I'm Sid Patnawala, I am a pharmacist and I'm based at the University of Sydney and the Royal Prince Alfred Hospital in Sydney, Australia. And I am going to present the second half of the guidelines that pertain to medications within the guidelines. So I have no conflicts of interest to disclose. I am an author for articles in PICO questions 7 and 10. So the questions that I'm going to talk about today, and hopefully I'm here to summarize and give you some insights into the thought processes behind the panel and how we came to some of these decisions. So there are three questions that I'm going to talk about that pertain to the induction agents. Induction versus no induction, etomidate versus other induction agents, etomidate with or without using a corticosteroid, and then the other two pertain to neuromuscular blockade. Now question six is a best practice statement, so I won't go into details about that. But let's just say that the background on this is that we considered, you know, would we not use an induction agent in some specific patients who were in a minimally conscious state and who are hemodynamically instable? The bottom line is that there was really no direct evidence to support that, but the panel still felt that the benefits outweighed the risks of giving, so we should give an induction agent. So that was the best practice statement. So I'll cover questions 7 to 10 in a little bit more detail. The outcomes listed on the right here, you know, if you look at them, it's intuitive in how they pertain to the question. So for example, with the etomidate, we're concerned about adrenal suppression, so that's why, you know, the outcomes are hypotension and multiple organ dysfunction. And the questions related to neuromuscular blockers, it's more about, you know, first pass success and complications. So that's how the questions are set up. So question seven is, in critically ill patients undergoing RSI, the difference between etomidate and other induction agents with respect to some of these outcomes. Now, acknowledging that these different agents, although they're combined, they have different pharmacological properties, they were still combined in that question. But in the guidelines, we've sort of separated out while discussing them. So here are some of the reasons of why we came to our recommendation. Just on the right is the certainty assessment. It's part of the grade evidence decision framework, but it's not the whole thing. It's just one part of it, so I'll just draw your attention to that. But the rationale is, so there was no, you know, significant difference in mortality between etomidate and the other agents. And most of them had, you know, etomidate has a favorable profile, hemodynamic profile. When you look at the risk of bias assessment, they're all serious. So most of the studies had some flaws in them. And so that's why at the end of the day, you know, it was a moderate sort of a recommendation. There was some evidence gaps in certain subsets of patients. So if people had, you know, preexisting HPA suppression, they were on corticosteroids to begin with. And there was one meta-analysis showing that perhaps in people with high severity of illness, they were at higher risk for poor outcomes with etomidate. But that being said, it's really hard to differentiate what are those cut points of where you make that decision. So at the end of the day, we came down to, we suggest that there is no difference between etomidate and the other induction agents, and it was a conditional recommendation with a moderate quality of evidence. So building on question eight, sort of builds on question seven, and this is, should you use a corticosteroid in addition to using etomidate? So use etomidate with or without a corticosteroid, and the outcomes being, you know, infection, mortality, vasopressor use, and these others listed. And most, so the studies, a lot of them showed overall, you know, there was no difference in mortality or multiple organ dysfunction syndrome, but there was a lot of heterogeneity in the corticosteroids used. So for example, one study would have this 40 plus hour infusion of hydrocortisone, 200 milligrams over that time period, versus another one had 200 milligrams as an infusion per day. So they were very different doses. Also sometimes it was an infusion versus other times it would be a bolus dose. So there was some heterogeneity in the regimens used. So there was overall a low certainty of evidence, and the evidence gaps, you know, pertain to, there was some populations, for example, people with sepsis with cirrhosis, there were some small trials showing that those patients could potentially benefit. But when you look at the trials, they were really small sample. And that's why when you look at this, there was some serious imprecision in a lot of this because of wide confidence intervals. And a lot of that is driven by small sample size. So we suggest against administering corticosteroids following RSI with etomidate. So remember that beyond the evidence, the framework for GRADE, also we look at other things, right? So the values, the adverse effects, other risks and benefits by the panel. And we came on, and while we were sort of debating this, we came on the position that we wouldn't recommend giving, you know, people corticosteroids because they also have their own adverse effects, and the evidence wasn't that great. Okay, moving on to question nine is, so now we're shifting gears to neuromuscular blockade. And this question is, in people, particularly adults undergoing intubation, is there a difference between using a neuromuscular blockade with a sedative or using the sedative by itself? So the background here is that, so we're considering the situation where you have the cannot intubate and cannot oxygenate scenario. And so are there situations maybe where you don't use neuromuscular blockade? So when you look at a lot of the studies, when they look at first-class success rates, they were higher with neuromuscular blockade. So I've listed the ranges there. So there was some wide ranges for some of these, and that's where you see some serious imprecision here, and also risk of bias. A lot of these were observational studies, but generally it was higher success rates with having a neuromuscular blockade. The other thing was with safety outcomes. So the safety outcomes, they're not reported as well. Which are the safety outcomes that are different between the different studies? Sometimes they're grouped together, sometimes they're mentioned separately. So overall, it was a low, very low certainty of evidence. And in terms of an evidence gap, we considered that, is it really feasible in a future study looking at safety outcomes? So that's something to, how would you actually do a study? And that's something that we thought about. So we recommend administering a neuromuscular blockade agent when an induction agent is used. And that was a strong recommendation overall because of the success rates, but the quality of evidence was low. And finally, the last question is that, in adults undergoing RSI, is there a difference between rocuronium and succinylcholine? This is the perpetual debate of rock versus sucks, and so that was of value to have in the guidelines. So there was no significant difference in forest bath success. It was driven by, so there was a lot of observational studies, and a lot of them were small samples. But there was one large clinical trial you probably saw, the French study, which was a pre-hospital study, where it was inconclusive, basically. But there was one small retrospective study which showed a higher mortality rate in those subset of patients with high severity traumatic brain injury. But we considered low certainty because of the, you know, it's an observational study and small sample. So evidence gaps, risks of patients with TBI, perhaps another future trial should consider that. The optimal dose is, it depends, so the doses might vary. And then post-intubation outcomes, because when you use rocuronium, there's the perception that someone is sedated when they may not be sedated, they're just paralyzed. So some of the studies that have looked at post-intubation sedation use have shown that there have been delays in using that sedation. So maybe a future study looking at outcomes such as awareness might be useful. So we suggest administering either rocuronium or succinylcholine when there's no known contraindications to succinylcholine. And these are the final recommendations summarized. Thank you very much. Thank you.

induction agents

etomidate

neuromuscular blockade

intubation

rocuronium