Emergency Neurological Life Support:

Approach to the Patient with Coma

Sara Stern-Nezer, MD, MPH1*, Katrina Peariso, MD, PhD2 and

Prem A Kandiah, MD3
1Departments of Neurology & Neurosurgery, University of California, Irvine, Irvine, CA
2Department of Pediatrics, Division of Neurology, Cincinnati Children’s Hospital,
Cincinnati, OH
3Department of Neurology, Emory University School of Medicine

Abstract
Coma is an acute failure of neuronal systems governing arousal and awareness and rep-
resents a medical emergency. When encountering a comatose patient, the clinician must
have an organized approach to detect remediable causes, prevent neurologic injury, and
determine a hierarchical approach for diagnostic testing, treatments, and neuromonitor-
ing. Coma was chosen as an Emergency Neurological Life Support (ENLS) protocol
because timely medical and surgical interventions can be lifesaving and need implemen-
tation in a rapid manner. The initial work-up of such patients is critical to establishing a
correct diagnosis.
Key words: Coma, Consciousness, Critical Care, Neurocritical Care, Encephalopathy

*E-mail: ssternne@hs.uci.edu

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1 Introduction
Coma is characterized by the absence of arousal (wakefulness, vigilance) and awareness
of self and environment, lasting for more than one hour.1 Certain causes of coma are
readily identified, while others may require extensive testing to discover an etiology and
it is important that diagnostic and therapeutic steps occur simultaneously.2
The ENLS suggested algorithm for the initial management of coma is shown in Fig-
ure 1. The initial step is to assess for coma and reversible conditions while incorporating
available history and physical exam findings to best diagnose and concurrently treat pa-
tients with acute coma. Table 1 has a list of suggested items to complete within the first
hour of patient evaluation; this is meant to provide a framework for the principles of di-
agnosis and emergent management of coma, which can be adapted to reflect global and
regional variations based on the local availability of diagnostic tools and treatments.

TABLE 1
Coma checklist for the first hour

Checklist
 Evaluate/treat circulation, airway, breathing and cervical spine
 Exclude/treat hypoglycemia or opioid/benzodiazepine13 overdose
 Serum chemistries, arterial blood gas, urine toxicology screen
 Emergent cranial CT (and CT Angio Brain if appropriate) to
determine if coma etiology is structural or vascular in etiology

2 Prehospital Considerations
If coma is identified in the prehospital setting, initial evaluation and management steps as
outlined in this protocol should be implemented as soon as possible to maximize chances
of neurologic recovery. Emergency medical services (EMS) teams will assess airway,
breathing, and circulation (ABCs); check Glasgow Coma Scale3 (GCS), pupils, and vital
signs, including blood glucose, and obtain intravenous (IV) or intraosseous (IO) access.
Based on assessment findings, EMS teams will establish an airway, ventilate if needed,
check for and correct hypoglycemia, administer naloxone, and treat for shock with fluids
and pressors if indicated. In addition, prehospital personnel should collect pertinent in-
formation from witnesses and from contextual or environmental observations. Witnesses
may be able to provide information on the time course of the neurological decline as well
as any prodromal symptoms. Family or friends may have information regarding the pa-
tient’s past medical history, prescribed medications, drug or alcohol use, any history of
recent illness that might suggest an infectious cause, signs that might suggest a drug or
medication overdose, seizure activity, or recent trauma. A quick look around the site in
which the patient was found can yield valuable information including signs of trauma or
environmental exposures, current prescription bottles, empty pill bottles, drugs, or alcohol
that might suggest overdose or intoxication.
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FIGURE 1: ENLS Approach to the Patient with Comaprotocol

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TABLE 2
Prehospital checklist and handoff
Prehospital checklist and handoff
• Airway, breathing, ventilation issues
• GCS, pupils, and vital signs on presentation
• IV or IO access, site and patency
• Ruled out Hypoglycemia
• History from bystanders, witnesses, contextual or environmental observations (pill
bottles, signs of trauma or seizure activity)
• Naloxone, dose administered and response
• Medications administered, dose and response (naloxone, benzodiazepine, dextrose
etc.)
• Time when patient was last seen normal
• Prodromal symptoms when last seen

2.1 ABCs and Cervical Spine Precautions

The unconscious patient’s ABCs should be quickly assessed and concurrently treated (see
the ENLS Airway, Ventilation, and Sedation protocol). Verifying patency of the airway is
an overriding initial priority to ensure adequate oxygenation and ventilation. The patient’s
cervical spine should be immobilized if the possibility of injury cannot be ruled out. A
rapid initial survey should follow to evaluate for notable physical findings of the head,
neck, chest, abdomen, and extremities.
IV or IO access should be established during the initial evaluation and, if possible,
in the prehospital environment. Prompt blood glucose testing should be performed in
all unconscious patients. Table 3 lists pharmacological treatment that are administered
for common toxic/metabolic causes of coma, as well as elevated ICP. These should be
administered in the prehospital setting based on syndromic presentation. Table 9 lists
common clinical findings for these toxidromes; elevated ICP often requires a high index of
suspicion but may also involve pupillary changes or the Cushing’s triad of (1) bradycardia,
(2) hypertension with widened pulse pressure owing to increased systolic pressure and
decreased diastolic pressure, and (3) irregular respiration.3

3 General And Neurologic Examination

A general physical examination should be performed including assessment of vital
signs/respiratory patterns, facial and motor symmetry, and cranial and peripheral
reflexes.4 If hypotension is present, the cause should be pursued while fluid repletion
and/or vasopressors are started. Blood pressure elevation in the comatose patient may be
a sign of an underlying life-threatening process, such as elevated intracranial pressure
(ICP) or acute stroke, which must be identified and treated promptly. Extremely high
blood pressure should be treated if intracranial hemorrhage is suspected as a cause of
coma (history of anticoagulation, fall).5 A search for signs of trauma and other conditions
that might require emergent surgical or medical management are central goals of the
initial survey.
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TABLE 3
Prehospital pharmacological therapy for coma
Cause of coma Pharmacological therapy
Hypoglycemia Dextrose 50% 20-50ml IV
(peds) 25% 2-4ml/kg
10% Dextrose 50-100ml IV (peds: 5-10ml/kg) can be given if
D50 unavailable
Thiamine should be given prior to dextrose in patients with risk
factor for nutritional deficiency (e.g., chronic EtOH use, bariatric
surgery, malabsorption states) or if history unknown
Opioid overdose Naloxone 0.04-0.4 mg IV/IM or 1-2 mg per nare into both nares,
can be repeated every 2-3mins for desired degree of counterac-
tion. If initial use intranasal, switch to IV/IM when possible.
Anticholinergic Physostigmine 0.5-2 mg slow IV push with rate not to exceed 1
toxicity mg/min. Dose can be repeated in 30-60mins if clinically effec-
tive to ameliorate symptoms. Atropine 1-2 mg IV must be kept
ready nearby for immediate use if bradycardia or other signs and
symptoms of cholinergic excess. Dose can be repeated every 3-
5mins if previous dose did not induce a response
Elevated ICP Hypertonic saline 3% 5ml/kg over 5-20min (range 2.5-5ml/kg)
can be given through peripheral IV as 250ml bolus over 30mins
or 500ml bolus over 60mins.
Mannitol 20-25% dose 0.5-1 gm/kg over 5-15min, can be re-
dosed every 4-6 h. Caution must be exercised in heart and re-
nal failure due to the high osmotic load infused and lower doses
(0.25-0.5 g/kg) may be used. Requires in-line filter (precipitates-
crystal formation); may require warming to dissolve crystals be-
fore administration.

The emergency neurological assessment of the unconscious patient has four parts1:
level of consciousness (LOC), brainstem assessment, evaluation of motor responses, and
appraisal of breathing patterns. Arousal is assessed by looking for spontaneous opening of
the eyes, visual fixation or pursuit (tracking), and spontaneous and purposeful movements
of the extremities. Altered motor strength can also be tested via resistance to movement.
The examination of a comatose patient should involve increasing intensity of stimulation
until a response is evoked or it is deemed that the patient is unable to respond. Start with
a simple verbal cue (e.g., “Are you ok?”) and progress to louder voice, physical stimuli,
and noxious stimuli. Noxious stimuli could include a sternal rub, nail bed pressure or
trapezius muscle squeeze.
The LOC can be expressed quantitatively by the GCS in adults and children (see
Tables 4 and 5).3 The GCS is most valuable for trending sequential LOC examination
responses of a particular patient. However, the GCS is limited by its inability to account
for alterations in brainstem function, hemiparesis, or aphasia or help differentiate between
different etiologies of coma. Patients with identical total GCS scores may have very
different clinical presentations due to different combinations in the motor, verbal, and
eye sub-scores. The Full Outline of UnResponsiveness (FOUR) score incorporates more
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detailed information on brainstem responses and has been validated in a variety of clinical
settings (Figure 2).5−7 Use of the FOUR score tool can assist the clinician in determining
the presence of a locked-in state vs. a true vegetative state.8 Similar to the GCS, each
section is scored separately and allows for a trending of LOC.

TABLE 4
Glasgow Coma Scale (GCS) for use in adult patients1
Glasgow Coma Scale (GCS)
Eye opening
Spontaneous - 4
To speech – 3
To pain - 2
No response - 1
Best motor response
Obeys - 6
Localizes – 5
Withdraws – 4
Abnormal flexion- 3
Abnormal extension - 2
No response - 1
Best verbal response
Oriented - 5
Confused conversation - 4
Inappropriate words- 3
Incomprehensible sounds - 2
No response - 1
*GCS range 3–15

3.1 Cranial Nerve Testing

Testing of the cranial nerves is focused on assessing the integrity of the afferent limb
of the brainstem reflex being tested, brainstem nuclei involved and the efferent tracts.9
Brainstem reflexes are key to the initial coma evaluation and include pupillary assessment
(size, reactivity, and symmetry), corneal reflex, response to visual threat, oculocephalic
reflex (performed only if cervical trauma or instability is not a consideration), gag and
cough reflex. Pinpoint pupils are suggestive of pontine damage, usually from hemorrhage
or ischemic infarction. Enlarged and nonreactive pupils suggest damage to the midbrain
or compression of the third cranial nerve. Pupillary changes can also be suggestive of a
drug overdose (see Table 6). Spontaneous roving eye movements suggest bilateral cortical
dysfunction and an intact brainstem. Dysconjugate resting gaze may occur with structural
or metabolic processes or extraocular movement impairment from cranial 3rd, 4th, or 6th
nerve palsies. Psychoactive and anti-seizure drugs have been associated with depressed
vestibulo-ocular responses. Jerky, nystagmoid movements may indicate non-convulsive
status epilepticus or brainstem or cerebellar ischemia. Fundoscopy may reveal retinal
hemorrhages or papilledema if there has been prolonged increased ICP; more acutely,
high ICP may manifest as optic disc blurring or lack of spontaneous venous pulsations in
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TABLE 5
Pediatric Glasgow Coma Scale (PGCS)1 Adapted with permission Pediatric Glasgow
Coma Scale PGCS

Pediatric Glasgow Coma Scale PGCS

>1 year <1 year Score
Eye opening Spontaneously Spontaneously 4
To verbal To shout 3
command
To pain To pain 2
No response No response 1
Motor Obeys Spontaneous 6
response
Localizes pain Withdraw to 5
touch
Flexion- Flexion- 4
Withdrawl Withdrawl
Flexion-abnormal Flexion-abnormal 3
(decorticate (decorticate
rigidity) rigidity)
Extension Extension 2
(decerebrate (decerebrate
rigidity) rigidity)
No response No response 1
>5 years 2-5 years 0-23 months
Verbal Oriented Appropriate Smiles/coos 5
Response words/phrases appropriately
Disoriented Inappropriate Cries and is 4
/confused words consolable
Inappropriate Persistent cries Persistent 3
words and screams inappropriate
crying and/or
screaming
Incomprehensible Grunts Grunts, agitated 2
sounds and restless
No response No response No response 1
Total Pediatric Glasgow Coma Score (3-15)
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FIGURE 2: Four Score

the optic disc. A thorough brainstem exam can uncover early signs of basilar stroke and
allow early therapies capable of minimizing long term disability. Brain stem reflexes may
be absent in hypothermic patients, up to a few hours after cardiac arrest, or in patients
who have received neuromuscular paralysis.
Motor function is assessed by observing spontaneous movements, responses to verbal
command or noxious stimulation or for posturing. Symmetric posturing, either exten-
sor (“decerebrate”) or flexor (“decorticate”), may occur in either structural or metabolic
coma. Generalized or symmetric findings raise the possibility of a toxic or metabolic
process that involves brainstem or thalamic and brainstem arousal centers. Muscle tone
of the extremities may be assessed by passive movement of the limbs, mainly elbow and
knee flexion. The examiner should distinguish purposeful movements from reflex activity.
Examples of purposeful activity include following commands: axial (sticking out tongue)
or acral (showing two fingers or thumbs up), pushing the examiner away, reaching for
the endotracheal tube, or localizing to noxious stimulation. Examples of reflexive activ-
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TABLE 6
Pupillary changes reflecting underlying etiology1
Pupillary change Possible etiologies/localization
Pinpoint pupil Opioids
Cholinergic intoxication
Pontine damage (interrupts descending
sympathetic pathways)
Dilated, non-reactive pupils Cerebral anoxia, global
Barbiturates
Atropine
Hypothermia
Brain death
Dilated, reactive pupils Pretectal lesions
Stimulants (cocaine, methamphetamine),
hallucinogens including PCP/LSD

Anisocoria (pupillary asymmetry) 3rd nerve compression from uncal herniation

Localized drug effect (e.g., ipratropium,
tropicamide)
Mid-position, fixed or irregular Midbrain lesion

ity include withdrawal, flexion or extensor posturing to noxious stimulation. Ability to

grasp should not be considered following commands without the ability to reproducibly
let go on command, as this too can be a reflex rather than a conscious movement. Deep
tendon reflexes should be performed with particular attention to briskness and symmetry
of findings.
Observed breathing patterns may also have localizing value in the evaluation of coma.
Lesions of the pons or midbrain can result in neurogenic hyperventilation. Central hy-
perventilation may also be a sign of underlying acidosis and compensatory respiratory
alkalosis. Cluster (Biot’s) breathing may be seen resulting from a pontine lesion. Ataxic
or absence of spontaneous breathing (apnea) may be seen in medullary injury (Chart 1).1

4 Focused Presenting and Past Medical History

Historical information elicited from witnesses, friends, family, co-workers, or EMS per-
sonnel may suggest the cause of coma. EMS personnel may have valuable details about
the circumstances in which the patient was found. The time course of the alteration of
consciousness may be helpful in suggesting an etiology. An abrupt or acute onset of
symptoms suggests a stroke, seizure, or a cardiac event with impaired cerebral perfusion.
A more subacute onset of encephalopathy evolving into coma could suggest a metabolic
or possibly infectious process. Past medical, surgical, or psychiatric history; alcohol or
illicit drug use history; and any environmental toxic exposures should be included in the
information gathering. Medication history is paramount in identifying a possibility of
overdose and may also provide valuable clues to the medical history in the absence of
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CHART 1: Respiratory patterns reflecting underlying etiology 1

other sources.10 The electronic medical record may provide rapid access to the patient’s
past medical history if the patient can be reliably identified.11

5 Recommended Labs
Unless a readily reversible cause of unresponsiveness, such as hypoglycemia, has been
discovered and corrected, additional laboratory testing should be obtained. Serum
chemistries, a basic hematological panel, and blood gas analysis should be considered.
Point of care (POC) testing should be utilized where available. Co-oximetry may be
beneficial in selected patients suspected of carbon monoxide poisoning. Toxicology
testing such as ethanol level and urine toxicology screen should be obtained, though vari-
ability and availability of exhaustive toxicology screens is limited in emergent settings.
Microbiologic studies, including cultures of blood and urine, are helpful in many cases.

6 Initial Formulation: Structural, Non-Structural, or

Unclear Causes of Coma
Information obtained during initial stabilization, physical assessment, neurological as-
sessment, focused history, and stat laboratory results will typically help in classifying
patients into likely structural or non-structural causes of coma and direct further investi-
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gations and emergent therapies. This is a critical early distinction since structural coma
may require emergent medical or surgical intervention and/or advanced neuromonitoring
(see Tables 7, 8, 9). If there is concern for a structural etiology of coma, or if the cause
of coma cannot be identified after initial assessment, brain imaging should be obtained
immediately.

TABLE 7
Primary neurological etiologies of coma

Primary neurological etiologies of coma

Cause Exam/History findings
Trauma
Subdural hematoma focal weakness, seizure, altered level of consciousness,
aphasia
Epidural hematoma Lucid period with rapid decline
Parenchymal Focal neurological findings
hemorrhage
Diffuse axonal injury Nonfocal exam, dense coma
Neurovascular
Intracerebral Focal neurological findings; Coma if bithalamic (Artery
hemorrhage of Percheron) or brainstem
Subarachnoid Coma with/without focal findings,
hemorrhage
Ischemic stroke Focal findings consistent with vascular distribution
CNS infections
Meningitis Coma or stupor, meningismus, seizures
Encephalitis Coma or stupor, seizures
Abscess Focal neurological deficits, exposure history, seizures
Neuroinflammatory disorders
Acute disseminated History of preceding illness, headache, fever, N/V, acute
encephalomyelitis coma, focal motor deficits, brainstem findings
Autoimmune Subacute progression, seizures, psychiatric symptoms
encephalitis
Neoplasms
Metastatic History of primary cancer, focal findings, slow
progressive symptoms
Primary CNS Focal neurological deficits, neuropsychiatric symptoms,
seizures, ocular symptoms
Carcinomatous HA, meningismus, encephalitis/stupor, seizures, cranial
meningitis neuropathies, cerebellar symptoms
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TABLE 8
Primary neurological etiologies of coma (cont’d)

Primary neurological etiologies of coma

Cause Exam/History findings
Seizures
Non-convulsive Epilepsy/recent seizure, unexplained coma
seizures or status
epilepticus
Postictal state Recent seizure, focal neurological deficits (Todd's
paralysis), EEG without ongoing seizure
Other
Reversible posterior Severe hypertension, history of immunosuppressant use.
leukoencephalopathy Pregnancy
syndrome
Osmotic History of polydipsia, excessive alcohol use or prior low
demyelination sodium levels
syndrome
Anoxic-ischemic History of cardiac arrest or asphyxiation
encephalopathy
Hydrocephalus History of ventriculoperitoneal shunt, cerebral
hemorrhage, stroke, SAH, meningoencephalitis,
congenital infections, intracranial mass
 TABLE 9
Metabolic/toxic & environmental etiologies of coma
Metabolic Exam/History findings Tests to consider
encephalopathies
Hypoglycemia Coma, seizures, evidence of adrenal insuffi- Glucose, proinsulin
ciency
Hypoxia, hypercapnia Respiratory distress, tachypnea Arterial or venous blood gas, pulse oximetry
Diabetic ketoacidosis; hyperosmo- coma, seizures, focal neurological findings glucose, osmolar gap, ketones, basic metabolic panel,
lar non-ketotic hyperglycemia ABG. Remember to correct sodium level for hyper-
glycemia
Hepatic encephalopathy Jaundice, hyperreflexia, rigidity, myoclonus, Ammonia, hepatic function panel, coagulation panel
bradykinesia, asterixis
Uremia Prior lethargy, disorientation, hallucinations; Basic metabolic panel, renal ultrasound
diffuse weakness, tremor, myoclonus, asterixis
Hyponatremia Moderate Symptoms: Nausea, Headache, Con- Basic metabolic panel, serum & urine osmolarity, serum
fusion & urine sodium level
Severe Symptoms: Vomiting, Seizures, Coma,
Cerebral edema on imaging
Hypernatremia Clinical signs of dehydration, subdural hygro- Basic metabolic panel; Urine osmolarity (if diabetes in-
mas or pituitary on CT, history of diabetes In- sipidus is suspected)
sipidus, history of lithium use
Myxedema coma Hypothermia, hypotension Thyroid function panel
Thyrotoxicosis Tachycardia, hypertension, cardiac arrhythmias Thyroid function panel
Adrenal failure Hypotension, hypothermia Cortisol
Hypercalcemia Calcium
Continued on next page

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 Table 9 continued
Wernicke’s disease
Sepsis
Drug/medication overdose
Abuse (opioids, alcohol, am-
phetamines, cocaine)
Methanol, ethylene glycol,
Sedative-hypnotics
Benzodiazepines, Non-
benzodiazepine hypnotics, muscle
relaxants and barbiturates
Confusion, ataxia, ophthalmoparesis, history of
vomiting and malnutrition, hyperemesis gravi-
darum, malabsorption or short gut.
Fever, cold clammy extremities
Pupillary changes, HR changes, stigmata of cir-
rhosis suggesting ETOH, injection markings on
skin, respiratory failure
Obtaining a history of quantity and time of in-
gestion is critical. Coma, seizures, hyperp-
nea, hypotension, afferent pupillary defect for
methanol, tetany, cranial nerve palsies. Examine
patient’s clothes, mouth, vomitus, or urine for
fluorescence due to fluorescein content in com-
mercial antifreeze preparations.
Bradycardia, respiratory depression, Cariso-
prodol can produce anticholinergic side effects,
Baclofen overdose can cause seizures.
Thiamine level (history and clinical exam more impor-
tant than lab testing)
Complete blood count, blood, urine and and/or respira-
tory cultures and serum lactate
Toxicology screen
Consider Quantitative pupilometry in nonreactive pupils
Toxicology screen, measure anion gap, osmolar gap;
send Toxic Alcohol panel for serum methanol & ethylene
glycol levels; basic metabolic panel, Urine microscopy
for oxalic acid crystals and EKG
Toxicology screen, EKG
Continued on next page
14
 Table 9 continued
Narcotics
Opium, Heroin, Codeine, Oxy-
codone, Hydrocodone, Tramadol,
Morphine, Hydromorphone, Fen-
tanyl, Carfentanyl
Aspirin
Acetaminophen
Serotonergic medications: i.e.,
SSRI, SNRI, MAO inhibitors, fen-
tanyl
Tricyclic antidepressants
Antipsychotics
Anticonvulsants
Constricted or pinpoint pupils, decreased respi-
ratory rate, Tramadol overdose can present with
Seizures and Serotonin syndrome
Tinnitus, vertigo, nausea/vomiting/diarrhea, hy-
perpyrexia, noncardiac pulmonary edema, Cere-
bral edema is a rare complication of salicylate
toxicity
Acute liver failure -Nausea/vomiting, diaphore-
sis, pallor, oliguria, hepatomegaly, jaundice, en-
cephalopathy, asterixis, coma
Agitated delirium, seizure, diaphoresis, mydria-
sis hyperthermia, ocular clonus, hypertonia, hy-
perreflexia, tremor, ankle clonus, seizures, rigid-
ity. Hunter criteria for diagnosis.
Refractory hypotension, arrhythmias, dilated
pupils, dry warm skin and mouth, constipation,
hyperthermia, seizures, prolonged QRS
Variable: mild hypotension, pupils variable,
tachycardia, hyperthermia, extrapyramidal side
effects, acute dystonia, akathisia, anticholinergic
toxicity, ventricular arrhythmias
Variable depending on drug used
Toxicology screen; Fentanyl analogues such as carfen-
tanyl may not be detected on standard urine drug screens
Arterial blood gas, toxicology screen, serum ac-
etaminophen level, consider head CT
Acetaminophen level, hepatic function panel, coagula-
tion panel, basic metabolic panel and plasma ammonia
level
Toxicology screen, creatine kinase, basic metabolic
panel, calcium, magnesium, and phosphate; coagulation
panel and serum lactate
Electrocardiogram, urine/serum tricyclic antidepressant
screen if diagnosis is uncertain, arterial blood gas
Electrocardiogram, toxicology screen, basic metabolic
panel, magnesium, calcium
Drug levels, toxicology screen, electrocardiogram
Continued on next page
15
 Table 9 continued
Environmental causes
Heat stroke Hyperthermia, tachycardia, tachypnea, widened Complete blood count, basic metabolic panel, electrocar-
pulse pressure, hypotension. diogram, creatinine kinase, liver function panel
May develop rhabdomyolysis and acute liver
failure due to shock liver
Hypothermia Hypoventilation, hyporeflexia, pulmonary Complete blood count, basic metabolic panel, electrocar-
edema, hypotension, bradycardia, arrhythmia, diogram
oliguria if severe
Carbon monoxide Variable: seizures, syncope, coma, arrhythmia, Complete blood count, co-oximetry, electrocardiogram,
pulmonary edema, lactic acidosis basic metabolic panel, chest x-ray

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7 Brain Imaging
Non-contrast cranial computed tomography (CT) imaging should be obtained emergently
in unconscious patients with a presumed structural cause of coma and in patients with an
unclear cause of coma after initial assessment of the ABCs and stabilization of the cer-
vical spine. Head CT identifies structural etiologies of coma such as cerebral infarction,
intracranial hemorrhage, brain masses, cerebral edema, and acute hydrocephalus. Case
Vignette 1 illustrates the rapidity with which hydrocephalus can lead to coma, as well as
the need for emergent and life-saving management. Rapid sequence magnetic resonance
imaging (MRI) may be helpful if brainstem involvement is suspected.12
If acute ischemic stroke is suspected, CT angiography and CT perfusion can provide
valuable information on vascular patency and regional perfusion. Non-contrast head CT
imaging in the hyperacute phase of ischemic stroke is often normal, this can be another
reason to consider rapid sequence MRI if the patient can be cleared from metal risks
swiftly. In this setting, the clinical diagnosis of stroke rests on a reliable history and focal
findings on exam. Ischemic stroke does not typically cause coma acutely unless ischemia
involves the arousal systems located in the pontomesencephalic tegmentum (e.g., basilar
artery thrombosis). While infrequent, large bilateral acute hemispheric strokes or bilat-
eral medial thalamic strokes (e.g., artery of Percheron infarct) have also been described
to cause coma. Sub-acutely, coma may develop due to progression of a hemispheric in-
farct with transtentorial herniation or non-communicating hydrocephalus. If there is any
suspicion for basilar artery thrombosis, a CTA should be obtained emergently. When a
central nervous system (CNS) infection is being considered, cranial CT or MRI with and
without contrast should be ordered to evaluate for abscess, extra-axial fluid collections,
hydrocephalus, hemorrhagic changes, and infarctions prior to lumbar puncture and cere-
brospinal fluid analysis.

8 Causes of Coma
8.1 Non-Structural Causes of Coma
Common non-structural causes of coma include anoxic-ischemic encephalopathy,
seizures, metabolic alterations, endocrinopathies, systemic infections, CNS infections,
overdose of medications or toxic substances, illicit drug and alcohol use, and exposure
to toxins (Table 8B). Treatment is guided by the underlying etiology. Where appro-
priate, specific antagonists or antidotes should be administered. The opioid toxidrome
should prompt administration of naloxone as discussed above. In some cases, a primary
metabolic encephalopathy may evolve toward a structural process, such as hyperam-
monemia leading to cerebral edema and herniation (figure 3). In this setting, treatment
should focus on management of cerebral edema while simultaneously investigating the
primary cause of hyperammonemia (Table 10). Severe hyponatremia in the setting of
coma requires immediate treatment, but rapid correction of chronically low sodium
can lead to osmotic demyelination syndrome, as illustrated in Case Vignette 2.13−15
Recommended management of severe hyponatremia is listed in Table 11.15−17 While
 18

some metabolic derangements may be immediately apparent, others will require a high
index of suspicion for diagnosis. Wernicke’s Encephalopathy is such a diagnosis, as
thiamine should be replenished in these patients prior to serum thiamine levels resulting.
High dose IV thiamine is required to halt and reverse Wernicke’s Encephalopathy and
diagnosis is dependent on clinical exam with classic findings of ophthalmoplegia, ataxia
and encephalopathy, although many patients will lack the complete triad. Patients with
coma and risk factors for malnutrition should be treated empirically for Wernicke’s
encephalopathy (see Table 12). A Cochrane review found evidence for optimum dose
lacking, however multiple studies favor a minimum dose of 500mg IV three times a day
for 2-3 days followed by 250mg IV or IM for 3-5 days if there are signs of improvement
with empiric therapy. Magnesium should be aggressively repleted as it is a cofactor
in thiamine uptake. High risk patients should be treated with prophylactic doses of 100-
250mg daily.18

FIGURE 3: MRI findings of severe hyperammonemia

Diffuse gyriformrestricted diffusion (DWI & ADC) and with gyral swelling and sulcalef-
facement (FLAIR). Areas involved include bilateral insular cortex, cingulategyri, frontal,
parietal, and temporal lobes with relative sparing of theoccipital poles.

Meningoencephalitis may present with new onset seizures and collateral history may
support preceding symptoms of sepsis coupled with signs and symptoms of meningis-
mus. Suspicion for meningoencephalitis should prompt early initiation of CNS dosing of
antimicrobials, including acyclovir for suspected cases with herpes simplex virus (HSV)
infection, and should not be delayed for a lumbar puncture or other diagnostic studies.
Steroid administration is recommended prior to or concomitant with the first dose of
antimicrobial medications. Autoimmune encephalitis may be suspected in a more sub-
acute presentation which is often preceded by a myriad of psychiatric, motor symptoms
or behavior changes prior to a more acute change in mental status. Patients suspected to
have acute meningoencephalitis may also have ongoing seizures with the possibility of
nonconvulsive seizures and status epilepticus and should be treated empirically for both
etiologies when suspicion is high. Patients who are immunosuppressed, neonates, elderly,
alcoholic patients, or pregnant women should also be covered for Listeria meningitis with
ampicillin.
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TABLE 10
Causes of Hyperammonemia1
Mechanism Causes
Acute Liver Failure – Acute Viral Hepatitis
Hepatocellular Toxin/drug induced–acetaminophen, amanita,
Injury with Multiorgan failure toluene, weight loss medications
Idiopathic
Inherited disorder
Fatty Liver of Pregnancy
Heat Stroke
Sickle Cell Hepatopathy
Chronic Liver Failure or Precipitants
Acute-on-chronic Liver Fail- • Infection
ure – Nodular sclerosis of the • Acute renal failure
liver or macro-steatosis of the • Variceal bleed
liver with evidence of portal • Constipation
hypertension • Opioid use
• Catabolic state
• Cachexia
• Large portosystemic shunt
Portosystemic shunting TIPS
Large spontaneous portosystemic shunt
Hereditary hemorrhagic Telangiectasia
Malnutrition or Micronutrient Gastric bypass surgery
deficiency Short gut syndrome
Deficiency in Carnitine, Biotin, zinc
Idiopathic Fatal Hyperam- Post Lung Transplant Hyperammonemia
monemia
Inborn Errors of Metabolism Urea Cycle Disorders
(see table 13) Other metabolic diseases including organic acidemia
Infection Urease Splitting Organism
• Proteus
• Pseudomonas
• Klebsiella
Toxicology - Mitochondrial Rye syndrome
and Urea Cycle toxins Valproic Acid Toxicity
Ackee Fruit Poisoning
Cyclophosphamide
Malignancy End stage multiple myeloma or post bone marrow
transplant - mechanism unclear
 20

TABLE 11
Management of Severe Hyponatremia17
Presentatio Management
Acute or symptomatic hyponatremia
Severe Symptoms: Seizure, coma 3% NaCl (100-150cc bolus; peds 1-2
mL/kg) over 20mins may be repeated X3
as needed until resolution of severe symp-
toms.
Moderate Symptoms: Headache, Nausea, 3% NaCl (150cc bolus; 1 mL/kg) over
or confusion 20mins once
Goal rate of sodium correction 4-8mmol/L per day
If high risk for ODS: 4-6mmol/L per day
Chronic Hyponatremia
SIADH Fluid restriction (first line)
Oral Urea or Demeclocycline or Loop di-
uretics+ oral Sodium (second line)
Hypovolemic Hyponatremia Isotonic Crystalloid solution
Anticipate rapid autocorrection of sodium
once ADH suppressed by volume expan-
sion. This can be controlled with D5W
10mL/kg infusion +/- Desmopressin 2µg
IV
Hypervolemic hyponatremia Fluid restriction
Goal rate of sodium correction 4-8mmol/L per day
If high risk for ODS: 4-6mmol/L per day
Management of overcorrection (if ex- Start D5W 10mL/kg infusion +/- Desmo-
ceeds 4-8mmol/L per day) pressin 2µg every hour IV until goal
sodium achieved

TABLE 12
Risk factors accompanying severe or selective malnutrition that are associated with
Wernicke’s Encephalopathy21
Risk factors
Chronic Alcohol abuse
Pregnancy and Hyperemesis Gravidarum
Malnutrition; malabsorption, short gut syndrome; anorexia; staple diet of polished
rice; Cachexia; AIDS
Gastric bypass surgery, gastrectomy, short gut syndrome
Cancer and chemotherapeutics
Latrogenic malnutrition. i.e., prolonged withholding of nutrition, re-feeding
syndrome, hypomagnesemia, unbalanced intravenous hyperalimentation,
Inflammation of GI tract i.e., Crohn’s, Gastritis, peptic ulcer, pancreatitis, chronic
diarrhea
Dialytic therapies, Chronic diuretic therapy
Drug: High dose IV nitroglycerin; Tolazamide; Metronidazole
 21

8.2 Structural Causes of Coma

Structural causes of coma are important to recognize early since ongoing acute brain in-
jury may occur through elevated intracranial pressure in the presence of space occupying
lesions including hemorrhage or hydrocephalus; management of these patients should be
focused on temporizing the elevated intracranial pressure. For patients suspected to have
high ICP, head positioning, mild hyperventilation, and administration of osmotic ther-
apy (mannitol or hypertonic saline) should be rapidly initiated and evaluation for external
ventricular drainage should be accomplished early, concurrently with evaluation for more
definitive treatment if applicable (see Table 3). Cerebellar infarcts or hemorrhage may
cause unresponsiveness resulting from brainstem compression or 4th ventricular com-
pression causing obstructive hydrocephalus. A history of headache, nausea, and vomiting
with focal motor or brainstem findings may suggest the diagnosis. A non-contrast head
CT is diagnostic. Early surgical intervention can prevent irreversible brainstem damage
and herniation in these patients.
The symmetry or focal nature of neurological findings is a critical differentiating char-
acteristic in coma assessment. Asymmetric or focal findings on physical examination sug-
gests a localized brain lesion or disturbance. Unconscious patients with a unilateral dilated
unreactive pupil, asymmetric eye movements, or asymmetric motor responses should be
rapidly evaluated with cranial CT to identify a potential herniation syndrome, stroke, or
intracranial hemorrhage. Thrombosis of the basilar artery may produce a state of sudden
unresponsiveness.19 The non-contrast CT may show a hyperdense basilar artery. Emer-
gent CT angiography should be considered in any patient with an exam concerning for
focal brainstem findings or suspected vertebrobasilar ischemia. A high degree of suspi-
cion is necessary to appropriately diagnose basilar artery thrombosis in a timely fashion.
Hyperintensity on brain MRI that spares the cortex and is predominantly posterior
should raise the suspicion of posterior reversible encephalopathy syndrome (PRES).
PRES is a clinical syndrome comprised most of acute neurological symptoms and
symmetrical posterior-predominant vasogenic edema in the setting of associated risk
factors, including arterial hypertension, renal disease, autoimmune and hematological
diseases, pregnancy, immunosuppression, history of solid organ or bone marrow trans-
plant, systemic inflammation and use of cocaine or amphetamines.20,21 CASE Vignette 3
illustrates a typical presentation and imaging findings.20−23
Focal weakness or coma may also be a manifestation of nonconvulsive seizure activ-
ity or resulting Todd’s paralysis, which should be evaluated with electroencephalography
(EEG). Non-convulsive seizures or status epilepticus should be suspected in patients with
a history of epilepsy if a seizure was observed during the clinical course followed by pro-
longed unresponsiveness. There may be subtle involuntary movements in the absence of
tonic-clonic activity, such as an eyelid twitch or fine tremors of face, hands, or shoulders.
EEG is required for definitive diagnosis. However, caution should be used in tethering a
diagnosis to these subtle convulsive seizures. Spontaneous posturing, nystagmus, or sub-
tle involuntary movements in the hands and around mouth may also be signs of basilar
ischemia and can be hard to differentiate from subtle convulsive seizures clinically with-
out a CT angiogram. When uncertainty exists as to the cause of involuntary movements,
 22

patients should be treated with anticonvulsant drugs while concurrently ruling out basilar
ischemia with a CT angiogram.24

9 Persisting Uncertainty
If diagnostic uncertainty persists after the initial evaluation and non-contrast CT scan
and CT angiogram, a lumbar puncture and EEG may be indicated. Major indications for
lumbar puncture include suspicion of CNS infection, neuroinflammatory and autoimmune
disorders, and suspected central nervous system involvement of hematological or solid
organ cancers. An MRI may be necessary if there is a presumption of hyperacute ischemic
stroke or when the cause of coma is not explained by other tests.

10 Patient Transport
Transfer of coma patients is sometimes necessary depending on the etiology of the under-
lying coma and availability of evaluation and management modalities at each institution.
For patients with suspected mass lesions or increased intracranial pressure, close attention
and clear communication on head positioning, management of invasive devices (specifi-
cally external ventricular drainage parameters), blood pressure goals and ventilator man-
agement including hyperventilation are critical during transport. Information should be
transmitted to the transport team about any infectious risks or if there is clinical concern
for seizures with appropriate therapies available en-route should a patient decompensate
or have a clinical seizure. Evolution of clinical exam and focal findings if found should
be clearly communicated.

11 Pediatric Considerations
The algorithm for evaluation and initial management of pediatric coma is like adults and
must begin with an assessment of the child’s ABCs. In children less than 5 years of age,
level of consciousness is graded with a modified version of the GCS (see Table 5) which
deemphasizes language comprehension in the verbal and motor subscores25 or the FOUR
Score Coma Scale.26 Early recognition of the potential for catastrophic deterioration is
essential.27 Traumatic brain injury and infection are the leading causes of coma in the
pediatric population. Other common causes are hypoglycemia, hypothermia, acid-base
and electrolyte imbalances, seizures, diabetes, and intoxications9,28, both accidental in-
gestions and those secondary to inborn errors of metabolism (IEM).29,30 Neuroimaging
should be obtained promptly in the presence of focal neurological deficits or if the eti-
ology of coma is not rapidly determined. Though helpful, a normal head CT does not
exclude the possibility of intracranial hypertension; this is true in adults as well. Diffuse
brain swelling, raised intracranial pressure, and cerebral herniation are greater risks in
children with moderate and severe brain injury. Septic shock is a common presentation of
meningitis in children28, but IEM can also present with a septic shock-like appearance.
Symptoms that persist or are not explained after the initial treatment and stabilization may
 23

be due to an IEM, and that symptoms should not be mistaken for etiology. As IEMs may
initially become symptomatic in the setting of other more common metabolic stressors, it
is important to consider and attempt early diagnosis potentially treatable IEMs that may
be the causing or contributing to the child’s depressed neurological status.29,30 Table 13
lists examples of treatable IEMs, although this list is in no way exhaustive, and consul-
tation of pediatric neurology should be utilized in suspected cases. The main clinical
signs are variable and may involve lethargy, coma, hiccups, hypothermia, decreased tone
and movement abnormalities. Total prevalence of IEM is estimated at 50-60/100,000 live
births globally with regional variation.31,32 Any child presenting with a suspected IEM
should have the following lab work-up: complete blood count, liver function tests, chem-
istry panel, ammonia, blood gas (anion gap calculated), glucose, lactate, and urine and
blood ketones.33
TABLE 13
Examples of Treatable Inborn Errors of Metabolism causing Metabolic Coma

Disease (example) Global Laboratory Findings History/Exam

Prevalence
(per 100,000
LB)
Amino Acidurias 14.69 Metabolic acidosis, May have odor
(Maple Syrup Urine Ketosis, hypoglycemia; Many tested on
Disease) serum amino acid profile newborn screens
diagnostic
Organic acidurias 8.71 Metabolic acidosis, May have odor
(Methylmalonic ketosis, hyperammonemia, Many detected on
Aciduria) high anion gap; urine newborn screen
organic ester testing
diagnostic
Fatty Acid Disorders 6.51 Low ketones, Cardiomyopathy/
(MCAD) hypoglycemia, +/- cardiomegaly
hyperammonemia,
respiratory alkalosis;
plasma acylcarnitine
profiles provide keys for
diagnosis/management
Mitochondrial 8.16 Hyperlactatemia, normal +/-hepatomegaly;
Disorders (PDH) glucose, -ketones elevated lactate
Carbohydrate 6.19 Metabolic acidosis, Hepatomegaly; some
Metabolism hypoglycemia, with dysmorphic
Disorders hyperlactatemia features
(Galactosemia)
Urea Cycle Disorders 2.91 Hyperammonemia, normal +/- hepatomegaly;
(Ornithine glucose, - ketones, normal stroke-like events
transcarbamylase bilirubin, slight
deficiency) transaminitis
 24

12 Special Considerations in the Pregnant Patient

Pregnant women are susceptible to the same causes of coma as the general population,
with some additional unique risks, such as amniotic fluid embolus, eclampsia, Sheehan’s
syndrome and postpartum cerebral angiopathy.34 Pregnant women are also susceptible to
other causes of coma like the general population, such as stroke35, but pregnancy compli-
cates standard management decisions, such as radiation risk from imaging, timing of de-
livery, and risk vary based on gestational age of the fetus. Obstetric and neonatal involve-
ment is recommended as early as possible for these patients. Wernicke’s encephalopa-
thy can also occur in the setting of hyperemesis gravidarum. Case Vignette 4 demon-
strates classic presentation and representative imaging findings for such a patient.18,36,37
Eclampsia & HELLP syndrome require aggressive symptomatic treatment, but definitive
treatment requires emergent delivery.38 Table 14 lists special considerations for coma in
the pregnant patient with possible treatments, however standard of care may vary based
on individual circumstances.34
 TABLE 14
Special considerations for coma in the pregnant
Disease Clinical findings/Pathophysiology patient Treatment pearls

Cerebral venous Hemorrhage, cerebral edema on CTH Anticoagulation

thrombosis CTV or MRV showing flow voids in sinuses
Postpartum cerebral Reversible narrowing of large and medium cerebral arteries; ICH, May include steroids, blood pressure reduction,
angiopathy strokes on imaging; posterior watershed leukoencephalopathy, HTN, magnesium
visual complaints
Amniotic fluid em- Hemodynamic collapse, signs of DIC, cerebral hypoperfu- Hemodynamic stabilization & respiratory sup-
bolism sion/thrombosis/hemorrhage, multifocal neurological signs, coma port PRN
Accounts for 30% of maternal deaths Management of hemorrhage and coagulopathy
PRN
Delivery of fetus often necessary
Aneursymal subarach- Headache, focal deficits, seizures, coma Standard of care for aSAH
noid hemorrhage Most commonly occurs in 3rd trimester Delivery of fetus depending on gestational age
and risks
Choriocarcinoma Metastatic disease can cause SAH, ICH or SDH; trophoblastic tissue Management depends on stage and disease bur-
invades blood vessels and can cause aneurysmal dilatation den
Seen in 1 in 50,000 pregnancies
Continued on next page

25
 Table 14 continued
Preeclampsia- Seizures or coma with some indications of pregnancy-induced hyper- Magnesium sulfate IV bolus and drip
Eclampsia tension and/or proteinuria Aggressive treatment of BP
Can occur postpartum Transfusions PRN
Delivery if safe
Many patients will not have all cardinal features
& seizures may appear without proteinuria or
HTN
HELLP Syndrome RUQ pain, nausea/vomiting, malaise Magnesium bolus and drip
Can lead to ICH from coagulopathy Aggressive treatment of BP
Elevated LFTs with hemolytic anemia and hemolysis Transfusions PRN
Wernicke’s Triad of ophthalmoplegia, ataxia and encephalopathy Requires high dose IV thiamine repletion
encephalopathy Seen in hyperemesis gravidarum
Sheehan syndrome Severe HA, meningismus, vomiting, acute shock, coma Requires immediate high dose steroids IV fol-
Also, ophthalmoplegia, ptosis, pupil changes, 3rd nerve palsy lowed by thyroid hormone repletion
Anterior pituitary infarction, hemorrhage or necrosis seen classically Consult endocrinology
after hypovolemia from maternal hemorrhage Give cortisol before thyroid replacement

26
 27

13 Nursing Considerations
Nursing assessment of the comatose patient should include serial assessments, like the
medical assessments listed above (GCS or FOUR; vital signs; and physical assessment,
paying special attention to motor movements, respiratory rate and rhythm, and the
pupils).4 These assessments, laboratory results, and imaging may provide clues to the
diagnosis of coma in the patient. The nurse is with the patient continuously, allowing for
identification of subtle changes that may be meaningful for the patient care team, and any
changes should be reported swiftly. Subtle movements may be the only diagnostic clue to
basilar ischemia, locked-in syndrome, or non-convulsive seizures. Physical assessment
may identify neurological changes prior to a change on an electronic monitor; changes
to vital signs and hemodynamic parameters may be delayed in patients with neurological
decline.
As with any complex assessment, serial exams should be done in a consistent method,
allowing for reproducibility across all nurses. Nurses should work with physician and
entity leadership to identify best practices for time and type of neurological assessment
that address patient care needs. Hand-off between departments/shifts should include the
evidenced-based method of performing a neurological assessment with both nurse care-
givers present. This allows for consistency of ongoing assessment, and the swift ability to
determine differences if there is a subtle change in patient’s neurological exam.39
Other areas of attention of the comatose patient include hygiene, prevention of pres-
sure ulcers/skin breakdown, and provision of nutrition needs. Nursing care should have a
holistic view of caring for the patients who cannot communicate or advocate for their own
needs. Education and identification of social support for the family or loved ones visiting
the comatose patient for the first time or the need for pastoral care falls in the realm of the
primary nurse4.

14 Communication Checklist
When communicating the transfer of care of a comatose patient to an accepting physician
or advanced practice provider, consider including the key elements listed in Table 15.

15 Case Vignette
15.1 Case Vignette 1: Pediatric Hydrocephalus
A 15-year-old male who presents with a 4-day history of left sided weakness, decreased
appetite, vomiting, and increasing somnolence. He has a history of prematurity (32-week
gestation) complicated by intraventricular hemorrhage causing secondary hydrocephalus
s/p ventriculoperitoneal shunt (VPS) placement, cerebral palsy, and epilepsy. Parents have
noted right sided weakness and post-ictal sleepiness after seizures in the past, but this time
he seems to be progressively sleepier and unsteady on his feet. This morning when they
went to wake him, he would not arouse.
 28

TABLE 15
Coma communication regarding assessment and referral
Physician & Advanced Provider Communication
• Clinical presentation
• Relevant past medical history/surgical history
• Findings on neurological exam including details on GCS components and any
abnormality with brainstem reflexes, if found
• Relevant labs including glucose, blood gas, renal and hepatic function
• Brain imaging, LP, or EEG results (if available)
• Treatments administered so far
Sample Signoff Narrative
"64-year-old male patient was found unresponsive at home with agonal respirations.
He was intubated on scene without sedatives, paralytics. Received no medications or
infusions hypertensive in 190s SBP with no spontaneous respirations on ventilator on
controlled mechanical ventilation at 100% FiO2 with tidal volume of 350ml and
PEEP 8 saturating 95%, PaCO2 on blood gas was 38mmHg; 5.06kPa (goal PCO2
35-40 mmHg; 4.6-5.3kPA), absent brainstem reflexes or motor response to pain but
pinpoint pupils. GCS 3. Toxicology screen showed cocaine. Neurological consults or
neuroimaging CT-angiogram are not available here; hence being transferred."

Clinical Pearls
• Key findings on neurological exam of comatose patients can identify changes to
suggest toxic syndromes that can lead to rapid treatment of coma
• Suspect basilar thrombosis in comatose patients with degree of coma out of
proportion to imaging findings or metabolic derangements/intoxication; early
identification and revascularization is key to improve outcomes
• Elevated intracranial pressure (ICP) can be seen in a variety of processes and cannot
be excluded by imaging alone

Emergent head CT demonstrates marked dilation of the ventricles with mild trans-
ependymal interstitial edema and effacement of the cerebral sulci on the left more so than
the right (Figure 4A). Shunt series was performed showing a 6 cm discontinuity in the
catheter within the patient’s neck (Figure 4B). Patient came back from the scanner to the
ED with systolic blood pressures in the 130s and heart rates in the 30s. He was taken to
surgery emergently for EVD placement and proximal shunt catheter removal.
Comments: This case illustrates the importance of prompt diagnosis and treatment
in pediatric hydrocephalus, the most common disease treated by pediatric neurosurgeons.
Assessment of coma in patients with history of VPS should always include a shunt-series
x-ray to assess the integrity of the shunt. Emergent treatment of hydrocephalus regardless
of the cause is lifesaving and should be done even in patients with poor exam at the time
of presentation, as reversal of hydrocephalus often leads to rapid improvement in clinical
exam.
 29

FIGURE 4
Imaging: Head CT reveals marked dilation of the entire ventricular system and sulcal
effacement on the left greater than the right. Figure B demonstrates a 6 cm discontinuity
in the patient’s shunt catheter (denoted by the stars), providing the likely etiology for the
patient’s ventriculoperitoneal shunt malfunction.

15.2 Case Vignette 2: Severe hyponatremia & Osmotic Demyelina-

tion Syndrome16
45-year-old male with history of chronic alcohol abuse was found down by family and
minimally responsive. EMS responded and confirmed that the patient was in shock with
BP of 75/30, heart rate of 120 bpm (sinus tachycardia) and initiated a bolus of crystal-
loid. On arrival to the emergency department, the patient remained hypotensive requiring
additional isotonic crystalloid fluid boluses with simultaneous initiation of vasopressors.
BP was 80/50mmHg, HR110 beats per minute, SpO2 90% on a nonrebreather mask,
RR30 breaths per minute, Temp of 101.5 ºF (38.6ºC). Code sepsis was called whereby
blood cultures followed by rapid initiation of antibiotics. Blood glucose was in the nor-
mal range and patient was given intravenous thiamine. GCS was 8 (E2,V1,M5) without
lateralizing signs. CT head was unremarkable. Admission laboratory values (reference in-
tervals) were significant for leukocytosis 18 X103/mcL (4.0–10.0 X103/mcL), Lactic aci-
dosis [Lactate] 4.4 mmol/L (0.51–2.2 mmol/L), severe hyponatremia [Na+], 109 mmol/L
(135–145 mmol/l) and hypokalemia [K+], 2.8 mmol/L (3.5–4.5 mmol/L). Upon transfer
to the ICU with improving vasopressor requirement, serum sodium however was noted
to have corrected to [Na+], 130 mmol/L (135–145 mmol/l) over 24 hours. Hypotonic
IV fluid was initiated to lower serum sodium level as soon as this was recognized. With
weaning of sedation, he exhibited agitation, tremors with limited movement which wors-
ened over 24 hours to absent motor response with eye-opening only to pain. Stat MRI was
unremarkable. Patient remained minimally responsive aside from spontaneous eye open-
ing and generalized tremors for 4 to 5 days which triggered a repeat MRI brain revealing
 30

findings consistent with osmotic demyelination syndrome (ODS) (Figure 5).

F IGURE 5
Imaging: Fluid-attenuated inversion recovery (FLAIR)MRI has hyperintense signal
symmetrically within the thalami (arrows) andputamina (asterisk) (A). FLAIR MRI has
hyperintense signal abnormality in the pons(arrow) (B) (C).

Comments: Severe hyponatremia may manifest with severe symptoms such as vom-
iting, cardiorespiratory arrest, deep somnolence, seizures or coma. Treatment recommen-
dations are listed in Table 11. In, patients with chronic hyponatremia (hyponatremia >
48 hours), rapid sodium correction increases the risk of developing ODS. Rate of sodium
correction in chronic hyponatremia should not exceed 8mmol/L in 24 hours to mitigate
the risk of ODS. Encephalopathy is the most common presentation of ODS however other
symptoms include dysarthria, dysphagia, other bulbar symptoms, limb paresis, movement
disorders, locked-in state, and seizures. Controlling sodium correction can be a challenge
when need for volume resuscitation is imperative. These scenarios include septic, hem-
orrhagic or hypovolemic shock, resuscitation during surgery, trauma, or liver transplanta-
tion. In hypovolemic hyponatremia, rapid auto-correction of sodium should be anticipated
after initial volume expansion despite minimal additional fluid resuscitation. Patients with
the diagnosis of ODS should be provided the best supportive and rehabilitative care espe-
cially since the outcomes have noticeably improved in recent decades.
A 55-year-old woman with history of HTN, sickle cell trait, polysubstance abuse
(EtOH, cocaine, opioid) is admitted for encephalopathy with GCS 7 (E3,V2,M2), severe
hypertension BP 230/140mmHg (MAP 170mmHg), acute hypoxic respiratory failure re-
quiring intubation and acute kidney injury. Urine drug screen was positive for cocaine
and opioids. Stat CT head revealed a hypodensity bilateral in parieto-occipital lobes sus-
picious for posterior reversible encephalopathy syndrome (PRES). A spot EEG ordered
for face and hand twitching wit right gaze deviation was consistent with status epilepticus.
She was given 4 mg of IV Lorazepam, started on a propofol infusion, and loaded with in-
travenous fosphenytoin followed by IV levetiracetam. Blood pressure was lowered to a
MAP of 140 in the 1st hour followed by a gradual reduction over the next 2 days. MRI
brain was performed.
 31

15.3 Case Vignette 3: Posterior Reversible Encephalopathy Syn-

drome [CiteOu,Chen]
A 55-year-old woman with history of HTN, sickle cell trait, polysubstance abuse (EtOH,
cocaine, opioid) is admitted for encephalopathy with GCS 7 (E3,V2,M2), severe hyper-
tension BP 230/140mmHg (MAP 170mmHg), acute hypoxic respiratory failure requiring
intubation and acute kidney injury. Urine drug screen was positive for cocaine and opi-
oids. Stat CT head revealed a hypodensity bilateral in parieto-occipital lobes suspicious
for posterior reversible encephalopathy syndrome (PRES). A spot EEG ordered for face
and hand twitching wit right gaze deviation was consistent with status epilepticus. She
was given 4 mg of IV Lorazepam, started on a propofol infusion, and loaded with in-
travenous fosphenytoin followed by IV levetiracetam. Blood pressure was lowered to a
MAP of 140 in the 1st hour followed by a gradual reduction over the next 2 days. MRI
brain was performed.

F IGURE 6

Imaging: Extensive confluent and symmetric cortical and subcorti- calT2/FLAIR signal
abnormality consistent with PRES (A). Interval improvement in T2/FLAIR
signalabnormality 3 weeks later with residual signal abnormality most promi- nently
inparieto-occipital lobes (B).

Comments: Although the pathophysiology of PRES remains controversial, the neu-

rological deficits and imaging findings are usually reversible. Commonly reported acute
neurological symptoms include, headache, visual disturbances, seizures, status epilepti-
cus and coma. PRES can present atypically with restricted diffusion on MRI suggesting
ischemia, asymmetric vasogenic edema and intraparenchymal hemorrhage. Less com-
monly, cerebellar spinal cord involvement has been reported. With cerebellar involve-
ment, the patient needs to be monitored closely for compression of the 4th ventricle
with resultant hydrocephalus which would require emergent CSF diversion. Treatment
 32

includes gradual control of BP, early recognition, and control of seizures and where pos-
sible, stopping the offending agent at least until resolution of PRES and good supportive
care. In this case hypertension, acute kidney injury and cocaine use likely contributed
to development of PRES. In this case, neurologic deficits and imaging findings improved
significantly over 4 weeks with appropriate intervention.

15.4 Case Vignette 4: Hyperemesis gravidarum4

A 25-year-old woman, who was pregnant at 16 weeks of gestation, presents to the emer-
gency department with generalized confusion, weakness, unsteadiness, blurred vision.
She reported ongoing, severe emesis for 7 weeks with 10kg weight loss. She complained
of blurred vision and was noted to be lethargic with a low blood glucose of 60mg/dl and a
low magnesium level of 1.0mg/dl (1.9-2.7mg/dl). After fluid resuscitation and correction
of hypoglycemia, she became progressively more encephalopathic and was intubated for
airway protection. CTH was unremarkable but MRI brain revealed bilateral symmetric
increases in T2 and FLAIR signals in the medial thalamus, midbrain tectal plate and peri-
aqueductal region. Enhancement of mammillary bodies was visible on post-contrast T1.
On closer evaluation, ophthalmoplegia was apparent. High dose IV thiamine and reple-
tion of magnesium was initiated with resolution of ophthalmoplegia the same day and
resolution of MRI findings a week later.

FIGURE 7
Imaging: Abnormal diffusion restriction and hyperintensity of bilateral thalami and
periaqueductal grey enhancement of mamillary bodies can also be seen (not shown
here). Picture care of Dr. Anton Hasso, UCI Department of Radiology.

Comments: This case illustrates that Hyperemesis Gravidarum can cause Wernicke’s
encephalopathy (WE) that may progress to coma 4. The classic triad of ataxia, ophthal-
moplegia and altered mental status may not always be apparent. 5,6 MRI findings are
specific but not sensitive. Unrecognized WE can be exacerbated by glucose administra-
tion. In addition to parenteral high dose thiamine infusion, correcting hypomagnesaemia
should be considered given that magnesium is a cofactor in thiamine activity and cellular
uptake 6 . Delay in treatment may lead to chronic cognitive disorders, pregnancy loss and
maternal death
 33

16 Starred References
#1*** (Posner, et al): This is the classic book originally from Drs. Plum & Posner on
coma and provides a thorough framework to understand and treat coma, from the physi-
ology of consciousness to the pathophysiology of coma, causes of coma and management.
#11*** (Edlow, et al): This articles provides a good review of reversible causes of
coma and provides a framework for early treatment of reversible causes of coma.
# 15** (Verbalis et al): Great review of hyponatremia, diagnosis and management
with practical recommendations for treatment
#19*** (Kirkham, et al): This article includes a succinct and thorough summary of
causes of non-traumatic coma in children focusing on approach to diagnosis, management
and prognosis.

17 References
1. Posner JB, Saper CB, Schif MD, Plum F. Plum and Posner’s Diagnosis of Stupor and
Coma. 4th ed: Oxford University Press; 2007.
2. Stevens RD, Bhardwaj A. Approach to the comatose patient. Crit Care Med
2006;34:31-41.
3. Teasdale G, Jennett B. Assessment of coma and impaired consciousness. A practi-
cal scale. Lancet 1974;2:81-4.
4. Hickey JV. The clinical practice of neurological and neurosurgical nursing. 7th ed.
Philadelphia, PA: Wolters Kluwer/Lippincott Williams & Wilkins. ; 2014.
5. Wijdicks EF, Rabinstein AA, Bamlet WR, Mandrekar JN. FOUR score and Glas-
gow Coma Scale in predicting outcome of comatose patients: a pooled analysis. Neurol-
ogy 2011;77:84-5.
6. Stead LG, Wijdicks EF, Bhagra A, et al. Validation of a new coma scale, the FOUR
score, in the emergency department. Neurocrit Care 2009;10:50-4.
7. Wijdicks EF, Bamlet WR, Maramattom BV, Manno EM, McClelland RL. Valida-
tion of a new coma scale: The FOUR score. Ann Neurol 2005;58:585-93.
8. Iyer VN, Mandrekar JN, Danielson RD, Zubkov AY, Elmer JL, Wijdicks EF. Va-
lidity of the FOUR score coma scale in the medical intensive care unit. Mayo Clin Proc
2009;84:694-701.
9. Michelson DJ, Ashwal S. Evaluation of coma and brain death. Semin Pediatr
Neurol 2004;11:105-18.
10. Bachhuber MA, Hennessy S, Cunningham CO, Starrels JL. Increasing Benzo-
diazepine Prescriptions and Overdose Mortality in the United States, 1996-2013. Am J
Public Health 2016;106:686-8.
11. Edlow JA, Rabinstein A, Traub SJ, Wijdicks EF. Diagnosis of reversible causes of
coma. Lancet 2014;384:2064-76.
12. Haupt WF, Hansen HC, Janzen RW, Firsching R, Galldiks N. Coma and cerebral
imaging. Springerplus 2015;4:180.
13. Aegisdottir H, Cooray C, Wirdefeldt K, Piehl F, Sveinsson O. Incidence of os-
motic demyelination syndrome in Sweden: A nationwide study. Acta Neurol Scand
 34

2019;140:342-9.
14. Singh TD, Fugate JE, Rabinstein AA. Central pontine and extrapontine myelinol-
ysis: a systematic review. Eur J Neurol 2014;21:1443-50.
15. Verbalis JG, Goldsmith SR, Greenberg A, et al. Diagnosis, evaluation, and treat-
ment of hyponatremia: expert panel recommendations. Am J Med 2013;126:S1-42.
16. Spasovski G, Vanholder R, Allolio B, et al. Hyponatraemia diagnosis and treat-
ment clinical practice guidelines. Nefrologia 2017;37:370-80.
17. Sterns RH, Nigwekar SU, Hix JK. The treatment of hyponatremia. Semin Nephrol
2009;29:282-99.
18. Sechi G, Serra A. Wernicke’s encephalopathy: new clinical settings and recent
advances in diagnosis and management. Lancet Neurol 2007;6:442-55.
19. Ferbert A, Bruckmann H, Drummen R. Clinical features of proven basilar artery
occlusion. Stroke 1990;21:1135-42.
20. Racchiusa S, Mormina E, Ax A, Musumeci O, Longo M, Granata F. Posterior
reversible encephalopathy syndrome (PRES) and infection: a systematic review of the
literature. Neurol Sci 2019;40:915-22.
21. Fugate JE, Claassen DO, Cloft HJ, Kallmes DF, Kozak OS, Rabinstein AA. Pos-
terior reversible encephalopathy syndrome: associated clinical and radiologic findings.
Mayo Clin Proc 2010;85:427-32.
22. Chen TH. Childhood Posterior Reversible Encephalopathy Syndrome: Clinicora-
diological Characteristics, Managements, and Outcome. Front Pediatr 2020;8:585.
23. Ou S, Xia L, Wang L, Xia L, Zhou Q, Pan S. Posterior Reversible Encephalopathy
Syndrome With Isolated Involving Infratentorial Structures. Front Neurol 2018;9:843.
24. Saposnik G, Caplan LR. Convulsive-like movements in brainstem stroke. Arch
Neurol 2001;58:654-7.
25. Tatman A, Warren A, Williams A, Powell JE, Whitehouse W. Development of
a modified paediatric coma scale in intensive care clinical practice. Arch Dis Child
1997;77:519-21.
26. Cohen J. Interrater reliability and predictive validity of the FOUR score coma
scale in a pediatric population. J Neurosci Nurs 2009;41:261-7; quiz 8-9.
27. Kirkham FJ, Newton CR, Whitehouse W. Paediatric coma scales. Dev Med Child
Neurol 2008;50:267-74.
28. Kirkham FJ. Non-traumatic coma in children. Arch Dis Child 2001;85:303-12.
29. Saudubray JM, Garcia-Cazorla A. Inborn Errors of Metabolism Overview:
Pathophysiology, Manifestations, Evaluation, and Management. Pediatr Clin North Am
2018;65:179-208.
30. Seshia SS, Bingham WT, Kirkham FJ, Sadanand V. Nontraumatic coma in chil-
dren and adolescents: diagnosis and management. Neurol Clin 2011;29:1007-43.
31. Haberle J, Chakrapani A, Ah Mew N, Longo N. Hyperammonaemia in classic
organic acidaemias: a review of the literature and two case histories. Orphanet J Rare Dis
2018;13:219.
32. Waters D, Adeloye D, Woolham D, Wastnedge E, Patel S, Rudan I. Global birth
prevalence and mortality from inborn errors of metabolism: a systematic analysis of the
evidence. J Glob Health 2018;8:021102.
 35

33. Guerrero RB, Salazar D, Tanpaiboon P. Laboratory diagnostic approaches in

metabolic disorders. Ann Transl Med 2018;6:470.
34. Kaplan PW. Coma in the pregnant patient. Neurol Clin 2011;29:973-94.
35. Beighley A, Glynn R, Scullen T, et al. Aneurysmal subarachnoid hemorrhage
during pregnancy: a comprehensive and systematic review of the literature. Neurosurg
Rev 2021.
36. Oudman E, Wijnia JW, Oey M, van Dam M, Painter RC, Postma A. Wernicke’s
encephalopathy in hyperemesis gravidarum: A systematic review. Eur J Obstet Gynecol
Reprod Biol 2019;236:84-93.
37. Liu YL, Xiao WM, Liang MQ, et al. Clinical characteristics and magnetic reso-
nance imaging findings in nine patients with nonalcoholic Wernicke’s encephalopathy: a
retrospective study. Neuropsychiatr Dis Treat 2019;15:2433-41.
38. WHO Recommendations for Prevention and Treatment of Pre-Eclampsia and
Eclampsia. Geneva2011.
39. Bader MK, Littlejohns LR. AANN Core Curriculum for Neuroscience Nursing.
6th ed. Chicago: American Association of Neuroscience Nursing; 2016.

Acknowledgements
The authors are grateful for the contributions and insight provided by the following re-
viewers: Ebonye Green, Jorge Mejia-Mantilla, MD, MSc, FNC, William Meurer, MD,
MS, Amina George, PharmD, BCCCP