Determination of Brain Death

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219 Determination of Brain Death

Teresa L. Smith Jacobs, Thomas P. Bleck

Determination of death by neurologic criteria is a clinical diagnosis. After certain prerequisites are met, there are three essential components to the determination: irreversible coma or unresponsiveness, absence of brainstem reflexes, and apnea. Before the diagnosis is made, it is essential to rule out alternative causes for the patient’s neurologic status, including hypothermia, drug-induced coma, and severe metabolic disarray.

image Prerequisites

Determination of death can be made in patients who continue to have cardiac function during mechanical ventilation in the appropriate clinical scenario. A clear irreversible cause must be known based on history, brain imaging, or cerebrospinal fluid examination. Determination of death by neurologic criteria cannot be made in patients with a temperature below 36°C or in those who may have drug intoxications or poisoning without a confirmatory study indicating the absence of intracranial blood flow. If neuromuscular junction blocking agents have been administered, electrical stimulation should be performed to document the presence of transmission at the neuromuscular junction. Severe acid-base, electrolyte, or endocrine abnormalities also cannot be present.

image Unresponsiveness

The examination shows that the patient has no eye movements or motor response to verbal or noxious stimulation, with the exception of spinally mediated responses. Standard points of pressure application for administration of noxious stimuli are nailbeds, supraorbital nerve, and temporomandibular joint.1

image Absence of Brainstem Reflexes

Pupillary Response

Pupillary responsiveness should be assessed using a bright flashlight. Using an ophthalmoscope allows for magnification of the iris and pupil so that even a subtle response can be detected. Pupils are usually mid-position (4-6 cm in diameter); rarely, they may be more dilated if spinal sympathetic pathways are intact.

Facial Sensation and Motor Response

A very gentle stimulus such as a wisp of cotton should be gently touched to the cornea of each eye individually. We prefer to use a small squirt of saline from the plastic containers used for saline administration during airway suctioning, as saline will not harm the cornea. In patients with a diagnosis of death by neurologic criteria, no blink will be induced. There can be no grimace to painful stimuli or jaw reflex.

Gag and Cough Reflexes

Patients being examined for a determination of death by neurologic criteria will all be on ventilatory assistance. The gag response can be difficult to determine in patients with endotracheal tubes in place. The endotracheal tube itself should not be maneuvered to stimulate a gag response, as this could lead to tracheal damage; a tongue blade should be used instead. Cough in response to deep bronchial suctioning should be sought. Absence of these responses is required for a determination of death by neurologic criteria.

Assessment of Eye Movements

Cervico-Ocular Reflexes (“Doll’s-Eyes Maneuver”)

This maneuver is only performed in the absence of cervical instability. With the eyes held open, the head should be briskly turned from side to side (mid-position to 90 degrees), looking for any eye movements. If an endotracheal tube is in place, it should be moved together with the head movements to avoid tracheal damage or unplanned extubation. No eye movements occur in patients with a diagnosis of death by neurologic criteria. The term doll’s eyes refers to the expected horizontal movement in the direction opposite to the head movement, indicating that the brainstem centers for conjugate horizontal gaze are functional, but the cerebral cortex is not controlling them. However, the likelihood of inaccurate use of this term is so great that it should be avoided.

Vestibulo-Ocular Reflexes (“Cold Calorics”)

Once the absence of the cervico-ocular reflex is determined, or in circumstances in which it cannot be tested owing to cervical instability, caloric testing should be performed. First, the tympanic membranes are examined for perforations and to ensure no obstructions are present. The caloric test is sufficiently important, however, that it should proceed when death by neurologic criteria is being proved even if a perforation is present. The head of the bed should be elevated to 30 degrees. Ice-cold water, 50 mL, should be placed in a syringe. Soft tubing connected to the syringe (for instance, from a butterfly intravenous line) should be inserted into the external auditory canal, and the water irrigated into the ear while the patient’s eyelids are held open. In cases of coma with intact brainstem pathways, the eyes should deviate toward the side of the cold water instillation. Absence of any eye movement will be present in a case of death by neurologic criteria. The eyes should be scrutinized for 1 minute after the cessation of icewater irrigation. After 5 minutes, the identical procedure should be repeated for the opposite ear.

Apnea Testing

Before a formal apnea test is conducted, the patient should have fulfilled all previously discussed criteria for death by neurologic criteria. Severe chronic obstructive pulmonary disease or morbid obesity should not be present. Care should be taken to ensure that the patient has a systolic blood pressure of at least 90 mm Hg, has an adequate intravascular volume, and is treated with vasopressin if diabetes insipidus is suspected.

The patient should be preoxygenated to a PaO2 exceeding 200 mm Hg. The ventilator should be disconnected, and 100% oxygen at a rate of 6 L/min placed at the carina or delivered directly into the trachea. Alternatively, 10 cm continuous positive airway pressure may be used. Maximal respiratory drive is believed to occur with a PaCO2 of 60 mm Hg, which should occur within 8 minutes after disconnection.1 The patient is observed during this period for respiratory movements, and the electrocardiographic monitor examined for signs of respiratory artifact. If an arterial blood gas assessment shows a PaCO2 exceeding 60 mm Hg with continued apnea, the diagnosis of death by neurologic criteria is completed. The pH is the major determinant of respiratory drive, and if the patient’s baseline PaCO2 is markedly abnormal, the equivalent change in the arterial pH should be employed.

If cardiac arrhythmias, hypotension, or arterial desaturation ensue, apnea testing is abandoned, and a confirmatory test must then be performed.

image Confirmatory Testing

If apnea testing is not possible or cannot be completed, or if specific brainstem function testing is not possible, a confirmatory test must be performed. Numerous tests are available. Ranked from highest to lowest sensitivities, they are angiography, electroencephalography, transcranial Doppler echography, technetium-99m hexamethylpropyl-eneamineoxime (99mTc-HMPAO) brain scan (single photon emission computed tomography), and somatosensory evoked potentials.2

Cerebral Angiography

Demonstration of lack of intracranial flow on angiography can be used to confirm death by neurologic criteria. Internal carotid artery flow usually stops shortly after the carotid bifurcation.3 Vertebral flow usually stops at the atlanto-occipital junction.

Electroencephalography

Confirmation of death by neurologic criteria can be made by establishing electrocerebral silence by electroencephalography (EEG). Since the EEG is affected by the same confounding factors as the physical examination (hypothermia and sedative drugs), it should be used only when such confounding factors have been disproved. Tracings are performed for at least 30 minutes with these settings: sensitivity greater than 2 µV/mm, high-frequency filter greater than 30 Hz, low-frequency filter less than 1 Hz, interelectrode impedance less than 10,000 Ohms, and a minimum of 8 scalp electrodes placed at least 10 cm apart. Guidelines for the minimal technical criteria for using EEG in confirming the diagnosis of death by neurologic criteria are available.4

Transcranial Doppler Blood Flow Velocity Measurement

Transcranial Doppler echography can also be used to confirm death by neurologic criteria. Early transcranial Doppler findings include oscillating flow signifying nearly equal forward and reverse flow, followed by a small systolic spike pattern suggesting lack of diastolic flow from severely increased intracranial pressure, and finally no signal. Because the absence of the transcranial Doppler signal can be due to technical difficulties, extracranial oscillating flow can be helpful when no signal is detected intracranially. Sensitivity and specificity for detecting death by neurologic criteria have been found to be 91.3% and 100%, respectively, when compared with the EEG.5 Guidelines for the use of transcranial Doppler in confirming the diagnosis of death by neurologic criteria include two separate examinations at least 30 minutes apart demonstrating bilateral oscillating flow or systolic spikes in conjunction with bilateral common carotid artery, internal carotid artery, and vertebral artery oscillating flow.6

Single Photon Emission Computed Tomography

Single photon emission computed tomography with 99mTc-HMPAO can be used to document absent intracranial flow as noted by absent uptake of the tracer, which is administered 15 to 20 minutes prior to the scan.7 This gives the appearance of an “empty skull.”

Somatosensory Evoked Potentials

Somatosensory evoked potentials are useful in predicting outcome in patients who are comatose. N20 potentials are typically absent in those who have a diagnosis of death by neurologic criteria but are also absent in 15% to 20% of those who are comatose but do not have the diagnosis of death by neurologic criteria.

Other Tests

Magnetic resonance angiography and computed tomography angiography can show absence of intracranial flow, but experience with these modalities is limited.

image Children

The determination of death by neurologic criteria has some differences in children. For those between 7 days and 2 months of age, two examinations and EEGs should be performed at least 48 hours apart. For those 2 months to 1 year of age, a second examination and EEG are required 24 hours after the first, unless a radionuclide angiographic study fails to visualize cerebral vessels. For those older than 1 year, a repeat examination after 12 hours is typically recommended. In the case of hypoxic-ischemic cause, a longer period of observation is often recommended unless a confirmatory test is performed.8

image Regional Rules and Laws

Unfortunately, there has been no standardization of legal determination of death by neurologic criteria internationally or even among the states in the United States. The basis for laws concerning the determination of death by neurologic criteria in most states is the Uniform Determination of Death Act, which indicates that death can be determined by irreversible lack of all brain function made in accordance with accepted medical standards. In 2010, the American Academy of Neurology published an updated practice parameter for the determination of brain death.2 Individual institutions and some states have required additional standards to these guidelines. Local laws and regulations should be understood before a determination of death by neurologic criteria is made.

Key Points

1 After certain prerequisites are met, there are three essential components to the determination of death by neurologic criteria: irreversible coma or unresponsiveness, absence of brainstem reflexes, and apnea.
2 Patients being examined for a determination of death by neurologic criteria will all be on ventilatory assistance. The gag response can be difficult to determine in patients with endotracheal tubes in place.
3 Demonstration of lack of intracranial flow on angiography can be used to confirm death by neurologic criteria.
4 The determination of death by neurologic criteria has some differences in children.
5 Local laws and regulations should be understood before a determination of death by neurologic criteria is made.

Annotated Reference

Wijdicks EF, Varelas PN, Gronseth GS, Greer DM. American Academy of Neurology. Evidence-based guideline update: determining brain death in adults: report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2010;74:1911-1918.

These provide guidelines for determining death by neurologic criteria.

References

1 Wijdicks EFM. Brain Death. Philadelphia: Lippincott Williams & Wilkins; 2001.

2 Wijdicks EF, Varelas PN, Gronseth GS, Greer DM. American Academy of Neurology. Evidence-based guideline update: determining brain death in adults: report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2010;74:1911-1918.

3 Greitz T, Gordon E, Kolmodin G, et al. Aortocranial and carotid angiography in determination of brain death. Neuroradiology. 1973;5:13-19.

4 American Electroencephalographic Society. Guidelines three: Minimum technical standards for EEG recording in suspected cerebral death. J Clin Neurophysiol. 1994;11:10-13.

5 Petty GW, Mohr JP, Pedley TA, et al. The role of transcranial Doppler in confirming brain death: Sensitivity, specificity, and suggestions for performance and interpretation. Neurology. 1990;40:300-303.

6 Ducrocq X, Braun M, Debouverie M, et al. Consensus opinion on diagnosis of cerebral circulatory arrest using Doppler-sonography: Task force group on cerebral death of the neurosonology research group of the World Federation of Neurology. J Neurol Sci. 1998;159:145-150.

7 Facco E, Zucchetta P, Munari M, et al. 99mTc-HMPAO SPECT in the diagnosis of brain death. Intensive Care Med. 1998;24:911-917.

8 Guidelines for the determination of brain death in children. Pediatrics. 1987;80:298-300.

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