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Host Diane C. McLaughlin, DNP, AGACNP-BC, CCRN, FCCM, welcomes Matthew Kirschen, MD, PhD, FAAN, FNCS, to discuss what critical care professionals need to know about determining brain death/death by neurologic criteria (BD/DNC).
In October 2023, a revised consensus practice guideline for the determination of brain death in both children and adults was published in Neurology (Greer DM, et al. Neurology. 2023;101;1112-1132). The guideline integrated guidance for adults and children to provide a comprehensive, practical way to evaluate patients with catastrophic brain injuries to determine whether they meet the criteria for brain death.
The Society of Critical Care Medicine (SCCM) offers several additional resources to support critical care clinicians’ understanding of the updated guidelines, including an article published in the March 2024 issue of Critical Care Medicine addressing what the critical care team needs to know about the guidelines (Kirschen MP, et al. Crit Care Med. 2024;52:376-386). Dr. Kirchen was the lead author of that article and shares key points in this podcast episode.
Other resources include:
Transcript:
Dr. McLaughlin: Hello and welcome to the Society of Critical Care Medicine Podcast. I’m your host, Diane McLaughlin. Today I’ll be speaking with Dr. Matt Kirschen about the article, “The 2023 American Academy of Neurology, American Academy of Pediatrics, Child Neurology Society, and Society of Critical Care Medicine Pediatric and Adult Brain Death by Neurologic Criteria Determination Consensus Guidelines: What the Critical Care Team Needs to Know.” To access the full article, visit ccmjournal.org. Dr. Kirschen is an associate professor and critical care attending at the Children’s Hospital of Philadelphia and the University of Pennsylvania. Welcome Dr. Kirschen. Before we start, do you have any disclosures to report?
Dr. Kirschen: Thank you very much for having me. I have no relevant disclosures to report. I do have some NIH grant funding, but it is not related to the determination of brain death.
Dr. McLaughlin: All right. Well, congratulations on the work. Whenever I see this many organizations on one paper, that’s kind of the first question that I ask is, how do you get so many big organizations together to collaborate on such a project like the updating of the brain death determination guidelines?
Dr. Kirschen: Thanks for the question. It was really important to us to have all the relevant societies participating in this updated guideline statement. The prior adult guidelines were composed by the American Academy of Neurology, and the prior pediatric guidelines were written by a combination of the American Academy of Pediatrics, the Child Neurology Society, and SCCM. By creating a set of guidelines that was intended to be used for both adult and peds populations, because death determination should be independent of age, it was important for us to bring all these relevant societies to the table to really get agreement and consensus on the criteria and the definition of brain death.
Dr. McLaughlin: All right. Now we’ll get into the little bit of juice here. Is it difficult when you have that many organizations that each might have specific interests? We want the tea. Did anything happen? Were there any fistfights trying to get the guidelines out?
Dr. Kirschen: There were no fistfights and everybody played nicely in the sandbox together. Different groups have different interests. Particularly, the pediatric organizations wanted to make sure that the interests of children were being respected. The critical care and neurology communities wanted to make sure that the guidelines were appropriately tailored to both the neurology community and the critical care community.
While there were some administrative hurdles that needed to be overcome, the participants who were at the table were really all centered around the same mission, which is: We need to set out the most clear and comprehensive guidelines for the determination of brain death in adults and children such that we do this process 100% right 100% of the time.
Dr. McLaughlin: Well, it sounds like you had the right people in the sandbox then. What are the big differences? It’s been over 10 years since the last set of guidelines, so I imagine a lot has changed. What are the big differences that you can highlight in this set of guidelines as opposed to the previous?
Dr. Kirschen: The big thing in this set of guidelines is that we amalgamated the adult criteria and the pediatric criteria into one document. There are some places where there are some differences for the adult and the pediatric populations, primarily owing to differences in the pathophysiology of brain injury related to the pediatric population. Other than bringing the two documents together, the fundamental definition of brain death has not changed over the past 10 years.
You still need to have a catastrophic brain injury. That brain injury needs to be permanent, such that you observe the patient for a period of time and ensure that there is no recovery of any clinical brain function. Then you have to evaluate the patient for brain death, and they need to be comatose and unresponsive to all stimuli. They need to have brainstem areflexia, and they need to not breathe with an appropriate CO2 and acidotic challenge after you have excluded relevant confounders.
That definition has maintained the same in this revision of the guidelines. One of the things that we did is we added recommendations for special situations, for example, evaluating pregnant persons for brain death, doing the apnea test, and the rest of the evaluation in patients supported on VA and VV ECMO. We talk about patients with primary infratentorial pathology that led to brain death, and we talk about issues of consent and hypothalamic dysfunction. Many of those were not addressed in prior iterations of either of the guidelines.
Dr. McLaughlin: A lot of those were pretty controversial throughout the community, so it’s nice to have guidelines that specify what to do in those situations. Even though we’re going to encourage everyone to read the guidelines, can we get into some of those specific groups and kind of tease what’s there?
Dr. Kirschen: As you said, many of those issues are controversial, and there are people with very strong viewpoints on both sides of many of those issues. In a lot of ways, in this document, we really chose to focus on the medical determination of brain death, recognizing that some of the issues that we’re going to discuss that are more controversial have to do with the agreements between the legal criteria for death and the process and the criteria with which brain death is evaluated in the medical criteria through these guidelines.
Dr. McLaughlin: You’re a pediatrics guy, and I think a lot of people listening, particularly the pediatrics community within SCCM, is very robust. Can you talk a little bit about that group and what these guidelines say for pediatrics?
Dr. Kirschen: For pediatrics, again, the fundamental criteria have not changed from the prior guidelines 10 years ago to the guidelines now. We provide a little bit of additional clarity in terms of doing the neurologic examination. In this set of guidelines, both for adults and pediatrics, but for one special circumstance for pediatrics, we really emphasize that the important waiting period is the period after the brain injury before you begin the evaluation, that by beginning the evaluation, a clinician is saying that this brain injury is permanent, that it is not possible for this individual to regain any brain function.
In pediatrics, we’re required to have two neurologic examinations and two apnea tests, and those are separated by an interval of 12 hours. Previously, that interval used to be a variable duration based on the patient’s age. We have standardized that in these guidelines to be a minimum of 12 hours for all patients, but we also acknowledge the fact that that interval is a little arbitrary. And while the two exams need to be separated in time, and we have chosen 12 hours primarily for historical reasons, that we really want to emphasize that both for adults and kids, it is that period between the time of the injury and the initiation of the evaluation that that is the time period that you use to determine that the injury is permanent and not the time period between the two examinations.
Dr. McLaughlin: So in pediatrics, it’s 12 hours. Is there any specific recommendation in adults for time between tests?
Dr. Kirschen: In adults, one exam and one apnea test are required. We recommend that a second exam can be done, which will help decrease the likelihood of a false-positive brain death determination. However, one exam and one apnea test are required in adults. Two exams and two apnea tests are required in kids, with the caveat that we do provide recommendations for a second exam in adults to try to decrease the likelihood of a false-positive determination.
Dr. McLaughlin: I have to say, if I were sitting around the table, I would want to know why the difference between these requirements for pediatrics versus adults. What makes these populations that different to have such different recommendations? It feels very different to me.
Dr. Kirschen: It does feel different. I will start by saying that there is historical precedent, that the historical precedent for pediatrics was that they needed two exams and the adults needed one exam. Unfortunately, in this domain, we are lacking in data in terms of being able to have evidence that demonstrates that two exams are better than one exam or one exam is sufficient and there is little to be gained or none to be gained by doing a second evaluation.
The way I look at it is that this is one of the few decisions in medicine that we can’t take back, right? After we make a diagnosis of brain death, then the ventilator and other organ support is turned off and the heart subsequently stops. So I want to be as absolutely confident as possible when making that brain death diagnosis.
And because this is something that we need to do 100% right 100% of the time, I think that it makes sense to have an independent second examination by another practitioner who is able to conclude the same thing, that they have independently gone through the prerequisites, gone through the confounders, did the entirety of the neurologic examination and similarly concluded that there is no evidence of any brain function. And I think, given that we are dealing with a decision of this magnitude, being life and death, that having a second practitioner come to the same conclusion increases our confidence and reduces the possibility of a false-positive determination.
Now, we have to balance that with, there are potentially some communities or some hospitals that may have a limited number of practitioners who are trained in doing the evaluation. That’s certainly a consideration that needs to be thought through. But, in my opinion, I think having a second person do the evaluation can only be beneficial and it’s not harmful to the process.
Dr. McLaughlin: Knowing the importance of an accurate declaration of brain death, is there specific training or a competency that’s required for whoever’s performing these evaluations?
Dr. Kirschen: Yeah, that’s a good question. One of the things that we emphasize in the guidelines that were published at the end of last year is that practitioners who perform the evaluation should be adequately trained and competent in performing the evaluation. We do not specify the exact training that needs to be held or there’s no exam to determine competence at this point in time.
There is local credentialing that happens within individual institutions and hospitals. This is often training that has gotten through residency and fellowship programs. There are many high-quality online and in-person simulation-based courses that can augment that training. One that I was involved in creating was through the Neurocritical Care Society. So there are several of these programs available that can train you how to be competent in doing the brain death evaluation.
Dr. McLaughlin: This hopefully will also help protect people from some of the legal concerns that you kind of alluded to earlier. But what are the legal foundations for brain death determination in the United States and how do these guidelines align with those?
Dr. Kirschen: In the United States, the legal basis for brain death stems from the UDDA, the Uniform Determination of Death Act, which was enacted in 1981 in the United States. It states that an individual who has sustained either irreversible cessation of circulatory and respiratory functions or irreversible cessation of all functions of the entire brain, including the brainstem, is dead. It goes on to further say the determination of death must be made in accordance with accepted medical standards.
The 2023 multi-society guideline statement that we have been talking about here is considered the accepted medical standard. It is based on the whole brain formulation of death. However, there are some people who interpret the UDDA more literally and, rather than interpret irreversible cessation of all functions of the entire brain as all clinical functions of the brain and the functions of the brain that enable us to maintain consciousness, have brainstem reflexes, and have spontaneous respirations, they interpret that statement more literally, that it’s really all functions or really any function of the brain that is retained means that the patient does not fulfill criteria for brain death.
The most common place where we see this discrepancy and has led to the discussion of the discordance between the legal criteria and the medical criteria has to do with neuroendocrine function, because patients who do not have diabetes insipidus can still be evaluated for and fulfill criteria for brain death according to the 2023 guidelines.
Dr. McLaughlin: Going into some of these controversial points, two of the things that I’ve heard discussed are, how do you handle primary posterior fossa injuries, and also, should you have to obtain consent to perform brain death evaluation?
Dr. Kirschen: Sure. Let’s deal with the primary posterior fossa injury first, because that one is a little bit easier. You can envision a situation where somebody has primary posterior fossa injury and, because of that, they have lack of all brainstem reflexes and they are unresponsive to your bedside neurologic exam. There is the remote possibility that that person could retain some cortical function and, even if you put an EEG on them, you may see some EEG activity. According to the 2023 guidelines, it is not permissible to evaluate that patient for brain death because they do not fulfill the whole brain criteria of brain death.
In order to evaluate somebody with primary posterior fossa injury, that posterior fossa injury needs to have secondarily led to supratentorial brain injury. That could be hydrocephalus with increased ICP and decreased cerebral perfusion. That could be from secondary ischemia and lack of perfusion and hypoxic ischemic injury to the brain. But you need to have a neuroimaging study that demonstrates that you’ve got irreversible injury to the supratentorial brain in addition to the primary posterior fossa process. So, with respect to primary posterior fossa injury, you can only evaluate somebody for brain death if they have secondarily had catastrophic supratentorial injury as well.
Dr. McLaughlin: That makes a lot of sense. It’s brain death, not just one specific area of the brain that is dead. I think the guidelines do a good job of addressing that. And I think you’re about to get into one of the other controversies, which is that not everybody accepts the diagnosis of brain death at all. Should we have to get consent for it or, if that’s what’s happening, should we go ahead and declare if that’s what’s occurred?
Dr. Kirschen: Yeah, this is a really complicated issue that involves many different facets of death determination and biomedical ethics. What the panel decided and what has been written into the guidelines is that you have a duty to inform families that you are going to proceed with a brain death evaluation. However, you do not need to obtain consent for doing the evaluation, that we have an obligation as clinicians to know whether the patient who we are taking care of in front of us is alive or dead. And, just like we do not need permission to put a stethoscope on a patient to assess whether they have any cardiac activity or circulatory activity, we also do not need to obtain consent prior to doing an evaluation for brain death.
One of the arguments that is used by people who advocate that consent should be obtained is that the apnea test has risks. And it is true, the apnea test does have risks. You can become hypotensive, you can become hypoxic, you can have arrhythmias. There have certainly been published cases of pneumothoraces and cardiac arrest and other deleterious consequences of the apnea test.
However, in the guidelines, we lay out a very detailed procedure that can be followed both in adults and children for how to do the apnea test safely. It involves apneic oxygenation to avoid hypoxemia and clear criteria for when to abort the apnea test early if the patient is at risk for further cardiopulmonary decompensation. The clinician at the bedside also always has the option to say, in this patient, because of the severity of their cardiopulmonary disease, I do not feel that it is safe in order to proceed with the apnea test. In those situations, the apnea test can be deferred and ancillary testing can be done.
There have been studies in adults and children showing that the apnea test is safe when performed under these conditions. People also talk about the concern that, as the CO2 rises during the apnea test, that may increase the intracranial pressure and cause further injury to the brain. However, in studies that have been done looking at patients with invasive intracranial monitoring who undergo brain death evaluation during the apnea test, either the ICP does not change or, if the ICP does go up, the mean arterial pressure goes up as well.
In fact, it actually goes up a little bit earlier, whereby the cerebral perfusion pressure is maintained. And in all these patients, the ICP is at a significantly elevated level with oftentimes cerebral perfusion pressures that are very low or negligible given the cerebral circulatory arrest that happens in the context of brain death.
So, while there are potential safety concerns with doing the apnea test, those for the most part can be mitigated by following a very standardized protocol and having well-established stopping rules. And, while there may be a theoretical concern of further brain injury in the context of the hypercarbia, that has not been borne out in the data, such that there is not evidence that anybody has had worsening brain injury in those situations.
Dr. McLaughlin: But there definitely are situations when the patient’s unstable and doesn’t tolerate apnea testing or you do believe the risk is too great. You mentioned the ancillary testing. Is there a preferred ancillary test? In what other situations might you consider ancillary testing?
Dr. Kirschen: Let’s address which ancillary test first. There are a variety of ancillary tests that are permissible by the guidelines. The first is four-vessel conventional angiography. There is nuclear medicine-based cerebral blood flow and perfusion studies. Then there is transcranial Doppler. Transcranial Doppler is only validated in adults and should not be used in kids.
I would say by far the most commonly used technique is nuclear medicine, cerebral blood flow, and perfusion studies. Notably, in this iteration of the guidelines, EEG has been removed as a permissible ancillary test. It was in prior iterations of the guidelines. The reason for that is because, when you are doing an ancillary test, the primary reason why you do an ancillary test is because you are unable to fully assess the brainstem. In this case, you can’t complete the apnea test, which is looking for functioning of the medullary chemoreceptors. And the EEG only looks at the supratentorial cortex. So we did not want to have it be permissible to use an ancillary test that tells you about cortical functioning when what you are unable to assess on your neurologic examination is the brainstem.
In terms of when to use an ancillary test, we have clarified in this revision of the guideline that you should really only use an ancillary test in situations where there is an aspect of the neurologic examination that you are unable to do or a confounder that you are unable to resolve. For example, if a patient had trauma and they have ocular injuries such that you are physically unable to assess the pupil, then you should proceed with ancillary testing.
If the clinician at the bedside deems that it is unsafe to do the apnea test or the apnea test is attempted and the patient does not tolerate it, that is also an indication to do ancillary testing. If there is a confounder that is expected to resolve with time, then one should wait that additional time and not use ancillary testing. For example, if a patient was treated with a high dose of a sedative medication as part of medical management of refractory ICP, then you should wait sufficient amount of time for that sedative medication to be cleared out of the patient’s system rather than using ancillary testing.
If time will resolve the confounder, then you should give the patient time. There may be situations where you cannot resolve the confounder. For example, a patient has refractory kidney injury and significant uremia and it is determined that it is not medically appropriate to initiate dialysis for that patient, then in that case, the high BUN and the uremia confound the exam. Time is not going to resolve that confounder, so it is appropriate to use ancillary testing in that situation.
If you are going to use ancillary testing, prior to doing that ancillary testing, you must confirm that the entire neurologic exam that you are able to do has been performed and all the findings are consistent with brain death. If any part of that exam is not consistent with brain death, then there is no reason to proceed to ancillary testing because the patient does not meet criteria for brain death.
The last thing I’ll mention about ancillary testing is ancillary testing should be the last thing that is done in the brain death evaluation process such that your prerequisites, your confounders, your neurologic examination, all to the extent possible, must be done and must be consistent with brain death. Then, if you have a confounder that you’re unable to resolve, ancillary testing is the final step in the pathway.
Dr. McLaughlin: Speaking of time and final steps, we’re already at time and I feel like we’re really just scratching the surface. It tells you that there’s a lot in these guidelines. But I think a good place to wrap up would be that brain death has historically not been consistent despite very clear guidelines as to how to perform this testing. How would you recommend healthcare institutions implement these guidelines effectively?
Dr. Kirschen: I think that’s really, really important, and I think we need to think of this in a variety of action items. Hospitals need to take the guidelines and they need to revise their institutional protocols to be consistent with the guidelines, keeping in mind state and local laws and regulations that also need to be adhered to.
They need to ensure that physicians who are going to evaluate patients for brain death are adequately trained and competent in doing the evaluation. As I mentioned before, there are courses that are available and a variety of different mechanisms that institutions have come up with in order to deem clinicians competent to perform the evaluation.
Checklists are vital in this domain, right? This is an area where we’ve got to be 100% right 100% of the time. So having checklists either within your EMR or as part of your institutional protocols, that even those of us who have done substantial numbers of brain death evaluations still pull out the protocol every single time and check every single box and read every single line because this is not an area where we want to take shortcuts. We want to make sure that we address every single aspect of the evaluation every single time that we do it.
I think a combination of having updated protocols and policies at each institution, having physicians undergo training or retraining to familiarize themselves with the new guidelines and to reiterate and solidify for themselves how to do all of the various details within the brain death evaluation protocols, and then having checklists either automated or on paper is a really essential step to making sure that we do this appropriately.
Dr. McLaughlin: Well, there really are a lot of updates in this 2023 set of guidelines. I think anybody listening can tell that we’ve only started to get into this. So hearing about specialty populations like the pregnancy population or the ECMO population, there’s a lot to read. I encourage everybody to grab hold of the 2023 consensus guidelines. Matt, thanks so much for joining us today. Do you have any last words that you want to add?
Dr. Kirschen: No, thank you for having me. I appreciate the opportunity to talk to your SCCM listeners about the guidelines and the paper that we published in Critical Care Medicine that really distills down the essential elements of the brain death evaluation for critical care providers. As I’ve tried to say multiple times, this is an area in medicine where we’ve got to be 100% right 100% of the time.
If at any point during the brain death evaluation process, you are unsure of how to proceed, there’s a neurologic exam finding that you’re unclear how to interpret, there’s a confounder that you’re not sure whether it necessitates either additional time or ancillary testing, please stop and ask for help. There are resources available through SCCM, through the Neurocritical Care Society, through other organizations, as well as those of us who do research and educate in the brain death space who are happy to provide further guidance because this is an area in medicine where we can’t afford to be wrong. So please use this as an opportunity to get additional education for yourself and to reach out if you have any questions or concerns.
Dr. McLaughlin: All right. Well, thank you again. Thanks so much. With that, this will conclude another episode of the Society of Critical Care Medicine Podcast. If you’re listening on your favorite podcast app and you liked what you heard, consider rating and leaving a review. For the Society of Critical Care Medicine Podcast, I’m Diane McLaughlin.
Announcer: Diane C. McLaughlin, DNP, AGACNP-BC, CCRN, FCCM, is a neurocritical care nurse practitioner at University of Florida Health Jacksonville. She is active within SCCM, serving on both the APP Resource and Ultrasound committees, and is a social media ambassador for SCCM.
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Find more episodes at sccm.org/podcast. This podcast is for educational purposes only. The material presented is intended to represent an approach, view, statement, or opinion of the presenter that may be helpful to others. The views and opinions expressed herein are those of the presenters and do not necessarily reflect the opinions or views of SCCM. SCCM does not recommend or endorse any specific test, physician, product, procedure, opinion, or other information that may be mentioned.
