16/3/2020 Mechanisms, causes, and evaluation of orthostatic hypotension - UpToDate

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Mechanisms, causes, and evaluation of orthostatic

hypotension
Author: Horacio Kaufmann, MD
Section Editor: Michael J Aminoff, MD, DSc
Deputy Editor: Janet L Wilterdink, MD

All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: Feb 2020. | This topic last updated: May 28, 2019.

INTRODUCTION

When autonomic reflexes are impaired or intravascular volume is markedly depleted, a significant
reduction in blood pressure occurs upon standing, a phenomenon termed "orthostatic
hypotension." Orthostatic hypotension can cause dizziness, syncope, and even angina or stroke.

Symptomatic falls in blood pressure after standing or eating are a frequent clinical problem. The
prevalence of orthostatic hypotension varies from 5 to 20 percent in different reports. Many
disorders can cause orthostatic hypotension, which can also be a symptom of acute or chronic
volume depletion as well as a side effect of drugs, particularly antihypertensives. A related
problem, postprandial hypotension (a fall in blood pressure occurring 15 to 90 minutes after
meals) is also common in older subjects.

Chronic orthostatic intolerance (COI) describes the association of lightheadedness, dizziness,

faintness, or syncope that occurs with prolonged standing or upright posture. These symptoms
may be sometimes associated with an exaggerated tachycardia but no fall in blood pressure, a
disorder that is called the postural tachycardia syndrome (POTS).

This topic will review the pathogenesis and causes of orthostatic and postprandial hypotension.
The treatment of these syndromes is discussed separately. POTS is also discussed separately.
(See "Treatment of orthostatic and postprandial hypotension" and "Postural tachycardia
syndrome".)

NORMAL BLOOD PRESSURE RESPONSE TO STANDING

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Assumption of the upright posture results in the pooling of 500 to 1000 mL of blood in the lower
extremities and splanchnic circulation, which initiates the following sequence [1]:

● A rapid decrease in venous return to the heart.

● The ensuing reduction in ventricular filling results in diminished cardiac output and blood
pressure.

● The fall in blood pressure and thoracic volume provokes a compensatory reflex involving the
central and peripheral nervous systems that increases sympathetic and reduces
parasympathetic outflow (ie, baroreceptor reflex).

● The increase in sympathetic outflow raises peripheral vascular resistance, venous return, and
cardiac output, thereby limiting the fall in blood pressure.

Because of these compensatory mechanisms, normally, assumption of the erect posture leads to
a small fall in systolic blood pressure (5 to 10 mmHg), an increase in diastolic blood pressure (5 to
10 mmHg), and an increase in pulse rate (10 to 25 beats per minute).

In patients with orthostatic hypotension, one or more of these compensatory mechanisms fail,
leading to a decline in blood pressure with assumption of upright posture. (See 'Diagnosis' below.)

EPIDEMIOLOGY AND RISK FACTORS

The reported prevalence of orthostatic hypotension varies with age and the clinical setting [1].

Orthostatic hypotension is more common in older adults due, at least in part, to impaired
baroreceptor sensitivity [2-5]. Epidemiologic surveys have found postural hypotension in as much
as 20 percent of patients over age 65 [6-9]. In the Cardiovascular Health study, for example, the
prevalence of orthostatic hypotension was 18 percent in subjects age 65 years or older, although
only 2 percent were symptomatic (defined as dizziness with standing) [6]. There was a modest
association (odds ratio 1.4 to 1.9) with systolic hypertension when supine, carotid stenosis greater
than 50 percent, and the use of oral hypoglycemic agents. There was only a weak association with
the use of beta blockers and no association with other antihypertensive drugs (including diuretics).

However, other studies have found the use of antihypertensive medications to be related to
postural hypotension in older adults [7,10]. Other drugs associated with postural hypotension,
especially in older adults, are vasodilators, including nitrates and calcium channel blockers,
antidepressants (tricyclics and phenothiazines), opiates, and alcohol (table 1).

Orthostatic hypotension is a common reason for, or contributor to, hospitalization in older adult
patients. A report from the Nationwide Inpatient Sample estimated an orthostatic hypotension
hospitalization rate of 233 per 100,000 patients over 75 years of age, with a median length of stay

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of three days and an overall in-hospital mortality rate of 0.9 percent [2]. Among various inpatient
series, the prevalence of orthostatic hypotension in older adult patients is as high as 60 percent
[11,12].

Orthostatic hypotension can also occur in younger, middle-age, or older subjects, who, in the
absence of volume depletion (due to diuretics, hemorrhage, or vomiting), usually have chronic
autonomic failure.

ETIOLOGIES

Many disorders can cause orthostatic hypotension, with the two major mechanisms being
autonomic failure, which can be caused by multiple disorders, and severe volume depletion. In
addition, reflex syncope (also referred to as vasovagal or neurally mediated syncope) causes
acute orthostatic hypotension due to a transient, paroxysmal dysfunction of the autonomic nervous
system [13,14]. (See "Reflex syncope in adults and adolescents: Clinical presentation and
diagnostic evaluation".)

When autonomic reflexes are impaired, blood pressure falls progressively after standing because
the gravitational pooling of blood in the legs cannot be compensated by sympathetic
vasoconstriction, referred to as neurogenic orthostatic hypotension. Patients with significant
anemia or severe intravascular volume depletion may experience orthostatic hypotension despite
normal autonomic reflexes.

The relative frequencies of various causes of orthostatic hypotension vary according to the setting.
Up to 40 percent of patients have no definite cause [3,15]. In one study from a tertiary center of
100 consecutive patients with moderate to severe postural hypotension [15]:

● 27 percent had primary autonomic failure, including multiple system atrophy (MSA) and pure
autonomic failure (PAF)
● 35 percent had secondary autonomic failure, such as diabetic neuropathy or paraneoplastic
autonomic failure
● 38 percent had no evidence of generalized autonomic dysfunction
● The use of antidepressant drugs was found to be a major overlooked cause

Autonomic failure — In patients with autonomic failure, orthostatic hypotension occurs because
postganglionic sympathetic neurons do not release norepinephrine appropriately. Subnormal
norepinephrine release results in impaired vasoconstriction and reduced intrathoracic vascular
volume, both of which contribute to orthostatic hypotension. The absence of an appropriate reflex-
induced increase in heart rate as the blood pressure falls is a useful clinical clue to the presence
of autonomic failure. However, the presence of a heart rate increase does not exclude autonomic
failure (figure 1). The ratio between the increase in heart rate and the fall in blood pressure
provides the most sensitive and specific bedside differentiator between neurogenic (ie, due to
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autonomic failure) and non-neurogenic orthostatic hypotension (ie, due to volume depletion). In
one study, a change of 0.5 beats/minute per mmHg of systolic fall in blood pressure (bpm/mmHg)
or less was diagnostic of autonomic failure [16]. By contrast, heart rate usually decreases during
reflex syncope [13]. (See 'Reflex syncope' below.)

The neurodegenerative diseases that most often produce clinically significant autonomic
dysfunction are the synucleinopathies described in the next section, a group of diseases with
abnormal accumulation of the protein alpha-synuclein in neurons and glia. Several types of
neuropathy may also cause autonomic dysfunction.

Neurodegenerative disease — Autonomic dysfunction, particularly neurogenic orthostatic

hypotension, is a common clinical feature of the synucleinopathies, which are characterized
pathologically by cytoplasmic neuronal (Lewy bodies) or glial inclusions containing alpha-synuclein
found in the brain and peripheral autonomic nerves of affected patients [17]. These include the
following:

● Parkinson disease (PD) presents with motor abnormalities and varying degrees of autonomic
failure. The prevalence of neurogenic orthostatic hypotension increases with age and disease
duration and is present in 20 to 60 percent of patients [18]. (See "Clinical manifestations of
Parkinson disease", section on 'Autonomic dysfunction'.)

● Dementia with Lewy bodies (DLB) presents with cognitive impairment that is accompanied by
parkinsonism and autonomic dysfunction. (See "Clinical features and diagnosis of dementia
with Lewy bodies", section on 'Autonomic dysfunction'.)

● MSA (Shy-Drager syndrome) affects the central autonomic system but mostly spares
peripheral autonomic neurons and has two phenotypes: parkinsonian and cerebellar, both
with prominent autonomic failure [19]. (See "Multiple system atrophy: Clinical features and
diagnosis".)

● PAF (Bradbury-Eggleston syndrome) presents with idiopathic autonomic failure as the sole
clinical finding. While orthostatic hypotension is the most common presenting feature,
impotence and urinary and gastrointestinal symptoms may occur as well [20].

Patients with PAF may progress to develop PD or DLB [21], and less frequently MSA.
However, PAF may also remain confined to the peripheral autonomic neurons [22]. In those
cases, patients respond well to therapy and have a substantially better prognosis than those
with PD, DLB, or MSA [23].

Neuropathies — Autonomic failure can result from peripheral neuropathies or from

autoimmune blockade of ganglionic autonomic transmission:

● Small fiber peripheral neuropathies can affect postganglionic autonomic nerves and cause
autonomic dysfunction [17]. Orthostatic hypotension, rarely the presenting feature, usually
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develops along with or after distal neuropathic pain and/or sensory loss, erectile dysfunction,
and urinary or gastrointestinal symptoms.

Diabetes is the most common cause of autonomic neuropathy; the duration or severity of
diabetes does not correlate with the development of this syndrome. Amyloidosis, Sjögren
syndrome and other collagen vascular disorders, renal failure, B12 deficiency, toxins, certain
infections (syphilis, Lyme, HIV, Chagas), sarcoidosis, and porphyria are other causes of
autonomic neuropathy [24-26]. (See "Screening for diabetic polyneuropathy" and "Overview
of polyneuropathy".)

Prominent autonomic symptoms, including orthostatic hypotension as well as episodes of

hypertension and tachycardia due to involvement of afferent baroreflex neurons, can be a
feature of acute inflammatory demyelinating polyneuropathy (Guillain-Barré syndrome) as
well. (See "Guillain-Barré syndrome in adults: Clinical features and diagnosis".)

● Autoimmune autonomic impairment with ganglionic nicotinic acetylcholine receptor (nAChR)

autoantibodies (autoimmune autonomic ganglionopathy) is usually associated with subacute
(less than three months) clinical onset of dysautonomia. In addition to orthostatic hypotension,
patients also have dry eyes and dry mouth, severe upper gastrointestinal dysautonomia, large
pupils that react poorly to light and accommodation, and neurogenic bladder [27,28]. There is
usually no objective sensory loss or motor or reflex changes. Patients are young to middle-
aged adults and are more likely to be female than male (ratio 2:1). Other autoimmune
disorders may be present. Detection of the nAChR antibodies confirms the diagnosis. This
disorder may improve but rarely remits with treatment (plasma exchange, intravenous
immunoglobulin).

● Paraneoplastic autonomic neuropathy occurs commonly in association with anti-Hu

antibodies (also known as type 1 antineuronal nuclear antibody [ANNA-1]), most often in
patients with small cell lung cancer, but it can be seen in other malignancies. Also associated
with paraneoplastic autonomic neuropathy are Purkinje cell cytoplasmic antibodies type 2
(PCA-2) and antibodies to the neuron cytoplasmic protein, collapsin response-mediator
protein-5 (CRMP-5). The nAChR antibodies discussed above are sometimes paraneoplastic
as well [29]. Bowel hypomotility, intestinal obstruction, bladder dysfunction, orthostatic
hypotension, pupillomotor and sudomotor dysfunction, and xerophthalmia are prominent
clinical findings. (See "Paraneoplastic syndromes affecting spinal cord, peripheral nerve, and
muscle", section on 'Autonomic neuropathy'.)

● Familial dysautonomia (Riley-Day syndrome) is a hereditary sensory and autonomic

neuropathy (HSAN type 3) expressed at birth with impaired pain and temperature sensation,
along with autonomic dysfunction due to afferent baroreflex failure. Patients experience
recurrent hypertensive episodes with severe retching, vomiting, and excessive sweating

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combined with orthostatic hypotension. (See "Hereditary sensory and autonomic

neuropathies", section on 'HSAN3 (Familial dysautonomia)'.)

Volume depletion — Acute or subacute volume depletion (due to diuretics, hyperglycemia,

hemorrhage, or vomiting) is usually an easily recognizable cause of orthostatic hypotension.

Chronic hypovolemia, a frequent feature of autonomic failure, exacerbates orthostatic symptoms.

Normally, norepinephrine increases sodium reabsorption in the proximal tubule [30]. This is an
appropriate response to minimize sodium losses when reductions in effective circulating blood
volume stimulate reflex sympathetic activity. Thus, a reduction in sympathetic activity, as in
autonomic failure, will increase urinary sodium excretion until a new steady state is achieved at a
lower plasma volume [31]. (See "General principles of disorders of water balance (hyponatremia
and hypernatremia) and sodium balance (hypovolemia and edema)", section on 'Regulation of
effective arterial blood volume'.)

Medications — Orthostatic hypotension is a common side effect of medications. Many

medications can cause or exacerbate orthostatic hypotension through a variety of mechanisms,
including peripheral vasodilation, autonomic dysfunction, and volume depletion. A partial list is
provided in the table (table 1) [32].

Aging — In addition to the above autonomic disorders, a decrease in baroreceptor sensitivity is

assumed to be involved in the milder, frequent form of orthostatic hypotension seen in older adult
patients.

● One study, for example, showed a diminished response in the older patients to tilt (a
baroreceptor-mediated response) but not to non-baroreceptor-mediated stimuli such as the
cold pressor test or isometric exercise [33]. The reduced baroreceptor response in older
adults (when compared with younger controls) was seen in both hypertensive and
normotensive subjects.

● Another study, measuring blood pressure and heart rate responses to Valsalva maneuver,
found that both the vagal and adrenergic components of the baroreceptor reflex became
blunted with increasing age, each independent of the other [4].

Others — Orthostatic hypotension may also be a clinical feature of cardiac pump failure (aortic
stenosis, pericarditis/myocarditis, arrhythmias) [32].

The clinical features of adrenal insufficiency (and less commonly pheochromocytoma) may also
include orthostatic hypotension [32]. (See "Clinical manifestations of adrenal insufficiency in
adults", section on 'Hypotension'.)

RELATED CONDITIONS

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Postprandial hypotension — In postprandial hypotension, blood pressure falls occur within one
to two hours after a meal [1].

Postprandial hypotension is also common in older subjects and in patients with diabetes and
different types of autonomic failure [34]. Among older residents of nursing homes, for example, 24
to 36 percent have a 20 mmHg or greater fall in systolic blood pressure within 75 minutes after
eating a meal [35]. In another series of 401 consecutive older adult patients with hypertension
referred to an outpatient cardiology clinic, 73 percent were found to have a 20 mmHg or greater
fall in systolic blood pressure within two hours after a meal [36].

The etiology of postprandial hypotension is not understood completely. Affected patients have
inadequate sympathetic compensation to meal-induced pooling of blood in the splanchnic
circulation, leading to impaired maintenance of cardiac output and systemic vascular resistance
[35]. Other possible contributors include vasodilatation induced by insulin or vasoactive
gastrointestinal peptides.

Reflex syncope — Orthostatic hypotension occurs acutely and transiently in reflex syncope.
Vasovagal, neurocardiogenic, carotid sinus hypersensitivity, and syncope associated with
micturition and defecation are examples of reflex syncope.

The clinical syndrome of reflex syncope differs from that of autonomic failure. In the latter,
sympathetic efferent activity is chronically impaired, and upon standing, blood pressure always
falls. By contrast, in reflex syncope, the failure of sympathetic efferent vasoconstrictor traffic (and
hypotension) occurs episodically and typically in response to a trigger (emotional stress, painful or
noxious stimuli, etc). During reflex syncope, concomitant with withdrawal of sympathetic efferent
activity, parasympathetic (vagal) activity increases, slowing the heart (figure 1) [13]. The
pathogenesis and clinical features of vasovagal and other reflex syncopes are discussed
separately. (See "Reflex syncope in adults and adolescents: Clinical presentation and diagnostic
evaluation".)

Postural tachycardia syndrome and chronic orthostatic intolerance — Chronic orthostatic

intolerance (COI) is the term used to describe the association of lightheadedness, dizziness,
faintness, or syncope that occurs with prolonged standing or upright posture.

Younger patients have been described with COI who develop a variety of symptoms such as
fatigue, lightheadedness, exercise intolerance, and cognitive impairment with assumption of the
upright position. These symptoms are associated with an exaggerated tachycardia but no fall in
blood pressure. This disorder has been called the postural tachycardia syndrome (POTS). POTS
is discussed separately. (See "Postural tachycardia syndrome".)

SYMPTOMS

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Symptoms of orthostatic hypotension typically occur in response to sudden postural change, but
also in association with meals, exertion, and prolonged standing [17]. Symptoms result from
cerebral hypoperfusion and include generalized weakness, sensations described as dizziness or
lightheadedness, visual blurring or darkening of the visual fields, and, in severe cases, loss of
consciousness (syncope). Less frequently, orthostatic hypotension leads to angina or stroke.

Complaints less easily recognized as hypotensive in origin, such as generalized weakness,

fatigue, cognitive slowing, and leg buckling, may also occur. Neck pain and headache localized in
the suboccipital, posterior cervical, and shoulder region (the "coat-hanger headache"), are
reported by 50 to 90 percent of patients according to different case series [37-39].

Symptoms of orthostatic hypotension vary in severity from mild to incapacitating; severely afflicted
patients are unable to leave the supine position without experiencing presyncope or syncope
[40,41]. In rare cases, orthostatic hypotension has been linked to cardiovascular and
cerebrovascular events [6,42,43]. By contrast, some patients with orthostatic hypotension are
asymptomatic.

Up to 50 percent of patients with orthostatic hypotension, particularly those who have underlying
autonomic dysfunction, have systolic hypertension when seated or supine [6,7,44].

DIAGNOSIS

Postural (orthostatic) hypotension is diagnosed when, within two to five minutes of quiet standing
(after a five-minute period of supine rest), one or both of the following is present [1]:

● At least a 20 mmHg fall in systolic pressure

● At least a 10 mmHg fall in diastolic pressure

The heart rate normally rises immediately on standing. The absence of an appropriate reflex-
induced increase in heart rate as the blood pressure falls is a useful clinical clue to the presence
of autonomic failure; however, the presence of a heart rate increase does not exclude autonomic
failure. An increase in heart rate of >30 beats per minute suggests postural tachycardia syndrome
(POTS), which usually does not include orthostatic hypotension. (See "Postural tachycardia
syndrome".)

A phenomenon of delayed orthostatic hypotension has also been described. In one study, 108 of
230 patients investigated with tilt table testing had abnormal test results [45]. In more than half of
these, orthostatic hypotension occurred after five minutes of tilt, and in 40 percent it occurred after
10 minutes. These patients had milder abnormalities of sympathetic adrenergic function,
suggesting the possibility that this phenomenon may be a milder or earlier form of impairment.

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EVALUATION

A diagnostic evaluation in patients with documented orthostatic hypotension focuses on identifying

treatable conditions that may be causative or contributory and distinguishing between neurogenic
and non-neurogenic orthostatic hypotension. Relevant features to elicit in a history and
examination include [46]:

● Detailed medication list, prescription and nonprescription. Some of the medications

associated with orthostatic hypotension are shown in the table (table 1).

● Recent medical history of potential volume loss (vomiting, diarrhea, fluid restriction, fever).

● Medical history of congestive heart failure, malignancy, diabetes, alcoholism.

● Evidence on neurologic history and examination of parkinsonism, ataxia, peripheral

neuropathy, or dysautonomia (eg, abnormal pupillary response, history of constipation or
erectile dysfunction).

Laboratory testing (hematocrit, electrolytes, blood urea nitrogen, creatinine, glucose) and a 12-
lead electrocardiogram should be obtained in selected patients to evaluate for underlying anemia
or dehydration or heart disease when there is reason to suspect these conditions, or when the
cause of orthostatic hypotension is otherwise unclear.

When the history or examination suggests a neuropathy (distal sensory loss, areflexia),
electromyography and nerve conduction studies may be useful to characterize the abnormality.
However, normal nerve conduction studies do not exclude a small-fiber neuropathy, which is
associated with autonomic dysfunction. Fasting blood sugar, syphilis serology, serum protein
electrophoresis, and other testing may be used to identify the underlying cause. (See "Overview of
polyneuropathy", section on 'Diagnostic evaluation'.)

Noninvasive autonomic testing, including beat-to-beat blood pressure and heart rate changes
induced by Valsalva maneuver or other standardized stimuli, as well as measurements of plasma
norepinephrine concentration and its response to standing, can be obtained to ascertain abnormal
autonomic function in patients with orthostatic hypotension (thus distinguishing them from those
with volume depletion or severe physical deconditioning) and to localize the site of abnormality.
Detailed autonomic testing is not widely available but can be useful in documenting an underlying
dysautonomia and establishing prognosis. Regardless of the cause, treatment of orthostatic
hypotension is symptomatic. (See "Treatment of orthostatic and postprandial hypotension".)

Even after extensive evaluation, up to one-third of patients will have no identified cause [3].

COMPLICATIONS

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According to several population-based studies, orthostatic hypotension is a risk factor for

cardiovascular and all-cause mortality, usually due to underlying causes and associated diseases
[24,43,47-53]. A prospective study using ambulatory blood pressure monitoring in 374 older adults
(age 70.2 ± 8.5 years) found that systolic orthostatic hypotension was a strong predictor of future
cardiovascular events (hazard ratio [HR] = 2.4) [54]. Orthostatic hypotension has also been linked
to a risk of congestive heart failure [55-57] and to incidental atrial fibrillation [58].

Orthostatic hypotension, particularly when symptomatic, can cause falling, which has significant
associated morbidity, particularly in a frail older adult population [8,59]. In one study of older
nursing home resident patients, orthostatic hypotension was associated with an increased risk of
recurrent falls (relative risk [RR] = 2.6) [60].

Some investigators have questioned whether orthostatic hypotension produces cognitive decline
in the absence of an associated neurodegenerative condition. The presumed mechanism is
neuronal injury from chronic or repeated episodes of cerebral hypoperfusion. One study found that
orthostatic hypotension was associated with periventricular white matter lesion burden [61], which
in turn is a marker of vascular cognitive impairment in some studies. Studies examining an
association between orthostatic hypotension and cognitive decline or dementia have had
conflicting results, perhaps as a result of varying lengths of follow-up and the different cognitive
measures used in their studies [62-66].

Orthostatic hypotension, particularly when disabling, is associated with impaired quality of life.
While anxiety, depression, and other psychosocial problems appear to be associated with
orthostatic hypotension, the direction of a possible causal relationship is unclear and may be
mediated in part by medications [67-69].

INFORMATION FOR PATIENTS

UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics."
The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading
level, and they answer the four or five key questions a patient might have about a given condition.
These articles are best for patients who want a general overview and who prefer short, easy-to-
read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and
more detailed. These articles are written at the 10th to 12th grade reading level and are best for
patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or
e-mail these topics to your patients. (You can also locate patient education articles on a variety of
subjects by searching on "patient info" and the keyword(s) of interest.)

● Basics topics (see "Patient education: Orthostatic hypotension (The Basics)")

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SUMMARY AND RECOMMENDATIONS

● Orthostatic hypotension is more common in older patients and may affect up to 20 percent of
patients over the age of 65 years. (See 'Epidemiology and risk factors' above.)

● Orthostatic and postprandial hypotension are features of autonomic dysfunction that may
result from certain neurodegenerative diseases affecting the central and peripheral nervous
system as well as certain peripheral neuropathies. (See 'Autonomic failure' above.)

● Orthostatic hypotension may result from volume depletion (due to diuretics, hemorrhage, or
vomiting). (See 'Volume depletion' above.)

● The use of antihypertensive and other medications (table 1) often contributes to postural
hypotension, particularly in older adults. (See 'Medications' above.)

● Patients with reflex (also called vasovagal) syncope, outside the acute event, have normal
blood pressure response to standing. Patients with postural tachycardia syndrome (POTS)
complain of symptoms that are similar to those of orthostatic hypotension, but are not
associated with postural hypotension on examination. (See 'Related conditions' above and
'Postural tachycardia syndrome and chronic orthostatic intolerance' above.)

● Symptoms of orthostatic hypotension occur in response to postural change (sometimes

exacerbated by recent meal, heat, exertion) and include generalized weakness, sensations
described as dizziness or lightheadedness, visual blurring or darkening of the visual fields,
and, in severe cases, loss of consciousness (syncope). Some patients with orthostatic
hypotension are asymptomatic. (See 'Symptoms' above.)

● Postural (orthostatic) hypotension is diagnosed when, within two to five minutes of quiet
standing (after a five-minute period of supine rest), one or two of the following is present (see
'Diagnosis' above):

• At least a 20 mmHg fall in systolic pressure

• At least a 10 mmHg fall in diastolic pressure

● A diagnostic evaluation in patients with documented orthostatic hypotension focuses on

identifying treatable conditions that may be causative or contributory, in particular medications
and potential volume loss. (See 'Evaluation' above.)

● Orthostatic hypotension is a risk factor for cardiovascular and all-cause mortality, can cause
falls and attendant morbidity, and is associated with comorbid psychiatric symptoms. (See
'Complications' above.)

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ACKNOWLEDGMENT

The editorial staff at UpToDate would like to acknowledge Roy Freeman, MD, and Norman Kaplan,
MD, who contributed to an earlier version of this topic review.

Use of UpToDate is subject to the Subscription and License Agreement.

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Topic 5103 Version 20.0

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GRAPHICS

Examples of drugs that can cause or exacerbate orthostatic hypotension

Alcohol

Alpha blockers: Terazosin (eg)

Antidepressant drugs: Selective serotonin receptor reuptake inhibitors, trazodone, monoamine oxidase inhibitors,
tricyclic antidepressants

Antihypertensive drugs: Sympathetic blockers (eg)

Antiparkinsonism drugs: Levodopa, pramipexole, ropinirole (egs)

Antipsychotic drugs: Olanzapine, risperidone (egs)

Beta-blocker drugs: Propranolol (eg)

Diuretic drugs: Hydrochlorothiazide, furosemide (egs)

Muscle relaxant drugs: Tizanidine (eg)

Narcotic analgesic drugs: Morphine (eg)

Phosphodiesterase inhibitors: Sildenafil, tadalafil (egs)

Sedatives/hypnotic drugs: Temazepam (eg)

Vasodilator drugs: Hydralazine, nitroglycerin, calcium channel blockers (egs)

Reproduced with permission from: Perlmuter LC, Sarda G, Casavant V, Mosnaim AD. A review of the etiology, associated
comorbidities, and treatment of orthostatic hypotension. Am J Ther 2013; 20:279. DOI: 10.1097/MJT.0b013e31828bfb7f.
Copyright © 2013 Wolters Kluwer Health, Lippincott Williams & Wilkins. Unauthorized reproduction of this material is
prohibited.

Graphic 89955 Version 9.0

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Heart rate and blood pressure patterns observed in head-up tilt table
testing

Shown are the heart rate and blood pressure responses seen during tilt table testing in patients
with various etiologies of syncope, including autonomic failure, neurally mediated syncope, and
postural tachycardia syndrome (POTS). The absence of an appropriate reflex-induced increase in
heart rate as the blood pressure falls is a useful clue to the presence of autonomic failure. During
neurally mediated syncope, parasympathetic (vagal) activity increases as blood pressure declines,
slowing the heart. With POTS, tilt table testing typically reproduces the clinical symptoms in
association with a heart rate increase ≥30 beats/min or a maximum heart rate ≥120 beats/min
within the first 10 minutes; these changes are not associated with hypotension.

Graphic 56293 Version 2.0

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Contributor Disclosures
Horacio Kaufmann, MD Grant/Research/Clinical Trial Support: Familial Dysautonomia Foundation [Familial
dysautonomia]; National Institutes of Health [Parkinson disease, multiple system atrophy]; US Food and Drug
Administration [Familial dysautonomia]; Michael J Fox Foundation [Parkinson disease]; Multiple System
Atrophy Coalition [Multiple system atrophy]. Consultant/Advisory Boards: Lundbeck [Neurogenic orthostatic
hypotension]; Theravance Biopharma [Neurogenic orthostatic hypotension]. Michael J Aminoff, MD,
DSc Equity Ownership/Stock Options: Trust [The portfolio may include medical or drug companies]. Equity
Ownership/Stock Options (Spouse): Trust [The portfolio may include medical or drug companies]. Janet L
Wilterdink, MD Nothing to disclose

Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are
addressed by vetting through a multi-level review process, and through requirements for references to be
provided to support the content. Appropriately referenced content is required of all authors and must conform
to UpToDate standards of evidence.

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