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Episode Transcription

Kali Dayton 0:05
This episode, let’s dive deep into alcohol withdrawal. We all have and will continue to fight the tenuous battle of alcohol withdrawal that often turns into delirium. I brought an expert with valuable insights into some of the most recent and important tools we had to help patients survive and thrive during and after alcohol withdrawal.

Dr. nosey, Anosie, Thank you so much for coming on the podcast. Do you mind introducing yourself to our listeners?

Dr. Obiajulu Anozie 1:35
I am at Northeast Georgia Medical Center. And I work in the department of Critical Care Medicine. And my main interests in critical care, quite frankly, are I love vents.I love cardiac physiology. I love anything to do with physiology, but in particular, cardiac physiology, those are the two main two things that I that I’m highly passionate about in the field of critical care. But I mean, as an intensivist, we, you know, you we manage so many different different things.

Kali Dayton 2:09
All of it right?

Dr. Obiajulu Anozie 2:10
Yeah, exactly.

Kali Dayton 2:12
And I reached out to you, because I saw a really great post on your social media, which I’ll include the handle in the show notes here. But you had mentioned certain medications to avoid. And what sparked my attention is that you mentioned benzodiazepines.

Dr. Obiajulu Anozie 2:31
Yes.

Kali Dayton 2:32
And I really wanted to dive into that, especially into alcohol withdrawal, as you know that this podcastis all about advocating for patients to be as awake and mobile as possible. But alcohol withdrawal can make a big barrier to that, and especially with the way we’ve been treating patients.

So I know we’re all critical care clinicians here on this podcast, but just to give a big overview. Why are we concerned about alcohol withdrawal? What are some of the risks and why do we use that sedative so often?

Dr. Obiajulu Anozie 3:05
Yeah, you know what, when I think about alcohol withdrawal, and when you think about the risks, and and the morbidity and of course mortality as it progresses, that it can cause a patient. I like to think about neurophysiology and and view, you know, alcohol use disorders as something that imbalances brain chemistry.

And you think about the seesaw effect between excitatory and inhibitory neurotransmitters, and the effect that alcohol has chronically over time, kind of down regulating, inhibitory neurotransmission. And with an adaptive, adaptive response being upregulation of excitation to have balance, and then when someone stops drinking alcohol or after a certain amount of time when there’s that much downregulation of an inhibitory neurotransmission.

People develop tolerance and then withdrawal, and that withdrawal can start within six hours of seizing alcohol, but the effects can be quite dramatic. It’s more than just behavioral effects. There’s physiological effects, there’s effects on cardiac physiology, there’s electrolyte abnormalities, there’s impediments just towards normal braintransmission between excitation and inhibition resulted resulting in confusion, seizures, altered cognition.

And when you think about, you know, mobilizing patients and liberating them from intensive care units, it’s definitely you know, going to be a barrier.

Kali Dayton 4:53
Absolutely. And I think because of this fear for seizures, throughout the decades we’ve run to benzodiazepines. And initially, I think that was our only tool. Right? I don’t think we knew we had access to anything else, historically. And now, I mean, alcoholism is a public health crisis. It’s the high rates of patients withdrawing in our ICUs are so high. And we’ve been treating this for a long time. But now we have this huge spectrum of how we’re treating alcohol withdrawal.

And I’m seeing that as I’m working with teams, that some are still using CIWA protocols with Ativan and Valium, and hightest dose benzodiazipines.

And I think that initially started because we’re worried about them seizing, right, we have to prevent the seizures. But why are benzodiazepines so dangerous? even and especially during alcohol withdrawal?

Dr. Obiajulu Anozie 5:55
Well, I think, firstly, you can definitely benzos are classically, you know, the mainstay are considered first line therapy when it comes to alcohol withdrawal disorders. But I think it’s quite interesting, because when we think about, there are other classes of medications that people have used. If you look, even back in the 70s, they were using barbiturates even, you know, all the way back in the 70s. And like, there’s some there’s some scanty literature out of Europe for that, but um, didn’t know that.

Kali Dayton 6:29
It just didn’t get standardized?

Dr. Obiajulu Anozie 6:31
Well, it what you saw was really small studies, nothing standardized, I think the fear with benzodiazepines or is, you know, we think about the spectrum of alcohol use disorders and an alcohol withdrawal syndrome.

You’re looking at patients that develop agitated delirium. But in the intensive care unit, there are people there are patients that develop agitated delirium, and some of them are related to, and some of them are not related to, to alcohol use. And there’s considerable overlap when it comes to agitated delirium. And alcohol withdrawal being kind of a diagnosis of exclusion is sometimes it’s hard to, to to delineate what’s what. So if, if it’s not an alcohol use disorder, and we’re just joining benzos at it, then what are we really treating? There are patients that are just a little bit more susceptible to the overall effects of benzos, especially in the elderly, who may have disorders of cognition, that are only potentiated by giving benzos.

I think, the pharmacological profile of benzodiazepines in general, especially when it comes to, to alcohol use disorders, it lends itself to a lot of dose stacking, especially in people that are patients that are benzo refractory. So you keep stacking on and stacking on and stacking on and eventually just kind of worsens delirium. I think it’s also there’s something interesting.

That has also been described, as I’ve seen it, rarely, I mean, but you do see them patients have benzos don’t work, they get this paradoxical agitation, there’s actually papers and you know, small studies on this. But you’ve seen in people in patients that are that have been given benzodiazepines have actually developed this paradoxical agitation where they develop more autonomic hyper excitation, more tachycardia, more restlessness, more delirium when they’re getting benzos. So if we’re not trying something as an alternate strategy, and just throwing more bentos at it, all it really does is increased morbidity and mortality in those patients. So at some point, we need to try and under strategy.

Kali Dayton 8:56
Absolutely. And the irony is terrible. Because we know repeatedly there are dozens of studies that benzos always lose. Their I mean, when we see that they increase mortality, then it it makes it really hard when we’re giving it to theoretically help patients survive. Exactly. They can never be used, but do use it for prolonged periods of time, especially in the acute care setting where we have altered renal function, we have these things that increase this dose stacking. We’re not always looking at the big picture.

Coming from a nursing perspective, having treated the CIWA or alcohol withdrawal patients with a CIWA protocol with Ativan and some of these facilities when I was a travel nurse….there was a huge contrast in workload, danger, just exhaustion. When I was treating it with Ativan because you give that dose, and then a few hours later, they’re coming out wild again, sometimes even more agitated, like you’re describing.

Then you run and you give them another dose. When you’re following a CIWA protocol it just says, “if they’re being restless, agitated, if they’re confused…” if they’re, you know, sometimes they’re so delirious, they can’t even tell you what they’re experiencing.

Dr. Obiajulu Anozie 10:12
mmhmm.

Kali Dayton 10:12
But they don’t have to, you don’t have to necessarily have reports of hallucinations. You don’t even have to have tremors or sweating or tech Acharya, you can just have agitation and that can validate a dose of Ativan.

Dr. Obiajulu Anozie 10:26
Exactly.

Kali Dayton 10:27
So when do you know when the alcohol withdrawal has subsided, and now you’ve got emergency agitation. And because our educational delirium is so poor, and poor nurses are left with these patients that are thrashing, they’re agitated, they’re dangerous. —-The only tool you really have left is that PRN and Ativan dose and it’s there and we’re going to run to it and give it and it makes them stop moving.

And we think that “we’ve treated their anxiety”, “we’ve made them more comfortable” now we’re keeping them “safe from seizures”. And we’re good for few hours, but it’s just gonna come back. And it’s just going to keep happening until they become over sedated. And then now they have to be intubated. Right?

Dr. Obiajulu Anozie 11:05
Exactly.

Kali Dayton 11:06
And I love that you’re asking….sometimes we mix up what we’re treating. An example I can give is a patient that I was made aware of. I didn’t personally have any contact with his patient, but it made a really good case study. A man that had a tumor on his tongue. He was a smoker. He was an alcoholic. So he had surgery, a neck resection for this mass. And he already had a peg to before he went in. He had already been lowering his dose of alcohol throughout the weeks because he couldn’t swallow effectively. He had already gone through alcohol withdrawal, I think four days before arriving to the hospital for this elective surgery, essentially.

His wife wrote down on the paper, “He has already withdrawn from alcohol four days before. He was shaky. He threw up the next day, he was fine. Please don’t treat him like an alcoholic.” She wrote that on paper and gave it to the surgeon. He had surgery. He had a trach placed during surgery.

For whatever reason, they kept him on the ventilator after after the surgery sent him up to the ICU because he was connected to a ventilator despite having tracheostomy, they kept sedation going. Two days later, they finally took off sedation. And of course, he comes out agitated.

Because he has “alcoholic” written on his history….. Boom. He started on the CIWA ativan protocol.

Dr. Obiajulu Anozie 12:33
Yeah,

Kali Dayton 12:34
it’s already, what? Five? Six daysoutside of the window from his last drink. So that he get put on CIWA protocol and gets sucked into this roller coaster of agitation- Ativan- agitation -Ativan. Being treated like an alcoholic, he continues to be on the ventilator for another few days. They take him off vent, but he still just lays there sedated with Ativan, doesn’t mobilize. He’s there for a few. I think another week.

Finally sent to the floor. Granted, they did not put them on a pulse ox. But because he’s continued to be on the floor. agitated, continued on Ativan, no one was looking at” when was his last drink? What window? What timeframe? Are we at? Is this still alcohol withdrawal? Or is this delirium? They continued to give him Ativan. He did not mobilize. He was too sedated, too confused to participate with PT and OT.

He ended up having poor secretion clearance, developed a mucus plug, and died.

Dr. Obiajulu Anozie 13:28
Oh, wow.

Kali Dayton 13:29
And we can say okay, “He wasn’t monitored. He wasn’t on a pulse ox on the floor.” But I would definitely rewind back to say, “He was mismanaged. We caused delirium, then we mistreated delirium, and mistreated this non-existent alcohol withdrawal with Ativan.”

Dr. Obiajulu Anozie 13:49
yeah. So I think that that requires one fundamental like basic knowledge. You know, I think I mentioned earlier, withdrawl could start within the the first six hours after alcohol cessation, or it could also start while someone is consuming alcohol. Just reduced your amount simply from what we mentioned before, you know, you have downregulation of GABA receptors and, and they’re not quite as sensitive. So you need that alcohol to mitigate the excitation effect of the NMDA receptors, but even that might lose its effect if you’re over time or if you’re reducing your alcohol intake.

But I think the fact that this patient, you know, had stopped taking alcohol…. you know, you can progress through autonomic hyperexcitation, starting in six hours. Withdrawal seizures you might see within 24 hours, as well as alcoholic hallucinosis which is just hallucinating, but people are still cognitively intact. And then around 48 hours, you know, 48 to 96 hours, I believe, you know, that’s when people can really go into DTS. And then they say that, you know, DTS can last up to like five days. And then you know, that’s it.

But what stands out about this patient that you’re describing is that he went through withdrawal, and it looks like he came in at his baseline state. You know, so, that should have said something right there. You know. And then another thing that stood out from what you said, is this vicious cycle. I feel like, you know, not just in critical care medicine, but on the floor, during the ER, we can get into these vicious cycles of, you know….. for instance, someone on a ventilator.

You know, they’re auto peeping, but they’re have respiratory acidosis. So we get into this vicious cycle where we increase the respiratory rate and tidal volume to blow off more co2, but really, you’re just making things worse, because they’re auto pooping worse, and co2 is actually gonna get worse, because you’re not ventilating. And you just keep turning up and turning it up until they go into cardiac arrest from mad barotrauma. So in this case, you know, he was put on maybe a benzodiazepine infusion, which only makes which which lends itself to delirium. And he developed as…

Kali Dayton 16:16
even just propofol. He didn’t even start with benzos. But that alone can cause delirium as well, you can have an emergence agitation.

Dr. Obiajulu Anozie 16:27
Yeah, it can. And then, because he had agitation, when he emerged from sedation, he was given benzos, which increased his confusion and made him more agitated. And to treat that, he was given more and more benzodiazipines. So he went into kind of a vicious cycle, where he was given more agitated, more benzos, to treat a problem that needed a different, you know, a different form of therapy.

And granted, sometimes it’s tough to avoid these kinds of cycles. But I feel like as providers, we need to be very cognizant of that, and keep our minds open to alternative diagnoses. And the history and just the history is so indicative of many things, you know, you mentioned the thing you said at first and what stood up, and he went through his withdrawal. So by all means, you know, we should have been looking for an alternative diagnosis. I mean, if he just emerged from sedation, and he was a little, you know, delirious, it might have just been sedation. You know, and that happens, but you just give them a little bit of time. And, and typically, patients are fine.

Kali Dayton 17:32
Another interesting thing in the medical record was that the family finally was able, they weren’t able to go into the ICU. During COVID, they did a brief visit on the floor. And the daughter was trying to say, “This is not him at all, whatever you’re giving him isn’t helping.” And this is documented by the nurse saying, “I explained to the family member, that this is helping him be comfortable. This is helping him.” They were trying to show how, how oblivious and how annoying that this daughter was, and saying, “I educated them on the fact that this is helping their comfort.”

Dr. Obiajulu Anozie 18:09
Yeah,

Kali Dayton 18:09
So that is such a gives a cultural insight into why we’re giving it. Because no one wants them to languish. No one wants them to be agitated and uncomfortable. But we deeply believe that that is the solution to their comfort, the more the better.

Dr. Obiajulu Anozie 18:24
Exactly, yeah. And that and that’s, and that’s a philosophy that I often challenged with people that rotate with me the trainees that typically rotate under me, my, my philosophy is usually that less is more, you know, I try to I try to take a little bit of a, of a minimalist approach, and then try to be a little bit more reactive. I tried to keep an open mind and look for alternative diagnoses. And I think another thing that people forget is, especially when it comes to agitated, agitated delirium, when patients become a little bit of a harm to themselves or to others around them because they’re agitated. There’s also another class of medications we can use, you know, some haldol, Geodon, Zyprexa, you know, those are other medications that can actually be quite beneficial adjunctively. I’ve used the medications. I’ve used those medications in patients with agitated delirium with success, and I’ve been able to liberate patients from the ventilator, just from that alone, too.

Kali Dayton 19:29
Absolutely. And I think we have to remember that antipsychotics don’t necessarily treat delirium, that’s not the solution to delirium. But when you have this hyperactive delirium, you have a rash of three or four. And there are risk to themselves, to others, but they especially then can’t use tools to treat the delirium. They can’t connect with family. They can’t mobilize, they can’t get real sleep because they’re constant motion. So then, we can use these other tools, sometimes low dose antipsychotics, dexmedetomidine, so that we can then bring in the holistic tools.

So I think that’s a that’s a great suggestion because I, I would never advocate for letting someone be a RASS of three or four. Yeah, absolutely. It’s just it’s not safe. But we have to change our expectations for safety to not just be a comatose patient, but rather a patient that’s as close to zero as possible so that we can mobilize them, so that we can get them back to reality and treat the delirium. But a lot of that comes down to recognizing and treating the delirium.If we don’t recognize that it’s delirium. And we expect patients to just be quiet and “sleeping”, then we’ll never be able to utilize those tools.

Dr. Obiajulu Anozie 20:42
Absolutely.

Kali Dayton 20:44
I will throw another case study at you if that’s okay.

Dr. Obiajulu Anozie 20:46
Sure

Kali Dayton 20:47
This is a real story. 76 year old man had a history of bipolar disorder and lithium use, as well as alcohol abuse. He lived at home with his wife and worked as a delivery driver, even at 76 years old, so he was pretty functional. He had a prolonged period of sobriety and then had a relapse and was attempting to withdrawal again at home. He came to the ED already suffering DTS, and it was unclear when his last drink was. He was combative in the ED and was loaded with 16 milligrams of Lorazepam.

Then he was sent to I think, the ICU and continue to be on a Ativan and diazepam, Valium protocol, where he was getting about 40 milligrams of diazepam and four milligrams of Lorazepam, Ativan throughout the day. But first few days, these doses kind of increase for a bit, and then about six days after the doses decreased.

So he’s down to two milligrams of Ativan, 20 milligrams of Valium. And then the doses started to increase again. So, he was admitted on January 5, by January 15, he was still getting eight milligrams of Ativan a day and 15 milligrams of Valium. And by the 16th, he was fairly obtunded, febrile and now needed BiPAP. But he continued to be intermittently agitated. And so they gave him more out Ativan, more Valium. And by the 18th, he was intubated.

Dr. Obiajulu Anozie 22:22
okay.

Kali Dayton 22:22
And they had him again on a propofol drip. And so about 11 days plus after his last drink, he was still being treated like an alcoholic or as as an alcoholic withdrawl. So maybe we all probably know, but what are your theories about what what was going on here?

Dr. Obiajulu Anozie 22:44
Well, I mean, it. And I think this, this plays back to thinking about the timeframe for withdrawal. When to search for alternative diagnoses, and also just the effect of what we do to patients and, and, and in the hospital. Like the effects of the medications that we give, you know, and how we can impact delirium, and even prolong agitated delirium with our own interventions.

It sounds like he was getting heavy doses of different benzos for prolonged periods of time, each of them with their own half lives, and taking a certain amount of time to elimination half lives that take a certain amount of time to clear the body, and with lingering effects on his mental state, and its ability to protect his own airway that ultimately got him intubated, and on the ventilator. So you know, it’s hard to just say that this is just, you know, alcohol withdrawal, DTS, without something else superimpose. I feel like, you know, on top of delirium tremens that he came in with, there were some superimposed agitated delirium, just from prolonged infusion of benzos. That’s what it seems like to me.

Kali Dayton 24:07
Yeah. And again, I didn’t to this patient, but that’s what it seemed like to me, because he’s finally getting on BiPAP 11, 12 days after admission. That’s not quite a normal DT course, right?

Dr. Obiajulu Anozie 24:21
Exactly.

Kali Dayton 24:22
He was also febrile and his white count was up by the time he was intubated. And I think he had some aspiration pneumonia.

Dr. Obiajulu Anozie 24:29
Yes,

Kali Dayton 24:29
Likely because he had been having these prolonged periods of time of being over sedated, not being mobilized. Probably developed, hospital acquired pneumonia / aspiration pneumonia.

Dr. Obiajulu Anozie 24:43
Another thing too, that’s important for people to note is that, you know, anytime the body is under stress it can react with, with with fevers, you know, tachycardia, there’s a lot there’s such there’s consider It will overlap in the realm of agitated delirium, whether it’s from withdrawal or just, or just mood disorders, or just from getting prolonged infusions of benzos.

And if the body under stress, there can be a white count there can be patients can be febrile, regardless of what they’re withdrawaling from. So I think it’s really important to keep that in mind as we search for different diagnoses for the patient, so for him, yeah, definitely, you know, a patient like him, whose mental status changed during the course of the admission and lost the ability to protect the airway definitely could have had fevers from an aspiration pneumonia, and also could have been febrile from just being able to draw on the initial face of the admission, or the high fever and high white count.

Kali Dayton 25:55
Right. And if we’re still on a CIWA protocol, looking at, you know, even though he’s now almost 14 days, out from admission to the hospital, you would fit that criteria: Febrile, tachycardic, agitated, then you goes by the just those symptoms, and you fit into that, that criteria for more Ativan.

Dr. Obiajulu Anozie 26:17
Exactly, because, and I’ve seen that too. You know, that’s another important thing, in terms of like looking over your order. And looking over your order sets, and knowing when you need to switch things up. Because having someone on a sealed protocol indefinitely, isn’t the way to go, you know, especially two weeks into the course. We know that, you know, the alcohol withdrawal itself, is unlikely to go beyond 10 days, you know, there’s a time timeframe for when these things start. And generally when they end.

I’m not saying that there can’t be patients that are outliers, but generally, especially like a two week timeframe, you know, once you’re getting towards that two weeks, if you’re still on a CIWA protocol, and the patient isn’t getting better, then you know, we really need to be looking for a different strategy. You know, it’s very easy to anchor on a diagnosis. And I really, that’s one thing that, at least in my practice, I always try to make that I’m devoid of any anchoring biases, you know, I like to make sure that everything fits in terms of tempo, timeframe, everything should fit. Otherwise, if it doesn’t fit, then you need to look out and start thinking outside the box to see what else may be happening.

Kali Dayton 27:33
Absolutely. And I think this is why we need to be talking to each other. If a pharmacist had said, “Wow, it’s day seven. And I see. And now we’re starting to increase doses again, what’s going on here, right? I see yesterday, he only needed this amount. And today, we’re increasing. And now looking at the timeframe, the window, this doesn’t add up…”— that would have been really helpful.

But the fact that has tapered down, and then started to go up, just from the records that that seems really concerning. And granted this, where this occurred, it’s a population that has probably a lot of alcoholism. It’s a really difficult thing. So I and I, admittedly have experienced it myself, you kind of get burnt out on these diagnoses. On these patients, Especially when your system has a protocol that creates this kind of scenario. And you’re always, as a nurse, having to wrangle patients and try to deal with this, it’s really difficult.

So I think that, in my experience, when we were doing a lot of the same, I worked in an ICU that had a lot of liver failure patients. You get burned out on encephalopathy, and you kind of start seeing them all the same. And so I think that might have a role to where you’re like, well, he’s an alcoholic. So this is alcoholism. And you just, you just like to have your conveyor belt approach and just give him more benzos. But what are your thoughts on have been 76 years old? And on an Ativan and Valium VIWA protocol at 76 years old?

Dr. Obiajulu Anozie 29:02
Yeah, I mean, I think at that age, it’s one of those things where, you know, you would prefer to have some adjuncts on board rather than just relying on benzos. Especially given the the elevated risk of worsening delirium in a patient that age. So for a patient like him, you would like to minimize how much you give it like, at least upfront, and hopefully, you know, if there’s a way to avoid giving it do so I think precedex is great, adjunctively. Dexmedetomidine is great, but at the same time, it doesn’t treat withdrawal.

But I certainly feel that especially, you know, we talk about this concept of neuro excitation and dexmedetomidine is one of those adjuncts that can help medicate neuro excitation. So In a long run that might mitigate how much benzos you have to give to relieve withdrawal. So I think in that population of patients, we need to look for alternative strategies and potentially adjuncts that we can use to really minimize drugs that can be potentially harmful.

Kali Dayton 30:20
I love that before phenobarbital came into vogue, I really liked to use librium, and much lower doses of librium than was even used on the detox unit. But I found that we needed some low dose librium to cover for that seizure threshold and then some dexmedetomidine on top of it. We could keep keep patients awake and mobile off the ventilator through severe DTS. For the most part, I’ve even been able to start librium on come on that was intubated on propofol and then take them off appropriate ball get the next debate it as I continue to withdraw it, that’s an exception. But I love that the adjuncts therapy and understanding that we do have to prevent seizures, but we don’t need to use just benzodiazepines to keep them comatose, or keep them free of this agitation. And then at this point with this patient when he was intubated, he was about a RASS of one or two floridly delirious, and that he continued on the CIWA protocol.

Dr. Obiajulu Anozie 31:26
And that’s another thing too, you know, when we talk about what things precipitate delirium, agitated delirium, beyond looking beyond the scope of withdrawal, you know, what about pain? You know, when you have someone on a ventilator, you have a breathing tube, you know, down their throat and or their bed bound, you know, that’s not very comfortable. And pain is a very highly potent precipitator of delirium. So once again, it’s that it’s that it’s that vicious cycle that you, too, but that’s being precipitated from biota reasons and that you’re identifying, you’re identifying agitated, delirium, Ras, have one and two or three, because they’re an alcohol withdrawal, when in fact, they’re just not comfortable. And you need to take the edge off their pain, you know.

Kali Dayton 32:19
Thank you and cue in PADIS guidelines, Right?

Dr. Obiajulu Anozie 32:22
Exactly, exactly. I’ve seen a lot of patients go on a ventilator and just precedex or propofol without fentanyl, you know, but have you taken away their pain? Have you made them comfortable, you know, from a pain standpoint. And then, like you mentioned, using the gut is a beautiful thing, if you can for for for withdrawal syndromes, because rather than giving you know, IV, we’re not exactly sure what the effect is, at least if you give something orally, it gets absorbed in a more like organized manner. And the absorption is also longer. So I think the farmer the way it reaches steady state is probably more natural physiologically than just giving, you know, a big push of IV and having a drug just jump up in its level, and then come back down pretty quickly and having to give more and more doses, if you can use the gut. That’s amazing.

Kali Dayton 33:18
Absolutely. And, again, I’m a nurse practitioner, but having done this as the nurse for so long, it was a complete roller coaster to use Ativan. It was exhausting, you don’t know exactly when they’re gonna come out of it. And so you, suddenly you’ll have a comatose patient, you leave the room, check in your other patient, and now they’re on the floor or not that I hit really hard that happened that often. But that was always my fear, “I’m going to turn my back. And they’re going to come out of this and be thrashing and be wild. And it’s going to come down to me and the liability behind it.” Whereas with librium, it was just a slow absorption over time. They had more control. They didn’t have to be comatose, we could keep them again, mobilizing and doing all these other things. For the most part, it was just so much easier.

And then understanding when he’s in that moment intubated. Again, someone has to be asking what’s actually going on here. When was his last drink? Where where are we at timewise? Okay, so he’s that alcohol withdrawal. Now he’s intubated. Why did he end up intubated? Okay, we over sedated him or he’s, he can’t protect his airway, or he’s too weak and all these other all these, this compilation of factors led him to be intubated that moment.

What are we going to do? How are we going to keep him safe?

He was probably to weak even pull his endotracheal tube out, but…. unless because he looked so uncomfortable… They started one propofol and had him at a RASS of negative three, the next six days. And so he could not have any intervention for his delirium. No family, no mobility. He couldn’t report his pain. We had no idea what he was going on. Finally, and fortunately, he was extubated after the six days and then he spent ended an additional eight days in the ICU.

And I can only imagine what that was like with him being so agitated and confused, but maybe he was two weak at that point, maybe he was had hypoactive delirium. But finally he made it onto the floor. And he spent another 16 days on the med surg floor. During his time in the ICU, he had developed to stage two pressure injuries on the bridge of his nose and on the sacrum. And he continued to develop a foley catheter infection on the floor.

Then psych said in his notes, because remember, he has bipolar disorder, that they still they insisted that this was not psychosis. It was an acute delirium. He was transferred to rehab facility after those 16 days on the floor and was still delirious and unable to walk. So he spent a total of six weeks in the hospital. He had two hospital acquired infections that foley and the pneumonia, two pressure injuries, preventable intubation with six days in mechanical ventilation, lots of work, and a lots of extra work then trying to rehabilitate him, re-mobilize him, and turn him q2 during that time.

And then what is his life going to be like as a 76 year old? That just came in for alcohol withdrawal, now what? So recommend? Let’s rewind to go back to the ER.

Dr. Obiajulu Anozie 36:20
Yes.

Kali Dayton 36:22
What would you recommend in that moment, knowing that he’s an active and serious DTS?

Dr. Obiajulu Anozie 36:28
Active and serious DTs. So for me, I would have probably started him on precedex to see how he reacted to it. And if the response is good to the sense that I could use his gut… you know, he was able to, he’s in DTS, but at least he can, he has enough and he’s cognitively intact enough to follow some commands. And using Dexmedetomidine, I can calm some of the autonomic hyper excitation, those kinds of symptoms, then I would probably put him on oral phenobarbital and add some IV phenobarbital pushes for you know, PRN.

If I couldn’t do anything, if he was just completely, completely agitated- If this is clear DTS, he’s completely agitated, he’s not going to cooperate. He’s completely tachycardic, flush, diaphoretic. And, you know, there’s no option of using the gut, then my move would have been to give them a loading dose of phenobarbital to really see if I can take those symptoms down, give him a loading dose, and then see what the response is.

You know, if after one loading dose, if a lot of the autonomic symptoms have calmed down, and cognitively there’s an improvement, then I would switch to PRN doses and start putting just phenobarbital in his in his belly along with thiamine. That’s one big thing. Don’t forget the thiamine.

Kali Dayton 38:09
Yes! absolutely. Otherwise, there’s a whole nother differential down the line for…

Dr. Obiajulu Anozie 38:13
You know, very wise, very wise neurologist taught me once, you know, give every encephalopathic patient thiamine. Like, why not?

Kali Dayton 38:25
Exactly. Yeah, no, absolutely. Yep. You kind of cross that off your list of potential patients. Right?

Dr. Obiajulu Anozie 38:32
Exactly. So, so yeah, that would have been my strategy for him, you know, can if, if, if I couldn’t get him to cooperate with me, if he’s just not there from mental state to be able to respond, I’m not gonna be able to get an NG tube down without, you know, fighting with him or anything like that. And then he needs to, I think he needs a loading dose of phenobarbital, or with precedex, and to see what the response is.

Kali Dayton 39:03
I love that concept of using precedex to then make him safer to swallow and to take orals. And I love that, um, and again, yeah, it depends on the timing, the severity where we’re at with things. But for that to be the goal to have him take orals to have a more consistent dose, lower dose. But if that fails, then we’ve got IV available.

Dr. Obiajulu Anozie 39:26
And you mentioned you mentioned timing, and you know, what I’ve what I think and one thing that I think stands out, is the concept of, you know, the what I try to frame as the illusion of time as in, we are often lulled into thinking that we have less time than we truly do, you know, and it’s perhaps because I’m an intensivist I’m a little bit more comfortable seeing patients in a state of extremists and trying things you know, before jumping to, you know, rapid sequence intubation.

At the end of the day, people have to understand that rapid sequence intubation, when we intubate patients, you know, for critical illness or whatnot that’s associated with increase in mortality. So, and for me, it’s, it’s a victory for me when I can keep a patient off the ventilator. That’s where I take my ventilator, my victories by by, you know, the patients that I don’t intubate, you know, when I was a fellow just learning how to intubate than I was, I was my victories were the people that I intubated, like, yeah, I got the airway. But now like, you know, you’re out there practicing even towards the tail end, like, you know, after my first year of fellowship, it was, it became more about prevention for me, and as an attending, it’s about prevention.

So, and being comfortable managing an airway, I feel more comfortable watching people for a while, you know, and I think, if you’re the provider in the room, you need to demonstrate that strength so that everyone draws that strength from you. Because, you know, you have an agitated person who’s, you know, not cooperating, they’re tachycardic, you know, and a big thought will be, “oh, let’s intubate, you know, this is, you know,”

Kali Dayton 41:08
It can feel like an emergency.

Dr. Obiajulu Anozie 41:10
Yeah, it’s an emergency, but even, you know, and exactly, it feels like an emergency. But even in an emergency, you often have more time than you really think. It’s this concept of the “Illusion of Time”, or as we think we don’t have any. You have time, you know, to try and start something, start some precedex, and give it a little bit of time and see if that works.

You know, start some precedex. When it comes to loading doses of, you know, Phenobarbital, it’s doesn’t have to be, you know, it ranges from, you know, 20 mgs per kg to 15, to 10, to even five. You know, there’s different doses you can give. And if you’re on precedex, or if they’ve already gotten benzos, and it’s not working, you can just alter your loading dose strategy and see if that works. But you know, more often than not, in these patients, you have time, you know, now if they’re desating down to 70s. Like that, then maybe that’s, you know.

Kali Dayton 42:10
Or actively seizing. But seizures are so rare. I don’t think we realize how rare seizures are withdrawal. But that’s our big fear. Right? And I think that adds into this sense of emergency we see severe agitation, yes, we’re worried about safety for the staff, safety for the patient. That’s why I love precedex. That buys you time that gets them down off of that danger zone of RASS of three or four. But I think we also… because of this culture of wanting our patients to be comatose and lifeless, to see such an extreme contrast makes us really nervous. And we feel safer, and more controlled, when we literally have our patients controlled and chemically restrained. But that’s sounds like that’s not your objective is to keep them chemically restrained. What is your objective with phenobarbital.

Dr. Obiajulu Anozie 43:01
me the objective with phenobarbital. If so, if I’m going to talk about the objective within a phenobarbital I have to think I have I first have to kind of talk about why I’m using the drug to begin with, you know, you’re using phenobarbital. l because you think it offers better a better pharmacological profile that is superior to benzos, you know, the seesaw effect where you’re trying to balance excitation with inhibition.

My thought process is that in patients that are benzorefractory, either there’s not enough GABA neurotransmitters to go ahead and bind to the receptors to open chloride channels to stimulate neuro inhibition, or there’s just way too much excitation. And you need something that can directly open chloride channels directly. So that’s one thing phenobarbital offers over benzos.

They both to GABAergic receptors in the open and they facilitate opening of chloride channels. Benzos makes the chloride channels open more frequently, whereas barbiturates will increase the duration that those chloride channels are open. And that all adds to neuro inhibition. But what barbiturates can do that benzos can’t is that they can actually directly open chloride channels themselves.

So if you’re talking about a patient that could be in a potentially benzorefractory state, because they’ve used all their GABA neurotransmitters are spending all their GABA transmitters just try to just to try to keep that baseline, you know, just trying to keep some kind of balance between excitation and inhibition that they’re already losing, and they’re already depleted. So then your benzos won’t do anything for you, because you’re in a GABA-depleted state.

So if you don’t have any GABA neurotransmitters then benzos cannot work. If you’re GABA-depleted, barbiturates can. Not only can they bind and open chloride channels, they can actually cause inhibition at x NMD. At, well, NMDA, actually, I think they found that it causes it inhibits other excitatory neurotransmitters in the brain, all towards the same effect. So it helps you reach achieve balance.

So with barbituates, all I’m looking for is balance. And balance, you’ll see when you’re reaching balance, you’ll see. You’ll see in the patient, you know, their their vital signs will start stabilizing, and there’ll be more calm, and that’s all you’re looking for. And for me, I’m looking to get to a point where I can start using their gut. Because for me, my strategy with using barbituates is to get a steady stream of it in their bellies. And then use PRN doses just when, you know, I need a little…. because at the end of the day, I mean, patients can still exhibit withdrawal symptoms, even if you’re on barbituates.

Kali Dayton 46:11
Yep. Yeah. And do we is the goal to make them completely free of symptoms? Can we? Should we?

Dr. Obiajulu Anozie 46:19
Well, you know, and that’s the thing, you know, shooting for perfection is, in my opinion, shooting for perfection as a perfect way to hurt somebody.

Kali Dayton 46:28
Wow.

Dr. Obiajulu Anozie 46:28
you know, you know, it’s you want tolerance, you want things to be manageable, you want them to be comfortable, but they don’t necessarily have to be made completely perfect. You know, or what the CIWA would be like a CIWA score, zero or whatever. As long as it’s manageable, you know, as long as it’s manageable, and you’ve given them a chance for their body’s chemistry to kind of correct itself, then I believe that safe.

But when you’re shooting for complete elimination of all symptoms, and it’s possible that, you know, you you give a little bit more doses than you need to. And while I don’t believe that barbiturates cause respiratory depression, or if they do, you would need an awful lot to do so. I mean, you can cause a little bit more neuro depression than you want. If you’re just chasing that perfect, completely symptom free.

Kali Dayton 47:30
Even like with precedex. I think it’s a great drug, but we can use it to get down to RASS of negative two or lower. And in my mind, for most patients, that would be an abuse of precedex. I think we can also be abuse phenobarbital. When I talked about having an Awake and Walking ICU, that most patients can and should be awake, walking, communicative, interacting with their family, and environment. All these things, and then often comes up with up is, “but we have a lot of alcoholic patients.”

Like there’s, they can’t be awake, they can’t be mobile, because they’re an alcohol withdrawal. So I think we have to kind of change this cultural expectation of how patients should present. For many ICU nurses, they’ve been trained that perfection is a comatose patient that appears to be sleeping. But a tool like phenobarbital is so that they can become manageable, safe and continue to be human. To be awake during the day sleep at night mobilized, communicate, we can treat them in a way that’s going to prevent harm and risk.

Dr. Obiajulu Anozie 48:34
Yes.

Kali Dayton 48:35
I love it you bring up this decreased risk of respiratory depression decreased are almost zero risk, right of respiratory suppression, which is one of the big setbacks of benzodiazepines, in addition to delirium is that it has respiratory depression. And so that’s how we get into these situations of over sedation and intubation whereas phenobarbital…. What do we see in the studies as far as intubation rates?

Dr. Obiajulu Anozie 49:00
Actually, a lot. So there are a few studies granted, I’ve not seen very large randomized control trials. I would say I don’t think there are out there, but the studies that I’ve, I’ve seen, have shown lower rates of ICU admission in some of the ER studies. The ICU itself, lower rates of intubation and lower lengths of ICU stay when using barbiturates. Now I have seen some, I did see where they used an upfront dose of a barbiturate, and then used the benzo and then they had increased success there too. There was reduced admissions to the ICU.

And I think that’s that’s not you know, it’s not a it’s not a terrible strategy. You know, after all, there is a rule you know, I would not, you know, in my personal practice, I will I prefer to use phenobarbital mana therapy, but I would not knock somebody else. If you’re using benzos, as long as you know, when enough is enough, like if your strategy isn’t working, try something else, you know. But, um,

Kali Dayton 50:11
The benefit to that, that that approach is that we minimize the benzodiazepine dose. That phebnobarbital is the primary drug that we’re using. And if we use benzodiazipines, we’re using it so minimally. And I think that’s partially why there was such an improved outcome.

Dr. Obiajulu Anozie 50:28
Yeah, my thought process for that study was that it’s possible that maybe the barbiturate kind of facilitated the effect of the benzo. And so they were able to use benzos successfully. And if that’s the strategy that works, then that’s great. You know, we’re all different providers, we all have different strategies, but I think people should just keep an open mind. And the data with barbiturates is pretty is pretty convincing.

And like I said, I mean, barbiturates are old, they’ve been around for a long for decades, you know, for a long, long time. And they’ve been used in DTS before even in the 70s. Or even in the thought it was kind of astonishing. Wow, even. Yeah, they had seen a superior profile with with with barbituates.

Kali Dayton 51:19
But we stuck with what we know. We talked about keeping an open mind. I’ve had people reach out with questions about a phenobarbital protocol, and asking, How do I convince my intensivist to change the protocols? So I think generation make difference, you get older providers, and we like to stick with what we know. Like to not have to think through it or just or change, and that applies to all aspects of our life. Yeah. But what would you recommend for maybe nurses or other providers that want to change this approach to alcohol withdrawal within their facilities?

Dr. Obiajulu Anozie 52:00
Yeah, it’s communication is everything. If it was me, I would probably go to my medical director with with evidence and from experiences. So I, the facility that I trained at and fellowship, when I started my fellowship, we were still mostly using benzos. But shortly into my fellowship, that started changing and we had good results with just using barbiturates. So I would bring experiences from fellowship combined with data.

And there are protocols out there to you know, some protocols that other institutions are using or that are published online, including like, you know, a 10 mg per kg, I think what’s generally recommended is to not exceed over 20 mg per kg cumulatively in one day. So, you know, there’s protocols where people are given somewhere between five to 10 MPs per kg. And then they’re given, you know, push doses of 130 to 260 milligrams every 30 minutes. And that’s, for the most part is that kind of the standard protocol that I mostly use? And it depends on if they’ve had other medications on board, I might alter that. But you know, present the protocol. Present the physiology.

You know, I think in everything that we do. I mean, especially in the ICU, ICU is all about physiology. So if you’re going to talk about altering a strategy, the physiology is your basis behind why you want to alter that strategy. You know, it has to make sense make it make sense, and you make it make sense by explaining the physiology behind it.

And that starts with NMDA receptors and GABA receptors, the fact that alcohol will down regulate those GABA receptors. And actually, one thing I feel dimensions, it down regulates those receptors. But apparently, there’s also the in the GABA a receptors that actually alters their responsiveness to so that could be part of the reason why there’s so much resistance and tolerance and dependence and withdrawal, even in patients that are still drinking alcohol, and why taking benzos may not work, you know, you need an alternative strategy, you need an alternate strategy that can directly open chloride channels to precipitate neural inhibition. And that just makes sense. You know, it just makes sense.

You know, so I feel like if you’re working in institution with reasonable open minded people, if you make if you make something makes sense by bringing forth the physiology, the data mined from other institutions, and a protocol that I think you can start opening some minds, and then, you know, maybe some anecdotal evidence that you might present from just trying it out in some of your own hospitalized patients, you know.

Kali Dayton 54:44
I love it. And we’re in this era of lots of sharing of ideas, whether on social media, but even with our within our travel nurses. I’m having travel nurses come up to me saying, “Hey, I’ve used phenobarbital in other facilities and now I’m here and they’re using Ativan still, and it’s killing me, it is so much work, I’m seeing this harm. How do I get them on board?”

So to have just an open mind, open table for discussion, to say, “What have you seen? What has worked? What does the evidence say?” And so, for the listeners, check out this transcription for this episode, and therein I’ll provide citations to a lot of these studies and some of these protocols. So you can just print them out and bring them to your medical directors and whoever needs to be joining in on this discussion. Thank you so much for all of your insight and wisdom. I appreciate it. And I will also include your Instagram handle so people can follow your incredible Instagram page. Thank you. Appreciate it.

Transcribed by https://otter.ai

 

References

Dr. Obiajulu Anozie, MD on instagram : @ICUexplained

Pulmcrit’s excellent explanation and guidelines of phenobarbital: https://emcrit.org/ibcc/etoh/

https://pubmed.ncbi.nlm.nih.gov/30876654/

https://pubmed.ncbi.nlm.nih.gov/35569673/

https://pubmed.ncbi.nlm.nih.gov/32830517/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9922035/

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