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After decades of research revealing the price patients pay from benzodiazepines, where are we now in the ICU? Dr. Wes Ely and Brenda Pun share with us the latest COVID study and how COVID-19 patients are being cared for around the world.
Episode Transcription
Kali Dayton 0:29
Hello, it’s been a while. Thanks for hanging in there and continuing to support this podcast and the overall movement to humanize the ICU. Thank you critical care community for all the backbreaking, and heart wrenching work you were doing right now. These are crazy times with COVID. Literally, there’s a new study in Atlanta Journal that exposes a perfect storm that is causing startling rates of delirium in COVID patients throughout the world.
Today, we have two renowned researchers with us to tell us about their COVID D study. The link to the study is in the medium blog connected to this episode. Dr. West Ely is one of the main pioneer researchers of delirium. And one of the primary developers of the A to F bundle, I would invite all listeners to go back to the powerful information he shares. And episode five, I let the famous brand upon introduce herself.
Brenda Pun 1:28
Sure. My name is Brenda Pun, as you said, and I am a nurse, a critical care nurse. And I work with the SIB Center at Vanderbilt with all of our research studies with all of our data and looking at the things that happen to patients whether in the ICUs and through survivorship. So that whole spectrum of critical illness and how it impacts patients after they leave the hospital.
Kali Dayton 1:52
I’m a little star struck because I’ve seen your name all over some of my favorite research. And so it’s an honor to actually talk to you and see you face to face via zoom. But thank you so much for sharing with us your most recent research and Wesley share with us a little bit about yourself. And I would invite everyone to go back to his episode, the big picture delirium at the beginning the podcast.
Dr. Wes Ely 2:15
Sure, yes, my name is Wes Ely and I have been working with Brenda for over 20 years, it’s been a great privilege. And I’m an intensivist at Vanderbilt, pulmonary critical care. I see a physician who helps to create these studies that we do at the SIB center that stands for critical illness, brain dysfunction and survivorship Center, which is a combined Vanderbilt and VA Research program where we have over 90 investigators across the institution and many other institutions helping us to enroll patients across the country. And Brenda was actually humble and you’re right to be starstruck, Kali, she’s probably the most famous nurse in the world. The most famous critical care nurse in the world regarding delirium. So it’s, it’s a privilege to have her here with us today.
Kali Dayton 3:01
Truly, truly, tell us about your most recent study, Brenda, that just came out.
Brenda Pun 3:08
Yeah, so we, we’ve been in a whirlwind, like the whole rest of the critical care world over the past, really in the past year. Now that we’re in January, as we as we tape this podcast, or February as we take this podcast. And so we wanted to know what we could do from the CIP center to help contribute to understanding how to best manage COVID patients. And since we’ve already mentioned that delirium, and sedation and acute brain dysfunction are really the things that our group has had our feet in for for the past 20 years, is we were having our antenna open to ideas of things we could do.
And we were, we were contacted by some researchers in Spain, asking, “Hey, we’re seeing a lot of delirium. What can we do? Like, let’s track this? Let’s define it. And let’s look at what the risk factors are for in this specific population.” The question really bein: Is this different? Is what we’re seeing different? And are the risk factors for this delirium? Are this acute brain dysfunction? Is this different than what we typically see?
And therefore should we be changing our practice because, as you know, in in March and April, and really now there hasn’t been a ton of data to guide the decision making at the bedside. So we set out to do the study to help build that, that really that base of data that we would use to help guide decisions. And so that’s where we started, was we we, we worked we partnered with the Spanish investigators, and Raphael but Dana’s and Gabrielle Gabrielle house, and they, together with our network of of past groups in sites that we’ve worked with, we really were able to recruit a ton of sites that were ready interested and motivated to work with us.
So we recruited 69 sights from 14 countries. And we collected data on over 2000 patients during that first from the first COVID patient that came to the each individual site up until the end of April of 2020 20. So we got these 20,000 patients, and we, we just we had all of their data in a database that included their baseline information, and three weeks of their ICU stay. So really asking what happened to them while they were in the ICU? How can we describe acute brain dysfunction in these COVID patients that were severely ill? And 80% of them were on the mechanical ventilation, basic mechanical ventilation?
And just asking, what, what are we finding, because we had a lot of suspicions that this delirium, the COVID, was putting the patients at a greater risk for delirium because of the disease itself, but also because of our practices that were building around it. And our reactions to how contagious this was, and that we had, we had changed our visitation policies pretty dramatically in most of our hospitals, all but one of our ICS that partnered with us completely, dramatically limited visitors, there was only one ICU that didn’t. And so all of these reasons, we were looking at all these risk factors. It asking what’s different in this population?
Kali Dayton 6:23
And what did you find what was different? And how have we differently have we treated COVID versus other respiratory infections?
Brenda Pun 6:30
Yeah, let Wes, why don’t you? Why don’t you speak to that? And then I can tell that tell the results of the study, but what have you seen that’s been different with these patients, what’s been challenging about them, and putting them more at risk, you think for acute brain dysfunction?
Dr. Wes Ely 6:45
I think that my anecdotal comments will then be supported by the data and to get 2000 people into this study, in that short period of time, you know, from 70, different ICUs, 14 countries, that’s a robust amount of data to analyze, and it gives you a lot of power to really understand and go beyond anecdote. So that’s gonna be backing up what I’m about to tell you, you know, when people come in with a COVID, cough, and they are just hacking away like crazy, and you’re trying to keep an ET tube down, it really scares you as as an intensivist.
And you’re in the room with them, and they’re saturating, and really, what it kind of does is it drives you to feel the need and Kali you’re, you know, very seasoned ICU nurse, you and Brenda both. So you’ll get this that, like, “Whoa, I don’t want them to cough that tube out. I don’t want to see their SATs go down to the 70s. And I just barely got them up in the 90’s.” And, and so you slam them down with sedation. And what happened was in early on in the New England Journal, a study by Julie helms from Germany said that 90 something percent of people, I think it was 88% Actually were treated with benzos.
I think the world took that New England paper and said, okay, so you’re supposed to treat COVID patients with benzos. So this New England paper comes out and says, you know, nine out of 10 are getting benzos. And the rest of it goes Okay, so we’re back to benzos. And that’s a scary thing, because we had worked for two decades to use the ATF bundle and the concepts that were shown in large Lancet, New England journal JAMA studies, that GABAergic slamming of a brain down into the ground deep coma was dangerous, and we have reduced and reduced benzo use to the point that we actually had some ICU nurses at Vanderbilt, who had never used a benzo they’ve been ICU for four years. And they got red faced when one day we had to use a benzo. They’re like, “Well, I’ve never done that. How do I even dose it?”
Kali Dayton 8:40
Oh, how refreshing is that?
Dr. Wes Ely 8:42
Oh, I know. I was like, wow, we did it. This is Yeah. It actually be, you’d actually worked and and then you know, COVID hits and you feel like you’re back in the 1990s. With these benzo induced comas, I got an A text last week from one of our former attendings. I won’t mention a name or an institution but it he showed me just the IV pump which said 8.5 mg Versed per hour. So that person is receiving, what 8.5 times 24 You know, 100 or so? Or was at 200 averse at a day. So Crazy, right? So that’s what I had noticed. And I noticed that we were doing this and that there wasn’t any evidence to support it. And yet it was happening. And with that backdrop, we gathered these data on these 2000 people. So Brenda, what did we find? What was the data show?
Brenda Pun 9:42
Yeah, and I think that the that some parts of the results surprised us and other parts. Were right on track with what we thought would be things that put patients more at risk. And so what we found was that there was a lot of acute brain dysfunction and so just Just for comparison, if we look at past studies that we’re looking at similarly, ill patients, so patients with a very similar ARDS sepsis patients, so really sick ICU patients, we see less than a week of overall acute brain dysfunction.
So just a couple of days of coma, and a couple of days of delirium. But what we saw in this study was that we had 80% of our patients had coma for a median of 10 days. So remember, we went from a few days, so less than a week overall to now we’ve got coma for 10 days. And then delirium once they they were up high enough to have delirium so out of the coma and have delirium that 55% had delirium for another three meeting of three days. So we’ve got two weeks of acute brain dysfunction between the coma and the delirium that these patients were not normal. They weren’t, they weren’t either able to communicate or able to interact, they were so deeply sedated.
They were in a coma, or they were delirious for two weeks, when it’s usually less than a week. And so then we wanted to know, okay, there’s a lot of this a lot more than we were expecting a lot more of the coma than we were expecting. What about the risk factors or the practice habits, what those look like, and exactly what Dr. Ely had just mentioned, was truly happening that 64% of the patients in this study had benzodiazepine use. So continuous infusions, just exactly what he just described, for a meeting of seven days.
So a week of benzo infusions, along with a week of propofol infusions, and around four days of dexmedetomidine infusions. And so this is, this is a lot of sedation the patients are getting, and they’re not getting frequent awakening trials or breathing trials. So less than a quarter of the patients were getting those. And then we found when we’re when we’re asking about practice habits, what what so we’re having deeply sedated patients that aren’t being reevaluated on a daily basis of whether we can come off that sedation and lighten the sedation. So those, those practice habits that keep us from getting stuck in a bad cycle weren’t happening. And yet, we were using a ton of these drugs.
And these drugs that we’re not familiar with using and we’re not, we hadn’t used this much. And so we were keeping them deep, we’re using a lot of it and staying there. And then the other, the other factor that we suspected was that there was very little family interaction happening with the patients. And so of all of the days that we had in a study, which was over 20,000 days of data, we found that only 17% of those days, so less than 20% of the days had any type of visitation from the family, and that was in person or virtual. So we counted virtual visits.
And so only only 8% of them were in person. And so we found that the that really the patients were getting drugs that were against clinical practice guidelines, and they weren’t getting the recommended family visits, and they weren’t getting the daily awaking trials and breathing trials. So the practice habits that we were seeing and hearing were happening and struggling with ourselves at Vanderbilt were widespread, and patients were having the impact. We’re feeling the impact of that. I’ll pause there anything that you want to add to that, Dr. Ely.
Dr. Wes Ely 13:34
If you if you put this through a multivariable analysis, what comes out is the two most robust predictors of acute brain dysfunction, delirium and coma were overuse of benzos and under use of family, so the benzo use increased delirium risk by 60%. And the and the absence of family or I should say the presence of family reduced the risk of delirium by 25%. So, drugs increased, family decreases, and yet the families weren’t getting used, and the drugs worse have the opposite. It was opposite day. out of 21 days, they only had five days free of delirium and coma on average. So what’s going through your head Kali, as you hear us report back to you about COVID?
Kali Dayton 14:24
Um, I can’t help but think back to all of these survivors that I’ve interviewed. And some of these episodes that I have where people are talking about what it’s like to have delirium. The episode, I would say three, and a few episodes ago, where they’re talking about the hallucinations, the tears, they are on a hamster wheel of terror throughout the whole time. So I’m trying to fathom what it’s like to spend 10 days thinking that you are an enemy, territory, kidnapped, your kids are kidnapped, being tortured. genital mutilations, all of those things.
How did you experience that for 10 days, having that vivid reality, having not not having real sleep for 10 days, what is going to happen to people afterwards the PTSD that cognitive deficits, how many people have died just because of over sedation, delivering immobility, rather than COVID. We came out thinking that these high mortality rates are just COVID. But I think I feel like a lot of the high mortality rates that happened during the surge in New York, were because of the deep sedation and immobility, and they were in a hard situation with a staffing and everything that was going on there. But I think that was a prime example of how of how these risk factors combined cause high rates of mortality. So how many people are dying because of our poor treatment versus just COVID in and of itself?
Dr. Wes Ely 15:55
Right now, you know, one thing for your listeners to remember is that these survivors describe the delirium as not like a dream. They say it’s actually not like a dream, because it’s more real than real. And what’s interesting is that months and years later, a dream will go away. And we actually have our, our real memories fade. But they say these memories stay with them, so intact, and so crisp, that it’s more real than real. It’s like a tattoo, it’s stuck on their brain, it stuck on their body, and it won’t go away. So that horror that you’re talking about is, is indelible in their in their whole self, which, which is a hard thing, when we say that, you know, “I think I have to take myself, considern ourselves responsible for this personal imprint in their brain. if, if I’m doing something to them that I don’t have to do.”
The listener might be thinking, “Well, what can we do?” Well, I mean, we can quickly try at the very beginning of mechanical ventilator, we can say, “You know what, I’ve got to have them beat for the day, I’ve got to have them beat so they don’t desaturate.” Fine.
But when the sun comes up tomorrow, why not do a spontaneous awakening trial and see what they need, and maybe they have already received so much drug on Monday, or Tuesday morning, you can shut it off completely, and that drug will still go on and be effective enough. Or as the SAT was tested in the ABC study in Lancet 2008, where we actually saw a survival advantage to just stopping the drugs once a day. You can just restart them and half the dose.
And then the second big tip I’ll give you So first is to stop them everyday to some rises, see what you need to do, you have to restart doing it half the dose. But the second thing is at the very beginning, we can start with that propofol drip- propofol and fentanyl, perhaps. Within the second day, we can try and go with just fentanyl and dexmedatomidine, so we can go with with with conversion over to a lower dose of propofol and fentanyl, this analogous sedation thing where we just use fentanyl to keep them deep after that initial day is very real and doable. We’ve proven that in JAMA study and our main study, we show that high dose fentanyl could keep you deep. And so people should resort to that drug more often than the GABA ergic drugs. And either of these approaches, I think will help us avoid the benzo approach, which is the worst.
Kali Dayton 18:18
Right? And benzodiazipines are like you say, THE WORST. And I’m not sure that nurses fully understand that I think that’s part of the problem is that we didn’t really get this common ground that delirium is lethal, the long term causes of or long term effects of delirium. And benzodiazepines are bad. And then here we are, and we’re having medications shortages for short is the profiles referring to all these other medications, especially the benzodiazepines. But I think part of it’s because we didn’t start out with good education for the nurses.
Dr. Wes Ely 18:56
Well, you know, and there’s a there’s a we can we can let ourselves off the hook a little bit in this you know. If you look at the way medical literature is created, if you have one big study that’s in the New England Journal, it can sway things like I told you a minute ago, with a HELM study saying, “Let’s use benzos”, but but the the data incriminating the benzo accumulated slowly over 15 years. And and what happens is when it dribbles out like that, nurses come and go in their careers, and they don’t realize it.
So a few years ago, I was allowed in CHEST to accumulate all of the evidence in a pro vs con about benzos and I was just there, “here’s a take home for all the nurses and anyone else listening. Um, there have been about 28 randomized controlled trials.”- This was a few years ago so there’s there’s more now, but at the time, there were 28 randomized controlled trials of a benzo compared to anything else for mechanically ventilated patients, and not in a single study. Not once did the benzo come out superior to whatever had been compared to it was always inferior or in some cases equivalent. But, you know, when you study something almost 30 times and it never wins. That kind of is pretty obvious. That is not our best choice.
Kali Dayton 20:20
So kids these days are using “the worst”- as a kind of a catchphrase, right? But when you say benzodiazepines are the worst, you’re saying that with so much evidence behind it that they are literally THE WORST.
Dr. Wes Ely 20:32
YES! Listen, by medical literature, data driven analysis, you can say with absolute certainty that all the choices of what we can commit our patient to for five days on a ventilator, they are the worst choice and that they’re the worst because they because of these outcomes, greater length of stay, higher cost, longer term on the ventilator, more long term long term complications, including complications, like subsequent nosocomial pneumonia, things like immobility, problems, pics, post intensive care syndrome, which would be neck down, mild sensory neuropathy, so inability to get up and walk again.
And then also, of course, neck up stuff like long term dementia. And we showed that in our New England Journal paper in 2013, with a brain ICU study that Brenda helped to lead that the benzos were the largest predictor of the long term complication of cognitive impairment. And that’s greater that’s even after adjusting for patchy scores and organ dysfunction and lots of other comorbidities.
Kali Dayton 21:42
And that is such a good reminder that though COVID is a novel disease, it’s new. These principles are, in my mind, eternal. They apply even more so to the setting in which people are going to be on a ventilator for a while. And the “Awake and Walking ICU”. Sedation continues to be the very, very my minority of all the patients with COVID. They’re still awake and walking in their rooms, there’s still discharging home, it is still possible.
And I was working in a setting in which I could oversee a lot of COVID patients throughout multiple states. And I have seen note saying that “patients don’t tolerate being off sedation.” And I’m not sure really, I think that’s very subjective. Sometimes people say, “well, their vent settings are too high.” So I saw a patient that was very normal for that ICU. They were on assist control, FI02 of 60% and a PEEP of 10, I’m not seeing them in person, but they were on precedex, fentanyl, Depakote, Seroquel, Klonopin and reset all at once.
Dr. Wes Ely 22:55
Yikes.
Kali Dayton 22:57
And I asked every intensivist around me, I asked lots of people, because I thought maybe, you know, I knew it was bad. But I wanted to see the perspective- “Why would you put someone on all of those things? How do you know what’s doing what? How long is that going to take to clear out?”- No one could really explain it to me, but yet, I mean, this person has been on those medications for many, many days and even weeks. And so they’ve gone through many intensivists nurse practitioners, nurses, everyone’s passed through. I don’t know I wasn’t there in that situation. But it was really startling and haunting to me that human beings are going through that experience that this person and these people that I’ve seen on these levels of sedation, this combination, these cocktails are going to have their lives completely altered, they’re gonna be forever haunted by what we gave them.
Brenda Pun 23:54
And I think that 111 really important thing to point out here is not only are those things happening with the sedation, and control and all these medications that the patient is getting- but is that lack of the North Star. Their families aren’t there you know, there’s no family there to be with them. We frequently hear from ICU survivors. “I thought this was happening this really bizarre thing was happening, but when my husband but always comes but when my husband came I knew I was going to be okay”. Or, “I knew that he knew how to get me out of that. Or when my daughter showed up…”
You know we have this great video of a patient testimonial on our website www.icudelirium.org , if you go to the the the patient and families portal portion of it and look at the patient testimonials. Scroll down there’s one from a wonderful woman named Marie. She talks about and I think it’s really applicable to these COVID patients she talks about being prone and what it really crazy experience like every day I’m gonna get spun around on this lazy susan she says “All these things are gonna come crashing into me.” And she talks about how everybody looked like Shrek coming in and out of the room because they were in isolation.
And it makes me think this is exactly what a lot of these these patients are going through. And but she says, “But when my daughter showed up, and she put the lotion on my legs, I just knew I knew she was there. And that something that I was experiencing wasn’t real. Like in my the way that my mind was interpreting wasn’t real.” And so what we saw in the study, and I think what we’ve all in a very moral distress way that’s been really hard at the bedside is this lack of family, and families, whatever the patient defines his family.
So these lack of these people that are important in their lives, and their Northstars, because they don’t know whether they should trust us, but they can trust that person. And in so it’s finding, you know, and I really encourage all the all the listeners, so think about what are the creative ways to help those connections be made with these patients, whether there are COVID positive patients, or non COVID patients that are experiencing this isolation and restriction of all the all the visitation policy being more restrictive at this time.
And so it’s fine, I’ve heard wonderful creative stories of using electronic devices, iPhones, iPads, you know, FaceTiming, patients in zoom calls, dedicated iPads for a unit, you know, take this podcast, to your your C suite, take it to your executives and say we need iPads for our unit. That’s an easy fix here, we need a patient services liaison Chaplain that can come through and help facilitate some of these volunteers that will help facilitate this communication between the patient and their family. And in the you know, I’ve just heard of lots of really cool and creative ways to help make that connection happen.
So that the patient hears, and if possible, sees somebody that’s in their tribe, that’s not a part of the ICU. And that helps to be this, this standard, or this constant for them, that brings them out of those crazy dreams and this crazy misinterpretation of everything. And that also helps the family be that support person because they see what’s going on. They see this in context, they can help them debrief this life experience, because they shared it in some different perspectives, but it was a shared experience. And when no family’s there, it’s no longer a shared experience. And they lose that.
And so when the patient goes home, the family can’t interpret anything. They can’t even say, “oh, yeah, you know, there was this crazy noise outside your room, or that one nurse did look like our cousin Sally” or, you know, whatever it was, is they have no ability to see how stinking sick they might have been, or what you know what all this noise in the room was. And so I think that’s a real big challenge is getting them awake, more awake as we can, but also less benzos less drugs, but getting that family there, however creatively we need to be
Kali Dayton 28:11
Such a good point. Your thoughts, Wes?
Dr. Wes Ely 28:16
I love those teaching points. And I know we’re bringing it to a close here rendered has brought up some beautiful, very humanistic aspects to this care that we need to make sure we re humanize our care in the ICU. And those are some beautiful tips. I think that people lose hope, when they don’t have anyone there. And I don’t know, you can’t measure the quantify this, but some measurement of that loss of hope translates into death.
And so if we can bring hope back, and how do you do that? Well, that thing you described earlier that that patient anecdote that Kali described, with all those different, you know, five or six different drugs, there’s not a single person on this planet, who can tell you neurotransmitter was what has happened in that person’s brain when all those drugs were given. That’s an absolute mad experiment.
And I’m not saying that it was wrong. I don’t have to say it’s right or wrong, I can. I can still say though, whether it was right or wrong, I can say that nobody knows what it was doing, that I can be confident of. And if you don’t know what it’s doing, it’s like a lab where you can’t measure. And everybody knows in a lab, you need to be able to measure. So if we’re doing something that might be creating Bernie juice, we’re how stick and stick they were. Let’s talk about “stinkin’ thinkin'”. You know, that’s going to create “stinkin’ thinkin'” in their brain. It’s not going to work for them, and they’re going to lose their way.
And I always say that the brain speaks a language to the other organs that the other organs understand. So organ crosstalk is an important way that the body heals itself. Well, if the brain starts speaking gibberish to the rest of the organs, that’s not the language they know. So when the brain goes into to delirium, it speaks gibberish. And then the lungs, the liver, the kidney, the heart, they get an a non-understandable miscommunication from the brain, and you start to get organ dysfunction.
And there have been great animal studies to show that when brain damage is induced, the other organs begin to fail. So how much multiorgan dysfunction, multi organ failure, are we inducing by these drug induced, you know, add ons to the amount of brain dysfunction they would have already had from the COVID sepsis. That’s the way I would close this out. This is COVID sepsis. It’s a viral form of sepsis. And it’s, it’s something that we need to do as little androgenic injury to the patient as we can. And one of the ways that we can do less androgenic injury is to follow the A2F bundle.
So that’s our website, you can go read about it, if you wish. It’s www.ICUdelirium.org. And also, I’ve found Twitter to be a very useful way of communicating. If anybody wants to tag me in Twitter. It’s just at @weselymd. And Kali knows, I will respond and chime in and we can all learn from one another because there’s a world of people out there who this is the way they’re getting their medical knowledge right now. And the hashtag #A2fbundle, literally the letters A to F bundle. That’s been a very good way of communicating information throughout COVID. And I think that’s a way of us paying it forward. Thank you, Kali.
Kali Dayton 31:32
Yes, I’m so glad you’re on Twitter. It’s been so great to hear your updates and your stories and even pictures. I would invite everyone to add Dr. Wes Ely on to their own Twitter and follow along. There is a huge community out there that is trying to humanize the ICU. And you guys have been leaders in doing that. And we’re so grateful for your research and the heart of why you do what you do, which is to restore and preserve humanity in the ICU. So thank you so much for all you do, and we hope to hear more from you guys later. Thank you.
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