All right. Good morning, everyone. Um, thank you very much for the kind, um, introduction and thanks for taking care of sound and video. I really appreciate. Um, how are you guys doing on the second day? Still up there? Good, good. So we have an entire day of CPR, which is awesome. We never get to do this. Um, normally we get an hour there and here and there and then you just go through your BLS and ALS stuff. So this is really a great opportunity to, um, immerse ourselves, I guess, in the world of resuscitation as we have it. Um, and, uh, it also required us to, um, indulge in a lot of new material, um, uh, which is a great opportunity from our end as well. And so I guess our proceedings reflect some of our endeavors to acquire that, um, material. Also, unfortunately, um, there were a couple of editorial mishaps on my end regarding the proceedings. I hope you find the proceedings helpful. Um, but there are errors and some of the errors are maybe, um, somewhat misguiding you when you read it, but I think they are so silly. The errors is almost like mad lips style, right? So you have random words in there. Uh, so you're going to find out about it, but, um, to compensate you a little bit for that issue of those errors, I brought a couple of giveaways. So if you find a significant error that you think is particularly disrupting to you, then come to me. And I think the first couple of people get an ITD, an impedance threshold device, um, for, I guess if, for whatever, if you want to enhance your own circulation, for example, during a long day of lectures, feel free to read a little bit through it, um, or yeah, for whatever. So, um, whenever you come across one of those errors as you maybe read along through the lectures, then, um, let me know. Um, and the first, I think I have six or so of them. I'm gonna have go home with an ITD. Yay. Um, good. So we have a series of lectures and Dan and myself, in order to kind of keep it a little bit colorful for you, kind of swap forth and back quite a bit. Um, the program is maybe not exactly the same sequence as we do it here, but you're going to find out eventually. So the first thing we thought we're going to do some fluff as Dan says, Manu do some fluff on history in a way. Um, and the fluff turned out to be really, really interesting, um, and huge. Like I have now a library of 20,000 page volumes about history of resuscitation at home. Um, it's a pretty wide topic, but it's highly fascinating. And so I, um, I want to start with that first. Um, I have nothing to disclose. So this is a one and a half hour lecture. The first part is, um, the fluff, right? So it's the history of CPR and how we moved a little bit from myth to evidence, um, over the past, I would say two and a half thousand years of history of CPR. And then Dan is going to cover the remaining 45 minutes where he's mostly going to talk on the recover initiative, um, and its contribution there. Good. So I want to start with that. Who knows the Wiggles? Yay. All right. Somebody. So the Wiggles are a really, really famous kids band, um, in Australia. They are Australian, right? But I think they also tour around the world, including the US. Um, and you know, they've been around for many, many years, 20 plus years, and they got a little bit older right now. And as you maybe all know, there were tremendous, terrible bushfires in Australia and pretty much everybody who can do some fundraising, got some fundraising, including the Wiggles. So they made a little reunion concert, um, just actually a month ago, right? Um, where they all came together and this is how it looked, right? It was a lot of fun. And that was to the end. You see the yellow wiggle there in the middle. All of them are kind of in their late forties now, early fifties, something like that. Very exciting. It was, um, January the 18th. And so they move out and you see the yellow wiggle Peng crashes down. And so while on TV, he basically experienced a cardiac, cardiopulmonary arrests and people were rushing there and trying to resuscitate him. And indeed, um, several steps unfolded that led to a favorable outcome. First of all, it was right there, right? Everybody saw it. People diagnosed a cardiopulmonary arrest right away. They knew what they were dealing with. There were bystanders there that started chest compressions right away. There was somebody in the audience actually as well, that was a nurse that then got involved and she knew how, was quite familiar with defibrillators. So she got the, um, the AED out and, um, was able to defibrillate him quite well. The EMS was, system was activated right away. It's triple zero in Australia. Um, and so then several trucks were delivered and by the time the EMS was here, the, um, Greg Page, who was the yellow wiggle, well still is the yellow wiggle, luckily, um, already had the pulse back and, you know, was getting the ambulance to the hospital, uh, got a coronary stand placed and did actually quite well. And so that's an image in the media because the wiggles are like, you know, they are so popular. So that was all over the news right away. Um, so the next day he was already thumbs up, right in the bed. Um, happy nurse because she saved the yellow wiggle. Who gets to save a wiggle, right? If you save a wiggle, like you're, you're a God almost, right? Um, but about the God aspect of it a little bit later. Um, and then four days later, Greg Page goes home, right? It's amazing, right? Somebody who basically died, if you want to say so, um, survived and goes home four days later. And this is really what this lecture is a little bit about. Um, this kind of paradigm shift of where people thought back in the days that there is a strict line between life and death. You're either alive or you're dead and there is nothing in between, right? To where we believe, um, we are today, right? Where there's life on one side and death on the other side. And there's this space in between where you're not quite dead, right? So where there's an opportunity for resuscitation and that's journey from that, um, strict delineation to that space where everything is possible that took like thousands of years, literally. Um, and so let's talk a little bit about how we got where we are and, um, probably the first report, um, in the literature, if you want to say so in the, in this case, the literature is the Bible. Um, that is the, uh, the, um, the old Testament. And in there, there is maybe the first report of resuscitation. Um, and that was the prophet Elijah that was called to a boy's bed, the bed of a boy where he, um, was found lifeless essentially. And he went there, um, and he did a couple of resuscitation measures, which included he putting his mouth on his mouth, his eyes and his eyes and his hands and his hands. Then he lay on him and gave him warmth and all of this type of things. And so then the boy had a couple of big sneezes, um, where people think that maybe the God bless comes from that because it was sneezing a bunch of times until he came back to life. I'm not sure whether in these days, this is a particularly good looking thing when an older man lays on a boy and puts his mouth on the other mouth, but at the time it worked quite well. Um, and you know, it's, it's probably not thought to be at the time when it was written a resuscitation story. Right. Um, but rather, because at the time God was the only person, person, the only entity basically that could people bring people back to life. And it was highly, um, inappropriate to consider that somebody could bring somebody back from, from the dad right at the time. But it may be is the first time that the thought of resuscitation actually was raised, right? So that somebody who is passed away can, um, can be resurrected. And then, um, what though wasn't available at all at the time and probably for several hundred years afterwards was the fundamental fundamental understanding how the respiratory system and the cardiovascular system actually works. Um, and without that, I guess, modern resuscitation is not possible at all. So some of the early physicians such as like Glenn in the second century after, um, in the second century developed some fundamental, um, concepts on how the circulatory system works. So in his world, um, and he was a physician back in Rome. Um, so in his world, the circulatory system looked like that. And so the liver produces all the blood and then the blood goes from the liver to all the tissues and the tissues use up all the blood, right? So it was like a one way street if you want to say so. Um, and you can see that here. So the liver delivers all the blood through the veins to the tissues and that's it. It's an open ended system. Some of the blood also goes through the septum of the heart through some perforations to the, to the left side of the heart where it is mixed in with air. Um, and that then also goes out to the tissues and the air is kind of really, um, is, is, is in a way, um, uh, the, the, the, the spirit of life, if you want to say so spirit of life is required to keep the fire in the heart life. So that fire was really the furthest of life was what kept life going. And without that fire, there was no life. So that was the thought at the time. And so once that fire is extinguished, um, and that's what people thought would happen if somebody drops that, right? Then that fire cannot be realized. It's the end of it. And so that idea, um, through the, um, through the tremendous impact of Gallen and everybody really believed in this physician for like the next 1500 years, that idea was so cemented in everybody's mind that bring somebody back to life was essentially another thing, right? So that fire is extinguished, the end of the story. Um, and so that was really important and it took quite a while. So this is like 12, 1300 years later, right? When William Harvey threw mostly experiments in dogs as so many things at the time, um, found out that there is actually a circulatory system, right? Up until then, this system here was the accepted way, accepted way of how the blood turns around the tissues. Um, and it took quite a long time until the closed circulatory system was established by William Harvey. Um, even though he didn't really have the capability yet to look at capillaries and stuff, but important part here was that the blood now was able to go through the lungs from the right side to the left side and the septum here was not any longer, um, perforated. All right. So then, um, a couple of things happened. And so some of the resuscitation reports came out where, um, where people really believe, started to believe in the fact that people actually can be brought back to life. So this is really interesting. This is probably one of the first really detailed reports at all in the literature. So that's the story of Anne Green. Anne Green, um, was a servant to a rich man, um, in England and that rich man had a son and the son raped Anne and Anne got pregnant, all of which was completely legal, um, until she gave, uh, she, um, had stillbirth, stillbirth child, stillborn child, um, and then was accused that she would have killed the child, right? So at that time, then she was immediately, um, um, she was basically hanged for that reason, right? Executed. Um, and her friends, because they want to make sure that she absolutely dies, were hanging on her legs and talking and doing all of this type of things until people thought that she's really, really dead, right? So they put her in a coffin. The coffin went to the anatomy lecture because they wanted to do a dissection as it was at the time customary. Um, and so when they opened the coffin, they saw that she was still breathing at the time. And so instead of doing the dissection, they called in a couple of doctors. The doctors did some resuscitations, which included hot cordial in her mouth, um, rubbing her fingers, arms, and feet, um, more hot cordial, right? All the hot stuff really has to do with the fire, right? Do you remember, like before, like the, the, this heat, this inner heat was really important. They also tickled her throat with a feather, um, of course, also a bunch of bloodletting. Um, so they cut some of her veins in her arms and, you know, got like two, three hundred mils of blood out, um, some compression bandages, hot plasters, again, to put some heat in there, and also some hot clist tears to give even more heat. Um, and then once she was successfully resuscitated, she had to stay warm with another woman in a bed for like two days or so. And that all was a great story and everything went really, really well. Um, and people came from far and wide to see the woman that survived, right? And her dad actually charged a bunch of money to see her, um, to make a little bit of extra, extra of an income. So that was the first report. That was maybe, you know, it's the first report where there was a little bit of a crack between life and death finally showing up. Um, so that was her. But, you know, there was no breeding here, obviously, like nobody thought that maybe we have to do some mouth-to-mouth ventilation or deliver any kind of other ventilation. So that was not yet a thing. Although the first accounts of ventilation were quite early. So this one is from a guy named Bagelardus who wrote in Latin on the right side. Um, and his report on, or his instructions to midwives how to resuscitate neonatals clearly included mouth-to-mouth ventilation. It says, if she, the midwife, finds the newborn warm, not black, she should blow into its mouth if he has no respiration. Um, and then that all sounds very normal, but it also has that blow into the anus, um, which is really weird. Um, and I thought I have to double check on that. So I was reading some of the Latin here and it says out in anu eius, which really, I mean, it's exactly the same sentence, just Latin. Um, that's where my Latin comes to fruition here. But, um, so it's, it's true. So somehow they had still this weird concept. So the breeding was maybe not really, they didn't really understand the gas exchange thing, I guess entirely, but they saw somehow the concept of inflating different orifices with air as meaningful. Um, so that was in the 14th century. Then Paracelsus, a little bit later, is, um, known to be the person that instructed people to use the typical, um, fire bellows, fireplace bellows to inflate people's lungs. Um, maybe again has to do with the fire, right? And so if you light a fire, why not lighting the, you know, the fire in the body, not necessarily a respiratory thing, maybe to some extent, but maybe it had also to do just with the fire on it in itself. So that was, um, actually a technique that was probably used for several hundred years. And we talk about it a little bit later. The first case of really mouth to mouth ventilation occurred, um, in the 18th century. And that was the story of a coal miner who was exposed to some toxic gases in a coal mine in Scotland. Um, and so he was found without a pulse and on breeding was brought up by his colleagues. And the doctor, William Tussack at the time, um, employed mouth to mouth ventilation to resuscitate him. And he actually did quite well, uh, recovered from that. Of course, he also got a little bit of bloodletting, a couple of cordials again, some smelling cells, rubbing the skin, and all the other things that are standard resuscitation fare at the time. But this was really the first mouth to mouth ventilation, um, um, report. And, um, and it was a big difference, made a big difference because it was really the first report where they showed that somebody can be brought back to life. This person didn't have a pulse. This person was absolutely dead, but yet he kind of survived. So a crack was opening here a little bit. Um, and this kind of concept of not being life nor dead was, um, was brought up in one of my favorite movies of all times. And I think my kids would agree with me, The Princess Bride. And there they bring a person in, um, Leslie, uh, Le, Le, Le, Leslie, I think, um, to, um, Miracle Max and Miracle Max was known to do miracles, right? Um, so they bring him in to, um, ask Miracle Max for help. And, um, that's how it is. Well, it just so happens that your friend here is only mostly dead. There's a big difference between mostly dead and all dead. Please open his mouth. All right. And you see historically accurate bellows. Mostly dead. He's slightly alive. All dead. Well, with all dead is usually only one thing that you can do. What's that? Go through his clothes and look for loose change. All right. So, um, that is actually quite accurate in a way, you know, like I think reflects the sentiment of the time relatively well. There's the bellows. There's this really, this, this, this, this space that opens up between mostly dead and, and, and entirely dead, right? Um, unfortunately the mouth to mouth ventilation, as you see here in the video as well, um, hasn't really come through very much. Um, people were worried about antidepressants or the CO2 that is exhaled by the, by, um, by the person that would deliver mouth to mouth ventilation. And CO2 was just detected or found for the first time around in the 18th century. And also oxygen was measured for the first time. So they found that oxygen is really low. CO2 is really high. And so they figured that that exhaled gas may actually be toxic to the victim. So then there were some other things. Um, it was felt that it's a little bit inappropriate to do mouth to mouth ventilation. And then later on, maybe a hundred years later, there was also some concerns regarding germs and those kinds of things. Um, but John Hunter at the same time found again in animal experiments that breeding is essential for the beating of the heart. And so that with the animal or the human is not breeding, then that is actually what stops the heart from beating, right? So this kind of asphyxiation idea of cardiac arrest was developed at that time as well. And so the whole importance of breeding was, um, was identified at that time. So that was really, really important. So the, the, that breeding is so such a huge deal. Um, and drowning was the major issue at the time, right? So there were cities built around rivers, people fell into the rivers, they drowned. And so asphyxiation is a huge deal. And so now knowing that breeding is a very, very important part of resuscitating those asphyxiated people, um, a lot of rescue associations and societies came out, um, and they recommended some things. So, and the bellows were a really big, um, thing there. And so those are some of the pictures at the time. Um, so their bellows, they have various adapters, adapters to put it in the mouth in the, in the, the, there were tracheostomy adapters as well, adapters for the rectum and so on, and also tobacco. So tobacco smoke was a big deal at the time. So they felt that smoke is invigorating. Um, tobacco smoking was just coming up at the time. So it's very invigorating. Um, it's another heat providing element. Um, so some of those bellows actually have, um, little chambers where you can put in the, uh, tobacco so that you can ventilate them with tobacco smoke. Or what was commonly used once more is tobacco insufflation into the rectum was a common part of resuscitation as well, for some reason, I guess it has to do with the heat again and the stimulation, um, that was considered really important at the time. So if the yellow wiggle would have been resuscitated in the 1750s, you can imagine how it would have looked probably some, um, hot cordials, maybe some tobacco front and end, um, and, and, um, and possibly some bloodletting as well. So that was kind of the state probably wouldn't have gone all that well in, in, in, um, in this particular situation. So artificial ventilation though was then moved on. People use mechanical ways of delivering, um, what they thought ventilation, and that's mostly again for drowning victims. So because on boats, there was a lot of barrels, that was a very pragmatic approach was to roll somebody on a barrel. So that was very, um, commonly used or trotting somebody on a horse. And then this rhythmic motion from the trotting on the horse would create a little bit of ventilation as well. But there were really tons of other, um, kind of mechanical or manual ventilation, uh, methodologies proposed. Um, and that is one of the very first, first ones, um, Marshall Hall, mostly they were, um, those methodologies included lifting the arms, decreasing the arms, pushing on the back, um, or in this particular situation, rolling the person forth and back, all of which should have led to some form of inspiration and expiration over time. Interestingly, and of course, people were successfully resuscitated every now and then, and people got really worried about the fact that, um, that they would be buried alive, right? So what was a more and more popular thing at the time was also the development of, um, coffins that had alarm bells attached to them, so that if somebody would have been put into the ground and they would wake up, for some reaction, they could ring a bell and then somebody would hear it on top and could get them out of the coffin. Um, why this is important in this context is that it really, um, reflects the fact that people now thought about being dead is maybe not the final thing, right? So there is a way to actually wake up. So those, those kind of patents came out quite frequently in the 18th, 19th century, and there's still some of those coffins available in modern style today with like cell phones and all of that kind of stuff. Um, but at that time, it was really the first time that maybe people thought like, oh wow, if I'm dead, maybe I wake up again, right? It's not the final thing. My light may not go out forever, right? There is a way to actually come back. And that shift in their minds, I think was quite remarkable. Um, so now there was a little bit of an ego, um, an ego dance there regarding all those different techniques. Um, so every person that was, that had their name on a resuscitation methodology thought that it's the best one, right? Um, and then eventually, uh, it became a huge cacophony of different resuscitation methods. Um, Sylvester's methods also was used to resuscitate by the way, Abraham Lincoln, when he was shot in his head, uh, a while ago, and he was successfully resuscitated at a time actually initially. So he was breathing spontaneously again until he succumbed to, uh, the brain injury associated with the, um, shooting. Um, then there's a shaffer method here as well. And those methodologies, those trainings were rolled out really widely. You see here, um, a school class that is training on each other. Um, so this kind of bystander CPR with just those arm lifts and back pressure methodologies, right? Um, and so by the end, well, that's around 1950, right? So by the mid of 20th century, that's what people were doing, right? Um, so that's now around 1950 and there were around 105 different methodologies available. Like everybody basically thought their own one is the best one. And some of them were more popular than others, but there was not really much science to distinguish which one is actually the best one and which one is not until, um, Archer Gordon came in and really started to measure all of the things like what are, what is the inspiratory volume? What is the expiratory volume? And so on and so forth. And so I think that's maybe the first time when really scientific rigorous evaluation of those methodologies came in and helped people to understand a little bit what actually works and what not doesn't. And what they, what he mostly found is that none of those are really good, right? So nothing comes in, nothing goes out essentially. Um, and people certainly have been using that for a long period of time, but now we had some hard facts that this is maybe not the most effective way of going about. And that's really what brought in the mouth to mouth ventilation again. The mouth to mouth ventilation really, as we know it today, came back from James Elam. Elam, um, at the time was a young doctor when the polio epitome was, um, at its height. And so he describes that one kind of essential event for him was when a little boy was brought in, he was all cyanotic. Um, and he delivered mouth to mouth ventilation to this boy and his cyanosis went away right away. Um, and then ultimately, you know, like he was continued to be treated with an iron lung, such as like here. Um, and polio obviously is an infectious disease, so it would have been a potentially a big issue right at the time, but he thought that he was, um, immune against it because he has been doing that for a while. Um, and that really was one of the circumstances where he found out and had some good cases to report that mouth to mouth ventilation is actually works really fine, right? The CO2 is not toxic. There's enough oxygen. It's actually quite effective. Um, and so he, together with Doyle, which is a friend of his, went on to a little road tour to, um, to show everybody that's that mouth to mouth ventilation works fine. And so how it worked basically is that Doyle got paralyzed, um, with curare. Um, and then depending on which methodology of breeding they use to either desaturated or not. Um, and so they had a little roadshow. They went around to all the police departments of the fire departments, because those are normally the people that were mostly involved in those cases, um, and showed that little show. And so here's how it goes. So you see, he's now paralyzed. He's not breeding. Watch the oxygen. That is the Nielsen methodology. You see, this is like ventilation back in the days. You see the pulse oximeter slowly going down. So there's a little earlobe pulse oximeter attached. You see it slowly desaturates. Yeah. He was sedated as well, not just paralyzed. Um, but you know, they did that basically on a daily basis. The arm lift method is not working at all. Yeah. So then somebody of course has to come in and pre-therm it. So that's where the nurse comes in. And then they demonstrate that. So you see, the fears were very much this kind of problem of not people being reluctant. So they really tried to make this not watch the indicator and you'll see how effective the rescue breathing method is. So you see this, the oxygen comes up right away. And so they went around the country and did that for quite a bit, carbon dioxide or something. If you breathe deeply, his carbon dioxide level will be normal, but most important, he will be getting even more oxygen than he needs. All right, cool. So they toured around that, but as a two-man team that just couldn't have that much impact. So they needed other people to help them out. And so they met up with Safar, Peter Safar, which is one of the fathers of modern time CPR. And he, um, came, um, he was an anesthesiologist at the time. And you see that he demonstrated here mouth to mouth ventilation on a paralyzed volunteer as well. So his residents basically, uh, got paid a few dollars and then they volunteered to be paralyzed, um, for a period of time and he, uh, he resuscitated them. So, so together they, um, created quite a bit of evidence to show that mouth to mouth ventilation is actually effective. And finally, we're able to convince the major resuscitation relevant organizations that mouth to mouth ventilation is the way to go. It's much more effective than the previous, uh, Sylvester, Niels, Shaffer, like all this, this other, um, methodology. So at the time towards the end of the 50s, probably, you know, the yellow wiggle would have received some mouth to mouth ventilation, but he may also have noticed that we haven't talked about chest compressions at all. So that was not a thing yet, right? So everybody basically just got the treatment for asphyxia, cardiac arrest, maybe for drowning, but the chest compression thing wasn't really there quite yet. And so that took a little bit more time, even though, um, from, uh, from, uh, the idea of compressing the heart was quite old. So the first report of internal chest compression was from Moritz Schiff in Geneva, Swiss guy. Um, and he describes quite, um, precisely on how you do open chest CPR in a dog at least. Um, and the, the motivation for those people to do all of, to look into that at the time was that, um, ether and chloroform was coming out. And so there, there was a lot of anesthetic arrests. Um, so that's now different from the drowning, right? So now you have these cardiac arrests, um, from the overdoses of those anesthetics. And so that's triggered a whole lot of interest in kind of getting the heart started independently. And so that was the same for Moritz Schiff here, but then also for Rudolf Boehm, who, um, in Estonia was a professor there. And, um, he describes his, um, he, um, describes the first external chest compressions in a cat actually, or in cats rather. Um, and, um, he describes in, for those who can read German, uh, how he went about, about that. And basically he describes how he did grab around the sternum with his hands and does lateral, lateral chest compressions in the cat. And then he also cannulated the carotid artery at the same time. And he describes that whenever he squeezed the chest, that's the fountain kind of, you know, sprayed up depending on how hard he squeezed. He also measured the blood pressure. He saw that the systolic pressure with doing that is around a hundred, right? Um, and, um, and so on and so forth. So it was quite detailed at the time. And, um, then soon there, and those things were like all in German, right? So those were German publications. Nobody read them essentially. So it's not that external chest compressions then became popular right away, it took quite a while. Nevertheless, Friedrich Maas is the first external chest compression description in a human, and also a German. And he describes a case where a boy with a palatal cleft was underwent anesthesia with chloroform. And because he was screaming in the process, they re-dosed the chloroform. And so finally, he arrested. And so he started external chest compressions for like 10, 20 minutes in the surgical suite. But then he was kicked out because the next surgery was to occur. So he had to move him to the next room and continue the chest compressions over there. The economic constraints were already pretty significant, it seems, back in the days. And so he went on for quite a while, for like an hour or so, and finally resuscitated him successfully. And he already made some quite significant observations, such as that when he compressed with 30 to 40 per minute, then it wasn't really let. His pupils were just not responsive at all. But when he compressed with 120 per minute, the pupils became more responsive. And yeah, so he described two cases that he successfully resuscitated, although recovery was relatively slow. So here it says, for example, that for 8 to 10 days, the boy was surprisingly stupid. And he only slowly recovered his normal capacities, although he wasn't of very high intelligence to begin with. So it's like a very frank description of what's going on. But that's how the scientific literature was at the time. So it was very interesting. And nevertheless, so that really didn't percolate through to the larger profession. And so most of the people just stuck with interthoracic open chest cardiac compressions or massage. And so this is just one of those papers that describes a little bit how much information there was gathered, right? So they had 1,200 cases of in-hospital cardiac arrest, all treated with interthoracic cardiac massage. And the thing there really was that that really limited the resuscitation to the hospital environment. Nobody would necessarily do that out of hospital. And it worked reasonably well, right? You had 28% of permanent survival. But for out-of-hospital arrest, not really that big of a deal. And so that took a little bit longer until 1960. It's the time when the three people that you see there, Jude, Cohenhofen, and Knickerbocker, kind of came up with the first reports on external chest compressions that were based on scientific observations. And so the story goes that Knickerbocker, who is seen there on the right with the bow tie, he wasn't a young engineer in Chicago at the time. He worked together with Cohenhofen, which was an electrical engineer and was working on defibrillators, on dog resuscitation experiments. And so Cohenhofen was accidentally shocked by the defibrillator, right? And so he developed the pedals such that the shock could only be delivered if you pushed really hard on it, right? So it couldn't deliver a shock if you were just holding the pedals. You have to push really hard, and then the mechanism is released such that the shock can be delivered. So that required Knickerbocker, when he did his defibrillation, to push with several kilograms of weight on either side of the chest, right? And so those animals were fully instrumented. They had an arterial catheter in place. And he saw that when he did that, that there was an arterial pressure wave generated, right? And he thought, oh, wow, the pressure on the chest actually does something. So they looked a little bit further into that and found out that the chest compressions actually is related to a hemodynamic response, and they quantified that response. And then one day, an animal accidentally went into ventricular fibrillation when they were not prepared for it. The animal was under anesthesia in their laboratory, and the defibrillator was not up there. And the defibrillator is like a 100-kilogram kind of device and wheels. So they were up on the fifth floor. They had to go all down to the bottom floor to get the defibrillator. With the elevator, it was like going very, very slowly. So they knew that if they wouldn't defibrillate the animal within a few minutes, they wouldn't be successful to do that. And so Knickerbocker started doing chest compressions because they thought if there's a little bit of blood flow, maybe the defibrillation works better even after that long period of time. And so somebody went down, got the defibrillator, came back up, and maybe 10 minutes later or so, they shocked the animal, and it came right back. And so that kind of observation together with the chest compression data that they got made them believe that this is actually really effective. And so they then also used some of that external chest compressions in some humans and described that results. They got some survivors and published that in JAMA in 1960s. And that's really kind of the birth time of contemporary CPR. Then, of course, they had to put the chest compressions together with the ventilation, which happened a couple of years later, 1966, when kind of the first modern CPR guidelines, if you want to say so, appeared. And so that was with the support of the American Heart Association, the National Resuscitation Council. And so they had to, or research council, they had to do quite a significant tour around the country to get all of that support for that methodology. But ultimately, that was what they settled on. They didn't know yet whether to call it cardiopulmonary resuscitation or heart-lung resuscitation. So that term alone needed to be settled on. And I think the American Heart Association decided on CPR at the end, which is what we call it today. Of course, defibrillation wasn't really that much of a thing that was commonly used yet. So the first clinical external defibrillation was described by Paul Soule in 1955. But once more, those defibrillators were huge. And it was Dr. Bernd Lohn that developed small little DC defibrillators that you could actually, they were small enough to carry them around at the end of it because that was really, really important. And he also had some other activities, such as getting the Peace Nobel Prize later on in his life for his work as he was founding the group International Physicians for Prevention of Nuclear War, which was a really big deal at the time, the whole nuclear threat. And so a very fascinating person, by the way. So if you're interested in reading more about him, go for it. It's absolutely fantastic. Good. So by now, we have a pretty large crack. There's the spark of life. We have a lot of VF arrest in humans. So with smaller defibrillators, that seems to be quite reasonable. So if the yellow wiggle now would have been experienced, his ordeal in the early 60s, then probably you would have received bystander CPR, some BLS, including mouth-to-mouth ventilation, chest compressions. And defibrillator technology would have been available. But probably nobody dared to bring it to him. So he probably would still have had to go to the hospital. And so it needed some kind of an ambulance system or some kind of an infield medical care system to help those people with sudden cardiac arrest. And ambulance systems were around for quite a while. So this is one in Queensland in Australia in 1892. And you see the ambulance there on the right, which is the cart. So they were basically just fetch-and-run type of systems, whereby people were loaded up and brought to the hospital for further care. They wouldn't provide any medical support at all. And it's the same here a couple of years later. So those vehicles oftentimes had the double effect of being a hearse or an ambulance, because they were just the same size. So it was quite easy to do. But they weren't intended to deliver, actually, any medical care to the patients out in the field, as we see it today with the EMT system. So they were just basically a fetching system. And that changed slowly over time. The pioneer here was probably Frank Pantridge in Ireland, Belfast, who basically, out of his own will, if you want to say so, against the opinion of the bigger medical community, unearthed an old ambulance and staffed it with a doctor and a nurse and a student, basically. And they drove out to people's homes where sudden cardiac arrest was experienced, such as here in this picture. And they created these mobile intensive care units, essentially, MICUs. And yeah, they brought the defibrillators with them. And they had the car batteries to run the defibrillators, and so on and so forth, so very basic. But they had some first successes. But they also came across several issues And this is from basically Dr. Noggle in Miami, who pioneered the system here in the US. So there were several roadblocks that were quite significant. So for example, there was the disbelief that CPR pre-hospital is actually effective at the first place. So they wouldn't believe that it would save any people. Then they really were hesitant that people that were not doctors were allowed to do any of those things. So they shouldn't defibrillate. They shouldn't give drugs. And non-doctors should also not intubate. And so there was no such system in place to allow non-doctors to do all of those things. And there was huge hesitations from the doctor's side that this would be a good thing to do. And so when they started with those ambulances first with non-doctors on board, and having doctors in all those ambulances in the US here was not financially feasible, right? There were just not enough doctors to go around. You couldn't staff them all with doctors. But they had rescuers in those ambulances that were trained in doing CPR, for example, in the fire trucks. And they would bring them back to the emergency room. But most of the people in the emergency room, when they brought in those folks, was like, hey, why do you bother me, right, with this person? And come on, stop and forget about it. So there was really not a big support that this is a meaningful thing to do. So it took a little while to build up the whole system. But by now, the EMT system is quite well developed. It's very clear that if you have paramedics on those ambulances, for example, paramedics are people that are highly trained. They can intubate people. They can deliver ALS, that the resuscitation efforts are actually quite good. And the area around Kings County, which is Seattle area, do really well. So this is some data over the years from the group of Mickey Eisenberg in Kings County that shows how good the resuscitation rates can be, how high, if the system works really well. So this is for witnessed ventricular fibrillation out of hospital cardiac arrests, 62% survival rate with good quality of life, which is pretty good. That's witnessed and only shockable rhythms. But if you flush it all out, then it can be really, really effective. And they kind of coordinate the train barriers with the ambulances and so on so that the response time is really short. So it needs a major system approach to do it as good as they do. But it ultimately comes down really to how well people do that as a system. Several American Heart Association guidelines followed. 1974 was the second one, and so on and so forth. In 1992, the 911 number was finally mentioned for the first time. Because at the end of the 80s or so, 50% of the country maybe had 911 numbers available to them. Not everybody. That was just about to roll up. So that was an important thing to activate the EMS system that now was relatively well in place. There was this whole chain of survival thing there as well. And in 1992, people also came together and thought, hey, we around the world actually have the same issue here, right? So why don't we join together and kind of get our scientific effort all under the same roof and to advance the field? And so that's where basically ILCOR was formed, right? So the International Liaison Committee on Resuscitation has a huge global collaborative effort to advance the field and not just have the myth anymore, but actually have outcome science-driven resuscitation there. And so from there on, they developed various advisory statements on consensus on science of resuscitation. And it's going on to this day. They also met at some point at the Udstein Abbey in Norway there to come up with some guidelines on how to best report resuscitation science event, resuscitation events. That was really important as well, because not everybody would understand necessarily what a shockable rhythm is and a non-shockable rhythm and so on and so forth. So they had to have the same language across the board in order to pool their resuscitation science, right? Or what is return of spontaneous circulation? For some people, it's just any return of spontaneous circulation is RASC, while for others, it would be only for 20 minutes it would be RASC and so on and so forth. So they needed some consensus on what all of that terminology means. And those led to that Udstein guidelines. And Udstein, as a kind of a think tank of those resuscitation scientists, also brought up this formula of survival that shows that in order for a system to be effective as a resuscitation environment, you need to have the medical science. The medical science leads to guidelines. Those guidelines need to be teached, right? So you have to have a really educationally effective way in delivering those guidelines. And then it also needs to be locally implemented, what we saw at the very end with those ambulances and so on and so forth. So it needs to be put into place effectively. And only if all of those things together work really, really well, you have the optimal survival rate, right? Ideally, 100%. But clearly, that's not possible. And you see here, if each of those elements is not functioning 100%, it ultimately has a cumulative effect on the overall survival at the end, right? Cool. All right. Then there is technological advantage. So we have now very small little defibrillators. There's ambulances with mechanical chest compression devices here. There are some devices also that deliver feedback to the resuscitator on how fast they compress, how deep they compress, and so on and so forth. And so that basically helps people to deliver high-quality CPR according to the guidelines. And so that's ultimately what got our wiggle back to life as well, right, to this day. There's some more modern technologies as well. So this is exocorporeal CPR. And we're going to talk about that a little bit later today as well. So this is in the French environment. You see that this is out-of-hospital ECMO, basically, where a person that didn't respond to regular ALS is resuscitated with cardiopulmonary bypass in the metro or in the loofer. So those technological advances really widen that resuscitation gap quite a bit so that today it's kind of an expectation that life is not necessarily the same like death, but that there's a subset of population that can be returned back to life after a sudden cardiac arrest. In veterinary medicine itself, it probably started way earlier than 1960, right? So how many dogs were used for all of those experiments? I think a lot, a lot, a lot of dogs and cats. And so I think we have a lot of information there if we go further back on veterinary resuscitation, right, as I kind of showed a little bit here. But as soon as the first guidelines were kind of delivered, or this Coven-Hoven paper in 1960 was published, a veterinary article came out as well that described how that new approach to human CPR could be applied to veterinary CPR. You can see that here as well. And subsequent, there were a couple of other articles coming out which were mostly expert opinion-driven recommendations rather than being a consensus group recommendations. And most of our veterinary resuscitation approaches were based on the human guidelines until the recovery initiative came around around 2010, I think. And yeah, that was our first meeting at IVEX, I guess, 2011. And then the guidelines were finally published 2012 with those various articles that we are now mostly familiar with. And those guidelines really helped to now deliver effectively and efficiently training to a large cohort of people and also delivering some standardized certification training. We also developed our own Utstein approach to things so that we can deliver effectively new knowledge because that knowledge ultimately is critical for improving our guidelines and so on. So I think Recover was involved in that as well. And we developed these Utstein-style guidelines on uniform reporting of CPR in 2013. And those Utstein guidelines then also helped us to deliver CPR or develop a CPR registry, which is an ongoing effort. We have around 15 hospitals, university hospitals mostly, but also large private practices involved. And some data is coming out of that slowly. We hopefully present an abstract content on IVEX as well. But it's a work in progress. But the registry really helps us developing some of the new knowledge that then can hopefully help with the guidelines as well. Generally, I think in veterinary medicine, CPR is, at least in the ECC community, a accepted technique in these days. So here, that was in 2010, we asked veterinarians on what they think, whether CPR is an essential skill for small animal veterinary medicine or not. And you see that the majority of them felt that it is. There's probably some response bias here. But I think overall, people think that CPR is a meaningful thing to do for the right patient. And so I would argue that we also are aware of the fact that life is not automatically synonymous with death. But there is this opportunity in between where we can bring animals back to life, right? Cool. And with that, I wanted to conclude this short little panopticum on the history of CPR. Thank you very much. And hand over to Dan, unless you have any questions right now. No? If you find any errors in the manuscript, let me know. All right. Cool. Thank you, guys. We'll talk this afternoon about how useful these might be. Excellent. Well, I was excited, actually, to learn that the first, was it the first American Heart Association guidelines that were published in 1966? I was born in 1966. It's like kismet. It's amazing. Very cool. I'm excited to be here today. I really appreciate the invitation to come. For us, this is very exciting to have a full day to talk about CPR. So we're really happy to see so many faces out there. We're going to have all of the PowerPoints we'll have available to you guys for you to download later. So don't feel like you have to scribble a lot of stuff down. I think both of us included a whole bunch of data in our presentations, just to try to present some of the evidence to you. So what I'm going to talk about today is the second part of this, which is really the CPR guideline process we went through in veterinary medicine, so that you guys know where the recovery guidelines came from and where the next version is going, which is what we're working on actively right now. So I have a very busy disclosure slide that basically says I have nothing to disclose. So I don't make any money from CPR, sadly. So maybe someday. So the overview for this talk, where we started, I'm going to talk a little bit about the origin of the recovery initiative. We'll talk about how we did the 1.0 guideline process. And we'll talk about what we've implemented now to go through the 2.0 revision that we're working on right now. And then I'm going to try to finish up with just a little bit about why this might matter to you, not just because I'm sure you all want to know how to do CPR well, but maybe what the process might provide to you in terms of your ability to ask other types of clinical questions, and maybe thinking about how we've gone through this recover process, and how you might apply the same approaches when you're thinking about other types of clinical questions. So as Manu said, the recovery initiative really started, we probably first started talking about this in 2009, 2010. I became very interested. I've always been very interested in education, and I got very interested in trying to develop standardized CPR training. Manu at the time was working in a resuscitation research lab at Penn doing cutting edge research on cardiopulmonary resuscitation. So I thought he'd be the perfect person to talk to about what we should be teaching, and ask him if he would collaborate with me to develop a set of standardized training methodologies. And what he said to me was, I would love to be involved, but nobody knows how to do CPR in dogs and cats, because nobody's actually asked the question. And we really sort of realized at that point that everything that we'd done up until that point, all the papers that have been published, were taking the human guidelines and saying, well, this is probably how we would do it in dogs and cats. But nobody had ever really gone back and exhaustively looked at the primary literature to try to answer these questions. And so really, we were motivated by Manu's paper that he published back in 2010, looking at the practice of cardiopulmonary resuscitation and sort of seeing that there was a lot of work to be done to keep people updated on what the current recommendations were. So just specifically on the question of how fast you should do chest compressions, which is probably one of the simplest and most important aspects of how to do good quality basic life support, we have really good evidence about the right rate for chest compressions, and it had been known for quite some time. So one of the questions Manu asked in this study was how fast should you do chest compressions? And when he looked at the data from general practitioners, if you think that 100 to 120 is probably the optimal, which is this little blue bar right here, you can see that about 15% of general practitioners knew that they were supposed to do compressions at that rate in 2010. And this had been known for quite a long time. We'll look at some data later today about where this comes from, but it was very well known at this point. But because we don't have standard ICPR training in veterinary medicine, many, many veterinarians didn't know that. So huge, huge opportunity here to improve outcomes just with very simple things like chest compression rate. Looking at ER doctors asked the same question. They did a little better, but still not great. Only about 20% of them actually knew the correct compression rate. And then really interesting, if you looked at boarded diplomats from the critical care college, the anesthesia colleges, you would think they obviously are gonna know the right answer, right? This is 2010. They've gotta know that compressions have to be done at 100 to 120 per minute, right? But these are the data that were collected. So about 40% of them knew the correct rate. And you can see that it was pretty much a tie with 80 to 100, which is probably what they learned when they were in vet school, which was outdated by that point by quite a few years. So this was really eye-opening data. And again, I think Menuh did a great service to the veterinary community by sort of really ferreting out that there was a problem here, that we really need to get more information out there to people about how to best do CPR. So again, this arose from this desire to create standardized CPR training. So then we had to ask ourselves the question, okay, 100 to 120, there seems to be consensus in human medicine that this is what we should target, but where did this recommendation actually come from and does it apply to our patients? And so this was one of these motivating factors to say we needed our own guidelines. We needed to go back and look at the data that allowed the folks in human medicine to come up with their recommendations and make sure that it actually made sense for our patients as well. And the only way to do that is really to look at that primary literature. And so that's what we set out to do. So our goals for the Recovery Initiative were to develop true evidence-based veterinary CPR guidelines so we wanted to look at that primary literature, but we also wanted to try to establish consensus around these guidelines. So any of you who have read the CPR literature and have read the recovery guidelines recognize that although we worked very hard to find all the available literature and try to figure out what the best recommendations would be, a lot of our guidelines don't have a huge amount of evidence behind them because there's just not the clinical data out there to answer the questions. And so we thought it was important not only to look at the literature, but also to try to establish consensus around the recommendations we come up with. At the end of the day, we have to have recommendations for how we think it's best to do CPR, but we also have to have buy-in and we have to have people generally agree to those. So we wanted to accomplish both of those goals. We also wanted to identify knowledge gaps and there are tons of those. So part of this process, in addition to developing consensus, was to really be upfront about our level of evidence in our guidelines, how confident we could be that they were truly applicable, and to identify the big picture items that we need to do more research on. So that was another one of our important outputs. And then finally, we wanted to disseminate those guidelines. So going back to my newspaper, we had guidelines that were consensus somewhat, that were sort of expert opinion that were out there, but people weren't following them. And so another really important aspect of what we wanted to do through the Cover Initiative was to disseminate that information and to try to get people to do CPR to the highest level we know how to do at this point, and to recognize that it's an organic process that's gonna continue to change over time as we get more evidence. So where do we start with this? We started by going to the human side of these things and trying to figure out how they had gotten to the point they were at. So by 2010, when we were starting this process, they were very well-established communities of people who were working on CPR guidelines in people and had established consensus around them, had developed standardized training that was very widely, not only available, but required for most health professionals. They had to take CPR training. And so we were very lucky in that Manu had connections with the International Liaison Committee on Resuscitation through his work at Penn, and we were able to actually talk to them, and they could not have been more helpful to us. They were a huge, we would never have been able to figure out how to do this on our own. And so we were able to really borrow methodology from ILCOR, and they were extremely generous with their time and also with their knowledge about how to do this best. So, oops, went a little fast there. I went backwards. So as Manu said, ILCOR was established in 1992, and it was really a collaboration of a bunch of human resuscitation organizations around the world, and their goal was to create resuscitation guidelines, and it's a multidisciplinary group. So exactly what we wanted to accomplish in veterinary medicine, they had already done in human medicine. And they really wanted to foster international discussion on CPR. They wanted to disseminate information about CPR and how to do it. They wanted to collect data to try to keep improving their approach to CPR and produce these consensus statements. So exactly our goals, exactly what we wanted to accomplish. So we came up with them ourselves, and then we realized someone else had already done them in a different context, and so we borrowed heavily from them in their approach to things. So the recovery guidelines process that we went through the first time was first to figure out what questions we wanted to ask, so devise those clinically relevant questions, then try to answer those questions based on a review of the primary literature. Then we wanted to develop draft clinical guidelines for how best to do veterinary CPR, and then establish consensus around those guidelines as well. And then finally, once we had the guidelines and we established consensus around them, we wanted to disseminate them as widely as possible so that we could try to improve the way people were doing CPR to try to maximize our outcomes. So starting out with devising the questions, we used the standard PICO approach, and hopefully you guys are at least somewhat familiar with this approach. It's a standard way to ask a clinical question. So split into four parts, the patient population you're interested in, the intervention, the comparator to the intervention, and then the outcomes that you're interested in assessing. So this is an example from a cover 1.0. In dogs and cats with cardiac arrest, so that's the patient population, does the use of vasopressin, that's the intervention, compared with standard treatment recommendations like epinephrine as the presser of choice, that's the comparator intervention, improve outcome. And so the way we wrote these questions for Recover 1.0, you can see we said improve outcome, and then we list a bunch of examples of different types of outcomes that we might look at. We're gonna talk in just a little bit about Recover 2.0 and how it's different. And one of the major differences is our PICO questions are gonna be a lot less sloppy the next time around. So it's not just whatever outcomes you wanna think about, we're being a lot more specific with our outcomes, which is important to do a really rigorous evidence evaluation. You really need to be thinking about what outcomes you're interested in. So we'll talk a little bit more about that in a minute. So the benefit of using PICO questions is that they really allow you to organize your thoughts and really build a question that you can actually answer. And once you have a very specific question you wanna answer, you can much more easily do your literature search, find the relevant literature, and try to answer that specific question. So using this PICO approach, this is one of those places where I think the recovery guidelines are one thing, but thinking about any questions that you have when you're dealing with your patients in the clinic, if you're thinking about doing a research project, or even if you're just trying to answer a question that you're facing in the clinic, trying to rephrase that question in this PICO format can really take you a long way towards answering it. And that doesn't mean that you have to do a full meta-analysis. It doesn't mean that you have to get a cadre of 100 people to help you do it. It means that you can really devise a clinical question that makes sense. Do your literature search, see if there's an answer out there. And if there's not, maybe design some studies around it. So the whole goal here is to develop what we call foreground questions. So rather than questions about sort of general knowledge about something, we want a very specific question. So the question is not, what's the best presser? That would be a question, it's kind of what we're trying to get at here, right? Is what's the best presser to use during CPR? It's very difficult to answer that question and do a literature search on what is the best presser, right? That's more YouTube video kind of searching rather than actual scientific inquiry. And so by really narrowing your scope and asking a very relevant specific question using this PICO format, you can actually come up with something that not only can you try to see if there's an answer to out there, but even devise studies yourself to try to answer if you can't find the answer already out there. So then the next step, once we devise these questions and we picked the questions by starting with the ill core questions. So they had lots of them out there that were published that they had used for their evidence evaluation. We went through all those, ranked them, figured out the ones that were relevant and the ones that weren't, and then added some specific ones for veterinary medicine that we thought were important. And then once we had our list of PICO questions, the next step was to answer them. So we used a worksheet, and this worksheet was very, very heavily adapted from the ill core worksheets, and they were divided into a series of sections. So we had a question assigned, we developed a worksheet around it, tried to answer the question, and that was done by an evidence evaluator, a volunteer, most of whom were board-certified veterinary specialists in either anesthesia or critical care, with a few other folks involved as well. So the first part of the worksheet was the basic demographics of the person who was doing it, so who was actually writing it, the clinical question in PICO format, any declaration regarding conflicts of interest that the person who was doing the evidence evaluation might have. We had none, not surprisingly in veterinary medicine. Their search strategy, so what they decided to do to try to get to the relevant literature around that question, so they had to search both Medline and CAB, and they had to write out completely what their search strategy was so that we knew what they used to try to find their answers. And then they wrote a summary of the evidence that they read, so they read all the papers, and then they wrote a summary of what they found and what knowledge gaps they found. They could write a series of comments about their feelings about the question, and based on all the reading they had done. And then finally, they had to write a conclusion, and that was the clinical recommendation, so what do they think the answer to the PICO question is based on all the research they had done. So all of these separate sections that they filled out, and then finally they had an acknowledgment section where they could acknowledge help that they got from others. So each PICO question, one of these was generated really to try to be as transparent as possible about how we came to the answer to the question we did. Sorry, and then finally a citation list. So for each paper that they evaluated, they had to assign some quality metrics to that paper to try to figure out how much weight it should be given. So one of the quality metrics we used was the level of evidence, and so that was rating from 1 to 6, where the most powerful level of evidence would be a randomized controlled clinical trial in the target species, or a meta-analysis of randomized controlled clinical trials. You can imagine we didn't have a lot of those, there aren't a whole lot of randomized controlled clinical trials in veterinary medicine, and certainly not around CPR, but that would be our highest level of evidence. And then you can see we go down, down, down, down, down, a whole bunch of them until we get to this final one where we have studies that may not directly be related to the specific patient population. And interestingly, for this first round, randomized controlled clinical trials in humans would be considered a low level of evidence. So we had a fair number of those papers, but because they weren't in our target species, they were ranked down a little bit in terms of their level of evidence because they weren't in the species that we were interested in. And then for each paper, in addition to the level of evidence, we would assign a quality score to how well that paper answered the question, and an important thing here was it was not the quality of the research, it was just the quality of the paper in the context of how directly it answered the question that was asked. And so you can see we rated it as either good, fair, or poor, and it was a little wishy-washy here in terms of the number of quality items, and these are some examples of the quality items for randomized controlled clinical trials, experimental studies, and then observational or retrospective studies. So you're going to see when I talk about Recover 2.0, a lot of these same quality metrics are going to be coming in in Recover 2.0, but in a much more deliberate way and a much more reproducible way. So this was a little bit wishy-washy. We said look for some of these things. These are some ideas about things that you might want to look for in individual studies. All of these things are things that can lead to bias in studies that are published. And so really what we're looking for is how likely is it that the results of this study are biased in some way, and you'll see when we get to Recover 2.0 that the new methodology we're using is a lot more explicit about this. But this was our first attempt, and this is how that worked. So every paper was read. Every paper had a level of evidence and a quality score assigned to it. And then to answer the questions, we used these evidence grids. And so there were three separate grids that were made for each paper. One was for evidence supporting the clinical question. So is it true that the intervention is better than the comparator? Evidence neutral to it, do they look like they're about equivalent? And then evidence opposing it, does it look like actually the intervention is worse than the comparator that it's being assigned to? And you can see that for this particular question, the vasopressin question, they had a bunch of studies that were put at different levels here. You can see that level of evidence for most of them was not great. It was way down in the sixth level, a few fives here. But you can see that you had a fair number of papers here in the evidence supporting that vasopressin is better than epinephrine. You had a whole lot of papers that said it was probably about equivalent, and then just one paper that showed that epinephrine was better than vasopressin. So this sort of gave you a visual representation of how much evidence was there that the intervention was better than the comparator. And then really, it became subjective at that point. Overall, looking at this, do we think that it mostly falls in favor of the intervention, or does it mostly fall in favor of the comparator? And we sort of made a subjective call at that point based on what these grids look like. Then the, I'm not going to read these obviously, but then the reviewer would write their final comments on the benefit-risk ratio of the intervention compared to the comparator. And then they would write a conclusion basically supporting their answer to the question. So they would tell us what they thought the answer was, and then this was their opportunity to really describe, based on the evidence, why they felt that that was the answer. So this was quite a labor-intensive process. So we had 72 questions that we asked in Recover 1.0, and we had an evidence evaluator for every one of those questions. A few evidence evaluators did more than one, but most only did one question. So we had quite a large number of people involved in this. And after we finished the project, we asked them how much time it took them to actually go through this evidence evaluation process. There was quite a widespread, but the median was about 69 hours that people spent on this, and they had about eight weeks to get this finished. So this was a big undertaking for most of the people who did evidence evaluation, and it's a real testament to the fact that it seemed like there were a lot of people out there who thought this was important and were willing to donate a whole lot of time to make it happen. And if you do that across, if you sort of take that on average across all of the evidence evaluators who were involved, about 3,500 hours spent on evidence evaluation. So you can see this is not a small process. It took a lot of time to get this, and I think it's exciting that we have that much enthusiasm in our profession and our specialty to really try to answer some of these questions. But it takes a lot of work to do it. OK, so then once the evidence evaluation was done and we had answers to the individual PICO questions, then the time came to develop the actual clinical guidelines. And so these were drafted by the co-chairs, Manu and I. We said we'd hold ourselves up in a library room for about a week, took all of the evidence evaluation and all of the answers to the PICO questions, and we devised draft clinical guidelines for the first round based on all of that. Those were then sent through an iterative editing process where they went back to the domain chairs, the people in charge of the groups of questions that we asked, so they could comment on them, and back to the original evidence evaluators so everybody could have their input. And that went through an iterative process where we tried to really fine-tune them and make sure that everybody was on the same page about the answer or the guidelines that we wrote. After that all happened, then we assigned a class and level to each of the guidelines to sort of represent how much evidence we had to support those guidelines so we could be as transparent as possible about whether this was mostly expert opinion based on the review of the literature or if there was truly evidence to support what the guidelines said. So the class of the guideline was an assessment of the benefit-risk ratio of the intervention compared to the comparator. So if it was clear that the benefit was much, much, much greater than the risk, then it was assigned a class 1. If the benefit was greater than the risk, but not much, much greater than the risk, then it was assigned the terminology, it's reasonable to do this, and was assigned a class 2A. And if the benefit-risk ratio was sort of greater or equal, so maybe it's equivalent, maybe it's a little bit better, then that was a 2B, and we used the terminology that this intervention may be considered in CPR. And then finally, if the risk was greater than the benefit, then that was assigned a class 3, and then we shouldn't perform that. So that was how we sort of gave the class. And then the level of the guideline was related back to how much evidence there was to support that. So an A meant that there were multiple high-quality or high-level of evidence studies, and a C meant that there was really not much literature to support it, and that this was ultimately a consensus opinion, that we looked at everything we had and we made the best guess we could. So the level C guidelines are the ones where a lot more research needs to be done to really figure out whether they're accurate or not. So this is an example from the PICO question we've been looking at. So for the vasopressin question, the guideline we came up with was the use of vasopressin as a substitute or in combination with epinephrine every three to five minutes may be considered. And that was because we felt the benefit-risk ratio was greater than or equal to, if you remember the grid. There were quite a few studies that said it was better, but there were even more studies that said they were equivocal to each other, and so this got a class 2B. And then it was a level B. So there were some pretty good quality evidence if you were a human, if you were treating humans, but not such great quality evidence if you're treating dogs and cats, and that's why it came up with a level B as opposed to a level A. So this is the process we went through for Recover 1.0 to try to actually establish these guidelines. So then once all of that was done with the folks within Recover, the job was then to try to establish consensus around these. So our hope was that we weren't going to establish this kind of consensus where it's easier to go down the ship when everyone is on board. We didn't want to go down with the ship. We were hoping that maybe we could get to the point of long and lasting bliss by really trying to pull people together and get everybody on the same page, which is often difficult to do, especially when the evidence isn't that strong and you're trying to get everyone to agree on an approach without a lot of evidence to go on. So it was presented at IVEX 2011. Manu had a picture of that session in his section on the talk. And then it was open for 30 days for comment in general. So we presented some of the more controversial guidelines at IVEX and then we had this website set up where people could go and look at each individual guideline and then they could click to enter comments and people could say, you know, if they thought that they knew about something that we hadn't considered, those kinds of things, to really try to get some consensus around it. And then the goal of all of that was really to get guidelines that everyone could live with. And this is something that's really hard because everybody wants to have their, you know, they want to be really happy with this guideline. They want everybody to be really excited about what it is and really agree on it. And sometimes when there's not a lot of evidence, you can't ever get to that point where everybody leaves the room, you know, high-fiving and excited about it. So what we tried to set, the tone we tried to set, and we borrowed this from Ilcor, was when we're making these guidelines, our goal is to find guidelines that everyone can live with. Not necessarily that everyone is super happy about and 100% agrees with, but they can live with this being the standard for now until we can fill in some of these knowledge gaps. And I think we were mostly able to achieve that goal. So then disseminating the guidelines was the next step. It was published in a special issue of JVAC in 2012. This is the most downloaded issue of JVAC. It's one of the few open access issues of JVAC, so maybe that's why. But more than 50,000 downloads of that one since it was first published back in 2012. As we were releasing the guidelines, we also worked with Pfizer Animal Health, which ultimately became Zoetis, to develop some online CPR courses to try to teach this. And that set of courses has gone through quite a lot of change over the years since they first happened, but this is the way that we've been trying to disseminate these guidelines by making online training available for people to learn these guidelines and really sort of solidify them for them. About three years ago, we started with in-person rescuer courses on top of that, so the certification process starts with an online course, and then people have the option to come in and do a hands-on lab for both basic and advanced life support and get rescuer certification that way. And now we just launched a recertification process where every two years, people can take a short online course to recertify, just to sort of refresh. And we're going to talk this afternoon, oh actually no, sorry, we're going to talk in the next session about training and what we know about training CPR, and we'll talk a little bit more about this timeframe and how it may not be the most ideal, but it's what we've got right now. And we're excited that over the last couple of years, we've really seen a big increase in the number of people going through certification. So this blue line is BLS online certifications. You can see by the end of 2019, we had almost 10,000 veterinarians and veterinary technicians who had completed the online BLS course. For ALS, we're pushing 8,000 at this point, so again, very exciting. In-person rescuer courses, definitely a lot fewer because we don't have a ton of instructors out there, but those are starting to see a little bit. We're hoping to see a hockey stick kind of thing happen soon with more and more people coming to those in-person certifications as well. And then we have a small group of instructors right now who are certified to actually go out and teach those rescuer courses, and we're working on tightening up that training and really getting more people out there to do some of this in-person training. So really trying to get a good system in place to offer this standardized training. Okay, so Recover 2.0 is what we're working on now. It is alternately, for me, something I'm really excited about and something that I feel like might crush me under its weight at some point, so it's a big process. But we're excited about the changes that are coming, and we really think that this new process we're going to use for the next set of guidelines will be a lot better than that first round and I think will be something really unique in veterinary medicine. So I'm just going to talk about a few of the things that have changed in our approach for Recover 2.0. First, I'll talk about some new domains that we're going to cover, and then I'm going to go through the new evidence evaluation process and how we've sort of tried to tighten that up a little bit. So in 2012, we had five domains. We looked at prevention and preparedness, basic life support, advanced life support, monitoring, and post-cardiac arrest care. For 2020, we're adding in three new domains, so we're going to redo those domains using this new approach. Whoops. Let's see if I can figure out how to go back. There we go. But we've added in three new domains. So we've got a newborn resuscitation domain, a first aid domain, and then we tried to do a large animal domain the first time around and unfortunately never got off the ground, but we have a really great enthusiastic group of large animal folks who are taking on viewing large animal guidelines this time around, which we're very excited about. So we'll be doing that sort of dovetailing with the small animal folks. They'll be doing the same basic literature review and they'll have the large animal folks look at it with a large animal lens and the small animal folks look at it with a small animal lens. So it's kind of used a little bit of economy of scale there, but I'm excited that we'll finally have some large animal guidelines to share with you in 2020. So the evidence evaluation process is going to use a new approach called GRADE. So GRADE is the approach that's used by most of the human medical guidelines organizations these days, including ILCOR. So ILCOR has moved to this for their new CPR guidelines that they published and we're excited to be, I'm pretty sure, the first veterinary group that's going to be using this approach. It's meant to be very robust and resilient and reproducible. It's also a little complicated, which is why it's taken us a little bit of time to get it up and running. So GRADE stands for the Grading of Recommendations, Assessment, Development, and Evaluation. I'm pretty sure they came up with GRADE and then they came up with the words because I don't even know what that means, but it's basically a standardized approach to developing evidence-based guidelines and it's gotten really broad sort of adoption in human medicine. So the goals of the GRADE process are really to reduce the confusion around evidence-based clinical guidelines. And it does that by providing this consistent set of domains for evaluating. So each paper that's evaluated to write the guideline has a very consistent set of questions that are asked about it and then they get ranked based on the answers to those questions. And then by the time the guideline is written based on the evidence evaluation, you can define the strength of the recommendation based upon those criteria. So very, very consistent criteria and then you develop a guideline that gives an answer to the question, but you can assign a strength to that based on these very specific criteria. And so what that allows you to do is to separate the assessment of the effect of the intervention that you're looking at and your confidence in that estimate. So you could have a big effect of an intervention, but you may not be very confident in it because of the way the studies were done. And so it really allows you to separate those things out. So this little cartoon is actually from the GRADE manuscript, the first manuscript in a British Medical Journal article, a set of articles that defined it to really try to make this point. And it says, I figure there's a 40% of showers and a 10% chance we know what we're talking about. And so hopefully it's not quite that extreme with the guidelines, but the idea is you can say what the effect size of the intervention is, but you can also say, but there were some issues with the studies and so we're going to downgrade this a little bit because we're not 100% convinced that those studies were valuable based on our very rigorous assessment of them. So the GRADE process involves first identifying the relevant studies for the PICO question you're asking and then assessing the effect size and the quality of each study that was used to try to answer it. So it's sort of a mini meta-analysis where you look at each study and you look at the actual patients in it and you do an actual overall meta-analysis of the data to see how big of an effect it actually has. Now when you have observational studies and case series, you can't obviously contribute that kind of data, but if there are randomized controlled trials or experimental studies in animals, we can actually pull all that data and come up with an estimate of the effect size. How much of an effect does this intervention actually have at the same time that we're evaluating the quality of the studies that contributed to it. Then you devise a clinical guideline recommendation and assess the strength of that recommendation. So identifying the relevant studies is the really important first step, trying to figure out what papers we're actually going to evaluate. In Recover 1.0, we left that pretty much completely up to the evidence evaluator. So a person who volunteered to do an evidence evaluation would get a PICO question and we'd say, OK, go search it and find what papers are relevant to this question. And they did a great job and they worked very hard to do that, but each person probably has a different level of competence in that. And I know there are times when I go searching for a paper and I'm like, I can't find anything on this. And then one of my residents hands me a paper that's exactly answering the question I was trying to answer and I couldn't find it. So I think we all have our strengths and weaknesses in our ability to find papers. And one of the goals for Recover 2.0 was to actually try to the extent we could to make sure that we found all of the relevant literature out there. So we really wanted a reproducible, robust, and practical literature searches for 2.0. And so we've been able to, I think and hope, accomplish that by recruiting a group of 19 information specialists. So these are veterinary librarians from all over the world who have volunteered to help and they're working in pairs for each of the domains. And they're actually the ones who are devising the searches to try to find the relevant papers. So we actually have people whose specialty it is to find the research literature doing these searches this time around, which we really hope is going to improve our ability to find the relevant literature. The other thing that we're doing this time around is for every question that we're asking, we're having two evidence evaluators evaluate it and try to come up with the answers so that we can hopefully increase our ability to sort of pick up any nuances that might be there that an individual person might miss. But also to really screen the papers that we think are relevant and make sure that we get consensus among two individuals rather than just one person about whether a paper is relevant. So our hope is that this is really going to increase the robustness of this process. So the way the literature search process is working, and it's happening right now, we're doing a bunch of searches at this very moment in seven of the eight domains, is that the information specialists look for meta-analyses answering these questions. A lot of those are coming from ILCOR, but there are other meta-analyses that they're tapping into. And then they send those to the domain chairs for that domain. And the domain chair picks the best meta-analysis, the most recent and best meta-analysis that describes the literature to that date. And that's mostly going to be the human literature at that point. And then we use that as a way to pull an initial set of papers. All the papers in the meta-analysis that were used for analysis get pulled and put into the hopper to be evaluated. Then the information specialists search the human and veterinary literature based on the PICO questions. So they do a separate search now that they have their meta-analysis. And then the domain chairs do what we call a title screen. So they're going to do a big search. They're going to cast a wide net. They're going to get a huge list of papers. And then the domain chairs go through that and pick titles that they think are most relevant. And then once they pick those titles, they send those back to the information specialists, and they use that information to refine that search. So this is an iterative process back and forth. Kate Hopper in the back is dealing with this right now on basic life support. And I think maybe she has a few new gray hairs based on this process. But hopefully, it's going to allow us to actually come up with really robust searches that pick up the really important papers. Then once they finish that iterative process, they have their final search. And that's now set in stone, and that's what we're going to use to find the relevant literature. Once we have that final search done, then we take the results of that search, and we just get the abstracts together. And both evidence evaluators read all of the abstracts. And then for each paper, they vote yes or no. This should be included or this shouldn't be included. So both of them go through, pick the relevant papers out of that just based on the abstracts. And then the domain chairs resolve any conflicts. So if one votes up and one votes down, then they have to have a conversation and try to figure out whether this is one that should be included or not. So again, the goal of this is to make sure that we don't take in too much extraneous data, but that we also don't miss important papers that might allow us to inform a better guideline. So this is a much more robust process than last time, and we're working through it. It's taking a little bit longer, obviously, than the last time we did it. But I think it'll give us much better searches. And then once we have the actual list of papers that are going to be fully evaluated, we download the full papers, and then the evidence evaluators do the evidence evaluation on the full papers at that point to try to answer the clinical question. So a more involved process, but hopefully a more robust process. So as I said before, once we have all those papers identified, we do a mini meta-analysis for each PICO question. So the evidence evaluator actually extracts the data from each individual paper and puts it into our online system of the numbers of subjects in each of the groups in the paper. And then the system will calculate for them a relative risk and a confidence interval for each individual paper. So we can actually look at numbers and try to figure out how big is this effect size of this intervention for this specific question. And then after all of the papers have been reviewed, all of that data is pooled into a meta-analysis, and we get an overall relative risk and confidence interval. And so this is where we can really get an idea. Maybe there's a huge effect. Maybe there's a really big relative risk, but there's also giant confidence intervals because there's so much inconsistency between the papers. And that will allow us to really figure out how strong can we make this recommendation based on the data. So this is a lot more precise than the way we did it last time, which was put it all into a big grid and try to figure out based on the overall status of the paper. So for each of the individual papers, we'll assign a quality score to that. And that can be anywhere from high to very low. So high means further research is very unlikely to change the recommendation that we would make based on this paper. Low means that the estimate of the effect of the intervention is really uncertain. So either there's a small effect size, or there's a huge confidence interval, or the paper just isn't really answering the question very well. So each paper gets one of these grades, and then we can look overall at some of the evidence. So when we think about the evidence quality, when we're trying to figure out the evidence quality of a paper, we first, for an individual paper, assign an initial quality. And that will be based on the type of study. A randomized controlled trial is a higher quality than an observational study. Then we downgrade papers if there are specific quality issues. So we ask a number of specific questions about the paper. And if they find that there are these quality issues, then the paper gets downgraded for that. And then there's also an opportunity to upgrade a paper if it has specific characteristics that make it more valuable to us. And we'll talk about those in just a second. So when we're starting with an individual paper, we assign it an initial quality. So a randomized controlled trial in the target species, so a randomized clinical trial in a dog, is going to start high. It's going to be the highest level we can hope for. Experimental studies in target species or clinical trials in non-target species are going to be more at a moderate level of evidence. So they get downgraded a bit because they're not exactly what we're looking for for clinical patients. So they're not as useful. Observational studies and experimental studies in non-target species start out at a low. So they're not going to be as useful to us. But they still might provide information that will inform a guideline. So we'll look at that as well. But we'll sort of take it relative to that link. So that's where each study starts. And then we go through a downgrade process. And this is a series of questions, and we have an online system developed for this. So the evidence evaluator will go in, and they'll just answer a series of questions about the paper after they read it. So within a study, they'll look at the risk that there's bias in that study. And so that could be issues with the randomization or the blinding. It could be issues with the way patients in certain groups left the study. So if there's difference in attrition between the two groups, they can look at the statistical analysis and see if it was done correctly, if there was any bias in that. They'll also look for evidence of indirectness. So are there aspects of the study that don't actually directly address the PICO question? Is there a problem with the patient population? Is this a human study when what we're really talking about is dogs? Or is there indirectness in the intervention? Was the dose of the drug used not the one that we're asking the question about? And then finally, there will be questions about imprecision. So this is looking at the effect size, the overall relative risk, and the confidence intervals. So if there's a very small effect size or a very large confidence interval, then we will downgrade for that. And then across studies, once we have all the studies done, we'll look at that overall relative risk and the confidence interval across them. And if there's a problem with those, we can downgrade for imprecision there. So if we have a very small effect size or a very large confidence interval. So it's just a little more methodical in the way we're rating these studies, rather than just looking at it and saying, oh, this is high quality or this is low quality. And then finally, upgrading can happen. If it's a moderate low or very low quality study, we can potentially upgrade it. So if there's a very large magnitude of the intervention, so let's say the relative risk is greater than 2 for the intervention, so it looks like it's really, really powerful, then we could upgrade it for that. If there's an obvious dose response effect, so if they looked at multiple different doses of the intervention and it's very clear that there's a dose response effect, that could upgrade it. And then if there was a confounder in the study that would decrease the effect size, then we can upgrade for that as well. So maybe they found a small effect, but it was clear that there was a confounder that would make finding a difference at all highly unlikely. So the fact that they found a significant effect is actually really useful, and maybe we want to upgrade for that. So lots of different ways that we can move these things up and down, but done in a very specific way with very specific question. So then we get to the guideline part of this. So once we've got the answer to the question to the best of our ability, we use the summary of evidence table to look across all of the different studies, the quality of each study, and then the overall effect. We come up with our overall quality metrics for each of those guys, and then for each study, we'll have its own quality, and then we'll sort of pool that and come up with an overall quality of the studies across all of the studies that were done. And then ultimately, we'll develop the clinical guideline and assign a strength to it based on that evidence evaluation process. So same basic approach as last time, but just a lot more specific with the questions we're asking and the way we're answering the questions. So when it comes to assigning a strength of guideline, it's a little simpler than what we did last time. It's basically either a strong or a weak recommendation. So a strong recommendation means that the desirable effects clearly outweigh the undesirable effects and that the assumption is that most or all individuals who get this intervention will benefit from it, as opposed to a weak where maybe there's not quite as much on the strong side. It still seems like the risk-benefit ratio is in favor of making the recommendation, but the evidence isn't quite as strong, and so maybe not all individuals would be benefiting from it. All the recommendations, the guidelines, will ultimately have this strong or weak strength associated with them, but all the individual data will be available for people to review. So this, I love Grumpy Cat. So you may be asking yourselves, OK, so this is great. This is this huge project, and I'm glad somebody else is doing it, and I'm not the one who's in charge of it. I feel your pain. I feel that way as well. I wish someone else were in charge of it some days. But what does this have to do with you and your daily basis? And I would say there are some things about this process that I've learned that I think are useful to anyone who's practicing in a clinical environment. So I would encourage you that as you're sort of in your daily practice, think about the guidelines that you're following right now. So we have lots of published guidelines, and then we have lots of local guidelines that we follow in our own practices, the way we manage individual cases. And I would really encourage you to sort of, as often as you can, think about what the evidence is. Think about the quality of that evidence. Where did it come from? You can look at the questions that we're asking about these papers in the recover process. That may help you get a little bit more critical in your reading of papers. It's sort of a way you could practice in your journal clubs and things like that, really thinking about these risk of bias questions and these imprecision and indirectness aspects of papers that may help you be a little more open-minded in your approach to clinical cases. Because a lot of what we do, as you guys know, is not super evidence-based. And those guidelines that we have really strong feelings about often don't have a lot of evidence to support them. And so keeping your mind open allows you to really think a little bit more. Are we really doing the best we can? Are there other options here? And they may open in your mind some research questions that you might want to look into, because maybe the evidence for these things that we take for granted isn't as strong as you might think. And then, again, think about those questions you have that you don't have specific guidelines for, and just think about this grade process. Think about the way that you could try to answer those questions that come up for you when you're in your clinical practice. But don't just search for the first paper that has the answer that you want, which I'm really guilty of all the time. So if I want to do something a certain way, I'll go searching for the papers, and I'll look at the title, and I'll pick the one that actually is the answer that I want to have. And I look at the paper, and I'm like, oh, this is great. I have a reason to do this. So try not to do that. It's very easy to fall into that trap. But really think about being critical. Look at all the literature that's out there, and use that more rigorous approach to really try to set your guidelines. So I think outside of CPR, using an approach like this can really help you guide your own decisions.

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