Thank you so much for this opportunity to share a few of the nuances and most of the controversies around brain death declaration. How many of you feel comfortable approaching a patient for evaluation of death monological criteria in whatever roles you play in the ICU? So majority of you. How many of you feel comfortable implementing the new guidelines that have just been released by American Academy of Neurology and SCCM Collaboration? A little less. So these are a few of my disclosures, nothing really relevant to this talk by itself and my standard disclosure of being a neurologist. So when we're talking about controversies of brain death, let's first talk about what is not controversial. So what is not controversial is it's the law of the land. You may disagree with it philosophically, religiously, ethically, for whatever cultural issues that you have with it, but at this point in time, based on the Uniform Determination of Death Act, which is decided at a state level since 1981, when it was introduced by President's Commission, every single state in the United States accepts brain death. They may describe it differently, but they accept it as a form of legal death. This is the New York Times front page news when this brain death was originally introduced at a federal level. The challenge obviously is every state gets to decide how to implement that legal definition of brain death as a part of definition of death, but this is the law of the land, that brain death is death. What's also pretty clear and non-controversial is that we have a very systematic guideline-based approach to clinically evaluate these patients who meet the criteria for death by neurological criteria. 1995 was the first time American Academy of Neurology released guidelines. 2010, these were revised. World Brain Death Project put together a global consensus addressing the realities of today's world and some nuances that were not addressed by previous guidelines, and put together a framework which currently has become the basis for recent American Academy of Neurology guidelines. Most major critical care societies in the Western world do have established criteria and approach towards physical exam eligibility criteria for what we call as brain death. These are the Canadian guidelines and the reference to the recent SCCM guidelines. One component of the physical evaluation of death by neurological criteria is apnea test, which is the last function in our body to go. So our medullary origin of respiratory drive is typically refractory to most insults, and evaluation of our ability to breathe spontaneously is a key component of clinical evaluation of brain death. And we have extensive decades of experience now, not just evaluating these patients for apnea test, the only place where this procedure is performed. We have questioned the safety and the validity of apnea tests in the last few decades, and now we also understand the nuances of using apnea test in patients with chronic CO2 retention, COPD, and even things like mechanical circulatory support. We have established ancillary tests. The focus has moved away from confirmatory tests to the use of the term ancillary test, where we have looked at various neurodiagnostic modalities over the years. Initially, there was a whole gamut of electrophysiological testing, including EEGs and SSEs, EPs, that were part of this, but the four most validated and the currently acceptable North American consensus behind imaging criteria have extensive evidence behind them. So currently, cerebral angiography, here you can see absence of intracranial blood flow with external carotid artery showing a lot of blood flow. The nuclear flow scan, which could be radionuclide angiography or scintigraphy. It's just how the procedures are done. Complete absence of blood flow in the cranium is consistent with cerebral circulatory arrest, which is a hallmark cerebrovascular pathophysiology of brain death, and then transcranial Doppler showing oscillating patterns where there's no net forward flow into the brain. These are valid criteria of addressing nuances where the clinical evaluation fails to give you a definite answer to whether patient has any confounders or patient has indeterminate results on the apnea testing. We also understand respecting the medical legal ethics involved with this nuance that just a prelim report, like we do in CT scans, is not good enough. Somebody who's a specialist needs to be able to look at these reports, and the final reports put by attending physicians need to be considered when ancillary testing is considered as a part of evaluation. Every society guideline that is responsible for the evaluation and conduct of these tests has evaluated brain death as a valid indication and laid forth criteria for how these tests should be done to standardize them, to increase their diagnostic accuracy, address their nuances, and even address their clinical application scenarios where straightforward application was not clear. The logistics of evaluation and declaration have been addressed as well. Hopefully all of you guys at this point have no qualm addressing the fact that when you have a patient presenting with what seems like a comatose state that is permanent, you really have a mechanism and severity of brain injury behind why that patient would be brain dead, and that is consistent with patient's absence of spontaneous breathing. There is coma, there is absence of brainstem reflexes. Even in the presence of spinal mediate reflexes, the whole pathophysiology is of an acute brain injury mechanism that is irreversible and permanent. Because of the whole ethics of why brain death as a concept was originated to begin with, you heard a very good perspective on different aspects of organ donation. It is also logical and common sense that people who have anything to do with surgical recovery of the organ for transplantation should be dissociated from this process itself. And little logistics like when's the exact time of death with a beating heart have been addressed in guidelines as well. That the time and the process of brain death declaration, whether it's clinical or using an ancillary test is done, that's the time of death. There are always these little qualms of, you know, when the heart stops beating, should I be declaring the patient again? But at least the time of death has been legally addressed. So these are the things that are not controversial. What is controversial about brain death? Well, in the last two decades, there has been significant improvement in our ability to offer our acute brain injury patients novel evaluation and therapeutic regimens. The whole gamut of neurocritical care has changed in the last two decades. And one thing that we've shifted our gears is, rather than calling brain death, which thanks to our audiovisual media, as well as social media, has kind of become a term that is often confused with a persistent coma or minimally conscious state. We are emphasizing the term death by neurological criteria. So the controversy whether brain death is really dead, mostly dead, or kinda dead, goes away. And these patients are treated dead by neurological criteria or dead by cardiopulmonary criteria. Some people also use the word neurorespiratory criteria, although that has not quite gathered significant acceptance yet. The other thing that has happened is that lots of acute brain injuries that we used to think are irreversible have now been proven. If you really resuscitate a patient long enough, you may not be able to offer them a quality of life, but you still can offer them survival through an acute brain injury, which two decades ago was considered irreversible. So in the new guidelines, that controversy has been addressed by changing the paradigm that instead of using the word irreversible, we're trying to determine if this injury is permanent. And the second part, if you go through the nuances of the guidelines, which I really applaud the investigators that led to this publication, they address that it's not just that the acute brain injury that is leading the patient to the situation is permanent, that in all logistics, in all common sense, in a reasonable environment, you will not offer medical therapies to escalate and try to salvage that situation. Because if you really give salt, mannitol to a patient with malignant cerebral edema, can you really squeeze some brain out where they can be pulled back from the threshold where they will meet the criteria? Theoretically, yes. So having that keen understanding that no medical surgical therapy is going to reverse the patient's permanence of injury is important part of that controversy as well. And we've also emphasized neuroimaging markers of that clinical evaluation. That is just not my bias that this patient's injury is permanent. The patient's neuroimaging shows a catastrophic supratentorial injury before I even approach this patient clinically for brain death evaluation. The other controversy is when we used to be taught brain death, we typically would think of these catastrophic injuries with our supratentorial, whether this is a malignant cerebral edema caused by intracranial hemorrhage with malignant herniation, or this is anoxic brain injury leading to global cerebral edema, and then the patient progresses. But then with increasing critical care of these patients, we found this very strange subset of patients that would be brain death mimics. Their brain stem function has gone. Clinically, they meet all the criteria, but all they have is a brain stem pathology or a posterior fossa pathology. And that became controversial because some countries, especially UK, at this point accept brain stem death as a form of death. In North America at this point, you need to have total brain death, and that controversy whether whole brain death versus brain stem death needs to be considered is not something that I'll be able to answer in this particular scenario, but at least to our clinical comfort, North American guidelines, both Canadian and US, at this point, especially emphasize whole brain death. That means there needs to be supratentorial catastrophic injury that typically will occur in these patients if they were not resuscitated. So if this patient develops obstructive hydrocephalus, you may or may not offer EVD based on the pathology, but despite EVD, or by the time the patient comes to you, the malignant cerebral edema resulting from that has caused permanent global supratentorial injury. Those are the patients that you will evaluate. But in the absence of supratentorial injury, in the absence of supratentorial hydrocephalus, a brain stem injury, a cerebellar injury will not qualify for evaluation for brain death. Neurological examination obviously has been emphasized over several decades now, but we have learned that body's ability to create spinal reflexes is real, and we have identified all these movements that sometimes even in the hands of a very experienced neurologist, neurosurgeon, or critical care provider can be extremely hard to distinguish whether these are cortically mediated or spinal mediated. In which case, now we emphasize, rather than addressing the controversy clinically, do the confirmatory test, or the ancillary test, which is the accepted term right now, to look for cerebral circuity arrest in these patients. The other confounder is, we give these patients a lot of sedation as a part of the primary injury that brought them to the ICU. Especially if they had an ICP-creating crisis that brought them to the ICU, they may have been put through deep sedation for tier three ICP crisis therapies. So what do you do in these patients? We used to say get drug levels, or just wait five half-lives. But with increasing critical care and understanding of pharmacodynamics and pharmacokinetics, we now know that serum drug levels by themselves don't really tell you that the effect of the drug has gone away. We've learned that there's a train of four, when you reverse a patient, regaining patient's train of four is not good enough to tell you that the patient is not paralyzed. It still takes some time for the patient's motor function to recover. And thanks to our pharmacology colleagues, we've realized that this discordance in pharmacodynamics and pharmacokinetics, which could be because of delayed GI clearance of these drugs, hypothermia, and therapeutic circulation, or the kinetics of the drug elimination kinetics are saturated. The other common example where this came to light was Baclofen. It is very common knowledge for people who manage Baclofen overdose that the classical half-life is two to four hours, but sometimes these patients can take up to seven to 10 days to regain their brain function, and they do recover. These confounders have been addressed by multiple societies. Initially, the ACMT, the toxicology organization, addressed and agreed that just following this oversimplistic method of saying five half-lives or getting drug levels is not enough. You do need a patient-centric approach, incorporating multi-professional input, which should involve toxicologists as well, in addressing a patient-based duration. So when your neurologist says, I understand you gave the patient this much fentanyl, but I'm gonna wait three days rather than the prescribed two days, that's the reason behind it. It's not that they're just trying to be a pain in your wrong end. And you do have, which sometimes we are, and you do have these confounders that really don't get addressed. In the past, we were able to do ancillary tests in these patients, but the challenge with that is you're trying to bypass a physiology that you don't quite understand really well. And this is a process, because of the ethical conflicts behind it, should not be taken lightly. It needs to be a black and white situation. It should not be on a spectrum. We need to acknowledge that we have absolutely no studies that tell us the validity of using ancillary testing in patients who have received drug overdoses or very high doses of sedative agents. So the new guidelines address this controversy. We do not use ancillary testing now to bypass the process of clinical evaluation hypothermia. You have to let the patient warm up before you declare them. You cannot bypass waiting for the drug clearance, and it's not just a simplistic formula of five half-lives or getting serum drug levels. You need to make a clinical judgment of how much you will wait to ensure adequate drug clearance in these patients. The controversy of hypothermia, because of rapid institution of some form of temperature modulation in most of our cardiac arrest patients and some acute brain injury patients was addressed as well. We all know, anybody who's dealt with frozen injuries, that you're not dead until you're warm and dead. So we've addressed that, and we all know this phenomena of, some people reflect as brainstem stunning, that your clinical exam could show absence of brain and brainstem reflexes for hours, sometimes days, after you've been exposed to cold. So that duration has been incorporated to address this controversy. Now, the other confounders are absence of neuromuscular activity, because of severe GBS, absence of neuromuscular disorders, or you gave the patient some kind of therapy, osmotic therapy, steroids for abscess. Would that work over time? So if you were to give that therapy some time to work, would the patient be pulled back from the threshold that made the patient meet the criteria for brain death? This has been addressed in the guidelines by basically addressing that, if you did institute medical and surgical interventions that manage the patient's ICP or whatever caused their acute brain injury, give them time. Time is your best friend in this particular case. There is no reason to hurry this evaluation. The other neuroimaging controversy that we have to deal with as a neuroimaging community is which ancillary tests are valid, which are not. Now, our experts concluded that the only ancillary test that we are valid is digital subtraction in geography, transcranial Doppler, and nuclear scans, but the British Society of Anesthesiologists regards CT-ANGIO as a valid test. The challenge with that is the protocol for performing CT-ANGIO is very commonly used now because of our acute stroke algorithms and everybody being a stroke center. So this request keeps on coming, why can't we just use a CT-ANGIO when British people are using it? The challenge with that is that any patient that received contrast in the past, any thrombus that forms because of stasis when the patient was undergoing ICP crises creates this hyper-dense signals here that it takes a very special level of expertise and sometimes advanced software to distinguish absence and the false positives are real. And those have been addressed in the North American guidelines as well. And then some of you may be taking care of patients with mechanical circulatory support and there have been significant advances in MCS. Now we are doing VA ECMO, we are doing Impella, we are doing combination balloon pumps with these ECMO and we found significant return in a patient's ability to be hemodynamically stable enough and evaluation of these patients for brain death because half of these patients, if you look at the ELSO registry, pass away. And a majority of them pass away because of malignant cerebral edema that led them to cardiogenic shock or cardiac arrest that put them on ECMO to begin with. So each of these nuances, which tests are valid, apnea test, ancillary test, has to be validated on a large scale although we have some guidance on this but there needs to be further studies in how we manage these patients. And then demonstration of competence. With such a complicated medical ethical scenario, you have to keep up with literature from head to toe. Can you really understand the nuances enough that you can understand the controversies in a complicated patient? So there are frameworks that have been suggested. Neurocritical Care Society has a brain death toolkit and a brain death certification module that is now undergoing revision based on the new guidelines. Lots of people have looked at different simulation formats on how to improve this competency. So the new guidelines address this by addressing for the first time in a guideline format that you need to have a framework for competence demonstration. It needs to be in a supervised environment and the supplementary education can involve online and in-person training but just doing a health online module over a 10 minute when you were doing your email routine of checking emails is not enough to be brain death savvy. Both requirements for physicians and APPs have been addressed to address the interprofessional care that we provide to our patients. And then lastly, the big controversy that we probably will not be able to solve in a 15 minute session like this, the issue of consent, the issue of objections and the issue of exceptions. In patient-centric care, we have to give them autonomy as a part of this clinical decision making and when this autonomy comes to bioethical applications of the concept of brain death, if we allow patients to decline procedures, they should be allowed to demand procedures. So can the patients decline evaluation for brain death? Right now we don't have that framework because we say if I found you cardiopulmonary dead, I don't ask your permission to see if I can check for ursus delay or check for lack of perfusion. The same way I don't need your consent to check you for death pathological criteria but are we really incorporating patient autonomy in that or I declare the patient dead but the patient's family demands ongoing treatment and does not accept that. That is part of the bioethical application of autonomy and has not been addressed. There are lots of patient communication clinical decision aids created by multiple organizations. The brain death kit itself by Neurocritical Care Society addresses that. Lots of organ procurement organizations have pamphlets for patients but that will require a lot of effort on our side as a scientific community, not just to educate our community about it but also to regain the trust that we have lost because of misgivings in the past. And then what do you do in the steps after declaration of death? What if the patient family says no, I'm not gonna accept this? What's the framework around that? So the guidelines for the first time actually address, they don't give you the solution but they at least empower your institution or you to go to your leaders and say, we need to have a process in place, our policy needs to address, what do we do when the patients decline this process? We at Wake Forest were lucky enough to have as a part of our death pathological criteria policy what we call as the DNC support team. We called it support team because the purpose of this team was to support both the providers as well as the families through a difficult process when these ethical conflicts arise or the mistrust arises. It's a very multidisciplinary team comprising of physicians, risk management, legal, pastoral care, chaplaincy, patient experience officers and patient advocates and this is part of our policy where anybody can call this what we call as the DNC consult team or the DNC support team and our hope is that in future more and more people as a result of these guidelines create such teams both for provider-centric care policy implementation as well as patient-centric care. And lastly, the AHRQ has a significant emphasis on diagnostic safety management teams. If you manage patients with anticoagulation and you're a pharmacist, you understand the concept how incorporation of interprofessional care and having these diagnostic safety measures has improved our ability to anticoagulate patients. The same way, do we need diagnostic management teams for brain death evaluation? We have piloted this at Wake Forest as well and I wonder if these guidelines will lead to more quality safety and patient safety metric implementation of what we call as incorporation of response teams to address these ethical conflicts. So I hope I gave you a little perspective of how the new guidelines address majority of the controversies but this is a very complicated challenging scenario with significant social, medical, legal and ethical constructs to it that we really can't solve in a 15-minute discussion but at the end of the day, the one message I want you to take is that a standardized guideline-based approach towards evaluation and management of patients undergoing evaluation of death pathological criteria is key to maintaining provider family trust. Thank you.

brain death

Uniform Determination of Death Act

clinical evaluation

ethical concerns

guidelines

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