Unexplained collapse

Unexplained collapse is a sudden fall or loss of postural tone, with or without loss of consciousness, for which no cause is evident at first contact. It includes true syncope (transient loss of consciousness from global cerebral hypoperfusion with rapid onset, short duration and spontaneous complete recovery), seizures, falls, metabolic collapse, intoxication, psychogenic episodes and sudden cardiac events.

Clinical relevance. Syncope accounts for about 1% to 3% of emergency visits. Cardiac causes carry the highest mortality (about 18% to 33% at 1 year) while reflex syncope is benign. Collapse in a young person or during exertion may be the only warning of sudden cardiac death.

Classification of transient loss of consciousness.

• Syncope: reflex (vasovagal, situational, carotid sinus), orthostatic hypotension (drugs, volume depletion, autonomic failure), cardiac (arrhythmia, structural, ischaemic, pulmonary embolism).
• Epileptic seizures.
• Psychogenic pseudosyncope and functional seizures.
• Rare: subclavian steal, vertebrobasilar transient ischaemic attack, cataplexy.

Collapse without loss of consciousness. Falls (mechanical, gait and balance disorders), drop attacks, metabolic (hypoglycaemia), cataplexy, functional weakness.

Mechanism of syncope. Systolic blood pressure falls under about 60 mmHg or cerebral blood flow falls for 6 to 8 seconds, producing loss of consciousness. Reflex syncope follows an abnormal vagal and sympathetic response. Orthostatic hypotension follows failure of compensatory vasoconstriction. Cardiac syncope follows a drop in cardiac output from rhythm or structural disease.

History. (Obtain a witness account.)

• Circumstances: standing, sitting, lying, during exercise (high risk), after exercise, on standing up, during or after micturition, cough, defaecation, swallowing, turning the head or neck, emotion, pain, heat, crowd, prolonged standing.
• Prodrome: nausea, sweating, pallor, warmth, visual dimming (suggests reflex); palpitations (arrhythmia); no warning (cardiac); aura, déjà vu, smell (seizure); chest pain or breathlessness (cardiac, pulmonary embolism); severe headache (subarachnoid haemorrhage); abdominal or back pain (aortic or bleeding cause).
• Event: duration of unresponsiveness (under 30 seconds in syncope, minutes in seizure), colour, myoclonic jerks (brief, after collapse in syncope), tongue biting on the side, incontinence, head turning, rhythmic movement, eyes open.
• Recovery: rapid and clear (syncope), prolonged confusion for over 5 minutes, headache, muscle pain (seizure).
• Past history: heart disease, arrhythmia, heart failure, diabetes, epilepsy, anaemia, bleeding, pregnancy, psychiatric illness, previous collapses.
• Family history of sudden death under 50, cardiomyopathy, long QT syndrome, Brugada syndrome, unexplained drowning or single vehicle accidents.
• Drugs: antihypertensives, diuretics, nitrates, alpha blockers, beta blockers, calcium channel blockers, digoxin, antiarrhythmics (QT prolonging), antipsychotics, tricyclics, macrolides, fluoroquinolones, insulin, sulphonylureas, phosphodiesterase inhibitors, alcohol, recreational drugs.
• Fluid intake, vomiting, diarrhoea, haemorrhage, recent illness, recent long travel.

Examination.

• Pulse (rate, rhythm), blood pressure lying and after 1 and 3 minutes standing (orthostatic hypotension: fall of 20 mmHg systolic or 10 mmHg diastolic, or standing systolic under 90 mmHg), blood pressure in both arms, temperature, oxygen saturation, respiratory rate, capillary glucose.
• Cardiac: murmurs (aortic stenosis, hypertrophic cardiomyopathy, mitral stenosis), heart sounds, signs of heart failure, jugular venous pressure.
• Carotid bruits, carotid sinus massage (if over 40 years with no bruit or stroke, with monitoring).
• Neurological: focal deficit, gait, tongue bite, cognitive state, signs of Parkinson disease.
• Abdomen and rectal examination for bleeding, pulsatile mass, pregnancy test in women of reproductive age.
• Injury from the fall: head, neck, spine, hip, ribs.

Red flags.

• Collapse during exertion or lying down.
• Chest pain, breathlessness, palpitations before collapse.
• Abnormal ECG, heart failure, structural heart disease, murmur.
• Family history of sudden death under 50.
• Syncope with no prodrome, injury, or older age with multiple comorbidities.
• Systolic blood pressure under 90 mmHg, anaemia, gastrointestinal bleeding, haematocrit under 30%.
• Severe headache, neck stiffness, focal neurological signs.
• Abdominal or back pain with hypotension, pulsatile mass.
• Pregnancy with abdominal pain (ectopic pregnancy).
• Recurrent syncope with injury.

Reflex (neurally mediated) syncope. Vasovagal (emotional or orthostatic stress), situational (micturition, defaecation, cough, swallowing, post exercise), carotid sinus syndrome, glossopharyngeal neuralgia.

Orthostatic hypotension.

• Drugs: antihypertensives, diuretics, vasodilators, alpha blockers, antidepressants, antipsychotics, levodopa, alcohol.
• Volume depletion: dehydration, haemorrhage, adrenal insufficiency, diabetes insipidus, hyperglycaemic osmotic diuresis.
• Autonomic failure: diabetes, amyloidosis, Parkinson disease, multiple system atrophy, pure autonomic failure, paraneoplastic.

Cardiac.

• Arrhythmia: sinus node disease, atrioventricular block, supraventricular tachycardia, atrial fibrillation with rapid rate, ventricular tachycardia, long QT syndrome (congenital and drug induced), Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia, pre-excitation, pacemaker malfunction.
• Structural: aortic stenosis, hypertrophic cardiomyopathy, dilated cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, cardiac amyloidosis, mitral stenosis, atrial myxoma, prosthetic valve thrombosis, congenital heart disease, cardiac tamponade.
• Ischaemic: acute coronary syndrome, coronary spasm, anomalous coronary artery.
• Vascular: pulmonary embolism, pulmonary hypertension, aortic dissection, subclavian steal.

Neurological. Generalised and focal seizures, transient ischaemic attack (vertebrobasilar), migraine with brainstem aura, subarachnoid haemorrhage, cataplexy and narcolepsy, hydrocephalus, Chiari malformation.

Metabolic and toxic. Hypoglycaemia, hypoxia, hyperventilation (hypocapnia), hyponatraemia, hypocalcaemia, hypokalaemia, adrenal crisis, carbon monoxide poisoning, drug and alcohol intoxication, organophosphate poisoning.

Haemorrhage and volume loss. Gastrointestinal bleeding, ruptured ectopic pregnancy, ruptured aortic aneurysm, trauma, postpartum haemorrhage, severe anaemia, dehydration.

Psychogenic. Functional seizures, pseudosyncope, panic attack with hyperventilation, conversion disorder.

Falls without loss of consciousness. Gait and balance disorder, vertigo, drop attack, visual impairment, muscle weakness, foot problems, environmental hazards.

1. Initial evaluation (history, witness account, examination including orthostatic blood pressure, ECG) establishes the cause in about 50% of patients. Risk stratify: high risk features indicate admission and monitoring.
2. All patients: capillary glucose, haemoglobin, and pregnancy test in women of reproductive age.
3. All patients: 12 lead ECG. Look for rhythm, PR interval, QRS width, delta wave, QTc over 450 ms in men and 460 ms in women, Brugada pattern in leads V1 to V3, epsilon waves, left ventricular hypertrophy, Q waves, and bifascicular block.
4. Blood tests: full blood count, urea, creatinine, electrolytes, calcium, magnesium, troponin when ischaemia is possible, D-dimer or CT pulmonary angiography when pulmonary embolism is possible, lactate and creatine kinase if seizure or prolonged lie, cortisol, toxicology and carboxyhaemoglobin as indicated.
5. Cardiac monitoring: continuous telemetry in hospital for high risk patients; ambulatory ECG (24 to 48 hour Holter), external loop recorder (up to 4 weeks) or implantable loop recorder (up to 3 years) when the events are infrequent.
6. Echocardiography for structural heart disease, murmurs, abnormal ECG, heart failure or suspected pulmonary hypertension. Cardiac MRI for cardiomyopathy.
7. Exercise testing for exertional collapse. Electrophysiology study for syncope with bifascicular block or ventricular scar where non invasive tests fail.
8. Orthostatic testing: active standing blood pressure for 3 minutes; head up tilt test (60 to 70 degrees for 20 minutes then glyceryl trinitrate 400 micrograms sublingually) for suspected reflex syncope when diagnosis is unclear.
9. Carotid sinus massage (5 to 10 seconds supine and erect) in patients over 40 with unexplained syncope: ventricular pause of 3 seconds or more or fall in systolic pressure of 50 mmHg or more is positive. Avoid in patients with carotid bruit, recent stroke or transient ischaemic attack.
10. Neurological: electroencephalogram, CT or MRI of the brain when seizure, focal signs or head injury are present. CT or lumbar puncture when subarachnoid haemorrhage is suspected.
11. Imaging for aortic dissection (CT angiography), gastrointestinal bleeding source (endoscopy) and ectopic pregnancy (ultrasound).
12. Genetic testing and family screening for channelopathies and cardiomyopathies when diagnosed.

Limits. Tilt testing has modest specificity. Loop recorder results may be negative if symptoms do not recur. Electroencephalogram is often normal between seizures. In about 20% to 30% of cases no cause is found after full assessment.

Immediate resuscitation. Airway, breathing, circulation. Lay the patient flat and raise the legs. Check pulse and rhythm. Cardiac arrest: start CPR and follow advanced life support.

Treat the following:

• hypoglycaemia (glucose 10% 150 to 200 mL intravenously or glucagon 1 mg intramuscularly)
• haemorrhage (large bore access, blood)
• arrhythmia (synchronised cardioversion for unstable tachycardia; atropine 500 micrograms intravenously repeated every 3 to 5 minutes to a maximum of 3 mg, or temporary pacing, for symptomatic bradycardia)
• seizure (lorazepam 4 mg intravenously, repeated once after 10 minutes)

Cause directed treatment.

• Reflex syncope: education and reassurance, recognise prodrome, counter pressure manoeuvres (leg crossing, hand grip, squatting), avoid triggers, increase fluid to 2 to 3 litres and salt to 6 to 10 g daily if blood pressure is low, review hypotensive drugs.
• For frequent recurrences: midodrine 2.5 to 10 mg orally three times daily (during daytime) or fludrocortisone 100 to 200 micrograms daily (monitor potassium and blood pressure).
• Pacing is considered for cardioinhibitory carotid sinus syndrome and selected older patients with documented asystole.
• Orthostatic hypotension: stop or reduce offending drugs, hydrate, compression stockings (30 to 40 mmHg) and abdominal binders, head up sleeping position (10 to 20 degrees), slow staging when standing.
• Drugs: fludrocortisone 100 to 300 micrograms daily or midodrine 2.5 to 10 mg three times daily (avoid after 6 pm; contraindicated in supine hypertension).
• Arrhythmia: pacemaker for sinus node disease and high degree atrioventricular block. Catheter ablation for supraventricular tachycardia and some ventricular tachycardia.
• Implantable cardioverter defibrillator for survivors of cardiac arrest, ventricular tachycardia and high risk channelopathy or cardiomyopathy.
• Stop QT prolonging drugs and correct potassium (over 4.0 mmol/L) and magnesium (magnesium sulphate 2 g intravenously over 10 minutes for torsades de pointes).
• Beta blockers for long QT syndrome (nadolol 1 to 2 mg/kg daily or propranolol 2 to 4 mg/kg daily) and catecholaminergic polymorphic ventricular tachycardia.
• Aortic stenosis and hypertrophic cardiomyopathy: avoid exertion and dehydration, valve replacement for symptomatic severe stenosis, septal reduction, and beta blocker (metoprolol succinate 50 mg daily, maximum 200 mg) in obstructive hypertrophic cardiomyopathy.
• Pulmonary embolism: anticoagulation (rivaroxaban 15 mg twice daily for 21 days then 20 mg daily, or apixaban 10 mg twice daily for 7 days then 5 mg twice daily; enoxaparin 1 mg/kg twice daily initially).
• Thrombolysis (alteplase 100 mg intravenously over 2 hours) for massive embolism.
• Aortic dissection: intravenous beta blockade to heart rate 60 and systolic pressure under 120 mmHg, and surgical review.
• Subarachnoid haemorrhage: neurosurgical referral, nimodipine 60 mg orally every 4 hours for 21 days.
• Seizure: antiseizure medicine after a second seizure or high risk first seizure (levetiracetam 500 mg twice daily increasing to 1,500 mg twice daily; lamotrigine start 25 mg daily).
• Adrenal crisis: hydrocortisone 100 mg intravenously then 200 mg over 24 hours, with 0.9% sodium chloride 1 litre over the first hour.
• Anaemia and bleeding: transfuse to haemoglobin 70 to 80 g/L (higher with cardiovascular disease), find the source, and give tranexamic acid 1 g intravenously for major haemorrhage.
• Psychogenic episodes: confident explanation of the diagnosis and referral for psychological therapy and neurology follow up.

Risk stratified disposition.

• Admit for monitoring: abnormal ECG, structural heart disease, exertional collapse, family history of sudden death, severe anaemia or bleeding, heart failure, systolic pressure under 90 mmHg, age over 60 with comorbidities, injury, syncope with chest pain or breathlessness.
• Discharge with follow up: typical reflex syncope, orthostatic syncope with clear cause, no high risk features and normal ECG.

Driving and work. Advise not to drive until a cause is found and treated. For reflex syncope with a clear prodrome, driving may resume after a symptom free interval; for unexplained syncope or cardiac causes, stop driving for a period set by local law (commonly 4 weeks to 6 months, longer for commercial drivers). Avoid heights, swimming alone and operating machinery.

Monitoring. Review at 1 to 2 weeks, with results of ambulatory monitoring and echocardiography. Orthostatic blood pressure after drug changes. Recurrence log.

Referral and escalation. Cardiology for suspected cardiac causes and arrhythmia, neurology for seizure, geriatrics for falls and orthostatic hypotension, endocrinology for adrenal and diabetic problems, psychiatry or psychology for functional episodes.

Safety netting. Return at once for further collapse, chest pain, palpitations, breathlessness, severe headache, black stool, or injury.

Special groups. Young people: reflex syncope is common but screen for channelopathy and cardiomyopathy, especially with exertional events. Athletes: sudden collapse during exercise needs cardiac evaluation before return. Pregnancy: supine hypotension, ectopic pregnancy, pulmonary embolism, peripartum cardiomyopathy. Older adults: multifactorial; combine orthostatic, drug, cardiac and fall assessment. Endemic regions: malaria, Chagas disease, rheumatic valve disease, severe anaemia and organophosphate exposure.