Good afternoon. My name is Ulrich Schmidt from San Diego and I will be the moderator for a session for the next two hours for Must Know Controversies in Venu Arterial ECMO Support. It is really a pleasure and I'm looking forward for a wonderful session the next two hours. Thanks so much for attending. Good afternoon. My name is Shibashis Chatterjee. I'm a cardiovascular surgeon and an intensivist at the Baylor College of Medicine Texas Heart Institute in Houston and today we'll discuss upfront veno arterial ECMO for massive pulmonary embolism. I'd like to thank the meeting organizers at the SCCM for the opportunity to discuss this topic. So today what we'll begin with is first characterizing massive pulmonary embolism. We'll talk about real quickly the treatment options that are available, what the results with ECMO are, and what the specific role might be for upfront ECMO as opposed to salvage ECMO. So massive pulmonary embolism is acute PE characterized by either cardiac arrest or sustained hypotension and that's defined as a systolic blood pressure less than 90 millimeters of mercury, a systolic drop of 40 or more for at least 15 minutes, or requiring inotropic support consisted with both American and European guidelines. The categories of PE are relevant here because massive pulmonary embolism, which represents less than 5% of all PEs to begin with, has a high degree of mortality. This is especially true when it's associated with cardiac arrest, where the mortality ranges somewhere between 50 to 70 percent, but yet even without cardiac arrest in the setting of shock, the mortality can still be in the 10 to 35 percent range. So clearly definitive treatment is necessary as well as supporting end-organ perfusion. Now the pathophysiology that's relevant here is that when there is about a 25 to 30 percent occlusion of the PAs, you'll start to see increased pulmonary artery pressures. When there's between 50 to 75 percent occlusion, that's when RV failure ensues. And thrombus resolution will typically start from the inside out. So it starts with the main and low bar PAs and then works its way out to the segmental and sub-segmental PAs. Now there's an increase in recognition that massive PE has a similar sort of golden hour, similar to that which we're very familiar with in trauma, STEMI, and strokes. And that is that it's been shown that about two-thirds of the mortality during PE occurs in the first hour after diagnosis. So it's critically important to move and support the patient as quickly as possible. Now the fundamentals of management are first anticoagulation. This is necessary to stop the clot from getting bigger. It prevents recurrent clot from developing and allows for intrinsic fibrinolysis. Oxygen, when necessary, mechanical ventilation is critical. Volume optimization cautiously is important, as well as the need for vasoactive medications. Now when a patient is treated along the massive PE algorithm, there typically is a decision point. And that is when to use medical therapy or thrombolytics, catheter directed therapy, or surgical embolectomy. Now what are these treatment options that are available? So without going into too much detail within that, lytics in both the American, European, and CHESS guidelines have a one- to two-way class of recommendation with level of evidence B. Catheter directed therapies are appropriate with a whole lot of tools that are available to procedure lists with a wide range of recommendations. And then finally surgery, which is how cardiopulmonary bypass started, as well as a clear role in those patients, especially those who have failed lytics or who are contraindicated to lytic therapy. So how do you decide between catheter directed and surgical embolectomy? It really depends on a number of different factors. Poor candidates for surgery, limited life expectancy might be more appropriate for catheter directed therapy. Younger patients might be better for surgical embolectomy. However, probably the most important aspect of this might be the local institution and the practice algorithms accordingly. So the reason this is relevant, this also illustrates the difference where cardiac arrest makes a difference. So this is a large review looking at surgical embolectomy versus catheter directed therapy. Here you can see that the overall mortality was about more than twice as high in the surgical group than the catheter group. However, when you look closely, the surgical group had four times as many patients who had CPR. And because of the high mortality associated with CPR, if you actually exclude the CPR group, you'll see that the surgical group had very similar mortality results to catheter therapy. And so that's why it's important to characterize and it'll help us understand why it's so important to understand what the results are with CPR or cardiac arrest. Now, this is a surgical paper, but it really helps characterize that there is such a thing as arrest or arrest. So depending on how an individual publication will define it, is it continuous versus intermittent? The results can be very highly variable. What's the timing and the duration of an arrest? So these are all associated with it. And I think this review really showed very nicely that the more an individual series had a greater proportion of patients who had preoperative cardiac arrest, the higher the mortality. So we come to a decision point. We're not sure what to do next or what would be the appropriate therapy. So this is a publication that we wrote this year, which reviewed sort of our current management for MassaPE and where ECMO fits in. And basically, whether they're a candidate for lytics or not, we're increasingly using ECMO within our own experience. And we'll talk about how that can be done. So with that in mind, what are the results of ECMO for massive pulmonary embolism? First of all, we first started with isolated case reports that were out there. Once we knew that, there were more and more case series that were available. And pretty soon, systematic reviews became available as well. The largest review initially published came from USUF. It showed 19 papers, 78 patients, 71% survival, which looks excellent. However, it really underscores how important it is for patient selection. Only three of these papers had more than 10 patients, and we had no idea what percentage of patients had CPR. And this will become more relevant as we go forward. What was interesting in this systematic review was just the variety of options that are available with ECMO. ECMO either by itself or with various therapies can all be utilized as an individual center deems appropriate. In this series, what I thought was quite interesting was that if you look at the ECMO alone cohort here, 16 out of 16 patients survived. In other words, 100% survival. So this might suggest that ECMO alone, just supporting the ventricle, supporting the patient, may be a reasonable option with reasonable results. Now, this is a multi-center series coming from nine centers in France, 180 patients, 52 of whom with massive PE were treated with ECMO. What's interesting here is that the ECMO group had over 60% mortality compared to the no ECMO group, which had slightly over 40% mortality. Obviously, a much higher major bleeding complication rate in the ECMO group. Here, however, when you look at the patients who were treated just with ECMO alone, the results are dismal, 78% mortality, including cerebral anoxia, multi-organ failure. So whereas the previous systematic review suggested that just ECMO alone would have a highly favorable outcome, this multi-center study, perhaps in the real world, tells us that might not be the whole story. So now we have a little bit of a confusing picture. So let's see what we can learn further. What's important to understand about this series and why it's really relevant is you can see here that 75% of the patients presented with cardiac arrest, the median pH was 7.1, the lactate was almost nine, the bicarb was 14. So this is an extremely high risk cohort of patients. So you'd expect these patients to have a very low survival, which is what they did with or without ECMO. This supports the golden hour theory. In this multi-center study that we just described, a third of these patients died on day one, two-thirds of the patients died by day four. So the timing of this was critical. And here, one other way to look at it, which is that we know that 75% of the patients had CPR. Of the group of patients who had CPR, 87% of those patients died. So the number of patients in a series that have CPR will really determine what the outcomes are. So is there a role for VV ECMO? I introduced this as a minor tangent. We at our center have not used VV ECMO for PE, but this center in Germany did use it over a 10-year period of time. 75 patients with ECMO, 46 VA, 29 VV. I will characterize this. You can see here that these are not similar cohorts. The VA ECMO patient had a much higher lactate level than the VV patient, and 83% of the VA patients had CPR compared to less than 40% in the VV group. Thus, when you look at survival to discharge and you see that the results are very similar, it would not be an appropriate conclusion to draw that VV ECMO has comparable results to VA ECMO. These are just not the same group of patients. Now, more recent updated systematic reviews can also give us some insight. Here, what we see is almost 637 patients, overall 65% survival, but just like we emphasized, we don't have the full picture of CPR. About 70% of the patients were CPR cases in the group of patients that we did have that information, which was less than 60% overall. So, it's hard to interpret the survival outcomes without knowing the full CPR outcomes. So, how do we decide who is indeed salvageable on ECMO? This is an important point because this sort of overlaps with the decision making with respect to eCPR. How do we decide who we should put on ECMO, or perhaps more importantly, who we should not put on ECMO? So, this comes from Kentucky, 32 patients who went on ECMO for PE, 53% overall survival to discharge. What they found that the key determinant really was the lactate level, as well as you can expect cardiac arrest. So, the lactate of 11 was the median lactate in the non-survivors, 4 was the median lactate in the survivals. When they then broke it down to a lactate greater than 6, you could see very good AUC curves underneath, both for ECMO survival and for hospital survival. So, a lactate prior to going on of greater than 6 is really associated with poor survival, and so one should be very cautious with respect to age and other criteria, just as one would evaluate eCPR candidates. Here's another study that looked at inotrope score, the amount of inotropes required, clearly associated with survival, as well as lactate as well. So, these are all determinants on who are appropriate patients with more likely to survive and who are not. What about upfront ECMO versus salvage ECMO, which is what we're really trying to decide based upon what we've learned so far. Who are the patients who can benefit, and why would you use ECMO up front? So, the reason would be allowing up front or early ECMO allows for immediate decompression of the right ventricle by instituting inotropic support, as well as ECMO. This allows for augmentation of cardiac output, and most importantly, circulatory support for end-organ perfusion to the kidneys, the liver, and the rest of the body. This can be done anywhere. It can be done in the ED. It can be done in the ICU. It can also be done in the cardiac cath lab, which is often where we do ours in the setting of shock without CPR, with the rationale being that this also allows for catheter directed therapy or any other specific additional therapies that may be necessary. Otherwise, if we don't do it early, then we're often doing it in extremis on very high dose inotrope suppressors after lytic therapy with resulting higher degree of end-organ dysfunction, as well as bleeding complications. So, I think the leaders in this arena of early ECMO for massive PE are the University of Maryland group. SACOME has really been a leader of this prior to moving on to another institution. So, this is on the left, their first series. They published 20 cases of ECMO for massive PE. On the right is the same group, this time with 29 patients instituting an early ECMO protocol, and they compare it to their historical surgical pulmonary embolectomy group to see what the differences were in outcome. So, if you look at the protocol group compared to the historical control group, and basically to understand it, the historical control group is really a surgery group. Here you have about 20% of patients underwent CPR, and what you'll really notice is interesting is that the time for consultation to intervention was very quick in the protocol group. So, the time they got the PERT team together and they had the response team, the protocol approach worked very quickly and very efficiently. So, what was the protocol that they utilized? So, patients with massive pulmonary embolism basically were decided very quickly. Here, if they had any evidence of end-organ dysfunction, unclear neurologic status, they went right to VA ECMO. So, standard venous cannula, arterial cannula, preferably cannulated, usually done at the bedside. They always put a distal reperfusion cannula as well. They often were able to cannulate while the patient was awake, or they would certainly try to extubate very quickly, and then certainly proceeded with full systemic anticoagulation. Now, this I think is really important. So, they continued the ECMO on average for about four days, and that was really to determine what the neurologic status was, especially in the 20% of patients who were rested, until end-organ function was optimized, and they wanted to give a full five-day trial of systemic anticoagulation. And then what they did was they then gave the chance, if the patients didn't recover neurologically, then they moved towards palliation. If the RV function was normal, then they went ahead and decannulated. But if they saw evidence of persistent RV dysfunction, they would get a repeat CT angio and proceed with surgical pulmonary amylectomy. They then went on to IVC filters. I think that's probably controversial, and I think most centers now would only do IVC filters in patients who had contradications to systemic anticoagulation. So, this was their algorithm. You can see here the results were excellent. Overall, 96% one-year survival. About half the patients required surgery. About half of them were treated with ECMO alone. Now, I will introduce the caveat that this is patients who followed a strict protocol. So, I think there are, for example, patients who first tried thrombolytics or tried catheter therapy, are rested, and then went on ECMO. They were not included within this algorithm. And there are certainly patients who had a massive PE and never really got consulted with the surgeons. They either just got thrombolytics alone. So, they, at their center, did not eliminate the use of thrombolytics. This just represents a different algorithm in which the PERT team was initiated. I think the interesting aspects with respect to the outcomes, a couple of variables, you'll see about half the patients recovered with anticoagulation alone. So, I think that's certainly an important consideration. You'll see that in the historical control group, the survival was still 82%. So, their outcomes at their center are very good. Obviously, now, with the ECMO protocol group, they got it up to 97%. And when you look at the Cox regression for mortality, certainly the big determinants was their protocol approach and moving from ECMO to surgery efficiently when it was indicated. So, this is the last publication in this series. So, the key thing is, so, if there's about a 50-50 recovery between anticoagulation and those who are going to need surgery, how do you figure out who are the people who are going to benefit from surgery or people who are the people who are going to fail from anticoagulation? So, here, they looked at 41 patients, three-quarters recovered with anticoagulation alone and about a quarter required embolectomy. So, what can we learn from that group? So, I think it's interesting to note that the people who were unlikely to recover with anticoagulation alone were patients who were short of breath for more than two weeks. Those patients who presented with elevated BNP or BNP troponin ratios, and those patients who, on CT, had higher, or by echo, had higher PA diameter measures. So, what they then developed was a scoring tool that was characterized by those variables amongst others and gave a classification system for something to consider for those patients who are more likely to not require, more likely to fail versus not. I think I would use, I think it's reasonable to consider this group of characterizations as patients who are probably more likely, if they're characterized by massive PE, probably more likely to require ECMO or more likely to have cardiac arrest who might be potential candidates for earlier utilization of ECMO. Now, another publication that's in press right now comes from the University of New Mexico group. Here's, they published their experience with upfront first-line ECMO, 17 consecutive patients utilizing the PERT team, almost 60% needed CPR, and three-quarters survived overall. Median duration of needing ECMO support was three and a half days. You can see here in their algorithm here on the left-hand side, basically anyone with severe hypotension, certainly anyone with CPR, went on to ECMO. And so, basically, how do you define severe hypotension? I think that's a little bit up in the air, but certainly I think we kind of know what severe hypotension is. I would say patients who are in the 70s and 80s, despite pressers, that would certainly be a candidate for earlier initiation of ECMO. Here, the New Mexico group characterized their survivors versus non-survivors. Not surprisingly, those patients who needed CPR were less likely to survive and certainly those who needed it during cannulation. And obviously, things like lactate, pH, and creatinine were more characteristic of the non-surviving group. So, if you're going to get to these patients quicker, if there's evidence of end-organ malprofusion, certainly those are patients who not only are more likely or not to do as well, but they're certainly the group that would be more likely to benefit from earlier ECMO. So, what they found with the group of patients who did the best were those who demonstrated lactate clearance, typically within 10 hours, and also freedom from vasopressors within six hours. So, those are sort of determinants to be able to determine who's going to do better. This is an abstract form. This was presented at the European Society of Cardiology this past year, looking at a systematic review, 68 sick studies, almost 600 patients with massive PE on ECMO. You'll see here almost 60% with cardiac arrest and a little over 60% presented with upfront ECMO. So, how were those results? So, you'll see here that the ECMO group was divided relatively evenly between those who got ECMO plus lytics, ECMO plus either catheter therapy or surgery versus ECMO alone. The average support for ECMO was four days, obviously a higher bleeding rate, and certainly this was higher if patients received lytics ahead of time. What they found was that there was not a survival difference between upfront and so-called bailout survival, but this will be interesting to see this manuscript when it comes out for further analysis. So, upfront ECMO offers a paradigm shift because whereas traditionally we always focused our attention on rapid clot remover, either with lytics or with catheter directed therapy or even surgery, now this represents the earlier ECMO is prioritizing, optimizing end organ function upfront. In other words, circulatory support first, clot removal second. I would think of this as an analogy to the damage control abdomen in trauma, whereas when you go in in trauma, the first thing you do is you basically stop the major bleeding, you pack everything, you prevent soilage, you might staple bowel, but you're not there to fix everything all perfect. You're basically there to quickly control the abdomen, wrap them up, and then move towards resuscitation, and then come back in 24, 48, 72 hours for more definitive surgery. I think that might be, I think, one way to think about this. So, the management of high risk PE, I think the patients with massive PE that are quote unquote low risk of bleeding, those are people who certainly should move towards lytics. It's really that higher risk of bleeding and the high risk massive PEs that really might be the people who are beneficial from ECMO. So, this basically shows how this group, number of different therapies that were utilized within this series. So, how can we predict who may need ECMO? Again, this further insights, this is a series of 16 patients from Taiwan, three quarters of patients needed CPR, half of them survived. And what they found was clearly cardiac arrest was associated with not surviving, but certainly not, it was the time of cardiac arrest too. So, the difference in CPR makes a difference as well, not surprisingly. What was interesting here is this group found that the bigger the RV to LV ratio, the faster the time necessary towards ECMO or that required CPR. So, basically, whether all of this sort of indicates that more severe RV dysfunction, our patients are more likely to arrest and probably might benefit from earlier ECMO. So, in other words, who would I say right now are appropriate candidates for upfront VA ECMO? And this is sort of the way we approach things at our institution. Obviously, cardiac arrest, this is an eCPR situation. We treat this very similar to the way we treat eCPR as a whole. Uncleared neurologic status, this I think is important, and organ malprofusion, and both of these, you know, putting them on ECMO, seeing if they wake up okay, seeing if the kidneys recover, liver recovers, you know, etc., before going ahead to proceed with surgery. I think that those are reasonable considerations. And then finally, those patients who are at high risk of deteriorating from shock to arrest, high BNP, high RV to LV ratio, a number of other factors might be the patients who would most benefit. I think the important thing, this is from the MGH group, Ken Rosenfeld and his colleagues have really been leaders in this, is that in order to make this decision, you really need a PERT team. It needs to be something that's multidisciplinary. It needs to be something that's dedicated with a number of different ideologies, disciplines, because the type of treatment that's available is variable, and you really want to individualize it for the patient. And this here, the MGH team, certainly they've reported that even in the high-risk patients, they can have very good survival outcomes with that. So I think that certainly in this field, part of the challenge, you know, is that you need to interpret results with caution. I think you've seen that I've emphasized time after time that the number, CPR is very important, and anytime you look at a series, you really need to look at what proportion of patients had CPR, because that will most definitely influence the outcome. I don't think there's ever going to be a randomized trial that's going to be performed through this. I think it's just very difficult to organize such a thing, but we're going to have to glean information from registry propensity score match criteria to be able to determine how this will be beneficial. I think the more and more familiar we are with eCPR, it'll make earlier ECMO more likely, and I think we're going to also benefit from longer-term data on RV dysfunction, on chronic thromboembolic pulmonary hypertension to help guide us. And ultimately, the local institutional practice will help direct your center towards catheter therapy or surgery, as well as the availability of ECMO, which will all be available. And with that, I'm happy to participate in the panel discussion and look forward to any questions. And you can also email me as well. Thank you. Hi, everyone. My name is Karen Ritter-Rice. I'm an associate professor at the School of Nursing and the School of Medicine, Department of Pediatrics in the Division of Critical Care Medicine at Duke University. And it's my pleasure to be here today to talk to you on cerebral vascular physiologic considerations in VA ECMO management. I'd like to thank the organizing committee for the invitation to speak on this important topic and to be part of a panel of experts who are gonna share with you, I think some, I hope, some high-level conversation around this. And I'm looking forward to the dialogue that we're gonna have when we wrap up our sessions. So I have no disclosures. This presentation, I'm actually going to be focusing in on the fourth objective here, which is to describe unique VA ECMO considerations in current clinical practice. And I wanna just mention that that's within the caveat of neurologic complications. So this slide is really just a placeholder slide. And it's just to remind us that we're actually talking about VA ECMO, that this is really a temporary support mechanism, and that also VA ECMO comes with its own risks for neurologic complications simply because of the type of access and the disruption that that access can cause. So VA ECMO and survival since 1990, when you look at the ELSO registry, shows that adults have about a 40% survival rate to hospital discharge. Where children, they tend to have about a 65% survival rate and neonates are somewhat higher at 80%. I think one of the things to keep in mind is that, you know, ECMO survival is improving as we get more survivors. It's improving as we get more sophisticated with recognizing neurologic compromise, because that's a large contributor to ECMO death. And I wanna talk just very briefly, this session isn't focused on COVID, but I did wanna talk very briefly about COVID and ECMO and survival. And so there's a really nice article by Barbaro and the ELSO registry in September of 2020 in the Lancet, where they really looked at multicenter patients on ECMO with COVID-19 who are older than 19 years of age. And what they found was there was about a 30% hospital to discharge survival rate with about a 37% death rate. And I think this is an important component because when we think about ECMO use in COVID-19, we need to also be always mindful that the use of ECMO comes with its own risks along with the COVID-19 risks that we're seeing in patients. And so there may be some strategies that are being used in these patients, but we need to be mindful of the fact that there are also strategies of ECMO we need to keep into consideration. So I'm gonna preface this talk with, in no way am I doing justice to the global comprehensiveness of ECMO, neurologic events, neurologic complications. And so what I've done is I've provided a pretty comprehensive list of references at the end, but I'm gonna speak to some of the studies that I reviewed here for you and the citations that you'll note throughout the slides, because I hope that for those of you that are interested in specific areas that you'll maybe go to these sources and get more information around them. Well, in a study by Matin of adult patients treated with ECMO, he had about 87 patients in the study, 66 experienced a neurologic event. And I think that's pretty high. Of these 66, 25 survived to discharge and 25 had support withdrawn and 16 died. And I put this caveat that the distinction may affect data. And I think this is really important because when we're talking about 16 patients having died and 25 who had support withdrawn and who likely have presumed to die as well, it's really kind of murky as to how do we really capture these neurologic events when we have patients on VA ECMO. Importantly, it's because U.S. costs for individuals who have neurologic complications as a result of ECMO are about $100,000 more in each patient when compared to those who don't experience complications. Neurologic risk factors are challenging. You know, from the studies that I've been able to pull for poor long-term outcomes in adults, we find that those with increased age both with or without comorbidities, heart disease, diabetes, chronic renal disease, and COPD, they themselves have been shown to have poor long-term outcomes. Lactic acid levels greater than 10, hyperpyrexia, and even more severe than anorexia, hyperglycemia, and metabolic acidosis have also been known to affect long-term outcomes. And in adults, other potential contributors to overall injury in the central nervous system prior to and during ECMO that may be considered an independent predictor of poor outcome include high ventilatory pressures while on ECMO, disseminated septic embolism, and air embolisms, of course. Whereas in children, there's a really nice study that was conducted by Mistry and team who looked at a single center retrospective chart review of pediatric patients on VA ECMO who had support because of cardiac indications. And this was about the time period of 2004 to 2015. They included about 68 patients of which 65% were male, 84% were white, 38% had prior surgery, 13% had prior transplants, 10% had prior ECMO support, and 87, almost 88% of them required vasoactive support within six hours of cannulation. And what they found were significant predictors of both transplant and or death within six hours of cannulation were epinephrine use, elevated creatinine. Both of those tended to show that these patients were at higher risk for long-term outcomes, worse outcomes, thank you. This study also reiterated the need for VA ECMO cardiac support. When VA ECMO was used in supporting cardiac, underlying cardiac morbidities, that these patients also had a much higher mortality rate and also morbidities post-ECMO. So when we look at ECMO, we think about cannulation risks. It's important to think about, we know that there are different considerations for neurologic risks based on VA versus VV ECMO. So in neonates who typically have VV ECMO, they have significantly lower risks for neurologic complications when comparing with VA ECMO. Whereas in children, the ECMO cannulation approach represents a significant risk by altering blood flow after ligation of the internal jugular vein and common carotid arteries. Whereas in adults with extensive aortic or atherosclerotic disease, arterial cannulation can result in retrograde disruption of debris from the high pressure and flow and result in diffused microvascular emboli events. So taking into consideration the patient as well as the type of approach can matter as far as what type of patients we place at risk when they are cannulated. So when we think about VA ECMO and neurologic events, it really has much to do about cerebral blood flow. And that's because mechanical aspects of ECMO can affect cerebral circulation, which can lead to profound neurologic complications. So this study here just basically helps you understand, or sorry, the schematic here on the slide helps you understand that about 15 to 20% of cardiac output is devoted to the brain. And importantly, what we know is that average perfusion is about 50 to 55, 100 grams of brain tissue per minute. Gray matter, which is much more metabolically active, receives higher cerebral blood flow, about 75 mils per 100 grams of brain tissue per minute. And white matter receives a lower cerebral blood flow, about 45 mils per 100 grams of brain tissue per minute. So that any decrease in cerebral blood flow could compromise cerebral perfusion. And so studies have shown that if you've measured cerebral blood flow around 30 mils per 100 grams of brain tissue, usually it's tolerated well and they don't typically lead to any kind of neuronal dysfunction. However, blood flow below 25 mils has been found to have associated changes on EEG and cerebral blood flow less than 15 mils is been found to indicate loss of tracing on EEG. And so again, flow matters. So when we think of cerebral blood flow, we know it's all about regulation and that there are three important paradigms we need to consider in this. It's not completely fully understood how cerebral blood flow is regulated in the human brain and we know it's very complex, but these are the three main ones that I can speak to. And those are cerebral autoregulation, which is the ability of the cerebral arterioles to maintain a constant cerebral blood pressure within a wide range of cerebral perfusion pressures, flow metabolism coupling, a functional hyperemia or coupling between a cerebral metabolism in a given area of the brain with a matched increase in regional cerebral blood flow, and then neurogenic regulation, which is a prominent role of neurovascular units comprising of extensive fine-branching structures of the nerve ends of the fibers, such as perivascular nerves, endothelial cells, and astrocytes. And so moving on to what kind of impairments do we need to be aware of, this slide is heavy with text and I'm sorry for that, but I'm gonna just share with you in the impaired cerebral autoregulation, there's some really, really good early work that's been done, not just looking at ECMO patients, but overall looking at cerebral autoregulation in brain injured patients. And so what I wanted to highlight on this slide was that essentially impaired cerebral autoregulation does change the outcomes of patients on VA ECMO. And so one of the studies I wanna highlight is this one by Tian and his team who wanted to identify a degree of cerebral autoregulation impairment in children during VA ECMO and whether it was predictive of the neuroimaging abnormalities. What they did was they measured spontaneous fluctuations of mean arterial pressure and cerebral tissue oxygenation while on ECMO. They also measured dynamic relationships between the MAP and the cerebral tissue oxygenation saturation fluctuations based on a wavelet transform coherence. Neuroimaging was conducted during and or after ECMO as standard of care and the abnormalities were evaluated based on scoring systems that had been previously validated among the ECMO patients. What they found was of the 25 patients, 32% or eight children had normal neuroimaging, 28% or seven children had mild to moderate neuroimaging abnormalities and the other 10 children or 40% of the sample had severe neuroimaging abnormalities. And so what's important to note is that what they found was the degree of cerebral autoregulation impairment was quantified based on the wavelet transform coherence showed significant correlations with neuroimaging scores. And so one of the thoughts is that if you have this impaired cerebral autoregulation that you are going to naturally expect that your child is gonna have a worse outcome and I think that would be true for adults as well if their cerebral autoregulation becomes impaired. But what's really important to note is the fact that even with adequate cerebral blood flow that can be maintained on VA ECMO by adjusting the flow rates, there are still anomalies in cerebral autoregulation that could impair the patient and lead to poor neurologic outcomes. So when we think about cerebral blood flow, we wanna think about can we measure it? And I think it's important to note here that recognition of potentially hypoperfused brain is an important part of being able to identify the child or the adult who needs to have some type of care plan change or intervention to support either neuroprotection or to promote as much perfusion as possible. And so multimodal monitoring, brain monitoring is incredibly important in not just any neurologic patient or risk for a neurologic injury, but particularly in VA ECMO patients and VV ECMO patients to be said. And so I wanna talk about this one citation that I have here by Kazmi, 2018, who did a really, really nice job in looking at the pathophysiology of ECMO, both pitfalls in daily clinical management. I think it's a great one to refer to. But what's important to note is that there are some really nice studies that speak to what does cerebral blood flow look like in individuals with ECMO. And so I belong to a group of individuals who do a lot of work with TCD. And so what we've known is that TCD is a fairly nice non-invasive portable monitoring device that we can bring to the bedside and ultrasound and have a look at cerebral blood flow velocities. We can detect emboli. We can also look for pulsatility indexes. So a colleague of mine, Dr. O'Brien and Hall at Nationwide wanted to examine TCD measurements in 18 children that they wanted to show that in these patients that didn't have neurologic injury, they wanted to measure the middle cerebral artery flow velocities and decide whether or not they looked predicted for age and sex. And what they found was that it was much lower than predicted. And upon return, excuse me, and their mid cerebral artery blood flow velocities were turned closer to baseline after cannulation. However, in the patients that did have a cerebral hemorrhage on ECMO, supranormal flows were noted in the days preceding the event. And the study really also kind of tweaked our interest to say, you know, could there be perhaps a way for us to be more vigilant in monitoring children on ECMO while having TCD at the bedside? And one of the things that we want to highlight in the study is this was kind of a mixed patient group of VA and VV ECMO. So what we did was there was a group of us in another study, we had five sites where we explored changes in age-related TCD measurements during pediatric ECMO. We enrolled and analyzed the TCDs of 52 children. In 44 of the children, there was no acute neurologic injury, but there was a significant reduction in systolic and mean flow velocities compared with predicted values over time. And the other thing that we found was we looked at the pulsatility indexes, and we thought it was interesting that we found increased pulsatility indices in young children on ECMO, and that perhaps this could be an early marker for those that were at risk for ischemic injury because the ones that had ischemic injury on neuroimaging findings also had increased pulsatility indices. So important just to think about what are your available tests and how can you best use those to help you understand what's happening within the brain. And so thinking a little bit more about this, thinking about flow patterns, they're often characterized by decreased systolic upstroke, lack of diachrotic notch, and continuous diastolic flow when you're actually looking at VA ECMO. And so the last thing I wanted to speak to was this neurogenic regulation, and it's thought to be influenced by sympathetic and cholinergic pathways, and so therefore any disruption or alteration in these pathways can significantly impair. So I want to just very briefly, this one slide, touch on plasma biomarkers because wouldn't it be nice if we had a specific and sensitive test at the bedside that we could run instead of bringing imaging devices to the bedside or the patient to the imaging device. And so what we know is there's really no ideal sensitive blood biologic marker at this point that can detect ischemic or hemorrhagic injury. But there is a team, Bambia and her team who have conducted two studies to look at whether or not there may be elevations in plasma brain injury biomarkers that were associated with outcome at hospital discharge in children who required ECMO. And so what they found in the one study is that increased levels of GFAP in patients on ECMO were associated with higher risk for brain injury, odds ratio was about 11.5, and then death, odd ratio of 13.6. And then in a second study, what they did is they looked at a combination of six different biomarkers, GFAP, MCP1, CCL2, NSE, S100 beta, and intracellular adhesion molecule and brain-derived neurotrophic factor. And what they did is they measured it daily while the patient was on ECMO. And they found that GFAP, MCP1, CCL2, NSE, and S100 beta were all significantly higher in patients with unfavorable outcomes, and that peak concentrations of GFAP, NSE, S100 beta, and MCP1, CCL2 were higher in the non-survivors. So just a little bit of a beginning tease to see whether or not could we find more specific and sensitive biomarkers, and may that be that they need to be a combination of biomarkers that will give us some time of insight into what's happening in the patient. So I want to go on to exploring these common neurologic markers, and I want to tell you it's important because neurologic complications are about 95% in infants, 85% in pediatric and adults in the first three to four days of ECMO runs. And so there's really no consensus as to the minimal recommended neurologic type of assessment pre, during, or post-ECMO. And so keeping in mind both your physical assessments, your pupillary responses, the level of consistency in routine, thinking about rotation of sedation, thinking of lifting of paralytics when possible, all of those things to better get at what the neurologic status is. Remembering to include very first and upfront key personnel like neurology, hematology, and brain injury specialists is also very helpful. And then one other thought is the somatosensory evoked potentials, which can also be very informative and may help you with some of your management strategies going forward. But knowing that it's going to be multimodal monitoring, and we'll talk a little bit about that going forward. So again, remember, I'm not going to do true justice to these very prevalent common neurologic complications that I pulled out to discuss today, and that there's plenty of references for you if you need more information. So you can see here the most prevalent and the less common. And I think what's most challenging is that because ECMO is initiated in emergent circumstances, a neurologic examination can be limited. On top of the fact that the level of complexity in identifying ECMO-associated neurologic complications, which can develop both prior to the initiation, during, or even after decannulation makes the whole thing very challenging. And that's why oftentimes our studies don't give us the best type of information. So reviewing some of these very broad and common neurocomplications, I want to be very mindful that these are much more complex and much more multifocused than what I'm going to provide you with here. But essentially, here you can see the incidence of ICH. It's about two to 19%. It's most common in the supratentorial. Females tend to be at higher risk, as do those with thrombocytopenia, acute renal failure. And the mortality rate on ECMO is about 92%. So it's pretty impressive. Additionally, in children, the reason I put most frequently because of the use of TCD, what I'm trying to say is the reason we know of ICH is because we use TCD in neonates. And here you can see the incidence is much higher, 26 to 52%. The cerebellum is the most common location. And unfortunately for mortality rates, it's very difficult to define because the literature tends to have very heterogeneous populations. They often mix VA and VV ECMO together. And so we don't really have good prognostications for mortality from ICH. Management, of course, we always prefer the CT scan. I think everybody who could take a patient into the CT scanner would appreciate that. But I think what's gonna be really important here is thinking about portable, whether that's your CT or whether it's a TCD, thinking about your anticoagulant management and having hematology on board. And then also always considering heparin-induced thrombocytopenia, which we happen to see more commonly in children. And so while I just wanna point out one study here and it's by Lindgren, where she actually looked at 37% of patients, about 123 patients, 54 children, 69 adults, who underwent cranial CT scanning during ECMO and were found to have ICH. About 37% of them were found to have an ICH. And that the imaging findings weren't always associated with clinical findings, particularly by neurologic exam. The exam alone really didn't provide enough information to determine whether or not these patients had ICH. And so the imaging was really crucial and essential. Stroke, on the other hand, is the most common complication, but the true incidence is really unknown. And that's because it's very difficult to differentiate among the mechanisms of stroke, characteristics of the infarct, and the timing of the infarct, particularly in patients who are on ECMO. One single site study by Omar, who did a retrospective look at adults from 2004 to 2014, found the incidence to be about as high as 5.8%. Those who had high lactic acids were at higher risk for incidence of stroke, particularly if that was before. And then it was impossible to generalize a prediction in the prognosis of stroke. One caveat I want to remind you of is that cannula embolization or air embolisms are potential mechanisms and are far more common with VA ECMO, and particularly when abnormal or high pressures and often retrograde flows in the arterial system occur. And so just be mindful of that. And then management of stroke, absolutely no justice to the slide. There's so much more information that you need. Get your team involved, particularly your specialists, but think about your anticoagulation. Think about cerebral blood flow dynamics, detection of increased ICP and microembolism, and then CT scanning. And seizures, these are very common as well. They're about 2% to 10% incidence of clinical seizure rates, which are higher in the younger children. Subclinicals run about 17% in non-convulsives. Status is about 11%. Fever, metabolic changes, and medications all contribute to this risk. And then presentation can vary because we know that people on ECMO, it's very difficult to assess whether or not they're seizing. And management, really, there's no formal recommendation for continuous CEG for seizure management patients who are on ECMO, but it's really an optimal way to record continuous CEG because it serves three main purposes, early identification, recognition, and then assisting with prognostication. And then, of course, thinking about presence of an unexplained birth suppression pattern has been associated with increased risk for death and severe disability in patients who are on ECMO. And last, the most controversial, of course, is brain death. And what I wanted to talk about here is that we've given you different survival numbers, but brain death alone, it's anywhere between 5% to 21%. And in one recent series, about 21% of patients were given a diagnosis of brain death. And if you look here, it's the presence of generalized edema, persistent coma, or physical exam findings that were suggestive of it. I think what's really challenging is there are formal guidelines that lack ECMO. It's not included, and so most people will follow the American Academy of Neurology criteria. But there's a really, really nice article that I've put on the slide here, Apnea and ECMO, which was written in 2015. I think it's really worth a look if you want to get better insight. It's a beautiful lit review and also a case. And so one of the things that we know is if we really needed to take them to have a cerebral angiogram or nuclear scanning, that is the highest risk for our patients is moving them from their location in the ICU. And so sometimes these tests make it almost very, very challenging to determine brain death. But often it should also be noted that many of these patients go to brain death within about the first 72 hours. So there's a lot of controversy about how to best define that, and I would suggest that you look at the AA neurology recommendations and then also this Apnea and ECMO article. So with that, I would like to go on and thank you very much for your time. It's been a pleasure being here with you. I look forward to our conversation, and I wish you all well. Thank you. So, thanks so much for great talks and getting us engaged in this really difficult topic. As a moderator, I take the privilege to ask the first question. And this question goes about the PE staff. And my question is, most of the PEs do not happen in a hospital where ECMO is readily available. It's not like we have our PEs in the ICU where the ECMO set is set up and ready to go. So, how do you practically do it in your hospital to get on time? Or how much time do I have? Because none of the studies I saw said, how long should I wait for my TPA or whatever I'm doing versus when should I go in with ECMO? So I think that's a very good question. So, I think it depends. And this is what makes it, I think, difficult too, is that there's massive PE that's hypotension, one inotrope, patient looks okay. And then there's massive PE, you know, on two to three inotropes, you know, patient is an extremist. You know, those, as we know, those results are very different, in terms of one versus another, in terms of degree of severity. So, the way that we've approached it is that we basically have a very early approach to initiation of VA ECMO. I would say that in our hospital, the interventional cardiologists are probably the first line for peripheral cannulation of VA ECMO. So, we have found that patients with ECMO who are sort of metastable, you know, who need something done, we have taken them often directly to the cath lab, placed them on ECMO, and then often use catheter-directed therapy with the ECOS catheter and initiate, you know, low-level TPA in that setting. And so, that sort of gives you a little bit of both. It gives you the protection of being, of supporting the end organ function sort of right away. It also allows for reducing the overall clot burden. So, I discussed how there's a little bit of a paradigm shift, you know, for example, that Maryland group, the way they looked at it, and I think the caveat to their study is that they didn't include every mass of PE that was in their hospital. They included every mass of PE who was referred to them. So, those patients who just got lytics, those patients who went to catheter-directed therapy first, those people were not included. But if they were referred a massive PE, they basically made the decision that they're going to put them on ECMO first and then reassess in two, three days and see what the RV function was like, see what the neurologic status was like, and then basically do that. So, I think, you know, I think your point is well taken that it requires, you know, and I think institutionally as our eCPR program has sort of developed and matured and people sort of are sort of thinking, you know, eCPR sooner, that has sort of, you know, correspondingly facilitated that. Any other comments on this? What do you think? What are you guys doing in your institutions? Because I think this is what people want to know. For example, we are a little bit careful with it and the problem is right now it's a resource utilization stuff. So, somebody who would arrest from a PE during COVID would not, would right now not even get it because you already, we know that the risk of death or mortality is so high to do it on somebody who arrests right now, we would not do it as salvage because we only have 10 circuits and you don't want to give one of your 10 circuits up during COVID when you would need it. However, based on this, it still comes down to who is the right patient and you got into this a little bit, but whom are you doing? Whom are you really selecting? So, I think that, you know, this is not, I think that the, it's not a simple question because as you know, there are multiple factors that go into it. You don't treat a 40-year-old the same as a 70-year-old. You treat, you know, somebody on dialysis is different than somebody else, but I would say what, what we have learned and I think what I think as we sort of more discuss this over the last couple years is that salvage ECMO is really difficult to initiate and, and, and those results are basically ECPR-like results, which is, you know, if you're doing chest compressions and then you start calling, you know, and you never get them back, that's why those are going to take 40, 45 minutes to cannulate and I think the results reflect that. The, the real difficulty when you interpret the literature is how CPR is defined because there is, if somebody arrested for 30 seconds, got compressions, got rust back, and then you put them on ECMO, then people call that ECPR as opposed to another patient where you're actively doing chest compressions and you cannulate, people are calling that ECPR too. Those are not the two, those are not the same thing. I mean, as a surgeon, one of the earliest dictums I learned for patient outcomes, the three most important determinants of patient outcomes are patient selection, patient selection, patient selection, and so that's, that's clearly the case. I would say that, who are we putting on? Here's what we've learned. So I think somebody who is an early recognition for CPR, I'm sort of taking the COVID out of it, like, you know, because I, you know, we're all in the same sort of constraints, it's a challenge, but say, like, you know, a year ago, what we were doing is that if somebody was like CPR, a good candidate, we got to them early, we would give them a chance, but the patient who presented with massive PE was hypotensive, then we started to take into account, okay, if the RV is really big, if they've had symptoms for a while, BMP or troponins are elevated, if there's certain things that are pushing us to think that this patient is more likely to deteriorate, we took them to the cath lab, we put them on ECMO, and then went ahead with ECOS catheter and whatnot, and I think that was sort of the thing. There are also patients within our algorithm that are stable, who we take to the cath lab for ECOS therapy without necessarily putting them on ECMO up front, and, but you're in the lab, and you have access, and you can do it relatively quickly if we did it. I think what we're learning, and I think this is really what the interesting thing is, is that the mindset might change in the sense that, you know, maybe it's what circulatory support, maybe it's the ECMO supporting, you know, kidneys, liver, etc., in the shock state, that's what's ultimately the ultimate determinant, and then, you know, kind of getting the, you know, you're already on heparin, but getting like catheter directed therapy or whatnot to be able to reduce the clot burden, then ultimately maybe that's the second priority. I think your question is dead on. It's something that's evolving, but I think that, you know, I think it's one of those things also that as a program, if the only people you ever put on ECMO for PE are just eCPR cases, and you have a 50 to 70 percent mortality, administratively, institutionally, people will think, uh-oh, ECMO for PE, you know, dismal outcomes, why do we ever do it? So I think you do need to balance a little bit of having some successes. Again, it's a short ECMO run. It's three to four days. They're already anticoagulated. They're going to have to be, you know, on top of it. So while ECMO certainly has a risk, you know, early ECMO in massive PE when they're already anticoagulated probably doesn't carry, I would say, probably the spectrum of ECMO is probably certainly on the lower risk of new complications. Thank you, Uli. It's such a privilege to be a co-moderator today. I worked with Uli a decade ago in Boston, and Dr. Chatterjee is our ECMO director at Baylor. So, of course, I really need to applaud the effort from the program committee. They wanted this session. Right now, Dr. Chatterjee, Dr. Smith, Dr. Reuter, we have over 225 attendees to the session. So I probably will make some direct questions, and some of them will be a little bit, I would say, you know, controversial. But let's try to really elevate this discussion in a high quality. My point of view is this. I think in the last 70 years, the PERT teams became really something that the hospitals wanted to implement. And based on the data you were showing, there was one study that actually the size of the right ventricle was kind of like predictive that things are not going to go well. In your opinion, and based on our practice here in the Texas Medical Center that you write, we are proactive, we put the ECMO probably in preparation to do the intervention. How are you seeing this transition from a PERT team that was not that actually open to have that ECMO from the get-go to what you are proposing right now, what is coming up, like the new Mexico experience, etc. How are you seeing the transition, the evolution of the PERT teams in the United States? Sure, I think that's a great question. I would say that the important thing about the PERT team is that it's not a one-size-fits-all formula. That you really have to respect the institutional culture and the institutional referral patterns and the practice patterns that exist within that. So for example, you can have one center that is, CV surgeons are very engaged and very interested in aggressive therapy with surgical pulmonary embolectomy. And perhaps you have interventional cardiologists or radiologists, you don't have much expertise or minimal expertise or interest or whatnot in doing advanced catheter directed therapies. On the other hand, you can be in a center where it's the exact opposite. The cardiologists are very aggressive, their ECOS is something that's very popular and very aggressive, and the surgeons don't really want to be as aggressive with earlier embolectomy and really want to reserve it for those cases where somebody goes on ECMO, there's persistent RV dysfunction, there's still a lot of clot, and that person needs it. So I think that the important principles are someone from the emergency department, someone from critical care, the vascular slash interventional cardiologist, I think a surgeon, whether it's CV surgery or vascular, I think those are probably the critical components to be able to develop that. And then at the end of the day, like all of this, data is king. I think you have to always be honest with your outcomes. You have to constantly reassess where you were yesterday, where you are today, where you think you can go tomorrow in terms of really gauging and not just, again, ECMO and isolation or surgical embolectomy and isolation. You want to know institutionally, how many PEs did we have this year? How many were massive PEs? And what's our survival outcomes? And where are there opportunities to do better? So I would say that there's ongoing evolution. And I think the key thing to understand about the PERT team is that you have, it has to work locally. If you come and try to impose something that's not consistent with the culture, it'll just die of inertia, and we'll get by it. We have good time here. Uli, let me try to do this. Give Dr. Chatterjee a break and take advantage of Dr. Brutter now. There are a couple of questions for her talk, and then you follow up on that. Is that okay? Yeah. Okay, great. So this question actually comes from Brazil, Dr. Brutter. Actually, it's a high esteem colleague of mine, Dr. Felerico, and she said, do you have any TCD protocol for patients using VA ECMO? If you do, please let me know if you do it daily or in any other fashion. Thank you. Yeah, I think that's a great question. So although no distinct protocols have been published as of yet, we do have new practice recommendations for all children who are at risk for neurologic injury in the pediatric ICU, which includes that ECMO population. And I would be happy if she puts her email in the chat box to send her the published paper that's out, and also link her to all of the other ancillary materials we have for actually how the TCD should be conducted and what kind of protocol she could actually adapt to her center and what would work for her. Thank you. And the other question is one of our cardiology intensivist leaders, Dr. Hollenberg. To what extent do you think the findings in pediatric populations might be extrapolated to adults, some of whom have cardiovascular atherosclerosis? Yeah, I think that's a great question, right? And I think, you know, we've been doing pediatric ECMO a little longer than the adults have been doing their ECMO. And I would say that our outcomes have been pretty good, particularly in the neonates. And then, of course, in the children, ECMO rates are getting better as well. I think underlying atherosclerotic disease, you know, is problematic just because of the vasculature itself. And we don't really know the extent of that disease presentation, particularly in children. We have really very little information around it. So what I would say to you is that I think, you know, much to I think what we've talked about earlier is this whole idea about who is the right patient and what makes them the right patient for ECMO. And that ultimately is always going to be the discussion at every ECMO cannulation. We're having that discussion, right? And I think, too, I just want to, you know, follow up on something that Dr. Chatterjee said, and that is that, you know, we have a lot of heterogeneous data out there. There's a lot of mixed studies that don't purely look at VA ECMO alone. You know, they mix in VB ECMO. They don't always bifurcate who those patients are and what they look like, what are their unique characteristics. And then we don't really have a good idea about what does that outcome look like, right? So many people say, well, okay, they made it to discharge, but then we don't really know what those patients look like, you know, 30 days later, 60 days later, a year later, have they ever reestablished employment, gone back to school, whatever their day-to-day life. And so although we have great studies for what we can accomplish in the inpatient setting, we know very little about the outpatient setting. And I know ELSO is doing some tracking around that, but really there's a lot to be learned. So I think who is the right patient? Are we going to have the best scenario to have a good outcome? And I mean, a quality outcome, like downstream all the way through a quality of life is really important for us. And we don't have enough studies that really encapsulate that. I have a quick question. So we looked at TCD in adults. We did about 30 patients and the results were all over the place and we didn't really know what to do with it. So my question for you is, in your practice or your understanding of the literature, how much can we use TCD to, for example, drive a higher hemoglobin or to run a higher mean arterial pressure or, you know, modify our clinical assessment, you know, our clinical practice on ECMO to be able to use that? Where does that stand or how close are we using it to sort of, you know, instead of the cool pictures, you know, to kind of give us some clinical, like adopt our management? Yeah, I think that's a really, it's a good question because, you know, no one really is using it consistently with ECMO patients. And that's even true for pediatrics, of course, right? And I think it's such a beautiful, non-invasive, portable way to get some quick and dirty trending data. You know, the problem is it's difficult because unlike NIRS, where you can, you know, slap the sticker on the forehead and then you pretty much get, you know, cerebral NIRS for, you know, a trending pattern, you can kind of get a global, you know, oxygenation perfusion picture. You can't really do that with TCD. Our headsets are just crappy. And so even though we continue to, you know, try to build better headsets that you can leave on long-term, you know, you're not really getting that best type of data. So it is kind of that snapshot data. When you go in, you insinuate the vessel, you hold it for a while and you're like, okay, what do I make of this? I think the beauty of it though is if you have a good sonography team and you can have daily TCDs, particularly as kind of a screening mechanism, I think there would be some help. And I think it would be helpful in the way that you can say, well, what do their diastolic and systolic flows look like? You know, are we really ensuring that we're meeting norms for, you know, gender and age? Because I think that's the other big piece of it. And then on top of that, you know, are they maybe hyperemic or are they really truly struggling to perfuse because we don't have a high enough hemoglobin or hematocrit for these patients? I think there's some, what I would say is some organic data that you're getting, but I don't think we're at the point now where we could say, oh yeah, we have an absolute, if we see this, this and this, we know we're in trouble. I think it's very individualized. I think it'll be kind of part of that personalized care, but a good trending, a good trending diagnostic. My question is, I wanted to actually take a bow to Dr. Smith is actually practicing in one of perhaps the most experienced center in the United States for, you know, and thromboendacterectomy. And you were mentioning that question about the outpatient and what's the aftermath after having this, you know, high-end technology addressing pulmonary embolism. Dr. Smith, I mean, we would love to hear from you. Why are you seeing, let's say a survivor receive all this high-end treatment and then now coming to your institution for, you know, pulmonary thromboendacterectomy? I can, I can say something about this. I can on, we started a survivor clinic in an ICU survivor clinic, and mainly it is for ECMO patients here. And the stories range very much from all over. Some people surprisingly doing really, really well. And some patients that we thought they would do well to really, really poorly and need a lot of psychiatric help and said that they would have died to, to put a very, and, but I would, we put a lot of, and this is not a talk on ICU survivor clinics, obviously, but we put a lot of our emphasis on this early interventions, but not, but no money by the hospital is put on in the long term outcome. But how can we follow up? And so, and what can we do in the long term? This is our 80% survival rate. Maybe we get there after PE, but really what we want are 80% of these patients sitting in a nursing home. And these are the questions we should ask. And I don't know whether anybody in the survivor clinic is a start, but it's only a start. Well, I think in the, five years ago, I was a little bit closer to the Pulmonary Hypertension Society Association. And I know that are roughly in the country for 40 pulmonary hypertension excellence centers. And I think if you are having this kind of programs, it will be good for those patients to be followed in the long term and probably be following that good way. I know there are more advanced imaging, CT imaging, et cetera. And you actually, the software is getting better and better that you can reasonably have some idea that this patient might transition in a condition such as chronic thromboembolic pulmonary hypertension. That's what you want to catch those patients. You don't want to spend all these resources and then they go nowhere and nobody follows them. And then 10 years later, now they have a very, very bad right ventricular failure. So at this point, because right now we as an intensivist, we should be more invested in the outcomes in the community, going back to the community and see what is there for what we did in such acute setting. But this is a good way to continue the conversation. Right. And I would say Dr. Diaz-Gomez, I mean, consistent with that, there's a good study out of Emory and Brett Keeling's group. This is probably, I want to say at least five or six years ago. So submassive PE is sort of a black box, right? Like you don't typically operate on submassive PE, ECMO is not really indicated. And depending on submassive PE, depending on the European definition, some can have a very high BNP, some can have RV dysfunction, some have a troponin, so there's a spectrum. So what the Emory group did was they looked at people with submassive PE and with RV dysfunction, and they operated, did surgical embolectomy on a lot of those patients and compared it to a natural cohort. And they found a significant reduction in the development of CTEP, so chronic thromboembolic pulmonary hypertension, because, you know, any cardiac surgeon in the country can do an acute PE operation. There's probably like 10 in the country who can do a good pulmonary endarterectomy, and probably three of them are in San Diego. So, you know, if you can save CTEP, that's a real interesting thing. So I think this needs to be prospectively looked at, but, you know, those patients that submassive or that massive PE who are not, you know, not bad, but they do have some persistent RV dysfunction, you know, those patients might be candidate for something more than just lytics or something like that. I have a question for both of you, and again, this is, a lot of what we do in the critical care arena is based on very strong pathophysiology. You probably are aware of this publication showing the right ventricular performance when you have a VA ECMO versus having a right RP impella or having a tendon heart, and I know you, we are talking here about VA ECMO, but it seems to me, and the way you support the right ventricle, it's not the most optimal mechanical circulatory support to promote recovery and actually having blood flow through the pulmonary circulation. I want your thoughts on that, and the reason I want to, I want to focus this immediately over the cardiovascular system, but ultimately, I have seen some reports on the impact on NIRS, you know, the brain oximetry, just because whatever you do from that standpoint ultimately will influence the brain. So, I think that there's, the thing about VV ECMO that I think it's interesting, and this was the, one of the studies that was included, which was a direct head-to-head comparison of VV versus VA ECMO. So, the survival outcomes were the same, so you think, okay, well, they're comparable, but in reality, the VA ECMO patients were just a much sicker group of patients. So, I think if you get to the question of who are sort of shock sort of patients who could probably get by with VV ECMO, I think that's probably a group of people, you know, most of these patients don't present with isolated respiratory failure as a predominant symptom. I mean, the massive PE is a hemodynamic disturbance, and so, to me, it's always been very limited in terms of the scope of what VV ECMO really can do. I think there is a, and because it's only short-term support, I think you get away with it. If you did VA ECMO on a PE patient with preserved LV function, it probably wouldn't work very well for an extended period of time, but you're basically just trying to get through the acute shock phase, support the organs, and that's why I think it really can. Thank you. Are you, my follow-up question, are you anything, are you venting when you do your VA ECMO, or what are you doing? Because in PE, that becomes obviously a much more difficult question than even the usual VA ECMO. Since all of it, we vent patients with severe LV dysfunction. So, in the PE setting where it's isolated RV dysfunction, we typically won't bother venting. It's just basically peripheral cannulation and bypassing it, you know, altogether. So, typically, we can avoid that, you know, in terms of that. So, I would say, like, by and large, you know, we're able to sort of do that. And again, the PE ones are very short runs. You're talking about three to five days, typically, at most, because, you know, when somebody arrests with, when somebody arrests, and they have to go on ECMO, one of three things will happen. They're either will not recover neurologically, and it moves towards palliation. They'll either recover just fine, and, like, you can withdraw and decannulate, or there'll be some that are in that gray zone of, well, there's some RV dysfunction. They're better. Their head's intact. Now, what do you do with those? And those are, I think, a little bit of an interesting algorithm. The Maryland group went to surgery right away, in our experience, because our group of patients will get ECOS therapy and lytics relatively early. If people fail that, we have taken one or two people to a second round of thrombolytics through an ECOS catheter. If there's some element of RV dysfunction, we've also sent patients to surgical embolectomy as well, you know, in terms of that. So, I would say that would be sort of the general approach. So, my question goes earlier, goes to very early. Is, I mean, are you, do you have a reach, community reach out, because mobile ECMO comes in here? Would, is there a vision to see, all right, my center 30 miles away calls, I'm sending my mobile ECMO team out, or is the timeframe too long, or what do you, where are you, are you experimenting with this for PE? Yeah. So, in our center, we don't really have a, we don't really have mobile ECMO capability. At the medical center, there are three large centers that do ECMO, each over 120 ECMO runs. One of them does have a mobile platform. It's not used in an out-of-hospital cardiac arrest setting. It's typically used in a, go out and cannulate somebody in respiratory failure and bring them back setting. But there is, I mean, I think there is, you know, the Minneapolis group writes extensively about their really good experience with out-of-hospital cardiac arrest and STEMI, and they have a real streamlined platform. I think they have a bus, like an ECMO bus where they can go out and cannulate anyone and whatnot. I think that that step, I think we're still a pretty, a significant waste for. I think that if we are going to do that, then you're talking about a pretty extensive utilization of resources in terms of that. And I think one of the other things that I think is really interesting is if you looked at the in-hospital cardiac arrest versus the CPR survivors versus non-survivors, the median duration of CPR in survivors was six minutes. The median duration of CVR in non-survivors was 36 minutes. So in an out-of-hospital cardiac arrest, you're almost never going to cannulate, you know, if you can cannulate somebody in 36 minutes, that's a phenomenally fast process. So I think that would be probably pushing it. Do you have any idea what the, what their mortality rate is with their mobile ECMO? You know, it's a good question. I don't have that offhand. If anyone else on the, if any of the moderators are more familiar with it, I certainly, you know, I mean, I think one way to look at it is that typically the mortality for out-of-hospital cardiac arrest without ECMO is probably on the order of about 95%, 90 to 95%. So if you have that mortality, I mean, that's a pretty dramatic, you know, difference, but I'll be honest, I don't know if anyone else does it, I'd be more than curious. It's high. What I remember, we use it for advanced heart failure. So we, a ECMO mobile mobile team for advanced heart failure in San Diego and the data are different, you know, difficult to say because his patients would die without it. So it always, it gets to a 90 to 100%, when you get a 90 to 100% mortality and get it down, the question is, you can argue this is always a good thing as long as you have the resources. Right. And that's exactly the question. Exactly. Because then you can also imagine a scenario where your ICU is filled with people who are brain dead on ECMO and it's hard to, as anyone knows, despite the best efforts with palliative care, once you put someone off, not everybody's ready to come, you know, not everybody's ready at that point. So, you know, then it becomes, you know, you know, like, you know, appropriate selection and whatnot. So I don't see any other questions from the outside yet. Maybe I missed it. But my other question is, do you have a protocol back to the pediatric? Do you have a protocol for when you have neurologic changes? What are you doing? Or is it all individualized? And I say, oh, my TCDs are going down a little bit. Let's try a little more blood. Let's try a little more volume. Let's try some inotropes. Let's try whatever we can do, some basic dilators. What can we do? What do you have a protocol? Yeah. Yeah. So I'm going to just tell you, I think across, you know, most of the ICUs who do ECMO or even the cardiac ICU, ICUs who do ECMO, majority of them don't use TCD. It's still very new to pediatrics. It's been much more established within the adult population. And its utility is, you know, I think for pediatrics has always been for the sickle cell children, evaluating them for stroke on the outpatient side. And so a group of us actually brought TCV into the ICU simply because we thought there is utility in this type of ultrasound diagnostic. And so protocol-wise, there isn't one. I think there are most centers, you know, depending on, you know, what their resources are. And I think that's a really, really important part that you brought up, Dr. Chatterjee, is the fact that, you know, most of them will do ultrasounds if the children are young enough. Others will try to do some type of portable imaging, but the majority of children, it's very hit or miss. Even standard EEG to look for subclinical seizures is not consistent across all ECMO patients. So, you know, TCD is kind of like on that extreme of do you even have the resources and sonographers and individuals who can interpret the TCD at your center? And so I would say to you, for us, it's been very research-driven. Our group does a lot of research around TCD nationally. And I think that research is starting to drive TCD closer to patients at the bedside, particularly ECMO patients. And also patients who are coming in with any kind of high risk for neurologic complications because of a central nervous system infection. Let me ask Dr. Ritter-Rice, how do you use, one of the real challenges that we find with ECMO is how to use the apnea test. And so, you know, I think it's, I don't know how to use it. So the argument then becomes, well, you really need a confirmatory test, you know, in terms of this. So how do you advise the, you know, sometimes to be honest, like you don't need to actually go all the way to brain death, people sort of realize, but if you need to pursue brain death, how do you recommend people pursuing brain death while on ECMO? Yeah, I think, you know, like that was like kind of my last slide, what do you do, right? And there are a lot of parameters that don't work based on the standards for brain death declaration in our patients, both for pediatric and for adult. I think, you know, there's been some interesting papers about introduction of carbogen and then looking at apnea. I think that, you know, the whole apnea test is always in question, even in those patients who aren't on ECMO, right? You know, there's always a discussion around, well, did we actually, you know, is the apnea test, you know, conducted exactly the way it needs to be conducted? So I don't have an answer for that, really. I wish I did, maybe someone in the audience does or one of our moderators. I think the majority of patients that we end up taking off ECMO, it's because they truly have multi-system organ failure. You know, we know we're starting to see neurologic sequelae and then, you know, you bring parents to the bedside and they, you know, they're starting to make decisions around the quality of life of the child who's on ECMO. And the second question I had for you is that, so the neuron-specific enolase and other sort of biomarkers, we always get those after the fact, and if they're bad, they sort of confirm our clinical picture and it's one more piece of information. What would be really invaluable would be a point of care, comparable sort of test, so that if somebody's undergoing CPR, that almost in the setting, just like we would get a rapid like blood gas, you know, things like that, as we're making the decision to decide, is this an appropriate candidate for eCPR cannulation? Where, how close are we to developing a sort of neuro-specific rapid point of care test to sort of direct us in something like that? Yeah, so I talked about the two papers from Bambia and her group doing the work around, you know, looking at brain biomarkers, particularly for patients who are at risk and ECMO happens to be the category of patients she was looking at. And I think we're still quite far away, particularly from a rapid diagnostic, right? And I think the challenge is this, is that, you know, even in probably the most highly defined, you know, population of brain injured individuals or risk for brain injury, like stroke or traumatic brain injury, we still haven't nailed anything down. Like, yes, we have S100 beta, yes, we have GFAP, but those are just kind of the quick and dirty, but are they truly gonna give you a good idea of whether or not this is an acute incident? Is this something that's been going on for a while? And I think, you know, when we look at our, particularly our ECMO patients, they're under so much cardiopulmonary strain, and then they also have perfusion issues to their central nervous system that I'm not really sure that if individuals actually got a whole, you know, barrage or a whole compliment of neuro-specific biomarkers that they might even be able to understand whether or not there's true cellular death or are they actually just, you know, in a state of brain shock or brain stress, right? Are they truly moved to brain crisis? And do we need to say, no, absolutely, don't go any further? And I think that's a real, the struggle is we haven't, you know, we're looking at these patients and we're trying to think of predictors, but what we haven't been able to do is really find biologic predictors, right? Like, who is that biologic candidate that's the perfect patient for ECMO? Or when are we, you know, who is the patient who has been on ECMO is showing, you know, optimal biologic markers to say that we're doing a good job. I mean, yes, you know, we have, you know, the common, what I would consider common biologic markers that we use today for, like you said, lactate or blood gases or, you know, but truly at the level of the neuron, no, we're not there yet. And that's unfortunate because it's a big problem when we have patients who, you know, end up, you know, making it through a run of ECMO, but then they are incredibly neurologically debilitated. And then we don't have actually the resources for many of these patients as they go forward. Yeah. And I think the other thing that I always emphasize in the eCPR case with ECMO, sometimes once people go on ECMO, there's a very different mindset. Okay, well, they're on ECMO, but I think all the evidence-based targeted temperature management, avoiding, you know, sodium and glucose disturbances and opto, I mean, things like it's extremely important to make sure that all those things are preserved. Yeah, I think it's kind of that, the thinking around neuroprotection, right? I mean, the strategies that we use for neuroprotection for those that are at obvious risk for brain injury, right? So whether those are the children or adults who come in with a central nervous system infection, or those that are coming in from either an acquired or a traumatic brain injury, you know, we automatically, our brains go to pay neuroprotection. And what are some of the strategies around that? Like, for example, you know, for adults, they can certainly tolerate more hypothermia than children can. Children can tolerate some very mild hypothermia. Babies tolerate it quite well, actually. They tolerate hypothermia well. So, you know, are those strategies we're using when we put patients also in ECMO? No, not really. No, because nobody's thinking about, oh, are we putting cooling blankets and all the other accoutrements to keep, you know, the patient thermally, you know, hypothermic? No, we're not thinking that. We're just thinking about, let's just, you know, make sure we get them cannulated so we can stop doing CPR and we can try to, you know, preserve as much as the patient as we can. So it's a challenge. It's really a challenge. And I've not yet seen, at least in my experience, I haven't seen individuals actually on cooling blankets as a neuroprotective strategy, but rather more of a reflex for hyperthermia when they evolve hyperthermia, right? I have a similar, and I can chime in a little bit. Yeah. What is your strategy? Are you keeping these children more awake? Because all our, your neuro, all these parameters don't help me much. When the kid can sing a song, I don't need it to be singing. Or when the adults can answer questions, I don't need a TCD. So my question is, what is your strategy on VA ECMO? Are you keeping them really deeply sedated or are they even paralyzed? Or are you trying to keep them similar to what was discussed in the PE population, awake and active? So, you know, it's a great question because children developmentally are so different than adults, right? So you can have the older child who is very comfortable, who we can even get up and walk on ECMO, right? So the level of sedation is mostly to manage pain and to keep their anxiety levels low, but then having some mobility for them. And then, yes, they are awake. You know, I think that, you know, by and large, our younger patients, it's much more difficult because, you know, they developmentally move regardless of what's in, you know, what kind of cannulas they have and what kind of bed they're in, they're still gonna move. And so most of those children tend to be kept a little more deeply sedated. You know, paralytics are only used now if they're refractory and they cannot, you know, we can't manage their blood pressure and we can't keep their heart rate, well, not their heart rate, but their blood pressure somewhat under control and that we think that there's some underlying pain or anxiety or fear going on, then what they'll do is they'll use more sedatives as well as paralytics should they be needed. We're really trying to move away from paralytics. But again, like I said, in ECMO, a lot of times it has to do with how much is the child moving and how just, you know, how much at risk do they place the cannulas? Because remember those cannulas are pretty short in kids too, right? It doesn't take much for a cannula to move in a baby or in a young child. But the other question that you asked about, you know, can we actually, you know, determine some sense of neurologic? Yes, we can, but I've watched a lot of patients who, and it's unfortunate because the majority of pediatric ECMO is not, you know, quick and dirty like you were talking about the PE, that the healthy PE patient, you know, not healthy, but the previously healthy PE patient who comes in and gets a run of ECMO, you know, they're on and off within three or four days. That's not typically pediatrics. You know, they tend to be a longer course of ECMO. It gets a little more challenging. They tend to have more end organ dysfunction with it, you know, and then we're adding CVBHD to, you know, to keep the kidneys going. And now it gets to be multi and complex. And then that whole idea around what, you know, how awake can they be? And then what is the introduction of all of these sedative and opiates that we use and their state of delirium, their state of wakefulness and arousal gets to be very difficult. So it's a very, what I would consider, it's almost like a Van Gogh. It's gotta be beautifully tuned and beautifully, you know, just illustrated. And just the colors have to be right in the right mix for that child to do really, really well. And be that up and walking, you know, kind of, you know, thriving ECMO patient that we can decannulate. Long-winded. Sorry, Olie, I don't know if that helped or not, but. Yeah, no, of course. And I would add to that, like in our setting. So for example, ECMO for post-cardiotomy shock, that is typically like a three to five day ECMO run. The patients are typically going to be intubated. You know, we might lighten up sedation a little bit, but the expectation is decannulation and then really work on the ventilator after that. Those patients who come in with decompensated heart failure, who can go on ECMO, then they're looking at a bridge to something else. You know, some of them will bridge to an Impella 5-5 with an extended period of time. But then some of them increasingly, you know, because of the way the heart transplant allocation score is, you know, some of them might stay on ECMO for a little bit longer and probably wait towards heart transplant. And so those are patients that we will extubate and, you know, work on getting them up and ambulatory and whatnot. And, you know, try to work on the cannulation configuration to try to put it up in the neck and the chest and try to, you know, give them something where they can be ambulatory for a period of time. And then I think VV is quite different. So I think depending on the indication and the bridge therapy that it's planned or recovery helps dictate how to go. Yeah, I think that's really important because, you know, they're very different entities to me. Like you can have the child who's maybe been on ECMO 24 to 48 hours and was just that quick bridge because we couldn't ventilate them. We got them ventilated. They underlyingly have a healthy heart and we can get them extubated with no problem. Then we have the other set if they have an underlying cardiac anomaly and they've had a cardiac repair and they end up coming back to the OR on ECMO or they need to go on ECMO after they've come back from the OR. Those are much trickier cases by far. And I think I would add one other thing that's important with respect to neurologic complications. When we looked at our program, about five years ago, we had a higher incidence of neurologic and bleeding complications. We convened experts in hematopathology, neurology, critical care, cardiology, CV surgery, and we really revamped the way we do anticoagulation monitoring. In general, we're less aggressive. We aim for lower targets. We do multiple forms of monitoring and we've seen a corresponding decrease in both vascular hemorrhagic and neurologic bleeding complications. So I think, you know, to Dr. Ritter's points, like all of these things are true, but it really does warrant a multidisciplinary approach to taking anticoagulation management very strict. Thank you, Dr. Chatterjee. So you were mentioning something actually I wanted to ask, which is I have personally struggled with this scenario when you have patient with possible long-standing COPD or some kind of pneumopathy, chronic pneumopathy, and then now you have to face the situation that you are doubtful whether or not this patient has EE, and you know that there will be some echocardiographic findings of a chronicity that limits sometimes your ability to say, well, this is acute and chronic, it's purely chronic, but at the same time, you're thinking about VA ECMO, it will be a breach to what? Based on the review that you did, did you see anything particularly on this specific patient population of chronic lung disease with possible PE, what to do? So I think that's a difficult and challenging question. The people who are unlikely to come off of ECMO are patients who have had lung symptoms for just, as you mentioned, tend to have symptoms longer and perhaps are more consistent with chronic thromboembolic disease. And so I think that workup, probably right heart cath in terms of looking at, you know, like right heart cath measurements and doing the appropriate workup along those lines is probably what's necessary. That's a difficult topic. And I'll be honest, I don't have a lot of command in terms of understanding what that is. Fortunately, it doesn't come up too often for us, you know, for me at least. And the other question I have for you, you being an ECMO director, I know you have revamped the program significantly. I have learned from you how important it is to have the right candidacy. I think that will be your legacy forever at Baylor. But can you share with us that case that you believe the patient wouldn't make it and ended up making it inspired us? Sure. I think that the first COVID ECMO patient that we had, so it's a VV case, 42-year-old patient came in, was, you know, needed ECMO. Everybody wanted to give up after 30 days. Everyone wanted to give up after 40 days. And, you know, he just, his kidneys, you know, he was on dialysis. He had a couple of small little, like, bleeding complications and whatnot. But, you know, on day one, before he was transferred, his wife called, got my number, and asked if she could FaceTime, and I FaceTimed. And it was her, and there were two kids in the back. And she just said, I don't care whatever you have to do, but if he has any chance, please return him home to me. And I think that that's a struggle. You know, I mean, everybody wanted to give up at some point. And I think that was, the number of conversations that I would have, I mean, even when I was not on service and I was on something else, I know, like, I would have about a 25-minute commute home. I would, like, call her from the car, knowing what was happening. And I think it really showed kind of what we can do. And so, you know, he, after 45 days on ECMO, another month and a half in the hospital, finally comes home, and then they send me pictures of him, you know, playing with his kids and all of that. And so, and, you know, she sent, over the Christmas holidays, she sent a nice gift for my kids, you know, to really enjoy, you know, some treats for the holidays. I will say that, like, that's a win. We have a number, and I think COVID has challenged us all, you know, we have 400,000 plus, you know, gravestones. And I think that at the end of the day, you just have to do, you know, at the end of the day, we just have to try to help as many people as possible. I think this meeting that you've co-chaired, I think is so dedicated to just doing that, that we can't win everything, but each day, I think there's a saying in sports, you have to have a short memory, meaning that in sports, if like, you know, somebody, you know, like you lose or you have a bad play, you have to forget about it, learn real quick, forget about it and move to the next. And I think that's part of what we have to do is, you know, if there's a lesson to be learned, learn from it, but forget about it and treat that next patient as if it's brand new and the patient in front of you. Thank you. Dr. Ritter, I will be really, really interested to listen to your story, anything you want to share with us, because there is a humanizing component of this high-end technology. And this is what probably really bring everybody up to speed and be able to do a real team building for better outcomes in ECMO. So would you mind to share with us? Yeah, and so this is a story of a young infant who came in and essentially was coming in for cough, cold, runny nose, which, you know, everybody around winter season attributes to RSV. The child was not RSV positive, but instead was positive for pertussis, which as you can imagine, has a lot of pulmonary hypertension components to it and ended up going on VA ECMO and was on VA ECMO, not, you know, clear, well over the amount of time that we typically have kids on ECMO. And then we start to become alarmed. Luckily, the child actually didn't have too many multisystem organ dysfunction. And so we actually had the child on longer, hoping the, we always worry about the brain and that there aren't any bleeds. And by ultrasound, the child's brain looked fine. So we continued the ECMO until we could get the child's flows down enough to convert them to, you know, conventional ventilation. And the child actually did really well, but it was a daily conversation around, you know, are we doing the right thing? Are we going to have a good outcome? And what, you know, what are the risks for long-term ECMO? And the baby's thriving. Now is already a young preschooler. So I think it's kind of a plus minus for me is that we've sometimes been put in situations where, you know, when we're putting emergency ECMO in place without good conversation around, what are we really doing for the patient and the family and what messaging are we providing them? I think it's something that the team often grapples with because in the end, when it doesn't go well, we have to, you know, kind of think back, well, did we make the right decision? And at the time it always seems like the right decision, or perhaps we didn't have, you know, the information we should have had to make a better decision. So, you know, there are wins and losses. And I think in pediatrics, it's particularly difficult because, you know, this is a family who often just had a completely healthy child and now is, you know, struggling to understand whether or not their child will ever be healthy again. I think ECMO can be amazing and give much hope. And I've also seen ECMO where it's been in place where, you know, even as a provider, you're saying, what are we doing here? And are we doing the best for this patient? Because the outcome typically can be very devastating. So I kind of, I sit on the fence with it. I think as we continue to learn more about the right time to put a patient on ECMO and who, and what those patients look like over a longer period of time for follow-up, you know, are they having quality of life? I think, you know, for us as IC providers, it's important to remember that on the outside of this, we have to ensure that the work we do and the science that we're trying to drive is that there's truly good outcomes as well. And so for me, I'm very outcome-driven. I like to think that the work in both pediatrics, but also in adult research around topics, particularly around the cerebral vasculature is very important for me, that we know we're doing the right thing by the patient and the family. So a little long-winded, but yeah. Dr. Smith, you are a very experienced clinician. You are a very smart individual who trained me. You have been exposed to, you know, anything as an intensivist. And you are part of the program committee. And I want your vision on what will be those controversial aspects of ECMO that we should address in the next couple of years to come back and kind of have established a pathway to have that continuous improvement on such a controversial topic. What do you think? What would you like to revisit a couple of years from now? What I would really like to know is something which just was brought up by Karen. And to know, are we, because we are always risking and pushing or pushing forward. And it's on one hand that I'd seem to do, but at what point are we pushing, are we pushing too far? And I remember from Dr. Sabro, who is more or less a starter of ECMO, who told me his first 10 patients, first 10 kids on ECMO all died. And so right now we could have stopped these 10 kids. We would have lost millions. Maybe not millions, but many, many, many kids. On the other hand, we have this 90 year old patient with end stage heart failure. We are putting, we are pushed to put on ECMO by, and I don't know, with no EF and no, and a bridge to nowhere. And we need to find, we are really, I really wanna, my hope is that we find out that we can say, when this patient comes in, that we have a much better chance to say, to direct the family correctly. Because right now, sometimes we have a feeling, but as was pointed out, our gut feeling might be wrong. And if we are not just on my gut feeling, but if I could say, Jose is coming in right now, I'm putting in on VA ECMO and I can tell his, look his wife in the eyes and said, in 30 days, he will look better. Or I could also say, sorry, we should not do this. This is my hope for the next 10 years. Now, unfortunately we are so far away from this, said it's still very controversial and so much resource intensive, said, should I really put so many people in ECMO and I cannot support the next hospital, this even PPE? I'm just, these are questions which also have to be asked in this high risk endeavor. And I do not know, and thank God I don't have to answer. I think that's a very good point, because I think there's a very good, I think if you look at the technological advances in mechanical circulatory support over the last 10 to 15 years, the technology has evolved much faster than our ethics with respect to ECMO and end of life situations. And I think that it really underscores that when a patient presents in cardiogenic shock, in the heat of the moment, and somebody just asks a family member, do you want us to do everything? Most family members then just say, yeah, do everything you can, without realizing kind of what the implications of all of that are. What we have found, especially in our ECPR settings and in our COVID ECMO settings, is routine consultation of palliative care and even our ethics committee. But I think palliative care sometimes, because they talk to the families outside of the physician, outside of the treatment thing in a different context with a different conversation, I think they provide an invaluable service in terms of that. And so I think we have to sort of continue to do that. There are programs that actually have, before patients get an LVAD, they have a routine palliative care consultation, and it's really designed for that conversation. And they can sometimes successfully avoid situations where things might not go well and whatnot. And if they choose, like they don't want an LVAD, then they're not also really an appropriate candidate for ECMO, because in terms of all of that. So I think this requires not just critical care, but this requires cardiology and all aspects of medicine to be able to help with this. Well, thank you so much. I want to make a final comment. And I haven't told you this, Dr. Chatterjee, but one of the things I have enjoyed the most after joining Baylor has been the fact to be participative in the final decision to start mechanical circulatory support. And you know, we have been really challenged with very tough cases, but I'm making this comment because what my previous attendant, Dr. Smith, mentioned, the gut feeling, I have gut feeling and still try to be as humble as I can be. And I just dialed your number and you always have answered the phone and give me your opinion, straightforward opinion, or I have called other colleagues. We need to elevate that kind of camaraderie whenever we are not sure what we're doing with our patients. And ECMO is probably one of the best settings to enhance that kind of collegiality because these are very tough cases. It's a young guy with kids and we go by his scores. Oh, maybe he's not a candidate. I'm being very uncomfortable, but thank you for being there for me. And I think we are probably learning more and more, but definitely we're going to need probably help from IT, AI, other kind of sources to be more predictive of who really needs the technology. So I hope life will give me the opportunity to be a co-moderator of you guys in the future, but I think that this dialogue will continue in the years to come. And I think that's all appreciated. And this is where I think it goes back to, we have to be mindful of what our survival outcomes are because I know that the easiest way I can drive my ECMO survival numbers higher is I can never take any case that's bad and I could take really good cases and my numbers will look great. And if we get to a point where everything comes down to survival outcomes, people will cherry pick just for that reason. It goes back to the three most important determinants of outcomes are patient selection, patient selection, patient selection. So I think we have to understand within the context that a successful ECMO program is not just about survival outcomes, it's about the entire process and reduction of complications and all sorts of things. So that's where one of those things, it's not like somebody who's doing cabbage surgery where I can tell the surgeon with a 1% mortality is always better than the surgeon with a 8% mortality. ECMO is not the same way. Thank you. Great closing words. These were fantastic closing words. ECMO is really not the same and we need to see that we get better overall, just get better over time. I think we also need more long-term research in our ECMO patients. I think we need to start, I love the idea that Dr. Schmidt has the post ECMO clinic because there's at least the beginning thought that these patients look different and might need post-op and follow-up care that looks different than our other type of patients. So I think if we could start focusing on what do those patients look like and how do we not just bridge them from time of hospital but beyond, what kind of resources do they need and how do we start front-loading that already in the ICU with ECMO patients? I want to say congratulations to all the speakers and my co-moderator, Dr. Schmidt, Dr. Chatterjee, Dr. Reuter. We have finally 237 attendees. I claim this a real success. Thank you so much for your contribution and I really hope that you submit similar sessions for our future SEC and Congresses. Thank you. Thank you, it was my pleasure. Thank you, enjoyed it. It was an honor.

ECMO

extracorporeal membrane oxygenation

patient selection

underlying condition

severity of symptoms

likelihood of improvement

diagnostic tests

monitoring

TCD

transcranial Doppler

biomarkers

brain function

organ health

multidisciplinary approach

communication