Tim, thank you so much for having me out here. Okay, so thank you, Dr. Pepe. Okay, we have a slideshow up here, good. All right, so thank you very much, everybody, for being here, and just wanted to say that it is really a privilege to be up here once again with all of you, and thank you very much. I've been doing this for over half a century on the streets or in the ICUs, and promoting and researching CPR. I really feel I can say this has been the biggest advance that we've had in almost six decades now, and you'll see why. I hope you agree with me when we're finished here. And thanks again for the society for having me up here. All right, so as we heard the title of this thing, and we don't have any titles there, I used to be a distinguished professor, I'm more of an extinguished professor now, so we'll see as we get along. Before I get started, you gotta do the usual disclosures, clinical trials, IRB, you know, these devices we're gonna talk about today are all FDA cleared, and none of my speakers, I'm sorry, co-authors here, including Dr. Kerry Bacchista, which is the one right next to me there, the first author, nothing, no disclosures whatsoever. All right, let's move on. So this is kind of like a fun, provocative question of the day, right? Why are you upright? Why are you listening to this thing sitting or standing? Why aren't you, wouldn't get better blood flow to your head if you were in a supine condition? So I'll leave that with you as the provocative statement, and you come to your own decision after we go through this today, okay? So let's begin. In the U.S. alone, 1,000 persons will die today from sudden, unexpected out-of-hospital cardiac arrest, and CPR, as we've known it for the last, is a clear miracle of modern medicine. I've witnessed the cases, and myself have brought back people from the dead, so to speak, clinically dead, with such a, you know, this action. It's been fantastic. The problem is that most cardiac arrests do not receive CPR, and also, the majority are not shockable cases, which are often the ones that we can get back. In fact, most, or 80%, at least, are non-shockable cases, both in the hospital as well as out of hospital. And so people will present with asystole, like a brady-asystolic arrest, or get near there with pulseless electrical activity, PEA, as we call it, and generally, that's associated with longer periods of rest, and that's why people have always felt that they've carried very poor prognosis. In fact, the survival odds with good recovery nationwide remain about 1.5% across the U.S. systems, and those are the progressive ones that are actually monitoring this. And keep that number in mind, that 1.5%, and you'll see why that's gonna be kind of a fun number to remember. But here's the but part. It's not just long response times, yes, they've been unwitnessed arrests, you'll see in almost half the cases that's asystole, but there's physiological limitations of conventional supine CPR we began to appreciate about two or three decades ago. And even if it's performed optimally and early, supine chest compressions themselves, I mean, they do create an arterial pressure wave, get stuff up to the brain, right? But on the other hand, there is also a problem on the other end, because we're not only, when we're compressing the chest, we're also get relatively equivalent retrograde venous pressure waves going up various venous channels up there, and they collide in the brain, and when they do that, you get spikes in ICP at that time, and of course, that would limit blood flow not only into, but across the brain as well. So, outward blood flow has been measured over and over again in various studies to be only 15 to 20% of normal, and maybe even less in the brain given the situation. But what's a potential resolution for this limited blood flow into and across the brain? One thing is maybe to pull some of that blood out of the brain and back into the chest. So, if you think about something as simple as like a toilet plunger-like device that can not only push down, but then pull up, create a vacuum, negative enthoracic pressure that helps drain blood out of the brain and back into the chest, and literally helps to pull it that way. Now, another thing, you just keep in mind, by the way, some of you, there are studies that show even by itself this thing works on its own, but there are mechanical versions of it. I wanted to make sure you see that because in various slides, you'll see this equipment, and a lot of you are already using it, but keep in mind, what those have on it are those plunger devices that are doing this. They may not pull up as far, and hopefully they will in the future, as the pump itself, but we'll see. It's been very useful in some of the studies that we're about to show you. Now, there's another device called the impeded threshold device, and that thing is, by itself, again, it's applied to the airway, and it's a valve that prevents air during the recoil phase of CPR. When you're recoiling, you can suck things in, you're sucking air in, but by inhibiting the airflow for just a brief period of time, you can tug in a little bit more blood. And what we've shown, actually, in human studies here, where they put art lines out in the field, and after 14 minutes of CPR alone, they're getting systolic blood pressures of 85, which is more than double what you usually see out there in most of the circumstances. But tell you what, when you put the two of these together, it's impressive. In an NIH-funded, supervised clinical trial, we got 50% improvement in neuro-intact survival in that situation, and for me, this was a true proof of concept that you can pull blood out of the brain and into the chest and get much better outcomes and better flows and so on, even up to one year survival of 49% improvement in neuro-intact survival. All right, so if lowering ICP and enhancing blood flow back to the heart is so important, right, can gravity help? Well, the answer, I think, is yes, and you'll see why. But yes has to be done correctly, and that's really critical to anything you take home today. You can't just lift the head up. In fact, lifting the head up is detrimental because you can't get blood uphill when you're doing standard CPR. You've got to first do the priming with that ACD and ITD. You've got to basically get active compression, decompression, ITD going. Then you get enough flow. Now you can get that blood uphill, and if you gradually elevate the head over a period of time, which we'll tell you about in a second, then you really can get some great effects here. And specifically, over the last 10 years, we've looked at should you just have reverse Trenton-Dolenberg? Can you just put the head up? Should you put the chest up? And we found having both head and chest up was important. You actually lower comorbid vascular resistance and various other things we found in the lab. But most importantly, as you see here, you've got pre-arrest cerebral perfusion pressure in the pigs, and it goes down to, you know, whatever, and there we are, 15 to 20% of normal as you would get with standard CPR. And we know that this combination of the ACD, active compression, decompression, and ITD will give you much better flows and better outcomes as we know in humans. But how long should you prime it for? Should it be for one minute, five minutes? And how fast should you elevate the head? Should that be done in two minutes or 10 minutes, whatever it is? So we carefully worked it out, and it turns out you do about two minutes of ACD-ITD priming, and then you have a two-minute gradual elevation of the head that gets you, basically, it's phenomenal, it's synergistic. You get near-normal blood flows established there. So a device is now available that provides the correct automated gradual elevation of the head, and it gets you sort of up to, I think, around 10 inches. For those here from the U.S. crowd, just wanna make sure you guys know what centimeters are, so that's cool. But anyways, it gets you about 10 at the occiput, and the heart's about six inches up as you do it. These, again, are all FDA-clear devices, and so people have begun to use these, all right? So, let's see now. Oh, let me just make sure you understand the point. Again, we wanna enforce that before you do the elevation, you gotta do those other things first. So what's the study purpose today? Primarily to see if such robust outcomes are also applicable for patients with non-shockable presentations. I've done studies where we were able to get almost everybody back if they had early CPR in the first couple minutes and shocking right away, but that's a very small fraction of people. And even those who we think are candidates for ECMO are not in the non-shockable group. So look at this. How are we doing along this line? And more importantly for me, I wanted to find out how fast this should be on. Is there an association with time to application? And I think you'll find out the answer in just a second. So, the methods where we were just comparing the neurointact survival for non-shockables, and those of you who wanna know what neurointact means, CPC1, CPC2, and it's in the paper if you don't follow that and you'll see. And we looked at patient care data from our Head Up Registry, which are all prospectively collected data, very comprehensive data set. And we compared it with corresponding data for conventional CPR. Now where that was taken from, and purposely taken from, were these NIH trials that were done. And we used the controls there because they required electronic recordings, documentation that you're doing quality CPR before they even let you enroll into those studies, et cetera. So we thought that would be the most, I guess strictest kind of comparison we could make. And just for those of you who are interested, tomorrow I'll be doing a presentation looking at the current data. They haven't changed at all. These are gonna be the same numbers, okay? So, results. Well first of all, they're good. The survival rates with good neurological outcome for non-shockable patients. Remember, some of these have very lengthy response times already in large percentage, like they're, I think, almost 40% on unwitnessed asystole. And if you've taken all these, even a 20 minute response time or 30 minute response time, what we found was that we were getting threefold odds ratio of getting them back under these circumstances. And remember, we told you that 1.5% number, that's what you're seeing in the gray there at the bottom. And now we're way up in the 4.5% survival rates here. And then we did, by the way, lessons learned from critical care, many of them here, have been propensity score matching for these circumstances. And what we did was, clinical trials have been a challenge. There's been so many confounding variables in the out-of-hospital setting. But what we do know are those factors that are associated with good outcomes. So this is a really appropriate way to do this, and you'll see. And it turns out, you know, that gets you up to maybe fourfold, but you're still way up there in terms of your survival chances, okay? All right, so now, one thing I wanted to know was the time factor. Looking at the application of automatic positioning devices, as we call it, you know, the head-up thing. And what we did is, if you could get it on within 11 minutes, by the way, which is the median time, and there's another little digression, eight minutes, 911 call, triple nine call, wherever you're from, 1122, the start of CPR was eight minutes in every group we looked at, every study, whatever, and even today. The time of application and activation of this thing was, median time was 11, so half the time you can get there, and look what you're getting there. Odds ratios are off the charts in that situation. In fact, since there's no more survivors after eight or nine minutes, what we were finding that in the standard group, that if you look at, I thought quarter hour is a pretty good thing to look at, turns out 80% of the patients can get there in that period of time to them. Well, look at this, the odds ratios still climb even further under those circumstances. So, one of the things I have to note here is that this is facilitated by easy carrying and a pretty correct approach, because when these guys, only two or three people are needed to get this thing there, they open it up and everything's all set and ready to go, so they've really taken it to the next level, because the faster you do this, I was here on stage in 1982 saying, the earlier their intervention, the better results, that's been my mantra, and that's what we're finding here too. One last thing I said in terms of data, I wanna show you that, did the presenting ECG affect the scale of the differences, you know, because we talked about asystole, just, you know, no chances, and is this all, you know, these PEA cases? Well, interestingly enough, when you do these comparisons, yes, the PEA cases are 10% now, versus the, you know, 3% we have been traditionally seeing nationwide and in the past, et cetera, and that odds ratio is good, but if you look at the worst case scenario, asystole, unwitnessed case, you arrive, they're flatlined, most people would say they're gone, you know, that's it, but what we were finding is that we're actually getting neuro-intact survival in these cases in almost 2% of the cases, and what's really striking about that is you do break it down, and you'll see a presentation I'm doing on Tuesday, down to like, you know, less than half the time you get there, 11 minutes, we're approaching 3%. Now, 3% sounds low, but compared to like no percent, it's high, and also, you're talking about 400 people a day in the United States alone, you know, this is pretty, it's a great, another proof of concept from my point of view, okay? Just those numbers alone, regardless of your methodology, is important, and by the way, we're seeing a kind of an important new signal. The guys that are doing this out of Edmond, Oklahoma, are reporting that in the past, they would get a mixture of CPC1 and CPC2, now they're seeing nothing but CPC1s. We're looking across the other systems right now, and they're seeing the same thing, but I just wanted to at least let you know that. Before closing, I do have something important I wanna relate to you, is that I'm so grateful to this organization, and the people that are in it. Critical care practitioners lead EMS, often in other places around the world, and in your own ICUs, I wanna challenge you to say, hey, take this to the next level, if we can get there so fast, well, you could have it right there, put this on, and you have people instrumented, so you can tell me whether or not, what I did in the study in the animal lab, is that we found out that after resuscitatum, you get better cerebral oximetry, you get better cerebral perfusion pressures, but I can't measure that on the streets. I would love to have you, this is just the beginning, a starter kit, where you can start doing a lot of great work here. In conclusion, I wanna say that rapid application of this triad of non-invasive CPR adjuncts is associated with markedly improved out-of-hospital cardiac arrest outcomes, and I bet you it'll be in-hospital as well. And it is, in a sense, it's an AED equivalent for non-shockable, automated defibrillator equivalent for non-shockable out-of-hospital cardiac arrest, but with much wider window for life-saving, as we've shown here, and it can be implemented correctly, and again, if it's implemented correctly, I strongly recommend it for all first-in responders, which could be not only firefighters and lifeguards, but ICU, emergency department, cath lab people. And on the road to the 2030s, I hope that we'll get back people we never got back before, right? And make life-saving more routine for future generations. Had to put the perfunctory slide in, the family, right? I'm Paul Pepe, and I approve this message, okay? Thank you very much, everyone. Okay, good, thank you so much.

CPR advancements

non-shockable cardiac arrest

active compression-decompression

impedance threshold device

resuscitation outcomes