going to be talking about death by neurological criteria. My disclosures are listed below, but there shouldn't be any conflicts with the material here. Many of you may be unfamiliar with the term death by neurological criteria because this area has been more commonly called brain death. I have tried to sponsor, and I think many of us have tried to push the term death by neurological criteria as an alternative because the term brain death has been used for a long time and is part of the collective zeitgeist of America and the world actually, but critics have noticed that it gives both a false sense of hope to doctors and families because the word brain modifies death and second is inaccurate because you cannot technically be brain dead or other kind of modified death. You are either dead or you are not dead. So the term death by neurologic criteria suggests that the person is dead, which is not modified, and that we know they're dead because of their neurologic criteria are met. And then there are a couple of donation terms that get confused in this literature frequently that have nothing to do with brain death or death by neurological criteria. Donation by determination of death by neurologic criteria and donation after determination of circulatory death, which really are donation terms and won't be really dealt with here. So the history of death by neurological criteria is quite interesting. In reality, the term didn't exist and the entity didn't exist before the advent of mechanical ventilation because before mechanical ventilation became prominent, patients who had a brain stem injury that prevented them from breathing would simply stop breathing and die, or simply stop breathing and then their bodies would stop. So therefore they would be easily diagnosed as dead because of lack of cardiorespiratory function. With the onset of mechanical ventilation, Molire and Goulon in France in 1959 described a term coma de passé, which pretty much went unnoticed in the English speaking world, but described patients who were on mechanical ventilation and who had no other signs of life, but could not be called dead in their current definition because their heart was still beating and their lungs were still moving. This became an important problem in the United States with the advent of organ transplantation, and I know that there's been a big push around the country and around the world to dissociate organ transplantation and death by neurologic criteria, but the truth of the matter is that the history suggests otherwise. That in reality, the Molire and Goulon paper became noticed in the United States when transplantation became was considered in the mid-1960s. In Harvard, they developed a landmark committee to look for a definition of death in patients who were on mechanical ventilation. The interesting thing about this is that there was a meeting of organ transplantation that was proposed to have occurred in Kansas City, where there was a lot of discussion about where we could get orthotopic organs for people for transplantation. People suggested things such as mentally retarded individuals or people who were in prison and that sort of thing. At that point, the head of this Harvard group, who was Murray, was Joseph Murray, actually basically said, we have to find some sort of a definition so that we could actually then say that a patient is actually dead on a ventilator and we can use their organs. Interestingly, the group met once on March 14th in 1968, and the rest of the drafts were all done over correspondences, and all the elements of the exam didn't show up until June 7th, and they were all published in JAMA without ever having any tests done to show that these things were actually a way of defining whether somebody's dead or not. This is an excerpt from this letter that was written by Joseph Murray that said, as you're well aware, many of the ethical problems associated with transplantation hinge on appropriate definition. With a pioneering interest in organ transplantation, I believe that we should be the leaders in this. So after the Harvard committee, there was a relatively rapid acceptance of this concept of what they called brain death to the point where there was a Uniform Determination of Death Act in 1980 that was done by a council that is appointed by the Congress to deal with issues like this. So it's the National Conference of Commissioners, and what they are is it's the federal government's attempt to try to persuade states to make uniform laws, and they suggested that there should be a medical standard or there should be an acceptable standard for determining when a patient's dead, even though their mechanical ventilation, their heart's still beating, and their lungs are still working. Interestingly, they didn't weigh in on what the appropriate determination should be. They just suggested that accepted medical standards should be used, and the United States very quickly, all 50 states accepted the death by neurological criteria. New York and New Jersey have made some exceptions and have made some specific guidelines, but pretty much all the 50 states have accepted this and had accepted it very early in the 1980s, and as of 2002, 189 countries and nine nations had accepted this. I'm sorry, 80 of them had published guidelines and the acceptance was almost 100 percent. Unfortunately, because they decided not to weigh in on what the appropriate evaluation of a patient was to determine them dead, we have a great deal of variability in testing, and it's not uncommon to have very different rules from state to state or even hospital to hospital. A good example of this that I have from my own life is that when I was in my first job in Philadelphia, Thomas Jefferson University, there were two hospitals that had neurological intensive care units. One was in the Will's Eye Hospital, which had one brain death criteria, and one was in the main University Hospital, which is a different one, and we had one patient in whom his temperature met criteria in one hospital but not in the other, so he was functionally declared dead in one place and then not declared dead in the next hospital he went to, and which ends up being a real problem. It also means that without clear guidance about what is an appropriate evaluation, it's left up to doctors who sometimes don't have very good training in this area, and we have cases such as this one in Oklahoma in 2008, where a 21-year-old man was told, the family was told he was brain dead by a physician who never did an exam, and that ultimately his family members started jabbing and poking him and realized that he was moving, and then he made a good recovery, and it turns out, if you actually look at the records of this case, the organ donation organization came to the hospital and said he wasn't a suitable candidate for organ donation, which is code for he wasn't dead, and then there's a case of Jahi McMath, which is a young girl who actually had a tonsillectomy and had bleeding, and then ultimately was declared brain dead and had a big court case issue, and she got moved to a different hospital, and it was problematic, so lack of standards really have issues towards the credibility of them. So my group took a stab at this in the past, doing something interesting by asking a questionnaire of physicians who take care of patients who are oftentimes declared dead by neurologic criteria. We had 30 or 50 respondents who reported they were attending physicians who specifically explained the findings of DNC and the means of diagnosis to families, and there were a number of inconsistencies, but many of them included physicians who said that they just followed whatever the OPO or the organ procurement organization suggested, and many of them who didn't know what their brain death criteria were or what elements had to be included. In some very interesting studies done by David Greer, it was very clear that there's a wide variation in the types of medical practitioners who declare death by neurologic criteria, and there's a very wide variation in the policies for death by neurologic criteria across hospitals in what they require and what they don't require. This isn't to say that all the physicians don't follow the current standard practice, it's just that the hospitals didn't delineate them in their protocols. More recently, there's been a big push by a lot of physicians to try to make DNC a diagnosis again. For a long time, it was really considered to be relatively mechanical, that if a patient met these criteria, you did these tests, and if the tests came up positive, then the patient was actually declared dead. But over the last 10 years or so, there's been a push to reclaim the fact that it's a diagnosis and that it's made by a physician or an MP or PA in some states, but that ultimately you have to have a reason for why a person's dead and that everything has to be consistent even if the testing looks like they are dead. So let's go to the first audience response question, which I realize you can't do in this format, but we're going to read the question anyway and we're going to go through the answers. So which of the following elements are not part of the evaluation for death for neurological criteria? One, absence of cranial nerve function. Two, evidence of willingness to be considered for organ donation. Three, evidence of irrevocable injury to the whole brain sufficient to cause death. Four, the absence of ventilatory drive with CO2 challenge. And five, absence of confounding factors. And the correct answer or the incorrect answer in this case is the willingness to consider organ donation. Although many physicians are reticent to declare somebody brain dead if they are not organ donors, there is no stipulation that you need to be an organ donor or even considering organ donation to make the diagnosis of death by neurologic criteria. In fact, making the diagnosis of death is really a physician's job and probably should just be included as part of that. So in our new way of thinking about this, we have four common elements that we say to make the diagnosis of death by neurological criteria. One, one must understand the cause of the irrevocable injury. If no cause is found, then really you need a longer period of observation and examination to tell. The truth of the matter is in America nowadays, with the ease of getting MRIs and CAT scans and even higher order imaging, it's very uncommon to have a patient who meets the criteria for DNC without a known cause. Children, interestingly, need longer periods of observation because sometimes their exams can be quite muted even when they have diseases that are not irreversible. And in this case, having a mechanism is really a good safeguard into figuring out whether this is really a child who's dead or whether they're going to make some recovery. The second element is the absence of confounding factors. And as with the first element where you have to have a definition of death, the definition of death doesn't necessarily, or a good cause for death, the cause for death doesn't necessarily have to be that the patient will recover to full normalcy. That in reality, death is a line that you cross. And if you are severely disabled, you're still alive. The same thing goes with confounding factors. That sedative medicines, drug intoxications, hypotension, hypothermia, and all but neuromuscular blockade seldomly make a patient look like they're dead when they're not in the absence of severe injury. But in the presence of severe brain injury, a person who already looks like they are close to death can get an exam that looks like they are dead if they have confounding sedatives, drug intoxications, or these other problems. Now things like hypotension, hypothermia, and neuromuscular blockade are easy to diagnose and to fix. Sedative medicines and drug intoxications can be quite difficult. In fact, the other thing on this list is actually electrolyte abnormalities. And this is where the diagnosis issue becomes important. Because if a patient's on a sedative medicine, such as a benzodiazepine, six hours later they should have cleared enough of that medicine if they have normal renal function. The same thing goes with medicines like penobarbital or phenobarbital. That those things are cleared in a very clear time point if the patient's liver function is normal. If there's polypharmacy, that can confuse things as well. All these things have to be considered when considering these things. And there's no good algorithm for it. The physician or the person who's making the diagnosis simply has to weigh all these factors and say, are the sedative medicines, drug intoxications, electrolyte abnormalities sufficient to make a person who looks like they're close to being dead look dead? And with electrolyte abnormalities, that ends up being a time component as well. If your sodium falls from 150 to 128 within four hours, you're going to be very encephalopathic. If your sodium falls from a normal level to 122 over nine weeks, that may not affect your sensorium quite as much. So again, this is where the diagnosis comes into play. Physical exam is what most of us consider when we talk about doing brain death testing. And I always tell our trainees this is the most important examination any doctor makes. It needs to be done carefully and conscientiously. We are left with only the neurological exam elements that can be completed without the patient's cooperation. It turns out that the brain death exam is just the neurological exam in a patient who can't really cooperate with gripping hands or moving arms or anything else. It's important to know that you have to be able to complete the physical exam before doing specialized neurological testing. That one of the mistakes that some people make is to go forward and do specialized testing before doing the neurological exam and find out that the patient has pupils that work or some other cranial nerve finding that proves that they're alive no matter what the other tests say. The other thing that I didn't think I'd ever have to say, but I do, is the exam can't be done in a patient who's not in a coma. If a person's awake, they are clearly not dead. And finally, confounding factors. There are some things that really inhibit the ability to do a complete examination, such as trauma to the face or difficulty doing an apnea test. Patients who have panic membranes or surgical pupils can be problematic for doing certain parts of the test as well. So what do we test? What we test basically is what we can test. The cranial nerves in general can be tested pretty easily. Cranial nerve 2 and 3 can be tested by using the pupillary exam. Cranial 2 being the visual system, so you can see the inbound signal, and 3 is a pupillary response. Cranial nerve 3 and 6 by the corneals. Cranial nerve 5 and 7 with facial pain. Cranial nerve 8 and 11, which is a spinal accessory nerve, can be tested with cranial nerve 3 and 6 with the doll's eyes maneuver or the oculosyphallic maneuver. Cranial nerve 8, 3, and 6 can be done can be tested with cold calorics and then cranial nerve 10 and 12 can be tested with a gag. Cough is not really a cranial nerve but can be tested by doing deep suctioning. Peripheral motor responses to pain can be tested by giving painful stimuli and seeing if there's other than reflex activity and then the reflex to breathe is typically called the apnea test. The apnea test is a physiological test that's basically done on the premise that as the co2 rises in our blood and our brain becomes more acidic that that is an impetus of the brain to signal the lungs to breathe and therefore the test is basically devised to increase the co2 levels in your blood and look to see if there's a stimulus to breathe. One of the most important misunderstandings about this test is that it's not the level of co2 that matters, it is whether the patient initiates a breath. So we typically use a 20 millimeter per mercury increase or a level above 60 millimeters of mercury in a patient without COPD as a strong enough stimulus to ask to make a person want to breathe and if there is no initiation of a breath the thought is the stimulus cannot be given because the brain doesn't work. Interestingly there's never been a scientific consensus on how low you need to go or how reliable the stimulus is until recently there was a paper in 2015 that showed that the types of the part of the brain and how much of a signal you needed in order to initiate a breath response. So if one goes about testing and has a good reason to suspect that the patient could be dead, does a cranial nerve examination, does an apnea test and looks for confounding issues but can't come to a consensus either because the confounding issues are an issue and they can't be corrected or if the exam can't be completed then ancillary tests can be helpful to add more data points. There's consensus agreement that EEG, transcranial Doppler's, angiography or digital subtraction cerebral angiography which is a typical angiogram or digital scintigraphy have all have good enough sensitivity and specificity to be able to be used as ancillary tests for the determination of brain death. There are other tests CT angiograms, MR angiograms, brain evoked potentials that have all been studied but don't have quite the sensitivity or specificity to be useful currently. So we recommend these four tests and every hospital has different limitations about which of these tests it can do. The technically most difficult test to do is the EEG. It's a special type of EEG that has to be done with with electrodes that are spaced out very far leading them to have to be very susceptible to noise including 60 Hertz signals from inside the the ICU room which is pretty common. But all four of these are acceptable. So let's move on to the second audience response question and this has to do with talking to families. So which phrase would be confusing for family members during the discussion about the patient's diagnosis as dead by neurologic criteria? One, there's no evidence of brain function due the brain injury your loved one incurred. Because of this evaluation we determined that he has passed away. Two, I'm sorry to inform you that your loved one has passed away. We were able to determine this based on testing of his brain function. Three, we have determined that your loved one is brain dead. We would like your permission to withdraw life support. Four, our testing has shown that your loved one has passed away. I can explain the test we did to determine that he passed if you wish. The correct answer to this question or the incorrect and confusing mention to the family is the third one. That if you mention the patient is brain dead, asking permission to withdraw life support from a patient who's passed away doesn't make any sense and gives family hope that if they're withdrawing life support they must be alive. And if they're alive then why would they say that they were dead? So I personally favor the second response that I'm sorry to inform you that your loved one has passed away. This actually makes the most sense because it's really what happens. How you determine that the patient is dead is less important to the families. If you can talk to the families before, then you can explain the brain testing that you're doing and then this statement makes much more, excuse me, much more sense. So as you can see from the question before, talking to families ends up being paramount because if you make a diagnosis of death, the hardest part that you're going to achieve is to convince families that the patient's passed away. Because having a patient on a ventilator with their lungs moving and their heart beating is inherently going to give families hope that the patient is not yet passed. So there are a couple of important axioms that we talk about and there are four of them that I'll mention. Number one is that the health care team is not comfortable the diagnosis of DNC. The family will sense it. So one of the things that I typically do is to huddle everyone together, including the nurses, housekeepers, trainees, everywhere to make sure that everyone has their questions answers and feel comfortable with the diagnosis. And if there are people who don't feel comfortable with the diagnosis, to find out why and maybe even make an agreement that they won't talk to the family. Make sure that everyone knows how to talk about DNC. You can't withdraw life-supporting measures from a dead person and not to mention that and not to say things like, I don't think they're going to recover. The second one is to explain DNC over a few hours or days before making the diagnosis, which makes it easier for families to understand. Sometimes this clearly isn't possible, but when it is possible, it's really helpful to have them understand what you're doing and what you're thinking so that when the diagnosis comes about, they've already had time to mentally process it. So talking to families. The third point, start the conversation with I'm sorry to inform you that your loved ones passed away instead of a long description of the testing to determine death. Families don't want to wait 20 more 20 minutes to hear if they if they should be grieving. And this is one of the issues that I find many physicians, particularly trainees, make is that they want to spend their time explaining how they came to the diagnosis they did without saying that there's that there's a problem. If you put yourself in or the patient's dead, if you put yourself in the family's shoes, somebody comes in and says we did a lot of testing including this test of the cranial nerves and yada yada, and they start thinking themselves if they're explaining all this to me, the patient must still be alive because they wouldn't go all to this trouble if he was just dead. And I think this it's really important to start with your patient, your family members passed away. Now let me explain the rest of it as opposed to going the other way around. And the second one is do not attempt to consent the family for organ donation during the discussion of death. I oftentimes like to huddle with the OPO, the organ procurement organization, prior to meeting with a family if possible, and to have a strategy about how you're going to approach organ donation after the discussion of DNC, but they should be separate discussions. The other thing that I find very important is that in America it has become very common that physicians hear this statement that they should not consent families for organ donation, and they turn this into they should not discuss organ donation at any cost. And it turns out that just like there's nothing wrong with a physician discussing burial arrangements or donations to charities after death, there's nothing that says that a health practitioner can't talk about organ donation as one possible outcome after a person's passed away. That's different than consenting them for organ donation. There are a lot of studies that show that when medical practitioners who are taking care of patients try to consent families without proper training, that the organ donation rates are quite low and families are oftentimes confused. So I always tell people this, we don't consent families, but I don't shy away from the subject either. If somebody wants to talk about organ donation and what I feel about it, I'm happy to do that. It's part of life, it's part of dying. If they ask me whether they should do it or not, I always say it's a very personal decision that requires a lot of information and that we have specialists that will come and talk to you if we get to that point. And then when the diagnosis of death is discussed with a family, I always say now that the person is dead there are some considerations and I'd like to have somebody from the Organ Procurement Organization come and talk to you about one of those considerations, organ donation, and see if that's something that fits with your loved one's wishes. And that's how I approach them. As you've all probably sensed in your day-to-day functioning as intensive care practitioners, there are a lot of unanswered questions in a lot of areas that we could do better in. And one of them is who and how do we educate? So most hospitals in the United States, the diagnosis of DSC is reserved for physicians with particular neurological training. But most neurology and neurosurgery training programs don't have a lot of education that's easily identifiable in determination of brain death. Typically the residents get that that training only when they experience a patient. There's oftentimes confusion among practicing neurologists about the mechanism, the declaration of DNC, because they don't have a lot of education. And then the other issue is that intensive care doctors see much more death than neurologists do on average, and may actually be better qualified to do this exam than a neurologist, even though they have less neurological training. And then who should be allowed to examine patients? That's what we talked about now, is that the intensive care doctors may be more experienced in death and maybe actually be better at doing the testing, understanding the testing, and explaining it to families. So now we'll go to the third audios response question. Two DNC tests by different physicians separated by at least six hours are necessary to pronounce a patient dead throughout the United States. True or false? The answer is that is false. Not every hospital requires this and not every state requires this. One exam or two has become a very big debate point among people who do this for a living or understand this for a living. There are two rationales for two exams. One rationale is that one examiner might miss a finding that the second examiner catches a confirmation test. The other rationale for two exams is that during the time between exams, a patient who looked dead improved to not being dead. The tincture of time argument. For one exam, there's little evidence that more than one exam done conscientiously by a well-educated examiner is necessary for confirmation. And if the mechanism of injury and confounding variables are taken into account, one time point should be sufficient. For two exams, the argument is there's no take backs. If you get the exam wrong, you don't understand the mechanism well, you may make a mistake that's not reversible. That would be the same argument you could use for five exams or six exams or a time period of six months. Unfortunately, it's a very difficult argument in today's medical world. So I favor the one exam done by a well-trained person as opposed to two exams. Now the pediatric literature is quite different where they really suggest two exams because of the variability of presentation of children, but that's a different issue. A third area of the controversy is somewhat more subtle. So in the UK, as well as in other countries, patients who have brain stem injury, such as a large brain stem stroke or hemorrhage, can be declared dead based on the absence of brain stem function. The argument being that the brain stem is the battery of the brain and that if that doesn't work, the rest of the brain is simply not useful, and therefore the patient can be declared dead. In the United States, there is a stipulation that says that you must have whole brain death, and whole brain death would mean a mechanism that includes the hemispheres, and that can be problematic in the sense that in someone with a severe brain stem injury, it's difficult to declare them dead, but that if you stop supportive care and the brain stem injury with swelling cuts off the CSF fluid, the patients eventually develop massive hydrocephalus, and then their whole brain does stop functioning. This has not been settled anywhere, but there are differences in country to country about what is the appropriate amount of injury, the minimal appropriate amount of injury, to declare somebody dead. The last controversy I'll talk about is what constitutes a strong enough confounding variable, and I talked about this a little bit before, is that if somebody is on multiple medications that might have effects on their half-lives, is that difficult, or how do we deal with that? If somebody has a sodium of 128 that developed over six hours, not six weeks, how does that go into the calculation? And the hardest decisions have to do with multiple confounders, and one of the biggest problems is if a patient overdoses on drugs, you may not know what exactly that patient took, and we do know that certain drugs like opiates may decrease the gastric motility and decrease the transmission of drugs, other drugs, in the system, and they may stay in the stomach and be distributed less quickly. Again, there's no clear answer to what the right way to approach this is. The physicians or the practitioners who are declaring brain death just have to make the diagnosis based on their best understanding of the information. I'm going to leave you now with a few tools that are available. One is there's a tool from the American Academy of Neurology that has an appendix which includes a checklist for how to do the examination, including the prerequisites and ancillary testing. It's a very good tool that you can find simply by going to the AAN website, the American Academy of Neurology website, and looking under brain death, and it's in a toolkit, and you can find this checklist, which I find very helpful to bring to the bedside, both as a teaching tool as well as to make sure you don't forget anything. There was a recent consensus paper that was done in 2020, the World Brain Death Project, which is part of the World Health Organization, and that goes over many of the international aspects of some of these controversies we talked about. It's actually a very good read if you're interested in the subject, and it may actually inform how you put together your policies in your hospital. There are tools from some unlikely sources. The Alliance for Organ Donation and Transplantation, which is a group that's dedicated towards appropriate organ donation, actually has a brain death declaration webinar. They've got a course called OTC, which has to do with brain death declaration, and they have a toolbox. Finally, a number of hospitals have in-person simulations and workshops in order to go through typical case scenarios that might be helpful in determining death by neurologic criteria. If you do this frequently, one of these workshops or in-person simulations may be very worthwhile. Well, I appreciate your time. I know I've gone longer than I would have gone had we met in person, but I felt that given this format, it was better to go a little bit slower and explain things a little more clearly. If you have any questions, please email me.

brain death

neurological criteria

organ transplantation

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education

ancillary tests