Module 4 - Approach To The Comatose Patient
Module 4 - Approach To The Comatose Patient
Module 4 - Approach To The Comatose Patient
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: [email protected]
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2
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.
3
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
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
6
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
TABLE 5
Pediatric Glasgow Coma Scale (PGCS)1 Adapted with permission Pediatric Glasgow
Coma Scale PGCS
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-
9
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
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.
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
TABLE 8
Primary neurological etiologies of coma (cont’d)
13
Table 9 continued
Wernicke’s disease Confusion, ataxia, ophthalmoparesis, history of Thiamine level (history and clinical exam more impor-
vomiting and malnutrition, hyperemesis gravi- tant than lab testing)
darum, malabsorption or short gut.
Sepsis Fever, cold clammy extremities Complete blood count, blood, urine and and/or respira-
tory cultures and serum lactate
Drug/medication overdose
Abuse (opioids, alcohol, am- Pupillary changes, HR changes, stigmata of cir- Toxicology screen
phetamines, cocaine) rhosis suggesting ETOH, injection markings on Consider Quantitative pupilometry in nonreactive pupils
skin, respiratory failure
Methanol, ethylene glycol, Obtaining a history of quantity and time of in- Toxicology screen, measure anion gap, osmolar gap;
gestion is critical. Coma, seizures, hyperp- send Toxic Alcohol panel for serum methanol & ethylene
nea, hypotension, afferent pupillary defect for glycol levels; basic metabolic panel, Urine microscopy
methanol, tetany, cranial nerve palsies. Examine for oxalic acid crystals and EKG
patient’s clothes, mouth, vomitus, or urine for
fluorescence due to fluorescein content in com-
mercial antifreeze preparations.
Sedative-hypnotics Bradycardia, respiratory depression, Cariso- Toxicology screen, EKG
Benzodiazepines, Non- prodol can produce anticholinergic side effects,
benzodiazepine hypnotics, muscle Baclofen overdose can cause seizures.
relaxants and barbiturates
Continued on next page
14
Table 9 continued
Narcotics Constricted or pinpoint pupils, decreased respi- Toxicology screen; Fentanyl analogues such as carfen-
Opium, Heroin, Codeine, Oxy- ratory rate, Tramadol overdose can present with tanyl may not be detected on standard urine drug screens
codone, Hydrocodone, Tramadol, Seizures and Serotonin syndrome
Morphine, Hydromorphone, Fen-
tanyl, Carfentanyl
Aspirin Tinnitus, vertigo, nausea/vomiting/diarrhea, hy- Arterial blood gas, toxicology screen, serum ac-
perpyrexia, noncardiac pulmonary edema, Cere- etaminophen level, consider head CT
bral edema is a rare complication of salicylate
toxicity
Acetaminophen Acute liver failure -Nausea/vomiting, diaphore- Acetaminophen level, hepatic function panel, coagula-
sis, pallor, oliguria, hepatomegaly, jaundice, en- tion panel, basic metabolic panel and plasma ammonia
cephalopathy, asterixis, coma level
Serotonergic medications: i.e., Agitated delirium, seizure, diaphoresis, mydria- Toxicology screen, creatine kinase, basic metabolic
SSRI, SNRI, MAO inhibitors, fen- sis hyperthermia, ocular clonus, hypertonia, hy- panel, calcium, magnesium, and phosphate; coagulation
tanyl perreflexia, tremor, ankle clonus, seizures, rigid- panel and serum lactate
ity. Hunter criteria for diagnosis.
Tricyclic antidepressants Refractory hypotension, arrhythmias, dilated Electrocardiogram, urine/serum tricyclic antidepressant
pupils, dry warm skin and mouth, constipation, screen if diagnosis is uncertain, arterial blood gas
hyperthermia, seizures, prolonged QRS
Antipsychotics Variable: mild hypotension, pupils variable, Electrocardiogram, toxicology screen, basic metabolic
tachycardia, hyperthermia, extrapyramidal side panel, magnesium, calcium
effects, acute dystonia, akathisia, anticholinergic
toxicity, ventricular arrhythmias
Anticonvulsants Variable depending on drug used 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
16
17
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
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.
19
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
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
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.
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
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).
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.
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.
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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