So, first, I'm going to tell you I have no financial conflicts. I do other things that do not conflict with my position in favor of eCPR. What I want to do is give you a little bit of the history of CPR and why is that I and many others believe that eCPR is filling a gap in resuscitation, in this case from out-of-hospital cardiac arrest. The debate was focused for out-of-hospital eCPR. It's important to keep in mind that despite a huge effort for many, many years to address the issue of sudden cardiac arrest, the American Heart Association estimated about 360,000 individuals will suffer an episode of sudden cardiac arrest every year in the United States. CPR is attempted in about 67 percent, and of those, only less than 10 percent will survive with good neurological outcome, and if we count all the victims who suffer sudden cardiac arrest, we have a very low survival. The data came from a publication from 2020, but things have not changed that much recently. I wanted to just briefly display the chain of survival that I'm sure everybody knows. It's important to realize that each of the links can be making stronger and stronger. Activating the system is already probably in our genes. Hopefully more people are ready to do bystander CPR. The percentage probably is around 40 to 50 percent, but in other communities can be much, much higher. The idea of the free population as early as possible is very important, and we have more technology coming with citizen activation as well as drones to deliver and AED to the site. I would say advanced life support we're going to fuck today, and probably this is the one as the other link becomes stronger, this one kind of lags behind. I think we still have good, I'm sorry, oops, yeah. So what I wanted to do is go a little bit to the basics of cardiopulmonary resuscitation. And the most important thing to reestablish cardiac activity is to provide adequate coronary blood flow. And the coronary blood flow during cardiac arrest, when there is ischemia of the myocardium and the coronary arteries are fully dilated, becomes pressure dependent. And the pressure that matters is the gradient between the aortic pressure and the right atrium. Not when you compress, when you let go, at that moment it's a gradient. And the larger the gradient, the more the flow. So when we talk about chest compressions and conventional CPR, our effort really is to increase the coronary blood flow. And there are two things that we do. One is to ensure that we optimize the amount of blood flow when we compress the chest, but it's not enough. So we administer a vasoconstrictive agent that's going to raise the aortic pressure for the given amount of coronary blood flow. And the agent that we have today is epinephrine. Now this is what we, by standard, we want them to do. To do good, high quality CPR, basically the compression of the chest to squeeze blood out of the heart and to let the blood in so that we can maintain certain cardiac output. I would say that with optimal condition, high quality CPR is very difficult to generate more than 25%, 30%, and probably most of the time it's less than that. And that's the reason why one of the focus of the American Heart Association and many others is to ensure that we do the best we can. And that's the concept of high quality CPR that I would assume most of you know. Essentially we want to compress at least 5 centimeters, the rate between 100 and 120. Very important not to lean to enable blood return to the heart for the next compression. We don't want to pause too much, and we want to make sure that at least more than 60% of the time we're doing CPR. It's important to have a choreographed approach as opposed to sequential, so that you have the whole team engage in CPR quickly. And in terms of performance, I would say that the best that we have is capnography. And if we control for ventilation, the end tidal CO2 is a very good surrogate of the blood flow that is being generated. CVP drives coronary perfusion pressure, and the data is very, very convincing that animals in this case that have a higher coronary perfusion pressure during CPR have a high likelihood of being resuscitated. But there was a very interesting study that was Norman Paradis many years back, published in 1990. What he did was to take patients who had sudden cardiac arrest outside the hospital that were not successfully resuscitated, brought him to the emergency department of Henry Ford Hospital that instrumented and continued doing CPR, and they monitored the coronary perfusion pressure. It turns out that if the coronary perfusion pressure was not increased above 15, none of those patients survived. But as soon as the coronary perfusion pressure was generated above 15, and especially above 20, then the initial resuscitation increased dramatically. So what I wanted to say first is that this is a very important physiological parameter that drives the success of the resuscitation effort. And that's what we do basically when we attempt to resuscitate and do CPR. What we're doing is driving blood flow through the coronary artery to deliver oxygen to the myocardium. And if we succeed, the chances of achieving BRAS increase significantly. Now as I said before, the amount of blood flow generated by chest compression is not enough. And that's the rationale for giving a vasoconstrictive agent that cause peripheral vasoconstriction. As a result of that, the aortic pressure increases, and therefore the coronary blood flow. And this is one study in animals back in 1986 showing the dramatic increase in the coronary blood flow when epinephrine is administered. It's important to keep in mind, we're going to talk about that very soon, that the amount of flow diminishes over time. So whether we give the epinephrine or we don't, there's a progressive deterioration of the ability of chest compression to maintain the blood flow. In the same study, you will think that that increase in flow is really good. Look at the amount of flow that was increased. But when we look at the metabolic effect in the myocardium, there was no difference in terms of the amount decrease of ATP and the increase in lactate. The point is that despite good CPR administration of epinephrine, it's not possible to reverse myocardial ischemia using conventional CPR. And that most likely explains why the window of time to achieve successful resuscitation rarely goes beyond 30 minutes, or in most instances, you have 30 minutes to bring the heart back. It's very difficult past that point. Now you will think that epinephrine did something that would be beneficial. I always want to bring this study back to everybody. This is Perkins. It was published in 2018 in the New England Journal of Medicine. This is the first large study of out-of-hospital cardiac arrest in which the victims were randomized to CPR with and without epinephrine. What's important to keep in mind that epinephrine actually was very good to reestablish cardiac activity. In fact, ROSC was achieved in 36.3% of the patient, which is threefold the control. But that benefit rapidly disappeared. And at the time of hospital discharge, and at the time of 30 days after, there was no difference whatsoever in terms of survival with good neurological outcome. So I think this basically seals the problem with conventional CPR. We can do a great effort to bring people back, but not many really survive with good neurological outcome. That is what have triggered to look for alternative beyond conventional CPR, seeking hemodynamically more effective intervention. And there's a good history of many efforts. Early on, we have the Michigan Thumper that basically what it does is simulate what a person is going to do. The good thing about this device is that the depth of compression can be controlled. But it was designed mostly to be able to transport somebody receiving CPR in a moving vehicle. We also got this device that was initially developed at Kid Lurie, which enables not only to compress, but also to lift the chest to decrease the intrathoracic pressure and favor venous return. When used in conjunction with an impedance threshold device, the hemodynamics significantly improve, but we don't use it many more, at least routinely. You all know the Lucas device. We compress, we lift, but because the depth is fixed, we don't take advantage of further expansion of the chest using the Lucas device. This was a device that was developed by my mentor, Professor Weil, many years back. It's a piston with a band around the chest, which I think is probably sort of a combination between a compressor and the otopulse that generates pressure around the chest. So this is what we have done in terms of the mechanical devices. And more recently, and Dr. Paul Pepe talked about this yesterday, which is a head-up CPR. Essentially, it's a combination of the Lucas device with impedance threshold device to enhance forward blood flow and using gravity to facilitate the increase in cerebral blood flow. And he showed yesterday an improvement in patients who were resuscitated after pulsed electrical activity. Having said that, now we move into the topic of today, which is extracorporeal membrane oxygenation for CPR. And this is, in a nutshell, what the technique is. We first have to be able to cannulate the vein, use the femoral vein here, with a cannula that goes all the way up to the right atrium, and the blood is returned into a femoral artery. Ideally, the cannulation should be done under tonography ultrasound. That seemed to be the preferred approach. You can see here we use a femoral vessel for that purpose. What I wanted to show you, a few studies in which the investigators were looking at the outcome compared to conventional CPR. This was a Japanese study known as the Study of Advanced Life Support for Ventricular Fibrillation with Extracorporeal Circulation in Japan, SAVE-J trial. This is a subset. It's a secondary analysis of the study. And what the author wanted to see was whether the rhythm at the time of initiation of eCPR influenced the outcome. In the original one, they did not have the data. So here, what they did was, it's a very large study of 450 patients that were eligible through 39 institutions in Japan. And they were looking at those who were treated with eCPR compared to conventional CPR. That's first. And within each group, they look at those in which there was VF or ventricular tachycardia that was not being terminated at the time of eCPR. The other group was the one in which VF transitioned into PEA. And the same thing here, the same separation of subgroups, but here was conventional CPR was continual. So you have two things that we're looking here. Number one is the effect of eCPR versus conventional CPR. And within each group, does it make a difference whether the heart was still fibrillating or the heart went into PEA? And I'm going to comment on that in a second, because I think that's very interesting. So this is essentially what they found. In blue are the patients who have sustained VF or pulsative ventricular tachycardia at the time of eCPR. And they compared this group with the one in which they still have the same, but only conventional CPR was attempted. You can see the big difference in terms of survival. This survival here is 33%. The other one is very, very low, less than 10%. Of this 30%, I don't have the data here, but 20%, about 60% of those survived with good neurological outcome. But it's interesting that in the group that converted to PEA systole, despite eCPR, survival was much, much less. And that's very intriguing. And of course, with conventional CPR, there was almost no outcome. Statistically, only the group that had VF, pulsative VT at the time of the event, benefited statistically from the administration of eCPR. Now, if you look at the time, time from collapse to hospital arrival. So this is out of hospital, sudden cardiac arrest. The patient's taken to the ED, the closest, with ongoing CPR. And then the eCPR is initiated. The time from hospital arrival to implementation was 22 minutes. And so from collapse to eCPR was a little bit about an hour. And that's a very important element that's important to take in mind. And we're going to talk about that briefly later. The time from the event until eCPR. Now why is it that that makes such a big difference when the time was not? The authors speculate that this group in which VF was maintained received higher quality CPR. There was a higher incidence of bystander CPR. So in a way, you can think that perhaps the persistence of VF indicate a heart that somehow is receiving certain blood to maintain VF. And it's a better condition for subsequent resuscitation with a more aggressive approach using eCPR. So that's the interpretation of the authors. And I think it makes perfect sense because the time was exactly the same. This is the other study I wanted to share with you. This is experience from the group from Minnesota, Dr. Bartos, Dr. Yiannopoulos, and we can see Dr. Tom after Heidi that maybe many of you know him. So what they did here, they have a lot of experience already with eCPR that initially was done in the cat lab. Now they have a mobile unit. But what they did here was compare the outcomes, and especially the neurological outcome. And it was not a randomized study. However, what they did was to compare their experience here at the University of Minnesota with the amiodarone arm of the ALPS, identifying the patient that had similar characteristics. The ALPS was a study using conventional CPR, randomizing patient to receive amiodarone, lidocaine, or placebo. And amiodarone was better than the other options. So you can see here that in the University of Minnesota, about 160 patients were included. At the end, there were 121 that were analyzed. And of those, 39% survived with good neurological outcome. When we compare with ALPS, in which there was no eCPR, it was a conventional CPR, the survival with good neurological outcome was 23% only. Now this is another interesting aspect of the same data set. Here, what they're looking is at the relationship between the duration of CPR. They call it professional CPR. So the bystander is not included. These are the paramedics doing CPR. And in the ALPS studies, once again, this is a conventional CPR. You can see very good survival early on. But the window of time is very short, as we discussed earlier. Probably no more than 40 minutes before there is no response to conventional CPR. When eCPR comes on board, you can see a very dramatic improvement here. Even if eCPR was given after 20 minutes of conventional CPR, there has an effect. So on top of the conventional CPR, we get eCPR and survival with good neurological outcome improved dramatically. So that was an important message, in my opinion. The effect that it opened the window for successful resuscitation with survival with good neurological outcome beyond what conventional CPR can generate. How's my time? You're almost done. Almost done. OK. I'm going to fast forward a little bit. I want to point out a few things that there's a lot of effort that goes into. You can see here, I'm going to show you a few data. The time in which the patients were without ECMO was about five days. So there's a lot of resource being used any time that you use eCPR. One important piece of information that we can discuss, the thickening of the left ventricular wall during conventional CPR. That is one of the reasons why the heart becomes smaller and conventional CPR is less effective. When you compress the chest and the heart is small, there's less blood flow being generated. And that was very nicely shown in this study. The challenge is basically, does the rhythm matter? Probably yes. Is there an optimal time to initiate? Probably yes. I would say ideally, no more than 30 minutes, but you can still get it after one hour. There's risk for lymph ischemia because we're cannulating the femoral artery. It's important when you transfer somebody to the hospital to continue doing CPR. And for that, mechanical CPR is better in route. And I'll talk about that. You need a team. And it's going to use a lot of resources. So from that point of view, I think it's an add-on to conventional CPR, assuming that everything else in the conventional CPR is working well. Since my time is running fast, what I'm going to do is give you the last slide, which I wanted to make a point here. Number one, it opened the door to a whole bunch of other investigations in resuscitation. You can modify the composition of the blood. You can use post-attack fluid. So it opened the door to more research. And this is my last slide. It's the same chain of survival. And the message I want to tell you is the following. When we optimize each link, this is the only one that we cannot do what we have today. And here's where eCPR can help. So eCPR will enhance ALS, and that would lead to improvement in the recovery with good neurological function. Thank you.

eCPR

cardiac arrest

CPR

extracorporeal membrane oxygenation

survival rates

resuscitation