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.1Legal 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 Hospital 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.
brain death – apnea test – irreversible coma – brainstem reflexes – cerebral edema
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.”
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).
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.
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
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).
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
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).
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
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.
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