Coma and Unconsciousness

Coma is a clinical state of being not aware and not awake due to impairment of the ARAS-thalamic-cortical pathway. Lesion may be in:

More precisely, “a completely unaware patient unresponsive to external stimuli with only eye opening to pain, with no eye tracking or fixation, and limb withdrawal to a noxious stimulus at best.”

Epidemiology

Associated with NCSE in 10-50% of cases.

Aetiology

Major causes can be classified by:

  • Pathophysiology
    • Structural
      • Cerebral hemispheres
      • Intrinsic brainstem injury
      • Cerebellar injury
    • Functional
      • Metabolic or endocrine derangement
      • Diffuse physiological dysfunction
  • Clinical features
    • No focal signs
    • Focal neurology
    • Meningism
Causes of Coma by Clinical Features
No focal neurology Focal Neurology Meningism

Infection:

  • Encephalitis
  • Septic encephalopathy

CVA

  • Typically due to a posterior circulation lesion
  • Both cerebral corticies must be disrupted to produce coma from an anterior circulation CVA

Infection:

  • Meningitis
Vasculitis

ICH:

  • SDH and EDH may cause global depression and seizures
  • Effects may be due to ↑ ICP, or damage to key pathways

Vascular:

  • SAH
    SAH depresses conscious state through direct anoxic-ischaemic injury, or indirectly due to hydrocephalus.

Seizures:

  • NCSE
 Trauma
Brainstem

Tumour (including lymphoma and metastases):

  • May have slow progression of findings
  • Via direct pressure on key areas, or by diffuse ↑ in ICP
Drugs
See below.		 Abscess
Metabolic
See blow.

Acute hydrocephalus:

  • Spasticity due to stretching of motor cortex
  • Diplopia due to CN III or CN VI compression
Hyopoxic-Ischaemic Encephalopathy

Posterior Reversible Encephalopathy Syndrome (PRES):

  • Patchwork vasodilation and vasoconstriction due to severe hypertension, producing visual disturbances and altered conscious state

Drug Causes

Drugs which may cause CNS depression can be classified broadly into:

  • Sedative/hyponotics
    • Alcohols
      • Ethanol
      • Methanol
      • Ethylene glycol
    • Barbiturates
    • Benzodiazepines
    • Baclofen
    • GHB
    • Clonidine
  • Opioids
  • Dissociatives
    • Ketamine
    • PCP
  • Toxins and overdoses
    • Carbon monoxide
    • Serotonin syndrome
    • Neuroleptic malignant syndrome

Metabolic Causes

A mnemonic for the metabolic causes is COMATOSE GREAT APE:

  • CO2
    Mechanism unclear, but possibly related to ICP or altered neurotransmitter function.
  • O2
    Coma may occur within minutes of severe oxygen deprivation.
  • Metabolism (of drugs)
  • Ammonia
    Hepatic encephalopathy, as well as:
    • Valproate in the setting of carnitine deficiency
    • Urease-producing bacterial infection
    • Hyperalimentation
    • Inborn errors of metabolism
    • Surgery
      • Lung transplantation
      • Bariatric surgery
      • Ureterosigmoidostomy
  • Temperature
    Typically requires temperatures <28°C.
  • Overdose
    • Neuroleptic malignant syndrome
  • Seizures
  • Encephalitis

  • Glucose
    • Hypoglycaemia
      Wide variety of neurologic signs, including coma.
    • Hyperglycaemia
      May cause coma in the setting of HHS/DKA
  • Renal failure
    Uraemic encephalopathy.
  • ETOH
  • Adrenal Insufficiency
  • Thyroid
    • Acute hypothyroidism
      Myxedema coma.
    • Panhypopituitarism

  • Autoimmune
  • pH
  • Electrolytes
    • Hyponatraemia
    • Hypernatraemia
    • Hypercalcaemia
    • Addisons IDisease

Clinical Manifestations

Level of consciousness is graded using the GCS or FOUR score:

Glasgow Coma Scale Scoring
Score Eye Verbal Motor
6 - - Obeys unambiguous command.
5 - Orientated. Coherent and appropriate response. Moves towards pain in a meaningful attempt to alleviate it.
4 Open spontaneously. Confused. Appropriate (but incorrect) response. Withdraws to pain.
3 Opens to voice. Inappropriate response. Response does not match questions. Abnormal flexion (decorticate posturing) to pain.
2 Opens to pain. Incomprehensible response. Moaning/sounds, but no words. Abnormal extension (decerebrate posturing) to pain.
1 No response. No response. No response.

FOUR Score

The FOUR (Full Outline of UnResponsiveness) score is:

  • A coma scale (similar to GCS)
  • Designed to be valid in intubated patients
  • Able to further separate patients with low GCS scores
    Greater separation between patients with severe neurological injury.
    • Able to identify locked-in syndrome and vegetative states
  • Has similar inter-rater reliability to GCS
  • Measured on a 16-point scale
    Consists of four components, each scored from 0-4.
  • An overall score of 0 should prompt brain death evaluation
FOUR Score
Score Eye Motor Brainstem Respiration
4 Open, tracking, or blinking to command Thumbs up, fist, or peace sign Pupillary and corneal reflexes present Not intubated, regular breathing
3 Open but not tracking Localising to pain One pupil fixed and dilated Not intubated, Cheyne-Stokes breathing
2 Open to loud voice Flexing to pain Pupil OR corneal reflexes absent Not intubated, irregular breathing
1 Open to pain Extending to pain Pupil AND corneal reflexes absent Intubated, breathing above ventilator
0 Closed to pain No response or generalised myoclonus/status epilepticus Pupil, corneal, AND cough reflex absent Intubated, breathing at ventilator rate OR apnoeic
Notes
  • If closed, eyes should be opened to test for tracking before inflicting pain
  • Tracking requires at least 3 excursions
  • Blinking requires at least 2 blinks
  • Best upper limb response
  • Localisation requires supraorbital nerve compression results in the patient touching examiners hand
  • Myoclonus: Persistent, multisegmental, arrhythmic, jerking movements.
  • Best possible response.
  • Tests mesencephalon, pons, and medulla function

Diagnostic Approach and DDx

Two key pitfalls in coma assessment are:

  • Locked-in Syndrome
    Denervation of motor tracts in the ventral pons, leading to:
    • Ability to blink to command and move eyes vertically
    • Intact hearing, vision, and peripheral pain sensation
  • Psychogenic Unreponsiveness

Presence or absence of other findings will narrow the differential:

  • C
    • Bradycardia
      • Hypnotic toxicity
      • Raised ICP
        With hypertension (Cushing’s Triad).
    • Tachycardia
      • Sympathomimetic toxicity
      • Intracranial haemorrhage
    • Hypotension
      • Sepsis
      • Drug toxicities
    • Hypertension
      • PRES
  • E
    • Hyperthermia
      • Intracranial infections
      • Heat injury
      • Anticholinergic toxicity
      • Pontine stroke
    • Hypothermia
      • Drug
        • Alcohol
        • Barbiturate
      • Cold exposure
      • Sepsis
      • Drowning
    • Paralysis
      • Neuromuscular blockade
  • HENT
    • Signs of trauma
      • Haemotympanum
      • Bony deformities
    • Miosis
      • Toxicity
        Opioid, clonidine.
      • Pontine haemorrhage
    • Mydriasis
      • Anticholinergic toxicity
      • MDMA
    • Horizontal nystagmus
      • ETOH
      • Antiepileptics
    • Vertical nystagmus
      • Dissociate agents
      • Brainstemi lesion
    • Gaze deviation
      • Ipsilateral hemispheric lesion
      • Contralateral pontine lesion
      • Focal seizure
    • Cold-caloric reflex
      • Loss of (normal) deviation of eyes towards irrigation suggestive of midbrain or pontine lesion
      • Loss of (normal) rapid nystagmus away from the irrigation suggestive of cortical lesion
      • Loss of neither normal response suggests psychogenic coma
    • Dry mucous membranes
      • Dehydration
      • Anticholinergic toxicity

Coma Mimics

Related categories of altered conscious states that do not have their own page.

  • Locked-in syndrome
    Severe neurological lesion secondary to bilateral pontine lesions with destruction of pontine motor tracts, resulting in:
    • Tetraplegia
    • Preservation of spontaneous respiration
    • Preservation of upward eye movements and blinking
      Other eye movements may be preserved, depending on the severity.
  • Psychogenic unresponsiveness
    Profound impaired conscious state (classically GCS 3) without impairment of respiration, airway protection, or pupillary abnormalities.
    • Eyes
      • Resistance of passive eye opening
      • Blink response
      • No spontaneous roving movements
      • Occulo-cephalic reflex negative
      • Rouses with vestibulo-ocular testing
  • Akinetic mutism
    Frontal lobe injury characterised by absence of communication and minimal movement to complete specific tasks.
  • Persistent Vegetative State
    Persistent (>1 month) state of lack of awareness despite possible wakefulness (eyes open), defined defined by:
    • No awareness of self or environment
    • No sustained, reproducible, purposeful, or voluntary response to a stimuli
    • No language comprehension or expression
    • Mostly intact cranial nerve reflexes
    • Roving nystagmoid eye movements
    • Presence of a sleep/wake cycle
    • Stable unsupported blood pressure
    • Intact respiratory drive
    • Double incontinence

Patients with PVS < 3 years may (rarely) partially recover; there are no known predictors though it is usually after TBI. Patients with PVS for >3 years do not recover.

  • Minimally Conscious State
    May further recover, but no predictors are known. Patients with MCS:
    • Make eye contact and turns head when talked through
    • Eye tracking
    • “Abulic emotionless state”
    • May mouth words or fend off pain
    • Some intelligible verbalisation
    • May hold or use objects when asked
  • Isolated frontal lobe injury
    Characterised by:
    • Apathy
    • Abulia
      Loss of motivation.
    • Delayed response to external stimuli
  • Global aphasia
    Inability to speak and understand speech due to dominant hemispheric injury, classically a stroke. Patient can still perform meaningful tasks.
  • Postictal state
    Minutes-to-hours period following a seizure where a patient may appear alert but unresponsive.

Investigations

Blood:

  • Glucose
  • Blood gases
  • UEC
  • Osmolality
  • LFT
    • Blood
    • Alcohol
    • Paracetamol
    • Salicylates
    • Benzodiazepines
    • TCA

Radiology:

  • CTB
    • ICH
    • SAH
    • Trauma
    • CVA
    • Cerebral oedema
    • Space-occupying lesion
    • Hydrocephalus
      Particularly prior to LP.
  • MRI
    • Better detection of:
      • Acute ischaemia
      • DAI
      • Cerebral oedema
      • Tumour
      • Abscess
    • Better posterior fossa imaging

Pathology:

  • LP
    • SAH
    • Infection

Urine:

  • Drug analysis

Management

Resuscitation:

  • A
    • Ensure patency and oxygenation
      Decision to secure will depend on the level of consciousness.
  • C
    • Intravenous access
  • D
    • 50% Dextrose
      Empiric treatment of hypoglycaemia is low-risk.
    • Thiamine
      100mg IV.
    • Naloxone
    • Mannitol 0.5-1g/kg
      If concern of ↑ ICP.

Specific therapy:

  • Pharmacological
  • Procedural
  • Physical

Supportive care:

Disposition:

Marginal and Ineffective Therapies

Anaesthetic Considerations

Complications

Prognosis

Generally poor:

  • 15% of non-traumatic coma return to pre-morbid state
  • Traumatic coma generally better to non-traumatic causes

Key Studies

References

  1. Yartsev, A. The Unconscious Patient. Deranged Physiology. Accessed 11/2017.
  2. Wijdicks EFM, Bamlet WR, Maramattom BV, Manno EM, McClelland RL. Validation of a new coma scale: The FOUR score. Ann Neurol. 2005;58(4):585-593.
  3. Fischer M, Rüegg S, Czaplinski A, et al. Inter-rater reliability of the Full Outline of UnResponsiveness score and the Glasgow Coma Scale in critically ill patients: a prospective observational study. Critical Care. 2010;14(2):R64.
  4. Traub SJ, Wijdicks EF. Initial Diagnosis and Management of Coma. Emerg Med Clin North Am. 2016 Nov;34(4):777-793. doi: 10.1016/j.emc.2016.06.017. Epub 2016 Sep 3.
  5. Wijdicks EF. The bare essentials: coma. Pract Neurol. 2010 Feb;10(1):51-60.