Diaphragm Pacing in Children: Update Course 2017

Pediatric surgeons, and I'll talk a little bit about this. Many of you are familiar with the phrenic nerve pacer. It's been around since the late 1960s, Avery in the United States, Glenn's work out of Yale developed it, and at University Hospitals in Case Western Reserve, we wanted to go to Intramuscular electrodes, a different way of doing it, which is very important because we can remove it, as you'll see in some of my later talks. I don't see it. He may need this to advance it. 00, here, use, use this to advance and that to point maybe. Oh, we're not. Yeah, try it now, just a big button. And full disclosure, everything you hear about today, uh, was developed at Case Western Reserve, my hospital. I've, uh, intellectual property rights. I founded the company. Um, as you're all familiar, in pediatric surgery, uh, everything I'm talking about is off-label use of an FDA approved device. As we all know, to get something approved for pediatrics is, uh, difficult. It makes it difficult for all of your daily practices. I'm gonna talk a little bit about a case study. A 16-year-old previously healthy, nationally ranked wrestler, ranked number 2 in the United States was here in Akron, uh, during a match, and he went head down. It was a C3, C4 spinal cord injury, uh, sudden quadriplegic. You can see he's a great young man. He had an ESPN segment just two months ago talking about his injury. So he's day one, he had fixation of it. They briefly extubated him. Uh, 36 hours post-op, he had respiratory failure. He failed NIV, reintubated, had a pneumonia, which is almost universal for a high quadriplegic patient. Um, day 9, tried to extubate again, failed. Day 20, he's still intubated. Chest x-ray looks completely good. No abnormalities on it. Just cannot get enough respiratory drive. So, the question I'll have for the people on the staff, since I didn't make a multiple choice question, what would you do for this patient? Day 20. Still not tra, intubated. I, uh That's a great question. I don't have a good answer for you. I mean, I'm sure you you would just, he should be he'd betrayed. Yeah, yeah, trick and pegged, Drake and pegged. Well, you should never do that anymore. Let me ask that question again. Well, I'd diaphragm. I'd pay, yeah, calls. It's interesting because we, we all look at this, and obviously he sees an incomplete. He has a little movement in his arms, so he probably has a little control of his diaphragms, and, and we have a lot of interesting aspects. So I kind of, as, as I'm sure Todd knows, I could talk about this for 20 hours after 20 years of research. I've done various animal models. I have actually 14. IRB protocol. So I need to do IRB research. I think I have one nurse who's doing our annual reviews cause it's due every month, basically. I've actually spent $60 million on this project so far from various grants and funding and everything else. I've actually been involved in over 2000 patient implants, 27 countries, as, uh, Todd knows, I flew back from Dubai after their first implant, uh, what's today? Maybe Monday, had surgery there. Um, it's been a very interesting project. And really it comes down to how do we breathe. At the end of my talk, I'll talk about two new pediatric diseases we've just published on, uh, Pompeii's disease and SMA. And it has to go with how we breathe in our brain stem, which is a huge area of research right now. I can make my diaphragm move with my cerebral cortex. I can actually, but most of us aren't using our cerebral cortex for breathing. We use our brain stem, the lateral medulla, the preserine complex, what you're all familiar with because of Onine's curse. Um, it just affects the prevascular complex, and they have central sleep apnea. They can, can control their diaphragms while they're thinking, but they have to go on a ventilator at night. Uh, initially, the phrenic nerve pacemaker was initially developed for Undine's Kirsten pediatrics, direct phrenic nerve stimulation. So, we do know that you have to have C3, 4, and 5 alive to keep your diaphragm there. And you'll hear a little bit, and I know the cardiologists here where they do atrial fibrillation or problems can injure the phrenic nerve, because the franked nerve runs, runs along the right atrium. So phrenic nerve injuries, we've done a lot of work now in rehabilitating the diaphragm, and you have to have an intact diaphragm. Our diaphragm muscle atrophies faster than any other muscle. Within 12 hours of being on a ventilator, you lose 50% of your diaphragm muscle mass. It converts to type 2B muscle fiber, fastest muscle fiber. So, if you're on a ventilator, You're going to have to recondition your diaphragm. In the United States, in the adult world, 120,000 tracheostomies were done for failure to wean and non-spinal cord injured patients last year. It's going to be worth $64 billion is spent on long-term mechanical ventilation in the United States in any given year. So this is a continual problem of a die from rehabilitation. In the pediatric world, you know, your most common spinal cord injury is actually a cervical spinal cord injury. We know that 75% will require intubation with their initial trauma. Um, many of them, almost 20% of all cervical injuries will require a tracheostomy. Um, and 53% of your patients that you have coming in with trauma and event will go to a rehab facility on a ventilator. We do know that if you're on a ventilator, it changes everything. Parents' fatigue if they go home, inadequate social support, extremely expensive. It costs about $170,000 a year for a patient to be home on a ventilator. We know officially that you have to go home with two ventilators and a backup generator. We do know that in the United States, we have lack of electricity. The people that died in Hurricane Katrina and Rita in the hospitals were all on ventilators. People couldn't handbag them anymore. So the lack of electricity is a big problem for these children going home. We developed this aspect. This is a laparoscopic visualization of the right diaphragm. Key thing you'll see here is nothing's happening. It's a complex gunshot wound to the neck where they knocked out the phrenic nerves on the right. I'll work around the Ponsky peg, named after Todd's father. On the left side, great diaphragm contraction. This goes to an external, uh, neuro stimulator that we have for this. Die from contraction, you're gonna breathe. This diaphragm. And this patient has been on a ventilator for 10 years. Everything's intact. Now, if I stimulate that consistently, it would fatigue and not be able to work well. So we know years after I've implanted patients after 28 years after a spinal cord injury. We then developed this little electrode. The electrode that we implant in the diaphragm is a little bit different. It was developed that case reserve. It's actually a, um, actually, it's a non-patented electrode because it was published before it was patented. Universities weren't as money hungry back in the days. And again, anterior diaphragm, posterior diaphragm. We put 2 electrodes in each diaphragm, and you get the diaphragm to contract. The diaphragm contracts, you breathe. So when I look at any child on a ventilator now, we, we only consider how can we get that diaphragm to move? Is there an intact system, which has led to a lot of our different research on the, all the pediatric diseases that I'll talk about here briefly. When you say is there an impact system, you're talking about phrenic nerve at that level or what a phrenic nerve. And phrenic motor neurons. If you cut a nerve, the muscle will die off. I'm sure you've seen somebody with a brachial plexus injury, the hand that, so you need an intact nerve and muscle, and intact phrenic motor neurons and nerve, the muscle will stay alive. Now you can have injured nerves that we can bypass. Which button for this one? Uh, can you advance the slide until we get this fixed? No, I'm done with the video. Again, what we developed, this is a percutaneous system because it's less expensive. Everybody asks, why don't you make this implantable, um, because we just didn't have enough money for it. And we'll talk a little bit because we now just use temporary devices now for people that brief term. So, it's a percutaneous device we can program it. and we can actually measure the title by it might implanted a 4 year old, uh, last week where, you know, we can contract the dot. you need 5 to 7 ccs per breath. And I was getting 500 ccs per breath, which is way over what he needed. It was only 30 kg. So we turned it down to maintain minute ventilation. And everybody says, what happens if they're going to run around? Nobody that actually needs this device is going to run around. These are not normal people. Minute ventilation maintain CO2. So we just program it for a nice smooth breath. Probably one of the biggest differences. We have between direct phrenic nerve pacing is that we modulate the breath. When we all breathe, we slowly ramp up our diaphragm. So that was kind of in our 1st 50 spinal cord injured patients, we figured out the right dose of electricity, basically. So now we can ramp up so you get a smooth breath, so you don't aspirate. If you sudden breath like a hiccup, if everybody's done that phrenic system. Next slide. And really, it's just weaning from the ventilator, and this becomes a simple thing. Everybody says, well, how do you use this? We just turn it on and they breathe. And, and it's an interesting process until you see this. So you just take them off the ventilator, turn it on, and see how many minutes they go before their tidal volumes drop or their 02 sat drops. We're just rehabilitating the diaphragm. And really, when we talk about my first case, I'll show you what we decided to do on him. Next slide. Um, so Todd and I published the first when he was back up in Cleveland. This is our first in the journal here, uh, Journal of Pediatric Surgery, excellent journal. Accepted my work. This is our 1st 6 patients that we implanted. And again, um, it showed it was successful in the initial pediatric group. We've subsequently have done a whole series of different patients. So, next slide. And I updated this in May for a presentation or in April, and it's been interesting. It's my 1st 20 patients at my facility, and I've done that at various other facilities across the world in pediatric surgery. We've gone now from 2 to age 17. Average time on ventilator is 9 years, motor vehicle accidents. We've been seeing them. Sure, as you've all seen acute flaccid myelitis, the enterovirus that leads to the polio-type aspect. We've been doing a fair amount of work on that. And literally since I updated these results, we've had a run on children. I've now gone down to 1 year's age. You have to be at least 10 kg. Your chest cavity isn't formed just enough if you're a true quadriplegic. Um, if you go too young, the chest will collapse where you're contracting and die from. So I've kind of now gone to 1 year. I think it's worth, at least in the 1 year old we've done, at least 10 kg. And many of these kids, as you know, have had gastrostomy tubes, VP shunts. It really doesn't affect anything. In the long term, almost all these patients, quadriplegics will get severe scoliosis. We've gone through their spinal straightening operations without difficulty pacing them through. Next slide. And overall, and again, this goes down to if we can stimulate at surgery. If we can't stimulate at surgery, this won't work. So we know immediately at surgery. I feel for all of you pediatric surgeries because it's the worst talk I have when I come out. If we can't stimulate at surgery, that child will never get off the ventilator. You just can't do it with accessory muscle. We're doing a little bit more work now with nerve transfers. Um, they're a little bit better than the old nerve transfers. We've actually done a, a lake muscle transfer to the diaphragm. It's worked in the short term. We don't know what the long term is for adults. But overall, um, we've had two unrelated deaths, uh, recurrent sepsis after recurrence of a brain stem tumor, and unfortunate heat stroke in a child. Uh, again, many of these patients do have problems with parasympathetic and sympathetic abnormalities as a high quadriplegic. Um, about 50% are full-time pacing, 24 hours a day, every minute of the day. 4 patients just pace during the daytime. This has become a problem with insurance carriers. If you get off the ventilator, you lose 24 hour care. So, many families just put them on the ventilator at night, cause then they get 24 hour care. It's unfortunate, but you have to do what's best for the child. Um, we have some patients still weaning. And two patients, um, we did a little work on brittle bone disease, a very unfortunate disease, as you're all more familiar with IM. We were able to get the child, um, uh, we just kept on having other problems with rib fractures and stuff, so we just abandoned pacing. It was a, an attempt to try to get her home off the ventilator. She fractured her spine with her brittle bone disease. We had one other child with some, just some chronic skin reactions to her electrodes. We ended up just removing the electrodes, which we can do percutaneously. So, it, it did, obviously, in those two patients, this was not the correct treatment. Next slide. But obviously, the benefits of pacing, um. You can see in the lower slide here, he's on that device. It's in a little thing. He's a quadriplegic in his pool. I don't know what, yeah, as you guys know, families will do anything. A sister can carry her brother who's a quadriplegic with that as opposed to a ventilator. It's a 500 hour battery life. You just, external battery, change it. You don't have to worry about electricity anymore. Um, we've done so much work on lung compliance, decreased secretions. If you're on a ventilator, you're going to get secretions from posterior low ventolectasis. It's been very good in that area. I'm gonna talk about one of our adult trials that we think is very important for pediatric trauma centers. This is a group of, uh, that we presented at AST that was published several years ago. What we used to do in my initial FDA trial, we waited a year to see what would happen. Then we realized as we're doing a lot more work for temporary diaphragm pacing, why are we waiting a year? So we did this, uh, multi-center area. Most adult trauma centers, depending on what state you are, you're a quadriplegic on a ventilator, there's nowhere to go. There's no facilities in the state of Ohio. There's only one facility to take a ventilator presently, an adult patient. And so we actually just started putting these in early. Hospitals found that it's the most cost-effective way at $5000 a day in your ICU, if you do this early, it'll work well. So we actually showed by implanting early, we had 82% completely off. We had some suspicions of recovery. For this. One of the things we developed is a way to read dye from EMG from our implanted electrodes. So I can read dye from burst activity. We have abilities now to read differential muscle fiber types. So we can see the recovery of breathing. Uh, for these patients. In the spinal cord world right now, functional electrostimulation helps recover an injured spinal cord. We all know that it's just a bruised spinal cord, and it's the electrical circuitry problems. If you start doing FES spikes or other distal electrical stimulation, there's a trophic effect that maybe you'll talk about during your gastric stimulation, um, where actually, when you're stimulating distally, it goes to the brain stem. The brain, the spinal cord knows you're stimulating a distal muscle. And so we, we identify that it may change aspects of recovery. Next slide. You can do left click, by the way. This. And so what we identified is that 1, 80% we, but 36% of the time, we just pulled the electrodes. And so this is like, you know, several years ago, and it really began as we started working on temporary use in our ICU. What I mean by this, this is a patient here. I can read the EKG. So this is like the ultimate reading of both respiration and cardiac function. And then we could see burst activity. That's a patient breathing on their own. So, in numerous patients, we've seen this. This is a patient actually a child we implanted who actually Uh, I had transverse myelitis. Then she said, you know, 3 years later, she said, hey, you know, I've, I've recovered my accessory muscles, and I started reading her EMG and she had recovered years after her spinal cord injury. This is, um, the patient or case study. So, at day 21 from Akron Children's, he was transferred up to me and I put him on my OA schedule. Day 22, I implanted him. Day 24, I extubated him with no tracheostomy. Again, I could read his EMG. He had very little control. Much later when I pulled the electrodes, that's a great guy from burst string. Let's see if this video will play. Ian Malaszewski, I broke my C4 vertebrae wrestling at the World Team Trials in in Akron, and long story short, I couldn't breathe by myself and I got a diaphragmatic pacer. And there's no reason that pacers shouldn't be allowed, because the sooner you get them, the faster you're off them. Trachs suck, obviously. You see this beautiful neck, I got no hole in it, and shout out to the diaphragmatic pacer. That was his little uh shout out um for this. And I'll talk a little bit about Pompeii's disease. We just published this last year. Pompeii's disease, you know, it's primary muscle disease. What? How can die from pacing? We know with enzyme replacement, many of these kids can't get off the ventilators. So we had a suspicion, the group at Gainesville that actually has done some work on pediatric, a lot of work on Pompeii's disease, we started considering maybe we'll die from pacing. And they very elegantly identified what we see in many pediatric neuromuscular diseases is brain stem involvement. They lack respiratory drive. We can correct their muscles, but again, as you can see in the study, very little die from burst activity. We pace them, they recover. So we showed this, what occurs on people on ventilators, they get abnormal neuro respiratory neuroplasticity. They start using accessory muscles. When we start pacing that, it's an, it changes how their brain stem thinks about breathing. They recover natural breathing. So, we've also done this in adult, adult Pompey, and this initial series, I think, of 3 or 4 patients, and the numbers have been growing as we're looking at that group. And I'm sure you've all realized new drug therapy for SMA. SMA is thought to be a primary lower motor neuron disease. So, of course, in our, my ICU somebody comes in on a ventilator, we start thinking, why? This is an SMA 2, and most SMA 2s will become dependent on NIV by late teens, early twenties. And if something happens, they don't have any reserves because they really don't have any accessory muscles. They may end up trachea vent. This is a young man who actually aspirated during an outpatient. Uh, dental procedure. It's interesting. She talked about outpatient, not correct anesthesia, became trach vented and came to our ICU. So I said, why don't we take a look? And I was surprised. That he had very good phrenic motor neurons. We got him off the ventilator within about a week or so, and we did a lot of work on his EMG. And again, once we started pacing him, he now just is on the pacer at night. And I took a second pacer who was completely dependent on NIV, couldn't tolerate it. PCO2 is in the 60. She's now off of NIV. PCO2 is normal. So an SMA type 2, we've now identified and in other sites also that they have intact phrenic motor neurons, which again are phrenic motor neurons are different than other lower motor neurons. So it's worked well in that group of patients. So overall, diaphragm pacing is easily implanted in children. It can decrease or replace MIV. I think early diaphragm pacing may. Eliminate the need for tracheostomy in the right patient group. We know that identification, this is the tough aspect in our adult ICU. If you have a trauma and we identify that we can't pace the diaphragm, we stop weaning. We go from low tidal volume to high tidal volume, which really shortens your ICU case there. Obviously, getting off the ventilator does quite well. The future and what I've worked on, I won't talk, I presented at Central Surgical and Midwest Surgical, two separate patients on temporary pacing for anybody with failure to wean. It's worked quite well in those groups of patients. And again, and anybody that does research, after 1 year of being involved or 2 years, all my studies are ongoing. You always ask anybody, do you want to go back on your ventilator? And nobody says, you know, it's a great, I'd love to go back on my ventilator. I hated being pacing. So, thanks for letting me talk here a little bit for the, about this, and I'm open for any other questions or comments. Does, do you have any mechanism? Of getting CO2 feedback to the device, or how do you avoid either underventilating or overventilating? Is it just trial and error until you figure it out for that patient? Mostly just picking their minute ventilation. We did have an adult Ondine's curse who had C2 PCO2s. 60, I implanted him and he came back to the emergency room, uh, with a PCO2 of 20, um, because we were over ventilating. It can. There is tissue CO2 monitors now and a case less in reserve. We've developed some where we could have an internal feedback. What we found is the more Feedbacks you have, the higher, you know, a lot of my stuff I do, I have to figure out. It's great research, but how am I going to get through the FDA. Right? So we can measure tissue CO2, and they can monitor it, and that's the future of all this injectable neurostimulators to monitor it and then feedback for it. Uh, most of these patients, I go purely by Min. I can measure the t. I just go by that. So, Ray, I didn't understand, and maybe I wasn't paying close enough attention. But how do you or how can you remove the wires at some point? How does, how does that work? It's a percutaneous electrode. It's just like. No, no, but I mean, uh, physiologically, why can, why, why are you able to remove rehab? This is they recover breathing. So in the spinal cord injury, there's multiple pathways. So if we think about and anybody with a spinal cord injury, it's trying to rehabilitate pathways past that injury. If you're a C2 quadriplegic, there's pathways going through there. In that bruise of the spinal cord, the frenic motor neurons have multiple pathways. I have my cerebral cortex sending signals down laterally to my phrenic motor neurons. I have my preboerum complex in the lateral medulla, not only getting signals from my carotid, but I'm also sending signals crossing over in the brain stem. So when we talk about neuroplasticity, is, is can one of those pathways go down to my phrenic motor neuron and start functioning again. So, we've seen that in many spinal cord injuries now. I mean, there's electrical current is very good. There's another, uh, device out there where you, you do a, a spinal cord operation, you put electrical current, and you're just flowing electricity and your nerves will recover faster with that. And so, it's just opening up that pathway, which then recovers its control. It's a fascinating area in spinal cord injury. So some pathways opens up and the body controls it. And we're very careful before I pull the wires. We know that occurs in ICU with abnormal neuroplasticity. Most patients on a ventilator lose their respiratory drive, especially elderly patients. They just lose that respiratory drive. And once we rehabilitate that, they recover it on their own because they, they, you reform that diaphragm. And, and part of that, when you have a spinal cord injury, your phrenic motor neurons or any motor neurons below that injury atrophy. So, when we stimulate the diaphragm, the motor neurons, as you convert from type 2B to type 1 muscle fiber, the motor neurons change size. And therefore, the synaptic connection may be able to read again. And so, that's how we believe it's happened in our animal models. Ray, how many children's hospitals are doing this now? Um, In the United States, Gainesville, myself, and I think Mayo Clinic has done one implant worldwide, and we have an implant center in Vancouver, uh, Chitelden's, um, in Germany, and in Spain, in Israel, and, uh, Saudi Arabia. And is the reason that it's not more widespread in children's hospitals because there's not, what's the reason, uh, reasoning is just rare. I mean, obviously this is a, um, nobody's ever seen an advertisement for this, right? This is a nonprofit little company, basically. There's no advertising. It's just like getting knowledge out there. That's what formats like this is great for. I mean, this really is, I mean, if you have a spinal cord injured child, this technology is. It should be offered to it now. I mean, we have a great enough data or the phrenic system. Avery's been around. We know in the United States that Avery, the phrenic nervous stimulator, has been around since 1969. Overall, there's only really two sites, LA and one site, Yale, still does some children. That technology has been around. Overall, only about 2% of all eligible patients ever got direct. There's a risk of injuring the front or very small or mild risk. This is removable. What we believe is like this patient, I pulled his electrodes on my case example. So you're shortening your initial ICU care, and that's probably, you know, by shortening that, knowing that you can pull these electrodes out, it'll really help these kids. Is there any, uh, Is there, is there any way to do, uh, percutaneous pacing of the diaphragm? Uh, yes, there is. So, um, when I've published a notes diaphragm pacing, I can put these electrodes in popping up through the stomach at the time of a peg. We've also just developed a way under ultrasound guidance. Previously, I've always risked, cause you have to get to the dome of the diaphragm. I did the lung, the liver, the spleen. I don't know why I didn't think this early. I cause a pleural effusion, and then at the bedside with the pleural effusion as my window, I can put the electrode in. It, that's for temporary use. For long-term use, I want to map the diaphragm to make sure I capture enough of the diaphragm. I think for temporary ICUs, percutaneously work. OK I have a question. I guess as a follow up to Mark's question, is there a role for this in the, just the prolonged intubation or maybe that's what you're getting at. At what point would you think this might help prevent atrophy and maybe tremendously reduce our lengths of, of intubation? Um, I was able to, um, I did an FDA trial, IDE at the time of an open heart operation, just like you put in temporary cardiac pacing wires. You put these electrodes in the diaphragm. I did this during major abdominal wall reconstructions, during whipples, during esophagectomies. So one of the things we all put drains in there in case it leaks, although maybe drains aren't good from your earlier talk. We put these electrodes in that open surgery and I pull them like temporary cardiac pacing wires. Um, that actually just received CE mark approval in Europe. I've been negotiating with the FDA for about a year now. Unfortunately, in your pediatrics to go, um, you know, I don't know when it'll be approved, but we did studies now in our ICU. We do this for failure to wean patients. I presented that central surgical, uh, last week, 16 patients, uh, after open heart surgery, uh, where we just put them in and got them off. Again, it's that lack of respiratory drive, and that's really what we're looking at now is how to drive respiration through the brain stem. There's technology now where I can actually The carotid body, kind of like it's interesting with sympathetic parasympathetic. The carotid body stimulates the brain stem. And so could I just inject a microprocessor in the carotid body and drive ventilation? That's all we're doing with this is driving ventilation. So that's what people are looking at. That's what many of these larger corporations, when you look at the cost for all of us for chronic ventilation is huge. Long term acute care hospitals are all for-profit hospitals, and they're all just trying to wean patients. So, it's an interesting aspect that many people are looking at to shorten the ICU time for these patients. Great. Well, Ray, thank you very much. It's always, uh, exciting to watch because it's so new.