Syncope

Syncope is a transient loss of consciousness characterized by an inability to maintain postural tone, rapid and spontaneous recovery, and the absence of clinical features specific to another cause of transient loss of consciousness such as an epileptic seizure.^[1] The presumed shared final pathway across every cause is transient global cerebral hypoperfusion — reflex (neurally mediated) syncope, orthostatic hypotension, and cardiac syncope all reach that endpoint through different mechanisms, and distinguishing among the 3 drives everything downstream: the urgency of workup, the specific investigations ordered, and the treatment selected.^[2] Most syncope is benign, but a minority of patients — those with structural heart disease, an inherited arrhythmia syndrome, or high-risk findings on initial assessment — are at real short-term risk of a serious cardiac event, which is why the core task of the initial assessment is not just naming a cause but assigning a risk category.^[3] For pharmacists specifically, syncope is disproportionately a medication-sensitive presentation: antihypertensives, diuretics, vasodilators, and QT-prolonging agents are common precipitants or contributors, especially in older adults on multiple interacting drugs, and a careful medication review belongs in every syncope assessment regardless of which etiologic category the patient ultimately falls into.

Syncope is a single final common pathway reached by 3 mechanistically distinct routes. The history — especially the patient's position, any trigger, the presence and character of a prodrome, and how quickly they recovered — is usually enough to sort a patient into one of the 3 categories below before any testing is done.

• Older age — atypical, prodrome-free presentations are more common, and the consequences of a fall (fracture, head injury) are more severe.
• Known structural heart disease, prior myocardial infarction, reduced left ventricular ejection fraction, or a prior arrhythmia diagnosis.
• Family history of sudden cardiac death, or a known inherited arrhythmia syndrome (long QT syndrome, Brugada syndrome, hypertrophic cardiomyopathy).
• Polypharmacy, particularly antihypertensives, diuretics, vasodilators, antiparkinsonian drugs, and other agents that cause hypotension or are proarrhythmic (QT-prolonging drugs) — see the medication-differential table in Assessment & Diagnosis.
• Volume depletion from any cause: diarrhea, vomiting, diminished oral intake, polyuria, heat exposure, or prolonged standing.
• Autonomic neuropathy — diabetes mellitus, Parkinson disease and other synucleinopathies, amyloidosis, or uremia.
• Recent significant blood loss or anemia.
• Pregnancy — physiologic vasodilation, and later in pregnancy, inferior vena cava compression in the supine position.
• A prior episode of syncope — the single strongest predictor of recurrence.
• Situational triggers: cough, micturition, defecation, venipuncture or other pain, prolonged standing, or a hot or crowded environment.

Differentiating syncope from other causes of transient loss of consciousness

Syncope, an epileptic seizure, and a psychogenic non-epileptic event can all present as an apparent collapse with loss of responsiveness. The history — from the patient and, ideally, a witness — is usually the most powerful diagnostic tool available.

History

• Establish the position at onset (supine, sitting, standing, or during a position change), any trigger (emotional stress, pain, prolonged standing, cough, micturition, defecation, exertion), and how quickly the patient recovered.
• Ask specifically about a prodrome and its character (diaphoresis, warmth, nausea, visual blurring for reflex syncope; lightheadedness on standing for orthostatic hypotension; palpitations or chest pain for cardiac syncope) — and note explicitly if there was no prodrome at all.
• Obtain a witness account whenever possible: duration of unconsciousness, motor activity during the event, colour change, and the speed and completeness of recovery.
• Take a complete medication history, including over-the-counter and recreational drug/alcohol use, and cross-check every agent against the medication-differential table below.
• Ask about prior syncope episodes, structural heart disease, and family history of sudden cardiac death or inherited arrhythmia syndromes.

Physical examination

• Supine and standing vital signs using a formal stand test: measure blood pressure and heart rate after the patient has been supine for 5 minutes, then again after 2, 4, 6, and 8 minutes of standing.^[4]
• Cardiovascular exam, including auscultation for a murmur suggesting aortic stenosis, and a full neurologic exam to identify any focal deficit that would point away from syncope and toward a different cause of transient loss of consciousness.
• Unless contraindicated (avoid in patients with a carotid bruit), perform carotid sinus massage in patients over 50 years of age to screen for carotid sinus hypersensitivity.

Interpreting the stand test

Investigations

• A 12-lead ECG is indicated for most patients and is inexpensive and high-yield.
• Younger patients with a secure diagnosis of vasovagal syncope from the history alone do not require further investigation.
• Tilt table testing can help when the diagnosis is uncertain, when distinguishing syncope from an epileptic seizure is unclear, or when distinguishing a faint from a mechanical fall is unclear in an older patient.
• Patients over 50 years of age with ongoing diagnostic uncertainty should have extended ECG monitoring — a 2-day admission, Holter monitoring, or more prolonged ambulatory ECG monitoring.
• An implantable loop recorder can be useful for infrequent syncope that has eluded diagnosis on prior monitoring, reserved for cases where the diagnostic yield justifies the more invasive approach.
• Refer patients with known or suspected structural heart disease for electrophysiologic assessment.

Canadian Syncope Risk Score (CSRS)

The CSRS is the preferred emergency department risk-stratification tool in Canadian practice, used once a serious cause has not been identified on initial ED assessment, to decide whether a patient can be safely discharged with outpatient follow-up or needs further monitoring.^[6] It is not a uniform point-sum: each of its 9 criteria carries its own weight, ranging from -2 to +2, and 2 of the 9 are the clinician's own diagnostic impression rather than an objective finding.

Total scores run from -3 to +11. The validated 30-day risk of a serious adverse event rises with each risk category: very low risk (score of -2 or less), low risk (-1 to 0), medium risk (1 to 3), high risk (4 to 5), and very high risk (6 or more) — with risk climbing from under 1% at the very-low end to roughly half of patients at the very-high end.^[7]

San Francisco Syncope Rule (SFSR)

The SFSR (mnemonic CHESS) is a simpler, US-derived alternative ED risk tool, included here for completeness and comparison rather than as the primary recommended tool.^[8] Unlike the CSRS, every criterion is weighted equally and the rule is a single any-one-positive threshold rather than a tiered point sum.

The rule is positive — indicating higher risk for a serious outcome — if any single CHESS criterion is present.

Medication review: drug classes commonly implicated in syncope

Checking the full medication list against this table belongs in every syncope assessment, regardless of the eventual etiologic category — a causative or contributing drug is one of the few truly reversible findings available at the first visit.

• Correctly categorize the episode as reflex, orthostatic, or cardiac syncope, and assign a short-term risk category using history, exam, ECG, and the Canadian Syncope Risk Score where applicable.
• Identify and remove or reduce reversible, medication-induced contributors.
• Ensure any cardiac (arrhythmic or obstructive) cause receives definitive cardiology-directed treatment.
• Reduce the frequency and severity of reflex syncope and orthostatic hypotension to a level that restores functional independence.
• Prevent injury from unwarned falls.
• Support safe, guideline-concordant return to driving.

Reflex (vasovagal) syncope

• Reassure the patient that vasovagal syncope is not life-threatening and is a physical, not a psychiatric, problem.
• Increase dietary salt (3-5 g elemental sodium daily) and fluid intake (up to 2.5 L daily) in the absence of contraindications such as hypertension or heart failure.^[1]
• Teach the patient to recognize premonitory symptoms — progressive presyncope, diaphoresis, warmth, flushing, nausea, abdominal discomfort, visual blurring — and to use physical counterpressure maneuvers immediately at onset: squatting, crossing the legs with isometric contraction if standing, or vigorous hand clenching with upper-girdle isometric contraction.^[9]
• These maneuvers should be tried in every patient under 40 years of age; they may be less effective in older patients, who should not be relied on to abort every episode with a maneuver alone.
• Pacemaker therapy is reserved for older patients with confirmed, recurrent, cardioinhibitory reflex syncope refractory to the measures above, assessed at a tertiary referral clinic — it remains a specialist decision, not a routine option.

Orthostatic hypotension

• Review the full medication list against the medication-differential table in Assessment & Diagnosis, and deprescribe or dose-reduce every hypotensive or volume-depleting drug that is not essential — this is the single highest-yield intervention available and should happen before any other non-pharmacologic step.^[10]
• Increase dietary salt and fluid intake if not contraindicated.
• Elevate the head of the bed 15-30 cm on blocks or bricks (often not well tolerated, but genuinely effective when used).
• Instruct patients to avoid hemodynamic stress: rising quickly from lying or sitting, large meals, warm environments or hot baths, and heavy exertion.
• Consider compression garments (e.g., abdominal-high compression garments) to reduce venous pooling.

Every patient

• Counsel on driving restrictions specific to the syncope cause and any therapy started, per the current Canadian Cardiovascular Society fitness-to-drive guidance.^[11]
• Revisit the medication review at every follow-up — a newly added drug is a common, preventable cause of a recurrence that looks like "treatment failure."

Breastfeeding

Data on midodrine, fludrocortisone, and pyridostigmine in lactation are limited — use only if clearly needed and monitor the infant. Fluoxetine and paroxetine have a more established lactation safety record from their use in postpartum depression.

Pediatric

Reflex (vasovagal) syncope is common and typically benign in children and adolescents. Non-pharmacologic measures (salt and fluid intake, counterpressure maneuvers) are 1st line, exactly as in adults, and drug therapy is rarely needed. Fludrocortisone specifically is not established for routine pediatric use — a randomized, placebo-controlled trial in children found no benefit over placebo.^[12] Refer any child or adolescent with an exertional or otherwise cardiac-pattern presentation for pediatric cardiology assessment given the possibility of an inherited arrhythmia syndrome.

Older adults

This is the population where syncope management matters most. Counterpressure maneuvers are less reliably effective over 40 years of age. Polypharmacy review and deprescribing of causative drugs (see the medication-differential table) is the single most important intervention. Perform a formal orthostatic stand test after any fall or syncopal episode — a single quick reading can miss both initial and delayed orthostatic hypotension. Midodrine carries a higher urinary retention risk in this group, and fludrocortisone carries a higher risk of precipitating heart failure or worsening hypertension. Frame management explicitly around falls and fracture prevention, and revisit driving eligibility at every relevant visit.

Renal impairment

Midodrine's active metabolite, desglymidodrine, is cleared mainly by active renal secretion — use a lower starting dose (2.5 mg) and titrate cautiously in renal impairment, and assess renal function before starting. Fludrocortisone requires closer monitoring of potassium and fluid status in renal impairment.

Hepatic impairment

No specific dose adjustment is established for midodrine or fludrocortisone in hepatic impairment, but fludrocortisone's fluid-retention effect warrants closer monitoring if hepatic synthetic function or fluid balance is already compromised.

See the patient at least yearly to attempt discontinuation of any ongoing drug therapy (fludrocortisone, midodrine, an SSRI used for vasovagal syncope) — reflex syncope and orthostatic hypotension both commonly remit over time, and indefinite therapy should not be assumed necessary.^[13] Check supine blood pressure 2 hours after any midodrine dose increase, and check serum potassium and supine blood pressure 1 week after starting or increasing fludrocortisone. Encourage a home blood pressure log that includes supine readings, since emerging supine hypertension is easy to miss otherwise. Re-screen the full medication list at every visit for a newly added hypotensive, volume-depleting, or QT-prolonging drug. Confirm and update driving-restriction status as the clinical picture evolves and as therapy changes.^[11] For confirmed cardiac syncope, monitoring cadence is set by the treating cardiology/electrophysiology service rather than by this chapter. At every follow-up, explicitly track syncope and presyncope frequency and any injury from a fall, since this — not just BP numbers — is the true measure of whether therapy is working.

1. Confirm non-pharmacologic measures were genuinely implemented — salt and fluid targets actually met, counterpressure maneuvers practiced correctly — before escalating to drug therapy.
2. Re-review the full medication list for a still-present causative agent that was missed or only partially addressed at the first visit.
3. For reflex syncope not controlled on non-pharmacologic measures alone: add fludrocortisone; if inadequate or not tolerated, switch to or add midodrine.
4. For orthostatic hypotension not controlled after deprescribing, non-pharmacologic measures, and an adequate trial of fludrocortisone or midodrine: consider pyridostigmine (alone or combined with midodrine) under specialist direction, and evaluate for an underlying autonomic neuropathy that needs its own workup.
5. Reassess the diagnosis itself before adding a third drug — repeat the stand test, arrange tilt-table testing if the diagnosis remains uncertain, and re-screen for a cardiac cause that may have been missed initially.
6. Refer to a tertiary syncope/pacing clinic for confirmed cardioinhibitory reflex syncope with recurrent, injurious episodes refractory to drug therapy — pacemaker therapy may be considered in this specific, typically older-patient population.
7. For suspected but unconfirmed cardiac syncope despite an initial negative workup, arrange extended ambulatory ECG monitoring or an implantable loop recorder rather than simply repeating a single-point ECG.

• Ordering brain MRI/CT, EEG, or carotid ultrasound as routine syncope workup — none is indicated without a specific neurologic finding.
• Stopping a medication review at "the blood pressure pills" instead of screening the entire drug list against the medication-differential table, including diuretics, antiparkinsonian drugs, antipsychotics, SGLT2 inhibitors, and QT-prolonging agents.
• Using a beta-blocker specifically to try to prevent vasovagal syncope — it is not effective for that indication.
• Starting drug therapy for infrequent reflex syncope with a clear prodrome, when non-pharmacologic measures alone are the appropriate 1st-line approach.
• Dosing midodrine too late in the day, causing supine hypertension overnight.
• Starting fludrocortisone in a patient with heart failure or hypertension without reassessing whether it is truly appropriate.
• Treating a single orthostatic vital-sign check as sufficient — both initial orthostatic hypotension (the first 15 seconds of standing) and delayed orthostatic hypotension can be missed by a single reading at one time point.
• Forgetting to counsel on driving restrictions after a syncope diagnosis, or failing to update that counselling once therapy changes the risk category.
• Labelling a recurrent episode in an older adult as simply "a fall" without considering syncope as the underlying mechanism.

How to use this table: doses are adult doses and require patient-specific confirmation, including renal adjustment. Select any drug name to open its complete Pharmasist Drug Database page.

Alpha1-adrenergic agonists

For refractory reflex syncope or orthostatic hypotension.

Electrolytes

Dietary sodium/fluid supplementation is a 1st-line adjunct for both reflex syncope and orthostatic hypotension.

Mineralocorticoids

For refractory reflex syncope or orthostatic hypotension in healthy, normotensive patients.

Acetylcholinesterase inhibitors

For refractory neurogenic orthostatic hypotension, alone or combined with midodrine; evidence remains limited to short-term trial data.

Selective serotonin reuptake inhibitors

Alternative for refractory reflex (vasovagal) syncope when other measures fail; screen carefully for serotonergic and QT-prolonging interactions before starting.

Nonselective beta-blockers

For orthostatic hypotension only, and only when a nonselective beta-blocker is already indicated and tolerated for another reason — not started specifically to prevent vasovagal syncope, for which beta-blockers are not effective. Timolol and other nonselective agents share this class effect but do not have a distinct oral monograph in this database; propranolol or nadolol are the practical choices below.