Brain Death: Pearls and Pitfalls

Educational Objectives

The goal of this program is to improve methods for clinical determination of brain death. After hearing and assimilating this program, the clinician will be better able to:

1. Identify criteria needed to proceed with a clinical assessment for determination of brain death.
2. Develop strategies for performing clinical assessments to make a determination of brain death.

Summary

Criteria for brain death: in 1968, a group at Harvard Medical School published a definition of irreversible coma that became known as the Harvard Brain Death Criteria and included components of unresponsiveness or unreceptivity, lack of movement or breathing, lack of reflexes (including the absence of brainstem reflexes), and a flat electroencephalography that, when repeated over a 24-hr period, remains flat; the Uniform Determination of Death Act states that, “an individual who has sustained either irreversible cessation of circulatory and respiratory functions or irreversible cessation of all functions of the entire brain, including the brain stem, is dead, and a determination of death must be made in accordance with accepted medical standards”; the World Brain Death Project advocates transitioning to the more accurate term “death by neurological criteria” rather than “brain death”

Prerequisites for clinical determination of brain death: the golden rule is to avoid declaring brain death unless absolutely certain; first, the nature of the neurologic injury should be established, and the neurologic catastrophe must be severe enough to cause irreversible brain injury (confirmed by neuroimaging); second, the loss of function of the entire brain must be permanent and irreversible; if these two prerequisites are met, clinical brain death can be determined; in addition, the patient should have a core temperature of 36°C and systolic blood pressure ≥100 mm Hg or a mean arterial pressure (MAP) of ≥60 mm Hg with or without the use of vasopressors and inotropes as needed

Confounders: must be excluded after prerequisites have been met; drug levels of central nervous system depressants (eg, opioids, benzodiazepines, barbiturates) should be within the therapeutic range; if the hepatic and renal functions are normal, wait 5 half-lives of the drug before performing clinical determination of brain death; a toxicology screen should be performed on patients suspected of ingesting intoxicants; severe metabolic abnormalities (eg, abnormal blood levels of glucose or sodium) should be corrected before proceeding with clinical determination of brain death

Clinical determination of brain death: involves a detailed neurologic examination to assess for irreversible coma and document brainstem areflexia and an apnea test to evaluate the operation of the respiratory control center in the lower medulla, which is the last area of the brain to die

Assessment of coma: ensures lack of responses to any noxious stimuli (the most noxious stimulus should be provided); auditory — call their name or clap loudly in their ears; visual — look for a blink to visual threat; tactile stimulus — applied to all 4 extremities and torso; assess cranial responses by compressing the supraorbital nerve at the supraorbital notch and looking for facial grimaces (especially in patients with significant cervical cord injury or peripheral neuropathy); another method is to apply bilateral pressure to the temporomandibular joint and look for a facial grimace response; a third method is to use a cotton swab (Q-tip) to tickle the nose and look for facial grimace response

Assessment of brainstem reflexes: pupillary light reflex — used to observe the pupil's sensitivity to light; absent in patients who are brain dead; corneal reflex — contact the eye with cotton wool adjacent to the iris, and look for any eyelid movement; avoid performing the test too laterally because the nerve fiber density is lower; oculocephalic reflex — involves rapidly moving the head of the patient side to side horizontally; when a patient is brain dead, the eye follows the movement of the head, whereas the eyes normally remain fixed on the observer; oculovestibular reflex or cold caloric testing — look for any movements of the extraocular muscles or eye movements; inspect the tympanic membrane and external auditory meatus to rule out perforated eardrums or evidence of external trauma to the meatus; keep the head of the patient at a 30-degree angle; instill ≈30 mL of cold water in the ear for ≈60 sec and observe for eye movement; after 5 min, repeat the test on the contralateral ear; no eye movements occur in patients who are brain dead; normal response is an initial horizontal nystagmus to the opposite ear followed by correction of the eye toward the ipsilateral ear; cough reflex and gag response — a suction catheter is passed down the endotracheal tube to irritate the tracheobronchial tree and look for a cough response; to check for gag reflexes, place a suction catheter along the endotracheal tube and touch the posterior pharyngeal wall

Modifications if brainstem reflexes cannot be assessed: oculocephalic reflex is the only part of the neurologic assessment that can be skipped; typically skipped in high cervical spinal cord injuries; if unable to perform any other brainstem reflexes, proceed with ancillary testing

Apnea test: systolic blood pressure must be ≥100 mm Hg, body temperature should be ≥36°C, and patients should be eucapnic and euvolemic; in patients who are CO2 retainers, CO2 should be at their baseline; partial pressure of oxygen (PaO2) in arterial blood should be ≥200 mm Hg; patients are normally preoxygenated with 100% fraction of inspired oxygen (FiO2) for ≥10 min; once disconnected from the ventilator, patients usually become acidemic, causing hemodynamic instability; having a buffer for systolic blood pressure is optimal (speaker recommends 110-120 mm Hg); patients should be on telemonitor with continuous pulse oximetry and blood pressure monitoring; look for any form of respiratory excursion that suggests respiratory drive or effort; check arterial blood gases (ABGs) and adjust the partial pressure of carbon dioxide (PaCO2) to 35 to 45 mm Hg and ensure pH is normal; disconnect from the ventilator and ensure the patient is not extubated; administer 4 to 6 L/min of 100% oxygen via nasal cannula; if the patient is not breathing, obtain serial measurement of blood gases (5, 8, 10, or 15 min of observed apnea); establish the cause of chest wall movement; observe for hemodynamic instability, cardiac dysrhythmia, and desaturation; a patient who becomes unstable (eg, blood pressure <90 mm Hg or oxygen saturation <85% for 30 sec) must be reconnected to the ventilator

Discontinuation of the apnea test: recommended if any spontaneous respirations are observed, patient becomes hemodynamically unstable, or significant cardiac dysrhythmia or oxygen desaturation occurs; if patient becomes unstable, obtain ABGs, reconnect the patient to the ventilator, and terminate the apnea test; if the CO2 does not reach the target (>60 mm Hg or >20 mm Hg above baseline in patients with chronic CO2 retention) after apnea test is terminated, diagnosis of brain death cannot be made, and ancillary testing should be performed

Interpretation of the apnea test: lack of respiratory movements and CO2 level that is >60 mm Hg or has changed by ≥20 mm Hg from baseline is consistent with brain death

Clinical pearls for conducting apnea test: the catheter for administering oxygen should be ≤70% of the inner diameter of the endotracheal tube; flow rate should not exceed 4 to 6 L/min because high flow rates can cause barotrauma and washout of CO2; after reconnecting the patient to the ventilator, hyperventilate for ≥1 min to correct respiratory acidosis

Requirement of tests: 2 tests are commonly required in pediatric patients; state and national policies vary; the American Academy of Neurology states that one test by attending physicians is adequate; if 2 tests are performed, the second evaluation can be performed immediately after the first evaluation; ideally, 2 different examiners should perform each test, and examiners should be blinded to each other’s conclusion to reduce bias

Ancillary testing: should be considered if complete neurologic examination or apnea test cannot be conducted; flow studies — digital subtraction angiography is the gold standard but rarely used; nuclear medicine flow studies are another form; anteroposterior and lateral views must be obtained to visualize the brainstem; transcranial Doppler ultrasonography is a bedside test but is operator dependent and requires demonstration of a specific pattern of flow in anterior and posterior circulation bilaterally; absence of flow does not confirm brain death; computed tomography angiography and magnetic resonance angiography are not validated against the gold standard; electrical studies — do not assess the function of the brainstem; combining electroencephalography with evoked potentials is likely better than either test alone, but the World Brain Death Project advises against using electrical studies to determine brain death

Patients with veno-arterial extracorporeal membrane oxygenation (ECMO): maintain MAP >60 mm Hg; adjust the sweep gas flow rate to 0.5 to 1 L/min; serial ABGs may be needed because the CO2 may take longer to reach the target; ABGs should be drawn from the distal arterial line or from the postoxygenator ECMO circuit

Patients with therapeutic hypothermia: rewarm the patient and wait ≥24 hr after the target temperature (36˚C) is reached before assessing for clinical brain death; obtain neuroimaging, especially in patients with postcardiac arrest, to obtain evidence of anoxic brain injury

Involuntary spinal movements and reflexes: reexamine the patient; spinal-mediated reflexes should be stereotyped if the patient is brain dead; if in doubt, have a colleague examine the patient separately; studies found that one-third of people who are clinically brain dead have reflexive movements mediated by the spinal cord

Readings

Busl KM, Lewis A, Varelas PN. Apnea testing for the determination of brain death: A systematic scoping review. Neurocritical Care. 2021; 34:608–620; Greer DM, Shemie SD, Lewis A. Determination of brain death/death by neurologic criteria: The world brain death project. JAMA. 2020; 324(11):1078-1097; Kramer AH. Ancillary Testing in Brain Death. Semin Neurol. 2015; 35(02):125-138; Machado C, Korein J, Ferrer Y, Portela L, García M, Manero JM. The concept of brain death did not evolve to benefit organ transplants. J Med Ethics. 2007 Apr; 33(4):197–200; Machado C. Diagnosis of brain death. Neurol Int. 2010 Jun 21; 2(1):e2; Nguyen D. Evolution of the criteria of “Brain Death”: A critical analysis based on scientific realism and Christian anthropology. Linacre Q. 2019 Nov; 86(4):297–313.

Disclosures

For this program, members of the faculty and planning committee reported nothing relevant to disclose.

Acknowledgements

Dr. Athar was recorded at 11th Annual Jefferson Neurocritical Care Symposium, held virtually on February 4-5, 2022, and presented by the Sidney Kimmel Medical College at Thomas Jefferson University. For information on future CME activities from this presenter, please visit cme.jefferson.edu. Audio Digest thanks the speaker and the Sidney Kimmel Medical College at Thomas Jefferson University for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 1.00 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 1.00 CE contact hours.

Lecture ID:

NE131101

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.