Article Author:
J. Stephen Huff
Article Editor:
Scott Dulebohn
10/19/2018 9:03:40 AM
PubMed Link:


Coma is best defined as an eyes-closed unresponsive state. Altered mental status is a catch-all term that includes a spectrum of behaviors from a coma to confusion. There are gradations of consciousness that are described by the terms stupor, obtundation, and lethargy. Though these are explicitly defined, they are often used inexactly and hamper communications. It is suggested that providers should determine the patient’s response to stimulation and describe that response rather than use imprecise jargon. The first goal of the clinician is to stabilize the patient and recognize the emergency condition. Then, one can focus on determining the cause of coma. The initial sorting that occurs is to discover and treat rapidly remedial causes of coma such as hypoglycemia, then to pursue evaluation that will sort the case into structural or nonstructural causes of coma.[1][2][3]


Coma may result from diffuse neuronal dysfunction from metabolic,  infectious, or toxicologic causes or organ failure. It may also result from structural brain diseases such as subdural or epidural traumatic hematomas, spontaneous intracerebral hemorrhage, venous thrombosis, tumor, and other structural causes. The most common presentations of coma are the result of metabolic or infectious etiologies. Hypoglycemia and systemic infections likely account for the majority of patients presenting with coma.[4][5]


Though coma is a common clinical presentation to the emergency department, the frequency of presentation is difficult to discern. Coma is a descriptive clinical condition, and diagnostic coding often reflects the etiology of the altered mental status. The use of many terms to describe patients with depressed mental states also leads to multiple coding options, making any retrospective reviews challenging.[6][7][8]


The pathophysiology of coma reflects either substrate supply to the brain–glucose and oxygen diffuse neuronal dysfunction from other toxic or metabolic causes or structural injury. A myriad of medical processes may lead to substrate disruption and central nervous system (CNS) dysfunction, with coma as the extreme clinical condition. For example, any clinical process that causes circulatory collapse or profound hypoxemia may manifest as coma. It is thought that 15 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 will occur. [9][10][11]

Hypoglycemia is encountered frequently in clinical practice, most often in the association of treatment for diabetes mellitus or as a complication of alcoholism. The pathophysiology of other causes of metabolic coma is not clear but may involve false neurotransmitters as is suggested in hepatic encephalopathy. Electrolyte abnormalities such as hyponatremia or hypercalcemia may disrupt normal neuronal metabolism.

Structural lesions of the CNS, such as intracerebral hemorrhage, may lead to the direct destruction of brain structures as well as secondary damage from either shifting of intracranial structures or increased intracranial pressure. Herniation Syndromes describe clinically recognizable physical examination features that suggest the anatomic location of the CNS lesion. The most discussed of the herniation syndromes is the uncal herniation syndrome, where the medial portion of the temporal lobes shifts with resulting loss of consciousness from brainstem compression. The pathophysiologic findings are brainstem compression with compression of Cranial nerve 3 as it exits the brainstem and crosses the tentorium cerebelli. This results 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.  

Likely more frequent than the herniation syndromes is coma from increased intracranial pressure. The brain exists within a largely closed cranial vault, and processes that increase intracranial pressure will disrupt 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). Very simply, if ICP approaches MAP, cerebral perfusion diminishes. Thus it is important to maintain CPP by avoiding hypotension and reducing increased intracranial pressure. 

Ingestions or poisonings may cause coma from several mechanisms, but the cause is most commonly a global depression of neuronal functioning.

Prolonged unresponsiveness associated with generalized convulsive status epilepticus may occur. With the increasing use of EEG monitoring in intensive care units, patients are now being identified with abnormal electroencephalograic findings suggesting seizure activity but are clinical are without generalized seizures. Following episodes of generalized convulsive seizures, the transformation of status epilepticus does occur in some patients to a persistent unresponsive state; this is sometimes termed subtle status epilepticus or transformed status epilepticus.

History and Physical

While evaluation is occurring, it is axiomatic that the fundamentals of emergency care – airway, breathing, circulation – be addressed. Physical examination should include the response to pain, a brief assessment of motor function, eye-opening, and verbalization. These may be summarized in the Glasgow Coma Scale or other rating scales. Cranial nerve examination will include an assessment of pupillary and extraocular movements. The presence of a large or reactive pupil suggests the uncal herniation syndrome with compression of the third cranial nerve from a mass or edema. Generally speaking, asymmetric findings on physical examination suggest a structural cause of coma. Lack of focal findings suggests a metabolic, infectious, or toxicologic cause of coma. Physical examination should be directed to detect any signs of trauma.


The differential diagnosis of coma is very large. Unless a recognizable infectious or metabolic cause is established, additional testing including imaging will be necessary. CT scanning may detect hemorrhage, mass effect, or other structural abnormalities. EEG should be considered in a patient following generalized convulsive status epilepticus with continued altered mental status.[4][12][13]

Treatment / Management

Some empirical therapy is warranted. Determination of the serum glucose by the point of care testing or empiric administration of glucose is recommended. Naloxone is served for patients when slow respiratory rate, small pupils, and altered mental status suggests a narcotic toxidrome. Thiamine should be administered to individuals at risk for poor nutrition such as alcoholics, bariatric surgery patients, or patients with chronic malabsorptive states. Maintenance of cerebral perfusion pressure by assuring that mean arterial pressure is preserved by avoiding hypotension is the current management strategy. One should consider the possibility of increased intracranial pressure and continue supportive care with attention to airway protection and blood pressure.[14][15][16]

Pearls and Other Issues

Patients with common, easily remediated causes of coma, such as hypoglycemia, may be discharged if the cause is discovered, appropriate interventions are performed, and the patient has a safe home environment. Patients with persistent coma need admission to the hospital with ongoing monitoring, supportive care, and care directed to the underlying cause of coma. The etiology of the coma will determine the admission service.

Enhancing Healthcare Team Outcomes

There are many causes of coma but irrespective of the cause, the treatment is similar. These individuals require care of many organ systems and thus a multidisciplinary team approach is essential. Patients with coma require care in the ICU and many may be on a ventilator. Since the 1970s, the prognosis of patients with coma has markedly improved. However, very few long-term data are available on people who survive coma. While short-term prognosis varies from good to poor, depending on the cause, it appears that full recovery often takes months or years. Two negative prognostic factors include the depth of coma and the duration. In addition, those without any brain stem reflexes tend to have the worst outcomes. There are some patients who remain in a persistent vegetative state and the recovery of these individuals remains debatable. Current recommendations are that once a patient had developed coma, a team of healthcare professionals should determine the prognosis and if a decision of hopelessness is made, this should be communicated to the family, who may or may not accept the decision. Life support should not be withdrawn until one is absolutely sure that recovery is not possible. Prematurely deciding to end life can lead to medicolegal disputes and tarnish the reputation of the healthcare provider(s).[17][18][19]