Thank you for the introduction. It's my pleasure to talk to you all. I'm an ER doc and resuscitation scientist in Minneapolis at Hennepin Healthcare. My disclosures, I don't have a financial conflict of interest. I am a co-PI and a co-investigator on several grants. So first, we're going to go over sudden cardiac arrest epidemiology. We're going to review patient positioning device and circulatory adjuncts during CPR, and I'll talk about our preclinical work with a head-up based CPR-based bundle, and then clinical studies looking at our head-up CPR-based bundle as well. So as Dr. Lurie just alluded to, although we have closed chest cardiac massage, which was state of the art in 1960, not a lot has changed since that time. And let's look at our overall survival with good brain function here from the national. This is the best data that I know of, of what's going on with cardiac arrest in the United States with the CARES Registry. Around 150,000 patients in 2021, 7.2% walk out of the hospital essentially. You know, we just, we have to do better. We have to do better, and this is kind of the focus of my career in this talk today. From animal studies, we know that conventional CPR yields very poor blood flow of around 20 to 40% of normal blood flow, and so it's not really surprising that we see these poor survival numbers. Advances, as I talked about, are desperately needed, and as we move forward and talk about the research at hand, the goal of all these therapies is to improve pressure and flow to the heart and brain during cardiac arrest. So we'll review head-up CPR with the use of a patient positioning device, active compression, decompression CPR, and or the use of automated CPR with an impedance threshold device. I'll show you how these devices work synergistically together to improve organ perfusion and outcomes. So active compression decompression CPR, it pulls up on the chest during the decompression phase of CPR. If done correctly, it's pulling up with about 22 pounds of force with a distance of about three to four centimeters. Commercially available in the United States with this handheld device, you're pulling up on the chest again with that 22 pounds of force or three to four centimeters. While you're pulling up on the chest, the impedance threshold device is at the patient airway and it's blocking airflow going in the airway during the decompression phase. So these two devices are working together to improve venous return and create space for forward blood flow. In animal models, it's been shown to improve cardiac and cerebral blood flow. I like to think about this physiology as we're trying to help the patient take their own intrinsic breath. When we take a deep breath, we're creating negative endothoracic pressure. When we're breathing for somebody during an arrest, we think we're breathing for them, but we're not physiologically breathing for them, right? We're providing, by the name, positive pressure ventilation. And this is exactly the opposite of that. This device combination was studied and published in the Lancet in 2011. Conventional CPR versus, I'll refer to this as ACD-ITD CPR. So the primary outcome was survival with intact neurologic function at hospital discharge. This was a prospective randomized trial, multi-center, seven U.S. sites, something like 48 EMS agencies, NIH funded, comparing these two therapies. And survival was higher with ACD-ITD. And this persisted up to a year after hospital discharge. While this study was going, or shortly after this study was going on, and while it was getting FDA approved, the ACD-ITD, this guy came on the scene. And so I don't know about what your EMS system is like, but this is kind of the standard in the Minneapolis area during transport, the Lucas device. This provides around 3 to 5 pounds of decompression, or around maximal 1 centimeter decompression. So something that's very common is people see a suction cup and they think, oh, they're doing the same things. They're not doing the same things. So I want to emphasize that point as we go forward. And this slide shows nicely what happens with active decompression. So this was in an animal model. And so we have a swine lab at our hospital. And so this shows exactly the principle nicely. So the top line, the blue line, is aortic blood pressure. The green line is capnography and tidal CO2. And the bottom line is cerebral perfusion pressure. So these animals also have an intracranial bolt, and so we're measuring the mean arterial pressure minus the ICP. So you can see here we're kind of cruising along. This animal's getting head up CPR with ACDITD with about 3 centimeters of decompression force, and we drop off to zero. Our blood pressure goes kaput. And then we gradually add centimeter by centimeter decompression back in, and we regrow the blood pressure with around 4 and 1 half centimeters of decompression. You can see we have a corresponding increase in our capnography and our cerebral perfusion pressure. And so now we're getting to head up CPR. So the question, how this came about was what position is best to transport a patient in active cardiac arrest? If you have to go downstairs or you have to go down a tiny elevator where a patient can't be in the traditional supine position, should you go head up or feet up? And so we studied this in our animal laboratory. This is a schematic. We use pigs instead of mannequins on the right here where animals were either flat, head tilt up, or head tilt down. A Lucas device was used with the ITD. And so the physiology behind this is not foreign. This is something that I learned when I was a medical student. When you have a patient with a neurosurgical emergency, what do you do to buy time before you get into the OR? You sit them up. You reduce ICP. This is what we're doing with head up CPR. You have to provide a good uphill driving pressure with circulatory adjuncts during CPR in order to get this benefit, but this is the principle behind it. You have a good mean arterial pressure, driving pressure. You're reducing your ICP by sitting the head of your patient up, and therefore you're improving your cerebral perfusion pressure. And in animal studies, we've also shown that it improves cerebral blood flow and neurologically intact survival. So there's a balance here between your MAP and your ICP. In our first study, this is a nice schematic showing what happened. So the red line is the AO, aortic pressure. Pink line is the intracranial pressure. Blue is the cerebral perfusion pressure. With the head tilt down, you can see the ICP went up and the cerebral perfusion pressure correspondingly went down. With the head up position held up tilt position, the ICP went down and the cerebral perfusion pressure went up while we maintained our MAP in both positions. And as I said, cerebral perfusion pressure and cerebral blood flow were significantly higher with the head up position. And skipping forward to my most favorite diagram of all time that I've ever published is our animal survival study where we showed that our ACDI-TD head up animals had neurologically higher neurologically intact survival compared to conventional CPR animals at 24 hours. And so moving forward, our laboratory developed a patient positioning device that is now commercially available. Again, I don't have any financial conflicts of interest with that device. It's been FDA approved. I started a head up CPR registry at that time to track patient outcomes. So any system that was interested in using this patient positioning device with the Lucas CPR with an ITD and or ACD CPR were eligible to voluntarily enroll in this registry. And these were all systems that were routinely using this as part of their out of hospital cardiac arrest care. Our initial study of 227 patients focused on what happens when you get the head up CPR bundle of care on quickly versus later and the probability of ROSC. This was published in Resuscitation a few years ago. And so we noticed in the six sites that were using the technology early adopters, the green is the ROSC percentage. So as we noticed as ROSC went down, the time to 911 call to head up CPR placement was increasing. So this was a relationship that we looked at further. Because some sites, this one, number six in particular, they were just having really poor outcomes. And we couldn't really understand why they were having poor outcomes when site number one was doing great. Their numbers are even better today. And so we looked at what they were doing. Site number one developed this basic, this BLS response bag. So at the bottom of this is a backpack with a head up CPR device. There's a bag valve mask. There's ACDI-TD CPR. We have eye gel in place. Everything that you would need at the patient's side within minutes of the arrest. And then people also brought in the Lucas CPR device and a defibrillator. And so those three items were the things that they would bring to the patient's side immediately. In that paper, we showed that the longer it took to get to the head up device on, the decreased probability of ROSC. And so this was significant for all rhythms and also for shockable rhythms. The problem with that study is we didn't have a comparison group, right? All of those patients in that study received our head up CPR basic bundle of care. And so in a follow up paper, we looked at survival outcomes. And we used conventional CPR control data from three notorious trials that have been published in big journals. NIH funded prospective randomized trial, two ROC studies, and then the rescue trial. We compared survival outcomes between groups stratified by the time of 911 call to the start of conventional CPR or the start of automated head up CPR bundle. We performed propensity score matching because this is observational data. Each head up CPR patient was matched with up to four conventional CPR controls. And we adjusted for imbalances and baseline characteristics. Importantly, the propensity score was calculated with age, sex, bystander witness arrest, bystander CPR attempt, shockable rhythm, and then we got the propensity score from that. Then each patient was exactly matched between the two groups on the time elapsed from 911 call to first responder CPR. This shows a patient flow diagram. I can't read it from here. So I'm sorry. It's probably too small of a print. But we have our automated control elevation CPR group down here on the right. And this shows how we funneled through these three studies to get our conventional CPR controls. This is a cumulative, this is a force plot of cumulative survival to hospital discharge. And so what we've done with this here is I discussed each patient had a propensity score and then we plotted them out based exactly on the time from either time of start of CPR and 911 call to start of conventional CPR. Or they both had the equal time of CPR accounted for. And so we could see the odds ratios here trail off the longer the time from 911 call to the start of head up CPR. And so a maximal kind of odds ratios in the eight to nine minute range. And we see a nearly identical graph for a secondary outcome of good neurologic function. I will stress this is an association right with survival and not a causation. Following this up now as the registry has been going on we're getting more and more patients. This was presented at this conference just yesterday I believe by Dr. Pepe et al. And we're looking specifically at our non-shockable patients here. And so we did a similar propensity score matching for this with 353 in each group. And so this is greater than even our 227 patients in our initial two studies. And so we see with our survival to hospital discharge here in our unmatched sample we have a higher odds of survival to hospital discharge with the head up CPR based therapy. With matched the odds ratio is essentially around the same. And you can see again the importance of this time. If you get the devices on quickly within the time of 911 call while matching for these other factors we still see higher odds ratios compared to if you get them on later 11 versus 16 minutes. And so we're looking at these odds ratios here around 5, 3.6 maybe it says. And then look at how different this is with our good neurologic function. We see the same trends but the numbers are higher with the odds ratio of 10 over 10 for both groups. This is for a non-shockable patients. Historically I've had nothing to offer these patients. So it's really exciting that we could have something that this could be applied to every patient. So in conclusion the triad of head up CPR active compression decompression and or automated CPR with an impedance threshold device. They all work together to improve organ perfusion and all are essential components. Our animal models have shown improved cerebral perfusion brain flow decrease intracranial pressure and improve survival with this device triad. In human observational studies the probability of ROSC is higher the sooner these devices are applied suggesting this is a BLS device combination. These are by definition these are first responders are the ones who are at the patient side the fastest. And these are the ones these are the people who should be carrying this device combination. The probability of survival and neurologically intact survival was associated and higher in active automated head of CPR bundle patients compared to conventional control patients across multiple time points. As we go forward it's important to remember that this could be a therapeutic window and it's important to study this within a therapeutic window because there is a difference between being a little dead and a lot dead. The survival association is also increasingly observed in patients with non-shockable rhythms. So I think I actually have time for a video kind of explaining or showing these device combinations in action. I walked through this area this morning on my way to the gate to come here. This is really fast, but it feels like forever, you know. The clinician in me is like, touch him, do CPR on him, do something. He's gasping, associated with good neurologic outcome. I don't know what they're chatting about. Look at the people at the ramen place just chilling. So here's the first responders, aside from the TSA at the airport. And so these are the brand names of these technologies I talked about. That's the active compression decompression CPR pump. And IT is being put on the airway. We're now under factory VFVT. This device was newly acquired by the airport first responders right before it was used here. And so when the patient is placed on the head up CPR device at the lowest level, the head and thorax are minimally elevated. And so we recommend doing CPR for two minutes at that lowest level to prime the cardio cerebral pump. And then you push a button on the device and it raises the head gradually over another period. Head and thorax gradually over another period of two minutes. In animal studies we have shown that this is the best time period to improve, to get the best cerebral perfusion pressure. So we're about 15 minutes into the arrest here. This is automated CPR going on with the ITD. So we're nearly half an hour into the arrest now. I suspect most of the clinicians in this room have played this game before, and usually it does not turn out well. But we did get Ross ground 30 minutes in, and I'm pleased to say that I have met this patient in person, and he's doing great. He celebrated his one-year wedding anniversary, was it, in Paris with his wife. He lives in San Diego, California, and has a successful succulent business with his wife. So that was a nice showing of the devices that we used there. And that's all I have. There they are, three weeks later, two weeks later. Thank you, everyone. Thank you.

cardiac arrest treatment

head-up CPR

active compression decompression CPR

automated CPR

impedance threshold device

patient outcomes