Of the acute problems in clinical medicine, none is more challenging than the prompt diagnosis and effective management of the patient in coma. The challenge exists in part because the causes of coma are so many and the physician possesses only a limited time in which to make the appropriate diagnostic and therapeutic judgments. Coma caused by a subdural or epidural hematoma may be fully reversible when the patient is first seen, but if treatment is not promptly undertaken, the brain injury may become either irreparable or fatal within a very short period of time. A comatose patient suffering from diabetic ketoacidosis or hypoglycemia may rapidly return to normal if appropriate treatment is begun immediately but may die or be rendered permanently brain damaged if treatment is delayed. In epidural hematoma, meticulous evaluation of acid–base balance and substrate availability may not only be useless, but it is also dangerous because precious time may be lost. In untreated diabetic coma, time spent performing imaging may interfere with life-saving treatment.
Outcomes of patients with severe acute brain injury in general and those with impaired consciousness in particular have improved significantly in the past decades, but what has become increasingly clear is that timeliness of interventions is crucial for patients with life-threatening neurological presentations. Millions of neurons, synapses, and myelinated fibers are lost every minute after onset of an ischemic stroke,1 and seizures become increasingly difficult to control the later that treatment is initiated.2 Time to deliver treatments is possibly the greatest variable to determine survival and functional outcome. This principle was put to the test in a number of clinical trials demonstrating the importance of early administration of intravenous thrombolytics3 and endovascular clot removal4 in patients with ischemic stroke, antiepileptic medications for patients with status epilepticus (SE),5,6 and dexamethasone in adults with bacterial meningitis,7 to highlight a few.
The physician evaluating a comatose patient requires a systematic approach that will allow directing the diagnostic and therapeutic endeavors along appropriate pathways. The preceding chapters of this text presented what may appear to be a bewildering variety of disease states that cause stupor or coma. However, these chapters have also indicated that for any disease or functional abnormality of the brain to cause unconsciousness, it must either (1) produce bilateral dysfunction of the cerebral hemispheres, (2) damage or depress the physiologic activating mechanisms in the upper brainstem and diencephalon, or (3) metabolically or physiologically damage or depress the brain globally. Conditions that can produce these effects can be divided into (1) supratentorial mass lesions that compress or displace the diencephalon and brainstem, (2) infratentorial destructive or expanding lesions that damage or compress the upper brainstem, or (3) metabolic, diffuse, or multifocal encephalopathies that affect the brain in a widespread or diffuse fashion. In addition, (4) the clinician must be alert to unresponsiveness of psychiatric causes. Examiners need to actively search for conditions without impairment of consciousness but limited ability to express consciousness, such as those associated with loss of motor response but intact cognition (e.g., brainstem infarction, degenerative loss of motor nerves, or acute peripheral neuropathy [Guillain-Barré syndrome] producing a locked-in state8).
These insights have led to efforts to streamline the initial management of patients with neurological emergencies, particularly those with impaired consciousness, and efforts to initiate targeted interventions in the emergency room or ideally prior to arrival to the hospital.9 Using physiologic principles, one may considerably narrow the diagnostic possibilities and start specific treatment rapidly enough to make a difference in outcome. This chapter outlines a clinical approach that both stabilizes the patient to assure survival in most instances and allows the physician to assign the cause of unresponsiveness promptly into one of the preceding four main categories to start delivering targeted therapies to minimize irreversible damage to the patient’s brain.
A Clinical Regimen for Diagnosis and Management
The initial objective of the first medical encounter with the comatose patient is to secure adequate vital body functions including airway, breathing, and circulation, which will be discussed in detail later. In addition to these measures focusing on cardiopulmonary resuscitation, a categorical clinical diagnosis for the underlying cause of coma should be made to guide the emergent management. The key to making a categorical clinical diagnosis of the patient in coma consists of two steps: first, the accurate interpretation of a limited number of physical signs that reflect the integrity or impairment of various levels of the brain; and, second, the determination of whether structural or metabolic dysfunction best explains the pattern and evolution of these signs (Figure 7.1). As Table 7.1 indicates, each of these pathophysiologic categories causes a characteristic group of symptoms and signs that usually evolve in a predictable manner. Once the patient’s disease can be assigned to one of the three main categories, specific radiographic, electrophysiologic, or chemical laboratory studies can be employed to make disease-specific diagnoses or detect conditions that potentially complicate the patient’s management. Once the diagnosis is made and treatment started, changes in these same clinical signs and laboratory tests can be used serially to extend or supplement treatment (medical or surgical), to judge its effect, and, as indicated in Chapter 9, to estimate recovery and prognosis.
Table 7.1 Differential Characteristics of States Causing Sustained Unresponsiveness
I. Supratentorial mass lesions compressing or displacing the diencephalon or brainstem
Signs of focal cerebral dysfunction present at onset
Signs of dysfunction show a rostral-to-caudal progression through the brainstem
Neurologic signs at any given time point to an anatomic level of progression (e.g., diencephalon, midbrain-pons, medulla)
Motor signs often asymmetric
II. Subtentorial masses or destruction causing coma
History of preceding brainstem dysfunction or sudden onset of coma
Localizing brainstem signs precede or accompany onset of coma
Pupillary and oculomotor abnormal findings usually present
Abnormal respiratory patterns common and usually appear at onset
III. Metabolic, diffuse, or multifocal coma
Confusion and stupor commonly precede motor signs
Motor signs, if present, are usually symmetric
Pupillary and oculomotor responses are usually preserved
Asterixis, myoclonus, tremor, and seizures are common
Acid-base imbalance with hyper- or hypoventilation is frequent
IV. Psychiatric unresponsiveness
Lids close actively
Pupils reactive or dilated (cycloplegics)
Oculocephalic responses are unpredictable; oculovestibular responses physiologic for wakefulness (i.e., nystagmus is present)
Motor tone is inconsistent or normal
Eupnea or hyperventilation is usual
No pathologic reflexes are present
Electroencephalogram is normal
Many efforts have been made to find an ideal clinical approach to the unconscious patient. Most such approaches repeat or even enlarge upon the complete neurologic examination, which makes them too time-consuming for practical daily use. A few are admirably brief and to the point (Chapter 2) (e.g., Glasgow Coma Scale) but have been designed for limited purposes, such as assessing patients with head injury; generally, they provide too little information to allow diagnosis or the monitoring of metabolic problems. The FOUR score scale (Chapter 2) gives more information, but is still limited.10 The clinical profile described in Chapter 2, which has been employed extensively by ourselves and others, has advantages. The examination judges the normal and abnormal physiology of functions described earlier in Chapter 2: arousal, pupillary responses, eye movements, corneal responses, the breathing pattern, skeletal muscle motor function, and deep tendon reflexes. Most of these functions undergo predictable changes in association with localizable brain abnormalities that can locate the lesion or lesions. The constellation and evolution of these abnormal functions in a given patient can determine the cause of altered consciousness, whether supratentorial (focal findings start rostrally and evolve caudally), infratentorial (focal findings start in the brainstem), metabolic (lacks focal findings, but evidence of diffuse forebrain dysfunction), or psychiatric (lacks focal or diffuse signs of brain dysfunction). Of equal importance is that this examination is brief and does not delay implementation of effective treatment.
The need to initiate interventions as early as possible has generated interest in exploiting the out-of-hospital setting to start treatments. Success and challenges of initiating targeted therapy in the out-of-hospital setting are illustrated by randomized clinical trials for SE5,6 and ischemic stroke.11 Challenges of this setting include limited access to diagnostics such as imaging or EEG, limitations in medication choices such as those that need to be refrigerated, and, in most healthcare delivery systems, reliance upon nonphysician providers to assess and manage patients. Algorithms for out-of-hospital management of patients with decreased level of consciousness need to take these limitations into account while supporting optimally a relatively wide differential of underlying etiologies.
One problem that is frequently encountered is the tendency for paramedics in the field to intubate almost any patient with impaired consciousness “to protect the airway.” Not all unconscious patients need to be intubated and, in fact, not infrequently unconscious patients can also be extubated. As long as patients have preservation of medullary reflexes that protect the airway and there is no concern for intracranial pressure (ICP) crises, many patients with coma caused by metabolic disarray, supratentorial mass lesion, and psychiatric conditions do not need to be intubated. Patients with impairment of the lower brainstem will require intubation. Because intubation usually involves giving patients sedative and paralytic drugs, the in-hospital evaluation of the patient requires either relying on the paramedic exam or stopping the drugs and waiting for them to clear. Initial assessment should therefore focus on determining if the out-of-hospital assessment/treatment was adequately provided so that this is not merely repeated, causing delay in more advanced treatment. In addition to stabilization of vital functions of the patient, diagnostic and interventional steps should be initiated as early as possible, taking the underlying cause of impaired consciousness into account.
Algorithm and Principles of Emergency Management
Support Vital Signs: Airway, Breathing, and Circulation
In patients with stupor or coma, vital cardiovascular and respiratory functions are frequently compromised and need to be supported. The primary injury linking consciousness and life-supporting vital body functions may either be directly in the cardiovascular or respiratory system (i.e., cardiac arrest leading to hypoxic brain injury; see Chapter 5), in the central nervous system (CNS) affecting both respiratory control pathways and pathways crucial to maintain consciousness (e.g., brainstem injury involving the respiratory centers in the ventrolateral medulla and that, at the same time, involve the ascending arousal system bilaterally such as seen with cerebellar hemorrhages with herniation causing mass effect on large areas of the brainstem; see Chapter 1, Figure 1.9 and Chapter 2, Figure 2.4), or conditions with effects both on cardiovascular and respiratory functions as well as brain areas crucial for supporting consciousness (e.g., tricyclic intoxication, see Chapter 5).
No matter what the diagnosis or the cause of coma, certain general principles of management apply to all patients with stupor or coma and should be prioritized as one pursues the examination and undertakes definitive therapy (Figure 7.1). All patients need to be screened and continuously monitored for development of cardiovascular and respiratory decompensation. In the out-of-hospital setting, diagnosis of cardiovascular and respiratory compromise typically consists of assessment of heart auscultation to determine rate and rhythm, blood pressure measurements, lung auscultation, observation of the breathing pattern, and oxygen saturation. In addition to the tests introduced in the out-of-hospital setting, laboratory tests, imaging, and ultrasound are readily available in most emergency room and intensive care unit settings. This allows rapid diagnosis, for example, of free fluid in the abdomen raising concerns for intra-abdominal bleeding in the trauma victim; pneumothorax for those with respiratory distress; or cardiac tamponade and function, as well as fluid status for those with hypotension. Initial evaluation of patients with impaired consciousness focuses on assessment and delivery of clinical interventions that are a fundamental part of the cardiopulmonary resuscitation protocol: airway, breathing, and circulation.
Ensure Oxygenation, Airway, and Ventilation
Stuporous or comatose patients with inadequate respirations will rapidly acquire additional brain injury from lack of oxygen, have worsened impairment of consciousness from hypercarbia, and poor overall medical outcome from aspiration pneumonia. The initial focus needs to be an emergent assessment of the need for intubation, which can be categorized into a failure to oxygenate (assess skin color, check for cyanosis; if available and depending on the urgency of the respiratory decompensation, take into account pulse oximetry and arterial blood gas measurements), failure to ventilate (assess for excessive or inadequate work of breathing; if available and depending on the urgency, expiratory carbon dioxide and arterial blood gas measurements may be obtained), failure to protect the airway (to assess bulbar function, cough reflex and amount of secretions as well as presence of vomiting have to be weighed against each other), and anticipated neurological or cardiopulmonary decline. A protocol for assessment of the airway should take into account the risks and benefits to predict the level of airway difficulty as well as the ease of bag-mask ventilation.12
Providing an adequate airway includes basic maneuvers such as clearing mechanical obstructions and opening the airway using the jaw-thrust technique, as well as more advanced steps including the use of supraglottic devices (i.e., oropharyngeal or nasopharyngeal airways), tracheal intubation, and surgical approaches such as cricothyrotomy. Depending on the clinical scenario, level of expertise, and availability of the equipment, basic or more advanced airway support may be necessary and available. Breathing support includes application of artificial breaths via mouth-to-nose or mouth-to-mouth, and use of respiratory aids such as bag-valve-mask or ventilator-assisted respiratory support. Once the decision for endotracheal intubation has been made, the rapid sequence intubation is preferred to secure the airway, particularly of patients with suspected elevation of intracranial pressure.13,14 This involves protection from the reflex sympathetic response induced by mechanical manipulation of the larynx during intubation resulting in tachycardia, hypertension, and ICP elevation. Steps include elevation of the head of the bed, intravenous access (allowing administration of pressors and fluids), preoxygenation for up to 5 minutes, and pretreatment with intravenous lidocaine (1.5 mg/kg 60–90 seconds before intubation; this may also be given topically) to prevent the reflex sympathetic response, with fentanyl being an alternative.15,16 Induction medications for patients with suspected elevation of ICP include the combination of etomidate and succinylcholine (2 mg/kg IV push), but alternative regimens including ketamine are available. For further details on intubation, please refer to published protocols.15
These primary resuscitation interventions are highly protocolized, but a few frequently encountered causes of unconsciousness require slight modification of these protocols. Stabilization of the cervical spine and replacing the head-tilt/chin-lift maneuver with the jaw-thrust technique is crucial for patients with any suspected trauma or any other cause for cervical spine instability as these interventions may otherwise further worsen the neurological injury. It is important to monitor all comatose patients carefully for hypotension as this may be a complication from medications given during intubation and worsen the outcome of all neurologically injured patients, particularly those with ischemia. Vagal discharge may occasionally lead to bradycardia or cardiac arrest, particularly in hypoxemic patients. As a general rule, keeping the mean arterial pressure between 70 and 90 mm Hg may serve as a guide to provide adequate cerebral perfusion.
Avoid hyperventilation in general but particularly if the underlying etiology is brain ischemia as this may cause cerebral vasoconstriction. If a patient shows signs of herniation, hyperventilation may be needed as an emergency temporizing measure. However, more definitive treatment of herniation and elevated ICP needs to be instituted as quickly as possible, as discussed later. Supraphysiologic oxygen levels are frequently provided to comatose or stuporous patients but have the potential to worsen outcome following traumatic brain injury17 and cardiac arrest18 due to formation of reactive oxygen species and impairment of mitochondrial function.17
Following intubation, appropriate placement of the endotracheal tube should be confirmed by checking for bilateral chest rise and lung sounds, lack of sounds on gastric auscultation, condensation in the endotracheal tube, and carbon dioxide measurements in the exhaled air (capnometer). Once confirmed, the patient should be connected to the ventilator (basic ventilator settings: volume-cycled ventilation at 8 cc/kg of ideal body weight and a respiratory rate of 12–14 per minute, unless the patient is herniating or medical conditions, such as adult respiratory distress syndrome, require adjustments), a pulse oximeter should be placed, an arterial blood gas sent, and a chest radiograph ordered. Patients comatose from drug overdose or who are hypothermic have depressed metabolism and require less ventilation than awake individuals. The comatose patient ideally should maintain a PaO2 greater than 100 mm Hg and a PaCO2 of between 35 and 45 mm Hg. All intubated patients should receive frequent chest physical therapy and suctioning of the airway, and many may need nebulizer treatments to loosen secretions. Sedation should be interrupted daily to assess spontaneous respiratory patterns and need for continued ventilation.19 Caution is called for in any patients with suspected or confirmed elevation of ICP as mechanical manipulation may elevate the ICP. The optimal timing of tracheostomy in critically ill patients with neurological injury, such as those with stupor or coma, is controversial but many will discuss this option with families between the first and second week following the injury. Control of the airway and safety of regular feedings can be considered temporary measures that secure patient safety during a vulnerable period that can be re-evaluated over time.
Maintain the Circulation
Adequate blood supply to end organs including the brain is only achieved with an intact circulation. Emergent assessment of adequate circulation is crucial and involves checking the pulse, heart rate, cardiac rhythm, and blood pressure. When these are abnormal, additional diagnostic tools may be required to diagnose and treat the underlying problem, including electrocardiogram (EKG), arterial line placement, and emergency transthoracic echo.
Checking for a pulse should be the first diagnostic step. All pulseless patients are either already or will rapidly be comatose, and the primary treatment includes chest compressions (recommended ratio of 30:2 chest compressions to ventilations at 100 compressions/min).20 The underlying cardiovascular abnormality needs to be identified rapidly and treatments initiated following the American Heart Association Advanced Cardiac Life Support (ACLS) protocol.21 Treatments include defibrillations; cardiac medications such as epinephrine, atropine, adenosine, and others; intravenous fluids, and vasopressor support. Severe hypotension in patients with a pulse seen in all forms of shock needs to be addressed rapidly as additional brain injury will occur if untreated, and the cardiovascular condition may rapidly progress if untreated. Treatments include intravenous fluids, vasopressors, transfusion of red blood cells or other products, and stopping a bleeding source.
While treating the circulatory deficiency, the provider should focus actively on a search for the underlying cause as this may further guide the management. Hypotensive comatose patients with traumatic brain injury may also have a pelvic fracture resulting in hypovolemic shock from abdominal hemorrhage or have cardiac tamponade from chest trauma. However, damage to the brain above the level of the medulla does not cause systemic hypotension (see Chapter 2). The goal of maintaining an adequate blood pressure will depend on the underlying etiology, but, as an initial target, mean arterial pressure (MAP = 1/3 systolic + 2/3 diastolic) should be maintained between 70 and 90 mm Hg using hypertensive agents as necessary. In young, previously healthy patients, particularly those with depressant drug poisoning, a systolic blood pressure of 70–80 mm Hg is usually adequate.
In general, it is not necessary and may be dangerous to treat hypertension initially unless diastolic pressure exceeds 120 mm Hg or the patient is actively bleeding for example from a vascular cause. The elevation of blood pressure may be a reflex response to vascular occlusion (see Chapter 2), and, unless this is excluded, reducing blood pressure could worsen brain ischemia. In an older patient with known chronic hypertension, do not allow the blood pressure to fall below previously accustomed levels because the relative hypotension may cause cerebral hypoxia. However, if ICP is elevated, a higher MAP may be necessary to maintain cerebral perfusion pressure (e.g., MAP of 55–60 mm Hg above the ICP). When indicated, a number of intravenous agents are available to treat hypertensive emergencies, including labetalol (20–80 mg bolus over 10 minutes) and nicardipine (2–10 mg/hr).22
History, Exam, and Basic Diagnostics
History and exam are crucial and also need to be assessed by first responders in the out-of-hospital setting as this information may be crucial to guide resuscitative efforts and be unobtainable at a later time point. Assessments should involve determination of the circumstances in which the patient is found (e.g., in an auto with the engine running, suggesting carbon monoxide poisoning), brief past medical history from bystanders or family (e.g., known polysubstance abuse may suggest overdose and prompt administration of naloxone), medication that the patient is taking (e.g., such as antiepileptic medication leading to administration of lorazepam or an antidepressant suggesting a suicide attempt), and a focused exam (e.g., may indicate herniation leading to administration of a hyperosmolar agent such as mannitol prior to obtaining imaging studies).
Emergency Neurological Examination of the Comatose or Stuporous Patient
Once the vital functions have been protected, proceed with the history and examination. The examination of the unconscious patient is covered in detail in Chapter 2, but a brief reprise is included here with emphasis on the elements that need to be covered quickly while initiating therapy in an emergency setting. Although the coma exam is, by necessity, relatively brief, the examiner has the luxury of time in doing the assessment when the patient has been under the continuous observation of other physicians on the ward or in an intensive care unit. In the emergency department, it is often necessary to weave obtaining the history and examination with urgent interventions. This goal of this emergency examination, together with the history and vital signs, is to allow the provider to categorize the etiology of unresponsiveness into one of four major categories (Table 7.1) that will guide emergent treatments.
The history should, to whatever extent possible, be obtained from relatives, friends, paramedics, bystanders, or sometimes even the police. If it has not already been done, search the patient’s belongings and check for a medical alert bracelet. Implanted computer chips that give full medical information are currently available but are not yet in common use. The history of onset is important. Coma of sudden onset in a previously healthy patient usually turns out to be self-induced drug poisoning, subarachnoid hemorrhage, head trauma, or, in older persons, brainstem hemorrhage or infarction. Most examples of supratentorial mass lesions produce a more gradual impairment of consciousness, as do the metabolic encephalopathies.
In the general physical examination, after assessing and dealing with abnormalities of vital signs, look for evidence of trauma or signs that might suggest an acute or chronic systemic medical illness or the ingestion of self-administered drugs. Evaluate nuchal rigidity, but take care first to ensure that the cervical spine has not been injured.23
It is the neurologic examination that is most helpful in assessing the nature of the patient’s unconsciousness. Table 7.2 outlines the clinical neurologic functions that provide the most useful information in making a categorical diagnosis. These clinical indices have been extensively tested and applied to patients. They have proved themselves to be easily and quickly obtained and to have a high degree of consistency from examiner to examiner.10,24,25,26 Furthermore, they give valuable information upon which to base both diagnosis and prognosis. When serially recorded on a vital signs sheet during each 24 hours, the result reflects accurately the patient’s clinical course. The following paragraphs give a detailed description of each clinical sign.
Table 7.2 A Score Sheet for Examination of the Comatose Patient
Name of examiner
Date and time
History (from relatives or friends)
Onset of coma (abrupt, gradual)
Recent complaints (headache, depression, focal weakness, vertigo)
Previous medical illnesses (diabetes, uremia, heart disease)
Previous psychiatric history
Access to drugs (sedatives, psychotropic drugs)
Occupation (pesticides, CO exposure)
Exposure to pathogens (ticks, mosquitoes)
Eye positions at rest
Conjugate or slight symmetric exo- or esodeviation
Asymmetric deviation (describe)
Spontaneous eye movements
Abnormal movements (describe)
Oculovestibular responses (if oculocephalic responses are minimal or not obtainable)
Normal awake (nystagmus)
Localizing (describe if asymmetric)
Abnormal flexion posturing
Abnormal extension posturing
Deep tendon reflexes
Skeletal muscle tone
General physical examination
Evidence of trauma
Evidence of acute or chronic systemic illness
Evidence of drug ingestion (needle marks, alcohol on breath)
Nuchal rigidity (examine with care)
Response to verbal stimuli
Response to noxious stimuli
Present and symmetric
Assessment of the verbal best response allows assessment of orientation implying awareness of self and the environment. The patient knows who he or she is, where he or she is, why he or she is there, and the year, season, and month. Confused conversation describes conversational speech with syntactically correct phrases but with disorientation and confusion in the content. Inappropriate speech means intelligible isolated words, which may not be responsive or appropriate. The content can include profanity but no sustained conversation. Incomprehensible speech refers to the production of word-like mutterings or groans. The worst verbal response, no speech, applies to mutism.
The pattern is recorded as regular, periodic, hyperpneic, ataxic, or a combination of these. Respiratory rate is best determined in patients not being mechanically ventilated.
Patients with spontaneous eye opening have some tone in the eyelids and generally demonstrate spontaneous blinking, which differentiates them from completely unresponsive patients whose eyes sometimes remain passively open. Though spontaneous eye opening rules out coma by our definition, it does not guarantee awareness. Some patients remaining in a vegetative state, who by definition show eye opening, have been shown postmortem to have total loss of the cerebral cortex (see Chapter 9). Eye opening in response to verbal stimuli means that any verbal stimulus, whether an appropriate command or not, produces eye opening. More severely brain-injured patients demonstrate eye opening only in response to a noxious stimulus applied to the trunk or an extremity. The worst response, no eye opening, applies to all remaining patients except when local changes such as periorbital edema preclude examination.
Pupillary reactions to an intense flashlight beam are evaluated for both eyes, and the better response is recorded; use a hand lens or the plus 20 lens on the ophthalmoscope to evaluate questionable responses. Record pupillary diameters and shape as well as if they are ectopic (i.e., not centered).27 Increasingly, video-assisted quantification of pupillary reaction using pupillometer devices is used in clinical practice.28,29
Eye Position at Rest
During sleep or metabolic coma, the eyes typically are slightly but symmetrically in exodeviation, although they may be conjugate or even have a slight symmetrical esodeviation. Any asymmetry in eye position should be noted, including exo-, eso-, superior or inferior deviation that is most marked in one eye, or skew deviation, when both eyes are out of the neutral position at rest. However, this must be interpreted in light of the baseline eye positions for that individual, as many people have congenital or acquired strabismus. Examining a photo ID or other photograph of the patient may be helpful.
Spontaneous Eye Movement
The best response is spontaneous, orienting eye movements in which the patient looks toward environmental stimuli. Record roving conjugate and roving dysconjugate eye movements when present, and reserve a miscellaneous movement category for patients without orienting eye movements who have spontaneous nystagmus, opsoclonus, ocular bobbing, or other abnormal eye movement. Absent spontaneous eye movements should be noted.
These are evaluated in conjunction with passive, brisk, horizontal, and vertical head turning. Patients with normal waking responses retain orienting eye movements and do not have consistent oculocephalic responses. Full oculocephalic responses are brisk conjugate eye movements opposite to the direction of turning. Abnormal responses, which may include selective loss of horizontal or vertical movement of one or both eyes, should be described. Minimal responses are defined as conjugate movements of less than 30 degrees. Absence of response is the poorest level of function. Remember, do not test oculocephalic reflexes in patients suspected of having sustained a neck injury.
Caloric Vestibulo-Ocular Responses
In the absence of oculocephalic responses, it may be necessary to apply more intense and long-lasting vestibular stimulation by irrigating each external auditory canal with up to 50 mL of ice water with the head 30 degrees above the horizontal plane (Chapter 2). An intact response in an unconscious patient consists of tonic responses with conjugate deviation toward the irrigated ear.
Note that this procedure should not be done in a patient with a suspected psychiatric presentation who may be nonresponsive but awake. A normal (awake) response includes horizontal nystagmus with the rapid phase toward the nonirrigated ear, accompanied by severe vertigo and nausea.
Responses to a cotton wisp drawn fully across the cornea or—safer—sterile saline dripped onto the cornea are recorded as present, asymmetric (describe), or absent.
These should be tested and recorded in all extremities and the strength noted as normal or weak. The best score is given to patients who obey commands; care should be taken to avoid interpreting reflex grasping as obedience. If a command evokes no response, apply a noxious stimulus gently but firmly to each extremity (compression of finger or toenail beds, or of Achilles tendon) and to the supraorbital notches or temporomandibular joints. Localizing responses indicate the use of an extremity to locate or resist a remote noxious stimulus (e.g., the arm reaching toward a cranial stimulus on the face or one on the trunk). Asymmetries in sensation (neither arm moves toward stimuli on one side of the body) or motor response (one arm moves less toward both sides) may indicate lateralized damage to the ascending sensory or descending motor pathways and should be noted. A more primitive response consists of a nonstereotyped, rapid withdrawal from a noxious stimulus; this response often incorporates hip or shoulder adduction. An abnormal flexion response in the upper extremities is stereotyped, slow, and dystonic, and the thumb is often held between the second and third fingers. Abnormal flexion in the lower extremities (the reflex triple flexion response) sometimes can be difficult to distinguish from withdrawal. An abnormal extension response in the upper extremity consists of adduction and internal rotation of the shoulder and pronation of the forearm. No response is recorded only when strong stimuli are applied to multiple sites on each side of the body and when muscle relaxants have not recently been administered.
These reflexes are recorded for the best limb as normal, increased, asymmetric, or absent; minimal responses are best regarded as normal. Asymmetric tendon reflexes should be described, as these may be a clue to lateralized brain or spinal cord injury.
Emergent Treatment for All Patients with Stupor or Coma
Emergent interventions must be guided by history, exam findings, and basic diagnostic tests if a possible or likely cause of stupor or coma is identified. The goal of these emergent interventions is to reverse progressive medical conditions that, if untreated, will rapidly lead to further worsening of the underlying condition and accumulation of irreversible brain injury. These interventions often must be initiated even before the physician completes a comprehensive diagnostic workup.
Examples include treatment of hypoglycemia or hyperglycemia, antibiotics for infections, steps to lower ICP, antiepileptics to treat seizures, treatment of hypo- or hyperthermia, correction of acid–base abnormalities, and administration of antidotes. In addition, patients with stupor and coma may need interventions for pain and agitation. Nearly all patients with impaired consciousness will require a non-contrast head computed tomography (CT) scan, as some intracranial processes that cause coma may leave few if any clues on the neurological examination (e.g., bilateral subdural hematomas, subarachnoid hemorrhage, acute hydrocephalus). Certainly if the patient has evidence of a supratentorial mass lesion (e.g., asymmetric sensory or motor exam, uncal herniation syndrome) or a brainstem catastrophe (e.g., due to a cerebellar hemorrhage or basilar occlusion), it may be necessary to begin attempts to reduce ICP and move immediately to a CT scan. But, for the many patients who have nonfocal exams at this point (as described in Chapter 2), it is important to perform basic diagnostic testing (e.g., finger stick glucose, oximetry, possibly arterial blood gases, drawing blood for toxicology, fluid and electrolytes, and blood counts), as well as consider the following emergent interventions before the patient is consigned to the inevitable 5- to 15-minute delay required for CT scanning (in even the best of facilities).
Hypoglycemia or Hyperglycemia
The brain depends not only on oxygen and blood flow, but also on the obligate use of glucose for energy (see Chapter 5). Both hypoglycemia and hyperglycemia have deleterious effects on the brain (see Chapter 5). If the bedside blood glucose test reveals hypoglycemia, glucose should be given. This is often done empirically along with thiamine and naloxone by paramedics, before the patient arrives at the hospital; if not, glucose and thiamine should be given after reaching the hospital. Exact recommendations vary but 50 mL of a 50% intravenous solution of glucose is frequently used. Once stabilized and in the intensive care unit, studies have shown that tight glucose control using insulin decreases morbidity in non-neurologic severely ill patients. However, patients with acute brain injury may be harmed by this approach, and more liberal glucose targets are advocated for these patients.30 Even after a hypoglycemic patient has been treated with glucose, care must be taken to prevent recurrent hypoglycemia. Therefore, ongoing monitoring of finger stick glucose and possible infusion of glucose and water intravenously may be necessary until the situation has stabilized. The comatose patient who is diagnosed with hyperglycemia may be treated with appropriate doses of intravenous insulin and normal saline fluids containing potassium, as glucose causes potassium to move intracellularly and blood levels can drop.
Wernicke’s encephalopathy is a rare cause of coma.31 However, many patients admitted as emergencies in stupor or coma are chronic alcoholics or otherwise malnourished.32,33 In such a patient, a glucose load may precipitate acute Wernicke’s encephalopathy.34 Therefore, it is important to administer 100 mg thiamine intramuscularly or to put it into the intravenous fluids at the time glucose is given or shortly thereafter. Oral thiamine is often poorly absorbed in malnourished individuals.
Many patients entering an emergency room in coma are suffering from drug overdose. Any of the gamut of sedative drugs, alcohol, opioids, tranquilizers, and hallucinogens may have been ingested singly or in combination. In addition, patients suffering from psychiatric disorders who attempt suicide may have ingested antidepressant or neuroleptic drugs. Most drug overdoses are best treated by the supportive measures considered in a subsequent section. Because these patients often have ingested multiple agents, specific antagonists may not be useful.35 Even the so-called “coma cocktail”3 (dextrose, thiamine, naloxone, and flumazenil) is rarely helpful and may be harmful.36 However, when there is a strong suspicion that a specific agent has been ingested, certain antagonists specifically reverse the effects of several coma-producing drugs (Table 7.3).
Table 7.3 Specific Antidotes for Agents Causing Delirium and Coma
Anticholinergic overdose (? gamma-hydroxybutyrate toxicity)
Methanol, ethylene glycol toxicity
? Tricyclic overdose
a Acetaminophen overdose does not impair consciousness but is often taken as part of a polydrug overdose; if not treated promptly, it may cause liver failure that does impair consciousness.
Data from Ries and Dart.39
For opioid overdose (usually signaled by pinpoint but reactive pupils), intravenous naloxone may be given at 0.4–2.0 mg every 3 minutes or by continuous intravenous infusion at 0.8 mg/kg/hr until consciousness is restored. This drug must be used with great care because in a patient physically dependent on opioids, the drug may cause acute withdrawal symptoms requiring opioid therapy.37 (If the patient is a known or suspected opioid addict, 0.4 mg naloxone should be diluted in 10 mL of saline and given slowly.)
One should use the minimum amount necessary to establish the diagnosis, as demonstrated by pupillary dilation and reversal of the comatose state. Naloxone has a duration of action from 2 to 3 hours, much shorter than the action of several opioid drugs, especially methadone. Thus, patients who have taken an overdose of opioids, and whose toxic reactions are reversed by naloxone, may lapse back into coma after a few hours and require further treatment.
If there is reason to suspect a benzodiazepine overdose, the patient can be treated with flumazenil, a specific competitive benzodiazepine receptor antagonist38 (0.2 mg/min to a maximum dose of 1 mg intravenous). Flumazenil acts within minutes and has a half-life of about 40–75 minutes. However, caution is recommended as this may precipitate acute withdrawal in chronic users or seizures in patients who have ingested medications such as tricyclic antidepressants or theophylline that lower seizure thresholds.38 In addition, flumazenil may cause nonconvulsive SE to transition into refractory SE, which has been associated with high morbidity and mortality.
Certain effects of sedative drugs that have anticholinergic properties, particularly the tricyclic antidepressants and possibly gamma-hydroxybutyrate, can be reversed by the intravenous injection of 1 mg physostigmine. However, its use is controversial as it may cause seizures and cardiac arrhythmias; because of its potential side effects and short duration of action, it is rarely used.39 Specific antidotes for several other agents are discussed in Chapter 5 and indicated in Table 7.3. Extracorporeal treatments have a role in certain intoxications, particularly if combined with acute respiratory distress syndrome.40
Many different systemic or CNS infections cause delirium or coma, and infection may exacerbate coma from other causes. Systemic infections are thought to impair consciousness via systemic inflammatory mediators, including cytokines and prostaglandins, which also cause fever that may further reduce alertness. On presentation, patients may be either hyperthermic (febrile) or hypothermic, often have tachycardia, and, if they are septic, may also have hypotension. If the infection involves the CNS there may be focal neurological signs in addition to stupor or coma. Successful treatment of systemic or CNS infections to a large extent depends on rapid administration of antibiotics. Details of meningitis treatment will be discussed in Chapter 8 but a generalized approach to the patient with suspected infection will be presented here. Empiric treatment of sepsis or meningitis treatment should not be delayed by diagnostic studies if the suspicion is high. Choices of antibiotics should be guided by the likely pathogens, and local antibiograms should be taken into account when selecting the most appropriate empiric antibiotic regimen, as well as the immune competency of the patient (e.g., chemotherapy or acquired immune deficiency disorders), the clinical setting of onset of the symptoms (nursing home vs. community vs. in-hospital setting), type of infection (sepsis vs. meningitis), and age of the patient. Blood cultures should be drawn on all comatose patients who are febrile or who are hypothermic without obvious cause. For suspected bacterial meningitis, a third-generation cephalosporin together with vancomycin should be started. In elderly or obviously immunosuppressed patients, ampicillin should be added. Current evidence suggests that dexamethasone should added to the regimen7 (see Chapter 8 for details). As discussed in Chapter 3, it is generally necessary in a comatose patient to obtain a CT scan prior to attempting lumbar puncture. If cerebrospinal fluid (CSF) cultures can be obtained within the first hour or two after antibiotics are administered, it may still be possible to identify the organism and its antibiotic sensitivities.
In comatose patients with suspected elevation of ICP (e.g., after head trauma), it is important first to establish cardiovascular stability and C-spine stabilization., followed by rapid-sequence intubation after premedication with lidocaine (see earlier discussion). A number of general measures to treat elevated ICP should be employed, but these should be administered simultaneous (not sequentially) to lower ICP (Figure 7.2). The head of the bed should be raised to 30 degrees and the head kept straight to allow optimal drainage of venous blood via the jugular veins. Mild hyperventilation is recommended as a temporizing measure only (never allow the PCO2 to drop below 25 mm Hg) until more definitive treatment such as surgical evacuation of a mass lesion. Adequate oxygenation should be assured with pulse oximetry checks, and an arterial blood gas sent as soon as possible. Isotonic intravenous fluids with inotropic medications if needed should be given to maintain a mean arterial pressure (MAP) of 80 mmHg or higher to allow adequate cerebral perfusion in the setting of elevated ICP. Hypotonic fluids should be avoided and blood products given as needed. Pain needs to be controlled, ideally with short-acting analgesics with the least effect on blood pressure (fentanyl 20–200 μg/hr, alternatives in the patient without central access include intravenous morphine 2–4 mg q2–4h). Agitation should be controlled emergently, often requiring sedation with short-acting sedatives such as propofol (propofol 0.1–5 mg/kg/hr) or benzodiazepines.
If the clinical exam raises the concern for herniation, emergent pharmacologic treatments should be initiated based on the clinical exam alone and not withheld until imaging confirms the suspected diagnosis. However, a head CT needs to be obtained for all patients with suspected ICP elevation as soon as possible to allow potential treatment of the underlying cause while initial empiric therapeutics for ICP elevation are administered. Whenever possible, one should attempt to treat the underlying cause for the ICP elevation. Treatment of the underlying cause may involve placement of external ventricular drainage catheters which can be a life-saving procedure and may need to be placed in the emergency room. Other surgical interventions include emergent evacuation of space-occupying lesions such as cerebellar hemorrhages.
Emergent pharmacologic agents that lower the ICP include intravenous mannitol (typically given as 0.5–1 gm/kg total body weight over 15 minutes, with normal saline replacement of the volume lost in the subsequent diuresis). Hypertonic saline in a variety of concentrations is available as an alternative; however, data are limited and caution is warranted for patients with chronic hyponatremia, cardiac instability, and lung pathology such as pulmonary edema. Serum sodium and osmolality should be measured regularly for both patients receiving mannitol or those receiving hypertonic saline. If these interventions fail to lower the elevated ICP, barbiturate treatment may be used (pentobarbital or thiopental). Pentobarbital is given as a load 20 mg/kg over 60 minutes followed by 1 mg/kg/hr. The dose is titrated up to 3 mg/kg/hr as needed to achieve burst suppression on EEG with 4–6 bursts per minute. It is important to observe for hypotension, which is a major side effect. The role of hypothermia in the treatment of traumatic brain injury patients with elevated ICP is not clear at this point.41 Steroids have no role in the treatment of patients with traumatic brain injury42 or other forms of cytotoxic edema but are given frequently for vasogenic edema, as seen in patients with brain tumors.
When treating suspected ICP elevation, it is often useful to place ICP monitors. ICP monitoring is typically performed with pressure monitors placed into the ventricles (external ventricular drainage) or brain parenchyma (typically placed in the frontal lobe ipsilateral to the injury).
In a randomized controlled trial that compared two ICP treatment protocols, in one in which ICP treatment was guided by clinical examination and serial imaging, and the other by ICP measurements exceeding 20 mm Hg,43 the latter arm showed a trend toward more efficient delivery of care, although outcomes were similar. Experts have since suggested that the best treatment would include both ICP monitoring and clinical and imaging evaluation to take the underlying evolving pathophysiology into account,44 but this has not been directly tested. Relating other measures of brain physiology to the elevation in ICP (Figure 7.3) may help guide management and is being tested in clinical trials (for details, please refer to the traumatic brain injury section in Chapter 8).
Ongoing seizure activity as seen in status epilepticus (SE), of whatever etiology, can cause brain damage and must be stopped (for details please refer to Chapter 5). Important principles for the treatment of SE include early treatment at adequate dosage (80% respond to the first antiepileptic drug if treatment is initiated within 30 minutes of onset, while only 40% respond when treatment starts 2 hours or more after seizure onset).2 It is important to monitor the patient continuously during treatment for continuing seizure activity as well as cardiovascular or respiratory complications either from ongoing seizures or seizure treatment. In the VA cooperative study, 20% of patients in whom medication stopped the clinically visible manifestations of seizures remained in electrographic SE.45 Hence, if the patient does not return to the pre-status baseline within 15–20 minutes after convulsions have stopped, it is important to continue monitoring using EEG to detect ongoing nonconvulsive seizure activity.
Clinical trials have established intravenous lorazepam as an acute treatment for SE (4 mg with the option of giving another 4 mg after 5 minutes if seizures continue)45 and support intramuscular midazolam (0.2 mg/kg; max 10 mg) as an alternative.6 Personnel and equipment must be available to perform emergency respiratory support if needed; because both ongoing seizure activity and many antiseizure medications may depress breathing, many patients with SE will ultimately require intubation. However, as ongoing seizure activity is more likely to cause respiratory decompensation than benzodiazepine treatment, it is still important to start the treatment of SE as soon as possible, including in the out-of-hospital setting.5 Adding levetiracetam as a second antiepileptic agent in the pre-hospital setting was not associated with better seizure control or outcomes for patients with convulsive SE.46
As lorazepam typically suppresses seizures only for 20–30 minutes, it is important to begin concomitant treatment with either phenytoin/fosphenytoin (20 mg PE/kg IV administered at a rate of 50 mg/min for phenytoin and 150 mg/min for fosphenytoin; may give additional 5 mg/kg for ongoing seizures activity) or intravenous valproic acid (20–40 mg/kg; may give additional 20 mg/kg).47 Many investigators advocate for more aggressive and rapid escalation of treatment for patients who do not respond to the initial benzodiazepine because only 7% of patients who did not respond to the first-line antiepileptic drugs responded to the second-line drug in the VA cooperative trail.45 For example, some authorities propose going straight to continuous infusion of midazolam (initial 0.2 mg/kg; maintenance 0.05–2 mg/kg/hr)47 but controversy regarding the early use of continuous application of antiepileptic agents at anesthetic dosages still exists.48 The role of alternative agents such as levetiracetam or lacosamide is not clear at this point.
On the other hand, for patients with refractory SE whose seizures persist after first- and second-line treatment, most experts recommend advancing to anesthetic dosages of either midazolam or propofol because refractory SE is associated with high morbidity and mortality. Although most seizures occurring at this stage are nonconvulsive, they still should be treated in the same way as convulsive SE. No adequately powered randomized controlled trial has compared midazolam and propofol treatments, but efficacy of either treatment is highly dose dependent.49,50 Alternatives include treatment with valproic acid or levetiracetam if not given at an earlier stage, particularly for those patients with prior directives not to intubate. Doses of anesthetics are titrated up until seizures are controlled and typically continued for 24–48 hours, at which point weaning will start if seizures have been controlled.
Seizures that occur despite treatment with midazolam or propofol are called super refractory SE and carry a very high mortality rate. They are typically treated with intravenous pentobarbital infusions (load 5 mg/kg up to 50 mg/ min; repeat 5 mg/kg boluses until seizures stop; maintenance, 0.5–10 mg/kg/hr).51 A long list of additional treatments has been proposed, including ketamine, which, as an N-methyl-d-aspartate (NMDA) antagonist, may be attractive for benzodiazepine-unresponsive seizures,52 and hypothermia, which not only suppresses seizure activity but also is neuroprotective.53
Focal continuous epilepsy such as epilepsia partialis continua, by contrast, frequently occurs with metabolic brain disease but is less threatening to the brain and does not require the use of anesthetic doses of anticonvulsant drugs.
Patient Vignette 7.1
A 30-year-old woman presents with sudden onset of fluctuating unresponsiveness on postpartum day six with a sudden onset of fluctuating unresponsiveness after an uncomplicated pregnancy and delivery of a healthy baby. At an outside hospital, her blood pressure was 152/88 mm Hg and she was found to have a large frontal lobe intracerebral hemorrhage; she underwent emergent placement of an external ventricular drainage catheter and an attempted clot evacuation. Post intervention she remained unconscious and was transferred to a tertiary care center. Here she was found to be unconscious, pupils were reactive to light, present corneal reflexes, present doll’s eye movement, but she had no eye deviation and no motor response to stimulation. Head computed tomography (CT) scan showed persistent right frontal intracerebral hemorrhage (Figure 7.4, Panel A), but the level of consciousness was judged to be out of proportion depressed compared to the CT findings. Electroencephalogram (EEG) monitoring showed continuous right hemispheric seizure activity (Figure 7.4, Panels B and C). A digital subtraction angiogram showed beading of the arteries most consistent with postpartum reversible vasoconstriction syndrome (Call-Fleming syndrome). Her seizures were controlled with levetiracetam and phenytoin. Following seizure control, she had prompt recovery of consciousness and was extubated the following day.
Patient Vignette 7.2
A 39-year-old woman presented with a history of cerebral palsy and epilepsy well controlled on Tegretol. During pregnancy, Tegretol was stopped and levetiracetam started. Seizures occurred with increasing frequency despite adding Lamictal and phenobarbital. She presented with three generalized tonic-clonic seizures and subsequent frequent episodes of right arm numbness followed by head and gaze deviation to the right that evolved into nonconvulsive status epilepticus (see Figure 7.5, Panels A and B) at 30 weeks of gestational age. The obstetrics team strongly felt that eclampsia was unlikely as her blood pressure ranged from 120–130s over 70–80s mm Hg and no proteinuria was present. Despite this, with eclampsia high on the differential, the neurocritical care team treated her with magnesium infusions in addition to phenobarbital 100 every 8 hours, Lamictal 200 every 12 hours, levetiracetam 2 g every 12 hours, carbamazepine 800 mg every 12 hours, midazolam infusion up to 2.9 mg/kg/hr, and ketamine 100 mg bolus twice. Initially the fetal heart rate monitor and ultrasound showed a healthy baby. Seizures became more frequent, up to every 2 minutes and the fetal heart rate monitor showed absent decelerations and no movement on ultrasound. An emergent cesarean section was performed at the bedside (see Figure 7.5: Panel C displays quantitative EEG measures summarizing an 8-hour period initially showing increasing seizure frequency with abrupt cessation of seizures following the caesarian section). Not a single seizure was recorded subsequently, and she was rapidly titrated off the midazolam infusion. She was transitioned back to her prepregnancy antiepileptic regimen with good seizure control. Both, mother and baby recovered fully.
Hypo- and Hyperthermia
Several metabolic and structural abnormalities lead to either hyperthermia or hypothermia, and these states may exacerbate abnormalities of cerebral metabolism.54 Hyperthermia is dangerous because it increases cerebral metabolic demands and, at extreme levels, can denature brain cellular proteins.55 The body temperature above 38.5°C of hyperthermic patients should be reduced using antipyretics and, if necessary, physical cooling (e.g., cooling blanket). Significant hypothermia (below 34°C) can lead to pneumonia, cardiac arrhythmias, electrolyte disorders, hypovolemia, metabolic acidosis, impaired coagulation, and thrombocytopenia and leukopenia.54 Patients should be gradually warmed to maintain a body temperature higher than 35°C.
With severe metabolic acidosis or alkalosis, the pH should be returned to a normal level by treating the cause, as metabolic acidosis can lead to cardiovascular complications and metabolic alkalosis can depress respiration. Respiratory acidosis presages respiratory failure and warns the physician that ventilatory assistance may soon be needed. The elevated CO2 also raises ICP. Respiratory alkalosis can cause cardiac arrhythmias and hinders weaning from ventilatory support.
Many patients who are delirious or stuporous are grossly agitated. The hyperactivity is distressing to patients and family and may lead to self-injury. Sedative dosages of drugs should be avoided until the diagnosis is clear and one is certain that the problem is metabolic rather than structural. Agitation can be controlled by keeping the patient in a lighted room and asking a relative or staff member to sit at the bedside and talk reassuringly to the patient. Antipsychotic medications (i.e., haloperidol 0.5–1.0 mg orally or intramuscularly)56 are preferred by some as benzodiazepines may complicate the examination due to sedative side effects and have been associated with the risk of developing delirium. While parenteral haloperidol is often used acutely to sedate an agitated patient, it can cause sleepiness as well as extrapyramidal side effects (dystonia, parkinsonism) that can cloud the neurological exam. Hence it should not be used prophylactically.57 In an intensive care unit setting, if prophylactic sedation is needed and nasogastric access is available, quetiapine is the preferred neuroleptic medication as it generally does not cause extrapyramidal side effects. If benzodiazepines are chosen, small doses of short-acting medications, such as lorazepam 0.5–1.0 mg orally with additional doses every 4 hours, are preferred. In patients who have habitually abused alcohol or sedative drugs, larger doses may be necessary because of cross-tolerance. For very short-term sedation, as might be necessary to perform a CT scan, intravenous sedation with dexmedetomidine, propofol, or midazolam may be used, but ventilation and circulation must be continuously monitored as these drugs may cause respiratory arrest or hypotension. Physical restraints should be avoided whenever possible, but may be necessary for severely agitated patients to prevent self-harm. Care must be taken to ensure that body restraints do not interfere with breathing and that limb restraints do not occlude blood flow or damage peripheral nerves. The restraints should be removed as soon as the agitation is controlled.
Protect the Eyes
Corneal erosions can occur within 4–6 hours if the eyes of comatose patients remain partially or fully opened. Exposure keratitis may lead to secondary bacterial corneal ulcerations. To prevent such damage, lubricate the eyes with a lubricating artificial tears ointment every 4 hours58 or apply a polyethylene corneal bandage.59 Repeated testing of the corneal reflex with cotton can also damage the cornea. A safer technique is to drip sterile saline onto the cornea from a distance of 4–6 inches.10
More Definitive Diagnosis and Treatment of Specific Etiologies of Stupor and Coma
Initial treatment of comatose patients is most successful if a multidisciplinary team approach with well-established protocols is employed, as illustrated by the highly successful strategies commonly used for patients with traumatic brain injury. These initial efforts stabilize the patient and minimize the chances of further brain injury while more definitive diagnostic steps are taken. This workup is guided by the history and clinical examination, as well as by basic diagnostic tests (as discussed earlier) and initial response to treatment. Depending on the setting, additional workup may include imaging (CT and MRI studies; CT, MRI or digital subtraction angiography), EEG, ultrasound, or neurosurgical procedures such as placement of an intraventricular catheter. The workup and subsequent treatment for specific disorders that impair consciousness are discussed in the next chapter.
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