Syncope: Causes, Pathophysiology and Approach

Syncope is a transient, self-limited loss of consciousness due to acute global impairment of cerebral blood flow. The onset is rapid, duration brief, and recovery spontaneous and complete. Other causes of transient loss of consciousness need to be distinguished from syncope which includes:

• Seizures.
• Hypoxemia.
• Hypoglycemia.
• Vertebrobasilar ischemia.

A syncopal prodrome (presyncope) is common, although loss of consciousness may occur without any warning symptoms. Typical pre-syncopal symptoms include:

• Dizziness.
• Lightheadedness or faintness.
• Weakness.
• Fatigue.
• Visual and auditory disturbances.

Causes of syncope

The causes of syncope can be divided into three general categories:

• Neurally mediated syncope aka reflex or vasovagal syncope.
• Orthostatic hypotension.
• Cardiac syncope.

Neurally mediated syncope:

Vasovagal syncope: Provoked fear, pain, anxiety, intense emotion, sight of blood, unpleasant sights and odors.

Situational reflex syncope:

• Pulmonary: Cough syncope, sneeze syncope, airway instrumentation.
• Urogenital: Postmicturition syncope, urogenital tract instrumentation, prostatic massage.
• Gastrointestinal: Swallow syncope, glossopharyngeal neuralgia, esophageal stimulation, gastrointestinal tract instrumentation, rectal examination, defecation syncope.
• Cardiac: Bezold-Jarisch reflex, cardiac outflow obstruction.
• Carotid sinus: Carotid sinus sensitivity, carotid sinus massage.
• Ocular: Ocular pressure, ocular examination, ocular surgery.

Orthostatic hypotension:

Primary autonomic failure due to idiopathic central and peripheral neurodegenerative diseases; the synucleopathies:

• Lewy body diseases: Parkinson’s disease, Lewy body dementia, pure autonomic failure.
• Multiple system atrophy (Shy dragger syndrome).

Secondary autonomic failure due to autonomic peripheral neuropathies:

• Diabetes.
• Hereditary and primary amyloidosis.
• Hereditary sensory and autonomic neuropathies (HSAN).
• Idiopathic immune mediated autonomic neuropathy.
• Autoimmune autonomic gangliopathy.
• Sjogren’s syndrome.
• Paraneoplastic autonomic neuropathy.
• HIV neuropathy.

Postprandial hypotension.

Iatrogenic (drug induced).

Volume depletion.

Cardiac syncope:

Arrhythmias:

• Sinus node dysfunction.
• Atrioventricular dysfunction.
• Supraventricular tachycardias.
• ventricular tachycardias.
• Inherited channelopathies.

Cardiac structural disease:

• Valvular disease.
• Myocardial ischemia.
• Obstructive and other cardiomyopathies.
• Atrial myxoma.
• Pericardial effusions and tamponade.

Pathophysiology of Syncope

The upright posture imposes a unique physiologic stress upon humans; most, although not all syncopal episodes occur from standing position.

Standing results in pooling of 500-1000 ml of blood in the lower extremities and splanchnic circulation. 

There is a decrease in venous return to the heart and reduced ventricular filling that result in diminished cardiac output and blood pressure.

These hemodynamic changes provoke a compensatory reflex response, initiated by the baroreceptors in the aortic arch and carotid sinus, resulting in increased sympathetic outflow and decreased vagal nerve activity.

These reflex increases peripheral resistance, venous return to the heart, and cardiac output and thus limits the fall in blood pressure.

If this response fails, as is the case chronically in orthostatic hypotension and transiently in neurally mediated syncope, global cerebral hypoperfusion occurs resulting in syncope.

Thus, syncope is a consequence of global cerebral hypoperfusion and thus represents a failure of cerebral blood flow autoregulatory mechanisms. Myogenic factors, local metabolites, and to a lesser extent autonomic neurovascular control are responsible for the autoregulation of cerebral blood flow. The latency of the autoregulatory response is 5-10 s.

Typically, cerebral blood flow ranges from 50-60ml/min per 100gm brain tissue and remains relatively constant over perfusion pressures ranging from 50 to 150 mmHg. Cessation of blood flow for 6-8 s will result in loss of consciousness while impairment of consciousness ensues when blood flow decreases to 25ml/min per 100 g brain tissue.

From the clinical standpoint, a fall in systolic blood pressure to ~ 50 mmHg or lower will result in the syncope.

A decrease in the cardiac output and/or systemic vascular resistance (the determinants of blood pressure) underlies the pathophysiology of syncope.

Sequence of changes occurring in syncope after cerebral perfusion/ oxygenation cut off for 8 to 10 s,

• Loss of consciousness and postural tone.
• Pallor and sweating.
• Brief (lasting few seconds) extensor stiffening or spasms.
• Few irregular myoclonic jerks of limbs.

 Whole episode is brief, usually < 10 s.

Approach to Syncope

Careful history:

• Full a description as possible of the first faint.
• precipitating factors.
• Posture.
• type of onset of the faint (abrupt or gradual).
• the presence and duration of preceding and associated symptoms.
• duration of LOC.
• rate of recovery and sequalae.

Question an observer about:

• clonic movement.
• color changes.
• Diaphoresis.
• Pulse.
• Respiration.
• urinary incontinence.
• nature of recovery.

Clinical examination

• Valsalva maneuver.
• Orthostatic drop.
• Asses BP in both arms when suspecting cerebrovascular disease, subclavian steal or Takayasu arteritis.
• Pulse rate and rhythm.
• Extra cardiac auscultation: cardiac, ophthalmic and supraclavicular bruits.
• Carotid sinus massage in older patients suspected of having carotid sinus syncope (the response to carotid massage is vasodepressor, cardioinhibitory or mixed).

Investigations

• Doppler flow of cerebral blood vessels.
• MR angiography.
• EEG has a low diagnostic yield (To do only when a seizure disorder is suspected)
• Tilt table testing in unexplained syncope in high-risk settings or with recurrent faints in the absence of heart disease.
• ECG.
• Prolonged Holter monitoring.
• Radionuclide cardiac scanning.
• Echocardiography.

Differential diagnosis of Blackouts:

• Syncope
• Epilepsy
• Psychogenic non epileptic seizures
• Cataplexy
• Drop attack
• Transient CSF obstruction
• TIA of anterior and posterior circulation
• Panic attack
• Falls / trauma
• Hypoglycemia
• Basilar migraine
• Malingering
• Intoxication

Comparison Of Syncope and Seizures

Features	Syncope	Seizures
Relation to posture	Common	No
Time	Diurnal	Diurnal or nocturnal
Precipitating factors	Emotion, pain, crowds, heat exercise, fear, dehydration, coughing, micturition	Sleep loss, alcohol/drug withdrawal
Skin color	Pallor	Cyanosis/ normal
Diaphoresis	Common	Rare
Aura or premonitory symptoms	Long	Brief
Convulsions	Rare	Common
Other abnormal movements	Minor twitching	Rhythmic jerks
Injury	Rare	Common with convulsive jerks
Urinary incontinence	Rare	Common
Tongue bite	No	Can occur
Post ictal confusion	Rare	Common
Post ictal headache	No	Common
Focal neurological signs	No	Occasional
Cardiovascular signs	Common (in cardiac syncope)	No
Abnormal findings on EEG	Rare (generalized slowing may occur)	Common

Treatment

High Risk Features Indicating Hospitalization or Intensive Evaluation of Syncope:

• Chest pain suggesting coronary ischemia.
• Features of CHF.
• Moderate or severe valvular disease.
• Electrocardiographic features of ischemia.
• History of ventricular arrhythmias.
• Prolonged QT interval (> 500 ms).
• Repetitive sinoatrial block or sinus pauses.
• Persistent sinus bradycardia.
• Bi or tri-fascicular block or intraventricular conduction delay with QRS duration ≥ 120ms.
• Atrial fibrillation.
• Non sustained ventricular tachycardia.
• Family history of sudden death.
• Pre-excitation syndromes.
• Brugada pattern on ECG.
• Palpitations at time of syncope.
• Syncope at rest or during exercise.

Treatment Of Vasovagal Syncope:

• Reassurance
• Avoidance of provocative stimuli
• Plasma volume expansion with fluid.
• Isometric counterpressure maneuvers of the limbs (leg crossing or handgrip and arm tensing) to maintain pressure in the autoregulatory zone.
• Pharmacotherapy: fludrocortisone, vasoconstricting agents and beta-adrenoreceptors antagonists.

Treatment Of Orthostatic Hypotension:

   Remove the reversible causes (usually vasoactive medications).

   Non-pharmacological interventions:

• Education: staged move from supine to standing position.
• Warnings about the hypotensive effects of large meals.
• Isometric counterpressure maneuvers that increase intravascular pressure.
• Raising the head of the bed to reduce supine hypotension.
• Intravascular volume expansion: fluid and salt.

  Pharmacologic interventions:

• Fludrocortisone acetate
• Vasoconstricting agents: Midodrine, 1-dihydroxyphenylserine, Pseudoephedrine
• For intractable symptoms:
  • Pyridostigmine
  • Yohimbine
  • Desmopressin
  • Erythropoietin

Treatment Of Cardiac Syncope:

• Cardiac pacing for sinus node disease and AV block
• Ablation
• Antiarrhythmic drugs and
• Cardioverter-defibrillators