Everybody, I wanted to thank everybody for coming today. I know what the alternative is. We're all in Hawaii, so thank you very much. We have a great panel today with, you know, starting off with Dr. Gay, followed by Dr. Wolf in a pro-con debate and considering initiating long-term non-invasive ventilation in COPD patients while they're hospitalized, followed by myself, and I will be discussing initiating long-term non-invasive in patients with obesity hypoventilation while hospitalized for an acute on chronic hypercaptic respiratory failure hospitalization. And then, wrapping things up will be Dr. Malhotra discussing different modes of non-invasive in the ICU with an emphasis on VAPs. And to further ado, I will let Dr. Gay kick things off. Well, thanks, folks. I'll move quickly. I know we had some competition here, but we'll try to entertain you. Let's see if this works right. I have no particular things to disclose here, and I'll dive right in. I want you to appreciate the difference in the details of what's pretty high-grade evidence of what we're gonna talk to you about. And I wanna propose that this is not as much of a debate of the concept as it is a tale of two cities. One's reality and one's a research-based event. And we really want to address the approach to chronic non-invasive ventilation in hypercapnic patients. And we're looking for that holy grail, getting the right COPD patients home with NIV. We all agree with that. What is very interesting is how fast this has moved in the last decade so far. In 2013, you have the Cochrane Library that was done by the Dutch here. You'll hear a lot about the Dutch. Peter Wichser has handled a lot of data through there. And then, six years later, Mike Wilson, who is actually a student of mine, like Atul was, at Mayo put together this at behest of the AHRQ. And there's completely different conclusions here. So Mike Wilson's group published this in the JAMA that either home BiPAP or home mechanical ventilation in patients with hypercapnic COPD had, in the case of the home BiPAP, where there was the most data, a lower risk of mortality, all hospital admissions, and there was a lower risk of hospital admissions with home mechanical ventilation. And six years before, the Dutch said it made no difference. So there was no good data at that time. So what's the difference in the data? So the studies that both Lisa and I, I'm sure, are gonna talk about have very common ground here. Severe COPD with either current or recent exacerbation, not too far behind them. There are randomized controlled trials with reasonable numbers. They used high intensity or no noninvasive ventilation. They targeted trying to get the CO2 down as much as they can. And the subjects were initiated in trials over usually several days, and they're in the hospital, and a lot of intensity to get these patients in the trials. Now, there's a striking difference between the Dutch data here. Where's my mouse? My mouse, there, there it is. The actual difference in survival here is nil. They're a third are gonna die with hypercapnic COPD, whether they're in the controls or they're in the treated group. We're gonna look at this group here from Pat Murphy's group. Ultimately, there was a profound, you won't see any cardiovascular trials where you get this profound a difference in mortality. And this is flipped over, this is actually mortality rather than survival. But the same thing from the cone line data, which was actually the original group. So this is striking that, wow, if you can do that with your patients, you gotta do something right here. So if you look at the groups here, I just noticed real quickly, they're fairly good trial, fairly good size. They use large pressures here. They do it for many hours a day. But in the Stuart group, there was no difference in the change in their CO2 level. There was no difference in their quality of life. So it was essentially a negative trial for a fairly large group. Contrast that with the cone line data that really got everybody excited where they had a significant drop in their CO2 and improvement in quality of life. But again, good adherence here. But look at these people. I want you to try and imagine how many people you have coming in with BMIs at 22 to 25 in your hospital. Same group here. Pat Murphy a few years later in the British group. Quality of life's improved, CO2's improved. So what is really going on here? Well, let's look at the concert diagrams here. When you finally get these groups that are now stable, have gone through an exacerbation, or at least are not acutely ill at this time, when they come down to enrolling their groups here, there's pretty good adherence in these trials. In this even large trial that the Germans, and the Germans have the tenacity that they will finish this trial, that ultimately they have very good adherence in these groups. What's going on in the Netherlands? This is the trial we're gonna contrast here, and I'm gonna make a point here of making decisions to treat here. There's a huge dropout in this group, and most of them dropped out because they just didn't finish the trial here, and ultimately there's a different kind of approach here in the Netherlands than there is in the United States and elsewhere. She published this study, and Lisa's gonna say, well, why the hell did you use this one? This just confirms that this is a good idea to wait, because you can do it at home as well as you can do it in the hospital. They had the same reduction in CO2. This is a positive trial for her. But let me tell you, this study took five to six years to find these people with a BMI of 22, and ultimately, they have the help. They can get respiratory therapists in the home. They can do this with a support system that does not exist in the United States. You do not have respiratory therapy service provided to you so that you can help your patients outside of the hospital, and this is why I think you have to think about the difference between the recommendation here and the reality here. So the European Respiratory Society, because they had the support, the rescue trial was the Dutch trial. It said inpatient hospitalization ultimately says that you can provide a clinical pathway to initiate NIV, but if you do it in the hospital after termination of the acute respiratory failure, it doesn't improve patient outcomes. So they said just wait until this is done before you employ non-invasive ventilation. This will be Lisa's pro debate in this case. But the ATS, I think, was more introspective about what's happening in the real world here, and they agreed, look, the data says that we suggest not initiating long-term NIV during an admission of acute respiratory failure and reassess in two to four weeks after resolution. Now, it's a low level of certainty because there is some bias here, but it was the recommendation of the group. But look what they ultimately thought about. Now, if you use home oxygen therapy versus mechanical ventilation, over 20% of these patients are no longer hypercapnic at the end of their hospitalization. So your indication to treat these people disappears, and that's really what you saw in the Struik trial that Marieke Duverman debated, and when she lost this debate ultimately last year, she had to recognize that these patients are very exclusive, and I want you to keep in mind what comes into your hospital and how many of them look like the old pink puffers rather than have comorbid disease of obesity, and particularly, most important, as they've recognized, known or suspected obstructive sleep apnea were excluded from many of these studies, but they need to be considered separately, and I'll show you that ultimately COPD is a disease of nocturnal hypoventilation. That's sleep-disordered breathing. Those, obviously, that are persistently hypercapnic that you have trouble getting off of NIV in the hospital, you're not gonna say, oh, well, we gotta wait two weeks before we can treat you, so we're running out of days. The DRG is up. Good luck to you. We'll see you in a week when you bounce back to the hospital. Here's what I learned almost 25 years ago. I think this is a clue to the Holy Grail here. So there are three negative studies. This is Nick Hill's group. So in the 90s, and some of you probably weren't even born here, we were struggling to find out where to treat these patients because at that time, there was a high level of prescription for COPD patients when the bi-level devices were first coming out. So in the early 90s, when they were publishing data to show advantage in obesity hyperventilation, huh, hypercapnic COPD, oxygen reimbursements going down, why don't we prescribe NIV for everybody? So this is where Medicare was saying, hey, listen, we're not gonna pay for this unless you give us better data to support this. Well, here's three trials, and you'll notice that it was relatively modest IPAP levels that we were using, and we didn't get any benefit from treating hypercapnic COPD patients. But the one study, Mark Elias was actually a retrospective study. It was very small, but it got people excited in the early 90s about treating people because he had a pretty significant drop in CO2. But Meacham Jones' group was the only study that had a positive outcome, and it was a very modest, but significant drop in their CO2 levels using a higher level intensity. So they were already onto something there back in the 90s if you use a higher level, but this was an intensely complicated group. This was a very clever way that they did this. So they had a run-in trial. They did a sleep study here. This is their daytime blood gases. These were pretty hypoxic and pretty hypercapnic patients that you'll see here. But look at the clue here. They had a crossover arm where they had them on oxygen for three months, and then they randomized them to either oxygen or oxygen and noninvasive, and this was the daytime gas as they entered that part of the trial. So as they did get three months of therapy, their oxygenation improved, and their CO2 came down. But look what happens to the oxygen group. It's a very subtle elbow here that they don't even really mention here, but there's an increase in the CO2 in these patients. This is a clue to the patients that might benefit to using this early in the hospitalization here. But if you look at this amalgam of data, there's a real subtle thing here. They don't have obstructive sleep apnea. We ruled it out with polysomnography. Hey, HIV-10, I kind of call that mild sleep apnea. So these patients actually had overlap syndrome, and that 10, since they were hypopneas, that's not really sleep apnea. But this is crucial to me, because look what happens to them. Their mean peak CO2 at the start here, you give them oxygen alone, it goes up after the three-month trial. So those are the patients who really have a hyperventilation syndrome coupled with their severe COPD. If they're in the hospital, this is important. So I'm gonna leave time for questions here, because I think this will be more fun. I think all of us agree that hypercapnic COPD patients benefit from NIV. In the USA, you have to wait and get criteria to give them a device, but once you hit 52, they will qualify for home NIV therapy even in the acute hospitalization phase. But if you look at these patients in the real world, it's very rare that you're gonna eliminate all of the hypoventilation obstructive sleep apnea component. Most of them have the overlap syndrome, and the best candidates are gonna be heavier than a BMI of, if I see a COPD hypercapnic patient, the number that have a BMI of 25 or less is 10% in Minnesota. They're well-fed, it's cold up there, we eat a lot. So ultimately, keep your eye on the BMI is my mantra. But beware the hypercapnic with the worsening PCO2 with nocturnal oxygen, and look, we know the patients that really need this acutely. The Australians, I love this term, they call them boomerangs. These are the people who, let's see, let's go back down again. These are the people who keep coming back to the hospital. If they're coming back for the third time, don't wait till they're CO2 out of the hospital, still meets criteria, treat them in the hospital. The centurions are the people who come into our hospital with a CO2 of 100. So we call them the century club. When the CO2 is 100, treat them, you don't need to wait. And then finally, those with comorbidities are certainly gonna be those that have an opportunity to say they're gonna come back within a couple of weeks that you're gonna end up treating them again. So I think it's fairly simple to conclude here. Are you gonna listen to St. Peter who has birds in the hand and treats them when they come into the hospital? Are you gonna listen to Sister Lisa, the flying nun, who's gonna look around for a few birds and finally treat them when she has that opportunity to? I say treat them when you have a bird in the hand. Thank you. Okay, so I'm gonna take a little bit different of a tack here than Dr. Gay was looking at. But I knew to start with these two cases. This is where it all stems from. The first is the CONLINE study that Dr. Gay just spoke to you guys about. And the second is the HOT-HMV study, which is the Murphy study with Nick Hart. Now, in these studies, we find this fabulous improvement in mortality and a reduction in hospital readmission. And this is all linked to what we think is the best biomarker. And that biomarker is CO2. Why is it important? Because we think that CO2 actually changes the milieu increasing risk of infection and re-exacerbation. So I understand where he's coming from. But I think that it's more important to then say it's not the whole picture. And this is the STROKE study that also Dr. Gay was talking about because he knew that was gonna be the next thing out of my mouth. So this was an RCT that did show that there was a reduction in CO2. But the CO2s were obtained during acute exacerbation while the patient was in the hospital, not allowing that two to four week time period for the actual monitoring of the CO2 at baseline to see what the milieu actually was going to look at. And so because of that, they did not see a statistical difference between their groups. And so if we then look not just at their mortality, but we also look at the readmission rates, we see the same thing. So those two benefits that we saw, one from the Conline study, one from the Murphy study, neither were able to be repeated unless we saw that their home baseline post exacerbation CO2 was still elevated. And so the question in then, why is it that all of us are starting to send home our acute COPD patients from the ICU with a device? Now I wanna see a show of hands here. How many people have been told by their hospital, hey, readmissions, we get slapped on the wrist for that. I want you to write a protocol. I'm seeing more hands go up to help reduce these readmissions, right? And virtually all of these are using a home mechanical ventilator, okay? These are not using BiPAP or RAD devices. And because of that, there's going to be a huge cost factor here. Now I can't beat Dr. Gay looking at the science that he's just showed you, right? Because our biomarkers are our biomarkers. But I think that we can talk about what's broken in the US system. Let's talk about where those cost factors are and see if I can maybe get some juice from there. So if we look here, these are the RAD criterion. This is what it takes to get a BiPAP machine. And you'll see that we need to have both a PCO2 of 52. And by the way, that's a PaCO2. What was the last time you told your house staff, get me a blood gas? And they came back with an arterial stick and not a venous stick, right? That's a big challenge there. And they also need to have an overnight polysomnography that's performed on their usual level of oxygen. And in an exacerbation and in the ICU, they're gonna rack it up and rack it up. It's not gonna be two liters, it's gonna be four liters. And the first time they desat, the nurse is gonna crank it up, even though you say to the nurse, please allow me to record the desaturations. What we need to see is greater than five minutes over the entire night of recording on oxygen. And they need to have both that elevated CO2 on a PaO2 and the overnight oximetry. Basically, what we're saying here is meeting the RAD criterion is tough. It is not easy. And because it is not easy, it forces us into the home mechanical ventilation. Now, when we look at that, there are a couple of important sentences in the national coverage determination on vents. Notice how I'm not giving you a local coverage determination on vents, it's because there isn't one. Not for lack of both myself and Dr. Gay trying. But what are the things that are in the criterion that we do have? So the first is that adequately provided by bi-level with an EO466 needs to be demonstrated. Meaning you have to show that a typical bi-level PAP or a bi-PAP machine won't work. Two, you have to be able with good conscious to put into the chart that the bi-PAP is needed because the condition they have is life-threatening. And that interruption of the bi-PAP at any time would cause a life-threat risk to the patient. Now, in a CO2 exacerbation, that's gonna be very, very difficult to find. That being said, we continue to use these devices. Now, if you look at the diagnoses, the diagnoses that we have available to us are neuromuscular disease, restrictive thoracic disorders, or chronic respiratory failure due to COPD, okay? So we've now added a new diagnosis, chronic respiratory failure. We don't have a good definition for it, but it's in there. So let's look at what that cost factor was because I said to you, I can't beat them on the science, I can only beat them on the cost. If we look at the cost of a bi-PAP machine, and this is a little old now, but rounded numbers, it's pretty close. The average cost per month for a bi-PAP machine is $500. It goes to purchase at 12 months, and you're done. The average cost for a ventilator, at least in Chicago, is gonna be $1,500 a month, and it never goes to purchase. And even if you have a secondary policy, you're still gonna have to pay 20%, and it's 20% of a much higher number. So we're really putting a lot of burden onto our patients. And then if we look at this, there is not just the cost of the ventilator involved. So a bi-PAP machine, we're just paying for the bi-PAP and that's it. For the vent, we're also paying under frequent and substantial servicing, that we are going to have caregivers in the home, respiratory therapy is available, and patients are going to be looked after in general, but at a huge increase in cost. So let's look at what these numbers are. Now, this is an older paper now to 2016, but you'll see with the blue line that if you look at an E0464, which is the home mechanical ventilator, that there's been a huge increase in the amount of devices that have been ordered, mostly because it's the same time that CMS went back to you and said, reduce your admission rates. We know that from 209 to 2015, there was an 89 fold increase, going from 3.8 million to 340 million for the cost to Medicare. And I can guarantee you those costs have gone up since that time. And if we look at the epidemiology of it, if you look back in 2009, that blue pie part on the graph is neuromuscular disease. If you look by 2015, that's all chronic respiratory failure, most of which is COPD. And so COPD is truly driving the horse here. So then recently, last year in 2022, CMS did a retrospective review looking at their data group, and I know this is too small to be seen, but let me just tell you that what they did was look at costs for COPD exacerbation patients. They did a good job of taking out anybody that had obstructive sleep apnea, anybody who had previously been diagnosed or diagnosed anywhere throughout the study, and they followed these people over a year. And what they found was that there was a significant reduction in hospital readmissions for patients who got a home mechanical ventilator with the COPD exacerbation at the time of discharge. Well, guys, wasn't that the Strzok study? Did something happen when they hopped over the Atlantic that suddenly Strzok couldn't show it, but we could show it in the US? Well, I'm gonna tell you a couple of things. First of all, when those patients got the home mechanical ventilator, they got an RT to come to the house. They had a home care company that was looking after them. If they got a BiPAP or they got nothing at all, they got no support in terms of their care. And even though this was a large database reviewed by Medicare, guess what they didn't look at? The minimal things that you and I would have. Compliance, CO2 reduction. They didn't even look at settings. We didn't know if it was high flow, we didn't know if it was low flow. They didn't know, they didn't care. So to prove that this benefit was from the use of NIV, specifically high intensity, is gonna be super hard given the environment that we're in. So in summary, this is what I would say. European data may not be relevant in the US. And even Dr. Gay admits that a big part of that is due to obesity and failure of MDs to use high intensity pressure support. The use of NIV at discharge will not predict baseline hypercapnia and over treatment will reduce efficacy over therapy. Meaning that because they didn't look at this, we don't know what the benefit was. The cost of NIV is super high. Very difficult to support given the numbers that we've seen. And the studies in the US that do support NIV start that hospital discharge due to the healthcare system needing a fix, not our patient's lungs. Lastly, patients should be evaluated once they have returned to clinic at approximately two to four weeks. Start NIV then. That's what worked for Murphy. That's what worked for Conline. And it's probably the right way to go. In the upper corner here, we have our best friend, Bob Hoover, who it turns out, Peter, did you know he has his own channel on YouTube? Yeah, it's crazy. He says on that channel that all the LCDs in the whole country are exactly alike. Yeah, that was interesting. But if Bob Hoover was with us today, he would say that we do need to fix the problem. He is one of the medical directors of the DEMIMAX who has a big influence on how we do home-based NIV. And what he would say is that if we can't fix the money problem, we can't fix the ventilation problem. Thank you, guys. Hello, everyone. I'm going to be discussing initiating long-term non-invasive in obesity hyperventilation patients who are hospitalized with an acute on chronic hypercapnic respiratory failure admission. My name's Jovica Belianovsky. My friends and colleagues call me John. My patients call me Dr. V. I work for Henry Ford Health out of Detroit, Michigan. I was informed as I was walking in that the Detroit Lions are playing right now. And just to let you know, if you're a Lions fan, and I know a couple of you are, they're winning 14-0. So we're based out of Detroit, Michigan, and we're affiliated with both Michigan State University as well as Wayne State School of Medicine. I do have some disclosures. I participate in research grants from Santa Fe, Pecorian, F&P, Fisher, and Paykel. My objectives today is to discuss if we should initiate long-term non-invasive in hospitalized OHS patients admitted with an acute on chronic hypercapnic respiratory failure admission. Which mode of pap therapy should they be discharged? And just briefly touch on, like Lisa did, with some of the challenges out there in qualifying patients. I do have a few questions. So you can either point your phone at the camera to get the QR code or navigate through the chest app. So I always try to tie in a little history when I talk. And Pinkwickian syndrome was first described in a 1956 paper. And they were discussing a professional poker player that put on a significant amount of weight and he became somnolent at the poker table, even fell asleep during a championship match. And they compared him and coined the term Pinkwickian syndrome after Joe from the Pickwick Club, which was from Charles Dickens' Pickwick Club, which was published in 1837. And as you know, Joe would often fall asleep, was described as a jovial person who would fall asleep constantly throughout the day. And likely had OSA and snored even when he was sleeping. He was actually modeled after a real life person named James Budden. And as you know, Pinkwickian syndrome is now obesity hypoventilation. And with increased obesity, the prevalence of OHS has really been on the uprise. 90% of patients with OHS do have sleep disorder, breathing with obstructive sleep apnea. And 73% of these patients have severe obstructive sleep apnea. And up to 40% of patients with obesity hypoventilation syndrome first manifest with an acute hypercapnic respiratory failure hospitalization. It's really the topic of today. And Joe really is the main character as he's participating in my clinical vignette. He's a middle-aged male who's morbidly obese and with no known past medical history, presents the hospital with an episode of acute onchronic hypercapnic respiratory failure. His ABG PaCO2 was 88. He was responsive to invasive ventilation, ultimately stabilized on non-invasive bi-level ventilation while in the ICU. His PaCO2 was 54. And he's now only requiring nocturnal, non-invasive, and is ready to be transferred to the GPU. So there are, my slide was taken out for some reason. I just noticed this. So the three questions I wanted to ask was should we initiate long-term home non-invasive? If so, when? Yes, while they're hospitalized and prior to discharge, they shouldn't leave the hospital without non-invasive. Yes, during a follow-up appointment within two to four weeks. And please answer as I'm reading these out. They will undergo a formal outpatient evaluation and titration with pap therapy in the sleep lab, ideally within three months. No, there is no indication to initiate long-term non-invasive ventilation. Thank you. So a perfect segue to the ATS guidelines, the clinical practical guidelines that were published a few years back. They attempted to answer the question, should hospitalized adults suspected of having OHS in whom the diagnosis has not yet been made, be discharged from the hospital with or without pap treatment until the diagnosis of OHS is either confirmed or ruled out? And this was a meta-analysis of 10 observational studies with 1,162 hospitalized patients with either OHS or suspected of having OHS. We often have just their BMI and ABG. And just like Joe, we don't know their past medical history. Often don't have PFTs as well. And within this meta-analysis, 10% of the patients were discharged without pap therapy while 90% were discharged with pap. And the group that was discharged without pap therapy had a three-month mortality rate of 16.8%. And the group that was discharged with pap had a mortality rate of 2.3%. And after there's an adjustment for age, sex, and baseline PaCO2, you can see the relationship held up and with the odds ratio and the estimated risk difference was 136 fewer deaths per 1,000 patients that were discharged with pap therapy. And so to paraphrase, we should, the recommendation was to discharge these patients on non-invasive ventilation therapy and then undergo a formal workup. So absolutely, these patients should be discharged from the hospital with some form of non-invasive ventilation, ideally. Which really brings me to my second question. Which form of pap therapy should we discharge the patient with? CPAP, BPAP, BPAP or a backup rate? So it could be an EO-471 or a VAPS first generation with a SETI-PAP EO-471, a VAPS home mechanical ventilator or an AE, or whatever I can get approved. Solving the Rubik's Cube is easier than figuring out the national coverage determinants slash insurance guidelines. Please take a second. Okay. Great, thank you. Thank you. So it's a perfect segue to the technical expert panel from a few years back. And Dr. Gay chaired the session, Dr. Malhotra and Dr. Wolfe were part of this panel as a collaboration between CHESS, ASM, the American Association for Respiratory Care and ATS as well. And the goal of this was, it was a virtual summit in 2020, which crafted written documents designed to achieve the provision of the right device for the right patient at the right time. So we're trying to figure out for Joe the right device for him. And we know already it should be before discharge. And so these suggestions were used in hopes of revising the current national coverage determinations. And the suggestion as it relates to obesity hyperventilation, if these hospitalized patients have persistent hypoventilation at the time of discharge, that they should be discharged with a form of BiPAP ventilation with a backup rate. Sorry. So either an ST or a VAPS mode with an EO471. But specifically in this case, Joe was denied a BPAP, BPAP ST, VAPS first generation. And per the case manager, and this, it's dot, dot, dot. The options were auto CPAP or VAPS home mechanical ventilator, even though he doesn't have COPD. And it really highlights the current disconnect between the national coverage determinations and our current guidelines and consensus expert opinion. It's highly variable. I have fellows that I trade, and there's a saying I say, which I'm about to, and they'll reach out to me and ask me for my advice in trying to qualify patients like this. And I tell them, life is like a box of chocolates. You never know what form of NIV you're gonna get next. So what happens is, you know, providers, clinicians often take the path of least resistance. And it can be, and Dr. Wolf had a similar slide. And the reason they, it's, they take the path of least resistance, they find a way to, or their case manager really finds a way to prescribe a home mechanical ventilator in these cases. And you could see the stress that it's putting on, on our medical system. Ideally, you know, if we could discharge these patients directly with BPAP ST, and know that we could do it every time, it would be ideal. And I'm going to leave you with this study. I think it's a great study by Patrick Murphy, who's been mentioned quite a bit already today. It was a dual center perspective randomized control study where they compared lab titrated VAPs versus lab titrated pressure support in super obese patients. And they measured multiple parameters for O2 and CO2. I have oxygen saturations and TCO2 charts up there. And then compared baseline, then at three months. And they also looked at blood gases as well. And they found equivalence, non-superiority. And it's interesting because you can look at it a couple different ways. You could say, hey, why should I change what I'm doing now? You know, they could follow up in the sleep lab, I'll secure follow up on the one hand. But on the other hand, you could also say, hey, I'm not sure if this patient's going to follow up. I'm not sure about access. I have so much on my plate already. So why not discharge them with a VAPs? And I know that there's equivalence in this study. Another interesting finding was that this study also strongly suggested using a target tidal volume in obesity hyperventilation patients that were super obese with 10 cc's per kg. So as you can see, Joe's doing much better now. And in summary, obesity hyperventilation patients really should be discharged from the hospital with some form of PAP therapy. And you know, it really should be non-invasive and not necessarily PAP therapy. And it should be a BPAP ST or VAPs first generation or anything with a backup rate ideally. And then I would say a BPAP and then a CPAP or auto CPAP if you can't get anything else covered. And then as you can see, qualifying patients for non-invasive may be challenging and it requires us to be creative. So thank you. All right, well, thanks very much to the organizers for having me here today. It's a pleasure to share the podium with these distinguished speakers. I'm gonna talk today about non-invasive modes. And some of you know I do work in mechanical ventilation. I do work in sleep. I don't usually talk about the transition between them, but that's my charge for today. I will say we have some data in critically ill patients looking at these mixed modes of mechanical ventilation, these volume target pressure control and whatnot. It's similar to what Kevin Gibbs in Wake Forest is seeing. About 12% of his patients have evidence of parameters that suggest they're at risk of ventilator-induced lung injury. I'm actually a little bit worried about these mixed modes and I'll talk more about that as we go. But my charge for today wasn't to talk about invasive but rather non-invasive, so that'll be my focus. I do have some disclosures which are listed down here. I did steal some slides from some of the prior speakers, including Dr. Wolfe and others. So just by way of outline, I'm gonna talk about indications for non-invasive ventilation in the ICU. I'll talk about outpatient indications. I'll do a little bit on VAPs. And I'll show you a slide to be provocative on the hospital to home transition, recognizing it's controversial at best. And then I'll summarize. So in terms of non-invasive ventilation, what's proven? We know for acute exacerbations at COPD, Laurel Borshardt showed that back in the 1990s. In acute congestive heart failure, we know CPAP works pretty well. Andrew Bernstein from Adelaide showed that in New England Journal some years ago. Post-extubation patients, high risk of re-intubation. Doing it preemptively can be quite helpful. If you wait for rescue, then Esteban had the paper suggesting worse outcomes. So post-extubation, high risk. I'll talk more about that. Somebody's bone marrow transplant, immunocompromised host. New England Journal paper about 20 years ago looked pretty good. And end-of-life care, we won't talk about a lot, but Mitch Levy and Bob Kesmeric wrote the trials on that, suggesting you can facilitate eating and communication and other things as people are dying. So this is the paper I mentioned from Andrew Bernstein from Adelaide, Australia, looking at CPAP for congestive heart failure by face masks. New England Journal, 1991. It's kind of cool to go back and look at the history of these things. And what I circled there over on the right just suggests you can make intubations go from 60 to zero in the sense you can get marked improvements with CPAP in that context of mortality in terms of in-hospital deaths. The reason I show this slide now is we have some brand new data we just published. Matt Light was the first author, and he actually went into private practice, so we didn't get to pursue this line of research. We did measure troponins in heart failure patients on the inpatient side before and after sleep. And in some cases, at least, they'd spill troponin. The sleep disorder breathing they were having on the inpatient side was enough to release a little bit of troponin and show some myocardial injury. So just, this mouse isn't behaving for me. All right, so CPAP for congestive heart failure works. We knew that from 30 years ago. Sometimes a bi-level may be worse, although it's controversial and I don't particularly believe it, but Gita made out a paper on that that often gets quoted. And then some patients will spill troponin overnight, which is something I think is new information and potentially quite interesting. I did want to talk a little bit about post-extubation non-invasive ventilation, because I think it's an important topic. It was looking at high-flow nasal cannula versus non-invasive ventilation. What's interesting here, and this is my bias as well, among critically ill patients at high risk of extubation failure, NIV works better than high-flow nasal cannula. I'm a strong believer that stabilizing the upper airway is important post-extubation, and so I see a lot of people using high-flow in the context of that, and it probably works, but I think NIV is better. There have been some direct comparisons done. This was published recently in European Respiratory Journal. You can see high-flow nasal oxygen shown here looks somewhat better, NIV perhaps better. Hard to say that directly comparing them in these meta-analyses, there's much difference, but my bias is that non-invasive ventilation does better than high-flow post-extubation. And then this is just a word of caution that I think people remember from Esteban, New England Journal, from 2004 now. If you wait for rescue, so you look at patients who are extubated and they start struggling, if you wait for rescue, this paper suggests worse outcomes. Non-invasive positive pressure ventilation does not prevent the need for re-intubation or reduced mortality in these patients. So NIV is worse if you do it for rescue, but it works preemptively. Sorry, that's the typo there. And NIV is better than high-flow nasal cannula. That's at least my bias post-extubation. Did wanna say a little bit about outpatient indications for non-invasive ventilation as we talk about this transition. So previous speakers already touched on this. Hypercapnic COPD, we have the Conline and the Murphy papers that we know about. And neuromuscular disease, there's not a lot in terms of randomized trials, but certainly clinical experience would just mark benefits there. Obesity hyperventilation, we just heard about, and certainly there's some benefits there, although debatable whether anything is better than CPAP. There's CPAP rescues for obstructive sleep apnea patients who are struggling with CPAP. We recently published that they may do better at the bi-level using a big data analysis. And Matt Naughton down in Melbourne, Australia has some data on cystic fibrosis. In a very small but randomized crossover study, did see some better outcomes in the outpatient setting. So Conline study we've already heard about, and I won't dwell on it because it's already been covered. The goal here was to attack aggressively hypercapnia and lower the CO2 by at least 20%. And in that context, they did see the survival advantage. Very aggressive inspiratory positive airway pressures that don't seem to lead to pneumothorax. They're very stoic patients, as was alluded to in Germany and Austria, that are very adherent with therapy. And you can see this marked improvement as far as outcomes are concerned, comparing controls and intervention in terms of mortality. It's also worth pointing out, if you look at quality of life, there's really some separation here. The better quality of life is down here. The intervention group is slightly worse maybe in terms of, or slightly better, I'm sorry, in terms of quality of life, but not by much. And here it's also very toying with significance. Worse down here, the control group slightly worse perhaps. There's also this rescue study that was already talked about in COPD patients. The goal here was to give inspiratory pressures at 14, expiratory pressures at four. And looking at nocturnal nonvasive ventilation, this is the STRUX study we've already heard about. These patients weren't very hypercapnic. At least some of them would have recovered following the hospitalizations and aggressively managing these patients more than 40 hours after termination of ventilatory support showed no benefits. This has already been talked about, so we'll dwell on it. The bottom line is the curves look the same in terms of survival shown here in time on the x-axis. And the Murphy study we've already just heard about is the HOT-HMV study where they did show some benefits. The difference here was aggressive IPAP and these patients were hypercapnic with aggressive lowering of CO2. And clear separation here in terms of admission-free survival favoring intervention. I did want to say a little bit about this rescue situation. So if you have CPAP-treated obstructive sleep apnea patients and they're struggling, we did this big data analysis. This is from MedxCloud, which is an academic industry partnership where we look at these big data things and the academics in the group are Jean-Louis Pepin, Peter Sestilli, and myself. And looking at thousands of patients we're able to draw conclusions that aren't obvious in randomized trials. So we're looking at adherence here, average daily use shown here, and then looking at the days of switch. The patients, when they switch from CPAP to bi-level, in fact, you do see some improvements in average daily usage. And perhaps the earlier they switch, the better. And so these are big data analyses from hundreds of patients shown here. There is potentially some benefit of switching patients to CPAP to bi-level and perhaps the earlier, the better. And there are very few data showing bi-level does much in obstructive sleep apnea per se. But this is at least one big data analysis showing potential benefits, albeit not a randomized trial. I did want to say a little bit about the cystic fibrosis thing as well, just because this is often overlooked. Matt Naughton down in Melbourne, Australia did this randomized crossover study, a very small study, but six weeks of non-invasive ventilation did show some benefits as far as dyspnea was concerned, ventilation, exercise, et cetera. And so I think we probably underutilized this and we see some improvements in cystic fibrosis patients when we discharge them from hospital. Okay, so a little bit about volume-assured pressure support. As I say, I'm a little bit nervous about these in the invasive side. When you look at volume-targeted pressure control, there's some evidence that some of those patients will get ventilator-induced lung injury or at least be at risk of that from high transpulmonary pressures. So we know the volume-targeted pressure support, these are hybrid modes of non-invasive ventilation that self-adjust the pressure and respiratory rate, perhaps, and use proprietary negative feedback algorithms which are defined to target a preset level of tidal volume or minute ventilation. Different companies use different algorithms which I won't get into today. You can see if you have a certain set tidal volume, it'll go up on the IPAP until you target, until you reach the target tidal volume. In patients who have variable respiratory effort, you can sometimes exceed the desired volume as well. You can target alveolar volume with different modes here, and as you can see, the maximum pressure support shown here, the volumes can sometimes exceed. This was mentioned already, but in terms of obesity hyperventilation syndrome, long-term clinical effectiveness of CPAP versus non-invasive ventilation for obesity hyperventilation syndrome, really no difference whatsoever. So CPAP is probably okay for obesity hyperventilation syndrome. My bias is that some of these patients will do better with non-invasive, but certainly the existing data has suggested that CPAP is probably pretty good. I did want to say a little bit about this paper we just published as well, looking at the effectiveness of long-term non-invasive ventilation. This is looking at downloads from the machines, and there are different things that change over time in terms of ALS patients and non-ALS patients. Bottom line here is the ventilator needs change over time, perhaps more in ALS patients than non-ALS patients. These volume-assured pressure support may be more stable ventilation over time, and when we did see death, it was related to proportion of use and not necessarily based on the ventilatory parameters. Again, these are observational data, so I don't want to make too much of them, but they suggest at least that there may be some value in keeping ventilation stable with these volume-assured modes. It is hard to find very much in the way of positive studies in terms of this type of technology. If you look at volume-targeted pressure support, automatically titrates the IPAP to generate a certain target volume. I mentioned the Pickwick study already. And a bunch of other studies, I think this is Lisa's slide, the Stora study, the Janssen study, and the Murphy study, all showing surrogate outcome benefits, but really nothing to write home about in all very small samples here. So I think there's considerable room for improvement, at least in obesity hypermethylation syndrome. If you look at these in COPD, again, very small studies, and again, in aggregate, the data are equivocal whether there's any benefit to these types of approaches. I did want to show one slide just to be provocative in terms of the hospital-to-home transition, then I'll wrap up. This is a study out of Israel. They studied about 600 patients, and they looked at different groups here. The NIV group is shown in blue. And this is, sorry, it's hard to read here. Survival probability on the top graph, and readmission probability on the lower graph. And if anything, it looks worse with the non-invasive ventilation than the controls. This is transition from hospital-to-home with non-invasive ventilation. Who benefits? The answer is they look like they're doing slightly worse. It was already mentioned that assess these patients two weeks later may be adequate. You wonder if it might actually be even worse to aggressively intervene too early. I'm sure this is confounded. I'm sure the sicker patients are getting more aggressive interventions for a reason. But it was a reason for pause. Transitioning to home non-invasive ventilation after hypercapnic hospitalization may be useful in younger, cooperative patients with chronic respiratory disease. That's perhaps wishful thinking because the data are going in the opposite direction for the overall group. But for older patients and those with cardiac disease, home non-invasive ventilation may not be beneficial. May actually be harmful. And again, just a reason for pause because we often complain that the insurance won't cover these things, so we need to aggressively treat things. But I think we need more randomized trials as well to really prove benefit for this approach. So I'll summarize by saying a couple things. I miss a lot of obesity hyperventilation syndrome even though I look for it, both in the ICU and in the outpatient setting. One study out of Spain suggested the majority of OHS actually presents in the ICU because that's where we check blood gases. In my view, the sleep field is overused nocturnal oxygen. I don't know any positive studies for anything for nocturnal oxygen. Volume-assured pressure modes need more data, at least in my view. These intelligent backup rates of various kinds may have some value. Time will tell. Bi-level without a backup rate is usually okay for hypoventilation. For obesity hyperventilation, CPAP may be fine. And some of this is more art than science and a lot of troubleshooting, a lot of back and forth with individual patients and dealing with insurance things is part of the game here. So I'll stop there. I'd like to thank you all for your attention. ♪♪

long-term non-invasive ventilation

hypercapnic COPD

home bi-level positive airway pressure

mortality

obesity hypoventilation syndrome

CPAP

non-invasive ventilation

reintubation

randomized controlled trials