orthostatic hypotension

To maintain sufficient blood pressure, the body has several compensatory mechanisms. Baroreceptors, a kind of mechanoreceptors, play a crucial role in conveying data about blood pressure in the autonomic nervous system. The data is conveyed to regulate the peripheral resistance and heart output, keeping blood pressure within an established normal limit.{{cite journal |last1=Bradley |first1=JG |last2=Davis |first2=KA |title=Orthostatic hypotension. |journal=American Family Physician |date=15 December 2003 |volume=68 |issue=12 |pages=2393–8 |pmid=14705758}} There are two kinds of baroreceptors: high-pressure arterial baroreceptors and low-pressure volume receptors, both activated by the stretching of vessel walls.

Arterial baroreceptors are situated in the carotid sinuses and the aortic arch, while the low-pressure volume receptors, known as cardiopulmonary receptors, are in the atria, ventricles, and pulmonary vasculature. Arterial baroreceptors detect changes in blood pressure and transmit this information to the brainstem, the nucleus of the solitary tract, which modulates the activity of the autonomic nervous system (ANS).{{cite journal |last1=Ringer |first1=Matthew |last2=Lappin |first2=Sarah L. |title=Orthostatic Hypotension |journal=StatPearls |date=2024 |url=https://www.ncbi.nlm.nih.gov/books/NBK448192/ |publisher=StatPearls Publishing|pmid=28846238 }} This results in decreased blood pressure, which leads to an increase in heart rate. What's more, the venoarteriolar axon reflex, which results in the constriction of arterial flow to muscles, skin, and adipose tissue also helps stabilize blood pressure.

Orthostatic hypotension is characterized by symptoms that occur after standing (from lying or sitting), particularly when done rapidly. Many report lightheadedness (a feeling that one might be about to faint), sometimes severe, or even actual fainting with associated fall risk.{{cite journal | vauthors = Shaw BH, Borrel D, Sabbaghan K, Kum C, Yang Y, Robinovitch SN, Claydon VE | title = Relationships between orthostatic hypotension, frailty, falling and mortality in elderly care home residents | journal = BMC Geriatrics | volume = 19 | issue = 1 | pages = 80 | date = March 2019 | pmid = 30866845 | pmc = 6415493 | doi = 10.1186/s12877-019-1082-6 | doi-access = free }}{{cite journal | vauthors = Mol A, Bui Hoang PT, Sharmin S, Reijnierse EM, van Wezel RJ, Meskers CG, Maier AB | title = Orthostatic Hypotension and Falls in Older Adults: A Systematic Review and Meta-analysis | journal = Journal of the American Medical Directors Association | volume = 20 | issue = 5 | pages = 589–597.e5 | date = May 2019 | pmid = 30583909 | doi = 10.1016/j.jamda.2018.11.003 | hdl = 1871.1/3c04fc8f-8520-4a7e-bf5c-8ba541a61acb | s2cid = 57898094 | url = https://research.vu.nl/ws/files/101284496/Orthostatic_Hypotension_and_Falls_in_Older_Adults.pdf }} With chronic orthostatic hypotension, the condition and its effects may worsen even as fainting and many other symptoms become less frequent. Generalized weakness or tiredness may also occur. Some also report difficulty concentrating, blurred vision, tremulousness, vertigo, anxiety, palpitations (awareness of the heartbeat), unsteadiness, feeling sweaty or clammy, and sometimes nausea. A person may look pale.{{cite book |vauthors=Kasper DL, Fauci AS, Hauser SL, Longo DL, James JL, Loscalzo J |title=Harrison's principles of internal medicine |publisher=McGraw-Hill Medical Publishing Division |location=New York |year=2015 |edition=19th |isbn=978-0-07-180215-4 | volume=2 | page=2639}} Some people may experience severe orthostatic hypotension with the only symptoms being confusion or extreme fatigue. Chronic severe orthostatic hypotension may present as fluctuating cognition/delirium. {{citation needed|date=October 2021}} Women who are pregnant are also susceptible to orthostatic hypotension.{{cite journal | vauthors = Miyake Y, Ohnishi M, Fujii TK, Yamamoto T, Yoneda C, Takahashi S, Ichimaru Y | title = The effects of postural changes of baroreflex gain in normal and hypertensive pregnancies | journal = Clinical and Experimental Hypertension | volume = 24 | issue = 1–2 | pages = 23–31 | date = 2002-01-01 | pmid = 11848166 | doi = 10.1081/CEH-100108712 | s2cid = 777855 }}{{cite journal | vauthors = Lucini D, Mela GS, Malliani A, Pagani M | title = Impairment in cardiac autonomic regulation preceding arterial hypertension in humans: insights from spectral analysis of beat-by-beat cardiovascular variability | journal = Circulation | volume = 106 | issue = 21 | pages = 2673–2679 | date = November 2002 | pmid = 12438292 | doi = 10.1161/01.CIR.0000039106.89299.AB | s2cid = 9826957 | doi-access = free }}{{cite journal | vauthors = Easterling TR, Schmucker BC, Benedetti TJ | title = The hemodynamic effects of orthostatic stress during pregnancy | journal = Obstetrics and Gynecology | volume = 72 | issue = 4 | pages = 550–552 | date = October 1988 | pmid = 3419734 | url = https://pubmed.ncbi.nlm.nih.gov/3419734 }}{{cite journal | vauthors = Brooks VL, Dampney RA, Heesch CM | title = Pregnancy and the endocrine regulation of the baroreceptor reflex | journal = American Journal of Physiology. Regulatory, Integrative and Comparative Physiology | volume = 299 | issue = 2 | pages = R439–R451 | date = August 2010 | pmid = 20504907 | pmc = 2928618 | doi = 10.1152/ajpregu.00059.2010 }}

The disorder may be associated with Addison's disease, atherosclerosis (build-up of fatty deposits in the arteries), diabetes, pheochromocytoma, porphyria,{{cite journal | vauthors = Sim M, Hudon R | title = Acute intermittent porphyria associated with postural hypotension | journal = Canadian Medical Association Journal | volume = 121 | issue = 7 | pages = 845–846 | date = October 1979 | pmid = 497968 | pmc = 1704473 }} long COVID,{{Cite journal |last=Lee |first=Cassie |last2=Greenwood |first2=Darren C. |last3=Master |first3=Harsha |last4=Balasundaram |first4=Kumaran |last5=Williams |first5=Paul |last6=Scott |first6=Janet T. |last7=Wood |first7=Conor |last8=Cooper |first8=Rowena |last9=Darbyshire |first9=Julie L. |last10=Gonzalez |first10=Ana Espinosa |last11=Davies |first11=Helen E. |last12=Osborne |first12=Thomas |last13=Corrado |first13=Joanna |last14=Iftekhar |first14=Nafi |last15=Rogers |first15=Natalie |date=1 March 2024 |title=Prevalence of orthostatic intolerance in long covid clinic patients and healthy volunteers: A multicenter study |url=https://onlinelibrary.wiley.com/doi/10.1002/jmv.29486 |journal=Journal of Medical Virology |language=en |volume=96 |issue=3 |doi=10.1002/jmv.29486 |issn=0146-6615}}{{Cite journal |date=24 September 2024 |title=Is long COVID linked with orthostatic intolerance? |url=https://evidence.nihr.ac.uk/alert/is-long-covid-linked-with-orthostatic-intolerance/ |journal=NIHR Evidence}} and certain neurological disorders, including autoimmune autonomic ganglionopathy, multiple system atrophy, and other forms of dysautonomia. It is also associated with Ehlers–Danlos syndrome and anorexia nervosa. It is also present in many patients with Parkinson's disease or Lewy body dementias resulting from sympathetic denervation of the heart or as a side effect of dopaminomimetic therapy. This rarely leads to fainting unless the person has developed true autonomic failure or has an unrelated heart problem.{{citation needed|date=October 2016}}

Another disease, dopamine beta hydroxylase deficiency, also thought to be underdiagnosed, causes loss of sympathetic noradrenergic function and is characterized by low or extremely low levels of norepinephrine, but an excess of dopamine.{{cite book | vauthors = Robertson D, Garland EM | chapter = Dopamine Beta-Hydroxylase Deficiency | date = September 2003 | pmid = 20301647 | chapter-url = https://www.ncbi.nlm.nih.gov/books/NBK1474/ | publisher = University of Washington, Seattle | veditors = Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJ, Stephens K, Amemiya A | title = GeneReviews | via = NCBI Bookshelf }}

Quadriplegics and paraplegics also might experience these symptoms due to multiple systems' inability to maintain normal blood pressure and blood flow to the upper part of the body.{{citation needed|date=October 2016}}

Some causes of orthostatic hypotension include neurodegenerative disorders, low blood volume (e.g. caused by dehydration, bleeding, or the use of diuretics), drugs that cause vasodilation, other types of drugs (notably, narcotics and marijuana), discontinuation of vasoconstrictors, prolonged bed rest (immobility), significant recent weight loss, anemia,{{cite web|title=What Causes Hypotension? - |url=https://www.nhlbi.nih.gov/health/health-topics/topics/hyp/causes|work = National Heart, Lung, and Blood Institute (NHLBI) | publisher = U.S. National Institutes of Health |access-date=27 March 2017 }} vitamin B₁₂ deficiency, or recent bariatric surgery.{{cite journal | vauthors = Christou GA, Kiortsis DN | title = The effects of body weight status on orthostatic intolerance and predisposition to noncardiac syncope | journal = Obesity Reviews | volume = 18 | issue = 3 | pages = 370–379 | date = March 2017 | pmid = 28112481 | doi = 10.1111/obr.12501 | s2cid = 46498296 }}

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Orthostatic hypotension can be a side effect of certain antidepressants, such as tricyclics{{cite journal | vauthors = Jiang W, Davidson JR | title = Antidepressant therapy in patients with ischemic heart disease | journal = American Heart Journal | volume = 150 | issue = 5 | pages = 871–881 | date = November 2005 | pmid = 16290952 | doi = 10.1016/j.ahj.2005.01.041 }} or monoamine oxidase inhibitors (MAOIs){{cite journal | vauthors = Jones RT | title = Cardiovascular system effects of marijuana | journal = Journal of Clinical Pharmacology | volume = 42 | issue = S1 | pages = 58S–63S | date = November 2002 | pmid = 12412837 | doi = 10.1002/j.1552-4604.2002.tb06004.x | s2cid = 12193532 }} Alcohol can potentiate orthostatic hypotension to the point of syncope.{{cite journal | vauthors = Narkiewicz K, Cooley RL, Somers VK | title = Alcohol potentiates orthostatic hypotension : implications for alcohol-related syncope | journal = Circulation | volume = 101 | issue = 4 | pages = 398–402 | date = February 2000 | pmid = 10653831 | doi = 10.1161/01.CIR.101.4.398 | doi-access = free }} Orthostatic hypotension can also be a side effect of alpha-1 blockers (alpha₁ adrenergic blocking agents). Alpha₁ blockers inhibit vasoconstriction normally initiated by the baroreceptor reflex upon postural change and the subsequent drop in pressure.{{cite web | vauthors = Shea MJ, Thompson AD | title = Orthostatic Hypotension | url = https://www.msdmanuals.com/professional/cardiovascular-disorders/symptoms-of-cardiovascular-disorders/orthostatic-hypotension | work = Merck Manual }} Other antihypertensive medications may also cause orthostatic hypotension, in addition to anticholinergics, dopaminergic drugs, opiates and psychoactive medications.

Patients prone to orthostatic hypotension are the elderly, post partum mothers, and those having been on bed rest. People with anorexia nervosa and bulimia nervosa often develop orthostatic hypotension as a common side effect. Consuming alcohol may also lead to orthostatic hypotension due to its dehydrating effects.{{citation needed | date=April 2015}}

Orthostatic hypotension happens when gravity causes blood to pool in the lower extremities, which in turn compromises venous return, resulting in decreased cardiac output and subsequent lowering of arterial pressure. For example, changing from a lying position to standing loses about 700 ml of blood from the thorax, with a decrease in systolic and diastolic blood pressures.{{EMedicine|article|1154266|Idiopathic Orthostatic Hypotension and other Autonomic Failure Syndromes}} The overall effect is insufficient blood perfusion in the upper part of the body.{{citation needed|date=March 2017}}

Normally, a series of cardiac, vascular, neurologic, muscular, and neurohumoral responses occurs quickly so the blood pressure does not fall very much. One response is a vasoconstriction (baroreceptor reflex), pressing the blood up into the body again. (Often, this mechanism is exaggerated and is why diastolic blood pressure is a bit higher when a person is standing up, compared to a person in the horizontal position.) Therefore, some factor that inhibits one of these responses and causes a greater than normal fall in blood pressure is required. Such factors include low blood volume, diseases, and medications. {{citation needed|date=October 2016}}

Orthostatic hypotension can be confirmed by measuring a person's blood pressure after lying flat for 5 minutes, then 1 minute after standing, and 3 minutes after standing.{{Cite web|url=https://www.rcplondon.ac.uk/projects/outputs/measurement-lying-and-standing-blood-pressure-brief-guide-clinical-staff|title=Measurement of lying and standing blood pressure: A brief guide for clinical staff|date=2017-01-13|website=RCP London|access-date=2019-09-23}} Orthostatic hypotension is defined as a fall in systolic blood pressure of at least 20 mmHg or the diastolic blood pressure of at least 10 mmHg between the supine reading and the upright reading. Also, the heart rate should be measured for both positions. A significant increase in heart rate from supine to standing may indicate a compensatory effort by the heart to maintain cardiac output. A related syndrome, postural orthostatic tachycardia syndrome (POTS), is diagnosed when at least a 30 bpm increase in heart rate occurs with little or no change in blood pressure. A tilt table test may also be performed.{{cite journal | vauthors = Natale A, Akhtar M, Jazayeri M, Dhala A, Blanck Z, Deshpande S, Krebs A, Sra JS | display-authors = 6 | title = Provocation of hypotension during head-up tilt testing in subjects with no history of syncope or presyncope | journal = Circulation | volume = 92 | issue = 1 | pages = 54–58 | date = July 1995 | pmid = 7788917 | doi = 10.1161/01.CIR.92.1.54 }}

Orthostatic hypotension (or postural hypotension) is a drop in blood pressure upon standing. One definition (AAFP) calls for a systolic blood pressure decrease of at least 20 mm Hg or a diastolic blood pressure decrease of at least 10 mm Hg within 3 minutes of standing.{{cite journal | vauthors = Bradley JG, Davis KA | title = Orthostatic hypotension | journal = American Family Physician | volume = 68 | issue = 12 | pages = 2393–2398 | date = December 2003 | pmid = 14705758 | url = https://www.aafp.org/afp/2003/1215/p2393.html }} A common first symptom is lightheadedness upon standing, possibly followed by more severe symptoms: narrowing or loss of vision, dizziness, weakness, and even syncope (fainting).{{citation needed|date=October 2021}}

Orthostatic hypotension can be subcategorized into three groups – initial, classic, and delayed.{{cite journal | vauthors = Wieling W, Krediet CT, van Dijk N, Linzer M, Tschakovsky ME | title = Initial orthostatic hypotension: review of a forgotten condition | journal = Clinical Science | volume = 112 | issue = 3 | pages = 157–165 | date = February 2007 | pmid = 17199559 | doi = 10.1042/CS20060091 }}{{cite journal | vauthors = Moya A, Sutton R, Ammirati F, Blanc JJ, Brignole M, Dahm JB, Deharo JC, Gajek J, Gjesdal K, Krahn A, Massin M, Pepi M, Pezawas T, Ruiz Granell R, Sarasin F, Ungar A, van Dijk JG, Walma EP, Wieling W | display-authors = 6 | title = Guidelines for the diagnosis and management of syncope (version 2009) | journal = European Heart Journal | volume = 30 | issue = 21 | pages = 2631–2671 | date = November 2009 | pmid = 19713422 | pmc = 3295536 | doi = 10.1093/eurheartj/ehp298 }}{{cite journal | vauthors = Gibbons CH, Freeman R | title = Delayed orthostatic hypotension: a frequent cause of orthostatic intolerance | journal = Neurology | volume = 67 | issue = 1 | pages = 28–32 | date = July 2006 | pmid = 16832073 | doi = 10.1212/01.wnl.0000223828.28215.0b | s2cid = 33902650 }}

Initial orthostatic hypotension is frequently characterized by a systolic blood pressure decrease of ≥40 mmHg or diastolic blood pressure decrease of ≥20 mmHg within 15 seconds of standing. Blood pressure then spontaneously and rapidly returns to normal, so the period of hypotension and symptoms is short (<30 s). Only continuous beat-to-beat BP measurement during an active standing-up maneuver can document this condition.

Classic orthostatic hypotension is frequently characterized by a systolic blood pressure decrease of ≥20 mmHg or diastolic blood pressure decrease of ≥10 mmHg between 30 seconds and 3 min of standing.

Delayed orthostatic hypotension is frequently characterized by a sustained systolic blood pressure decrease of ≥20 mm Hg or a sustained diastolic blood pressure decrease ≥of 10 mm Hg beyond 3 minutes of standing or upright tilt table testing.

Apart from treating underlying reversible causes (e.g., stopping or reducing certain medications, treating autoimmune causes), several measures can improve the symptoms of orthostatic hypotension and prevent episodes of syncope (fainting). Even small increases in the blood pressure may be sufficient to maintain blood flow to the brain on standing.

In dysautonomic patients who do not have a diagnosis of high blood pressure, drinking 2–3 liters of fluid a day and taking 10 g of salt can improve symptoms, by maximizing the amount of fluid in the bloodstream. Another strategy is keeping the head of the bed slightly elevated. This reduces the return of fluid from the limbs to the kidneys at night, thereby reducing nighttime urine production and maintaining fluid in the circulation. Various measures can be used to improve the return of blood to the heart; the wearing of compression stockings and exercises ("physical counterpressure maneuvers" or PCMs) can be undertaken just before standing up (e.g., leg crossing and squatting), as muscular contraction helps return blood from the legs to the upper body.

The medication midodrine, an α₁-adrenergic receptor agonist, can benefit people with orthostatic hypotension,{{cite journal | vauthors = Izcovich A, González Malla C, Manzotti M, Catalano HN, Guyatt G | title = Midodrine for orthostatic hypotension and recurrent reflex syncope: A systematic review | journal = Neurology | volume = 83 | issue = 13 | pages = 1170–1177 | date = September 2014 | pmid = 25150287 | doi = 10.1212/WNL.0000000000000815 | s2cid = 5439767 }} The main side effect is piloerection ("goose bumps"). Fludrocortisone is also used, although based on more limited evidence.

Droxidopa, a norepinephrine prodrug and hence non-selective adrenergic receptor agonist, has been shown to be effective as well,{{cite journal | vauthors = Mathias CJ | title = L-dihydroxyphenylserine (Droxidopa) in the treatment of orthostatic hypotension: the European experience | journal = Clinical Autonomic Research | volume = 18 | issue = Supplement 1 | pages = 25–29 | date = March 2008 | pmid = 18368304 | doi = 10.1007/s10286-007-1005-z | s2cid = 29861644 }} with few, mostly mild side effects reported.{{cite journal | vauthors = Kaufmann H, Freeman R, Biaggioni I, Low P, Pedder S, Hewitt LA, Mauney J, Feirtag M, Mathias CJ | display-authors = 6 | title = Droxidopa for neurogenic orthostatic hypotension: a randomized, placebo-controlled, phase 3 trial | journal = Neurology | volume = 83 | issue = 4 | pages = 328–335 | date = July 2014 | pmid = 24944260 | pmc = 4115605 | doi = 10.1212/WNL.0000000000000615 }}

A number of other measures have slight evidence to support their use – indomethacin, fluoxetine, dopamine antagonists, metoclopramide, domperidone, monoamine oxidase inhibitors with tyramine (can produce severe hypertension), oxilofrine, potassium chloride, and yohimbine.{{cite journal | vauthors = Logan IC, Witham MD | title = Efficacy of treatments for orthostatic hypotension: a systematic review | journal = Age and Ageing | volume = 41 | issue = 5 | pages = 587–594 | date = September 2012 | pmid = 22591985 | doi = 10.1093/ageing/afs061 | doi-access = free }}

Ampreloxetine (TD-9855), a norepinephrine reuptake inhibitor, is in late-stage development for treatment of the condition.{{cite web | title=Ampreloxetine - Theravance Biopharma | website=AdisInsight | date=21 November 2023 | url=https://adisinsight.springer.com/drugs/800026474 | access-date=26 September 2024}}{{cite journal | vauthors = Hoxhaj P, Shah S, Muyolema Arce VE, Khan W, Sadeghzadegan A, Singh S, Collado GF, Goyal A, Khawaja I, Botlaguduru D, Razzaq W, Abdin ZU, Gupta I | title = Ampreloxetine Versus Droxidopa in Neurogenic Orthostatic Hypotension: A Comparative Review | journal = Cureus | volume = 15 | issue = 5 | pages = e38907 | date = May 2023 | pmid = 37303338 | pmc = 10257554 | doi = 10.7759/cureus.38907 | doi-access = free | url = }}

Robotic devices, such as the Erigo medical device, have been proven to help orthostatic hypotension in some patients. These machines adjust a patient's position from 0 degrees to 90 degrees in progressive increments, allowing the blood pressure to adjust more slowly.{{cite journal | vauthors = Sorbera C, Portaro S, Cimino V, Leo A, Accorinti M, Silvestri G, Bramanti P, Naro A, Calabrò RS | display-authors = 6 | title = ERIGO: a possible strategy to treat orthostatic hypotension in progressive supranuclear palsy? A feasibility study | journal = Functional Neurology | volume = 34 | issue = 2 | pages = 93–97 | date = Apr–Jun 2019 | pmid = 31556389 | url = https://pubmed.ncbi.nlm.nih.gov/31556389 }}

Orthostatic hypotension may cause accidental falls.{{cite journal | vauthors = Romero-Ortuno R, Cogan L, Foran T, Kenny RA, Fan CW | title = Continuous noninvasive orthostatic blood pressure measurements and their relationship with orthostatic intolerance, falls, and frailty in older people | journal = Journal of the American Geriatrics Society | volume = 59 | issue = 4 | pages = 655–665 | date = April 2011 | pmid = 21438868 | doi = 10.1111/j.1532-5415.2011.03352.x | hdl-access = free | s2cid = 31596763 | hdl = 2262/57382 }} It is also linked to an increased risk of cardiovascular disease, heart failure, and stroke.{{cite journal | vauthors = Ricci F, Fedorowski A, Radico F, Romanello M, Tatasciore A, Di Nicola M, Zimarino M, De Caterina R | display-authors = 6 | title = Cardiovascular morbidity and mortality related to orthostatic hypotension: a meta-analysis of prospective observational studies | journal = European Heart Journal | volume = 36 | issue = 25 | pages = 1609–1617 | date = July 2015 | pmid = 25852216 | doi = 10.1093/eurheartj/ehv093 | doi-access = free }}{{cite journal |last1=Kim |first1=Michael J. |last2=Farrell |first2=Jennifer |title=Orthostatic Hypotension: A Practical Approach |journal=American Family Physician |date=January 2022 |volume=105 |issue=1 |pages=39–49 |pmid=35029940 |url=https://www.aafp.org/pubs/afp/issues/2022/0100/p39.html |issn=1532-0650}} Also, observational data suggest that orthostatic hypotension in middle age increases the risk of eventual dementia and reduced cognitive function.{{cite journal | vauthors = Rawlings A, Juraschek S, Heiss G, Hughes T, Meyer M, Selvin E, Sharrett AR, Windham BG, Gottesman R | display-authors = 6 |title= Abstract 28: Orthostatic Hypotension is Associated With 20-year Cognitive Decline and Incident Dementia: the Atherosclerosis Risk in Communities (ARIC) Study |journal=Circulation |date=7 March 2017 |volume=135 |issue=suppl_1 |doi=10.1161/circ.135.suppl_1.28 }}

• Orthostatic hypertension
• Orthostatic intolerance
• Vasovagal response

{{reflist|30em}}

• [https://stacks.cdc.gov/view/cdc/30739 Postural hypotension : what it is and how to manage it] – Centers for Disease Control and Prevention

{{Medical resources

| DiseasesDB = 10470

| ICD10 = {{ICD10|I|95|1|i|95}}

| ICD9 = {{ICD9|458.0}}

| ICDO =

| OMIM =

| MedlinePlus =

| eMedicineSubj =

| eMedicineTopic = 2860

| MeshID = D007024

}}

{{Autonomic diseases}}

{{Vascular diseases}}

Category:Vascular diseases

Category:Hypotension

Category:Peripheral nervous system disorders