He's back! Dr Bob Docking, Consultant in Anaesthesia and ICM, joins us for another round up of the top critical care trials of the year 2023. Join us as he presents the most significant critical care trials of the year in a way that is easily accessible to all critical care healthcare professionals.
SICS Evening Education Update : Critical Care Trials of 2023 - Dr Bob Docking
Summary
During this on-demand teaching session, Dr. Docking discusses the top ICU trials of the year, which are crucial for healthcare professionals dealing with critical care settings. He also highlights the values of the Scottish Intensive Care Society and the benefits of becoming a member. The Society is dedicated to enhance the delivery of care to critically ill patients through education, research, and audit. Furthermore, he introduces a new course for senior registrars, ST3 candidates and new consultants – the Consultant Intensivist Transition Course. This course focuses on equipping doctors with the non-clinical skills needed to excel in their first consultant post. The highlight of the session is Dr. Docking's insightful discussion about the Clover study for patients with sepsis-induced hypotension, emphasizing the benefits of fluid therapy and vasopressors. All healthcare professionals attending would have ample opportunity for interaction and live questions.
Description
Learning objectives
- Understand the role and drawbacks of fluid therapy in managing sepsis-induced hypotension.
- Differentiate between a "restrictive" and "liberal" protocol in fluid management for patients with sepsis.
- Analyze the findings of the Clover study and its implications for clinical practice in treating sepsis-induced hypotension.
- Understand the concept of central and peripheral presses and their usage in treating sepsis-induced hypotension.
- Explore and debate the current guidelines of sepsis management, including the "Surviving Sepsis Campaign".
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Hello, good evening everybody and welcome to the December edition of the sixth evening education update. Um Thank you everybody for joining us on this kind of dark and slightly g er Thursday evening. Um We are delighted to have stock back for a second consecutive year, talking about the top ICU trials of the year. Um I know that many of you here will already be six members, but for the benefit of those who maybe are joining us in for the first time or from further afield, the Scottish Intensive Care Society is an organization which aims to improve the care delivered to critically ill patients through Scotland. And we really have focused on three main areas, education, research and audit. We have a number of different membership categories which span different healthcare, professional backgrounds and a number of benefits of membership including reduced delegate rates are meetings, comprehensive travel insurance, and access to travel and education bursaries. So if you're interested, have a look at the six websites and a couple of and, and in terms of the interests of shameless promotion, a couple of things to tell you about. So, um six esm is uh in on the 7th and 8th of March next year at the um the Fairmont Hotel in ST Andrews. Um We've got a number of really interesting speakers, a number of parallel streams catering for different clinical and nonclinical interests. And then a new course that six will be running in collaboration with the Faculty of Intensive Care Medicine. Next year is the consultant intensivist transition course. And this course is aimed at senior registrars seizure candidates and new consultants. And really that's about exploring the rewards and challenges of consultant life and equipping yourself with some of the nonclinical skills that are required to establish yourself in your first consultant post. Um There's lots of international faculty are coming across for us and from various places including Australia. So um if you're able to join us for that, we'd be delighted to have you. Um Now our speaker this evening. Um uh So just a brief introduction. So, Doctor Docking is a consultant in critical care and anesthetics at the Queen Elizabeth er in Glasgow. He grew up in Newcastle but was naturalized to Glasgow by work wife and Ways, which if you're ways is if you're joining us from outside Scotland is a nice Scottish word for kids. Uh He is a full time intensivist with occasional forays into urological anesthesia. He is the faculty tutor and has interest in education, ventilation and Liverpool football club. Um And so on that note, I'm going to hand over to you doctor Stocking. Um on the right hand side, you will see a chat box. If you have any questions, please feel free to pop them in there throughout his talk. And we can either, um you can either address them through if you want Bob or, or we can come back to them at the end. Great. I see. Excellent. Right. Hopefully everybody could see that. Um So, er, well, thank you very much for having me jelly and, and Helen, um absolute pleasure to be back um as a, as you said, consultant in mainly it of a QE and uh this is becoming a recurring theme. Uh So, um becoming AAA fixture maybe a little bit like Jules at Christmas time, although I haven't prerecorded this. Um uh I am not an expert and I think that's the point of this talk is that I'm not an expert. Um I have an interest in, in um consuming research in applying research uh to my practice um as, as much as I can, but I'm not an expert. Um uh If you like, I'm like the comedian on question time, he gets invited in to uh give his, his hot take on the situation. Uh which means I'm not too proud in terms of um there are things I don't know, there's things that I don't understand trials, I'm keen to learn and um I can see quite a few research gurus who have signed up to uh to um listen today. So I'll keen to be keen to be put, right? So, um when it comes to these things, uh trial selection, how do you choose what you're gonna talk about over a year? Um So it's a little bit about what you're interested in uh where you work, um uh what your colleagues are like and who influences you in terms of, in terms of uh of what you read. Um So I work in a large city center, um hospital itu uh trauma center, Hemato oncology Center of the Car um service and the transplant service there. Um So that probably influences some of the things that I read. Um that can be a good thing or a bad thing you can see here, my Spotify R for the year which has been utterly destroyed by my Children um to a point where I ICI can't listen to it on shuffle anymore because uh I get a selection of these, although number five is a bona fide Banger. So anyway, um I thought we'd talk about six studies today um could have talked about many more, but it just gives us time to have um a slightly closer look at those six studies. Um And they are all things that interest me and hopefully will be applicable to many people's practice as, as we go along. So, first thing uh first paper I thought we'd talk about is the Clover study. So, um New England Journal paper RCT, um, that looked at uh, early um restrictive or liberal fluid management for, as it says, sepsis induced hypotension. So I spend a lot of time working in medical dependency as well as itu and this is a common, common presentation, isn't it? So, patients who we think have infection, who present hypotensive with, er, plus minus evidence of hypoperfusion. And what do you do? And it's probably, you know, a story as old as time in terms of what you do. Um if you work in a ward, uh well, you know, if all you've got is a hammer, everything looks like nails. So you get fluid, you give fluid, you give fluid and you get fluid. Um if you have access to the sweetie cupboard of um IU in critical care, then maybe you can choose presses, be very peripheral presses, central presses. Um So we, this is dry argument that continues in a kind of fairly circular fashion um in terms of evidence that's out there. Um Well, what do we know? We know that? Um certainly observationally, um the more fluid you get, generally, the worse outcome is although open to massive bias and they probably a sweet spot. Um where that sweet spot lies is gonna be different for different patients at different times with different diseases. Um The classic study had suggested there was no difference in liberal versus standard, but that was patients who were um recruited in itu where you're probably a good bit of your along your journey of of critical illness. Um And that is not where Clover is aimed at. Um And it is difficult to capture patients early. Um Scotland's currently kind of hosting the EIS trial uh similar kind of thing looking at peripheral, the use of peripheral presses in patients with septic shock. And it's difficult to capture these patients early when they come in. Obviously, the studies, as I say are completely fraught with bias and we've seen the challenges are out there too early called directive therapy where uh a kind of targeted fluid therapy, targeted vasopressor therapy. Initially, it looked like it was going to be the the panacea for um sepsis induced hypertension, septic shock, maybe not so much. And that's the standard care is caught up with things. It has the paradigm of treatment has changed. The knowledge and the information around er treating patients with sepsis has changed. So have the outcomes. So what did Clovis say? Well as I say us, Multicenter RCT and based on so just over 90% of all the patients in the study in both arms were, were recruited in the emergency department. So patients adult patients with sepsis and that's kind of defined as uh susp suspicion of infection. Antibiotics have been given or a plan to give antibiotics. And hypotension defined as, as you can see uh BP, less than 100 systolic after a liter of intravenous fluid um you could get up to 3 L before you were no longer deemed recruitable. Um But it was after a liter, they tried to capture people and you were randomized to have a restrictive honorable protocol with a primary outcome of reducing 90 day mortality by 5%. Um The next slide is gonna show you what the protocol looked like and it's really busy. But essentially if you were randomized, a restrictive thing, your fluids got stopped. And that was, that was the starting point was switching off on any maintenance or any bolus and saying presser first approach using either peripheral or central presses, ideally noradrenaline targeting the targets that you can see. The liberal group had a fluid first approach uh aiming to give you up to 2 L in the 1st 180 minutes after randomization. And that was a very tight time frame to get that turned around. Then um kind of mirroring the surviving sepsis campaign, 30 mills per kilogram that the Americans are still very fond of. Both groups could receive rescue therapies if not meeting targets. And I mean, the crossover was allowed. So you could use extra fluid in the restrictive group, you could use presses in the er liberal group. Um with the specific tricks you can see you were in that treatment after 24 hours and the rest of it was very pragmatic. They didn't tell you how to manage sepsis or how to manage infections that was deemed to be left to the clinicians who were there. As I say, this is where you get flashbacks to terrible meetings of, of your way. This is a pretty busy study, but I'm going to tell you all about it. I'm not, it's there. You can see, you can read it for yourselves when you get to it, but very tightly governed as to what you were meant to do. So what happened? I was stopped for futility reasons. So, um like many good modern trials, there's a data monitoring committee um with specific intervals where they picked up on people and they said two thirds of recruitment. So just over 1500 patients futility, we're not going to show a difference here. Um The primary and secondary outcomes were different. So 90 day mortality before discharge home of around 14.5% in both, both groups. Um remarkable protocol adherence. I mean, that is a really, really busy protocol. You're dealing with this in the kind of high octane environment of uh ed um where you're trying to do lots of different things to patients. So procedures, investigations, um more randomization and things that go with that. But still an adherence of 97 and 93 is remarkable and they managed to separate the fluids really nicely. Some of these fluid studies, when you look, there's not much in it at all 24 hours, you can see it's almost, yeah. Well, just over um 2 L difference. Um at 12 hours, um the mean fluid that had gone into the restrictor group was only 500 mils um and a separation of vasopressor use as you would expect. Uh It wasn't protocol but patients went into it, but it was far higher in the restrictive group as you might expect with a higher proportion of patients uh needing uh central access monitoring where you could look after these patients uh in your, in your hospital setting. The same for us in the QE. So what to make of that? Well, it's an ideal population. These are the patients that get phoned through to medical, high dependency or high dependency of any setting when you're, when you're working in, in the UK. And it is pragmatic, there are some problems there. Um You could argue they weren't that sick. So at time of randomization, medium BPS, over 90 systolic lactates only of two, but there was still about 50% 90 day mortality. So it probably hammers home to those of us who underestimate, you know, what a wee touch of a sepsis can do to you. It's, it's a serious condition. Um It did treat sepsis the same regardless etiology. And that I think is a problem. I think all of us as clinicians will, will recognize that um your treatment is going to be guided a little bit by what you think the etiology of the sepsis is both in your choice of antibiosis, but also in your kind of feeling of what the patient trajectory is going to be like, which patients are far more likely to be vasoplegic. You know, which patients do you think are going to have a real sudden idea at, you know, kind of 12 to 24 hours. But then they turn around quite quickly and other ones, um, that, er, aren't, somebody said the video stopped and there's no sound. Is that a problem for other people? No, I think it's fine, Bob, you're ok. Um Maybe I've not paid my bills on my electricity and my wifi. Um So, um there's no formal measures of fluid requirement. That's the other thing uh you could use uh echocardiography. That's one of the um uh one of the rescue points was if you did an echo in your ob they were profoundly hypokalemic, you were allowed to get fluid. Um but it's maybe not prot in the same way that some studies might be. I mean Andromeda Shock two is, is, is on its way with a kind of CRT based protocol er, fluid versus pressor approach and maybe that's where we should be going rather than, you know, just kind of 11 size fits all. But again, you balance that against the pragmatic nature of trying to do this where we don't have in every hospital, 24 access to echos or 24 access to clinicians who can do echocardiography So it's probably reassuring you argue a case either way. And you know, I think you have to go down the line of saying you target your treatment to the patient who's in front of you. Um But that, you know, go with your gut instinct and you'll probably come out um uh about the same so very different things. So we're gonna move on to another new England journal um paper. This is the device trial and what you can see here is a man um explaining his choice of laryngoscope to uh an audience who are frankly bored. Um And that's pretty much what I think where um Med Twitter or er med social media boils down to when it comes to airway things. Um A lot of highly held strong opinions about how you should do things but then little in the way of evidence and this is an attempt to try and sort this out. So this is video laryngoscope versus dial laryngoscope for intubating a critically ill adult. So, what do we know already? Well, we know there's very strong opinions. Um So Cochrane review that came out this year by uh lead over by Hansel supporting video laryngoscopy mainly in the theater setting with, with papers that they pulled out from there. Um And again, pretty strong, although, you know, some of the evidence base around it is mm moderate or mild, the overwhelming wealth of it would point to use using video laryngoscopy and the critically ill, there is varying evidence, there's certainly a lot of observational stuff out there would suggest video laryngoscopy allows you to get good views of the airway. It doesn't necessarily speed things up in terms of intubating. But what we do know is that the risk of failed intubation is significantly higher and the uh the um consequences of failed intubation are really, really, really high when we're dealing with uh the critical. And certainly over the last 10 years or so, there's been a rise in the ubiquity of the use of video laryngoscopes to the point where devices like the mccoy blade that you can see on the slide, there have pretty much been chucked in the dustbin of history. So what do we do? Unblinded? RCT? Unsurprisingly, cos you can't be blinded. What you've got in your hands are video, laryngoscopy versus DL. And this was any VL versus any DL um with trained assessors to the outcomes. So this isn't one way you could easily gain it as, as an intubator. If you had a a priori idea of what you wanted to use, the primary outcome was going to be first pass success. So um first pass success of passing a tube into the, into the Carina. Um and there's some criticisms of that and we'll talk about that. In due course, the majority of the intubator were doctors in training um America. So, you know, residents and attend uh which way is that residents and fellows are often attending um with relatively low number of intubations, uh 50 was the median number of intubations in each of the groups that were done. The conduct of the RSI was very similar to the UK COS that was one of my things when I looked at it because again, you read quite a lot about practice in, in, in the US and it sounds quite different. There's lots of people talking about doing er nonparalytic intubations, semi awake intubations, spraying the cord using ketamine, doing lots of crazy stuff. Didn't look like it from here. Vast majority of people got a hypnotic G A with a neuromuscular relaxant. And importantly, all patients had er capnography used um during their intubation. So what happened here? Again, data monitoring stopped at 1000 patients are meant to recruit 2000 stopped at 1000 because of the vast difference in first class success. So 85% video allowing the groups versus 70 in scos, all of the pre specified analyses were, were pretty much the same. Um With the caveat, more experienced, you were as an intubator, the lower the difference was. So you were probably equally as adept at intubating or getting close to being equally adapt to intubating with DL as you were VL. Um and the difference dropped down, but the difference was still there. Um Key points, majority of intubator had trained just as much with V LS as they had with D LS. So you don't have that learning curve to what learning curve of another paper later on. Um But that is a real thing, isn't it? We know it takes time to get used to devices, but people seem to know what they were doing. So great positive paper we should be using VL for all. However, the incidence of complications was very similar. It was about 20% and they ranged from, you know, ding people's teeth to profound hypoxemia to er initiating vasopressor support because of hypotension, cardiac arrest. That's always, I think overrepresented in these papers um when I compare it to my own practice, um but it's overrepresented because it does happen and you see it in observational studies and importantly, you see in RCT S as well. However, I would argue this is not a complication that's caused by the device. This is a complication that is caused by the process of intubating the critically ill. So what to make of all of that? Well, I think it pretty much shatters by theater different. We have to do our own thing down in critical care. I don't think it's that and it loses that whole thing that other papers have had off where you can get a great view, but you can't get the tube in probably because the majority of intubations in this study at least were done using adjuncts like bots and stets. People have criticized this paper because they say first pass, success is not patient centered. I think if I was a patient to get my er, intubated, I'd quite like it to go in the first go and, and in the hole that goes down to the lungs rather into the stomach. And I personally cannot see a good reason not to use VL in the modern world. I think there's unmeasured benefits that exist out, out with this RCT training, team involvement. I can see what people are doing. I can see when they say it's a very anterior larynx instead of being glib and saying that's because the larynx is an anterior structure. You can say no, I see what you mean. It's gonna be difficult to achieve and here's what we're gonna do to make it better. Lots of critics about what, what type of VL do you use? I mean, that goes back to this kind of pub ball thing, you know, you use what you have in your institution and you get good at it. Um But I really think this paper changes the argument of, well, I think we should still be able to use this. What happens if the batteries fade on you? You know, that's back to where we were with ultrasound 20 years ago of, well, I can't possibly not put a line in uh you know, using an ultrasound. What happens if all the ultrasounds exploded at once? Um That's not where we are. We should be doing 21st century medicine for 21st century patients. So that, so he photo of me out my marathon run er, on the Glasgow streets today. Er, we're gonna talk about the Pacer trial. So again, something quite close to my heart because we get a lot of, a lot of um hematology patients from the cui. So this is looking at platelet transfusion before you put CVC S in, in patients who are thrombocytopenic uh Dutch RCT. So what's a background here? Well, we always have concerns rebleeding with procedures. We do a lot of procedures to patients. Um We can potentially make things worse. Um There's a growing knowledge of transfusion risks out there. I'm just doing my learn pro again uh to keep me, keep me right. Um And a lot of emphasis placed on the uh immune response transfusion, on the cost of transfusion on trolley, on tackle on using what is a, you know, still a very scarce resource uh in most healthcare settings. Um The use of ultrasound again, 21st century medicine has reassured practitioners far less likely to worry about digging around in somebody's neck or under their clavicle when you can use ultrasound and that's probably reduced our, our use of transfusion down. Er, the BS H guidelines currently sit at er, recommending a transfusion trigger for platelets of 20,000 or 20 depending on which metric you want to use for CVC S excluding. And I think many of us would go probably even lower if we could, felt that we could get away with it and you know, what effect time has on this and the urgency of need for it and also the etiology of where the thrombocytopenia has come from. So, uh this Dutch um study group said, well, let's let's look at this properly. So, non inferiority, randomized trial, multicenter looking at patients getting all manner of CVC S. So dialysis catheters tunneled Heckman, um Subclans I Js, you name it on a mixture of hematology wards and critical care units to enter into the trial. You had to be an adult and you had to have a platelet count between 10 to uh 1000 bleeding risks which started off stories of bleeding, reporting of bleeding and inr 1.5 that got budged up to an I NR three halfway through the trial. And at that point, as long as it wasn't told to be an emergent device, um or there wasn't clinician exclusions. You were randomized to either getting a pool of platelets and then the line went in or not getting a pool of platelets and putting your line in pretty experienced inserter. So you had to have at least 50 CVC S and they all had to be ultrasound guided. Um The rest of it was reasonably pragmatic. So, however, you put your lines in was, was done as long as you an ultrasound. Um, an outcome measure was bleeding essentially So grade 2 to 4 bleeding. So if you look at the classification of this, zero is no bleeding. Uh One is uh a wee bit of bruising two, you need to put pressure on it. Three, you're needing to think about hemostatic um uh interventions to stop the bleeding. Um and for massive bleeding, largely for transfusion, um uh hemorrhagic hypertensive shock or death. So it's a pretty, pretty big, big difference between 0 to 4, but that's what it is. So grade 2 to 4 bleeding was the primary outcome. Secondary outcomes are looking at red cell transfusions mortality. All the sensible things you would think would be looked at. So, results um just shy of 400 CBC S were included in the I TT analysis. And if you l to a primary outcome, 12% of the patients who didn't get um uh a platelet transfusion er had grade 2 to 4 bleeding compared with just shy of 5%. So, uh risk reduction of 2.45 and this was interpreted by the authors as absence of non inferiority, absence of non inferiority of non transfusion. Um if you dig a little bit deeper into this, um there didn't seem to be significantly higher grade four bleeding. So a lot of the bleeding, there was hematoma was stuff needing pressure on it. Pat red cell transfusions were similar between the two groups. There wasn't a significant difference between them or if again, if you dug down into it. The transfusions that were needed for CBC specifically was higher in the nonplatelet transfusion group. But again, really interesting paper, there's lots there in the supplements, but the more you dig in, the more you see, so the majority of this bleeding happened in the hematology patients. Um and actually, if you really dig into it, a lot of it happened in two specific hospitals. So, you know, it's maybe more of a meets the eye here. The lower the platelet count was more likely that if you weren't in the transfusion group, you would need a platelet pool, which kind of seems sensible. The more from a you are, the more likely you are to have a bleeding complication and people did increment their platelet count factory, usually peaking at about three hours and then dropping down a little bit further at 24. So what to do with all of that? And what would I do with all of that? Cos I have to say I've been reasonably blase about these things. Um Well, we also cl as I say that non transfusion was not non inferior, always go ev negative when it comes to inferiority studies. Um I would say while an RCT is commendable and it's very well carried out. Um For the question that we're looking at, I guess from critical care clinicians, the wide range of those patients may not be to give us the answer that we want with the patient who's in front of us. And why is that? Well, because not every thrombocytopenic patient is created equal and equally not every CBC insertion is created equal. I mean, I think, you know, when you look at the patient in front of you, uh where you're gonna stick that line, what type of line you're having to put in and what um the state of the patient who's in front of you is like, is all going to go through your clinical clinician gestalt of what you need to do. Can you just back on that platelets or can you not? So I think personally, um I'll continue to be reasonably careful but not stick around most of the time in itu. Um But for hematology patients, hematological situations where you have far more of a kind of um uh marrow failure, thrombocytopenia, uh be immune, be cancer, whatever rather than a consumptive uh thrombocytopenia in ITU. I'd be probably more likely to transfuse the hematological uh manifestations of thrombocytopenia. Uh So moving on. Um, so this is a, oops. No, let's go back. Uh moving on a stress l study. So, um, I kind of was vaguely involved in this one and that we, we tried to act as a recruiting center um for this, um, Jama paper that came out earlier this year, uh UK based, led by um, uh Tony White House as you can see that. Um So what are we looking at? We're looking at beta blockers in septic shock and specifically beers in tachycardic septic shock. Um Now there's been a lot of work that's been going around. Um I've stuck a graph in here not from stress out. This is from a paper published in 2011 by um Morei et al, but was looking at esmolol in tachycardic patients who are on vasopressin. Um And they had shown that um, it was a paper that was powered on uh reducing heart rate and unsurprisingly, esmolol reduces your heart rate very well. Um But one of the secondary things, they, they looked at mortality and look at that, you know, separation of a Kia that would, you know, just makes her heart swell. Um but caveat. So obviously, that was not what this trial was designed to do. So, why might that happen? However, is there, is there biological plausibility here? Well, yeah, there is, you know, reducing myocardial oxygen consumption, uh increasing diastolic time, improving uh ventriculoatrial coupling, immunomodulation loads of stuff out there that you can put scientific merit in the use of beta blockers in some of these patients and meta analysis. Um using a lot of Chinese data but morelli paper as well suggested benefit and said we could do with looking at this in an RCT basis. Um uh And as I say, we're looking at septic patients with tachycardia, not all septic patients. So er Landiolol is super selective beta one antagonist um, about eight times more selective than esmolol. Ultra short acting has infusion, er, patients, er, included, were judged, er, as shocked as per sepsis. Three, on noradrenaline, um, for greater than 24 hours with a heart rate of greater 95. And you, the clinician had to follow with the word tachycardic for other reasons, which wasn't cos you were hypovolemic, it wasn't cos er, you were in, er, cardiogenic shock or, or for another reason and you were randomized to standard care where you were allowed no beta blockers. If you went into a tachydysrhythmia, uh if you went into atrial fibrillation, for example, um you weren't allowed beta blockers. Um but you got all other standard care or you went on to a Lanol infusion which titrated to your heart rate by a very, very tight protocol. Um And the study was powered on sofa scores up to day 14 minus the neurology component of, of your sofa score because obviously majority of these patients were sedated and therefore unable to, to fulfill the sofa score from that point of view. Um So stressed out like many of the people we're looking at had uh had halts because of the pandemic. Um er, but the trial has been halted at er, just about 50% of recruitment um because not because it showed harm, but it, because it was felt that it was unlikely on a statistical basis to show difference between the two arms um there was no primary or secondary outcome difference, er, demonstrated, um there is gonna be a lot more kind of uh exploratory um er, biological analyses done because these patients got a lot of blood taken from them. Um, but for the basis of the primary, um, er, the primary outcomes, um there were no differences. Um these were really sick patients. So you, your minimum, no, you had to be on was 0.05 mics per kig per minute. Um But there's your inclusion over both groups, they were super sick, which is probably why they're in that cohort where um you become tachycardic. Um But the Land Dialogue did not make this better. And in fact, there were significantly higher adverse events in the Land Dialogue Group. And a lot of those adverse events were attributable to being on a be block infusion. So it profound hypotension, heart block. Um uh Yeah, not, not good things, but again, adherence to a very strict protocol is amazing actually how, how, how tightly people adhere to it. So what a shame. Another great idea dies. Um But it shows a value of asking a very direct question. Um And instead of, you know, getting drawn as I clearly did as very eager registrars idea that I should be starting people on an ESM. It says, no, no, you really shouldn't. You could argue as to the outcomes, but they're all pretty aligned and all secondary and primary outcomes are aligned. Um You could argue it didn't target its issue. So um you weren't taking patients who you felt may benefit from what you were just saying. Are you tachycardic? And are you on noradrenaline? Are you septic? You get it? And maybe we're missing some pathologies here where an ultra short acting beta blocker may, may be useful. Um But overall, I think you commended on, on a trial delivery, a very complex trial um in a very sick patient cohort and I've, I've, I've delivered the goods on that on that ground. Ok. So, uh again, work in a major trauma center, um er, is one of these things that gets talked about an awful lot and sometimes gets used. Um So we should look at it and again, we should get good evidence for it. So, another Jamma paper led by Jan Jansen, um er, and Robbie LM and others um um looking at the use of Ribo. So, uh what is Ribo? Um it is a endovascular device with a balloon on it um that can occlude your aorta. Um and it can be placed in different, different positions depending on where your, where your hemorrhage is felt to come from. So, um what is the background here? Background is that hemorrhagic shock with, with trauma is a leading cause of death in certain groups of population that's worldwide. Certainly true in the UK as well. Um There's lots of interest in hemostatic control. We often look at, you know, what, what, er, hemostatic control do we get from our, uh, transfusion requirements? What do we get from surgery? Um, what can we do, um, radiologically to try and get control of these, these things? And boa is an appealing concept. So you can have a patient, um, that isn't in theater or is in theater. You can by inserting a pin, it's device in the common femoral artery, you can get into zone one, which is in your descending thoracic aorta just after your um supplying comes off or er zone three where you're just above the aortic. And depending if you've got abdominal hemorrhage or you've got ap hemorrhage, you can elude that blood flow. You can allow times for your surgeons to catch up. You can allow time for your anesthesiologist to catch up a critical care team to catch up with transfusional requirements um to improve dynamics and to give you time to save what is on all young patients. Um lots of observational stuff out there for a lot of UK uh us trauma centers saying this is a good thing to do and we should do it. So what should we do? What we should do in RCT, shouldn't we? So pragmatic again, this word keeps coming up. I'm blinded because you can't blind people to stick in a massive cannula in your femoral artery registry. So using Batan database to capture a lot of the patient details. Bayesian RCT. So again, not a frequentest RCT but Bayesian RCT using expert input beforehand and throughout to aid your analysis. Lots of time by the study group spent training staff in major trauma centers saying here's how you put these things in wet labs, dry labs. Um Here's how you put it in. Here's how you maintain your skills. Um A summary of the expert input that went into the Bayesian planning of this trial was that this should work. This is a, this is an intervention that should work for adults with blunt or penetrating torso hemorrhage. Um and clinicians in the Ed used a randomization app without a need for consent, which is why one of the reasons why Scotland didn't take part in it because of the different needs of consent in Scotland. So sick patients, a substantial amount of prehospital and in hospital arriving in the hospital, uh getting CPR pretty hypotense with high injury severity scores. There were some subtle differences in, in, in how the injury patterns were. Um But overall they were pretty well matched as you would hope. And we were looking at these patients getting wheeled into Ed and very rapidly. A decision being made. Yes, you're getting standard care or you're getting a Robo put in your femoral artery and it's gonna be blown up and we're going to try and get hemorrhage control using that. However, 90 day mortality. Nope, nope, nope, uh odds ratio of death with Ribo of 1.58 with a prior probability. So again, based on analysis of saying it was an 87% chance of having an odds ratio greater than one using Ribo. So an 87 chance 7% chance of dying with Ribo in compared to standard care. That's pretty daunting. Um, it certainly goes against what the experts had thought. Ok. Well, maybe it's cos early on it will help, but later on it wouldn't. Well, no, actually it was far worse if you looked at the three hour mortality versus, er, um, er, er, later on, lots of problems out there, it took longer for a AA group to get hemorrhagic control, um, of the Ribo group. Only 40% got a catheter in them that was inflated. Lots of reasons there problems getting into the femoral artery problems, deploying the, the balloon when it was there, patients who declined substantially to the point of dying before the balloon was up and some people who got better with it in, um, but the evidence is not there from this trial to say that Ribo is something that we should be offering these patients in the ed. So amazing achievement. That's still a pretty small study when it comes to this. Um, the sample size was based on needs paper that was previously done and that may be true and this may be true because it took a long time to recruit for this, uh, albeit you know, through a pandemic and all the rest of that, maybe that's just reflecting the UK, you speak to the Americans. They seem to use an awful lot of rebo catheters is, that's because we've got a different pattern of trauma. It cos we've got a different set up. Um How are we meant to train, how are you meant to get the right person doing that? We talked about the learning curve. You have a video laryngoscopy that's just sticking some pen in somebody's mouth. This is getting into femoral artery, a large gauge device and inflating it in the right place at the right time. Um With the numbers that are recruited into this study around the number of major trauma centers there are in the UK, you are very unlikely to have the same clinician doing it again and again and again. So how are we meant together? Also? It doesn't particularly marry up with my exposure to, to Ribo where I've seen it used has been by vascular surgeons or by um a interventional radiologist in patients who are already on the table, who have a kind of hybrid theater suite in place where you have an operation or a series of operations where it's not going right and you need brief control of, of hemorrhage while you sort the problem out or catch up with your recessive efforts. That's not the same as just putting it into anybody who gets wheeled into your date. So did it happen by the right person by the right place by the right time? I don't think we can say that from this paper, what we can say is just putting it into patients who come into Ed is not the way forward in the UK, at least. Ok. So last trial, uh the arrest trial. Um So again, very common, probably more common than the user. Ebo is patients who have an now possible cardiac arrest uh in the UK. Clearly not this because that's an American wagon. There you go. So very common presentation, we deal with it all the time and there's a lot of focus on how do we improve um outcomes in out possible cardiac arrest. There's been an organizational drive that we have cardiac arrest centers. Um and the observation of data that's out there, some of it by um authors from a study group would suggest that there is benefit in having cardiac arrest centers. So, uh some of these observational studies up to 30% absolute risk reduction um of mortality by transferring patients to cardiac arrest centers. Why access to the specialist, access to advanced therapies, um mechanical support, uh PC um interventional er doctors of all types downsides diagnostic mistakes. So, if you have a sub right, no hemorrhage and you have an ST elevation pattern on your ECG you get taken to a cardiac arrest center, that's probably not where you want to be transfer time. Um er, getting further away from maybe not all of the experts you need because if you have a cardiac arrest center that's predominantly cardiac, that may be not where you need to be. But I said you need an RCT and you need to get an answer. So what did this trial do? So I'm doing study again, you know, hats off prehospital setting ambulance service. So adults with return of circulation after our, our cardiac arrest but weren't stem, weren't pregnant and didn't have a DNR in place were presumed cardiac cause. And that's very, very hard to do to call in the back of an ambulance got randomized er, by ambulance control who did a stratified 1 to 1 randomization depending um where you were when you had it and you were randomized to a destination, you were not randomized to a therapy, you were randomized to a destination to either 32 hospitals around the greater London Metropolitan area or seven cardiac arrest centers around the er London metropolitan area. There was no protocolization of care. After that bar, clinicians were told to try and really, really not withdraw life sustaining therapy until 72 hours on neurological grounds, which is very similar to TTM to try not to get that massive early drop off of people just saying, oh, I don't think they're going to do because they're not waking up on day one because we know that that is not helpful. So very well matched cohorts just over 800 patients. Um, what do we make of the patients who came into this? They were relatively young. Uh, they had a lot of high levels of bystander cpr short CPR relatively low doses of adrenaline, all the kind of patients you feel you would get Rosin. And that is why they ended up in this, in this trial, I think, um, when they got to the hospital, er, only about 60% 60% were found to have a cardiac cause. And that, that goes back to how hard that is to call back when you were back in an ambulance. Um but the primary outcome, there was no difference in mortality. So 63% mortality uh bang on the nose at the both standard and cardiac arrest center. So again, high high mortality in this group considering they got ros um higher proportion of those in the cardiac arrest centers got PCI got intubated, went to itu got R RT higher proportion, got cardiogenic shock diagnosed in uh the cardiac arrest center. Um I'm presuming that's due to the ability to diagnose and the knowledge of cardiac shock and the the access to 24 hour echo of being able to call that early on cos it is a very difficult diagnosis to make often as we all know secondary outcomes, no long term differences at all. Maybe a maybe a hint towards worse neurologic outcomes in the cardiac arrest centers. Why that is, is difficult to tease out. Um And maybe the younger cohort may have fared better, but that's a secondary outcome. It is hypothesis generating that again, kind of feeds into the observational stuff where younger patients who get to these, these centers may do better due to their access to specialists. So should we bend over c should we get rid of them? Probably not. This is an RCT of a subset of out of hospital cardiac arrest. It's also an RCT of a very dense urban set up. And when you look at the map in the supplements of where these hospitals sit, you are getting quickly to, to, to hospitals, the standard care I think mirrors what I can do in that I can get a hold of a cardiologist quickly. I can't get to PCI in my hospital quickly. Um I don't necessarily have access to echo out of hours um or sorry, somebody who can echo in a very high, high grade fashion. Um But I can give good care. I have a difference with observational studies because they're inherently biased. We know that um you're far more likely to be taking the patients, you think are going to do well to a cardiac arrest center in an observational study, what it does. It means that we have to focus on a high quality standard care that we can give in general I CS nonspecialist ICU S with careful decision making. Highlighting the fact that you do not just willy nilly withdraw life sustaining therapy early on in this uh in this cohort but very important trial. Nonetheless, um it is clearly hard to call cardiac, this is noncardiac. Um We have clear card PC, I am, our cardiac centers work really hard and do a lot of work. And if we are inundating them, I think this adds to other papers like Tomahawk saying that if you don't have a clear criteria for PC, we should be trying to add to that workload, um wasting potentially wasting money and um reducing access to, to what specialist er services are. Um And it shows that we should standardize our standard care, which I think on the UK as a whole, we are of interest through that through, through the I CS, through sex as well of, of, of how we do that and we should focus the fact that we do provide important care in standard uh hospitals for this patient cohort. So another year over um I think I'm pretty much on time. Um There's loads of other good stuff out there and you know, time is too short to mention it all aid ICU haloperidol study. Really interesting cape cod steroids and pneumonia, really interesting er nut three looking at um intensity of protein and, and calorie loading in the critically ill and loads I have missed. Um I think it's a really exciting time uh to be practicing it ui think the studies, the design is getting better. We're asking better questions in a better fashion and the growth of things like that. You know, the um er non pandemic platform adaptive trials is superb and uh um very excited to carry on reading studies in ICU. So, thank you very much. Thank you so much, doctor. Do I know that many of you might have questions for him and if you do just uh type them in the chat box and we can put them to him. Um Would you mind if I asked a question? Is that all right? So um I don't want to start a video laryngoscopy, laryngoscopy debate. That is not what I'm interested in doing, but going back to something like the device trial where there is building evidence that something is, you know, is a better treatment than the alternative or you know, laryngoscopy is better than laryngoscopy. And you have this kind of thing of experience l care where people are really familiar and comfortable with what they know and changing treatments. How can we, how can we encourage our colleagues who hold really strongly onto the kind of thing they're familiar with? How can we encourage them to change their practice in our kind of units? What do you think the approach to that is? Um I think you have to build bridges, don't you? I mean, I think you have to say that I think there's so much evidence out there that we less experienced intubator will get better outcomes with the dual laryngoscopy. You be training people using video Lagos copy. And I think you've got now pretty much every airway guideline that you've I've read will have do laryngoscopy as a rescue. Um And I don't understand why we wouldn't use the best device for the critically ill. So I think it's behooven, you know, I mean, I started off using a and it took me until I think I've done about eight years of training before I used the video endoscope. Um I think I could probably inspect more people still with ad, but I've recognized that that is not, the technique is going to do my patients best. And after all, at the end of the day, it's the patients and the doctors in training and, you know, and ps in training around us that we should be benefiting. So I think it's behooven upon us to take these skills on in the same way that we did with ultrasound in the same way we have done with using modern imaging for patients. Um you know, it's not an E or it shouldn't be an eagle game. Um She is one of our master students has actually joined, she doesn't work in the UK. She's asking about video laryngoscopy availability in the UK. It's growing um It's growing, it's not universal is is answer. Um And yeah, I am again, you know, this is a, you know, it's a, this is a very privileged take on it. Mine, you know, I work in a tertiary center in the developed world and of course, I can get access to it. And II, you know, I'm, I'm not saying by any means that if you're working in an LM IC, that I'm saying you should put all of the uh Barre laryngoscopes in the bin because that's clearly not realistic uh to be able to achieve. Um, but currently in the UK, uh, ever growing whenever I think the, the surveys, uh, people pretty much every hospital will have access to some form of VL and some hospitals are throwing, um, some hospitals like Tim Cook's Hospital is obviously that had, you know, we're at 10 years on, but from em binning all direct laryngoscopes, um, uh, that's, that's one approach. Um, I think that probably would be a bit hard to swallow for people. But, um, yeah, there's a question that's come through and from your brain, which it says thanks for talk. Uh, do you think questions like the best patients to transfer to cardiac arrest centers and do we transfer enough or conversely do we transfer too many? What are your thoughts on that? Um, I don't know, Neil, Neil Woos in the cardiac arrest. He's probably better to answer that than I am. Um, er, I swear. Um, from a, from a PCI point of view, I think we probably have it about right in in the west of Scotland. And that's all I can really, really speak to, er, from that point of view. Um I think from a cardiogenic shock point of view and maybe access to mechanical support, we probably don't transfer enough because it's hard to diagnose. And that goes back to a lot of these scoping things that have been been going on. Obviously, there's been a recent, recent Scottish paper, uh impressed looking at that and trying to diagnose it and therefore trying to get people into that scheme is, is different, but from a card arrest point of view, um I think we're probably on the money and um it looks from the arrest paper like the London approach is the same in my head. I had this idea that all London hospitals had PCI availability and they'd all be, you know, um able to do this. But actually the majority of the hospitals, er who took part in the study said if they were a non cardiac arrest center, they would transfer their patients out for PCI. Uh even if they had access to it in, in working hours. So the interpretation of that is avoiding kind of undifferentiated transfer of lots and lots and lots of people and just focusing more on the early identification of cardiogenic shock and those that might benefit from going to a specialist center for management of that. A uh Angus has a question around views on what platelet counts in hematological patients. You would give patients platelet PC, considering how much of a precious resource they are. And infrequently, we have issues with low supplies of platelets and so it can be challenging. I think sometimes we have a about discussion with, they told us about whether or not they're needed. Yeah, that's a really good question. I think, you know, the BS H guidelines do say, you know, above 20 you should be fine. Um I would say from this paper if you're looking at the hematological subset of patients, an awful lot of them ended up getting platelets anyway. So by not transfusing before you do a line, you're not saving them from platelet transfusion. Yeah. Um it's, it's, it's completely different from uh um uh from, you know, yeah, a patient who comes in with septic shock who develops two days in, you know, a consumptive thrombocytopenia. I think you can be pretty, you know, stick to the BSH guidelines and say, you know, that's, that's absolutely fine. And I think with ultrasound that is absolutely fine. Um But they definitely, definitely and, and I think we will, we will see that um when we, when we put lines in um that the line generally goes in fine because we're generally pretty slick operators and we use ultrasound and blah, blah, blah, but then you get called back on the and stuff. So you're actually so through three dressings and you're pouring on and, you know, praying to the gods of Ktar to make it better. And actually the answer is you need some platelets. OK. I cannot see any other questions as such. Um There's a comment about, about the team, the team benefits of the laryngoscopy, which is absolutely every everybody agree. So a high five for that comment in the absence of any other questions. Um I just have to thank you very much doctor do for giving up your Thursday evening um to, to bring a really, really good comprehensive review of some critical, really important critical care trials to us. Um I am just going to pop a feedback link in the chat box for you all. And if you fill in that feedback link, that's how you'll generate your um, CPD certificates that you can use. Um I guess in your appraisals and um uh and um the, I hope everybody has a lovely Christmas. The six education updates will be back at the end of January um with Dr Arlene Wise from the royal in of Edinburgh who will be talking about management of the critically ill pregnant patient, which I'm sure everyone will agree is a thing that fills us all with absolute terror. So I hope you all have a lovely Christmas and we look forward to seeing you in the new Year. Thank you very much. Take care. Bye.