Brain Death Guidelines

Dhimant Dani, MD discusses updated brain death guidelines, highlighting advances in accuracy, consistency, and communication in brain death determination.

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Introduction: Neuro Pathways, a Cleveland Clinic podcast exploring the latest research discoveries and clinical advances in the fields of neurology, neurosurgery, neurorehab, and psychiatry.

Glen Stevens, DO, PhD: Brain death is a diagnosis that requires absolute certainty, yet evolving guidelines and limited clinical exposure mean many providers remain uncomfortable with its determination.

In this episode of Neuro Pathways, we break down updated brain death guidelines and how best to navigate one of the most difficult moments in clinical care.

I'm your host, Glen Stevens, neurologist, neuro-oncologist in Cleveland Clinic's Neurological Institute, and joining me for today's conversation is Dr. Dhimant Dani. Dr. Dani is a neurologist within the Cerebrovascular Center at Cleveland Clinic's Neurological Institute. Dhimant, welcome to Neuro Pathways.

Dhimant Dani, MD: Thank you.

Glen Stevens, DO, PhD: So, let's first start by having you tell our audience a little bit about yourself, where you did your training, where you came from, why you came to Cleveland, what you do here at the clinic.

Dhimant Dani, MD: Absolutely. My name is Dhimant. I am a neurointensivist. I did my training in internal medicine and neurology in New York and Texas and, after that, decided to move to Wisconsin, Medical College of Wisconsin, for training in neurocritical care and critical care medicine. I have been at Cleveland Clinic since 2010 at Cerebrovascular Center, serving in a role of neurointensivist. Recently, I also serve in the role as a director of Neuroscience ICU at Akron General Hospital, one of the hospital affiliated with Cleveland Clinic, and also serving the role of co-chair for eye, tissue, organ donation committee for Northeast Ohio. Where my role focus on policies and procedure and supporting hospitals on mainly brain death, brain death-related process, as well as organ donation process to making sure that supporting caregivers through the process and challenging situations.

Glen Stevens, DO, PhD: So, just as an aside before we get into it, I find neurointensivists an interesting group because they're a little bit variable. Not everybody's neuro-trained in their training, right? You said you did medicine and neurology, but some people will do just medicine and then do a fellowship in neuro. Is that correct?

Dhimant Dani, MD: Neurocritical care fellowship training can be supported with a prior training in emergency medicine, anesthesia, as well as general surgery, neurosurgery, or emergency medicine. What it requires is a prior training, basic training, residency in those branches. And then any one of those physicians trained in those branches can pursue further career in neurocritical care. So, you're absolutely right. It doesn't have to be a neurology training, but of course, being a neurologist, it does help because we focused on a neurological care for those patients with brain injury.

Glen Stevens, DO, PhD: The other thing that I'm sure the wide audience of listeners have out there, and I've had this experience here over 35 years, is that intensive care units can be open, they can be closed, you can write orders in there, you can't write orders in there. They can be very different, and I think that individuals just need to understand within the parameters of the practice they're at what their role is in the neurologic intensive care, if you're a neurologist or if you're a neurosurgeon.

Dhimant Dani, MD: The way I put neurocritical care in the form of open or closed unit, the way I put it, is neurocritical care is a multidisciplinary approach to a patient suffering from brain injury. So when you think of this, there are high stakes in patient care which requires a multidisciplinary approach in the form of anesthesiologist is needed, neurointensivists who focus on a critical care when patients are admitted in ICU, but also equal roles are played by neurosurgeons as well as neurologists, specifically vascular neurologists and general neurologists who are focusing on a subset of disease process and specialized management where their expertise would definitely help. By the way, putting this in an open or closed unit, I would rather put this as a co-managing unit where it requires a all-hands-on-deck. A person... any physicians or a caregiver involved in a neurosurgery side or a neurology side or a anesthesia side, everyone brings a tremendous amount of value to patient care, and I think in a way that it does help patient care at all on every angle.

Glen Stevens, DO, PhD: Yeah. For what it's worth, I share the same feeling that you do. I think that multidisciplinary we are, somebody may think of things that you may not think of or could be important to the case. So, we're going to jump right in, of course, on a very difficult topic with brain death by neurologic criteria. But before we start that, can you define brain death?

Dhimant Dani, MD: It's a very interesting diagnosis because brain death is a death of a brain and brainstem as a whole function, which is a equivalent of death, which could be sometimes difficult for many people to understand because they sometimes see as a brain is not working, but then they also see that heart is beating. So it creates a sort of a complex situation where people are not able to understand what is exactly true means of brain death. A definition of brain death is a death of a brain and a brain function, which includes brain as brainstem, and it is a irreversible cessation of function. It is not a prognosis. It is a complete loss of brain function, and which defines brain death.

Glen Stevens, DO, PhD: And my understanding is there also needs to be a known cause.

Dhimant Dani, MD: Absolutely. In order to have a loss of brain function, there has to be a correlation with known cause, which also supported by a neuroimaging. When neuroimaging in those patients is being done, it should support and correlate with that loss of brains and brain function.

Glen Stevens, DO, PhD: So, there's new criteria that are out. What's different about the new criteria versus the previous criteria? Or, maybe you can just list the criteria.

Dhimant Dani, MD: Recently, in 2023, American Academy of Neurology, as well as supported by many other organizations, came up with a new guideline, which is a sort of a very, very changing in a way that there is more specificity. There is a lot of nuances on the relative normalization of brain physiological parameters, and everything has been taken away, and there is a... Specific guidance is being given. For example, temperature of patients should be always 36 degree and about for at least minimum 24 hours of period of time. There is also a focus on a specific blood pressure goal for a hemodynamic support to making sure that patient is not in a shock. As you know, that there are many metabolic and physiological parameters can affect the level of consciousness. So, a new guideline has given us a more guidance, strict prerequisite to support more focus on a evidence-based support on those parameters and help physician to develop a more robust criteria to focus on and stick to it.

Glen Stevens, DO, PhD: Yeah. I think one of the issues is that the lay public will confuse just coma with brain death itself, and coma is one of the parts of brain death, but it is not the only part of it. You go to the grocery store and the magazine's over there and somebody was in a coma for five years and woke up, and I think this is what the lay public hears, and that's what makes it difficult for the lay public.

Dhimant Dani, MD: Absolutely. There has been... a lot of controversies has been around specifically for a brain death, and specifically, largely, it has started to become relatively rare condition in a way that, if it's modern day science and neurosurgical technique, less and less patients are actually brain dead, and partly because of the advances in science and techniques. But at the same time, it is also important to know that it is different from a vegetative state or a comatose state because those state can have a biological recovery, while brain death is a permanent loss of brain function and brainstem function, which leads to a complete loss of brain function and which is equivalent to death.

At some point, people also feel a little bit more confused because when they see brain death and see that there is a loss of brain function, but they also see that there are patient have a warm skin and beating heart. Sometimes it can be challenging for patient's family to understand those challenges, to understand that patient, even though considered brain death or dead, they are still showing signs of vital organ functions, and which sometimes is perceived as a signs of life. That can be sometimes challenging, and it is hard for people to understand.

Glen Stevens, DO, PhD: Why don't we go through a few of the brainstem things that aren't working or some people even say brainstem areflexia. What types of things are you checking for brainstem-wise?

Dhimant Dani, MD: When we think of brain death exam, it starts with the very important aspect, it's the first thing, it's a prerequisite. Is patient meeting that prerequisite? When you think of this prerequisite, very important thing is that, first of all, the injury to the brain has to be permanent. There should not be any form of reversibility. Once you determine that, then you also have to understand that making sure that there are other prerequisite, like temperature, making sure that patient is not hypothermic, making sure that patient is not in state of shock. And also, there are certain metabolic derangement and medications that can look like patient comatose, but also can mimic as a brain death, but patient is not brain dead. So, making sure that patient is not under the influence of certain medications, like sedatives and hypnotics or paralytics, which can mimic like... At the same time, there are certain injuries, especially in the setting of trauma, like a spinal cord injury, can make patient look like not able to move any arms or legs, and that can may mimic like a brain death.

After making sure that major confounders are ruled out, we also have to make sure that brain imaging CAT scan should support the diagnosis of irreversible brain injury. Once patient meet that criteria, then we start with the functions of brain as a whole, as well as function of brainstem checking, the reflexes in the form of pupil, shining a bright light to the eye and looking at the reflex in the form of pupillary constriction, or gag reflex by stimulating the posterior pharyngeal wall as well as trachea, as well as motor response in the form of deep stimulus to the upper and lower extremity, as well as for the central part of the body, and see that any movements are there or not.

Once you meet those criteria where there is a lack of brainstem reflexes in the form of lack of pupillary response, lack of corneal response, lack of cough response, lack of oculocephalic and oculovestibular response, the way that brainstem function is tested, it's tested from midbrain points and medulla combination of whole brain stem, on top of it, a function of cerebral cortex in the form of movements and response and eye opening.

Once patient meet those criteria, then there will be a second part of the exam, which we'll call apnea testing, where patient will be taken off ventilator, given adequate amount of oxygen, and see if there is a carbon dioxide buildup causes brain to stimulate respiratory center and see if there is a further movement of chest or a breathing initiation in response to a carbon dioxide buildup. And if that is not there, there is no respiratory movement despite having a carbon dioxide buildup, it will consider as a positive apnea test. So, it's a complex exam which goes from testing of cerebral cortex as well as testing of brainstem function. It is also important to know that the exam confirms the finding of brain death. It does not cause the death, and this is very important when you share this with family. What you are plan to do when patient is concerned to be brain dead or meeting those criteria, it is important to explain this to the family too, that this testing is confirming that death of brain and brainstem as a whole rather than it is not causing a death.

Glen Stevens, DO, PhD: Any specific challenges to performing the exam?

Dhimant Dani, MD: I think one of the most important challenge that I see in this setting is timing. Timing of performing this exam is very important. On many occasions, when I see that, on a day one, patient may show signs of brain death, but sometimes there are medications that are lingering around, which can actually cause brain function to suppress markedly, which could lead to signs of brain death, but patient may not meet... even though they're meeting criteria, but they are not brain dead. So, it is very important to give a ample amount of time to making sure that any confounding factors mimicking brain death are cleared out of system. Either it's a form of medication or a metabolic derangement, like extremely low sodium or extremely high sodium, or medications, like pentobarbital or a midazolam or a paralytics, which can mimic patients like a brain death, but they are not brain dead.

Glen Stevens, DO, PhD: Yeah, that's a good point. And I think that when I used to round in the hospital on the consult service and we would see somebody who wasn't waking up from surgery or those types of things, I would always tell the residents, "In the first 24, 48 hours, you have to be really careful about terms that we use and prognosis and all these types of things." Because as you say, these people that had medications, they may clear out very slowly. Sodiums could be affected. Their electrolytes are out of whack. So, I think water under the bridge is important for these.

Dhimant Dani, MD: The best thing specifically with the new guidelines through American Academy of Neurology, as well as American Heart Association, there has been focus on giving ample timing before proceed with this kind of testing or prognostication because of same reason. It takes time for those medications to get clear out of the system, so as the metabolic derangement to get stabilized first.

Glen Stevens, DO, PhD: The new guidelines, do they add specificity? Are they more objective? I assume that answer would be yes to that, but any specific examples?

Dhimant Dani, MD: There is more specificity, as well as there is more objectiveness to the new guideline, which really helps a physician to take a lot of nuances, like normalization of metabolic derangement, or a broader term, like fixing metabolic issues or no major metabolic derangement has been taken off. Giving you an example that a specific temperature goal, which is important, 36 degrees centigrade and above, which was, in the past, it was not that as specific as what it is in 2023 guideline. Same thing with hemodynamic parameters, like a systolic blood pressure, but also adding a mean arterial pressure together that has also added further guidance and more stricter guidance for physicians to apply when they are performing brain death.

And also, there is a new support and guideline for when to perform ancillary testing, which is getting a much more as... more and more stress on that. Ancillary testing does not replace brain death examination, but it supports the brain death examination. As you know, that ancillary testing does not focus on a brain function, but they focus on a blood flow, which is a combination of when we think brain is dead, we think that that means that there should not be any blood flow to the brain. The ancillary test actually supports the diagnosis of lack of blood flow to the brain, which is something that is important. Ancillary testing, more focus on a strict guideline on a metabolic derangement. Specifically, there has been more guidance on what level of metabolic derangement can cause changes in mental status and so forth has been described better way in a newer guideline, and that is a very helpful and more accurate. It has given a precision and take the things like lack of metabolic derangement is not just a term that is being used, now it is becoming more specific as compared to prior guideline.

Glen Stevens, DO, PhD: How often would somebody require a four-vessel angiogram?

Dhimant Dani, MD: With the modern-day science, there are three major ancillary test that has been supported. To me, I always believe that we should always follow least invasive to most invasive testing. There are least invasive ancillary tests which are available in the form of transcranial Doppler, which can be done at bedside, and also a radionuclide scan, which is also can be done very effectively without a further invasive. So, in my opinion, I would say that very rarely you need a four-vessel angiogram to diagnose brain death specifically or support brain death in the form of ancillary test. I think, as you know, that transcranial Doppler as well as radionuclide scan would definitely support this without going that aggressive invasive procedure.

Glen Stevens, DO, PhD: We're a big medical center here and, obviously, see a lot of patients and have a lot of neurologic care, so certainly trainees would get exposed to these types of things. But people training in smaller centers, I imagine it would be difficult for people to get a lot of actual exposure and doing brain death exams. Or, am I wrong about that?

Dhimant Dani, MD: No, you are absolutely right. In a center where a limited support, when there is a very small number of patients, as we discussed before, that with modern-day science, a number of patients are... Declaring brain death are getting less and less, and partly because advanced neurosurgical techniques, as well as advanced trauma care, and more cardiac life support. All those numbers of patients who being declared brain death are getting smaller and smaller. So, in a center where a number of those brain dead patient population is getting smaller and smaller, it has been challenging for trainees. I would imagine that, especially in a smaller center, sometimes it will be even harder for trainee to even go through with complete brain death examination, only few times in their lifetime of training. So, yes, it is absolutely challenging.

Glen Stevens, DO, PhD:  Yeah. I remember, and maybe this doesn't happen anymore, 30 years ago, I remember some of the intensivists here would go to other hospitals to evaluate patients because they didn't have anybody that was trained to make the diagnosis or-

Dhimant Dani, MD: Absolutely. There is more and more support, has been, educational support. At Cleveland Clinic, we have a sort of a educational support in the form of online modules, which is available to many centers. And outside Cleveland Clinic, caregivers who are interested in learning brain death, it's available for many caregivers. But it is also important that, because of more awareness, a lot of professional organizations has also came up with a lot of online modules to bring awareness as well as give education to the trainees, as well as caregivers involved in a care of those patients.

Glen Stevens, DO, PhD: So, as you know, medicine is art and science, and we've talked a lot about the science, but I'm sure there's the art part. A lot of it is in dealing with families and helping them through this very difficult transition for a loved one. Talk to me about the approach that you take with families in these situations. Obviously, you don't know at the very start where it's going to go, but you may have a pretty good idea.

Dhimant Dani, MD: I think it can be a challenge. Specifically, as we discussed before, when we think of brain death and how family perceives this, because they see that heart is beating, skin is warm, while brain has no function, convincing to the family at times can be challenging. When I come across these challenges, I always try to make sure that I adapt a multidisciplinary approach. When I see this, first of all, I try to be very objective with the family. It has to be very important that I should always consider myself and always tell others that, "Refrain from using term like your love one has gone or passed." I would be very objective by defining death and making sure that avoid using terms like withdrawal of life support because we are not withdrawing life support, because the life support is just sustaining the function of other organs, which is not something that is needed in a patient who is brain dead. So, it is very important that this is not a question about withdrawal of care. This is about transition to stopping measures that support other organs. So, it is very important to be very objective.

It is very important that when second opinion or any form of other concerns are needed, involving ethics as well as religious support is very important. And it is also important that making sure that giving family a clear answer and supporting their belief, but at the same time making sure that it does not change their mindset. I think time may support, but it will not change the process. And I think it is very important to share this with family that, "I'm happy to give you a time to process this, but this will not change the outcome," which is very important.

Glen Stevens, DO, PhD: Well, as you can imagine, there can be a degree of mistrust if you then start talking to them about organ donation and organ harvesting. Depending on where the patient is or what their beliefs are, now, there may be more mistrust, right, that their loved one really isn't gone and now you just want to take their organs? I can imagine it can make it complicated.

Dhimant Dani, MD: You made a very good point. I think what I see, that is a very two different process. As a physician, my role is focus on defining the function of brain, which is there or not. And once we define that process, the process of focusing on an organ donation, which is completely a separate process, that is not supposed to be a physician's role to focus on organ donation. That is supported by CMS guideline and mandate, which requires a patient's family and patients to have that anatomical gift to be given or not based on decision made by patient's prior wishes or patient. But this is not a physician's role to focus on an organ donation.

In my role, when I involved in a patient care, my focus solely remain is towards defining patient's brain function and communicating with family. The process of organ donation is a completely separate process where hospital is not involved in that process. This is a support that is given by hospital, by a government-mandated organizations, who are completely separated from patient care before, and they are the one who gets involved.

Glen Stevens, DO, PhD: Yeah, I agree with that completely, although you can see that the patient may not see the nuance.

Dhimant Dani, MD: Again, as a physician, my role remains completely focused on what is important at that time is defining the process of brain death, explain to the family, communicate effectively, and the organ donation is a byproduct. It's not the reason for defining patient brain death.

Glen Stevens, DO, PhD: And, of course, if there are big families out there, not everybody's going to agree.

Dhimant Dani, MD: Absolutely. I think, as I always say, that giving time to grieve family is important, the grieving process, but it does not change the diagnosis. So, I always remain focused on making sure that family is communicated effectively, and there should not be any form of focus towards any other process other than defining the process of brain death.

Glen Stevens, DO, PhD: Right. I agree completely. Biggest unanswered questions in the field, things that we need help with?

Dhimant Dani, MD: I think it is important to develop more awareness and focus on defining, as you know, that the science has advanced more and more, so there will be more and more testing is coming, and develop more certainty. Hopefully, with the help of modern-day science and research, we will bring more closure for family and for more technique which can define more certainty and hopefully will give closure to the family.

Glen Stevens, DO, PhD: Role of the EEG these days?

Dhimant Dani, MD: Role of EEG has been actually relatively... it's obsolete at this point and partly because there are many factors that affect when EEG is being used to get one of the ancillary tests. But because of EEG cannot test a brainstem, EEG can only test the cerebral cortex. Because of that, EEG has been actually becoming less and less supportive of brain death. Because of that, EEG has been actually obsolete. In new guideline, EEG is not a part of, and so as, similarly, there are other tests, like CT angiogram or a MR angiogram, where there is more human factors are involved and which lead to a false positive cases, too. Those tests are also being taken off the new guidelines. So, that's why, with new guideline, there is more specificity, more accuracy, more focus on a less and less objectivity side on a human factor side, and more focus on a more precision and accuracy.

Glen Stevens, DO, PhD: Hard to believe, but we're up against the clock. Final takeaways?

Dhimant Dani, MD: I think brain death is... I always try to tell people brain death is a legal death. Diagnosis should lead to a withdrawal of all medical support, and ultimately errors are irreversible. Unlike coma and vegetative state, there is no biological recovery in brain death. Once the brain is dead, patient met the criteria, it is important to be as objective as possible with the patient's family so that there should be less and less controversy.

Glen Stevens, DO, PhD: Well, Dhimant, I appreciate your joining us today and sharing your expertise and appreciate your knowledge-

Dhimant Dani, MD: Thank you.

Glen Stevens, DO, PhD: ... and all you do. Thank you.

Dhimant Dani, MD: Thank you.

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