Orthostatic Hypotension: A Practical Approach

Michael J. Kim; Jennifer Farrell

MICHAEL J. KIM, MD, AND JENNIFER FARRELL, DO

This is a corrected version of the article that appeared in print.

Am Fam Physician. 2022;105(1):39-49

Patient information: See related handout on orthostatic hypotension, written by the authors of this article.

Author disclosure: No relevant financial relationships.

Orthostatic hypotension is defined as a decrease in blood pressure of 20 mm Hg or more systolic or 10 mm Hg or more diastolic within three minutes of standing from the supine position or on assuming a head-up position of at least 60 degrees during tilt table testing. Symptoms are due to inadequate physiologic compensation and organ hypoperfusion and include headache, lightheadedness, shoulder and neck pain (coat hanger syndrome), visual disturbances, dyspnea, and chest pain. Prevalence of orthostatic hypotension in the community setting is 20% in older adults and 5% in middle-aged adults. Risk factors such as diabetes mellitus increase the prevalence of orthostatic hypotension in all age groups. Orthostatic hypotension is associated with a significant increase in cardiovascular risk and falls, and up to a 50% increase in relative risk of all-cause mortality. Diagnosis is confirmed by measuring blood pressure and heart rate after five minutes in the supine position and three minutes after moving to a standing position. [corrected] If the patient is unable to stand safely or the clinical suspicion for orthostatic hypotension is high despite normal findings on the bedside test, head-up tilt table testing is recommended. Orthostatic hypotension is classified as neurogenic or nonneurogenic, depending on etiology and heart rate response. Treatment goals for orthostatic hypotension are reducing symptoms and improving quality of life. Initial treatment focuses on the underlying cause and adjusting potentially causative medications. Nonpharmacologic strategies include dietary modifications, compression garments, physical maneuvers, and avoiding environments that exacerbate symptoms. First-line medications include midodrine and droxidopa. Although fludrocortisone improves symptoms, it has concerning long-term effects.

Orthostatic hypotension is defined as a decrease in blood pressure of 20 mm Hg or more systolic or 10 mm Hg or more diastolic within three minutes of standing from the supine position or on assuming a head-up position of 60 degrees during tilt table testing.¹ It is classified as neurogenic or nonneurogenic based on etiology and heart rate response.

Clinical recommendation	Evidence rating	Comments
The test for the diagnosis of orthostatic hypotension should consist of blood pressure and heart rate measurement in the supine position for five minutes followed by standing position for three minutes, instead of sitting to standing position.^24,26–28 [corrected]	C	Expert opinion, consensus guidelines, and a single retrospective study
If clinical suspicion for orthostatic hypotension is high, head-up tilt table testing should be performed even with normal bedside orthostatic vital signs.^{24,28,33,43,44}	C	Expert opinion and consensus guidelines; three small cohort studies of older patients showing low sensitivity of bedside orthostatic vital signs compared with tilt table testing
Patients with neurogenic orthostatic hypotension and supine hypertension should be evaluated with a 24-hour ambulatory blood pressure monitor.⁴⁵	C	Expert opinion and consensus guidelines in the absence of clinical trials
Treatment of orthostatic hypotension should be aimed at reducing symptoms to improve quality of life, rather than normalizing blood pressure.^2,22,24,46	C	Expert opinion and consensus guidelines in the absence of clinical trials with head-to-head comparisons of blood pressure vs. symptom control
Nonpharmacologic management strategies should be attempted before prescribing a medication.If nonpharmacologic management is insufficient alone, it should be used in combination with medications.^{2,22,24,33,66}	C	Expert opinion and consensus guidelines
First-line pharmacologic therapy should include midodrine or droxidopa (Northera) titrated to relieve symptoms.^{2,22,24,56–61,66}	B	Consensus guidelines; four small double-blind randomized controlled trials showing improved blood pressure and global symptom scores compared with placebo

With increasing age, there is a normal decline in baroreceptor sensitivity and increase in autonomic neurodegenerative disease.² Orthostatic hypotension occurs in only 5% of middle-aged adults but affects approximately 20% of those 60 years and older.^3–5 Prevalence in nursing homes and geriatric wards is as high as 50% and 68%, respectively.^1,6

Orthostatic hypotension is associated with significant morbidity and mortality, with the greatest risk in those who have comorbidities. Several large meta-analyses reported that orthostatic hypotension is associated with up to a 50% increase in relative risk of all-cause mortality (relative risk [RR] = 1.50; 95% CI, 1.24 to 1.81).^7–9 In middle-aged, community-dwelling patients, it is associated with an increased risk of death (hazard ratio = 1.19 [95% CI, 1.09 to 1.30] to 1.70 [95% CI, 1.40 to 2.00]) after adjustment for other risk factors.^10,11

Orthostatic hypotension is also associated with increased rates of coronary heart disease, myocardial infarction, heart failure, stroke, and falls.^3,8–10 Older people especially are at risk of myocardial infarction and recurrent falls.^12,13 Patients with diabetes mellitus are more likely to develop orthostatic hypotension and have an increased risk of mortality, microvascular and macrovascular complications, and cardiovascular events.^14–18 In the United States, the rate of hospitalizations related to orthostatic hypotension is 36 per 100,000 adults and increases to 233 per 100,000 adults for those 75 years and older.¹⁹

Pathophysiology

Approximately 500 to 1,000 mL of blood pools in the splanchnic circulation and lower extremities when a person stands, causing a decrease in venous return and cardiac output.^2,20–22 Baroreceptors detect decreased stretch and activate the sympathetic nervous system, which elevates the heart rate, bolsters contractility, and increases peripheral resistance through vasoconstriction.^2,21 Baroreceptors also sense decreased blood volume, prompting upregulation of renin release, sodium reabsorption, and vasopressin activity, resulting in enhanced water retention.^2,21 Orthostatic hypotension occurs when there is inadequate intravascular volume or when sympathetic nervous system–mediated vasoconstriction is unable to compensate for gravitational pooling, leading to decreased organ perfusion and associated symptoms ^20,23 (Figure 1).

Clinical Presentation and Evaluation

Symptoms of orthostatic hypotension appear while assuming a standing or upright position and are relieved by returning to a supine position (Table 1).^2,22,24 These symptoms are due to organ hypoperfusion compensation, but they do not have to be present for a diagnosis.^2,5 A history and physical examination aimed at identifying underlying causes of orthostatic hypotension should be performed. Risk factors for orthostatic hypertension are outlined in Table 2.^19,24,25

Orthostatic hypotension is diagnosed by measuring blood pressure and heart rate after five minutes in the supine position and three minutes after moving to a standing position.²⁶ [corrected] There is no standard timing of measurements (e.g., one-minute intervals, one-minute and three-minute intervals) or positioning (e.g., supine to sitting, supine to standing, sitting to standing, all three).^19,24,26,27 Supine to standing measurements evoke the greatest hemodynamic changes and are more sensitive.^27,28 A sustained decrease in blood pressure of 20 mm Hg or more systolic or 10 mm Hg or more diastolic within three minutes of standing is diagnostic of orthostatic hypotension.^1,26

Variations in the time it takes for blood pressure to fall allow orthostatic hypotension to be classified as classic (within three minutes), initial (within 15 seconds), and delayed (after three minutes).^2,22,26 Although the clinical significance of these variants is not completely understood, it suggests that orthostatic hypotension is a spectrum of disordered physiology.^1,29–31 A large prospective study reported an association with adverse events (e.g., fall, fracture, syncope, death) in patients 45 to 64 years of age if orthostatic hypotension occurred within one minute of standing.³²

Orthostatic hypotension is further classified as neurogenic or nonneurogenic^{2,4,6,22,24,33} (Table 3^{2,4,6,20–22,24,33}). Neurogenic orthostatic hypotension is caused by an intrinsic failure of the autonomic nervous system to create a normal physiologic response (baroreflex dysfunction). The differential diagnosis includes neurodegenerative disorders, pure autonomic failure, small fiber neuropathies, and acquired disorders.^2,4,6,22,24 Nonneurogenic orthostatic hypotension is secondary to external factors (often medication use) inhibiting the body's normal compensatory pattern.

Measuring heart rate with each position change can help detect baroreflex dysfunction.^2,22,24,27 The compensatory rise in heart rate is maintained in nonneurogenic orthostatic hypotension, whereas the heart rate response is markedly reduced or absent in neurogenic orthostatic hypotension.^2,26 An increase in heart rate of 0.5 beats per minute or more for every mm Hg decrease in systolic blood pressure has a high sensitivity (91%) and specificity (88%) for nonneurogenic orthostatic hypotension.^34,35 Additional features that differentiate the two are outlined in Table 4.^2,22,34,35

Parameter	Neurogenic	Nonneurogenic
Heart rate compensation ratio (change in heart rate/change in systolic blood pressure)	Decreased or absent (< 0.5 beats per minute/mm Hg)	Marked (≥ 0.5 beats per minute/mm Hg)
Symptoms of systemic autonomic failure	Urinary dysfunction, gastrointestinal dysfunction, postprandial hypotension; symptoms worse in the morning	None
Neurologic deficits	Parkinsonism, cognitive dulling, cerebellar signs, peripheral sensory abnormalities	None

Postural orthostatic tachycardia syndrome is a distinct entity from orthostatic hypotension and is associated with symptoms of orthostatic intolerance and tachycardia without hypotension^36–40 (Table 5^1,36–41).

Definition	Clinical features
Postural orthostatic tachycardia syndrome
Symptoms occur with upright positioning and are relieved with laying down; symptoms commonly include lightheadedness, palpitations, generalized weakness, tremors, and fatigue and Increase in sustained heart rate ≥30 beats per minute within 10 minutes of standing from supine or head-up tilt (patients who are 12 to 19 years of age must have a heart rate increase of ≥40 beats per minute) and Absence of orthostatic hypotension (decrease in systolic blood pressure of ≤20 mm Hg)	Prevalence of 0.2% to 1% in the general population Standing heart rate is typically ≥120 beats per minute Symptoms are worse in the mornings Typically chronic (three to six months) Most prominent between 15 and 25 years of age; most cases are in those younger than 50 years Significantly affects quality of life, although there is no clear mortality risk
Orthostatic intolerance
Syndrome defined by frequent symptoms that make it difficult to remain in an upright posture; symptoms typically include lightheadedness, palpitations, generalized weakness, tremulousness, blurred vision, and fatigue	Symptoms associated with standing position Can occur with or without orthostatic hypotension, syncope, and tachycardia

For unclear cases of orthostatic hypotension or when patients are unable to safely stand, head-up tilt table testing is recommended. Indications and example procedures for this test are described in Table 6.^20,33,35,42 Limited studies suggest that head-up tilt table testing has higher sensitivity for orthostatic hypotension than bedside orthostatic vital signs. If findings on the initial assessment for orthostatic hypotension in moving from the supine and standing postion are normal, but the clinical suspicion for orthostatic hypotension is high, head-up tilt table testing should be considered.^{24,28,33,43,44} Head-up tilt table testing is also recommended for detecting suspected delayed orthostatic hypotension in patients with syncope.³⁹

Supine hypertension is defined as blood pressure of 140 mm Hg or higher systolic or 90 mm Hg or higher diastolic after five minutes in the supine position and affects about 50% of patients with neurogenic orthostatic hypotension.^{2,21,22,25,45} Anti-hypotensive medications may worsen supine hypertension; therefore, screening for supine hypertension is recommended for all patients with neurogenic orthostatic hypotension.^22,45 Because of a higher baseline blood pressure in patients with supine hypertension, orthostatic hypotension is diagnosed with a decrease in systolic blood pressure of 30 mm Hg or more.^1,45 If supine hypertension is suspected, 24-hour ambulatory blood pressure monitoring can be used to assess severity (particularly nocturnal hypertension) and tailor therapies based on activities throughout the day.⁴⁵

Additional evaluation is focused on ruling out nonneurogenic orthostatic hypotension.²⁴ Table 7 includes initial testing for patients presenting with orthostatic hypotension.^24,33,45 The overall approach to the diagnosis and management of orthostatic hypotension is summarized in Figure 2.

Test	Reasoning
B₁₂ methylmalonic acid	Evaluate for evidence of B₁₂ deficiency
Basic metabolic panel	Evaluate for electrolyte disturbances, acid-base disorder, renal dysfunction, or diabetes mellitus
Complete blood count	Evaluate for anemia or infection
Electrocardiography*	Evaluate for arrhythmia that is causing symptoms of orthostatic hypotension requiring cardiology referral
Screening for supine hypertension	Supine hypertension affects about 50% of patients with neurogenic orthostatic hypotension; supine hypertension changes the diagnostic criteria for orthostatic hypotension; antihypotensive medications may worsen supine hypertension, requiring close monitoring
Thyroid-stimulating hormone	Evaluate for evidence of thyroid dysfunction

Management

Treatment goals for orthostatic hypotension are reducing symptoms and improving quality of life, rather than normalizing blood pressure.^2,22,24,46 Management begins with identifying and treating the underlying cause. The patient's current medications should be evaluated and potentially causative agents adjusted if safe to do so (Table 8).^{2,20,22,24,46,47}

The discontinuation or tapering of opioid, psychoactive, dopaminergic, and anticholinergic medications should be considered.^2,20,22,24 A retrospective study demonstrated a 23% increased prevalence of orthostatic hypotension in older patients taking even one of these medications.⁴⁸

Antihypertensives can exacerbate orthostatic hypotension symptoms because they reduce intravascular volume, trigger vasodilation, and have negative chronotropic effects.^22,24 Nighttime dosing of antihypertensives should be considered to reduce orthostatic hypotension symptoms.^22,24,49 Use of a 24-hour ambulatory blood pressure monitor may be helpful in guiding this decision.^22,45,49

Anemia can exacerbate orthostatic hypotension by reducing blood viscosity and increasing nitric oxide–mediated vasodilation. Therefore, treatment for anemia should be optimized as part of the patient's comprehensive management.^2,22

NONPHARMACOLOGIC MANAGEMENT

Initiating lifestyle-based treatments, such as avoiding or modifying exacerbating activities, is the first-line approach for the management of neurogenic orthostatic hypotension.^2,22,24,46 Although there is conflicting evidence of their effectiveness, expert consensus guidelines advocate the use of nonpharmacologic treatments because of minimal risk of harm.^2,22,24,33

Hot and humid conditions can exacerbate symptoms via vasodilatory cooling. Patients should be vigilant in avoiding environmental exposures and exacerbating activities.^2,22,24 Postprandial hypotension is common in neurogenic orthostatic hypotension because of redistribution of blood volume to the splanchnic circulation. Diets should include frequent small meals to minimize this effect.^2,22,24,50 Physical fitness should be encouraged because bed rest can further exacerbate orthostatic hypotension.² Exercise regimens in older people have been shown to improve head-up tilt table testing results.⁵¹ Modifications should be made as needed to alleviate symptoms during exercise, such as avoiding frequent position changes.^2,24

Appropriate volume status is maintained by adequate hydration and sodium intake. Physicians should assess the risks of increased water and sodium intake in patients with comorbid conditions such as heart failure, cirrhosis, or chronic kidney disease. Consumption of 2 to 2.5 L of fluids per day is recommended to counteract expected urinary losses.^2,20,22,24 Increased salt intake has been shown to provide short-term symptom improvement.⁵² Patients should aim for at least 2 to 3 g of sodium intake per day through dietary sources or salt tablets. A urinary sodium excretion of more than 170 mEq per L (170 mmol per L) every 24 hours and a urinary volume of more than 1,500 mL indicate adequate fluid and sodium intake.^2,20

Physical counter maneuvers, including leg-crossing or squatting, in addition to wearing waist-high compression garments with graded pressures of 30 to 40 mm Hg, may be used to reduce venous pooling in the legs and splanchnic circulation.^53,54,46 However, the use of compression garments is limited by poor compliance.^22,53,54

Elevating the head of the bed by 30 to 45 degrees at night can theoretically prevent supine hypertension, which exacerbates morning orthostatic hypotension by promoting nocturnal diuresis and natriuresis. One trial demonstrated that this did not change 24-hour ambulatory blood pressure values or urinary volume.⁵⁵

PHARMACOLOGIC MANAGEMENT

Two medication strategies can be used to augment nonpharmacologic management if it is insufficient alone. Midodrine and droxidopa (Northera) act to increase peripheral vascular resistance, whereas fludrocortisone expands intravascular volume.^2,22 The choice of medication is guided by underlying etiology, patient preference, adverse effects, cost, and therapeutic response.²² Specific medication dosages and considerations in the management of orthostatic hypotension are summarized in Table 9.^{2,21,22,24,56–65}

Drug*	Dosage	Comments	Cost†
Midodrine	Start at 2.5 mg three times per day orally, and titrate up to 10 mg three times per day	Dosage of 10 mg three times per day improves standing blood pressure measurements and symptom scores during a six-week course^56–58 Avoid three to five hours before bedtime^22,24	10 mg: $33 (—) for 60 tablets
Droxidopa (Northera)	Start at 100 mg three times per day orally, and titrate up to 600 mg three times per day	Improvement in symptom score based on validated assessment tool with medication titrated to symptom and blood pressure response over 14 days (mean dose = 430 mg)⁶⁰ Avoid five hours before bedtime²⁴ Effects may be blunted if coadministered with carbidopa²²	Only available at specialty pharmacies
Fludrocortisone	Start at 0.1 mg once per day orally, and titrate up to 0.2 mg once per day	Improvement in symptoms based on validated assessment over three-week treatment period with 0.1 mg once per day orally⁶² Use caution in heart failure Potassium level should be monitored ^2,22,24	0.1 mg: $13 (—) for 30 tablets
Atomoxetine (Strattera)	18 mg once per day orally	Improvement in standing blood pressure and validated symptom scores^2,64,65	18 mg: $27 ($392) for 30 tablets
Pyridostigmine (Mestinon)	60 mg once per day orally	Improved postural diastolic blood pressure reduction with 60-mg dosage⁶³	60 mg: $9 ($508)for 30 tablets

Midodrine, a short-acting alpha-1 adrenergic agonist that acts via vasoconstriction, has been shown to alleviate symptoms of orthostatic hypotension and elevate blood pressure in multiple randomized placebo-controlled trials.^{22,24,56–58,64,66} It is approved by the U.S. Food and Drug Administration for the treatment of orthostatic hypotension and is a recommended first-line medication.^{2,22,24,56–58,64,66} A double-blind, multicenter, randomized controlled trial of 171 patients demonstrated significant improvement in global symptom scores and standing systolic blood pressure in patients treated with midodrine, 10 mg, three times per day.⁵⁶ Midodrine can cause supine hypertension and should be avoided within three to five hours of bedtime.^2,22,24,66 Other common adverse effects include piloerection, scalp itching, and urinary retention.^{2,22,24,64,66}

Droxidopa, a short-acting norepinephrine precursor, is another first-line medication approved by the U.S. Food and Drug administration for the treatment of orthostatic hypotension. Based on validated symptom scores, this medication increases standing systolic blood pressure and alleviates orthostatic hypotension symptoms.^2,24,59,66 Droxidopa should also be avoided before bedtime because it can cause supine hypertension.^2,24,59 The most common adverse effects are headaches and nausea. Falls, dizziness, and urinary tract infections have also been reported.⁶⁵ Patients with neurogenic orthostatic hypotension secondary to Parkinson disease who are treated with droxidopa have a reduced risk of falls.⁶⁷

Fludrocortisone is a synthetic mineralocorticoid that promotes renal sodium reabsorption, thereby increasing intravascular volume.^2,24 Additionally, it increases vascular alpha-adrenergic receptor sensitivity, promoting vasoconstriction.^2,24 Expert consensus recommends the off-label use of fludrocortisone in the treatment of orthostatic hypotension.^2,22,24 One small (n = 17), short-term (three weeks) study demonstrated an improvement in symptom scores with the use of this medication.⁶⁰ There are significant adverse effects,^2,22,24,66 and its use is cautioned in patients with heart failure. Fludrocortisone has long-term risks, including left ventricular hypertrophy, renal failure, and hospitalization.^22,68

Off-label use of atomoxetine (Strattera) and pyridostigmine (Mestinon) can be considered as adjunctive therapy.^63,69 Atomoxetine has been shown to reduce symptoms of orthostatic hypotension compared with placebo and is comparable with midodrine in improving standing blood pressure.^61,62

Referral

There are limited evidence-based referral criteria for orthostatic hypotension. Symptoms that are incapacitating or severely impact activities of daily living and a 30 mm Hg or more drop in systolic blood pressure may warrant a specialist evaluation.²⁴ Cardiology referral may be considered for known heart disease or abnormal electrocardiogram findings.^33,70 Other reasons for referral include treatment failure, significant gastrointestinal impairment, or physician discomfort in treatment.^24,46

This article updates previous articles on this topic by Lanier, et al.,^²⁰ and Bradley and Davis.^⁷¹

Data Sources: PubMed searches were completed using the key terms orthostatic hypotension, neurocardiogenic syncope, neurogenic orthostatic hypotension, tilt table test, Schellong test, synucleinopathies, neurocardiogenic syncope, orthostatic intolerance, postural orthostatic tachycardia, syncope, supine hypertension, neuropathy. The searches included systematic reviews, meta-analyses, randomized controlled trials, cohort studies, and review articles. We also searched Essential Evidence Plus and Clinical Evidence, Trip database, and Agency for Healthcare Research and Quality. Search dates: September 2020, October 2020, December 2020, and September 2021.

The opinions and assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of Defense, Uniformed Services University of the Health Sciences, or the Department of the Air Force.

Freeman R, Wieling W, Axelrod FB, et al.; Consensus statement on the definition of orthostatic hypotension, neurally mediated syncope and the postural tachycardia syndrome. Clin Auton Res. 2011;21(2):69-72.

Freeman R, Abuzinadah AR, Gibbons C, et al.; Orthostatic hypotension: JACC state-of-the-art review. J Am Coll Cardiol. 2018;72(11):1294-1309.

Juraschek SP, Daya N, Appel LJ, et al.; Orthostatic hypotension in middle- age and risk of falls. Am J Hypertens. 2017;30(2):188-195.

Lei LY, Chew DS, Raj SR. Differential diagnosis of orthostatic hypotension. Auton Neurosci. 2020;228:102713.

Rutan GH, Hermanson B, Bild DE, et al.; Orthostatic hypotension in older adults. The Cardiovascular Health Study. CHS Collaborative Research Group. Hypertension. 1992;19(6 pt 1):508-519.

Farrell MC, Shibao CA. Morbidity and mortality in orthostatic hypotension. Auton Neurosci. 2020;229:102717.

Xin W, Lin Z, Mi S. Orthostatic hypotension and mortality risk: a meta-analysis of cohort studies. Heart. 2014;100(5):406-413.

Ricci F, Fedorowski A, Radico F, et al.; Cardiovascular morbidity and mortality related to orthostatic hypotension: a meta-analysis of prospective observational studies. Eur Heart J. 2015;36(25):1609-1617.

Angelousi A, Girerd N, Benetos A, et al.; Association between orthostatic hypotension and cardiovascular risk, cerebrovascular risk, cognitive decline and falls as well as overall mortality: a systematic review and meta-analysis. J Hypertens. 2014;32(8):1562-1571.

Fedorowski A, Stavenow L, Hedblad B, et al.; Orthostatic hypotension predicts all-cause mortality and coronary events in middle-aged individuals (The Malmo Preventive Project). Eur Heart J. 2010;31(1):85-91.

Rose KM, Eigenbrodt ML, Biga RL, et al.; Orthostatic hypotension predicts mortality in middle-aged adults: the Atherosclerosis Risk In Communities (ARIC) Study. Circulation. 2006;114(7):630-636.

Luukinen H, Koski K, Laippala P, et al.; Orthostatic hypotension and the risk of myocardial infarction in the home-dwelling elderly. J Intern Med. 2004;255(4):486-493.

Ooi WL, Hossain M, Lipsitz LA. The association between orthostatic hypotension and recurrent falls in nursing home residents. Am J Med. 2000;108(2):106-111.

Gaspar L, Kruzliak P, Komornikova A, et al.; Orthostatic hypotension in diabetic patients-10-year follow-up study. J Diabetes Complications. 2016;30(1):67-71.

van Hateren KJJ, Kleefstra N, Blanker MH, et al.; Orthostatic hypotension, diabetes, and falling in older patients: a cross-sectional study. Br J Gen Pract. 2012;62(603):e696-e702.

Spallone V, Ziegler D, Freeman R, et al; Toronto Consensus Panel on Diabetic Neuropathy; Cardiovascular autonomic neuropathy in diabetes: clinical impact, assessment, diagnosis, and management. Diabetes Metab Res Rev. 2011;27(7):639-653.

Vinik AI, Erbas T, Casellini CM. Diabetic cardiac autonomic neuropathy, inflammation and cardiovascular disease. J Diabetes Investig. 2013;4(1):4-18.

Zhou Y, Ke S-J, Qiu X-P, et al.; Prevalence, risk factors, and prognosis of orthostatic hypotension in diabetic patients: a systematic review and meta-analysis. Medicine (Baltimore). 2017;96(36):e8004.

Shibao C, Grijalva CG, Raj SR, et al.; Orthostatic hypotension-related hospitalizations in the United States. Am J Med. 2007;120(11):975-980.

Lanier JB, Mote MB, Clay EC. Evaluation and management of orthostatic hypotension. Am Fam Physician. 2011;84(5):527-536. Accessed September 13, 2021. https://www.aafp.org/afp/2011/0901/p527.html

Freeman R. Clinical practice. Neurogenic orthostatic hypotension. N Engl J Med. 2008;358(6):615-624.

Palma J-A, Kaufmann H. Management of orthostatic hypotension. Continuum (Minneap Minn). 2020;26(1):154-177.

Kaufmann H, Norcliffe-Kaufmann L, Palma J-A. Baroreflex dysfunction. N Engl J Med. 2020;382(2):163-178.

Gibbons CH, Schmidt P, Biaggioni I, et al.; The recommendations of a consensus panel for the screening, diagnosis, and treatment of neurogenic orthostatic hypotension and associated supine hypertension. J Neurol. 2017;264(8):1567-1582.

Low PA. Neurogenic orthostatic hypotension: pathophysiology and diagnosis. Am J Manag Care. 2015;21(13 suppl):s248-s257.

Fanciulli A, Campese N, Wenning GK. The Schellong test: detecting orthostatic blood pressure and heart rate changes in German-speaking countries. Clin Auton Res. 2019;29(4):363-366.

Carlson JE. Assessment of orthostatic blood pressure: measurement technique and clinical applications. South Med J. 1999;92(2):167-173.

Cooke J, Carew S, O'Connor M, et al.; Sitting and standing blood pressure measurements are not accurate for the diagnosis of orthostatic hypotension. QJM. 2009;102(5):335-339.

Wieling W, Krediet CTP, van Dijk N, et al.; Initial orthostatic hypotension: review of a forgotten condition. Clin Sci (Lond). 2007;112(3):157-165.

Finucane C, O'Connell MDL, Donoghue O, et al.; Impaired orthostatic blood pressure recovery is associated with unexplained and injurious falls. J Am Geriatr Soc. 2017;65(3):474-482.

Gibbons CH, Freeman R. Clinical implications of delayed orthostatic hypotension: a 10-year follow-up study. Neurology. 2015;85(16):1362-1367.

Juraschek SP, Daya N, Rawlings AM, et al.; Association of history of dizziness and long-term adverse outcomes with early vs later orthostatic hypotension assessment times in middle-aged adults. JAMA Intern Med. 2017;177(9):1316-1323.

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.

Norcliffe-Kaufmann L, Kaufmann H, Palma J-A, et al; Autonomic Disorders Consortium; Orthostatic heart rate changes in patients with autonomic failure caused by neurodegenerative synucleinopathies. Ann Neurol. 2018;83(3):522-531.

Cheshire WP, Goldstein DS. Autonomic uprising: the tilt table test in autonomic medicine. Clin Auton Res. 2019;29(2):215-230.

Sheldon RS, Grubb BP, Olshansky B, et al.; 2015 heart rhythm society expert consensus statement on the diagnosis and treatment of postural tachycardia syndrome, inappropriate sinus tachycardia, and vasovagal syncope. Heart Rhythm. 2015;12(6):e41-e63.

Zadourian A, Doherty TA, Swiatkiewicz I, et al.; Postural orthostatic tachycardia syndrome: prevalence, pathophysiology, and management. Drugs. 2018;78(10):983-994.

Bryarly M, Phillips LT, Fu Q, et al.; Postural orthostatic tachycardia syndrome: JACC focus seminar. J Am Coll Cardiol. 2019;73(10):1207-1228.

Shen W-K, Sheldon RS, Benditt DG, et al.; 2017 ACC/AHA/HRS guideline for the evaluation and management of patients with syncope: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on clinical practice guidelines and the Heart Rhythm Society [published correction appears in Circulation. 2017;136(16):e269–e270]. Circulation. 2017;136(5):e25-e59.

Olshansky B, Cannom D, Fedorowski A, et al.; Postural orthostatic tachycardia syndrome (POTS): a critical assessment. Prog Cardiovasc Dis. 2020;63(3):263-270.

Stewart JM, Boris JR, Chelimsky G, et al; Pediatric Writing Group of the American Autonomic Society; Pediatric disorders of orthostatic intolerance. Pediatrics. 2018;141(1):e20171673.

Lamarre-Cliche M, Cusson J. The fainting patient: value of the head-upright tilt-table test in adult patients with orthostatic intolerance. CMAJ. 2001;164(3):372-376.

Jamnadas-Khoda J, Koshy S, Mathias CJ, et al.; Are current recommendations to diagnose orthostatic hypotension in Parkinson's disease satisfactory?. Mov Disord. 2009;24(12):1747-1751.

Aydin AE, Soysal P, Isik AT. Which is preferable for orthostatic hypotension diagnosis in older adults: active standing test or head-up tilt table test?. Clin Interv Aging. 2017;12:207-212.

Fanciulli A, Jordan J, Biaggioni I, et al.; Consensus statement on the definition of neurogenic supine hypertension in cardiovascular autonomic failure by the American Autonomic Society (AAS) and the European Federation of Autonomic Societies (EFAS) : endorsed by the European Academy of Neurology (EAN) and the European Society of Hypertension (ESH). Clin Auton Res. 2018;28(4):355-362.

Shibao C, Lipsitz LA, Biaggioni I; American Society of Hypertension Writing Group; Evaluation and treatment of orthostatic hypotension. J Am Soc Hypertens. 2013;7(4):317-324.

Subbarayan S, Myint PK, Martin KR, et al.; Nonpharmacologic management of orthostatic hypotension in older people: a systematic review. The SENATOR ONTOP Series. J Am Med Dir Assoc. 2019;20(9):1065-1073.e3.

Poon IO, Braun U. High prevalence of orthostatic hypotension and its correlation with potentially causative medications among elderly veterans. J Clin Pharm Ther. 2005;30(2):173-178.

Hermida RC, Ayala DE, Mojón A, et al.; Decreasing sleep-time blood pressure determined by ambulatory monitoring reduces cardiovascular risk. J Am Coll Cardiol. 2011;58(11):1165-1173.

Puvi-Rajasingham S, Mathias CJ. Effect of meal size on post-prandial blood pressure and on postural hypotension in primary autonomic failure. Clin Auton Res. 1996;6(2):111-114.

Carroll JF, Wood CE, Pollock ML, et al.; Hormonal responses in elders experiencing pre-syncopal symptoms during head-up tilt before and after exercise training. J Gerontol A Biol Sci Med Sci. 1995;50(6):M324-M329.

Loughlin EA, Judge CS, Gorey SE. Increased salt intake for orthostatic intolerance syndromes: a systematic review and meta-analysis. Am J Med. 2020;133(12):1471-1478.e4.

Newton JL, Frith J. The efficacy of nonpharmacologic intervention for orthostatic hypotension associated with aging. Neurology. 2018;91(7):e652-e656.

Henry R, Rowe J, O'Mahony D. Haemodynamic analysis of efficacy of compression hosiery in elderly fallers with orthostatic hypotension. Lancet. 1999;354(9172):45-46.

Fan CW, Walsh C, Cunningham CJ. The effect of sleeping with the head of the bed elevated six inches on elderly patients with orthostatic hypotension: an open randomised controlled trial. Age Ageing. 2011;40(2):187-192.

Low PA, Gilden JL, Freeman R, et al; Midodrine Study Group; Efficacy of midodrine vs placebo in neurogenic orthostatic hypotension. A randomized, double-blind multicenter study [published correction appears in JAMA. 1997; 278(5): 388]. JAMA. 1997;277(13):1046-1051.

Wright RA, Kaufmann HC, Perera R, et al.; A double-blind, dose-response study of midodrine in neurogenic orthostatic hypotension. Neurology. 1998;51(1):120-124.

Jankovic J, Gilden JL, Hiner BC, et al.; Neurogenic orthostatic hypotension: a double-blind, placebo-controlled study with midodrine. Am J Med. 1993;95(1):38-48.

Kaufmann H, Freeman R, Biaggioni I, et al; NOH301 Investigators; Droxidopa for neurogenic orthostatic hypotension: a randomized, placebo-controlled, phase 3 trial. Neurology. 2014;83(4):328-335.

Schoffer KL, Henderson RD, O'Maley K, et al.; Nonpharmacological treatment, fludrocortisone, and domperidone for orthostatic hypotension in Parkinson's disease. Mov Disord. 2007;22(11):1543-1549.

Ramirez CE, Okamoto LE, Arnold AC, et al.; Efficacy of atomoxetine versus midodrine for the treatment of orthostatic hypotension in autonomic failure. Hypertension. 2014;64(6):1235-1240.

Patel H, Simpson A, Palevoda G, et al.; Evaluating the effectiveness of atomoxetine for the treatment of primary orthostatic hypotension in adults. J Clin Hypertens (Greenwich). 2018;20(4):794-797.

Singer W, Sandroni P, Opfer-Gehrking TL, et al.; Pyridostigmine treatment trial in neurogenic orthostatic hypotension. Arch Neurol. 2006;63(4):513-518.

McClellan KJ, Wiseman LR, Wilde MI. Midodrine. a review of its therapeutic use in the management of orthostatic hypotension. Drugs Aging. 1998;12(1):76-86.

Isaacson S, Shill HA, Vernino S, et al.; Safety and durability of effect with long-term, open-label droxidopa treatment in patients with symptomatic neurogenic orthostatic hypotension (NOH303). J Parkinsons Dis. 2016;6(4):751-759.

Eschlböck S, Wenning G, Fanciulli A. Evidence-based treatment of neurogenic orthostatic hypotension and related symptoms [published correction appears in J Neural Transm (Vienna). 2018;125(2):273–274]. J Neural Transm (Vienna). 2017;124(12):1567-1605.

Hauser RA, Heritier S, Rowse GJ, et al.; Droxidopa and reduced falls in a trial of Parkinson disease patients with neurogenic orthostatic hypotension. Clin Neuropharmacol. 2016;39(5):220-226.

Grijalva CG, Biaggioni I, Griffin MR, et al.; Fludrocortisone is associated with a higher risk of all-cause hospitalizations compared with midodrine in patients with orthostatic hypotension. J Am Heart Assoc. 2017;6(10):e006848.

Okamoto LE, Shibao CA, Gamboa A, et al.; Synergistic pressor effect of atomoxetine and pyridostigmine in patients with neurogenic orthostatic hypotension. Hypertension. 2019;73(1):235-241.

Olshansky B, Muldowney J. Cardiovascular safety considerations in the treatment of neurogenic orthostatic hypotension. Am J Cardiol. 2020;125(10):1582-1593.

Bradley JG, Davis KA. Orthostatic hypotension. Am Fam Physician. 2003;68(12):2393-2398. Accessed September 13, 2021. https://www.aafp.org/afp/2003/1215/p2393.html

Pathophysiology

Clinical Presentation and Evaluation

Management

NONPHARMACOLOGIC MANAGEMENT

PHARMACOLOGIC MANAGEMENT

Referral

Continue Reading

More in AFP

More in PubMed