NEUROINTENSIVE CARE
Clinical approach to Learning objectives
comatose patients After reading this article, you should be able to:
C define consciousness and coma
Rosie May C discuss a structured approach to the diagnosis and manage-
Katharine Hunt ment of a patient who presents with coma
C identify situations where time is critical and understand the
reasons for and methods of neuroprotection
Abstract C identify relevant prognostic factors in acute coma
Coma is a state of unarousable unconsciousness and can occur as
result of many general medical and neurological conditions. In this
article we present a structured approach to the investigation and man-
agement of a patient who presents with coma and discuss the impor-
tance of identifying the underlying cause in attempting to prevent Causes of acute coma
secondary brain damage, as well as for prognostication.
Keywords Coma; consciousness; Glasgow coma scale
Primary neurological/structural
Royal College of Anaesthetists CPD Matrix: 2F01, 3F00, 3A01
C Haemorrhage (subarachnoid, extradural, subdural or
intraparenchymal)
C Vascular occlusion (thrombotic or embolic)
C Space occupying lesion (tumour, abscess)
C Hydrocephalus
Introduction C Infection (meningitis, encephalitis)
C Inflammation (vasculitis, demyelination)
Consciousness is described as a state of awareness of self and the C Traumatic brain injury
environment, enabling responsiveness to external stimulus and C Non convulsive status (this could also be systemic)
inner need. The two fundamental components of consciousness
are arousal and awareness, the former mediated by the ascending Systemic/diffuse
reticular activating system and the latter by the cortex and the C Endocrine (hypothyroidism, Addisonian crisis, diabetic
thalamus. Disruption to signalling pathways of these structures ketoacidosis, hypopituitarism)
results in coma, a state of unarousable unconsciousness. The C Metabolic (hypoglycaemia, hyponatraemia or
disruption is either structural or of a diffuse systemic nature. hypernatraemia)
Where the former is the cause, bilateral cortical damage or C Hypothermia
brainstem compression must occur to lead to coma.1 C Hyperthermia
The differential diagnosis for cause of coma is vast and in- C Hypertension (posterior reversible encephalopathy
cludes a variety of neurological and general medical conditions syndrome)
(Box 1), many of which can be life threatening if not identified C Hypovolaemia
and managed promptly. As such, a structured approach to the C Sepsis
management of a patient who presents with coma is key. Prog- C Toxins (sedatives, opiates, carbon monoxide, alcohol,
nosis is primarily determined by the underlying cause, and antidepressants, illicit drugs, lead, anti-epileptics)
ranges from full recovery to severe disability, persistent vegeta- C Thiamine deficiency - Wernicke’s encephalopathy
tive state and death. C Hypoxic ischaemic encephalopathy
C Respiratory (hypercarbia)
Initial assessment and management C Genetic (inborn errors of metabolism, mitochondrial
disorders)
The initial step of management of a comatose patient should
C Liver failure (hyperammonaemia or cerebral oedema)
involve a rapid assessment to facilitate resuscitation, stabiliza-
C Renal failure (uraemia)
tion and identification of life-threatening reversible causes. This
should be performed in an environment where continuous Coma mimics
C Locked-in syndrome
C Guillain-Barre syndrome
Rosie May MA(Cantab) MBBS MRCP FRCA is a Clinical Fellow in
C Akinetic mutism
Neuroanaesthesia and Neurocritcal Care at the National Hospital for C Botulism
Neurology and Neurosurgery, London, UK. Conflicts of interest: none C Psychogenic unresponsiveness
declared.
Katharine Hunt MBBS FRCA FFICM is a Consultant in
Neuroanaesthesia and Neurocritical Care at the National Hospital for Box 1
Neurology and Neurosurgery, London, UK. Conflicts of interest: none
declared.
ANAESTHESIA AND INTENSIVE CARE MEDICINE 21:1 16 Ó 2019 Elsevier Ltd. All rights reserved.
NEUROINTENSIVE CARE
haemodynamic and neurological monitoring can be carried out,
and where senior help is available. Subsequent management will Examination findings and clinical significance
be determined by the findings of the initial examination and Examination finding Potential significance
investigation but must include measures to prevent secondary
cerebral damage. Meningism Subarachnoid haemorrhage,
An ABCDE approach for initial assessment is appropriate. If meningoencephalitis
the patient is in cardiac arrest, cardiopulmonary resuscitation Localizing signs Structural lesion
should be immediately commenced and advanced life support
Fundoscopy
algorithms followed. Where there is a history of trauma, cervical
Papilloedema Raised ICP/asphyxia
spine immobilization must be implemented. Adequate oxygena-
Vitreous haemorrhages Subarachnoid haemorrhage
tion must be assured, and this may be through the use of simple
Pupillary responses
adjuncts to provide supplemental oxygen, or endotracheal intu-
Fixed constricted pupils Brainstem insult or opioid
bation. Indications for endotracheal intubation include GCS <8,
overdose
inadequate ventilation, loss of ability to protect airway or loss of
Unilateral dilated pupil deviated Pressure on oculomotor nerve,
protective laryngeal reflexes and refractory seizures although this
down and out Posterior communicating
is a clinical decision that should be assessed on an individual
aneurysm or uncal herniation
basis. Assessment of adequacy of ventilation can be aided by
Unilateral constricted pupil Horner’s syndrome
arterial blood gas analysis, where initial targets should be PaCO2
4.5e5.5 kPa, and PaO2 >13 kPa until information regarding the Brainstem reflexes
cause of the coma can be established, in attempt to optimize Corneal reflex absent Pontine lesion
cerebral perfusion and oxygenation. Intravenous fluids with or Absent cough Medullary Injury
without vasopressors should be used to target a mean arterial Motor function
pressure of 90 mmHg to achieve an adequate cerebral perfusion Decerebrate posturing lesion below midbrain
pressure, although this will be guided by individual patient cir- (pronation, extension upper
cumstances and comorbidities. Arterial blood gas analysis will limbs)
also provide indication of glucose and sodium levels, abnor- Decorticate posturing Brainstem lesion above midbrain
malities of which may be the cause of the coma. In case of (upper limb flexion, lower limb
hypoglycaemia (capillary blood glucose <4 mmol), immediate extension)
intravenous administration of 25 ml of 50% glucose is required. Myoclonic Jerking Hypoxic-Ischaemic
If there is any suspicion of vitamin B deficiency, for example, in encephalopathy
chronic alcohol dependence, thiamine 100 mg must be co-
administered with glucose to prevent potentially fatal precipita- Table 1
tion of Wernicke’s encephalopathy. Where hyponatraemia or
hypernatraemia is identified as a possible contributing factor, medical and surgical history particularly including metabolic,
this must be carefully corrected in a high dependency care setting endocrine and known neurological and psychiatric conditions.
as too rapid correction can precipitate cerebral oedema or central A focused medical and neurological examination should then
pontine myelinolysis. It is recommended that the maximum rate follow assessing for signs of meningism, lateralizing signs and
of correction is 8 mmol/L within 24 hours. brainstem reflexes. Meningism is a feature of subarachnoid
If there is evidence of opiate toxicity from history or initial haemorrhage and meningo-encephalitis. Lateralizing signs sug-
assessment, naloxone 400mcg can be administered intrave- gest a structural lesion and should prompt urgent imaging. The
nously. If a response is seen, it is important to be aware that this most common form of coma is that without localizing signs or
may need to be repeated or an infusion commenced. Manage- meningism, and this usually results from a diffuse systemic
ment of benzodiazepine overdose needs to be carefully consid- cause, such as anoxic-ischaemic injury or metabolic, toxic or
ered, as use of flumazenil for reversal can precipitate seizures in post-ictal states.
those who have a chronic dependence. If there is a suspicion of Examination of the eyes including fundoscopy, pupillary re-
seizures, or non-convulsive status epilepticus contributing to sponses, occulo-motor function and corneal reflexes can reveal
coma, loading with intravenous phenytoin or levetiracetam is important signs to help aid diagnosis (Table 1).2 Papilloedema is
advised. Where sepsis is suspected, blood cultures should be indicative of raised intracranial pressure (ICP) although its
taken and administration of intravenous antibiotic and antiviral absence does not exclude this, and it may also be a sign of
drugs within one hour. asphyxia. Vitreous haemorrhage can be seen in subarachnoid
haemorrhage, and the presence of this is an adverse prognostic
Further history and examination sign. Fixed constricted pupils may indicate opioid overdose or a
brainstem pathology, and a unilateral fixed dilated pupil with the
Once stabilized, a detailed collateral history should be taken if affected eye being deviated down and out is suggestive of raised
available, and further clinical examination and investigations ICP causing pressure on the oculomotor nerve. It is important to
instituted to facilitate a diagnosis. The history should focus on consider that findings on pupil assessment may be affected by
the time course of the deterioration, potential precipitating fac- previous ocular injury or cataracts, and also by drugs used in
tors, associated prodromal symptoms and the patient’s past resuscitation such as adrenaline or atropine. Absence of the
ANAESTHESIA AND INTENSIVE CARE MEDICINE 21:1 17 Ó 2019 Elsevier Ltd. All rights reserved.
NEUROINTENSIVE CARE
corneal reflex and cough reflex are seen in midbrain and med-
Coma scales ullary lesions respectively.
Motor examination may reveal abnormal posturing, spas-
Glasgow Coma Scale ticity, flaccidity or involuntary reflex movements such as myoc-
Best eye opening Spontaneous 4 lonus or tremor. Decerebrate posturing refers to bilateral upper
To Voice 3 and lower limb extensor posturing and is usually indicative of a
To pain 2 mid-brain or pontine lesion, whereas decorticate posturing is
No response 1 characterized by bilateral upper limb flexion and lower limb
Best verbal response Orientated 5 extension and is seen with upper brain stem lesions. Myoclonic
Confused 4 jerking is commonly seen with anoxic-ischaemic encephalopa-
Inappropriate words 3 thy. Throughout the examination it is important to be aware of
Incomprehensible sounds 2 confounding factors that may affect findings, such as hypother-
No verbal response 1 mia, sedation, shock and drug intoxication. Hypnotic agents, for
Best motor response Obeys commands 6 example, can suppress brainstem reflexes and create false
Localizing pain 5 localizing signs.
Withdrawal from pain 4
Flexion to pain 3 Coma scales
Extension to pain 2 The most widely used initial assessment for coma is the Glasgow
No motor response 1 Coma Scale (GCS). This is a 15-point scale composed of motor,
Full Outline of verbal and eye-opening scores to verbal and painful stimulation.
Unresponsiveness It is not of diagnostic value, but it provides a reliable way of
(FOUR) Scale objectively monitoring the clinical course of a coma patient. The
Eye response Spontaneous eye opening, 4 Full Outline of Unresponsiveness (FOUR) Scale, is an alternative
tracks, blinks to command to GCS which can be used in intubated patients. This comprises a
Eyes open. No tracking or 3 16-point scale, assessing eye opening, respiration pattern,
blinking to command brainstem reflexes and motor response (Table 2).
Eyes open to loud voice 2
Eyes open to pain 1 Investigations
No response 0 Bloods should be sent for full blood count, electrolytes, liver
Motor response Obeys commands 4 function, clotting profile and thyroid function and urine sent for
Makes a sign toxicology. Where a rapidly reversible cause for coma has not
e.g. thumbs up been identified by the above, an urgent computerized tomogra-
Localizing pain 3 phy (CT) head scan CT angiogram is indicated. This is
Flexion to pain 2 particularly of importance for identifying intracranial pathologies
Extension to pain 1 where a time critical intervention may be warranted, such as
No response or 0 thrombolysis or thrombectomy for acute ischaemic stroke, hy-
myoclonic status drocephalus requiring urgent CSF diversion or decompressive
Brainstem reflexes Pupil and corneal reflexes 4 craniectomy for raised ICP. Blood cultures should be taken where
and cough present patients are febrile over 38oC or hypothermic without an iden-
One pupil unreactive. Corneal 3 tifiable cause. Lumbar puncture is indicated following CT scan in
reflex and cough present patients with suspected central nervous system (CNS) infection
Pupils OR corneal reflex 2 or inflammation, although this should not delay administration
unreactive of antibiotics. Where non-convulsive status epilepticus is sus-
Pupils AND corneal reflex 1 pected, an electroencephalogram (EEG) should be considered.
absent, cough present Magnetic resonance imaging (MRI) with diffusion-weighted
Absent pupil, corneal and 0 imaging (DWI) or fluid-attenuated inversion recovery (FLAIR)
cough reflex sequences may be indicated to aid diagnosis where the above
Intubation Normal breathing pattern, 4 investigations have not revealed a cause. DWI abnormalities
not intubated usually result from acute stroke, whereas FLAIR sequences can
Cheyne-Stokes breathing, 3 reveal abnormalities suggestive of an underlying inflammatory or
not intubated demyelinating condition. Where CT angiogram has identified a
Irregular breathing pattern, 2 likely underlying vascular cause, digital subtraction angiography
not Intubated may be performed to investigate this and guide further
Intubated and triggering 1 management.
ventilator
Apnoeic or Intubated and 0 Coma mimics
not triggering It is important to be aware of coma mimics where a person’s
arousal and responsiveness may appear to be absent, but their
Table 2 conscious level is not affected. These include locked-in
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NEUROINTENSIVE CARE
syndrome, Guillain-Barre syndrome, psychogenic unresponsive- the bleed, a GCS of <6, requirement for early neurosurgical
ness and other neuropsychiatric disorders. evacuation or the presence of a massive haematoma with a poor
expected prognosis.5
Time critical situations
Where structural lesions with evidence of raised ICP are identi- Prognostication
fied on imaging, immediate neurosurgical opinion should be The outcome after coma largely depends on the underlying
sought. cause, but also the presence of secondary cerebral insult, dura-
In patients with traumatic brain injury or raised ICP from a tion and depth of coma and other factors such as age, bilaterally
structural lesion, interim measures to control high ICP and pre- absent pupillary light reflex and hypotension at presentation.
vent secondary neurological damage include deepening of seda- There is an increasing probability of better outcome with higher
tion with propofol or barbiturates and the use of hyperosmolar GCS at presentation and those who maintain normal brainstem
therapy (mannitol 0.25e1 g/kg or hypertonic saline 3% 3 ml/kg) reflexes throughout. Better outcomes are associated with coma
ensuring that systolic blood pressure (SBP) does not drop below secondary to toxic and metabolic insults compared to structural
90 mmHg.2 Hyperventilation can be used acutely to target PaCO2 causes, and with traumatic coma when compared to non-
4.0e4.5 KPa but must not be prolonged and it should be noted traumatic coma. In patients with hypoxic-ischaemic injury
that cerebral blood flow is often significantly reduced anyway in following cardiac arrest, current guidelines recommend that
the first 24 hours following injury. Cerebral venous drainage prognostication should not be performed before 72 hours after
should be encouraged by elevating the head of the bed to 20 return of spontaneous circulation.6 Prognostication should
degrees with the head in a neutral position and avoiding venous involve a multimodal approach incorporating radiological, elec-
compression from endotracheal tube ties. Where possible, ICP trophysiological and serum biochemistry testing. Magnetic
monitoring should be instituted in all patients with a GCS <8 and resonance Imaging (MRI) is the imaging modality of choice in
abnormal CT scan, or if the CT scan is normal where two of the evaluating the extent of axonal injury, and somatosensory
following are present: age >40 years, motor posturing, SBP evoked potentials and EEG have been demonstrated to have a
<90 mmHg. Targeted temperature management (TTM) should predictive value in patients following hypoxic events and trau-
be carried out to normothermia except in those patients who matic brain injury. High serum levels of neuron specific enolase
have had an out of hospital cardiac arrest with a shockable are also associated with poor outcome in these patients. A
rhythm. In this case, TTM should be carried out to between 32
and 36 degrees Celsius for at least 24 hours. If the GCS at pre-
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ANAESTHESIA AND INTENSIVE CARE MEDICINE 21:1 19 Ó 2019 Elsevier Ltd. All rights reserved.
