Thanks so much for joining this session. Today, we're going to be talking about the role of ECLS during and after resuscitation. I have no disclosures except that I'm a pediatric intensivist and so that's the bias that I bring to this. We'll start with some definitions. We're talking about ECLS or extracorporeal life support, also known as ECMO in the setting of cardiac arrest. Cardiac arrest event happens to a patient, we initiate CPR. Some of those patients will not have ROSC or return of spontaneous circulation. Typically, we define that as lasting at least 20 minutes. If the patient does not have ROSC, then one of two things can happen. If they don't have ROSC and they are not offered ECPR and cannot achieve ROSC, then the patient ultimately dies. In some centers, we can offer rapid deployment of ECLS during ongoing CPR and that is termed eCPR. eCPR is initiation of veno-arterial ECLS while either active chest compressions and CPR are happening or in that first 20 minutes after getting a pulse. That's the current also definition of eCPR. On the other hand, you may have some patients that get high-quality CPR that achieve ROSC, and then they transition immediately to post-arrest care. Some of those patients may require more support for any number of reasons, and so be put onto VA ECLS in that setting, and that's termed post-arrest ECLS. Since eCPR and post-arrest ECLS are different entities and often reported differently in the literature, we're going to approach them separately here as well. It should be really clear, as you'll see, that eCPR has pretty clear guidelines about what the protocol should look like and is fairly well-reported in the literature, whereas post-arrest ECLS tends to be less frequently reported. We don't have as much literature to guide us and certainly not as much in the way of guidelines and formal processes. We need to say at the outset that in an ideal situation, you go into ECLS without a proceeding cardiac arrest, and then avoid this whole mess on the right to begin with. But since today we're talking about ECLS for the patient who has suffered a cardiac arrest, we are going to be on the right-hand side of this. Let's start with eCPR. Just a reminder, eCPR, eCLS during active CPR or before 20 minutes of ROSC. Look at the eCPR trend use overall. On the right-hand side of the slide, you can see this graph shows that there has been steady growth in both the number of cases as well as the number of sites offering eCPR that contribute their data to the ELSO database. Then if we look at the absolute numbers in 2020, there are about 7,800 cases of pediatric eCPR. This represents about seven percent of all in-hospital cardiac arrests in this population. Depending on the cohort you look at, that's in the CICU, it's even a larger proportion, 19-27 percent of arrests. The adult side, we are also seeing growth with over 10,000 cases reported in 2020 to the ELSO registry. When we look at patient selection, this is a really important factor for the success of an eCPR program and also for outcomes. There are a few pieces here that are pretty consistently agreed upon, and then some things that tend to vary from site to site. In general, the arrest event needs to be witnessed and have high-quality eCPR ongoing to be considered eligible for eCPR. We need to have a potentially reversible condition. Sometimes you don't know for sure either way, but at least something that we think might be able to be reversible, and so eCPR would make sense in that context. You need to really clear local guidelines. Every context can have different capacity and see a different patient population. Deciding as a group of people who offer eCPR as a team, who you're going to consider a candidate and who you're not going to consider a candidate can really help both with making sure we put the right patients on, and also that things are less chaotic in the moment when we have to decide about whether a patient is a candidate or not. In a perfect world, we discuss candidacy ahead of time, and so particularly for ICU patients who are complex or high acuity, this can be done daily at handoff, can be handed off whether they're a candidate for eCPR, or in a daily safety huddle or something like that. This facilitates more thoughtful discussion about the pros and cons, and then also sets up the person at the bedside who ultimately has to make that decision with all the information they need to make that call. Then adequate vascular access is an important logistical consideration. Depending on the patient's anatomy, if they're congenital heart surgery patient, or if there are known clots that exist in large vessels, some patients may or may not have the vascular access required to facilitate rapid accumulation to eCLS. In those patients who might have known clots, using a vascular map at the bedside can be really useful, or if their access is unknown, again, looking at really high-risk patients who are really high acuity, you think might have an event, looking with an ultrasound and mapping out their large vessels in advance can really help make things much more efficient if something were to happen. This slide sets out the steps required for implementation of eCPR. This is a simplification, but it's really complicated. A lot of things need to happen and they need to happen quickly. At time zero, the patient has an arrest, it's witnessed and recognized, somebody starts CPR, an airway is obtained, and then at some point, and the trigger time is a little different in each context, but at some point, someone calls an eCPR and activates the team. The team, the equipment, any supplies required from blood bank are rapidly mobilized, and so they all come to the bedside, and then the patient has cannulation during ongoing CPR, and eventually you get onto full eCLS flow and start the post-arrest care. This is clearly complicated, requires a huge team of people with a variety of expertise to work together. There's a lot of things that have to happen really quickly and really smoothly for this to go well. Having a formalized protocol, having training, and then using simulation to maintain the capacity of the team is really important. I've highlighted here the CPR piece because we need to remember that eCPR is still CPR, and it's really important to provide high-quality CPR throughout. A portion of the team needs to be focused really just on CPR quality throughout this resuscitation to make sure that the brain is getting adequate perfusion through what can be a fairly lengthy process. Median time to cannulation is around 40-50 minutes or so, depending on the cohort and the team. They certainly can take much longer than that, and so really ensuring that you have adequate resuscitation throughout is the most important thing from the brain's perspective. What's the goal of eCPR? Clearly, eCLS is not a destination therapy, not at this time anyway, but it buys you time, so think about it as a bridge. A bridge to recovery for patients who have an underlying illness that could recover on its own. Maybe a bridge to a device. In some places that use a lot of ventricular assist devices or other devices, they'll sometimes use eCPR for the immediate rescue and then quickly transition to a device. It could be a bridge to transplant, and sometimes it's a bridge to decision. We just don't have all the information we know when the patient has their event, and this gives us some time to make decisions, to get more information, and decide what to do going forward, and sometimes that includes providing compassionate end-of-life care. How do patients do after eCPR? This is in pediatrics. About 40 percent survive to discharge, and of the patients who survive, about 93 percent of them have a favorable neurologic outcome. It's normal or mild as one or two or unchanged from baseline on the pediatric cerebral performance category scale. This has been noted in studies to be higher survival and better outcomes than conventional CPR for prolonged cardiac arrests. We have to keep in mind that there's really important bias introduced there. There may be good reasons that patients are not considering eCPR candidates that also are associated with their outcome, but certainly 40 percent survival is encouraging. Mortality is associated with older age, with complications during the ECLS run, with severity of illness, and then with non-cardiac diagnosis. In fact, the current AHA guidelines recommend consideration of eCPR for pediatric patients with cardiac diagnoses, but they do not necessarily recommend this. There's inadequate evidence to recommend using this in the general pediatric population. I should say though, in practice, many centers offer eCPR outside of their cardiac patients. It's just a matter of not having as much evidence in that group, and we know that the patients with cardiac diagnoses tend to have a better outcome. This is split up into in-hospital and out-of-hospital cardiac arrest. Again, there are some reports of pediatric out-of-hospital, but the vast majority of out-of-hospital eCPR is provided in the adult population. In-hospital, about 30 percent survive to discharge with 84 percent of those patients having a favorable neurologic outcome. Out-of-hospital cardiac arrest, it's about 24 percent survival to discharge, about 75 percent favorable neurologic outcome of survivors. Again, this really varies from center to center. Patient selection has a huge impact on outcomes after eCPR, and so there is quite a bit of variability. We'll switch gears and look at patients with post-arrest eCLS. As a reminder, these are patients who have a cardiac arrest, they achieve ROSC, they receive routine post-arrest care, and then in the post-arrest period are cannulated for eCLS. We don't have as much data on this group of patients, and so we'll go through what we know and really highlight some gaps in the current literature. Patient selection, which patients are most likely to benefit from eCLS after return of spontaneous circulation? Patients with evidence of shock and cardiogenic shock in particular, these patients may, just like patients who have not had a cardiac arrest, you may consider them for eCLS cannulation in that situation. Patients who aren't meeting post-arrest goals, and we'll go into that in a moment. Then patients at high risk for current cardiac arrest. This group is hard to define, but might be an important high-risk group, so we'll go through this a little bit more. We'll start with patients not meeting post-arrest goals. This is the post-cardiac arrest care algorithm for adults from the AHA. The goals of post-arrest care, whether it's pediatrics or adults, are similar. Maintain adequate and normal oxygenation, a normal CO2 to optimize blood flow to the brain, and then adequate perfusion. Depending on your age, so for adults and pediatrics, those definitions are going to be different. But making sure that you have adequate hemodynamics to support good neurologic perfusion and support neurologic recovery. If a patient is not able to achieve these goals, or is having a lot of difficulty, you're having difficulty achieving these goals in your patient, then this is a group of people that you might consider cannulation for eCLS to ensure that they have optimal neurologic perfusion and hemodynamic stability. Another group of patients we think about are patients who are at high risk for recurrent arrest. Here we're going to turn to the pediatric literature for recurrent cardiac arrest. We know that patients who have children who have an in-hospital recurrent cardiac arrest event are less likely to survive to hospital discharge. In this study, the PD Rescue Database, which is a multi-center collaborative quality improvement database, they found that patients who had a recurrent cardiac arrest were less likely to survive to hospital discharge, so their survival, actually, this is only part of the survival curve, but their survival to hospital discharge was 31 percent versus 64 percent in the single arrest. Clearly, having a second arrest is not a good thing. If we look at when the recurrent cardiac arrest event happened, this graph, each bar is an individual patient, and the yellow bars are the patients who survived, the blue bars are the patients who died, and along the x-axis, we can see time out to about 24 hours. You can see here that about 50 percent of the patients in this study had their recurrent event within six hours of their index event, and the majority of those patients did not survive. The blue bars are certainly over-represented there. These patients had a recurrent arrest event that happened quickly and then did not survive to discharge. If we could identify these patients, maybe this is a group who would benefit from early ECLS and early post-arrest period. How can we identify patients who are at risk for a recurrent cardiac arrest event? This comes from two studies. One is one I just showed you, and then another is our single-center experience from Seattle Children's where we looked at early recurrent arrest as well. The overall factors that are associated with recurrent arrest in children are their primary diagnosis, having more pre-existing comorbidities, and also a shorter CPR duration was associated with the second event. Then early recurrent arrest, and I will say the previous study identified that as, I defined that as six hours or less. In our single-center study, we used 48 hours as the cutoff. But these early arrests were associated with older age. We found severe pre-arrest acidosis and pre-arrest multi-organ dysfunction syndrome was associated with an early arrest. Then also hypotension is the primary cause of the event or immediate cause of the event. This is promising. There are things that we can identify that help us find these patients at high risk for recurrent arrest. The problem is that none of these, they all have low sensitivity and specificity, and so we certainly need further work to try to find ways to identify these patients more reliably. Who are the patients who receive post-arrest ECLS and how do they do? In pediatrics, we really don't have a lot of data on this, honestly. Especially compared to the ECPR cohort, we have this meta-analysis here that was published in 2008 that demonstrated that patients who had post-arrest ECLS had shorter duration of CPR than their patients who had an ECPR event, 34 versus 55 minutes. That study, unfortunately, did not report survival in each group. They only reported accumulative survival. We don't know how they did in comparison to the ECPR cohort. We look at the ELSO registry report from 2016. Cardiac arrest was listed as the primary diagnosis leading to cardiac ECLS in about three percent of patients. They had a similar survival to ECPR, which is about 44 percent. I think we can assume that this is an underestimate because the cardiac arrest was listed as the primary diagnosis, and there's certainly other children that would have had a primary diagnosis of something else that also had no cardiac arrest event, but this is just the best data that we have currently. In adults, we have a little bit more data. This comes out of the study to develop the SAVE score for prognosis after cardiogenic shock in ECLS. In their cohort of patients with ECLS for cardiogenic shock, 32 percent of those patients had a preceding cardiac arrest before they were accumulated and 28 percent survived to hospital discharge, and that's quite similar to the overall ECPR survival for in-hospital cardiac arrest in adults. Where are we going next? What's next in this field? There's some important gaps in the literature that need to be addressed for sure. For ECPR, we really need studies of CPR quality. We don't have much in the way of CPR quality data for these patients and understanding how quality mediates the relationship between the length of resuscitation and outcome is important. We also need studies and guidelines for post-arrest care of these patients, including neurologic monitoring and having a standardized approach to how best to provide high-quality post-arrest care for these patients. In post-arrest ECLS, there's even more opportunities there, really trying to identify who the high-risk patients are, who are the patients who are most likely to benefit from ECLS after a return of spontaneous circulation. Then hopefully, evidence-based guidelines for use of ECLS in the post-arrest period can follow that. This study here in the bottom, it's a really nice review of pediatric ECPR and also nicely outlines the opportunities for growth in the field and the gaps that exist in the current literature. Thank you so much for your attention. If you have any questions or comments, I'd be happy to answer those in the Q&A. Please don't hesitate to reach out to my Twitter there. I'd be happy to chat more with anyone who's interested. Thanks so much.

extracorporeal life support

ECLS

ECMO

pediatric patients

resuscitation