Coma, Disorders of Consciousness, and Brain Death

Epidemiology

The most common causes of coma include trauma, toxic-metabolic, global anoxia, and lesions that result in herniation and compression of the brain stem ( Table 373-2 ).

Pathobiology

Wakefulness arises from the ascending reticular activating system, which is a neural network that originates in the central tegmentum of the pons and midbrain in the rostral brain stem, receiving input at each level as it ascends into the central basal forebrain, thalami, and cerebral cortices. Arousal can be affected by damage or dysfunction anywhere along these pathways, but thalamic and cortical neurons are more susceptible to damage because of their higher metabolic demands. The classic scenario is a global anoxic insult from a cardiac arrest, which selectively injures specific cortical laminae, the thalami, basal ganglia, and the hippocampus owing to their high oxygen demands and relatively high metabolic activity. By comparison, phylogenetically older and less metabolically demanding neurons of the ascending reticular activating system are relatively spared. This selective injury helps explain the unresponsive wakefulness syndrome (also called the vegetative state), which is characterized by wakefulness without awareness.

Coma can be caused by (1) structural damage as a result of trauma, edema, inflammation, ischemia, hemorrhage, or mass lesions or (2) diffuse toxic and/or metabolic effects on neurons. Structural lesions can affect the ascending reticular activating system directly by neuronal damage or indirectly by extrinsic pressure or displacement, thereby causing ischemia and/or edema. Metabolic and toxic encephalopathies diffusely affect all brain neurons but preferentially the metabolically sensitive neurons in the cortex and thalamus. However, several acute metabolic derangements or toxicities can also cause structural brain injury by altering blood pressure or oxygenation (e.g., opioid toxicity [ Chapter 365 ]), brain edema (e.g., acute hepatic failure [ Chapter 140 ] with hyperammonemia), or acute demyelination (e.g., central pontine myelinolysis owing to rapid osmolar shifting, such as seen in rapid correction of chronic hyponatremia [ Chapter 102 ]).

Structural lesions causing coma typically present with clinically recognizable herniation syndromes, in which shifts in intracranial pressure produce caudal and lateral displacement and ischemia of the midbrain and medial temporal lobe through the tentorial incisura. Herniation results in dysfunction of cranial nerves (pupillary dilation followed by more complete third nerve palsy), breathing, and motor systems. Most commonly, central herniation occurs with global events such as meningoencephalitis ( Chapter 383 ), global anoxic brain injury, massive brain swelling from toxic-metabolic insults, or hydrocephalus. Uncal herniation results from rapidly expanding and laterally placed lesions that trap the ipsilateral oculomotor nerve against the uncus of the temporal lobe. Lateral displacement of brain structures can match or exceed downward displacement. Brain stem compression can also result from structural lesions in the posterior fossa. The ascending reticular activating system also can be damaged directly by primary brain stem injuries, such as from hemorrhage or infarction, or indirectly by downward-directed pressure produced by hemispheric mass lesions, such as from brain trauma ( Chapter 368 ), neoplasms ( Chapter 175 ), abscesses ( Chapter 382 ), hemorrhages ( Chapter 377 ), or large infarctions ( Chapter 376 ).

Encephalopathy in the setting of metabolic disturbances results from perturbation of the neuronal microenvironment by altering the precise metabolic conditions necessary for normal neuronal conduction and excitability. These disturbances can occur due to changes in blood flow, oxygen delivery, glucose concentration, temperature (hyperthermia or hypothermia), electrolyte concentrations, and intracranial pressure. Other causes include meningitis, seizures, and organ failure. The severity of the insult matches the impact: more profound metabolic insults cause greater encephalopathy. The rapidity of onset also is an important factor. Sudden metabolic changes, such as in serum sodium concentration, may result in seizures and coma, whereas a slow decline, even to a low level, may cause little clinical impact ( Chapter 102 ). Toxic encephalopathies, with indistinguishable clinical manifestations, can result from exogenous poisoning with illicit (e.g., opiates, hallucinogenics) or therapeutic (e.g., antidepressants, anticholinergics) substances, or endogenous toxins that result from renal or hepatic failure. Acute meningoencephalitis, with inflammation of both the meninges and cerebrum, causes coma by direct inflammation, vascular insults, cerebral edema, and hydrocephalus.

Clinical Manifestations

A patient in coma displays neither wakefulness nor awareness. There is no purposeful response to noxious stimulation. Reflexive posturing may be present. The eyes are typically closed, except in the rare situation of “eyes open coma, ” which occasionally follows cardiac arrest ( Chapter 50 ) with global anoxic brain injury. The eyes do not open in response to noxious stimulation. The patient does not express any interpretable sounds reflective of responsiveness, only sounds associated with attempts at breathing.

Coma should be differentiated from stupor, in which the patient is able to be aroused temporarily during vigorous stimulation but then immediately resumes unresponsiveness once stimulation is stopped. However, this differentiation serves only to distinguish levels of brain stem dysfunction and does not imply reversibility, which depends on the underlying etiology. The pattern of brain stem dysfunction usefully localizes the anatomic extent of a structural injury or impingement.

Diagnosis

Rapid diagnosis of the etiology of coma is crucial for expeditious and targeted treatment ( Table 373-3 ). A detailed history, physical examination, laboratory testing, and neuroimaging should be performed in a parallel manner. Immediate attention should be focused on whether the patient has signs of trauma (cranial or cervical), meningitis (fever, nuchal rigidity), drug intoxication (which may be rapidly reversed), seizures (including nonconvulsive status epilepticus, which may manifest only with eye deviation), or focal findings suggestive of a mass lesion or vascular event.

The history should focus on any witnessed events or recent history according to others, such as feeling unwell or suffering any trauma or medication changes. Information should be obtained regarding any preceding headache, vomiting, confusional state, prescription and illicit drug use, alcohol use, fever, metabolic disturbances (including a history of diabetes), seizure history, abnormal recent behavior, and preexisting medical conditions, particularly atrial fibrillation or prior neurologic events (e.g., stroke, hemorrhage).

The general physical examination should include assessment of vital signs, otoscopy, funduscopic examination, and a search for physical signs of head trauma, nuchal rigidity, or needle track marks. The respiratory rate and pattern should be carefully noted ( Table 373-4 ). Cheyne-Stokes respiration is a periodic breathing pattern whose amplitude forms a sine wave, with 5- to 45-second periods of apnea alternating with periods of hyperpnea. It can be seen in patients with primary cardiac/respiratory disorders or in patients with metabolic encephalopathy, and it is typically reversible by treating the underlying cause. Central neurogenic hyperventilation consists of continuous hyperpnea and tachypnea that leads to a pure respiratory alkalosis; it occurs with lesions of the rostral brain stem tegmentum at the level of the midbrain, or damage to the central pons. Kussmaul respiration, which consists of rapid deep breathing, is seen as a compensatory mechanism in the setting of severe metabolic acidosis, often with hyperglycemia ( Chapter 210 ). Ataxic or irregular breathing patterns, with or without apneic periods, are associated with lower brain stem dysfunction and can represent an agonal pattern.

A detailed neurologic examination is important to discern if there are localizing signs that may point to a structural etiology to assess the level of brain function and to look for evidence of trauma or drug use.

The patient’s limbs should be uncovered to view any movements, either spontaneously or in response to stimulation. Responsiveness should be checked by increasingly noxious stimulation, starting with loud auditory stimulation. Noxious physical stimulation should include not only stimulation of the extremities (typically starting with pressure on the nail bed), but also on the cranium, including the supraorbital ridge and temporomandibular joint. Only when adequate stimulation has been provided can one say that the patient is truly unresponsive and comatose.