Brain Death
K. Jane Lee, Binod Balakrishnan
Brain death is the irreversible cessation of all functions of the entire brain, including the brainstem. It is also known as death by neurologic criteria and is legally accepted as death in the United States.
Epidemiology
In children, brain death usually develops after traumatic brain injury (TBI, including brain injury from nonaccidental trauma) or asphyxial injury. Pathogenesis is multifactorial, with the end result being irreversible loss of brain and brainstem function.
Clinical Manifestations and Diagnosis
Current guidelines do not apply to preterm infants <37 wk gestational age (Fig. 86.1 ).
Brain death is determined by clinical assessment. Although ancillary tests such as electroencephalography (EEG) and cerebral blood flow (CBF) studies are sometimes used to assist in making the diagnosis, repeated clinical examination is the standard for diagnosis. The 3 components for determining brain death are demonstration of coexisting irreversible coma with a known cause , absence of brainstem reflexes , and apnea .
Before a determination of brain death may be made, it is of utmost importance that the cause of the coma be determined using the history, any radiology, and laboratory data, to rule out a reversible condition. Potentially reversible causes of coma include metabolic disorders, toxins, sedative drugs, paralytic agents, hypothermia, hypoxia, hypotension/shock, recent cardiopulmonary resuscitation (CPR), hypo-/hyperglycemia, hypo-/hypernatremia, hypercalcemia, hypermagnesemia, nonconvulsive status epilepticus, hypothyroidism, hypocortisolism, hypercarbia, liver or renal failure, sepsis, meningitis, encephalitis, subarachnoid hemorrhage, and surgically remediable brainstem lesions. Confounding factors must be corrected before initiation of brain death assessment.
Coma
The state of coma requires that the patient be unresponsive, even to noxious stimuli. Any purposeful motor response, such as localization, does not constitute coma. Likewise, any posturing (decerebrate or decorticate) is not consistent with coma, and therefore not consistent with brain death. The presence of spinal cord reflexes—even complex reflexes—does not preclude the diagnosis of brain death.
Brainstem Reflexes
Brainstem reflexes must be absent. Table 86.1 lists the brainstem reflexes to be tested, the brainstem location of each reflex, and the result of each test that is consistent with a diagnosis of brain death.
Table 86.1
Brainstem Reflex Testing to Determine Brain Death
| BRAINSTEM REFLEX | AREA TESTED | HOW TO PERFORM EXAM | EXPLANATION OF RESULTS |
|---|---|---|---|
| Pupillary light reflex | Cranial nerves (CNs) II and III, midbrain | Shine a light into the eyes while closely observing pupillary size. |
Midposition (4-6 mm) or fully dilated pupils that are not reactive to light are consistent with brain death. Pinpoint pupils, even if nonreactive, suggest intact function of the Edinger-Westphal nucleus in the midbrain and are therefore not consistent with brain death. |
| Oculocephalic reflex (doll's eyes reflex) | CNs III, VI, and VIII; midbrain; pons |
Manually rotate the patient's head side to side and closely watch the position of the eyes. Should not be performed in a patient with a cervical spine injury. |
In the intact patient, the eyes remain fixed on a distant spot, as if maintaining eye contact with that spot. In an exam consistent with brain death, the eyes move in concert with the patient's head movement. |
| Corneal reflex | CNs III, V, and VII; pons | Touch the patient's cornea with a cotton swab. |
In the intact patient, the touch results in eyelid closure, and the eye may rotate upward. In an exam consistent with brain death, there is no response. |
| Oculovestibular reflex | CNs III, IV, VI, and VIII; pons; midbrain | Irrigate the tympanic membrane with iced water or saline and look for eye movement. | Absence of eye movement is consistent with brain death. |
| Gag and cough reflex | CNs IX and X, medulla |
Touch the posterior pharynx with a tongue depressor or a cotton-tipped swab to stimulate a gag. Advance a suction catheter through the endotracheal tube to the carina to stimulate a cough. |
Absence of both a cough and a gag is consistent with brain death. |
Apnea
Apnea is the absence of respiratory effort in response to an adequate stimulus. An arterial partial pressure of carbon dioxide (PaCO 2 ) value ≥60 mm Hg and >20 mm Hg above baseline is a sufficient stimulus. Apnea is clinically confirmed through the apnea test. Because the apnea test has the potential to destabilize the patient, it is performed only if the 1st 2 criteria for brain death (irreversible coma and absence of brainstem reflexes) are already confirmed.
The apnea test assesses the function of the medulla in driving ventilation. It is performed by first ensuring appropriate hemodynamics and temperature (>35°C) and the absence of apnea-producing drug effects or significant metabolic derangements. The patient is then preoxygenated with 100% oxygen for approximately 10 min, and ventilation is adjusted to achieve a PaCO 2 of approximately 40 mm Hg. A baseline arterial blood gas (ABG) result documents the starting values. During the test, oxygenation can be maintained with 100% oxygen via a T -piece attached to the endotracheal tube or via a resuscitation bag such as a Mapleson device. Throughout the test, the child's hemodynamics and pulse oximetry oxygen-hemoglobin saturation (SpO 2 ) are monitored while the physician observes for respiratory efforts. An ABG sample is obtained approximately 10 min into the test and every 5 min thereafter until the target PaCO 2 is surpassed; ventilatory support is resumed at that time. If at any point during the test the patient becomes hypoxic (SpO 2 <85%) or hypotensive, the test is aborted and ventilatory support resumed. Absence of respiratory efforts with a PaCO 2 ≥60 mm Hg and >20 mm Hg above baseline is consistent with brain death.
Observation Periods
To determine brain death in the United States, the findings must remain consistent for 2 examinations performed by different attending physicians (apnea testing may be performed by the same physician) separated by an observation period. The 1st exam determines that the child has met the criteria for brain death, whereas the 2nd exam confirms brain death based on an unchanged and irreversible condition. Recommended observation periods are 24 hr for neonates from 37 wk gestation to term infants 30 days old, and 12 hr for infants and children >30 days old. An observation period of 24-48 hr before initiation of brain death assessment is recommended after CPR or severe acute brain injury.
Ancillary Studies
Ancillary studies are not required for the diagnosis of brain death unless the clinical examination including the apnea test cannot be safely or reliably completed. Examples include cervical spinal cord injury, presence of high therapeutic or supratherapeutic levels of sedative medications, or hemodynamic instability or SpO 2 desaturation during an apnea test. Ancillary studies may also be used to shorten the recommended observation period. In this case, 2 complete clinical examinations, including apnea test, should be carried out and documented along with the ancillary study. Ancillary studies are no substitute for the neurologic examination.
The 2 most widely used ancillary tests are EEG and radionuclide CBF studies. A valid electroencephalogram to support suspected brain death must be performed according to the American EEG Society standards and technical requirements, under conditions of normothermia and appropriate hemodynamics, and in the absence of drug levels sufficient to suppress the EEG response. An EEG that demonstrates electrocerebral silence over a 30 min recording time under these conditions supports the diagnosis of brain death. Advantages of this study are its wide availability and low risk. Disadvantages include potential confounders, such as artifact in the tracing and the presence of suppressing levels of drugs such as barbiturates.
A radionuclide cerebral blood flow study consists of intravenous (IV) injection of a radiopharmaceutical agent followed by imaging of the brain to look for cerebral uptake. As with EEG, nuclear medicine scans are widely available and low risk. Unlike EEG, radionuclide CBF studies are not affected by drug levels. A study that shows absence of uptake in the brain demonstrates absence of CBF and is supportive of brain death. Four-vessel intracranial contrast angiography was previously used as the definitive ancillary test, but practical technical difficulties and risks have led to the use of nuclear medicine scans instead.
Interpretation of both EEG and radionuclide CBF studies should be done by appropriately trained and qualified individuals. If the studies show electrical activity or presence of CBF, brain death cannot be declared. A 24 hr waiting period is recommended before repeating the clinical examination or ancillary study.
Documentation
Documentation is an important aspect of diagnosing brain death. Complete documentation should include statements of the following:
- 1. Etiology and irreversibility of the coma.
- 2. Absence of confounding factors: hypothermia, hypotension, hypoxia, significant metabolic derangement, and significant drug levels.
- 3. Absence of motor response to noxious stimulation.
- 4. Absence of brainstem reflexes: pupillary light reflex, oculocephalic/oculovestibular reflex, corneal reflex, cough reflex, and gag reflex.
- 5. Absence of respiratory effort in response to an adequate stimulus; ABG values should be documented at the start and end of the apnea test.
Supportive Care
Following a diagnosis of brain death, supportive care may continue for hours to days as the family makes decisions about potential organ donation and comes to terms with the diagnosis. A diagnosis of brain death may not be accepted by the family for personal, religious, or cultural reasons. It is important for care providers to be patient and supportive of the family dealing with this difficult situation.
Objections to the Idea of Brain Death
Although the concept of brain death is widely accepted and very useful in facilitating organ transplantation, it is not accepted by all. Several countries do not recognize brain death, and some individuals, both medical personnel and laypeople, object to the idea of brain death.
It has been pointed out that some patients who meet brain death criteria continue to show evidence of integrative functioning, such as control over free-water homeostasis (absence of diabetes insipidus), control of temperature regulation, capacity for growth and wound healing, and variability of heart rate and blood pressure in response to stimulus. Along with scientific arguments, there are also philosophical arguments about what constitutes death and whether a person who lacks function of the brain, but not of the body, is truly dead.