Brain Death

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Chapter 60 Brain Death

Corey R. Fehnel, MD , Ala Nozari, MD, PhD , Lee H. Schwamm, MD, FAHA

1 What is brain death?

Brain death is a universally accepted medical and legal standard for determining death. A determination of brain death is equivalent to cardiopulmonary death. Brain death is a complete and irreversible loss of brain and brainstem function when other body organ systems may persist. The advent of modern critical care intervention, primarily mechanical ventilation, necessitated a new definition of death because it was now possible to maintain vital functions for extended periods of time. The advent of organ transplantation in the 1950s brought into focus the need for a clear and precise definition of death of the brain in the face of preserved cardiopulmonary function to identify under what circumstances organ removal could occur.

2 When should the diagnosis of brain death be considered?

Active debate continues regarding minimum time of observation before determining brain death. The diagnosis is rarely if ever considered before the first 6 to 24 hours after injury. A variety of toxic and metabolic derangements associated with the onset of critical illness make brain and brainstem function difficult to assess in the hyperacute setting. Patients being considered for brain death uniformly have endotracheal tubes in place and are receiving mechanical ventilation. Sedatives, narcotics, and paralytics used for intubation must be allowed several half-lives of elimination. Pharmacokinetics are often prolonged in patients with multiorgan dysfunction who make up many of these patients.

3 What are the current guidelines for determination of brain death?

Mollaret and Goulon first reported 23 cases of irreversible coma in 1959. This was followed by early standards produced at Harvard Medical School in 1968. The Uniform Determination of Death Act (UDDA) has been adopted as law in most U.S. states. It defines as dead an individual who has sustained either:

image Irreversible cessation of circulatory and respiratory functions, or

image Irreversible cessation of all functions of the entire brain, including the brainstem. A determination of death must be made with accepted medical standards.

The American Academy of Neurology (AAN) practice parameter for determining brain death in adults set forth “accepted medical standards” left open by the UDDA in 1995. In adults, there are no published reports of recovery of neurologic function after a diagnosis of brain death using the criteria presented in the 1995 AAN practice parameter. Brain death should be a diagnostic entity and never used as a prognostic statement about poor chances of recovery.

4 Who can perform a brain death examination?

In most U.S. states, any physician is allowed to determine brain death. Neurologists, neurosurgeons, and intensive care specialists may have specialized expertise. Brain death statutes vary by states within the United States, and certain hospital guidelines may require examiners to have specific expertise. Given the complexity of the examination, the examiner should have extensive experience with the brain death examination and full understanding of accepted standards.

5 What prerequisites must be met before performing a brain death examination?

These are defined in Box 60-1.

Box 60-1 Prerequisites to be Met Before Performing a Brain Death Examination

image Coma, irreversible and cause known. (Glasgow Coma Scale score must be 3)

image Neuroimaging explains coma

image CNS depressant drug effect absent (if indicated, perform toxicology screen; if barbiturates given, serum level should be <10 mcg/mL)

image No evidence of residual paralytics (verify by electrical nerve stimulation if paralytics used)

image Absence of severe acid–base, electrolyte, endocrine abnormality

image Normothermia or mild hypothermia (core temperature >36° C)

image Systolic blood pressure ≥100 mm Hg (pressor agents are okay to use)

image No spontaneous respirations

6 What findings should be present on brain death examination?

These are defined in Box 60-2.

Box 60-2 Findings that Should be Present on Brain Death Examination

image Pupils nonreactive to bright light, corneal reflex absent bilaterally

image Oculocephalic reflex absent (test only if C-spine cleared)

image Oculovestibular reflex absent (cold-water caloric testing)

image No facial movement to noxious stimuli at supraorbital ridge or temporomandibular joints

image Gag reflex absent

image Cough reflex absent to deep tracheal suctioning

image Absence of motor response to noxious stimuli in all four limbs (spinally mediated reflexes are permissible; see question 6)

image Apnea testing (see question 8)

7 Can a patient make movements and still meet criteria for brain death?

Yes. Spinally mediated reflexes and automatisms can be present in the setting of brain death. These movements are often misinterpreted by laypersons as signs of purposeful brain function. Careful neurologic examination can differentiate between reflexive movements and purposeful motor movements.

8 What are the common spinally generated movements?

These are nonpurposeful movements released by lack of descending inhibition of primitive spinal motor reflex pathways.

image Deep-tendon reflexes: For example, Achilles, patellar, and biceps are by definition monosynaptic spinally mediated reflexes and hence often preserved despite brain death.

image Abdominal reflexes: Deviation of the umbilicus toward a light stroking of the skin. Often preserved in brain-dead patients, it may be absent in normal or obese patients.

image Triple flexion response or limb posturing: Stereotyped, nonpurposeful flexion or extension and internal rotation in response to noxious stimulus. (A movement may be purposeful if the limb reliably moves away from, rather than toward, an applied noxious stimulus.)

image Lazarus sign: Considered a variant of opisthotonus. It consists of extensor posturing of the trunk, which may look like chest expansion, simulating a breath. It may be accompanied by raising and crossing of the arms in front of the chest or neck. This sign most often occurs in the setting of apnea testing or disconnection from the ventilator. Hence it may be upsetting for family members or health care providers to witness this reflex.

9 What other movements may exist in brain-dead patients?

Rare reports exist of facial myokymia, transient bilateral finger tremor, repetitive leg movements, ocular microtremor, and cyclic constriction and dilatation in light-fixed pupils. Many patients may retain plantar reflexes, either flexion or transient stimulation-induced toe flexion.

10 How do you perform apnea testing?

Brain-dead patients must demonstrate an absence of respiratory drive. This is defined by an increase in PaCO2 and no discernible respiration. Prerequisites for apnea testing include the following:

image Normal blood pressure (systolic blood pressure >100 mm Hg)

image Normothermia

image Euvolemia

image Eucapnia (PaCO2 35-45 mm Hg)

image Absence of hypoxia

image No prior evidence of CO2 retention (i.e., chronic obstructive pulmonary disease, severe obesity)

See Box 60-3.

Box 60-3 Procedures for Apnea Testing

image Preoxygenate for at least 10 minutes with 100% oxygen to a PaO2 >200 mm Hg.

image Reduce ventilation frequency to 10 breaths per minute to eucapnia.

image Reduce positive end-expiratory pressure (PEEP) to 5 cm H2O (oxygen desaturation with decreasing PEEP may suggest difficulty with apnea testing).

image If pulse oximetry oxygen saturation remains >95%, obtain a baseline blood gas level (PaO2, PaCO2, pH, bicarbonate, base excess).

image Disconnect the patient from the ventilator.

image Preserve oxygenation (e.g., place an insufflation catheter through the endotracheal tube and close to the level of the carina and deliver 100% O2 at 6 L/min).

image Look closely for respiratory movements for 8 to 10 minutes. Respiration is defined as abdominal or chest excursions and may include a brief gasp.

image Abort if systolic blood pressure decreases to <90 mm Hg.

image Abort if oxygen saturation measured by pulse oximetry is <85% for >30 seconds.

image Retry procedure with T-piece, continuous positive airway pressure 10 cm H2O, and 100% O2 12 L/min.

image If no respiratory drive is observed, repeat blood gas analysis (PaO2, PaCO2, pH, bicarbonate, base excess) after approximately 8 minutes. If there is any reason to abort the test because of instability of the patient’s condition, draw an arterial blood gas sample immediately before reconnecting the ventilator.

image If respiratory movements are absent and arterial PaCO2 is ≥60 mm Hg (or 20 mm Hg increase in arterial PCO2 over a baseline normal arterial PCO2), the apnea test result is positive (i.e., supports the clinical diagnosis of brain death).

image If the test is inconclusive but the patient is hemodynamically stable during the procedure, it may be repeated for a longer period of time (10-15 minutes) after the patient is again adequately preoxygenated.

11 Can brain-dead patients falsely trigger delivery of breaths on ventilators?

Yes. Numerous case reports exist of ventilator autocycling in patients who in fact have no respiratory drive. Pressure-triggered ventilation in pressure support modes can be seen with endotracheal tube cuff leak and bronchopleural fistula. Flow-triggered ventilators can be initiated by cardiogenic oscillations. These potential confounders may be accounted for by switching between flow- and pressure-triggered ventilatory modes. In patients who meet all brain death clinical criteria yet continue to ventilate beyond the set ventilator rate, or breathe spontaneously, the patient should be closely observed off the ventilator circuit for evidence of spontaneous breathing. If no spontaneous breathing is present, then formal apnea testing may proceed as described above.

12 Is there a single ancillary test that can confirm brain death?

No. Brain death remains a clinical diagnosis, and no ancillary test can replace a clinical determination of brain death. However, situations occur where the full brain death examination is not possible (e.g., apnea testing due to hemodynamic instability, severe facial trauma, prolonged sedative exposure). In these situations, one additional test may help to confirm the diagnosis. Ordering multiple ancillary tests is not advisable. No data support superiority of one test over another. Multiple tests increase the odds of indeterminate or false-positive results due to artifact.

13 What ancillary tests can help with diagnosing brain death?

Testing can be divided into either cerebral arterial anatomic or flow studies versus studies of brain electrical activity.

image Flow studies

image Cerebral scintigraphy (technetium Tc 99 m exametazime [HMPAO]):
image A noninvasive and safe measure of cerebral blood flow. No patient transport required if a portable gamma camera is available. Sodium pertechnetate technetium 99 m (15–21 mCi per adult) is given by intravenous bolus. A gamma camera then obtains anterior images every 3 seconds for a total of 60 seconds. External carotid flow is either digitally subtracted or excluded by forehead tourniquet. The isotope should be injected within 30 minutes of its reconstitution. Anterior and lateral planar image counts of the head should be obtained immediately, at 30 to 60 minutes, and then at 2 hours. A positive scan reveals no radionuclide localization in the middle cerebral artery, anterior cerebral artery, or basilar artery territories of the cerebral hemispheres (hollow skull phenomenon). Because prior recent craniotomy may cause a false signal of extracranial blood flow to be suspected in the intracranial compartment, it is important to inform the nuclear medicine staff if this has occurred.
image Conventional cerebral angiography:
image Contrast medium is injected in the aortic arch under high pressure to reach both anterior and posterior circulations. A confirmatory test reveals absence of intracerebral filling beyond the carotid or vertebral arteries’ entry to the skull. Patent external carotid (extracranial) circulation should be demonstrated.
image Transcranial Doppler:
image Useful only if a reliable waveform is found. Abnormalities should include either reverberating flow or small systolic peaks in early systole. Complete absence of flow may not be reliable if inadequate insonation windows exist. All traditional cranial windows should be evaluated for flow. The orbital window can be considered to obtain a reliable signal. Prior craniotomy can complicate the study.

image Measures of brain electrical activity

image Electroencephalography (EEG):
image A positive EEG for brain death reveals a lack of reactivity to intense somatosensory or audiovisual stimuli. Isoelectric EEG or the finding of electrocerebral silence may be mimicked by conditions such as hypothermia, systemic hypotension, barbiturates, or other central nervous system (CNS) depressants. Hence the patient should meet the same physiologic and hemodynamic standards during EEG as would be required during the brain death clinical examination.
image Somatosensory evoked potential:
image A peripheral stimulus is given, typically at the median nerve, and a response is measured at the contralateral primary sensory cortex. Absence of transmission measured 20 ms (N20 response) after stimulation suggests brainstem dysfunction.
image Brainstem auditory evoked response:
image May be useful in evaluating patients in whom coma of toxic etiology is suspected (i.e., barbiturate coma). Brainstem and auditory short-latency responses that are absent in brain death but preserved in toxic and metabolic disorders can make this a useful test.

14 Are any blood tests helpful in establishing brain death?

No. Neuron-specific enolase and the glial protein S100 are the most studied. Neither marker is used for brain death determination. Clinical examination remains paramount. In cases where brain death is not being considered, serum markers may aid in determining prognosis after hypoxic ischemic injury.

15 What neuroimaging should be ordered to confirm brain death?

There is no requirement for a particular neuroimaging modality to diagnose brain death. However, a structural cause by brain imaging must be established as prerequisite for brain death diagnosis. Hence computed tomography or magnetic resonance imaging of the head must be consistent with the diagnosis of brain death.

16 How many examinations are required to pronounce a patient brain dead?

Individual states have different guidelines and standards. Many states require only one full brain death examination. In states that require a second independent examination, organ donation rates may be adversely affected without any cases of incorrect brain death diagnoses being discovered.

Key Points Brain Deathimage

1. Brain death is the irreversible loss of both brain and brainstem function from a known cause.

2. Brain death is rarely determined before 6 to 24 hours from neurologic injury.

3. The brain death examination should be performed by an experienced and knowledgeable physician.

4. It is not uncommon for brain-dead patients to make spinally mediated reflexive movements that are not indicative of preserved brain function. Families should be educated about this.

5. Brain death is a clinical diagnosis.

6. Ancillary tests may be helpful in confirming brain death but are not necessary or sufficient to make the diagnosis.

Bibliography

1 American Encephalography Society. Guideline three: minimum technical standards for EEG recording in suspected cerebral death. J Clin Neurophysiol. 1994;11:10–13.

2 Greer D.M., Varelas P.N., Haque S., et al. Variability of brain death determination guidelines in leading US neurologic institutions. Neurology. 2008;70:284–289.

3 Imanaka H., Nishimura M., Takeuchi M., et al. Autotriggering caused by cardiogenic oscillation during flow triggered mechanical ventilation. Crit Care Med. 2000;28:402–407.

4 Lustbader D., O’Hara D., Wijdicks E.F.M., et al. Second brain death examination may negatively affect organ donation. Neurology. 2011;76:119–124.

5 McGee W.T., Mailloux P. Ventilator autocycling and delayed recognition of brain death. Neurocrit Care. 2011;14:267–271.

6 Practice parameters for determining brain death in adults (summary statement): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 1995;45:1012–1014.

7 Wijdicks E.F.M., Varelas P., Gronseth G., et al. Evidence based guideline update: determining brain death in adults. Neurology. 2010;74:1911–1918.

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