12 Brain Death in Adults
Abstract
Since the passage of the Uniform Determination of Death Act of 1981, the concept of brain death has become widely accepted. Actual policies for determination of brain death have been developed by local institutions and vary with personnel and equipment availability. Unfortunately, there is great variability.1 Legal requirements for the declaration of brain death differ by states and hospital policy, while protocols for determining brain death vary by institutions. Brain death is defined as the irreversible cessation of cerebral function due to an identified proximate cause. Reversible causes of coma must be excluded. A properly performed brain death examination establishes the diagnosis in the absence of ancillary tests. The presence of confounders in the brain death examination necessitates ancillary testing. The preferred ancillary tests are cerebral angiography, cerebral scintigraphy, transcranial Doppler, and electroencephalogram (EEG). This chapter describes the clinical evaluation of brain death as per Thomas Jefferson University protocol. Reversible causes of coma are discussed. The brain death examination is described. The indications and proper selection of ancillary testing in brain death evaluation are presented.
Keywords: brain death, apnea test, irreversible coma, brainstem reflexes, cerebral edema
12.1 Definition of Brain Death2,3,4,5
Irreversible cessation of cerebral function due to an identified proximate cause. According to the American Academy of Neurology, brain death is defined as “irreversible loss of function of the brain including the brainstem.”
12.2 Clinical Evaluation2,3,4,5
Clinical evaluation of brain death involves establishing a proximate cause and irreversibility. A proximate cause of brain death can be established through history, examination, and neuroimaging. Irreversibility is established through exclusion of reversible causes and proper performance of the brain death examination.
12.2.1 Establishing the Proximate Cause of Coma
• History, examination, laboratory testing, and neuroimaging should help inform the cause of coma.
• Neuroimaging usually demonstrates structural lesions such as a mass or stroke causing significant midline shift, or profound diffuse cerebral edema.
• Normal neuroimaging may be seen early after certain conditions such as cardiopulmonary arrest. In these cases, repeat neuroimaging may reveal structural lesions.
• Exclude reversible causes prior to clinical examinations (▶ Table 12.1).
12.2.2 Clinical Examination to Establish Irreversibility General Examination
• No awakening; coma (no responsiveness)
• No cerebral motor response to noxious stimuli in all four limbs:
◦ No decerebrate or decorticate posturing
◦ Spinal reflexes such as tendon reflex or triple-flexion may be present2,3,4,6
Table 12.1 Reversible causes of coma
Reversible causes | Clinical evaluations |
Profound hypothermia | Core body temperature should be ≥ 36 °C (96.8 °F). |
Drug intoxication/CNS depressants effect | Ensure there is no history of CNS depressants use. Check drug screen. If prior CNS depressants were used: • Calculate clearance using five times the drug’s half-life (assuming normal hepatic and renal function). • Confirm drug plasma levels below the therapeutic. • Hypothermia and shock liver (i.e., after cardiopulmonary resuscitation for cardiac arrest) may delay drug metabolism; therefore, there should be adequate time prior to initiating the formal examination. • The legal alcohol limit for driving (blood alcohol content 0.08%) is a practical threshold below which an examination to determine brain death could reasonably proceed. |
Neuromuscular blockade | Often patients are paralyzed for procedures or intubation. The presence of a train of four twitches with maximal ulnar nerve stimulation confirms the absence of neuromuscular blockade. |
Severe metabolic disturbance | Rule out profound acid–base, endocrine, or electrolyte disturbances. Note there is no standard for metabolic disturbances. It is physician’s preference. |
Abbreviation: CNS, central nervous system. | |
• No facial movements to noxious stimuli, including blinking
• No spontaneous respiration (patient is not overbreathing on ventilator)
• Confounder: High cervical cord lesion may abolish motor response5
Absence of Cranial Nerve Reflexes
Confounder: Pre-existing cranial neuropathies or neuromuscular disease may render cranial nerve examination unreliable (▶ Table 12.2).
Absence of Respiratory Drive2,3,4,5,7
The apnea test relies on rapidly increasing PaCO2 to > 60 or 20 mm Hg above baseline to trigger the respiratory drive center in the medulla (▶ Table 12.3 and ▶ Table 12.4).
12.3 Ancillary Tests2,3,4,9
In the United States, ancillary tests are not required for the diagnosis of brain death in adults. Ancillary tests are indicated when clinical examination is unreliable or when apnea test cannot be completed (▶ Table 12.5). Existing ancillary tests either measure cerebral blood flow or cerebral electrical activity.
• Preferred tests include cerebral angiography, cerebral scintigraphy, transcranial ultrasound (TCDs), and electroencephalogram (EEG).
• Ancillary tests that are being investigated but are still awaiting validation include cerebral CT angiography and MR angiography, as well as evoked potentials (▶ Table 12.6).2,10
12.4 Legal
In the United States, the Uniform Determination of Death Act mandates the determination of death in accordance with accepted medical standards at the national, regional, or local level, which leads to institutional variations in brain death protocols.1
Check with local laws and hospital policies regarding required number of clinical examinations and requirements regarding medical specialist allowed to perform examination (any physician vs. intensive care physician vs. neurologist vs. neurosurgeon, etc.). The indication of ancillary testing will vary based on hospital policy and availability.
Any patient who had been pronounced brain dead by neurologic criteria should be evaluated for suitability for organ donation (see ▶ Fig. 12.1). Involvement of the organ procurement organization will vary by hospital.
Table 12.2 Evaluation of cranial nerves
Cranial nerve | Examination | Confounders |
CN II, III | Pupil unreactive and midposition or dilated | Pre-existing pupillary abnormalities renders the examination unreliable. Medication may influence pupil size. |
CN III, VI, VIII | Absence of spontaneous ocular movements Absence of oculocephalic reflex (doll’s eyes) • Rapid lateral head turn from midline to 90 degrees on both sides • Ocular movements should be absent Absence of vestibulo-ocular reflex (caloric testing) • Elevate head to 30 degrees • Inspect ear canal prior to testing, ensure that ear canal is patent • Inject 50 mL of ice water into each ear canal • Observe for 1 minute after each irrigation • Allow for 5-minute interval between the irrigation of each ear • Ocular movements should be absent | Chemosis, eyelid edema, and other structural abnormalities may impair ocular movements. Placing the patient in a cervical collar due to traumatic injury will not allow for the oculocephalic reflex to be performed. The lack of vestibulo-ocular reflex would be considered adequate; however, both should be performed when able. Obstructed ear canal may render the caloric testing inaccurate. Inspect ear canal prior to testing. Pre-existing lesions from trauma (e.g., skull base fractures) or medication intoxication may abolish the vestibulo-ocular reflex. |
CN V, VII | Absence of corneal reflex Absence of facial movement to noxious stimulation | No grimace or response to noxious stimulation |
CN IX, X | Absence of gag reflex (both sides) to stimulation of posterior pharynx Absence of cough reflex to stimulation of the trachea through in-line suctioning |
|
12.5 Management of the Brain-Dead Patient for Organ Donation
Maintain physiologic goals to prepare organs for transplantation.17,18,19
• Continuous hemodynamic monitoring
• Placement of arterial and/or central venous catheter may be needed if not already in place
Table 12.3 Evaluation of respiratory drive prerequisites
| Prerequisites for apnea test | Comments |
1 | Core body temperature ≥ 36 °C (96.8 °F) | Carbon dioxide production rate is slowed in hypothermia secondary to decreased metabolic rate.5 |
2 | Pre-oxygenate for a minimum of 10 minutes prior to initiation of the apnea test to target PaO2 > 200 mm Hg | Pre-oxygenation minimizes the risk of early desaturation during the apnea test.5,7,8 |
3 | Euvolemia (or exclusion of hypovolemia) | Minimize the risk of hypotension during the apnea test. |
4 | Systolic pressures > 100 mm Hg | Minimize the risk of hypotension during the apnea test. Vasopressors should be at the bedside during the test if needed. |
5 | PaCO2 within normal range (35–45 mm Hg) | Adjustments to the ventilator may be necessary in order to obtain proper PaCO2. |
6 | No prior evidence of CO2 retention such as history of COPD or severe obesity | Chronic CO2 retention may blunt the respiratory drive stimulated by rapid increase in PaCO2.5,7 If present requires confirmatory test. |
Abbreviation: COPD, chronic obstructive pulmonary disease. | ||
• Central venous pressure (CVP) monitoring with CVP goal of 5 to 10 mm Hg
• Maintain euvolemia
◦ Diabetes insipidus is common after brain herniation and careful attention should be paid to urine output hourly and sodium changes
– Goal is to maintain urine output less than or equal to 300 mL/hour
– Desmopressin (DDVAP) 2 to 4 mcg/day IV or vasopressin 50 units/100 mL (0.5 units/mL). Start between 1 and 5 units/hour and titrate to desired urine output (UOP).
• Maintain temperature between 36 and 38 °C
• Maintain systolic blood pressure (SBP) above 100 mm Hg
• Frequent labs to assess electrolytes and replete as needed
• Thyroid protocol may be applied in certain circumstances:
◦ Levothyroxine 20 mcg IV bolus; followed by infusion 200 mcg/500 mL NSS (0.4 mcg/mL); start at 20 mcg/hour and titrate to SBP > 100 mm Hg (max dose 40 mcg/hour)
◦ Solumedrol 2 grams IV bolus
◦ Dextrose 50% 1 amp (50 mL) IV bolus
Table 12.4 Performance of apnea test
| Apnea test | Comments |
1 | Disconnect ventilator and provide O2 via cannula into the trachea at approximately the level of the carina at a flow rate of 6 LPM. | Baseline blood gas should have CO2 in normal range as described in Table 12.3. |
2 | Observe for respiratory movements. If respiratory movements are present, replace ventilator and abort test. | Bring patient’s gown to the pelvic area exposing the chest and upper abdomen. Note that carotid pulsations in the neck and chest can often be seen and should not be misconstrued for respiratory movement. |
3 | Continue the test for 8 minutes. During that time the SaO2 should be maintained by > 90% and the SBP > 100 mm Hg. Vasopressors should be used to maintain SBP and O2 flow can be increased to continue proper saturation. | If unable to maintain these measures, a blood gas should be drawn and the patient should be placed back on the ventilator. If PaCO2 > 60 or 20 mm Hg above baseline, then the apnea test is considered positive (confirmation of lack of respiratory drive). |
4 | After 8 minutes, draw arterial blood gas. The test can be continued while waiting for the results if the patient remains stable. If the initial blood gas does not meet criteria another gas can be sent. | If the patient is unable to tolerate the full test and/or the blood gas does not show a PaCO2 > 60 or 20 mm Hg above baseline, the test is considered inconclusive. The test can be repeated later if labs and vitals remain stable. |
5 | If the test is unable to be performed or remains inconclusive then an ancillary test should be performed. |
|
Abbreviation: SBP, systolic blood pressure. | ||
Table 12.5 Indications for ancillary testing
| |
1 | Reversible causes cannot be excluded, e.g., severe metabolic disturbance cannot be corrected. |
2 | Clinical examination may be unreliable due to presence of confounders as listed Table 12.4. |
3 | Inability to achieve prerequisite conditions for apnea testing as listed Table 12.4. |
4 | Inability to complete an apnea test. |
5 | Use of extracorporeal membrane oxygenation (ECMO). |
List of ancillary tests | Confirmatory findings | Comments |
Cerebral angiography | Positive study is marked by absence of cerebral perfusion after contrast injection into the common carotid and vertebral artery origins bilaterally from the aorta.2,4,11 | Considered “gold standard” in assessing intracranial blood flow Disadvantages: Invasive procedure, requires two injections at least 20 minutes apart, requires transport, difficult to coordinate in hemodynamically unstable patients, potential for allergic reaction to contrast |
Cerebral scintigraphy Nuclear Medicine Technetium Scan | Confirmatory finding is characterized by the “hollow skull” appearance with visualized flow only in the external carotid circulation.12,13 | Advantages: Includes its long history of use Disadvantages: Lack of availability, time consuming, requires transport, lack of uptake with hypothermia and barbiturates, difficult to coordinate in hemodynamically unstable patients |
EEG | Confirmatory finding is characterized by electrocerebral silence demonstrated by an isoelectric pattern, as well as a lack of reactivity to visual, auditory, and sensory stimuli. | Testing requirements include2,14: • Sensitivity settings of at least 2 μV for a testing duration of at least 30 minutes. • Interelectrode impedances should be under 10,000 Ohms and over 100 Ohms. • Interelectrode distances should be at least 10 cm. Advantages: Performed on bedside, noninvasive, quick Disadvantages: Affected by electrical artifact, susceptible to false positives |
Transcranial Dopplers | Positive findings include oscillating flow which represents reversal of diastolic flow and small systolic peaks in early systole which represent lack of net forward flow.15,16 | Advantages: Safe, noninvasive, inexpensive, performed on bedside Disadvantages: Operator dependence, lack of acoustic window in some patients, bilateral anterior and posterior vessels must be insonated4 Absence of flow is not reliable as it may indicate absence of suitable acoustic window |
Abbreviation: EEG, electroencephalogram. | ||
