The Neurotransmitters: Clinical Neurology Education

Brain Death with Dr. Ashley Paul

• Michael Kentris • Episode 29

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This episode of The Neurotransmitters podcast offers an invaluable look into the latest updates to the American Academy of Neurology's guidelines for adult brain death, with our co-host Dr. Ashley Paul, a Movement Disorders neurologist at Johns Hopkins.  We shed light on the nuances of catastrophic brain injuries, the impact of sedation on prognoses, and the rigorous prerequisites necessary before a declaration of brain death.

We discuss the profound human element of our practice. It's not just about the medicine; it's about the people and their loved ones. We delve into the significance of clear communication, preparing families for potential reflexive movements during evaluation, and the process of obtaining informed consent for brain death evaluations, ensuring families are part of the journey.

Join us as we navigate these profound responsibilities with the expertise and humanity that such matters demand. 

Find Dr. Ashley Paul at @ShakingPaulsy on Twitter/X. 

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Michael Kentris:

Hello and welcome back to the Neurotransmitters. I am your host, Dr. Michael Kentris, and today we are in for a special treat. I am joined by my old friend, Dr. Ashley Paul, a neurologist in Baltimore and a Movement Disorders Specialist. Welcome, Ashley.

Ashley Paul:

Hello and thank you for having me back.

Michael Kentris:

Long time listeners of the show will remember that you were with me way back on episode 1. And due to scheduling conflicts we haven't been able to record, but here we are once again meeting up. So thank you so much for joining me today.

Ashley Paul:

Absolutely.

Michael Kentris:

So we've been talking a lot. We've been wanting to do this for a while and we were kind of mulling over some topics, but one that recently you know you were covering the inpatient consult service and some recent guidelines that came out from the Academy of Neurology the adult brain death or slash death by neurologic criteria consensus guideline has been updated just this last month from their previous ones in when was it 2010? 2010. So this seemed like a good topic. So what are your thoughts?

Ashley Paul:

Yeah, my first thought was I haven't thought about brain death in a while, since I'm primarily an outpatient neurologist and I do four weeks of inpatient per year, and so this was very timely because, as you said, I was called to do a brain death examination and it's something. There's not really a lot of margin for error, right? You don't want to declare someone brain dead if they're not actually brain dead. That would just be terrible.

Michael Kentris:

Right. Right, it's definitely a no take backs type situation. So that is kind of the whole point of a lot of this research in the critical care, neurocritical care type field is how can we be accurate without delaying determination of brain death, which I'm going to use kind of colloquially? Some people use the death by neurologic criteria, but I'm just going to say brain death, because it's shorter but right, we need to have as close to 100% specificity as we can, and so that's why a lot of these guidelines. So, looking at this paper that came out, it's quite a monster. There were 85 recommendations developed, which is it sounds like a lot and it is a lot, but I think if we look at it compared to the previous criteria, it's more useful to think of it in terms of like what's new. So I think maybe starting with our definitions and kind of primary principles and then looking at what's new in the recommendations as opposed to a decade ago or so, yes, and I feel like the definition doesn't change a whole lot.

Ashley Paul:

We're talking about irreversible brain injury, so the cause of dysfunction should be something that we know will not be reversed, and so they use the word catastrophic brain injury, and I think that's something that most people can agree on, that that's what it should be.

Michael Kentris:

Right Right. It definitely shouldn't be a minor injury, and they do give some examples in here things like subarachnoid hemorrhages, massive cerebral edema, hypoxic ischemic injury, a lot of times from cardiac arrest, things like that.

Ashley Paul:

Yes, and it's tricky because you don't always see the extent of that injury on ancillary testing, right. So that's why the brain death examination is so important and so informative. But there are many contexts that can affect your examination. For example, even when I'm called for prognostication on somebody who's in critical care, my first questions are usually about what's the level of sedation if this person's intubated, because my exam might be useless. If they're very sedated, right, even some of their brain or nerves may be suppressed. So even some of their brain dysfunction may not be obvious on heavy, heavy sedation. And so when you think about brain death criteria, there are certain prerequisites that have to be met to declare someone brain dead, and I think it can be hard in somebody who is critically ill to meet all these prerequisites, right, yeah. And that's where it can get very dicey or tricky, right.

Michael Kentris:

And I do think of it as kind of this thing where, at the one very severe extreme of things, we have our brain death assessments, but a lot of times we are being called in for more of this neuro-prognostication, which is an entirely different can of worms in terms of accuracy and giving to the best of our ability, likelihood, and it's an entirely different body of research To an extent where we're not going down this brain death. It's kind of like this bifurcation in the road Do they have brainstem reflexes or do they not? And then we kind of diverge a little bit at that point and then try and do our best with the assessment tools that we have.

Ashley Paul:

Yeah, you know. Something that you and I were talking about earlier, though, is the sodium levels. What is the range that sodium should be in, as well as many other metabolic derangements that can happen?

Michael Kentris:

Right, yeah, and it is one of these things where I think it does require a bit of clinical context still where, yes, some of these things can cause confusion. Some of the ones they list here ammonia, blood urea, nitrogen, ionized calcium, glucose, magnesium, potassium, sodium, ph and T4 levels. So a lot of these things can be, and often are, deranged in critically ill patients and trying to factor in to what extent are these playing a potential role in someone's depressed neurologic function? I think that's very difficult in a lot of cases. I think the example I was talking and I see this a lot with folks on certain kinds of seizure medications you know there's sodium maybe is like 128, right, the range here is like 130 to 160. They're walking around out in the public, they're not in the ICU bed and certainly not in a coma, and I think, again, they're aiming for this very, very high specificity.

Michael Kentris:

So anything that could potentially cause deviation in levels of consciousness is really kind of thrown into here and I think that's going to make things very challenging for some of these patients who are having, say, multi-organ failure, like maybe they're having renal dysfunction, hepatic dysfunction, all these kinds of things, and we can't get these levels within range.

Michael Kentris:

But otherwise, clinically, they very well may meet these brain death criteria. So I think that is going to probably cause some questions as far as like is this appropriate, is this not appropriate? So it's one of those things where I guess we'll have to see when things are put into practice. I know there already have been, and a lot of institutions have some variability in their requirements, whether that's state by state in the US or institution by institution, and part of the problem is there aren't universally accepted legal criteria for this declaration. So that does, I think, still lend a bit of professional clinical judgment as far as those pieces go, and so everyone will have to kind of think about it in terms of their own locality. So I think there's still going to be a little bit of variability out there in the world.

Ashley Paul:

That was also that variability from state to state came to mind this week as I was called for brain death examination. My recollection when I was in Ohio was that two attendings needed to say that someone was brain dead, and the residents told me that here that it did not have to be two attendings. And then, looking at the specific criteria, at my institution it is at least one attending for one of the brain death exams. So they had to have two exams at least six hours apart, and one of them at least one needed to have an attending present.

Michael Kentris:

Yeah, yeah, and that's the variability.

Ashley Paul:

Yeah, exactly.

Michael Kentris:

Yeah Right, I mean I think a lot of times you do have two attendings doing assessments. But I think legally that is one of the big variability points and you see that more we're talking mostly I should specify about adults in our conversation today. But, like in the pediatric guidelines, it does have that particular stipulation for two different attendings and usually at least 24 hours apart. So there definitely is a bit more variability on the pediatric side of things. I should say variability from the adult. So I think that's always something to keep in mind is the population you're working with, as well as where you are working, definitely going to have some factors, and I've noticed even I've worked primarily in Ohio and just going from one corner of the state to the other there are some differences in terms of how things are done, what boxes need checked, in, the forms and so on and so forth. So I think that is something that isn't probably going away anytime soon.

Ashley Paul:

Yes, and so knowing what your local institution and state says about brain death is very important. These guidelines are very helpful but at the end they are guidelines of your thing about the legal standpoint. You want to make sure you're also following that.

Michael Kentris:

Yeah. So I think let's go back. We kind of started off on the prerequisites for even considering brain death. So you mentioned the catastrophic permanent brain injury and I think the other piece of that is the by a known mechanism or a mechanism known to cause such an injury. So it's not uncommon sometimes where we'll find people coming into the hospital maybe they're unidentified, kind of you know, john Doe's, etc. And we suspect a cardiac arrest or we suspect maybe a drowning or something like that. But that can sometimes, sometimes there is no known history and that can complicate things in as much as we don't have a known mechanism.

Michael Kentris:

So in those patients there certainly is some likelihood that they may not be candidates for this, even if they would clinically meet criteria, unless a proper until such time as a proper investigation is done to assess that more fully, which comes to a kind of like bullet point number two here that they should have some imaging of the brain that is consistent with the suspected brain injury, whether that is again this, you know, like a diffuse cerebral edema or some sort of other like hypoxic, ischemic, anoxic type injury, what have you because and I think that kind of brings up a common thing that we would see in the ICU during consultations is that sometimes you get these patients and the MRI gets done in the first 24-48 hours and it doesn't show findings that you're expecting.

Michael Kentris:

One of the things that they do recommend is potentially repeating that imaging at a further time point down the road to make sure that it is consistent, because if it's not showing the kinds of injuries and anecdotally, what I've found is that a lot of times when you have patients who you suspect a partial anoxic brain injury not necessarily to the point of brain death they have some intact brainstem reflexes but maybe they're missing one or two and they're certainly not waking up as expected. The MRI is. The sensitivity is not particularly great. I think it's around 60-70% sensitivity, especially in those first 48 hours. It definitely is something that should be revisited if the clinical course is worsening particularly, but we should see something ultimately if we give it enough time.

Ashley Paul:

Yes, I was going to say, timing really matters and getting an MRI of the brain too early is often not very helpful. Very true Although there's always a rush to do so.

Michael Kentris:

Right, I know everyone wants to know as soon as possible, obviously, but yes, sometimes the limitations of the testing modalities does limit things. That is one of the things that you also see in terms of again more in that neuro prognostication bucket. Rather than brain death per se, is that 72-hour kind of waiting period after people have been, say, rewarmed after cardiac arrest or things of that nature?

Ashley Paul:

Yes, yeah, from my training time it's not the most appropriate saying, but there's that morbid saying well, you're not dead until you're warm, warm and dead.

Michael Kentris:

Yeah, yes, yes, I have definitely heard that phrase also, which is true that core temperature being low certainly can obfuscate the neuro exam.

Ashley Paul:

Yeah, the process of brain death.

Michael Kentris:

I feel like every other year the guidelines on targeted temperature management are changing. I'm not going to say that I'm an expert necessarily on when and when it is not appropriate. I think it's starting to vary based off of what type of cardiac arrhythmia, whether it's in hospital, out of hospital. All these kinds of variables I will defer to our critical care colleagues. As far, as that piece, but you definitely have to wait until they're back up to a normal body temperature over 36 Celsius.

Ashley Paul:

Yes, there's also blood pressure requirements too. Obviously, if you have very low blood pressure, then you could be hyperperfusing the brain, which means that you will also have suppression of brain stem findings potentially, or other findings. To say you don't want to mistakenly say someone, I guess is brain dead If their pressure is too low and they're just not even getting a chance of perfusion.

Michael Kentris:

Right, obviously, that is super important.

Ashley Paul:

At the same time, though, when somebody is critically ill, it could be very hard to sustain a normal blood pressure.

Ashley Paul:

For many reasons, and some of that originating from the brain itself, which is, to me, then, very interesting, because if you have brain death, you could have, basically, dysautonomia, and so it's going to be hard to control the blood pressure, which, in this particular case where I was called, they had to put the patient on pressers to help elevate the blood pressure so that we could do and to me that was a strange thing in a way, because we're artificially elevating the blood pressure in order for me to be able to do a brain death examination.

Michael Kentris:

I've been in that exact same scenario, actually, and I do recall we talked with our hospital expert on that pathway, as well as some of our intensivists, and there was some debate about that. But, yes, we ultimately did agree. This is appropriate in as much in that context, and you can even titrate the drip during apnea testing and we're jumping a little bit far forward there but you can still use those if they are becoming slightly hypotensive. You can still use some of your titrations on your vasopressors, which I know is perhaps a little more debatable, but we have done that at times, and it's more if they start having desaturations or things like that, which we'll get more into the apnea test in a minute.

Michael Kentris:

But yeah, it does become one of those things where you wanna make sure you're doing everything by the book, all above board. You don't want there to be any shadow of a doubt as far as any of those things. But I mean, from my perspective, I think maintaining blood pressure is appropriate. Right, you wanna maintain that brain function, because that's what you're assessing Ultimately, is the brain function not necessarily the cardiopulmonary function per se.

Ashley Paul:

Exactly, yeah, so it does make sense and I wouldn't argue with AN on that one.

Michael Kentris:

Let's see next, they talk about exclusion of pharmacologic paralysis, which I think that one's pretty obvious.

Ashley Paul:

Yes.

Michael Kentris:

There are a lot of things that can look like brain death in as much as obviously being paralyzed. They also talk about some other entities in the paper, like Yonbaray, a high cervical spine lesion, botulism, poisoning, all these kinds of things that could cause the absence of potentially brainstem reflexes or very basic motor function. So I think those are good things to obviously check for.

Ashley Paul:

Yeah, imagine how terrible it is if you're sort of trapped in your body and it doesn't move, but you're still there and people are mistakenly thinking that you are brain dead.

Michael Kentris:

That would be terrible, and I just wanna mention this because I know of a lot of trainees I've worked with in the past haven't been familiar with this train of four stimulator. It's kind of this little muscle stim device and it shocks the muscle four times the train of four and so essentially it makes the muscle twitch and you should be having ideally four twitches in normal function. Some people say three to four. So if someone has been paralyzed, like say it's shortly after intubation where they had like rapid sequence intubation, things like that got a sexual calling or other paralytics, then you wanna make sure that is worn off beforehand. And similarly you should be seeing a train of four in someone who's not paralyzed. So if you're not seeing that, then it does beg the question a little bit, why? So I think it does. Certainly it's a nice little thing to have included in there. If you are worried about any of these other kind of mimics as well, I would think.

Ashley Paul:

Oh, that's good to know. I didn't actually think about that.

Michael Kentris:

I didn't either, till just now, to be honest.

Ashley Paul:

Well then, that's very timely. A and also recommends waiting at least five half lives for sedating medications to wear off.

Michael Kentris:

Right, and so before we hit record, I know we were talking a little bit. So someone I enjoy reading is the kind of Palmcret M Critt website which is by Dr Josh Farkas and he brought up an excellent point. There was a statement from the American College of Medical Toxicologists talking about brain death and kind of how this can be problematic, and I thought this was a very valid concern and as much as like we always talk about five half lives for hitting steady state or clearing a drug or what have you. But a lot of times if we're saying like an overdose or something like that, right, these aren't going to be normal pharmacokinetic type situations, and so clearances might be significantly variable.

Michael Kentris:

So add to that that a lot of hospitals don't have the clinical capabilities of checking for every potentially CNS depressing medication, and then even those ones that we can test for the presence or absence of are not usually a quantitative test. So we wind up in a situation where we aren't getting timely clinical information. And so essentially they were recommending the use of some of this ancillary testing like cerebral blood flow, like angiography specs, brain nuclear scans, all that kind of jazz. So, and we'll talk about those when we get to that bit, but I think this was a little way in which the recommendations diverged a little bit. So I think, yes, five half lives is a good starting point, but if there is a definite concern for overdose, I think we just have to be extra careful in terms of making sure that we again are giving it sufficient time, because there are certainly a lot of drugs, and more every year, that our tests just aren't picking up.

Ashley Paul:

I was just gonna say that, like a urine toxicology screen is not the greatest because, there are things that are missed on it.

Michael Kentris:

Yeah, like even some of our really old drugs like clonazepam. Right, it's not routinely picked up onto the benzodiazepine category. It is. So I think it's just important for us to be cognizant of the accuracy and utility of the tests that we're using to guide our clinical judgment.

Ashley Paul:

So what's next, after we waited five half lives for our CNS depressants to wear off?

Michael Kentris:

So next, these ones are a little more straightforward. So a basically normal alcohol blood level, so less than 80 milligrams per deciliter if clinically indicated Toxicology screen urine and blood is negative, right Again kind of a screening, different situation, I think, if you have a definite clinical history that suggests overdose. We talked a little bit about some of the metabolic endocrine acid-based type of arrangements and this was a little bit different as well. So there's been some debate should you obtain informed consent before performing a brain death evaluation? So I thought this was kind of interesting and this was something like to jump ships for just a moment, like when we would give TPA for acute stroke in the past.

Michael Kentris:

I remember the nursing staff be like you only have to get informed consent, et cetera, et cetera, like, say, the patient say phasic or what have you, and like because obviously we're coming very much from the time as brain type perspective and it has shifted that way, I was perhaps a little more resistant as to like, well, this is standard of care, this is what we should offer if the patient's unable to speak for themselves. But getting informed consent is. I mean, this is usually a non-emergency type situation. So there is time to make that effort. So, contacting the family, it is recommended that perhaps informed consent not necessarily is a contraindication to performing the examination, but it is recommended to communicate that this is something we are evaluating and basically being like a frickin' human being and having a genuine conversation.

Ashley Paul:

I'm gonna say, putting even consent aside, right, I think the main point is that this person that you're examining has loved ones who may want to have an understanding of what's happening. I think it's much easier for the general public to understand cardio pulmonary arrest, and now we have machines that keep those organs artificially going, and brain death is just another entity that I think can be very difficult for people to understand, and so I think it is very important that we talk to family. I'm sure people out there, in terms, from a guideline perspective, it would say well, you know, as somebody dies from a heart attack, right, we don't get informed consent to declare them dead right.

Ashley Paul:

Like they've packed away, they're hard-stopped, pumping. They're clearly dead and we don't. There's not an informed consent process for that, and so if somebody has brain death, which is the equivalent of being dead right, someone might say like well, why would you get informed consent? But I think the most important point really is, like you said, just being human and treating the family as family. And yeah, and you do have time for those conversations- and so you should have them.

Michael Kentris:

I wanted to highlight from the paper this recommendation statement 35B, so they talk about clinicians should provide the option for the family to observe the clinical evaluation, including apnea testing, which is something I usually do, to be honest, because I think it is one of the things where it is very abstract.

Michael Kentris:

Right, you know, if someone doesn't have a pulse, if someone's not breathing, that is very obviously apparent to the eye. But if we're talking about, you know, the eyes don't react to light or the corneas don't blink to a light touch with a piece of cotton, all these kinds of things that's like. What does that mean? You know, it's not something that someone outside of the medical field would have any familiarity with. And then the other piece that they mentioned here is to warn them ahead of time about reflexive movements, so these spinal cord reflexes. I had a case a year or two ago where I was a young man, you know, after an overdose, and he had a Lazarus sign, if you're familiar. So this is one that doesn't come up super often, but when it does, it engenders a lot of those.

Ashley Paul:

Do you want to explain the Lazarus sign for our listener?

Michael Kentris:

Yeah, so the Lazarus sign is essentially they get this like kind of abrupt flexion of the arms where they'll kind of like pop up in the air and then like fall back onto their chest almost like a month.

Ashley Paul:

Someone coming back from the dead right, I mean that's kind of the name, right.

Michael Kentris:

So it is one of these things where it appears as if they're having these volitional movements and you have to tell people like no, this is a spinal reflex. And these can be even for people in the medical field very challenging types of spinal reflexes where you can get these complex posturing type movements, and it is thought that these kinds of spinal reflexes are one of the not necessarily common but more common reasons for delaying brain death declaration.

Ashley Paul:

Yes, families see that and they think that this is a purposeful movement.

Michael Kentris:

Yeah, yeah Right, especially because they often happen in response to stimulation, whether that's auditory, tactile, what have you. And so I think that is, in particular where neurologists can help out with these assessments, in terms of helping our intensivist colleagues is being like oh, this is a well-described spinal reflex or what have you Making sure it's stereotyped, all these kinds of things that we would normally do in our assessments.

Ashley Paul:

I do like that the guideline mentions telling family ahead of time. Right, and not just as it's happening, because once I think a family member sees something like that, whatever you say is gonna go out the window.

Michael Kentris:

Right, they're not gonna be as receptive when they see that the person that they love is Moving in some form or fashion right, yeah, it becomes more of an emotional kind of conversation rather than a logical kind of conversation, and that that is really really hard, especially with with emotions running as high as they likely are in that situation.

Ashley Paul:

I mean I haven't seen. I know of the Lazarus, I haven't actually seen it, but I have seen commonly triple flexion and I think that can be hard even for clinicians to distinguish whether Someone is withdrawing to pain or having. I got this a spinal pathway reflex, where they flex at the hip and at the knee and at the ankle, and so sometimes we do it a few times and make sure right that this is triple flexion. It's a stereotyped movement and not a purposeful withdrawal from pain or from a noxious stimuli.

Michael Kentris:

Do you have any tricks that you like to use at the bedside for differentiating withdrawal from triple flexion?

Ashley Paul:

Oh, that's a good question. All I can remember is one of our former attendings using a key, squeezing the toes between Um with the idea that you don't want to miss. You know, you do want to make sure that this is very painful so that you don't miss Actual withdrawal movements. But do you have? Do you have a trick at a bedside too?

Michael Kentris:

I do have one trick and it's kind of, like I always think of of tactile and, you know, by association, noxious stimulation In comatose patients, kind of in a series of escalations, if you will so, kind of going from peripheral to central. So you know, a lot of times we will do like deep nail bed pressure, which, for people who aren't familiar, you squeeze the toe hard, yes, and so a lot of times we're we'll see, you know, maybe, maybe there's a concern for, like this triple flexion, or what we call sometimes partial triple flexion. So you are wondering, like, is this a spinal reflex or is this true withdrawal? And so a lot of times, then, if there is that question, then I will go to the thigh and I will, you know, pinch the thigh A lot of times.

Michael Kentris:

And so if you're still seeing that, that dorsiflexion at the ankle and the knee Rather than Abduction at the hip, then that would be to me suggest if, like, why are they flexing the ankle when I'm applying pain, like way away from there? Yeah, so that's that's one way that I usually help to differentiate that Because the movement should be like it's withdrawing, they should be pulling away. That's the entire point of withdrawal. So if it's not actually getting away from me as the irritating person which I'm sure lots of people would vouch for, then it doesn't seem like it's actually purposeful in that sense, and I think that applies to like the upper limbs as well, although it's not usually quite a stereotype, at least, again, anecdotally, in my experience.

Ashley Paul:

Yes, yeah, that's a great. That's a great way to distinguish, because when I think about some patients who are not, you know, not during a brain-dead evaluation, but maybe they're just somnolent and you're trying to make sure that they're okay and you pinch them or you do noxious stimuli and the type of movement that happens there is right is to get away from you, right and you know, for for everyone listening out there, who's who's seeing patients in the ICU, right, I think it's important to remember A lot of these patients are older, they're frail, they bruise easily.

Michael Kentris:

So, you know, look look at their limbs before you start, just you know, cranking away. I remember in particular this one older woman. I Don't know how many times she must have been sternal rub, but she had this big bruise right over a sternum. Now, granted, she'd also been through CPR. So you know there's a lot of reasons, but you know, don't keep sternal rubbing this person on this giant bruise on their chest.

Michael Kentris:

Yeah so I think we just have to be cognizant of that. You know there's, there's ways that you can you can cause pain without Injuring someone you know, like applying pressure, like, you know, over over, like the Shoulder joint, like kind of the AC Fossa, things like that, or like the super orbital notch, things like this. So there are other ways and you aren't gonna, you know, bruise somebody up. I mean, it's important to do our clinical assessments, but it's also important to remember that you know these are, these are still people.

Ashley Paul:

Yeah, and you want to be respectful of them and and their family too, who are watching Um right easy to become clinically detached when you have to do these types of exams over and over again. It's right away.

Ashley Paul:

Clinicians often try to protect themselves. A bit right that we get too emotional or too attached. It's hard to do your job but at the same time you still Want to remember that they're human. And even if this is a person who has passed right and this is a brain-dead examination, there's still a person with loved ones and yeah. Yeah, absolutely, absolutely it can be very challenging, though, to try to be mindful, and especially if you have to do these kind of exams so many times right?

Michael Kentris:

Yes, it is, and you know. Going back to what we we talked about having the family in the room while you're doing these assessments and Just telling them, like like any other procedure, you know what you're doing, why you're doing it, and just explain it as you go, I think is a very essential part of making sure that you know people aren't misperceiving what you're doing as being cruel and that there is a rationale for for why we're doing these things exactly. So We've gotten through, kind of our prerequisite checklist.

Ashley Paul:

Yes, well, one thing, and the prerequisite to is timing right. Did we talk about that?

Michael Kentris:

We didn't. Would you care to?

Ashley Paul:

so you want to make sure that there is sufficient time that has passed to say that someone has the permanency of brain injury causing brain death and so Waiting at least 72 hours from time of, I guess, of the injury it's appropriate. Yeah, and a lot of times you end up waiting that long anyway. If you're waiting, you know, however many half-lives for drugs to wear off and to meet the other prerequisites, it takes time right to things to clear, to try to get metabolites and everything as normal as possible in the context of the individual. But, yeah, it's not fair to a person who just came in. They, you know, oh, they don't have brain some reflexes. This must be brain death when, when not enough time has passed, yeah, yes, well, actually that was one of the things they.

Michael Kentris:

They had a little bit different here for the older than two years old Was more than 24 hours For a hypoxic ischemic, specifically.

Ashley Paul:

Mm-hmm.

Michael Kentris:

So I think that was for that specific population. And then the other one is it just says a sufficient amount, which a lot of times we do default to that 72 hours. So I think they are trying to break that down a little bit more. But but yeah, there is still, like you said, a little bit of vagueness and I think if you look at a lot of the neuro prognostication literature, it is moving more towards that. Give them time, a type of perspective.

Ashley Paul:

Yes.

Michael Kentris:

So I think that that is an important thing to keep in mind. You know, families want a quick decision. A lot of times our colleagues and in other specialties want a quicker decision and I think it's important, especially kind of coming from from our background as neurologists, that's, we are more used to Slow recoveries. Right, the brain doesn't bounce back necessarily.

Ashley Paul:

Oh my gosh, yes, the number of consults that are. Well, we got this person off sedation and they've been completely weaned off, but we can't get them off the vent or they're just not quite waking up yet. I'm like, of course, have them intubated for two weeks and they've had multiple complicated medical things happen to them.

Michael Kentris:

Would you?

Ashley Paul:

wake up that quickly Wait.

Michael Kentris:

I know, yeah, it is. It is definitely one of those things. It's just like you know, like give it time. Yeah, just give them a minute.

Ashley Paul:

It's kind of funny because sometimes, you know, the residents go see the console first, right, and then by the time I come around they start responding. Right now a sufficient time has passed and I'm like. I like to think I just had that effect on on people, but you know the attending effect yes, exactly.

Michael Kentris:

So, so let's we've kind of hinted at some pieces of it, but let's talk about kind of the, the clinical exam that we actually do at the bedside. So Do you want to start us off nationally?

Ashley Paul:

Sure. So one thing to think about is if they have any Brains temporary flexes, and there's many ways to check that. I always get annoyed when people say that because someone is not conscious that they could not do a neuro exam, which we know is not true.

Michael Kentris:

It's such a pet peeve.

Ashley Paul:

Yes.

Michael Kentris:

But we'll skip over that for the moment. Yes, we don't have to yes there's always information to be had if you know how to look for it.

Ashley Paul:

Exactly. So you can look at pupillary response, corneal reflexes, vestibular ocular reflex testing and cough gag, although those are part of checking for brainstem reflexes which, to be fair, when someone has had devastating brain injury, I always feel like the brainstem is the hardest part of the brain to die.

Michael Kentris:

I think that's kind of the point. Yeah, yes, I definitely agree with you as far as that goes. It seems like you're more likely to have these diffuse cortical injuries, more so than brainstem injuries, and they do reference in the paper as well, like posterior fossa types of injuries and things like that as well as kind of related like the neuroendocrine hypothalamic type axis, in as much as cerebral salt wasting, siadh, those types of things which can make correcting some of these electrolyte abnormalities incredibly difficult. But they don't include that necessarily as a criteria because technically the hypothalamus is part of the brain, but if it's still working, like, is the person truly brain dead, right? And you get kind of into these more philosophical quandaries in as much as like well, how is that going to affect quality of life, right? Is that a primary determinant? I don't have the answer to that.

Ashley Paul:

We need the brainstem to be conscious right, like your reticular activating system lives in your brainstem Right, and you need your brainstem to also just even breathe spontaneously, and so and that's of course the other thing you have to check too, right, if there's any evidence of spontaneous breathing.

Michael Kentris:

Right.

Ashley Paul:

But I actually wanted to talk more, or you and I were talking about vestibular arcular reflex versus oculosophallic, and do you want to speak more about that? I do think that's it.

Michael Kentris:

Yeah, so this is always an interesting thing to me, right? So the oculosophallic reflex, or, as some people know it, the doll's eyes test, is looking, right, you turn the head briskly one direction. You expect the eyes to remain kind of looking up towards the ceiling. If we're assuming someone lying on their back in a bed and it should be in, you know, the eyes should look that direction. Whether you move it to the right, to the left, what have you. But it does depend on the speed with which you, you know, apply the force. So a lot of times, right, we're doing brain death evaluations on patients who maybe came in as a trauma after a vehicular accident or what have you, and so maybe the C-spine is immobilized and you can't do that. So that becomes a bit of a question.

Michael Kentris:

Now we also have the oculovastibular reflexes, or the cold caloric testing, and you know that is the same pathway essentially, and the thermal testing is a stronger response, generally speaking. Now, in my own practice, you know, the hospital I've worked at in the past did not necessarily provide for that as an alternative in these patients. So I was always left in a bit of a quandary as far as like, can I still declare someone by neurologic criteria, even if I can't do an oculosophallic reflex, even in a setting where the oculovastibular reflex, the cold, caloric are abnormal, and so I do like that. In the new guidelines here they do say that, yes, you can Specifically.

Michael Kentris:

Let me get back where was this? This was in recommendation 18. And this was specifically 18C. If you can't do the oculosophallics because of concern for C-spine or skull-based integrity, you may diagnose brain death without ancillary testing, provided that the oculovastibular reflex can be tested and is absent bilaterally and all other criteria are satisfied. So I do like that statement a lot because, like pathophysiologically it makes sense. But it wasn't something that had been explicitly stated in the past. So I do appreciate that bit of clinical guidance for people kind of out there in the field taking care of these patients.

Ashley Paul:

Yeah, and what I noticed was that at my institution we do the oculovastibular reflex and we don't do doll's eye maneuver and brain death testing, or we don't have to, that is.

Michael Kentris:

Right, which again right, it makes sense it just makes sense.

Ashley Paul:

yeah, and in terms of exam to examiner variation you were talking about, the speed of thrusting someone's head right could alter the response. I think, there'll be less variability with colchaloric testing.

Michael Kentris:

Should be, and just a note for those out there performing the test or learning how to perform the test. So I think it's always too important to remember that we have function during normal awake people and then we have function in comatose people, which is different.

Ashley Paul:

Good point.

Michael Kentris:

So first, especially going back to trauma patients, you want to make sure that the ear canal is intact, the tympanic membrane is intact, it's not occluded by like seramen or anything obstructing the flow of cold water to the tympanic membrane, because that can invalidate your testing. Also, also, you want to make sure that there's no perforation in the tympanic membrane because, let's say that you perform this test, the patient is not brain dead, but that cold water theoretically could introduce a risk for developing mastoiditis, meningitis, these other kinds of nasty complications. So we do have to be cognizant of these rare but potentially serious risks in our evaluations. And I think this is more for the trainees out there, but I know, like many other people, I learned cows during medical school, which means cold, warm, same. That is to say, you put cold water in the ear, the eyes go the opposite direction. However, again, this is not normal physiology. So how do you usually explain it to students and residents and such?

Ashley Paul:

Well, I mean it has to do with the also the fast and slow phase rate of the reflex response.

Michael Kentris:

Right.

Ashley Paul:

I don't know if I do a good job explaining this. Actually, I'm going to hear your explanation.

Michael Kentris:

Okay. So I was hoping, as a movement disorder, you would take the nystagmus off my plate, but the way I always think of it is that a lot of times, what we are talking about when we're describing these things is the fast phase right, kind of the corrective saccadic movement. But this is a comatose person. We are assuming that there is not going to be corrective, frontally mediated saccadic movements Right. So, instead of opposite, what we will see instead is a tonic deviation of the eyes towards the cold ear, so it's kind of the opposite. In reality, though, like any eye movement during infusion of cold water into the ear canal would be considered positive. It is a reaction, and then they would not meet brain death criteria, but I mean, the classic one would be the eyes should look towards the cold ear.

Ashley Paul:

Yes.

Michael Kentris:

Conceptually, if you want to think of it, ignore all the endolymphatic fluctuations, blah, blah, blah. Cold means slow. Look towards a slow ear.

Ashley Paul:

I think that's actually a better memory device than cows, right? Because then the cold opposite forms the same, because I think that confuses students. That's what they remember and that's what they carry forward, and then in these situations it doesn't apply and it's very confusing.

Michael Kentris:

Right, right, and that is right because we're learning normal physiology, normal function. This is not normal, so it does add that extra wrinkle, right, we expect certain things to be different in different situations and it's again one of those things where and that's kind of why it goes back in these recommendations it does say right, you should be someone as a clinician who is familiar with how to assess these patients, so you should know, if you're doing the exam, what a normal and abnormal clinical finding is. And some people may not. Right, if you're, only if you're a family medicine doctor who works 90% of the time in the outpatient setting, I wouldn't necessarily expect them to be intimately familiar with brain death assessment. And that's not a knock against them, it's just reality, right, yeah, yeah.

Ashley Paul:

To keep it simple, as you pointed out, in brain death testing, oftentimes users just no response. Right, what's whatever.

Michael Kentris:

And I would say that's usually what I see clinically. Yes, I would say it's rare that I've gotten to the point where I'm doing cold caloric testing and I don't have a high suspicion for brain death, just because it is a little tedious, right, you have to bust out your you know tympanoscope and look in there and oh, tympanoscope with helmetsane otoscope.

Ashley Paul:

I accepted it. I used to nodding along. I'm like, okay, we'll go with a panopioca.

Michael Kentris:

It sounds like a real thing, right? Yes, the NT docs are going to crucify me in the comments, but yeah, like, you have to look in the ear canal right, which you know it's like. Yeah, I got one in my bag. A lot of times I have trouble finding specula, to be honest, though, but then you have to, like, get the ice water. You know you have to keep from making a huge mess.

Ashley Paul:

All the way. Yeah, you can't just squirt it like for five seconds and say you did cold caloric testing.

Michael Kentris:

No, no, it's a slow infusion into the ear canal. Yeah, You're holding the eyes with the other hand and you know you're watching the eyes for a good few minutes of there on each side. Yes, and you're waiting in between each year. So, yes, it takes time. Yeah, so you want to.

Ashley Paul:

There was a student that read with me when we were doing this and that was his exact question like oh, so do we have to do both sides? And like, yes, yes, we do One side does not tell you information about the other side, right?

Michael Kentris:

Right. So yes, I think that's kind of like the primary neuro piece, I would say. And then, like the last piece of the clinical assessment is the apnea testing, which you know I always lean pretty heavily on my ICU colleagues for just because if anything does happen with it, then I want someone who can manage the vent.

Ashley Paul:

Yes, right, because we don't do that regularly. So yes, Right.

Michael Kentris:

But I do like again, like there are prerequisites here for the apnea test and I think you'll see this a lot like where people will try and tee them up a little bit, if you will, in terms of you know optimizing, you know making sure they're not hypoxic, hypotensive, making sure that their fluid status is good, and so you need to check before you even start the apnea testing, you have to get an ABG and making sure that the pH and the PCO2 are in range, and so you get the pre-apnea and then you get the post-apnea.

Michael Kentris:

So recommendation 25, you should pre-oxygenate the patient with 100% oxygen for at least 10 minutes before apnea testing, perform an ABG measurement 8 to 10 minutes after 8 to 10 minutes of apnea. So the physiologic threshold for brain death, death benerologic, right to your determination may be reached before 8 to 10 minutes of apnea. Point of care blood gas testing may be used to perform ABG measurements earlier and more frequently. If the patient has cardiopulmonary instability, blood gas measurements might be necessary sooner. So, and again, I think this ties a little bit more into like known lung disease, like chronic COPD things like that, who have chronic CO2 retention, things like that. So that may complicate things a little bit in terms of shifting the levels and I like that they give like hard and fast criteria for when you must abort the apnea testing. So they say hemodynamic instability, so a systolic blood pressure at less than 100, map less than 75, or a map less than the.

Michael Kentris:

This is more for the children, less than 5th percentile for aging children, despite titration of vasopressors, inotropes or IV fluids. So this is kind of what we were talking about earlier, where you can use vasopressors and other similar things to maintain stability from a cardiovascular standpoint. So I think that is a good thing to know and it was something, to be honest, not too long ago I was ignorant of myself. The other piece they mentioned here is a progressive decrease in oxygen saturations under 85% or a cardiac arrhythmia with hemodynamic instability, which those are all the reasons again why I want the intensivist there if we're doing apnea testing.

Ashley Paul:

And this is also stating the obvious. But obviously you want to abort apnea testing if they do take a spontaneous breath.

Michael Kentris:

Right watching that chest rise. Yeah, so yes.

Ashley Paul:

Because then they don't meet criteria for brain death and you should not withhold their life-saving treatments.

Michael Kentris:

So exactly, and just to go back a little bit, one of the things, and I neglected to even think about this, they were talking about some other things that may invalidate or complicate the neurologic portion.

Ashley Paul:

So people who don't have eyes, oh, I never, to be honest, I have not thought about that or I'm not in a situation like that.

Michael Kentris:

Right, I've seen plenty of people with one eye but not two false eyes. Facial trauma or transplantation that could potentially impair your corneal reflexes, skull-based fractures, high cervical cord injuries, ophthalmic surgery that influences pupillary activity. I think we've all seen plenty of people with those unusually shaped pupils for various reasons Severe facial trauma, severe orbital or scleral edema, which certainly is not uncommon for folks who've been in the ICU for prolonged periods of time. You get the kind of like goopy looking eyeball or a severe preexisting neuromuscular disorder. So thinking like you're severe myasthenias, people with motor neuron disease, things like that, and that can certainly color our assessments in these patients.

Ashley Paul:

I do want to take that moment to highlight for people with neuromuscular disease and their response to paralytics. This is, I think, very important for people to know, and I ran into the situation not that long ago on consult service where the medical ICU was mystified by this person who had a more longer paralytic effect than they expected in a person with known myasthenia gravis.

Ashley Paul:

And so trying to explain that because they have myasthenia gravis right that you can't expect them to follow normal physiology, and so I think that would apply here too, in brain death testing, to be aware of these kind of things.

Michael Kentris:

That God forbid.

Ashley Paul:

I mean, he was so uncomfortable because he was, so he was still paralyzed, but not sedated. But they didn't realize he was not sedated because he could hardly communicate, that.

Michael Kentris:

Yeah.

Ashley Paul:

So not a great situation, right?

Michael Kentris:

No, that's not great.

Ashley Paul:

So, yeah, if you're at the point of thinking about brain death testing, certainly those things need to be considered.

Michael Kentris:

Oh, yeah, yeah, and that's again right. I think that is an appropriate role for neurologists when we have these patients who have no neurologic disorders, weighing in on how those may complicate or affect these neuroprognostic situations.

Ashley Paul:

Exactly. Yeah, sorry though I drilled you a bit.

Michael Kentris:

No, no, I think that's an excellent point. It happens more often than we probably know about Exactly. So we've gone through our clinical exam but let's say we aren't able for some time. For some reason we aren't able to perform a test, or there's some question as to whether or not maybe the imaging doesn't show that anoxic brain injury that we're expecting, or we can't do certain maneuvers due to head injuries, et cetera.

Ashley Paul:

Or perhaps we can't correct for all the metabolic arrangements because it's a multi-organ failure.

Michael Kentris:

Exactly. We just can't yeah, we can't hit those numbers per se, so let's talk about ancillary testing. So which ones are you most familiar with?

Ashley Paul:

So I've seen cerebral perfusion scans done. I feel like that's the one that people tend to start with, those type of studies that are looking at basically blood flow to the brain, right, yeah, and I do think that's the recommended one at my institution too, that if you're going to do ancillary testing, that this is probably the better one to do. Doing like a SPECT. It's preferred because it's also non-invasive and there might be less potential for confounders.

Michael Kentris:

Right and I would agree with that. I'm a fan of SPECT. I've seen the four-vessel angio also done by some people and, to be honest, they mentioned transcranial Doppler ultrasonography as well. I've never seen that done personally for brain death assessment.

Ashley Paul:

I have not either.

Michael Kentris:

Yeah, one big change that I'm a fan of and I say this as a neurophysiology epilepsy person they have removed EEG as one of the ancillary tests, which, to be honest, I think is good. They have rationale for it in as much as it does not assess deep brain structures. If you look at the American Clinical Neurophysiology Society criteria that were for talking about this, though, you have very strict criteria and, to be honest, almost nobody met them. I think I was able to interpret it as electrosyribilinactivity or ECI. That can be once or twice in my entire career thus far.

Ashley Paul:

That's what you're saying is just adds to the confusion.

Michael Kentris:

Right Right. It's like if I write a severe encephalopathy or something like that, well it doesn't add anything useful to the conversation and there's very strict technical criteria. So if those technical criteria aren't even met, then you can't even use it for ECI. So I think that's an important thing to remember also.

Ashley Paul:

Yeah, I think that makes a lot of sense, that if you are going to the point of ancillary testing because you weren't able to get the information you need clinically, that the EEG is just going to give you that same type of information. Right, it's just going to support your lack of definitive knowledge on whether this person meets brain death criteria.

Michael Kentris:

Right.

Ashley Paul:

So that's the point. How about SSCPs?

Michael Kentris:

Yes, evoked potentials also are on the outs. So I think that's again the rationale is that it's not assessing the entire brainstem, it's only a piece of it. They had good diagnostic specificity in past tests but again they were very technically challenging to do in the ICU setting. So I think that's the point, that that is still reasonable to remove them. Right, they're not assessing the entire thing. So I would agree overall with the removal of these tests. Like they're technically challenging, they are very often unreliable from that technical aspect and they aren't really telling us kind of the basic pathophysiologic information that we're looking for. At least that's kind of how my mental framework is putting it.

Ashley Paul:

And so I test, at least at my institution. They emphasize that it's not a replacement for two exams. So I'm not sure is this part of the guideline or not? I can't remember between the 80 something recommendations versus what's recommended by my individual institution, but at my institution a brain death exam should be done at least six hours apart. So there's two exams done six hours apart and ancillary testing is not a substitute for a second exam and I guess this is a way to make sure you're very confident and in your examination. The apnea test doesn't have to be done twice, it's only done once. But the actual exam itself, where we're looking at brain stem reflexes and response to noxious stimuli and things like that, is done twice.

Michael Kentris:

I don't see anything specifically about adults, they just say the 24 hours after onset. Let's see, here we go. Actually, in the first A and practice parameter in 1995, the initial exam for determination, a repeat clinical exam six hours later was advised, but no firm recommendation could be provided and it was acknowledged that the interval is arbitrary.

Ashley Paul:

So yeah, I don't know where six hours came from, but it looks like it was arbitrary.

Michael Kentris:

But yeah, in adults it does not have a specific one in children. There are some recommendations there though. So yes, clinicians must perform a minimum of one examination, level A recommendation statement 13b. But it does say two independent examinations may decrease the risk of a false positive due to diagnostic error.

Ashley Paul:

So Okay, so it's almost. It's kind of suggested.

Michael Kentris:

Yes, it seems like it would be recommended, but it you know, depending on the limitations of the institution, maybe there aren't enough qualified people. So that is something to consider as well, I would suppose, kind of in the real world. Yeah Well, any final thoughts about this? Is this going to change your practice in any significant way?

Ashley Paul:

It's helpful to be mindful of how we do this and to I don't know. I do like to think from a philosophical perspective too. I think it's important to retain that humanity aspect and not to become callous and which is? It is unfortunately very easy to to shed the humanity and try to get through these things. But it's helpful to I don't know. Yes, going through those guidelines and thinking about all of this helps me to know for myself what do I know and what do I not know.

Ashley Paul:

And right knowing that we're also trying to do our best to determine these guidelines right it's. It's not perfect, it's not legally uniform across the country. Right, there are guidelines but they're not legal terms, right. And so, trying to keep all of that in mind, it can be a lot, and I do appreciate that they say that you need a qualified clinician to do these things.

Michael Kentris:

For that reason, Right, and I think we were talking before we hit record that I suspect that this will likely lead to some clinical competency training and recommendations from kind of like the critical care, neurocritical care societies in the future. So I think that will be beneficial for both training the general physician APP population as well as kind of standardizing some of the way these things are done, Because I know there can be some certainly some variability, even though there isn't supposed to be. But I think that will be an important step forward for people to kind of get that training and get that experience. Personally, as someone who reads a lot of EEGs, I am a fan of the removal of EEG and I'm glad that next time someone orders one of these for a brain death assessment I can just say it's not indicated. And now I should say it's still fine to get an EEG to make sure there's not nonconvolsa status of electrocuse or things like that, but don't use it for brain death assessment Right.

Ashley Paul:

Yes, if you're worried that we're missing some other pathology like nonconvolsa status, that is actually reasonable, so it certainly still has a role.

Michael Kentris:

Absolutely Well, ashley. Thank you so much for joining me. Hopefully we'll be able to do more of these in the future. Where should people track you down online if they want to reach out to you?

Ashley Paul:

Well, I do have a Twitter. I must be honest, I'm not always good at using it, but my Twitter handle is shaking palsy, so it's a play on my name and movement disorders for the nerds out there. So that's probably the best way to follow me and reach me at this point.

Michael Kentris:

Awesome and if you're looking for me, I'm on Twitter, slash X, that's right. X, formerly known as Twitter, at Dr Kentris D-R-K-E-N-T-R-I-S. And you can also find the Neuro Transmitters podcast at neuro underscore podcast, and you can also find us at the neurotransmitterscom for other ways to reach out. Find other ways to contact us. Thank you again, Ashley. I appreciate it and hopefully we'll talk again in a minute.

Ashley Paul:

Yes, looking forward to it. Thanks for talking about a somewhat grim topic, but very important it is, I agree.

Michael Kentris:

Thank you again for listening. This episode was edited and produced by Rita Farhan. If you enjoyed this podcast, please leave a five star review for us on Apple or Spotify or wherever else you might get your podcasts. This really helps with giving a show noticed and spreading the word. Thank you again for listening and we'll see you next time.

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