Introduction
Brain death is one of the most important diagnoses to be made in the neurocritical care unit (NCCU). The increasing ability to maintain the heart and other vital organs in the face of devastating brain injury has made it mandatory to recognize circumstances in which further intervention is futile because of widespread irreversible brain destruction. Implementing criteria for brain death is important for:
- 1
Family and patient decision making
- 2
Effective use of expensive technology and resources
- 3
Potential organ donation to allow other patients a new life
Bioethicists, physicians, philosophers, religious leaders, and those in the legal profession, among others, will continue to discuss (and disagree) about how to best define human death. These theories can range from the Harvard Criteria of Brain Death that defines death as the cessation of all brain activity, through the Irreversibility Standard that defines death when the capacity for consciousness is lost forever, to the Cognitive Standard that defines death as the loss of almost all core mental properties (e.g., memory, self-consciousness, moral agency, and the capacity for reason). This chapter emphasizes the practical determination of brain death in the NCCU in adults and relevance to organ donation, and discusses the philosophical concepts of brain death. End-of-life care, brain death criteria, and the concept and understanding of brain death vary in different countries. In this chapter, the focus is on how brain death is diagnosed in the United States.
Historical Background
Death was described for many centuries as cessation of circulation and respiration. This definition was no longer valid when modern medical devices, increasingly sophisticated ICUs, and greater understanding of physiology in the face of severe brain injury made it possible to maintain artificial respiration and circulation indefinitely despite massive brain destruction. This brought a need for more precise criteria to define brain death.
An early landmark was the publication of criteria for irreversible coma in 1968 by an ad hoc committee at Harvard Medical School. This group described a condition known as irreversible coma that they equated with cerebral death or brain death. They created a set of practical steps that could be used to make this diagnosis. Although the field has changed in the 40 years since the report, the fundamental criteria have not changed markedly—lack of brainstem reflexes, lack of cortical activity as shown by electroencephalography (EEG) and clinical examination, and irreversibility.
The initial development of this concept was marked by two major refinements, both of considerable importance for intensive care worldwide. The first was acceptance of the concept of brain death. In most Western cultures, acceptance of this concept is complete; in Japan and other Eastern traditions, this concept is increasingly being accepted. In the United States, an important landmark was the drafting of a model act in 1980 known as the Uniform Determination of Death Act, which states:
An individual who has sustained either irreversible cessation of circulatory and respiratory functions or irreversible cessation of all function of the entire brain including the brainstem, is dead. The determination of brain death must be made in accordance with accepted medical standards.
The adoption of this statute by many states helped establish the concept that brain death was death. Uniform acceptance of the concept in case law in other states confirmed the idea that brain death equates to human death. The concept of brain death became standard. Although there are two explicit definitions of death in this statute, cardiorespiratory function can be said to be important only to perfuse the brain, so death of the brain becomes the major criterion for death in both definitions. Since the adoption of the Uniform Determination of Death Act, all court rulings in which brain death has been challenged in the United States have upheld the medical practice of death determination using neurologic criteria according to state law. Two major issues that arise in court rulings are consequences of documentation of the time of brain death and family-physician discord on withdrawal of intensive care support.
The second area of increasing refinement has been the criteria used to make the determination of death. With time, increasing emphasis has been placed on blood flow determination to establish this diagnosis, although the fundamental criteria of absent brainstem and cortical function and irreversibility remain the core criteria.
Brain Death Medical Criteria
The American Academy of Neurology has provided evidence-based practice parameters to determine brain death in adults. However, there still is variance in how this is done in different hospitals, states, and countries that can create potential pitfalls in the process. Parameters that commonly vary include prerequisites to declare brain death, qualification of physicians, acceptable body temperature when the examination is performed, number of required examinations, need for a second physician to confirm the diagnosis, and documentation. Despite these variances, the basic medical criteria for brain death include:
- ▪
Coma or unresponsiveness (with a known cause)
- ▪
Absence of purposeful motor responses in all extremities
- ▪
Absence of brainstem reflexes including apnea
- ▪
Demonstrated irreversibility
The details of the clinical testing are described later. It is important to know the cause of the patient’s coma and to determine that the condition is irreversible. This means excluding conditions that may mimic brain death, such as barbiturate intoxication, valproic acid intoxication, severe alcohol intoxication, sedative overdose, organophosphate poisoning, baclofen overdose, high cervical cord injury, or hypothermia. In rare instances, snake bites, Miller Fisher syndrome (cranial nerve palsy, ataxia, areflexia), fulminant Guillain-Barré syndrome that includes both central and peripheral nervous system involvement, and brainstem encephalitis also may mimic brain death. It also means observing the patient for long enough that it is clear that the condition is not going to resolve—a minimum of 6 hours in most current protocols. Finally, some protocols require confirmation of brain death by a neurologist or neurosurgeon. While there can be potential mimics that neurointensivists should be aware of, there are no published reports in adults of recovery of neurologic function after a brain death diagnosis using the criteria described in the 1995 American Academy of Neurology practice parameter. In children, brain death may be more complicated to diagnose. Guidelines add a component of continued unresponsiveness for up to 48 hours. Table 13.1 presents these criteria in summary form.
| Coma |
Absence of reversible medical conditions:
|
| Absent pupillary light reflex |
| Absent corneal reflex |
| Absent caloric response |
| Absent gag reflex |
| Absent cough in response to tracheal suctioning |
| Absent sucking and rooting reflex |
| Absent respiratory drive at PaCO 2 that is 60 mm Hg or 20 mm Hg above normal baseline values |
Interval between two evaluations is age dependent:
|
Determination of Brain Death
Clinical Examination
A careful well-documented clinical examination is central to the diagnosis of brain death. The time and detailed set of tests performed should be noted in the record; the apnea test needs to be done only once, usually at the end of the time period used for the determination (6 hours in most cases). Prerequisites to the examination include the following: (1) establish the cause and irreversible nature of the coma, (2) exclude the use of any central nervous system depressant drugs or neuromuscular blockade, (3) ensure normal temperature (>36° C) and systolic blood pressure (>100 mm Hg, and (4) ensure laboratory values are close to normal.
Coma
Brain dead patients are in a state of deep coma. The cause of coma should be determined and should be irreversible. If the cause is not known, then longer observation is required. Based on the Glasgow Coma Scale (see Chapter 11 ), the patient should have a score of 3; based on the FOUR Score, the patient should have a score of E(0)M(0)B(0)R(0).
Motor Responses
There should be no purposeful motor response to painful stimuli such as pressure on the supraorbital ridge or nail bed. Pinching a patient on the chest is not an adequate way to elicit these responses. Reflex motor responses that do not preclude the diagnosis of brain death include the following: facial myokymia (spontaneous twitching of the cheek); undulating toe movements, reflecting L5 and S1 activity; the Lazarus sign (movements of upper limb from spinal cord integrated reflex activity); abdominal reflexes; flexion reflexes; and periodic leg movements, especially if they are generated during apnea testing, respiratory acidosis, or brisk neck flexion. It is important to understand the origin of these movements because they may pose concern to nurses, physicians, and family members about whether there is whole brain destruction. These spinal cord reflexes occur more often in young adults than in older adults.
Brainstem Reflexes
The following tests are performed to evaluate brainstem function.
Pupillary response: The pupils may be round, oval, or irregularly shaped. They are usually midsize (4 to 6 mm) but may be dilated. Drugs and preexisting anatomic ocular abnormalities may be a confounding factor. The pupillary light reflex (testing the second and third cranial nerves) must be absent. Pilocarpine supersensitivity due to denervation following instillation of 0.06% of the drug also may be seen. In some instances spontaneous asynchronous pupillary constriction and dilation may occur, which should not be a confounding factor for brain death diagnosis.
Ocular movements: Both oculocephalic (doll’s eye response) and vestibulo-ocular (caloric test) reflexes must be absent in brain death patients. The oculocephalic reflex is elicited by rapidly and vigorously turning the head to 90 degrees laterally on both sides. A normal response is deviation of the eyes to the opposite side of the head turning; in brain death, there is no deviation of eyes. This test should not be done if there is a suspected fracture or instability of the spine. The vestibulo-ocular reflex is elicited by raising the head to 30 degrees and irrigating both tympanic membranes with 50 mL of iced saline or water. In brain death patients, there is no eye deviation. The patient should be observed for up to 1 minute following irrigation, with a 5-minute wait between testing for each ear. Contraindications to the test include rupture of the tympanic membrane.
Drugs including sedatives, aminoglycoside antibiotics, tricyclic antidepressants, and some antiseizure agents can diminish the oculocephalic and vestibulo-ocular reflexes. Facial trauma involving auditory canal and petrous bone also can inhibit these reflexes.
Corneal and facial motor responses: Both corneal and facial reflexes are absent in brain death patients. The corneal reflex is elicited by touching the cornea of the patient with a cotton swab; the normal response is a blink, which is absent in brain death. The facial motor response is elicited by applying pressure to the temporomandibular joint, supraorbital ridge, or nail bed. A normal response is facial grimacing, which is not seen in patients with brain death. Interpretation of these maneuvers can be difficult in patients with facial trauma.
Pharyngeal and tracheal reflexes: Both of these reflexes are absent in brain death patients. The pharyngeal reflex is elicited by touching the posterior pharyngeal wall with a tongue blade that normally results in a gag. The cough reflex is elicited by using bronchial suctioning. These reflexes may be difficult to evaluate in orally intubated patients but may be feasible with deep suctioning in the orally intubated patient.
Apnea testing: The medulla controls the central breathing center via chemoreceptors. These receptors sense changes in pCO 2 . During apnea testing, target pCO 2 levels are up to 60 mm Hg. To do this test, the patient is removed from the ventilator; 100% oxygen may be administered via the endotracheal tube. In case of chronic hypercarbia (e.g., a patient with chronic obstructive pulmonary disease), higher target values of pCO 2 are required. Cardiac dysrhythmias and hypotension are complications associated with apnea testing and can be reduced by taking precautionary measures, such as preoxygenation and adequate maintenance of the baseline systolic blood pressure up to 120 mm Hg with pressors. Both hypocarbia and hypercarbia diminish viability of the organs for organ donation; one suggestion is to administer CO 2 exogenously after preoxygenation to shorten the interval for hypercarbia. Many patients who undergo apnea testing are on vasopressors, and an apnea test is not possible in between 5% and 10% of patients because of hemodynamic instability or inadequate lung function. In hemodynamically stable patients, it is rare that apnea testing is aborted (<5%). Patients who fail completion of apnea testing tend to be younger, have significantly greater A-a gradients, and are more acidotic. Confirmatory tests then are needed if apnea testing is not possible or is aborted.
Unstable blood pressure and heart rate: Unstable blood pressure and heart rate may provide an early indication of hypothalamic disturbance and impending death. Patients who subsequently meet the criteria for brain death have a higher heart rate and less variability as a result of loss of vegetative impulses from the brainstem. This may be a useful finding in deeply comatose patients.
Time of Observation
The clinical examination should be repeated after 6 hours before labeling a person brain dead. The need for repeat examination and the timing of repeat examination may vary among institutions. In some described criteria for brain death, the examination should be done by two physicians. In practice, however, the observation time to a second neurologic examination is often much greater. For example, in a recent review of 1229 adult and 82 pediatric patients pronounced brain dead in New York hospitals serviced by the New York Organ Donor Network, the mean brain death declaration interval between two examinations was 19.2 hours, that is three times longer than the state guideline. Brain death examinations were less frequent on weekends and the interval longer in smaller hospitals. A longer interval was associated with a decrease in organ donation. The authors found that none of the patients declared brain dead regained brainstem function upon repeat examination and so suggested that a single brain death examination for patients older than 1 year may suffice and so increase organ donation and reduce intensive care unit (ICU) costs. Longer brain death duration (i.e., time between declaration of brain death and organ harvesting), however, may not adversely affect organ survival on transplant. Newer practice parameters support a single examination rather than dual examination; the impact is unclear, although early studies suggest equivalence.
Confirmatory Tests
Confirmatory tests are not mandatory unless clinical tests are inconclusive. While there are several reports where the value of ancillary radiologic imaging is described in decisions about brain death, a comprehensive clinical evaluation performed by skilled examiners is considered to have perfect diagnostic accuracy. Possible confirmatory tests are listed in Table 13.2 and are presented briefly here as tests of cerebral blood flow (CBF) and electrodiagnostic tests.
| Confirmatory test | Results |
|---|---|
| Cerebral angiography | No circulation at level of carotid bifurcation and circle of Willis Patent external circulation |
| Electroencephalogram | Electrocerebral silence for 30 minutes |
| Transcranial Doppler ultrasonography | Brief systolic flow and reverse diastolic flow Brief systolic flow and no diastolic flow No flow at all in previously documented flow patients |
| Somatosensory and auditory evoked potential | No response |
| Technetium 99 scan | No radionuclide uptake by brain parenchyma |
| Xenon computed tomography | Average global flow of less than 5 mL/100 mL/min |
| Brain tissue oxygenation | Persistent zero value for more than 30 min |
| Blood pressure and heart rate variability | Absent variability |
Tests of Cerebral Blood Flow
Cerebral angiography. Cerebral angiography is the “gold standard” to demonstrate absent CBF. It is the most reliable test to confirm brain death, and can save time and reduce an unnecessary stay in the ICU. However, it is cumbersome and requires moving a critically ill patient into an angiography suite for several hours. In brain death patients, cerebral circulation is absent at the level of the carotid bifurcation, although flow may be demonstrated in the external carotid circulation. Extravasation of contrast may result from autolysis.
Transcranial Doppler ultrasonography (TCD). TCD is an important noninvasive confirmatory indirect blood flow test that can be done daily in the NCCU. When criteria recommended by the Task Force Group on Cerebral Death of the Neurosonology Research Group of the World Federation of Neurology are used, TCD is a reliable method to establish brain death. Brain death patients may show the following findings: (1) brief systolic flow and no diastolic flow, (2) no flow at all in a patient who previously had documented flow, and (3) brief systolic forward flow with systolic spikes and diastolic reverse flow. In patients with open skull fractures, external cerebrospinal fluid drainage, or large decompressive craniotomies, oscillating flow can be seen, and TCD should be carried out by an experienced person to avoid misinterpretation of collateral flow signals.
Radionuclide studies. Cerebral planar scintigraphy or cerebral scintotomography with Tc-99 hexamethylpropyleneamine oxime is a safe, sensitive, and cost-effective test that may be extremely helpful in patients with a skull defect or scalp trauma in whom angiography may be difficult to interpret or when there are other confounding factors that may make diagnosis equivocal. Approximately 25 mCi is given intravenously and images are obtained with the help of a mobile scintillation camera.
Xenon computed tomography (CT). Xenon CT is an important tool to measure CBF arrest as a confirmatory test for brain death. An average global flow of less than 5 mL/100 mL/min confirms brain death. This also is a clinically useful tool to determine prognosis of the patient. Presently, the U.S. Food and Drug Administration limits the use of xenon to research protocols only in the United States.
Brain tissue oxygenation and other tests. Monitoring of brain tissue oxygenation in the comatose patient may help establish the diagnosis of brain death. A sustained (>30 min) partial pressure of brain tissue oxygen of zero is consistent with brain death. This measurement may be helpful in pharmacologically depressed patients, including children, to suggest when formal brain death assessment should be performed. However, brain oxygen levels have yet to be incorporated into definitions of brain death. Newer diagnostic tests, such as bispectral index, magnetic resonance imaging, CT angiography (CTA), and CT perfusion (CTP), have been suggested as useful, but there is insufficient evidence to determine whether newer ancillary tests can confirm the cessation of brain function.
Electrodiagnostic Testing
EEG. An EEG is usually performed for 30 minutes before concluding brain death because of electrocerebral silence. It is recommended that a minimum of eight scalp electrodes be used with a distance between electrodes of at least 10 cm. However, the EEG is not entirely reliable as a confirmatory test to document brain death in that minimal electrical activity may be seen in some patients who otherwise fulfill brain death criteria, and the EEG may appear flat in cases of comatose patients with intact brainstem functioning. According to the American Encephalographic Society guidelines, electrocerebral silence is confirmed when there is absence of cortical activity greater than 2 µV for 30 minutes. EEG results may be contaminated by electromyographic artifacts from scalp motor units.
Somatosensory and brainstem auditory evoked potentials. The somatosensory evoked potential (SSEP) is a bedside test done with a portable instrument via stimulation of the median nerve. When SSEP is used for brain death determination, it presupposes that there is absent pathology in the intervening structures between the peripheral nerve and the cortex (e.g., cervical spine injury). Patients with brainstem death have no response. These tests are useful in patients in whom misleading factors such as depressant drugs, hypothermia, and metabolic disturbances are present. These tests are less sensitive and not recommended for children younger than 6 months of age.
Related posts:
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
