Key Aspects of Brain Death That Critical Care Clinicians Should Know
In 2023, the American Academy of Neurology published the Pediatric and Adult Brain Death/Death by Neurologic Criteria Consensus Guideline with several recommendations and updates. This article will help summarize key aspects that critical care clinicians should know.*
What is Brain Death or Death by Neurological Criteria?
Brain death, or death by neurologic criteria (BD/DNC), is defined as the “irreversible cessation of all functions of the entire brain, including the brainstem”1 in a person who has suffered catastrophic brain injury. The guidelines interpret permanent loss of function of the entire brain as a state resulting in (1) coma, (2) brainstem areflexia, and (3) apnea in the setting of an adequate stimulus. All three elements are required to meet the definition.
Consideration for BD/DNC testing begins when a clinician identifies a brain injury that is likely to be catastrophic and permanent, with neuroimaging often being used to help identify the mechanism and severity of brain injury. Once a patient with suspected permanent brain injury is identified, a sufficient waiting period is needed prior to BD/DNC testing to ensure no potential for recovery or observed improvements are seen. This is especially important if medical or surgical therapies are utilized to treat elevated intracranial pressure. For patients older than 2 years, an observation period of at least 24 hours is considered “reasonable” by the authors, though specific scenarios may vary. Due to anatomical differences, patients younger than 24 months require a 48-hour waiting period after the acute brain injury before initiating testing.
Who Can Perform Testing?
Clinicians performing BD/DNC examinations must be appropriately credentialed and adequately trained. Unlike in pediatrics, where two exams and two apnea tests are required, only one clinical exam and one apnea test are required for adults. The 2023 guidelines state that APPs who perform BD/DNC evaluations independently, in accordance with local laws and institutional standards, must be appropriately credentialed and trained. In settings where APPs are not permitted to perform BD/DNC evaluations independently, direct supervision must occur.
What Should the APP Know Before Testing?
Following the waiting period, a patient with suspected irreversible brain injury (with neuroimaging consistent with the diagnosis) must meet several criteria prior to initiating testing to ensure the validity of the exam. Below are some of the key requirements (non-exhaustive):
- Patient’s core body temperature must be maintained at ≥36°C. If core body temperature has been ≤35.5°C, wait a minimum of 24 hours after the patient has been rewarmed prior to testing.
- Adults should have a SBP ≥100 mm Hg and a mean arterial pressure (MAP) ≥75 mm Hg; in children, maintain SBP and MAP ≥ the fifth percentile for age. If on VA ECMO, target MAP ≥75 mm Hg for adults and MAP ≥ the fifth percentile for age for children.
- Metabolic derangements, intoxication, and medications that depress the CNS should be “excluded, adequately corrected, or eliminated” before evaluation. The guidelines note that pharmacokinetics and pharmacodynamics can be altered in these situations, and additional time for drug clearance should be considered.**
Physical Exam
Once a patient meets criteria for testing, there are several elements of a thorough and structured physical exam that must be completed.
Briefly, the exam centers around seven key elements:
1) Assessment for Unresponsiveness
2) Assessment for Motor Response
3) Assessment of the Pupillary Light Reflex
4) Assessment of Occulcephalic and Occulovestibular Reflexes
5) Assessment of the Corneal Reflex
6) Assessment of the Gag and Cough Reflexes
7) Assessment of Sucking and Rooting Reflex (infants <6 months)
The exam should be aborted if the patient displays any evidence of consciousness, intact brainstem reflexes, spontaneous respiratory effort, or has any motor movements not consistent with spinal origin, as these findings would not meet the criteria for BD/DNC.
Apnea Testing
An essential part of BD/DNC evaluation is the assessment of brainstem function by analyzing the response to a hypercarbic and acidotic challenge via apnea testing. At least 1 apnea test is required in adults, and a minimum of 2 tests are required in pediatrics. There are several methods of performing apnea testing safely; however the basic elements of testing involve: 1) hyperoxygenation prior to testing and adequate oxygenation throughout the testing period; 2) normalization of pH and PaCO2 levels prior to testing (or, if a patient is known or suspected to have chronic PaCO2 retention, ensuring the PaCO2 level is at the patient’s known or estimated baseline); 3) stopping intermittent mandatory ventilation for 8-10 minutes and observing for spontaneous respirations and; 4) serial ABGs. In a patient who does not have chronic PaCO2 retention, a pH level <7.30 and a PaCO2 level ≥60 and ≥20 mm Hg above the patient’s pre-apnea test baseline level is consistent with brain death. There are several nuances to the apnea testing criteria in patients with known or suspected chronic PaCO2 retention, and in some cases, ancillary testing may be required.
Ancillary Testing
Ancillary testing is required if certain elements of the physical exam cannot be performed, if there are metabolic or toxicological alterations that cannot be corrected, if the patient is suspected to have chronic PaCO2 retention with an unknown baseline, or if the apnea test could not be performed or is inconclusive. There are four acceptable testing methods: 4-vessel catheter angiography (gold standard), radionuclide angiography, radionuclide perfusion scintigraphy, and transcranial doppler ultrasound (adults only). An EEG is not an acceptable ancillary test. In many institutions, cerebral radionuclide perfusion scintigraphy is the most common testing mechanism and has excellent specificity.
Time of Death
For patients who meet clinical criteria for BD/DNC, the time of death assigned is when the arterial blood gas results are reported that demonstrate that the PaCO2 and pH levels are consistent with BD/DNC criteria. In patients who are undergoing ancillary testing, the time of death is the time an attending clinician (e.g., nuclear medicine physician or angiographer) documents in the medical record that the ancillary test results are consistent with BD/DNC.
Support for Families
Loss of a family member is a traumatic event, and clinicians should provide support and guidance for families of a loved one being evaluated for BD/DNC. Using supportive, simple terminology that families can understand may help families navigate the complexity of testing and comprehend testing results.
*Clinicians performing testing are encouraged to access the comprehensive guideline and testing checklists provided by the AAN and to follow hospital policy and local state laws
**A helpful pharmacokinetic table with serum drug levels for common CNS-depressing medications, as well as ranges of metabolic and electrolyte thresholds that warrant correction and/or the need for ancillary testing, can be found within the guidelines.
References
- Greer DM, Shemie SD, Lewis A, et al. Determination of Brain Death/Death by Neurologic Criteria: The World Brain Death Project. JAMA. 2020;324(11):1078-1097. doi:10.1001/jama.2020.11586.
- Greer, D. M., Kirschen, M. P., Lewis, A., Gronseth, G. S., Rae-Grant, A., Ashwal, S., … & Halperin, J. J. (2023). Pediatric and adult brain death/death by neurologic criteria consensus guideline: report of the AAN Guidelines Subcommittee, AAP, CNS, and SCCM. Neurology, 101(24), 1112-1132.
