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Hi, everybody. Welcome to our education evening update. Um, I'll just give it a couple of minutes to, uh, let a few more people join, um, and then we'll get started. Okay. Okay. So I think we'll get started. Um, so welcome to our education evening update for s I C s. I'm Helen. I'm on the training committee. Um, it's really exciting. We've got a great talk lined up for you tonight. Um, we've got a full program of talks until next summer. So please kind of keep an eye on Twitter and your emails for for those as well. Um, as you can see, you can put the questions in the chat to the right of the screen. Um, so if you're not a member of S I C. S, um, and you work in intensive care across Scotland. This is your society, um, represents you. Uh, there's various categories of membership for members of the M d t. Um, and with your membership, you get reduce rates. Um, for the meetings, you get transfer insurance. If you do transfers, um, you can apply for our study bursaries, travel bursaries as well, which is very valuable. Um, so I need to mention our meeting, which is happening in March. Um, we're very excited about that as well. Um, so that's the second and the third of March is the first in person meeting we've had back. Uh, I've just heard that are abstract. Deadline has also been extended until the 20th of January. So if you do have some work that you would like to present, um, then please submit it. Um, we've got sessions for all members of the M d t. And as the training committee got to mention our training session, um, so that's gonna be on the Friday morning with talks for hard to reach areas of the curriculum. Um, and all are welcome to attend that, um, and without much further ado do, I'm going to hand you over to Duncan, um, to introduce, uh, Bob. Thank you very much. Helen, My name is Duncan. I'm part of the trainee committee with Helen, and I get the honor of introducing Doctor Robert docking, uh, have the pleasure of working with Bob for a number of years Now, uh, he's a consultant in critical care in anesthesia at the Queen Elizabeth University Hospital in Glasgow. Uh, he's the lead for clinical governance. He's got significant interest in medical HD you. And he's here to talk tonight about all of the fascinating research trials that have happened in critical care 20,022. So I'll hand over to Bob to let him get on with this talk, and I'll take some questions from everybody towards the end. Thank you. Thank you very much, Duncan. Thank you, Duncan, Helen and Jilly for inviting me, inviting me along and thank you to everybody online for taking time out of your Christmas schedule to to listen to me. Um uh, get your apologies in early is someone I've learned quite early in in my medical career. So I do have a bit of a rip roaring cold at the moment. So apologies if I sound a bit croaky, I've got knows that looks like I've been parting with Michael Govan and Aberdeen Club. So, uh, it's not a great start Anyway. We're here to talk about the top trials, as I see it in 2022. So proviso those and see oh, eyes. So, like any end of the year, Best of like you get your broadsheets, and you start reading the the best books for best films. The best. Whatever there is, bias are plenty here. I definitely will have missed some really good trials are keen to here in your comments, any ones that have missed, um, like all of us, we have our fields of interest, the things that pop up when we go looking, the journals that we look at, the areas that we look at, the people we follow on Twitter. And it's very easy to Ms stuff because of the nature of this talk, there is no time for gonna in depth forensics. Uh, there won't be any kind of, uh, deep inspection of bon throw. Any corrections which some of you may be Glad about. Some of you might be very disappointed to hear. Um, it's just gonna be headlines, stuff, conflicts of interest. I've got to see. I have been paid by MSD for previous educational talks, but it wasn't promoting anything. Um, and, um, and that's the only person I've convinced to give me any money. So, um, that's where we are. So, um, the story of critical care trials in the last year, I think has been, ms, but you can't always get what you want. But sometimes you find you get what you need. Um, a lot of these trials, I think with with the proviso of the final trial I'm going to talk about you could say are all negative trials in that they did not find, uh, this is this is a spoiler for the rest of the doc. They didn't find a significant difference between any of the primary outcomes until the last one. Um, but maybe that's not how should we should view these things? A. Calling it a negative trial is, is something that always will kind of get you on the back foot straightaway. It's just a negative trial. There's nothing that has shown things to work. You get that quite a lot, especially from, um, some people on the more kind of cynical end of critical care. Nothing works. Nothing works. If you look at research, nothing is shown to make a difference. Are we've looked at this before? We see, we saw it didn't work there. Well, that's not how these things work, is it? Um, finding that there's no difference for something is an important finding um we should embrace trials that are well designed but have solid findings that General Izabal findings and things that we can take into our own practice and we shouldn't be above, um we shouldn't be above the fact that we can inspect her own practice. And if there's something that says what you've been doing for the last in my case, you know, 15 years now, um, doesn't work. We shouldn't be above having the humility to turn and say, Well, actually, that doesn't work, and maybe I shouldn't be using that. So that is a message of of a lot of these trials as well as we're going to go through them. But it does give us challenges as a speaker to keep people interest. When you say this one to ensure that difference either, but that's where we are. So without further a do first trial. So the first time we're gonna talk about is, uh, Do co is how I've been saying about It's probably just cause it looks like so Duke Oh, maybe you should pronounce it slightly differently. Siddiq, You possibly, um So what we're looking at we are looking at STD. So first the first unit that I worked as a consultant used STD. So what we're looking at, we're looking at a different paradigm and trying to reduce hospital acquired infection. Uh, so selective decontamination of the digestive tract. Uh, so what do we know already? Well, we know there's a lot of research out there, um, to say that this does work for various outcomes. So at the last point of of counting, there were 11 positive systemic, uh, systematic analyses out there saying that it worked for various outcomes. Some of that was mortality. A lot of it was for hospital wide infection, especially ventilator associated pneumonias. However, critics would say that they were a mishmash of varying quality of different ages of trials, a lot of it based coming out of benevolence where it is, uh, an often used intervention. Um, so you have to ask, Ask yourself if there is such a broad spread of of, uh, positive evidence, why don't we use it as a superb thematic paper that came out in sort of a type of 2020? Um, with Brian Cough person is one of the co authors, um, that that tried to pick out thematically. Why people worried about using STD And this was part of the like lead up to this to this, uh, this paper, Um, and the main things that came out from clinicians saying, Why don't you use it? Was this idea that it engendered antibiotic resistance? So for those of the people in the audience who haven't used STD essentially taking ventilated patient's and giving them a mix of antibiotics non, uh, non absorbable antibiotics via an oral paste via a gastric suspension that you delivered to them via gastric tube for the first four days, STD approved antibiotic that had gram negative cover. Um, the idea being that you would eradicate some of the pathogens that we commonly find in hospital acquired infections, especially VAPs. So, uh, do co as I'll carry on calling it said, Can we finish this chick? So can we put this one to bed? So what? What is it? What was it cloth. So a crossover cluster trial with the centers that took part randomizing initially to whether they were starting with standard care or where they were starting with STD. And what you saw in the plan was you have a running you don't have any intervention, you then have a run out, period and then you have your next intervention throughout this in the background as well as the intention to treat analysis, you had a separate ecological assessment going on with the microbiological changes in that unit trying to identify. Is there significant resistance going on? Initially, plans being United Kingdom, Australia and Candida UK didn't take part in the end. The this article is only Australia Candida are going to publish or the Canadian centers are going to publish. But that will will follow. Um and there's various reasons for our recruitment numbers. Mainly, um, there was a waiver of consent because everybody who came into those centers was being, uh, due to that kind of cluster nature effect was being given that treatment if they were ventilated, and that means we have big numbers. So for the intervention paper, we have just shy of 6000 patient's and ecological one just shy of 9000. The headlines Primary outcome was mortality, and as I kind of gave away my spoiler, there was no difference. You see an artery issue a bear mortality of 0.91 for the intervention of STD. But as you can see, the confidence intervals in that are pretty close to showing that there may be a difference. Then we'll come back to that secondary outcomes. Uh, there were fewer positive blood cultures found in the STD Group, and, uh, of the organisms that were found, there were far fewer resistant organisms sound in the STD group. Then there were in the standard care group and there was no difference in C diff infections, which was a big worry as well. Coming out on that thematic paper, uh, what problems did they find with a trial? It was hard to give STD over time. And a lot of STD proponents have looked at this trial and said, Well, you just didn't give it properly. There was about a 10% day drop out of giving STD. Um, that wasn't sourcing stuff that was giving it the palatability of having patients who are very weak. Getting the oral paste. The I/O chance of losing your access to the upper GI tract was a big problem. I would say that's pragmatic. That is what happens if you try and give STD too patient. But There we are. There was the standard group got quite a lot of STD, appropriate antibiotics. So there's a crossover there. You may have ended up accepting the null hypothesis because of the use of STD antibiotics. What has happened after that? Well, the there's a quick on the heels of of publication of Espinoza Beijing Metron assets that came up by the same office, which gives you, uh, pretest probability that STD is 99.3% sure to work. Um, and that is probably not that unpredictable. People say, Well, how does that happen? If you've had a relative negative trial, what's because you're putting into a basic meta analysis where you already have predisposing ideas as to as to how this is going to pan out by the data that's there? The Canadian data is yet to come, and some may say, Well, you hold off the problem we have. If we try and say, Well, let's bring STD into things is going to be that you need belief. And that thematic paper, I think, highlighted that problem. That there is a lot of there is a significant lack of belief. STD is something that should be done, especially when that stuff that you're going to do is a bit of a Pfaff takes up a fair bit of time. It's not particularly pleasant given the oral paste, both patient's and to nursing staff, and it's not particularly glamorous. And this is something that comes up time and time again in, UH, two trials. If it's not glamorous, things don't reliably get done. Um, and I saw that when I moved from a unit but used STD to an hour unit but doesn't use STD is it's it's hard to get people on board. Uh, so that's the Duke of now moving on to glamorous things. What we see here is a lot of people in fancy red uniforms coming to save a day. So this has to be a pre hospital hero story. So this is refill. Um, this is a trial of pre hospital transfusion in trauma. So where do we start from here? Well, we know that bleeding is a major cause of death in patients with trauma. Uh, there has been a move over the last 20 odd years of binning. The kind of a TLS passed a water, uh, paradigm of if you have a patient, Hypertensive has had trauma. What they need first is two layers of crystalloid towards the kind of military side of things extrapolating from experience in Iraq, Afghan, Afghanistan and other, uh, combat areas, saying that we should be using whole blood. The evidence of that it's relatively light. We have obviously the challenges of getting hold of whole blood, which is a big problem in the UK civilian practice. But there has been an increasing trend for use of prehospital blood. We have multiple services who take prehospital blood with them. It forms part of pre alerts, uh, code red coming, etcetera, etcetera. But again, the evidence is lacking there. And there are multiple reasons why that evidence maybe lacking. And one of those things. Maybe it's not just blood blood is not a great resuscitation fluid if you're trying to To improve cardiac output and deal to blood is probably not the first thing that you would reach for. There are two trials on using prehospital plasma Pampa and Combat Pampa. Sure, the difference, um, showing that prehospital plasma work in combat didn't what refill tried to do was have a multi center approach with a strong question. So where was it? What happened? So you have four pre hospital services in the UK taking part? Uh, the allocation was concealed but was obviously unblind into the treated clinicians. So the when they went off on their, uh, missions to use, uh, them phrase they took with my box, and that box may have in it, uh, the intervention or it may have had the control. Um, so we'll look at mixed adult trauma mix of as is it usually in the UK mainly blunt trauma, some penetrating trauma who were hypertensive in this particular trial? A systolic BP. Less than 90 or thready. Radio pulse. The intervention was whatever was in your box. So the intervention group was two units of packed red cells and two liar plaice, which is reconstitute toble. Plasma product comes, freeze dried, and you can reconstitute it out there. So it's about 900 mils in total. If you had the liar plans and the PRC's together, control was up to a liter of of 9000.9% soup and chloride, both of them going through warming devices. If the patient was still hypertensive at the end of their intervention. You were, uh, treated pressures were able to then give further 0.9 n A c uh, until they go to hospital. Um, so results. So it was a combination outcome. Now, you know, combination outcomes are often used in trials, especially if you are looking at something where you have a low rate, um, of, uh, of your primary outcome. So the combination that they decided to use in this one was death in hospital or, uh, non, a non sustained lactate full. So a lactate full from peak of less than 20%. And they had prehospital lactate pock devices, uh, to to to give you this, um, again, I have spoiled this one. There was no difference between the groups with absolute risk reduction. 1.1. I suppose, reassuringly, it makes it a lot easier to to read this paper mortality and lactic Clarence both behavior. Same. It might be different, maybe more difficult to interpret if, like they went one way and mortality than the other. And there was very little found in any other subgroup analysis. Physiologically, these patient's look the same when they came in heart rate BP liked it, as I say was was pretty much the same. Hemoglobin was higher on arrival, as you would expect that the volume that those patient's got transfused was similar during mistake. Regardless of whether you got pre op so bloody you didn't it didn't quite reach its target recruitment. It's about 75%. That was due to the Covid pandemic, basically putting a damper on things. So what you do now? So again, there's another meta-analysis with vision analysis going on that said, there is no difference likely to giving pre hostile transfusion in trauma Patient's uh uh taking this this evidence into account with all the other ones that came before. But it's almost the inverse of what happened with stucco. It's very difficult to put the genie back in the bottle with this one. You have, um, uh, you have clinicians who are going out there. I don't do prehospital care, but I can imagine if I was confronted with somebody who had a bleeding extremity who was hypertensive, and I had the ability to give them blood. I would find it very difficult to not given blood if I had it next to me at that time. Um, I wonder if we're gonna see something very similar coming up now with pre op I and singers. It's just been, uh, not included. It's not an I t u paper, but, you know, uh, some pretty convincing evidence. Now, the preop iron doesn't work in perioperative care, but it's very difficult if you put up a service and you've got the ability to give it and and you have patients who have low iron coming in anyway. Are all questions answered? Probably. Maybe not. So, um, there may be some subsets there. Do we want to take out? Do we want to just include penetrating trauma? Small numbers in the UK Are we happy with the ratio that we're doing things there? Um, albeit when we've looked at ratio transfusion, uh, within hospital populations. We've not been able to mirror the military findings that we've seen with whole blood transfusion. And you do have to ask yourself, do the cost and logistics add up? That's a guess. That is a question for prehospital set up as to as to what we want to do. Uh, so next trial, completely different. So, uh, set 0.2. So this is track. He's in stroke patient's. Um So what do we know before this? This this trial happens. Well, um, the the answer in terms of early track is for as long as I've been doing I t u has been that there's no evidence for early tracheostomy help patients'. And that obviously came out trackman trial again. A big trial that was halted early, although not because of a pandemic, but because of recruitment speech. Um, however, that was a very mixed group and we all as clinicians see potential early wins. I think we've all said to ourselves here is a patient who will not do without getting a track e and therefore I accept the evidence of TRACKMAN gives us. But I am going to push for an early track e here, Uh, and that's why stroke comes up in there. So only 5% of trackman patient's had a neurologic. A neurological diagnosis that may have may push you towards that. And there are multiple reasons why track your Susan stroke might help or might be needed. So we have persistently reduced conscious level. We have Bulba dysfunction. We have secretion management. We have sedation and the muddying of the water the sedation gives us with neurological assessment. So there are reasons there why we might do that. And I'm certainly sure these words that come out of my mouth before I think this person is going to need a tracheostomy because of the stroke that they have had or because the intracranial believe that they've had, uh so this group did. A small study called Set Point, which was a pilot study, came out with German center of the trial. They found no change in the ICU left the state, but mortality was reduced, albeit it was a pilot map was not powered on mortality. Those same offers then contributed to a score predicting tracheostoma need in Neurological Patient's again. It's a small study, a, uh, using air in of curve analysis to to give you to give you a set score and a set score prediction. Need for for, uh, for for tracheostomy at two weeks. So set 0.2 was the next, the next step along. So us and Germany so multi center and quite a lot of centers over 50% of the patients who were recruited came from four centers. So quite a quite a quite a concentration of recruitment ventilated adults with a wide mix of brain injury and some pretty severe brain injuries in there. If you look at it, they use the set score predicting that these patient's going to lead a prolonged INB needs or set score. Great content. I'm a treating clinician had to feel that a tracheostomy is a reasonable thing to do and similar to track man randomized to early. So within five days of being ventilated or late, great and 10 days of being ventilated so decent separation of of time, I think we would all agree. And this was piloted on a 15% difference in a modified ranking scale outcome. And that was based on my pilot. So primary outcome was an M. R S of 0 to 4, and you could maybe argue about the utility of ours, quite a wide range for include some pretty dependent outcomes. And there was no difference between the early group, the late group in terms of that primary outcome. If you looked at the secondary outcome differences, let us stay duration of mechanical ventilation, uh, mortality. Both 28 90 day hostile mortality. There was no difference between the two groups. 95% of the early group got a tracheostomy Uh, two. I think there was two patient's who somehow managed to get excavated before they got tracheostoma sized, which showed just how well the set score worked. Um, there was a loss of data, and I think one patient and to patient's died before they got their tracheostomy, Uh, 67% in the late group. So again, a significant drop off a little bit when we look at similar to when we look at early versus late renal replacement therapy, you will get a significant drop off due to various things. Attrition, uh, lack of need of the intervention. And that certainly happened here and over late. Group, as I say they're 22% managed to get excavated before before being tracheostoma sized, despite their set score predicting that they were going to need ventilated at at at two weeks. Complication rate was, I'm gonna say significant, but it's probably in line with with published data when it comes to this kind of stuff. About 70% of those complications were related to tracheostomy around 5% of that with periprocedural i e in the 1st 40 hours following the tracheostomy. Um, none of them were fatal injury, fatal events. But some of them were significant events. And we should be, uh, speakers. Somebody who who who is a procedure to track customers, track customers. We should be open that we do have complications and and they are they are potentially significant. So is this game set match? I think it highlights the challenge of of, of, of being able to say this patient definitely needs this. It shows that we are not good at predicting that even if we put kind of some semi scientific score on it, we're not that great. This was a pretty sick cohort. It was a wide mix of of different stroke injuries from, uh, from ischemic strokes to, uh, intra para comma bleeds to subarachnoid hemorrhages with some pretty, pretty nasty kind of, uh, enrollment injuries. Maybe there should have been a focus on less devastating injuries. The ones that we we feel would have maybe made that recovery of the M. R. S scale. However, um, it was a world liver trial when going back to as I said Write the introduction. This is what we're looking for. World liver trials, Impeccable supplementary. Um uh, files online showing the real nitty gritty of the patient who were coming into here and the problems that they had. But I do think now it's pretty hard to push a very early tracheostomy in this cohort, and it is probably worth giving people the time to see where we get to. But yeah, total Q Q Does to the trial ists Really good trial. So very hard not to do, uh, not to not to talk about shoehorn in Liverpool. And so the team trial So mobilization, Um, when we're starting off from this So, um, early mobilization in ventilated patient's as a focus, Um, I see required weakness is very common as we know, um, it starts early in this day as multifactorial. We see it largely in in in, you know, in ventilated groups, we see large number of patients coming into this, and there's a feeling that mobilization, especially early mobilization, may mitigate against this. The trials that have been out there have been small if they've been varying in their quality of in varying their findings when we audit ICU mobilization, Um, we see that it's far less common is often claimed we often if you speak to people who say yes, we are very proactive Physio team. We do this all the time, but actually, if you audit it, it is far less common than it's claimed. And there are very, very real and very understandable concerns raised about about lines about tubes and about this events that could happen if we mobilize patient's before we're ready to be ready to be done. There's been a lot of focus done by individual units by, uh, our colleagues in physiotherapy in terms of trying to identify patients who are safe to be mobilized. So patient's who have appropriate physiology who have appropriate interventions. Um, but every unit that you go into will have stories of we got this patient up and they were on X. We got this patient upon why we took this patient who's on mechanical support. We put this patient with an impeller and managed to get into a cycle on the bike. But you have to ask, Question doesn't make a difference. So what made what was the big kind of difference in the team trial was this was a trial that was based on maximizing physio input. So taking patient sedation down, engaging the effort was there and starting off instead of kind of building up from on day one or whatever Day one maybe, uh, we'll start with the smallest move they went from. We'll go for as long as possible. The highest effort when we start to see a patient tiring will reduce that efforts. Probably keep that going, and we'll keep that going for 28 days. Standard care that was delivered was physio if feasible, but delivered by non study staff. So your your physio team, we're not going in and trying to mirror what was being done by the, uh, by the study team. Uh, it should be said that a key part of the team trial, uh, study group was, uh, consultant physiotherapist 750 patient of the six countries, including the U. K and 49 hospitals. And this was powered on these alive and out of hospital by day. 180 pretty sick population. So two thirds in with sepsis, 1/5 receiving r r t again a really, really nice trial. If you look at the evidence that is there of what they did, who they treated and what we're able to do to these patient's, there was a significant separation of mobilization times, as you would hope between the intervention and the control group. Even so, critics of a trial have said that there wasn't nothing There wasn't enough separation between the two. So if we take it for the whole 28 day duration, the mean of the intervention with 21 minutes a day of active mobilization this is just shy of nine minutes in the in the control group. So about 12 minute difference. Um, there was no difference in the primary outcome. There was no difference in the ventilator. Three days. There's no difference in the ICU three days. So by doing this targeted, uh, high intensity physiotherapy, we weren't getting these Patient's off a ventilator quicker. We won't get them out of I t u quicker. If we then went and looked at them with cognitive and psychological assessment tools, we were really similar, so you weren't seeing patients who had a lower amount of psychological or physical stress that was put upon them with with a wide range of assessment tools. What you did see was there were more adverse outcomes in the early intense physio group, which were mainly driven by tacky dysrhythmias and desaturations. Uh, the majority, which required medical input to try and ameliorate, get better. No difference. Mortality. There were no falls or no line dislodgement on a tube dislodgement. But we did put these patient's through, uh, physical stress, and that has seen time and time again in these mobilisation studies. So what to make about, um, again, I think it goes back to this thing of just because you think that something works doesn't mean it's going to, So I'm as guilty as anybody. I've always thought Physio is really important. Physio is important, but what this trial did, maybe it put that really to the test of saying right, doing what we see as being aggressive, aggressive, the wrong with high intensity Physio is maybe not making a difference. We think it's going to be very easy to criticize it, and a lot of people in in Med, Twitter and and and Online have said 20 minutes is really short, but in black and white, it is, but still the intervention group. 22% of them were walking while still ventilated by day seven. And that is pretty remarkable judging that on many of the units that that I've worked and, um, Standard Group, I felt got decent levels of mobilization. You know, we are, We are, we have to be realistic. And I think that's the prior audits of of ice. You mobilization Show this. It's very difficult to do early or even late mobilization in these groups because you need a lot of staff to do it. Uh, some people said, Oh, sedation was a real barrier, and it is if you look at the barriers to these patient's getting mobilized. Sedation was a barrier, but especially in a barrier Day one is not surprising with patient's who were coming in 66% of them. As I say, septic large number of one presses a large number of being filtered. They were a sick cohort, the follow up. So the primary outcomes were there was no no follow and no loss to follow up. But the patient reported outcomes. There was a significant loss of outcome, and maybe maybe that's because these patient's weren't reporting it because they were better. But you just can't tell that from from from a paper itself, right. So box trials next very, very different. So two trials for the price of one so two by two factorial design. So I'm not seen one of these trials for a while. Um, a similar to those seen going back to kind of classic trial like fact trial where you had a cardiac output monitoring or a way of cardiac output monitoring and ARDS um, and fluid management, uh, put side by side, similar to the kind of initial design of approaches, which was the, uh, initially designed as cortical steroids, um, and activated protein C, but obviously changed into just cortical steroids. But it allows for dual allocation of interventions. Uh, in this case, patient's who are comatose following out of hospital cardiac arrest, looking at the effect of auction targets and BP targets. So these are really good, reasonable questions. This is a common presentation. We see this in six AG. Over time, it's right up there as a as a presentation to Scottish intensive care units like it is worldwide. And there is echo points we're not entirely sure what we should be doing. We are aware that neurological damage both primary neurological damage and potentially secretary neurological damage is a common thing. But we have experts about what we're meant to do about that. Do you? Do you treat it like a traumatic brain injury, do you not? Do you do this? Do you do? Do you not do that? And this factorial design allows you to test two interventions with a common endpoint using the same patient cohort. So it was delivered into Danish cardiac arrest centers. So there are the limitations that come here, and there are limitations that work both ways. Number one, it's a single country number two, You have, uh, centers that are set up primarily to care for patients with cardiac arrest, and that's not necessarily a set up. We have widespread in the UK and certainly not in Scotland. Uh, and that may color some of the the outcomes that we see. But to describe it very, very briefly if we look at the oxygen group, they had a restrictive auction group of 9 to 10 killer Pascal's and a liberal of 13 to 14 for the low. Uh, for the BP group, we have a low map of 63 millimeters of mercury in a high of 77. Um, interesting. And how they how they did this. So the auction Asian was on blinded, the map target were blinded and they did this by calibrating a device and saying to the treating teams aim for a map of 70 in these patient's and, uh, the calibration device that they put on to the BP. If you were randomized to to the low group bumped your BP up. And if you're a man randomized to the low group bumped your BP down. So you aim for 70 and you got what the trial lists wanted you to get. Primary outcome was death again combined outcome of death or discharge with a disability again. Slightly different, uh, disability scale. But similarly looking at pretty, pretty disabled CPC three or four. All other interventions were protocal ized, including, uh, targeted temperature management, not hypothermia, but targeted temperature management in in in this cohort. So the headlines of a take homes um, there was no difference with either intervention for the primary outcome and all the predefined secondary outcomes. There was no different seen, uh, interestingly, they looked at the interaction between the two factory interventions, which is obviously very important to do if you're doing a two by two factorial study, Um uh and there was no interaction between the two, so it wasn't like, Well, maybe you would be better with high F i o too high SATs, but low BP or vice versa. That doesn't doesn't seem to be to be borne out by the study. What I would say, um, of note, there was a significant low mortality, another out of hospital cardiac arrest studies. So if we take the TTM studies, for example, so the the the mortality was about 32 between 32 35%. Uh, in both of the box trials comparing to about 50% in, uh, in the TTM studies. Uh, if you look at the Australasian data that that's coming out that looked at how they can touch the ms on my last talk, if you look and see over time, how mortality outcomes have changed in our hospital categories, we seem to have after having coming down significantly since the early two thousands. We seem to be stuck around 50%. Now, these were expertly run trials all being a single country again, really worthwhile looking at, uh, if you're interested in in how how to design trials, Um, what would I take from a take home from this? I think that personally air on the side of doing less. And I think this is something that has come out in the hospital. Garda Crestor's doing it less, but doing it reliably. I think the desire to drive blood pressure's higher has not been borne out by this trial, and I think isn't borne out in other trials. So I'll be happy to go for a more conservative BP. BP target. Um, but yeah, that that was my take take home from these, um so coming towards a the end here, And, uh, as I said at the start, we would finish with one positive trial. So, you know, striding to the finish line Here comes Usain Bolt and striding to finish finish line. Here comes our single trial with with With With a traditional positive outcome. So this was the brilliant named cosmic end of life trial So, uh, we are looking at how we look after our families. Uh, patient's we have who die and do not survive. R i t You stay. So what was known beforehand was that, uh, persisting grief reactions in these families are very common. PTSD is very common. And what happens in I t u and what happens and how we deal with things has long lasting effects. And anybody who has spent any time doing, uh, spending times with follow up visits biv a through, uh, follow up programs. Bereavement programs will see this. Uh, there is some evidence out there that poor communication worsens these family outcomes and can emphasize especially PTSD. But there is little way of RCT evidence of this, and generally when you look at it, it's seen as soft skills. So it's seen as something that's maybe been harder to study because it's not seen as being a particularly scientific field. So what was it? So French study? Uh, multi center. Um, it was a cluster RCT, um, but unlike Stuka, it wasn't running out your either allocated to the intervention or your allocated to standard care. That standard care was whatever you did in your normal day to day practice. The primary outcome was a portion of families who had persistent grief, and that was measured using a scale called a PG 13 scale. That is not an ICU specific score, but it is, uh, it is a grief scale that is used commonly by psychologists. Um, there were a lot of secondary outcomes here again. All of it. Largely driven by, uh, kind of psychology, psychological tools, stuff like Hades. But it's obviously been used a lot of ICU trials, uh, PTSD specific skills as well. Um, the intervention was that the the the caring, um, team would have three separate visits to the family, and they were temporally separated. And they were also physically a bit separated as well. So the first visit was to establish that there was going to be a withdrawal of life sustaining therapy, an institution of end of life care, and that was done separate from a bed space. Um, and that was that could be done. Uh, it was designed to be done by doctor and this together. It could be done by by by by separate, but designed to be together. And that was to go through what was going to happen to talk about what's going to happen to explain the concept. The second was that the team were were heavily, um prompted to drop into the bed space during the dying process. Um, it was commented on by the trial list that there was generally a feeling that, you know, we should give patient space and we should do obviously, and I'm sure we all do as as as as as critical care practitioners, however, it was dropping in to show your ongoing presence and to show that, uh, they were still under under your care and your remit. And the third was a meeting following death. And again that was to be done separate from the bed space. Um, it could be, uh, ideally done, uh, on the day of death, but could be maybe temporary separated if a family would then coming back at a later date, to pick up the paperwork or to go over things. And again, it was a meeting to reemphasize what had gone on the process that had had had been delivered and to answer questions at that space. And training was given to the team by the trialist, including videos of of ideal interventions, if you like, as we're done, um, what do they find? Well, what they did find is they found a significant reduction in persistent grief. The Secretary outcomes were all positive as well, in terms of reduced amounts of PTSD, reduced prolonged depression of the family, uh, increased positive feelings about death and the dying process. And all of that follow up was done by psychologists were blind into the allocation close. The trial was appropriately chosen as a design, I think, uh, so you didn't have to separate interventions going on in the same unit. It's difficult when we assess these things because we're using assessment tools that we're not used to using. And you know what? What, what? Reduction of grief is appropriate. You know what reduction of grief is a reduction of grief that you want to see. Uh, to my mind, however, it reinforces the value of spending time at end of life discussions, and it it reinforces the value of spending time. I think I think we all as collisions. Uh, and I see you carers have these kind of things that we say to families, and I've certainly said families before I'm around, I'm going to be around all day. If you need me, just holler, and I'll come by. But actually, maybe I'll start to drive myself more to actually just going in as I often do, but not always do, and just showing showing face. But you're there and your present during the dying process. Um, so that's that's me. Thank you for your time. Merry Christmas to you all. And I'm happy to answer. Uh, well, I say answer any questions. I'm happy to give my ongoing opinion to to any fimosis ongoing Thank Thank you very much, Bob, That was really interesting. And I feel completely up to date now with critical care research. Um, if everybody just post their questions in the chat, then I can, uh I can read the might for the people who are listening and hopefully, um, probably happy to answer them just from my own interest, Bob, to ask a question like, uh, rotating through the West of Scotland as a trainee in intensive care. There's a huge amount of variation in tracheostomy procedures getting carried, and some units do almost none, and some do loads, I guess. On the back of that trial on the back of previous trials, do you think the Queen Elizabeth, specifically that you work in is going to change their practice? I would say that maybe one of the more higher users of tracking ostomies maybe you wouldn't agree with that. Um um I So I I do think we do a fair amount of tracheostomy. He's, um we're not having having looked at Scottish data previously were not completely. We're not completely out, out, out of on the wild then. But there is a big variation. There's a big variation, I think, by set up by, um, specialist back up in terms of, uh, teams who are on site case mix. Um, I honestly do think it will change what I do in terms of identifying these patient's, especially neurological patient's who Obviously, there's a significant portion of these patient's end up from my from my point of view over in the neuro Institute, but it would it would change the ones we admit, Um, where I think, uh, they're definitely gonna need a tracheostomy, so we'll we'll crack on. We'll just do it on day one. day two. Um, I think it strongly point you towards saying just give a better time and wait, which is similar with a lot of neurological, uh, patient's in terms of prognostication in terms of, um, in terms of imaging in terms of intervention is is just as as as the great move. And Singer said, you know, jump up and sit on your hands. It's it's, like, just just wait. So, yes, I think you might cohort. Definitely. Okay. Thank you very much. And, well, we're just waiting for other questions to come in. Um, again, I've never worked in a unit that uses, uh, selected become decontamination. Where was it you worked in? And is there? Is there? Units in Scotland are using it at the moment. So my best, my knowledge. No unit in Scotland uses it anymore. But Western and the Western for Marie did did for 25 odd years. Um, well established, well established practice, uh, the only unit I've ever worked on that used STD. Um, the reasons for not doing it. I mean, it's there's a cost. There's a cost to to to using it. Sourcing stuff was difficult for a while. the stucco try lists used the first ever to my knowledge, Uh uh, Specifically produced STD medication. Uh, you had to kind of source it, um, on a fairly ad hoc basis via via pharmacy. Um, uh, anecdotally, I would say, since since we moved to the QE, Uh, I think we see more gram negative. Uh, chest infections especially, um uh, than than when we didn't use it. Um, is that a problem where the trial would suggest that maybe maybe it isn't. And maybe, and that's always been the challenge with lapses. Do VAPs cause mortality? Debate, debate, debate massively lengthen your your length of stay. Is it an issue if you're using lots of gram negative antibiotics, I would say, as we as we face antibiotic Valhalla. Yes, that is a real worry. Um, but it is a difficult thing to get everybody on board with, and I think that's the reason why it's not. It's not taken off in the UK. I mean, I remember being, uh, Shue level and seeing an S i c s pro con debate. Um, where? Where the person who said Yeah, it works. The argument was, here's all the trials that say it works. And the person who said it didn't work. Um said it didn't work because I don't use it. And I've never worked in the unit, but uses it. Yeah, I think that's that's the problem. If it's not around and it's not a sexy intervention, it's hard to get people on board. Yeah, I think no act more. Unfortunately, 35 I am studying for thick, um, at the moment, and I must have done about five questions today on selective decontamination. I feel like the proportion of questions have been asked about it. A natural experience of it is quite a kind of a bit skewed. Um, I have a question. If that's okay, I just wanted to ask. I thought the team trial was really interesting and quite surprising with the results. Um, I guess either showing less is more or there's maximum effect. Do you think that the results will change what happens in clinical practice with regard to, you know, mobilization early with with Wild Patient's still on a lot of support? Uh, I think it's very important. We don't view it as being that it's This isn't saying that mobilization doesn't work. It's not saying that that physio is not important. It's clearly clearly it is. I think it's saying doing doing it in the manner that was done in the trial, um, is, um, doesn't carry it doesn't seem to carry with it the benefit that we all think it it does. Um, so Paul Young, who's obviously one of the one of the trial, is involved trying to remember where I saw. I remember him talking about teams before, just as it was just as they were designing it. And it was it was in the midst of, um in fact, it was at State of the Art and, uh, and he said, He said, Well, we just don't know. We just don't know is a problem because I think there's There's several speakers who came on and said out We've done all of us and we do this and we mobilize all our patient's on ECMO. And we've done loads of, uh, you know, cross sectional muscle biopsies. And you know, they're they're really bad. And therefore if we got amount of bed quicker, their muscles would look better, and it's like, well, and you don't know that you don't know what what you do. What you're doing is you're you're you're you're taking different intervention, different, different findings and saying we're gonna apply an intervention to it and it will make it better. Um, and we don't know that because it's obviously a lot more complex than that. But but equally, um, uh, they've they've as a group of trialist. I think they will come out and said, This doesn't mean Sacco, your physiotherapist. What it does mean is don't necessarily aim to get your ventilator patient out of bed on day one and try and get them standing. And if you look at a description in the in the supplements of of what they got, these patient's doing pretty pretty impressive. You know, when we're often aiming for let's let's go for a bandage sets. That would be a good thing. Um, and I said, Well, let's let's get you walking on the bed space. Um, Thank you, Doctor Myles by way for the comment of a I never saw an MRSA Midwestern. It must have just been the older consultancy so that thank you. And if there's any other questions, please put them in the chat. Um, before we allow Bob to to finish off the evening, what I'll do is I'll, um, tell you all about our next event. Thank you so much. Shorter talking, um, for bringing those trials alive for us. Um, so our next event it is on the 19th of January. Um, So Doctor Paul McConnell is going to talk to us about ethical dilemmas. So, uh, the sign up link will be coming out soon If you want to sign up for that, Um, and if there's no other questions, um, I just want to say thank you very much. It was a great talk and a really apt one for the end of the year. Um, I hope everybody has a great Christmas festive period and Happy New Year and see you all in January. Thank you very much.