Thank you very much for being here. I just checked the temperature in New York. It's 20 degrees. So, nice to be in the warm weather, but hopefully we're not going to miss the playoffs today. So, I'm going to be talking about respiratory failure and ARDS and how we're going to address that. First, I have to really thank Javier for helping me with this talk and all the text. Please check your email, the due date to upload the slides today. And he was very, very supportive during the whole process. Here's the disclosure, and nothing has to do with that in the meantime. We're going to cover at least four aspects of how we treat ARDS. First, what is the pathophysiology of ARDS? Is how are we going to apply oxygen supplementation? What are modalities? Not going to go in details on event management, but we're going to explore a couple of new things, how we treat ARDS, which just came after COVID. And also, what the other adjuvant therapy. Is there anything else other than the ventilator? And we're going to talk about ECMO, and I'm going to talk to you about transplant. First of all, ARDS, it's an old disease. I mean, 200 years ago, there was the first talk about ARDS. It's not until 1964 when the first article came about ARDS. Since then, there are multiple definitions over the course of the year about ARDS. Certain things stayed the same, which is like dyspnea, hypoxemia, abnormal chest X-ray. All that, we'll see it from one year, from one definition to another. Except one thing. In 1967, it was done on autopsy. And hopefully, this is basically our definition, not going to depend on what we found on autopsy, but on, you know, hopefully keep this patient alive and gone. I think it's 1994 was basically the most, the first, I would say, reasonable or where really the changes started. And ARDS is defined that you really have, you know, hypoxemia, where it stayed the same, mild, moderate, and severe, depends on PO2, FiO2 ratio. But also, you're going to have to have bilateral infiltrated in the X-ray. In that time, everybody was getting swan, and we maintained a low filling. We have to have a low filling pressures on the pulmonary artery catheters. But what happens since then? So, this is about 20 years after, and they came up the Berlin definition. And the Berlin definition, a few years after, basically in this publication that came in in January of this year, that was online at the end of last year, there's some changes. And thank God for COVID and how we treat ARDS, incorporated the new changes on the technology and our understanding of ARDS. First of all, we'll touch on the ARDS by Berlin definition, which came about in 2012. Timing, and this is one of the new things that was different from the previous one, is it has to be within the seven days. So, you have to have respiratory failure not older than one week. Because I think at that time, you go into the fibrotic changes and you really go into a totally different pathology. It will have to be still maintained that it's not a cardiac. That means it's not pulmonary edema. It is purely pulmonary process, which could be related to pulmonary or extra pulmonary causes of ARDS. So, that is kind of more state the same, a little more explanation. But the new thing is it has to be intubated and using a PEEP about five or more. Imaging, state the same, chest X-ray or a CT scan that shows by lateral incisional infiltrate that is not explained by alexis, pleural fusion, or pulmonary edema. And the definition of severity maintained the same, PO2, FI2, 300, 200, and 100. That's maintained the same. But over the course of 10 years, and having COVID, and we all ran out of ventilators, we all got afraid to intubate these patients, and we kept them on noninvasive ventilation high flow. So, from that, we treated ARDS differently. And we did proning, you know, weight proning. So, I think it was, it took less than 20 years to adjust the modification of ARDS. The first two items, timing and origin, stayed the same. But what happened if you're not going to intubate the patient? And now, what if you put a patient on high flow, or you put the patient on noninvasive ventilation? That incorporated in the new definition. So, you don't have to have intubated and have the patient on the PEEP. But you can have the patient at least more than 30 liters per minute high flow or a noninvasive ventilation with a CPAP or EPAP of a pressure of 5 centimeter of water. So, that is basically something new incorporated in that. Imaging, we mentioned about the POCRs. And it comes back again. We use all ultrasounds. So, you can use the ultrasound. Everybody gets an X-ray. But sometimes, we confirm if this is a B-line or not a B-line, this is fluid overload and not fluid overload. So, that's where the ultrasound is, you know, input here that we're not dealing with pulmonary edema. We're dealing with pulmonary pathology. And we can go into how ERDS looks on the ultrasound. But it's a totally different topic. But now, we don't use A-lines. We're doing SWANs. But, you know, we don't use A-lines anymore. We put less and less A-lines at this point. And we use SAT. I ran a trial during COVID. And we used the SAT. There is a lot of articles now using that, you know, qualify using the SAT. So, what they incorporated in this, which is new, the SAT FIA-2 ratio less than 350. One of the things is, or we started to pay attention, is pre-war experience. We're, you know, we're not going to practice medicine in academic center with residency and fellowship programs. There are certain places around this globe that don't have that technology, don't have the resources that we do have in the United States or other developed countries. So, one thing, and I think it was really fair to, this is a global initiative. And this is what the title of the article that came, Global Definition of ERDS. So, they put here is, what is the definition in countries that don't have the resources that we have in a developed country? That you really don't need a high flow, don't need 30 liters, that you can use the SAT and FIA-2. So, this is actually, made it very simple. And I know a lot of major institutions like NIH is really incorporating pre-war experience in the definition. And I think this is something to broaden the aspect and really involve people that not a privilege as like how we practice here. So, from here, to open the discussion, we really understand what is ERDS. And now, we have the definition. But as you see, ERDS, what S stands for. It stands for syndrome. Syndrome means it's a local inflammatory process that affect every organ in the body, but it's not just the lung. The lung is one element. And there's a very nice article in the Respiratory Lancet that goes really in details in what is the inflammation. Yes, in autopsy or pathology, you got a high-lying membrane, you got high-rich protein, and a lot of inflammatory cells filling the alveoli, and all such things, good things. But this is related to mediators that is created in the body that give you that serous or the systemic effect. Why you got a, you know, why we got a renal dysfunction? Why we get liver dysfunction? Why we get a GI dysmotility? What happened to the heart? So, the lung is one organ that is involved in the whole process that involve every organs. But what happened in the lung, and we're going to focus here because we're talking about just ERDS and respiratory, how we're going to treat ERDS from respiratory point of view, it's all physiology. It's raising when you have a high-lying membrane, alveoli, filled inflammatory process, and statistician, maybe infiltration in the statistician, you got a little bit of basically decrease in the lung compliance. And we understand physiology, how you're going to, you know, expand and get in your tidal volume as the gradient between the pressure in the alveoli and atmospheric pressure, then you need to generate that intraplural pressure, and that is generated by the respiratory muscles need to act. So, if you have a lot of work, then you're going to get tired, and basically the work of breathing is going to be more. And then where you get the VQ scan and the shunting, and also we know the alveolar and the dead space ventilation is easy. The end point is the minute ventilation, but when you have decreased alveolar ventilation, increased dead space ventilation, then you really start having this hypoxemia and CO2 retention. But one thing we started to pay attention to is the vascular. What happened to the pulmonary circulation? Yes, we talk about positive pressure ventilation, and that how much of that positive pressure ventilation that transmitted to the pulmonary vascular bed, and whether your lung compliance is poor or good, how much of this PEEP and transmitted. But we forget that a part of this systemic reaction is, there's some mediators that really vasoconstricting to pulmonary pressure. And hypoxemia is one factor, you got vasoconstriction when you got pulmonary hypertension, and then after that, you get strain on the right ventricle. And you heard from the previous speaker that right ventricular assist modalities is what you're gonna use to help the heart. But how the heart fail is, part of it is from the pulmonary hypertension as part of the end point of all the passive physiology, whether this is from hypoxemia, this is from positive pressure ventilation, and other factors. So understanding a little bit, this is kind of first how we're gonna treat that. This article is from 2019. And I said, understanding of ARDS and how we treat it dramatically changed. And anybody saw that from the Blue Journal in the first week of January, and actually updated the slides today to see what happened in the last five years, what changed in the last five years. But you can see here at the bottom, first, you know, this segment here, I don't know, is one thing we need to do is before we start playing is understand and confirm is it ARDS or not. I think this is first thing is we need to confirm that we're not dealing with a cardiac etiology. As you said, our patients are older, are patient on a lot of drugs, and make sure that we're not dealing with a cardiac, the treatment is gonna be different. We're not gonna apply treatment ARDS when you're treating with pulmonary edema. So once you confirm this, this slide talks about intubation and pushing the patient on a P. And it goes in a step way fashion, it depends about the severity of ARDS. First thing is we all know that the great work that was done about lung protection ventilation and keeping the tidal volume at six ml per kilogram predictive body weight and use, you know, people five or more that keep the plateau pressure of 30. Some people clinically try to keep the plateau pressure at less than 30 or as low as you can. I'd like to keep it at 20 if you can be, but the cutoff is not more than 30. And this is the reason why for that we're trying to use ventilator-induced lung injury. And after that, you know, using on a higher PEEP and proning, ear muscle blockade, and the last thing in ECMO and everything is really depends on PF ratio. That means we have a lot of options. One thing on the right hand of the slide, you see different colors, the red, light of lead. So one thing they really agree on, and this hasn't changed, recruitment maneuver. I, you know, how many here did recruitment maneuver and things that we know that the blood pressure is dropping and is exactly is what the impact on the right side of the heart and maybe causing better trauma or not. But at that time, the recommendation was totally against recruitment, high-frequency oscillation also was not recommended. And this is actually in 2024, that I'll show you in the next slide, it still stayed the same. But ECMO or ECMO-C2 removal, driving pressure was questionable, but using nitric acid as a part of the treatment was not really still, was really questionable. But to talk a little specifically about the neuromuscular blockade, the neuromuscular blockers, you can use it within 48 hours, you can use proning within at least 16 hour a day, and you can use ECMO, but the data was not as strong in that. But you can look at this graph here, it's not, this is not the sign of the cross at the end of the life, but this is a really summary, a kind of more of a direction. The three more thing is, six millimeter per kilogram predicted body weight, the P is greater than 30, and we assess the patient. So this is kind of more as a campus, this is basically where the three main elements you can use and go from there. But I added this slide this morning, and this is the 2024 guidelines for management of ERDS. There were two articles back to back in the journal, the new definition, and also the new guidance for treatment. Nothing major, but I think it's the outline here is better, because it give us exactly what to use and when to use. And one thing in element is the steroids about ERDS, this is basically for decades now, came out now as conditional recommendation to use it. So the lung protective ventilation here is not six, four to eight. So this is variability is, that's four to eight. Sometimes we have a lot of, we use the six, but I think the patient was still air hungry, and we had to go to eight ml per kilogram predicted body weight, but it still give you a nice range between four to eight. So I think this is confirming up to date, the data really support protective lung ventilation with the target volume. And also that stand also for non-invasive ventilation. We all know about ventilation induced lung injury that been published recently in the guidelines. So even if you use non-invasive ventilation, you need to worry about that. Proning is actually coming up a little higher on the ladder. And this is the experience that we gained from COVID. And I think also the few things that proven to affect the outcome on ERDS, proning and neuromuscular blockade, anybody will take the boards that always get there. Steroids went in there and wasn't in the previous definition, but steroids is coming in the definition and also neuromuscular blockade. And you can see, you can map down what exactly, if we know the neuromuscular proning, you have to have a PF ratio about 150. I think this is a good parameters that we can follow. And they follow this with a little bit, kind of more summarize the article in the table. So steroids, it's basically give you where to do it, but it's a good things that they say, be careful when the patient that has metabolic syndrome. I don't want to put the guy in a patient in DKA. Also the patient has some infectious process. So use your own judgment. It's not a slam dunk. I put steroids as a patient. Yeah, yeah. Have a patient that has an infectious process, but also there's no guidance about the dose. But one thing is good point here. Once the patient's starting to improve, start lowering the dose, she would be off by the time the patient extubated. So use whatever dose you think right. And then, but take it off once the patient extubated. The ECMO guidelines. Don't use it as somebody who's really, has an irreversible disease, or already has a poor prognosis. Save your resources. This is a very high resource. It's got an investment in high, but high resource. So it give us there when not to use it, but also you have to, you know, exhausted all other resources before you go to ECMO. So it's not something you rush into it, but something you have, this is the last point. Also with neuromuscular blockade, you also have to be aware about critical illness, perineuropathy, and myopathy, and the weakness. Use it, but not more than within the 48 hours, and not more than 48 hours. Once the patient is getting better, start taking them off the neuromuscular blockade. Hypeep is very cautious in here of Hypeep. Make sure as the peak pressure is less than 30. No matter what parameters, how are you going to titrate the peep, but there's a really good word about barotrauma, keep your peak pressure as low. So I thought this is really nice area to talk about. And basically is, this is what we have in the lung transplant, vasodilators, all the other stuff that controversial, but we have more to talk about. So what in this is the European Society of Intensive Care Medicine in June of this year came up with the recommendation, and they broke it down mortality, risk of intubation, COVID, and non-COVID. So when you're high flow, actually, I was really surprised, you all did. Remember in 2020, when everybody say high flow and non-invasive, it's like all this drama about it, and we used it in a way because we didn't have any other choices. It basically, it works and decrease intubation, but not mortality. And the same thing for COVID, it came in a stronger recommendation to use it and to decrease the risk of intubation, but not mortality. I'm happy with that. And this is another meta-analysis, were published in 2023. See all the articles is very new articles within the last year, within a year. And actually you can see that all the articles became positive about high flow. You know, high flow is good, high flow, use it, but use the ROCS index, so you'll see when you're gonna fail. Intubate early, you have to, as good as non-invasive ventilation. Even some of the articles went to say it's better than non-invasive ventilation or even improve mortality. But the summary is, it's a new approach, it can be used, can decrease the risk of intubation, but also decrease the side effects from being on the ventilator, sedation, paralytics, and oh, patient get out of the bed, but also be aware of what the underlying challenge is. If you have, you know, a tissue-aligned disease is not gonna work. So just, it's gonna fail, unless you have end of life, we're talking about this. So, but there's a caveat here. All the articles says is high mortality is when to escalate, when to switch gears. And I think if we're gonna use it, and people are telling us, use it and decrease the risk of intubation, but we need to know why it didn't change mortality, because maybe we didn't intubate earlier. So this is kind of the parameters. People went to look at the respiratory rate, the pressure, oxygenation, delirium, some scores, but the most important things is the ROC score, which is basically your SAT FA2 divided by the breathing test. So ROC's index is very important to work. And this article actually answered the question, did I use it within two hours, or how long should I wait before I say I failed? Two hours, six hours, 12 hours, and what a good number to use. So this article actually compared the two arms, a failed and successful trial, they found is there's no difference between two hours and 12 hours. So we can put them a high flow, look at the ROC's index, and average is about between four to three and a half. And if you find after two hours, you're not moving, why wait? Two hours is good at six hours. If you're not gonna move, that means you need to escalate. Maybe this is what the factor is. And we did it around the curve, and it had a good sensitivity, but its specificity was not that great, but the curve was pretty good, and uses a good parameter that we can follow. Non-invasive ventilation and CPAP. You think you're gonna come up with a good recommendation, but no, and actually it does not differ if you have COVID or non-COVID. They really were unable to make a recommendation for mortality or intubation, but maybe CPAP and COVID might help decrease intubation. So non-invasive ventilation, the numbers were not bad. First, the graph about how to use that the driving pressure was not there. The driving pressure is a reflection of lung compliance. And the more bigger type of volume, the more compliant lung, you're gonna need less peak pressure. You'll have a, I'm sorry, less plateau pressure, and have a less peak. But this is actually the article showed that the driving pressure is correlates mortality. The lower the driving pressure, the better is survival rate. And this article actually, you can see the lower the driving pressure, the lower the tidal volume, and the better mortality. And what they concluded is, one standard deviation, and the driving pressure improved mortality, and recommended to keep the driving pressure 15. And I think this is a reflection of a lung compliance as we re-extend data from our clinical practice. PEEP, I think PEEP is very good. Here to come in PEEP for either what to use, whether use compliance, use plateau pressure, whether use the oxygen requirement, it doesn't matter. But they came with a strong recommendation. They're unable to recommend any parameters, but maybe in COVID, that really is really did not come in with their recommendation to get PRONI. PRONI, we know it works, and it came as supported over the strong recommendation. It works in cases. But the idea is, I'm sorry, I'm speeding. I wanna keep on time, is awake PRONI. I would experience it worked. And one thing is I take from our faculty is we start forgetting about PRONI after the COVID. It works. Why are we not using in non-COVID? Yes, they're still here. And why? Because maybe you don't have many much trials, and maybe we're not using it, but then we're not able to give us any recommendation. But it was kind of weak recommendation. It can decrease risk of intubation in COVID, but not mortality. We saw nothing really affect mortality. ECMO, everything is coming after EOLA trial and the stronger recommendation that can use it in ERDS. This is the EOLA trial. We showed that the primary end point was not much difference between the control and the trial, but the secondary end points was there. When you look at the different outcomes here, it found that when they lived longer, 90 days, they stayed in the ICU longer, they stayed in the hospital longer, they used more ventilator. But anyway, less PRONI, less recruitment, because it doesn't have nitric oxide. And it was really safe. There was really much difference. The only difference in the adverse event is thrombocytopenia and bleeding tendency. So it looks like they came up with the conclusion is it looked like it lasted a graph for 60 days. There's really not much mortality. But also, it's a last resort. We had a patient, 37 years old, went into ERDS. Why can't I say, okay, the statistic is not significant? Anyway, a patient's gonna die. What's the worth of trying? But this is kind of more where you use your clinical judgment. Here was really touched on, but I'm gonna talk at tandem heart. Really need to know when you're gonna use any right assist, right tandem heart, which goes from the right atrium to the pulmonary artery. You're unloading the right heart, but you're increasing the filling pressure. It might increase the native coronary cancer input. So I think there's something we talk about maybe next year or the year after. We'll have more to talk about. Right ventricular assist, this is all last resort. And thank you for listening. And I hope I didn't put you to sleep after the heavy lunch. It was good. Thank you.

respiratory failure

ARDS

treatment approaches

Berlin definition

COVID impact

individualized care