Unresponsive patient

An unresponsive patient shows no purposeful response to voice or physical stimulation. Coma is a state of unrousable unresponsiveness (Glasgow Coma Scale 8 or less).

Mechanisms. Consciousness requires an intact ascending reticular activating system in the upper pons and midbrain and both cerebral hemispheres. Coma results from bilateral hemispheric dysfunction, direct brainstem damage, or both. A unilateral hemispheric lesion causes coma only when it compresses the brainstem (herniation).

Classification.

• Structural: supratentorial mass lesion with herniation, brainstem or posterior fossa lesion.
• Diffuse and metabolic: hypoglycaemia, hypoxia, toxins, drugs, organ failure, infection, seizure related, temperature and electrolyte disturbance.
• Psychogenic (functional) unresponsiveness: a diagnosis of exclusion.
• Mimics: locked-in syndrome, severe neuromuscular paralysis, akinetic mutism, catatonia, and hypoactive delirium.

Assessment scales. AVPU (alert, responds to voice, responds to pain, unresponsive). Glasgow Coma Scale: eye opening 1 to 4, verbal 1 to 5, motor 1 to 6, total 3 to 15. Use the best motor response. Record each component, since the total hides difference.

Key distinctions. Structural coma tends to have asymmetric signs, brainstem reflex loss, and a stepwise or rapid course. Metabolic coma tends to be symmetric with preserved pupillary reflexes, apart from some drug effects. Cardiac arrest recognition (no normal breathing, no pulse) takes priority over every other step.

Immediate approach. Check responsiveness, open the airway, look for normal breathing for up to 10 seconds, and check a central pulse. If there is no pulse or no normal breathing, start chest compressions and defibrillation without further assessment. Otherwise assess airway, breathing, circulation, disability and exposure, and check capillary glucose within the first minutes.

History from others. Paramedics, witnesses, relatives, medical alert items, medicine packets, empty containers, suicide notes, recent illness, headache, trauma, seizure, fever, rash, travel (malaria), alcohol, substance use, diabetes, anticoagulants, psychiatric history and the time last seen well.

Examination.

• Airway and breathing pattern: snoring, stridor, Kussmaul breathing (acidosis), Cheyne-Stokes (bilateral hemispheric or metabolic), ataxic or gasping (medullary), apnoea.
• Circulation: pulse rate and rhythm, blood pressure (hypertension with bradycardia and irregular breathing is the Cushing response to raised intracranial pressure), temperature, capillary refill, saturation.
• Skin and general: needle marks, jaundice, petechiae or purpura (meningococcal disease), cherry red skin (carbon monoxide, an unreliable sign), injuries, bruising behind the ear or around the eyes (skull base fracture), tongue bite, incontinence, breath odour (alcohol, ketones, uraemia, hepatic fetor).
• Neck: stiffness suggests meningitis or subarachnoid haemorrhage, but do not flex the neck if there is trauma.
• Pupils: pinpoint (opioids, pontine lesion, organophosphates), dilated and fixed (anticholinergics, midbrain lesion, deep hypoxia), unilateral dilated fixed pupil (uncal herniation, third nerve compression), small reactive (metabolic).
• Eye movements: oculocephalic reflex (avoid with suspected cervical injury) and oculovestibular testing. Roving eye movements indicate an intact brainstem. A conjugate deviation indicates a hemispheric or pontine lesion.
• Corneal, cough and gag reflexes.
• Motor: asymmetry, tone, decorticate (flexor) or decerebrate (extensor) posturing, reflexes, plantars, myoclonus, subtle facial or eye twitching (non-convulsive status).
• Functional clues: resistance to eye opening, eyes deviated away from the examiner, normal pupils and reflexes, avoidance of facial injury when a hand is dropped, and a normal caloric response with fast phase nystagmus.

Red flags.

• Glasgow Coma Scale 8 or less, or a fall of 2 or more points.
• Unequal or fixed pupils, or Cushing response.
• Airway compromise, absent gag, inadequate ventilation.
• Capillary glucose under 4.0 mmol/L.
• Fever with rash or neck stiffness.
• Temperature over 40 °C or under 32 °C.
• Penetrating or blunt head or neck injury.

Special groups. Children: glucose 10% 2 mL/kg IV for hypoglycaemia and weight based dosing for all drugs. Pregnancy and postpartum: eclampsia and intracranial haemorrhage. Older adults: hypoactive delirium, drug accumulation and subdural haematoma. Endemic areas: cerebral malaria must be excluded in every unresponsive febrile patient.

Structural.

• Intracerebral haemorrhage, subarachnoid haemorrhage, ischaemic stroke with oedema, basilar artery occlusion, cerebellar haemorrhage, pontine haemorrhage.
• Subdural haematoma, extradural haematoma, traumatic brain injury.
• Brain tumour, brain abscess, hydrocephalus, cerebral venous thrombosis.

Metabolic and endocrine.

• Hypoglycaemia, diabetic ketoacidosis, hyperosmolar hyperglycaemic state.
• Hypoxia, hypercapnia, hyponatraemia, hypernatraemia, hypercalcaemia, hypomagnesaemia.
• Uraemia, hepatic encephalopathy, hyperammonaemia.
• Myxoedema coma, adrenal crisis, Wernicke encephalopathy.
• Hypothermia, heat stroke.

Toxic.

• Opioids, benzodiazepines, alcohol, barbiturates, gamma-hydroxybutyrate, tricyclic antidepressants, antipsychotics, anticholinergics, clonidine.
• Salicylate and paracetamol poisoning, methanol, ethylene glycol, carbon monoxide, cyanide, organophosphates.
• Serotonin syndrome and neuroleptic malignant syndrome.

Infection. Bacterial meningitis, viral encephalitis (herpes simplex), cerebral malaria, sepsis, cerebral abscess, neurosyphilis, typhoid encephalopathy.

Seizure related. Post-ictal state, non-convulsive status epilepticus, status epilepticus.

Cardiovascular and circulatory. Cardiac arrest, arrhythmia with syncope, severe bradycardia, shock of any cause, aortic dissection, hypertensive encephalopathy, posterior reversible encephalopathy syndrome, eclampsia.

Psychiatric and functional. Catatonia, functional (psychogenic) unresponsiveness.

Mimics. Locked-in syndrome, Guillain-Barre syndrome with severe paralysis, myasthenic crisis, neuromuscular blockade.

Concurrent with stabilisation.

• Capillary glucose immediately (treat if under 4.0 mmol/L).
• Arterial or venous blood gas with lactate and carboxyhaemoglobin: pH, pCO2 (hypercapnia), bicarbonate, anion gap, sodium, potassium, calcium, lactate (over 2 mmol/L abnormal).
• 12 lead ECG and continuous cardiac monitoring: QTc (over 500 ms is high risk), tricyclic effects (QRS over 100 ms), ischaemia, arrhythmia.
• Bloods: full blood count, urea, creatinine, electrolytes, corrected calcium, magnesium, phosphate, liver tests, ammonia, coagulation, creatine kinase, troponin, CRP, blood cultures, thyroid function, cortisol if adrenal crisis is suspected, serum osmolality (osmolar gap over 10 mOsm/kg suggests toxic alcohols), paracetamol and salicylate levels in every unexplained coma, ethanol level, and malaria film or rapid antigen test in endemic or travel settings.
• Urine drug screen is supportive only.

Imaging.

• Non-contrast CT head as soon as the patient is stable and the cause is not clear, and before lumbar puncture. CT cervical spine with trauma.
• CT angiography when basilar artery occlusion, subarachnoid haemorrhage or venous thrombosis is suspected. CT is insensitive for early brainstem infarction, posterior fossa lesions, encephalitis and diffuse axonal injury, so MRI is needed when CT is normal and the cause is unclear.
• Chest radiograph for aspiration and pulmonary disease.

Lumbar puncture. After CT excludes mass effect and coagulopathy is addressed. Do not delay antibiotics for CT or lumbar puncture. Opening pressure, cell count, protein, glucose with paired plasma glucose, Gram stain, culture, viral PCR (herpes simplex), and a sample stored for later tests.

EEG. Urgent when non-convulsive status epilepticus is possible (fluctuating consciousness, subtle twitching, unexplained coma after seizure, coma after cardiac arrest).

Limitations. Glasgow Coma Scale is limited by intubation, sedation, facial swelling and aphasia. Toxicology screens miss many agents. A normal CT does not exclude stroke or encephalitis. Brain death testing is valid only after exclusion of sedatives, hypothermia and metabolic disturbance.

Stabilisation.

• Airway: jaw thrust or head tilt with chin lift (jaw thrust only if cervical injury is possible), suction, oropharyngeal airway. Intubation by an experienced operator for Glasgow Coma Scale 8 or less with inability to protect the airway, hypoventilation, or rapid deterioration.
• Breathing: oxygen at 15 L/min via reservoir mask, then titrate to saturation 94 to 98% (88 to 92% if at risk of hypercapnic respiratory failure). Support ventilation, aim for normocapnia (PaCO2 4.5 to 5.0 kPa) unless herniation is present.
• Circulation: IV or intraosseous access, 500 mL isotonic crystalloid bolus for hypotension (reassess after each bolus), and target systolic blood pressure over 100 mmHg in unexplained coma.
• Position: head up 30 degrees if raised intracranial pressure is suspected and spinal injury excluded, or recovery position if breathing spontaneously with no trauma. Stabilise the cervical spine after trauma.
• Temperature: cool to under 38 °C if hyperthermic, rewarm gently if under 35 °C.

Targeted treatment (give while the cause is being determined).

• Hypoglycaemia (capillary glucose under 4.0 mmol/L): glucose 10% 150 to 200 mL IV over 15 minutes, or glucose 20% 75 to 100 mL IV; repeat capillary glucose at 10 to 15 minutes and every 15 minutes initially; if no IV access, glucagon 1 mg IM, which may be repeated after 10 to 15 minutes (maximum 1 mg a dose); glucagon is less effective in starvation, liver disease and alcohol misuse; give thiamine first or with glucose in alcohol misuse or malnutrition; sulphonylurea hypoglycaemia recurs, so observe for at least 24 hours.
• Possible Wernicke encephalopathy (alcohol misuse, malnutrition, vomiting): thiamine 500 mg IV over 30 minutes three times daily for 2 to 3 days, then 250 mg IV once daily for 3 to 5 days; monitor for anaphylaxis (rare, but resuscitation facilities should be at hand), replace magnesium, and continue oral thiamine after.
• Opioid toxicity (respiratory rate under 10 breaths/min, pinpoint pupils, sedation): naloxone 0.4 mg IV, repeated every 2 to 3 minutes; in chronic opioid users or frail patients use 0.04 to 0.1 mg increments to avoid withdrawal; titrate to a respiratory rate over 10 breaths/min; maximum about 10 mg before the diagnosis is reconsidered; IM or subcutaneous 0.4 to 0.8 mg if no IV access; naloxone lasts 20 to 90 minutes, shorter than most opioids, so consider an infusion of about two thirds of the reversal dose each hour and observe; monitor respiration, saturation and sedation; aspirate or ventilate if respiratory effort is inadequate.
• Benzodiazepine oversedation (iatrogenic only, not for mixed or unknown overdose, long term benzodiazepine users, epilepsy or tricyclic co-ingestion because of seizure risk): flumazenil 0.2 mg IV over 15 seconds, then 0.1 mg every 60 seconds; maximum 1 mg in one course; resedation is likely since the half life is short; monitor respiration and watch for seizures.
• Seizure activity: lorazepam 4 mg IV (0.1 mg/kg to a maximum 4 mg), repeat once after 10 minutes if seizing; monitor respiration and blood pressure; reduce dose in frail older adults and respiratory disease.
• Raised intracranial pressure or herniation signs (unilateral dilated pupil, posturing, Cushing response): head up 30 degrees, avoid hypotension and hypoxia, mannitol 20% 0.5 to 1 g/kg IV over 15 to 20 minutes, or 3% sodium chloride 150 to 250 mL IV over 10 to 20 minutes; monitor serum sodium every 4 to 6 hours (stop if over 160 mmol/L), serum osmolality (stop mannitol if over 320 mOsm/kg), urine output and blood pressure; avoid mannitol in anuria and pulmonary oedema; urgent neurosurgical call.
• Suspected bacterial meningitis or encephalitis: ceftriaxone 2 g IV every 12 hours (maximum 4 g daily) within 1 hour of recognition without waiting for CT or lumbar puncture; dexamethasone 10 mg IV every 6 hours for 4 days, started before or with the first antibiotic dose; add amoxicillin 2 g IV every 4 hours if aged over 60 or immunocompromised (Listeria); add aciclovir 10 mg/kg IV every 8 hours (infused over 1 hour, with hydration, for 14 to 21 days if herpes encephalitis is confirmed) when encephalitis is possible; monitor creatinine, and reduce aciclovir to every 12 hours for CrCl 25 to 50 mL/min and every 24 hours for CrCl 10 to 25 mL/min.
• Cerebral malaria (fever, travel or residence in an endemic area, positive test): artesunate 2.4 mg/kg IV at 0, 12 and 24 hours, then once daily until oral therapy is tolerated (minimum 24 hours of IV treatment), followed by a full oral antimalarial course; use 3 mg/kg for children under 20 kg; monitor glucose every 1 to 2 hours (hypoglycaemia is common), parasitaemia, haemoglobin, creatinine and for delayed haemolysis for up to 4 weeks.
• Unknown ingestion with possible paracetamol: send a level and start acetylcysteine 150 mg/kg IV in 200 mL glucose 5% over 1 hour, then 50 mg/kg in 500 mL over 4 hours, then 100 mg/kg in 1000 mL over 16 hours (use a maximum weight of 110 kg); monitor liver tests, INR, creatinine and for anaphylactoid reaction (slow or pause the infusion and give an antihistamine, restarting when settled); adjust fluid volume in children.
• Carbon monoxide poisoning: oxygen 100% by non-rebreather mask until carboxyhaemoglobin is under 3% (under 10% in smokers) and symptoms resolve; pulse oximetry reads falsely normal.
• Diabetic ketoacidosis or hyperosmolar state: isotonic saline 1 L over the first hour (500 mL in the first 15 to 30 minutes if shocked), then 1 L over 2 hours, with potassium replaced to match the serum level, and fixed rate insulin 0.1 units/kg/hour started after the first hour of fluids and a potassium over 3.5 mmol/L; hourly glucose and ketones.
• Adrenal crisis suspected: hydrocortisone 100 mg IV immediately, then 50 mg IV every 6 hours (or 200 mg over 24 hours by infusion); monitor sodium, potassium, glucose and blood pressure; give isotonic saline for hypotension.
• Eclampsia or severe pre-eclampsia in pregnancy or after delivery: magnesium sulphate 4 g IV over 5 to 15 minutes, then 1 g/hour for 24 hours after the last seizure; monitor reflexes, respiratory rate over 12 breaths/min and urine output over 100 mL in 4 hours; reduce the infusion in renal impairment; left lateral tilt in the third trimester, and urgent obstetric review.
• Hyponatraemia with severe neurological symptoms: 3% sodium chloride 150 mL IV over 20 minutes, repeated once if symptoms persist; monitor sodium every 20 minutes to 1 hour; limit the rise to 8 to 10 mmol/L in 24 hours.

Special groups and other causes. Treat hyperkalaemia, hypocalcaemia, hypothermia and sepsis on their own findings. Toxic alcohol and tricyclic overdoses need poison centre advice and critical care. Do not give flumazenil for tricyclic overdose.

Monitoring. Continuous ECG, saturation, capnography when ventilated, and blood pressure. Glasgow Coma Scale and pupils every 15 minutes at first, then hourly. Capillary glucose hourly until stable, then every 4 hours. Temperature, urine output through a catheter, and electrolytes every 4 to 6 hours.

Referral and escalation. Critical care for Glasgow Coma Scale 8 or less, airway compromise, or deterioration. Neurosurgery for haematoma, hydrocephalus, abscess or herniation. Neurology for encephalitis, non-convulsive status and unexplained coma. Toxicology or poison centre for overdose. Infectious diseases for suspected meningitis, encephalitis or cerebral malaria. Obstetrics for pregnant patients. Brain death assessment by two experienced clinicians is considered only after reversible causes are excluded and the cause is established.

Admission criteria. All patients who remain unresponsive or have a Glasgow Coma Scale under 15 go to a resuscitation area, then to critical care or a high dependency unit. Patients with opioid toxicity reversed by naloxone are observed for at least 2 hours after the last dose with normal respiratory rate and consciousness, and for longer (up to 6 hours) after methadone, modified release opioids or large ingestions. Hypoglycaemia in a patient taking insulin or a sulphonylurea needs observation for sulphonylurea cases and review of therapy.

Discharge and safety netting. Discharge only when fully recovered, the cause is clear and treated, the patient has a responsible adult, and a plan is in place for the underlying condition (for example hypoglycaemia education, naloxone supply, driving advice after loss of consciousness). Patients and family are told to return for recurrent unresponsiveness, seizure, severe headache, confusion, vomiting, weakness or fever.