Thanks very much for the invitation to speak and my talk goes very nicely with Asad, who's already basically told you the whole story. I have more questions than answers for you, unfortunately, about what we should do. Here are my disclosures and I'm going to be speaking about any specific products. And, oh, I have more slides in the recorded presentation, realize this is over the time, so there are some patient photos there of proning on ECMO, which I'll briefly mention, but if you want to see some more information, it's available in the recording. So the objectives are really just to talk about the types of mechanical support that could be pursued in patients with RV failure, and I focus mostly exclusively on sort of giving the flavor of the session on acute causes, so ARDS, and to review the current evidence that we have for those mechanical supports in these patients. So, again, speaking about the neglected ventricle, I want to give a shout-out to one of my friends and colleagues from the Cleveland Clinic, Max Zuba, who's very active on social media, is constantly promoting the forgotten or neglected ventricle, the right ventricle, he calls it the people's ventricle, and so we're really, like, not thinking too much about it, but to talk, again, about ARDS in general, because many of the principles, and that's where our data is, apply on ECMO patients, and, in fact, you might surmise, and that's our hypothesis at the moment, is that ECMO facilitates the delivery of some of these RV protective strategies. We focused exclusively for many, many years on the lung, lung protection, lung protection, lung protection, we're now understanding that we need to think more holistically about protecting all kinds of other things, right, the diaphragm, lung and diaphragm protective ventilation, and maybe lung, diaphragm, and RV protective ventilation. So we're talking about ventilatory strategy, prone positioning, not going to speak too much, again, because this is mostly my focus on the lung, so hemodynamic support and inhaled pulmonary vasodilators, then, of course, extracorporeal support. The first thing to recognize, again, this idea that it's under-recognized, is that it's exceedingly common. I think we don't think about this very much when we see ARDS patients, and maybe we've thought about it more with the slew and onslaught of COVID-19 patients that many of us have faced in the last three years, but RV failure or RV dysfunction in patients who have ARDS is extremely common. A lot of this great work has been done by our colleagues in France, led by Antoine Villar-Boron, showing that across a number of studies, the incidence of RV dysfunction or RV failure ranges from like 10 to 60 percent, and certainly increases with increasing severity of illness, and again, COVID was another good example. So it's very common, and we don't, I would say, I may be able to speak for myself, in my ICU, we're not typically thinking too much of our strategies or what we're doing in terms of how they affect the RV until, of course, there's shock or some other reason to think about that other organ dysfunction. We're typically, again, very focused on lung protection, but the first thing to recognize is that we're not thinking about RV failure or RV dysfunction enough, and it happens very commonly in patients with ARDS. Now, then the idea is that a lot of things we do, the good news is that a lot of evidence-based things that we do with mechanical ventilation, prone positioning, the setting of PEEP, actually has beneficial effects on the right ventricle. So again, primarily the idea that fixing hypoxemia, solving hypercapnia, these things which are, have a strong vasoactive influence on the pulmonary circulation and can reduce pulmonary vascular resistance, we typically try to target these things in ARDS with our mechanical ventilation strategy, so ways to solve hypoxemia and hypercapnia can be very important, and again, this idea that lung stress, not only is it bad for the lung, ventilator-induced lung injury, ventilator- induced lung injury, ventilator-induced lung injury, but limiting tidal volume to limit plateau pressure, and again, now maybe perhaps a focus on driving pressure, strategies to protect the lung also seem to have salutary effects on the right ventricle, and again, Antoine Villar-Baron has done a number of studies suggesting that keeping plateau pressure below 27, and that probably has a driving pressure correlate, can lead to benefits because of the stress, the pleural pressure, the heart lives inside the chest, and those stresses can be transmitted in the wrong patients to the right heart and cause more RV dysfunction. And perhaps a good graphical example of that is this nice study by Luciano Gannoni, published a few years ago in the New England Journal, showing this idea that when you apply high pressure ventilation, whether that's driving pressure or in particular PEEP, to patients where you're not recruiting lung, all that pressure is just getting transmitted to the heart and probably exacerbating the underlying RV failure. So if you look at these two CT scans, here's a patient who has probably milder ARDS, not a lung of parenchymal disease, mostly in the dependent regions, not a lot going on there, has a low potential for recruitment. There's not a lot of collapsed or atelitic lung that could be recruited with PEEP or recruitment maneuvers or that sort of thing. Contrast that with here on the right, you could see a person who is probably more moderate to severe ARDS, lots more disease, lots more potential for recruitment. And if you apply higher levels of PEEP, the interesting thing here is because we're talking about the RV, focus on the mediastinum, right? So you see on the left, when you apply higher pressure, you go from a pressure of 5 centimeters of water up to 45 centimeters of water, everything in the mediastinum is getting squished because the lung is already pretty compliant, there's not much to recruit, all that gets transmitted to the heart and you're going to probably have hemodynamic collapse and shock. Versus in the person who has a higher potential for recruitment, there's not much change because again, the balance is in recruiting lung that probably again leads to a more optimal lung volume, maybe a drop in pulmonary vascular resistance and improvement in RV function and no hemodynamic change. So we want to apply these things. I mean, of course, you come to these meetings, we'll be talking about optimal PEEP till the end of time, right? In 2050, SCCM will take place on the moon and we'll still be talking about what optimal PEEP will be. We don't really know the answer to that. The other interesting thing is prone positioning, which we know has a dramatic mortality benefit for patients with moderate to severe ARDS, also has a very important role in unloading the right ventricle. And again, probably because some patients who have a good response to prone positioning in terms of gas exchange, there's better control of hypoxemia, perhaps less hypercapnia at no expense of increasing ventilatory pressure, right? And prone positioning then homogenizes the distribution of ventilation in the lungs, sort of making the forces quite even. And again, that probably leads to better function for the RV. And again, this is a nice study by Antoine V. Arberon showing that again, not surprisingly in black is acute core pulmonality or RV failure. It increases with increasing CO2. It increases with increasing plateau pressure before prone positioning. And then in a group of 21 patients, maybe just focus on this. I apologize, it's very small. But in those who get proned after 18 hours, there was an improvement you already heard from our previous speakers, that improvement in the end diastolic area when we compare RV to LV and decreasing in eccentricity sort of echo correlates suggesting there's better RV performance in the prone position rather than in the supine position. So we put this all together and we try, of course, these conservative measures. We try to use lung protective ventilation, low driving pressures, low tidal volumes, try to put optimal PEEP to recruit lung where it's possible. Try to not apply high PEEP in patients who don't have a lot of recruitable lung and are at risk of overdistension. Again, I'm not going to speak specifically. You might have a trial of inhaled pulmonary vasodilators. Again, if there's RV dysfunction with hemodynamic compromise and prone positioning in patients who don't have a contraindication. And when those fail, that might be the patients that then we want to consider for extra corporeal support. And the idea here, of course, is that all these concepts that we talked about could be, if you will, better applied or more dramatically applied when the patient's on ECMO. So the ECMO will correct the hypoxemia, will correct the hypercapnia, and again we don't have to worry too much about, for instance, reducing intensity of mechanical ventilation or these sorts of things because the consequences, higher CO2, worsening acidosis, more hypoxemia, we could correct those with the extra corporeal circuit. So we can, in fact, deliver lower driving pressure while maintaining gas exchange, maybe to have these beneficial effects exemplified. When I go to meetings in Europe, often our colleagues say, yeah, but if you apply ultra-low mechanical ventilation in these patients with tidal volumes in the one to three sort of mils per kilo range, you're gonna have shock because the lung will collapse, it'll increase PVR, and you're gonna have a lot of RV failure. The interesting thing is that we don't actually see that clinically, at least in my ICU. We didn't see that in a small study that we did where we looked at RV function, we looked at many of the parameters that you heard our previous speakers talk about, and even when we dramatically reduced tidal volume down to an average of two mils per kilo and the driving pressure dropped from 18 to 10 following cannulation, really, again, we saw that RV dilatation and dysfunction was already common in the pre-ECMO setting, these are very severe ARDS patients, that it really didn't change very much. So it didn't get very better in this small sample of patients, but it didn't worsen, and we certainly clinically didn't see any RV-related shock in these patients. And in fact, we now know that probably you could reverse a lot of these things, again, by fixing hypoxemia, fixing hypercapnia, and reducing intensity of mechanical ventilation. This is a nice study in COVID patients from our colleagues in La Petite in Paris, published in the Blue Journal just recently, showing, again, no matter how you measure it, you put the patients on ECMO, there's a reduction in CO2, there's improvements in echocardiographic signs of RV performance after you put them on ECMO, which, again, might be related to the improvements in gas exchange, but probably also related to the subsequent or concomitant reduction in mechanical ventilation intensity. It's important, though, to understand that even though we try these things in ECMO, some patients who are very severe, and again, COVID was a very good example, will still have serious RV dysfunction or failure while on VV-ECMO, and we did this nice study led by our colleagues in Europe, showing systematic review, showing that if you still have RV dysfunction after you try to do all these optimizations, that's associated with increased mortality. So again, very important for us to start focusing more on RV dysfunction in these patients, even the most, especially the most severe ones, who even get on to VV-ECMO, because they still can have some residual RV dysfunction and failure. And then, as already mentioned by Asad, we're very interested with the idea, then again, broadening the scope. We want to protect the lung, we want to protect the diaphragm and the muscles, we want to protect the RV, but we also want to protect the patient. We want them awake, calm, cooperative, mobile, off the ventilator, no ventilation, no ventilator induced lung injury. Very interested by this report from our colleagues in Chicago, showing in COVID, these weren't the COVID patients I saw in my ICU, but they put in like a VV-ECMO with a venopulmonary configuration, where the tip is in the pulmonary artery, conjectured that a lot of the benefits that they saw were related to more stable oxygenation, less recirculation, and perhaps RV protection. They got these patients off the ventilator, some of them with a tracheostomy, they were up and moving and awake. So we're very interested in seeing that perhaps there are benefits to using this kind of oxy-RVAD or this venopulmonary route. There's some data that suggests, again, in a systematic view, that this could be associated with lower mortality, less AKI, less need for dialysis. So very interesting hypothesis that obviously needs to be tested in some prospective studies. And I just want to end with the idea that what we really need is the questions are, so how do we do these things? In what order? How quickly? When should we implement? Because again, the idea is that you got to do these things early, because if you wait too late, even if they're very efficacious, they're not going to work. So I like to call this the black hole theory of rescue therapy. So we already heard from our colleagues that prevention is better than treatment. If you wait too late and you pass the event horizon, even if some of these things are very useful, the patient's going to die. So even if the therapy is actually successful when you add it early, if you wait too long, it's not going to work. They're already going to be unfortunately circling the event horizon and then heading towards the singularity, which unfortunately in this situation is death. So we really need research to help us clarify the optimal timing of interventions and treatment algorithms for all of these interventions in these very sick patients. Again, including the optimal ventilatory strategy, prone positioning, maybe some inhaled vasodilators, and what the role of extracorporeal support might be, and perhaps if there are some additional benefits of using this phenopulmonary configuration. So with that, I'll finish. Happy to answer questions at the end of the session. Thanks very much.

right ventricular failure

acute respiratory distress syndrome

mechanical ventilation

prone positioning

extracorporeal support