Chapter 17. Coma

See Figure 17–1.

General Considerations

Coma is defined as the total absence of arousal and awareness lasting at least 1 hour associated with injury or functional disruption of the ascending reticular activating system in the brainstem or bilateral cortical structures. Comatose patients demonstrate no eye opening, speech, or spontaneous movements, and motor activity elicited by painful stimuli (if present) is abnormal or reflexive rather than purposeful. Coma must be differentiated from other pathologic changes in consciousness such as brain death, vegetative state, and delirium, although it may be difficult to do so in the emergency department.

Initial Management

Initial management of the comatose patient involves the same steps needed to manage any critically ill patient presenting to the emergency department. Immediate assessment and support of airway, breathing, and circulation should be performed before efforts to diagnose or address specific causes of coma are undertaken, with the caveat that consideration may be given to postponing intubation until administration of empiric therapy for coma. Empiric therapy, often abbreviated by the acronym “D.O.N.T.” consists of IV dextrose, supplemental oxygen, IV naloxone, and thiamine. Dextrose (50 mL of 50% solution in adults) reverses coma secondary to hypoglycemia and is indicated if rapid testing of blood glucose is unavailable. Oxygen therapy should be initiated to immediately correct possible hypoxemic induced coma. Naloxone (0.4–2.0 mg IV) rapidly reverses coma and respiratory depression secondary to narcotic overdose but because of short half-life, multiple doses may be required. Thiamine (100 mg IV) is commonly given along with dextrose to avoid precipitating Wernicke encephalopathy in predisposed patients. Flumazenil (0.2 mg/min IV) specifically antagonizes benzodiazepines but is not routinely given empirically as it may precipitate seizures that are then refractory to benzodiazepines. It may be indicated in iatrogenic coma secondary to excess benzodiazepine administration.

If coma persists following the administration of naloxone and dextrose, definitive management of airway and breathing should be considered. IV access with two large-bore IVs should be obtained and blood pressure (especially hypotension) managed aggressively. A complete set of vital signs, including temperature and pulse oximetry, is essential to avoid missing coma complicated by severe hypo- or hyperthermia and hypoxia. Cervical spine immobilization should be maintained if there is any suspicion of trauma. A focused physical examination should be performed to evaluate for potential precipitating factors (evidence of drug use, systemic trauma, etc). Obtaining additional history from friends, relatives, bystanders, and EMS personnel is essential.

Neurologic Assessment

Neurologic assessment in comatose patients is of paramount importance, and a structured evaluation should be conducted as soon as possible once immediate threats to life have been addressed. Level of consciousness, cranial nerve examination, and motor examination should be performed. Lateralizing deficits and a rostrocaudal progression of brainstem dysfunction are seen with structural lesions, while involuntary movements are suggestive of a metabolic cause of coma. Although originally developed for traumatic brain injury, the Glasgow Coma Scale (GCS) has been shown to have predictive value in many different types of coma. Both total and component (eye, verbal, motor) scores should be documented (see Table 17–1).

Cranial nerve examination (especially pupillary response) is an essential part of the neurologic examination and may assist in determining the level of brainstem dysfunction (see Table 17–2). Normal pupillary function and eye movements may be seen in lesions rostral to the midbrain. Pupillary abnormalities (especially unilateral) may be an early indicator of herniation, and pupillary function should be assessed frequently when increased intracranial pressure (ICP) is a concern. Symmetrically reactive pupils that are unusually large or small are commonly secondary to drug ingestions.

Motor examination should focus on the presence of movements and whether they are involuntary, reflexive, or purposeful. Purposeful movements such as localization require some degree of cortical processing, while reflexes are stereotypical responses that occur in the absence of cortical input. Structural lesions may result in posturing. Decerebrate posturing, characterized by extension of both upper and lower extremities, is seen in lesions caudal to the midbrain. Decorticate posturing, characterized by flexion of the upper extremities and extension of the lower extremities, is seen in lesions rostral to the midbrain.

Increased Intracranial Pressure and Herniation

Herniation syndromes result from increased ICP and lead to brainstem compression, manifested by arterial hypertension, bradycardia, and respiratory irregularities (Cushing triad). Herniation may be classified as uncal, central, or cerebellar (see Table 17–3). Increased ICP commonly results from a space-occupying lesion such as a tumor or hematoma but may also result from cerebral edema secondary to trauma, infection, or severe metabolic derangements.

Treatment of increased ICP focuses on maintaining cerebral perfusion pressure, defined as mean arterial pressure (MAP) minus ICP. The goal is to keep CPP > 70–80 mm Hg. The Monro-Kellie principle states that the volume within the skull is fixed and contains three components: brain, blood, and CSF. Increase in the amount of these components (eg, cerebral edema, hematoma, hydrocephalus) or the addition of other components (eg, tumor) results in increased ICP. Using this principle, treatment is aimed at either reducing the volume of the components or expanding the volume available through surgical decompression.

Emergency department care of herniation consists initially of prompt recognition and maximizing resuscitation. Hypoxia and hypotension must be avoided and other adverse systemic factors such as hyperglycemia and fever treated aggressively. The patient's head should be elevated at 30° and adequate sedation and analgesia provided. Seizure prophylaxis should be considered, particularly when paralytics have been given. When available, further treatment should be guided by ICP monitoring. In the absence of ICP monitoring, hyperventilation to a Paco2 of 30–35 mm Hg should be initiated, followed by mannitol (0.25–1.0 g/kg IV) or hypertonic saline (2 mL/kg of 7.5% solution IV). If the ICP remains high and craniectomy is not indicated or not available, barbiturates may be used to decrease cerebral metabolism and thus cerebral blood flow. Induced hypothermia to 32–34°C has been shown to effectively lower otherwise refractory ICP.

The differential diagnosis of coma is broad and includes primary cerebral disorders (bilateral/diffuse, unilateral with mass effect, and brain-stem disorders) as well as a number of systemic derangements (see Table 17–4).

History

History should be obtained from whatever sources are available, including friends, bystanders, police, and EMS personnel. Crucial points include the following:

• Recent head trauma, even seemingly trivial
• Drug use (including alcohol), recent or past
• Past medical history, including a history of seizures, diabetes, cirrhosis, or other neurologic disease
• Medications, including narcotics and benzodiazepines use
• Precomatose activity and behavior (headache, confusion, vomiting)
• Sudden versus gradual onset of coma
• Other individuals with similar symptoms

Physical Examination

The physical examination (other than the neurologic examination) should focus on ruling out other threats to life such as hypovolemia and systemic trauma. Evidence of trauma elsewhere on the body is presumptive evidence of head trauma in the comatose patient.

Imaging

Non-contrast head CT is an integral part of the workup for coma that is not obviously related to hypoglycemia, overdose, or other metabolic cause, and should be strongly considered in any patient who remains comatose after dextrose and naloxone. Contrast-enhanced head CT or MRI may be indicated in certain patient populations.

Laboratory Evaluation

Electrolytes, LFTs, CBC, UA, glucose, urine/serum toxicology screens, thyroid function studies, BUN/Cr, and ABG should be obtained early in the evaluation of coma. Lumbar puncture and CSF analysis should be performed if not contraindicated (eg, mass lesions or other evidence of increased ICP) in patients for whom the cause of coma is unclear or in whom an infectious cause or SAH is suspected. ECG should be obtained and cardiac monitoring instituted to eliminate cardiac arrhythmias as a contributing factor. An EEG should be obtained when possible, especially in intubated patients receiving paralytics and in those for whom nonconvulsive status epilepticus is a consideration.

Structural Lesions

Intracerebral Hemorrhage

See also Chapter 37.

Essentials of Diagnosis

• Headache, nausea, vomiting
• Hypertension
• Focal neurologic deficit with signs of increased ICP

General Considerations

Intracerebral hemorrhage (ICH) can be classified as primary (unrelated to congenital or acquired lesions) or secondary (related to vascular malformations, tumors, or other lesions). The vast majority of primary ICH is related to hypertension and occurs in characteristic areas of the brain: cerebral lobes, basal ganglia, thalamus, pons, and cerebellum. Secondary ICH is more variable in location. Smoking, advanced age, and anticoagulant use are other risk factors for ICH. Early hematoma growth is more common than previously thought and is most likely responsible for sudden deterioration within the first 6 hours of initial presentation. Cytotoxic and vasogenic edema surrounding the hemorrhage may result in ischemia and are likely responsible for delayed deterioration.

Clinical Findings

Presentation is related to the size and location of the hemorrhage (see Table 17–5). Patients with large areas of hemorrhage are often comatose on arrival. The majority of patients with brainstem or cerebellar hemorrhage present with a decreased level of consciousness necessitating intubation. Headache is universally present in awake patients and may accompany other signs of increased ICP. Seizures occur in 10% of all ICH but in 50% of patients with lobar hemorrhage. Most patients are hypertensive on presentation, even if previously normotensive. Non-contrast CT scan is the diagnostic study of choice with CT angiography being useful in certain patient populations.

Treatment and Disposition

Care is primarily supportive and aimed at reducing ICP and controlling blood pressure. Aggressive blood pressure control using IV labetalol, esmolol, or nicardipine should be instituted with a target SBP < 180 mm Hg or MAP < 130 mm Hg. CPP should be maintained > 70. Patients on anticoagulants should receive reversal agents (FFP and vitamin K for warfarin, protamine for heparin) promptly. The use of prothrombin complex concentrate, factor IX complex concentrate, and rFVIIa have been shown to reverse the elevation of the INR very rapidly (often within 1–2 hours) and is faster to prepare than FFP. Corticosteroids are contraindicated. Prompt neurosurgical consultation should be obtained for all patients with declining neurological status or evidence of hydrocephalus on CT scan. Cerebellar hemorrhages > 3 cm require surgery. Hemorrhages in typical locations may not need further diagnostic evaluation and are rarely amenable to surgery. All patients should be admitted for further care.

Subdural Hematoma

Essentials of Diagnosis

• Headache
• Confusion
• Depressed level of consciousness
• Hyperdense crescent-shaped (biconcave) extra-axial collection of blood on CT scan

General Considerations

The possibility of subdural hematoma must be considered in any comatose patient. Trauma is the most common cause, but in about 25% of cases, there is no history or evidence of trauma. Elderly patients are particularly likely to present with absent or trivial trauma. Other risk factors include history of alcoholism, seizures, and coagulopathics.

Clinical Findings

Symptoms and signs are notoriously nonspecific, nonlocalizing, or absent and may be either stable or rapidly progressive. The frequency of bilateral hematomas makes localization of the lesion even more difficult, as does the coexistence of associated cerebral contusion. Hemiparesis, when present, is contralateral to the lesion in approximately 60% of cases, and ipsilateral pupillary dilatation occurs in approximately 75% of cases. Seizures may occur. When associated with trauma, a subdural hematoma is most frequently found contracoup to the side of injury. CT scan is the diagnostic study of choice, revealing a hyperdense extra-axial crescent-shaped collection of blood, which rarely crosses the falx or tentorium. Sub-acute lesions (2–3 weeks) may appear as isodense, and patients receiving anticoagulation may demonstrate layering of blood in acute-on-chronic subdural hematoma.

Treatment and Disposition

Immediate hospitalization and emergency neurosurgical consultation are indicated. Unstable patients with rapid worsening (minutes to hours) of their neurologic deficit thought to be due to an expanding subdural hematoma should be treated for increased ICP as discussed previously. Steroids have not been shown to be beneficial.

Epidural Hematoma

Essentials of Diagnosis

• Headache
• History of trauma with overlying skull fracture
• Classic lucid interval: “talk and die”
• Lens-shaped (biconvex) extra-axial collection of blood on CT scan

General Considerations

Epidural hematoma is a collection of blood between the dura and the inner table of the skull and occurs almost exclusively in the setting of trauma. The majority of epidural hematomas occur in the temporoparietal region secondary to laceration of the middle meningeal artery. Occipital epidural hematomas may progress rapidly and extend beneath the tentorium, resulting in apnea.

Clinical Findings

Symptoms are progressive. The classic presentation of head trauma followed by a brief loss of consciousness, return to alertness (“lucid interval”), then worsening headache and vomiting with subsequent coma is seen in only 1/5 of patients. Non-contrast CT scan is the diagnostic study of choice, revealing a hyperdense lenticular (biconvex) collection of blood that does not cross suture lines, differentiating it from a subdural hematoma. Ipsilateral pupillary dilation and contralateral hemiparesis are ominous findings suggestive of impending herniation. When associated with trauma, hematoma is most frequently found on the coup side of the injury.

Treatment and Disposition

Immediate neurosurgical consultation is required. In the event a neurosurgeon or CT confirmation of the diagnosis is unavailable and the patient is herniating, a burr hole performed ipsilateral to the area of trauma (or to the dilated pupil if external trauma is not apparent) may be life-saving. Care is otherwise supportive and aimed at decreasing ICP.

Cerebral Infarction

Essentials of Diagnosis

• Hemiparesis
• Hemisensory losses
• Aphasia (dominant hemisphere)

General Considerations

The brain swelling of cerebral edema following massive hemispheric infarction can produce contralateral hemispheric compression or transtentorial herniation that will result in coma. Such cerebral swelling becomes maximal 48–72 hours after the infarct.

Clinical Findings

The principal findings are hemiparesis or hemisensory loss (and aphasia if the dominant hemisphere is involved). Evolving transtentorial herniation progresses slowly over many hours or several days to stupor and coma. Non-contrast CT scan is the initial diagnostic test of choice.

Treatment and Disposition

Hemicraniectomy may be life-saving in younger patients. Patients who are comatose from massive cerebral infarction have likely progressed to coma secondary to increased ICP rather than the infarction itself, and initial treatment is supportive and aimed at lowering ICP. Blood pressure management is controversial; in severe hypertension (SBP > 220 mm Hg, DBP > 120 mm Hg), IV labetalol or nicardipine are preferred with a goal of reducing the SBP by 15% in first 24 hours.

Basilar Artery Occlusion

Essentials of Diagnosis

• Coma, altered mental status
• Respiratory pattern irregular
• Pupillary abnormalities, absent or abnormal horizontal eye movements
• Hemiparesis, hyperreflexia, positive Babinski sign

General Considerations

Basilar artery thrombosis and embolic occlusion are relatively common vascular syndromes that cause coma because of direct involvement of the penetrating arteries supplying the central core of the brain stem. Patients are usually elderly and often have a history of hypertension or transient ischemic attacks or evidence of other atherosclerotic vascular disease.

Clinical Findings

Basilar artery transient ischemic attacks are characterized by (in order of frequency of occurrence) dizziness, diplopia, weakness and ataxia, slurred speech, and nausea and vomiting. Basilar artery occlusion causes coma in half of affected patients, and almost all present with some alteration of consciousness. Focal subtentorial signs are present from the onset, and the respiratory pattern is irregular. Pupillary abnormalities vary with the site of the lesion. Skew deviation of the eyes is common. Horizontal eye movements are absent or asymmetric during the doll's eye maneuver or caloric testing. Conjugate eye deviation, if present, is directed away from the side of the lesion and toward the hemiparesis. Vertical eye movements in response to the doll's eye maneuver may be intact. Symmetric or asymmetric motor signs (hemiparesis, hyperreflexia, and Babinski sign) may be present. The classic “locked in syndrome” is characterized by complete quadriplegia, lower cranial nerve palsy, and mutism with retained consciousness and vertical gaze. CT scan of the head with CT angiography is the diagnostic study of choice, with MRA useful in special populations.

Treatment and Disposition

Current therapy recommendation is recanalization with intravenous or intra-arterial thrombolytics in combination with mechanical manipulation, depending on the institution. While specific guidelines are lacking, time to recanalization is of prognostic importance. In situations where recanalization may be delayed, “bridging therapy” with IV abciximab has shown to improve survival. Even with aggressive treatment, mortality ranges up to 70%. Hospitalize the patient for treatment and supportive care.

Brain Tumor

Essentials of Diagnosis

• Headache
• Focal weakness
• Altered mental status
• Seizures
• Papilledema
• CT scan, MRI findings

General Considerations

Coma is seldom the presenting symptom in primary or metastatic tumors of the CNS, although coma may result from seizures induced by the tumors. Acute bleeding into a tumor may also result in coma secondary to a sudden increase in ICP.

Clinical Findings

The patient typically has a history of days to weeks of headache, focal weakness, and altered or depressed consciousness. Papilledema is present in 25% of cases. CT scan (noncontrast followed by contrast-enhanced if needed) is the initial diagnostic study of choice.

Treatment and Disposition

Glucocorticoids (Dexamethasone 10 mg IV) are remarkably effective at reducing surrounding edema and should be initiated early in consultation with neurosurgery. Hospitalization for supportive care and further evaluation is indicated.

Brain Abscess

Essentials of Diagnosis

• Fever (often low grade)
• Leukocytosis
• Contrast-enhanced CT scan or MRI findings of intracranial mass

General Considerations

Brain abscess accounts for only 2% of intracranial masses. Brain abscess should be considered in patients who are immunocompromised who develop changes in mentation. Bacterial brain abscesses most commonly are the result of contiguous spread of infection from the oropharynx, middle ear, and paranasal sinuses. Cranial trauma and hematogenous spread from distant infection are also causes.

Clinical Findings

Progression to stupor and coma may be rapid, occurring over days or, rarely, hours. Symptoms include headache (∼70%), mental status changes (70%), focal neurological deficits (> 60%), and seizure (25–35%) at time of presentation. The usual signs of infection are frequently absent. The temperature is normal in half of patients, and the white blood cell count is below 10,000/mL in over one-fourth of patients. CT scan (non-contrast followed by contrast-enhanced if needed) or MRI will reveal almost all abscesses. Lumbar puncture is contra-indicated.

Treatment and Disposition

Initiate antibiotic therapy early, prior to imaging if possible when the clinical suspicion for CNS infection is high. Antibiotic choice should cover anaerobes as well as aerobes, and coverage for fungal or other organisms may be indicated depending on the patient's history. Empiric therapy with a combination of vancomycin 1.0–1.5 g IV plus metronidazole 7.5 mg/kg IV plus a third- or fourth-generation cephalosporin is indicated. Carbapenems can be used in placed of the combination of cephalosporins and metronidazole. Neurosurgical consultation should be obtained with operative intervention necessary of abscesses > 2.5cm. The use of steroids remains controversial and is generally deferred for this indication. Seizure prophylaxis should be initiated early during hospitalization.

Metabolic Encephalopathies

Essentials of Diagnosis

• Progressive somnolence
• Intoxication, toxic delirium
• Agitation, stupor, coma
• Headache
• Symmetric neurologic findings
• Reactive pupils
• Hypoventilation, abnormal respiratory pattern
• Loss of extraocular movements

Clinical Findings

Metabolic encephalopathies are characterized by a period of progressive somnolence, intoxication, toxic delirium, or agitation, after which the patient gradually sinks into a stuporous and finally comatose state. Headache is not an initial symptom of metabolic encephalopathy except in the case of meningitis or poisoning due to organophosphate compounds or carbon monoxide.

Neurologic examination fails to reveal focal hemispheric lesions (hemiparesis, hemisensory loss, aphasia) before loss of consciousness. Neurologic findings are symmetric except in some patients with hepatic encephalopathy and hypoglycemic coma, which may be accompanied by focal signs (especially hemiparesis) that may alternate sides. Asterixis may be present.

The hallmark of metabolic encephalopathy is reactive pupils (a midbrain function) in the presence of impaired function of the lower brain stem (eg, hypoventilation, loss of extraocular movements), an anatomically inconsistent set of abnormalities. Respiratory patterns in metabolic coma vary widely and may help establish the cause of coma.

Treatment and Disposition

Treatment depends entirely on the cause of coma. All patients require hospitalization for supportive care and specific therapy.

Hypoglycemia

See also Chapter 43.

General Considerations

Unlike other organs, the brain relies mainly on glucose to supply its energy requirements. Abrupt hypoglycemia rapidly interferes with brain metabolism and quickly produces symptoms. Insulin and oral hypoglycemic drug overdose are the most common causes of hypoglycemia.

Clinical Findings

Signs of sympathetic nervous system activity (tachycardia, sweating, and anxiety) may warn patients of impending hypoglycemia, although these signs may be masked by β-blockers and may be absent in patients with diabetic autonomic neuropathy. Common neurologic abnormalities are delirium, seizures, focal signs that often alternate sides, stupor, and coma. Hypoglycemic coma may be tolerated for 60–90 minutes, but once the stage of flaccidity with hyporeflexia has been reached, glucose administration within 15 minutes is mandatory to avoid irreversible damage.

Treatment and Disposition

Give glucose, 50 mL of 50% solution intravenously (adult dose). Once the diagnosis of hypoglycemia is confirmed by analysis of blood drawn before treatment, give an additional 50 mL as needed or begin an infusion of dextrose 5% in water. Subcutaneous or intramuscular glucagon should be considered in patients in which IV access cannot be obtained. Although case reports of octreotide use in hypoglycemia have been shown to be effective, the indications and dosage have not clearly been defined. Patients should be observed for 1–2 hours after glucose supplementation has been discontinued to ensure that hypoglycemia does not recur before they are discharged from the hospital. In some cases, hospitalization may be necessary, especially if hypoglycemia recurs despite treatment or in the event of long-acting insulin or oral hypoglycemic agent overdose (eg sulfonylureas).

Hypoxemia

Clinical Findings

Hypoxemia produces brain damage only as a result of concomitant cerebral ischemia. Cerebral blood flow diminishes and brain ischemia occurs when the arterial Po2 falls to 20–45 mm Hg. In cerebral anoxia due to cardiac arrest, where the duration can be timed precisely, 4–6 minutes of asystole begins to result in permanent CNS damage. Following asystole, the pupils dilate rapidly and become fixed, and tonic posturing is observed. A few seizure-like tonic–clonic movements are common.

Treatment and Disposition

Treatment of hypoxemia depends on the cause. Support cardiac output and maintain arterial Po2 above 60 mm Hg by supplemental oxygen or mechanical ventilation. Induction of mild hypothermia (∼33°C) after cardiac arrest has been shown to improve survival and neurological outcome. Hospitalize all patients for diagnosis and treatment.

Drug Overdose

See also Chapter 47.

Drug overdose is one of the most common causes of coma in patients presenting to the emergency department. Many drugs may be implicated, including sedative–hypnotics, opiates, tricyclic antidepressants, and antiepileptics. Details of management can be found in Chapter 47.

Ethanol Intoxication

Alcohol intoxication produces a metabolic encephalopathy similar to that produced by sedative–hypnotic drugs, although nystagmus during wakefulness and early impairment of lateral eye movements are not as common. Peripheral vasodilatation is a prominent manifestation and produces tachycardia, hypotension, and hypothermia.

In individuals who are not chronic alcoholics, stupor occurs when blood alcohol levels reach 250–300 mg/dL, and coma occurs when levels reach 300–400 mg/dL. Because alcohol has significant osmotic pressure (100 mg/dL = 22.4 mOsm), alcohol intoxication is one cause of hyperosmolality.

Management is discussed in Chapter 47. Patients should be observed until improvement has occurred with normal orientation and judgment, and satisfactory coordination. Hospitalize patients who have abnormalities that would usually require hospitalization (eg, metabolic abnormalities, Wernicke encephalopathy).

Narcotic Overdose

In narcotic overdose, hypoventilation is almost always present, along with pinpoint pupillary constriction and absent extraocular movements in response to the doll's eye maneuver. Pinpoint pupils are also associated with other disorders that must be ruled out: use of miotic eye drops, pontine hemorrhage, Argyll-Robertson pupils from syphilis, and organophosphate insecticide poisoning.

Narcotic intoxication is confirmed by rapid pupillary dilation and awakening after administration of a narcotic antagonist such as naloxone, 2 mg, by rapid IV injection or intranasally. Note: Patients who have overdosed on certain narcotics (eg, propoxyphene) may not respond to 2 mg and may require 4 mg or more. The duration of action of naloxone varies with the dose and route of administration (20–90 minutes). Repeat doses are frequently necessary, especially following intoxication with long-acting narcotics (eg, methadone).

Treatment of drug overdose and poisoning is outlined above and discussed in more detail in Chapter 47. Hospitalization should be considered for patients who do not recover completely in the emergency department or who have taken long-acting narcotics.

γ-Hydroxybutyrate

γ-Hydroxybutyrate is a CNS depressant and can induce coma. The drug has become popular at rave parties and has also been called the “date rape drug.” Detection of the drug is difficult, because most of it is eliminated through the lungs. Treatment is primarily supportive and may involve endotracheal intubation. Some patients require hospitalization for prolonged supportive care.

Hepatic Encephalopathy

Clinical Findings

Hepatic encephalopathy can occur in patients with severe acute or chronic liver disease. Jaundice need not be present. In the patient with preexisting liver disease, encephalopathy may develop rapidly following an acute insult such as gastrointestinal hemorrhage or infection. Patients with surgical portacaval shunts are especially predisposed to encephalopathy.

Mental status is altered and ranges from somnolence to delirium or coma. There is increased muscle tone; hyperreflexia is common. Prominent asterixis occurs in the somnolent patient. Seizures, either generalized or focal, occur infrequently. Ammonia levels correlate poorly with disease severity. Hyperventilation with respiratory alkalosis is nearly universal and may be demonstrated by measuring arterial blood pH. CSF is normal but may appear xanthochromic in patients with serum bilirubin levels higher than 4–6 mg/dL.

Treatment and Disposition

Emergency department care is supportive. Treatment aimed at decreasing intestinal ammonia absorption (lactulose, neomycin) may be initiated but should not take the place of hospitalization for definitive treatment. Studies on induced hypothermia in acute liver failure are inconclusive to this point.

Hyponatremia

Delirium and seizures are common presenting features of hyponatremia. Hyponatremia may cause neurologic symptoms when serum sodium levels are below 120 mEq/L, and symptoms are common with levels below 110 mEq/L. When the serum sodium level falls rapidly, symptoms occur at higher serum sodium levels.

Treatment and Disposition

The diagnosis and treatment of these entities are discussed in Chapter 44. Hospitalization is mandatory in symptomatic patients.

Hypothermia/Hyperthermia

Clinical Findings

Hypothermia and hyperthermia are associated with symmetric neurologic dysfunction that may progress to coma. All comatose patients must have rectal temperature taken with an extended-range thermometer if the standard thermometer fails to register.

Hypothermia

Internal body temperatures below 26°C (78.8°F) uniformly cause coma; hypothermia with core temperatures above 32°C (89.6°F) does not cause coma. Body temperatures of 26–32°C (78.8–89.6°F) are associated with varying degrees of obtundation. Pupillary reaction will be sluggish below 32°C (89.6°F) and lost below 26.5°C (80°F).

Hyperthermia

Internal body temperatures above 41–42°C (105.8–107.6°F) are associated with coma and may also rapidly cause permanent brain damage. Seizures are common, especially in children.

Treatment and Disposition

Diagnostic and treatment measures for both hypothermia and hyperthermia are discussed in detail in Chapter 46. Hospitalization is mandatory.

Meningoencephalitis

See also Chapter 42

Clinical Findings

The classic triad of fever, neck stiffness, and altered mental status is poorly sensitive for bacterial meningitis (40%). Any patient with altered mental status, seizure, focal neurologic deficit, or evidence of increased ICP should undergo neuroimaging prior to lumbar puncture to minimize the risk of herniation. CSF pleocytosis is common although depending on the stage of the disease, the differential may be variable. CSF glucose < 40 mg/dL is more consistent with bacterial meningitis.

Treatment and Disposition

Start antibiotic therapy immediately based on clinical findings, prior to obtaining imaging. Current recommendations are for vancomycin with a third-generation cephalosporin, and dexamethasone (0.6 mg/kg) should be given with or before antibiotic administration. Hospitalization is indicated for all patients with meningitis who present in coma or in whom bacterial meningitis cannot be excluded.

Other Disorders Causing Coma

Subarachnoid Hemorrhage

See also Chapter 37.

Essentials of Diagnosis

• Sudden onset of severe headache
• Nausea and vomiting
• Photophobia, visual changes

General Considerations

Aneurysmal subarachnoid hemorrhage (SAH) accounts for 80% of all cases of nontraumatic SAH. Risk factors include cigarette smoking, hypertension, cocaine and alcohol use, first-degree relatives with a history of SAH, female sex, African–American race, and connective tissue disorders.

Clinical Findings

Typical presentation of SAH involves nausea or vomiting (77%), sudden onset of severe headache (74%), meningismus (35%), photophobia, and may include decreased level of consciousness. A “thunderclap” headache may signify a sentinel leak, and the headache may resolve relatively quickly. The patient may lose consciousness at onset (53%) or may experience a seizure (20%). Retinal hemorrhages may be present on fundoscopic examination and blood pressure is usually markedly elevated. Noncontrast enhanced CT scan of the head is the initial diagnostic study of choice. Because the diagnostic sensitivity of CT scanners is only 98–100% for SAH within the first 12 hours, current recommendations are to follow a negative CT with CSF analysis. If CSF is normal (no xanthochromia, no elevated RBCs), SAH is effectively excluded. Positive or indeterminate CSF findings require CT angiography or traditional angiography to rule out the presence of an aneurysm.

Treatment and Disposition

Emergency department care is supportive. After stabilization, the patient should be admitted or transferred for definitive therapy by neurosurgery for craniotomy and clipping or interventional radiology for coiling. Blood pressure should be treated aggressively to be kept within normal limits until the aneurysm has been secured. Nimodipine (60 mg), an oral calcium channel antagonist, is commonly used to prevent delayed vasospasm and can be initiated in the emergency department.

Seizure

See also Chapter 19.

Essentials of Diagnosis

• Patient is unresponsive to pain
• Nonfocal neurologic examination
• Babinski sign (transient)
• Todd paralysis
• Signs of recent seizure: tongue trauma, incontinence, rapidly clearing anion gap lactic acidosis

General Considerations

Coma resulting from seizure disorders is usually not a difficult diagnostic problem, because recovery of consciousness is rapid following the end of the seizure. Prolonged postictal coma (several hours) followed by several days of confusion may occur after status epilepticus, in patients with brain damage (eg, multiple cerebral infarctions, head trauma, encephalitis, mental retardation) and in patients with metabolic encephalopathy that alters consciousness and induces seizures (eg, hyponatremia, hyperglycemia). Nonconvulsive status epilepticus is more common than previously thought and should be considered in any patient with no other apparent cause of coma, especially in those with a history of seizure disorder.

Clinical Findings

Patients may initially be unresponsive to deep pain and exhibit sonorous respirations. The neurologic examination is usually nonfocal, although Babinski sign may be transiently present. Uncommonly, there may be focal abnormalities (Todd paralysis) referable anatomically to the focus of seizure activity in the brain.

Other evidence of a recent seizure may be present, such as trauma to the tongue from biting, incontinence, or a rapidly clearing anion gap (lactic) acidosis. The rapid resolution of coma in a patient with a witnessed seizure or known seizure disorder should suggest the diagnosis of the postictal state as the cause of coma. Coma that is at first thought to be postictal but fails to improve should prompt an investigation for underlying processes contributing to mental status depression, including metabolic encephalopathy, underlying diffuse brain damage, encephalitis, and structural lesion. Appropriate investigations could include measurements of serum electrolytes, calcium, and magnesium; CT scan; and lumbar puncture.

Treatment and Disposition

Treatment depends on the underlying cause of the seizure. Be alert for metabolic causes and treat them appropriately. See Chapter 19 for details of management. Immediate hospitalization is required for all cases of status epilepticus and prolonged postictal coma and for seizures due to metabolic causes that are not quickly correctable.

Psychogenic Coma

Essentials of Diagnosis

• Patient is unresponsive
• Normal physical examination
• Flaccid symmetric decreased muscle tone
• Normal and symmetric reflexes
• Normal Babinski
• Nystagmus with ice water calorics
• Normal electroencephalogram findings

Clinical Findings

Psychogenic coma is a diagnosis of exclusion that should be made only after careful documentation. The general physical examination should elicit no abnormalities; neurologic examination generally reveals flaccid, symmetrically decreased muscle tone, normal and symmetric reflexes, and the normal downward response to Babinski plantar stimulation. The pupils are normal in size (2–3 mm) or occasionally larger and respond briskly to light. Lateral eye movements elicited with the doll's eye maneuver may or may not be present, because visual fixation can suppress this reflex.

Differentiating Psychogenic Coma from Organic Coma

Eye Movements

The slow, conjugate roving eye movements of patients in metabolic coma cannot be imitated and, if present, are incompatible with a diagnosis of psychogenic unconsciousness.

Eyelid Tone

The slow, often asymmetric and incomplete eyelid closure commonly seen in organic forms of coma following passive opening of the lids cannot be mimicked. In addition, the patient with psychogenic coma usually shows some voluntary muscle tone of the eyelids during passive opening by the examiner.

Ice Water Caloric Response

A helpful objective test in diagnosing psychogenic unconsciousness is the caloric test: there is no response at all or tonic deviation to the side of the irrigation in organic coma, but nystagmus occurs in psychogenic coma. Because the quick (return) phase of nystagmus requires an intact cortex, its presence is incompatible with a diagnosis of true coma.

Electroencephalogram

The electroencephalogram in psychogenic coma is that of a normal, awake person. In coma due to other causes, it is invariably abnormal.

Treatment and Disposition

Obtain psychiatric consultation. Hospitalization may be required.

Brain death is defined as the irreversible loss of function of the brain, including the brain stem. Before a patient may be evaluated for the diagnosis of brain death, the patient must meet certain criteria:

• Clinical or neuroimaging evidence of catastrophic CNS event compatible with the clinical diagnosis of brain death
• Exclusion or correction of medical conditions that may confound clinical assessment:
  • – Acid–base disorders
  • – Severe electrolyte disorder
  • – Endocrinopathies
  • – Absence of drug intoxication/poisoning
  • – Patient core temperature > 32°C (90°F)

Once these criteria have been met, the patient can be tested for the diagnosis of brain death. If the patient meets the following criteria, the patient is observed for at least 6 hours and clinical testing is repeated. If patient testing remains unchanged, a diagnosis of brain death can be made.

• Coma (unresponsiveness): no cerebral motor response to pain
• Absence of brain-stem reflexes (all of the below):
  • – No pupillary response to light
  • – No oculocephalic reflex (doll's eyes maneuver)
  • – No response to cold water calorics
  • – No corneal reflexes
  • – No jaw reflex
  • – No grimacing to painful stimulus
  • – No gag reflex
  • – No cough response to tracheal/bronchial stimulation
  • – Apnea over 8 minutes with Pco2 > 60 mm Hg

Confirmatory testing may be used when complicating factors are present such as severe facial trauma, preexisting pupillary abnormalities, or toxic drug levels. Confirmatory tests result in findings that are consistent with brain death and are not diagnostic. The standard confirmatory tests include cerebral angiography, transcranial Doppler ultrasonography, technetium-99m-hexamethylpropyleneamine brain scan, and somatosensory-evoked potentials. In some cases these tests may aid in the diagnosis and in others they may confuse the picture. Documentation of the diagnosis of brain death should include the cause and irreversibility of the condition, the absence of brain-stem reflexes, the absence of any motor response to pain, the formal apnea test results, and the justification for and results of any confirmatory tests. The initial and repeat examinations should be included. Currently most authorities feel that the same criteria above can be used for full-term infants more than 7 days old. Criteria for premature and newborns are still unclear.