- Postural or orthostatic hypotension (OH) is defined as a sustained and persistent drop in systolic blood pressure (SBP) ≥20 mm Hg or diastolic blood pressure (DBP) ≥10 mm Hg within 3 minutes of achieving a standing position. Delayed OH can infrequently occur with a slow decline in SBP over 5 minutes or longer, and may not be detected by routine clinical examination but can be detected by tilt table testing. OH may be the initial sign of autonomic failure in many primary and secondary neurologic disorders, and the precipitation of OH by medications or other inciting events may reflect an underlying autonomic pathology.
- Characteristic symptoms of OH are recurrent dizziness, lightheadedness, presyncope or syncope with assumption of an upright posture, typically relieved by achieving a recumbent position, and can be incapacitating. In the elderly, OH may be asymptomatic or present with nonspecific complaints of weakness.
80,095 hospitalizations for orthostatic-related causes occurred in the US in 2004; OH was the primary diagnosis in 35% (1).
OH affects 18% of individuals ≥ 65 years of age, being more common in those living in long-term care facilities (45% vs 6% living in the community) (1).
- Elderly, particularly in long-term care facilities
- Neurodegenerative disorders and neuropathy
- Avoid polypharmacy and monitor drug interactions.
- Adequate fluid balance
- Adequate glucose control
- During standing, 500–1,000 mL of blood pool in the lower extremities and the splanchnic vasculature. This reduces cardiac preload and is normally opposed by an increase in sympathetic tone and vasopressin release that results in an increase in peripheral vascular resistance that mantains cerebral perfusion pressure. Impairment of these compensatory mechanisms by autonomic dyfunction, or non-neurogenic causes such as medications, hypovolemia, or cardiac pump failure leads to an inability to maintain effective cerebral perfusion pressure. Autonomic dysfunction also impairs norepinephrine-mediated proximal tubule renal sodium reabsortion, which contributes to OH through urinary sodium wasting and a consequent reduction in circulating plasma volume.
- Supine hypertension (SH), due to baroreflex dysfunction and fluid redistribution upon assuming a horizontal position is common in patient with OH. Increased renal perfusion pressure in the recumbent position also leads to nocturnal natriuresis, which decreases circulating intravascular volume, worsening orthostatic tolerance in the morning.
- Medications (iatrogenic):
- Anticholinergics: Benztropine, orphenadrine, oxybutynin, trihexyphenidyl
- Antidepressants: TCA, MAOIs, SSRIs, and SNRIs
- Antihypertensives: Beta-blockers, calcium channel blockers, ACE-inhibitors, clonidine, vasodilators (alpha-blockers, hydralazine, nitrates)
- Dopamine agonists: Levodopa, bromocriptine, ropinirole, pramipexole
- Insulin (may exacerbate OH in the setting of diabetic neuropathy)
- Narcotics/sedatives: Morphine, benzodiazepines, barbiturates
- Neuroleptics: Chlorpromazine, quetiapine
- Neurotoxic drugs: Amiodarone, vincristine, cisplatin
- Neurogenic causes:
- Idiopathic OH (1/3 of cases of OH)
- Central autonomic nervous system diseases:
- Familial dysautonomia (rare, childhood)
- Lewy body dementia
- Multisystem atrophy (uncommon)
- Parkinson disease: 40% of patients with PD have OH.
- Pure autonomic failure (rare)
- Peripheral autonomic nervous system diseases:
- Acute autonomic neuropathy and Guillan-Barre syndrome (acute onset, frequently preceeded by viral syndrome)
- Alcoholic polyneuropathy
- Autoimmune autonomic ganglionopathy (rare)
- Chronic renal failure: Uremic or beta-2 microglobulin neuropathy (dialysis)
- Diabetes: Diabetic autonomic neuropathy (common)
- Exposure to neurotoxins
- Hereditary sensory and autonomic neuropathies: Dopamine-beta-hydroxylase deficiency (rare)
- HIV neuropathy
- Paraneoplastic autonomic neuropathy: SCLC, NSCLC, GI neoplasias, prostate, breast, bladder, kidney, testicle, and ovary
- Spinal cord pathologies: Trauma, myelitis, tumors, tabes dorsalis, multiple sclerosis, syringomyelia, infarction
- Vitamin B12 deficiency
- Nonneurogenic causes:
- Cardiac pump failure: Heart failure, arrhythmias, pericardial disease, severe aortic stenosis
- Intravascular volume depletion: Bleeding, diarrhea, diabetes insipidus, diuretics, poor oral intake, vomiting
- Metabolic: Adrenal insufficiency, hypoaldosteronism, pheochromocytoma, carcinoid syndrome, hypokalemia (severe), hypothyroidism
- Systemic mastocytosis
- Venous pooling: Heat or vigorous exercise, postprandial splanchnic dilation, prolongued recumbency or standing, severe varicosities
Commonly Associated Conditions
- Diabetes mellitus
- Hypertension (antihypertensive treatment)
- Parkinson disease
Initial approach: Detailed history and physical examination with a focus on neurodegenerative disorders and neuropathy, thorough medication review, screening for reversible causes, 12-lead ECG, CBC, and BMP
- Postural symptoms: Dizziness, lightheadedness, palpitations, syncope or presyncope:
- Elderly patients may have vague complaints even before frank syncope: Generalized weakness, fatigue, nausea, difficulty with concentration or cognition, leg buckling, pure vertigo, visual blurring, headache or “coat-hanger” pattern neck-shoulder pain, orthostatic dyspnea, or angina
- Aggravating factors: Warm environments, exertion, prolonged standing or eating (vasodilation)
- Volume depletion: Vomiting, diarrhea, poor p.o. intake, polyuria
- Cardiac pump failure: Orthopnea, edema, paroxysmal nocturnal dyspnea, angina
- Peripheral neuropathy: Numbness, pain, paresthesia, imbalance, or falls
- Associated diseases: Diabetes, Parkinson disease, dementia
- Autonomic symptoms: Altered sweating (hyper- or hypohydrosis), GI dysfunction (bloating, nausea, vomiting, constipation), impotence, bladder dysfunction, sicca symptoms
- Review all medications and herbal therapies.
- Measure BP while supine and standing: Patient should be supine for at least 5 minutes, then after standing, check the blood pressure at 3 minutes. Use sitting measurements only if the patient is too dizzy or weak to stand. Always use fall precautions:
- Do not check for OH in patients with supine SBP <90 mm Hg (shock) as it adds no useful information.
- Tachycardic response to standing may be a sign of hypovolemia or cardiac pump failure, while minimal or no change in heart rate may suggest a neurogenic cause. Orthostatic tachycardia without a significant drop in blood pressure does not meet criteria for OH and may suggest postural orthostatic tachycardia syndrome (POTS).
- Cardiac exam: Jugular venous distention, pulse irregularity, edema, murmurs, S3
- Neurologic exam: Hypomimia, gait, tremor, cogwheel rigidity, motor strength, fine-touch, pain sensation, proprioception, Romberg maneuver, cerebellar signs, and myoclonus
Diagnostic Tests & Interpretation
Initial lab tests
- CBC: Anemia (hemorrhage) or leukocytosis (sepsis)
- BMP: Hypokalemia, alkalosis, and renal insufficiency suggesting volume depletion
Follow-Up & Special Considerations
- If neuropathy is found on examination consider:
- Vitamin B12 levels
- Serum protein electrophoresis (amyloidosis)
- Adrenal insufficiency and pheocromocytoma evaluation is warranted in OH of uncertain cause:
- 8 a.m. cortisol level: If less than 18 ucg/dL, consider cosyntropin testing.
- 24-hour urinary or plasma fractionated metanephrines: Consider further testing depending on results.
- Ab to the neuronal nicotinic receptor (nAChR) in cases of suspected autoimmune autonomic ganglionopathy
- ECG: To rule out arrythmias and detect structural heart disease
- Echocardiogram: For abnormal ECG, new murmurs, or suspected heart failure
- Nerve conduction studies and electromyography: For suspected neuropathy
- MRI: For suspected neurodegenerative disorders or spinal disease
- Tilt table testing: Indicated if orthostatic symptoms are persistent, significant, and characteristic despite a nondiagnostic clinical examination. Provocation with nitroglycerin or IV isoproterenol is not recommended, as it may cause false-positive results (2).
- Autonomic testing: Useful in cases where neurally mediated syncope vs orthostatic syncope is unclear, and to diagnose subclinical cases. Includes HR and BP variability with deep inspiration and Valsalva maneuver, sudomotor evaluation, orthostatic vascular resistance, plasma norepinephrine response to orthostasis, and pharmacologic challenges (3,4).
- Nonorthostatic syncope: Neurally mediated (vasovagal syncope), situational syncope, carotid sinus hypersensitivity
- Falls related to a neurologic disorder
- Postprandial hypotension
- Postural orthostatic tachycardia syndrome (POTS)
- Shock (must have a normal lying BP before testing)
Nonpharmacologic general measures:
- Abdominal binder or compression stockings (not TED hose), preferably waist high with 20 mm Hg of pressure (worn before rising) (2,3,5)[B]
- Perform gradual staged movements with postural changes: Arise slowly from supine to seated and rest before standing (235)[C].
- Physical countermaneuvers (to increase vascular resistance and preload): Isometric contraction of leg muscles for 30 seconds at a time, repeated feet dorsiflexion, leg crossing and contraction, squatting, bending at the waist, leg elevation, and respiratory maneuvers like inspiration through pursed lips and inspiratory sniffing (235)[B]
- Moderate exercise (supine or sitting isotonic exercise if symptoms are severe): Improves orthostatic tolerance and reduces venous pooling (235)[B]
- Increase water and sodium intake: 2.0–2.50 L of fluid a day, and up to 10 g of sodium per day (if needed, salt tablets starting at 500 mg p.o. t.i.d. may be used). Encourage drinking water with meals and before exercise. Rapid ingestion of 2 8-oz glasses of water (500 mL) over 3–4 minutes elicits a market pressor response lasting for up to 1 hour (23,5)[B].
- Elevate the head of the bed 20 degrees (4-6 inches) to reduce supine hypertension and nocturnal diuresis (235)[B].
- Avoid: Prolonged recumbency, increased intrathoracic pressure (straining, coughing), large meals especially if high in carbohydrates, and alcohol (235)[C]
- 1st identify and discontinue all potentially aggravating medications.
- Indicated only when nonpharmacologic measures are insufficient to control symptoms
- Goal of therapy is to improve functional capacity and quality of life rather than to eliminate orthostatic drops in blood pressure.
- Fludrocortisone: Synthetic mineralocorticoid that increases sodium and fluid retention and increases peripheral vascular resistance. Starting at 0.1 mg daily, titrate for symptoms every week up to 0.5 mg daily. Contraindicated in patients with HF and chronic renal insufficiency due to volume expansion (235)[B].
- Midodrine: Selective peripheral alpha-agonist that increases vascular resistance. Only drug currently FDA approved to treat OH. Start at 2.5 mg t.i.d. and titrate for symptoms up to 10 mg p.o. t.i.d. Avoid within 4 hours of bedtime to prevent worsening supine hypertension, and use with caution in patients with coronary artery disease (235)[A].
- Caffeine: Methylxanthine with pressor effect due to blockade of adenosine receptors. 100–250 mg p.o. t.i.d., as tablets or caffeinated beverages [B].
- Erythropoietin: Increases red blood cell mass. Consider only when significant anemia coexists. Dosage 25–75 U/kg SQ 3 times a week (maintenance dose may be lower). Iron studies and supplementation usually required (23)[B]
- Pyridostigmine: Acetylcholinesterase inhibitor, increases sympathetic ganglionic neurotransmission. Dosage 30–60 mg p.o. t.i.d. (35)[B]
- Ephedrine: Mixed alpha and beta agonist. Dosage 25–50 mg p.o. t.i.d. (avoid within 4 hours before bedtime to prevent worsening supine hypertension) (23)[C].
- Pseudoephedrine: Mixed alpha and beta agonist. Dosage 30–60 mg p.o. t.i.d. (avoid within 4 hours before bedtime) (3)[C].
- Desmopressin: Vasopressine analogue. Dosage 5–40 mcg nasal spray daily, or 100-800 mcg p.o. daily (2,3)[C]
- L-dihydroxyphenylserine (Doxidopa): Prodrug that is converted to noradrenaline by dopadecarboxylase enzyme. Dosage 200–400 mg p.o. daily (2,4)[A].
- There is little or inconsistent evidence to recommend other agents such as NSAIDs, yohimbine, somatostatine, dihydroergotamine, beta agonists, or dopamine agonists (3).
Consider bedtime nitrates or nifedipine to treat severe, sustained supine hypertension. May increase the risk of syncope and falls (3)[C].
Issues for Referral
Consider cardiology referral if there is significant heart disease or tilt table testing will be required. Consider neurology referral for confirmed or suspected primary neurologic pathologies.
Monitor for significant supine hypertension, fluid overload, electrolyte abnormalities, and heart failure in patients under medical treatment. In patients without an apparent cause of OH, follow-up is essential because OH alone may be the initial presentation of neurologic disorders.
Recognize symptoms and avoid aggravating factors. Educate on nonpharmacologic measures and goals of therapy.
Syncope, falls (hip fracture, head trauma), and rarely stroke
1. Cyndya Shibao, Carlos G, Grijalva et al. Orthostatic Hypotension-Related Hospitalizations in the United States. The American Journal of Medicine. 2007;120:975–980.
2. Lahrmann H, Cortelli P, Hilz M, Mathias CJ, Struhal W, Tassinari M et al. EFNS guidelines on the diagnosis and management of orthostatic hypotension. Eur. J. Neurol. 2006;13:930–6.
3. Freeman R et al. Clinical practice. Neurogenic orthostatic hypotension. N Engl J Med. 2008;358:615–24.
4. Goldstein DS, Sharabi Y et al. Neurogenic orthostatic hypotension: a pathophysiological approach. Circulation. 2009;119:139–46.
5. Figueroa JJ, Basford JR, Low PA et al. Preventing and treating orthostatic hypotension: As easy as A, B, C. Cleve Clin J Med. 2010;77:298–306.
- OH is a clinical finding, not a disease. Treatment should be guided by symptoms rather than by absolute BP drop.
- Always check the medication list and volume status.
- Drug-related OH may be a sign of underlying autonomic dysfunction.
- Pharmacologic treatment is indicated only when nonpharmacologic measures are insufficient to control symptoms.
458.0 Orthostatic hypotension
28651003 orthostatic hypotension (disorder)