Thank you, Dr. Barr, for that kind introduction. I have nothing to disclose. So, my objectives today are going to be to describe the best practices for the management of analgesics and sedatives in the ICU, to describe how the COVID-19 pandemic has affected the ABCDF bundle, and to help provide strategies to resuscitate the letter C following COVID-19. So, we'll start out with a patient case. So, EB is a 57-year-old male that was transferred to the medical ICU from the CVICU with cardiogenic shock. He has no specific past medical history. His ventilator settings, he's on volume control with FIO2 50%, a PEEP of 8, a tidal volume of 420, and his current medication infusions include fentanyl of 400 mics an hour and midazolam at 5 milligrams an hour. So, this is a real case scenario that happened to me a couple months ago in the medical ICU. The nurse practitioner unrounds to me when I ask why the patient is on midazolam. Well, we used to use midazolam drips all the time in our COVID-19 patients, so I didn't change it. And this emoji is a really good depiction of what I look like that day. So, first, we're going to kind of review, like, what's the evidence behind what we should be doing with regards to the letter C. Then we're going to move on to see what the COVID-19 pandemic really did to that, and then we're going to talk about strategies to how to repair that problem. So, the 2013 pain, agitation, and delirium, and pain, agitation, delirium, early mobility, and sleep statements and recommendations say the following. The depth and quality of sedation should be routinely assessed in all ICU patients at least four times per shift, and we should use the widest level of sedation that is possible. And there's really two different level of consciousness assessment tools that are recommended, either the RAS, the Richmond Agitation Sedation Scale, or the SAS, the Sedation Agitation Scale. So, this is the RAS, if you're not familiar with it. So, a RAS of zero, in general, is what goal we should have for most ICU patients. They're alert and oriented. The positive numbers indicate degrees of agitation, and the negative numbers, negative one is they make eye contact or voice for less than 10 seconds. Negative two, they make eye contact to voice for, I'm sorry, less than 10 seconds. Negative one is more than 10 seconds. Negative three, they respond to voice but won't make eye contact. Negative four, they only respond to touch, and negative five, they don't respond to anything. So, in general, like I said, most patients should have a target RAS of zero to negative one. If someone's chemically paralyzed, they obviously need to be negative five. With the Sedation Agitation Scale, patients, as you can see, the higher numbers indicate degrees of agitation, and the lower numbers indicate degrees of sedation. And in general, we want patients to be a goal of four, in which they're calm and cooperative. So, it's important to show this data from Yaya Shahibi, which showed that deep sedation in the first 48 hours prolongs intubation. Historically, we all thought, hey, it's fine, I can sedate my patient for a couple days, right? It won't hurt anything. Additionally, he showed that every four hours, a patient is deeply sedated is associated with an 8% increase in risk. So, once again, this really highlights why we should be lightly sedating our patients, even if they need any sedation at all, and we should be discussing this every day on rounds and trying to wake up our patients. This is a secondary analysis of the ABC study that shows that nighttime sedation increases a delay in extubation. So, it's thought, historically, that, hey, I'll deeply sedate my patient at night because this helps them sleep well, right? We all know that is not correct, and in fact, what this showed was that if we deeply sedate our patients at night, then they won't get extubated the next day because the drug is still hanging around. Additionally, the PAT and PATAS guidelines state that we suggest sedation strategies using non-benzodiazepines, so either propofol or dexmedetomidine, may be preferred over sedations with benzodiazepines, such as midazolam or lorazepam. This is one of my favorite graphs to show any time that I discuss sedation, so this was a study conducted by Pratik Pandihari-Pandi that was published in Anesthesiology in 2005, and it shows that there is a 100% probability of being delirious the next day if your patient receives more than 20 milligrams of lorazepam, and this study has been replicated in numerous other studies, but this once again highlights why we do not want to use benzodiazepines. Unfortunately, we developed some bad habits during the pandemic, and we had to use them in some patients because they needed to be deeply sedated. We couldn't give them propofol because maybe they had high triglycerides or they had a high creatinine kinase, but this right here shows us why we should not be doing that. So this is a very good point, counterpoint, that Wes Ely and Tim Gerard put together a number of years ago that was published in Chest. They were trying to show why benzodiazepines should not be used for sedation. So this shows all the trials that have better outcomes with propofol as compared to benzodiazepines. So as you can see, there's a number of them. These show all the trials that show no difference, so there's a few, and these show the trials that have better outcomes with benzodiazepines, and as you can see, there are none of them. The next slide shows trials with better outcomes with dexamedetomidine as compared to benzodiazepines. There are a lot of them. Trials with no difference in outcomes with better outcomes with benzodiazepines. So once again, there are none of them showing that benzos are better than dexamedetomidine. So I added in this last slide to compare propofol and dexamedetomidine since we do have more evidence since this pattern point was published, and as you can see here, we now have two trials, and we have the SPICE 3 study and the MENS 2 study that have came out recently. They don't really show a difference in outcomes looking at propofol and dexamedetomidine, and then there are a couple studies with dexamedetomidine versus placebo and showing that with dexamedetomidine there are more ventilator-free days and another showing decreased delirium with seven days post-surgery. So I hope this really highlights for you why we do not want to use benzodiazepines and how we really want to use propofol or dexamedetomidine for sedation. So this is a graph or a picture that we published in a review that was submitted to intensive care medicine this past year and really just shows how the sedation has evolved. So if you look at the very first top picture, this were the initial guidelines that came out, and this was all based on expert opinion. There was no evidence, and people were like, yeah, let's deeply sedate everyone, and we thought we were doing a really good thing. And so it's just really, it's interesting to see how this has changed over time. First, we thought we had to deeply sedate everyone with benzodiazepines. Then we figured out this was associated with poor long-term outcomes. Then we found out maybe we should be using propofol over benzodiazepines. Then dexamedetomidine came into the picture, and we're considering dexamedetomidine versus propofol. Then we have post-intensive care syndrome coming into play. We have Yahya Shahibi showing us that we don't want to sedate people at all if we don't have to. And then lastly, if you come to the very end, we have the COVID-D study led by Brenda Pun showing how much delirium these patients had that had COVID. So I think this is really just an important picture to think about, and just we've came a very long way, over 20 plus years, and we really don't want to regress and be deeply sedating and giving all of our patients benzodiazepines. So going back to our initial patient case, I think this is an important study that I did discuss that day on rounds and did get a change in our sedation, thankfully. But this is a retrospective propensity score matching of patients that predominantly received propofol to those that predominantly received midazolam. So 174 patients received propofol, and they were matched to 174 that received midazolam. And as you can see here, patients that received propofol required less catecholamines, less catecholamines. So don't let anyone ever argue with you and tell you you should be giving, you can't give propofol because your patient is hypotensive, days one to four of ICU stay. And the mortality rate was 38% in the propofol group and 52% in the midazolam group after 30 days. And midazolam was associated with ICU mortality. So now that we have discussed all the data that really drives what we did pre-pandemic, what did the pandemic do to us? So this first study I'm going to show you is the association of sedation, coma, and in-hospital mortality in mechanically ventilated patients with COVID-19. So this study is from seven different ICUs in Boston. They were all mechanically ventilated patients between March and May of 2020. So these patients were propensity score matched. So patients either had ARDS that had COVID or they had ARDS from a different source. So as you can see, in-hospital mortality was higher in COVID-19 patients. They also had more comatose days and they also had a higher hypnotic agent dose. The hypnotic agent dose was associated with coma and mediated coma. And coma was associated with in-hospital mortality and mediated in-hospital mortality. Their sedation burden index was three times higher in the COVID-19 patients. And this was even after adjusting for neuromuscular blockers and proning of these patients. And COVID-19 patients had less delirium and coma-free days, not surprisingly. A second study was the ABCDF bundle during the COVID-19 pandemic. It was a one-day point prevalence study. This is a huge study from 54 different countries and included 135 different ICUs with 1,229 patients who met eligibility for this patient or for this study. So as you can see here, unfortunately, it shows performance in non-COVID-19 patients and performance in COVID-19 patients declined during the pandemic, which is really unfortunate. And really, none of the levels really have a great number, which is really unfortunate. It also showed that low income status was associated with poor implementation of letters A, C, and D. And also low income status was actually associated with higher compliance with the letter F. So the last study I will show you from the pandemic is the COVID CED study. So this was a Dole Center retrospective study that looked at sedation practices over 48 hours. So this, as you can see here, patients either were in the light sedation or deep sedation group. And unfortunately, there was a lot more propofol given. There was slightly high midazolam. There's a lot more ketamine. I don't think that's surprising to anyone in the room. A little more fentanyl and a lot more hydromorphone. Deep sedation patients experienced fewer ventilator, ICU, and hospital-free days and increased mortality when compared to the light sedation group. And early deep sedation remained significantly associated with higher mortality after adjusting for confounders. So very scary data. So this really shows, unfortunately, how far we regressed during the pandemic. You can see here that a lot of patients were unfortunately being really deeply sedated. A lot of patients were receiving benzodiazepines. And unfortunately, sometimes that was needed. But I think it's really important to highlight that the pandemic, although we're still seeing some COVID-19 patients, we're not seeing a lot of them. And we can't let that completely change our practice and really just destroy all the data that we have collected over such a long period of time. So what are some strategies to help with the letter C and to overcome barriers and what can be done to really sustain and to help us maintain all this evidence that we have obtained over the years? So all I can say is re-educate, re-educate, re-educate. Unfortunately, what we have seen from the pandemic is there has been a large leaving of nurses in particular, but also physicians, pharmacists, et cetera. A lot of people were leaving health care. So before the pandemic, sure, we were continually have to re-educate as we got new nurses and make sure that everybody knew how to do all these different tools and make sure they knew why we didn't want to use benzodiazepines. But unfortunately now some of the new hires that we have started during the COVID-19 pandemic and I think it's normal for everybody to be deeply sedated and they think it's normal for everyone to be on benzodiazepines. And if their patient moves, then they will deeply sedate them because that's what they learned and they don't understand it's harmful. So all we can do is continue to re-educate all the different key players and tell them that sedatives do indeed reduce time spent in both slow wave and rapid eye movement sleep. They do not help patients to sleep better. It's also important that we restart pre-hospital medications. This happened to me this past week. I walked in and I was on rounds and I had a patient that was agitated. And so a team member was like, hey, let's put the patient on quetiapine. And I was like, hey, we need to restart their home meds. This patient's on gabapentin. This patient is on buspirone. You have to look at their home meds and put them back on that before we're trying to put a band-aid on and start them with new medications to make the patient look better on paper. Also, clustering patient activity. So doing things like to help them sleep better at night and not giving them medications or labs that aren't necessary in the middle of the night. Using a now-go-sedation approach, we know that if we don't treat pain, they get agitated and delirium. So always treating pain first. Use your clinical pharmacist. I'm not just saying that because I am a pharmacist, but just remember physicians, I work with physicians that come to the ICU only two weeks a year, and we have such a rapid turnover of nurses. Use your pharmacist. We're always there. And also staff wellness. I think it's important to remember, I can promise you, if you show that you're turning off a sedation and analgesia on your patients and your patient is able to get up and walk around and gets off the ventilator faster, then everyone will want to do this to every patient in your ICU. So in conclusion, choosing the right analgesic incentives is imperative to providing the best ICU care. COVID-19 has severely regressed our utilization of light sedation and non-benzodiazepine sedatives. Let us not regress post-COVID-19 and forget 20 plus years of evidence. Re-educate all your staff and use your clinical pharmacist to best optimize the letter C. Thank you.

ICU management

sedation levels

non-benzodiazepine sedatives

COVID-19 pandemic

sedation practices