orthostatic hypotension; Bradbury-Eggleston Syndrome; postural orthostatic tachycardia syndrome (POTS)

Introduction

Low blood pressure with dizziness, fainting, & blurred vision upon standing or when standing motionless in a fixed position. Sometimes defined as a drop in systolic blood pressure of 20 mm of Hg with a change in position from supine to standing with a concomittant increase in heart rate of > 10/min.

More formal criteria from ref 2:

• a postural decrease of blood pressure, either:
  • 20 mmHg in systolic, or
  • 10 mmHg in diastolic
• sustained for at least 3 minutes* in standing position
  • assessment of BP at 1 minute may be more useful
• distinguished from sluggish baroreflex (see pathology)

* hypotension may be delayed > 10 minutes

Classification

• immediate type < 3 minutes (more common)
• delayed type > 3 minutes

Etiology

• inadequate vasoconstrictor mechanisms
  • precipitating factor: standing up
  • predisposing factors:
    • peripheral neuropathy affecting autonomic nervous system**
    • pharmacologic agents
      • antihypertensive agents
        • alpha-blockers (doxazosin, terazosin) - more likely than diuretic or timolol ophthalmic
        • diuretics
        • beta-blockers
      • vasodilators (includes PDE-5 inhibitors <Viagra>)
      • opiates
      • bromocryptine
      • tricyclic antidepressants
      • antipsychotic agents
      • anticholinergic agents
      • anti-Parkinson agents
        • L-dopa (Sinemet), benztropine (Cogentin), deprenyl
        • carbidopa blocks orthostatic effect of L-dopa outside the brain
      • ophthalmic agents: timolol > brimonidine (questionable)
        • timolol unlikely to cause orthostatic hypotension
      • > 4 medications
    • prolonged bedrest
    • vitamin B12 deficiency
• age-related failure of baroreceptor sensitivity
• hypovolemia
  • precipitating factor: standing up
  • predisposing factors
    • bleeding from GI tract or from trauma
    • diarrhea
    • vomiting
    • diuretics
    • polyuria
    • hemodialysis
• some cases occur after viral infection or bacterial infection
  • infectious mononucleosis
  • pneumonia
• idiopathic

** Orthostatic hypotension is the most disabling feature of autonomic system dysfunction. Pure autonomic system failure & multiple system atrophy, i.e. Shy-Drager syndrome, is relatively uncommon. Autonomic dysfunction more commonly occurs in association with Parkinson's disease, Huntington's disease, progressive supranuclear palsy, adrenomedullary insufficiency & diabetes mellitus

Epidemiology

• 50% of nursing home patients
• < 20% of healthy community-dwelling elderly
• prevalence increases with age
  • 4.2% 50-59 years
  • 18.5% >= 80 years
• more common in patients with hypertension
• associated with falls in patient with history of fall within the past 6 months

Pathology

• inadequate vasoconstrictor mechanisms in both arterioles & veins resulting in venous pooling, or
• hypovolemia - diminished blood volume
• diminished venous return
• standing causes a gravitational shift of 300-700 mL of intravascular fluid into the lower extremities & abdomen
  • the gravitational pooling of blood results in a decrease pressure detected by baroreceptors in the heart, intrathoracic vessels & carotids resulting in autonomic responses to maintain cardiac output & cerebral perfusion
  • these autonomic baroreceptor responses mainly involve an increase in peripheral vasoconstriction
  • a decrease in reflex peripheral vasocontriction is the most common cause of syncope
  • a decrease in reflex tachycardia is a less common cause of syncope
• age-related failure of baroreceptor sensitivity
• failure of compensatory tachycardia
• decreased cardiac output
• fall in blood pressure
  • most pronounced when standing
  • both initial & delayed
  • a drop in systolic blood pressure of ~35 mm Hg within 30 seconds with return to near-baseline within 2 minutes is the most common pattern
• decrease in cerebral blood flow
  • systolic & diastolic cerebral blood flow velocity decreased 44% & 60%, respectively
  • syncope results when cerebral perfusion is impaired
  • hypoperfusion of other organs
• alpha adrenergic receptor dysfunction may occur is some patients

Genetics

• associated with defects in SLC6A2

Clinical manifestations

• orthostatic tachycardia (may or may not be present)
• symptoms of orthostatic hypotension
  • lightheadedness
  • feeling faint & off balance
    • sensation may worsen with changes in position
    • feeling unsteady when standing
  • exercise intolerance
  • extreme fatigue
  • syncope (fainting)
  • polydipsia
• symptoms related to chronic or acute hypoperfusion of tissues
  • cold extremities
  • chest pain and discomfort
  • disorientation
  • tinnitus
  • dyspnea
  • headache
  • muscle weakness
  • tremulousness
  • visual disturbances: dimming or loss of vision
• symptoms related to autonomic dysfunction
  • abdominal pain
  • bloating
  • constipation
  • diarrhea
  • nausea/vomiting
• symptoms related to cerebral hypoperfusion
  • impaired vigilance
  • depression
  • anomia
  • inattention
  • sleep disorders
• inappropriate levels of epinephrine & norepinephrine
  • anxiety
  • chills
  • fear
  • flushing
  • hyperthermia
  • nervousness
• other
  • neck/shoulder pain

prompt return to normal when supine

Laboratory

• plasma norepinephrine may be abnormally high

Diagnostic procedures

• in assessment of orthostatic hyptension, going from supine to standing is more sensitive than going from sitting to standing
• tilt table testing may be useful if diagnosis in question

Complications

• increased risk of falls
  • slower gait speed & shorter step length ;25'
  • elderly with either immediate (< 3 minutes) or delayed (> 3 minutes) orthostatic hypotension at risk of falls (RR= 1.7)
    • risk slightly higher with delayed orthostatic hypotension
• 64% 10 year mortality vs 9% controls
• increased risk of overall mortality (RR=1.4); (RR=1.7)
  • mortality risk is less for delayed orthostatic hypotension (29%) but may progress to immediate orthostatic hypotension with 10 year mortality of 50%
• increased risk for stroke (RR=2.0)
• increased risk of syncope
• increased risk for cognitive decline & dementia
• cognition worsens when sitting or standing in patients with Parkinson's disease & orthostatic hypotension

Differential diagnosis

• generalized anxiety disorder

Management

• no treatment unless symptomatic
• general measures:
  • arise slowly
  • adequate hydration
    • IV hydration for orthostatic hypotension & syncope after hemodialysis
  • compression stockings for lower extremity edema
  • avoid trigger situations
  • raise head of bed 30 to degrees
  • exercise helpful but may be difficult
  • supine leg exercises prior to standing may reduce orthostasis
• dietary intervention
  • avoidance of alcoholic beverages
  • frequent small meals
  • increased salt intake
  • low carbohydrate diet
• drug therapy
  • midodrine (alpha-1-adrenergic agonist) is standard of care
    • atomoxetine (norepinephrine transporter inhibitor) seems to improve orthostasis more than midodrine
  • fludrocortisone (Florinef)
    • KCl supplementation if hypokalemia develops
  • droxidopa
  • for levodopa-induced orthostasis, increase dose of carbidopa
    • new onset orthostasis with Sinemet therapy
  • prostaglandin inhibitors
  • beta-blockers (diastolic dysfunction)
    • propranolol 20 mg QD
      • decreases heart rate
      • improves exercise capacity VO2max
    • pindolol
  • ACE inhibitor may improve cardiac output
  • calcium channel blocker
    • amlodipine less likely to cause orthostasis than diuretic
  • ivabradine lowers heart rate & improves quality of life
  • avoid diuretics
  • antidepressant for depression: SSRI
  • pregabilin useful for neuropathic pain
    • duloxetine probably better than pregabalin
  • benzodiazepines are effective for anxiety
  • vitamin B12 if deficient
  • ritalin & Adderall have been used
  • sympathomimetics
    • ephedrine
    • midodrine (ProAmatine) {expensive}
  • dopamine antagonists (metoclopramide)
  • venoconstrictors (dihydroergotamine)
  • desmopressin (minimizes fluid loss)
  • octreotide (inhibits release of gastrointestinal peptides, some of which have hypotensive properties
  • caffeine effects variable but worth a try
• supine hypertension a consideration & limiting factor
• intensive blood pressure lowering (target systolic BP < 120 mm Hg) is associated with reduced risk for orthostatic hypotension
  • editor notes this finding may seem couterintuitive

More general terms

• hypotension

More specific terms

• orthostatic hypotension in Parkinson's disease

Additional terms

• neuropathic tachycardia syndrome; neuropathic postural tachycardia syndrome
• orthostatic

Patient information

orthostatic hypotension patient information

Database

• OMIM: https://mirror.omim.org/entry/604715