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 (2) 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 HTN, 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, α-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-Barré 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