Acute Coma

a b,
Amra Sakusic, MD, PhD , Alejandro A. Rabinstein, MD *

KEYWORDS
 Coma  Disorder of consciousness  Diagnosis  Treatment  Prognosis

KEY POINTS
 The term coma should be used to identify patients who cannot be aroused and cannot
interact with the environment. Coma is an acute state that can evolve into prolonged dis-
order of consciousness, including unresponsive wakefulness, minimally conscious state,
with different semiological features.
 Coma can be caused by structural brain injury or generalized brain dysfunction. Correct
diagnosis of the cause of coma has enormous implications for treatment and prognosis.
 Evaluation of coma should be methodical. It is useful to keep a mental checklist to avoid
missing important elements of differential diagnosis, examination, and testing.
 When evaluating a comatose patient, it is imperative to concentrate first on identifying di-
agnoses amenable to specific emergency treatments.
 Causes of coma can be treatable, nontreatable but reversible, or neither treatable nor
reversible. After excluding diagnoses for which specific emergency treatment is available,
it is always prudent to wait for reversibility before estimating a prognosis.

DEFINITION

Consciousness is the brain function that makes people who they are. It is composed of
2 domains: level and content. Level of consciousness refers to the degree of arousal,
whereas content refers to the degree of awareness. Although there is no widely
accepted formal definition of consciousness, its absence is better understood and
is the topic of this review.
The deepest degree of impaired consciousness is known as coma. Comatose pa-
tients cannot be aroused and do not interact with the environment, even after painful
stimulation.1 A patient in coma is not alert and, consequently, is unaware.
Coma is not a disease, not even a syndrome. It is a state determined by the lack of
certain major brain functions. It can also be considered as a condition reached through
a final common pathway that many brain insults can follow when sufficiently severe.
Coma can be caused by structural brain lesions, toxic exposures, metabolic

a
Department of Neurology, Mayo Clinic, 4500 San Pablo Road South (Attention: Cannaday
Building 3W CIM), Jacksonville, FL 32224, USA; b Department of Neurology, Mayo Clinic, 200
First Street Southwest, Rochester, MN 55905, USA
* Corresponding author.
E-mail address: rabinstein.alejandro@mayo.edu

Neurol Clin 39 (2021) 257–272

https://doi.org/10.1016/j.ncl.2021.01.001 neurologic.theclinics.com
0733-8619/21/ª 2021 Elsevier Inc. All rights reserved.
258 Sakusic & Rabinstein

disorders, inflammation, and seizures, to name just the main causes. Thus, saying a
patient is comatose only indicates the manifestation of a critical brain dysfunction.
The job of the clinician is to determine the cause of that brain dysfunction and whether
it is reversible.

BASIC PATHOPHYSIOLOGIC CONSIDERATIONS

Although simplistic, the anatomic notion that coma results either from bilateral supra-
tentorial or diencephalic brainstem dysfunction remains correct.2 However, this cate-
gorization is not exclusionary in practice. For instance, unilateral hemispheric lesions
can cause contralateral hemispheric dysfunction and diencephalic-mesencephalic
dysfunction through mass effect.
A classification based on causative mechanism is pragmatically more useful. Major
categories include global anoxia-ischemia, cerebrovascular disease (ischemic or
hemorrhagic), traumatic injury, seizures, infection, noninfectious inflammation, hydro-
cephalus, neoplastic, metabolic and endocrine disorders, hypothermia, and various
toxins. A detailed list of common causes of coma is presented in Table 1.
Another classification scheme has been proposed within the framework of the
Curing Coma Campaign launched in 2019 by the Neurocritical Care Society.3 This
classification contemplates 4 categories (characterized as endotypes):
1. Disorder of consciousness (DOC) endotype without commensurate structural dam-
age, a category that includes conditions that could be reversible with or without
specific treatment (eg, seizures, drug overdose)
2. DOC endotype with structural or functional damage that is amenable to neurologic
replacement or bypass therapy (eg, global anoxia or major stroke that could in the
future be improved with stimulant drugs or brain-machine interfaces)
3. DOC endotype that is not amenable to pharmacologic or anatomic replacement or
repair therapy (eg, end-stage infectious or degenerative process)
4. DOC mimics endotype, including conditions in which structural damage causes
functional deficits that can be confused with coma (eg, severe abulia, locked-in
syndrome)
This classification does not include another acutely treatable cause of DOC; namely,
structural lesions amenable to emergency surgical therapy (eg, subdural or epidural
hematoma with brain compression treatable with craniotomy and evacuation or acute
internal carotid artery occlusion treatable with mechanical thrombectomy).

EMERGENCY EVALUATION AND MANAGEMENT

Every neurologist practicing in a hospital setting should have in-depth knowledge of

coma. Not only neurologists but also emergency medicine physicians and hospitalists
encounter comatose patients in their everyday clinical practice. Misunderstandings
and misinformation related to diagnosis and management of comatose patients are
common and may result in serious medical errors. Clinicians need to follow a method-
ical and efficient approach to the evaluation of coma to prevent these errors.
In the emergency department, coma should be considered a medical emergency
until proved otherwise. It often requires immediate action to prevent devastating com-
plications. The first priority is to ensure the patient has a secure airway, adequate
ventilation and oxygenation, and sufficient circulation. Once these vital functions
have been stabilized, the clinician should obtain a detailed history of recent events
and comorbidities, perform a focused but complete physical examination, and order
investigations following a rational approach in order to uncover the cause of the
 Acute Coma 259

Table 1
Common causes of coma organized by mechanism

Structural Intracranial Disease Diffuse Brain Dysfunction

Global anoxic-ischemic injury Seizures
Status epilepticus
Postictal state
Cerebrovascular disease Metabolic and endocrine disorder
Brainstem ischemia Hypoglycemia
Massive hemispheric ischemia Diabetic decompensation
Large areas of bilateral hemispheric ischemia Hypercapnia
Bilateral thalamic ischemia Hyponatremia
Poor-grade subarachnoid hemorrhage Hypercalcemia
Large supratentorial intracerebral hemorrhage Uremia
Large cerebellar hemorrhage Hyperammonemia
Brainstem hemorrhage Addison crisis
Deep venous sinus thrombosis Myxedema
Extensive dural venous sinus thrombosis Thiamine deficiency
Cerebral air embolism
Trauma Intoxications
Diffuse axonal injury Carbon monoxide
Bilateral contusions Cyanide
Extra-axial hemorrhage with mass effect Opiate
Edema with intracranial hypertension Alcohol and atypical alcohols
Cerebral fat embolism Sedative-hypnotics
Nonprescription sympathomimetics
Serotonin syndrome
Neuroleptic malignant syndrome
Malignant catatonia
Tumor Septic shock
Large supratentorial tumor with mass effect
Cerebellar tumor with mass effect
Brainstem tumor
Infiltrative tumor (glioma, lymphoma)
Pituitary apoplexy
Acute hydrocephalus Hypothermia
Infection —
Fulminant bacterial meningitis
Cerebral abscess with mass effect
Epidural abscess with mass effect
Viral encephalitis
Advanced fungal meningoencephalitis
Advanced tuberculous meningitis
Posterior reversible encephalopathy syndrome —
Fulminant demyelination —
Inflammatory
Osmotic
Autoimmune encephalitis —
Paraneoplastic
Nonparaneoplastic
260 Sakusic & Rabinstein

coma. Although most therapeutic decisions depend on the cause of coma, some
basic emergency interventions apply to all comatose patients.

Basic Tenets for the Emergency Management of Comatose Patients

The general principles of any medical emergency apply to the emergency manage-
ment of coma. First, always think about ABC (airway, breathing, circulation):
 Airway and breathing
 Assess the patient’s ventilation and oxygenation
 Supplement oxygen, if needed
 Proceed with intubation and mechanical ventilation if:
- Patient cannot protect the airway

- Gas exchange is poor, with low oxygen saturation or hypercapnia

- Breathing pattern is inefficient (note: Cheyne-Stokes breathing and central

neurogenic hyperventilation do not always require mechanical ventilation)

- There is a significant risk of aspiration

The concept that all comatose patients need to be immediately intubated is wide-
spread, but unproved. Although it is true that most comatose patients require intuba-
tion because of 1 or more of the indications noted earlier, there are exceptions that
generally involve coma causes expected to be short lived. For instance, a postictal pa-
tient who does not show compromise of airway patency, maintains a regular breathing
pattern, and does not have major oxygen desaturation may be carefully observed
without harm. Even if acidotic and hypercapnic initially, these patients typically clear
their acidosis spontaneously and wake up after a variable length of time without com-
plications, as long as recurrent seizures do not occur. Thus, the dictum that Glasgow
Coma Scale (GCS) score less than 8 indicates the need for intubation should not be
followed dogmatically. In contrast, noninvasive ventilation is not a safe option for
comatose patients because of heightened risk of aspiration. If mechanical ventilation
is deemed necessary for a comatose patient, tracheal intubation is indicated.
 Circulation
 Obtain intravenous (IV) access
 Ensure adequate blood pressure and sufficient organ perfusion
 If hypotension is present (systolic blood pressure <90 mm Hg or mean arterial
pressure <65 mm Hg), administer fluids
 If the patient’s blood pressure remains low after fluid resuscitation, consider
giving vasopressors
 Order 12-lead electrocardiogram and keep on continuous cardiac monitoring
to exclude arrhythmias and corrected QT prolongation
Additional considerations that should be remembered when first evaluating any
comatose patient include:
 If trauma is suspected, stabilize cervical spine.
 Give thiamine (100 mg IV) before dextrose (50% solution) to avoid Wernicke en-
cephalopathy in malnourished patients.
 Give naloxone 0.4 to 2 mg IV if opioid overdose is deemed possible. Watch for
delirium after rapid reversal of opioids caused by withdrawal.
Subsequent management steps should be guided by the results of the diagnostic
work-up, which should always be geared toward identifying treatable neurologic
and neurosurgical emergencies.
 Acute Coma 261

History Taking When Evaluating a Comatose Patient

Obtaining relevant historical details when evaluating a comatose patient can be chal-
lenging, especially if a companion is not available for interview and previous medical
records are not accessible for review. However, it is crucial to maximize efforts to
obtain relevant information on recent symptoms, previous illnesses, use of prescribed
and nonprescription medications, and possible toxic exposures.
Often, most of the significant details are obtained from bystanders, work col-
leagues, a significant other, police officers, friends, or prehospital personnel. If neces-
sary, phone calls should be made to reach out to witnesses even if they are already on
the way to the hospital to prevent loss of valuable time. Indirect information should al-
ways be taken cautiously, but still can provide important clues to trim the differential
diagnosis. Additional valuable sources of information are medical records, alert cards,
bracelets, and pharmacy phone numbers that can be found in patients belongings.
When possible, 1 team member should be assigned to seek out information while
others stay at the bedside caring for the patient.
It is very important to establish whether the onset of coma was witnessed, when the
patient was last known to be well, and the acuity of the presentation. It is crucial to
determine whether the patient had respiratory or cardiac arrest at onset, and whether
severe hypoxemia was noted on first evaluation.
Sudden onset of coma raises concern for stroke, seizure, or acute poisoning. A pre-
ceding headache points primarily to aneurysmal subarachnoid hemorrhage. Abnormal
movements, urinary incontinence, and tongue bite signal a preceding seizure. A stut-
tering course may be the clue to diagnose basilar artery occlusion. In contrast, a
gradual onset preceded by personality changes is more suspicious for an inflamma-
tory process or a slowly expanding mass. If the onset was insidious or the patient
had fluctuating decline, information regarding recent behavior at home and at work
should be obtained.
While obtaining the history, clinicians should also focus on recent medications or
changes in dosage of previously used medications, substance abuse, recent trauma,
previous suicide attempts or suicidal ideation, other possible toxic exposures, and
immunosuppression. When investigating comorbidities, it is important to pay attention
to vascular risk factors and other conditions that require anticoagulation, renal or liver
failure, epilepsy, brain tumor, and recent neurosurgery.

General Physical Examination

General inspection
The examination of a comatose patient should begin with a general visual inspection
free of any stimulation. Simply by observing, the clinician can identify irregular breath-
ing patterns, adventitious movements, asymmetry of movements, traumatic injuries
(such as periorbital and retroauricular ecchymoses indicative of basilar skull fracture),
and other signs that can be helpful in narrowing the differential diagnosis. Central
neurogenic hyperventilation (ie, sustained tachypnea and hyperpnea) typically indi-
cates bilateral thalamic lesions, whereas ataxic breathing (ie, irregular rate and irreg-
ular tidal volume) indicates pontine tegmentum lesions. Cheyne-Stokes breathing
pattern (ie, oscillating periods of hyperventilation and hypoventilation) is more com-
mon but has less localizing value.

Vital signs and systemic features

Vital signs, fever, lateral tongue bite, skin changes, cardiac murmurs, signs of heart
failure, and signs of portal hypertension can provide valuable information and help
in establishing the correct diagnosis in a timely manner.
262 Sakusic & Rabinstein

Fever should prompt consideration of central nervous system infection, but sepsis
from other sources can also provoke coma. Fever can also be seen with several tox-
idromes, such as organophosphates, neuroleptic malignant syndrome, serotonin syn-
drome, or withdrawal of cerebral depressants.4 Hypothermia and hyperthermia from
heat stroke can cause coma. Presence of tachycardia or bradycardia can help in
the differentiation of culprit toxins. Tachycardia can be seen with any cause of sympa-
thetic activation. Bradycardia should raise concern for increased intracranial pressure
and is especially prominent with acute hydrocephalus.
Detailed examination of the skin can be particularly informative. A purpuric rash can
be a manifestation of thrombotic microangiopathy, bacterial meningitis (most notably by
Neisseria meningitidis), rickettsial infection, disseminated intravascular coagulation, or
vasculitis.5 Needle puncture marks on the skin indicate IV drug abuse. Stigmata of liver
failure, dark pigmentation in patients with Addison disease, cool and yellowish skin with
myxedema, and extreme skin dryness with organophosphate intoxication are additional
examples of the value of a careful dermatologic examination.

Neurologic Examination
The neurologic examination, despite its inherent limitations in comatose patients, is
critically important to guide additional testing. It must be structured and efficient.
The first step is to confirm that the patient is unresponsive to verbal or nonverbal com-
mands and that arousal cannot be achieved with any form of auditory or painful stim-
ulation. It is important to remember that lock-in patients may only be able to respond
by blinking or vertical eye movements, which are often subtle and may be missed.
Once it is established that the patient is comatose, the examination should be focused
on assessing brainstem reflexes and motor responses to stimulation, and detecting
signs of meningeal irritation and adventitious movements. Confounding factors, espe-
cially sedation and residual pharmacologic paralysis, must be taken into account
when interpreting the findings of the neurologic examination. Hypothermia, hyperther-
mia, and hypotension can also act as confounders. Before reaching conclusions about
the implications of neurologic findings, the examination should be repeated after these
confounders are corrected or eliminated.

Examination of the eyes and brainstem

Careful observation of the eyes can be extremely helpful in comatose patients. First,
the clinician should note their position. A slight divergence of the eyes is common in
deeply sedated and comatose patients and it is often clinically insubstantial; however,
a frankly disconjugate gaze (particularly vertical misalignment) may reflect a brainstem
or cranial nerve lesion. Conjugate gaze deviation to one side can be seen with hemi-
spheric lesions affecting the frontal lobe (gaze deviates to the side of the lesion) or with
thalamic or pontine lesions (gaze deviates away from the side of the lesion). Downward
gaze may signal hydrocephalus. Abnormal biphasic vertical eye excursions, of which
the most common is ocular bobbing (with a fast initial phase downwards), can be seen
with pontine damage but also in cases of global cerebral dysfunction; therefore, they
have limited localization value.6 Subtle nystagmoid jerks may be the only manifesta-
tion of status epilepticus. Periorbital myoclonus may be noticed after global anoxia.
Size, symmetry, and light reactivity should be gauged when examining the pupils.
Very small pupils can be seen with pontine injury but also with opiate poisoning or
CO2 narcosis. Large reactive pupils are characteristic of hypersympathetic states,
such as serotonin syndrome. Pupillary asymmetry in a comatose patient should al-
ways be considered a potential emergency unless it is known to be chronic. The
typical unilateral large nonreactive pupil (so-called blown pupil) occurs from loss of
 Acute Coma 263

parasympathetic innervation caused by compression of the brainstem or third cranial

nerve and should raise immediate concern for uncal herniation when found in a coma-
tose patient. Although characteristically ipsilateral to the side of the mass lesion, it can
occasionally occur on the contralateral side.
Fundoscopy can provide additional useful information. Vitreous hemorrhage can be
noted with aneurysmal subarachnoid hemorrhage. Papilledema is a fairly reliable indi-
cator of increased intracranial pressure, but its absence does not exclude increased
intracranial pressure because it may take time to develop and, in some patients, it
may never occur.
Corneal reflexes should be optimally checked by touching the nasal aspect of the
cornea because it may have greater innervation that the lateral part,7 but what matters
most is to ensure that the cornea and not the sclera is being stimulated. Sterile saline
may initially be used for stimulation to reduce the risk of corneal damage; however,
when no response (ie, blinking) is observed, it is advisable to recheck using a sterile cot-
ton swab. Oculocephalic reflexes are tested by moving the head rapidly from side to
side. A normal response in a comatose patient is a conjugate movement of the eyes
away from the side of the head rotation (ie, so-called doll’s eyes). This maneuver should
only be conducted after the cervical spine has been cleared. Oculovestibular reflexes
are elicited by irrigating the external auditory canal with ice water. A normal response
in a comatose patient is a slow tonic deviation toward the irrigated ear. Gag and cough
reflexes should also be tested by stimulating the pharynx and trachea, respectively.

Motor examination
A complete motor examination should include assessment of the muscle tone, spon-
taneous movements, and responses to pain. Any asymmetry should suggest the need
to exclude a structural lesion. Motor response after central pain stimulation can be
evaluated by pressing on temporomandibular joints or supraorbital notches. Central
stimulation is necessary to determine whether the patient can localize pain. Peripheral
pain stimulation is provoked by pressing on nailbeds. Clear response to central stim-
ulation without response to stimulation of the extremities can be seen with cervical
cord injury and in patients with critical illness neuromyopathy. Pain stimulation tests
should be performed on all extremities and the best response should be recorded.
A normal response to peripheral pain is to withdraw from the source of pain. Distin-
guishing flexion withdrawal from decorticate posturing may be challenging. Extensor
(decerebrate) posturing is easier to recognize. However, it is important to realize that
many patients with disinhibited motor responses have an initial extensor response that
is followed by withdrawal; in such cases, the motor response should be consider with-
drawal. Instead, true extensor posturing is sustained. A triple flexion response in the
leg represents a spinal reflex. It can best be recognized by its stereotypical quality
where any stimulation of the leg results in exactly and repeatedly the same response.
Myoclonus can be caused by metabolic abnormalities (renal or hepatic insufficiency, elec-
trolyte disturbances), intoxication (opioid, lithium, serotonin agents, pesticides), anoxic-
ischemic brain injury, or nonconvulsive status epilepticus.8 Myoclonus can be differentiated
from seizures by lack of rhythmicity. Any rhythmic movements, even if subtle, segmental, or
solely visible after stimulation, should be considered highly suspicious for seizures.

Other aspects of the neurologic examination

Deep tendon reflexes, plantar responses, and presence of clonus should also be
checked on every comatose patient. A unilateral Babinski sign may be the only sign
of an underlying mass lesion. Clonus with preferential rigidity of the legs is character-
istic of serotonin syndrome.9
264 Sakusic & Rabinstein

The examination of a comatose patient is not complete without testing for signs of
meningeal irritation. Although it is true that these signs lack high sensitivity and spec-
ificity,10 they can be extremely helpful when unequivocally present.

Coma Scales: Value and Limitations

The 2 best-validated coma scales are the GCS11 and the Full Outline of Unresponsive-
ness (FOUR) score.12 These tools are helpful in facilitating everyday communication
among health care providers and for the serial monitoring of patients’ clinical evolution.
However, they should not replace a more complete neurologic examination. The GCS is
less useful in intubated patients because of the loss of ability to assess the verbal
component. A modified version designed to overcome this shortcoming by resorting
to certain assumptions has been proposed.13 The GCS and FOUR score assess eye
opening and motor responses, but the FOUR score also incorporates brainstem re-
flexes and respiratory pattern (Fig. 1).12 Some studies have indicated that the FOUR
score may outperform the GCS in predicting the prognosis of neurocritical patients eval-
uated in the emergency department14 or the intensive care unit (ICU).15

DIAGNOSTIC TESTING

When ordering tests for the evaluation of coma, clinicians should be guided by some
basic principles:
 First consider diagnoses that require emergency treatment
 Use the history and examination to steer the testing (ie, avoid a so-called gunshot
approach)
 Excessive testing may lead to errors
 Sometimes it is necessary to be patient (ie, the diagnosis will declare itself over
time)
The more tests are ordered, the higher the likelihood of finding abnormal results of
unclear relevance, which can create a lot of confusion and result in inappropriate treat-
ment. To avoid this, it is best to follow a methodical, stepwise approach directed by
the information obtained through history and examination. However, it is crucial to
think about the most common treatable causes of coma, particularly those for which
emergency treatment (or lack thereof) will determine the prognosis (Table 2).
Routine emergency testing should include serum metabolic panel (preceded by
point-of-care capillary glucose), complete blood count, serum lactic acid, serum
ammonia, arterial blood gas, coagulation parameters, serum alcohol concentration,
and urine drug screen. Febrile patients should have blood cultures. Noncontrast
head computed tomography (CT) scan is often obtained in the emergency depart-
ment, although the yield is low in patients without focal or lateralizing signs on neuro-
logic examination and without history of trauma.16,17
Additional testing requires individualized decisions, and having a mental checklist
may help avoid missing a relevant test (Fig. 2).18,19 CT angiogram of the head to
rule out basilar artery or intracranial carotid artery occlusion, lumbar puncture to
exclude meningitis or encephalitis, and electroencephalogram to evaluate for status
epilepticus need to be contemplated. MRI of the head (with gadolinium if possible)
can be very informative for multiple diagnoses that are typically missed on CT scan,
including global anoxic-ischemic injury,20 posterior reversible encephalopathy syn-
drome,21 herpes simplex virus-1 encephalitis,22 cerebral fat embolism, fulminant
demyelination, and some forms of autoimmune encephalitis (Fig. 3). When overdose
is suspected, testing for serum concentration of specific prescription (eg, antiseizure)
265
266 Sakusic & Rabinstein

Table 2
Most frequent causes of emergently treatable acute coma

Diagnosis
Hypoglycemia
Severe hyponatremia
CO2 narcosis
CO intoxication
Opiate intoxicationa
Intracranial hemorrhage
Basilar artery occlusion
Acute hydrocephalus
Cerebral venous thrombosis
Status epilepticus
Fulminant bacterial meningitis Antibacterial drugs with CNS penetration and
Herpes encephalitis
Hypertensive encephalopathy
Diabetic coma
Uremic encephalopathy
Hyperammonemic
encephalopathy
Sepsis
Treatment
Dextrose infusion (after thiamine)
Gradual serum sodium correction
Mechanical ventilation
Hyperbaric oxygen
Naloxone
Surgical evacuation
Reperfusion therapy (IV thrombolysis and/or mechanical
thrombectomy)
Ventriculostomy
Anticoagulation
Antiseizure drugs
dexamethasone
Acyclovir
Gradual blood pressure reduction
Insulin
Dialysis
Lactulose, rifaximin
Antibiotics, fluids

Abbreviation: CNS, central nervous system

a
Other less common intoxications with specific antidotes should also be considered when
appropriate.34

or nonprescription (eg, acetaminophen) drugs may be necessary. Autoimmune en-

cephalitis panels in serum and cerebrospinal fluid should be ordered prudently but
can be the only way to arrive to the correct diagnosis in pertinent cases.23

TREATMENT

After the therapeutic interventions noted earlier in relation to emergency management,

treatment of coma depends on the underlying cause.24 A list of emergently treatable
causes of coma is shown in Table 2. Other articles in this issue offer detailed discus-
sions on the treatment of various primary brain diseases that may result in coma. Addi-
tional practical advice includes:
 If an intoxication is suspected, contact the poison control center or local toxi-
cology specialist.
 When evaluating coma in the ICU, always remember to check the medication list
and discontinue any medications that might be potential culprits or contributors

=
Fig. 1. The FOUR score. B, brainstem reflexes; E, eye response; M, motor response; R, respi-
ration. Numbers indicate the score to be assigned for the response. (From Wijdicks EFM,
Bamlet WR, Maramattom BV, Manno EM, McClelland RL: validation of a new Coma Scale:
the FOUR score. Ann Neur, 2005:58:585-593; used with permission of Mayo Foundation
for Medical Education and Research, all rights reserved.)
 Acute Coma 267

Stabilization of vital functions

Initial evaluation
(history, physical exam, basic laboratory studies)

Trauma?
Focal or lateralizing
signs?
No Y
Yes

Investigate and Perform head CT

treat non-structural causes (with neck/head CTA if brainstem signs)

Improvement? Diagnostic?

Continue treatment and

nd Consider: Brain MRI Treat as pertinent
monitoring Electroencephalogram
Lumbar puncture
Additional toxicology

Fig. 2. Basic algorithm for the emergency evaluation of acute coma. Further details can be
found on the text. CTA, CT angiogram.

to the pathogenesis of the coma (eg, sedatives, opiates, cefepime, serotonin-

enhancing agents).4,9,25
 When the diagnosis remains uncertain and emergently treatable causes have
been excluded, often it is best to wait (ie, when unsure what to do, better not
to do anything).
 Supportive care is essential to optimize the chances of good recovery. Comatose
patients are at risk of pneumonia, urinary infection, ileus, venous thromboembo-
lism, gastroduodenal ulcers, cardiac arrhythmias, and medication toxicity. Pre-
vention and early treatment of these and other complications demands close
attention to detail. Sequential compression devices, deep venous prophylaxis
with subcutaneous heparin or enoxaparin (if not contraindicated), stress ulcer
prophylaxis, and a scheduled bowel regimen should be included in the routine
management of any comatose patient.
The Curing Coma Campaign has been created to find new ways to treat comatose
patients by refining the understanding of coma.3 The initial priorities identified by the
Scientific Advisory Council were defining coma endotypes with distinct recovery tra-
jectories and possibilities for intervention, identifying novel biomarkers, and designing
proof-of-concept clinical trials to promote recovery of consciousness.

PROGNOSIS

Prognosis is a major consideration in the care of comatose patients, and neurologists

are sometimes consulted solely to estimate a prognosis after some time from the
onset of the unresponsiveness. This delay is far from ideal. A neurologist should be
268 Sakusic & Rabinstein

Fig. 3. Illustrative examples of various causes of coma documented by MRI. (A) Bilateral
vasogenic edema predominantly affecting the occipital lobes in a patient with posterior
reversible encephalopathy syndrome (fluid-attenuated inversion recovery [FLAIR]
sequence). (B) Severe anoxic cortical injury after cardiac arrest (diffusion-weighted imaging
sequence). (C) Inflammatory changes affecting the right temporal lobe in a patient with her-
pes simplex virus-1 encephalitis (FLAIR sequence). (D) Bilateral inflammatory changes pre-
dominantly affecting the limbic regions in a patient with paraneoplastic autoimmune
encephalitis (FLAIR sequence). (Reproduced with permission from Rabinstein AA. Acute
Coma. In: Rabinstein AA (editor). Neurological Emergencies: a practical approach.
Switzerland: Springer Nature; 2020. p. 1-13.19)

involved in the management of these patients from their first evaluation in the emer-
gency department to assist in diagnosis and treatment. In general, prognosis should
not be the first priority, although there are exceptions, such as patients with massive
brainstem hemorrhages for whom aggressive treatment is likely to be futile. However,
the guiding rule should be to avoid early therapeutic nihilism and to focus on diagnosis
and emergency treatment first (Fig. 4).
Even more than for treatment, prognosis depends on the cause of coma. Discus-
sions on prognosis for individual critical brain diseases are provided in other articles
in this issue. Age, previous brain condition, degree of acute injury (severity, extent,
and eloquence), and duration of coma are the basic determinants of prognosis, but
many other factors need to be considered according to the primary diagnosis and
other individual considerations.26,27 Prognosis should always be expressed as estima-
tion; gaps in prognostic ability exist for all major neurocritical diseases28 and therefore
 Acute Coma 269

Fig. 4. A 32-year-old man without previous known medical problems was found unrespon-
sive in his bed. His breathing was agonal and was intubated in the field. At the local emer-
gency department he had bilaterally dilated, nonreactive pupils with extensor motor
response on the left and no response on the right. Head CT scan (A, B) showed a massive
right extra-axial hematoma with severe brain compression causing pronounced subfalcine
and uncal herniation, and hydrocephalus from trapping of the contralateral ventricle. He
was emergently transferred to our center while receiving 100 g of 20% mannitol en route.
On arrival, he had regained pupillary reactivity on the left. He was immediately taken to the
operating room where he underwent hematoma evacuation with right hemicraniectomy.
During the operation, the neurosurgeons noted a pial arteriovenous malformation that
was resected. Postoperative CT scan is shown in (C) and (D). The patient experienced a
remarkably favorable evolution and 6 weeks later only had mild right III nerve palsy and
very mild right hemiparesis (weakness ipsilateral to the side of the mass lesions can be ex-
plained by damage to the contralateral cerebral peduncle by the initial compression; this
false localizing sign is known as the Kernohan-Woltman notch phenomenon).

it is impossible to be entirely conclusive. That estimation should then be put in the

context of the patient’s preferences and values in conversations with the family or
other surrogates.
Our understanding of DOC is being enhanced by technology (functional MRI, PET,
special electroencephalogram techniques) that is offering new venues to identify some
270 Sakusic & Rabinstein

evidence of covert consciousness in patients who appear comatose at the

bedside.29–31 How to best apply this new knowledge in daily practice remains a matter
of debate.32 When communicating with families, it is important to clarify that emer-
gence from acute coma is a process in which some patients regain sleep-wake cycles
but remain unaware (unresponsive wakefulness), others recover consciousness but
only minimally and remain fully dependent (minimally conscious state), and those
with more favorable evolution regain alertness and awareness with or without motor,
behavioral, and cognitive deficits.33 Although chances of recovery diminish with the
duration of coma, improvement of consciousness is more likely after prolonged
coma from trauma than from global anoxia-ischemia.26

SUMMARY

Neurologists must be key players on the multidisciplinary team caring for patients with
acute coma. After initial stabilization of vital functions, history and physical examina-
tion (with emphasis on a focused neurologic examination) should provide the informa-
tion to decide on subsequent testing. Conditions for which specific emergency
treatment is possible should be considered first and therapeutic nihilism should be
avoided. Estimating prognosis is an essential role of neurologists, but it is important
not to rush to prognostication until it is clear that treatment or time cannot improve
the condition of the patient.

CLINICS CARE POINTS

 After initial stabilization of vital functions, identify treatable neurologic emergencies, such
as status epilepticus, stroke from large artery occlusion, and extra-axial hematoma.
 Always consider confounders (paralytics, sedatives, opiates, body temperature, metabolic
disorders) when interpreting the neurologic examination.
 Keep a rational approach to testing by letting the history, general and neurologic
examinations, and clinical evolution guide diagnostic decisions.
 When a treatable cause for the coma is not diagnosed, it is often best to just wait and follow
the patient closely. Do not feel obliged to search for obscure diagnoses without effective
treatment, do not embark on unsubstantiated empiric therapies, and do not rush
prognostication.

FINANCIAL DISCLOSURE AND CONFLICTS OF INTEREST

The authors declare no pertinent financial conflicts of interest.

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