The 2023 AAN/AAP/CNS/SCCM Pediatric and Adult Brain Death/Death by Neurologic Criteria Consensus Practice Guideline

Terminology

There are 3 notable differences between terminology in the 2023 guideline and the prior guidelines.^1,3,4 Although these differences do not affect the process or accuracy of BD/DNC determination, they warrant mention. First, like the WBDP, the 2023 guideline uses the term “brain death/death by neurologic criteria” (or “BD/DNC”) in lieu of the term “brain death,” to both embrace the colloquial terminology and emphasize the equivalence to death by cardiopulmonary criteria.^1,-,4 Second, the 2023 guideline uses the term “permanent” rather than “irreversible” to describe the severity of brain injury necessary for BD/DNC determination; “permanent” is defined as “(1) will not resume spontaneously and (2) medical interventions will not be used to attempt restoration of function.”¹ An extensive discussion of the rationale to use the term “permanent” in this context can be found elsewhere.¹² Finally, the 2023 guideline interprets the 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.”^1,9

Prerequisites for BD/DNC Determination

Table 1 provides a detailed comparison of the guidance about prerequisites for performance of a BD/DNC evaluation included in the 2023 guideline and prior guidelines.^1,3,4 Age-specific guidance is italicized. There are new recommendations (bold text) about the etiology of brain injury, observation period after brain injury and before initiating BD/DNC evaluation, severity of brain injury, neuroimaging results, temperature, blood pressure, exclusion of intoxication, exclusion of pharmacologic paralysis, laboratory parameters, and other considerations.

The 2023 guideline requires both a minimum systolic blood pressure (SBP) and a mean arterial pressure (MAP), whereas the prior guidelines required either a minimum SBP or MAP.^1,3,4 Because blood pressure is age-dependent, the 2023 guideline requires SBP ≥100 mm Hg and MAP ≥75 mm Hg in adults and both SBP and MAP ≥5th 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 SBP and MAP that approximate the known chronic baseline blood pressure.

To exclude intoxication, the 2023 guideline provides a pharmacokinetic table for common drugs that can depress the CNS and recommends ensuring serum drug levels are within the therapeutic or subtherapeutic range, when able, with specific mention that the pentobarbital level (if administered) must be < 5 µg/mL or below the lower limit of detection for the laboratory.

In addition, although the 2023 guideline acknowledges that there is no scientific rationale to identify acceptable electrolyte or metabolic thresholds for BD/DNC determination, it includes a table with ranges of values that warrant correction and/or performance of ancillary testing.

Examinations/Examiners

Table 2 compares the guidance in the 2023 guideline and prior guidelines about the examinations/examiners for BD/DNC determination.^1,3,4 Age-specific guidance is italicized. There are new recommendations (bold text) about the number of examinations/examiners, qualifications of examiners, observation period between examinations, and components of the examinations.

The most notable update in the 2023 guideline regarding examinations/examiners is the recommendation that clinicians must perform a minimum of one examination in adults, but a second clinician may perform a separate and independent examination because performance of 2 independent examinations may decrease the risk of a false-positive BD/DNC determination because of diagnostic error.¹ This differs from the guidance about the number of examinations/examiners in both the 2010 AAN guideline for adult BD/DNC determination and the WBDP, both of which only require one examination/examiner (although the WBDP suggests, rather than recommends, that a single examination is the minimum standard for BD/DNC determination in adults).^2,3 However, it is in accordance with the BD/DNC determination guidelines in most other countries around the world. A 2020 review found that 93% (57/61) BD/DNC determination guidelines that provided information about the number of examiners required ≥2 examiners and 86% (44/53) BD/DNC determination guidelines that provided information about the number of examinations required ≥2 examinations.¹³

In children, similar to the 2011 AAP, CNS, and SCCM guideline, the 2023 guideline recommends 2 clinicians perform independent examinations.^1,4 In consideration of the WBDP's recommendation for consideration of an interexamination observation period and the stipulated interexamination observation period in prior guidelines (1987: 48 hours for patients aged 7 days to 2 months, 24 hours for patients aged 2 months to 1 year, and 12 hours for patients older than 1 year; 2011: 24 hours for patients aged 30 days or younger and 12 hours for patients older than 30 days to 18 years), the 2023 guideline indicates that the interval between the examinations should be 12 hours for all children, independent of age.^1,2,4,6 Dissimilar to the prior pediatric guidelines, the 2023 guideline does not recommend use of ancillary testing to shorten the interexamination observation period.

In addition, the 2023 guideline includes a table of spinal reflexes (reproduced from the WBDP) and a table that summarizes how to perform each examination component, responses consistent with BD/DNC, and clinical considerations for each examination component (adapted from the WBDP).^1,2

Apnea Testing

Table 3 summarizes the guidance in the 2023 guideline and prior guidelines on apnea testing, including the number of tests, prerequisites, contraindications, techniques, targets, and reasons to abort testing (bold text indicates new recommendations and italicized text indicates age-specific guidance).^1,3,4 The 2023 guideline requires clinicians to perform at least one apnea test after the final examination in adults and 2 apnea tests, one after each examination, in children; the prior guidelines required one apnea test in adults and 2 in children.

The most notable change to the apnea testing recommendations in the 2023 guideline is the target: (1) PaCO₂ ≥60 mm Hg and ≥20 mm Hg above the pre-apnea test baseline level and arterial pH < 7.3 in patients known to not have chronic hypercarbia or patients known/suspected to have chronic hypercarbia whose baseline PaCO₂ is not known or (2) PaCO₂ ≥60 mm Hg and ≥20 mm Hg above the chronic elevated premorbid baseline level and arterial pH < 7.3 in patients known to have chronic hypercarbia whose baseline PaCO₂ is known.¹ This differs from the 2010 AAN guideline for adult BD/DNC determination (which recommended a target PaCO₂ of ≥60 mm Hg or ≥ 20 mm Hg above baseline normal PaCO₂) and the 2011 AAP, CNS, and SCCM guideline for pediatric BD/DNC determination (which recommended a target PaCO₂ of ≥60 mm Hg and ≥20 mm Hg above baseline), both of which did not include a pH target.^3,4 However, it is similar to the apnea testing target included in the WBDP (pH < 7.3 and PaCO₂ ≥60 mm Hg, unless the patient has preexisting hypercapnia, in which case the target should be ≥ 20 mm Hg above baseline if known).² Although very few BD/DNC determination guidelines around the world 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.^1,13

The 2023 guideline also includes a table with detailed guidance for performance of apnea testing which addresses prerequisites, preparatory steps, techniques to provide apneic oxygenation, cardiopulmonary monitoring during testing, instructions for performance of arterial blood gases, targets, and reasons to abort testing prematurely.¹

Ancillary Testing

Table 4 compares recommendations about ancillary testing in the 2023 guideline and prior guidelines.^1,3,4 There are new recommendations (bold text) about ancillary testing caveats, indications, and acceptable vs unacceptable tests. Age-specific guidance is italicized. The most notable change is the designation of EEG as an unacceptable test for all patients; it was previously considered acceptable for both pediatric and adult BD/DNC determination. This designation is consistent with WBDP guidance that EEG no longer be used as an ancillary test for adult BD/DNC determination.² The decision to denote 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 inability to fully assess brainstem function.¹

The 2023 guideline also includes a table that summarizes the diagnostic criteria, advantages, disadvantages, sensitivity/specificity, and comments about acceptable ancillary tests, which is adapted from the WBDP.^1,2

Communication About BD/DNC and BD/DNC Declaration

Finally, Table 5 presents the recommendations on communication about BD/DNC and BD/DNC declaration included in the 2023 guideline and prior guidelines.^1,3,4 There are new recommendations (bold text) about communication before initiating BD/DNC evaluation, need for consent to initiate BD/DNC evaluation, time of death, steps after death, and information to include in hospital BD/DNC determination policies about management of disagreements with families. Additional information about guidance on these new topics is addressed below.

BD/DNC Determination After Interventions to Lower Elevated ICP

The prior guidelines and the WBDP do not address BD/DNC determination after interventions to lower elevated ICP, but questions have been raised about BD/DNC determination in this situation.^2,-,4,14 The 2023 guideline indicates that after medical or surgical interventions to treat elevated ICP, clinicians must wait a sufficient amount of time to ensure there is no recovery of brain function before initiating BD/DNC evaluation as determined based on the pathophysiology of brain injury and the neuroimaging findings.¹

BD/DNC Determination in the Setting of Primary Infratentorial Injury

The UDDA requires that there be “loss of all functions of the entire brain, including the brainstem” for BD/DNC determination, but the prior guidelines did not address BD/DNC determination in the setting of primary infratentorial injury.^3,4,9 Review of BD/DNC determination guidelines in other countries demonstrated that BD/DNC determination in the setting of primary infratentorial injury is infrequently addressed and guidance is inconsistent and sometimes ambiguous.^13,15 However, a meta-analysis that included 3,602 BD/DNC determinations demonstrated that the mean prevalence of primary infratentorial brain injury leading to BD/DNC was 6% (range of 2%–16% across studies).¹⁶ The authors identified 38 cases of isolated brainstem death (cases in which the clinical evaluation was consistent with BD/DNC, but ancillary testing demonstrated cerebral blood flow or electrical activity); 28 of these patients ultimately had loss of cerebral blood flow and/or electrical activity, consistent with whole-brain death. To guide BD/DNC determination in regions that follow the whole-brain concept of BD/DNC, the WBDP suggests that in the setting of isolated brainstem pathology (primary infratentorial injury±supratentorial signs of intracranial hypertension on neuroimaging), ancillary testing be used to assess for the absence of cerebral blood flow even if the examination and apnea test are consistent with BD/DNC.²

To meet the UDDA's requirement (interpreted by the 2023 guideline 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 2023 guideline recommends that clinicians ensure a primary infratentorial injury has also led to catastrophic supratentorial injury, as demonstrated by conventional neuroimaging, before initiating a BD/DNC evaluation.^1,9

The Effect of Preserved Neuroendocrine Function on BD/DNC Determination

Because the UDDA requires that there be “loss of all functions of the entire brain, including the brainstem” for BD/DNC determination, some argue that BD/DNC determination requires loss of neuroendocrine function.^9,17 The 1995 AAN guideline for adult BD/DNC determination specifically noted that BD/DNC determination does not require the absence of diabetes insipidus.⁵ In a section on the need to exclude confounding conditions before the BD/DNC evaluation, the 2010 AAN guideline for adult BD/DNC determination mentioned that (1) there should be no severe endocrine disturbance at the time of BD/DNC evaluation, but (2) hypotension due to hypovolemia secondary to diabetes insipidus is common after BD/DNC.³ Neither the 1987 guideline nor the 2011 guideline for pediatric BD/DNC determination addresses neuroendocrine function.^4,6 Both the WBDP and a 2019 AAN position statement state that neuroendocrine function does not preclude BD/DNC determination.^2,18

As previously noted, the 2023 guideline interprets the UDDA's requirement 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.”^1,9 As such, the 2023 guideline recommends that clinicians may initiate a BD/DNC evaluation and declare BD/DNC despite evidence of neuroendocrine function.¹

BD/DNC Determination After Treatment With TTM

While the prior guidelines recommended a minimum core temperature for BD/DNC evaluation to address the fact that hypothermia may suppress brain function, they did not stipulate an observation period once the temperature has normalized to exclude the potential for recovery of neurologic function.^3,4 Review of BD/DNC determination guidelines from around the world demonstrated that only 3% (2/78) clearly indicated the amount of time to observe a patient who was hypothermic (because of the use of TTM or other etiologies) after rewarming; both advised waiting 24 hours.¹³ The WBDP also recommends delaying BD/DNC evaluation for 24 hours after the temperature has normalized and consideration of use of a cerebral blood flow study, in addition to examination and apnea testing, if medications or drugs that could depress the CNS were previously administered.²

The 2023 guideline recommends that for patients whose core temperature has been ≤35.5°C, clinicians (1) should wait a minimum of 24 hours after rewarming to ≥36°C before BD/DNC evaluation and (2) must not use ancillary testing to bypass this observation period.¹

BD/DNC Determination on ECMO

Although one-third of adult and pediatric deaths on ECMO are BD/DNC declarations, the prior guidelines did not address BD/DNC determination on ECMO.^3,4,19,20 Review of BD/DNC determination guidelines in other countries around the world demonstrated that only 3% (2/78) provided guidance about BD/DNC determination on ECMO.¹³ The WBDP includes recommendations about BD/DNC determination on ECMO, and these were used as the basis for guidance on this topic in the 2023 guideline.^1,2 The 2023 guideline recommends that when performing apnea testing for patients on ECMO, preoxygenation should be provided through both the membrane lung and the ventilator.¹ To achieve an adequate rise in PaCO_2, exogenous carbon dioxide can be added to the ECMO circuit and/or the sweep gas flow rate can be titrated down to 0.2–1 L/min. For patients on venoarterial ECMO, arterial blood should be sampled from both the distal arterial line and the ECMO circuit post-oxygenator, and values from both locations must meet the pH and PaCO₂ targets for BD/DNC determination.

BD/DNC Determination During Pregnancy

The 2010 AAN guideline for adult BD/DNC determination did not address BD/DNC determination during pregnancy, and a 2016 review of US hospital BD/DNC determination policies found that 3% (8/317) did not allow BD/DNC determination if the fetus was potentially viable; of policies that allowed BD/DNC determination in pregnant persons, 99% (305/309) did not include guidance about who was responsible for making decisions for the fetus and 94% (289/309) did not provide guidance about fetal management after maternal BD/DNC declaration.^3,21 Similarly, review of BD/DNC determination guidelines in other countries around the world demonstrated that only 1% (1/78) mentioned the need to consider pregnancy before discontinuation of organ support after BD/DNC declaration.¹³ The WBDP (1) recommends the decision about whether to continue organ support after maternal BD/DNC declaration for the sake of the fetus be made after multidisciplinary discussion with the decedent's family about potential fetal outcome, taking into consideration the decedent's advance directives or expressed wishes, and (2) provides detailed guidance about prevention and management of maternal systemic complications if the decision is made to continue organ support for the sake of the fetus.²

The 2023 guideline notes that pregnancy is not a contraindication to BD/DNC evaluation and that after BD/DNC determination in a pregnant person, 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) with the surrogate decision-makers about the risks and benefits to the fetus of continuing maternal organ support.¹ The AAN provides additional guidance about BD/DNC determination in pregnancy in a 2019 position statement.¹⁸

Requirements for Advanced Practice Providers to Perform BD/DNC Evaluations

The prior guidelines only addressed physician qualifications to perform BD/DNC evaluations, but a review of US hospital BD/DNC determination policies found that 2% (8/342) indicated that APPs could perform BD/DNC evaluations.^3,4,10 The 2023 guideline recommends that (1) in settings where acute and critical care APPs are performing BD/DNC evaluations independently in accordance with local laws and hospital policies, they must be appropriately credentialed and adequately trained and be competent in BD/DNC evaluation in children or adults, as applicable, and (2) in settings where APPs are not permitted to perform BD/DNC 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 hospitals' medical staff and is adequately trained and competent in BD/DNC evaluation in children or adults, as applicable.¹

The Absence of Obligation to Obtain Consent to Initiate BD/DNC Evaluation

Prior guidelines did not address the need for consent to initiate the BD/DNC evaluation, but the WBDP and a 2019 AAN position statement note that while reasonable efforts should be made to notify a patient's family of the intent to perform a BD/DNC evaluation, there is no obligation to obtain consent.^2,-,4,18 The 2023 guideline reiterates this recommendation.¹

Information to Include in Hospital BD/DNC Determination Policies About Management of Disagreements With Families About BD/DNC Determination

Prior guidelines did not address management of disagreements with families about BD/DNC determination, but surveys demonstrate that half of pediatric and adult clinicians involved in BD/DNC determination have dealt with disagreements with families about performance of a BD/DNC evaluation or discontinuation of organ support after BD/DNC determination.^3,4,22,23 A review of US hospital BD/DNC determination policies found that three-quarters do not address management of disagreements with families about BD/DNC determination.²⁴ The WBDP provides a number of recommendations about management of disagreements with families about BD/DNC determination including notation in hospital BD/DNC determination policies about (1) indications to accommodate objections and (2) the interventions that can be (a) initiated, (b) continued, or (c) withheld after BD/DNC determination.² A 2019 AAN position statement discusses management of disagreements with families about BD/DNC determination and encourages clinicians to ensure hospital BD/DNC determination policies address management of objections including the conditions and time frame for accommodation, as appropriate.¹⁸

The 2023 guideline recommends that hospital BD/DNC determination policies include (1) a process to resolve disagreements with families who object to the plan to initiate BD/DNC evaluation and/or terminate organ support after BD/DNC determination and (2) consideration of provision of a reasonable period to accommodate families.¹

Conclusion

The UDDA requires that determinations of death be made in accordance with accepted medical standards.⁹ With the retirement of the 2010 AAN guideline for adult BD/DNC determination and the 2011 AAP, CNS, and SCCM guideline for pediatric BD/DNC determination, because there are no other nationally recognized guidelines for BD/DNC determination in the United States, the 2023 AAN, AAP, CNS, and SCCM guideline for pediatric and adult BD/DNC determination will now be the accepted medical standard for BD/DNC determination.^1,8 It is thus the responsibility of clinicians involved in BD/DNC determination in the United States to coordinate with hospital administrators, legal teams, and ethicists, as appropriate, to update their hospital policies on BD/DNC determination to conform to the 2023 guideline.⁹