and the subjectiveness of assessment of pain and sedation at the neonate. And so I think

what poses a challenge with delirium as well is that one is that there's an under awareness and under recognition of it, but also the challenge that comes in assessing it, similar to the challenges of pain and sedation assessment, not just the subjectivity of it, I think, but also because it obviously is so hard for reasons like the child being non-verbal and things like that. But I think,

What is difficult, I think you point out Groves' paper, which I really liked, is that very commonly I think that people that were non-believers of delirium get converted to believers of delirium because you do encounter those complex, critically complex kids, whether it's that acute post-op period or a prolonged chronic kid in the NICU, those kids that just...

have that escalating need. And you would think that if it's pain or sedation, if you addressed it, you gave them a bolus, you would address that pain. would last longer. You would escalate your dosage, and it would address it, but it doesn't. And those are the kiddos with those escalating needs that seem to get almost worse as you give them more and don't respond to it, that those are the kiddos that then sort of shift.

Daphna Yasova Barbeau (07:05.907)

Mm-hmm.

Karishma Rao (07:23.094)

people's focus to maybe this is not pain and sedation needs that we're dealing with. Maybe we're dealing with something else like delirium.

Daphna Yasova Barbeau (07:30.813)

think that's so interesting as we are kind of dancing around the subtypes. And I think you're right. I think those are the kids that get a lot of attention. I kind of have a special interest in this irritable baby. The baby that the nurses, they're not flagging on the N-pass or the whatever pain score you're using because it's not flagging as pain, but every nurse that has ever taken care of the baby will say, gosh, that baby just is.

irritable, they're grouchy, they don't like to be touched. You know, nothing we do settles them. And we can all think about babies like that. There are babies who have wild, yeah, they won't stop moving. They never sleep, you know, kind of almost like, like an NAS picture of a baby who may or may not have been exposed to medication. So I'd love for you to talk a little bit about that, that group of babies.

Ben Courchia (08:07.788)

Wild is often used as like the, yeah.

Karishma Rao (08:29.651)

Go ahead, Alex.

Alex Oschman (08:31.428)

So Chris and I work together all the time, so we're used to finishing each other's sentences. You know, I think, that's what really prompted us at our institution to look at this a lot closer. We have a very large trach vent population. And so initially a lot of these patients were our VPD, CLD patients, where we saw exactly what you were saying. We would see patients who we were on

pain-incentive medications, I think as a neonatology group, somewhat other people, we use a lot of morphine for sedation, even though it's a pain medication with a sedation side effect. And we would see these babies that we had been adequately sedating, whether that's with morphine, midazolam, some Precedex, that seemed more irritable. We got this all the time that they were irritable, they were angry.

And a lot of people chopped it up to, well, they're becoming tachyphilotic for their meds. It's tolerance because we've been on these for so long. And I would make the argument of, well, yes, there's tolerance, but not to this degree. And yes, there's tolerance, but why isn't every other baby in this unit who's been on, know, sterling periods of time, doubling tolerance? And then sometimes it would be the, well, we're just not giving them enough.

And for a lot of these patients, these were doses of 0.1 to 0.18 mg/kg/hr of morphine with Versed on top of that. And so I'm like, this should be enough for this patient population. And so it really prompted us to look for other things to a Christmas point. We looked at, there underlying reasons for pain? So sometimes in some of our babies it was they had a kidney stone because we'd use a lot of waste eggs or...

Daphna Yasova Barbeau (10:01.501)

Mm-hmm.

Alex Oschman (10:24.739)

there were other things that we just hadn't really looked at. But we ended up going to, well, what else is there? And I think this is where it's really important now with our population is looking at, yes, there are NICU babies, but that doesn't mean it saves them from those other disease states that we would look at in pediatric or adults. And I think that's a mind shift for neonatology.

Ben Courchia (10:45.386)

Absolutely, absolutely. And I think that to go back to that, think it's interesting that in the papers that have been published, it seems to be pretty clear that the diagnosis of delirium, the presentation of delirium is a combination of what is described in your paper as well as both predisposing factors and precipitating factor. Predisposing factors being

the background characteristics of the patient, such as the age, the cognitive impairment, or mental delay, et cetera, and precipitating factors such as triggers, hypoxia, hypoglycemia, sepsis, surgery, mechanical ventilation, and medications. And Karishma, I didn't really like the fact that you said that people had to be believers because it is something that's been very well described in the adult population. It's something that is being addressed by our adult colleagues, something that is being addressed by our PICU colleagues. And looking at most of the papers,

Daphna Yasova Barbeau (11:26.771)

Yeah.

Ben Courchia (11:37.782)

It's interesting to me because we're definitely under diagnosing delirium and yet the incidence reported is reported to be 22%. And so taking that into account, we're probably seeing more delirium than we know. And so I think that there's definitely a need to be more attuned to that. I think one of the biggest issues that is brought up is obviously the fact that assessing delirium is difficult. And there are several tools that are

Daphna Yasova Barbeau (11:45.491)

Mm-hmm.

Ben Courchia (12:07.682)

being described, but it seems that they each have some limitations. Can you tell us a little bit about what's available for our neonates and which ones should we be looking at?

Karishma Rao (12:19.072)

Yeah, I didn't mean to call out the non-believers like that. But I do think it is a challenge, right? Like I think with anything that you're assessing or you're diagnosing, I think having it on your differential is the number one step in considering that it's a possibility. And like you said, it's largely under recognized. It's very well described in the adult literature. But I think when it comes to the neonatal population, the ability to diagnose it is or assess it is so challenging that it

Ben Courchia (12:22.062)

You

Karishma Rao (12:48.618)

automatically, I think, makes people either dismiss it or minimize the role that it could be playing.

Ben Courchia (12:55.064)

But what's interesting to me is that when you look at the potential risk factors for delirium in the adult population and in the PICU, first of all, it's all the things that we do. And it's all the things that we do to an extent way worse than the... So like our babies stay on mechanical ventilation way longer than adults. Our babies are staying in the ICU way longer. And so when you think about it, we should be the place where we should be seeing this probably more. it's definitely...

Daphna Yasova Barbeau (13:00.211)

It's, it's of.

Daphna Yasova Barbeau (13:04.027)

It's all the babies. Yeah.

Daphna Yasova Barbeau (13:11.431)

Way longer.

Karishma Rao (13:13.088)

Yes.

Daphna Yasova Barbeau (13:21.341)

that and the polypharmacy. We've touched on that briefly, but sometimes I think we don't recognize until the nurse says every single medication on rounds, which is rare, of how many meds the babies are on.

Karishma Rao (13:25.067)

Ha ha!

Karishma Rao (13:31.244)

Thank

think you're making Alex happy right now.

Alex Oschman (13:37.751)

been this big reprieve of like stop giving the baby all these meds like let's do non-pharmacologic let's do other things like let's not treat this with you know pain insubordination I'm not saying don't treat pain but I think we've swung the other way where now it's we have to make sure they're a hundred percent comfortable they can't have a withdrawal score higher than one they need to have pain scores of zero and I think that there's a balance and I think delirium is kind of showing that

these high doses long term. I we knew they probably had side effects. Everything does. And we're kind of seeing some of that now.

Daphna Yasova Barbeau (14:13.265)

I'm especially interested when we think about these babies who are on long-term medication, all the long-term medications. I think it's something clicked for me in these last few months of interviewing so many people is that we forget that these babies, especially when we're talking about medication metabolism and remembering how the organs of these, especially the preemie, there are lots of types of babies in the NICU, but most of these are long-term preemies, let's say.

I mean, their organs are literally developing as they're sitting in the unit with us and we're adding more medications to them. And then they're having these challenges like feeding and respiratory distress and illness. we're like, but the same meds should probably be the same. We'll just keep adding more meds. But I think it's hard for us to even recognize like the dynamic changes that are happening in that system, which in fairness, I think makes our patients

more complicated sometimes than the pediatric patient or the adult patient.

Karishma Rao (15:10.704)

Great. Yeah, I do, before I think I address Ben's exact question, I do want to say that, you know, that it's very true. I think you're talking about the most vulnerable population, right? So like delirium is going to occur even in an adult population in the most vulnerable, like the ones that are less mobile, the ones that are sicker. And so it's not a stretch to imagine then that our most vulnerable neonatal population are just going to be at that much risk if not higher.

But I think when it comes to your specific question about sort of assessing and tools, think the one thing that's really important in terms of the assessment, and we'll talk about the CAPD tool because that's the one that's used more commonly for delirium,

Ben Courchia (15:45.196)

Yeah, definitely hijacked my question a little bit.

Daphna Yasova Barbeau (15:49.549)

I'm sorry, especially since I have questions about pain scales moving forward.

Karishma Rao (16:03.86)

and is validated even in neonates. But the one big thing that I think stood out to me in kind of a lot of our reading was the role of the caregiver. So whether that is the parent or a nurse that is familiar with the patient, that role of them assessing and them seeing the changes in behavior or cognition is really, really critical in sort of allowing the physician and the team to kind of get to that conclusion.

because a lot of times when you talk through delirium, it's sort of this acute change in your cognition or your mental status and it sort of fluctuates. It doesn't stay the same throughout. It kind of comes and goes. And that's true for how it's described, I think, in adults and pediatric population and also in the neonatal population. So the role of somebody who's consistently there and knows the patient is very, very critical in kind of having it on your radar assessing.

And then I think one, when it comes to sort of pain and sedation scores, think our scales, I think Alex will talk a lot about this and we've had to do a lot of work with that even with an ARNQ to kind of get to the point where you could even consider a CAPD tool for our patient population. We first had to lay the groundwork over a couple of years to kind of transition from the scales that are just broadly used for every patient population. Alex, do you want to elaborate on that too?

Ben Courchia (17:29.134)

.

Alex Oschman (17:31.639)

I think a little bit with the CABD tool, your comment of which or question of like which tool should we be using, I think the CABD is one of the more commonly used ones in pediatrics. And I think the thing to remember is that it is validated in neonates. I will clarify that is not validated in premature neonates. And the CABD tool, while it was validated in neonates, it was not validated in NICU patients.

So when it was validated, it was mainly validated in like more, I would say healthy neonatal patients. So I like to say that because people always give me the caveat, well, they're not a NICU baby. But the thing that is very nice about the CABD tool is that the comment user can say, well, how can we extrapolate that to a neonate or a young infant? Well, it does have developmental milestones that it kind of has for you to look at to kind of help you say,

Well, how am I supposed to look for eye contact in a two week old? Well, it gives you like the behaviors that you should see. And so I do think luckily enough, the CAPD gives us a tool that to be honest, I feel like has a lot of validation and useful symptoms to look at compared to even some of the other tools that we have for withdrawal and pain observation.

Ben Courchia (18:56.558)

Yeah, and it takes a few minutes to complete. And it seems pretty straightforward in terms of interpretation. think, correct me if I'm wrong, in order to make a diagnosis of the delirium, I think you have to score nine or more, if that's correct? Yeah. And it seems that's something that could be done fairly routinely in the NICU on patients that are actually considered at risk. Daphne, I'm sorry. You were going to say something.

Daphna Yasova Barbeau (19:20.497)

No, I just wanted to clarify just for people who are listening, that's the Cornell Assessment of Pediatric Delirium. If people are wondering what CAPD stands for, but like you said, Ben, it's a really easy tool to use. But I think what you're highlighting is both, we've been mixing and matching, but one, in assessing pain to put babies on medications. And then two, once they're on all these things, like let's assess what their delirium scores.

It sounds like you're saying we should really have a standardized approach to those things in our units. And for people who are in their cars, listening, they're walking their dogs. Like, I think it's important. Do you know what's pain scores your scale your team is using? And I think most neonatologists don't. And if you do know, like, what is your pain protocol policy? so I'd love to hear about, I know this is a, kind of a benchmarking place for you guys at like.

How have you done this in your own unit about education and using a standardized approach and making sure then, you know, as a part of your QI, like how good are you guys at following that standardized approach?

Alex Oschman (20:29.047)

Well, I will say for we talk about the details of like our policies and how we've kind of standardize our approach. You're not wrong in terms of it sounds confusing. And I think it's because when you look at it, know, assessing pain, sedation, agitation, delirium, I'm going to say hyperalgesia, I want talk about it. It's complicated, right? Because they're all sort of intertwined, the ability to really delineate.

Is this pain? Is this agitation? Is this delirium? Is this air hunger? What is this? It's very hard to delineate. And so that's why I do think you may not have a black and white answer. It's probably honestly a little bit of multiple things, but having that standardized approach and having a somewhat objective way to look at, okay, what are pain scores? What are withdrawal scores? What are your delirium scores?

what's going on with the patient and then looking at it as a whole picture, I think will help us serve our babies so much better in terms of really trying to pinpoint why are we seeing what we're seeing because then we might be able to treat that more versus throwing like an all in approach.

So, Krish, if you want to talk about how we've kind of standardized our pain withdrawal and sedation.

Karishma Rao (21:48.94)

So one of the things I think that, because I was a bright-eyed bushy-tailed fellow when I was like, my god, delirium scoring, we ought to do this. And I went to Alex and I was like, Alex, help, you know, let's do this in the NICU. And she was like, Krishma, we don't even use the right, like, yeah. She was like, we don't even use the right withdrawal scale for like half of our population. We're, you know, using NAS.

Daphna Yasova Barbeau (22:08.327)

Best of

Karishma Rao (22:18.59)

scores for kiddos that are like six months old and that is wildly inappropriate. And so we, think the first step that we did was kind of figure out gestational cutoffs at which we figured that we would no longer use NAS sort of withdrawal scoring in our unit and kind of move to more watt scoring. that when

was that like a couple of years ago or maybe a year ago, Alex, that we kind of standardized that in our unit. We did a whole lot of education and kind of helping people understand why we would use a different scale. And ours is, think, what's score beyond 44 weeks corrected. And especially for a patient that is not, you know, especially for patients that have been in the NICU and it's not considered maternal exposure related. So that was our first step.

and kind of making sure that we're on the pathway to even appropriately using tools like CAPD. And the next part of our QI is we do it sort of selectively for patients that are on continuous drips now. So we mainly encourage the CAPD's tool. Sorry. Mainly encourage the CAPD scoring to be done in patients that are

that are on continuous morphine or versed drips at this time. So for a patient greater than 44 weeks or so that is on continuous drips, then we encourage CAPD scoring and then we go from there for those kiddos. But at this time, we're working on having cutoffs for gestational age and sort of more intentional.

monitoring of delirium in our unit. And it's a continuous work in progress where we worked on educating and ensuring that the CAPD tool is done. Because the other part that we had to work was to get it into our EMR system so that people could actually get to the CAPD tool in the NICU and not just in the PICU or the CICU and then had to educate the nurses on how to get it up. And the same thing that you said about, you know, or it's validated neonates, but

Daphna Yasova Barbeau (24:09.287)

Ha ha ha.

Daphna Yasova Barbeau (24:24.723)

Mm-hmm.

Karishma Rao (24:33.612)

know, eye contact and things like that. There's a whole chart for it that comes with the CAPD tool, but a lot of times nurses would get into it and be like, I don't know what to assess this for. And so we had to show them kind of how to get to those other pieces of charts. So we've, we've really had to chip away piece by piece and it's not as easy as saying,

Daphna Yasova Barbeau (24:37.351)

Mm-hmm.

Daphna Yasova Barbeau (24:42.846)

huh.

Karishma Rao (24:52.316)

we know delirium can happen, then let's start doing the CAPD scoring. I think you want to make sure you're using the right tools for pain and sedation assessment in your population in the NICU, because every NICU is a little different in terms of what population it houses. So making sure you have the right tools for your population and then working through the barriers with the bedside staff and implementing it and getting buy-in was critical.

Ben Courchia (25:17.818)

I was going to say in the article that I was reading, you mentioned a single study from the PICU where the ability to protocolized sedation along with environmental modification resulted in a 40 % decrease in the rates of delirium. So clearly there's a big role for that to play. I think I'd like to focus a little bit and not have to rush at the end of our interview to talk a little bit about how do we approach this. Because what's interesting about delirium is that

Karishma Rao (25:18.572)

Thanks.

Ben Courchia (25:47.966)

the consensus, and it seems to already be a consensus despite the fact that it's an under recognized pathology. It's not really about pushing medications. It's about reassessing your care overall. And it seems to me that I forget which paper mentioned this. There are things that are considered modifiable, but in the NICU may not be so modifiable. So duration of mechanical ventilation is sometimes something we're victim of, and there's not much we can do about that. However,

Daphna Yasova Barbeau (25:56.157)

Right.

Ben Courchia (26:15.746)

there are opportunities for us to actually work on what is known as, I love that term, the delirium genic medications. I really love that term. And especially limiting exposure to benzodiazepines. This is one that comes back very, very frequently. Another one obviously is limiting exposure to opioids. There's a lot of talk about Precedex, dexmedetomidine, and how maybe we could use these adjunctive medication to try to reduce the amount of exposure for our neonates.

Daphna Yasova Barbeau (26:23.315)

Yes, sir.

Ben Courchia (26:45.378)

The other term also that I saw coming more and more is multidisciplinary, trying to really have a 360 approach to patients in order to minimize the risk of delirium, but also a little bit like NAS, trying to maximize non-pharmacological interventions, decreasing noise, minimizing sleep disruptions, clustering cares, creating stable familiar environments for the infant. Can you talk a little bit about how do we approach

a comprehensive model for these babies in order not just to manage delirium, but also to stave off delirium.

Karishma Rao (27:21.416)

Alex, do you mind if I take the first part of that non-farm piece? I just want, I, I, I'm just very amused that you picked up on the word deliriogenic and actually highlighted it. was something that I think Alex and I even talked about whether we should include it our paper or not. So I love that it caught your attention. I think it's very, very important. I think delirium is probably one of those pieces that really highlights the importance of

Ben Courchia (27:40.802)

Yeah.

Karishma Rao (27:51.404)

Just looking at the baby as a whole. I can tell you it drives me absolutely crazy to see like one of our post-term BPD-year babies in a darker room or not a window room. And I think our charge nurses probably, I think they're probably a little sick of me to be honest because I always am asking for them to be like a lit up space or a better more appropriate space. But I think,

Daphna Yasova Barbeau (28:18.163)

I'm going to send this to my team after we're done, just so you know.

Karishma Rao (28:20.072)

Okay. It is so critical though. Like we are now in a place where we appreciate, right, that the premature baby needs to not be overstimulated. They need to have their light and dark cycled, et cetera. But why don't we do that same advocating for the older population, you know, where you can see a baby that's corrected like

three, four, five, six months that's just sitting in a dark room next to a baby in an isolette and you expect them to not have an impact on their mentation and that's think a little unfair to them. And so I think all of the delirium literature really focuses on simple pieces like that.

I think simple pieces of adjusting your sleep-wake cycles, light and dark stimulation therapies. And I think the multi-disciplinary piece is so, so important. One of the things that we are really fighting, and I want to put a plug in for, is early mobility. And it's sort of growing as a concept in NICU's. will admit that I was very uncomfortable with this piece at first, but over time I've become a believer and...

I've used that term so many times today, I guess. You can see it's hard to convince me of something, I guess. But the early mobility piece is very important. And they found that it actually helps reduce the onset of delirium in some patients by quite a significant amount. Some papers even quote 40%. But just goes to show sort of the importance of, even if you have a critically ill child, some of these therapy pieces, interaction pieces,

light and dark pieces are so critical in being able to reduce the overall burden of the morbidity for the patient. I think besides that, there'll always be always reassessing your patient for what is the etiology, what is the cause, what are the modifiable other factors besides medications like even morphine or benzos.

Karishma Rao (30:33.098)

What else can you modify? Is there other electrolyte imbalances? Are there other pieces to this that you could deal with so that it makes the other pieces a little easier to manage? I'll have Alex talk about our delirium medications.

Alex Oschman (30:48.811)

Yeah, before I touch on the medications really quick, I also want to add to Karishma’s comment about, you know, those non-pharmacologic pieces. So, you know, in the PANDEM guidelines, which are the pediatric guidelines for pain sedation and delirium. So also great that we have those. They're pretty recent. You know, they talk about, you know, management is really prevention and part of management and prevention. You know, they use that brain maps algorithm, which I really like. So brain maps is an acronym that says you should bring oxygen

remove reduced allergic medications, work on environment, solve some underlying issues like infection, immobilization, organ dysfunction, metabolic disturbances, wait full periods, pain-incentive medications. So really, that really goes to your point of like, really, we should look at the whole patient and look at all the things that we can maybe fix knowing that we're not going to be able to fix anything. And so before I talk about meds, I like to focus on the first one, which is brain oxygen.

So when you think of most of the patients we're talking about, while we're talking about all of NICU babies, a lot of these patients do tend to be our chronic older patients, particularly our BPD patients. And I think sometimes looking at the whole baby and looking at what we're doing, because we always want to wean the ventilator. That's our goal, we need to wean their ventilator. Well, sometimes when you wean their ventilator, they're not quite ready. They've already been in the unit for eight months.

them being in there a couple more months is probably not going to hurt them. But we wean their ventilator and their air hunger component, right? It's really hard to assess that. They can't tell us that they're air hungry and that they're struggling, that we see it in their agitation and irritability. And what do we do for that? We give them more drugs to make them more comfortable. And so I do think really trying to look at, are we being too aggressive with our ventilator weans? Are we not giving them enough oxygen? Is this air hunger? And sometimes even when you recognize that,

It's hard to say, okay, maybe we need to give them a little bit more support, knowing that it's going to take them a little bit longer to wean down, but then we can give less medication. And so just want to put a plug for that in. And talking about diligent medications, I think the guidelines have helped us a lot. There's a lot of data outright about benzodiazepines. Neonatology already hated benzodiazepines before in our preemies and our newer dates, and so it's easy for us to say, let's stop using them.

Alex Oschman (33:14.873)

I think the part I would like to emphasize too, and Ben you mentioned this when you talked about this, it's not just benzodiazepines, it's opioids too. And so I think it's easy to fall into this group of, we're minimizing benzos, but to minimize our midazolam and our lorazepam, we're going to turn the morphine up to make up for that. We struggle with that a lot.

And then you go up in your morphine and you're like, well, they're still really irritable. They're still really agitated. I'm like, well, you're giving Q2 morphine boluses and your morphine dose is double what it was. So you could get your benzodiazepines dose down and you're still contributing. So I think that's the recognition that your opioids can cause this too. And it's not just benzodiazepines.

Karishma Rao (34:03.902)

And I think to Daphna's point earlier that we need to also recognize that these are babies that are still developing, that their organs are not fully developing. Like their morphine metabolism is significantly different in your neonatal population compared to older populations. And all of these things contribute, I think, to making that our population particularly vulnerable. And so I think you need to have sort of

global recognition or understanding of those factors that probably interplay.

Alex Oschman (34:39.969)

And I think dexmedetomidine, so I didn't address dexmedetomidine or Precedex. You know, it's really kind of been the, I don't want to call it a miracle drug, right? But from a neonatology perspective, right, it's been the drug that we can use that, you know, there's not long-term studies, but right, if you look at the mechanism action, right, it works on alpha Y, alpha two receptors. We've used Clonidine for a long time in our NAS babies.

It doesn't seem to have, at least that we have found, really like a negative long-term effect for using it. So it seems to kind of be the drug that's great. We can provide some sedation and not have some of our side effects. I think part of the problem, and I don't know if you guys have noticed this too, dexmedetomidine is great, but it doesn't provide the level of sedation or relief of irritable agitation that we need it to.

It works really great for some patient populations. And I think that's where neonatology is having to go more for. We really need to look at every baby as an individual baby and not just say, and a few babies can get these things for pain dissipation. Because in your patients who are BPD, CLV, they have a significant degree of that air hunger component. It just doesn't get there most of the time. And then I think, know, medication-wise, I wish I had a magic answer for you, because I know we're sitting here talking about limit your benzodiazepines.

Daphna Yasova Barbeau (35:48.723)

Hmm.

Daphna Yasova Barbeau (35:59.325)

Yeah.

Daphna Yasova Barbeau (36:04.847)

Ha ha.

Alex Oschman (36:07.245)

limit your opioid exposure, use Precedex, which won't get you there. That's the main problem for us. It's probably the main problem for pediatric ICU patients too. We don't have good options. We don't have good options that don't bind to GABA receptors and benzodiazepine receptors and opioid receptors, all receptors that cause this deliriogenic effect. We don't have good drugs.

Daphna Yasova Barbeau (36:30.535)

Yeah. But I think your point is well taken though, despite not knowing that much about the medications, I feel like neonatal healthcare staff still knows more about those medications than they do about developmental care. And so I think that's such an important point that you highlight that if we really, really focus on developmental care, maybe we don't get there to begin with. Maybe the pain scores aren't so high. Maybe they don't need that medication. Maybe we don't have to look for withdrawal and delirium if we don't get there.

Ben Courchia (36:30.606)

Mm-hmm. Mm-hmm.

Daphna Yasova Barbeau (36:58.675)

I also wanted to highlight something that you guys said. We focus a lot on the delirium medications, but there are patients that can have delirium without being exposed to a lot of those medications. Is that right?

Daphna Yasova Barbeau (37:16.328)

Go ahead, Chris.

Karishma Rao (37:16.876)

Sorry, to agree a second. Yes, that is right. And I think it comes down to sort of the brain maps piece of it or the underlying causes of like your electrolyte imbalances or infection. Other factors that could already take the vulnerable neonatal brain and sort of precipitate the state with a sort of inciting factor or a precipitating factor on top of it for sure.

Ben Courchia (37:46.487)

And

Alex Oschman (37:47.257)

have the framework to show us that this non-pharmacologic and developmental approach can be very effective. So if we look at it's now called and it opioid withdrawal syndrome, I've been out long enough that it was not that before. Right? Like we thought that these kids needed scheduled morphine. We thought these kids needed Clonidine and not that they don't, but right? All the papers that came out in the Eat Sleep Consult is literally the poster child for non-pharmacologic

interventions can significantly decrease our medication use. And I think when we look at that and contribute this to the worm, I think we can find the same thing.

Ben Courchia (38:25.834)

So this is a terrible segue, but since we have very little time, let's talk about pharmacological options for these babies. Because obviously, it seems very clear from our conversation that, number one, delirium shines a very bright light on NICU management in general. I think that units that have very progressive feeding protocols, very aggressive sort of ventilation strategies might find themselves dealing less with delirium because

They'll minimize time on vent. They'll have babies on full feeds that are growing well. So it's interesting how this might underpin everything that we're doing. And it seems very clear that non-pharmacological options are the way to go. Reducing these offending stressors, stimulants, is what should be done. But there are situations where this doesn't work and babies need to be treated. And it seems that the medications that are considered for the management of delirium

include your typical antipsychotics, such as Haloperidol and the atypical antipsychotics like Risperidone, Quetiapine, Olanzapine, et cetera. But there's not really one that has been anointed as the right medication. seems like we all dislike every single one of them. But I'm just curious that in your experience, I've seen from the case reports Quetiapine mentioned frequently.

What should be the first thing that comes to mind in patients where all these non-pharmacologic interventions have not succeeded? And unfortunately, medical management is now considered. What is your advice and what is your approach?

Karishma Rao (40:10.22)

think you hit the nail on the head when you said that there isn't one sort of go-to drug for this and I think it's a little bit based on sort of center experience or comfort and we, think Alex, correct me if I'm wrong, but for the kiddo that we had initially done sort of our like case on, that little guy had gotten the atypical antipsychotic and those are sort of usually been the kind of go-tos. I honestly have not come across just even in like chatting with people or anything else a lot of haloperidol use. I don't know that we've really seen that in the neonatal population but I think a lot of people have gravitated towards like quetiapine or risperidone  or so. Alex.

Alex Oschman (40:59.769)

Yeah, so, you know, I think it's hard. think, I think initially when people hear the word delirium and like you should treat it with medication, hear HFLA and antipsychotics, that gives people a little bit of pause, as it should. I'm going to reference again the PANDEM guidelines, because again, I do love that we have, you know, this document that gives us some help. It does recommend that we should not routinely be using them, which I agree with. Right. It's really the use of those patients that have refractory delirium where you've tried a lot of other things. And that's

Daphna Yasova Barbeau (41:22.054)

you

Alex Oschman (41:28.867)

kind of where we have gone. We have used an atypical antipsychotic, I would say, probably three to five times. So not very frequently. We usually try to manage these patients with other methods. And so don't think there's a right or wrong answer. Your two main ones that are used, the ones in the literature the most is cation. You'll see risperidone in there a little bit as well. And they're both similar drug classes.

To me, your two big differences to look at between the two of them is what they're getting with dosing. So we have some dosing published for both of those. So to me, either one would be fine. Dose form, as the pharmacist, that's usually what I think about. And so when you look at cotyping, it only comes in a tablet. So you don't have to crush that, mix it with water, and administer that. So that can be a plus minus for your institution.

Risperidone comes as a commercially available liquid that's a mg/mL, which means you can often measure doses pretty easily with the commercial concentration. So we have only used Risperdal or Risperidone in our VEQ primarily because it comes in a commercially available liquid. That liquid does have benzoic acid in it, so some places don't like to use that because they don't like the excipients that are in that. Our PICU primarily uses cotyledons. That's because their patients are big enough that they can use the tablets and not have to crush them.

But I don't think there's enough literature out there to really say that versus Risperdal or Quetiapine, which one's better.

Daphna Yasova Barbeau (43:00.847)

Thank you for that review. We've talked a lot about babies on continuous strips and I recognize that a lot of units are saying like, okay, we're going to do what we can. We're not going to put babies on continuous strips, but they may have like a lot of intermittent dosing of short acting medications and that creates its own problems. I wonder maybe Alex, you can speak to the benefits of

the longer acting medications and kind of the med review of babies who are getting intermittent dosing.

Alex Oschman (43:36.129)

Yeah, so for a lot of our patients, know, we typically give benzodiazepines with confusion w midazolam. There is data out there to suggest that lorazepam may be less deliriogenic, primarily from the fact, you know, you're kind of doing it intermittently, giving a dose, it's coming down. So, you know, again, having some of that drug-free period in your interval while still able to maintain, you know, decreased irritability and agitation is beneficial.

And so we will typically, one of the things we try to do is come down on our benzodiazepines rip, but get them to like a scheduled lorazepam. And we try to do Q8 first and see if that will get them in a good a Q6. Something else that we have started doing, I don't know if this is going to hurt or help delirium, but I don't have a lot of tools. We have started using Gabapentin a lot more. We're selective in who we use it in. We try to go through and think of what's going on.

Do we think this mechanism of how gabapentin works might be helpful? Is this a chronic gut patient? Maybe there's some visceral hyperalgesia that maybe that's what this is manifesting as. And so gabapentin is another tool that we kind of use to help with that. And sometimes it works and sometimes it doesn't. And that's probably related to what's their underlying reasons. I don't know if that totally answers your question.

Daphna Yasova Barbeau (44:54.961)

Yeah, no, I think that was helpful. And as we're closing this show, our time together, I'm really invigorated, empowered by your collaboration. And I want to talk, I want to highlight that. I want people to recognize, I guess I'll, Krishma, maybe you'll tell me what, like, what is the value of having a, you know, a clinical pharmacist at the ready, on rounds, open for discussion? You know, what

Tell me about the value Alex brings to your team.

Karishma Rao (45:27.488)

Gosh, this is going to become like a love song to Alex, probably become really weird, I literally, so Alex, I primarily round on our chronic lung and BPD team. Those babies are my jam, our pre-trach and trach kiddos. And Alex rounds with our team almost consistently. I have actually texted,

Alex multiple times while she was on vacation and I suppose I'm slightly embarrassed to admit that but it is to me I think having of course everyone's going to say that and everybody does say that but it is invaluable and I don't think that I would have understood or recognized half as much as I do about these drugs about the interplay of the role of polypharmacy

or even how the neonatal metabolism might be different or impacting them differently from the pediatric population or adult population, I would have had a much more scant understanding of this, I think, had it not been for Alex's expertise. And so I think I would encourage anybody out there to really look at everybody that is working in your NICU and see how you can leverage.

people from all other disciplines to really use their experience to enhance yours. All I knew when I was a second year fellow was that we had a kiddo that just was on massive drips and we bolus and seemed to be getting worse and getting better. that's when

one of my attendings then and Alex were like, do you want to talk about this case and look at what we did? And then we did the anti-psychotic and then it worked. And that's what opened up my whole mind and world to this, to this world of neonatal delirium and try to advocate for that piece. So it is, you, got to have your pupils.

Ben Courchia (47:27.406)

I think it goes to show also that whenever these opportunities present themselves, to just say yes to discussing a case, to maybe partnering with someone else on a project can really open probably the doors to sometimes even a career defining project. mean, I think that's something that should not be lost on people. And it's always great to see clinical pharmacists.

Daphna Yasova Barbeau (47:27.964)

Hehehehe

Ben Courchia (47:53.238)

integrated into the team as well as Alex is and seems to have such an impact on your clinical day to day. Karishma, Alex, thank you so much for making the time to be with us today and to talk about this important topic. We're going to link all the various papers that we have discussed. One of the papers that was mentioned repeatedly obviously is the 2022 Society of Critical Care Medicine Clinical Practice Guidelines on Prevention and Management of Pain, Agitation, Neuromuscular Blockade, and Delirium.

in critically ill pediatric patients with considerations of the ICU environment and early mobility. We will link these papers in the show notes and people can find that on the webpage or on the episode player. Thank you both for making the time. Congratulations on this great work and see you around the bend.

Karishma Rao (48:40.374)

Thank you for having us.

Alex Oschman (48:41.699)

Thank you.