Podcast – Top papers 2023/24 – Part 2

Welcome to the St Emlyn’s podcast. I’m Iain Beardsell and I’m Simon Carley. And this is part two of our top 20 papers podcast special. Hopefully you’ve already heard part one where we covered many papers all about the airway, and in this section we’re going to be talking about Haemorrhage and Cardiac papers and a couple of other little nuggets too. I hope you enjoy it.

We’re going to move on to our next theme, which is Haemorrhage, and there’s a lot to talk about here. So we’re going to start with the emergency department, resuscitative endovascular balloon occlusion of the aorta with exsanguinating haemorrhage. And much easier to just say the UK REBOA Randomised Clinical Trial. We’ve covered this before, Simon. Worth a mention, this was in Jama last November. Lots of familiar names on that list of authors. The UK REBOA trial was looking at patients got examinating hemorrhage. In a low half of the body, putting a REBOA catheter in, in memost department, and that’s the key thing here. And seeing if it made a difference, so randomised to one thing or the other.

Now, if you’re going to do REBOA, it’s for the patients who are basically exsanguinating in front of you and you’ve got to do something about it to try and stop that bleeding and then get them into theatre as quickly as possible. But if you look at this trial, that’s not what happened, really. The average time for the balloon to be attempted was 90 minutes post-injury. So these patients are the ones who are bleeding in front of you. It delayed time in the emergency department. There were a number of press call violations arguably about who got included. So there’s some patients in there with head injury. They weren’t particularly successful at putting them in because there were small numbers in the centres that were involved in doing this. We didn’t do it in our sense.

So what this paper tells me is that if you’re going to base your REBOA service in the emergency department and try and train a whole bunch of people to do it on a very infrequent basis, it’s probably not going to work amongst emergency department staff. Does it mean the REBOA doesn’t work? No, it doesn’t. It means that this way of doing it is not the way to do it. And perhaps we need a little bit more evidence of doing it in different ways. But personal feeling is if in this group of patients, if you are going to make a big difference to them, you’re probably going to have to put it in close to seen and that means pre-hospital. And that’s what services like London have been doing for many years. And if you speak to them admittedly, they don’t do it about their case series, I think there probably are some significant survivors in there because of this technique. But concentrated experience, small numbers of patients, particular patient groups.

So just to reiterate the conclusions from this paper, which Simon says we’ve covered before, in trauma patients with exsanguinating haemorrhage, a strategy of REBOA and standard care. And the emergency department does not reduce and may even increase mortality compared to standard care alone. Watch this space. This is one of those technologies that I think we’d all love to be able to embrace. And we’d love it to find a part in our resuscitation pathways, but it’s not there yet.

Next one, another trial Simon, we’ve discussed at length. Early in empirical high-dose cry precipitate for haemorrhage after traumatic injury, the Cryostat 2 randomised control trial. Again, familiar names, Ross Davenport is the lead author on this. And this is from JAMA in November 2023. In fact, I think they were published in the same edition for those two papers. Great set of research trials. The CRYOSTAT 2 trial, we did recruit to that in Manchester, I don’t know what he did in Southampton. And that was looking at randomized patients who had their major haemorrhage protocol activated for trauma. And they either got the usual package or they got that plus three pulls of cry precipitate, which has got things in like prevention, which we know goes down in major trauma patients and is also associated with the adverse outcomes.

What they found, what they expected was that the cry precipitate would reduce the severity of the acute traumatic coagulopathy and get more survivors. What they found at 28-day mortality is no difference. So 25.3% versus 26.1%. So a little bit disappointing, really, that it didn’t make a difference. And the data within there that suggests that it might be about timing of when you get these things, it might be about selecting the right patients. But what this trial does tell us is that a blanket of just giving cry precipitate to all patients who have activated their MHP is not the right thing to do. But you should prioritize getting a fibrinogen level and then act on that if it’s like.

Brilliant to see that we’re using evidence to challenge the things that we think might be helpful. And even if they’re proven not to be confidence to publish those and help us move things forward. Getting fibrinogen levels using other devices to look at clotting and coagulation in trauma is obviously the way forward. And then a nuanced approach, I think, is what the evidence seems to be pointing us towards at the moment.

Paper number 10, the PATCH Trauma Study. This is pre-hospital tranexamic acid for severe trauma. American listeners, make sure you’re sitting down. This is from the New England Journal of Medicine in July 2023. Yes, and PATCH trial was the one that we’ve been waiting for. So we had things like CRASH one and CRASH two, which I think show a mortality benefit other people would argue that they don’t. But one of the big arguments against them was that they were done in quite a few low-income and medium-income countries. So they didn’t apply to America and didn’t apply to other high-performing systems. That’s not unreasonable argument back. So the PATCH Study was sort of designed to see the effect of TXA in a very good system. And there’s a good paper. It’s a randomized control trial where they looked in a high-performing trauma system. They selected the right patients, all the patients were pretty big sick patients. And they followed them up for six months to see whether or not they made any difference to their survival and also their main outcome measure, which was their functionality at six months, not the mortality.

So what they found on the basis of their measure was that there was no difference at six months, which is fine. But functional outcome at six months, I’m not sure if it’s the right outcome for something which is designed to stop bleeding. And where you put the marker in terms of whether or not you think is a successful failure, there are certainly more people who survive, particularly at 28 days, if you give them TXA. So there is no doubt from the data here. It’s completely consistent with the other trials that have seen the TXA. Then if you give TXA to your patients who’s bleeding from their trauma, then more likely to be alive at 28 days. Beyond that, then things like rehab and other things make a difference. And perhaps six months is a bit early. So for me, it’s just reinforces what I’m doing already. If I want my patient to live, I’m going to give him TXA. Beyond that, we may have to improve other things such as rehab and definitive care to get those gains to be persistent beyond six months. But yeah, an interesting study, well done to the investigators, hasn’t changed my practice. Keep giving the TXA.

And the key that I think worries some people, the number of serious adverse events, including vascular occlusive events, did not differ meaningfully between the groups. So this is a cheap intervention that we can give relatively easily. Summary, have you moved to the two gram thing as opposed to one gram? – One gram. – Yeah, us two. So now it’s a really straightforward thing to do, I think. And there’s no evidence it’s doing harm. It’s probably keeping your patients alive and how it affects them further down the line, more work is needed. So I’m going to a very quick series of papers now, which I think we can cover in double quick time. This first one is the safety and efficacy of Artesunate. Is that how you say it? – Artesunate. – Thank you. In severely injured patients with traumatic haemorrhage, the top art randomized clinical trial, this was published in intensive care medicine last August 2023. We’ve covered this before.

Hey, interesting study. So there’s good laboratory evidence that Artesunate can change the inflammatory type responses when you get traumatic chaglopthas. So they got good days from the lab, put it into humans. It’s really a pilot study, to be honest. And amongst 90 UK trauma patients, there’s fairly good evidence that it may be no difference at all, which is a bit of a surprise and a bit disappointing really, because it will be nice to have another drug which could actually change the inflammatory modulation that we see with these very, very severe patients. But yes, not for prime time yet, it probably isn’t gonna make it into practice.

Up next, the efficacy and safety of early administration of four factor pro thrombin complex concentrate in patients with trauma at risk of massive transfusion. The PROCOAG randomized clinical trial. This is from JAMA April 2023, more about bleeding. – There’s an RCT of just giving a load of plotting factors to patients who are activating a major haemorrhage protocol. In this case, not giving cryo, but giving four factor pro thumbing complex concentrate. So same kind of principle, same kind of study. And again, it didn’t make a difference. And it’s really interesting, isn’t it? So on the one hand, this trial is telling us like Christ, that just giving plotting factors randomly to people does not work. So then you think, “Oh, in which case, what I’ll do is I’ll measure exactly what’s going on and I’ll tailor what I’m gonna do to these patients and give them just what they need.” And that was obviously gonna be the way forward. And I think that’s probably the end. But we’ve also got studies from the past and a couple of years ago, I attacked a study again by the London group where they did exactly that. They used ROTEN or TEG to look exactly what we should be doing with the calculation of these patients. The randomized control trial doing that, and that didn’t make a difference either. It’s a fascinating, heavy-to-research. I think these researchers are gonna be busy for many years to come because we still don’t quite understand what’s going on with the key core traumatic coagulopathy.

Next paper, one that will be of particular interest of those people who involved with the current SWIFT trial. This is the association of whole blood with survival among patients presented with severe haemorrhage in US and Canadian adult civilian trauma centers, published in JAMA surgery in May 2023. – So in 2007, it’s observational retrospective data. So we’re always gonna be cautious about that. But definitely a significant improvement in mortality in those significantly bleeding patients. Again, America, most likely penetrating patients or like that and stuff, but significantly better with whole blood. So yeah, I’m really interested to see what the swith trial results show. The crew suggested somebody to the trial last week was all very exciting, lots of paperwork. But I think that’s doing quite well actually. I think they’re getting through the numbers.

Next one is understanding pre-hospital blood transfusion decision making for injured patients and interview study. Again, one we’ve covered on the blog before this is fascinating. Emergency medicine journal November 2023. How do we decide whether a patient needs blood in the pre-hospital environment? – It’s really hard, I think is the answer. Decisions are not easy, they’re not algorithmic. They’re often based on previous experience. These are recognition prime decisions. So that means you’re taking experts who’ve seen these kind of patients before and they kind of feel that it’s the right thing to do. And that’s okay. They use a whole variety of different information. So it’ll be physiological, it’ll be mechanistic. It’ll be where you are. There’ll be lots of different things coming together. You might call it gestault if you want to. I think that’s a reasonable thing to do, but it’s not precise. And it’s hampered by the fact that many of the people, even very experienced people, don’t really know what the impact of giving blood is gonna be in the moment. And we do struggle a little bit about finding out did our decision actually make a difference. But do we get the follow up and really have a good understanding about whether or not the impact of the blood did make a difference for our individual patients. So some work to do there with systems. So it’s a really interesting thing to read. Not just about doing it for pre-hospital, but I think just about how we make difficult decisions in the ED. And I think I’d like to see more paves like this. It’s a good one.

There’s also something here about the evidence with semi-structured interviews. And we do have a critical appraisal nugget. If you’re interested in trying to conduct this sort of research, this was 10 pre-hospital physicians who are interviewed and finding different themes amongst their discussion. It reminds me also of a tweet. I saw recently, please, if you have pre-hospital clinicians bringing patients to you in the emergency department, it’s not your place to be sniffy about the decisions they’ve made, whether that’s serious, difficult, tricky stuff like this or other serious, difficult, tricky stuff related to other patients. Every time they see a patient in the pre-hospital environment is serious, difficult, and tricky. So please don’t stand there touching one of our pre-hospital clinicians when they bring a patient in. It doesn’t help anybody. And until you’ve walked a mile in their shoes, perhaps it’s not your place to try and judge people about the decisions they’ve made. Anyway, little hobby horse.

On to the next one, the identification of major haemorrhage in trauma patients in the pre-hospital setting. This is diagnostic accuracy and impact on outcome, very similar to what we’ve just talked about. This is in the trauma surgery journal, acute care open version. And this is from January this year, 2024. Yeah, I think there’s two papers. Actually, a pair of very nice, you don’t need. So this is actually looking at the patients who go on to require major haemorrhage in hospital and whether or not they were picked up in those early stages. Bottom line, so sensitivity of 70%, so we miss a significant number of the patients who then need to go on to an MHP. But the specificity was high. So if you think they’re bleeding to death, then they probably are. What was really interesting though is that the ones that were missed had a tripling of their mortality. And I think that’s really interesting because if you think about it, the ones you miss are probably the ones who didn’t have the biggest number of signs. Because you’re not going to miss the one who’s got a BP of 15, a heart rate of 150, and they look like they’re about to die. Those aren’t the ones you miss. The ones you miss, the ones you aren’t, that sick when they first come through the door. But if you do miss them, those have a tripling of their mortality. So really interesting paradox there, really, really interesting.

That brings us to the end of that little section on haemorrhage; lots to take in there, quite a lot of negatives, actually. So, REBOA, we don’t see any evidence for that yet. Giving high dose, require precipitate blindly without other things, probably isn’t a helpful idea. A TXA seems to be a useful thing to do, although we can’t be necessarily equating that into long term survival. And then we’ve got a couple of things later down, which just accentuate how difficult these decisions are to make. And actually, I was watching Top Gun Maverick the other day. It’s all down to the person in the box, isn’t it? You’ve got to trust their decision making and decision making is difficult. Please remember that when you’re receiving patients into your emergency file. And Simon, we’re getting there. We’re on to paper 16.

And this is a bit of a cardiac theme, lots to think about with cardiac arrest. The first one we’ve covered, and this is defibrillation strategies for refractory, ventricular fibrillation. This was in the New England Journal of Medicine. This is a little old, Simon. This is 2022. But we have talked about this before, and I know that this is already being put into practice in some places. Yeah, and I had the delight and honour to meet Sheldon Cheskes, who is the lead author for this, when I was over in Gratz; what a lovely guy. And he’s a wife, Shelley, absolutely superb. People say he’s also one of the authors of the trial. The DOSE VF trial, what it tells us is that in a randomized control trial of patients in refractory VF, they’re still in VF after three shocks, and there’s still not been any other rhythms, they’re still just in VF, or VT. You get much better outcomes, much better outcomes, 30% improvement in mortality comes if you go to the DSD, which is dual sequence to defibrillation. So that’s putting them to defibrillators, one AP, and one, and trilateral, and bang, bang, one second apart, and you much more likely to get defibrillation of the entire myocardium. Because one of the major reasons why people don’t come out of the F is you’ve not actually defibrillated them. So you put the pads on, you’ve given the shock, but there’s still a little residual area, probably, of the F there in the background, and then that recaptures the rest of the ventricle and you go back into the F. So you have to do a proper defibrillation, more energy, more axes, two things. So they also tested anteroposterior, just changing the paddle positions. That appeared to be better, but not as good as doing the dual sequence. So the feeling now is if you’ve only got one defibrillation, you’ve given three shocks, probably changed the paddle positions go AP, and that’s in JR Calc in the UK, so you can do that pre-hospital and in hospital. And but you’ve got two defibrillators, then two seconds, one second apart, bang, bang, is the way to go. And let’s face it, on the basis of this, I’m sure that the little defibrillation companies are squirreling away somewhere, inventing a machine which probably does it straight off, and you have four pads that you put on straight away. But let’s wait and see.

And this is really for me where the big gains we made in cardiac arrest. Those patients in ventricular fibrillation or ventricular tachycardia, for me, cardiac arrest is very much now two different diseases. It’s those patients who are poorly and have lost their output because they’ve dropped their blood pressure and they are just on a downhill spiral. And there’s these patients who’ve had a sudden drop, they’ve got a sudden arrhythmia. And this for me is where the big difference can be made. And the idea that we’re seeing real improvements will fair play to this group. The little caveat we mentioned it when we first discussed this, please just be mindful that you may do something nasty to your defibrillation kit, and you need to check the manufacturers and all of your warranties and stuff. I don’t think that’s quite been nailed down, but as you say Simon, I am sure there are people currently trying to design machines that will do this and sell them to you.

Our next paper, we’re almost there. High dose versus low dose intravenous nitroglycerine for sympathetic, crashing acute pulmonary oedema, a randomized control trial. Acute LVF, one of those conditions that’s really, really satisfying to treat if you get it right. It reminds me that EMCrit, Scott, our great friend, his first ever M. Crit episode was on this condition, way back when it’s one we’ve all seen four o’clock in the morning where we’ve wanted to think about how much nitric we’re going to give. Is there a difference between high and low dose? Yeah, so nice small RCTs, not everything on the best RCT in the world, it’s pretty good. Yeah, give us a much nitrate as you can basically, and that’s been kind of my practice for many years is to give us much nitrates as they can, that the patient will tolerate, according to their blood pressure and other cardiac parameters. So yeah, go for it. And this was published in the EMJ in January 2024. So have a read of the paper. Nitrates are a good thing, and very much what I would go to for one of my first things in acute left ventricular failure.

Another paper, this one again, from the Emergency Medicine Journal, but this is February 2023. Adverse events from nitrate administration during right ventricular myocardial infarction, a systematic review of metanalysis. This is the idea that if you, vasodilate patients who have right heart failure, bad stuff will happen, is it true? No, in summary. So there’s quite a few trials that they looked at in this, and there doesn’t seem to be any real association with mortality or horrendous things in right ventricular infarction if you give nitrates. So the dogma that you should never give them is probably wrong, and by all means, if you feel that it’s appropriate, this data would suggest that it’s appropriate to do so. And finally for our cardiac section, this is a paper from the Lancet, October 2023, expedited transfer to a cardiac arrest centre from non-ST elevation out of Hospital Cardiac Arrest, the arrest trial, a UK prospective multi-centre parallel, a randomized controlled trial, does it help if you bypass your local hospital to go to another centre in patients with what we currently call non-NSTEMIs, although I am watching more and more as we talk more about occlusive myocardial infarction.

But let’s think about this in the phrase of non-stemmy, so patients where they don’t meet those criteria that we’re currently using to go straight to a cath lab should you bypass? Yeah, there’s people who would suggest not actually, so in this RCT in London, this group of patients, so remember the absolutely important to remember that you’ve taken out the VFs, the big ST elevation MIs, which are probably the most of the occlusive myocardial infarctions. So they’ve been taken out, the ones that are remained, they’re actually, they are a mixed bunch, aren’t they? So in here there’ll be people, not drawn, they didn’t do drawn, there’ll be people here who may have a sub-arachnoid haemorrhage, they may have a section, they may have a big PE, all of that kind of stuff. You’re gonna be careful in London as well that some of the places that they took these patients to are standalone cardiac centres. So it wouldn’t be like coming into my department, which has got a cardiac centre on-site, but it’s also got pretty much everything else on the site as well. So if you land up with us, you get to the right specialty pretty much. Whereas if you go to a standalone cardiac site and you don’t happen to be cardiac, which is the case in some of the region up here, it’s much more of a problem. So in this study, in this locality, it did not make a difference. It doesn’t mean that it won’t have a benefit in other centres around the world, which may have slightly different setups of their health economy.

So in our cardiac section, just to refresh what we just talked about, so defibrillation strategies, think about dual sequence defibrillation or changing path position, a patient refractory of the F. Nitrates are good in acute left ventricular failure. Even if you have right heart failure, they’re still a good thing. And as Simon says, not all my cardio infarctions are created the same. And so, bypassing going to a cardiac centre or an intervention centre may not be helpful in the long term when you have to think quite hard about where you go. We’ve really emphasized Simon how difficult pre-hospital decision making is here. And I think that’s one theme that I take away from this discussion we’ve had. Finally, we come to a bit of a fun paper, just in case you hadn’t seen it. This is one that I think we both came across from the M-Crit podcast mentioning Scott again. This is about how to mark the skin if you’re going to do an intervention that needs you to know where you’re going to go. And this is about using a syringe to create a, I think it’s called a hickey. Is that correct? – Yeah, well, it would be a love bite, wouldn’t it? But essentially a syringe hickey, which is the American word for a love bite, is you take a syringe, you just throw like a 10 mil syringe, you put it against the skin and then you pull the plunger back, so it creates a vacuum. And what that does is it causes a very small round bruise underneath the skin. So that marks, and of course, it because it’s underneath the skin, it doesn’t come off if you wash it, it doesn’t come off if you put ultrasound gel out, it chest all these sort of things, and it stays in the same place. So I’ve marked a sharp piece in the past, I’ve tried to the end of the, you know, the needle cap. That was one of the things that we used to do, so you used to take the needle cap off and used to push it against the skin, it was a round circle. But if you don’t catch it fairly soon after that, when it’s disappeared. So this is a way of marking the skin, and it doesn’t shift around or disappear. That’s really important, because I’ve seen a few errors over the years where people have thought that they were in the right place and then pull a chest drain in the wrong place. That’s not going down great.

Couple of the things they did, which I thought was really good, is they did this on a range of skin types, according to the Fitzpatrick scale. So it doesn’t matter whether you’re light or dark skinned, you’ll still be able to see it. So nice technique, nice little study done properly. Yeah, well, like this one. And you can read about it in the Journal of Emergency Medicine from March 2023, and we’ll finish that. That is a cheap, easy, patient-centered, really easy to do. Have a look at it.

Simon, what a marathon. 20 papers we’ve covered. We talked about airways, we talked about bleeding, we’ve talked about cardiac things, we’ve talked about little bits of other stuff. Hopefully we’ve given you an insight into all these papers. As again, we’ll always say, please do have a look. Simon’s put together a whole blog post about these with clickable links so you can read the paper yourself. There’ll be links in the blog post associated with this podcast as well. So you can have a read of those papers and come to your own conclusions. Don’t believe everything you hear on a podcast. And if you’ve enjoyed today, let us know. This takes an awful lot of work. And to be fair, this is all Simon’s work putting this together for a conference. But these are, I think, really high impact education events when we’re able to do this. So please let us know if you’ve enjoyed this podcast. Let us know what you think of it. As ever, do like and subscribe. And we’ll be back with our normal monthly podcast very soon.