Hello. Thank you for joining us on this panel discussion. I will be speaking about the rationale, highlights and future directions of the revised 2023 brain death guidelines. I hope that these slides do not overlap too much with the content that you have already heard. I have no disclosures of material conflicts of interest. There were several rationales for providing an updated brain death guideline. One purpose of the guideline in 2023 was to update the 2010 American Academy of Neurology brain death guidelines as well as the 2011 American Academy of Pediatrics Child Neurology Society and Society of Critical Care Medicine guidelines for infants and children. Another purpose was to clarify the brain death determination process by integrating guidance for adults and children into a single guideline. Brain death accounts for roughly 5% of intensive care unit deaths. As we know, there is significant variability across hospital protocols in terms of determining brain death. A uniform approach is sought. Brain death testing is referred to as a low frequency event in need of high precision. There are several aspects of the new guidelines that attempt to make the process more rigorous. For instance, a recommended observation period between brain injury and brain injury treatments are discussed. Additionally, details in terms of necessary prerequisite conditions are also discussed by the updated guidelines. As with many aspects of medical processes, terminology is key. Like the World Brain Death Project, the 2023 guideline uses the term brain death or death by neurologic criteria in place of the term brain death to incorporate colloquial terminology and show the equivalence to death by cardiopulmonary criteria. Second, the 2023 guideline uses the term permanent rather than irreversible to describe the severity of brain injury for brain death or death by neurologic criteria determination. Permanent is defined as will not resume spontaneously and medical interventions will not be used to attempt restoration of function. The 2023 guideline interprets the Uniform Determination of Death Act, abbreviated UDDA, which requires loss of all functions of the entire brain, including the brainstem, as loss of function of the brain as a whole, including the brainstem, resulting in coma, brainstem areflexia, and apnea in the setting of an adequate stimulus. The process of the determination always begins with presumption that the patient does not meet brain death or death by neurologic criteria, a presumption that must then be disproved. As was mentioned, one rationale for updating the guidelines was to provide more strict guidance to lessen the possibility of inaccurate determinations of brain death. The guidelines define the term child as a patient who is at least 37 weeks old and younger than 18 years of age. There are several individual recommendations that detail specific age ranges. Now, let's discuss several aspects that have been updated in the 2023 guidelines. The new recommendations regarding prerequisites are best summarized in the following tables, provided by a summary article from Drs. Lewis, Kirshen, and Greer. The following tables, presented on subsequent slides, will help describe the changes in the 2023 guidelines. Each table has the same format. The left-most column describes the component of the exam. The second column describes the 2023 guidelines. Words that are bolded indicate a change from prior. The third column describes the 2010 adult guidelines. The last column describes the 2011 child and infant guidelines. As you can see, in terms of etiology of brain injury, the 2023 guidelines suggest not performing a brain death evaluation if there is any evidence of consciousness, preservation of brainstem reflex, motor movements mediated by the brain or brainstem, or spontaneous breathing. Further diagnostic evaluation is suggested, and not proceeding with an evaluation of brain death is suggested if a patient is comatose, apneic, has no brainstem reflexes, but there is no identified mechanism of brain injury known to lead to brain death. A patient should be observed for at least 24 hours after hypoxic ischemic brain injury before initiating brain death testing in patients 24 months or older. A sufficient amount of time based on the pathophysiology of the brain injury after a brain injury should be undertaken before initiating a brain death evaluation to ensure there is no potential for recovery. A sufficient amount of time after medical or surgical interventions to treat elevated intracranial pressure should be allowed to ensure there is no potential for recovery. It needs to be established that the brain injury is permanent and that the function is lost and will not resume spontaneously or secondary to medical interventions. Neuroimaging results should show evidence of catastrophic supertentorial injury before brain death assessment proceeds. In terms of temperature guidance, it is recommended waiting at least 24 hours after rewarming to 36 degrees Celsius before brain death evaluation if the core body temperature has been less than 35.5 degrees Celsius. In terms of blood pressure guidance, the new guidelines suggest that systolic blood pressure is greater than or equal to 100 millimeters of mercury and mean arterial pressure is greater than or equal to 75 millimeters of mercury in adults. It is recommended that systolic and mean arterial pressure is targeted that approximates the known chronic baseline of a patient who has a baseline blood pressure that varies significantly from the age-based normal. The new guidelines provide more guidance regarding intoxication, specifically ensuring blood and urine drug screens are negative, ensuring the serum level is therapeutic or sub-therapeutic and not considered to contribute to the neurologic status of the patient, and ensuring that pentobarbital is below 5 micrograms per milliliter or below the lower limit of detection for the laboratory. The new brain death guidelines emphasize excluding pharmacologic paralysis if administered or suspected through the use of a Trana-4 stimulator or demonstration of deep tendon reflexes. In terms of laboratory parameters, a table of laboratory derangements that may confound brain death testing has been provided. Evidence of neuroendocrine function does not preclude brain death testing. Pregnancy is not a contraindication for a brain death evaluation. The new guidelines provide guidance on blood pressure. The guidelines require a minimum systolic blood pressure and a mean arterial pressure. The prior guidelines required either a minimum systolic blood pressure or mean arterial pressure. Because blood pressure is age-dependent, the 2023 guideline requires systolic blood pressure to be greater than or equal to 100 millimeters of mercury and a mean arterial pressure to be greater than or equal to 75 millimeters of mercury in adults. Both the systolic blood pressure and mean arterial pressure need to be greater than or equal to the fifth percentile for age in children. For patients who have a baseline blood pressure that varies significantly from their age-based normal blood pressure, the 2023 guideline recommends targeting systolic blood pressure and mean arterial pressure that approximate the known chronic baseline blood pressure. To exclude intoxication, a pharmacokinetic table for common drugs that can depress the central nervous system is provided. The guidelines recommend ensuring serum drug levels are within the therapeutic or sub-therapeutic range when able, with specific mention that the pentobarbital level must be below 5 micrograms per milliliter or below the lower limit of detection of the laboratory. While it is acknowledged that there is no scientific rationale to identify acceptable electrolyte or metabolic thresholds for brain death, a table with ranges of values that warrant correction and or performance of ancillary testing is included for clarity. In terms of examinations and examiners, the 2023 guidelines stipulate that clinicians must perform a minimum of one examination in adults. A second clinician may perform a separate and independent examination because performance of two independent examinations may decrease the risk of a false positive determination due to diagnostic error. A 2020 paper revealed that 93 percent of determination guidelines that provided information about the number of examiners required two or more examiners. 86 percent of determination guidelines that provided information about the number of examinations required two or more examinations. In other words, multiple examiners performing multiple assessments is a fairly common clinical practice. The 2023 guideline indicates that the interval between examinations should be 12 hours for all children independent of age. Dissimilar to the prior pediatric guidelines, the 2023 guideline does not recommend use of ancillary testing to shorten the inter-examination observation period. The 2023 guideline includes a table of spinal reflexes and a table that summarizes how to perform each examination component. Responses consistent with brain death and clinical considerations for each examination component. The 2023 guidelines stipulate a minimum of one exam in adults and suggest two exams to reduce error. The requirements for physicians includes language that trainees must be directly supervised by an attending physician as described in settings where local laws and institutional standards do not allow them to perform brain death evaluations independently. Advanced practice providers who work in settings where local laws and institutional standards allow them to perform brain death evaluations independently must appropriately be credentialed and adequately trained and competent in brain death determination in children or adults as applicable. Advanced practice providers who work in settings where local laws and institutional standards do not allow them to perform brain death evaluations independently must be directly supervised by an attending physician as described. In terms of competence, clinicians performing brain death evaluations should demonstrate competence by such means as completion of a supervised brain death evaluation in a clinical environment. Supplementary education can include completion of a well-designed online or in-person training course. In terms of components of the examination, an assessment for the absence of oculocephalic reflexes may proceed unless there is concern for cervical spine or skull base injury. Assessment for the absence of oculovestibular reflexes can proceed if the oculocephalic reflexes are absent or not assessed because of concerns for cervical spine or skull base injury. All elements of the brain death examination that can be assessed must be assessed and findings must be consistent with brain death. In other words, a patient that does not meet the criteria of brain death testing cannot be declared brain dead. The 2023 guideline requires clinicians to perform at least one apnea test after the final clinical examination in adults. Two apnea tests, one after each examination, must be performed in children. The prior guidelines required one apnea test in adults and two in children. The most notable change to apnea testing recommendations is the target. PaCO2 of greater than or equal to 60 millimeters of mercury and greater than or equal to 20 millimeters of mercury above the pre-apnea test baseline level and arterial pH less than 7.3 in patients known to not have chronic hypercarbia or patients known or suspected to have chronic hypercarbia whose baseline PaCO2 is not known. Or PaCO2 greater than or equal to 60 millimeters of mercury and greater than or equal to 20 millimeters of mercury above the chronic elevated pre-morbid baseline level and arterial pH less than 7.3 in patients known to have chronic hypercarbia whose baseline PaCO2 is known. Few brain death determination guidelines include a pH target for apnea testing. The rationale to do so is based on the understanding that the combination of hypercarbia and secondary acidosis should stimulate functional medullary chemoreceptors to prompt respiration. The 2023 guideline also includes a table with detailed guidance performance of apnea testing. The following table highlights these changes. At least one apnea test in adults is recommended after the final neurologic examination. In terms of technique, it is recommended that the patient have an invasive arterial catheter when possible. It is recommended that the patient's PaCO2 be maintained at a certain level and that the arterial pH is also at a certain level. Pre-oxygenation for at least 10 minutes with 100% oxygen on the ventilator to PaO2 of greater than 200 millimeters of mercury is recommended. Aptic oxygenation is also recommended through several measures including stopping intermittent mandatory ventilation and delivering 100% oxygen using continuous positive airway pressure on the ventilator. As was discussed, an apnea testing target is provided by the new guidelines. Reasons to abort testing include systolic blood pressure below 100 mmHg or mean arterial pressure less than 75 mmHg in adults, or below the 5th percentile for age in children despite titration of vasopressors, inotropes, or intravenous fluids. Cardiac arrhythmia with hemodynamic instability is also a reason to abort testing. The most notable change in ancillary testing is the designation of EEG as an unacceptable test for all patients. EEG was previously considered acceptable for both pediatric and adult brain death determinations. The decision to describe EEG as an unacceptable ancillary test is based on concern that while it assesses function of the cerebral hemispheres, it does not evaluate brainstem function, which is problematic given that ancillary testing is often performed because of the inability to fully assess brainstem function. The 2023 guidelines provides specific direction regarding the use of ancillary testing. It is recommended that ancillary testing only be performed to assist with brain death determination if the examination or apnea testing cannot be completed or the findings cannot be interpreted adequately. Ancillary testing should not be used to assist with brain death determination in the setting of hypothermia, in the setting of high levels of medication that depress the central nervous system, solely because of the presence of an open fontanelle, skull fracture, skull defect, or cerebrospinal fluid diversion device, or to avoid performing otherwise testable elements of the brain death evaluation. The neurologic exam and apnea test need to be performed to the fullest extent possible and the findings must be consistent with brain death testing before ancillary testing is performed. If any findings on the examination or apnea test are consistent with brain-mediated activity, ancillary testing must not be performed. The indications for ancillary testing include the inability to correct metabolic derangements adequately, but the neurologic examination and apnea test must be consistent with brain death. The inability to perform or complete an apnea test due to hypoxemia, hypotension, or cardiac arrhythmia with hemodynamic instability would all be indications to proceed with ancillary testing. Knowledge or suspicion of chronic hypercarbia without knowledge of a chronic baseline POCO2 may also lead to ancillary testing. The 2023 Guidelines make it clear that EEG and auditory evoked potentials are unacceptable ancillary tests for brain death evaluations. The 2023 Guidelines offers discussion regarding communication. The 2023 Guidelines recommend informing families about the potential for spinal reflexes and the fact that these movements do not preclude brain death testing. The 2023 Guidelines stipulate that there is no obligation to obtain consent for brain death testing unless otherwise required by institutional policy, state law, or regulations. It is recommended that documentation of the time of death occur as the time the arterial blood gas results from the final apnea test demonstrate that the arterial pH and PaCO2 are consistent with brain death criteria. It is also recommended the documentation of time of death as the time an attending clinician records that the ancillary test results are consistent with brain death if ancillary testing is required. The 2023 Guidelines attempts to provide guidance as to how families may be engaged after death. It is recommended that families be provided with a reasonable but limited amount of time with the deceased patient before discontinuation of organ support, the length of which is based on the judgment of the attending clinician of record in accordance with the institution's policies. It is important to educate families and discuss risks and benefits to a fetus of continuing maternal organ support for pregnant patients. Of course, involving clinicians who are knowledgeable, such as maternal fetal medicine, child neurology, and neonatology is necessary. Including a process to resolve disagreements with families who do not agree with the medical team's plan to initiate brain death testing and or termination of organ support after brain death determination may occur. Including consideration of providing a reasonable period to accommodate families after that death is recommended. There are several new topics discussed by the 2023 Guidelines. These will be highlighted in the following slides. The 2023 Guidelines recommends that clinicians initiate a brain death evaluation and declare brain death despite evidence of neuroendocrine function. Because the Uniform Determination of Death Act requires there be a loss of all functions of the entire brain, including the brainstem, for a brain death determination, some have argued that brain death determination requires loss of neuroendocrine function. The 2023 Guideline attempted to address this issue head on and provide specific guidance. The 2023 Guideline recommends that clinicians ensure a primary infratentorial injury has also led to catastrophic supratentorial injury as demonstrated by conventional neuroimaging prior to initiating a brain death evaluation. The Uniform Determination of Death Act requires loss of all function of the entire brain, including the brainstem. Prior guidelines have not addressed determinations of brain death in the setting of primary infratentorial injury. A meta-analysis found that the mean prevalence of primary infratentorial brain injury leading to a brain death determination was 6%. The 2023 Guidelines provide discussion regarding interventions to lower elevated intracranial pressure. After medical or surgical interventions to treat elevated intracranial pressure, clinicians are instructed to wait a sufficient amount of time to ensure there is no recovery of brain function before initiating a brain death assessment, as determined by the pathophysiology of brain injury and neuroimaging findings. Obviously, specific timelines cannot be stipulated as the pathophysiology of brain injury and neuroimaging findings vary between individual patients. The 2023 Guidelines find that pregnancy is not a contraindication to brain death evaluations. After brain death is determined in a pregnant woman, there should be a multidisciplinary discussion, including the clinicians involved in the care of the decedent and clinicians knowledgeable in maternal-fetal medicine, child neurology, and neonatology. This discussion should occur with the surrogate decision-makers about the risks and benefits to the fetus of continuing maternal organ support. The 2023 Guideline recommends that for patients whose core temperature has been less than or equal to 35.5 degrees Celsius, clinicians should wait a minimum of 24 hours after rewarming to greater than or equal to 36 degrees Celsius before brain death evaluation and must not use ancillary testing to bypass this observation period. The 2023 Guideline recommends that when performing apnea testing for patients on ECMO, pre-oxygenation should be provided through both the membrane lung and the ventilator. To achieve an adequate rise in PaCO2, exogenous carbon dioxide can be added to the ECMO circuit and or the sweep gas flow rate can be titrated down. For patients on veno-arterial ECMO, arterial blood should be sampled from both the distal arterial line and the ECMO circuit post-oxygenator. Values from both locations must meet pH and PaCO2 targets for brain death. Although one-third of adult and pediatric deaths on ECMO are brain death declarations, the prior Guidelines did not address brain death determination on ECMO. As was previously discussed, the 2023 Guideline recommends that in settings where acute and critical care advanced practice providers are performing brain death evaluations independently in accordance with local laws and hospital policies, they must be appropriately credentialed and adequately trained and also competent in brain death evaluation in children or adults as applicable. In settings where advanced practice providers are not permitted to perform brain death evaluations independently in accordance with local laws and hospital policies, they must be directly supervised by an attending clinician who is an appropriately credentialed member of the hospital's medical staff and is adequately trained and competent in brain death evaluation in children or adults. The 2023 Guideline reiterates that while reasonable efforts should be made to notify a patient's family of the intent to perform a brain death evaluation, there is no obligation to obtain consent. This specific language is quite helpful for clinicians in the trenches who are challenged by difficult social situations where patients' families may not be available or identifiable in a timely fashion. And instead of delaying care, this specific language allows for appropriate evaluations to proceed. Prior Guidelines did not address management of disagreements with families about brain death determination, yet surveys have shown that half of pediatric and adult clinicians involved in brain death determinations have dealt with disagreements with families about performing a brain death evaluation or discontinuing organ support after a brain death evaluation. The 2023 Guideline recommends that hospitals' brain death determination policies include a process to resolve disagreements with families who object to the plan to initiate brain death evaluations and or terminate organ support after a brain death determination has been made, and also consideration of a provision of a reasonable period to accommodate families. There are several possible future directions for subsequent Guidelines to discuss. For instance, the number of examinations and the qualifications of examiners remains an area of active discussion. Multiple examinations raises the possibility of reducing false positive testing results and providing a higher rate of accuracy. However, this is dependent on appropriately knowledgeable examiners. Thus, the qualifications of examiners is relevant. Training, in-person, online assessments are all valuable to help educate and standardize the knowledge base of brain death evaluators. An appropriate observation period is discussed in the 2023 Guidelines, but of course specific timelines are not provided. This is a vexing clinical question for those of us who care for patients at the end of life. What is an appropriate observation period after a devastating head injury? Are there markers on imaging or with the clinical exam that would suggest that a patient is more or less likely to have a permanent and devastating brain injury? These are areas of active clinical study and certainly future Guidelines may address suggested observation periods to provide additional clarity for practicing clinicians. There is continuous development and validation of ancillary testing. For instance, there are several CT and MRI modalities used for the brain, such as cerebral blood flow imaging with CT scans. As the definition of brain tissue becomes more precise with advanced technology, it is possible that ancillary testing, especially neuroimaging, may become more relevant in the diagnostic evaluation of brain death. It is important to be continually aware of advancements in radiologic techniques to see if these might offer a high-fidelity ancillary test for brain death evaluations. There are continuous efforts to harmonize the Guideline recommendations with hospital policies, as well as state and federal laws to provide optimal care. There is significant variability between hospitals in terms of brain death testing guidance, protocols, or even instructions. It is important that this process be standardized so that patients experience uniform care, no matter what type of hospital he or she is treated in. Finally, several papers have explored the possibility of developing a registry for reporting brain death determinations. The hope is that by accumulating data over large volumes of patients and across the country, understanding geographic variations and perhaps local practice patterns, further refinement of the techniques to assess brain death determinations can be made. Specifically, it would be helpful to identify situations in which brain death testing is not able to be completed so that a better understanding of which high-fidelity ancillary tests may be offered and tested. Registries offer the possibility of pooling large numbers of patients for a situation that is fairly uncommon. I hope that these slides have provided some information in terms of the 2023 Guidelines and the differences relative to prior Guidelines. I look forward to the question and answer to follow the panelists' presentation. Thank you for your time.

brain death guidelines

revised 2023

pediatric brain death determinations

standardized determination process

terminology adjustments

ancillary testing

future directions