Well, good morning, everyone. Happy Tuesday, last day of Congress. My name is Pat Posa, and along with Erica Setliff, we're going to be moderating today's session, 10 Years of Liberating Well, Advancements and Learnings from a Decade of Implementing the ICU Liberation Bundle. So the objectives for this session, upon completion, you should be able to describe updates and advances in the literature over the past decade of implementing ICU liberation, the A through F bundle, in critically ill patients. Also develop a plan for leadership buy-in to implement the ICU liberation bundle, and then learn strategies to overcome barriers and implementation of the ICU bundle. We want this to be interactive, so we're going to have questions come at the end, and we're going to leave a lot of time for those, because we want to hear from you, what are your struggles, what are your barriers, or what strategies you've found effective. So we have an esteemed faculty here today. Myself, I'm a quality and safety program manager at the University of Michigan in the HMS Sepsis Initiative. Erica Setliff is a clinical nurse specialist at Atrium Health in North Carolina, and we have Dr. Matt Ulrich, and he is a senior physician executive at the University of California San Francisco Medical Center. Chris Permay, who is a rehab education specialist at Houston Methodist, and Michelle Rassen, and she is our respiratory therapist, and she's the technical director of respiratory therapy at Sloan Kettering Cancer Center. So welcome to all of you, and we're excited to get started. None of our faculty have any disclosures related to this topic. I'm going to start off with a brief timeline of ICU liberation for those of you that might be familiar with it or not familiar with it, and this timeline is really not written anywhere, but when you see the slides, that QR code takes you to a Wes Ely presentation at the SCCM in Hawaii in 2017, and he tells the great story, and I've tried to kind of summarize that story as I've lived along with that story. So we started our journey in adding letters or creating the letters to science, first started in the late 1990s to early 2000s with spontaneous breathing trials and the spontaneous awakening trials. Now that spontaneous awakening trials were called sedation holiday back then, right? So that was the initial work that was done then. In 2008, they combined the awakening trial with the spontaneous breathing trial, and that's the ABC, and that was the beginning of the bundle, right? So now we have A, B, and C. As the researchers doing both the spontaneous breathing trials and spontaneous awakening trials, they found some difference in outcomes related to older patients, and they took a deeper dive, and they saw that delirium was a component in those patients, and so they began doing studies on delirium and created the CAM ICU at that time, validated that CAM ICU for the adult population, and found that delirium was independently a predictor of mortality, an independent predictor of mortality, increased length of stay costs, and long-term brain dysfunction. Also at that same time, Dr. Kress as well as Dr. Bailey and Schweitzer from Chicago as well as in Utah were doing study on mobility, and the Schweitzer study that was published in 2009, they did the ABC part of the bundle before they did mobility, so combining all of them. So now we have A, B, C, D, E, and in 2013 we have the updated PAD guidelines, and that was really where our 10 years is starting, right? So we're in 2023 now. We started to see outcome studies of the bundle in 2014. Dr. Michelle Ballas and her group at Nebraska studied the A, B, C, D, E bundle and found that the patients were off the ventilator three days sooner and also showed improved survival, so mortality benefit. Then there was work done both at Hopkins and in the Michigan ICU Keystone Project that again reinforced the positive outcomes of the A through E bundle at that time. Mary Ann Barnes-Daly then conducted a significant study and they added the F. Their study was funded by Gordon and Betty Moore. Gordon Moore had been an ICU patient and had delirium, and the family wasn't allowed to be in the room with them, and so in the funding part of the requirement was, hey, you need to have a focus on family, and so the F was born. And so they studied the A through F, Barnes-Daly, and using it as a way, as an implementation arm of the PAD guidelines from 2013, and they found significant improvement in multiple outcomes for our patients, and they found a dose-related response, so that every improvement, 10% improvement in bundle compliance significantly improved mortality and other outcomes. The Society of Critical Care Medicine launched the ICU Liberation Collaborative in 2015, and that's when the ICU Liberation Committee was also started in SCCM. The results of the ICU Liberation Collaborative, it was multiple hospitals, 68 hospitals over a 20-month period, and those results were published in 2019. And we had updated to the PAD guidelines, and they now added immobility and sleep because of the importance of mobility as well as the importance of sleep. And then in 2022, the pediatric guidelines were published. So that kind of gives us a little bit of a history of how we got here today, and why we're talking about ICU liberation at 10 years. I'm going to now turn it over to Matt Ulrich, and he's going to give us what did that decade from 2013 to now bring in literature. Good morning, everyone. Glad to be here in rainy Phoenix. I've been to Phoenix twice in the last 15 years. I think the previous time it was 31 degrees. It was the coldest in decades. So I'm... So I'm cheerful, Matt. That's pretty much me. But I am glad to be here and talking to all of you. So just a brief outline, Pat's already given a timeline, so I'm going to move through that fairly quickly. And my goal was to focus on a decade of literature, but if you'll bear with me, I'm going to extend back about 25 years, and we're going to move quickly. Because I want to show what led to the 2002 sedation analgesia guidelines, and then more importantly to the first decade of literature leading up to the 2013 PAD guidelines. And then I'll talk about some of the major investigations that have been published since 2018. And then Pat has already highlighted some of the outcome data. But I'll go into that in a little bit more detail. This is just, you know, another sort of sense of the timeline. You can see there was... You know, really about 25 years ago, we started to have a sense of ICU-acquired weakness and brain dysfunction in critically ill patients, and then that led to some early 2000s focus on delirium screening tools, and then the initial sedation analgesia guidelines, which I remember as a resident and fellow, and that's really what we had at the time, what we based our practice on. And then there was a really active 10 to 15 years, various really important randomized control trials that led to the PAD guidelines, and then onward. And Pat's covered a lot of that, so I won't spend too much time on this. But this is where we started, certainly what I remember at the beginning of my training. And as I mentioned, there was a recognition of the harms that we were doing, and certainly patients who were developing weakness and patients who were suffering the consequences of some of our standard practice. And one of the standard practice that I certainly remember as a resident and a fellow was deep sedation. This is very common, at least at the time. Although it's interesting, if you go back and look, there's some interesting editorials on ICU practices decades before this, and we've definitely gone through different phases where there have been times where there's been less of a focus on sedation, and there are some veteran intensivists who comment on in the 80s, actually, where there was a focus on turning down sedation. And then somehow or another, at the time of my training, we got to a point where everybody was deeply sedated until we came to this recognition that you had all of these harms when patients were deeply sedated all the time. So one of the first trials that I'll just highlight quickly was Kress and colleagues in the New England Journal in 2000, which looked at daily sedation interruption. We've all called it different things. We called it a sedation wake-up at UCSF, but showed that a daily sedation interruption decreased the duration of mechanical ventilation pretty substantially by about two and a half days, as well as decreased ICU length of stay. And this also was an important safety trial. It showed that this practice didn't cause increasing PTSD, didn't cause cardiac ischemia. And so in the total incidence of agitated-related complications, mainly self-extubation was manageable, I would say. And so this was an important safety trial as well. And then the ABC trial, and this had a huge impact on many of our practices, certainly in our practice at UCSF. And this really looked at the importance of coordinated care. And I would say, in some respects, I highlight this trial in part because it was my early recognition, and we didn't know it at the time, and I didn't call it interprofessional care at the time, but it was my sort of early recognition of the importance of interprofessional care in the ICU. Because really, to do this, to pair a sedation interruption of some type with a spontaneous breathing trial, you had to coordinate the entire team. The provider team, the bedside nurses, the respiratory therapists, all the pharmacists, everybody had to get coordinated. And this trial showed really a remarkable one-year mortality benefit, as well as benefits in length of stay and number of ventilator-free days. So you can see we're developing momentum here. This is building. This is 2000 through 2010. And many of you will recall the men's trial, which looked at dexmedetomidine and compared it to a standard practice in the use of a benzodiazepine drip, and showed that dexmedetomidine was essentially effective. More days alive without delirium or coma, a lower overall prevalence of coma, and more time within sedation goals, as well as also a good safety profile with dexmedetomidine. So another important trial that was guiding our practice. Pat mentioned Bill Schweikert and his colleagues and the work they did in Lancet. So now we're adding on to another piece of the bundle and looking at the impact of early mobility efforts. This was an important trial in mechanically ventilated patients that showed the benefits of early mobilization, 1.5 days after mechanical ventilation versus about 7.4 days in the control group, and showed decreased ICU length of stay and better functional status at hospital discharge. So a very important trial also, I would say, for many of us in the ICUs, really impacted practice and continues to impact practice. So this brings us up to 2013, and now this is where I'm supposed to begin my decade review. So thanks for bearing with me on the 25-year review. But this was a very important guideline and certainly something that had a lot of impact on practice really across the world. The trials that I've already reviewed, really the foundation, were some of the most important foundations of that guideline. But then, you know, what's happened in the decades since? So continued to be focused on mobilization. I'm going to go over a few early mobility trials. This was one of the first trials, perhaps the first trial, in looking at surgical patients in surgical ICUs. It basically looked at a protocol, again, an interprofessional approach to early mobilization and showed a reduced ICU length of stay. And similar to the Schweiker trial, also showed improved functional status at hospital discharge. So I think if you were an advocate for early mobility, and certainly at UCSF we had many advocates. We had built up a team. We had a growing group of physical therapists. We were all feeling pretty good about this. But a little bit of a pause here, and this is a single trial, I'll acknowledge a single center trial that looked at 300 patients with acute respiratory failure requiring mechanical ventilation. In this trial, with a standardized rehabilitation protocol, did not show any difference in the primary outcome of length of stay. There were some better, longer-term functional outcomes at six months, but interestingly, some like Schweiker and some other trials didn't show improved functional outcomes at hospital discharge. So certainly something to consider and something that has been considered ongoing. I will say this trial did not have a clear sedation protocol, and that may have had an impact on the intervention. Jumping over to another part of the bundle, Pat mentioned earlier the Gordon Betty Moore Foundation. This is certainly fundamental to what we were doing with the ICU Liberation Collaborative and really trying to understand the importance of family engagement and empowerment in the ICU. And this is when we see, in 2017, the first SECM guidelines focused on family-centered care across ICUs, across the age spectrum. So, I mean, this was really, at the time, this was published very much a nascent field of research, and I think still there's a lot of work to be done in this area, but I think this at least really focused our attention on the importance of family presence and family involvement in the care of ICU patients. So again, I mean, we've talked about early mobility, we've talked about sedation practices, we're sort of building, and we're still, I think for many of us who are practicing, and certainly when I was practicing at the time, there's still an ongoing focus on, are there any pharmacologic interventions that are gonna have value, particularly in the treatment of delirium? And dexmedetomidine, at this time, and continues to be a drug of great interest and of great use, and this is an interesting trial from 2018, Janice Scrooge and her group looked at nocturnal dexmedetomidine, and I'm sure many of you have seen various uses of dexmedetomidine, certainly at this point we were starting to use some nocturnal dex, partly it was driven by patient behavior at night, it wasn't necessarily protocolized, but this was a protocolized approach that looked at low to moderate dose dexmedetomidine delivered overnight in a protocolized format, and showed that there was a greater proportion of patients who remained delirium-free. So an interesting study, I brought this up on rounds a couple times, I got very stern looks from the pharmacist in our group, but I thought it was an interesting study, and continues to be an interesting study, that also did not show any significant adverse events in the treatment group. And then, speaking of treatment for delirium, this is, I think many of you are aware, a number of trials, the REDUCE trial, as well as the HOPE ICU trial, looking to see whether antipsychotics had any role. And for me, and I imagine for many of you, this became sort of the standard format in ICU rounds, where I would describe all the negative trials of the use of antipsychotics in the ICU, and then we would acknowledge all the patients who were getting antipsychotics in the ICU. And the challenge is, one of the challenges we face, and I think this is interesting to compare these trials, and if you compare sort of the use of catepine in the ICU, and what led to that, and what I recall led to that was a small pilot study that John Devlin and his group did, and John, I think, has various of, I've heard John talk about this, it was very much a pilot study, but a very small pilot study led to widespread use of catepine, certainly in our ICUs, and I imagine many ICUs, and you balance that against many large randomized control trials, multi-center trials, that didn't show any benefit, yet I think we probably all see a fair amount of catepine use in the ICUs. So, negative trials in this regard. And then I'll, this brings us up to 2018, and as Pat mentioned, now we have the inclusion of mobility and sleep in the guidelines, which is certainly an important development. But I will say, I mean, if you look carefully at these guidelines, and there are many questions asked and answered in these guidelines, we all still struggle. I mean, particularly on the issue of sleep, what's the best approach to sleep? And I think, I will say, we have wrestled with, do we develop a protocol for sleep that acknowledges the use of pharmacologic interventions, or do we sort of stay wedded to a non-pharmacologic approach to sleep? I'd say, in my institution, we felt like we had to provide some guidance around this, because people were using meds for sleep all the time. But the literature certainly is not particularly strong in this area. So, what's happened since then? So, in the five, six years since then, we continue to have more trials on delirium. The MindUSA trial, again, looked at the use of antipsychotics, both haloperidol and an atypical insoprazodone. A large trial of patients with acute respiratory failure or shock and delirium, although I'll note that 89% of these patients had hypoactive delirium. And so, they compared haloperidol and insoprazodone and placebo, did not show any difference in the primary outcome of days alive without delirium or coma. One critique of this trial, I think a legitimate critique, was, you know, is the treatment of hypoactive delirium, which is basically this study group, common practice, is the treatment of hypoactive delirium with antipsychotics, atypical antipsychotics, in particular, is this common practice? And I would say, for many people, the answer is probably no. More focused on hyperactive delirium. Another, in the same area, another trial looking at pharmacologic interventions for delirium, the AID-ICU trial published just over a year ago, a large randomized controlled trial that showed that treatment of delirium with haloperidol did not increase the number of days alive and out of hospital at 90 days when compared to placebo. There was some suggestion of a mortality benefit, but I think you need to be cautious with the interpretation. There's a lot of data dropout that may have biased the results. I will say it did show a good safety profile. They were given 2.5 milligram IV doses of haloperidol, up to 20 milligrams a day. I believe the average dose was about eight to nine milligrams a day for about three and a half days. So, how do you make use of this in practice? I think, for us, we focused on the fact that there wasn't clear benefit. On the other hand, the safety profile was good, and certainly for hyperactive delirium, I still think it's an option, although I think you just need to recognize that you are not necessarily treating the duration of delirium, but you may be making things safer for a short period of time. And then shifting over to sedation and some additional trials, again, dexmedetomidine is a study of, a focus of study in the SPICE-3 trial that looked at early dexmedetomidine versus usual care within 12 hours of mechanical ventilation. This trial did not show any difference in the primary outcome of rate of death at 90 days. Also important to note, there was frequent use of supplemental propofol in the dexmedetomidine group, and there were also more adverse events in the dexmedetomidine group. So I think like many trials that look at usual care, similar to sepsis trials that look at usual care, you see is over time, usual care changes. And so I think we see that usual care is different now than it was 20 years ago, and that may reflect the absence of difference in this trial. This is an interesting trial. Certainly, we've talked about this sort of in the ICU liberation group a lot of times about institutions that practice or try to practice a no sedation approach. And there are certainly institutions that have made an effort to do this. This was a non-blinded multicenter trial, over 700 patients that looked at no sedation versus light sedation in an SAT, did not show any difference in mortality. I think some important caveats to note about this trial, there were a lot of declinations, so a lot of people refused to be a part of this trial. I mean, that's, it was a big part of this. There were a lot of refusal of consent. An older population, and also the oxygenation threshold for exclusion was quite low. So they allowed patients to be in this trial that I think many intensives would have said, I'm just not comfortable with that. The PF ratio is way too low, I'm not comfortable, we're not gonna include it. For synchrony reasons, I'm gonna keep this patient on sedation and not allow them to be included. So, and also a very high crossover rate for sedation early in this trial. To me, I mean, this came up a lot for us on rounds where I'd have residents and fellows who'd go visit another institution or hear another institution that didn't use the sedation approach and would ask if we could try this. And when this trial came out, it certainly was a, I think it introduced some caution to the no sedation approach, but certainly a worthwhile trial to consider. And then MENS-2, follow up to MENS, we had MENS-2, we're looking at dexmedetomidine or propofol, did not show any difference in days alive without delirium or coma during the 14-day intervention period and no difference in secondary outcomes. So basically, I think showed that both have a role, both have, it's worth noting, though, that the doses of both medications were relatively low and a fairly high rate of the use of rescue meds in this trial. And then the last trial that I'll just highlight for right now before I move on quickly to outcomes would be the team study. And this is a trial on the mobility we've talked about, and I'm very interested to hear Chris's thoughts on this. This is a randomized control trial of 750 patients which compared early active mobilization versus usual care and didn't show any difference in the primary outcome of days alive and out of hospital in 180 days. So what to do with this trial? We can talk about some of this in the question and answer, but I do think it's interesting. It raises the question of what has happened with usual care. And if you look at the difference in actual therapy, I think it was about a 12-minute difference between the intervention and control group. So certainly the gap is shrinking between a protocolized intervention and what would be usual care, similar to what we've seen in sepsis trials as well. So just very briefly on outcomes, I'll move through this quickly just in the interest of time since Pat's already covered some of this. This was Barnes-Daly and colleagues study published in 2016 that looked at seven California community hospitals in bundle implementation and basically just showed that in this prospective cohort quality improvement initiative for every 10% increase in bundle compliance, whether it was total bundle compliance or partial bundle compliance, we saw an improvement in hospital survival, more days without delirium and coma. And then this was carried forward. Those of us involved with the ICU Liberation Collaborative and Pat mentioned the 68 hospitals, 68 hospitals if my number's correct, and the work that we did in this collaborative. And then this was the study of over 15,000 patients involved in that work. And this showed that complete bone performance was associated with a lower likelihood of all of these outcomes. I won't read them all, but again, showing the benefits of the A through F bundle and the impact. Just more recently, I wanna highlight Julia Barr's study that she did with her colleagues that was just published, a multicenter study of 11 adult ICUs at six community hospitals that again showed the value of bundle implementation on a number of different outcomes here and ICU length of stay, hospital length of stay. And so I think this is what we're seeing is just, these are challenging trials and certainly when we're doing large quality improvement trials, they are vulnerable to criticism. I mean, this is, we've all heard the critiques, but I think as you see, study after study demonstrating that bundle implementation really does have an impact on patient outcomes. I think it's important to highlight these studies. The one thing that I will mention, and I think I'm just gonna really, I think narrate many of our own experience here is certainly the impact of COVID-19 and the A3F bundle. I think many of us who worked in the ICUs during that time, before I was in my current position, I was the director of critical care at UCSF. So I spent a lot of time working with all of our colleagues trying to wrestle with this. What do we do with the A3F bundle when families aren't allowed to be at the bedside, when we're changing our sedation practices because we're out of option, because we've been on the vent with a patient for days and days and the triglycerides are 800 and we're back on benzos and the patient's in two pressure shock. And I think many of us struggle with this. Certainly, both this two-day point prevalence study as well as some survey data suggests that there was certainly reduced compliance. And I think that probably matches with everybody's experience. So part of the question is, and one of the questions we have at the SCCM is how do we move on from that? So how do we not slide? How do you re-engage your team? And we certainly saw that. I mean, it's interesting in getting feedback from various people at the bedside. I think people recognize the need to get back towards bundle compliance, but there was also, there were some ways in which some parts were easier. We used to have 24 hour a day visitation at our ICU and then that narrowed down. Getting back to 24 hours, I mean, I had to remind people that prior to the pandemic, we were doing 24 hour a day family visitation because in some respects it was just easier. Not always, but sometimes it was. And so that was something, for instance, that we had to wrestle with and still do wrestle with. So my last comment here, I just do wanna acknowledge, I am co-chairing the FOCUS PADIS update. Our target is next year at Congress. This is gonna be a more narrowed FOCUS update than previous, but certainly we have a lot to consider. We have a terrific group and various subcommittees looking at various questions related to the 2018 PADIS and then moving forward to the much more focused update. So I think we all look forward to that over the next year. And I just wanna thank everybody. Obviously I've reviewed a lot of trials. There's a huge amount of work that goes into all of these. Everybody from the clinical research coordinators to all of the clinical trialists who've done important work, many of whom are here these last few days. So thank you to all of them and thanks to all of you for your attention. Thank you.

ICU Liberation Bundle

critical care outcomes

sedation interruption

early mobility

COVID-19 impact

family engagement