Clinical approach to comatose patients

Published:December 20, 2019DOI:


      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 management of a patient who presents with coma and discuss the importance of identifying the underlying cause in attempting to prevent secondary brain damage, as well as for prognostication.


      After reading this article, you should be able to:
      • define consciousness and coma
      • discuss a structured approach to the diagnosis and management of a patient who presents with coma
      • identify situations where time is critical and understand the reasons for and methods of neuroprotection
      • identify relevant prognostic factors in acute coma


      Consciousness is described as a state of awareness of self and the environment, enabling responsiveness to external stimulus and inner need. The two fundamental components of consciousness are arousal and awareness, the former mediated by the ascending reticular activating system and the latter by the cortex and the thalamus. Disruption to signalling pathways of these structures results in coma, a state of unarousable unconsciousness. The disruption is either structural or of a diffuse systemic nature. Where the former is the cause, bilateral cortical damage or brainstem compression must occur to lead to coma.
      • Patel S.
      • Hirsch N.
      The differential diagnosis for cause of coma is vast and includes a variety of neurological and general medical conditions (Box 1), many of which can be life threatening if not identified and managed promptly. As such, a structured approach to the management of a patient who presents with coma is key. Prognosis is primarily determined by the underlying cause, and ranges from full recovery to severe disability, persistent vegetative state and death.
      Causes of acute coma
      Tabled 1
      Primary neurological/structural
      • Haemorrhage (subarachnoid, extradural, subdural or intraparenchymal)
      • Vascular occlusion (thrombotic or embolic)
      • Space occupying lesion (tumour, abscess)
      • Hydrocephalus
      • Infection (meningitis, encephalitis)
      • Inflammation (vasculitis, demyelination)
      • Traumatic brain injury
      • Non convulsive status (this could also be systemic)
      • Endocrine (hypothyroidism, Addisonian crisis, diabetic ketoacidosis, hypopituitarism)
      • Metabolic (hypoglycaemia, hyponatraemia or hypernatraemia)
      • Hypothermia
      • Hyperthermia
      • Hypertension (posterior reversible encephalopathy syndrome)
      • Hypovolaemia
      • Sepsis
      • Toxins (sedatives, opiates, carbon monoxide, alcohol, antidepressants, illicit drugs, lead, anti-epileptics)
      • Thiamine deficiency - Wernicke's encephalopathy
      • Hypoxic ischaemic encephalopathy
      • Respiratory (hypercarbia)
      • Genetic (inborn errors of metabolism, mitochondrial disorders)
      • Liver failure (hyperammonaemia or cerebral oedema)
      • Renal failure (uraemia)
      Coma mimics
      • Locked-in syndrome
      • Guillain-Barre syndrome
      • Akinetic mutism
      • Botulism
      • Psychogenic unresponsiveness

      Initial assessment and management

      The initial step of management of a comatose patient should involve a rapid assessment to facilitate resuscitation, stabilization and identification of life-threatening reversible causes. This should be performed in an environment where continuous haemodynamic and neurological monitoring can be carried out, and where senior help is available. Subsequent management will be determined by the findings of the initial examination and investigation but must include measures to prevent secondary cerebral damage.
      An ABCDE approach for initial assessment is appropriate. If the patient is in cardiac arrest, cardiopulmonary resuscitation should be immediately commenced and advanced life support algorithms followed. Where there is a history of trauma, cervical spine immobilization must be implemented. Adequate oxygenation must be assured, and this may be through the use of simple adjuncts to provide supplemental oxygen, or endotracheal intubation. Indications for endotracheal intubation include GCS <8, inadequate ventilation, loss of ability to protect airway or loss of protective laryngeal reflexes and refractory seizures although this is a clinical decision that should be assessed on an individual basis. Assessment of adequacy of ventilation can be aided by arterial blood gas analysis, where initial targets should be PaCO2 4.5–5.5 kPa, and PaO2 >13 kPa until information regarding the cause of the coma can be established, in attempt to optimize cerebral perfusion and oxygenation. Intravenous fluids with or without vasopressors should be used to target a mean arterial pressure of 90 mmHg to achieve an adequate cerebral perfusion pressure, although this will be guided by individual patient circumstances and comorbidities. Arterial blood gas analysis will also provide indication of glucose and sodium levels, abnormalities of which may be the cause of the coma. In case of hypoglycaemia (capillary blood glucose <4 mmol), immediate intravenous administration of 25 ml of 50% glucose is required. If there is any suspicion of vitamin B deficiency, for example, in chronic alcohol dependence, thiamine 100 mg must be co-administered with glucose to prevent potentially fatal precipitation of Wernicke's encephalopathy. Where hyponatraemia or hypernatraemia is identified as a possible contributing factor, this must be carefully corrected in a high dependency care setting as too rapid correction can precipitate cerebral oedema or central pontine myelinolysis. It is recommended that the maximum rate of correction is 8 mmol/L within 24 hours.
      If there is evidence of opiate toxicity from history or initial assessment, naloxone 400mcg can be administered intravenously. If a response is seen, it is important to be aware that this may need to be repeated or an infusion commenced. Management of benzodiazepine overdose needs to be carefully considered, as use of flumazenil for reversal can precipitate seizures in those who have a chronic dependence. If there is a suspicion of seizures, or non-convulsive status epilepticus contributing to coma, loading with intravenous phenytoin or levetiracetam is advised. Where sepsis is suspected, blood cultures should be taken and administration of intravenous antibiotic and antiviral drugs within one hour.

      Further history and examination

      Once stabilized, a detailed collateral history should be taken if available, and further clinical examination and investigations instituted to facilitate a diagnosis. The history should focus on the time course of the deterioration, potential precipitating factors, associated prodromal symptoms and the patient's past medical and surgical history particularly including metabolic, endocrine and known neurological and psychiatric conditions.
      A focused medical and neurological examination should then follow assessing for signs of meningism, lateralizing signs and brainstem reflexes. Meningism is a feature of subarachnoid haemorrhage and meningo-encephalitis. Lateralizing signs suggest a structural lesion and should prompt urgent imaging. The most common form of coma is that without localizing signs or meningism, and this usually results from a diffuse systemic cause, such as anoxic-ischaemic injury or metabolic, toxic or post-ictal states.
      Examination of the eyes including fundoscopy, pupillary responses, occulo-motor function and corneal reflexes can reveal important signs to help aid diagnosis (Table 1).
      • Bateman D.E.
      Neurological assessment of coma.
      Papilloedema is indicative of raised intracranial pressure (ICP) although its absence does not exclude this, and it may also be a sign of asphyxia. Vitreous haemorrhage can be seen in subarachnoid haemorrhage, and the presence of this is an adverse prognostic sign. Fixed constricted pupils may indicate opioid overdose or a brainstem pathology, and a unilateral fixed dilated pupil with the affected eye being deviated down and out is suggestive of raised ICP causing pressure on the oculomotor nerve. It is important to consider that findings on pupil assessment may be affected by previous ocular injury or cataracts, and also by drugs used in resuscitation such as adrenaline or atropine. Absence of the corneal reflex and cough reflex are seen in midbrain and medullary lesions respectively.
      Table 1Examination findings and clinical significance
      Examination findingPotential significance
      MeningismSubarachnoid haemorrhage, meningoencephalitis
      Localizing signsStructural lesion
      PapilloedemaRaised ICP/asphyxia
      Vitreous haemorrhagesSubarachnoid haemorrhage
      Pupillary responses
      Fixed constricted pupilsBrainstem insult or opioid overdose
      Unilateral dilated pupil deviated down and outPressure on oculomotor nerve, Posterior communicating aneurysm or uncal herniation
      Unilateral constricted pupilHorner's syndrome
      Brainstem reflexes
      Corneal reflex absentPontine lesion
      Absent coughMedullary Injury
      Motor function
      Decerebrate posturinglesion below midbrain
      (pronation, extension upper limbs)
      Decorticate posturingBrainstem lesion above midbrain
      (upper limb flexion, lower limb extension)
      Myoclonic JerkingHypoxic-Ischaemic encephalopathy
      Motor examination may reveal abnormal posturing, spasticity, flaccidity or involuntary reflex movements such as myoclonus or tremor. Decerebrate posturing refers to bilateral upper and lower limb extensor posturing and is usually indicative of a mid-brain or pontine lesion, whereas decorticate posturing is characterized by bilateral upper limb flexion and lower limb extension and is seen with upper brain stem lesions. Myoclonic jerking is commonly seen with anoxic-ischaemic encephalopathy. Throughout the examination it is important to be aware of confounding factors that may affect findings, such as hypothermia, sedation, shock and drug intoxication. Hypnotic agents, for example, can suppress brainstem reflexes and create false localizing signs.

      Coma scales

      The most widely used initial assessment for coma is the Glasgow Coma Scale (GCS). This is a 15-point scale composed of motor, verbal and eye-opening scores to verbal and painful stimulation. It is not of diagnostic value, but it provides a reliable way of objectively monitoring the clinical course of a coma patient. The Full Outline of Unresponsiveness (FOUR) Scale, is an alternative to GCS which can be used in intubated patients. This comprises a 16-point scale, assessing eye opening, respiration pattern, brainstem reflexes and motor response (Table 2).
      Table 2Coma scales
      Glasgow Coma Scale
      Best eye openingSpontaneous4
      To Voice3
      To pain2
      No response1
      Best verbal responseOrientated5
      Inappropriate words3
      Incomprehensible sounds2
      No verbal response1
      Best motor responseObeys commands6
      Localizing pain5
      Withdrawal from pain4
      Flexion to pain3
      Extension to pain2
      No motor response1
      Full Outline of Unresponsiveness (FOUR) Scale
      Eye responseSpontaneous eye opening, tracks, blinks to command4
      Eyes open. No tracking or blinking to command3
      Eyes open to loud voice2
      Eyes open to pain1
      No response0
      Motor responseObeys commands Makes a sign e.g. thumbs up4
      Localizing pain3
      Flexion to pain2
      Extension to pain1
      No response or myoclonic status0
      Brainstem reflexesPupil and corneal reflexes and cough present4
      One pupil unreactive. Corneal reflex and cough present3
      Pupils OR corneal reflex unreactive2
      Pupils AND corneal reflex absent, cough present1
      Absent pupil, corneal and cough reflex0
      IntubationNormal breathing pattern, not intubated4
      Cheyne-Stokes breathing, not intubated3
      Irregular breathing pattern, not Intubated2
      Intubated and triggering ventilator1
      Apnoeic or Intubated and not triggering0


      Bloods should be sent for full blood count, electrolytes, liver function, clotting profile and thyroid function and urine sent for toxicology. Where a rapidly reversible cause for coma has not been identified by the above, an urgent computerized tomography (CT) head scan ± CT angiogram is indicated. This is particularly of importance for identifying intracranial pathologies where a time critical intervention may be warranted, such as thrombolysis or thrombectomy for acute ischaemic stroke, hydrocephalus requiring urgent CSF diversion or decompressive craniectomy for raised ICP. Blood cultures should be taken where patients are febrile over 38oC or hypothermic without an identifiable cause. Lumbar puncture is indicated following CT scan in patients with suspected central nervous system (CNS) infection or inflammation, although this should not delay administration of antibiotics. Where non-convulsive status epilepticus is suspected, an electroencephalogram (EEG) should be considered.
      Magnetic resonance imaging (MRI) with diffusion-weighted imaging (DWI) or fluid-attenuated inversion recovery (FLAIR) sequences may be indicated to aid diagnosis where the above investigations have not revealed a cause. DWI abnormalities usually result from acute stroke, whereas FLAIR sequences can reveal abnormalities suggestive of an underlying inflammatory or demyelinating condition. Where CT angiogram has identified a likely underlying vascular cause, digital subtraction angiography may be performed to investigate this and guide further management.

      Coma mimics

      It is important to be aware of coma mimics where a person's arousal and responsiveness may appear to be absent, but their conscious level is not affected. These include locked-in syndrome, Guillain-Barre syndrome, psychogenic unresponsiveness and other neuropsychiatric disorders.

      Time critical situations

      Where structural lesions with evidence of raised ICP are identified on imaging, immediate neurosurgical opinion should be sought.
      In patients with traumatic brain injury or raised ICP from a structural lesion, interim measures to control high ICP and prevent secondary neurological damage include deepening of sedation with propofol or barbiturates and the use of hyperosmolar therapy (mannitol 0.25–1 g/kg or hypertonic saline 3% 3 ml/kg) ensuring that systolic blood pressure (SBP) does not drop below 90 mmHg.
      • Bateman D.E.
      Neurological assessment of coma.
      Hyperventilation can be used acutely to target PaCO2 4.0–4.5 KPa but must not be prolonged and it should be noted that cerebral blood flow is often significantly reduced anyway in the first 24 hours following injury. Cerebral venous drainage should be encouraged by elevating the head of the bed to 20 degrees with the head in a neutral position and avoiding venous compression from endotracheal tube ties. Where possible, ICP monitoring should be instituted in all patients with a GCS <8 and abnormal CT scan, or if the CT scan is normal where two of the following are present: age >40 years, motor posturing, SBP <90 mmHg. Targeted temperature management (TTM) should be carried out to normothermia except in those patients who have had an out of hospital cardiac arrest with a shockable 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 presentation is <6 and there is evidence of raised intracranial pressure, use of cerebrospinal fluid (CSF) drainage systems may be considered.
      • Carney N.
      • Totten A.M.
      • O'Reilly C.
      • et al.
      Guidelines for the management of severe traumatic brain injury, fourth edition.
      If acute ischaemic stroke is identified as a likely cause, urgent assessment by a stroke physician should be sought and thrombolysis with or without thrombectomy should be considered. Acute ischaemic strokes presenting with coma will usually affect the posterior circulation, although coma can be a presenting feature in anterior circulation stroke in those patients who have pre-existing contralateral hemispheric damage, or where associated oedema has caused brainstem compression such as is often seen in malignant middle cerebral artery stroke. If thrombolysis is being considered, blood pressure should be maintained below 185/110 mmHg.
      2018 Guidelines for the Early Management of Patients With Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association.
      In the case of acute intracerebral haemorrhage, systolic blood pressure should be targeted to <140 mmHg and this should be achieved in the first hour of treatment unless exclusion criteria are present. Contraindications to rapid reduction in blood pressure in the presence of acute intracerebral haemorrhage include; having an underlying structural cause of the bleed, a GCS of <6, requirement for early neurosurgical evacuation or the presence of a massive haematoma with a poor expected prognosis.


      The outcome after coma largely depends on the underlying cause, but also the presence of secondary cerebral insult, duration and depth of coma and other factors such as age, bilaterally absent pupillary light reflex and hypotension at presentation. There is an increasing probability of better outcome with higher GCS at presentation and those who maintain normal brainstem reflexes throughout. Better outcomes are associated with coma secondary to toxic and metabolic insults compared to structural causes, and with traumatic coma when compared to non-traumatic coma. In patients with hypoxic-ischaemic injury following cardiac arrest, current guidelines recommend that prognostication should not be performed before 72 hours after return of spontaneous circulation.
      • Sandroni C.
      • Cariou A.
      • Cavallaro F.
      • et al.
      Prognostication in comatose survivors of cardiac arrest: an advisory statement from the European Resuscitation Council and the European Society of Intensive Care Medicine.
      Prognostication should involve a multimodal approach incorporating radiological, electrophysiological and serum biochemistry testing. Magnetic resonance Imaging (MRI) is the imaging modality of choice in evaluating the extent of axonal injury, and somatosensory evoked potentials and EEG have been demonstrated to have a predictive value in patients following hypoxic events and traumatic brain injury. High serum levels of neuron specific enolase are also associated with poor outcome in these patients.


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