Coma

Etiology

Coma represents brain failure. It may be caused by neuronal dysfunction from many causes including structural or nonstructural processes affecting the central nervous system.

Metabolic or infectious etiologies may diffusely affect the brain and lead to a coma. Common toxic or metabolic causes of coma include hypoglycemia, hyperglycemia, excessive alcohol intake, and medication overdose or illicit drug use. Of all the nonstructural causes of coma, hypoglycemia and systemic infections likely account for the majority of patients presenting with coma.  Other less common metabolic causes include hepatic encephalopathy, hyponatremia, hypernatremia, hypercalcemia, endocrine abnormalities, and many others. Primary central nervous system infections such as meningitis or encephalitis may lead to coma but are relatively uncommon though vitally important to detect.

Structural brain diseases such as subdural or epidural traumatic hematomas, spontaneous intracranial hemorrhages, venous thrombosis, tumors, acute hydrocephalus, raised intracranial pressure, anoxic brain injury, or brainstem strokes may all cause altered mental status or coma.

Generalized status epilepticus may evolve to a subtle or nonconvulsive form, sometimes called transformed or end-stage status epileptics, where unresponsiveness predominates the clinical picture and there is only minor or even no associated motor activity. Additionally, with the increasing use of electroencephalogram (EEG) monitoring in intensive care units, patients are now being identified with highly abnormal electroencephalographic findings suggesting nonconvulsive status epilepticus in patients who are clinically without generalized seizures.

Epidemiology

Though coma is a common clinical presentation to the emergency department (ED), the actual frequency of coma at ED presentation is difficult to determine. The number of published studies of patients presenting with coma is surprisingly small.[4] The use of many terms to describe patients with depressed mental states leads to multiple coding options, making retrospective reviews challenging. Within a clinical record, there is often variation in assessments by different providers. Additionally, diagnostic coding frequently reflects the etiology of the altered mental status without specific coding for coma. The fact that a common cause of coma, hypoglycemia, is often treated by emergency medical service providers with resolution prior to emergency department arrival adds to coding confusion. 

A more recent single-center study of over 1000 consecutive patients with coma of unknown etiology that excluded traumatic brain injury and cardiac arrest survivors found that patients with coma of unknown etiology comprised 0.4% of all ED patients. The main diagnoses were classified into acute primary brain lesions such as hemorrhage and tumors (39%), primary brain pathologies without acute lesions, largely epilepsy (25%), and pathologies that affected the brain secondarily such as sepsis, intoxications, or metabolic conditions (36%). One-third of subjects had more than one coma-explaining pathology.[5]

Pathophysiology

The accepted pathophysiology of a coma involves neuronal dysfunction from a decrease in the supply of glucose or oxygen to the brain. A myriad of etiologies may lead to essential substrate disruption with diffuse central nervous system (CNS) dysfunction and coma as the extreme clinical condition. For example, any clinical process that causes circulatory collapse or profound hypoxemia may manifest as a coma. As little as fifteen seconds of circulatory collapse will result in loss of consciousness. If the cause of the circulatory collapse is brief and promptly restored, such as from a simple faint, consciousness is regained. If hypotension or hypoxemia continues, the altered mental state continues, and secondary CNS damage may occur. Hypoglycemia is encountered frequently in clinical practice most often in the association of treatment for diabetes mellitus or as a complication of alcoholism. Electrolyte abnormalities such as hyponatremia or hypercalcemia may disrupt normal neuronal metabolism. The pathophysiology of other causes of metabolic coma is not clear but may involve false neurotransmitters as is suggested in hepatic encephalopathy. Global depression of neuronal functioning is the most common mechanism of coma in toxins and poisonings.

Structural lesions of the CNS, such as intracerebral hemorrhage, may lead to coma from direct destruction of arousal areas of the brain or from secondary damage from shifting of intracranial structures, vascular compression, or increased intracranial pressure. Herniation syndromes describe clinically recognizable physical examination features that may suggest the anatomic location of the CNS lesion. The most discussed of the herniation syndromes is uncal herniation, where the medial portion of the temporal lobes shifts with resulting loss of consciousness from brainstem compression. The pathophysiologic findings are often compression of the brainstem and cranial nerve III as it exits the brainstem and crosses the tentorium cerebelli. This results in impairment of the parasympathetic fibers (pupilloconstrictors) that travel with the third nerve, and in most cases pupillary dilatation on the same side (roughly 90%) of the mass lesion.[6]

Increased intracranial pressure is a frequent cause of coma. Since the brain is enclosed in the closed skull, conditions that increase intracranial pressure may impair cerebral perfusion. The equation that approximates this relationship is unforgiving CPP (cerebral perfusion pressure) = MAP (mean arterial pressure estimated as 1/3 systolic BP [blood pressure] + 2/3 diastolic BP) - ICP (intracranial pressure). As ICP approaches MAP, cerebral perfusion diminishes. It is essential to maintain CPP by reducing increased intracranial pressure while avoiding hypotension.[7][8]

History and Physical

A paradox exists in the evaluation of the comatose patient. History would reveal the etiology of the altered mental status, but the altered mental status obscures information of recent events. After stabilization, efforts should be made to obtain information from EMS providers, family, co-workers, or any bystanders.

When evaluating the comatose patient, it is axiomatic that the fundamentals of emergency care – airway, breathing, circulation – be addressed. Physical examination should be directed to detect any signs of trauma during the general physical examination. Initial neurological examination should include the response to pain, a brief assessment of motor function, eye-opening, and verbalization. Cranial nerve examination should include an evaluation of extraocular movements, pupillary, corneal, cough, and gag reflex. Any abnormal posturing should be noted. The presence of ipsilateral dilation of the pupil suggests the uncal herniation syndrome with compression of the third cranial nerve from a mass. Lack of focal findings on examination suggests a metabolic, infectious, or toxicologic cause of coma.[1][9]

Recording of the neurologic examination and can be roughly quantified by the Glasgow Coma Scale, the FOUR score, or other rating scales. Brief rating scales are useful for sequential monitoring of the patient but do have limitations.[10][11][12][13][14]

Glasgow Coma Scale

Eye response

4 = eyes open spontaneously

3 = eye-opening to verbal command

2 = eye-opening to pain

1 = no eye-opening

Motor response

6 = obey commands

5 = localizing pain

4 = withdrawal from pain

3 = flexion response to pain

2 = extension response to pain

1 = no motor response

Verbal response

5 = oriented

4 = confused

3 = inappropriate words

2 = incomprehensible sounds

1 = no verbal response

Four SCORE

Eye response

4 = eyelids open or opened, tracking, or blinking to command

3 = eyelids open but not tracking

2 = eyelids closed but open to a loud voice

1 = eyelids closed but open to pain

0 = eyelids remain closed with pain

Motor response

4 = thumbs-up, fist, or peace sign

3 = localizing to pain

2 = flexion response to pain

1 = extension response to pain

0 = no response to pain or generalized myoclonic status

Brainstem reflexes

4 = pupil and corneal reflexes present

3 = one pupil wide and fixed

2 = pupil or corneal reflexes absent

1 = pupil and corneal reflexes absent

0 = absent pupil, corneal, and cough reflex 

Respiration

4 = not intubated, regular breathing pattern

3 = not intubated, Cheyne-Stokes breathing pattern

2 = not intubated, irregular breathing

1 = breaths above the ventilator rate

0 = breaths at ventilator rate or below

Evaluation

Initial evaluation of the comatose patient should always include assessment with intervention as necessary of the airway, breathing, and circulatory conditions (A,B,C's). The differential diagnosis of coma is extensive. Unless a recognizable infectious or metabolic cause of coma is promptly established, additional testing will be necessary. Laboratory and toxicologic tests should be obtained as indicated. Initial stat labs would include electrolytes, CBC, arterial or venous blood gas analysis, and possibly toxicologic testing. As the case progresses, neuroimaging may be indicated. CT and MRI brain scanning may detect hemorrhage, mass effect, or other structural abnormalities. Vascular imaging may reveal large vessel occlusion. Initial efforts will be to determine a likely structural or non-structural cause of coma leading to appropriate interventions and consultations. EEG should be considered in a patient following generalized convulsive status epilepticus with continued altered mental status since status epilepticus may continue with little or no associated motor movements. A checklist approach is suggested to indicate whether advanced imaging is needed or advanced laboratory testing.[3]

Treatment / Management

Determination of the serum glucose by the point of care testing or empiric administration of glucose is recommended for all patients with altered mental status. Naloxone should be considered in patients with elements of the narcotic toxidrome such as slowed respiratory rate, small pupils, or altered mental status. If a readily reversible of coma is not discovered, further evaluation is indicated. Simplistically, the treatment of a coma is treatment of conditions that lead to coma. Liberal neuroimaging is encouraged if history, physical, and stat laboratory results do not determine a treatment path.

Thiamine should be administered to individuals at risk for poor nutrition such as alcoholics, bariatric surgery patients, or patients with chronic malabsorptive states.[15][16] The routine administration of a coma cocktail is discouraged.[3][17] Maintenance of cerebral perfusion pressure by preserving the mean arterial pressure by avoiding hypotension is the key to the management strategy. Continuation of supportive supportive care with airway protection and blood pressure is necessary. If clinical findings or imaging suggest increased intracranial pressure, hyperosmolar therapy should be considered with appropriate consultation.[18][8]

Differential Diagnosis

Other states of altered consciousness may superficially resemble coma. Perhaps the most important of these is the locked-in syndrome. If questioned, patients cannot respond with speaking or any movements of the extremities. Their eyes may be open. Typically this is caused by pontine damage from ischemic stroke or hemorrhage. Higher brain centers are intact and functional and the patents have awareness. Patients are conscious and aware of their environment but cannot respond due to damage of the motor tracts. Careful examination may show responsiveness to questions with patients only able to respond with eye blinks and vertical eye movements. Caregivers should assume that patients might comprehend communications even though they might appear unresponsive.[19]

There has been a recent description of a minimally conscious state characterized by unresponsiveness with intermittent evidence of awareness. With prolonged observation, these patients may intermittently or inconsistently follow simple commands, visually pursue objects, or show other signs of responsiveness.[20]

Feigned unresponsive rarely is prolonged. Attentive observation and examination will often reveal intermittent responsiveness and alertness. Cranial nerve testing will be intact including caloric testing. A startle maneuver with loud sounds may be diagnostic. Demonstrating the presence of nystagmus with caloric testing is consistent with alertness and may be tested if there is a doubt.

Common causes of coma include:

• Anoxic brain injury
• Cerebral infarction
• Cerebral hemorrhage
  • Spontaneous
  • Traumatic
• Cerebral neoplasms
• Hypertensive encephalopathy
• Hypoglycemia
• Metabolic encephalopathy
• Myxedema
• Status epilepticus
• Toxic encephalopathy

Prognosis

Patients with reversible causes of coma, such as hypoglycemia, may be discharged after the appropriate intervention and with consideration of a safe home environment. Patients with persistent coma need hospital admission with ongoing monitoring, supportive care, and targeted care to the underlying cause of coma. The etiology of the coma determines the admission service.

Patients with traumatic coma will need monitoring, interventions as needed for mass lesions, and supportive care to prevent secondary injury. Prognosis is difficult and may become clear only after a period of observation. Outcomes of patients with post-cardiac arrest coma have improved significantly with the advent of therapeutic hypothermia. With the use of therapeutic hypothermia ability to judge outcomes must be delayed for several days. The prognosis of patients presenting with non-traumatic coma depends largely on both the etiology of coma and the level of consciousness on admission. One single-center study of patients with non-traumatic coma found a hospital mortality rate of 26.5% and accumulated two-year mortality of 43%. Mortality from poisonings was less than 15% while mortality from malignancy-related presentations was almost 90%. They found that a Glasgow Coma Score (GCS) of 3-6 at presentation was associated with a higher hospital mortality rate than a GCS of 7-10.[4]

Complications

Treatment is aimed at any identified causative process causing a coma. Additional attention is needed to prevent any secondary brain injury which may include advanced respiratory and cardiovascular support. Instrumentation for assessment of intracranial pressure and interventions for increased intracranial pressure may be indicated. Basic support such as bladder care and skin assessment with decubiti preventative actions should not be neglected.