ORTHOSTATIC HYPOTENSION

Timothy C. Hain, MD. Page last modified: January 21, 2012

Translations: Belorussion

Orthostasis means upright posture, and hypotension means low blood pressure. Thus, orthostatic hypotension consists of symptoms of dizziness, faintness or lightheadedness which appear only on standing, and which are caused by low blood pressure. Only rarely is spinning vertigo caused by orthostasis.

Symptoms that often accompany orthostatic hypotension include chest pain, trouble holding the urine, impotence, and dry skin from loss of sweating. Fainting (syncope) is covered in another page.

How common is orthostatic hypotension ?

According to Wu et al (2008), symptoms of dizziness provoked by standing ranges from 4.4% (young) to 5.8% (>=70).   Thus orthostatic dizziness is common and much more frequent than dizziness due to inner ear disturbances. 

What Causes Orthostatic Hypotension ?

Blood pressure is maintained by a combination of several things. The heart is the central pump, and a weak or irregular heart can cause orthostatic hypotension. Conditions such as arrhythmia, heart failure, deconditioning, and pregnancy are examples where the heart may not be up to the task of providing an adequate blood pressure.

The heart pumps blood, and if there is too little blood volume (anemia, dehydration, dialysis), the pressure drops. The blood vessels in the body also can squeeze (constrict) to raise blood pressure, and if this action is paralyzed, blood pressure may fall. Numerous medications affect blood vessels including most of the medications used for blood pressure, and many of the medications used in psychiatry and for anginal heart pain. Heat, such as a hot shower or from a fever can also dilate blood vessels and cause orthostasis. The nervous system senses and responds to regulate blood pressure. If something is wrong in this control system, blood pressure may fluctuate.

Blood pressure is usually lowered (in persons with orthostasis) by upright posture, food, infection, hyperventilation, hot weather, and lifting of heavy objects. General anesthesia may be unusually dangerous due to blood pressure fluctuations (Bevan et al, 1979).

Vestibular disorders may interact with blood pressure and heart rate control. The vestibular system is one source of information about uprightness (the otoliths), there are some effects of vestibular stimulation on the heart (Radtke, 1992), and there are some patients who have a combination of autonomic and vestibular symptoms.

Neurological disorders can also be caused by orthostasis. This usually takes the form of a transient ischemic attack (TIA) precipitated by a blood pressure drop (Brozman et al, 2002).

Diagnosis of Orthostatic Hypotension

Syndromes with orthostatic dizziness or lightheadedness, not associated with low blood pressure include:

1. Positional orthostatic tachycardia (POT) syndrome. Here, the pulse races on standing. See below for more information.
2. Low CSF pressure syndrome
3. Primary orthostatic tremor
4. Positional vertigo (i.e. BPPV)

Syndromes with orthostatic hypotension that may be diagnosed include:

1. Cardiogenic (heart related) orthostatic hypotension. In this instance the heart doesn't respond adequately to demands for greater pumping and blood pressure drops. Conditions such as arrhythmia, heart failure, deconditioning, and pregnancy are examples.
2. Low blood volume (e.g. anemia, dehydration, dialysis)
3. Medication related (usually too high doses of blood pressure medications or medications for depression)
4. Primary adrenal insufficiency. Persons with primary adrenal insufficiency usually also have symptoms of glucocorticoid (cortisone) deficiency. The skin may be dark, serum potassium high, and there may be associated hypothyroidism, diabetes, and vitiligo (Salvatori, 2005).
5. Neurogenic orthostatic hypotension
   1. Sensory neuropathies (diabetes, alcohol, syphilis, Holmes-Adie syndrome, carotid sinus obliteration by endarterectomy, Riley-Day syndrome)
   2. Central types:
      1. MSA - multiple system atrophy or Shy-Drager, Parkinson's, dementia with Lewy bodies. Orthostatic hypotension is nearly universal in MSA, present in about 50% of patients with dementia with Lewy bodies (Akaogi et al, 2009), and in 5-50% of patients with Parkinson's. (Thaisetthawatkul et al, 2004; Akaogi et al, 2009). However, since Parkinsonism is by far the most common disorder, there may be as many patients with orthostatic hypotension and Parkinson's disease as any of the former. Patients with MSA have intact sympathetic noradrenergic innervation.
      2. Medullary strokes or injuries (rare)
      3. Wernickes syndrome (rare, related to thiamine deficiency)
   3. Output types:
   1. Peripheral neuropathy, especially diabetes and amyloidosis
   2. Spinal cord lesions
   3. PAF - pure autonomic failure or idiopathic orthostatic hypotension. These patients have loss of cardiac sympathetic neurons, and in particular have loss of sympathetic noradrenergic innervation.
   4. Parkinson's disease (post-ganglionic sympathetic denervation). These patients also have loss of cardiac sympathetic neurons.
   5. Dopamine beta-hydroxylase deficiency (hereditary, very rare -- has very high serum dopamine, often ptosis (droopy eyes) and hyperextensible joints. Prolactin may be high)
6. Unknown type
   1. Orthostatic intolerance in chronic fatigue syndrome (this mainly seems to be a syndrome of adolescents)
   2. Orthostatic intolerance associated with basilar migraine
   3. Delayed orthostatic hypotension. Possibly due to fatigue of autonomic system over 3-20 minutes.

The diagnosis of orthostasis is made by finding that the systolic/diastolic blood pressure drops at least 25/10 mm mercury on going from lying to standing. After measuring the supine blood pressure, it is recommended that one should have the subject stand for 2 minutes (if tolerated) before measuring the upright blood pressure (Tarazi and Fouad, 1983).

Tilt table used at Chicago Dizziness and Hearing

An alternative and more quantitative method of determining if there is orthostatic hypotension is the tilt table test. This procedure uses equipment to record blood pressure and pulse after a 70 degree tilt using a motorized table.

Recently it has been point out that subjects who are stood for longer periods of time may exhibit progressive decline in blood pressure (Gibbons and Freeman, 2006). Delayed orthostatic hypotension (DOH ?) is defined as a greater than 20 mm Hg fall after 3 minutes or more of tilt-table or active standing. This seems to take a rather long time -- many (39%) subjects were positive only after 10 minutes of standing or tilt. A tilt (or stand) of 20 minutes was recommended by these authors for diagnosis.

The pulse (heart rate) should be checked also. The lack of a pulse response increase when the blood pressure drops implies a neurological cause.

An excessive pulse response is termed "POTS" or positional orthostatic tachycardia syndrome. POTS can be associated with considerable disability (Benrud-Larson et al, 2002). Note that pulse can increase due to anxiety and deconditioning as well as autonomic disorders and considerable caution must be used in making this diagnosis. http://cogprints.org/4802/2/raj.pdf is an external web page written for health-care providers concerning this condition.

Once an orthostatic syndrome is determined, additional tests are used to determine why the blood pressure isn't properly regulated.

Laboratory TESTS for orthostatic hyptension

Not every test is needed in every situation. More tests may be recommended based on the results of the previous tests. Tilt table tests are not needed in orthostatic hypotension, as the problem has already been idenfied, but may be indicated in persons with fainting (syncope) or simply an undiagnosed orthostatic syndrome.

CASE EXAMPLE:

A 57 year old man presented complaining of lightheadness on standing and a pressure sensation in the back of his neck (on standing). Other medical problems included a low thyroid. Blood pressure was 90/65 standing vs 130/80 supine (on medication). This documents a significant orthostatic hypotension. A sweat test showed about 50% anhidrosis. Norepinephrine level was about 30 units lower supine than upright. He was diagnosed as having neurogenic orthostatic hypotension. Present treatment includes Proamatine (mitodrine) 10 mg TID, salt supplements, and erythropoetin.

TREATMENT

Note that neither drug nor non-drug treatment can do as good a job as a  well working body. All of the strategies outlined in the next section are intended to alleviate symptoms, but they are unlikely to cure orthostatic hypotension.

Non-Drug Treatment for Orthostatic Hypotension

    Generally it is best to start with non-pharmacological treatment, and proceed to drug treatment only when this fails. Note that measures such as voloume expansion with increased salt and fluid, moderate exercise and tilt training are relatively safe but their effectiveness has not been demonstrated by controlled trials (Kapoor, 2003). Nevertheless, we think it is reasonable to give these things a try.

1. Use an automatic blood pressure cuff (about $30 at Walgreens or Radio Shack). Check blood pressure and pulse daily, preferably standing and lying flat, and record it. Also check blood pressure when you have symptoms.
2. If possible, eliminate medications that lower blood pressure (usually blood-pressure or heart medications). Check with your doctor first, however, to be sure that this is safe. Sometimes it is helpful to take the blood pressure medications in the evening, as well as to use longer acting ones rather than ones that act quickly.
3. Take in extra amounts of salt - about 10 gm/day total. Another way to get extra salt is to use salt containing beverages (e.g. "gatorade"). If you start to have trouble breathing or get excessive swelling at the ankles, you may have to use less than 10 gm. Similarly, be careful not to overdo it and end up with hypertension.
4. Wear Jobst stockings (tight custom made leotard like garment -- worn by both men and women). These are often not well tolerated, especially in the summer.
5. Sleep with head of bed elevated about 15-20 degrees (4-6 inches). This maneuver increases blood volume and, after a few days, is helpful.  It is also helpful in that it may reduce supine hypertension( sometimes blood pressure is too high lying flat, and too low standing up). Try to be up during the day, not lying in bed. Reconditioning may be helpful for persons who have been on bed rest for long periods of time.
6. Eat frequent small meals (because eating lowers blood pressure). Avoid sudden standing after eating.
7. Avoid straining at stool (because this may lower the blood pressure)
8. Avoid hot showers or excessive heat. Use air conditioners.
9. Get up gradually in the morning. Take 5 minutes to get up and use support. Perform isometric exercises before moving about.
10. Water injestion - -drinking 16 oz of water over 5 minutes can prevent a fainting spell (Lu et al, 2003).. This should not be done very often as it could lead to water intoxication.
11. Orthostatic training. Under the supervision of a physical therapist, gradually increased upright stance. Also use physical countermeasures (see page on tilt training). The literature suggests that this is very effective.

Tilt-training, a series of prescribed upright posture exercises may be helpful in vasovagal faints as well as orthostatic faints. Tilt training also includes some effective physical countermeasures such as leg-crossing with lower body tensing, squating, and arm-tensing (Benditt and Nguyen, 2009)

Certain medications may be helpful, usually as a combination. Most useful drugs are Florinef (fludrocortisone), erythropoetin and Midodrine.

• Two strong cups of coffee in the morning
• Fludrocortisone (Florinef) forces more salt into the bloodstream, 0.1 mg daily starting dose. Blood pressure raises gradually over several days with maximum effect at 1-2 weeks. Alter doses at weekly or biweekly intervals. Hypokalemia (low potassium) occurs in 50%, and hypomagnesemia in 5%. These may need to be corrected with supplements. Florinef should not be used in persons with CHF (congestive heart failure). Florinef does not work in the orthostatic intolerance syndrome of chronic fatigue syndrome (Rowe et al, 2001). Headache is a common side effect.
• Effexor (an antidepressant which raises blood pressure as a side effect).
• Inderal and other beta-blockers (small doses are used for positional-orthostatic-tachycardia syndrome (POTS), start inderal at 10 mg/d, increase to 30-60 mg/d over 2-3 weeks. Other useful agents are Nadolol (10 mg qd), Pindolol (2.5-5 mg 2-3 times/day) and atenolol (25). Several controlled trials did not show these agents to be effective in preventing syncope (Kapoor, 2003)
• Motrin or Indocin (blocks blood-pressure lowering effects of prostaglandins).
• Midodrine. An alpha-1 adrenergic agonist. Causes increased blood pressure, vasoconstriction, pupil dilation, and "hair standing on end". Other common side effects are paresthesia of the scalp or itching. Usual doses are 2.5 mg at breakfast and lunch or three times daily. Doses are increased quickly until a response occurs or a dose of 30 mg/day is attained (Wright et al, 1998). Midodrine levels peak at about 1-2 hours after administration, and have a half-life of about 3-4 hours. Midodrine does not cross the blood-brain barrier and it is thus not associated with CNS effects. In theory, Midodrine might work for the orthostatic hypotension of MSA (or Shy-Drager), but not that of Parkinsonism. Most patients on Midodrine also take Florinef (see above). Midodrine has been shown to be helpful in controlled trials (Kapoor, 2003).
• Erythropoietin. This agent is used if there is also anemia and other measures have failed. Doses of 25 to 75 U/kg TIW are used, by injection.
• Methylphenidate 5-10 mg orally 3 times/day given with meals. An amphetamine -- side effects may include agitation, tremor, insomnia, supine hypertension.
• Ephedrine 12.5-25 mg orally three times/day. Side effects may include tachycardia, tremor and supine hypertension.
• Fluoxetine 10-20 mg daily. Side effects may include nausea and anorexia. Paroxetine (Paxil) has also been shown to reduce syncope at 2 years.
• Phenobarbital may improve POTS.
• Desmopressin. This analog of vasopressin is used as a nasal spray. Low blood sodium is a possible side effect.

OTHER TREATMENTS:

Atrial pacing can be considered when the heart rate is very low. Pacing has been reported not helpful in treatment of recurrent vasovagal syncope by Connolly (2003) but is reported helpful by others (Wohrle and Kochs, 2003). We think it is best to be conservative and skeptical in situations where implantable devices are studied due to the impossibilty of obtaining placebo controls. Pacemakers may be effective in carotid sinus syndrome (a cause of syncope, not orthostatic hypotension).

3,4 Dl-threo-dihydroxyphenylserine (DOPS), an artificial amino-acid, may be helpful in certain situations (Freeman, 1996) including dopamine beta-hydroxylase deficiency and post-prandial hypotension from various etiologies. L-DOPS is a precurser of norepinephrine and epinephrine. L-DOPs has also been used on an investigational basis (Gibbons et al) in persons refractory to other drugs. It is also available in asian countries, and is sold under the brand name of Droxidopa. L-DOPS can be combined with a peripheral dopamine decarboxylase inhibitor such as carbidopa (Lodosyn) to increase levels of the drug within the CNS. L-DOPS, in doses up to 600 mg TID, is presently undergoing research trials to determine if it is effective. It is difficult for us to see how this medication differs substantially from other adrenergic agonists such as mitodrine or ephedrine.

REFERENCES:

• Akaogi, Y., M. Asahina, et al. (2009). "Sudomotor, skin vasomotor, and cardiovascular reflexes in 3 clinical forms of Lewy body disease." Neurology 73(1): 59-65.
• Benarroch EE, Schmeichel AM, Parisi JE. Involvement of the ventrolateral medulla in parkinsonism with autonomic failure. Neurology 2000:54:963-968
• Benditt DG, Nguyen JT. Syncope Therapeutic approaches. Journal of the American College of Cardiology, 53(19), 2009, 1741-1751
• Benrud-Larson L and others. Quality of life in patients with postural tachycardia syndrome. Mayo Clin Proc 2002:77:531-37
• Bevan, D. R. (1979). "Shy-Drager syndrome. A review and a description of the anaesthetic management." Anaesthesia 34(9): 866-73.
• Brozman B and others (2002). Postural vertigo and impaired vasoreflexes caused by a posterior inferior cerebellar artery infarct. Neurology, 59, 9, 1499-1500
• Connolly S and others. Pacemaker therapy for prevention of syncope in patients with recurrent severe vasovagal syncope. Jama 2003:289:2224-2229
• Freeman R, Young J, Landsberg L, Lipsitz L. The treatment of postprandial hypotension in autonomic failure with 3,4-Dl-threo-dihydroxyphenylserine. Neurology 1996;47:1414-1420
• Gibbons, C. H., S. A. Vernino, H. Kaufmann, et al. (2005). "L-DOPS therapy for refractory orthostatic hypotension in autoimmune autonomic neuropathy." Neurology65(7): 1104-6.
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• Goldstein DS et al. Orthostatic hypotension from sympathetic denervation in Parkinson's disease. Neurology 2002:58:1247-55
• Goldstein DS and others. Plasma levels of catechols and metanephrines in neurogenic orthostatic hypotension. Neurology 2003,60:1327-1332
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• LaMaca et al. Cardiovascular response during head-up tilt in chronic fatigue syndrome. Clin Physiol 1999:19:111-120
• Poole J and others. Results of isoproterenol tilt table testing in monozygotic twins discordant for chronic fatigue syndrome. Arch Intern Med 2000:160:3461-3468
• Radke A, et. al. Evidence for a vestibulo-cardiac reflex in man. The Lancet (356), 736-7
• Wright RA and others. A double-blind, dose-response study of midodrine in neurogenic orthostatic hypotension. Neurology 1998, 51:120-124
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• Soma, R., D. Nozaki, S. Kwak, et al. (2003). "1/f noise outperforms white noise in sensitizing baroreflex function in the human brain." Phys Rev Lett91(7): 078101.
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• Wohrle, J. and M. Kochs (2003). "Syncope in the elderly." Z Gerontol Geriatr 36(1): 2-9.
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Related Web pages

• www.dynakids.org
• NINDS orthostatic hypotension information page (National Institute of Health)
• http://www.dinet.org/what_helps.htm
• http://cogprints.org/4802/2/raj.pdf -- this is a review article written for health care providers on POTS

Relevant Books

• Orthostatic Disorders of the Circulation: Mechanisms, Manifestations, and Treatment by David H.P. Streeten
• Circulatory Response to the Upright Posture by James J. Smith (Editor)
• Clinical Autonomic Disorders: Evaluation and Management by Phillip A. Low (Editor)