Buy the Book PDA Download

Update Me E-mail alerts The Merck Manual Minute

Print This Topic Email This Topic

Coma is unresponsiveness from which the patient cannot be aroused. Similar, but less severe disturbances of consciousness may also occur. The mechanism involves dysfunction of both cerebral hemispheres or of the reticular activating system (also known as the ascending arousal system). Causes may be structural or nonstructural (eg, toxic or metabolic disturbances). Damage may be focal or diffuse. Diagnosis is clinical; identification of cause usually requires laboratory tests and neuroimaging. Treatment is immediate stabilization and specific management of the cause. For long-term coma, adjunctive treatment includes passive range-of-motion exercises, enteral feedings, and measures to prevent pressure ulcers.

Decreased or impaired consciousness or alertness refers to decreased responsiveness to external stimuli. Severe impairment includes

• Coma: The patient usually cannot be aroused, and the eyes do not open in response to any stimulation.
• Stupor: The patient can be awakened only by vigorous physical stimulation.

Less severely impaired levels of consciousness are often labeled as lethargy or, if more severe, obtundation. However, differentiation between less severely impaired levels is often imprecise; the label is less important than a precise clinical description (eg, “the best level of response is partial limb withdrawal to nail bed pressure”). Delirium differs because cognitive disturbances (in attention, cognition, and level of consciousness) fluctuate more; also, delirium is usually reversible (see Delirium and Dementia).

Pathophysiology

Maintaining alertness requires intact function of the cerebral hemispheres and preservation of arousal mechanisms in the reticular activating system (RAS—also known as the ascending arousal system)—an extensive network of nuclei and interconnecting fibers in the upper pons, midbrain, and posterior diencephalon. Therefore, the mechanism of impaired consciousness must involve both cerebral hemispheres or dysfunction of the RAS.

To impair consciousness, cerebral dysfunction must be bilateral; unilateral cerebral hemisphere disorders are not sufficient, although they may cause severe neurologic deficits. However, rarely, a unilateral massive hemispheric focal lesion (eg, left middle cerebral artery stroke) impairs consciousness if the contralateral hemisphere is already compromised.

Usually, RAS dysfunction results from a condition that has diffuse effects, such as toxic or metabolic disturbances (eg, hypoglycemia, hypoxia, uremia, drug overdose). RAS dysfunction can also be caused by focal ischemia (eg, certain upper brain stem infarcts), hemorrhage, or direct, mechanical disruption.

Any condition that increases intracranial pressure may decrease cerebral perfusion pressure, resulting in secondary brain ischemia. Secondary brain ischemia may affect the RAS or both cerebral hemispheres, impairing consciousness.

When brain damage is extensive, brain herniation (see Fig. 1: Coma and Impaired Consciousness: Brain herniation. and see Table 1: Coma and Impaired Consciousness: Effects of Herniation) contributes to neurologic deterioration because it directly compresses brain tissue, increases intracranial pressure, and may lead to hydrocephalus.

Fig. 1
Brain herniation. Because the skull is rigid after infancy, intracranial masses or swelling may increase intracranial pressure, sometimes causing protrusion (herniation) of brain tissue through one of the rigid intracranial barriers (tentorial notch, falx cerebri, foramen magnum). When intracranial pressure is increased sufficiently, regardless of the cause, Cushing's reflex and other autonomic abnormalities can occur. Cushing's reflex includes systolic hypertension, increased pulse pressure, and bradycardia. Brain herniation is life threatening. Transtentorial herniation: The medial temporal lobe is squeezed by a unilateral mass under the tentlike tentorium that supports the temporal lobe. The herniating lobe compresses the following structures: Ipsilateral 3rd cranial nerve (often first) and posterior cerebral artery As herniation progresses, the ipsilateral cerebral peduncle In about 5% of patients, the contralateral 3rd cranial nerve and cerebral peduncle Eventually, the upper brain stem and the area in or around the thalamus Subfalcine herniation: The cingulate gyrus is pushed under the falx cerebri by an expanding mass high in a cerebral hemisphere. In this process, one or both anterior cerebral arteries become trapped, causing infarction of the paramedian cortex. As the infarcted area expands, patients are at risk of transtentorial herniation, central herniation, or both. Central herniation: Both temporal lobes herniate because of bilateral mass effects or diffuse brain edema. Ultimately, brain death occurs. Upward transtentorial herniation: This type can occur when an infratentorial mass (eg, tumor, cerebellar hemorrhage) compresses the brain stem, kinking it and causing patchy brain stem ischemia. The posterior 3rd ventricle becomes compressed. Upward herniation also distorts the mesencephalon vasculature, compresses the veins of Galen and Rosenthal, and causes superior cerebellar infarction due to occlusion of the superior cerebellar arteries. Tonsillar herniation: Usually, the cause is an expanding infratentorial mass (eg, cerebellar hemorrhage). The cerebellar tonsils, forced through the foramen magnum, compress the brain stem and obstruct CSF flow.

Table 1
Effects of Herniation Type of Herniation Mechanism* Findings Transtentorial Compression of ipsilateral 3rd cranial nerve Unilateral dilated fixed pupil Oculomotor paresis   Compression of the posterior cerebral artery Contralateral homonymous hemianopia Absence of blinking in response to visual threat in obtunded patients   Compression of the contralateral 3rd cranial nerve and cerebral peduncle Contralateral dilated pupil and oculomotor paresis Ipsilateral hemiparesis   Compression of the ipsilateral cerebral peduncle Contralateral hemiparesis   Eventually, compression of the upper brain stem and the area in and around the thalamus Impaired consciousness Abnormal breathing patterns Fixed, unequal pupils   Further compromise of the brain stem Loss of oculocephalic reflex Loss of oculocephalic reflex Loss of corneal reflexes Decerebrate posturing Subfalcine (cingulate) Trapping of one or both anterior cerebral arteries, causing infarction of the paramedian cortex Leg paralysis   Expansion of infarcted area Edema Increased intracranial pressure Increased risk of transtentorial herniation, central herniation, or both Central Bilateral, more or less symmetric damage to the midbrain Pupils fixed in midposition Decerebrate posturing Many of the same symptoms as transtentorial herniation   Further compromise of the brain stem Loss of all brain stem reflexes Disappearance of decerebrate posturing Cessation of respirations Brain death Upward transtentorial Compression of the posterior third ventricle Hydrocephalus, which increases intracranial pressure   Distortion of the mesencephalon vasculature Compression of the veins of Galen and Rosenthal Superior cerebellar infarction due to occlusion of the superior cerebellar arteries Early: Nausea, vomiting, occipital headache, ataxia Later: Somnolence, breathing abnormalities, patchy and progressive loss of brain stem reflexes   Posterior fossa mass (eg, cerebellar hemorrhage) Ataxia   Progression Increasing somnolence Respiratory irregularities Patchy but progressive loss of brain stem reflexes Tonsillar Compression the brain stem Obstruction of CSF flow Acute hydrocephalus (with impaired consciousness, headache, vomiting, and meningismus) Dysconjugate eye movements Later, abrupt respiratory and cardiac arrest *Not all mechanisms occur in every patient.

Impaired consciousness may progress to coma and ultimately to brain death (see Coma and Impaired Consciousness: Brain Death).

Etiology

Coma or impaired consciousness may result from structural disorders, which typically cause focal damage, or nonstructural disorders, which typically cause diffuse damage (see Table 2: Coma and Impaired Consciousness: Common Causes of Coma or Impaired Consciousness). But causes are usually thought of as structural or diffuse.

Table 2
Common Causes of Coma or Impaired Consciousness Cause Examples Focal   Structural disorders Brain abscess Brain tumor Head trauma (eg, concussion, cerebral lacerations or contusions, epidural or subdural hematoma) Hydrocephalus (acute) Intraparenchymal hemorrhage Subarachnoid hemorrhage Upper brain stem infarct or hemorrhage Nonstructural disorders Seizures (eg, nonconvulsive status epilepticus) or a postictal state caused by an epileptogenic focus Diffuse   Metabolic disorders Diabetic ketoacidosis Hepatic encephalopathy Hypercalcemia Hypercapnia Hypoglycemia Hyponatremia Hypoxia Myxedema Uremia Wernicke's encephalopathy Infections Encephalitis Meningitis Sepsis Other disorders Diffuse axonal injury Hypertensive encephalopathy Hyperthermia or hypothermia Drugs Sedatives Other CNS depressants Toxins Carbon monoxide

Psychiatric disorders (eg, psychogenic unresponsiveness) can mimic impaired consciousness but are usually distinguished from true impaired consciousness by neurologic examination.

Symptoms and Signs

Consciousness is decreased to varying degrees. Repeated stimuli arouse patients only briefly or not at all.

Depending on the cause, other symptoms develop (see Table 3: Coma and Impaired Consciousness: Findings by Location*):

• Eye abnormalities: Pupils may be dilated, pinpoint, or unequal. One or both pupils may be fixed in midposition. Eye movement may be dysconjugate or absent (oculomotor paresis). Homonymous hemianopia may be present. Other abnormalities include absence of blinking in response to visual threat (almost touching the eye), as well as loss of the oculocephalic reflex (the eyes do not move in response to head rotation), the oculovestibular reflex (the eyes do not move in response to caloric stimulation), and corneal reflexes.
• Autonomic dysfunction: Patients may have abnormal breathing patterns (Cheyne-Stokes or Biot's respirations) or hypertension with bradycardia (Cushing's reflex). Abrupt respiratory and cardiac arrest may occur.
• Motor dysfunction: Abnormalities include flaccidity, hemiparesis, asterixis, multifocal myoclonus, decorticate posturing (elbow flexion and shoulder adduction with leg extension), and decerebrate posturing (limb extension and internal shoulder rotation).
• Other symptoms: If the brain stem is compromised, nausea, vomiting, meningismus, occipital headache, ataxia, and increasing somnolence can occur.

Table 3
Findings by Location* Location Abnormal Findings Bilateral hemispheric damage or dysfunction Symmetric tone and response (flexor or extensor) to pain Myoclonus (possible) Periodic cycling of breathing Supratentorial mass compressing the brain stem Ipsilateral 3rd cranial nerve palsy with unilateral dilated fixed pupil and oculomotor paresis Sometimes contralateral homonymous hemianopia and absent blinking response to visual threat Contralateral hemiparesis Brain stem lesion Early abnormal pupillary and oculomotor signs Abnormal oculocephalic reflex Abnormal oculovestibular reflex Asymmetrical motor responses Decorticate rigidity (usually due to an upper brain stem lesion) or decerebrate rigidity (usually due to a bilateral midbrain or pontine lesion) Hyperventilation (due to a midbrain or upper pontine lesion) Toxic-metabolic dysfunction Spontaneous, conjugate roving eye movements in mild coma Fixed eye position in deeper coma Abnormal oculovestibular reflex Decorticate and decerebrate rigidity or flaccidity Multifocal myoclonus *Not all of the findings occur in all cases. Also, brain stem reflexes and pupillary light responses are intact in bilateral hemispheric damage or dysfunction and in toxic-metabolic dysfunction.

Diagnosis

• History
• General physical examination
• Neurologic examination, including eye examination
• Laboratory tests (eg, pulse oximetry, bedside glucose measurement, blood and urine tests)
• Immediate neuroimaging
• Sometimes measurement of intracranial pressure
• If diagnosis is unclear, lumbar puncture or EEG

Impaired consciousness is diagnosed if repeated stimuli arouse patients only briefly or not at all. If stimulation triggers primitive reflex movements (eg, decerebrate or decorticate posturing), impaired consciousness may be deepening into coma.

Diagnosis and initial stabilization (airway, breathing, and circulation) should occur simultaneously. Glucose levels must be measured at bedside to identify low levels, which should be corrected immediately. If trauma is involved, the neck is immobilized until clinical history, physical examination, or imaging tests exclude an unstable injury and damage to the cervical spine.

History: Medical identification bracelets or the contents of a wallet or purse may provide clues (eg, hospital identification card, drugs). Relatives, paramedics, and police officers should be questioned about the environment in which the patient was found; containers that may have held food, alcohol, drugs, or poisons should be examined and saved for identification (eg, drug identification aided by a poison center) and possible chemical analysis. Relatives should be asked about the onset of the problem (eg, whether seizure, headache, vomiting, head trauma, or drug ingestion was observed), baseline mental status, recent infections, psychiatric problems and symptoms, drug history, substance use, previous illnesses, the last time the patient was normal, and any hunches they may have about what might be the cause (eg, possible occult overdose, possible occult head trauma due to recent intoxication). Medical records should be reviewed if available.

General physical examination: Physical examination should be focused and efficient and should include thorough examination of the head and face, skin, and extremities. Signs of head trauma include periorbital ecchymosis (raccoon eyes), ecchymosis behind the ear (Battle's sign), hemotympanum, instability of the maxilla, and CSF rhinorrhea and otorrhea. Scalp contusions and small bullet holes can be missed unless the head is carefully inspected. If unstable injury and cervical spine damage have been excluded, passive neck flexion is done; stiffness suggests subarachnoid hemorrhage or meningitis.

Fever, petechial or purpuric rash, hypotension, or severe extremity infections (eg, gangrene of one or more toes) may suggest sepsis or CNS infection. Needle marks may suggest drug overdose (eg, of opioids or insulin Some Trade Names
HUMULIN
NOVOLIN
Click for Drug Monograph
). A bitten tongue suggests seizure. Breath odor may suggest alcohol, other drug intoxication, or diabetic ketoacidosis.

Neurologic examination: The neurologic examination determines whether the brain stem is intact and where the lesion is located within the CNS (see Approach to the Neurologic Patient: Neurologic Examination). The examination focuses on the following:

• Level of consciousness
• Eyes (see below)
• Motor function
• Deep tendon reflexes

Level of consciousness is evaluated by attempting to wake patients first with verbal commands, then with non-noxious stimuli, and finally with noxious stimuli (eg, pressure to the supraorbital ridge, nail bed, or sternum). The Glasgow Coma Scale (see Table 4: Coma and Impaired Consciousness: Glasgow Coma Scale*) was developed to assess patients with head trauma. For head trauma, the score assigned by the scale is valuable prognostically. For coma or consciousness of any cause, the scale is used because it is a relatively reliable, objective measure of the severity of unresponsiveness and can be used serially for monitoring. The scale assigns points based on responses to stimuli. Eye opening, facial grimacing, and purposeful withdrawal of limbs from a noxious stimulus indicate that consciousness is not greatly impaired. Asymmetric motor responses to pain or deep tendon reflexes may indicate a focal hemispheric lesion.

Table 4
Glasgow Coma Scale* Area Assessed Response Points Eye opening Open spontaneously; open with blinking at baseline 4   Open to verbal command, speech, or shout 3   Open in response to pain applied to the limbs or sternum 2   None 1 Verbal Oriented 5   Confused conversation, but able to answer questions 4   Inappropriate responses; words discernible 3   Incomprehensible speech 2   None 1 Motor Obeys commands for movement 6   Responds to pain with purposeful movement 5   Withdraws from pain stimuli 4   Responds to pain with abnormal flexion (decorticate posturing) 3   Responds to pain with abnormal extension (decerebrate posturing) 2   None 1 *Combined scores < 8 are typically regarded as coma. Adapted from Teasdale G, Jennett B: Assessment of coma and impaired consciousness. A practical scale. Lancet 2:81–84; 1974.

As impaired consciousness deepens into coma, noxious stimuli may trigger stereotypic reflex posturing. Decorticate posturing indicates hemispheric damage with preservation of motor centers in the upper portion of the brain stem (eg, rubrospinal tract). Decerebrate posturing indicates that the upper brain stem motor centers, which facilitate flexion, have been damaged and that only the lower brain stem centers (eg, vestibulospinal tract, reticulospinal tract), which facilitate extension, are responding to sensory stimuli. Flaccidity without movement indicates that the lower brain stem is not affecting movement, regardless of whether the spinal cord is damaged. It is the worst possible motor response.

Asterixis and multifocal myoclonus suggest metabolic disorders such as uremia, hepatic encephalopathy, hypoxic encephalopathy, and drug toxicity.

Psychogenic unresponsiveness can be differentiated because, although voluntary motor response is typically absent, muscle tone and deep tendon reflexes remain normal, and all brain stem reflexes are preserved.

Eye examination: The following are evaluated:

• Pupillary responses
• Extraocular movements
• Fundi
• Other neuro-ophthalmic reflexes

Pupillary responses and extraocular movements provide information about brain stem function (see Table 5: Coma and Impaired Consciousness: Interpretation of Pupillary Response and Eye Movements). One or both pupils usually become fixed early in coma due to structural lesions, but pupillary responses are often preserved until very late when coma is due to diffuse metabolic disorders (called toxic-metabolic encephalopathy), although responses may be sluggish.

The fundi should be examined for papilledema, hemorrhages, and exudates. Papilledema or hemorrhages may indicate increased intracranial pressure (ICP). Subhyaloid hemorrhage may indicate subarachnoid hemorrhage.

Table 5
Interpretation of Pupillary Response and Eye Movements Area Assessed Finding Interpretation Pupils Sluggish light reactivity retained until all other brain stem reflexes are lost Diffuse cellular cerebral dysfunction (toxic-metabolic encephalopathy)   Unilateral pupillary dilation, pupil unreactive to light 3rd cranial nerve compression (eg, in transtentorial herniation), usually due to ipsilateral lesion   Pupils fixed in midposition Midbrain dysfunction due to structural damage (eg, infarction, hemorrhage) Central herniation Prolonged metabolic depression by drugs or toxins   Pupils tiny (1 mm wide) Massive pontine hemorrhage Toxicity due to opioids or certain insecticides (eg, organophosphates, carbamates) Eye movements Early abnormal pupillary and oculomotor signs Primary brain stem lesion   Spontaneous, conjugate roving eye movements but intact brain stem reflexes Early toxic-metabolic encephalopathy   Gaze preference to one side Brain stem lesion on the opposite side Cerebral hemisphere lesion on the same side   Absent eye movements Further testing required (eg, oculocephalic and oculovestibular reflexes) Possibly toxicity due to phenobarbital Some Trade Names LUMINAL Click for Drug Monograph or phenytoin Some Trade Names DILANTIN Click for Drug Monograph , Wernicke's encephalopathy, botulism, or brain death

In an unresponsive patient, the oculocephalic reflex is tested by the doll's-eye maneuver: The eyes are observed while the head is passively rotated from side to side or flexed and extended. This maneuver should not be attempted if cervical spine instability is suspected.

• If the reflex is present, the maneuver causes the eyes to move in the opposite direction of head rotation, flexion, or extension, indicating that the oculovestibular pathways in the brain stem are intact. Thus, in a supine patient, the eyes continue to look straight up when the head is moved.
• If the reflex is absent, the eyes do not move and thus point in whatever direction the head is turned, indicating the oculovestibular pathways are disrupted. The reflex is also absent in most patients with psychogenic unresponsiveness.

If the patient is unconscious and the oculocephalic reflex is absent or the neck is immobilized, oculovestibular (cold caloric) testing is done. After integrity of the tympanic membrane is confirmed, the patient's head is elevated 30°, and with a syringe connected to a flexible catheter, the examiner irrigates the external auditory canal with 50 mL of ice water over a 30-sec period.

• If both eyes deviate toward the irrigated ear, the brain stem is functioning normally, suggesting mildly impaired consciousness.
• If nystagmus away from the irrigated ear also occurs, the patient is conscious and psychogenic unresponsiveness is likely. In conscious patients, 1 mL of ice water is often enough to induce ocular deviation and nystagmus. Thus, if psychogenic unresponsiveness is suspected, a small amount of water should be used because cold caloric testing can induce severe vertigo, nausea, and vomiting in conscious patients.
• If the eyes do not move or movement is dysconjugate after irrigation, the integrity of the brain stem is uncertain and the coma is deeper. Prognosis may be less favorable.

Certain patterns of eye abnormalities and other findings may suggest brain herniation (see Fig. 1: Coma and Impaired Consciousness: Brain herniation. and see Table 1: Coma and Impaired Consciousness: Effects of Herniation).

Respiratory patterns: The spontaneous respiratory rate and pattern should be documented unless emergency airway intervention is required. It may suggest a cause.

• Periodic cycling of breathing (Cheyne-Stokes or Biot's respirations—see Approach to the Patient With Pulmonary Symptoms: Inspection) may indicate dysfunction of both hemispheres or of the diencephalon.
• Hyperventilation (central neurogenic hyperventilation) with respiratory rates of > 40 breaths/min may indicate midbrain or upper pontine dysfunction.
• An inspiratory gasp with respiratory pauses of about 3 sec after full inspiration (apneustic breathing) typically indicates pontine or medullary lesions; this type of breathing often progresses to respiratory arrest.

Tests: Initially, pulse oximetry, finger-stick plasma glucose measurements, and cardiac monitoring are done. Blood tests should include a comprehensive metabolic panel (including at least serum electrolytes, BUN, creatinine, and Ca levels), CBC with differential and platelets, liver function tests, and ammonia level. ABGs are measured, and if carbon monoxide toxicity is suspected, carboxyhemoglobin level is measured. Blood and urine should be obtained for culture and routine toxicology screening; serum ethanol level is also measured. Additional toxicology tests (eg, additional toxicology screening, serum drug levels) are done based on clinical suspicion. ECG (12-lead) should be done.

Unless a cause is immediately apparent, noncontrast head CT should be done as soon as possible to check for masses, hemorrhage, edema, and hydrocephalus. MRI can be done instead if immediately available. Contrast CT can be done if noncontrast CT is not diagnostic. MRI or contrast CT may detect isodense subdural hematomas, multiple metastases, sagittal sinus thrombosis, herpes encephalitis, or other causes missed by noncontrast CT. Chest x-ray should also be taken.

If coma is unexplained after neuroimaging and other tests, lumbar puncture is done to check opening pressure and exclude infection, subarachnoid hemorrhage, and other abnormalities. CSF analysis includes cell and differential counts, protein, glucose, Gram stain, cultures, and sometimes, based on clinical suspicion, specific tests (eg, cryptococcal antigen, Venereal Disease Research Laboratory [VDRL] tests, PCR for herpes simplex, visual or spectrophotometric determination of xanthochromia). In unconscious patients with or without focal neurologic deficits, cranial CT or MRI should be done before lumbar puncture to exclude an intracranial mass and obstructive hydrocephalus because if either is present, suddenly lowering CSF pressure by lumbar puncture could trigger brain herniation.

If increased ICP is suspected, pressure is measured. Hyperventilation should be considered under the care of an ICU specialist. Hyperventilation produces hypocapnia, which in turn decreases cerebral blood flow globally through vasoconstriction. Reduction in Pco₂ from 40 mm Hg to 30 mm Hg can reduce ICP about 30%. It is recommended to maintain Pco₂ at 25 mm Hg to 30 mm Hg as required with the initiation of other treatment modalities, but aggressive hypoventilation < 25 mm Hg should be avoided since this may reduce cerebral blood flow excessively and result in cerebral ischemia.

If pressure is increased, it is monitored continuously (see Approach to the Critically Ill Patient: Intracranial Pressure Monitoring).

EEG may be done if diagnosis remains uncertain. In most comatose patients, EEG shows slowing and reductions in wave amplitude that are nonspecific but often occur in toxic-metabolic encephalopathy. However, in the rare patient with nonconvulsive status epilepticus, EEG shows spikes, sharp waves, or spike and slow complexes.

Prognosis

Prognosis depends on the cause, duration, and depth of the impairment of consciousness. Prognosis is usually considered poor. However, if unresponsiveness lasts < 6 h, prognosis is more favorable.

After trauma, a Glasgow Coma Scale score of 3 to 5 may indicate fatal brain damage, especially if pupils are fixed or oculovestibular reflexes are absent. If pupils are unreactive or the motor response to noxious stimuli is absent or is only a reflex response 3 days after cardiac arrest, patients have virtually no chance of a good neurologic recovery. After coma, the early return of speech (even if incomprehensible), spontaneous eye movements, or ability to follow commands is a favorable prognostic sign. If the cause is a reversible condition (eg, sedative overdose, some metabolic disorders such as uremia), patients may lose all brain stem reflexes and all motor response and yet recover fully.

Treatment

• Immediate stabilization (airway, breathing, circulation)
• Supportive measures, including, when necessary, control of ICP
• Admission to an ICU
• Treatment of underlying disorder

Airway, breathing, and circulation must be ensured immediately. Hypotension must be corrected (see Shock and Fluid Resuscitation: Cardiogenic shock). Patients are admitted to the ICU so that respiratory and neurologic status can be monitored.

Because some patients in coma are malnourished and susceptible to Wernicke encephalopathy, thiamin 100 mg IV or IM should be given routinely. If plasma glucose is low, patients should be given 50 mL of 50% dextrose. If opioid overdose is suspected, naloxone Some Trade Names
NARCAN
Click for Drug Monograph
2 mg IV is given. If trauma is involved, the neck is immobilized until damage to the cervical spine is ruled out.

Endotracheal intubation: Patients with infrequent, shallow, or stertorous respirations, low O₂ saturation (determined by pulse oximetry or ABG measurements), impaired airway reflexes, or severe unresponsiveness (including most patients with a Glasgow Coma Scale score ≤ 8) require endotracheal intubation to prevent aspiration and ensure adequate ventilation. If increased ICP is suspected, intubation should be done via rapid sequence oral intubation (using a paralytic drug) rather than via nasotracheal intubation (see Respiratory Failure and Mechanical Ventilation); nasotracheal intubation in a patient who is breathing spontaneously causes more coughing and gagging, thus increasing ICP, which is already increased because of intracranial abnormalities.

To minimize the increase in ICP that may occur when the airway is manipulated, some clinicians recommend giving lidocaine Some Trade Names
XYLOCAINE
Click for Drug Monograph
1.5 mg/kg IV 1 to 2 min before giving the paralytic. Patients are sedated before the paralytic is given. Etomidate Some Trade Names
AMIDATE
Click for Drug Monograph
is a good choice in hypotensive or trauma patients because it has minimal effects on BP; IV dose is 0.3 mg/kg for adults (or 20 mg for an average-sized adult) and 0.2 to 0.3 mg/kg for children. Alternatively, if hypotension is absent and unlikely and if propofol Some Trade Names
DIPRIVAN
Click for Drug Monograph
is readily available, propofol Some Trade Names
DIPRIVAN
Click for Drug Monograph
0.2 to 1.5 mg/kg may be used. Succinylcholine Some Trade Names
ANECTINE
QUELICIN
Click for Drug Monograph
1.5 mg/kg IV is typically used as a paralytic. However, use of paralytics is minimized and, whenever possible, avoided because they can mask neurologic findings and changes.

Pulse oximetry and ABGs (if possible, end-tidal CO₂) should be used to assess adequacy of oxygenation and ventilation.

ICP control: If ICP is increased, intracranial and cerebral perfusion pressure should be monitored (see Approach to the Critically Ill Patient: Intracranial Pressure Monitoring), and pressures should be controlled. The goal is to maintain ICP at ≤ 20 mm Hg and cerebral perfusion pressure at 50 to 70 mm Hg. Cerebral venous drainage can be enhanced (thus lowering ICP) by elevating the head of the bed to 30° and by keeping the patient's head in a midline position.

Control of increased ICP involves several strategies:

• Sedation: Sedatives may be necessary to control agitation, excessive muscular activity (eg, due to delirium), or pain, which can increase ICP. Propofol Some Trade Names
  DIPRIVAN
  Click for Drug Monograph
  is often used in adults (contraindicated in children) because onset and duration of action are quick; dose is 0.3 mg/kg/h by continuous IV infusion, titrated gradually up to 3 mg/kg/h as needed. An initial bolus is not used. The most common adverse effect is hypotension. Prolonged use at high doses can cause pancreatitis. Benzodiazepines (eg, midazolam Some Trade Names
  No US trade name
  Click for Drug Monograph
  , lorazepam Some Trade Names
  ATIVAN
  Click for Drug Monograph
  ) can also be used. Because sedatives can mask neurologic findings and changes, their use should be minimized and, whenever possible, avoided. Antipsychotics should be avoided if possible because they can delay recovery.
• Hyperventilation: Hyperventilation causes hypocapnia, which causes vasoconstriction, thus decreasing cerebral blood flow globally. Reduction in Pco₂ from 40 to 30 mm Hg can reduce ICP about 30%. Hyperventilation that reduces Pco₂ to 28 to 33 mm Hg decreases ICP for only about 30 min and is used by some clinicians as a temporary measure until other treatments take effect. Aggressive hypoventilation to < 25 mm Hg should be avoided because it may reduce cerebral blood flow excessively and result in cerebral ischemia. Other measures may be used to control increased ICP (see Traumatic Brain Injury (TBI): Increased intracranial pressure).
• Hydration: Isotonic fluids are used. Providing free water through IV fluids (eg, 5% dextrose, 0.45% saline) can aggravate cerebral edema and should be avoided. Fluids may be restricted to some degree, but patients should be kept euvolemic. If patients have no signs of dehydration or fluid overload, IV fluids with normal saline can be started at 50 to 75 mL/h. The rate can be increased or decreased based on serum Na, osmolality, urine output, and signs of fluid retention (eg, edema).
• Diuretics: Serum osmolality should be kept at 295 to 320 mOsm/kg. Osmotic diuretics (eg, mannitol Some Trade Names
  OSMITROL
  RESECTISOL
  Click for Drug Monograph
  ) may be given IV to lower ICP and maintain serum osmolality. They do not cross the blood-brain barrier. They pull water from brain tissue across an osmotic gradient into plasma, eventually leading to equilibrium. Effectiveness of these drugs decreases after a few hours. Thus, they should be reserved for patients whose condition is deteriorating or used preoperatively for patients with hematomas. Mannitol Some Trade Names
  OSMITROL
  RESECTISOL
  Click for Drug Monograph
  20% solution is given 0.5 to 1 g/kg IV (2.5 to 5 mL/kg) over 15 to 30 min, then given as often as needed (usually q 6 to 8 h) in a dose ranging from 0.25 to 0.5 g/kg (1.25 to 2.5 mL/kg). Mannitol Some Trade Names
  OSMITROL
  RESECTISOL
  Click for Drug Monograph
  must be used cautiously in patients with severe coronary artery disease, heart failure, renal insufficiency, or pulmonary vascular congestion because mannitol Some Trade Names
  OSMITROL
  RESECTISOL
  Click for Drug Monograph
  rapidly expands intravascular volume. Because osmotic diuretics increase renal excretion of water relative to Na, prolonged use of mannitol Some Trade Names
  OSMITROL
  RESECTISOL
  Click for Drug Monograph
  may result in water depletion and hypernatremia. Furosemide Some Trade Names
  LASIX
  Click for Drug Monograph
  1 mg/kg IV can decrease total body water, particularly when transient hypervolemia associated with mannitol Some Trade Names
  OSMITROL
  RESECTISOL
  Click for Drug Monograph
  is to be avoided. Fluid and electrolyte balance should be monitored closely while osmotic diuretics are used. A 3% saline solution is being studied as another potential osmotic agent to control ICP.
• BP control: Systemic antihypertensives are needed only when hypertension is severe (> 180/95 mm Hg). How much BP is reduced depends on the clinical context. Systemic BP needs to be high enough to maintain cerebral perfusion pressure even when ICP increases. Hypertension can be managed by titrating a nicardipine Some Trade Names
  CARDENE
  Click for Drug Monograph
  drip (5 mg/h, increased by 2.5 mg q 5 min to a maximum of 15 mg/h) or by boluses of labetalol Some Trade Names
  NORMODYNE
  TRANDATE
  Click for Drug Monograph
  (10 mg IV over 1 to 2 min, repeated q 10 min to a maximum of 150 mg).
• Corticosteroids: These drugs are usually helpful for patients with a brain tumor or brain abscess, but they are ineffective for patients with head trauma, cerebral hemorrhage, ischemic stroke, or hypoxic brain damage after cardiac arrest. Corticosteroids increase plasma glucose; this increase may worsen the effects of cerebral ischemia. After an initial dose of dexamethasone Some Trade Names
  DECADRON
  DEXASONE
  HEXADROL
  Click for Drug Monograph
  20 to 100 mg, 4 mg once/day appears to be effective while minimizing adverse effects.

If ICP continues to increase despite other measures to control it, the following may be used:

• Pentobarbital coma: Pentobarbital Some Trade Names
  NEMBUTAL
  Click for Drug Monograph
  can reduce cerebral blood flow and metabolic demands. However, its use is controversial because the effect on clinical outcome is not consistently beneficial. Coma is induced by giving pentobarbital Some Trade Names
  NEMBUTAL
  Click for Drug Monograph
  10 mg/kg over 30 min, followed by 5 mg/kg/h for 3 h, then 1 mg/kg/h. The dose may be adjusted to suppress bursts of EEG activity, which is continuously monitored. Hypotension is common and is managed by giving fluids and, if necessary, vasopressors. Other possible adverse effects include arrhythmias, myocardial depression, and impaired uptake or release of glutamate.
• Decompressive craniotomy: Craniotomy with duraplasty can be done to provide room for brain swelling. This procedure can prevent deaths, but overall functional outcome may not improve much. It may be most useful for large cerebral infarcts with impending herniation, particularly in patients < 50.

Long-term care: Patients require meticulous long-term care. Stimulants and opioids should be avoided. Enteral feeding is started with precautions to prevent aspiration (eg, elevation of the head of the bed); a percutaneous endoscopic jejunostomy tube is placed if necessary. Early, vigilant attention to skin care, including checking for breakdown especially at pressure points, is required to prevent pressure ulcers. Topical ointments to prevent desiccation of the eyes are beneficial. Passive range-of-motion exercises done by physical therapists and taping or dynamic flexion splitting of the extremities may prevent contractures. Measures are also taken to prevent UTIs and deep venous thrombosis.

Last full review/revision January 2008 by Kenneth Maiese, MD

Content last modified January 2008