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Coma, Vegetative State, and Brain Death
Coma
Clinical Vignette
A 57-year-old man with coronary artery disease develops severe chest pain and heaviness on exertion, then loses consciousness while working in the garden with his wife. Emergency Medical Services is called immediately and arrives at the scene within minutes. The man is found pale, unresponsive, and flaccid. The systolic blood pressure is low, approximately 70–85 mm Hg, and he is found to be in ventricular tachycardia, but he promptly reverts to sinus rhythm with cardiac defibrillation. In the hospital, he is found to have roving eye movements and does not open his eyes even to noxious stimulus. He makes incomprehensible sounds but does not clearly produce or understand language, and he grimaces and withdraws his limbs to painful stimuli. Over a 3-day period, he becomes awake and conversant but has poor short-term memory and ataxia. These symptoms gradually resolve over a 3-week period.
Clinical Vignette
A 76-year-old man is found unconscious in bed at home. His wife informs the emergency physician that he has a history of prostate cancer but no risk factors for vascular disease. She denies knowledge of any recent head injury. He is totally unresponsive to verbal and painful stimuli. Neurologic examination shows he is comatose with pinpoint pupils. Eye movements to doll's-eyes maneuvers are full and conjugate, and cold caloric stimulation of the ear canals produces ipsilateral tonic deviation of the eyes without nystagmus. There are bilateral withdrawal responses of his extremities to noxious stimuli and bilateral Babinski signs.
Intravenous administration of 0.4 mg naloxone produces dramatic change, with full awakening within a few minutes. Results of a brain computed tomography (CT) are normal, confirming that there is no evidence of intracerebral, subarachnoid, or subdural hemorrhage, cerebral infarction, or mass lesions. When asked about narcotic use, the patient states that he was no longer able to tolerate the pain of metastatic prostate cancer; he had taken an overdose of an opioid analgesic.
The first vignette reflects a common clinical presentation for anoxic-ischemic brain injury secondary to cardiac arrest. The chance of good neurologic recovery depends on a number of factors that include age, extent or duration of brain ischemia, effective targeted temperature management (when appropriate), and the severity of coexisting medical conditions. A detailed history, review of in-field records, and serial neurologic examinations are the essential first steps in understanding the extent and mechanism of brain injury, identifying potential ingestions or exposures, and determining the need for further workup.
The second vignette illustrates the classic case of a “toxic-metabolic” coma. Despite profound unresponsiveness and miotic pupils, the patient's neurologic examination demonstrates retained brainstem reflexes, and CT results are normal. Although pontine hemorrhage is often suspected in a comatose septuagenarian with pinpoint pupils, intact reflexive eye movement strongly indicates a metabolic cause. Reversal of an opiate overdose with an antagonist such as naloxone can result in rapid neurologic recovery. However, more severe overdoses may be associated with respiratory suppression leading to anoxic brain injury or death.
Consciousness is the state of awareness of internal and external stimuli and is manifested by the ability to react to these stimuli through thought or by directed physical movement. Coma is a lack of consciousness characterized by the absence of wakefulness and awareness of surroundings. Full consciousness can be disrupted without total loss of arousal or wakefulness. Varying degrees of consciousness can be approximately delineated by the response to a particular stimulus, and terms such as drowsiness, obtundation, or stupor are sometimes used as a reflection of severity. However, the most useful means to communicate a state of altered level of consciousness remains the accurate description of patient behavior and reactions to specific stimuli. For example, it is preferable to indicate that a patient opens his or her eyes to voice but does not maintain eye opening and responds only after repeated questioning than to say that the patient is obtunded. Nevertheless, defining terms are often used as descriptors of a patient's level of consciousness, even though they tend to be imprecise. Lethargy consists of significant drowsiness in which a mild to moderate stimulus is required to arouse a patient's response to questions or commands. Obtundation describes a condition in which repeated stimuli are needed to draw the patients’ attention back to a task. Stupor is a state of more severely depressed level of consciousness in which wakefulness and minimal interaction with the examiner can be achieved only for brief intervals by repeated and/or noxious stimulation.
Delirium is a term used to describe a disorder of attention and orientation that may occur in association with an altered level of consciousness. It is an acute confusional state with a disturbance in attention, awareness, and cognition (see Chapter 26 ). This state develops over a short period of time, typically hours to days, and most often fluctuates in severity throughout the day. Delirium may be divided into hyperactive, hypoactive, or mixed subtypes depending on the clinical features. Hyperactive delirium is characterized by sympathetic nervous system overactivity with attention marred by hyperexcitability, tachycardia, perspiration, hypertension, hallucinations, and disturbance of the normal sleep-wake cycle. Hypoactive delirium manifests with decreased responsiveness and apathy. Mixed delirium involves a combination of features that are both hyperactive and hypoactive. Delirium is common in hospitalized individuals and is associated with prolonged hospitalization, increased healthcare costs, and mortality.
Because the examining physician can only infer thought from patients’ actions (e.g., speech or movement), a reliable and reproducible physical examination is essential in evaluating the patient with altered consciousness. The neurologist must make every effort to establish the presence or absence of a directed nonreflexive response and judge its quality. Discerning whether there is a disorder of consciousness or an inability to respond is sometimes challenging. For example, in basilar occlusion with infarction of the posterior circulation but preserved bihemispheric function, a “locked-in” syndrome occurs ( Fig. 13.1 ). In this condition, the patient will seemingly have no directed response to stimuli because disruption of the corticospinal and corticobulbar tracts results in severe quadriplegia and facial weakness. Yet on close examination, blinks or vertical eye movements may be preserved, and this patient may blink or move his or her eyes in an exact fashion to instructions, demonstrating full awareness and intact cognition. Similarly, in patients with severe acute polyneuropathies such as Guillain-Barré syndrome, consciousness is preserved but difficult to assess and quantify secondary to profound generalized weakness.
The Glasgow Coma Scale assesses and quantifies the degree of consciousness across three measures: eye opening, verbal response, and motor response. It is the most common scoring system used in prehospital and acute care settings as a fast and reliable way to describe level of consciousness and prognosticate, particularly in traumatic brain injury. Those with a Glasgow Coma Scale score of 3–8 are defined as having a severe injury ( Fig. 13.2 ).
The prevalence of the different etiologies for coma varies depending on the age and demographics of a patient. Overall, trauma, stroke, diffuse anoxic-ischemic brain insult (secondary to cardiorespiratory arrest), and intoxicants are the leading mechanisms. Infections, seizures, and metabolic-endocrine disorders account for many of the remaining cases of coma ( Fig. 13.3 ).
States that affect cognition and attention without affecting wakefulness such as the dementias (characterized by progressive cognitive deterioration) and structural brain lesions such as strokes or tumors when they cause focal or regional cerebral dysfunction do not fit within the designation of coma. Sleep is also distinct from coma because it is a normal patterned physiologic disconnection of the cortex from external stimuli (see Chapter 24 ).
Evaluation and Treatment of the Comatose Patient
The initial evaluation of a patient in coma must occur simultaneously with its management. Any delay in treatment while waiting to determine the exact cause should be avoided. Clearing the airway and ensuring adequate ventilation and oxygenation with a bag-valve mask or intubation, if needed, must be addressed immediately. Management of severe hypotension must be prompt, especially in suspected cases of increased intracranial pressure (ICP). Hemodynamic collapse should never be attributed to an intracranial process, without rapid and thorough evaluation and treatment of cardiac or circulatory causes. These form the “ABCs of coma management”: airway, breathing, and circulation ( Fig. 13.4 ). Immobilizing the neck until a cervical spine injury is excluded and performing a focused assessment with sonography for trauma (FAST) and CT scan of the cervical spine is also important in cases of suspected head or neck trauma (see Chapter 20 ).
Emergent evaluation of patients in coma of indeterminate etiology requires the following blood studies: a complete blood count, fingerstick glucose level, serum chemistry, urine and serum toxicology screens, ethanol level, liver profile, thyroid function tests, arterial blood gas, and blood cultures. Creatine kinase and troponin measurements, in conjunction with electrocardiography, are important for excluding myocardial infarction and transient cardiac arrest. Drug levels may be crucial in cases of suspected ingestion or overdose, including acetaminophen, lithium, or anticonvulsants based on available clinical history. Electroencephalography (EEG) can help to identify patients with nonconvulsive status epilepticus. Suspicion should be high for alternative causes of coma such as carbon monoxide poisoning in the proper clinical context, which may require additional laboratory tests.
Among the most common immediately treatable causes of coma are hypoglycemia and narcotic intoxication. These should be considered early and managed promptly, once oxygenation and hemodynamic status are stable. Infusion of 100 mg thiamine must precede the infusion of 50 mL of 50% dextrose in water as a precaution against Wernicke encephalopathy. This is postulated to be due to osmotic or metabolic damage to periventricular structures, such as the mammillary bodies and the medial thalamus ( Fig. 13.5 ). When a narcotics overdose is suspected, such as in comatose patients with miotic pupils, intravenous (IV) naloxone, a central opioid antagonist, can improve the level of consciousness within minutes. Repeated doses may be needed to maintain wakefulness and reverse respiratory depression. Caution should be exercised in those with long-standing known or suspected opioid dependency because abrupt or complete reversal of opioid effects by repeated doses may precipitate an acute withdrawal state.
Administration of flumazenil, a pure benzodiazepine antagonist (0.2 mg IV), given one to five times, can improve the mental state and reverse respiratory depression in benzodiazepine overdose. It must be used cautiously in those with a history of long-term benzodiazepine use or dependency because it can precipitate seizures. It should generally be avoided in patients with epilepsy and those at risk for seizures.
Urgent IV broad-spectrum antimicrobial coverage is indicated for patients presenting with coma and fever because early empiric treatment is crucial to improve clinical outcomes for meningitis and septicemia (see Chapter 44 ). In patients with altered consciousness, lumbar puncture should be performed only after brain imaging has excluded lesions that could lead to herniation, but imaging must not delay antibiotic administration.
Assessment of the comatose patient should include examination of the skin. Rashes may indicate streptococcal or staphylococcal meningitis, bacterial endocarditis, or systemic lupus erythematosus. Purpura may indicate meningococcal meningitis, a bleeding diathesis, or aspirin intoxication. Skin dryness suggests anticholinergic or barbiturate overdose, whereas excessive perspiration indicates cholinergic poisoning, hypoglycemia, or other causes of sympathetic overactivity. Dark pigmentary changes in the axillary and genital areas suggest adrenal insufficiency, whereas doughy pale skin is typical of myxedema. Renal failure may present with urea salt crystal skin condensations or “urea frost.” Facial or basal skull fractures often cause ecchymosis around the eyes (raccoon eyes or panda bear sign) or in the mastoid area (Battle sign), respectively. Extremities must be examined for needle and track marks that indicate IV drug use or subcutaneous self-injection.
The patient's breath may be uremic, fruity as in ketoacidosis, or have the musty fishy odor of hepatic failure. Fever may indicate meningitis or encephalitis but also occurs with sympathomimetic or tricyclic (anticholinergic) overdose or drug or alcohol withdrawal. Occasionally a low-grade fever can occur with subarachnoid hemorrhage or brainstem lesions. Cardiovascular examination in a febrile comatose patient should include investigation for stigmata of endocarditis such as a heart murmur.
A cautious and thorough neurologic assessment should be performed in any patient with coma. Particular attention should be paid to pupillary responses and other brainstem reflexes. Fundoscopic examination or ocular ultrasound may suggest papilledema indicative of intracranial hypertension. Motor examination (including noxious stimulation) may elicit signs of decorticate (flexor) or decerebrate (extensor) posturing and assist further in localization. In addition, it is important to assess for meningismus.
Focal neurologic signs on initial examination may implicate a structural lesion as the cause of coma and should be followed closely for signs of evolving herniation concurrently as urgent brain imaging is being obtained. Other causes of focal presentation are compensated old brain injuries clinically reemerging as a result of seizures, toxins, or metabolic derangements. However, metabolic disorders including nonketotic hyperosmolar hyperglycemia, hypoglycemia, and hepatic coma may cause focal seizures or lateralizing neurologic signs without focal brain lesions. Evolving signs of increased ICP or herniation must be treated promptly regardless of cause; additional neurologic injury may occur in waiting for brain CT results or other tests.
EEG is often helpful in evaluating patients with altered consciousness or coma. An abnormal EEG tracing makes psychogenic coma unlikely. EEG detects nonconvulsive status epilepticus, which can present without a history of epilepsy. Although nonspecific, diffuse EEG background slowing correlates with metabolic derangements and focal slowing with localized structural brain disease. Hepatic and other metabolic encephalopathies may show triphasic waves ( Fig. 13.6 ). In herpes simplex encephalitis, periodic lateralized epileptiform temporal lobe discharges are often seen and support the clinical diagnosis. In addition, when a basis pontis lesion with the “locked-in syndrome” is suspected, a normal EEG background rhythm shows that the patient is alert despite limited or no obvious response to stimuli (alpha coma pattern).
Neurologic Assessment
Clinical Vignette
A 76-year-old man is found lying on the floor at home. Examination in the emergency department demonstrates a left hemiplegia, with conjugate eye deviation to the right. He is awake, calm, and able to answer questions but with a left homonymous visual field deficit, dysarthria, and a left facial droop. He has no movement in the left arm or leg, and when his left hand is placed in his right visual field, he does not recognize it as his own. In spite of his hemiplegia, he denies having any difficulties with his limbs. Brain CT demonstrates a large right middle cerebral artery and anterior cerebral artery territory stroke. In the next hour, the patient becomes obtunded and progressively less responsive to external stimulation. Repeat brain CT scan shows a large intraparenchymal hemorrhage within the infarct territory and a right cerebral shift across the falx cerebri and downward through the cerebellar tentorium, with compression of the midbrain.
The patient undergoes endotracheal intubation due to his depressed level of consciousness and inability to protect his airway. Soon afterward, he cannot be aroused. On exam, he has right-sided flexed arm posturing and left-sided extension, with tonic leg extension and plantar flexion. His pupils are irregular and sluggishly reactive to light. Vestibuloocular reflex is absent. His examination does not improve with administration of hypertonic saline, mannitol, or hyperventilation. An emergency, right decompressive hemicraniectomy is performed; however, he remains comatose and the family choses to transition to comfort care. He dies hours after mechanical ventilation is discontinued.
Rostrocaudal Signs of Brain Compromise
As pressure from a hemispheric lesion increases, patients gradually move from being easily roused, but inattentive, to sleepy and unable to maintain wakefulness, then to coma. The ascending reticular formation, stimulated by sensory input, mediates arousal and consciousness to the cortex via the thalamic nuclei. Lesions that cause coma are at one of three levels along the neuraxis: bilateral cerebral cortex, the thalami, or the upper brainstem. The classic concept of coma stages produced by brain mass lesions pertains to a hemispheric process that worsens until it ultimately causes “rostrocaudal” deterioration of function from the hemispheres into the medulla. Although these stages rarely manifest symmetrically or in a strict and clearly delineated sequential pattern, this paradigm remains useful for evaluating patients with hemispheric lesions and deterioration of their neurologic examination (such as the patient in the vignette) and to conceptualize the associated functional brainstem neuroanatomy. In addition to the level of consciousness, important physical examination elements include pupillary size and reactivity, reflexive eye movements, limb posturing, and breathing pattern ( Fig. 13.7 ).
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