BASICS
Postural or orthostatic hypotension (OH) represents the failure of cardiovascular reflexes to maintain adequate BP on standing from a supine or sitting position.
DESCRIPTION
- OH is defined as a sustained and persistent drop in systolic BP (SBP) ≥20 mm Hg or diastolic BP ≥10 mm Hg within 3 minutes of achieving a standing position or head-up tilt to at least 60 degrees on tilt table (1). Delayed OH can infrequently occur with a slow decline in SBP beyond 5 minutes of standing and may be revealed by extending the period of orthostatic stress.
- Symptoms differ greatly in severity and can be precipitated by postural changes, postprandially, or by exertion. Characteristic symptoms of OH are recurrent dizziness, light-headedness, 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.
EPIDEMIOLOGY
Asymptomatic OH is far more common than symptomatic OH but importantly is an independent risk factor for mortality and increases the incidence of myocardial infarction, stroke, heart failure (HF), and atrial fibrillation. OH is also a manifestation of many underlying diseases and may be the initial sign of autonomic failure in many neurodegenerative disorders. The prevalence increases with age, hypertension (HTN), diabetes, and use of medications, particularly antihypertensive and antidepressant medications. In approximately 15% of syncope presentations, orthostasis is identified (Ricci) as the likely etiology.
Incidence
80,095 orthostatic-related hospitalizations occurred in the United States in 2004; OH was the primary diagnosis in 35%.
Prevalence
~5% of persons <50 years and 30% >70 years, more common in those living in long-term care facilities (45% vs. 6% living in the community). In those with HTN, prevalence is 13.4-32.1%
ETIOLOGY AND PATHOPHYSIOLOGY
- During standing, 500 to 1,000 mL of blood pools in the lower extremities and the splanchnic vasculature. This reduces cardiac preload but is opposed by an increase in sympathetic tone and vasopressin release that maintains cerebral perfusion pressure by increasing peripheral vascular resistance. Impairment of these compensatory mechanisms by autonomic dysfunction, or nonneurogenic causes such as medications, hypovolemia, or cardiac pump failure, leads to an inability to maintain effective cerebral perfusion pressure. Autonomic dysfunction also impairs proximal tubule renal sodium reabsorption, which contributes to OH through urinary sodium wasting and a consequent reduction in circulating plasma volume. In older people, vascular stiffening and decreased baroreceptor sensitivity predispose to OH.
- Supine hypertension (SH), due to baroreflex dysfunction and fluid redistribution on assuming a horizontal position, is common in patients with OH. Increased renal perfusion pressure in the recumbent position also leads to nocturnal natriuresis, which decreases circulating volume, worsening orthostatic tolerance in the morning.
- Medications (iatrogenic causes)
- Antidepressants (most commonly implicated): TCA, MAOIs
- Anticholinergics: benztropine, oxybutynin
- Antihypertensives: of classes including diuretics, Ī±-blockers, β-blockers
- Dopamine agonists: levodopa, rotigotine bromocriptine, ropinirole, pramipexole
- Ethanol
- Insulin (may exacerbate OH in the setting of diabetic neuropathy)
- Vasodilators: hydralazine, nitroglycerin
- Phosphodiesterase inhibitors: sildenafil, tadalafil
- Opioids/sedatives: morphine, benzodiazepines, barbiturates, promethazine
- Antipsychotics: thioridazine, iloperidone
- Neurotoxic drugs: vincristine, cisplatin
- Neurogenic (primary) causes
- Idiopathic OH (1/3 of cases of OH)
- Central autonomic nervous system diseases: familial dysautonomia (rare, childhood), synucleinopathies such as Lewy body dementia, multisystem atrophy (Shy-Drager syndrome), Parkinson disease (PD): (40% of patients with PD have OH) and pure autonomic failure (rare)
- Peripheral autonomic nervous system diseases: acute autonomic neuropathy and Guillain-Barr © syndrome (acute onset, frequently preceded by viral syndrome), alcoholic polyneuropathy, amyloidosis, autoimmune autonomic ganglionopathy (rare), chronic renal failure: uremic or β-2 microglobulin neuropathy (dialysis). Diabetes: diabetic autonomic neuropathy (very common). Exposure to neurotoxins. Hereditary sensory and autonomic neuropathies: dopamine-β-hydroxylase deficiency (rare). HIV neuropathy. Paraneoplastic autonomic neuropathy: small cell lung cancer, non-small-cell lung cancer, 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 (secondary)
- Cardiac disorders: HF, arrhythmias, pericardial disease, severe aortic stenosis, idiopathic hypertrophic subaortic stenosis, hypertrophic obstructive cardiomyopathy, acute aortic regurgitation, acute myocardial infarction
- Deconditioning
- Intravascular volume depletion: bleeding, diarrhea, diabetes insipidus, diuretics, poor oral intake, vomiting
- Metabolic: adrenal insufficiency, hypoaldosteronism, pheochromocytoma, carcinoid syndrome, hypokalemia (severe), hypothyroidism, porphyria
- Sepsis
- Systemic mastocytosis
- Venous pooling: heat or vigorous exercise, postprandial splanchnic dilation, prolonged recumbency or standing
RISK FACTORS
- Elderly, particularly in long-term care facilities
- Multiple comorbidities, including HTN, diabetes, neurodegenerative disorders, and neuropathy
- Polypharmacy (see "Epidemiology" section)
GENERAL PREVENTION
Avoid polypharmacy and monitor drug interactions: maintain adequate fluid balance.
COMMONLY ASSOCIATED CONDITIONS
Diabetes mellitus with neuropathy, uncontrolled HTN and antihypertensive treatment, PD, dehydration
DIAGNOSIS
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
HISTORY
- Postural symptoms: dizziness, light-headedness, palpitations, visual blurring, 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, ingestions of large/carbohydrate-rich meals, alcohol intake (vasodilation)
- Volume depletion: vomiting, diarrhea, poor oral intake, polyuria
- Cardiac pump failure: orthopnea, edema, paroxysmal nocturnal dyspnea, angina
- Peripheral neuropathy: numbness, pain, paresthesia, imbalance, or falls
- Associated diseases: diabetes, PD, dementia
- Autonomic symptoms: altered sweating (hyper- or hypohidrosis), GI dysfunction (bloating, nausea, vomiting, constipation), impotence, bladder dysfunction, sicca symptoms
- May be asymptomatic
PHYSICAL EXAM
- Measure BP while supine and standing: Patient should be supine for 5 minutes, then after standing, check the BP at 3 minutes. Use sitting measurements only if the patient is too dizzy or weak to stand. 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, whereas minimal or no change in heart rate may suggest a neurogenic cause. Orthostatic tachycardia without a significant drop in BP 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
DIFFERENTIAL DIAGNOSIS
Neurally mediated (reflex) syncope: vasovagal syncope, situational syncope (cough, micturition, defecation, swallowing), carotid sinus hypersensitivity. Falls related to a neurologic disorder, postprandial hypotension, POTS, shock (must have a normal lying BP before testing)
DIAGNOSTIC TESTS & INTERPRETATION
Initial Tests (lab, imaging)
- CBC, BMP (hypokalemia, alkalosis, and renal insufficiency suggesting volume depletion), thyroid-stimulating hormone (TSH) (2)[C]
- ECG and/or Holter monitor/event monitor: to rule out arrhythmias and detect structural heart diseasel; Echocardiogram: for abnormal ECG, new murmurs, or suspected HF (2)[C]; MRI: for suspected neurodegenerative disorders or spinal disease
Follow-Up Tests & Special Considerations
- If neuropathy is found on exam, consider additional laboratory testing such as vitamin B12 levels and serum and urine protein electrophoresis. Nerve conduction studies and electromyography may also be considered.
- Adrenal insufficiency and pheochromocytoma evaluation is warranted in OH of uncertain cause: 8 am cortisol level: if <18 Ī¼g/dL, consider cosyntropin testing. 24-Hour urinary or plasma fractionated metanephrines: Consider further testing, depending on results.
- Antibodies to the neuronal nicotinic receptor in cases of suspected autoimmune autonomic ganglionopathy
Diagnostic Procedures/Other
- 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 (1,3)[C].
- Autonomic testing: useful in cases where neurally mediated syncope versus orthostatic syncope is unclear and to diagnose subclinical cases. Includes heart rate and BP variability with deep inspiration and Valsalva maneuver, sudomotor evaluation, orthostatic vascular resistance, plasma norepinephrine response to orthostasis, and pharmacologic challenges (4)[C]. A skin biopsy also may be performed to evaluate for small fiber neuropathy.
- Consider 24-hour ambulatory BP monitoring (8).
TREATMENT
- Abdominal binder or compression stockings (not thromboembolism deterrent [TED] hose), preferably waist high with 30 to 50 mmHg for the legs and 20 to 30 mm Hg of pressure for the abdomen (worn before rising) (1,3,5,8)[B]. These measures are often not well tolerated.
- Moving gradually when switching to standing from a sitting position (3,4 and 5)[C]. Also, physical counter maneuvers (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, such as inspiration through pursed lips and inspiratory sniffing (1,4,5)[B].
- Moderate exercise (supine or sitting isotonic exercise if symptoms are severe): improves orthostatic tolerance and reduces venous pooling (1,5)[B]
- Increase water and sodium intake: 1.25 to 2.5 L of fluid a day and up to 6 to 9 g/day of sodium (if needed, salt tablets starting at 500 mg PO TID may be used). Encourage drinking water with meals and before exercise. Rapid ingestion of two 8-oz glasses of water (500 mL) over 3 to 4 minutes elicits a marked pressor response lasting for up to 2 hours (1,3,4)[B].
- Small and frequent rather than large meals
- Elevate the head of the bed 20 degrees (6 to 9 inches) to reduce supine HTN and nocturnal natriuresis (4,5)[B],(6)[C].
- Avoid prolonged recumbency; increased intrathoracic pressure (straining, coughing); large meals, especially if high in carbohydrates; and alcohol (4,5)[C].
MEDICATION
First, identify and discontinue all potentially aggravating medications. Medication is indicated only when nonpharmacologic measures are insufficient to control symptoms. Goal of therapy is to improve functional capacity and quality of life without causing excessive supine HTN rather than to eliminate orthostatic drops in BP.
First Line
- Fludrocortisone: synthetic mineralocorticoid that increases sodium and fluid retention and increases peripheral vascular resistance. Starting at 0.1 mg/day, titrate for symptoms every week up to 0.5 mg/day. Contraindicated in patients with HF and chronic renal insufficiency due to volume expansion (1,5,7)[B].
- Midodrine: selective peripheral Ī±-agonist that increases vascular resistance. FDA-approved to treat OH. Start at 2.5 mg PO TID and titrate for symptoms up to 10 mg TID. Avoid within 4 hours of bedtime to prevent worsening supine HTN, and use with caution in patients with coronary artery disease (1)[B],(5,7)[A].
- L-threo-dihydroxyphenylserine (droxidopa): orally active synthetic prodrug that is converted to norepinephrine by dopa decarboxylase enzyme, FDA-approved to treat OH, use up to 1,800 mg/day PO divided 3 times per day (6,7)[C]. Avoid using within 3 hours of bedtime to avoid SH. Use caution in patients with cardiac disease.
Second Line
- Pyridostigmine: acetylcholinesterase inhibitor, increases sympathetic ganglionic neurotransmission, 30 to 60 mg PO TID (1,5,7)[B]
- Caffeine: methylxanthine with pressor effect due to blockade of adenosine receptors, 100 to 250 mg PO TID, as tablets or caffeinated beverages, particularly for postprandial hypotension (3)[B]
- Octreotide: likely mechanism splanchnic vasoconstriction and shunting of blood from central circulation (12.5 to 25 Ī¼g SQ BID) (3)[B],(6)[C],(7)[B]
- Erythropoietin: increases RBC mass. Consider only when significant anemia coexists, 25 to 75 U/kg SQ 3 times per week (maintenance dose may be lower). Iron studies and supplementation usually are required (4,7)[B].
- Ephedrine: mixed Ī±- and β-agonist, 25 to 50 mg PO TID (avoid within 4 hours before bedtime to prevent worsening supine HTN)
- Pseudoephedrine: mixed Ī±- and β-agonist, 30 to 60 mg PO TID (avoid within 4 hours before bedtime) (3)[B],(4,6)[C]
- Desmopressin: vasopressin analogue, 5 to 40 Ī¼g/day nasal spray, or 100 to 800 Ī¼g/day PO (4)[C]
- Nonsteroidal anti-inflammatory drugs: may supplement treatment with fludrocortisone or a sympathomimetic agent. They are believed to act by limiting the vasodilating effects of circulating prostaglandins.
ADDITIONAL THERAPIES
Consider bedtime nitrates or nifedipine to treat severe, sustained supine HTN; may increase the risk of syncope and falls (4)[C]. Caffeine and octreotide are recommended for postprandial hypotension (3)[B].
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.
ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
Monitor for significant supine HTN, fluid overload, electrolyte abnormalities, and HF 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.
PATIENT EDUCATION
Recognize symptoms and avoid aggravating factors. Educate on nonpharmacologic measures.
COMPLICATIONS
Syncope, falls (hip fracture, head trauma)
REFERENCES
11 Lanier JB, Mote MB, Clay EC. Evaluation and management of orthostatic hypotension. Am Fam Physician. 2011;84(5):527-536.22 Lahrmann H, Cortelli P, Hilz M, et al. EFNS guidelines on the diagnosis and management of orthostatic hypotension. Eur J Neurol. 2006;13(9):930-936.33 Arnold AC, Shibao C. Current concepts in orthostatic hypotension management. Curr Hypertens Rep. 2013;15(4):304-312. doi:10.1007/s11906-013-0362-3.44 Freeman R. Clinical practice. Neurogenic orthostatic hypotension. N Engl J Med. 2008;358(6):615-624.55 Figueroa JJ, Basford JR, Low PA. Preventing and treating orthostatic hypotension: as easy as A, B, C. Cleve Clin J Med. 2010;77(5):298-306.66 Raj SR, Coffin ST. Medical therapy and physical maneuvers in the treatment of the vasovagal syncope and orthostatic hypotension. Prog Cardiovasc Dis. 2013;55(4):425-433.77 Ong AC, Myint PK, Shepstone L, et al. A systematic review of the pharmacological management of orthostatic hypotension. Int J Clin Pract. 2013;67(7):633-646.88 Ricci F, Caternina RD, Fedorowski A. Orthostatic hypotension: epidemiology, prognosis, and treatment. J Am Coll Cardiol. 2015;66(7):848-860.
CODES
ICD10
I95.1 Orthostatic hypotension
ICD9
458.0 Orthostatic hypotension
SNOMED
- Orthostatic hypotension (disorder)
- postural orthostatic tachycardia syndrome (disorder)
CLINICAL PEARLS
- 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.