|Coma is unresponsiveness from which the patient cannot be aroused. Impaired consciousness refers to similar, less severe disturbances of consciousness; these disturbances are not considered coma. The mechanism for coma or impaired consciousness 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
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
Brain death is loss of function of the entire cerebrum and brain stem, resulting in coma, no spontaneous respiration, and loss of all brain stem reflexes. Spinal reflexes, including deep tendon, plantar flexion, and withdrawal reflexes, may remain. Recovery does not occur.
The concept of brain death developed because ventilators and drugs can perpetuate cardiopulmonary and other body functions despite complete cessation of all cerebral activity. The concept that brain death (ie, total cessation of integrated brain function, especially that of the brain stem) constitutes a person’s death has been accepted legally and culturally in most of the world.
For a physician to declare brain death, a known structural or metabolic cause of brain damage must be present, and use of potentially anesthetizing or paralyzing drugs, especially self-administered, must be ruled out. Hypothermia < 32° C must be corrected, and if status epilepticus is suspected, EEG should be done. Sequential testing over 6 to 24 h is necessary (see Table 6: Coma and Impaired Consciousness: Guidelines for Determining Brain Death (in Patients > 1 Yr)). Examination includes assessment of pupil reactivity, oculovestibular and oculocephalic reflexes, corneal reflexes, and apnea testing. Sometimes EEG or tests of brain perfusion are used to confirm absence of brain activity or brain blood flow and thus provide additional evidence to family members, but these tests are not usually required. They are indicated when apnea testing is not hemodynamically tolerated and when only one neurologic examination is desirable (eg, to expedite organ procurement for transplantation).
The diagnosis of brain death is equivalent to the person’s death. No one who meets the criteria for brain death recovers. After brain death is confirmed, all supporting cardiac and respiratory treatments are ended. Cessation of ventilatory support results in terminal arrhythmias. Spinal motor reflexes may occur during terminal apnea; they include arching of the back, neck turning, stiffening of the legs, and upper extremity flexion (the so-called Lazarus sign). Family members who wish to be present when the ventilator is shut off need to be warned of such reflex movements.
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 or if it results in compression of the contralateral hemisphere (eg, by causing edema).
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 (ICP) 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 Table 1: Coma and Impaired Consciousness: Effects of Brain Herniation) contributes to neurologic deterioration because it directly compresses brain tissue, increases ICP, may lead to hydrocephalus, and results in neuronal and vascular cell dysfunction. In addition to the direct effects of increased ICP on neuronal and vascular cells, cellular pathways of apoptosis and autophagy, also detrimental to these cells, can become activated.
Impaired consciousness may progress to coma and ultimately to brain death (see Coma and Impaired Consciousness: Brain Death).
Coma or impaired consciousness may result from structural disorders, which typically cause focal damage, or nonstructural disorders, which most often cause diffuse damage (see Table 2: Coma and Impaired Consciousness: Common Causes of Coma or Impaired Consciousness).
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*):
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, police officers, and any witnesses should be questioned about the circumstances and 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 and time course of the problem (eg, whether seizure, headache, vomiting, head trauma, or drug ingestion was observed, how quickly symptoms appeared, whether the course has been progressive or waxing and waning), baseline mental status, recent infections and possible exposure to infections, recent travel, ingestions of unusual meals, psychiatric problems and symptoms, drug history, alcohol and other 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 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
). 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 is evaluated by attempting to wake patients first with verbal commands, then with nonnoxious 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 impaired 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.
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. Vital signs are usually not affected.
Eye examination: The following are evaluated:
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. If one pupil is dilated, other causes of anisocoria should be considered (see Symptoms of Ophthalmologic Disorders: Etiology).
The fundi should be examined. Papilledema may indicate increased ICP but may take many hours to appear. Increased ICP can cause earlier changes in the fundi, such as disk hypermia, dilated capillaries, blurring of the medial disk margins, and sometimes hemorrhages. Subhyaloid hemorrhage may indicate subarachnoid hemorrhage.
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 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.
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 Brain Herniation).
Respiratory patterns: The spontaneous respiratory rate and pattern should be documented unless emergency airway intervention is required. It may suggest a cause.
Testing: Initially, pulse oximetry, fingerstick 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.
If the cause is not immediately apparent, noncontrast head CT should be done as soon as possible to check for masses, hemorrhage, edema, and hydrocephalus. Initially, noncontrast CT rather than contrast CT is preferred to rule out brain hemorrhage. MRI can be done instead if immediately available, but it is not as quick as newer-generation CT scanners. Contrast CT can then 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. A chest x-ray should also be taken.
If coma is unexplained after neuroimaging and other tests and if there is no obstruction in the CSF flow or ventricular system that would significantly increase ICP, lumbar puncture is done to check opening pressure and to exclude infection, subarachnoid hemorrhage, and other abnormalities. Lumbar puncture is not done until after imaging studies are done to exclude an intracranial mass and obstructive hydrocephalus because if either is present, suddenly lowering CSF pressure by lumbar puncture could trigger brain herniation. CSF analysis includes cell and differential counts, protein, glucose, Gram staining, 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).
If increased ICP is suspected, pressure is measured. Hyperventilation, managed by an ICU specialist, should be considered. Hyperventilation causes 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 by about 30%. Pco2 should be maintained at 25 mm Hg to 30 mm Hg, but aggressive hyperventilation to < 25 mm Hg should be avoided because this approach 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).
If diagnosis remains uncertain, EEG may be done. In most comatose patients, EEG shows slowing and reductions in wave amplitude that are nonspecific but often occur in toxic-metabolic encephalopathy. However, EEG monitoring (eg, in the ICU) is increasingly identifying nonconvulsive status epilepticus. In such cases, the EEG may show spikes, sharp waves, or spike and slow complexes.
Prognosis depends on the cause, duration, and depth of the impairment of consciousness. For example, absent brain stem reflexes indicates a poor prognosis after cardiac arrest, but not always after a sedative overdose. In general, if unresponsiveness lasts < 6 h, prognosis is more favorable.
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. 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.
After cardiac arrest, clinicians must exclude major confounders of coma, including sedatives, neuromuscular blockade, hypothermia, metabolic derangements, and severe liver or kidney failure. If brain stem reflexes are absent at day 1 or lost later, testing for brain death is indicated. Prognosis is poor if patients have any of the following:
If patients were treated with hypothermia, 72 h should be added to the times above because hypothermia slows recovery. If none of the above criteria is met, outcome is usually (but not always) poor; thus, whether to withdraw life support may be a difficult decision.
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 undernourished 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 IV. If opioid overdose is suspected,naloxone
2 mg IV is given. If trauma is involved, the neck is immobilized until damage to the cervical spine is ruled out. If a recent (within about 1 h) drug overdose is possible, gastric lavage can be done through a large-bore orogastric tube (eg, ≥ 32 Fr) after endotracheal intubation. Activated charcoal can then be given via the orogastric tube.
Endotracheal intubation: Patients with any of the following 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; 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
1.5 mg/kg IV 1 to 2 min before giving the paralytic. Patients are sedated before the paralytic is given. Etomidate
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
is readily available, propofol
0.2 to 1.5 mg/kg may be used. Succinylcholine
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:
If ICP continues to increase despite other measures to control it, the following may be used:
Long-term care: Patients require meticulous long-term care. Stimulants, sedatives, 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.
Vegetative state: Patients show no evidence of awareness of self or environment and cannot interact with other people. Purposeful responses to external stimuli are absent, as are language comprehension and expression.
Signs of an intact reticular formation (eg, eye opening) and an intact brain stem (eg, reactive pupils, oculocephalic reflex) are present. Sleep-wake cycles occur but do not necessarily reflect a specific circadian rhythm and are not associated with the environment. More complex brain stem reflexes, including yawning, chewing, swallowing, and, uncommonly, guttural vocalizations, are also present. Arousal and startle reflexes may be preserved; eg, loud sounds or blinking with bright lights may elicit eye opening. Eyes may water and produce tears. Patients may appear to smile or frown. Spontaneous roving eye movements—usually slow, of constant velocity, and without saccadic jerks—may be misinterpreted as volitional tracking and can be misinterpreted by family members as evidence of awareness.
Patients cannot react to visual threat and cannot follow commands. The limbs may move, but the only purposeful motor responses that occur are primitive (eg, grasping an object that contacts the hand). Pain usually elicits a motor response (typically decorticate or decerebrate posturing) but no purposeful avoidance. Patients have fecal and urinary incontinence. Cranial nerve and spinal reflexes are typically preserved.
Rarely, brain activity, detected by functional MRI or EEG, indicates a response to questions and commands even though there is no behavioral response. The extent of patients’ actual awareness is not yet known. In most patients who have such brain activity, the vegetativestate resulted from brain trauma, not hypoxic encephalopathy.
Minimally conscious state: Fragments of meaningful interaction with the environment are preserved. Patients may establish eye contact, purposefully grasp at objects, respond to commands in a stereotypic manner, or answer with the same word.
A vegetative state is suggested by characteristic findings (eg, no purposeful activity or comprehension) plus signs of an intact reticular formation. Diagnosis is based on clinical criteria. However, neuroimaging is indicated to rule out treatable disorders.
The vegetative state must be distinguished from the minimally conscious state. Both states can be permanent or temporary, and the physical examination may not reliably distinguish one from the other. Sufficient observation is needed. If observation is too brief, evidence of awareness may be overlooked, resulting in a false-positive diagnosis. Some patients with severe Parkinson disease are misdiagnosed as being in a vegetative state.
CT or MRI can differentiate an ischemic infarct, an intracerebral hemorrhage, and a mass lesion involving the cortex or the brain stem. MR angiography can be used to visualize the cerebral vasculature after exclusion of a cerebral hemorrhage. Diffusion-weighted MRI is becoming the preferred imaging modality for following ongoing ischemic changes in the brain. PET and SPECT can be used to assess cerebral function (rather than brain anatomy). If the diagnosis of persistent vegetative state is in doubt, PET or SPECT should be done. EEG is useful in assessing cortical dysfunction and identifying occult seizure activity.
Vegetative state: Prognosis varies somewhat by cause and duration of the vegetative state. Prognosis may be better if the cause is a reversible metabolic condition (eg, toxic encephalopathy) than if the cause is neuronal death due to extensive hypoxia and ischemia or another condition. Also, younger patients may recover more motor function than older patients but not more cognition, behavior, or speech.
Recovery from a vegetative state is unlikely after 1 mo if brain damage is nontraumatic and after 12 mo if brain damage is traumatic. Even if some recovery occurs after these intervals, most patients are severely disabled. Rarely, improvement occurs late; after 5 yr, about 3% of patients recover the ability to communicate and comprehend, but even fewer can live independently; no patients regain normal function.
Most patients in a persistent vegetative state die within 6 mo of the original brain damage. The cause is usually pulmonary infection, UTI, or multiple organ failure, or death may be sudden and of unknown cause. For most of the rest, life expectancy is about 2 to 5 yr; only about 25% of patients live > 5 yr. A few patients live for decades.
Minimally conscious state: Most patients tend to recover consciousness but to a limited extent depending on how long minimally conscious state has lasted. The longer it has lasted, the less chance of patients recovering higher cortical function. Prognosis may be better if the cause is traumatic brain injury. Rarely, patients regain clear but limited awareness after years of coma, called awakenings by the news media.
Vegetative state has no specific treatment. Decisions about life-sustaining care should involve social services, the hospital ethics committee, and family members. Maintaining patients, especially those without advanced directives to guide decisions about terminating treatment (see Medicolegal Issues: Advance Directives), in a prolonged vegetative state raises ethical and other (eg, resource utilization) questions.
Most patients in a minimally conscious state do not respond to specific treatments. However, rarely, treatment with zolpidem
can cause dramatic and repeated improvement in neurologic responsiveness for as long as the drug is continued.
Last full review/revision September 2012 by Kenneth Maiese, MD
Content last modified November 2012