Syncope — aetiology, pathogenesis, differential diagnosis and management

Definition. Syncope is a transient loss of consciousness due to global cerebral hypoperfusion, characterised by rapid onset, short duration and spontaneous complete recovery. It is one cause of the wider syndrome of transient loss of consciousness (T-LOC). Cerebral perfusion fails when systemic blood pressure falls, which occurs through a fall in cardiac output, in peripheral vascular resistance, or both. In older people syncope frequently presents as a history of falls or drop attacks with no recall of loss of consciousness, so the diagnosis is systematically under-recognised.

Classification and aetiology.

Drugs and the older patient. A drug cause must be sought in every case. Implicated agents include ganglion blockers, diuretics, phenothiazines, antihistamines, antidepressants, benzodiazepines, barbiturates and antiparkinsonian drugs; among cardiovascular drugs, nitrates, beta-blockers and nifedipine are particularly important; and donepezil may increase the risk of syncope. Orthostatic hypotension and syncope are common in the elderly following haemodialysis. A postural fall of more than 20 mmHg is found in about 30% and of more than 40 mmHg in 10% of a large elderly population.

Clinical features — and why the classical picture misleads. The image of a patient falling, lying still for some seconds and then coming round is actually unusual. In a landmark study inducing vasovagal syncope in medical students, only a minority lay still; 90% had asynchronous myoclonic jerks of the limbs, in a few vigorous enough to be mistaken for a generalised clonic seizure. Other motor activity included limb posturing, head turning, complex movements, eye deviation and eyelid flicker, which may be misread as focal seizures, and vocalisation was frequent. The same high frequency of myoclonic movement has been documented in cardiac syncope (observed when arrhythmia is deliberately induced to test an implanted defibrillator) and in tilt-induced syncope, with simultaneous EEG showing no epileptiform activity. Anecdotally, a patient propped up rather than allowed to fall flat is more likely to jerk, presumably because the fall in blood pressure is more prolonged and severe; rarely the hypoxia may itself provoke a genuine epileptic seizure.

Differential diagnosis of transient loss of consciousness. Epileptic seizure — aura, prolonged tonic-clonic movement beginning at onset, lateral tongue biting, prolonged post-ictal confusion, cyanosis, incontinence (which occurs in syncope too and is not discriminating). Psychogenic pseudosyncope and non-epileptic attacks — prolonged apparent unconsciousness, eyes closed and resisting opening, high attack frequency, normal blood pressure and pulse during the event. Falls without loss of consciousness — mechanical, drop attacks, vestibular. Metabolic — hypoglycaemia, hypoxia, hyperventilation with hypocapnia (cerebral vasoconstriction), intoxication. Cerebrovascular — vertebrobasilar TIA, subclavian steal, subarachnoid haemorrhage. Cataplexy. The single most valuable investigation is a careful eyewitness account, and short-term video-EEG is useful in the diagnosis of attack disorders where the nature of the event remains unclear.

Initial evaluation. Take a meticulous history of the circumstances, posture, prodrome, duration, colour, recovery and any injury, plus a witness account. Cough syncope should be considered in patients with COPD, emphysema and chronic cough — an adequate witness account is essential since some patients fail to recall the bout of coughing that triggers the attack. Review all drugs. Examine for cardiac murmurs (especially aortic stenosis), pulse, blood pressure supine and at 1 and 3 minutes standing, neurological signs and carotid bruits. Baseline tests: 12-lead ECG, full blood count, urea, electrolytes, creatinine, glucose and calcium. The presence of underlying cardiac disease increases the probability of a cardiac cause, and timely and effective treatment of cardiac syncope may be life-saving — so risk-stratify at this first assessment.

Further investigation. Routine 12-lead ECG will occasionally demonstrate an arrhythmia or predisposing abnormality. 24-hour ECG can be diagnostic if an attack is recorded, but the yield is very small unless attacks are very frequent, and interpretation of asymptomatic rhythm disturbance is difficult — in an older population minor asymptomatic dysrhythmias are common and may be incidental. Therefore, for infrequent attacks use prolonged external monitoring or an implantable loop recorder, which has a good diagnostic yield and is safe in patients with and without structural heart disease. Add echocardiography if structural disease is suspected, exercise testing for exertional syncope, and electrophysiological study in selected cases. Use head-up tilt testing to support a suspected diagnosis of vasovagal syncope — it is safe in the elderly, and the yield increases with glyceryl trinitrate, but positive tests occur in a significant minority of controls, which limits the positive predictive value; provocation of the habitual attack is diagnostically very suggestive. Perform carotid sinus massage, since carotid sinus syndrome is a common cause of syncope in the elderly and is not confined to those who faint on neck movement — it is low-risk, but not if there is a carotid bruit unless ultrasound has excluded severe stenosis. When cardiac syncope is suspected, specialist cardiac referral is usually indicated.

Management by cause. Micturition syncope can usually be avoided by micturating sitting down. Cough syncope — direct treatment at the underlying chest condition. Cardiac syncope requires appropriate specialist treatment with antiarrhythmic medication, pacing, or insertion of an implantable defibrillator as appropriate — timely and effective treatment may be life-saving. Aortic stenosis with syncope is an indication for urgent valve intervention. Carotid sinus syndrome with a cardioinhibitory response — dual-chamber pacing reduces falls. Vasovagal syncope — education about prodromal recognition, trigger avoidance and physical counter-pressure manoeuvres.

Management of reflex syncope with postural hypotension in the older patient. This is a common and difficult management problem, and the approach is stepwise. Attention should first be directed to factors causing or exacerbating the problem. Review the medication — but recognise it is not always possible to discontinue relevant drugs; in Parkinson's disease the aggravating effect of dopaminergic drugs must be balanced against their therapeutic benefit. Exclude treatable conditions such as Addison's disease. Then: avoid factors causing vasodilatation — high temperature, marked exertion and alcohol; take small frequent meals rather than large ones; avoid dehydration; change posture slowly and reverse the change temporarily if symptoms supervene; use leg crossing, calf tensing and abdominal compression to ameliorate symptoms transiently. Elastic compression stockings make a significant contribution though patients may need help applying them and tolerance is poor in summer. Sleeping with a slight head-up tilt may help by expanding plasma volume, but more than about 10° is not tolerated. Patients should be encouraged to remain as active as possible, since chronic exposure to low blood pressure seems to improve cerebral autoregulation. If these measures fail, add drugs, recognising that most are used outside their licence and benefits may be limited: fludrocortisone 100–200 µg at night is usually first; ephedrine 15 mg three times daily, increasing if necessary to 30 mg three times daily (higher doses cause tremor, tachycardia and agitation); midodrine, desmopressin and erythropoietin have also been used. Supine hypertension is a risk of drug treatment, and pacing does not help. Finally, because the risks of serious injury and complications from falls are very high in an elderly population, it is important that the patient recognises these risks and understands the need to take precautions to avoid syncopal attacks wherever possible.

Structured emergency department risk stratification and the syncope unit model. The Canadian Syncope Risk Score — combining predisposition to vasovagal syncope, heart disease, systolic BP, troponin, QRS/QT abnormality, ECG diagnosis and ED diagnostic impression — has been externally validated across multiple countries and is now used to identify patients safely dischargeable from the emergency department, avoiding a hospital admission that in an older person carries its own risk of delirium, deconditioning and hospital-acquired infection. This is supported by randomised evidence that an ED observation syncope protocol is equivalent to routine inpatient admission, and by the EHRA/HRS position statement on the syncope unit, which recommends a dedicated multidisciplinary service with standardised protocols — an approach shown to increase diagnostic yield and reduce admissions and cost.

Implantable loop recorders early rather than last, and reappraisal of pacing in reflex syncope. Current practice, consistent with the 2018 ESC guideline and the 2020 Canadian Cardiovascular Society clinical practice update, is that in recurrent unexplained syncope with suspected arrhythmia the implantable loop recorder should be used early rather than after a long sequence of low-yield tests, because it documents the mechanism of the spontaneous attack, which tilt testing cannot. For refractory reflex syncope, closed-loop stimulation pacing (BIOSync CLS) markedly reduced recurrence in patients over 40 with tilt-documented asystolic vasovagal syncope, and this has been carried into the ESC pacing guideline — but pacing remains ineffective for the vasodepressor form and for orthostatic hypotension, which is the crucial distinction to state.