01OverviewDefinition, clinical context and the essential points that orientate the chapter.
Reduced consciousness spans mild inattention to unresponsiveness and reflects dysfunction of both cerebral hemispheres, the ascending arousal system or global physiology. A structural lesion is more likely with focal motor signs, asymmetric pupils or gaze, but toxic-metabolic coma can still be asymmetric and structural disease can initially look diffuse. Work in parallel: resuscitate, collect time-critical evidence, examine, test glucose and obtain targeted imaging and laboratory studies.
GCS is a communication and trend tool, not a diagnosis. Record the response elicited and the stimulus used, starting with voice and using peripheral pressure only when necessary. Localising or withdrawing should be distinguished from abnormal flexion and extension. In an intubated patient, record verbal response as not testable rather than assigning a misleading normal or minimum value; use serial pupils and limb findings alongside physiology.
Causes include vascular events, trauma, seizures, infection, hypoglycaemia and other metabolic derangements, hypoxia, hypercapnia, endocrine crises, hepatic or uraemic encephalopathy, temperature disorders, drugs and poisons. Thiamine deficiency, carbon monoxide exposure, pregnancy-related disease and occult sepsis can be missed without context. Toxicology screens have limited panels and detection windows and rarely prove causality on their own.
Diagnosis and confirmation of death using neurological criteria is a distinct, legally and ethically important process. The current Academy of Medical Royal Colleges Code applies across the UK and defines the prerequisites, exclusions, examination, apnoea assessment, professional responsibilities and communication. Testing and certification must never occur outside current national criteria, local governance and direct supervision by qualified clinicians.
Key points
- Use ABCDE before neurological taxonomy. Hypoxia, hypercapnia, hypotension and hypoglycaemia can cause or worsen brain injury and must be corrected while history and examination proceed.
- Record the best eye, verbal and motor responses that make up GCS, not only the total. Note intubation, language, hearing, sedation, paralysis, facial injury and baseline disability that limit components.
- Establish exact onset and trajectory from witnesses, ambulance records and digital or medication evidence; ask about trauma, headache, seizure, fever, toxins, diabetes, pregnancy, organ failure and psychiatric risk.
- Inspect pupils, gaze, eye position, motor asymmetry, tone, reflexes, plantar responses, breathing pattern, meningism, rash, temperature and signs of trauma while avoiding repeated painful stimulation.
- Pinpoint pupils and respiratory depression suggest opioid effect but are not diagnostic; unequal or newly fixed pupils may indicate herniation, ocular trauma, drug exposure or pre-existing disease.
- Postictal states usually improve. Persistent failure to recover, subtle twitching, gaze deviation, recurrent episodes or unexplained coma raises non-convulsive status and the need for urgent EEG advice.
- A normal initial CT does not exclude early ischaemia, meningitis, encephalitis, toxic-metabolic disease, non-convulsive seizure or all diffuse axonal injuries.
- Brainstem reflex examination used during resuscitation is not equivalent to formal neurological determination of death; sedatives, neuromuscular blockade and metabolic or temperature confounders must be resolved.
- The 2025 UK Code of Practice is the controlling reference for neurological criteria for death. Testing follows a documented plan, prescribed prerequisites, specified brainstem and apnoea components, and required examiner standards.
- Spinally mediated movement can occur after death has been confirmed using neurological criteria; clinicians should anticipate and explain this possibility without improvising interpretation.
- Communication with family should be staged, clear and separate diagnosis of death from possible donation discussions, using the terminology and support set out in national and local policy.
02AetiologyUnderlying causes, associations and risk factors, with why each one matters.
Structural brain injury
Haemorrhage, infarction, trauma, tumour, hydrocephalus and herniation reduce consciousness by damaging both hemispheres or the ascending arousal system in the brainstem.
Toxic and metabolic depression
Hypoglycaemia, hypoxia, hypercapnia, organ failure, electrolyte disturbance, sedatives, opioids and other toxins diffusely impair neuronal activity and may be reversible.
Seizure and infection
Postictal depression, non-convulsive status, meningitis and encephalitis can cause fluctuating or sustained unresponsiveness, often with subtle focal or systemic clues.
Temperature and endocrine emergencies
Hypothermia, severe hyperthermia, adrenal failure and thyroid-related crises can depress arousal and confound formal neurological assessment.
03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.
- 1Arousal-system disruption
Consciousness fails when the ascending reticular activating system, both cerebral hemispheres or their connecting networks cannot sustain wakefulness and awareness.
- 2Loss of integrated response
Cortical and brainstem dysfunction progressively impairs purposeful motor response, eye opening, language, breathing pattern and protective cranial reflexes.
- 3Secondary physiological injury
Airway obstruction, hypoventilation, hypoxia and hypotension further reduce cerebral perfusion and extend otherwise potentially reversible brain injury.
04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.
Falling consciousness with a newly dilated or unreactive pupil, progressive motor asymmetry, abnormal posturing, irregular respiration or Cushing-type physiology raises critical intracranial mass effect and requires immediate airway, neurosurgical and imaging action.
Reduced respiratory rate and tidal volume, impaired consciousness and small pupils with a compatible exposure suggests opioid toxicity. Hypoxia, mixed overdose and intracranial disease must still be considered, and response to naloxone does not end observation.
Fever, headache, photophobia, neck stiffness, rash, seizures, focal findings or behavioural change may indicate meningitis or encephalitis. Classic meningism can be absent in older, immunocompromised or deeply obtunded patients.
Unexplained persistent unresponsiveness, fluctuating cognition, subtle facial or limb twitching, eyelid myoclonia or eye deviation after a seizure or brain injury can represent ongoing electrical seizure and requires urgent EEG-supported assessment.
Symmetric motor findings, asterixis, multifocal myoclonus and fluctuating arousal with organ failure or biochemical disturbance suggests metabolic dysfunction, but new focal signs still mandate structural assessment.
05InvestigationsWhat to request, why it matters and how to interpret it.
Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.
- 01
Immediate glucose, blood gas and ECGFirst step - Why
- Identify rapidly reversible hypoglycaemia, ventilatory failure, acid-base disturbance and cardiotoxic or electrolyte effects.
- Interpretation and limitations
- Treat severe hypoglycaemia immediately and recheck. A venous gas can identify carbon dioxide retention or major acidosis; co-oximetry is needed for suspected carbon monoxide because pulse oximetry can appear normal.
- 02
FBC, U&E, calcium, magnesium, liver tests, CRP and targeted endocrine studies - Why
- Assess infection, organ failure and metabolic or endocrine precipitants of encephalopathy.
- Interpretation and limitations
- Interpret sodium, osmolality, renal and hepatic abnormalities with tempo and medication history. Use cortisol, thyroid, ammonia or toxicology testing selectively; an abnormal result may be contributory rather than sufficient.
- 03
Urgent non-contrast CT head with selected angiography - Why
- Detect haemorrhage, mass effect, hydrocephalus, large infarction, trauma and vascular occlusion or aneurysm.
- Interpretation and limitations
- Imaging follows the syndrome and stability. CT may miss early posterior-fossa infarction, encephalitis and diffuse axonal injury; persistent unexplained depression often needs MRI or repeat imaging after specialist review.
- 04
EEG or continuous EEG - Why
- Detect non-convulsive seizures and characterise diffuse cerebral dysfunction in selected patients.
- Interpretation and limitations
- An EEG is a time sample and sedatives alter the background. Urgency rises after status epilepticus, unexplained failure to wake and subtle motor phenomena; interpretation belongs with clinical neurophysiology.
- 05
Lumbar puncture after safety assessment - Why
- Investigate meningitis, encephalitis, inflammation or selected haemorrhage when clinically indicated.
- Interpretation and limitations
- Antimicrobial or antiviral treatment should not be delayed for unsafe or deferred puncture. Consider mass-effect risk, cardiorespiratory stability, coagulation and the need for imaging before the procedure.
- 06
Formal neurological-criteria documentation - Why
- Confirm that prerequisites, reversible confounders, prescribed clinical tests and apnoea assessment meet the current UK Code.
- Interpretation and limitations
- This is not a diagnostic test ordered for undifferentiated coma. It is undertaken only after irreversible brain injury is established, by clinicians meeting national competence and independence requirements, using current local forms and escalation for ancillary investigation when the Code permits or requires it.
06Differential diagnosisRealistic alternatives and the features that help distinguish them.
Locked-in syndrome
Quadriplegia and anarthria with preserved consciousness, vertical eye movement or blinking indicate ventral pontine motor disconnection rather than coma.
Postictal or medicine-related depression
A witnessed seizure or sedative exposure with steady improvement supports transient depression; persistent failure to recover requires EEG, toxicological and structural reassessment.
Neuromuscular paralysis
Neuromuscular blockers, severe junctional disease or peripheral paralysis can abolish movement despite awareness; pupils, eye movement, drug history and neurophysiology help prevent misinterpretation.
Functional unresponsiveness
Positive features such as resistance to eye opening may support functional unresponsiveness only after physiological, structural, toxic and epileptic causes are addressed.
Additional chapter-specific clues
A patient with ventral pontine injury may be conscious but quadriplegic and anarthric, retaining vertical eye movement or blinking. Deliberately test command-following through eye movements before concluding awareness is absent.
07ManagementImmediate care, first-line treatment, alternatives and escalation.
01Undifferentiated comaResuscitate and diagnose in parallelFirst stepA patient is unresponsive or substantially below their documented baseline without an established immediately reversible explanation.+
- 1Call for senior and airway help, use cervical-spine precautions when indicated, support oxygenation, ventilation and circulation, check glucose, gain IV access and treat active convulsive seizure.
- 2Obtain collateral history and examine GCS components, pupils, gaze, limbs, breathing, temperature, rash and trauma; send focused blood tests, ECG and toxicology samples without delaying urgent CT.
- 3Treat suspected infection, poisoning, metabolic crisis or intracranial catastrophe through the relevant protocol and repeat neurological findings after each intervention or deterioration.
02Failure to wakeRecheck confounders and occult seizureConsciousness remains impaired beyond the expected recovery from seizure, anaesthesia, sedation or initial physiological correction.+
- 1Reconcile every sedative, analgesic, paralytic and recreational exposure with timing, organ function and measured temperature; reassess glucose, gases, electrolytes and haemodynamics.
- 2Repeat focal and brainstem examination, review existing imaging and discuss MRI, vascular imaging, lumbar puncture and urgent EEG with the appropriate specialists.
- 3Provide neuroprotective supportive care, pressure and corneal protection, thrombosis and nutrition planning, and structured family updates while cause and prognosis remain under review.
03Possible neurological deathFollow the UK Code without shortcutsCatastrophic irreversible brain injury is established and the clinical team is considering diagnosis and confirmation of death using neurological criteria.+
- 1The responsible senior team verifies the established aetiology, irreversibility, timing and all physiological, pharmacological, neuromuscular and metabolic prerequisites and exclusions specified by the current Code.
- 2Appropriately qualified examiners perform and document the nationally defined clinical and apnoea testing through local governance, pausing when any element is unsafe, equivocal or confounded and obtaining expert or ancillary guidance where required.
- 3Record the legally relevant time and conclusions exactly as the Code directs, communicate compassionately with those close to the patient and keep any organ-donation conversation within the separate specialist pathway.
Key medicines and prescribing safety2 treatments · regimens, roles and cautions+
Intravenous glucose for severe hypoglycaemia
Give 150–200 mL glucose 10% or 75–100 mL glucose 20% intravenously, then recheck promptly and repeat or infuse according to response and local emergency policy.Ensure IV patency because hypertonic glucose extravasation injures tissue; investigate the cause, monitor for recurrence and do not delay glucose while arranging thiamine in a malnourished patient.
Naloxone for suspected opioid toxicity
Titrate intravenous naloxone in locally approved increments to restore adequate ventilation rather than full alertness; use the current emergency or toxicology protocol and repeat dosing or infusion when long-acting opioids outlast it.Abrupt high-dose reversal can precipitate severe withdrawal, agitation, vomiting and sympathetic stress; its duration may be shorter than the opioid, and non-response does not exclude another emergency.
08ComplicationsImportant consequences, why they occur and why they matter clinically.
Airway loss and aspiration
Reduced pharyngeal reflexes, vomiting and secretion retention cause obstruction, aspiration pneumonia and hypoxic injury unless airway protection is actively managed.
Immobility-related injury
Prolonged unconsciousness promotes pressure damage, venous thrombosis, contracture, corneal injury, infection and severe deconditioning during prolonged critical illness.
Progressive secondary brain damage
Hypoxia, hypotension, fever, seizures and raised intracranial pressure worsen neuronal injury and may convert a treatable cause into permanent disability or death.
Erroneous prognostication
Sedation, hypothermia, metabolic disturbance and paralysis can mimic absent brain function, so premature prognostic or death-testing conclusions risk profound ethical and clinical harm.
09Monitoring and follow-upTreatment response, safety checks and longer-term review.
- Record GCS components, pupils, limb responses and physiological observations at a frequency determined by acuity and the head-injury, stroke, toxicology or critical-care pathway.
- Trend ventilation with respiratory rate, tidal pattern, blood gases and airway protection; pulse oximetry alone can miss hypercapnic failure or oxygen-treated hypoventilation.
- Repeat glucose after correction and continue surveillance for recurrent hypoglycaemia, especially after long-acting insulin or sulfonylurea exposure.
- Monitor temperature, urine output, electrolytes and organ function because fever, diabetes insipidus, renal failure and hepatic dysfunction alter neurological status and drug clearance.
- After naloxone response, observe for recurrent respiratory depression for a duration based on the suspected opioid, co-ingestants and toxicology advice.
- Document sedative and neuromuscular-blocking doses, stop times and relevant clearance evidence whenever brainstem assessment or prognostication is being considered.
- Use structured, repeated family communication with named clinical contacts; uncertainty about cause or prognosis should be stated rather than hidden behind a consciousness score.
10Special situationsVariants, exceptions and circumstances that change the usual approach.
GCS components outweigh totals
A total of eight can represent several very different patients. Eye, verbal and motor responses, trend and confounders communicate localisation and airway risk far better than the sum alone.
Sedation may persist
Renal or hepatic failure, obesity, hypothermia and prolonged infusion can extend drug effect beyond familiar half-lives. Formal death testing requires evidence-based exclusion, not elapsed time guessed from routine practice.
Pupils are not a cause
Small pupils occur with opioids and pontine injury; large pupils occur with drugs, ocular disease and third-nerve compression. Size must be combined with reactivity, symmetry, breathing and motor signs.
Spinal movements can persist
Reflex movements generated below the brain can occur despite confirmed death using neurological criteria. Anticipatory explanation prevents misinterpretation, but unexpected responses still require the testing team to follow the Code.
Locked-in awareness is testable
Before assuming absent awareness in a quadriplegic, non-verbal patient, ask for vertical eye movement or blinking to command and reassess brainstem localisation and communication options.
Diagnosis and donation are separate
The criteria and clinical conclusion of death do not depend on transplant suitability. Specialist donation teams become involved through governed processes after appropriate family communication.
11Common pitfallsFrequent interpretation and management errors.
- 01
Calculating a GCS total while omitting the separate responses and confounders.
- 02
Sending a patient to imaging before securing an unsafe airway or correcting hypoglycaemia.
- 03
Assuming persistent unconsciousness is postictal without considering non-convulsive status, infection or structural disease.
- 04
Using urine toxicology as proof that a detected substance caused the current coma.
- 05
Equating an informal absent brainstem reflex with death using neurological criteria.
- 06
Underestimating sedative persistence in hypothermia or organ failure before prognostication or formal testing.
- 07
Combining the explanation of death with organ donation in a way that suggests the diagnosis was influenced by transplantation.