Clinical Diagnosis Of Brain Death

With increased reliance on clinical criteria for determining brain death, the approach to this diagnosis should be in a stepwise and systematic fashion. The clinical diagnosis of brain death involves three steps that are outlined below. Adherence to this logical and stepwise process assures that clinical testing is applied to properly selected patients; in pooled series, there have been no survivors among patients fulfilling these criteria.3

Preconditions

The patient must be in deep coma on the ventilator. Structural damage to the brain should be firmly established either clinically (open brain injury) or radio-graphically, usually by computerized tomography (CT) or magnetic resonance imaging (MRI) of the head. Once the cause of coma is established, irreversibility of brain damage must be ascertained. This involves vigorous efforts to treat or remedy the condition with potential reversal or improvement; such therapies may range from evacuation of intracranial hematoma to control of cerebral edema. A certain period of time may be needed on the ventilator to assure irreversibility. Usually a period of 12 hours is adequate; on occasions a longer period may be needed, although at times a period as short as 6 hours may suffice. During this period of observation, the patient should undergo aggressive resuscitation and correction of potential underlying metabolic abnormalities. Restoration of normal arterial oxygenation is essential. Hemodynamic instability can have potentiating effects on findings of brain dysfunction. Therefore, one should aim for a systolic blood pressure greater than 90 mm Hg. An unhurried and disciplined approach is the best safeguard against premature or unjustified diagnosis of brain death.

Exclusions

Drug intoxication can present a serious hindrance to the determination of death. Cessation of brain functions can be caused by barbiturates, benzodiazepines and anesthetics. The influence of anticonvulsants, alcohol and neuromuscular blockade must also be excluded. Other causes of total paralysis and areflexia must also be excluded. In addition to a waiting period until such intoxicants are me-

tabolized, in the absence of identified structural brain damage, confirmatory cerebral blood-flow studies may be essential.

Other conditions that may cause deep coma include hypoglycemia, uremia, hepatic failure, Reye's syndrome, hyponatremia, hyperosmolar coma, hypercalce-mia, panhypopituitarism, myxedema and adrenocortical failure. Before any attempt at determining brain death these conditions must be excluded and remedied if established. Shock (systolic blood pressure less than 90 mm Hg) or low cardiac output may also cause reversible suppression of cerebral function because of reduced cerebral blood flow. Hypothermia (below 90°F/32.2°C) can also mimic brain death and can protect against neurological damage due to hypoxia.

Clinical Examination

Once preconditions and exclusions have been rigorously refuted, clinical testing for absence of brainstem reflexes and total apnea can then be performed and brain death can be established with certainty. The examination is fairly simple and follows a logical and stepwise process looking for total absence of response to various testing maneuvers.

Brainstem Reflexes

There are six brainstem reflexes that need to be tested as part of brain death determination; all reflexes should be absent.

Pupillary response to light

This test should be performed under dim lights or darker surroundings. Both eyes should be closed initially to exclude a consensual response, minimizing the constrictor response. One eye is opened and a bright focused light is directed into the eye being tested. The light should be very bright; old household torches and ophthalmoscopes are not acceptable. The pupil is observed for a minute to allow time for a slow response to become evident. The procedure is then repeated for the opposite eye. The pupils are not invariably dilated during brain death, but fixation with no response to light is mandatory for this diagnosis. One should be aware of drugs that may have been used that may influence pupil size and response to light. In addition, prior ocular surgery and pathology, such as a cataract, may complicate this examination.

Corneal reflexes

During the initial examination, corneal reflexes are tested by touching the cornea with a wisp of cotton wool. If this fails to elicit a response, firmer pressure needs to be applied with sterile throat swab. Both eyelids need to be observed for any response as the cornea is being stimulated.3

Oculo-vestibular reflex (caloric response)

The external auditory canals should be wax-free prior to this test. A soft catheter is inserted into the canal which is slowly irrigated with at least 50 mL of iced water while the eyes are held open by an assistant. The stimulus should not elicit any movement whatsoever in either eye within one minute of completion of the test. Any movement of one or both eyes excludes the diagnosis of brain death. The

■ test cannot be performed as described with a perforated eardrum or with a basal skull fracture and cerebrospinal fluid leak from the auditory meatus. Certain drugs can diminish or abolish this response and these include sedatives, aminoglycosides, anticholinergics, anti epileptics and some chemotherapeutic agents.

Facial motor response

Painful stimuli applied as firm pressure over the supraorbital groove (trigeminal nerve sensation) should not result in any facial grimacing (facial nerve response). A painful stimulus applied to the limbs (pressing a pencil firmly over fingernail or toenail) also should result in no grimacing. However, a peripheral pain stimulus may elicit dramatic and disturbing limb movements called the Lazarus sign.3 These complex movements, which may resemble decerebrate or decorticate posturing, are spinal reflexes that may persist in the absence of all brain functions.

Oculocephalic reflex (doll's eye phenomenon)

The examiner holds the patient's eyes open and turns the head suddenly 90° from the starting position. The head is then turned briskly to the opposite side. Each position should be briefly held while eye position is observed. The reflex is absent when the eyes move with the head and do not move within the orbits. When the reflex is intact, the eyes turn opposite to the side of the movement as if lagging behind and may then turn gradually to the starting position. When testing brainstem reflexes to confirm brain death, any eye movement excludes the diag-nosis.12 Care must be taken in performing this test in patients with suspected cervical spine injury.

Gag reflex and cough reflex

The gag reflex is tested with a tongue depressor by stimulating each side of the oropharynx. The patient is observed for any pharyngeal or palatal movement. Presence or absence of the cough reflex is frequently noted by the nursing staff. A suction catheter is passed down the trachea through the endotracheal or tracheo-stomy tube and the carina is deliberately stimulated. The patient must be observed closely for any cough response or movement of the chest or diaphragm.12

Apnea Testing

Apnea testing seeks to establish lack of respiratory efforts or movements, in the presence of a powerful respiratory stimulus (hypercapnea with PaCO2 > 60 mm Hg) while avoiding hypoxemia during the testing period.

The patient will need to be disconnected from the ventilator for this test. In order to avoid hypoxemia, the patient is ventilated with 100% oxygen for 10 minutes before the apnea test (preoxygenation). When the patient is disconnected from the ventilator 100% oxygen is delivered through a tracheal catheter delivering oxygen at 6 L/min. This method (apneic oxygenation) produces full oxygen saturation for at least 45 minutes in man.3 Arterial CO2 is expected to rise through endogenous metabolism, and should reach or exceed 60 mm Hg before the patient is reconnected to the ventilator. The rate of CO2 rise varies among patients and averages 3.0-3.5 mm Hg/min,3 but can be as high as 6.7 mm Hg/min.4 Ventilation is adjusted during preoxygenation to bring the PaCO2 to 40 mm Hg or greater.16 An end-tidal CO2 monitor may help guide the examiner when to begin the apnea test (ETCO2 > 40 mm Hg) and when to end the test (ETCO2 > 60 mm Hg). If there are no respirations for 3 minutes or the ETCO2 is greater than 60 mm Hg, arterial blood is sent for blood gas determination and the patient is placed back on the ventilator. The PaCO2 must be greater than 60 mm Hg to assure maximal stimulation of the medullary respiratory centers.

A certain degree of respiratory acidosis is expected during this test.14,16 If hypotension or arrhythmias develop during the test, the patient is placed immediately back on the ventilator. One should safeguard against many potential pitfalls during this test. Absence of neuromuscular blockade must be assured. Patients with chronic obstructive pulmonary disease may have CO2 retention and be dependent on hypoxic stimulation for breathing. In the presence of acute lung pathology, patients may remain hypoxemic in spite of maximal oxygenation efforts. Such patients are not good candidates for the apnea test and death determination will require other criteria.12

Repeat testing, as recommended by the President's Commission, is necessary to establish irreversibility of brain death. The interval between examinations is frequently set at 6 hours.7 However, this interval may vary among institutions and may be made shorter for significant structural brain damage and extended for nonstructural brain damage and in children less than 5 years of age. Confirmatory tests of brain death have been utilized in certain instances to shorten this interval especially when hemodynamic stability is imminent. When transplantation of potential organs is being considered, members of the transplant team must not be involved in brain death determination. Finally, brain death examination must be made by two different physicians, both of whom must be qualified to perform this exam. Frequently, these may be neurologists, neurosurgeons, anesthesiologist or intensivists.

Determination of Brain Death in Children

Though controversial, it has generally been assumed that children's brains are more resistant than those of adults to insults leading to death. The report published by the President's Commission7 outlined brain death criteria valid in children older than 5 years. The criteria outlined are useful in determining brain death in infants and children.3 In full term newborns the criteria are applicable 7 days after the neurologic insult.

Determination of brain death should always begin with an accurate clinical history and examination. It is most important to determine the cause of coma and eliminate remediable or reversible conditions. The Task Force guidelines for the determination of brain death are outlined in Table 1.2. In general, more confirmatory tests are desirable in younger children and neonates. The interval between examinations depends on the cause of death and the age of the child. Generally, the interval is longer with patients of a younger age as outlined in Table 1.2. Current knowledge of the epidemiology, diagnosis and management of pediatric brain death has been well summarized in a recent report.3

Table 1.2. Guidelines for the determination of brain death in children

1. History a) Determination of the cause of coma b) Eliminate remediable causes

2. Physical examination criteria a) Coma and apnea b) Absence of brainstem function c) Absence of hypotension (for age) and hypothermia d) Flaccid tone and absence of spontaneous or induced movements e) Examination remains consistent with brain death throughout the observation and testing period

3. Observation period and confirmatory testing a) 7 days to 2 months: two examinations and EEGs at least 48 hours apart b) 2 months to 1 year: two examinations and EEGs at least 24 hours apart. Absence of cerebral blood flow on radionuclide angiography obviates the need for the second examination and EEG.

c) Over 1 year: two examinations at least 12 hours apart, 24 hours for hypoxic-ischemic brain damage. EEG and cerebral flow study not required but may shorten observation period.

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