– Thanks to Ed and to Rick and the rest of you for inviting me to share a little bit of this information. So I am going to talk about extracorporeal support or ECMO in pediatrics. It applies in many areas, but since you’re all in the pediatric area we can focus on that and also primarily on hearts. So this is the typical story. Here’s a little girl, she’s about six years old. Happy and healthy one day, dying the next day of H1N1 plus strep, pneumonia, then all the pressors and then septic shock and on maximum ventilator settings and dying. And this is the kind of patient that we would like to intervene with a mechanical life support system, so which we did. So this her x-ray the next day, with a big catheter in her right atrium, another catheter in her inferior vena cava and her gas exchanges being managed with a mechanical device. So this approach is called extracorporeal life support or extracorporeal membrane oxygenation.
Not a very descriptive word for what it actually does, but we tend to stay with it and refers to support of heart or lung function with mechanical devices, which is temporary, days to weeks, nowadays to months. Can be partial or total support. Most importantly avoids ongoing iatrogenic injury. So when we use this we can turn off all those pressor drugs which are wonderful but have bad side effects. We can turn off the ventilator which is wonderful but has bad side effects. It simply sustains life while bridging to organ recovery, which we hope will happen with this little girl or in some patients, replacement with a device or a transplant.
So the indications for doing this are acute, severe cardiac or pulmonary failure, which is unresponsive to other conventional management in which recovery can be expected, we used say within two to four weeks, and that’s probably right although, we’re getting to the point where it might be longer than that. So those are easy to describe in adjectives, quite hard to describe in nouns. When is cardiac or pulmonary failure so severe that it’s not gonna get better doing whatever we do and it’s worth the risk of something that has inherent risks of its own and is expensive and for a long time was experimental? So, how to get from straighforward indications and adjectives to defining it, is part of the challenge of developing this whole technology.
So some of the early history is shown here, sorry. Back in the middle ’60s cardiac surgery using a heart and lunch machine was a relatively new technology. I happened to be a resident at the Boston Children’s Hospital where the chief was Robert E. Gross deity in surgery to any of us and we were, he, was doing cardiac surgery in children and the mortality was 50%. Half those children died and I had the temerity to go to Dr.
Gross and say, why don’t we just keep these kids on the heart and lung machine for a couple of days. ‘Cause we knew if they go through the first day or two they’d be okay. Well he said, of course that’s why they’re dying. The heart and lung machine is lethal if you use it more than two hours, which it was, but why don’t you work on that, hence a 50 year career.
That’s mentoring, why don’t you try to solve that problem. Now this is a picture of an engineer named Phil Drinker and Phil and I and some others built membrane oxygenators to replace the bubble oxygenator that was being used at the time. And what do you know, that solved the problem of the mortality of the heart and lung machine itself. So this shows a dog that’s been on extracorporeal circulation for four days pretty exciting, in the early ’60s. And then as Ed said, when we left residency went on to UC Irvine. It turned out to be an important move, because it was a brand new medical school. It opened the day we arrived. And I say we, because another resident buddy, Alex Zaniga and I went out there and quickly got assigned the job of running a county hospital and doing whatever you wanna do. There’s was no one around to say, we don’t do it that.
So we did a lot of wild stuff, including working on this particular technology. In 1971, the first clinical case was done by a friend of ours, a surgeon named Don Hill from San Francisco. This was a patient who was in Santa Barbara. It was the first successful patient. We worked on this ourselves. We did, as I said, we were doing all the surgery in our little hospital, including the cardiac surgery, and the pediatric cardiac surgery, and we did mustard operation. A few of you remember that procedure.
And this little boy who was dying, post-op, low cardiac output syndrome and so on and we brought our machine from the lab and cleaned off the sheep saliva and things like that and hooked it up. What do you know? He recovered after a couple of days. That was the first cardiac survivor. And the system we used, sorry, very sensitive, is shown here. So you recognize, just a stripped down heart and lung machine. We’d gain access to the right atrium through the jugular vein. We’d drain blood, Heparinize it, run it through a membrane lung, warm it up again and put it back in the patient, into the systemic circulation, in this case through the carotid artery and we’re on veno arterial cardiopulmonary bypass, just like we were in the operating room, but with different access and with different devices.
So we learned that this would work and that we could do this for days at a time, with complications, but people could survive. In 1975 we were asked to see this little girl, a newborn infant with severe respiratory failure. You can see a nice, full term baby whose lungs didn’t work at all. So this was not unusual, because, again we were the pediatric surgeons to this hospital as well as the cardiac surgeons, and general surgeons and everybody else. So it was not unusual for the neonatologist to call us and say you wanna bring your machine over here and try it on this baby.
Well we did that, and what do you know, she recovered over about a week and she happened to be an orphan ’cause here mother had delivered her, was in the country illegally and left having been told her baby would die. So the nurses named her Esperanza. So she’s become kind of a famous patient in the ECMO world because she’s been to meet several of the people. People know about the story about Esperanza. She’s now 43 years old, has children of her own. But the important thing is that she recovered and did well and that led to another case and another case. So we learned that this particular technology would work in that particular group of patients. This describes the number of cases in red and the number of, in yellow, and the number of cases in red that were experimented with this technology.
In 1980 I moved backed here to University of Michigan so this technique has really grown here and Michigan is sort of the fountainhead of this technology. Ever since that time we continued lab studies, we did clinical trials, did a variety of things and this became a more widespread technology by about 1990. In 2008, important thing happened in this technology. One was a world wide epidemic of H1N1 flu.
You might remember the swine flu. It was very contagious. It was not particularly virulent except for some patients, but young patients, pregnant women tended to get this and had severe respiratory failure and it turned out that ECMO was the only treatment that was successful in those patients, with an 80% survival. Pretty unusual. The other thing that happened in 2008 was some companies decided to make actual ECMO machines. Prior to that, we took devices that were intended for cardiac surgery and used for cardiac surgery and modified them in various ways to use them for a longer period of time. But it was pretty complex and difficult to do. Required someone to sit at the bedside continuously to manage this in case something went wrong, which it often did and it looked sort of like this. With the new devices, and there are three of them, and they’re all made in Germany, they were much improved, they were simpler, they were easier to manage, the had much less complications. And so it became possible for anybody who was a good intensive care doc with a good surgeon could hook this up and get it to work, first time out of the box.
That made quite difference as you’ll see. So the application of this technology extends to any situation in which there’s a severe heart and lung failure that’s not responding to conventional management. It all depends how you hook it up. So for cardiac support, or support of the circulation, you have to use veno arterial access, cardiopulmonary bypass as I showed you earlier and we can hook this up through the neck vessels, through the femoral vessels, or in fact just through the right atrium and aorta as you’d use for cardiac surgery.
And in fact one significant application for all of you is that. It never happens to Ed, it occasionally happens to Rick, but every now and then you have a patient who can’t come off bypass in the OR. Oh some of you reckon. You might have been there. So you know, when you can’t get off bypass and you’re giving all the drugs and so on, an alternative is just to convert that to an ECMO machine ’cause it can go on for a few hours or a few days if you have to do that, so access directly through the chest is one way of hooking it up. If the primary problem is respiratory failure, like the little girl I’ve been telling you about, you can do veno arterial bypass and it works fine and we did that for the babies, for example. But you can hook it up in a veno venous mode, draining blood from the inferior and superior vena cava and pumping it back into the right atrium, which allows you to substitute for the lungs.
You can remove the CO2, you can add oxygen. Provides no cardiac support, so it’s a little different mode, but for this little girl like I’ve been showing you, her heart is fine, once we got through the septic shock area and we’re just supporting her lung function with veno venous access. That kinda gets to be important because all the blood goes through the heart and lungs including the damaged lungs, which we think is good and also any blood that comes out of the ECMO system goes into the venous circulation. So there are little crumbs and emboli that come out of that circuit all the time and if they go into the systemic circulation, they find their way into the brain and the kidneys and the lungs, so veno venous has access advantages for very long term support. So once you’re doing this, now managing the patient in the ICU, as all of you know who have taken care of ECMO patients is very different than what you were doing just two hours before when all you had to work with was a lotta drugs and the ventilator and now we don’t need that.
You can just turn all that off. So how to manage the patient requires a fair amount of orientation and education among the staff. The patient who used to have an arterial sat of 91 and we were worried about, now has an arterial sat with veno venous bypass of 80%. We say that’s fine. So you have to some education on old fashioned physiology. You have to decide when the heart or lungs are better enough to try to get off the machine. You need to have people who are really good at managing this.
That is day to day, hour to hour, minute to minute. Doctors are not good at that. We get bored pretty quickly, so even perfusionists who do this for a living, they do it for two or three hours in the OR. They hate sitting there at bedside for a day or two or three. So we developed a category, a professional group called ECMO specialists who come from nursing or perfusion or respiratory therapy backgrounds and have learned how to manage this technology at the bedside and that’s been a very important part of the development of this technology. So that by 1990 something, certainly by 2000, this became a fairly routine ICU procedure. Also, with the new technology that allowed us to take a totally different approach to managing these patients. So in the early decades, what we did was a lot of sedation often paralysis.
Patients were intubated, they were were on the ventilator, but on low settings. A specialist had to be at the bedside nonstop. We tried to recruit the lungs if there was lung failure and bleeding was a major problem, often the fatal problem in these patients, because the blood has to be anticoag`ulated and that creates problems. With the new machinery, we’ve evolved to a new method of managing these patients.
They’re in fact alert and awake and usually extubated, if they’re cardiac patients and we manage them either extubated or perhaps with a tracheostomy. A well trained ICU nurse can manage these patients. It’s no longer necessary to have someone specific at the bedside. We’ve learned that trying to recruit the lungs was a mistake. All it did was make pneumothoraces. It’s better to just watch and wait and wait for the lungs to get better. And bleeding is still the major complication, but it’s now an annoyance rather than a fatal problem.
Other centers around the world learned to do this. Mostly came here and we trained people how to do it and asked for them only that they let us know what their results were, so that led to the registry of patients and we have a fairly complete registry of most of the patients that have been managed with this technique and that led to the formation of a group called the extracorporeal life support organization, or ELSO which began in 1989. That was the first meeting. We just came from the 28th meeting where there were 900 people, kind of unlike the early days. And what ELSO does is maintain the registry of patients, but also provide a time when all the centers that are involved in this technology can get together, can meet, can share information, can decide what we’re doing poorly what we can do better, and so on. These are the ELSO member centers, about 600 of them currently. So I’ll show you a little bit of data from the registry.
These are the types of patients in the registry, so that in the early days they were almost all newborn infants here with respiratory failure, but that number of patients stays about the same, but as a percentage it’s gotten much smaller as we use this technique for children and adults with cardiac failure which is now the major application of this technology, or children and adults with respiratory failure where it’s currently growing quite rapidly. These are the results in the registry as of about a year ago and we collect this information and report it in three categories, neonates, which is up to 30 days, pediatric patients, and adults patients with primary indication being either pulmonary failure, cardiac failure, or there’s a category called ECPR, which is CPR for cardiac arrest supplemented with veno arterial ECMO, which in fact is fairly successful. So you can see there totally about 85,000 patients in the registry and the survival for ECMO itself is about 70%. About 10% of those patients still die in the hospital. That’s a problem we’re still working on. So the overall survival is about 50, 60%.
Not bad, considering we only put on patients who we think are gonna die otherwise. On the other hand, lots and lots of room for improvements. So we keep working on this in the laboratory and I’ll tell you a bit more about that in a while. So you can see the results in terms of survival are best for newborn babies, because their lungs are basically normally, they just need to live a little longer. And worst of all, as you might imagine, for ECPR for adults, people who arrested and we used this technique to try to help resuscitate them. So that’s the whole picture. From here on I’m just gonna talk about pediatric cardiac problems ’cause I know what you’re focused about and we can talk about some of the other categories later on if you wish.
So these are the number of cases in the registry each year. These are neonatal cardiac cases. Now this starts in 1988 when there weren’t any neonatal cardiac cases, thanks a large part to Ed and some of the rest of you. You can now operate on babies within the first day, week, month of life and fix those lesions, which we used to fix. We, when I was a resident with Dr. Gross. We would fix a tetralogy after the Blalock, after the Potts, after they graduated from high school, then they’d come into get fix. I’m not kidding.
So to fix these lesions early on, I don’t have to tell you, it’s a major step ahead. And what do you know, this technology works for newborn infants so that you can use this if you have a baby in the very early days who’s not doing well from a cardiac either preop or postop and provide reasonable success while other things are being fixed. You can see that this increases pretty dramatically starting at about 2008 for the reasons that I showed you. And the results in the neonates or infants for cardiac surgery almost all are operated on for congenital defects with overall about 40% survival.
Pediatric patients in our registry were run from 30 days of age to age 18 and as you can see there are about six or 700 a year in the registry and congenital defects are still the most common indication, but you start to see cardiomyopathy and myocarditis as indications for doing this. And the results in those patients are considerably better. Most of the congenital defects are, as we said, babies who can’t come off the pump in the OR or they get to the ICU, but they’re failing hours later. So the patients with intrinsically normal hearts to begin with do a little bit better. You will get involved with adult cases and as you can see, adult cardiac cases really took off after 2008 with the machinery became available and much of this is in patients with cardiogenic shock from myocardial infarction or other causes in the cath lab with a disaster or something like that, so it’s really a very different category of patient.
I see Frank Bagata. So Frank published the first paper, remember this Frank, of bridging to VADs from ECMO. When was that? Back in the mid-’80s or somewhere when everyone thought we were crazy. Why would you want to do that? But now it’s becoming fairly routine way to bridge from severe cardiac failure in adults to something else, which might be a VAD, might be a transplant. The indications in adults are cardiogenic shock, most of the cases and there are more cases with myocarditis and cardiomyopathy. Here at U of M, this is our experience since we’ve started in 1980, some 500 cardiac support patients in children with an overall 52% survival and of course most of the cases are congenital heart disease although cardiomyopathy or myocarditis have a little better results.
So the algorithm for managing these patients goes on for pages with respiratory failure. But for cardiac failure it’s become a lot simpler, because if the heart’s not recovering after a day or two or three, it’s very unlikely to. It’s probably not gonna get better. Myocarditis is different. That may take a week or two for it to recover, but everyone else, if you know, if you had a big myocardial infarction or if your repair of the tet or whatever is not working well and the heart’s damaged, it’s probably not gonna get better.
So the algorithm is on day two or three of management, how’s the brain? That’s the first question. Often times it doesn’t work and often times we just have to turn it off. The most common reason for failure is there was brain damage associated with the reason for cardiac failure. But if the brain’s working okay and cardiac function’s returning, you’re probably gonna be all right, so you just keep going. And the average run is about six or seven days and those patients get better. If not, then you have to think early on is this patient a transplant candidate? If the answer to that is no, you probably oughta have that discussion with the family and say you know, we’re trying this, it’s not working.
You know it’s not gonna work, so three days from now if we’re not better, we’re gonna have to turn this off. If the answer is maybe the patient’s a transplant candidate then you can go to a mechanical support device, a VAD of some type and sustain that patient long enough to get on the list and perhaps get a heart transplant or perhaps go home and wait for a heart transplant these days, as you all know how that works. So how to do it, we’ve talked about vascular access and the machinery itself is pretty simple. This is VA access again in the neonate. In a large child or an adult, we would prefer to go from the femoral vein that is draining the inferior vena cava to the femoral artery.
Now the reason is, it does not have to sacrifice the carotid artery. You might worry about whether that’s a bad thing to do, to ligate the carotid. But, I’m looking for Hannah, she’s a pretty good example of how you can get along without your right carotid artery, but the older you get the more you have to rely on collateral circulation. So for adults, if you use the carotid, which I’ve used a lot of times, the stroke rate is about 15%. Unacceptable. So what age would you say, okay we’re gonna go to the femoral vessels? Somewhere around age six to 12, somewhere like that is probably the time to do that. Now the problem there is that you’re perfusing retrograde so the bright red blood goes up the aorta, but it mixes with whatever blood’s coming out of the left ventricle, somewhere in the aortic arch. So if the lungs are not working, that blood’s gonna be hypoxic, so we have ways of dealing with that phenomenon. If we think about ECPR, ECPR is very successful in children. These are data from 10 years ago, but the current data’s still the same. The survival rate for ECPR is about 40% in cases in the registry as you saw there, couple thousand such cases in children.
This is a little misleading, because the only time we can use ECPR VA ECMO associated with cardiac arrest in children is when we’re all tooled up to do it. So what this means is, here’s a patient that’s doing poorly and not doing very well. We’ve got our ECMO machine and we’ve got it primed, we’re thinking about maybe going on, now the child arrests. Okay, quick, hook him up, ’cause we’re all ready to do it. To do it from scratch is nearly impossible, although that’s happening now in our emergency room and other emergency rooms around the world. Patient comes in with out-of-hospital cardiac arrest, if the ER team is trained, and that takes a couple of years, the ER docs can put that patient on VA ECMO and we’re just in the process of studying that phenomenon.
As you all know, nowadays, if you have a child who might be a transplant candidate, you can go to the Berlin Heart. What do you know? Isn’t that exciting. Well we have some responsibility for that. We’re very proud of that, because when the Berlin Heart company wanted to qualify their BIVAD, basically, with the FDA, the FDA said you have to do a controlled randomized trial. Said, what do you mean? The alternative is here’s a child who’s dying, about to be dead and we only use this for that kind of patient.
So the FDA, to their credit, said, why don’t you do matched pairs trial, so take the patients with your device and compare it to patients from the registry, which was there were 700 patients who were being bridged to transplantation. And of course they did very well and the device was on the market in 2011 and we in the ELSO community are very proud of that ’cause it’s the first time that the FDA has ever permitted registry data to be the control group for patients and it solved the ethical problem, it solved the logistic problem, it got the device approved.
So we’re particularly proud of that. So to summarize all of that, the details of managing a patient on ECMO, it’s all about physiology. So this is physiology that you all learned year one of medical school or nursing school, but it’s amazing how many intensive care people have forgotten this, so you have to go back and talk about what the oxygen requirements are, what the oxygen delivery system is, how much do you need, how do you measure it. And you measure it by measuring mixed venous saturation and so on. It’s great to talk to all of you, because you know about maintaining a normal hematocrit. Love it when the neonatologist say the hematocrit’s down to 50, we better do something. ‘Cause in the adult world, there’s a fad that’s going on that’s just crazy. The more anemic you are, the better it is and if you’re really sick you oughta be really anemic. And hospitals have rules, you can’t transfuse patients ’cause we all know how bad it is. And that’s all written by people who forgot all their freshman physiology.
But it is important in any of these patients to maintain a normal hematocrit, ’cause that’s the basis of oxygen delivery. You have to learn a lot about gas exchange. If you’re on for cardiac support and the heart’s not working at all, the left ventricle and left atrium will gradually fill with bronchial venous blood, so you have to vent that. That’s rarely a problem in children, ’cause they’re right ventricular dependent and usually the left side works all right. You have to anticoagulate these patients. It still is the major complication. It’s a big problem. We’re looking at different types of anticoagulants and different non-thrombogenic circuits. We haven’t solved it yet.
What is important is we now manage these patients fully awake and alert and if they’re old enough, meaning after the age of about four, because if you wake up a two year old, he’s gonna pull the catheters out in the middle of the night. It’s very different approach to the management of these patients, to manage them awake so you can talk to them. In fact, it has important implications that I’ll show you in a minute. Keeping it dry weight, using hemofiltration. So on maintaining some flow through the heart is important, otherwise if it’s just stagnant that blood will clot, even though the patient’s anticoagulant.
So this has now become the standard treatment for severe cardiac or pulmonary failure in children. And what that means is, any of your ICUs will have to have this technology or have a system to transfer such patients to a center that does it. So I’ll close by telling you a little bit about some of the new stuff that’s happening. And in lung failure it starts with this little girl. You can see her name is Reece. At the age of seven, about three and a half years ago, she had a 30% total body burn, plus severe smoke inhalation. She was treated at Hopkins. She had a cardiac arrest in the process. She was on VA ECMO for two weeks. Her heart got better but her lungs did not, so she was on VV ECMO for a couple of months.
Then the fibrosis got so bad that she went into right heart failure and so what they did was convert to a version that through by a thoracotomy cannulated the right atrium and the pulmonary artery, put an oxygenator in the circuit, and she’s on ECMO through that particular connection for 15 months of time. During that time her lungs recovered and what recovers first is always oxygenation so she didn’t need oxygen support, but still could not excrete CO2, which is part of the pathophysiology. She was on VV ECMO for another two months and then weaned off after 605 days of support. I just came from the ELSO meeting which was in Baltimore, which happened to be where this little girl was, so here you have a picture of Reese, this little girl, year and a half later and happy and healthy and getting along fine here with her mom and her doctor Chris Nelson at Hopkins.
And her doctor’s important, ’cause can you imagine how many times someone came around and said what in the hell are you doing here? It’s been, you know, her heart’s failed after being on ECMO for two months, turn her off, don’t you read the literature? Yeah, but she’s alert and awake and she’s in school, she’s typing with her class. Okay and then the administrator. You know how much money we’ve spent to have this little child here? She’s taking a bed in the ICU. After a while the cardiac surgeon comes around and said that’s very nice, but don’t you know someone’s talked about canceling my case for tomorrow, so get rid of it, take this kid out of here. So this one particular case is so incredibly instructive, because she’s not the only one, but she’s the most dramatic one.
And now we’ve learned in hundreds of patients that the lung has a remarkable capability to regenerate and recover all the way back to normal in patients that we used to say this is irreversible lung damage. And I’m looking around at some of my friends here. Remember when we turned patients off after a week, or two weeks or a month of time, because the lung wasn’t working? So this isn’t gonna work and we’d turn it off. Patient died, they’d go to the morgue, the pathologist would say, I don’t even know what tissues this is, this junk that’s in the chest. Now we know, it can recover back to normal function. Who would have guessed that? So there’s a whole new era in lung biology made possible by supporting these patients for a period of time with mechanical devices. Now that’s not new. You do all that with the heart, so if the heart doesn’t work you can use a mechanical device.
Sometimes the heart recovers. Sometimes you have to replace it and if you’re old enough to remember the days when we first used dialysis for acute renal failure in the ICU. Well I’m looking around, there’s no one who’s that old, but one of my first patients as an intern was a patient who was on dialysis because of acute renal failure. And what do you know, those kidneys all recover.
So we’ve been through this before. We’re just finding it out now with regard to the lung. So this offers new practical problems. How are you gonna take care of a patient for two or three months, let alone two or three years, in your ICU? So we have to develop systems that get those people out of the ICU, out of the hospital, just like we did with VADs and just like we did with dialysis in the past. And it offers new scientific opportunities. How does that happen? It’s clearly a stem cell phenomenon, but if you add stem cells to the lung in lung injured patients, to date at least nothing happens. But there are endogenous stem cells in the lung which eventually get turned on and will grow new lung tissue.
It’s really exciting. To get the patient out of the hospital is gonna involve getting the artificial lung hooked up to the patient and sending ’em home, just like a VAD. Some of you remember when a VAD patient had to stay in the ICU until they got a donor. Now they, you know, walk around and become vice presidents, things like that. So we’re working on this in the lab. And the approach for children is to go from the pulmonary artery to the left atrium, ’cause the problem is pulmonary hypertension, right ventricular failure, or perhaps a gas exchange, or perhaps just a growth problem. This is the problem in diaphragmatic hernia. For example, if the lung is just too small to support. So this was first done in St. Louis as a bridged transplantation in 2014. And there’ve been several hundred patients since then.
We’re working on this in the lab to try to simplify this technique and Ron Hershel has a nice grant to work on that particular problem. One other bit of research that’s going in is the problem with cardiopulmonary bypass. I said now, even for cardiac surgery, we use membrane oxygenators. We can use them for hours at a time without killing the patient. But if you are on cardiopulmonary bypass for not two, but four or six or eight hours, eventually that patient gets an extreme inflammatory response, the kidneys fail, the heart fail, the lung fail.
Why does that happen? Interestingly, well we think we’re getting clue to that and then comes this paper from Australia. So they put nitric oxide in the sweep gas during cardiac surgery for congenital cardiac cases and what do you know, it significantly decreased the surgery response, renal failure, cardiac failure, lung failure, and so on. How does that work? Well we’re working on that in the lab. We’ve developed a nitric oxide generator, because otherwise it’d be very expensive. And with that we’ve learned that nitric oxide as a sweep gas prevents white cell activation which we think will become standard treatment for cardiopulmonary bypass in children and adults probably in the future, eliminating the 5% or 10% that get post-op complications.
Dave Owens, who’s sitting over here, and Martin Box came to us a few years ago, saying, you know, the biggest problem with pediatric transplantation is you can’t get a donor. You have to have the right size and the right blood type. Why can’t we maintain hearts on an ECMO machine for a few weeks until we can match it up to a patient? Well we thought that was crazy, but we thought it’s worth looking at. So we’ve been focused on the question of why it is that you can’t perfuse an organ for more than about six hours.
And that remains the limitation in transplantation of any organ. But we got working on this and we like to think we might have solved the problem. – All right, again, – EBHP5-22-2017 without pericardium. This is hour 72. – So this is a three day heart perfusion. – Perfusion actually picked up speed. – Unprecedented. Isn’t that amazing? So we’re really excited about that possibility. We’re just getting onto it, but it’s pretty exciting stuff. And finally we’ve looked at this technology for extreme prematurity. I think George is gonna talk about this in a few minutes so I won’t go on, but it’s stuff we’re doing in the lab, which we’re working on to push this technology out to the next stage.
So in summary, in the future, the ECMO machine will have a variety of modules. So you can already plug in the renal failure module and soon you’ll be able to plug in the liver failure module and the sepsis module. We’ll be using materials that do not require systemic anticoagulation. Hooking the patient up is a big problem. It takes two experienced people, usually surgeons, to do this and we’re aiming to get that down to any one intensivist that can put in an IV can put a patient on ECMO. We’re building new membrane lungs. We’re automating the system. We’re working on the placenta and the organ culture aspects of it. So remember, Serena, the little girl I was telling you about, here she is day 32. We used to turn these kids off at day 14. But she’s alert and awake and still getting along so no one could quite bring themselves to turning her off. But you can see, there’s zero lung function. But a few days later, what do you know? The lung gets better. And what we’ve learned is this is what happens.
There’s no way you can speed it up, but when that regeneration reaches a point where it suddenly works and the patient recovers. So here she is about to go home. So I thank you for your attention and be glad to answer any questions. Rick, I don’t know what the format is. You wanna just proceed, or take some time. (man speaking in the background) Yes sir. (man speaking quietly) – Sure. (man speaking quietly) – And although I know we’re all been focused on the so called soluble coagulation system obviously, platelets have got a big piece of this.
For some years I tried to talk the Berlin Heart people into putting an extra little side cannula that would go right down to the inflow end of the cannula and maybe drip antiplatelet agents in there, adenosine being the one I’m particularly fond of, because it’s such a potent platelet aggregator inhibitor and also goes away pretty fast. – So John, hi John, good to see you again asks about a regional anticoagulation, just anticoagulating the blood that’s outside the patient and then reestablishing normally coagulation when it goes back in. And in fact, that’s done routinely in dialysis and hemofiltration, where we put a calcium chelator going into the dialysis circuit, and put calcium back going out of it. Works very well. We have tried to do that with ECMO patients, but you’re too close to the margin.
We either got bleeding or clotting and it’s because ECMO involves the entire cardiac output, not just 300 or 400 ccs a minute, but it’s a great possibility using another drug like adenosine, as you say, that is very short acting, would be a good approach. But it has to be so safe that it doesn’t fail on the downstream side. What we’ve worked on in the lab is something sort of similar. That is we developed plastic that secretes nitric oxide. So as you say, the real secret is the platelets, not the fibrin formation. So the way the normal endothelium works, it secretes nitric oxide and you all know it effects the smooth muscle on one side, but on the other side it prevents platelets from sticking to the endothelium. So we’ve been at this for several years. We can make plastic that secretes nitric oxide at the same rate that endothelium does and it really does prevent platelets from sticking to the surface.
So we’re still in the process of developing it. There are heparin bonded circuits and other type of circuits that prevent the fibrin formation but it doesn’t solve the problem because of the platelets. So, you’re quite right, that if we could solve the coagulation, as you heard me say earlier. I think we’re close to it. We’ll be able to do this without systemic anticoagulation pretty soon. Great, thank you very much.
(audience applauds) .
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