Orthostatic hypotension

Cardiovascular

Clinicals - History

Fact Explanation
A known predisposing medical syndrome Some syndromes are associated with chronic orthostatic hypotension, together with their respective characteristic features. i.e. Diabetes mellitus (due to autonomic neuropathy) , idiopathic orthostatic hypotension or Bradbury-Eggleston syndrome (due to idiopathic degeneration of the peripheral autonomic nerves) , familial dysautonomia (autosomal recessive condition) , baroreceptor dysfunction due to neck irradiation, trauma, surgery, oropharyngeal carcinoma ) and rarely, dopamine-beta-hydroxylase deficiency (which causes a severe orthostatic hypotension ) Some medical conditions cause peripheral neuropathy and thus causes orthostatic hypotension. i.e. diabetes mellitus, alcoholism, nutritional deficiencies (vitamin B12, folic acid), Guillain-barre syndrome, toxins, drugs, heavy metals, hereditary neuropathies, Hansen's disease, paraneoplastic syndrome, renal failure, recurrent peripheral neuropathy, amyloidosis, porphyria, infectious agents (diphtheria, tetanus, botulism), systemic collagen vascular disease, syringomyelia and Tabes dorsalis. A known predisposing medical syndrome
Some syndromes are associated with chronic orthostatic hypotension, together with their respective characteristic features. i.e. Diabetes mellitus (due to autonomic neuropathy) , idiopathic orthostatic hypotension or Bradbury-Eggleston syndrome (due to idiopathic degeneration of the peripheral autonomic nerves) , familial dysautonomia (autosomal recessive condition) , baroreceptor dysfunction due to neck irradiation, trauma, surgery, oropharyngeal carcinoma ) and rarely, dopamine-beta-hydroxylase deficiency (which causes a severe orthostatic hypotension ) Some medical conditions cause peripheral neuropathy and thus causes orthostatic hypotension. i.e. diabetes mellitus, alcoholism, nutritional deficiencies (vitamin B12, folic acid), Guillain-barre syndrome, toxins, drugs, heavy metals, hereditary neuropathies, Hansen's disease, paraneoplastic syndrome, renal failure, recurrent peripheral neuropathy, amyloidosis, porphyria, infectious agents (diphtheria, tetanus, botulism), systemic collagen vascular disease, syringomyelia and Tabes dorsalis.
A known predisposing drug The common drugs that cause orthostatic hypotension are nitrates, vasodilators, alcohol, narcotics, tricyclic antidepressants, prolonged use of sympathomimetics and phenothiazines. A known predisposing drug
The common drugs that cause orthostatic hypotension are nitrates, vasodilators, alcohol, narcotics, tricyclic antidepressants, prolonged use of sympathomimetics and phenothiazines.
Characteristic clinical symptoms on standing up Independent of the cause, almost all the patients feel dizziness, faintishness, lightheadedness or swaying when they stand up or sit up after recumbency. In some patients it may be short-lived , in some, comes suddenly and disappears after a short while , but in some case, may be even a chronic experience. Most of the time, the symptoms are relieved by recumbency, or kept standing up for a few minutes. The cause is cerebral hypotension due to failure of upright reflex. In patients with autonomic failure orthostatic hypotension results from an impaired capacity to increase vascular resistance during standing. The sequence of this is increased downward pooling of venous blood and a consequent reduction in stroke volume and cardiac output that exaggerates the orthostatic fall in blood pressure. Characteristic clinical symptoms on standing up
Independent of the cause, almost all the patients feel dizziness, faintishness, lightheadedness or swaying when they stand up or sit up after recumbency. In some patients it may be short-lived , in some, comes suddenly and disappears after a short while , but in some case, may be even a chronic experience. Most of the time, the symptoms are relieved by recumbency, or kept standing up for a few minutes. The cause is cerebral hypotension due to failure of upright reflex. In patients with autonomic failure orthostatic hypotension results from an impaired capacity to increase vascular resistance during standing. The sequence of this is increased downward pooling of venous blood and a consequent reduction in stroke volume and cardiac output that exaggerates the orthostatic fall in blood pressure.
Fits Prolonged cerebral ischemia in orthostatic intolerence can cause focal cerebral necrosis and seizures. They can be any type, tonic-clonic or aphasic. Fits
Prolonged cerebral ischemia in orthostatic intolerence can cause focal cerebral necrosis and seizures. They can be any type, tonic-clonic or aphasic.
Sudden onset weakness, facial deviation Features of stroke, which is possible following severe and long standing ischemia to the brain. Sudden onset weakness, facial deviation
Features of stroke, which is possible following severe and long standing ischemia to the brain.
Headache An atypical manifestation, could be misdiagnosed, and is due to cerebral ischemia. Headache
An atypical manifestation, could be misdiagnosed, and is due to cerebral ischemia.
Neck pain, backache Atypical presentation, and due to muscle hypoperfusion. Neck pain, backache
Atypical presentation, and due to muscle hypoperfusion.
Chest pain Due to compensatory autonomic over-reaction. Chest pain
Due to compensatory autonomic over-reaction.

Clinicals - Examination

Fact Explanation
Low blood pressure with a postural drop The blood pressure while recumbent and after standing up/sitting up should be measured. In one study the majority reached their maximum systolic decrease within 5 minutes of standing, but in 20-30% the maximum blood pressure drop occurred after 5 minutes or later, in 38%, the systolic blood pressure drop was more than 40 mm Hg. But according to the 1996 consensus definition, orthostatic hypotension is diagnosed when a fall in systolic blood pressure of at least 20 mm Hg and/or diastolic blood pressure of at least 10 mm Hg within 3 min of standing is recorded. Low blood pressure with a postural drop
The blood pressure while recumbent and after standing up/sitting up should be measured. In one study the majority reached their maximum systolic decrease within 5 minutes of standing, but in 20-30% the maximum blood pressure drop occurred after 5 minutes or later, in 38%, the systolic blood pressure drop was more than 40 mm Hg. But according to the 1996 consensus definition, orthostatic hypotension is diagnosed when a fall in systolic blood pressure of at least 20 mm Hg and/or diastolic blood pressure of at least 10 mm Hg within 3 min of standing is recorded.
Normal or mildly elevated pulse rate The reason behind reduced cerebral perfusion is lack of normal sympathetic reflexive response to suddenly low blood pressure. Unlike in syncopal attacks, the pulse rate is either normal or mildly elevated if any, and it also can be irregular. Normal or mildly elevated pulse rate
The reason behind reduced cerebral perfusion is lack of normal sympathetic reflexive response to suddenly low blood pressure. Unlike in syncopal attacks, the pulse rate is either normal or mildly elevated if any, and it also can be irregular.
Anhydrosis Because of dysautonomia. Amount of sweating in the dorsum of the foot is a tool used to assess autonomic dysfunction. Anhydrosis
Because of dysautonomia. Amount of sweating in the dorsum of the foot is a tool used to assess autonomic dysfunction.
Bladder distension A feature of dysautonomia and neurogenic orthostatic hypotension. Bladder stasis comes earlier than symptomatic hypotension. One must be aware to ask about erectile dysfunction in such patients. Bladder distension
A feature of dysautonomia and neurogenic orthostatic hypotension. Bladder stasis comes earlier than symptomatic hypotension. One must be aware to ask about erectile dysfunction in such patients.
Motor weakness There is a significant reduction of blood flow in brain in patients with orthostatic hypotension, which is a potent risk factor for cerebral ischemia and stroke syndromes later. Motor weakness
There is a significant reduction of blood flow in brain in patients with orthostatic hypotension, which is a potent risk factor for cerebral ischemia and stroke syndromes later.
Sensory deficit Due to cerebral ischemia. Sensory deficit
Due to cerebral ischemia.
Cerebellar signs Due to ischaemia in cerebellum. Commonly seen in multiple system atrophy. Cerebellar signs
Due to ischaemia in cerebellum. Commonly seen in multiple system atrophy.
A seizure Due to cerebral ischemia. A seizure
Due to cerebral ischemia.

Investigations - Diagnosis

Fact Explanation
Investigate for the cause Since there are one too many causes for orthostatic hypotension, specific investigations for the etiological diagnosis should be carried out. i. e. neurodegenerative diseases, parkisonism, amyloidosis, diabetes, anemia, and vitamin deficiency. The type of investigation should be decided by the the attending doctor. Investigate for the cause
Since there are one too many causes for orthostatic hypotension, specific investigations for the etiological diagnosis should be carried out. i. e. neurodegenerative diseases, parkisonism, amyloidosis, diabetes, anemia, and vitamin deficiency. The type of investigation should be decided by the the attending doctor.
Head upright tilt-test This examines the baroreceptor-reflex system as a whole entity in a non-invasive way. Staying upright requires rapid circulatory and neurologic compensation as soon as the posture changes, to maintain blood pressure and consciousness. If one of these are ineffective or if there is insufficient blood volume, the location of the brain above the heart and the presence of large venous reservoirs below the heart causes cardiac filling and blood pressure to decrease rapidly with consequent cerebral mal-perfusion and loss of consciousness. The mechanism behind the head tiling test is such, but the severity of orthostatic intolerance cannot be predicted by the positivity of the test. Most of the patients do become positive with three minutes of upright posture. Head upright tilt-test
This examines the baroreceptor-reflex system as a whole entity in a non-invasive way. Staying upright requires rapid circulatory and neurologic compensation as soon as the posture changes, to maintain blood pressure and consciousness. If one of these are ineffective or if there is insufficient blood volume, the location of the brain above the heart and the presence of large venous reservoirs below the heart causes cardiac filling and blood pressure to decrease rapidly with consequent cerebral mal-perfusion and loss of consciousness. The mechanism behind the head tiling test is such, but the severity of orthostatic intolerance cannot be predicted by the positivity of the test. Most of the patients do become positive with three minutes of upright posture.
Valsalva manoeuvre In the patients with orthostatic intolerence in three minutes, most had failed valsalva maneouvre especially stage two and four. Valsalva manoeuvre
In the patients with orthostatic intolerence in three minutes, most had failed valsalva maneouvre especially stage two and four.

Investigations - Management

Fact Explanation
12 lead Electrocardiogram To assess cardiac fitness of the patient and exclude other cardiovascular co-morbidities. 12 lead Electrocardiogram
To assess cardiac fitness of the patient and exclude other cardiovascular co-morbidities.

Management - Supportive

Fact Explanation
Compression garments i.e. Abdominal compression. Usefull in cases where there is adrenergic denervation of vascular beds, in those cases, there is an increase in vascular capacitance and peripheral venous pooling. Compression of capacitance beds (i.e, the legs and abdomen) improves orthostatic symptoms. The improvement is due to a reduction of venous capacitance and an increase in total peripheral resistance. Compressing legs is not as effective as compressing the abdomen. Once combined together with other postural maneuvers accelerates the recovery. Compression garments
i.e. Abdominal compression. Usefull in cases where there is adrenergic denervation of vascular beds, in those cases, there is an increase in vascular capacitance and peripheral venous pooling. Compression of capacitance beds (i.e, the legs and abdomen) improves orthostatic symptoms. The improvement is due to a reduction of venous capacitance and an increase in total peripheral resistance. Compressing legs is not as effective as compressing the abdomen. Once combined together with other postural maneuvers accelerates the recovery.
Postural adjustment Raising the head-end of the bed when patient is supine also reduced the drop of blood pressure thus symptoms when standing. During the day, adequate orthostatic stress, i.e, upright activity, should be maintained. If patients are repeatedly tilted up, their orthostatic hypotension is gradually attenuated, presumably by increasing venomotor tone. Combination with other treatment options yields better results. Postural adjustment
Raising the head-end of the bed when patient is supine also reduced the drop of blood pressure thus symptoms when standing. During the day, adequate orthostatic stress, i.e, upright activity, should be maintained. If patients are repeatedly tilted up, their orthostatic hypotension is gradually attenuated, presumably by increasing venomotor tone. Combination with other treatment options yields better results.
Counter-maneuvers Physical countermaneuvers are isometrical contracting of the muscles below the waist for about 30 seconds at a time, which reduces venous capacitance, increases total peripheral resistance, and augments venous return to the heart. These countermeasures can help maintain blood pressure during daily activities and should be considered at the first symptoms of orthostatic intolerance and in situations of orthostatic stress. Some of the known specific techniques include toe-raising, leg-crossing and contraction, thigh muscle co-contraction, bending at the waist, slow marching in place and leg elevation. Counter-maneuvers
Physical countermaneuvers are isometrical contracting of the muscles below the waist for about 30 seconds at a time, which reduces venous capacitance, increases total peripheral resistance, and augments venous return to the heart. These countermeasures can help maintain blood pressure during daily activities and should be considered at the first symptoms of orthostatic intolerance and in situations of orthostatic stress. Some of the known specific techniques include toe-raising, leg-crossing and contraction, thigh muscle co-contraction, bending at the waist, slow marching in place and leg elevation.
Education of the patient and the family It's the cornerstone of the management. Education about orthostatic stressors and warning symptoms empowers the patient to adopt easy lifestyle changes to minimize and handle orthostatic stress. Education of the patient and the family
It's the cornerstone of the management. Education about orthostatic stressors and warning symptoms empowers the patient to adopt easy lifestyle changes to minimize and handle orthostatic stress.

Management - Specific

Fact Explanation
Alpha-stimulating vasopressors Midodrine is the commonly used vasopressive agent, being an alpha-adrenergic stimulant, raises arterial blood pressure independent of the route of administration. It is effective and safe when used for treating neurogenic orthostatic hypotension. It has been shown to increase standing systolic blood pressure, reduce orthostatic light-headedness, and increase standing and walking time. The common starting dose is 5 mg three times a day; most patients respond best to 10 mg three times a day. As its duration of action is short (2 to 4 hours), it should be taken before arising in the morning, before lunch, and in the midafternoon. To avoid nocturnal supine hypertension, doses should not be taken after the midafternoon, and a dose should be omitted if the supine or sitting blood pressure is greater than 180/100 mm Hg. The patient should be educated about the side effects of the drug, being supine hypertension, scalp paresthesias, and pilomotor reactions (goosebumps). Alpha-stimulating vasopressors
Midodrine is the commonly used vasopressive agent, being an alpha-adrenergic stimulant, raises arterial blood pressure independent of the route of administration. It is effective and safe when used for treating neurogenic orthostatic hypotension. It has been shown to increase standing systolic blood pressure, reduce orthostatic light-headedness, and increase standing and walking time. The common starting dose is 5 mg three times a day; most patients respond best to 10 mg three times a day. As its duration of action is short (2 to 4 hours), it should be taken before arising in the morning, before lunch, and in the midafternoon. To avoid nocturnal supine hypertension, doses should not be taken after the midafternoon, and a dose should be omitted if the supine or sitting blood pressure is greater than 180/100 mm Hg. The patient should be educated about the side effects of the drug, being supine hypertension, scalp paresthesias, and pilomotor reactions (goosebumps).
Volume expansors Fludrocortisone is the commonest used volume expansor. It's a synthetic mineralocorticoid with negligible glucocorticoid action. The action is pressor effect as a result of its ability to expand plasma volume and increase vascular alpha-adrenoceptor sensitivity. This drug is helpful when plasma volume fails to adequately increase with salt supplementation, and for patients who cannot ingest enough salt or do not respond adequately to midodrine. The usual dose is 0.1 to 0.2 mg/day, but it may be increased to 0.4 to 0.6 mg/day in patients with refractory orthostatic hypotension. If the patient gains 1.2–2.3 kg and develops mild dependent edema, it's inferable that the plasma volume has expanded adequately. Fludrocortisone is contraindicated in congestive heart failure and chronic renal failure. The potential risks are severe hypokalemia and excessive supine hypertension, and the patient shoud be eductaed about these effects. Frequent monitoring of serum potassium, a diet high in potassium, and regular checks of supine blood pressure are advised, especially at higher doses, when added to midodrine, or in elderly patients who tend to poorly tolerate the medication. Volume expansors
Fludrocortisone is the commonest used volume expansor. It's a synthetic mineralocorticoid with negligible glucocorticoid action. The action is pressor effect as a result of its ability to expand plasma volume and increase vascular alpha-adrenoceptor sensitivity. This drug is helpful when plasma volume fails to adequately increase with salt supplementation, and for patients who cannot ingest enough salt or do not respond adequately to midodrine. The usual dose is 0.1 to 0.2 mg/day, but it may be increased to 0.4 to 0.6 mg/day in patients with refractory orthostatic hypotension. If the patient gains 1.2–2.3 kg and develops mild dependent edema, it's inferable that the plasma volume has expanded adequately. Fludrocortisone is contraindicated in congestive heart failure and chronic renal failure. The potential risks are severe hypokalemia and excessive supine hypertension, and the patient shoud be eductaed about these effects. Frequent monitoring of serum potassium, a diet high in potassium, and regular checks of supine blood pressure are advised, especially at higher doses, when added to midodrine, or in elderly patients who tend to poorly tolerate the medication.
Choline-esterase inhibitors It improves neurotransmission at acetylcholine-mediated neuronal reflexes of the autonomic nervous system. Because this pathway is activated primarily during standing, this drug improves orthostatic hypotension and total peripheral resistance without aggravating supine hypertension. Since the pressor effect is modest, it is most adequate for patients with mild to moderate orthostatic hypotension. Dosing is started at 30 mg two to three times a day and is gradually increased to 60 mg three times a day. The drug’s effectiveness can be enhanced by combining each dose of pyridostigmine with 5 mg of midodrine without occurrence of supine hypertension. The patient shoud be eductaed to look out for adverse effects of the drug i.e. abdominal colic, diarrhea. Choline-esterase inhibitors
It improves neurotransmission at acetylcholine-mediated neuronal reflexes of the autonomic nervous system. Because this pathway is activated primarily during standing, this drug improves orthostatic hypotension and total peripheral resistance without aggravating supine hypertension. Since the pressor effect is modest, it is most adequate for patients with mild to moderate orthostatic hypotension. Dosing is started at 30 mg two to three times a day and is gradually increased to 60 mg three times a day. The drug’s effectiveness can be enhanced by combining each dose of pyridostigmine with 5 mg of midodrine without occurrence of supine hypertension. The patient shoud be eductaed to look out for adverse effects of the drug i.e. abdominal colic, diarrhea.

Concise, fact-based medical articles to refresh your knowledge

Access a wealth of content and skim through a smartly presented catalog of diseases and conditions.

  1. AGARWAL A K, GARG R, RITCH A, SARKAR P. Postural orthostatic tachycardia syndrome. Postgraduate Medical Journal [online] 2007 July, 83(981):478-480 [viewed 01 July 2014] Available from: doi:10.1136/pgmj.2006.055046
  2. ARBOGAST STEVEN D., ALSHEKHLEE AMER, HUSSAIN ZULFIQAR, MCNEELEY KEVIN, CHELIMSKY THOMAS C.. Hypotension Unawareness in Profound Orthostatic Hypotension. The American Journal of Medicine [online] 2009 June, 122(6):574-580 [viewed 29 June 2014] Available from: doi:10.1016/j.amjmed.2008.10.040
  3. ASAHINA MASATO, YOUNG TIM M., BLEASDALE-BARR KATHARINE, MATHIAS CHRISTOPHER J.. Differences in overshoot of blood pressure after head-up tilt in two groups with chronic autonomic failure: pure autonomic failure and multiple system atrophy. J Neurol [online] 2005 January, 252(1):72-77 [viewed 06 July 2014] Available from: doi:10.1007/s00415-005-0609-2
  4. AUNG AK, CORCORAN SJ, NAGALINGAM V, PAUL E, NEWNHAM HH. Prevalence, Associations, and Risk Factors for Orthostatic Hypotension in Medical, Surgical, and Trauma Inpatients: An Observational Cohort Study Ochsner J [online] 2012, 12(1):35-41 [viewed 01 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3307503
  5. AXELROD FB. Familial dysautonomia. Muscle Nerve [online] 2004 Mar, 29(3):352-63 [viewed 28 June 2014] Available from: doi:10.1002/mus.10499
  6. AXELROD FB. Familial dysautonomia: a review of the current pharmacological treatments. Expert Opin Pharmacother [online] 2005 Apr, 6(4):561-7 [viewed 28 June 2014] Available from: doi:10.1517/14656566.6.4.561
  7. AXELROD FELICIA B., GOLDBERG JUDITH D., ROLNITZKY LINDA, MULL JAMES, MANN SANDRA P., GOLD VON SIMSON GABRIELLE, BERLIN DENA, SLAUGENHAUPT SUSAN A.. Fludrocortisone in patients with familial dysautonomia. Clin Auton Res [online] 2005 August, 15(4):284-291 [viewed 06 July 2014] Available from: doi:10.1007/s10286-005-0288-1
  8. BRIASOULIS ALEXANDROS, SILVER ADAM, YANO YUICHIRO, BAKRIS GEORGE L.. Orthostatic Hypotension Associated With Baroreceptor Dysfunction: Treatment Approaches. J Clin Hypertens [online] December, 16(2):141-148 [viewed 28 June 2014] Available from: doi:10.1111/jch.12258
  9. CHANDLER MARGARET P., MATHIAS CHRISTOPHER J.. Haemodynamic responses during head-up tilt and tilt reversal in two groups with chronic autonomic failure: pure autonomic failure and multiple system atrophy. [online] 2002 May, 249(5):542-548 [viewed 06 July 2014] Available from: doi:10.1007/s004150200062
  10. CHOBANIAN ARAM V., VOLICER LADISLAV, TIFFT CHARLES P., GAVRAS HARALAMBOS, LIANG CHANG-SENG, FAXON DAVID. Mineralocorticoid-Induced Hypertension in Patients with Orthostatic Hypotension. N Engl J Med [online] 1979 July, 301(2):68-73 [viewed 06 July 2014] Available from: doi:10.1056/NEJM197907123010202
  11. CLAYDON VICTORIA E., KRASSIOUKOV ANDREI V.. Orthostatic Hypotension and Autonomic Pathways after Spinal Cord Injury. Journal of Neurotrauma [online] 2006 December, 23(12):1713-1725 [viewed 01 July 2014] Available from: doi:10.1089/neu.2006.23.1713
  12. CRUZ DINNA N. Midodrine: a selective α-adrenergic agonist for orthostatic hypotension and dialysis hypotension. Expert Opin. Pharmacother. [online] 2000 May, 1(4):835-840 [viewed 06 July 2014] Available from: doi:10.1517/14656566.1.4.835
  13. EGUCHI K, PICKERING T G, ISHIKAWA J, HOSHIDE S, KOMORI T, TOMIZAWA H, SHIMADA K, KARIO K. Severe orthostatic hypotension with diabetic autonomic neuropathy successfully treated with a β1-blocker: a case report. J Hum Hypertens [online] December, 20(10):801-803 [viewed 28 June 2014] Available from: doi:10.1038/sj.jhh.1002066
  14. EIGENBRODT M. L., ROSE K. M., COUPER D. J., ARNETT D. K., SMITH R., JONES D.. Orthostatic Hypotension as a Risk Factor for Stroke : The Atherosclerosis Risk in Communities (ARIC) Study, 1987-1996. Stroke [online] 2000 October, 31(10):2307-2313 [viewed 01 July 2014] Available from: doi:10.1161/​01.STR.31.10.2307
  15. FIGUEROA JJ, BASFORD JR, LOW PA. Preventing and treating orthostatic hypotension: As easy as A, B, C Cleve Clin J Med [online] 2010 May, 77(5):298-306 [viewed 06 July 2014] Available from: doi:10.3949/ccjm.77a.09118
  16. FOUAD-TARAZI FETNAT M., OKABE MASANORI, GOREN HERSHEL. Alpha sympathomimetic treatment of autonomic insufficiency with orthostatic hypotension. The American Journal of Medicine [online] 1995 December, 99(6):604-610 [viewed 06 July 2014] Available from: doi:10.1016/S0002-9343(99)80246-0
  17. FREEMAN R. Treatment of Orthostatic Hypotension. Semin Neurol [online] 2003 December, 23(4):435-442 [viewed 06 July 2014] Available from: doi:10.1055/s-2004-817727
  18. GEHRKING JADE A., HINES STACY M., BENRUD-LARSON LISA M., OPHER-GEHRKING TONETTE L., LOW PHILLIP A.. What is the minimum duration of head-up tilt necessary to detect orthostatic hypotension?. Clin Auton Res [online] 2005 April, 15(2):71-75 [viewed 11 July 2014] Available from: doi:10.1007/s10286-005-0246-y
  19. GIBBONS CH, FREEMAN R. Delayed orthostatic hypotension: a frequent cause of orthostatic intolerance. Neurology [online] 2006 Jul 11, 67(1):28-32 [viewed 11 July 2014] Available from: doi:10.1212/01.wnl.0000223828.28215.0b
  20. GOLD-VON SIMSON GABRIELLE, GOLDBERG JUDITH D, ROLNITZKY LINDA M, MULL JAMES, LEYNE MAIRE, VOUSTIANIOUK ANDREI, SLAUGENHAUPT SUSAN A, AXELROD FELICIA B. Kinetin in Familial Dysautonomia Carriers: Implications for a New Therapeutic Strategy Targeting mRNA Splicing. Pediatr Res [online] 2009 March, 65(3):341-346 [viewed 28 June 2014] Available from: doi:10.1203/PDR.0b013e318194fd52
  21. GUPTA VISHAL, LIPSITZ LEWIS A.. Orthostatic Hypotension in the Elderly: Diagnosis and Treatment. The American Journal of Medicine [online] 2007 October, 120(10):841-847 [viewed 06 July 2014] Available from: doi:10.1016/j.amjmed.2007.02.023
  22. HIERONS R, SHELDON J. Attacks of Orthostatic Hypotension Resembling Focal Epilepsy Associated with Diabetes and Hypoparathyroidism Proc R Soc Med [online] 1956 Jun, 49(6):333-334 [viewed 01 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1888913
  23. HILSTED J, PARVING HH, CHRISTENSEN NJ, BENN J, GALBO H. Hemodynamics in diabetic orthostatic hypotension. J Clin Invest [online] 1981 Dec, 68(6):1427-1434 [viewed 28 June 2014] Available from: doi:10.1172/JCI110394
  24. HILZ M. J., EHMANN E. C., PAULI E., BALTADZHIEVA R., KOEHN J., MOELLER S., DEFINA P., AXELROD F. B.. Combined counter-maneuvers accelerate recovery from orthostatic hypotension in familial dysautonomia. Acta Neurol Scand [online] December, 126(3):162-170 [viewed 06 July 2014] Available from: doi:10.1111/j.1600-0404.2012.01670.x
  25. HOELDTKE ROBERT D., HORVATH GABRIELLA G., BRYNER KIMBERLY D., HOBBS GERALD R.. Treatment of Orthostatic Hypotension with Midodrine and Octreotide . The Journal of Clinical Endocrinology & Metabolism [online] 1998 February, 83(2):339-343 [viewed 06 July 2014] Available from: doi:10.1210/jcem.83.2.4534
  26. HOLLISTER AS. Orthostatic hypotension. Causes, evaluation, and management. West J Med [online] 1992 Dec, 157(6):652-657 [viewed 28 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1022100
  27. HUGHES RC, CARTLIDGE NE, MILLAC P. Primary neurogenic orthostatic hypotension J Neurol Neurosurg Psychiatry [online] 1970 Jun, 33(3):363-371 [viewed 11 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC493480
  28. HUSSAIN RM, MCINTOSH SJ, LAWSON J, KENNY RA. Fludrocortisone in the treatment of hypotensive disorders in the elderly. Heart [online] 1996 Dec, 76(6):507-509 [viewed 06 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC484603
  29. IDIáQUEZ J, KAUFMANN H, SOZA M, NECOCHEA C. [Pure autonomic failure. Bradbury Eggleston Syndrome. Case report]. Rev Med Chil [online] 2005 Feb, 133(2):215-8 [viewed 28 June 2014] Available from: doi:/S0034-98872005000200010
  30. ITOH H, UEBORI S, ASAI M, KASHIWAYA T, ATOH K, MAKINO I. Early detection of orthostatic hypotension by quantitative sudomotor axon reflex test (QSART) in type 2 diabetic patients. Intern Med [online] 2003 Jul, 42(7):560-4 [viewed 01 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/12879946
  31. JANKOVIC JOSEPH, GILDEN JANICE L., HINER BRADLEY C., KAUFMANN HORACIO, BROWN DAVID C., COGHLAN CECIL H., RUBIN MICHAEL, FOUAD-TARAZI FETNAT M.. Neurogenic orthostatic hypotension: A double-blind, placebo-controlled study with midodrine. The American Journal of Medicine [online] 1993 July, 95(1):38-48 [viewed 06 July 2014] Available from: doi:10.1016/0002-9343(93)90230-M
  32. KIRCHHOF K, APOSTOLIDIS AN, MATHIAS CJ, FOWLER CJ. Erectile and urinary dysfunction may be the presenting features in patients with multiple system atrophy: a retrospective study. Int J Impot Res [online] 2003 Aug, 15(4):293-8 [viewed 01 July 2014] Available from: doi:10.1038/sj.ijir.3901014
  33. KONG KENG-HE, CHUO ADELENE M.. Incidence and outcome of orthostatic hypotension in stroke patients undergoing rehabilitation. Archives of Physical Medicine and Rehabilitation [online] 2003 April, 84(4):559-562 [viewed 01 July 2014] Available from: doi:10.1053/apmr.2003.50040
  34. KREDIET C. T. PAUL, GO-SCHöN INGEBORG K., KIM YU-SOK, LINZER MARK, VAN LIESHOUT JOHANNES J., WIELING WOUTER. Management of initial orthostatic hypotension: lower body muscle tensing attenuates the transient arterial blood pressure decrease upon standing from squatting. Clinical Science [online] 2007 November [viewed 29 June 2014] Available from: doi:10.1042/CS20070064
  35. KUJAWA KATHY, LEURGANS SUE, RAMAN REMA, BLASUCCI LUCY, GOETZ CHRISTOPHER G.. Acute Orthostatic Hypotension When Starting Dopamine Agonists in Parkinson's Disease. Arch Neurol [online] 2000 October [viewed 29 June 2014] Available from: doi:10.1001/archneur.57.10.1461
  36. KURAMAE T, INAMASU J, NAKAGAWA Y, NAKATSUKASA M. Spontaneous intracranial hypotension presenting without orthostatic headache complicated by acute subdural hematoma after drainage for chronic subdural hematoma--case report. Neurol Med Chir (Tokyo) [online] 2011, 51(7):518-21 [viewed 29 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/21785248
  37. KöLLENSPERGER MARTIN, GESER FELIX, SEPPI KLAUS, STAMPFER-KOUNTCHEV MICHAELA, SAWIRES MARTIN, SCHERFLER CHRISTOPH, BOESCH SYLVIA, MUELLER JOERG, KOUKOUNI VASILIKI, QUINN NIALL, PELLECCHIA MARIA TERESA, BARONE PAOLO, SCHIMKE NICOLE, DODEL RICHARD, OERTEL WOLFGANG, DUPONT ERIK, ØSTERGAARD KAREN, DANIELS CHRISTINE, DEUSCHL GüNTHER, GUREVICH TANYA, GILADI NIR, COELHO MIGUEL, SAMPAIO CRISTINA, NILSSON CHRISTER, WIDNER HåKAN, SORBO FRANCESCA DEL, ALBANESE ALBERTO, CARDOZO ADRIANA, TOLOSA EDUARDO, ABELE MICHAEL, KLOCKGETHER THOMAS, KAMM CHRISTOPH, GASSER THOMAS, DJALDETTI RUTH, COLOSIMO CARLO, MECO GIUSEPPE, SCHRAG ANETTE, POEWE WERNER, WENNING GREGOR K.. Red flags for multiple system atrophy. Mov Disord. [online] 2008 June, 23(8):1093-1099 [viewed 01 July 2014] Available from: doi:10.1002/mds.21992
  38. LAEDERACH-HOFMANN KURT, WEIDMANN PETER, FERRARI PAOLO. Hypovolemia contributes to the pathogenesis of orthostatic hypotension in patients with diabetes mellitus. The American Journal of Medicine [online] 1999 January, 106(1):50-58 [viewed 28 June 2014] Available from: doi:10.1016/S0002-9343(98)00367-2
  39. LANIER JB, MOTE MB and CLAY EC. Evaluation and Management of Orthostatic Hypotension. Am Fam Physician. [online] 2011 Sep 1;84(5):527-536. [viewed 06 July 2014] Available from: http://www.aafp.org/afp/2011/0901/p527.html
  40. LANIER JB, MOTE MB and CLAY EC. Evaluation and Management of Orthostatic Hypotension. Am Fam Physician. [online] 2011 Sep 1;84(5):527-536. [viewed 29 June 2014] Available at http://www.aafp.org/afp/2011/0901/p527.html
  41. LOW PA, SINGER W. Update on Management of Neurogenic Orthostatic Hypotension Lancet Neurol [online] 2008 May, 7(5):451-458 [viewed 06 July 2014] Available from: doi:10.1016/S1474-4422(08)70088-7
  42. LOW PHILLIP A.. Efficacy of Midodrine vs Placebo in Neurogenic Orthostatic Hypotension. JAMA [online] 1997 April [viewed 06 July 2014] Available from: doi:10.1001/jama.1997.03540370036033
  43. MANO T., IWASE S.. Sympathetic nerve activity in hypotension and orthostatic intolerance. Acta Physiol Scand [online] 2003 March, 177(3):359-365 [viewed 29 June 2014] Available from: doi:10.1046/j.1365-201X.2003.01081.x
  44. MATHIAS C. J., MALLIPEDDI RAJEEV, BLEASDALE-BARR KATHARINE. Symptoms associated with orthostatic hypotension in pure autonomic failure and multiple system atrophy. [online] 1999 October, 246(10):893-898 [viewed 01 July 2014] Available from: doi:10.1007/s004150050479
  45. MAULE SIMONA, PAPOTTI GRAZIA, NASO DIEGO, MAGNINO CORRADO, TESTA ELISA, VEGLIO FRANCO. Cardiovascular & Hematological Disorders-Drug Targets. CHDDT [online] 2007 March, 7(1):63-70 [viewed 06 July 2014] Available from: doi:10.2174/187152907780059029
  46. MEDOW MARVIN S., STEWART JULIAN M., SANYAL SANJUKTA, MUMTAZ ARIF, SICA DOMENIC, FRISHMAN WILLIAM H.. Pathophysiology, Diagnosis, and Treatment of Orthostatic Hypotension and Vasovagal Syncope. Cardiology in Review [online] 2008 January, 16(1):4-20 [viewed 29 June 2014] Available from: doi:10.1097/CRD.0b013e31815c8032
  47. METZLER MANUELA, DUERR SUSANNE, GRANATA ROBERTA, KRISMER FLORIAN, ROBERTSON DAVID, WENNING GREGOR K.. Neurogenic orthostatic hypotension: pathophysiology, evaluation, and management. J Neurol [online] December, 260(9):2212-2219 [viewed 01 July 2014] Available from: doi:10.1007/s00415-012-6736-7
  48. NANDA RN, JOHNSON RH. Orthostatic hypotension associated with paroxysmal ventricular tachycardia. J Neurol Neurosurg Psychiatry [online] 1975 Jul, 38(7):698-702 [viewed 01 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1083250
  49. NASCHITZ J E. The patient with supine hypertension and orthostatic hypotension: a clinical dilemma. Postgraduate Medical Journal [online] 2006 April, 82(966):246-253 [viewed 11 July 2014] Available from: doi:10.1136/pgmj.2005.037457
  50. NASCHITZ JE, ROSNER I. Orthostatic hypotension: framework of the syndrome Postgrad Med J [online] 2007 Sep, 83(983):568-574 [viewed 29 June 2014] Available from: doi:10.1136/pgmj.2007.058198
  51. NOURIAN Z., MOW T., MUFTIC D., BUREK S., PEDERSEN M. L., MATZ J., MULVANY M. J.. Orthostatic hypotensive effect of antipsychotic drugs in Wistar rats by in vivo and in vitro studies of α1-adrenoceptor function. Psychopharmacology [online] December, 199(1):15-27 [viewed 29 June 2014] Available from: doi:10.1007/s00213-007-1064-9
  52. National Guideline Clearinghouse. Ortgostatic hypotension. [web] [viewed 11 July 2014] Available at http://www.guideline.gov/content.aspx?id=34904
  53. PAPATSORIS A.G., PAPAPETROPOULOS S., SINGER C., DELIVELIOTIS C.. Urinary and erectile dysfunction in multiple system atrophy (MSA). Neurourol. Urodyn. [online] December, 27(1):22-27 [viewed 01 July 2014] Available from: doi:10.1002/nau.20461
  54. PASSANT U, WARKENTIN S, GUSTAFSON L. Orthostatic hypotension and low blood pressure in organic dementia: a study of prevalence and related clinical characteristics. Int J Geriatr Psychiatry [online] 1997 Mar, 12(3):395-403 [viewed 29 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/9152727, DOI: 10.1002/(SICI)1099-1166(199703)12:3<395::AID-GPS527>3.0.CO;2-#
  55. REICHGOTT MJ. Clinical Methods: The History, Physical, and Laboratory Examinations. 3rd edition; Chapter 76: Clinical Evidence of Dysautonomia. [web] [viewed 1 July 2014] Available on http://www.ncbi.nlm.nih.gov/books/NBK400/
  56. RILEY TERRENCE L.. Stroke, Orthostatic Hypotension, and Focal Seizures. JAMA [online] 1981 March [viewed 29 June 2014] Available from: doi:10.1001/jama.1981.03310370035020
  57. RILEY TL, FRIEDMAN JM. Stroke, orthostatic hypotension, and focal seizures. JAMA [online] 1981 Mar 27, 245(12):1243-4 [viewed 01 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/6782252
  58. ROBERTSON D, GARLAND EM, PAGON RA, ADAM MP, ARDINGER HH, BIRD TD, DOLAN CR, FONG CT, SMITH RJH, STEPHENS K. Dopamine Beta-Hydroxylase Deficiency [online] 1993 [viewed 28 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/20301647
  59. ROBERTSON D, HAILE V, PERRY SE, ROBERTSON RM, PHILLIPS JA 3RD, BIAGGIONI I. Dopamine beta-hydroxylase deficiency. A genetic disorder of cardiovascular regulation. Hypertension [online] 1991 Jul, 18(1):1-8 [viewed 28 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/1677640
  60. ROBERTSON DAVID. Causes of Chronic Orthostatic Hypotension. Arch Intern Med [online] 1994 July [viewed 29 June 2014] Available from: doi:10.1001/archinte.1994.00420140086011
  61. ROWELL LB, DETRY JM, BLACKMON JR, WYSS C. Importance of the splanchnic vascular bed in human blood pressure regulation. J Appl Physiol [online] 1972 Feb, 32(2):213-20 [viewed 06 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/4550275
  62. SAKAKIBARA R, HATTORI T, UCHIYAMA T, KITA K, ASAHINA M, SUZUKI A, YAMANISHI T. Urinary dysfunction and orthostatic hypotension in multiple system atrophy: which is the more common and earlier manifestation? J Neurol Neurosurg Psychiatry [online] 2000 Jan, 68(1):65-69 [viewed 01 July 2014] Available from: doi:10.1136/jnnp.68.1.65
  63. SCHOFFER KERRIE L., HENDERSON ROBERT D., O'MALEY KAREN, O'SULLIVAN JOHN D.. Nonpharmacological treatment, fludrocortisone, and domperidone for orthostatic hypotension in Parkinson's disease. Mov Disord. [online] December, 22(11):1543-1549 [viewed 06 July 2014] Available from: doi:10.1002/mds.21428
  64. SCHROEDER CHRISTOPH, JORDAN JENS, KAUFMANN HORACIO. Management of Neurogenic Orthostatic Hypotension in Patients with Autonomic Failure. Drugs [online] December, 73(12):1267-1279 [viewed 01 July 2014] Available from: doi:10.1007/s40265-013-0097-0
  65. SCHUTZMAN JOHN, JAEGER FREDRICK, MALONEY JAMES, FOUAD-TARAZI FETNAT. Head-up tilt and hemodynamic changes during orthostatic hypotension in patients with supine hypertension. Journal of the American College of Cardiology [online] 1994 August, 24(2):454-461 [viewed 11 July 2014] Available from: doi:10.1016/0735-1097(94)90303-4
  66. SHI X, WRAY DW, FORMES KJ, WANG HW, HAYES PM, O-YURVATI AH, WEISS MS, REESE IP. Orthostatic hypotension in aging humans. Am J Physiol Heart Circ Physiol [online] 2000 Oct, 279(4):H1548-54 [viewed 01 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/11009440
  67. SHIBAO CYNDYA, LIPSITZ LEWIS ARNOLD, BIAGGIONI ITALO. ASH Position Paper: Evaluation and Treatment of Orthostatic Hypotension. [online] December, 15(3):147-153 [viewed 06 July 2014] Available from: doi:10.1111/jch.12062
  68. SHOHAT M, and HALPREN GJ. GeneReviews®: Familial Dysautonomia [web] [viewed 28 June 2014] Available at http://www.ncbi.nlm.nih.gov/books/NBK1180/
  69. SINGER W. Acetylcholinesterase inhibition: a novel approach in the treatment of neurogenic orthostatic hypotension. Journal of Neurology, Neurosurgery & Psychiatry [online] 2003 September, 74(9):1294-1298 [viewed 06 July 2014] Available from: doi:10.1136/jnnp.74.9.1294
  70. SINGER WOLFGANG, SANDRONI PAOLA, OPFER-GEHRKING TONETTE L., SUAREZ GUILLERMO A., KLEIN CAROLINE M., HINES STACY, O’BRIEN PETER C., SLEZAK JEFFREY, LOW PHILLIP A.. Pyridostigmine Treatment Trial in Neurogenic Orthostatic Hypotension. Arch Neurol [online] 2006 April [viewed 06 July 2014] Available from: doi:10.1001/archneur.63.4.noc50340
  71. SJOSTRAND T. Volume and distribution of blood and their significance in regulating the circulation. Physiol Rev [online] 1953 Apr, 33(2):202-28 [viewed 06 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/13055444
  72. SMIT AA, HALLIWILL JR, LOW PA, WIELING W. Pathophysiological basis of orthostatic hypotension in autonomic failure. J Physiol [online] 1999 Aug 15:1-10 [viewed 29 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/10432334
  73. SMIT ADRIANUSA.J., WIELING WOUTER, FUJIMURA JIRO, DENQ JONGC., OPFER-GEHRKING TONETTEL., AKARRIOU MOHAMMED, KAREMAKER JOHNM., LOW PHILLIPA.. Use of lower abdominal compression to combat orthostatic hypotension in patients with autonomic dysfunction. Clin Auton Res [online] 2004 June [viewed 06 July 2014] Available from: doi:10.1007/s10286-004-0187-x
  74. STEWART JULIAN M., CLARKE DEBBIE. “He’s Dizzy When He Stands Up”: An Introduction to Initial Orthostatic Hypotension. The Journal of Pediatrics [online] 2011 March, 158(3):499-504 [viewed 11 July 2014] Available from: doi:10.1016/j.jpeds.2010.09.004
  75. TIMMERS HJ, DEINUM J, WEVERS RA, LENDERS JW. Congenital dopamine-beta-hydroxylase deficiency in humans. Ann N Y Acad Sci [online] 2004 Jun:520-3 [viewed 28 June 2014] Available from: doi:10.1196/annals.1296.064
  76. TREGER IULY, SHAFIR OLEG, KEREN OFER, RING HAIM. Orthostatic hypotension and cerebral blood flow velocity in the rehabilitation of stroke patients. International Journal of Rehabilitation Research [online] 2006 December, 29(4):339-342 [viewed 01 July 2014] Available from: doi:10.1097/MRR.0b013e328010c87d
  77. TUTAJ M., MARTHOL H., BERLIN D., BROWN C. M., AXELROD F. B., HILZ M. J.. Effect of physical countermaneuvers on orthostatic hypotension in familial dysautonomia. J Neurol [online] December, 253(1):65-72 [viewed 06 July 2014] Available from: doi:10.1007/s00415-005-0928-3
  78. TYKOCKI T, GUZEK K, NAUMAN P. [Orthostatic hypotension and supine hypertension in primary autonomic failure. Pathophysiology, diagnosis and treatment]. Kardiol Pol [online] 2010 Sep, 68(9):1057-63 [viewed 01 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/20859904
  79. VASUDEV AKSHYA, O'BRIEN JOHN T., TAN MAW PIN, PARRY STEVE W., THOMAS ALAN J.. A study of orthostatic hypotension, heart rate variability and baroreflex sensitivity in late-life depression. Journal of Affective Disorders [online] 2011 June, 131(1-3):374-378 [viewed 01 July 2014] Available from: doi:10.1016/j.jad.2010.11.001
  80. VINIK AI, MASER RE, MITCHELL BD, FREEMAN R. Diabetic autonomic neuropathy. Diabetes Care [online] 2003 May, 26(5):1553-79 [viewed 01 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/12716821
  81. WARD CHRISTOPHER, KENNY ROSE ANNE. Reproducibility of orthostatic hypotension in symptomatic elderly. The American Journal of Medicine [online] 1996 April, 100(4):418-422 [viewed 01 July 2014] Available from: doi:10.1016/S0002-9343(97)89517-4
  82. WEISS AVRAHAM, BELOOSESKY YICHAYAOU, KORNOWSKI RAN, YALOV ALEXANDRA, GRINBLAT JOSEPH, GROSSMAN EHUD. Influence of orthostatic hypotension on mortality among patients discharged from an acute geriatric ward. J Gen Intern Med [online] 2006 June, 21(6):602-606 [viewed 29 June 2014] Available from: doi:10.1111/j.1525-1497.2006.00450.x
  83. WEISS AVRAHAM, GROSSMAN EHUD, BELOOSESKY YICHAYAOU, GRINBLAT JOSEPH. Orthostatic Hypotension in Acute Geriatric Ward. Arch Intern Med [online] 2002 November [viewed 29 June 2014] Available from: doi:10.1001/archinte.162.20.2369
  84. WENNING GREGOR KARL, GRANATA ROBERTA, KRISMER FLORIAN, DüRR SUSANNE, SEPPI KLAUS, POEWE WERNER, BLEASDALE-BARR KATHARINE, MATHIAS CHRISTOPHER J.. Orthostatic Hypotension Is Differentially Associated with the Cerebellar Versus the Parkinsonian Variant of Multiple System Atrophy: a Comparative Study. Cerebellum [online] December, 11(1):223-226 [viewed 01 July 2014] Available from: doi:10.1007/s12311-011-0299-5
  85. WIELING WOUTER, KREDIET C. T. PAUL, VAN DIJK NYNKE, LINZER MARK, TSCHAKOVSKY MICHAEL E.. Initial orthostatic hypotension: review of a forgotten condition. Clinical Science [online] 2007 February [viewed 29 June 2014] Available from: doi:10.1042/CS20060091
  86. WU J.-S., YANG Y.-C., LU F.-H., WU C.-H., WANG R.-H., CHANG C.-J.. Population-Based Study on the Prevalence and Risk Factors of Orthostatic Hypotension in Subjects With Pre-Diabetes and Diabetes. Diabetes Care [online] 2009 January, 32(1):69-74 [viewed 11 July 2014] Available from: doi:10.2337/dc08-1389