SCCM Pod-506 PCCM: Exploring Adverse Events in Pediatric Apnea

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Host Maureen A. Madden, DNP, RN, CPNP-AC, CCRN, FCCM, FAAN, is joined by William Sveen, MD, MA, to discuss the article “Adverse Events During Apnea Testing for the Determination of Death by Neurologic Criteria” (Sveen, W.N., et al. Pedtr Crit Care Med. 2023 May;24(5):399-405). Explore the prevalence of adverse events in pediatric apnea testing and gain insights from this single-center retrospective cohort study. Dr. Sveen is an Assistant Professor in Pediatric Critical Care Medicine at the University of Minnesota.

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Transcript:

Dr. Madden: Hello. I’d like to welcome you to the Society of Critical Care Medicine Podcast. I’m Maureen Madden, your podcast host, and I have the pleasure of having a conversation with Dr. William Sveen, who prefers to go by Billy. We will be discussing the article, “Adverse Events During Apnea Testing for the Determination of Death by Neurologic Criteria,” which is a single-center retrospective pediatric cohort that was recently published in the May issue of Pediatric Critical Care Medicine. Dr. Sveen is an assistant professor in the Division of Pediatric Critical Care Medicine in the Department of Pediatrics at the University of Minnesota in Minneapolis, Minnesota. Welcome Dr. Sveen, or Billy. Before we start, do you have any disclosures to report?

Dr. Sveen: No.

Dr. Madden: Very good. I’d love to proceed then to have this conversation. I am very, very interested in the concept of determination of brain death in infants and children, and I really appreciated that your work was being done evaluating apnea testing and seeing the number of adverse events associated with it to then see how it would impact the concept of brain death criteria in infants and children. Can you tell me a little bit of your background and how you came to look at this research?

Dr. Sveen: Yes, definitely, and thank you for the invitation to be a part of this wonderful podcast and have the opportunity to talk about our research. I am a physician, pediatrician, intensivist, and also ethicist. I have a master’s degree in bioethics and health policy. While I was doing my fellowship at Cincinnati Children’s, my mentor and I wrote a paper as a response to talk about whether or not consent is required for the apnea test in brain death, which is a bit of a current controversial topic that is discussed and published about somewhat frequently in the last five to 10 years.

In our position, it was a test that you are getting data from. It doesn’t determine what you need to do after it, but there shouldn’t be a reason to not do the test. While we were writing this paper, I had the idea of, we could just look back through all of our work and all of the series of patients that we’d had at Cincinnati Children’s and see what the rate of complications were. As we started looking through that, there was another paper then published in PCCM right as we were starting to do it, so we decided to follow a similar design to that.

Dr. Madden: Okay. Will you walk me through a little bit about what that design was?

Dr. Sveen: Yeah. We identified every patient who had an apnea test over a period of almost eight years, so 2013 all the way through 2020. We got the patients who actually donated from our organ donation network, our local network, but then we went through every death in the pediatric ICU to make sure that we weren’t missing people who didn’t donate but would have had an apnea test or weren’t even declared dead by neurologic criteria but maybe had one apnea test and had spontaneous breathing during it. We wanted to gather all of those data points.

Dr. Madden: I think I was going to ask that these were all formalized apnea tests in association with concerns for the determination of brain death or no?

Dr. Sveen: Correct.

Dr. Madden: Okay.

Dr. Sveen: Yes. So these were all formal tests, and the way we did them at our hospital was, there was a formal note that went into the medical record as a template so they’re very easy to identify and very easy to search for when we went through all the patients who had died over that period of time. We categorized all of the commonly described adverse events that happen that have been recorded for children and adults undergoing apnea tests. Those would include hypotension, hypoxia, pneumothorax, arrhythmias, intracranial hypertension, and cardiac arrest.

We then made definitions for all of those based on well-adhered-to practice within pediatrics, accounting for children growing and their ages, then gathered data on all of those things, so blood pressures, blood gases, chest x-rays. There are places in the notes to describe any reasons that the apnea test was stopped prematurely and we compiled all of those. We had a very low threshold to call something an adverse event so that we would be the most generous possible at finding as many adverse events.

Dr. Madden: When you say you had a low threshold, can you describe some of the thought processes behind that?

Dr. Sveen: Yeah. For example, with pneumothorax, we said that if they had a chest x-ray that had no pneumothorax or a small pneumothorax, and then anytime after the apnea test they had another chest x-ray that had a new pneumothorax or a bigger pneumothorax, that we would call that a pneumothorax for that patient. However, we can’t really say that it actually happened from that test and it doesn’t tell you anything about the clinical significance of that pneumothorax to that patient. So actually all of the pneumothoraces that we documented, none of them required chest tubes. All of them were found during routine imaging, so they were found during the morning chest x-ray, not gotten for a specific reason of deterioration for the patient. So in clinical practice, it’s unclear if a physician would have called that an adverse event.

Dr. Madden: Right. Because you commented in your manuscript that it could have been upwards to 12 hours later that that routine imaging was acquired.

Dr. Sveen: Exactly. Right.

Dr. Madden: Then, also, there wasn’t anything specifically stated, but during the time frame, there wasn’t a correlation to a change in blood pressure or heart rate with the patients who had documented pneumothoraces or increase. Is that correct?

Dr. Sveen: Correct. That is data that might have been hard to directly ascertain with the limitations of the retrospective review and just looking through our medical records.

Dr. Madden: Absolutely. We know, doing retrospective reviews, there’s always going to be a fair number of limitations that we can describe, but we do the best that we can with the information that we can look at. When I looked at your numbers, there were 58 patients in approximately eight years. From a very large pediatric ICU and trauma center, that works out to be just over seven patients per year. To me, that was kind of, I guess, a low number, but I don’t know. What did you think in terms of your, did you anticipate that that would be the number of patients you were able to have in your study?

Dr. Sveen: I guess I didn’t. I don’t know if I had a number in my head. When I started the study, I was late in my second year of fellowship, so that probably seemed about right for the one place that I had been in the ICU a lot. Before that, I did residency in a different place. One of those hospitals wasn’t a trauma center, so definitely the vast majority of brain death exams I had seen were at Cincinnati. So, yeah, in my mind, five to 10 sounded about right.

Dr. Madden: Okay. So it’s a level 1 trauma center, correct?

Dr. Sveen: Correct.

Dr. Madden: And how many beds in the pediatric ICU?

Dr. Sveen: At that time, they were in the low thirties, right around 32, and now they’ve expanded and it’s more like 48.

Dr. Madden: Okay. Just to give the audience a sense of what that unit looks like to appreciate some of those numbers. Then you had talked about there were total of 105 apnea tests. Going through the data that was supplied, 14 had one test, 41 patients had two tests, and then there were three patients who required three tests in total. Do you want to talk a little bit about that distribution and why patients may have had one versus two?

Dr. Sveen: Yep. For almost all patients who are pediatric to fulfill the criteria for neurologic death, they need two apnea tests separated by a period of time, which is different than for some adults. So the majority of our patients had two tests for that reason. However, if they were to have spontaneous breathing on the first test or something about their exam changed after a first test, then there would not be a reason to undergo a second test because it became not consistent with the neurologic criteria of brain death.

Another reason would be if there was a complication or a need to terminate the first test, then there would be a perception that the patient might not tolerate a second test, which is something that this data could potentially help with to determine the people at risk of not tolerating an apnea test means they end it prematurely. Then the possibility that after a first test, the family would decide that they did not want to undergo organ donation and no matter what the result of the next test would be, they were going to do extubation and allow natural death for their child. So they did not want to wait that period of time and wanted to proceed with extubation to allow natural death.

Dr. Madden: You bring up some interesting statements, and I think in different practice environments, clearly there’s going to be some differences in practices and how we can attempt to be uniform in this process. The article also mentioned that you had used the international guidelines as well as the SCCM guidelines for the determination of brain death in infants and children, which was most recently an update in 2011. Interesting in that, from my experience, oftentimes the conversation about organ donation doesn’t occur until actually the determination of death has been made. But you made the statement that that had come up in conversation prior to that determination in some of your population. Did I understand that correctly?

Dr. Sveen: Yes. We, as providers, don’t have that conversation directly with our patients. Our organ procurement network does that, so when we have a patient whom we are going to do our first brain death exam on, they are notified. They’re, depending on the situation, reviewing the chart or they might even be physically at the hospital. Then if the family wants to not proceed with a second brain death exam and instead extubate and allow natural death, then the organ donation network will usually talk to the family if we feel it’s appropriate, depending on the situation. So sometimes that conversation will happen before a second test because the family wasn’t wanting to have a second test.

Dr. Madden: Okay. Then looking at some of the other data that you had in the publication, 18 of your 58 patients went on and had ancillary studies as part of this process. And from that, 15 had determination of neurologic criteria of the EEG, and three had radionucleotide cerebral blood flow studies. Can you describe, if you have that information, why the decision for ancillary testing occurred?

Dr. Sveen: Yep. And my apologies for not listing that as a reason that someone would have only had one test previously too. It’d be for a number of reasons. If potentially part of the physical exam that goes along with the brain death evaluation couldn’t be performed. For example, if a patient had an injury where they had cerebral spinal fluid leaking out of their ear and then you couldn’t do the cold caloric reflex to that ear, or the patient had an injury to their eye and you could not open their eye and look at it. There were a few patients who had preexisting medical complexity at home and were known to have central apnea at times, not dense central apnea, but worse, had central apnea, especially, like, while sleeping, for example, and potentially worsening while they were sick. So those patients who often retained CO2 in general would undergo ancillary testing.

Dr. Madden: Okay. So to go more on the overall focus of the study, looking at apnea testing, which we know tends to be one of the more problematic components of determination of neurologic criteria just because of, as you said, the stability of the patient, whether or not they will tolerate it, etc., and also ensuring that we are seeing the absolute result that is required. We talked about that you had given them the PEEP that they were on consistent prior to the apnea testing starting. What other things did you employ as part of your testing or the process during the apnea testing?

Dr. Sveen: Sure. You want the patient to be hemodynamically optimized before you go into an apnea test. Often these are very sick patients, in general. These are patients who have had an out-of-hospital cardiac arrest, often. Sometimes they are trauma patients and they are often on vasoactive medications prior to the test, so you want to make sure that they are well optimized from that standpoint. You want to make sure that, from a respiratory standpoint, they’re well optimized with very good oxygenation, so you preoxygenate them. When you switch them off the ventilator, we put them to an anesthesiology bag and deliver 100% oxygen at that continuous pressure that matched their previous ventilator pressure. They’re just receiving pure oxygen without any initiated breath, so they’re no longer ventilating. So the concern is that, as they retain CO2, as their pH drops, they can get hemodynamic instability, which we did see with some of the patients.

Dr. Madden: Okay. But along those lines, you reported in your study that there were 20% of the patients who had adverse events, but only 5% of them resulted in termination due to the adverse event. Would you discuss that a little bit?

Dr. Sveen: Exactly. The overwhelming adverse event that we encountered was hypotension. Of all of the tests, out of 105 tests I performed, that occurred in 15 of the tests, so 14%. We define this as any blood pressure less than the fifth percentile for age, so if there was one blood pressure recorded, and they’re usually recorded minutely in the records that we had through an arterial line, if any one blood pressure, the mean arterial pressure, was below that, we count it as an adverse event even if nothing else happened, even if the vasoactive medications were titrated up and that made it go away, even if it resolved without any titration of the vasoactive medication, we counted that as an adverse event. Now, there were only those few tests that the adverse events actually led to stopping the test, and those were usually hypoxia related, but also blood pressure related too.

Dr. Madden: And your threshold for hypoxia was less than 85% saturation, correct?

Dr. Sveen: Correct.

Dr. Madden: All right. As a question, for the hypotension, as you talked about titration of vasoactive infusions, were any of the patients who exhibited hypotension previously already not on vasoactive infusions?

Dr. Sveen: Somewhere. I don’t have that exact number. I could tell you their vasoactive inotropic score, the median was 10, which is not a particularly high number, but most of the patients were on some vasoactive medication.

Dr. Madden: And, ultimately, when you talked about it in your discussion, all of the adverse events really didn’t require care beyond the termination of the apnea testing or the transient increase, say less than one hour, so really not something sustained at all.

Dr. Sveen: Right, which, part of the discussion that we had while writing this paper and having reviewed, was the question of what actually counts as a complication when you are in an ICU monitored by providers who can deal with the complication and not have long-term outcomes from it. There was debate about whether we use the word “complication” or “adverse event” or how exactly we describe these, and this is what terminology we landed on, and we decided to define them as broadly as possible so that people would get the most information that they could and go from there with the conclusions that they want to make.

Dr. Madden: Yeah. This is a high-stakes event. We, as clinicians, absolutely want to make sure that we are capturing and documenting the results in the most accurate way possible. This is not something we can turn around, so we accept what we do. So in terms of that, I think it’s admirable, first of all, that you’re trying to bring up and supply the data about adverse events associated with this test and criteria. You had said that in your paper, only 5% resulted in termination due to adverse events. Then in your discussion, you talked about Puccetti, who had less than 1% premature termination, and the adult studies had 0 to 2% premature termination. You said the results were similar, but tell me how that came about because, just looking at the percentages, one would think that that’s not the case.

Dr. Sveen: Yeah. It depends on the sample size. We did a chi-squared analysis that showed that the samples were essentially not significantly different.

Dr. Madden: Okay. How do you feel about that? Do you really think that, if you had a larger sample size, it would still bear out?

Dr. Sveen: There might be differences if we did a really large sample size. I think there are differences in the population between those two. I know, with the earlier Puccetti study, they had a lot less traumatic arrests, at least the way that they reported it, and this is anecdotally, I don’t have the exact, I definitely don’t have enough of a sample size to say this, but those patients seem like the most unstable patients.

Dr. Madden: As you already said, though, I mean, these patients are the sickest of our sickest. The fact that we’re even considering that they have had loss of neurologic function and meeting the definition for brain death or determination by neurologic criteria. They already fit in that category. It’s very interesting to me to go off a little bit. When you started in the introduction, you were talking about the safety of apnea testing, and parents and clinicians were questioning this. We know that in the past few years, there are clearly things that have come up in the news, in social media, in publication about, first of all, the concept of brain death actually being something that is to be held true, but you also talked about informed consent, whether or not it’d be required in going down the lines of litigation and legislation.

Why I want to bring some of this up is, first of all, you’re a bioethicist and you have a background that is much more robust than mine is. But I work in a state, New Jersey, and I’ve worked in New York as well, that views brain death differently than the majority of the United States, where parents and families can reject the concept, New York being a little bit more stringent in the criteria of how they can reject the concept and New Jersey being a little bit more open in why people do not accept that criteria. So I wanted to talk about that a little bit because I also have my own bias in regards to informed consent. What did you mean, or can you talk a little bit about informed consent for apnea testing? What’s the thought process behind that? What would you be disclosing to them?

Dr. Sveen: Yeah, sure. The idea of informed consent is that, without the permission of the patient or an appropriate surrogate, if you are doing something to the body of that person without their permission, that is battery. That is assault. That’s unethical and illegal in our country. So what we need specific informed consent for versus what’s in that general consent to treat, when someone is admitted to the hospital, is always a matter of discussion. There are a lot of things that we do by habit and legal and ethical precedent. In the ICU, we’re getting consent to put in lines, we’re getting consent to do a chest tube and very specific procedures.

But, for example, we don’t get consent to take an intubated patient and travel throughout the hospital to get a CT scan usually, and we know that that’s also a risky thing. Practice varies on getting consent to intubate a patient. There is also a question of, what does consent mean during an emergent situation? So there are lots of active questions about consent during critical care. With relation specifically to the apnea test, the question comes down to, I think there are a couple aspects, there’s the aspect of risk of the test itself. Is the test risky to the patient and can it damage the patient? Then there’s the question of, what does the test imply? The reality is that, in the vast majority of states with the exclusions that you discussed, the apnea test is often the last step in a declaration of death by neurologic criteria.

So it is the stronghold of delaying that possibility for a family that either disagrees with the concept of neurologic death or is psychologically and emotionally not available to accept that option for their child. It is, on one hand, in a more generous sense, people want to make sure the family is completely informed of what’s happening to their child, and everyone agrees that we should be doing that. Then the question is, do we actually need permission to do this, or are the people who are saying to you, we don’t give permission, are they saying it just to delay the declaration of death?

My coauthors and I, who have written also about this topic from an ethical stance without the empirical data that we now have, our concern is that, as a legal strategy to delay the testing, you are delaying information that we perceived as probably not very risky to receive and that it should be a separate question of what you then do with that information.

Dr. Madden: It’s fascinating to me. I appreciate your comments on that. My things that I kind of ruminate over at times, it’s not consent, but it’s informed consent, and what that connotation really means. As clinicians, I think we always have the background of approaching whatever we do as risk versus benefit and, to be honest, in the disclosure of information to our patients and their families about why we think something is appropriate to do. The delay piece, when you think about where the declaration of death by neurologic criteria stem from as well. I can be a little off in regards to, you know, it’s a pathway for organ donation for potentially the help of other individuals who require it.

We can go to resource utilization. I think from a legal perspective that the United States has a lot of different statutes and considerations in place that we don’t necessarily have the same legal or mindset that potentially other countries or cultures have. That may just come down to resources as well, that’s the reality of some of that. They may not even have a patient population that would get to this point.

I could make this really controversial. But as we said, we wanted to talk about your science, and I really do appreciate that you and your team have gone to the effort to bring this out. But it’s a changing world. If you would care to comment on any of the other things I just said, I’d appreciate it. If you would like to stay noncontroversial, that’s okay too.

Dr. Sveen: No, I’m happy to wade into some of that. I mean, I think there are some high-profile cases that have been in the news, and it seems clear that there are times that this strategy is used to delay and less, it appears to me, about the actual risk to the patient. Perhaps it’d be interesting, as an example, if I were to talk about informed consent with a patient, family about this. How I would describe it and how I describe these, except that I don’t ask for permission at the end, is: we are going to do this test, that is the final step of seeing if your child will have irreversible apneic coma, and it is giving them pure oxygen and allowing them the opportunity to breathe as they retain CO2 and their drive to breathe goes up.

I describe the test in more detail, and then I would say that the risks are decreasing oxygen and decreasing blood pressure, that’s why we’re monitoring really closely throughout all of that, and the benefits are that we get clarity on your child’s state. By this time, we’ve had lots of conversations about how sick their child is and that, regardless of the outcome, this test, unfortunately, their child is almost certainly never going to come back to the way they were before this hospitalization. These are children who, even if they had medical issues before, are now in a completely different realm with an acute event.

So I find that having some of those conversations early on about the grave nature of this situation, the prognosis, helps frame these conversations in a way that parents are potentially more accepting of the reality of the situation and then seeing this as a test that gathers information and less as a way that we are using our medical options to take away their child from them. I would say that, in having these conversations with other physicians, there are times that I feel that the apnea test is weaponized where, instead of like... For example, I’ve heard physicians say, let’s not have a conversation about end-of-life care and stopping ventilation, allowing natural death, those types of things, with the family because if the child meets criteria for brain death, then it’s a closed shut case and we can just be done.

I don’t feel comfortable with that way of moving forward. I would much rather put all of the information out there, let families know all of their options, be as transparent as possible but realize there are limits to what we can do medically and unfortunately that’s why children die and this is going to be my bias speaking through, but this is how I talk to family. If your child is never going to recover from this, we have to find a way to move forward. And the moving forward is for the family. The moving forward is for the child’s body and the child’s memory. The moving forward is for the medical team that has to do this work every day. We all have to move forward. I don’t know if I answered your question.

Dr. Madden: You very much did. As much as these conversations try to answer questions, I think it always then poses new questions and that’s the challenge of bioethics, first of all. There’s never, in my opinion, a clear-cut statement. But I really love how you phrased that and clearly the environments that we practice within are going to have differences and the people we practice with have differences and a lot of times over your years of experience, people find the most comfortable way to express themselves in regards to this to families. And I really do appreciate what you had to say. At this point though, I think that we’re pretty much to the close of our conversation, so I just wanted to ask if you had anything else you wanted to add before we concluded?

Dr. Sveen: Yeah. I’d like to thank my coauthors. All of them were, of course, very helpful in gathering the data and writing through all of this. I’d like to thank the people who reviewed the paper and edited the paper because that process really also made the paper a lot stronger. I also would just like to say that, regardless of people’s disagreements on this, because it can get heated at times, realizing that the patient remains at the center of all of the care that we are providing. None of us want a child to have a bad neurologic outcome, but we have to figure out how we’re going to move forward. The more data that we can get and analyzing that with an objective and open mind will help us figure out how to exist in those shades of gray.

Dr. Madden: Dr. Sveen, I really do appreciate your time and having the opportunity to talk about your article, “Adverse Events During Apnea Testing for the Determination of Death by Neurologic Criteria.” If you are interested, for our audience to access the full article, please visit pccmjournal.org. Again, it’s the May 2023 issue of Pediatric Critical Care Medicine. Billy, thank you so much today for this conversation. I really enjoyed it. This concludes 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 Maureen Madden.

Announcer: Maureen A. Madden, DNP, RN, CPNC-AC, CCRN, FCCM, is a professor of pediatrics at Rutgers Robert Wood Johnson Medical School and a pediatric critical care nurse practitioner in the pediatric intensive care unit at Bristol Myers Squibb Children’s Hospital in New Brunswick, New Jersey.

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