Chapter 30

Brain Death
Gregory Allam

Clinical Vignette
A 56-year-old man suddenly collapsed at home after experiencing severe chest pain. His wife called the emergency technicians, who found him pulseless and cyanotic. ECG demonstrated ventricular fibrillation, but he was successfully defibrillated. After an airway was established and 100% oxygen was given, he was transported to the ED. There, results of neurologic evaluation showed that he was unresponsive to any form of communication. His pupils were dilated and fixed, and he had decerebrate posturing to noxious stimulation and bilateral Babinski signs. He eventually became flaccid, and cold caloric vestibular stimulation showed no ocular response. The next day, he developed generalized myoclonus and continued to require cardiac and full respiratory support. Three days later, there was no change in his neurologic status. An apnea test showed no respiratory response to induced hypercarbia. Although he was declared brain dead, his wife asked that further testing be performed to confirm the clinical diagnosis. An EEG demonstrated electrocerebral silence, and she agreed to have life support withdrawn.

This vignette is the classic example of a patient with an acute myocardial infarction, cardiac arrhythmia, or both with prolonged cardiorespiratory arrest. The result is devastating diffuse cerebral ischemic damage. Until a precise determination of brain death is established, there are many medical and legal issues to address in caring for individuals who have no effective residual brain function despite the return of cardiopulmonary function maintained with modern intensive care therapies. In most medical communities, a person is considered dead once there is irreversible and total cessation of all brain function, regardless of a continuing functional circulatory system. The cause of brain damage must be clearly elucidated by history, examination, or medical tests before the diagnosis of brain death is entertained. Intoxicants, sedatives, and hypothermia may present similarly to brain death but are potentially reversible and must always be considered if the cause is not clear and well documented. In many countries, including the United States, brain death constitutes a legal definition of death, and all life support measures can be halted. When caring for an individual, it is best to respect the familys wishes, religious or personal, regarding the timing of life support discontinuation. It is important to continue to explain the situations finality and that circulatory collapse will

invariably occur within hours to days of the onset of this clinical picture. It is paramount to broach the subject of organ donation as soon as possible because it is vital to harvest organs early. The widespread difficulty in obtaining organs for an ever-growing list of patients awaiting transplant procedures emphasizes this necessity. The physician who has an established relationship with the patients family is perhaps the one best to initiate such discussion, before involving the transplant team.

BRAIN DEATH CRITERIA

The criteria for brain death vary among states and countries. Usually the determination is clinical, with testing used only as an ancillary or confirmatory measure. Following are the generally accepted principles of brain death determination: 1. A preceding coma of known irreversible cause must not be due to, or influenced by, CNS depressants, intoxicants, paralytic agents, hypothermia (less than 32C/90F), or endocrine or metabolic disturbances (Figure 30-1). 2. Cessation of all brain function must be documented as follows. a. There must be no response to stimuli in any way other than spinal withdrawal

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Figure 30-1

Differential Diagnosis of Coma

Clinical features Pathology (examples) Etiologies Increased subarachnoid or extracerebral pressure Meningitis Subarachnoid hemorrhage Bilateral subdural hematoma Metabolic encephalopathy Liver coma Kidney coma Carbon dioxide narcosis Hypoxia Hypoglycemia Hypercalcemia Hyponatremia Diabetic acidosis Hyperosmolar coma Toxins or drugs Barbiturates Alcohol Narcotics Other sedative overdose Lead Multifocal cerebral disease (usually developing sequentially Infarction Multiple abscesses Encephalitis Multiple areas of brain tumor Multiple cerebral contusions

Normal pupils (equal, reactive)

Bilateral cerebral hemisphere disease

Normal dolls head phenomenon

Normal corneal reflex

Bilateral hemispheric swelling (small ventricles, obliterated sulci, rounded edges)

Absent or minor focal features (lateral paralysis, sensory or visual loss)

Unilateral cerebral hemisphere Third cranial nerve palsy, nonreactive pupil, ptosis lesion with compression of brainstem Right temporal hemorrhage from trauma, with swelling of right hemisphere

Cerebral Tumor Hemorrhage Abscess Infarction Contusion Extracerebral Subdural hematoma Extradural hematoma

Contralateral hemiparesis

Primary brainstem lesion

Small pinpoint pupils, absent horizontal eye movements

Infarction Hemorrhage Servere metabolic disturbance, sedative or phenytoin overdose Severe anoxia Large pontine hemorrhage

Rigid limbs Vomiting Cerebellar lesion with secondary brainstem compression Inability to walk

Sixth cranial nerve palsy

Infarction Hemorrhage Tumor Abscess Contusion Large cerebellar hemorrhage

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movements in the legs and arms. Spinal reflexes such as muscle stretch reflexes or extensor responses of the toes (Babinski signs) can be seen, but there must be no other spontaneous limb movements or posturing to painful stimuli, including decerebrate rigidity. b. Brainstem reflexes must be absent, including pupillary response to light (without mydriatic agents), oculocephalic reflexes by passive head turning or caloric stimulation, corneal reflexes, oropharyngeal reflexes (gag or swallowing), respiratory reflexes (spontaneous breaths or cough), and snout or jaw jerk reflex. c. Apnea test must be positive, wherein the patient exhibits no evidence of respiratory effort or change in sinus heart rate with induced hypercapnia. In this instance, the patient is ventilated with 100% O2 for 15 minutes, then disconnected while an endotracheal catheter provides 6 L/min oxygen. Apneic oxygenation is maintained for 10 minutes or until the PCO2 is 55 to 60 mm Hg. 3. In the presence of a clear structural brain lesion without evidence of toxic or metabolic cause, neurologic reexamination should proceed 6 hours after the initial evaluation to confirm and document the findings. Repeat examination should be performed at 12 hours if the cause is uncertain or there is no evidence of irreversible severe structural brain damage. 4. When the clinical evaluation, apnea test, or both are unclear or unfeasible, confirmatory tests to document the absence of electrical or metabolic cerebral activity are conducted. CT may support the clinical examination (Figure 30-2). a. A minimum 30-minute EEG isoelectric tracing (obtained with a double interelectrode distance bipolar montage) is sought. The first test is obtained no sooner than 8 hours after cardiac arrest and reconfirmed after 6 hours (American EEG Society Recommendations). b. Documentation of cessation of cerebral circulation by conventional angiography, technetium isotope study, transcranial doppler, or CT angiogram. c. Absent auditory evoked responses and short-latency somatosensory evoked responses may also be used to indicate absent brainstem function. However, these studies may be affected by peripheral lesions and are technically difficult to perform, especially in an intensive care unit setting, and their utility as a confirmatory test has been questioned.

MITIGATING FACTORS
When a severe cerebral insult is suspected but brain death determination cannot be confirmed due to confounding issues, the utmost should be done to correct for these specific factors before brain death assessment can proceed. For example, hypothermia is best treated with a warming blanket to bring and maintain core body temperature above 36.5C. Fluid, and at times vasopressor agents, is administered for patients with systolic blood pressures lower than 90 mm Hg. Patients with chronic hypercapnia secondary to lung disease such as chronic obstructive pulmonary disease have a higher respiratory center PCO2 threshold, and a PCO2 of approximately 60 mm Hg may not necessarily drive the chemoreceptors, even with a functioning brainstem. The CO2 level may be allowed to climb to approximately 80 mm Hg, but such levels risks direct cardiac effect of ensuing acidosis with arrhythmias and hypotension. Therefore, it is preferable in these instances to obtain confirmatory tests to bolster the diagnosis and judge with more certainty without risking untoward and unnecessary complications. Although most centers in the United States uphold the general outline of the principles mentioned above, there are numerous variations and differences concerning how best to ensure diagnostic certainty. Most medical centers do not require confirmatory tests. The number of evaluations and the time span between them also differs. Many institutions require a brain death evaluation by two attending neurologists at different times and their presence at the apnea test. The specific brain death criteria and protocol for

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Figure 30-2
Brain death
Supraorbital pressure

Hypoxic Brain Damage and Brain Death

Feels for breath on cheek

Open your eyes. Pupils dilated, unresponsive to light No spontaneous respiration

Coma; no response to voice, pain or other stimuli

Corneal reflex lost Dolls eyes: head turned sharply to side, eyes remain centered

Ice water in ear: eyes do not move

Border zone ischemia (shock, circulatory insufficiency)

Cerebral artery zones Anterior Middle Posterior Border zone between artery zones

Infarction Pump with 3 outflows, one outflow blocked. Deficit occurs in zone supplied by it. If brain artery is blocked, infarction occurs in zone supplied by that vessel. If pump is weak, deficit is between zones supplied by 3 outflows.

Infarction If total blood flow is inadequate, deficit is mostly at border zone between supply zones.

Diffuse cortical necrosis; persistent vegetative state

Few anoxic neurons in early anoxia

Extensive laminar necrosis

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each medical center must be consulted before the evaluation is begun and a diagnosis is substantiated.
cephalographic Society. J Clin Neurophysiol. 1994;11:10-13. Piatt J, Schiff SJ. High dose barbiturate therapy in neurosurgery and intensive care. Neurosurgery. 1984;15:427-444. Presidents Commission on Guidelines for the Determination of Death. Neurology. 1982;32:395. Plum F, Posner JB. The Diagnosis of Stupor and Coma. 3rd ed. New York, NY: Oxford University Press; 1982. Qureshi AI, Kirmani JF, Xavier AR, Siddiqui AM. Computed tomographic angiography for diagnosis of brain death. Neurology. 2004;24;62:652-653.

REFERENCES
Conrad GR, Sinha P. Scintigraphy as a confirmatory test of brain death. Semin Nucl Med. 2003;33:312-323. Guideline three: minimum technical standards for EEG recording in suspected cerebral death. American Electroen-

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