Page 1198 - Hall et al (2015) Principles of Critical Care-McGraw-Hill

CHAPTER 88: Coma, Persistent Vegetative State, and Brain Death 835

hemorrhages, and infarcts) accounted for less than one-third, while first day after CPR predicted poor outcome. None of 52 patients
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subarachnoid hemorrhage, meningitis, and encephalitis accounted recovered, and only 3 regained consciousness. No patient who lacked
for another 5%. The majority of cases were the consequence of exog- corneal reflexes after the first day ever regained consciousness. After
1
enous (drug overdose) and endogenous (metabolic) intoxications and 3 days, a lack of motor responses or absent pupillary and corneal
hypoxia. reflexes predicted poor outcome in all patients (PVS or severe disability).
When the examination leads to the conclusion that the central neur- Certain early signs were associated with good recovery. At 1 day, the
axis is affected at multiple levels or diffusely, the etiology is most likely following signs were associated with at least a 50% chance of regaining
of toxic-metabolic origin. Metabolic causes and toxic ingestions account independent function: verbal responses of any type, purposeful eye
for the largest number of patients with depressed consciousness. The movements or motor responses, normal ocular reflexes, and response
single most important sign distinguishing metabolic from structural to verbal commands.
coma is the presence of the pupillary light response. 21,22 In metabolic The cause of hypoxic-ischemic encephalopathy is not a simple
coma, confusion and stupor commonly precede symmetrical motor response to circulatory arrest. Evidence has accumulated that the brain
signs. Asterixis, myoclonus, tremor, and seizures are common. Central can tolerate a longer period of ischemia than previously thought if
hyperventilation occurs frequently. certain conditions are met. After a 10-minute period of global brain
Supratentorial mass lesions causing compression or displacement of ischemia, if the circulation is adequately restored, there is marked
the upper brain stem usually present with focal neurologic signs that are hyperemia, subsequently followed by a delayed, progressive fall in
asymmetrical. Neurologic dysfunction usually progresses in a rostral- cerebral blood flow to levels considerably below prearrest values. In
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caudal fashion, and the examination usually points to one anatomic area some cases, cerebral metabolism remains high in the face of low blood
of the brain stem at a given point in time. flow, a situation that worsens the effects of the initial ischemia. There
Subtentorial masses or destructive lesions causing coma usually are is experimental evidence suggesting that if cerebral blood flow can
associated with brain stem dysfunction or sudden onset of coma. Brain be maintained at a hyperemic level, the brain can recover. It appears
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stem signs always precede or accompany the onset of coma and always that some of the damage is due to a lack of adequate reperfusion after
include abnormalities of eye movements. Cranial nerve palsies are usu- resuscitation, the no-reflow phenomenon. The mechanisms of delayed
ally present. Irregular respiratory patterns are common and usually hypoperfusion and no-reflow are poorly understood but may be due to
appear at the onset of coma. diffuse arterial spasm, calcium influx, vasoconstrictor prostaglandins,
■ SELECTED CAUSES OF COMA and intravascular coagulation. Even when adenosine triphosphate levels
recover promptly as evidence of successful reperfusion, neurons show
Cerebrovascular diseases, electrolyte disorders, head trauma and drug progressive morphologic damage, suggesting that injury may be in
intoxications are reviewed in Chaps. 84, 99, 118, and 124. large part due to reperfusion rather than ischemia, per se. Persistently
Hypoxic-ischemic encephalopathy is the most common and most impaired protein synthesis following reperfusion may prevent the cell
devastating cause of coma in most critical care units. The term is a from repairing damage. Apoptotic pathways appear to be activated,
pathologic diagnosis that refers to the effects of various degrees of triggering neuronal death. In addition, other biochemical changes are
global brain ischemia, sometimes complicated by hypoxemia. Cardiac initiated after ischemia that can cause delayed neuronal injury: elevation
arrest is the most common cause of global brain ischemia. 23-26 Each year of intracellular calcium, release of neurotoxic excitatory amino acids
there are 160,000 attempts at cardiac resuscitation, and only 70,000 are (glutamate and aspartate), reoxygenation injury from superoxide forma-
successful. As a result of permanent neurologic deficits of the early tion, and brain lactic acidosis. 35,36
survivors, 30% leave the hospital, but only 10% resume their former The pathophysiology of altered cerebral blood flow and metabolism
lifestyle. Other important causes of global brain ischemia include following CPR is complex and points to several windows of opportunity
severe hypotension, cardiac failure, strangulation, cardiopulmonary where the devastating effects of global brain ischemia may be amelio-
bypass, status epilepticus, diffuse cerebral arteriosclerosis, increased rated. Free radical scavengers and excitatory amino acid antagonists
intracranial pressure, cerebral arterial spasm, closed head trauma, and have also been considered potentially useful to improve outcome after
hyperviscosity. brain injury. To date, despite some promise in animal models of central
The degree of neuronal injury in this condition depends on the degree nervous system (CNS) injury, these agents have not shown benefits
of mismatch between metabolic demand and delivery of substrate in clinical trials. Animal studies show some benefit from nitric oxide
( oxygen and glucose) to the brain. For example, the brain can tolerate release pathways. The mechanism of benefit from induced hypothermia
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45 minutes of total circulatory arrest with complete recovery if hypo- following anoxic brain injury is unknown, and this topic is further con-
thermia to 18°C is induced. Conversely, a brain with metabolic activity sidered in Chap. 26.
that is eightfold above normal during status epilepticus will sustain neu-
ronal damage after 2 hours, even with perfect maintenance of arterial ■
oxygenation, glucose, and blood pressure. DIAGNOSTIC PROCEDURES IN EVALUATING THE COMATOSE PATIENT
The neurologic syndromes that follow cardiac arrest and resuscitation Keeping in mind the preceding differential diagnosis for states of coma,
are diverse and depend on the duration of ischemia (time from arrest the sequence of diagnostic studies becomes clear. Rapid identification of
to successful cardiopulmonary resuscitation [CPR]), adequacy of CPR, metabolic or toxic causes of coma is determined by laboratory testing
underlying cardiovascular disease, degree of arterial atherosclerosis, of blood, urine, and cerebrospinal fluid (CSF). A list of acute metabolic
adequacy of postresuscitation cerebral perfusion. Patients in a coma less derangements that may cause coma is provided in Table 88-7. Focal
than 12 hours after resuscitation usually make an excellent recovery. neurologic derangements causing coma are listed in Table 88-8. A list of
Those in a coma more than 12 hours have permanent neurologic deficits recommended laboratory tests is listed in Table 88-9.
due to focal or multifocal infarcts of the cerebral cortex in arterial border A variety of diagnostic tests are useful in evaluating comatose
zones. They may be left with permanent amnesia, dementia, bibrachial patients. Computed tomographic (CT) scanning of the head is useful
or quadriparesis, cortical blindness, seizures, myoclonus, and ataxia. 28,29 in detecting neurological lesions causing coma. It is utilized mainly to
If the coma persists for 1 week, recovery is rare, and most patients detect focal brain disease, being most sensitive for diagnosing acute
remain in a PVS due to laminar necrosis of the cerebral cortex with hemorrhage, which appears as an area of increased density. Conversely,
preservation of brain stem function. 30,31 infarction shows up as an area of lucency, subtly apparent at least several
Early in the course of hypoxic-ischemic encephalopathy, specific hours after onset. Neoplasms and abscesses are lucent on CT but often
neurologic signs can predict outcome with a high degree of reliability. accumulate IV contrast material due to alterations in the blood-brain
In a study of 210 patients, the absence of pupillary responses on the barrier. CT is the test of choice in acute trauma because it provides

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