Transcript
Speaker: Welcome to Critical Matters, a sound critical care podcast covering a broad range of topics related to the practice of intensive care medicine.
Speaker: Sound Critical Care provides comprehensive critical care programs to hospitals across the country.
Speaker: To learn more about our programs and career opportunities, visit www.soundphysicians.com.
Speaker: And now your host, Dr. Sergio Zanotti.
Speaker: The concept of brain death has
Speaker: was first described 60 years ago as coma de passe.
Speaker: In 1968, the first clinical definition, commonly referred to as the Harvard Brain Criteria, was published.
Speaker: Since then, many guidelines, protocols, and laws have been focused on brain death or death by neurologic criteria.
Speaker: Brain death remains an important topic within the practice of critical care medicine.
Speaker: However, there are still inconsistencies in concept, criteria, practice, and documentation of brain death.
Speaker: Today we will discuss this topic through the lens of the World Brain Death Project.
Speaker: Our guest is Dr. David Greer.
Speaker: Dr. Greer is a neurologist with additional training in vascular neurology and neurocritical care.
Speaker: He is the chair of the Department of Neurology at the Boston University School of Medicine.
Speaker: Dr. Greer is a renowned clinician, educator, and researcher.
Speaker: His research interests include predicting recovery from comma after cardiac arrest, brain death, and multiple stroke related topics.
Speaker: Dr. Greer is a leader in the Neurocritical Care Society, Society of Critical Care Medicine, and the American Stroke Association.
Speaker: He has an extensive list of publications and awards.
Speaker: He is the first author of the World Brain Death White Paper on Determination of Brain Death slash Death by Neurologic Criteria.
Speaker: We are honored to have him as our guest to discuss such an important topic.
Speaker: Dave, welcome to Critical Matters.
Speaker: Thanks so much, Sergio.
Speaker: It's great to be here.
Speaker: And I think a great place to start would be if you could just share with our audience, what is the World Brain Death Project?
Speaker: So the World Brain Death Project was kind of a brainchild that came out in about 2013 or 14, where we wanted to promote consistency to the worldwide practice of brain death determination.
Speaker: We've done some preliminary work in the 2000s regarding variability of brain death determination in the U.S.
Speaker: and a little bit about worldwide variation as well.
Speaker: And we were concerned that people were practicing brain death differently in different places.
Speaker: And unlike a lot of diagnoses in medicine, this is really one where there needs to be as close to 100% accuracy as possible.
Speaker: There really shouldn't be any false positive determinations of brain death.
Speaker: And you shouldn't be dead in Oregon, but alive in Georgia.
Speaker: or dead in the US but alive in India.
Speaker: And so we really wanted to promote consistency of determination worldwide and come up with minimum criteria, but also to provide guidance in specific areas such as in pediatrics, in the setting of ECMO, and in the setting of therapeutic hypothermia where there really was a dearth of literature and guidance on this.
Speaker: really took on a lot, but with the central premise of trying to educate people, promote consistency of practice, and provide guidance where it was previously lacking.
Speaker: And I think one of the aspects of medicine that I often see is that we focus very much on peaks and we kind of forget the plateaus.
Speaker: And it seems like what you're truly trying to do is provide the best available evidence to determine the floor, or this is the basic things that everybody should be doing.
Speaker: and there's obviously still things that we need to investigate, but really trying to set kind of the bar for where we should start based on the available evidence.
Speaker: Is that a fair assessment?
Speaker: Yeah, absolutely.
Speaker: And I think people, some people were concerned about us saying minimum criteria.
Speaker: Why wouldn't you use maximal criteria?
Speaker: Well, the actual, the minimum criteria err very much on the side of conservative, meaning that you don't declare somebody unless you're absolutely certain.
Speaker: So we really tried to make
Speaker: the bare minimum be very, very thorough and exhaustive so that people would not cut corners and understood exactly what it would take to do a clinical determination, including apnea testing, but also if ancillary testing was needed, exactly how that should be performed and to what specifications.
Speaker: So although some people might be uneasy about the word minimum criteria,
Speaker: It's actually really quite conservative and errors on the side of not declaring somebody brain dead unless you're absolutely certain.
Speaker: And this seems to be particularly important for this topic for two reasons, at least it seems from what you're explaining.
Speaker: One is how sensitive the diagnosis we're trying to get to is, which is a determination of death by neurologic criteria, but also by what's available in evidence.
Speaker: Even though we've been doing this for 60 years, it's very hard to do randomized trials in this area.
Speaker: Is that correct?
Speaker: Yeah, that's exactly right.
Speaker: And so a lot of times clinician judgment comes into play.
Speaker: And so providing some guardrails for that as to where can you not cut corners?
Speaker: Where do you have to be as meticulous as possible?
Speaker: You know, the obvious thing is in terms of laboratory values and intoxicants and things like that, which we were very, very explicit about.
Speaker: But yeah, from a scientific standpoint, this is a difficult thing to study.
Speaker: But nonetheless, you can still be practical and you can still use all the available data at your fingertips and you can still have as your golden rule, if in doubt, you don't declare.
Speaker: Absolutely.
Speaker: I would like to ask you about the nomenclature and I think it's very important.
Speaker: Words matter.
Speaker: What we call things obviously ultimately has a great impact in a lot of our behaviors.
Speaker: But I did notice that you have utilized for this particular paper and a lot of discussions I've seen brain death and a slash death by measure criteria.
Speaker: Is there a difference?
Speaker: Is there a terminology that we should be preferable using?
Speaker: Any comments on that, Dave?
Speaker: Well, it was a matter of great debate and it still goes on.
Speaker: There is no difference, but the more appropriate term technically should be death by neurological criteria.
Speaker: It is a criteria based on
Speaker: or rather it is death that's based on a different formulation than the cardiopulmonary.
Speaker: It's a neurological criteria for determination of death.
Speaker: But that's a mouthful, right?
Speaker: And everybody's used to the term brain death.
Speaker: It's a colloquial term.
Speaker: And so that's why we kind of put the two together because everyone can resonate with the term brain dead, whether you're a clinician or you're a lay person.
Speaker: But death by neurological criteria is actually the more accurate
Speaker: term and we'd like people to start adopting that as well.
Speaker: So we're stuck with this, you know, this hyphenated BD-DNC, brain death and death by neurological criteria.
Speaker: It's a little clunky, but it does kind of make the point that we're catering to both of those universes.
Speaker: Absolutely.
Speaker: So I would like to dive right into the clinical criteria that I think are most important and interesting for clinicians at the bedside to understand.
Speaker: And like you said,
Speaker: even though we're using the terminology of minimum clinical criteria for determination of death panoramic criteria, what it really means is this is what you absolutely must do and must do well in order to feel confident that you have a diagnosis that is consistent with brain death.
Speaker: So why don't we start with prerequisites?
Speaker: I think this is something very important that often people miss in the discussion.
Speaker: And I suspect that a lot of times when we hear
Speaker: lay press stories of people who were quote unquote brain death who didn't wake up, these prerequisites might've been part of the problem.
Speaker: Right.
Speaker: So there are basically two cardinal rules as you start your prerequisites.
Speaker: And one is that you must know the nature of the neurological catastrophe.
Speaker: You have to know why they're in coma and you have to usually have neuroimaging evidence that this has been some kind of severe injury to the brain.
Speaker: And you have to know that the loss of all clinical function of the entire brain is permanent.
Speaker: That there's no chance for reversibility.
Speaker: And so those are really the cardinal rules.
Speaker: You cannot skip those.
Speaker: You've got to know why they're in coma and you've got to know that it's irreversible.
Speaker: So without those, you're not doing any brain death testing at all.
Speaker: So with those, then you go into looking for any evidence of confounding.
Speaker: And the confounding typically comes in the,
Speaker: the setting of drugs, particularly sedative medications or intoxicants the patient might have received or ingested, sometimes paralysis if they've received paralytics, that can be a confounder.
Speaker: If there are significant metabolic abnormalities, such as hyper or hypoglycemia, hypernatremia, hyponatremia, acid-base disturbances, endocrine disturbances,
Speaker: Hypothermia, which we're using therapeutically, that can delay drug metabolism as well.
Speaker: So there are a number of things that can potentially confound the clinical diagnosis that these have to be satisfied first before a determination of brain death takes place.
Speaker: In terms of specific medications, are there any recommendations in terms of checking levels
Speaker: and waiting the tremendous amount of time that can assist a clinician at the bedside?
Speaker: Yeah, so we put a really nice table into the supplement number four, which is the minimum clinical criteria, which actually talks about the common drugs that can impact brain death determination, including opioids, sedatives, benzos, barbiturates, propofol, baclofen,
Speaker: It goes into all of those, including the half-lives and how long you have to wait.
Speaker: And it also talks about what can decrease or increase metabolism.
Speaker: The other caveat to all of this in terms of medications is you have to take into account whether they have normal metabolism or not.
Speaker: And if they've had renal or hepatic insufficiency that may be impaired, or if they're older or younger, that also might have an impact on their metabolism.
Speaker: one way or the other.
Speaker: So we did try to provide some very specific guidance for this in terms of how long you wait for which drug and what might throw off the consideration.
Speaker: Excellent.
Speaker: So once you've checked out both boxes, you have a very established diagnosis, consistent or compatible with brain death, and you've excluded any confounders.
Speaker: How do you proceed?
Speaker: What's next?
Speaker: So if you've excluded the confounders and you're feeling comfortable that you know the diagnosis, the etiology and the irreversibility, then your clinical determination can take place.
Speaker: And that's really in two pieces.
Speaker: One is a detailed neurological exam.
Speaker: And the second piece is an apnea test.
Speaker: And of course, you've already been doing neurological examinations along the way, obviously from the moment they came in to either your ICU or your emergency room.
Speaker: You've already been doing them and you've been looking for any signs of brain function, but that's really what you're looking for.
Speaker: There are three components.
Speaker: There's coma, which means absence of any responsiveness to all noxious stimulation.
Speaker: And then there's brainstem areflexia, meaning an absence of all brainstem mediated reflexes.
Speaker: And then there's apnea as a third part of it, which is tested through apnea testing.
Speaker: And that tests the last thing to go, which is your
Speaker: medullary function where your respiratory control centers are located.
Speaker: Can we dive a little bit deeper into each one of those components and maybe start with, is there any tips as a neuro-intensive neurologist you would give to other clinicians in terms of evaluation of coma?
Speaker: Yeah, that's a great question.
Speaker: So you have to give maximal noxious stimulation and that takes multiple forms.
Speaker: It's auditory, it's visual, and it's tactile.
Speaker: Auditory is, well, I like to joke that there's, everybody knows when I'm in the ICU because there's somebody yelling at the patients.
Speaker: I assume that everybody's deaf until proven otherwise.
Speaker: So I'm yelling their name, I'm clapping right into their ear, and you're looking for any responsiveness.
Speaker: The next is visual, which is a bit more challenging.
Speaker: You hold the eyes open because obviously in a comatose person, they're gonna have eyes closed.
Speaker: And then you do a visual threat where I come in with my hand flat
Speaker: so I don't create a wind wave which would check a corneal reflex and I see if they have any blinked visual threat.
Speaker: And then the tactile stimulation, you want to use NOXR stimulation.
Speaker: I think everyone knows how to use deep nail bed pressure to test it on the extremities.
Speaker: You always test in two points.
Speaker: You test at the nail bed but also proximally on the limb.
Speaker: But people may forget to test on the cranium as well.
Speaker: And keep in mind that some patients might have a C-spine injury
Speaker: or might have a severe peripheral neuropathy and might not respond to pain below the neck.
Speaker: So you have to check on the head as well.
Speaker: And so the ways to do this are, one is to stick a Q-tip up their nose and see if they grimace, that's a nasal tickle.
Speaker: Second one is to press on the supraorbital notch where the supraorbital nerve comes out.
Speaker: That's obviously a painful spot.
Speaker: And then the third is to give bilateral temporomandibular joint pressure.
Speaker: which is a painful stimulus as well.
Speaker: So you have to test on the cranium and the torso and the extremities to be thorough in assessing for coma.
Speaker: If you do this assessment and you don't have any response, you proceed, I presume, to the brain reflex.
Speaker: Can we talk a little bit more about the area of flex of the brainstem?
Speaker: Yeah, so the brainstem reflexes, you basically start from number two, because we don't test smell very often, and then you work all the way down
Speaker: to the bottom of the brainstem.
Speaker: So again, you've testing a blink to visual threat, that's testing too to see if they have any vision.
Speaker: You test their extraocular movements by doing the oculosephalic test, assuming that they don't have a C-spine injury, where you briskly rotate the head side to side and up and down.
Speaker: You have to take great care not to extubate the patient.
Speaker: Obviously, that's
Speaker: a risk as you're briskly moving the head.
Speaker: So you want to secure the tube as you're doing it.
Speaker: In brain death, you should not see the eyes move in relation to the head.
Speaker: They should stay fixed straight ahead.
Speaker: You should also do the oculovestibular test where you do the cold calorics and you instill cold water in one ear at a time and you look for any eye movements.
Speaker: In brain death, there should not be any eye movements again.
Speaker: You test a corneal reflex.
Speaker: I typically use a Q-tip
Speaker: and I press on the eye, the proper place to test is right adjacent to the iris.
Speaker: A lot of people go too far out laterally on the conjunctiva where the nerve fiber density is decreased and it's less sensitive.
Speaker: So you really want to go more centrally.
Speaker: I go adjacent to the iris to test a corneal reflex.
Speaker: Moving down the brainstem, so again, looking for any facial movement that was tested by doing
Speaker: the facial stimulation to noxious stimulation.
Speaker: And next you go and look for a gag and cough reflex.
Speaker: So a gag, you're going to sneak by the endotracheal tube with a Q-tip or a suction device and poke the posterior pharynx on both sides, looking for any kind of a gag.
Speaker: And a cough is with deep bronchial suctioning.
Speaker: where you take a catheter, usually an inline catheter, and you stimulate down to the level of the trachea and look for a cough reflex.
Speaker: You also want to make sure that they're not over-breathing the ventilator, the set rate on the ventilator.
Speaker: If they're already over-breathing the vent, you know that they're not brain dead.
Speaker: And then you also have to test, of course, for motor responses, which is testing brainstem as well.
Speaker: As I described before, you're testing on all four limbs, proximally and distally, and on the torso.
Speaker: you cannot see things like extensor or flexor posturing because that's a brainstem mediated reflex.
Speaker: So sometimes you'll see extensor like movements, but that can be secondary to a spinal immediate reflex.
Speaker: And sometimes it's unclear what you're seeing, whether it could actually be spinal or cerebral.
Speaker: And so if a situation like that occurs, you should get somebody with more experience to take a look at it.
Speaker: And you may need to get an ancillary test if you're still uncertain after further examination.
Speaker: So that's really walking through head to toe, literally, how you do the clinical examination.
Speaker: And obviously, the consistent findings with brain death would be that all these reflexes that we're testing are negative.
Speaker: If any of them are equivocal or if there's any situation, and maybe you could tell us an example of that, where you can't do one of those tests, is an ancillary test mandatory?
Speaker: Yeah, it's a great question.
Speaker: So if they have post-surgical pupils or they have bad facial trauma or facial swelling or eye edema, and that might preclude you seeing eye movements or pupillary reaction, then you'd have to get an ancillary test in a situation like that.
Speaker: The only thing that you can skip if you cannot perform it is the oculosephalic maneuver or the doll's head, as they like to call it, but I don't like the term.
Speaker: because if they have a C-spine injury, you can't test that, but you should always be able to test the oculovestibular test.
Speaker: And let's say you know you're going to end up having to get an ancillary test because the patient has post-surgical pupils.
Speaker: You still do the entire neurological exam because if you find signs of life, then you're not going to do an ancillary test, right?
Speaker: You have to make sure that whatever you can test is fully tested.
Speaker: And if you find signs of life,
Speaker: any signs of brain-mediated function.
Speaker: That's not compatible with a brain death diagnosis, and you don't get an ancillary test in a situation like that.
Speaker: So we talked about termination of coma.
Speaker: We talked about examining or evaluating the brainstem, and like you mentioned, the third component of our clinical exam or clinical testing would be the apnea test, which is probably the one fraught with most confusion, especially, I think, in the realms of critical care outside of neurology.
Speaker: But I suspect that even in the neurocritical care world, this is the one that sometimes is a bit more complicated or people are mostly misunderstood.
Speaker: So can you tell us a little bit more about the apnea test, Dave?
Speaker: Absolutely.
Speaker: So again, there are prerequisites for this part of the test as well that are very specific.
Speaker: First of all, again, they should have no spontaneous respirations breathing above the set rate on the ventilator.
Speaker: Secondly, you want them to be normotensive.
Speaker: and normothermic, so the lowest allowable blood pressure in adults is 100 systolic, and you have to be at least 36 degrees as your lower border of your temperature.
Speaker: You have to be euvolemic, and this is very important because oftentimes patients with brain death have diabetes insipidus, and they get a negative fluid balance.
Speaker: That puts them at high risk for getting hypotension during the test.
Speaker: So you want to make sure they have an even
Speaker: fluid balance and give them back whatever they've lost.
Speaker: You have to establish eucapnia, and I would say eucapnia for that patient.
Speaker: If they're a known CO2 retainer, then your baseline should be what their baseline is.
Speaker: So in other words, if they live at a PCO2 of 50, then that's your baseline for that patient.
Speaker: Otherwise, it should be 35 to 45 as normal.
Speaker: And they should have no hypoxia prior to testing.
Speaker: In fact, they shouldn't have hypoxia at any time during the test.
Speaker: If they get hypoxic, they're likely to get hypotensive.
Speaker: So you're maintaining oxygenation throughout the entire time.
Speaker: You actually want to start out with a PaO2 of greater than 200 so that they will hopefully stay well oxygenated during the test.
Speaker: I recommend disconnecting the patient from the ventilator because a lot of the modern ventilators will auto cycle, especially if they have condensation in the tubing.
Speaker: or somebody bumps the bed.
Speaker: So disconnect the patient from the ventilator.
Speaker: That way you have no doubt that the breath did not come from the patient.
Speaker: You want to preserve oxygenation by dropping a catheter down to the level of the carina with an oxygen source that should be going at about four to six liters per minute.
Speaker: If it's going faster than that, you may wash out CO2 and prevent you from getting your numbers.
Speaker: So four to six liters per minute is probably the right rate.
Speaker: And you want to make sure that that catheter is not greater than 70% of the lumen of the ET tube.
Speaker: Otherwise, you could cause barotrauma, especially at a higher flow rate.
Speaker: So those are very important steps to take.
Speaker: I also recommend uncovering the chest and the abdomen so you can see if there's any respiratory effort by the patient.
Speaker: I stand at the foot of the bed so I can see if they're breathing.
Speaker: And I can look at the monitor to see if they're dropping their blood pressure or dropping their O2 sat.
Speaker: If they drop their systolic less than 90, then you have to abort.
Speaker: If they drop their O2SAT to less than 85% for greater than 30 seconds, then you have to abort as well.
Speaker: So I recommend sending serial ABGs, five, eight, and certainly 10 minutes, because if they do decompensate systemically during the test, at least you've got your ABG.
Speaker: And if they didn't breathe and you get to your PCO2 numbers, then,
Speaker: then you can declare them brain dead.
Speaker: The numbers that you're looking for are at least 60 for your PCO2.
Speaker: And you have to be at least 20 points above the baseline in a patient who's a known CO2 retainer.
Speaker: So a patient who starts out at 50 has to get to at least 70, for example.
Speaker: And they should be getting acidotic during this time as well because the acidosis is what's going to trigger them to breathe, not just the hypercarvia.
Speaker: So one last thing to do, which is a little trick of the trade, is when you reconnect them to the ventilator, hyperventilate them for a minute.
Speaker: And that's going to rapidly correct the respiratory acidosis that you intentionally caused, and it'll prevent or correct whatever hypotension the patient may be having or be at risk for.
Speaker: So that's a really important step as well to rapidly correct the respiratory acidosis.
Speaker: So that's how you do the apnea test.
Speaker: If your numbers are not consistent, let's say you get to a PCO2 of 58 or 59, but they didn't breathe, you can repeat the test for longer.
Speaker: I've gone out to 15 minutes.
Speaker: But again, you have to reestablish a normal acid-base status, a PCO2 in the normal range for that patient.
Speaker: And you have to, again, pre-oxygenate the patient.
Speaker: But you can go on for longer.
Speaker: If they were unstable during the test, you can do it on a T-piece.
Speaker: You can do it with CPAP, knowing that you may need to take a little bit longer in order to get to your numbers.
Speaker: But you can do it on the vent.
Speaker: It's just a bit trickier to do it.
Speaker: But those are the steps of apnea testing, which are really pretty cookbook.
Speaker: But you're right.
Speaker: This is where people can often fall off the rails a little bit if they're not attentive to detail.
Speaker: Absolutely.
Speaker: So a couple of questions to dig a little bit deeper into the apnea test.
Speaker: First, you mentioned the blood pressure.
Speaker: Is it okay to do this if somebody has the required blood pressure on a stable dose of vasopressors?
Speaker: Yeah, that's a great question.
Speaker: So I like to have a buffer where their blood pressure is at least systolic of 110 or 120.
Speaker: So if that requires a lot of pressures to do it, then that may be a patient who might be slightly dangerous to do the apnea test on.
Speaker: So you want to be careful.
Speaker: So my general rule is that they're on a high dose suppressor and they're very
Speaker: barely above 100 or requiring multiple pressors, then you're going to have a really short trigger to abort the test because you don't want them to have cardiovascular collapse during the test.
Speaker: So try to get yourself a buffer.
Speaker: If they're just hovering above 100, at least have vasopressors connected to the patient at the bedside so you can dial them up quickly if you need them.
Speaker: Excellent.
Speaker: And in terms of interpretation, the way I look at it is,
Speaker: If the patient has no spontaneous breathing and we hit the targets you mentioned on the PCO2 as compared to baseline, we would call that a positive apnea test, and that would be consistent or would confirm if we did the other steps are a diagnosis of brain death.
Speaker: If the patient does not, if the patient breathes spontaneously, we stop the apnea test, and in that case, we cannot proceed with declaring that patient brain death.
Speaker: but you did talk about aborting the test.
Speaker: That's a different result.
Speaker: An aborted test is not a negative test.
Speaker: Could you detail that a little bit more, Dave?
Speaker: Sure.
Speaker: So you're right.
Speaker: So you would abort the test, obviously, if they were breathing because they're not brain dead.
Speaker: So that's one reason to abort it.
Speaker: But the other would be if you had cardiac or pulmonary instability.
Speaker: So again, the rules are when you start, you have to have a systolic of at least 100.
Speaker: you have to abort if you drop below 90.
Speaker: And you can do whatever you want during the apnea test to try to maintain it.
Speaker: If you're dipping into the 90s, you're dialing up your pressors so that you can try to keep them above the minimum range.
Speaker: In terms of the hypoxia, not much you can do about that.
Speaker: And if they are, I tell you, I don't wait 30 seconds.
Speaker: If they drop below 85%, I'm usually getting them reconnected to the ventilator pretty quickly at that point and thinking that I'm going to need to get
Speaker: an ancillary test because they weren't able to get through it.
Speaker: You could, again, retry it with a T-piece or CPAP, but that would be, those are the two reasons to abort from a clinical or medical standpoint.
Speaker: And an aborted test and those two situations obviously would be more along the lines of an inconclusive test and would either dictate to repeat the test under different conditions once you return to baseline or to proceed with additional testing, which we'll talk in a little bit.
Speaker: Is that correct?
Speaker: Yeah, that's exactly right.
Speaker: So it's an aborted test, but it does not mean that the patient is not brain dead.
Speaker: It just means that you could not complete that aspect of the testing.
Speaker: The only thing that would say that they're not brain dead is if they actually breathe.
Speaker: Before we go to additional testing or ancillary testing, I wanted to ask, what is the current literature, the opinion, and what's the stand of the World Brain Dead Project?
Speaker: on the number of examinations and examiners?
Speaker: So it's different rules in different countries.
Speaker: We said that the minimum is one and that two is likely to provide a greater degree of security.
Speaker: So I do recommend that there be two because it does provide greater security for the diagnosis.
Speaker: I actually recommend that the two clinicians who are doing this should both be attendings.
Speaker: They don't have to be neurologists.
Speaker: I think critical care doctors do great at this, but they should have adequate training and credentials to do this.
Speaker: But I think they should do them independently and blinded to the results of the other.
Speaker: I think that's the most sound way to do it.
Speaker: I know that not everybody does it that way, but let's say I, as the chairman of my department,
Speaker: do a clinical determination and the next person goes in knowing that I thought that the patient was brain dead, are they really going to be able to feel comfortable standing up to me and saying to their own chairman, like, I think you're wrong.
Speaker: I mean, it's a difficult thing to do.
Speaker: So I think independent and optimally blinded to evaluations would be the best, most sound way to do it.
Speaker: But that's just a personal preference.
Speaker: But the world, I think, at large is really moving back towards having
Speaker: two examinations be the standard.
Speaker: Maybe not everywhere, but most places.
Speaker: Okay.
Speaker: And is there a temporal relation other than not being done at the same time and being blinded?
Speaker: Does it have to be like, in some criteria I've seen, people have used an X amount of hours separating the examinations.
Speaker: Those are more policies than based on evidence.
Speaker: But what is the current thinking there, Dave?
Speaker: Well, I love that you asked that question.
Speaker: The waiting period should be before anyone does brain death testing, right?
Speaker: So you need to wait to ensure irreversibility.
Speaker: After that, like, why does there need to be an additional delay between examiners?
Speaker: Are you worried that the patient's going to recover?
Speaker: Well, if that's the case, you shouldn't have done the first examination, right?
Speaker: So it's completely illogical to have a separation in time between the two examinations.
Speaker: The only reason that you might have a delay is for logistic reasons, like it's the middle of the night, you don't have another examiner and you could wait if you need to, but not from a standpoint that you expect there to be any clinical change with the patient.
Speaker: If you expected that or you were worried about that, then again, you shouldn't be doing the determination in the first place.
Speaker: Does that make sense?
Speaker: It does.
Speaker: And I think it's a source of confusion in some hospital policies.
Speaker: that historically at least I've seen in different states here in our country have had timeframes like that, but you're absolutely right in terms of the logical sequence of how we're trying to get to the diagnosis, it doesn't make any sense.
Speaker: Correct.
Speaker: So let's talk about additional testing.
Speaker: And before we talk about like ancillary testing and the types of testing, is there,
Speaker: Is there a difference in terms of terminology between an ancillary test, a supplemental test, or a confirmatory test, and how they apply to brain death?
Speaker: Yeah, so I prefer the term ancillary test.
Speaker: When people say confirmatory test, that means you're confirming what you already know.
Speaker: And the whole reason why you're getting an ancillary test is because you can't confirm brain death, that you're not certain, or you've got confounding that you cannot get rid of.
Speaker: or you can't complete the exam fully or safely, speaking specifically about the apnea test.
Speaker: So it's an ancillary test.
Speaker: You're using it as your primary means of declaring brain death.
Speaker: But again, that does not mean that you don't do the clinical exam to the fullest extent possible.
Speaker: And I really have to emphasize that because this is where I've seen people run into trouble that they'll say, oh, let's get a spec study and see if they're brain dead.
Speaker: Well, that's really faulty judgment to do that because there are things that could potentially give you false positives or negatives with an ancillary test as well.
Speaker: And again, if you had signs of life based on a clinical exam, whatever you could complete, you shouldn't be doing the ancillary test in the first place.
Speaker: So those are some general rules around it.
Speaker: But I prefer the term ancillary test.
Speaker: And I think that that's really what most of the world is using at this point.
Speaker: If you can't complete a specific portion of your test, but you're still, everything else that you've done is consistent with brain death, an ancillary test is indicated and we'll talk about which ones are the ones that are available and recommended.
Speaker: But if you completed every single step of the clinical examination, is an ancillary test required?
Speaker: No, it is not.
Speaker: Unless it's required at your institution or in your country, there are some countries that
Speaker: do require an ancillary test in every case, but according to the American Academy of Neurology guidelines, no.
Speaker: An ancillary test really should only be used when you cannot trust or fully complete the clinical testing.
Speaker: What is the gold standard right now for ancillary testing?
Speaker: Well, there are two types of tests.
Speaker: There are flow studies and there are electrical studies.
Speaker: And flow studies are really
Speaker: the primary modality used and the gold standard remains to this day a catheter digital subtraction angiogram.
Speaker: That's not done very much for logistical reasons, but that's really how you're able to assess that there is no forward flow into the cranium.
Speaker: What are other tests that might be utilized if we can't have access or like you said, we can't take the patient to the neurointervention or the intervention radiology suite for that?
Speaker: Yeah, so the two tests that are used primarily, one is SPECT or nuclear imaging.
Speaker: And there are two kinds.
Speaker: You can use lipophilic and lipophobic agents.
Speaker: Lipophobic agents don't go into the brain parenchyma.
Speaker: They just show you whether you have vascularization or not.
Speaker: And so I favor the lipophilic ones where
Speaker: You can see both vasculature and uptake of tracer if there's metabolic activity.
Speaker: And so the spec studies are probably the easiest.
Speaker: There are even portable specs that can be used.
Speaker: You have to make sure that it's done correctly where you have both AP and lateral views because the lateral is the only way that you're able to see the brainstem and that's the last to go.
Speaker: So you need to look at the source images as well, looking carefully at the brainstem.
Speaker: Transcranial Doppler is another great bedside test.
Speaker: It's operator dependent though.
Speaker: You have to look bilaterally at the middle cerebral arteries and internal cerebral arteries, as well as posteriorly in the vertebral arteries and basilar.
Speaker: And absence of flow is not what you're looking for.
Speaker: In fact, that could just be operator dependent that you can't find any signal.
Speaker: What you're looking for is reverberating flow
Speaker: where in diastole the flow goes to zero or even negative, it reverses because that tells you that your intracranial pressure is higher than your mean arterial pressure and there's no effective forward flow in the brain.
Speaker: So it requires two examinations, 30 minutes apart, bilateral, anterior and posterior.
Speaker: So those are the other flow studies that are used.
Speaker: For electrical studies, we traditionally had used EEG
Speaker: We're really recommending against using EEG at this point because it doesn't measure the brainstem at all.
Speaker: And people don't use it in conjunction with evoked potentials, which would be the only way to look somewhat at brainstem integrity.
Speaker: So it's really not a good test to use in brain death.
Speaker: And we really recommend strongly against using electrical tests.
Speaker: They should just use closed studies.
Speaker: Is there any evidence to support the use of CTA or MRA?
Speaker: Obviously these are very commonly utilized today in hospitals and some people have talked about it for brain determination, but I'm not really familiar with where the literature stands there.
Speaker: Yeah, I'm so glad you asked that.
Speaker: CTA and MRA are not ready for prime time.
Speaker: They are subject to false positives and false negatives.
Speaker: and they should not be used.
Speaker: They've not been validated against the gold standard.
Speaker: We have published several reports of patients who've been, quote, positive on CTA, but then have been able to show forward flow on transcranial Doppler or other studies.
Speaker: The problem with CTA in particular is that it's a venous injection, as opposed to an arterial injection when you're doing a digital subtraction angiogram.
Speaker: During a DSA, you can actually do a hand injection and watch dynamic images.
Speaker: You don't have that luxury with a CTA and the timing to know when there is absolutely no flow intracranially in a patient with a high ICP like that.
Speaker: That has not been figured out yet.
Speaker: So until it's been validated against another gold standard, CTA can't be used and MRA can't be used.
Speaker: even worse problem because there's a lot of flow-dependent artifacts that makes both of them, unfortunately, not good tests.
Speaker: Believe me, I would love for one or the other to be validated, and it's something that we're working on as one of our research efforts, but please don't use it yet.
Speaker: There are certainly false positives and negatives, and so CTA and MRI are not ready for prime time.
Speaker: And I just want to emphasize, Dave, that
Speaker: actually three tests that I would say are most commonly utilized in the community setting, not for brain death necessarily, but for neurological patients, which includes CTA, MRA, and EEG, should not be applied in this situation as you're sharing with us.
Speaker: That's exactly right.
Speaker: Thank you for emphasizing that.
Speaker: So towards the final part of our conversation, I wanted to talk a little bit about special situations.
Speaker: We did mention some of them at the beginning when you were addressing the goals and the broad perspective of the World Brain Death Project.
Speaker: Obviously, this is a podcast directed mostly at critical care practitioners who take care of adult patients, so we won't talk about the pediatric situation, which has discussions that I think are unique to itself.
Speaker: But I did want to talk about ECMO,
Speaker: and targeted temperature management patients or therapeutic hypothermia, which I do think are increasingly common in our ICUs and obviously can suffer catastrophic injuries that lead to brain death.
Speaker: So I would like to hear a little bit more in terms of what are some of the caveats or some of the special considerations for these populations.
Speaker: Sure.
Speaker: So let's talk about ECMO first.
Speaker: This is coming up more and more often, and it's a challenging situation.
Speaker: As part of the world brain death
Speaker: project, we actually had an entire chapter devoted to ECMO and how you test for brain death on ECMO.
Speaker: And somebody who's on VA ECMO, you have to have a map of at least 60 while you're doing the test.
Speaker: You adjust the sweep gas on the ventilator and you make sure that the patient is on 100% inspired O2 by the ventilator and also through the membrane lung as well.
Speaker: again with pre-oxygenation so they don't get unstable.
Speaker: You measure the blood gases simultaneously from both the distal arterial line and from the post-oxygenator ECMO circuit.
Speaker: And the goals are for both sampling sites that you have to have a pH of less than 7.30 and a pCO2 of at least 60, but again, or higher if the patient has a higher baseline pCO2 with
Speaker: pre-existing hypercafnea.
Speaker: So they have to have 20 above their baseline as well.
Speaker: The sweet gas flow rate is adjusted to typically 0.5 to one liter per minute while maintaining oxygenation for this.
Speaker: So that's some of the specific guidance for ECMO.
Speaker: For hypothermia, we put in an algorithm in the chapter on hypothermia as to what you do and when.
Speaker: The first thing is to be patient.
Speaker: Somebody that
Speaker: well actually the first thing to do is try to rewarm them but then you also have to be patient because if they've been cold and they've received drugs you have to wait longer if they've been cold received drugs and have hepatic or renal insults due to a cardiac arrest for example you have to wait even longer we do recommend that the patient be determined clinically whenever possible because of the problems that people can encounter with ancillary tests so don't be in a rush with this diagnosis you will often wait
Speaker: 48, 72 hours waiting to make sure that there is no ongoing drug intoxication or other confounding in these patients.
Speaker: So we preach patients and only use ancillary tests when needed, and you have to take into account the additional confounding with hypothermia.
Speaker: I also like, especially in cardiac arrest patients, I like getting a CAT scan in a patient, especially if I'm going to be getting an ancillary test.
Speaker: And that's to ensure, again, that you've got a neurological catastrophe.
Speaker: You want to see neuroimaging evidence that they've got widespread herniation and that they shouldn't have any cerebral circulation based on their ICP being sky high if you were to stick a probe in their head.
Speaker: So that neuroimaging has to be consistent with that kind of catastrophe.
Speaker: So after a cardiac arrest, really important, especially if you're under the gun and feeling rushed, you got to have that CAT scan or MRI
Speaker: that shows you that you've had a devastating injury that's consistent with brain death.
Speaker: And I think, let me ask you a question, Dave, that it might be a tricky situation from a clinical perspective.
Speaker: And obviously, we can then go into longer discussion of when do you absolutely need to do a brain death determination versus there are situations, especially post-cardic arrest, where you might have enough evidence of significant brain damage that might dictate
Speaker: based on patient preference therapy or withdrawal therapy, but can you have a patient with significant anoxic brain damage and no recovery that is not brain dead but has that degree of neurologic injury without a finding that is conclusive on the imaging?
Speaker: No, you really shouldn't.
Speaker: If somebody's had a catastrophic injury from a cardiac arrest, for example, your first CAT scan, the one that you get from the emergency room, may look pretty normal.
Speaker: But you've got to have one subsequent to that that shows you that you really had widespread severe injury and herniation, uncle herniation, tonsillar herniation, that the intracranial pressure must be really high and you can't have any cerebral circulation.
Speaker: So you can't hide it.
Speaker: The normal imaging would only be in the very early setting or in a diagnosis like
Speaker: bacterial meningitis in the acute setting.
Speaker: But again, subsequent imaging has got to be consistent.
Speaker: So don't be fooled by the initial early benign-ish looking imaging.
Speaker: You've got to get follow-up imaging to make sure that it's compatible.
Speaker: Excellent point.
Speaker: And thanks for clarifying that.
Speaker: The other question I had regarding special situations are situations in which the patient has been determined to be dead by neurologic criteria, but there might be an indication for ongoing
Speaker: organ support, which is sometimes A, either a cause of confusion among intensivists or B, is a cause of disagreements and stress with the family.
Speaker: And what I wanted to ask you specifically is three groups of patients.
Speaker: A, organ donors, B, pregnant patients, and C, when there are family objections on religious grounds, which having practiced in New Jersey is part of the law and I have encountered in my career.
Speaker: So the first situation, repeat that again for me.
Speaker: I want to take them in order.
Speaker: Organ donation.
Speaker: Yeah.
Speaker: So organ donation.
Speaker: So you don't immediately withdraw the patient from the ventilator once you've done the brain death determination.
Speaker: Obviously, you go and you talk to the family and explain to them what the results of your testing have been, assuming that you've talked to them before that as well to say you're doing brain death testing or even they've been there and observing it.
Speaker: And then you're required by law, at least in the US, to have the organ procurement organization have the opportunity to evaluate the patient, assess them for potential donation, and then you introduce them to the family to have a discussion regarding possible donation.
Speaker: And during that time, you're continuing somatic support for the patient.
Speaker: And if they agree and consent to
Speaker: donation, then you're supporting the patient through the time to transplant.
Speaker: In the World Brain Death Project, we provided an entire chapter devoted to somatic support in terms of what do you do in terms of endocrine support, what do you do from a pulmonary standpoint, bronching the patient, cardiac standpoint, et cetera.
Speaker: And so we provided very specific guidance on that.
Speaker: In terms of the issue regarding pregnancy and what we call accommodation, which is when the family disagrees with or doesn't accept the diagnosis, we actually came out with a position statement from the American Academy of Neurology.
Speaker: And my friend Arianne Lewis is the first author on that, where we discussed what can be done.
Speaker: You want to get your high-risk OB people involved.
Speaker: You want to talk with the family and explain the likelihood of
Speaker: supporting the pregnant woman's body so that they can deliver a fetus, whether that's possible or not.
Speaker: So we provided some specific guidance on that, as well as the challenging issue of when families don't agree or don't accept it, the accommodation issue.
Speaker: And different states have different laws regarding that.
Speaker: These are very, very challenging and charged situations.
Speaker: They've gotten worse over the last decade.
Speaker: with multiple challenges in the legal system.
Speaker: We are lobbying for the UDDA or the Uniform Determination of Death Act to be updated so that the national standard in the U.S. becomes the AAN guidelines.
Speaker: And again, there will be new AAN guidelines coming out in the coming year that will provide very strict and supportive guidance for both adults and pediatrics.
Speaker: But until every state is consistent with this, we still have a case by case quandary when people challenge this.
Speaker: You really have to take your time, explain to the family, get hospital legal involved, get your hospital administrators involved, your ethics committee, and basically buckle up because some of these can be really challenging cases where the end result is unclear for a long time.
Speaker: And along those lines, obviously step number one is fulfilling all the requisites and all the steps that you detailed to us.
Speaker: But the second part, I presume, is also documenting what we're doing.
Speaker: And maybe to close our discussion on the minimum criteria, could you share with us your thoughts on documentation of brain death by the clinician?
Speaker: Yeah, absolutely.
Speaker: So the documentation is extremely important.
Speaker: And you make the diagnosis of brain death
Speaker: when it is medically indicated, meaning when the patient, you suspect that they are brain dead.
Speaker: You don't wait for permission to do it.
Speaker: You don't need consent from the family to determine brain death.
Speaker: It is a diagnosis, a medical diagnosis like any other.
Speaker: You determine the diagnosis when it's able to be met.
Speaker: For the documentation, you want to document the nature of the catastrophe, the irreversibility, the absence of confounding,
Speaker: all of the details of the clinical evaluation and examination, all of the details of the apnea test that's performed, including the ABG values, the details of what ancillary test was performed, and when it was formally interpreted.
Speaker: The time of death traditionally has been when the lab reports the ABG that is consistent with brain death, or if an ancillary test is performed, the time that the attending physician signs
Speaker: the report for whatever ancillary study was done.
Speaker: That is the official time of death.
Speaker: I do recommend that everybody use a checklist, that you can create these in whatever medical record system you use, that you just fill in the boxes and it creates your note for you.
Speaker: I still bring a checklist to the bedside every time I do a brain death evaluation.
Speaker: And I've done literally hundreds of them.
Speaker: You don't want to mess up.
Speaker: You don't want to forget anything or miss anything.
Speaker: There's no shame in bringing a checklist to the bedside and it provides great thoroughness and comfort level that you've done everything correctly.
Speaker: So that's what's required in your documentation.
Speaker: And I think that's a great recommendation.
Speaker: And that's why I was, I was going that direction because I have noticed having the opportunity to, to visit multiple of our practices throughout the country, that there is a lot of variation of how people are documenting this in many places.
Speaker: And like you said, the places that use a checklist or have integrated that into a standardized form in their medical record, I think, are doing a much better job and are really not only doing what's best for patients, but helping the clinicians provide high-value care, which is ultimately the goal.
Speaker: One of the things that we like to do in the podcast, Dave, as we close the discussion is really ask our guest a little bit about a couple of questions unrelated to the topic of brain death as we're discussing today.
Speaker: Would that be okay with you?
Speaker: That's fine.
Speaker: So the first question relates to books in terms of books that have influenced you the most or what books have you gifted most often to others?
Speaker: And I assume you mean medical books, not life books.
Speaker: Not necessarily.
Speaker: Books in general.
Speaker: We've had people offer medical books, fiction books, nonfiction, just books that have been important in your perception of the world or that you think are important for people who otherwise are in training or outside of medicine or interested in anything.
Speaker: Yeah, well, I don't know that many people that read books anymore, unfortunately, in medicine, but Elko Vedix has written a couple of really great sentinel books on brain death, and he's been kind of the grandfather of the field for a long time.
Speaker: From a non-medical book, I always recommend or gift a book called The Boys in the Boat, which is the story of the University of Washington Olympic
Speaker: team of all novices in the 1930s.
Speaker: And it emphasizes the importance of teamwork, of hard work, of not giving up.
Speaker: And I think a lot of these things are good lessons for people in medicine as well, because those are the same principles that you don't give up, you work together, you work hard, you take pride in your work and in each other.
Speaker: And so the boys in the boat is my
Speaker: my recommendation for reading.
Speaker: And we will link this to the show notes of the podcast, but it's a fascinating read.
Speaker: I remember reading it on a long trip and almost couldn't stop reading.
Speaker: And I think you're right.
Speaker: It exemplifies the real concept of teams, which is they are more than the sum of the individual parts, which is ultimately what we're looking for in our ICUs.
Speaker: That's exactly right.
Speaker: The second question relates to something you believe to be true in medicine or in life that most other people don't believe or don't behave like they believe it.
Speaker: Something, so sorry, can you say that again?
Speaker: It was a little bit confusing for me.
Speaker: Something you believe to be true in medicine or in life that most other people don't believe to be true or don't behave like they believe it's true.
Speaker: Well, that's a tough one.
Speaker: I am so passionate about medicine in general and academic medicine in particular that people have a hard time believing my enthusiasm for everything, whether it's clinical research or education or even administration.
Speaker: I mean, I love being a chairman of a department because I can have such a positive impact on everybody's life.
Speaker: But people sometimes don't think I'm for real because I'm always so excited and energized by this.
Speaker: I honestly think life is too short to not really love everything that you're doing.
Speaker: And you shouldn't be shy about expressing your passion and your enthusiasm because I think it can be really infectious.
Speaker: I mean, there's a lot of depressing things in the world right now.
Speaker: But gosh, to be a doctor and to be a critical care provider
Speaker: to be able to take care of sick people and touch people's lives and have saves, or even when you're helping people to die and helping families to come to terms with that, what a tremendous honor, right?
Speaker: I mean, to be able to be in that position to help people through situations like that, it's mind blowing.
Speaker: And so I think to be able to keep that humility for the great gift that we have to be in medicine and be able to touch people and to improve people's lives,
Speaker: I don't know, people need to always be reaching for excellence or never compromising for mediocrity.
Speaker: Always try to be exceptional, not for you, but for everybody else around you.
Speaker: And I think you touched on several very important aspects that unfortunately, a lot of times where people believe it or not,
Speaker: it's not reflected in their attitudes at the bedside in the hospital.
Speaker: The humility to understand that ultimately the goal is to create a difference in the life of somebody else and that we just have to keep learning.
Speaker: But also I believe that what you mentioned, which I find very important, is understanding that it's not about just doing what you love, but more about loving what we do, which I agree is a great privilege.
Speaker: I think you said it beautifully, much better than I did.
Speaker: The last question, Dave, is what would you want every intensivist listening to us today to take home or to know?
Speaker: Well, the main thing regarding brain death that I would emphasize is to be meticulous and be patient and err on the side of being conservative.
Speaker: Again, we don't want there to be any misdiagnosis of brain death.
Speaker: That has tremendous repercussions, such as the public losing faith in our process,
Speaker: And, you know, this very scary thing of maybe taking someone for organ donation who's not dead and violating the dead donor rule.
Speaker: So I would say brain death is a diagnosis that you should be very conservative, very meticulous.
Speaker: Don't be afraid to call for help for someone else to take a look.
Speaker: And when in doubt, don't declare, err on the side of not being brain dead.
Speaker: Those are the words of advice I would give.
Speaker: And I think it's a perfect place, a great place to stop.
Speaker: I want to thank you again, Dave, for your time, but also for sharing your expertise with us.
Speaker: I will link all the supplements and the article, obviously, that we mentioned to the show notes.
Speaker: And I hope to talk with you soon again about other interesting neurocritical care topics.
Speaker: Great.
Speaker: Thank you, Sergio.
Speaker: I appreciate you inviting me.
Speaker: Thank you for listening to Critical Matters, a Sound Critical Care podcast.
Speaker: Make sure to subscribe to Critical Matters on Apple or Google Podcasts and share with your network.
Speaker: Sound Critical Care is transforming the way critical care is provided in hospitals across the country.
Speaker: To learn more, visit www.soundphysicians.com.
