Hello, everyone. Welcome to Congress 2023, and thanks for joining me today. We'll talk about updates and pain, agitation, and delirium. My name is Thalia Froke. I'm the neuro ICU pharmacist at Johns Hopkins Hospital. And I have no financial conflicts of interest to disclose, and we're also going to talk about or focus on sedation strategies in COVID-19 acute respiratory distress syndrome patients, light versus deep sedation in these patients, alternative strategies in the setting of drug shortages, which I'm sure a lot of us are familiar with that. And then finally, we're going to look at some ICU delirium updates and a new publication that look at that. So first, let's look at how we practice sedation during COVID-19 surge. And just a disclaimer that a lot of these studies are looking at the first wave of COVID, meaning COVID patients during the early phase of COVID-19 in 2020. This was a retrospective study of two centers that got published in 2022, so very recent, and they looked at COVID-19 ARDS patients and non-COVID-19 ARDS patients. As far as the baseline characteristics go, as you can see, they're pretty comparable as far as their baseline characteristics. The only difference was that patients with no COVID had more congestive heart failure. What they found was that patients with COVID-19 and ARDS who had ARDS actually required more sedation, and in this study, they specifically looked at the first 24 hours of propofol consumption. As you can see, the numbers are there, and the numbers in bold are statistically significant. They also found that patients with COVID ARDS had higher need for IV benzodiazepines such as lorazepam. It wasn't surprising to see that they stayed intubated for a longer duration. The idea here was that, and the explanation was that patients with COVID-19 have higher need for sedation because of their higher respiratory drive and potentially this link between sedation need and this profound inflammatory response that we see in these patients. In fact, there were some studies from prior years in H1N1 ARDS cases that they also showed the same thing, that patients with viral ARDS, especially these types, may require higher levels of sedation given the profound inflammatory response that we see in these cases. If you practiced in any ICUs during the surge of COVID-19, I'm sure you've heard about drug shortages. A lot of institutions, including ours, we had significant issues with drug shortages such as opioid shortages, and we were really trying to make sure we had enough supply and then we were planning ahead and we were thinking about alternatives. This study that was published recently was pretty interesting to look at. This is a retrospective single-center study that was published from Germany. They actually labeled their ICU as a pulmonary ICU, which I thought was pretty interesting, and they actually had 20 patients that they looked at, and these are, again, patients with the first wave of COVID in 2020, so not vaccinated, pretty sick. This is the time that we're not really familiar with this disease at that point. Some patients had VMIs over 40, although not as many as I was expecting. Some people were on ECMO in this study, and as you can see, some patients were on isoflurane and some patients on propofol. Importantly, it wasn't that patients were classified as the propofol group versus isoflurane group that we're going to look at next because most patients received both, but we're going to look at isoflurane days and propofol days on the next slide because that's how they categorized these patients as far as what was the only agent that they received on a given day for longer than 12 hours or for 12 hours or longer, and we'll look at that. So, as you can see, patients who received isoflurane, they had lower rascals. They had lower need for neuromuscular blocking agents. They had lower polypharmacy use, and again, not surprising that they also required less amount of opioids. So, this kind of showed that maybe isoflurane or inhaled anesthetics could be, as a class, could be an alternative, although the study itself also talked about limitation of how this is not very resource-friendly. People need to be educated on how to give this, the agent itself, inhaled anesthetics as a group, they are pretty expensive, but this alternative exists, and they kind of looked at this and they showed some helpful outcomes that could be possibly utilized in the future if need be. Now let's look and see how our patients actually did. So, fortunately, we're getting more and more information and publications about outcomes. This is one of the early trials that got published, again, very recent in 2022. Look at two centers, again, patients with COVID and the very early surge. These are intubated people admitted to the ICUs, and instead of looking at COVID-19 versus not COVID-19 groups, they look at early light sedation versus early deep sedation, and as you can see, they obviously excluded people who were not intubated or people with neurological injuries. Some important information about our patients in these groups, patients with light sedation had lower severity of the disease, here shown by a lower SOFA score. Also, people with deep sedation, not surprisingly, more of those patients were COVID-19 ARDS patients, so that's just something to keep in mind. The results showed that patients with light sedation had more ventilation-free days, meaning they were extubated sooner, they had more ICU-free days, they were discharged sooner from the ICU, more hospital-free days, and also a lower mortality rate, which, again, a lot of this is not really surprising, and the Kaplan-Meier graph also, on your right, is showing more survival with early light sedation. Although this study did not really formally assess this, but they definitely discussed and talked about the fact that the results further suggest that we had lower adherence to our very gold standard of ABCDEF bundle in the ICUs during COVID, and I feel like even now with COVID becoming more and more under control, I think a lot of our practitioners are maybe more tolerant to higher doses of sedation in ARDS, and maybe that's something to consider and maybe something that we have to revert back to the pre-COVID era and reminding ourselves that lowest and minimal level of sedation needed is what we really need for our ICU patients. So this is just a question for active participation and see how different practitioners and different parts of the country practiced sedation strategies during drug shortages. Did you not change your sedation strategies because you had no drug shortages? Did you end up using more long-acting agents such as methadone? Did you use inhaled anesthetics just like what we saw in the German study? Or did you actually end up using more benzodiazepines in the setting of opiate shortages? Let's shift our focus from ICU sedation to ICU delirium, and let's see where we stand in 2022. I probably should rephrase and ask, where do we stand with IV haloperidol in 2022 for ICU delirium management? There has been a lot of interest and a lot of studies regarding ICU delirium and IV haloperidol use. The most recent study that is called 8-ICU was published a few weeks ago. This study was a multi-center randomized blinded placebo-controlled trial. They look at adult ICU patients with delirium. They gave one group, the Haldol group, or the intervention group, haloperidol 2.5 milligrams TID with a max dose of 20 milligrams per day, and then the other arm was the placebo group. The baseline characteristics are here. As you can see, pretty comparable groups. Of note, these people with ICU delirium mostly were medical patients as opposed to surgical patients in both groups. Also, in both groups, there were more patients with hypoactive delirium than hyperactive delirium. As you can see, their primary outcome was a composite outcome of days alive and out of hospital at 90 days. There was no difference. They also look at those individual parameters such as death and length of hospital stay, although the study was not powered for those. There was no difference. And also, as far as improvement of delirium as a secondary outcome, as you can see, there was no difference. So, they showed that IV haloperidol did not improve survival or delirium in the ICU. In summary, patients with COVID-19 ARDS required deeper level of sedation versus non-COVID-19 ARDS patients. Deep sedation resulted in worse outcomes, as we saw. Alternative agents, such as inhaled anesthetics, may help achieve target RAS during drug shortages. And finally, IV haloperidol failed to show improvement in survival or delirium. Thank you so much for joining me today, and I hope that you can join us in San Francisco live.

sedation strategies

delirium management

COVID-19 patients

IV benzodiazepines

inhaled anesthetics