Orthostatic hypotension and dizziness on standing

Orthostatic (postural) hypotension is a sustained fall in systolic blood pressure of 20 mmHg or more or diastolic blood pressure of 10 mmHg or more within 3 minutes of standing (or head up tilt to at least 60 degrees), or a fall of systolic pressure under 90 mmHg.

Dizziness on standing is the commonest symptom, with lightheadedness, visual blurring, weakness, fatigue, neck and shoulder ache (coat hanger pain), cognitive slowing, and, if severe, syncope.

It is common in older adults (affects 15% to 30% over 65) and carries risk of falls, fractures, cardiovascular events and death.

Clinical relevance. The cause is often reversible (drugs, volume depletion). Neurogenic orthostatic hypotension (autonomic failure) is often disabling and may signal Parkinson disease, multiple system atrophy, diabetic neuropathy or amyloidosis. Supine hypertension coexists with neurogenic forms and limits treatment.

Classification.

• By timing: initial (within 15 seconds, transient fall of 40 mmHg systolic or 20 mmHg diastolic), classic (within 3 minutes), delayed (after 3 minutes, up to 10 minutes of standing; consider in older adults with unexplained symptoms).
• By heart rate response: neurogenic (rise under 15 beats/minute for each 10 mmHg fall in systolic pressure, ratio under 0.5), or non neurogenic (compensatory tachycardia, rise over 15 beats/minute for each 10 mmHg fall, typical of volume depletion).
• By cause: medication induced, volume depletion, neurogenic (primary and secondary autonomic failure), cardiac, endocrine.
• Related: postural orthostatic tachycardia syndrome (rise of 30 beats/minute or more within 10 minutes without hypotension, symptoms for over 3 months), vasovagal (reflex) orthostatic intolerance.

Mechanism. Standing displaces 500 to 1,000 mL of blood to the legs and splanchnic bed; failure of baroreflex mediated vasoconstriction and heart rate rise, or of intravascular volume, reduces cerebral perfusion.

History.

• Symptoms and timing: dizziness, blurred or tunnel vision, weakness, fatigue, confusion, palpitations, neck and shoulder pain, breathlessness, chest pain, syncope; relation to standing, meals (post prandial), exercise, heat, hot showers, early morning, defaecation or micturition.
• Volume loss: poor intake, vomiting, diarrhoea, bleeding, polyuria, sweating, burns.
• Associated autonomic symptoms: constipation, urinary retention or urgency, erectile dysfunction, anhidrosis, dry eyes and mouth, nocturia, supine hypertension, nocturnal polyuria.
• Neurological: tremor, rigidity, slowness, falls, speech or gait change (Parkinson disease, multiple system atrophy), REM sleep behaviour disorder, anosmia, neuropathic symptoms.
• Medical conditions: diabetes, alcohol use, amyloidosis, Addison disease, anaemia, heart failure, valvular disease, arrhythmia, spinal cord injury, HIV, autoimmune disease, cancer, chronic kidney disease, malnutrition, pregnancy.
• Drugs: alpha blockers (tamsulosin, doxazosin, prazosin), antihypertensives (all classes), diuretics, nitrates, phosphodiesterase inhibitors, beta blockers, calcium channel blockers, ACE inhibitors, angiotensin receptor blockers, sacubitril, tricyclic antidepressants, monoamine oxidase inhibitors, antipsychotics, levodopa, dopamine agonists, opioids, benzodiazepines, baclofen, tizanidine, sodium glucose co-transporter 2 inhibitors, alcohol.
• Family history of autonomic or neurological disease.

Examination.

• Supine blood pressure and pulse after 5 minutes lying, then immediately on standing and at 1, 3 and 5 minutes (up to 10 minutes if delayed hypotension suspected); standing with back to a wall and legs relaxed; note symptoms and heart rate.
• Volume status: mucous membranes, capillary refill, jugular venous pressure, oedema, skin turgor.
• Cardiac: rhythm, murmurs, heart failure, aortic stenosis.
• Neurological: parkinsonism, cerebellar signs, cranial nerves, sensory neuropathy, power, reflexes; pupils.
• Anaemia, thyroid, pigmentation, signs of adrenal insufficiency, rectal examination for bleeding.
• Cognition and frailty, gait, fall risk (timed up and go over 12 seconds).

Red flags.

• Syncope, falls with injury, or exertional symptoms.
• Standing systolic pressure under 90 mmHg, or a fall over 40 mmHg.
• Acute or rapid onset with bleeding, sepsis, vomiting, diarrhoea or new drug.
• Neurogenic features with parkinsonism, cerebellar signs, urinary retention or REM sleep behaviour disorder.
• Supine hypertension over 180/110 mmHg.
• Chest pain, arrhythmia, heart failure.
• Weight loss, anaemia, or hyperpigmentation.

Drug induced (commonest in older adults). Antihypertensives, diuretics, alpha blockers, nitrates, phosphodiesterase inhibitors, antidepressants, antipsychotics, levodopa, opioids, benzodiazepines, alcohol.

Volume depletion. Dehydration, haemorrhage (gastrointestinal, trauma, ruptured ectopic), diarrhoea, vomiting, burns, polyuria (diabetes mellitus, diabetes insipidus, hypercalcaemia), adrenal insufficiency, salt wasting, heat, hypoalbuminaemia.

Neurogenic (autonomic failure).

• Primary: pure autonomic failure, multiple system atrophy, Parkinson disease, Lewy body dementia.
• Secondary: diabetic autonomic neuropathy, amyloidosis (primary and hereditary), alcohol neuropathy, vitamin B12 deficiency, paraneoplastic autonomic neuropathy, autoimmune autonomic ganglionopathy, Sjogren syndrome, HIV, Guillain-Barre syndrome, spinal cord injury and lesions, dopamine beta hydroxylase deficiency, Fabry disease, chronic kidney disease, porphyria, infections (Chagas disease, leprosy, botulism, tetanus).

Cardiac. Heart failure, aortic stenosis, hypertrophic cardiomyopathy, arrhythmia, bradycardia, constrictive pericarditis, myocardial infarction, severe valve regurgitation, pulmonary embolism, sepsis with vasodilation.

Endocrine and haematological. Adrenal insufficiency, hypothyroidism, hyperthyroidism, phaeochromocytoma (paradoxical), hypopituitarism, anaemia, hypoglycaemia.

Others. Postural orthostatic tachycardia syndrome, prolonged bed rest or deconditioning, pregnancy, venous insufficiency or varicose veins, post prandial hypotension, vasovagal orthostatic intolerance, anxiety and hyperventilation.

1. Measure lying and standing blood pressure and pulse (5 minutes supine, then at 1 and 3 minutes standing); confirm the diagnostic fall of 20/10 mmHg within 3 minutes (or 10 minutes). Repeat on a second occasion if borderline. Ambulatory or home blood pressure to find timing and relation to drugs.
2. Calculate the ratio of heart rate rise to blood pressure fall: under 0.5 beats/minute for each mmHg points to neurogenic cause.
3. Review the full medication list and stop or reduce likely culprits as a diagnostic step.
4. Blood tests: full blood count, urea, creatinine, electrolytes (sodium, potassium), calcium, glucose and HbA1c, thyroid stimulating hormone, vitamin B12, folate, 08:00 cortisol (short synacthen test if equivocal), ferritin, liver function tests, albumin, HIV test with consent, serum protein electrophoresis and free light chains, and urinalysis.
5. ECG and 24 hour ambulatory ECG; echocardiography when cardiac cause suspected.
6. Autonomic function testing: heart rate variability with deep breathing (expiration to inspiration difference under 10 beats/minute abnormal), Valsalva ratio (under 1.2 abnormal), blood pressure response to Valsalva (absent phase IV overshoot), sustained handgrip, head up tilt table test (to distinguish neurogenic, delayed and reflex forms), plasma noradrenaline supine and standing (low supine level, failure to rise on standing, in pure autonomic failure), quantitative sudomotor axon reflex test, and thermoregulatory sweat test.
7. Neurological imaging: MRI of brain (hot cross bun sign, putaminal changes in multiple system atrophy), dopamine transporter imaging, and MIBG cardiac scintigraphy (reduced uptake in Parkinson disease and pure autonomic failure, preserved in multiple system atrophy) in specialist assessment.
8. Skin biopsy for small fibre neuropathy and alpha synuclein; abdominal fat pad or rectal biopsy for amyloid; antibody tests (ganglionic acetylcholine receptor, paraneoplastic panel) and genetic tests where indicated.
9. Supine hypertension: record blood pressure supine and in bed at night; ambulatory monitoring.
10. Falls and frailty assessment.

Limits. Blood pressure response varies with time of day, food, hydration and drugs; a single measurement may miss orthostatic hypotension. Delayed forms need prolonged standing. Normal tilt does not exclude intermittent symptoms.

Immediate. If symptomatic or collapsing: lie flat with legs raised, rehydrate; treat bleeding, sepsis, adrenal crisis (hydrocortisone 100 mg intravenously then 200 mg over 24 hours with 0.9% sodium chloride 1 litre in the first hour) and arrhythmia.

Remove reversible causes. Stop or reduce antihypertensives, diuretics, nitrates, alpha blockers, tricyclics, antipsychotics and other culprits. Use bedtime dosing for unavoidable hypotensive drugs. Consider switching tamsulosin to a more uroselective option or reducing dose.

Correct the following:

• anaemia (ferrous sulphate 200 mg daily, hydroxocobalamin 1 mg intramuscularly three times weekly for 2 weeks then every 3 months)
• electrolytes
• hypoglycaemia
• adrenal insufficiency (hydrocortisone 15 to 25 mg daily in divided doses with fludrocortisone 50 to 100 micrograms daily)
• hypothyroidism (levothyroxine 1.6 micrograms/kg daily; start 25 micrograms in older adults)

Non pharmacological measures (all patients).

• Fluid 2 to 3 litres daily and, if no heart failure or hypertension, salt 6 to 10 g daily. Water bolus: 500 mL of water rapidly raises blood pressure by 20 to 30 mmHg for about 1 to 2 hours (drink before getting up in the morning and before planned activities).
• Slow postural changes: sit on the edge of the bed before standing, stand up in stages, flex ankles and calves.
• Physical counter manoeuvres: leg crossing, squatting, buttock clenching, handgrip, toe raising.
• Compression: waist high stockings or abdominal binder (30 to 40 mmHg) worn when upright.
• Head up sleeping 10 to 20 degrees (blocks under the bed head) to reduce nocturnal diuresis and supine hypertension.
• Avoid triggers: heat, hot baths, large carbohydrate meals (use small frequent low carbohydrate meals), alcohol, straining, prolonged standing, dehydration.
• Exercise reconditioning (recumbent bike, rowing, swimming), then upright.
• Caffeine 1 to 2 cups with breakfast may help.

Drug therapy for persistent symptomatic neurogenic orthostatic hypotension.

• Fludrocortisone 50 to 100 micrograms orally daily, increased by 50 micrograms every 1 to 2 weeks to a maximum of 300 micrograms; monitor potassium, supine hypertension, oedema and heart failure.
• Midodrine 2.5 mg orally three times daily (morning, midday, mid afternoon; last dose at least 4 hours before bed), increased by 2.5 mg to 10 mg three times daily; contraindicated in severe heart disease, urinary retention, supine hypertension or acute kidney disease; side effects: piloerection, scalp tingling, urinary retention.
• Droxidopa 100 mg three times daily increasing to 600 mg three times daily where available.
• Pyridostigmine 30 to 60 mg two or three times daily, particularly when supine hypertension limits other agents.
• Desmopressin 0.1 to 0.2 mg at bedtime for nocturnal polyuria (monitor sodium).
• Erythropoietin 25 to 75 units/kg three times weekly for anaemia with autonomic failure, in specialist care.
• Treat supine hypertension: short acting agents at bedtime (losartan 25 mg, captopril 25 mg, nitroglycerin patch 0.1 mg/hour removed in the morning) and head up sleeping.
• Post prandial hypotension: smaller meals, acarbose 50 to 100 mg with meals, caffeine, octreotide 25 to 50 micrograms subcutaneously before meals in specialist care.
• Postural orthostatic tachycardia syndrome: fluids and salt, compression, graded exercise, propranolol 10 to 20 mg two to three times daily, ivabradine 2.5 to 7.5 mg twice daily, midodrine 2.5 to 10 mg three times daily, pyridostigmine 30 to 60 mg three times daily, fludrocortisone 100 micrograms daily.
• Diabetic autonomic neuropathy: glucose control, treat gastroparesis (metoclopramide 5 to 10 mg before meals), plus fluids, salt and compression.
• Amyloidosis: specialist treatment (tafamidis 61 mg daily for transthyretin cardiomyopathy; chemotherapy and stem cell transplantation for light chain amyloidosis).
• Parkinson disease: adjust levodopa, avoid dopamine agonists, add midodrine.

Falls prevention. Review vision, footwear, home hazards, vitamin D and calcium, strength and balance exercise.

Monitoring. Reassess standing blood pressure and symptoms at 1 to 2 weeks after any change, then every 3 to 6 months; check potassium, weight, oedema, and supine blood pressure on fludrocortisone and midodrine; assess falls.

Referral and escalation. Geriatrics for drug review and frailty; neurology or autonomic clinic for suspected neurogenic orthostatic hypotension, parkinsonism or neuropathy; cardiology for cardiac causes; endocrinology for adrenal and thyroid disease; haematology for amyloid.

Admission. Syncope with injury, profound hypotension, bleeding, adrenal crisis, sepsis, arrhythmia, or inability to manage at home.

Safety netting. Return for fainting, falls, chest pain, black stools, severe headache, confusion, or very high blood pressure lying flat (over 180/110 mmHg).

Special groups. Older adults: most frequent group; deprescribe, treat dehydration, and screen annually. Pregnancy: supine hypotension and vasovagal; left lateral position; avoid midodrine and fludrocortisone unless essential. Young women: postural orthostatic tachycardia syndrome and deconditioning. Diabetes: glucose control, avoid hypoglycaemia. Endemic regions: dehydration, anaemia, HIV, Chagas disease, alcohol neuropathy and malnutrition.