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

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: 1) a postural decrease of blood pressure, either: a) 20 mmHg in systolic, or b) 10 mmHg in diastolic 2) sustained for at least 3 minutes* in standing position - assessment of BP at 1 minute may be more useful [5] 3) distinguished from sluggish baroreflex (see pathology) * hypotension may be delayed > 10 minutes [9] Classification: - immediate type < 3 minutes (more common) - delayed type > 3 minutes [35] Etiology: 1) inadequate vasoconstrictor mechanisms a) precipitating factor: standing up b) 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 [4] - vasodilators (includes PDE-5 inhibitors <Viagra>) [7] - opiates [4] - bromocryptine [4] - tricyclic antidepressants [7] - antipsychotic agents [7] - anticholinergic agents [7] - anti-Parkinson agents [7] - L-dopa (Sinemet), benztropine (Cogentin), deprenyl - carbidopa blocks orthostatic effect of L-dopa outside the brain [11] - ophthalmic agents: timolol > brimonidine [11] (questionable) - timolol unlikely to cause orthostatic hypotension [31] - > 4 medications - prolonged bedrest - vitamin B12 deficiency 2) age-related failure of baroreceptor sensitivity 3) hypovolemia a) precipitating factor: standing up b) predisposing factors - bleeding from GI tract or from trauma - diarrhea - vomiting - diuretics - polyuria - hemodialysis 4) some cases occur after viral infection or bacterial infection - infectious mononucleosis - pneumonia 5) 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 [7] Epidemiology: 1) 50% of nursing home patients 2) < 20% of healthy community-dwelling elderly [12] 3) prevalence increases with age - 4.2% 50-59 years - 18.5% >= 80 years [17] 4) more common in patients with hypertension 5) associated with falls in patient with history of fall within the past 6 months Pathology: 1) inadequate vasoconstrictor mechanisms in both arterioles & veins resulting in venous pooling, or 2) hypovolemia - diminished blood volume 3) diminished venous return 4) standing causes a gravitational shift of 300-700 mL of intravascular fluid into the lower extremities & abdomen [4] - 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 [4] - a decrease in reflex tachycardia is a less common cause of syncope [4] 5) age-related failure of baroreceptor sensitivity [30] 6) failure of compensatory tachycardia 7) decreased cardiac output 8) fall in blood pressure a) most pronounced when standing b) both initial & delayed c) 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 [12] 9) 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 10) 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 [4] - feeling unsteady when standing [4] - 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 Special laboratory: - in assessment of orthostatic hyptension, going from supine to standing is more sensitive than going from sitting to standing [28] - tilt table testing may be useful if diagnosis in question Differential diagnosis: - generalized anxiety disorder Complications: - increased risk of falls [12] - 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 [35] - 64% 10 year mortality vs 9% controls [9] - increased risk of overall mortality (RR=1.4) [19]; (RR=1.7) [21] - mortality risk is less for delayed orthostatic hypotension (29%) but may progress to immediate orthostatic hypotension with 10 year mortality of 50% [9] - increased risk for stroke (RR=2.0) [20,23] - increased risk of syncope - increased risk for cognitive decline & dementia [23] - cognition worsens when sitting or standing in patients with Parkinson's disease & orthostatic hypotension [22] Management: 1) no treatment unless symptomatic 2) general measures: a) arise slowly [4] b) adequate hydration [6] - IV hydration for orthostatic hypotension & syncope after hemodialysis [34] c) compression stockings for lower extremity edema [11] d) avoid trigger situations e) raise head of bed 30 to degrees f) exercise helpful but may be difficult g) supine leg exercises prior to standing may reduce orthostasis [16] 3) dietary intervention a) avoidance of alcoholic beverages b) frequent small meals c) increased salt intake d) low carbohydrate diet 4) drug therapy a) midodrine (alpha-1-adrenergic agonist) is standard of care [18] - atomoxetine (norepinephrine transporter inhibitor) seems to improve orthostasis more than midodrine [18] b) fludrocortisone (Florinef) - KCl supplementation if hypokalemia develops c) droxidopa d) for levodopa-induced orthostasis, increase dose of carbidopa [11] - new onset orthostasis with Sinemet therapy e) prostaglandin inhibitors f) beta-blockers (diastolic dysfunction) 1] propranolol 20 mg QD a] decreases heart rate b] improves exercise capacity VO2max [14] 2] pindolol g) ACE inhibitor may improve cardiac output h) calcium channel blocker - amlodipine less likely to cause orthostasis than diuretic [4] i) ivabradine lowers heart rate & improves quality of life [27] j) avoid diuretics [4] k) antidepressant for depression: SSRI l) pregabilin useful for neuropathic pain - duloxetine probably better than pregabalin m) benzodiazepines are effective for anxiety n) vitamin B12 if deficient o) ritalin & Adderall have been used p) sympathomimetics 1] ephedrine 2] midodrine (ProAmatine) {expensive} q) dopamine antagonists (metoclopramide) r) venoconstrictors (dihydroergotamine) s) desmopressin (minimizes fluid loss) t) octreotide (inhibits release of gastrointestinal peptides, some of which have hypotensive properties u) caffeine effects variable but worth a try [10] 5) supine hypertension a consideration & limiting factor 6) intensive blood pressure lowering (target systolic BP < 120 mm Hg) is associated with reduced risk for orthostatic hypotension [26] - editor notes this finding may seem couterintuitive

Related

neuropathic tachycardia syndrome; neuropathic postural tachycardia syndrome orthostatic

Specific

orthostatic hypotension in Parkinson's disease

General

hypotension

Database Correlations

OMIM 604715

References

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  37. NINDS Postural Tachycardia Syndrome Information Page https://www.ninds.nih.gov/Disorders/All-Disorders/Postural-Tachycardia-Syndrome-Information-Page/2836) organizations/1212 - NINDS Orthostatic Hypotension Information Page https://www.ninds.nih.gov/Disorders/All-Disorders/Orthostatic-Hypotension-Information-Page