SCCM Pod-525 PCCM: Extracorporeal Cardiopulmonary Resuscitation Outcomes in Pediatric Patients

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Host Marilyn N. Bulloch, PharmD, BCPS, FCCM, is joined by Catherine Beni, MD, PhD, to discuss a study aimed at determining outcomes of extracorporeal CPR (ECPR) in pediatric patients without congenital cardiac disease and identifying associations with in-hospital mortality of factors such as initial arrest rhythm and patient demographics (Beni CE, et al. Pediatr Crit Care Med. 2023 Nov;24:927-935). Catherine Beni, MD, PhD, is a resident physician in the department of surgery at the University of Washington in Seattle, Washington.

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Transcript:

Dr. Bulloch: Hello and welcome to the Society of Critical Care Medicine Podcast. I’m your host, Marilyn Bulloch. Today I’ll be speaking with Dr. Catherine Beni, MD, PhD, about the article, “Outcome of Extracorporeal Cardiopulmonary Resuscitation in Pediatric Patients Without Congenital Cardiac Disease: Extracorporeal Life Support Organization Registry Study,” published in the November 2023 issue of Pediatric Critical Care Medicine. To access the full article, visit pccmjournal.org. Dr. Beni is a chief resident physician in the Department of Surgery at the University of Washington in Seattle, Washington. Welcome, Dr. Beni. Before we start, do you have any disclosures to report?

Dr. Beni: Thank you so much, Marilyn. No, I have no disclosures to report.

Dr. Bulloch: The title of your article is a mouthful. It sounds like a very impressive advancement in medicine but, for our average listener, will you give us just a brief introduction about what extracorporeal cardiopulmonary resuscitation is?

Dr. Beni: Yes, absolutely, and you’re right, it is a mouthful. In medicine, we resort to acronyms to manage all these mouthfuls. But briefly, eCPR, extracorporeal cardiopulmonary resuscitation, is the rapid deployment of venoarterial ECMO, or extracorporeal membrane oxygenation, that provides circulatory support for patients for whom conventional CPR isn’t successful. And really, we define it as for patients who have not had sustained return of spontaneous circulation, which is actually recently defined. In 2018, it was formally defined as unable to have a return of spontaneous circulation after 20 consecutive minutes of chest compressions.

Dr. Bulloch: I can imagine. In a past life, as mentioned earlier to you when we were talking privately, I was an EMT, and CPR is something I think most of us in critical care are very familiar with. When does the team, especially a pediatric team, decide to employ this, I guess, from a practical standpoint? I mean, it doesn’t sound like it’s going to be something, obviously, that’s going to be employed in the field. Do you have people who are in the emergency room waiting for them to come in? Is it primarily for people who code while they’re already in the hospital?

Dr. Beni: Marilyn, that’s a great question, and I actually think that hits on a very critical aspect of eCPR, which is who it gets deployed to and how it gets deployed. As you alluded to, it’s a very specialized intervention. It requires a whole team of people to deploy, from the surgeons, who will actually cannulate the patient and place the cannulas, to the pediatric intensivists, who will be running the code and managing the resuscitation, to the perfusionists, who are going to be actually running the ECMO machine. So really, it’s currently used in specialized centers.

The use of ECMO in general, and eCPR in particular, has increased substantially over the last 20 years. Initially it was introduced in adults in 1972, and then 1993 in children, and then has really taken off more and more. Initially, eCPR was really used for patients after recent cardiac surgery because it’s essentially cardiopulmonary bypass. For these patients who had recent cardiac surgery who had had a recent sternotomy, you would be able to open the chest and centrally cannulate them, replacing the cannulas directly into the great vessels or into the atrium as a rescue maneuver after cardiac surgery.

And now we’ve moved on to peripheral cannulation. But to answer your question, basically, it requires a specialized center with a specialized team of people who are trained to deploy this. We can talk more about that later and what that looks like.

Dr. Bulloch: Absolutely. Now, your study was very unique in the fact that you purposefully excluded people without congenital cardiac disease. We’ll talk more about that in a minute. I can imagine, when talking about pediatrics, it would be really difficult to do a prospective study, at least to get the numbers that you would really want. Your team decided to do a retrospective study. Is that pretty much what you find in line with real-world practice?

Dr. Beni: Yeah. It’s honestly very challenging to do prospective studies, I think, for some of these almost end-of-the-line interventions, especially once we become introduced and adopted. To a certain degree, considered standard of care, it becomes very difficult to perform a prospective study, especially for here, when you compare what the controls would be, which would be potentially to continue CPR or to stop CPR.

Dr. Bulloch: That could be really difficult in a kid, you know, you want to, I don’t know, maybe it’s my heart, I want to do everything for that child, but that’s why I’m not in pediatrics. Now, your group used something called the Extracorporeal Life Support Organization database, which I’m sure was really a good wealth of information. For those of us who haven’t had a chance to be familiar with that database, tell us a little bit more about it.

Dr. Beni: The Extracorporeal Life Support Organization, or ELSO, database is a really fantastic resource for people who are interested in really understanding more about ECMO in general and eCPR in particular. It’s an international registry, 284 centers for pediatric patients, 284 centers for neonatal and pediatric eCPR, and it’s across more than 50 countries. For gleaning an understanding of this very complex and fortunately relatively rarely deployed intervention, it’s a really fantastic wealth of resources.

Dr. Bulloch: When you say it’s international, can you tell us broadly where most of your patients came from?

Dr. Beni: Actually, country was not available in the dataset. That’s something that they don’t make available to us.

Dr. Bulloch: That sounds like it would be good to know, but kids are, I think, very similar worldwide in a lot of ways. Some of the demographics you were able to get though were the main causes of what led to them needing eCPR. If I noticed correctly, respiratory disease and acquired cardiac disease were really your two main causes. Is that what you would see maybe in clinical practice?

Dr. Beni: Yes. I think we see a lot of respiratory arrest or cardiac arrest remaining the primary causes, but we’ve actually seen an uptrend in clinical and other causes. You can see that in Table 1 here where we see sepsis or cardiac arrest in the setting of severe sepsis, and septic shock being another uptrending diagnosis prior to eCPR deployment.

Dr. Bulloch: That’s interesting because I know there’s been a lot of movement toward sepsis in this age range. One other thing that I noticed, and it’s right in your title, that you excluded anyone with congenital cardiac disease. Why was that such an important exclusion for your research team?

Dr. Beni: Yes. It goes back to the reason for arrest and essentially the possibility of reversal of the cause of arrest. As I said, initially it was deployed in patients with congenital cardiac disease who had undergone open cardiac surgery, and now it’s spread beyond that.

But what we’ve noticed is that the majority of the outcomes data has been focused on patients with congenital cardiac disease as that’s kind of the classic group of patients where this spread from, and then pooled groups of patients with congenital cardiac disease and without congenital cardiac disease. But we had not seen a study that was devoted to patients without congenital cardiac disease specifically, and we really wanted to look at patient outcomes from eCPR in patients without a structural cardiac problem that might be addressed mechanically.

Dr. Bulloch: I really liked how you divided up your results based on age all the way up until age five. But in my mind, five and greater, that’s a long span going up to 18. But I think it accounted for about a third of your patients. Were they just spread pretty broadly from age five to 18? Or did you have any other chunks in between there?

Dr. Beni: They were spread pretty uniformly, a little bit more closer to the early grade-school age, you know, five to 12, and then fewer teenagers as it would taper off up to the age of 18. But within that age range even, I would say five to 12 is a pretty broad age range, we found essentially uniform distribution.

Dr. Bulloch: Are there any physiologic differences in this age group that we should think about in terms of how they might respond to eCPR? I know in the younger ages, obviously a month or two can be a big difference. But what about when you get older?

Dr. Beni: I think that when you get older, it really boils down more to the underlying diagnosis and the reason for the arrest in the first place. I think that some of the just purely mechanical issues change a little bit. Really what I mean by that is, how do you cannulate the patient and how do you place the cannula? I think that once you get to, especially when you have teenagers and larger patients or closer to adult-size patients, it’s basically placing a large central line. So if you compare that age range to infants and neonates, it’s kind of night and day in terms of the cannulation process.

Dr. Bulloch: The mortality outcome that you found in your study was about 59% in hospital mortality, is that right?

Dr. Beni: Yes.

Dr. Bulloch: I don’t know how to take that. Is that good? Is that not good? I mean, I guess this has got to be a perspective thing in terms of context.

Dr. Beni: That’s a great question. It’s something that I’ve been asking myself as well. On a personal level, I’m a parent of two children, so I think about this in the era of informed decision-making. What would I say if my pediatrician or the pediatric intensivist told me this statistic if it were my child who were in such a terrible situation?

But I think what we really need to look at in order to be able to understand what that means is longer-term outcomes. That’s something that several studies have looked at. I’ll refer readers to this great review paper that one of our coauthors wrote. Dr. Ivie Esangbedo wrote this fantastic review paper on a systematic review on pediatric eCPR that was published in Pediatric Critical Care Medicine in 2020. There she talks about what studies have really looked at these longer-term neurologic outcomes and what that means for the pediatric patient and for their family. I think that also plays a big role in understanding that mortality as well.

Dr. Bulloch: It also seems like it may not just be very cut and dried, to kind of look at individual patient characteristics and maybe even them collectively rather than one individually. Looking at this, I see different demographics that maybe increased or decreased your risk of mortality. I want to just touch on a few of them if that’s okay. You talked a lot about obesity in your paper, about why you thought obese children might not respond as well.

Dr. Beni: Yes, it was really interesting. This paper was purely a discovery paper. We really wanted to describe what the outcomes were in this patient population and then see if we could find any associations. We were surprised to find that obesity was associated with such a higher odds of mortality. It was over double the odds of mortality. I think there were a few thoughts that we had on why this might be.

The first might be efficacy of chest compressions in the obese population. That’s something that’s been explored. I’ll refer any interested readers to some great critical care work on looking at mortality associated with pediatric obesity and pediatric critical illness. But some other things to think about are the difference in the volume of distribution of resuscitative medications. Are we dosing patients appropriately? Differences in weight-based defibrillation voltages for those patients who have a shockable rhythm.

Then the other thing, I always consider this as a surgeon, the difficulty of cannulation. This is something that I’ve struggled with and I’m sure everyone who places central lines has struggled with, in obese patients, just finding a window and being able to access the vessels is harder and particularly harder when someone is concurrently undergoing chest compressions. That’s something that I would be really curious to explore more.

The ELSO database, as I mentioned earlier, is a phenomenal repository. But some of the things that were not collected in the earlier data included variables like time duration of chest compressions prior to cannulation. I think that would be really fascinating to see whether obese patients, for example, had longer duration of chest compressions. Maybe we could look into the duration of time from the decision to cannulate to actual initiation of ECMO.

Dr. Bulloch: That’s really fascinating. I was looking at the ages too in terms of mortality and, really, age didn’t make a big difference until you get into the older kids range. Those are over the age of five. Do you think that there’s some sort of connection there with a lot of the same considerations you were talking about with obesity being true as we get older?

Dr. Beni: I think that’s possible. I think that we did not break down obesity by age so I don’t have the answer to that, if that is true. I think that it’d be interesting to look at just the spectrum of disease processes in those older children. We noticed in particular that a trauma, which was associated with very high odds of mortality, occurred pretty much exclusively in that age range.

Dr. Bulloch: Interesting. That sounds like there’s a lot to explore later on. A lot of, like you said, a discovery study, so a lot to maybe like trigger or lead to later on down the line. Another thing that you noticed that actually had lower mortality was those pediatrics where their initial rhythm was V-tach. Why do you think that was true?

Dr. Beni: Well, I think that, in general, we’ve seen that V-tach and ventricular fibrillation have been associated with better outcomes after cardiac arrest than PEA or asystole, and potentially that has to do just with the underlying myocardial dysfunction and the ability for the heart to recover after it’s been supported for a period of time. Then the possibility of any reversible causes that triggered someone to go into that arrest rhythm in the first place.

We were really curious looking at one of the things that triggered the whole study in the first place. Then the reason why we did the subgroup analyses is because we were really curious to see if there was even an impact on mortality and to see if that could potentially guide future studies for inclusion and exclusion criteria. Who should get eCPR? Or who should we offer it to? Who has the highest chance of a successful eCPR run?

Dr. Bulloch: I’m going to put you on the spot. I know we need prospective studies to really hash this out a little bit better. But you said you’re a mom, I’m a mom. If this were your children coming in, just based off the stuff that you’ve seen from the data that you got, and maybe even some of your own experience with eCPR, is this something that you would want for your children? Do you think that it has a good benefit based on what you’ve seen and the results of the data that you found?

Dr. Beni: No, that’s a great question. I think it would really depend on why my child arrested. It would depend on how long they had gone without having a return of spontaneous circulation. Because I think about it being a big difference between compressions going on for 20 minutes with no return of spontaneous circulation, which is basically the minimal requirement of duration of time before eCPR, versus have chest compressions been going on for an hour or two hours? Because I think that really impacts the neurologic outcome, and that would really impact their long-term outcomes in terms of whether they would still be the same person again or not.

I think that’s a very personal question. And there’s no right or wrong answer. I think everyone is different. But those are the factors that I would think about to help answer those questions that I would be interested in exploring in further research.

Dr. Bulloch: I noticed in your data points, you mentioned time from the time compression started to the time you started eCPR, and one of the data points that you had was time from admission until ECMO was started. I imagine it’s probably very difficult, especially if some of these patients are having CPR started out in the field. But how often are you getting people in who are going an hour or longer before any of these interventions are being done? Or is the average kind of that 20 minutes? Is that sort of your standard of care?

Dr. Beni: You know, it wasn’t one of the pieces of data that’s collected in the registry that they are going to collect in the latest update of the ELSO database. So I’m really curious to see what that actually is. We’re a high-end center, but we don’t cannulate that often, so if you consider a high-end center cannulating maybe once or twice a month, then you’re talking about each center cannulating maybe 20 times a year on the higher end. So it’s a pretty rare circumstance and I think that, without having a broader data pool, that higher end that you can get from these international databases, I don’t think we’ll really know the impact of the duration of CPR.

Dr. Bulloch: You were saying what was right in my head. You really have to have this kind of database to get any sort of data in this patient population. As rare as it sounds like it is, even these huge academic medical centers. Is there anything else that maybe surprised you or you found really interesting from your study?

Dr. Beni: I think one of the other things that I would be interested to know about, and I think this would also help with decision-making for who we should recommend eCPR to, was in the dataset, it didn’t specifically collect, when a patient died on ECMO, whether it was due to withdrawal of ECMO or it was death on ECMO. I think the decision to withdraw ECMO due to poor prognosis is quite different from the decision to maintain ECMO and for someone to die while cannulated, which may happen for a variety of reasons, including complications. I think that would be really fascinating to delve into a little bit more.

Dr. Bulloch: It sounds like there’s really a wealth of information. Do you have any plans to take further into the future, maybe come back and revisit it later on, or maybe look at things more specifically?

Dr. Beni: Well, I’m personally starting fellowship in August, so I would be curious to know about this information when I catch a little bit of a clinical break.

Dr. Bulloch: We all understand that for sure. All right, well, we’re almost at our time here today. I’m just going to give you an opportunity to say any closing thoughts you might have or want the listener to be aware of.

Dr. Beni: I think that ECPR is a really phenomenal tool. It’s really cutting-edge, state-of-the-art. It requires an incredible team of dedicated people to implement and to deploy. I think the progress we’ve made is fantastic. I think that figuring out who the right patients are to offer it to is really critical. I think, if it were up to me, I would love to see a propensity match study for patients who arrested, whether they went on ECPR or not, and to be able to see what those outcomes were in both patient populations to compare and help to be able to shed some additional light on this really interesting subject.

Dr. Bulloch: Well, thank you so much, Dr. Beni, for joining us. I learned a lot today, and I’m sure that our listeners did as well. This is going to conclude another episode of the Society of Critical Care Medicine Podcast. If you’re listening on your favorite podcast app and you like what you heard, consider rating and leaving a review. For the Society of Critical Care Medicine Podcast, I’m Marilyn Bullock. Thank you for listening.

Announcer: Marilyn N. Bulloch, PharmD, BCPS, FCCM, is an associate clinical professor and director of strategic operations at Auburn University Harrison School of Pharmacy. She is also an adjunct associate professor in the Department of Family, Internal, and Rural Medicine at the University of Alabama in Tuscaloosa, Alabama, USA, and the University of Alabama Birmingham School of Medicine.

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