Oh, good. This first session, this first 90 minutes, I guess we're going to have six rapid fire, if you want to say. So short lectures of 15 minutes each. So hopefully it's not going to be too boring. I think Dan and I are going to flip back a little bit on those topics. Cool. So the first one is on physiology-guided CPR. And really, all of them are a little bit about how to optimize those outcomes in CPR. And there's a lot of new techniques and gadgets out there. And that's what people oftentimes like. So as we go about those lectures where we talk about how things work, we just each introduce one technique or approach that is relatively specific to CPR, I guess. And the first one is the one that I mentioned is about the physiology-guided approach to CPR, as opposed to a one-size-fits-all approach. So currently, I guess, all of our interventions that we do in CPR are guidelines-based. The guidelines are developed on best evidence. And so there are various guidelines. This is from the Adult Basic Life Support 2015 Guidelines. But we have similar guidelines also in veterinary medicine, recover, leading to certifications. And in order to adhere to those guidelines, there's also various devices that can help us to do that. There is songs that we can sing or think about, such as like, Staying Alive, or Another One Bites the Dust, or what was it? Baby Shark is a popular one in these days. There's metronomes that help us to stay with the compression rates. And then there is also those kind of pucks, as we call them. So they are accelerometers. They identify how fast you compress, how deep you compress, and so on and so forth. And then the device talks back to you and says, please compress a little bit faster. Please don't compress quite as fast. Compress deeper, and so on and so forth. So that is all targeted towards the provider ultimately delivering chest compressions according to the specifications of the guidelines, because we assume that the guidelines are the ideal approach. And when we adhere to the guidelines, then we perform the best possible CPR that we can. But it's definitely a one-size-fits-all approach. On the other side, it could be another kind of regulatory unit that drives our resuscitation that could be a perfusion target, because ultimately that's what matters, right? With our chest compressions, we want to optimize coronary perfusion, cerebral perfusion, and so on. And so why not choosing a personalized approach? I think that's what we ultimately want to achieve. And to some extent, the guidelines have the same goal. I mean, the guidelines ultimately, even though it's a one-size-fits-all approach, it assumes that when you adhere to the guidelines, you optimize the perfusion, reach all those perfusion targets, and ultimately also improves outcomes. But more recently, this perfusion-targeted approach really has found some additional support in the literature. So I want to talk about that. We already talked about some of those regulatory units that would help us to decide on how to do that best, such as coronary perfusion pressure, such as like in this study here, once more, animals with a coronary perfusion pressure of at least 20 seemed to be resuscitated successfully, but then went on dying if they had a little bit of higher coronary perfusion pressure. They were not only successfully resuscitated, but they also survived to 24 hours. So that's a potential target, right, that we could try to achieve during resuscitation. And it's much the same in humans as well. So this is from a human out-of-hospital cardiac arrest studies, included 100 people. They all had sudden cardiac arrest. And likewise, those people here that achieved ROSC had a coronary perfusion pressure of around 26 millimeters of mercury, while those that did not achieve ROSC, even though there's a wide variability between them, had a mean coronary perfusion pressure that is quite low. So definitely a possibility that if we aim for CPP of more than 20, then the chances for ROSC are probably better, right? Given that the right atrial pressure is probably around 5 millimeters of mercury at the end of relaxation phase, we could also, instead of CPP, aim for diastolic arterial blood pressure of at least 25 millimeters of mercury, right? So those are some of the targets physiologically that we could aim for. The other target, of course, could be end-tidal CO2, because we know that end-tidal CO2 is a pretty good surrogate marker for various tissue blood flows, including coronary perfusion, but for cardiac output altogether, also during CPR itself. And we found that a higher end-tidal CO2 is associated with better survival and return of spontaneous circulation in both people and animals. So looking for an end-tidal CO2 target would be an alternative way to go about that. And so, more recently, the study group around Berg, that's at the Children's Hospital in Philadelphia, has done a couple of experimental studies in swine, for most four of them, to be precise, where they looked exactly at that. They compared basically standard CPR compared to hemodynamically guided CPR, or hemodynamic-directed CPR. And so in this, this is the first out of four studies, and I'll just limit the discussion here to that one for time purposes. So they were all like swine, around 30 kilograms, sternal chest compressions, VF was induced and left untreated for seven minutes. And then the standard CPR group just received the American Heart Association guidelines, although at two different compression depths of the range that is recommended. And if somebody finds a typo here, then you get an ITD. It should be 51 millimeters, and not 55, to be precise. It doesn't really matter that much, I guess. You get an ITD. Yay. Thank you. So that's the typical standard CPR, right? Versus the hemodynamic-guided CPR was done such that the compression depth was adjusted so that the systolic arterial pressure was 100 millimeters of mercury. And then epinephrine administration was adjusted such that the coronary perfusion pressure was at least 20 millimeters of mercury, right? Do you remember from our earlier lecture on the physiology that with the epinephrine, we can just bring up the aortic root pressure a little bit? And so that will help us to kind of guide the CPP to a certain target. So that's what they did here. And with the compression depth, you basically get the peak arterial pressure up. So that was the idea. So those are the two standard groups. And this one here is the guided group. And so you see the mean coronary pressure goes up quite significantly in that hemodynamic-directed group. And that also has an impact on the survivors. So you see that the survivors have, on average, a much higher coronary perfusion pressure than the non-survivors. Once more, for that group that was hemodynamically-directed, all animals survived. And that was really short-term survival, full just for four hours, right? While that was the case for only three of the eight with the deeper compression of 51 millimeter. And only one of the eight with, like, what was it? 33 millimeters survived through those four hours, all right? So it seemed that based on that, that a hemodynamic-guided or personalized approach to the resuscitation, as opposed to standard American Heart Association guidelines, had actually a significantly better outcome there as well. And that was pretty much the same for all the other swine studies that they published, including those that were, I think, survival to 72 hours. So the outcomes were just markedly better, right? The other study that I found in the literature was regarding entitled CO2, since that's a little bit a different model. So that's a neonatal asphyxial model, where the animals were asphyxiated and then left untreated for 20 minutes before CPR was started. Once more, they underwent standard CPR with a third of the chest depth as compression depth and compression rate according to the American Heart Association guidelines. Or they had an entitled CO2-guided CPR, which is just pretty much trying to get the entitled CO2 as high up as possible. So there wasn't a particular value chosen, but really just trying to get it up as high as possible. With the standard CPR, we only had two out of 14 surviving while this, or to RASC, achieving RASC while that was the case in, like, half of the animals for entitled CO2. But it should also be mentioned that there was a little bit of a trend towards higher injury with the entitled CO2, because if you just keep pushing, right, as hard as you possibly can, naturally, there may be some injury associated with that as well. So one has to take that into consideration. None of those things were statistical here as far as the statistically significant injuries. But the animal number is so low that you need quite a consistent injury in order to reach a statistical significance there. So when you read the paper, that's a little bit misleading, I think I would say there. Another little evidence towards the fact that not everybody is the same was that study here in humans. That's, I think, out of Norway or Denmark. And a pretty small pilot study. But what they basically looked at is how the compression point on the chest actually affects entitled CO2, assuming that entitled CO2, again, is a marker of overall perfusion. And they found that there's really different optimal compression points in those people, right? And not everybody was the same. So they basically started compressing somewhere standardized. And then they moved around for, I think it was maybe 20, 30 seconds, and were looking on where the highest entitled CO2 could be achieved. And they found that each person had a little bit a different optimal compression point, right? Just indicating that doing exactly always the same thing may not be the best solution for all animals. And I think that is even the case in humans, right? While we in animals, obviously, we have so different chest shapes and forms that clearly the same compression point for all and each animal, even amongst round-chested animals, right, may not be always the best compression point. So it's worthwhile maybe looking a little bit at the feedback, physiologic feedback, that we basically get. So what are the current recommendations based on that? There's not really been any clinical studies on that whatsoever. In humans, at least not any prospective studies. But there's some information, I believe, that we can, now that there's really not much there. There may be some coming out now, but there's not. So the current guidelines say that, and the level of evidence is pretty interesting. It's EO, which means expert opinion, right? The recommendation is relatively good, 2B, which means that basically the benefit is at least on par with the risk, right? So you would assume that it's probably beneficial. But the evidence is really based on expert opinion, because there is not much evidence other than those animal studies that we just talked about. But it's very appealing. And so what they currently say is that it may be reasonable to use physiologic parameters such as like capnography, diastolic pressure, that is arterial diastolic pressure, when feasible to monitor and optimize CPR quality, guide vasopressors therapy, and detect ROSC. All right. So it would be meaningful to do all of those things. And one implementation, and some hospitals have implemented that despite a relatively low level of evidence basis here, such as like Bob Numar, who is the current ill court chair and was working with me in Philadelphia as well, but is now at the University of Michigan. And so his in-hospital approach is as follows. So you start with standard ACLS, because that's basically the easiest way to get started, right? You have to get started. You don't think very much as cardiac arrest, so you do your ACLS. And that is basically for in-hospital patients, right? And then you place your advanced airway. And then once you get your end tidal CO2 back, you see whether it's less than 20 or more than 20 in this particular situation. If it's less than 20, they assume that probably the blood flow generated with that standard ACLS is not ideal. So they first make sure that chest compressions are executed optimally, then reach to some of those devices that we already heard about that may improve circulation, such as like Lucas, which is a mechanical device with the active decompression function. They may also add a rescue pod, which is the ITD that you're going to hear about a little bit more later. Or you may also switch to the cardiopump, which is this active compression decompression device, just a manual device, or have a combination draft. So you really try to find out which kind of circulation enhancing methodology achieves the best flow for a particular patient, right? And you target this 20 millimeters of mercury. Then many of the in-hospital patients in ICU anyway have arterial catheters in place, or even central venous catheters. So that's a relatively easy thing then to go into the next phase. But you would like to have some arterial pressure access and some venous pressure access as well. And then you would determine what this diastolic blood pressure is, right? And so he set the target for the diastolic arterial blood pressure at 35 millimeters, assuming that that would allow at least a CPP of 20 or more, right? And so if it's less than that target, they would start EPI. In this particular situation, it would be a CRI and continue to do so until ROSC is achieved, or give intermittent boluses of one milligram per person, I guess, every five minutes until the diastolic pressure is reached, right? And the goal is really coronary perfusion pressure here, right? So those are the kind of how it could look like, right, if you would go about that. Naturally, for us, it's a little bit harder to have an arterial catheter in. At least we in our hospital do not have that available very often. But the end tidal CO2 definitely is a feasible thing for us as well to do. Doesn't seem to be rocket science. I think we always looked at that. I think in veterinary medicine, we were kind of a little bit more worried about the really low end tidal CO2, right? So, oh, it's 16. Great. Oh, no, it's 14. Now we really have to do something better, right? So it was like this dichotomous. And I see it with the training certification courses all the time, that people obsess about the 15 millimeter thing. And it's an important thing to probably learn from that, that it's not the minimum that we should aim for. But we should aim for how high we can actually get the end tidal CO2. Clearly, it should be more than 15. But 16 is not good enough. We should want to have the best possible blood flow outcome that we can get for a patient. Here, with this particular study, that is from Bobby Sutton. So he's also at CHOP now. And he's the same person that was involved in all those swine studies initially. And he also proposed a personalized resuscitation algorithm, so to say, how it could look like in five years down the road, right? None of that is very evidence-based. So don't just take this now for a black and white message. But it's kind of similar like before. So it's an iterative process where you have certain physiological goals, including in this particular situation also a hypovolemia assessment, so to say. So if you think that the animal is pretty underloaded, you can either add an ITD, or you can give some intervascular volume for that. And then there's also pressors, like before. And for the systolic pressure, they aim for at least 100. I guess you would increase your compression depth there as well, much as they did in the swine studies. So I don't have time to go through that in detail. But I would urge you to maybe visit this MCRT talk that describes it in greater detail. It's number 228 here. So it's actually really nice. It's an interview with Bobby Sutton where they go through that in more detail. So it's quite nice to listen to what their thoughts are. So what could we do in dogs and cats? I think N-tidal CO2 is pretty accessible to all of us. So we should probably aim to at least 20 millimeters of mercury, I would say, or at least should aim towards the best possible N-tidal CO2 that we can achieve and not just be happy with anything more than 15. Likewise, we could aim for some of those pressure goals that were suggested in the swine studies and achieve those with either adjusting our epinephrine dose or the compression depth. Having said that, we're still awaiting what the new guidelines will be. So maybe they will help us a little bit with that as well. There were some indicators that the palpation of the pulse, the presence of the pulse, and other presence of the arterial pulse, femoral pulse, that is, would potentially give us a little bit of an idea on whether Rusk is more or less likely. But the evidence there is really weak. And it would be really important to certainly compress as deep as we can without causing injury, but also explore different compression points and see what we can optimize there. I mean, ideally, we have a keel-chested dog and a round-chested dog. But many dogs are somewhere in between. So it's not always clear where the optimal compression point would actually be. And last but not least, blood gas analysis and electrolyte analysis will probably also help us, at least excluding some of the other physiologic arrangements that may be going on with those patients and treat them accordingly. So all of that together would then entitle more of a physiologic-guided CPR approach in dogs and cats. And that is it for that talk. So as I said, short talks, right? Not much fluff around it. Are there any pressing questions? Otherwise, I'll just move on. Was that disencouraging? Maybe it was. Any really, really important questions? Cool. Next topic, please. So the next one is on mechanical chest compression devices. And we just brought it up because we get asked every now and then, well, how about mechanical chest compression devices for our patients? And so I want to take a few minutes to just talk on that as well. Once more, I guess, what we really try to achieve during CPR is we want to optimize blood flow and chest compression quality. And one of the major downfalls that are known in humans, and we don't have that much data about that in veterinary medicine because we kind of measure quantitatively compression rates and depth and all of the things so well, is that people don't compress deep enough. They get tired. There is a lot of interruptions, right? So a lot of hands-off time, basically, during a two-minute cycle, all of which can be harmful. And so if you, oh, and then there is some situations during which it is not that easy to do good manual chest compressions, such as like during transport, right? Or it may not be safe. Or there may be interventional radiology happening at the same time. And so it's hard to do manual chest compressions while they do a coronary stent, let's say. And so for all of the reasons, mechanical chest compression devices have been developed. And once more, a lot of animals. So this is not a dog. Obviously, I think that must be some type of monkey thing. But just tells you how long that goes back, right? So Safar, for example, in the 60s has been using that for the first time in dogs, or at least reported about it. And he found that with sternal compressions, it's roughly similar like manual compressions, in that it generates a similar blood flow, like 10% to 30% of normal coronary blood flow, for example. In people, they also found that it works OK. Similar, maybe, like manual compressions in as far as the blood flow goes that is generated. But clearly, it negates some of the benefits of manual chest compressions, like that bystanders can do it everywhere, right? It's portable. It's easy to use. You can train large amounts of people. So for out of hospital, that's not really a very useful thing. So Safar was not really that happy about it. You remember, he's the guy that really initiated TPR back down into the 60s and hoped that everybody, whether they are medical professionals or not, would be able to serve as bystanders and save a lot of lives pre-hospital that way. So clearly, that didn't really seem to work that well. Kern used those devices, a thumper device, just like here in dogs in the 80s, to just see how it relates to manual CPR in dogs, in particular. And he also found that it generates similar CPPs like manual CPR. And so he was mostly interested on whether they could replace manual CPR in those research studies with the machine, and so whether they then could generate a more standardized experimental model, so to say. But that model would be a pretty good surrogate for manual CPR, knowing that out of hospital, in humans, they would probably use manual CPR rather than those in the field. And he found, yeah, it's roughly the same. So a lot of the studies from there on were done with compression devices rather than manual in the laboratories. But they were all with the dogs, typically in supine position and with sternal compressions. So what are some of the devices that are currently in use? So there are basically three types altogether. So there's the piston-driven ones that you see here on the left, then the active compression and decompression devices, and then some of the circumferential compression devices. I don't have any conflicts of interest here, by the way. I had to pick a few from each of those categories. But yeah, good. So the piston-driven device that is probably more commonly used is the Michigan device. It's pneumatic, meaning that it needs air to drive. And so it has this handy little carrier bag here for the respective air gas bottles. It pretty much is programmed to use the American Heart Association guidelines in as far as the rate being fixed at 100 compressions per minute. Also, the duty cycle is fixed, so the downstroke is 50% of the time and the upstroke is 50% of the time. The depth, however, can be adjusted. So it's not just this 33 to 51 millimeters of mercury that we've seen in the swine study. It can be adjusted to whatever. And the downside of this particular device is that it causes a little bit of trauma to the ribs and the sternum, maybe because it's a very focal compression point, and maybe because people also go a little bit crazy on the compression depth. I don't know. But it has more injury associated with it than some of the others. LUCCAS, that's the Lund University Cardiac Arrest System, so that's from Sweden. This is the LUCCAS-1 that was also pneumatic gas driven. So the newer ones now have batteries in them. They're quite portable, 6 and 1 half kilograms body weight. But really what makes this different is that it has this suction cup, so that it also allows activity compression, and therefore should have enhanced blood flow compared to the others. And it shows that it actually does so. So it generates more coronary perfusion pressure and cerebral blood flow than a comparative manual device, such as like the one here. So this is a manual standardized compression device, if you want to say so. So it's kind of mechanical, but it's not automated. So a person has to move the handle up and down. But it really allows to standardize just the manual compression, if you want to say so. And so that was used as the control for those studies that showed that the LUCCAS is doing a little bit better. Good old Siemens ventilators here in the back. But clearly for that particular suction cup, fur on the skin doesn't really help, because it has to have an airtight seal. We already talked a little bit about the VEST CPR, but this is the prototype for any circumferential compression devices. And it is also the classic optimization tool for thoracic pump CPR, because it really doesn't compress the heart in particular, but it maximally reduces the intrathoracic volume, therefore maximally increases the intrathoracic pressure. And it was found to be quite effective in dogs and humans in the 1890s, but really not portable at all. So it didn't really have a good out-of-hospital application. But it was kind of reinvented, if you want to say so, in a more simple portable device, the AutoPulse. That's a sole device. It's also a battery-driven thing. So there's a backboard. And this thing here goes around the chest of the respective victim. And it applies the pressure circumferentially around the chest, but still in a way that the sternum is depressed by this 33 to 51 millimeters of mercury. So it still has to adhere with the guidelines, because otherwise they wouldn't have it certified. It wouldn't be acceptable. But on top of that, it also probably optimizes intrathoracic pressure quite a bit. Found effective in swine, not really any superiority in humans compared to manual CPR. But here you see a little bit how it looks like this is a person that just gets PCI, like has a coronary stent placed, during ongoing chest compressions. So that happens quite a bit if they cannot get the people back, right, during regular ALS sometimes, or they have refractory ventricular fibrillation. Sometimes the approach to take is to reopen the coronaries. And that's a really hard thing to do with manual chest compressions, to do that procedure. So they use Lucas or this device at the same time. It's also quite helpful to, and you see the arm of the person here. It is also quite handy to transport people, of course, and also to use it in preparation for instrumenting a person for emergency cardiopulmonary bypass. All right, clinical trials all together, manual versus mechanical. As you can see here in this forest plot here, so everything here on the left of the midline would be that it favors manual. Everything here on the right would mean that the respective study results would favor mechanical. So it's pretty neutral, right? So there's no definitive, in the sum of all, benefit of it. And so I think the current status is that manual CPR remains the standard, but that there is special circumstances where it's impossible or dangerous to use manual CPR, such as in transport, where it has a specific role. And I think that role is pretty uncontested. People are a little bit worried that it takes more time until the first defibrillation if they have to put on a device that is quite complicated to wrap around the chest. But normally, yeah, so people need training to do that quickly. And it certainly is the exact counterpoint to personalized medicine, or personalized CPR, because it does always the same thing, right? So you cannot change anything on those devices normally. For us, I think there's not much clinic. Well, there's actually no clinical evidence at all. I think in animals, it works pretty much the same as in manual CPR would. This is the only picture I could actually find on a dog that's circumferential CPR in a dog as well. So it's definitely been studied, but it's probably similar to regular manual chest compressions. And because they are kind of a one-size-fits-all thing, meaning that they always compress 33 to 51 millimeters, that's very different than in a bigger dog, and so on and so forth. So the usability for us is very, very limited. So I guess we're stuck with the recovery guidelines, if you want to say so, with our manual chest compressions that just asks for optimal manual compressions with minimizing pauses and interruptions and with changing rescues every two minutes to avoid fatigue. And I think that would be it from that topic. And if there are any questions on that one, otherwise, we can chat more later. If not, then I hand it over to Dan. All right. It's the wrong one. Could I upload the wrong one a second time? OK. We'll fix it. at the next slide, at the next presentation. Sorry. I promise I wrote the lecture, I just clearly didn't upload it. That looks correct. So this is a call out to Dr. Hopper. I decided that we needed more sharks today. Real or fake? I have no idea. It looks pretty real to me. Okay, so I'm going to talk about three additional techniques, again, just short little talks, no disclosures to make for these. So I'm going to start by talking about ultrasound during CPR. How many of you guys are using or have used ultrasound during your CPR attempts? Cool. Yeah. So I've done some. It's interesting and embarrassing to admit that it was probably a year ago or so I had a dog that came in, arrested shortly after presentation, we started doing CPR, we got monitoring on, got to the first pause, clearly ventricular fibrillation, but I was convinced there was no way it was ventricular fibrillation. So we went back and did another cycle. And then we paused again, looked like ventricular fibrillation, and I'm like, there's no way. So I popped the probe on and sure enough, it was in ventricular fibrillation. So in that case, the ECG would have given me the answer if I had actually paid attention. But there are some interesting uses, I think, for ultrasound during CPR and a couple of different ways. So we're going to talk about using it to augment our rhythm diagnoses. So when boneheads like me get in there and refuse to believe the ECG, I might get some additional information. Identifying causes of pulselessness that aren't necessarily associated with true cardiac arrest, diagnosing return of spontaneous circulation, and then using it for prognosis. So our ECG rhythm diagnosis that hopefully you guys are all very familiar with, basically, we're asking ourselves during CPR to differentiate shockable from non-shockable rhythm. So if it's a shockable rhythm, that would be either pulseless VT or ventricular fibrillation, and we would treat that by continuing BLS and shocking every cycle. If it's a non-shockable rhythm, like asystole or pulseless electrical activity, then the question can be a little bit less clear. So sometimes asystole can fool you. And you can think that you're seeing a flat line when, in fact, there's maybe a little bit of activity that you're just not picking up on there. And that can be a case where maybe popping the probe on quickly and confirming that there's actually no mechanical activity in the heart. In general, for the non-shockable rhythms, taking a quick look and making sure there's no mechanical activity can be useful for multiple reasons. But one of them is to differentiate asystole from false asystole. And so sometimes what we'll have is a very fine ventricular fibrillation that, because of either artifact on your ECG or not good contact, you don't actually pick up. So if you put the probe on, you see a flat line, and there's no mechanical activity in the heart, then clearly that's asystole, and you'll treat it as a non-shockable rhythm by continuing BLS and considering pressors or potentially parasympatholytics, depending on your view on that. But if you look and you see actual fibrillation when you actually look at the heart, then that's actually going to change what you're going to do, right, because that's going to move you over to the shockable side of the algorithm, and you would consider shocking this rhythm. And that could have a pretty significant impact on prognosis. We know the earlier we shock the shockable rhythms, the more likely we are to get them back into a perfusing rhythm. So a quick look with the ultrasound probe, as long as you can do it fast and it doesn't increase your pause and chest compressions, could be a worthwhile thing. Pulseless electrical activity is another one of those areas where potentially using an ultrasound probe might be helpful. If you look, you see electrical activity that's repeatable, and you feel for a pulse and you don't feel one, you pop the probe on, and there's no mechanical activity in the heart, that's truly electromechanical dissociation, the old word we use for that. So electrical activity in the heart that's not generating any kind of movement, and we're going to treat that like we do the other non-shockable rhythms. But if you see that activity on the ECG, you don't feel a pulse, and then you pop the probe on, and you see mechanical activity in the heart, then there might be something else going on that you could potentially treat in a different way that might actually carry a better prognosis than true PEA. So these other causes are things that you could potentially differentiate by doing a quick thoracic ultrasound to try to figure out the possibilities. So there are going to be multiple typos in the pictures I'm about to show, which I pulled from this review article. These are not my fault. These are from the paper, okay? So don't get mad at me about these. But by looking quickly, we might be able to pick up some things we could fix. So one would be hypovolemia. So severe hypovolemia could potentially cause a patient to have a heart that's beating. They just can't generate any forward flow because they have no volume to push. And in that case, obviously, doing chest compressions, probably you could try them, and it may help a little bit. But if the heart's contracting, it's just that there's nothing to fill it with. Compressions aren't going to fix that. You need volume. And so doing any of the different types of maneuvers that you can do to assess volume status in patients is something that you could try in a heart that's beating. So you see underfilled chambers, but the heart's moving. You see a very flat caudal vena cava, maybe evidence of pleural effusion, which could potentially cause a decrease in venous return to the heart. And that may be what's causing you to not be able to generate forward flow. Severe peritoneal effusion could potentially be the cause of your hypovolemia that would drive you that way. And then ruptured abdominal aorta, which is probably much more of a thing in people than in dogs. But maybe in a trauma case, you might see something like that. Also, you could see cardiac tamponade. So we probably have all seen those cases where the tamponade is so severe that you're not able to generate any kind of appreciable pulses. But maybe you do still have activity in the heart if it's very acute. And maybe by doing a pericardiocentesis, you can stabilize that patient. In conjunction with that, you might see that the caudal vena cava is really big, because you can't get venous drainage anymore. And so you see this very large cava. And then this is not my typo. This is from the paper. Penumothorax is another cause, again. So same thing with the bad pleural effusions is if you have a very large, especially attention pneumo causing high intrathoracic pressure, compromising venous return. Again, you may catch it early enough that the heart's still beating. And if you can relieve that pleural space disease, you may be able to stabilize the patient. So it's important to do it quickly. But it's possible that it could give you an answer that may change the way you're going to treat that patient and may actually improve the prognosis. Ultrasound can also be used to diagnose return of spontaneous circulation. And there's at least one study that's shown that it may be a little more sensitive than what we typically use, which is pulse palpation. Probably not as great as end-tidal CO2, but for pulse palpation, we all know and we sort of hammer home in the guidelines that the pulse is probably the least reliable way to diagnose cardiopulmonary arrest. And yet we rely on it pretty heavily when it comes to diagnosing return of spontaneous circulation. So this was an interesting study that was just published back in 2018 where I love this little cartoon that they put in the paper. But you had a doctor up front who was actually doing a cardiac ultrasound during pauses in chest compressions. We had a doctor in the back who was using a Doppler ultrasound on the femoral artery to look for flow in the femoral artery. And then we had another doctor who was actually palpating the pulse. So three different people evaluating this patient. They had this setup in their treatment area where they had a curtain dividing these guys so they couldn't see each other. I can't even imagine doing this during a cardiopulmonary arrest, but apparently this is what they did. And what they found actually was they took the cardiac ultrasound as the gold standard because if you could see movement of the heart, you knew at least it wasn't a true complete cardiac arrest. So they would diagnose presence or absence of cardiac movement based on the ultrasound. And what they found was if you look at the manual approach here, they looked at the first cycle, the second cycle, and then the last cycle of CPR. And you can see this impressive false negative rate of 100%. That was only because it was interesting. There were seven cases where they thought the patient had arrested. They put the probe on and saw that the heart was still moving. And in all seven of those cases, they didn't feel a pulse. And so they called that the false negative rate for that. So it's 100%. It's seven out of 87 people. So it wasn't a huge number. But definitely a fair number of cases where the heart was actually still beating. And the only way they knew that was by doing the cardiac ultrasound. And then they could get to the bottom of it. But you can see that for both the Doppler and for the manual pulse palpation, there was a reasonably high false negative and false positive rate for detecting those pulses compared to cardiac ultrasound. So it's a reasonable thing to think about this maybe increasing the sensitivity of our measurements that we would more standardly do like pulse palpation to confirm or deny the presence of cardiac activity. And then this is just the time that it took to do these assessments. And interestingly, if you look at these p-values, that actually in this study, what they found was that the thoracic ultrasound was faster than either of the other two methods. They were able to do it more quickly than the manual pulse palpation or the Doppler ultrasound, which means they probably just had that probe in just the right spot. And they just kept going back to that right spot. And they had one person who was dedicated to doing it, which also probably increased their ability to do it quickly. But at least in this study, they did not show that it took longer to do the cardiac ultrasound and the pulse palpation actually took a bit longer at all those different stages. That has not been borne out in other studies. So this is another study that was actually published in the same year in resuscitation looking at the use of ultrasound during CPR. And what they actually found in this case was that the ultrasound actually delayed the pauses, made the pauses in chest compressions a bit longer and more so than really any of the other things they looked at. So here you can see this p-value that it took about 6.4 seconds longer to do the cardiac ultrasound than it did to do the pulse palpation in this particular study on average. And they did a univariate and multivariate analyses. And the only thing that really held up as being statistically significantly associated was that the ultrasound being done delaying it. And then the only other thing that was statistically significant was that the person doing it was a fourth-year resident, which is interesting. So the more experienced resident was the one who took a little bit longer. But aside from that, nothing else contributed to prolongations. So I think it's interesting that you can do this and do it relatively quickly if you get practiced at it. And maybe it would provide us a little bit more information. Then finally, using it to determine prognosis. So what we know for sure is if there is absolutely no mechanical activity in the heart, the prognosis is worse than if there is mechanical activity in the heart. At least that's what's been suspected. So this was a study published in Resuscitation in 2016, where they did cardiac ultrasounds on 793 patients who presented with arrest. And these were non-shockable rhythms only. So 414 of them had PEA, and 379 of them had asystole diagnosed on ECG. And then they looked to see whether they had any activity, any mechanical activity that they could pick up in the heart. And you can see, actually, a lot of them did in the PEA group. Over half of them actually had movement in the heart, whereas in the asystole group, very few of them did. But a few did, and that may have been a fine BF or something like that. And so when they looked at survival for these guys in terms of return of spontaneous circulation, much better for the ones that had movement. About 50% of those got return of spontaneous circulation compared to only about 15% who didn't have activity, mechanical activity in the heart. Survival to admission. So this was an out-of-hospital arrest study. 30% versus 7%, and then survival to discharge. Again, these numbers always get a little depressing, but 3.8 versus 0.6%. And again, these were all patients who were diagnosed with the non-shockable rhythms, which in theory, in human medicine, they would say correlate with worse potential outcomes. And so identifying that subgroup of patients who may have pulselessness for some other reason while they still have mechanical activity in the heart may have an impact on prognosis. So I think it'd be interesting to see whether we could find similar things in our patients now that we're all getting much better with our ultrasound skills. So any questions about that? Anybody using ultrasound for other exciting things? Yeah. Yeah, with transesophageal, yeah, so the comment was potentially using ultrasound to figure out if you're at the right location on the chest to get over the ventricles as opposed to over the outflow tracts and maybe compressing those if you're using the cardiac pump approach and if you can successfully use the cardiac pump approach in that individual patient. Yeah, it's an interesting thought of maybe using that to guide your position as long as it doesn't increase your hands-off time too much. It seems like it'd be a reasonable thing to try. Have you seen any, I haven't, I didn't come across any studies on that, have you seen a study on people looking at that? No, yeah, it'd be interesting to see, I don't know. Any other uses of ultrasound that you people, you guys have tried, you people, you people have tried out there? No? All right. So I think, I don't know, I have to say I am old enough that it makes me a little frustrated and cranky when I see one of my residents assess a case and use the ultrasound probe before they use the stethoscope. But I am getting more and more, I am seeing more and more the value of it and I understand, I don't think, Greg Lissandro is not here so I can say this, I don't see it replacing the stethoscope but I do think there are a lot more uses than maybe I've given it credit for and I think in the context of CPR it's interesting to think about whether there might be some other applications that might help us quite a bit. So things to keep an eye on. Okay, next I'm going to talk about these things we've been throwing all around the lecture hall so far, the impedance threshold devices and active compression decompression devices. So Manu has talked a couple of times briefly about these, I'm going to just try to go into just a little bit more detail about how they work and the data that we have and then the current recommendations from Ilcor at least about their use. So impedance threshold devices are meant to improve preload by basically decreasing intrathoracic pressure during the elastic recoil of the chest. So if you think about a patient who's having CPR, while you compress the chest, you're going to push air out of the lungs and then while the chest is recoiling, air will be sort of pulled back into the chest because we're now getting negative intrathoracic pressure as that chest is expanding and as we pull air into the chest, that's going to increase the pressure in the chest, it's going to make it less negative because we're pulling something in to fill up that potentially negative space. So the idea behind the impedance threshold device is that when you do the chest compression, you can still blow air out of the chest, but during elastic recoil of the chest, you block the airway so that you can't passively pull air into the chest. The thing to keep in mind is this doesn't mean that you can't ventilate the patient. So obviously when you go to give a positive pressure breath, you'll overcome that resistance in the impedance threshold device and you can still deliver the breath when you want to give it, but when you're not actively delivering a breath, it blocks that pulling of that air into the chest and so it makes the intrathoracic pressure more negative and that will facilitate refill of the heart so you'll get more of the blood returning to the heart because you get that negative intrathoracic pressure. And there's definitely data that it improves cardiac output by improving preload back to the heart from that increase in negative pressure. So this is just a short little video that I stole from the Rescue Pod site just to sort of show this. So when we do these compressions, you can see we get this little bit of preload during elastic recoil and then during compression, we shoot up our cardiac output. And then the idea here is that because we're pulling that air in during that elastic recoil, we don't get a lot of preload because intrathoracic pressure doesn't go as negative as it could. Now if we put the impedance threshold device, we push out the air, but then when elastic recoil happens, no air gets pulled back in through the impedance threshold device unless we deliver a positive pressure breath. So that's going to cause us to have more negative intrathoracic pressure. So it's blocking elastic recoil during this point. And then if we're patient, we'll get to the point where we can see the effect on the, come on, sorry, it seems to be, there we go. So now without the impedance threshold device, it looks like this. When we put the impedance threshold device on, because we get that negative intrathoracic pressure, we get this bigger drop in that pressure and we get the increased preload back to the heart from that. It just basically sucks the blood back into the chest. So that's the theory behind it and the physiology of it. So the device itself, it basically, it will close off this valve when intrathoracic pressure is less than atmospheric pressure. So this is showing the device during, say you're trying to inspire, and I played around with this, some of you may have seen that I was actually, I've never actually tried to breathe through an impedance threshold device. And you can feel it as you inspire, it pulls this little diaphragm down and it closes the air outlet so that you can't get any air to come in. But it has these little check valve out here. So there's a little spring that you can, the tension of it is set by how the spring is set up so that at a given pressure, if you generate enough negative intrathoracic pressure, you can open this check valve and you can actually get inspiration. So it goes around the diaphragm through this little check valve. So these are actually, can be used in people who are spontaneously breathing to increase cardiac output. So if a person is intubated and breathing spontaneously, or a dog, you can put the device on there. And so as they inspire, initially they'll get no airflow and they'll get an increase in that intrathoracic, a decrease, negative intrathoracic pressure. But then once you reach what they call the cracking pressure of the ITD, this check valve opens and you start to get airflow in. And most of these devices are set to either minus 10 or minus 15 centimeters of water cracking pressure. So for a person that works okay if you're spontaneously breathing. If you're a little cat, you may not be able to generate quite that much pressure and you may never be able to open the valve. So on a spontaneously breathing cat, I'm not convinced it would be a great idea. I just don't know that they would ever reach cracking pressure. But for a dog, it probably would work. And then certainly if they're being positive pressure ventilated, if you're applying positive pressure, you're going to drive effectively atmospheric pressure higher and you're going to overcome that. So you'll still be able to positive pressure ventilate them through it. But during CPR, in theory, you could use this to block it when you're not giving a positive pressure breath and improve preload. So again, about minus 10 to minus 15 centimeters of water, depending on the specific device you use, and you can overcome that with positive pressure ventilation. So in theory, you could use this in smaller animals as well as in people and dogs. So do they work? What evidence do we have? So this is the study that kind of initially put the nail in the coffin of the impedance threshold device. This was published in the New England Journal of Medicine in 2011. It was a large randomized controlled trial with an impedance threshold device and then a sham device that looked just like the impedance threshold device but didn't actually have the active components inside. And what they found looking at survival to discharge was no difference between the patients who got the sham and the patients who got the ITD. So this is what caused ILCOR to, I think they modified their guidelines saying basically that this is not necessarily a great intervention, not something that would be recommended. But then in 2016 in circulation, a reanalysis of that same data was done that actually showed some pretty interesting results. So it turned out that they had on a subset of the patients who got that were in the study, they actually had recorded data of CPR compression quality, so rate and depth of compression. And what they found was if they look just at the subgroup of patients who actually got compressions according to guidelines, so here you can see this is 80 to 120 compressions per minute, a little bit lower than what we would say at that low end, and a four to six centimeter compression depth. If they got that kind of CPR, you can see actually there was a statistically significant improvement in outcome. They were about 1.8 times as likely to get, in this case, return of spontaneous circulation in these patients who had good quality CPR and had an ITD in place. And then when they looked at even a tighter range, so I'm sorry, this is the poor quality. So if they looked at the patients who had poor quality chest compressions done, so less than 80 or greater than 120, this actually wasn't statistically significant. There was no difference between the ITD and not having the ITD. So the take home from this data analysis is the ITD doesn't fix bad chest compressions, but if you do chest compressions according to guidelines, it actually, in this data set at least, seemed to improve outcomes. People were more likely to survive if they had the ITD in place than if they didn't. And then when they narrowed that a little bit more, so they went instead of this 80 to 120, they narrowed the range to 90 to 110 compressions per minute. You can see the numbers are even better. So almost three times as likely to get return of spontaneous circulation with the ITD than with the sham. And then again, not significantly different if you looked at the ones with poor chest compression quality. So at the end of the day, that first data analysis may have been more an indictment of poor chest compressions than it was of ITDs. And this would provide some evidence that maybe the ITDs could be helpful during chest compressions or during CPR. And this is kind of a nice little diagram that was included in that where they showed the sham patients versus the ITD patients who had the correct chest compression approach applied. The more red this is, the more survivors you have. So you can see if you're right in the sweet spot of about 100 compressions per minute and about 4 and 1⁄2 to 5 centimeters depth of compression, more survivors in the ITD group than in the sham group. But once you move outside of that range, they're exactly the same. They all have poor survival. So again, as with everything, nothing makes up for bad chest compressions. But if you do good quality chest compressions, the ITD may be useful. So Manu also mentioned the active compression decompression devices during a couple of his talks. And this is looked at sort of at the same time as the ITD in most analyses because they're the same basic idea. We want to decrease intrathoracic pressure during the relaxation phase to try to increase preload to the heart. So same principle as the ITD. This is the cardio pump that Manu talked about. This is also cool because it has a chest depth of compression marker on it too. So you can get some feedback about your chest compressions. And again, increases preload by decreasing intrathoracic pressure. And at least in experimental dogs and pigs, as Manu showed, it does seem to improve hemodynamics. So this is that same data that Manu showed where they have the standard CPR versus the active compression decompression CPR. And in pretty much all the dogs, with rare exception, there was improvement in myocardial blood flow and cerebral blood flow and in renal blood flow. So it really did seem to have an impact by increasing that preload back to the heart. There's also evidence of improved outcomes when you combine the ITD with the ACD device. So both of them together seem to help outcomes. So this is a paper that was published in The Lancet in 2011. And you can see here that this modified Rankin scale is basically giving you an idea about neurologic function at discharge from the hospital. And you can see that comparing the standard group to the group that got the combination of the ITD and the ACD devices, they actually had more people survive to discharge with high scores, high neurologic function scores. So it did seem to improve neurologic function at discharge. And then you can also see significantly more, a higher proportion of them survived to 90 days after the event occurred. So it did seem to have an improvement in outcome in this clinical study by combining the two together. Sorry, I have those highlighted so we can see those. Come on, you can do it. So the 2015 recommendations from IllCore basically said that the routine use of the ITD as an adjunct during conventional CPR is not recommended. So I don't know if that evidence evaluation was done before or after that reanalysis of the data from the ROC registry. But it's hard to know. But I think at this point, it would be interesting to see whether this changes in the future. They have not updated them since the 2015 guidelines. And then they did say the combination of an ITD with active compression decompression CPR may be a reasonable alternative to conventional CPR where you've got the equipment that you need. So the reason that this is a weaker kind of recommendation is that they had very wide confidence intervals around those effects. So it's hard to know. And they felt that there was some bias in this study because the group that got the ACD plus the impedance threshold device, they were getting real-time feedback on their chest compressions from that device that they were using as opposed to the people who had standard CPR without those devices who were just doing standard manual compressions. So there was also the concern that maybe they were just doing better compressions because they were getting feedback. But at the end of the day, there's maybe some promise to these devices. As Manu said, the active compression decompression device, it's a little bit challenging to think about how we would do that in dogs and cats because they have fur. So you would theoretically have to shave them to use something like that because you have to get that suction cup attached to them. So I don't know. But maybe the impedance threshold device may have some benefit. I think we need to do some work on that. And then finally, interposed abdominal compression. So Manu also mentioned this a little bit. This is an example from one of the original papers of the technique to do interposed abdominal compressions to try to improve preload. So the idea behind this, as Manu suggested before, is that we're doing compressions in the abdomen during the relaxation phase in the chest so that we're hoping to increase the pressure in the caudal vena cava, which will push blood back into the chest and hopefully improve refill of the heart. So we're trying to improve preload by increasing intra-abdominal pressure by pushing, ideally, directly on the vena cava. So this was a study done in dogs. It was a crossover trial. Six dogs with induced ventricular fibrillation that either got standard CPR or interposed abdominal compression CPR. And then they switched over after they had the first intervention. This is what it looked like when they were doing this. And I put this up here because I think we're going to talk in a minute about technique. But I think it's really important to look at this closely. So you can see the way this dog is. I love the drawing. I feel like they could have hired an artist. I feel like I could draw that one better. But regardless, you can see that the front half of this body of this dog is in lateral recumbency. But then for the interposed abdominal compression part, they're actually opening up the hips and pushing directly up against the spine, which I think is important to remember because we're going to talk in a second about how I think many people do interposed abdominal compressions, including the video that Manu showed earlier today, which I think could be a problem. But this is how they set it up. So they were both mechanical devices. They were standardized in terms of the depth of compression and the pressure of the compression in the abdomen. So this is the experimental data from that study. So the blue is the interposed abdominal compression. The white is standard. And you can see significant improvements in aortic pressure. There were also increases in right atrial pressure during compression. But if you look at it during relaxation, yes, there was an increase. But it was smaller than the additional increase in the aortic pressure. So thinking about coronary perfusion pressures, this increase is bigger than this increase. So the difference between the aortic pressure and the right atrial pressure was bigger. And so coronary perfusion should have been improved by this device, even though we increased right atrial pressure a bit during that diastolic or relaxation phase. So this is really the important thing here, this difference between these two pressures, because that's aortic pressure during relaxation and right atrial pressure during relaxation. So the difference was bigger in the patients that had the interposed abdominal compressions. This is actually simulated data. So this is sort of based on the physiology. But just to sort of document this point, that was standard CPR. Looking at aortic pressures, which are these square boxes, and then the right heart pressures, which are the round guys. So the coronary perfusion pressure will be the difference between this guy and this guy. If we look at interposed abdominal compressions here, you can see that during diastole, you actually get this bigger increase in aortic pressure. And so you can, again, improve that coronary perfusion pressure by getting that increase up here in your aortic pressure. So in theory, this should improve coronary perfusion and should also just sort of improve blood flow out to the tissues in general. There have been some clinical trials looking at the use of interposed abdominal compressions. So this is a weird forest plot. This is called a cumulative forest plot. So this is one study. This is a second study added in. This is a third study added in. And then this is a fourth study added in. So in two of the studies, they looked at the survival to discharge. And then in four of the studies, the only outcome measure was return of spontaneous circulation, which is why we have two different plots. But if you sort of work your way down here, once you get to the last one looking at return of spontaneous circulation, there was a benefit, because it's to the right, of using interposed abdominal compressions in terms of return of spontaneous circulation. If you look at survival to discharge, don't quite make it. So those confidence intervals include one. So you're probably not actually going to see an improvement there. But if you include all of these guys together, you actually find that you've got an improvement in return of spontaneous circulation. Overall, very small number of patients in these four clinical studies. So I would interpret this cautiously. I think I would look at this as promising pilot data, that maybe there could be a potential effect here. Certainly, it doesn't seem like there's a detriment to doing it. So maybe there's a benefit. So the 2015 ill core recommendations say that interposed abdominal compression, CPR, can be considered during in-hospital resuscitation when sufficient personnel to do it are present. So that's probably the problem, that you need to have people who know how to do this. And that's where I think this question about technique comes from. So I, again, just sort of thinking about this approach, where they actually showed in the experimental study that we got an improvement in blood flow, I just did a little search on the internet to try to find pictures of dogs. And I think these are the two that I found. So this one's sort of the way that the video that Manu showed was happening, where we've got terrible chest compression technique here. So hopefully, this dog hasn't really arrested. But they're doing compressions sort of perpendicular to the chest, and also perpendicular to the abdomen with the dog in lateral recumbency, as opposed to this one. Again, horrible technique, but someone doing chest compressions over the heart, and then someone pushing sort of more ventral dorsally here. So I think this kind of approach makes more sense to me. Because again, what we're going after is we're trying to increase the pressure in the caudal vena cava and push blood up into the thorax. And I think that doing compressions this way, all we're going to do is compress probably the liver and the spleen, and potentially fracture them. If you look at the data from human medicine, there are very, very few complications reported associated with this type of compression, with interposed abdominal compression in people who get this. We don't really have good data in dogs. The study with the picture that I showed you, where they did the compressions with the dog sort of perpendicular to the abdomen, they didn't report any fractures of the spleen or liver. But I think doing this, I would worry very much that we could potentially cause liver or spleen injury and not actually compress what we're trying to compress, which is the cava. The other thing that people ask often is, well, how hard do I press if I'm going to do this? So there is actually data out on that. And so the goal is to try to get the caval pressures up to about 100 millimeters of mercury. So what they recommend in people is to take a blood pressure cuff, attach it to a sphygmomanometer, inflate it to about 20 centimeters of water pressure, and then do compressions until your sphygmomanometer goes up to 100 to 120. So you're going to get somewhere between, I'm sorry, yeah, 100 to 120. So that you're going to get somewhere between 80 and 100 millimeters of mercury of pressure. So you can use that to sort of guide. Because it's very difficult, because the abdomen is so compliant, it's difficult to know when you're actually getting that pressure generated in the abdomen. So if you're pushing up against the cava and you have that extra information, you can sort of titrate how hard you're pushing. So I will be honest, I have rarely done this. And after reading a little bit more about it and realizing that we could just use a sphygmomanometer to guide it, I'm kind of game for trying it. So how many of you guys routinely do or have ever done interposed abdominal compressions? So a fair number of you. How many of you routinely do them when you do CPR? Not many. Yeah, I don't know. It's interesting. I mean, I think the data are pretty compelling. And I think now that I understand a little bit better about the approach and the target pressure, I think it'd be interesting to try another one of those studies that would be a really easy one to do. So maybe someday. All right. I'm going to turn it back over to Manu, and then we'll just do all questions at the end. This is what it looks like at home right now. I'm very happy to be in Florida. All right. Cool. So whoever has used eCPR, cardiopulmonary bypass? No. Not. Yeah, it's not that. It hasn't found its way into veterinary medicine, clinical veterinary medicine quite as much. But I thought it's a technique that there's a lot of new information out there. And in the context of once more thinking about the gap between life and death, the discussion of it is quite appealing, I would say. Maybe let me start here with the three-phase model of CPR. So some time ago, it's now almost 20 years, Dr. Beckers and colleagues at Weisfeld have developed that model, where they say that there's basically three distinct phases during the resuscitation of a human person, an adult, with ventricular fibrillation arrest. So there's the electrical phase first, during one to four minutes of untreated cardiac arrest, whereby a shock alone, without any further chest compressions required, could lead to successful defibrillation and therefore spontaneous circulation. And that notion was kind of the background for all the AEDs. So that if you can have basically an AED nearby that allows a person to be shocked within a few minutes, then that's all that is needed, right? So casinos, there's good videos about that, where somebody falls off the slots, video camera sees it, somebody comes with the AED to shock them back, person wakes up, goes back to the slots, right? So not kidding. So during that electrical phase, there is essentially no ischemia or reperfusion injury. Things are really, really unproblematic, right? So that's the easy one. And that's really the rationale behind the AEDs. Then there's the circulatory phase, whereby when a person is left without any treatment for five to 10 minutes after onset of ventricular fibrillation, it's very unlikely that that person would be defibrillated successfully without preceding chest compressions, right? So it's recommended there that those subjects with that duration of untreated cardiac arrest would benefit from at least two minutes of good quality chest compressions so as to restore myocardial ATP, high energy phosphates, and so on and so forth, establish a reasonable membrane potential so that actually a rhythm transformation can occur. And so whereby with the metabolic phase, when that person is left without any circulation for 10 to 15 minutes or more, that even with chest compressions, the anoxic injury that occurs during that long untreated cardiac arrest is so large that just chest compressions alone may actually not be enough because the changes to reactive oxygen species and so on and so forth are too complicated and too profound to just recover with 10% to 30% of a normal cardiac output. So you need something more, right, in order to reverse that. Maybe you get them back, but the left ventricular function is so poor that it will just not be a sustainable, spontaneous circulatory function, right? And that's really the baseline, that metabolic phase, where there is significant, profound metabolic changes to the myocardial cells where the emergency cardiopulmonary bypass at the end comes in. And so how is that implemented? It's relatively straightforward. You basically put a cannula into the femoral artery and into the femoral vein, easily speaking, put it through a pump, right, that then pushes that blood through an oxygenator and reinserts that reoxygenated blood into the arterial circulation. The idea there is that the victim does not really depend on any oxygen exchange in the lungs, nor does it depend on any spontaneous circulation pump function of the heart. And so obviously, that has to all happen really, really quickly. And so it needs the skills of somebody to access those femoral arteries, which is, in particular with severely obese people, is not a trivial task. But people have gotten quite good in it altogether. Other than that, it basically has typically a centrifugal pump here and the gas exchanger here. And all of those can be preloaded with crystalloids so that they are basically there on standby. And as soon as you have the cannulas placed, you just plug and play, right? It's actually less complicated than one would think. And so the size of that equipment is also portable enough that, as I showed before, where legal environment and system environment allows that to happen, they bring it out into the field, right, into pre-hospital eCPR, such as shown here in France, in Paris, apparently. They have a medical intensive care, mobile intensive care, a MICU system that allows them to do those type of things, right, out in the field. In America, yeah, it's been a little bit slower. Asia apparently was really, really a frontrunner in that because chest compressions were not really all that popular because it's sometimes not polite to touch people, let alone push on somebody violently on somebody else's chest. It's just not a polite thing to do. And so whereby picking up the person and not do anything and bring it into hospital and then quickly instrument them within, you know, like 20, 30 minutes of arrest actually works relatively fine. So they're really quick with that. So there's huge, there's quite differences in implementation around the world with that. But I think the overall principle behind it and the opportunity also how that can be effective is that in that study and in others has been shown that a lot of the injury occurs during reperfusion. So this particular study here is an in vitro study, those are myocardial cells in a Petri dish essentially. And they are exposed to anoxia here for a period of time, like one hour. And during each of those time points here, their integrity of the cell membrane is measured. And so you basically can see here with a staining on whether those cells are actually intact or not. So the higher the PI staining is, the more necrosis essentially of the cell or the higher the cell death rate is, right? And you see that during that one hour of anoxia of those cells, there's essentially no cell death, right? The cell death only occurs at a time when reperfusion is induced. There's a little bit during ischemia as well, right? So if the ischemia goes on and on and on, eventually those cells die. But it's really accelerated during the reperfusion process itself. So that's kind of like a bizarre thing, because you think, oh, I'm going to put gas back into the empty tank of my car, and then the whole thing blows up, right? It doesn't really make a whole lot of sense. It's a little bit similar. You put oxygen back into the cells, and then they die now that they have the oxygen back. What the heck? So in a way, but that is a problematic thing. And so if we can manipulate that process here in order to prevent ischemia reperfusion injury to occur, that's when we can save a lot of the cells, hearts, brains, and so on and so forth. So that opportunity comes in with the bypass as well to fine-tune that reperfusion process such that we can potentially avoid that from happening. And various strategies, including in our own laboratory. So that was the cardiopulmonary bypass rep model that I was working on for years that we used. Same thing, femoral artery here, jugular vein here, goes through a pump, oxygenator, and then back into the animal, whereby there's also a leukocyte depletion filter in there, because all those activated neutrophils that were hanging around in the animal can actually be taken out to reduce some of that. We also took all the calcium out with citrate. The animal doesn't need any ionized calcium and can have ionized calcium of zero, because the heart doesn't have to beat. In fact, a little bit of cardioplegia for a period of time is actually not a bad thing to rest the heart, so to say. So we did all of that. You can cold reperfuse animals, which is highly protective as well. So it allows, in a lot of ways, to optimize the reperfusion process. And so when doing that, we, for example, found that once those animals have achieved return of spontaneous circulation, that the lactate clearance, for example, was massively quicker than in those that have just standard reperfusion. We found that lactate clearance was really dramatic. We also found that those animals that were reperfused cold, such as with moderate hypothermia, they typically lived to three days versus the ones that were normothermically reperfused all died. So when you have a good hold on this reperfusion process, I think it's a very powerful tool, potentially, although one needs to figure out what exactly the ideal reperfusion cocktail, so to say, would be to optimize that process. But yeah, is it effective altogether? I think some of the early eCPR studies were from Safar, again, from his Pittsburgh laboratory. And you see here in this particular study that they looked at different durations of untreated cardiac arrest as resuscitated with eCPR versus standard ALS. So the red one here is a group of dogs after 12 and 1 half minutes of untreated arrest that then were resuscitated with ALS. And you see that around 60% achieved return of spontaneous circulation. But ultimately, even though some of them lived, maybe half of them lived to 72 hours, none of them ever regained consciousness. While all these animals here that were resuscitated with cardiopulmonary bypass, all of them achieved return of spontaneous circulation, meaning that the heart, you know, they were weaned off bypass. It's not the circulation provided by the pump, because that would be pointless here. So they all regained good myocardial function. Most of all of them lived through 72 hours, and around 60% of them were conscious, although then later on, yeah, none of them really were entirely normal. After 20 minutes, it was roughly the same picture, but those are the dogs 20 minutes left dead. You know, they were not treated for 20 minutes, right? So that's a very large injury, if you think about that. But all of their hearts were started eventually, right? They all gained return of spontaneous circulation. Yes, brain may be not ideal, but at least the heart is very resilient. You can get them started. Same for the 30 minutes animals. You get the heart started, but they typically didn't live for 72 hours because of reperfusion injury, at least with intervention that they chose there was just too dramatic. How about humans? Not too much data there, and oftentimes they are just observational studies. It's really hard to randomize them to one or the other. So what typically happens is that they have ALS, they fail ALS after a certain amount of time, maybe they have 20 minutes of ALS, and then the eCPR system gets activated. And so then it takes a certain amount of time until bypass gets started. And so in this particular study, they use so-called propensity-matched controls. So those that got ALS and not eCPR, those subjects were the same age, gender, same degree of VF, and so on and so forth, same percentage of VF, and so on and so forth. So they were basically the same in all characteristics other than not having received eCPR, right? And so you see here that survival to discharge in those with ALS duration of less than 30 minutes was 20% in the ALS-only group versus 40% in the eCPR group, right? And that kind of similar trend is replicated with longer durations. So even with ALS durations of 45 to 60 minutes, right, we have a very low survival rate in the ALS-only people, while a third of those that were then transferred to eCPR actually did quite well, right? After 60 minutes, it's typically, you don't get any of the ALS people back. But it's a pretty significant, I mean, those were people that got eCPR for a long period of time, and yet their survival to discharge rate was actually relatively good, right? So that's up to an hour. So it's quite a powerful intervention. There's probably a selection of patients, typically they use the younger people, and so on and so forth, right? So it's kind of the idealized patient. But in this particular study, it's all propensity-matched. So the ages and so on and so forth should be similar. So then, when taking a couple of studies together, those are the results here regarding long-term survival, both for out-of-hospital cardiac arrest and in-hospital cardiac arrest, you see that there is an overall trend to a benefit, I would say, at least certainly no disadvantage. So the plots over here seem to, are all the studies that favor eCPR, right? The question, of course, is whether we have a reasonable functional quality, right, of those individuals. Obviously, the quality of life is really what you want, and not just a bunch of hospice care folks or vegetables, right? And maybe as we, this is a pretty drastic intervention, I would like you to listen quickly to Lance Becker, who has really been a pioneer in this situation, and he was asked exactly that vegetable question regarding eCPR. Dr. Saffer was the person who developed mouth-to-mouth ventilation and CPR in the 50s in this country. And before that, nobody knew how to do CPR, nobody knew how to really do mouth-to-mouth. And when he said he was going to teach it to the public, it was something only a trained doctor could do. It was called cardiac massage at that point, you know? And he said, I'm going to teach this to the public. And there were letters that appeared in the journal that said, Dr. Saffer shouldn't do this because it will fill the hospitals up with brain-dead people if you do that. And then when we moved AEDs, automatic external defibrillators, shock boxes, out into the airports at O'Hare, we made them available to the public. Previously it was a technique only a doctor could do. Now an eighth grader could do it. We got letters that said, you're going to fill the hospital up with brain-dead people if you take this technology out there, okay? And when we started cooling in 2002 and 2003, people were concerned. They said, you're going to fill that hospital up with brain-dead people, Dr. Becker, okay? And as we now start to talk about some of these future things coming down, like putting a patient on an artificial pump that would be the equivalent of a heart and lung machine, ECMO, whatever you want to call that kind of a device, the letters that I get are, you're going to fill that hospital up with brain-dead people, Dr. Becker. So the beautiful thing is, I just want to, we should sort of put that to rest because we actually have really good colleagues. So you see, like whenever a new intervention comes in, I think that's a really, and it's a good concern. You know, obviously that's, but once the survivors come out and you see a little bit what's happening, then I think those concerns are less so. And the studies that we have here is, yes, it's not just brain-dead people. I think they actually do neurologically relatively well as well. All right. Good. But yeah, there's no RCT. So currently the recommendations, and that's just from last year from an American Heart Association focus update, is that there is taking altogether insufficient evidence to recommend routine administration of eCPR, but that it may be considered for select patients where conventional CPR efforts are failing. So where basically ALS, there are non-responders to ALS, right, but have otherwise reversible diseases, such as like coronary disease, obviously you wouldn't do that in an end-stage cancer patient or something like that, and where it can be implemented as well. And so the barrier there is quite significant to do that. It's not a trivial task to implement that system. But I think what we learned from it is that the outcome contention essentially for heart and brain is considerable, that non-response to ALS, biologically speaking, does not coincide with death. It really depends on how good your technology is to some extent to reverse that process. And I bring that back. It's the last time now. But that gray zone really widens with the technology available to do those type of things. Because as I said before, much of the injury that we do is during the reperfusion process. So if you can't get a good hold on that, I think it's how the technique works in dogs and cats. I think there's ample, there is experimental studies that show that. And it's so therefore probably also effective in clinical dogs and cats. We just cannot do it, right? So it's a matter of theory. It's a complexity. It's the time sensitivity, the expertise, the cost, right, in a very resource-restricted environment that veterinary medicine is not a trivial thing to do, and that there are ethical considerations there as well, I would say. But in principle, it works. And it's really the barriers there that matter. So I guess we are back to optimizing our chest compressions and the blood flow, probably, and maybe physiology-guided. And the other thing, the best blood flow thing that we can probably do, as long as we transition early enough before significant cerebral injury occurs, is open chests, right, in those dogs where we, I think, are not able to generate good blood flow. I think many of those studies that you looked at, you know, in the human studies as well, they oftentimes waited quite long until the open chest step was made, whereby the benefit then is kind of quite diminished. And so that's probably a decision that has to be made quite early. And then there's obviously post-cardiac arrest care that is important as well that we're going to hear a little bit later. But that can help with ischemia and reperfusion injury as well, for sure, including potentially therapeutic hypothermia. Cool.

physiology-guided CPR

devices and techniques

optimize outcomes

personalized approach

coronary perfusion pressure

end-tidal CO2 levels

accelerometers

metronomes

ultrasound during CPR

rhythm diagnosis

return of spontaneous circulation

mechanical activity in the heart