Diagnosis: Orthostatic Intolerance (OI)
Orthostatic intolerance (OI) is the development of a set of characteristic symptoms while
standing or sitting upright.1 It has been associated with chronic fatigue syndrome (CFS) in both adults and children.2,3,4,5,6,7
The connection between OI and CFS was first introduced in 1995,8 by Peter Rowe, MD, and associates at Johns Hopkins University, who identified a type of OI called neurally mediated hypotension (NMH) in CFS patients. Since 1995, scientists have learned much more about the broader problem of OI in CFS. It is now thought that many CFS patients (up to 97% in some studies) have some form of OI and it seems to be a particular problem in young people with CFS. 7,8,9,10
Dr. Rowe presented a webinar about OI and its management on Sept. 1, 2010 as part of the Association's 2010 Webinar Series. The recording and his slides provide an excellent overview. He has also shared his clinic's written material about OI and medications, postural and dietary complements to comprehensive management of OI.
Types of OI
There are many types of OI, at least two forms have been linked with CFS in research studies: NMH and postural
orthostatic tachycardia syndrome (POTS).
NMH is a precipitous drop (at least 20-25 mm Hg) in systolic blood pressure when standing. The blood pressure drop is accompanied or preceded by an increase in symptoms.2
POTS is a rapid increase in heart rate (pulse) of more than 30 beats per minute (bpm) from baseline, or to more than 120 bpm total, during the first 10 minutes of standing.1
It is also known as chronic orthostatic intolerance, or COI.11
Symptoms of OI
The blood pressure and heart rate changes in NMH and POTS are accompanied by orthostatic symptoms such as lightheadedness, dizziness, nausea, fatigue, tremors, breathing or swallowing difficulties, headache, visual disturbances, sweating and pallor. Many patients develop swollen, bluish legs, providing evidence of blood pooling in the lower part of the body.10 These symptoms can become worse or be provoked more quickly in warm temperatures or hot indoor environments like saunas.
Most doctors are familiar with orthostatic hypotension (OH), which can result in fainting (or syncope,
pronounced "sin-coh-pee") very quickly after standing, and can be diagnosed with a simple in-office test
of taking the blood pressure first while lying down and again upon standing.
Unlike those with OH, which occurs within the first three minutes of standing,12 CFS patients with NMH or POTS often have a delayed form13,14 of orthostatic intolerance, meaning that heart rate and blood pressure changes don't develop for many minutes after standing, making the standard in-office test for acute orthostatic hypotension ineffective in diagnosis. A tilt table test in CFS is considered to be positive if a patient experiences orthostatic symptoms and blood pressure and/or heart rate changes, whether or not he or she faints.2 Patients typically undergo a head-up tilt table test (HUT)15 as an outpatient in a hospital or cardiology office to get a definitive diagnosis. Since the HUT reproduces the symptoms of NMH and POTS, patients often feel worse during and after the test. Some testers administer IV saline following the test to reduce
the occurrence of prolonged symptoms.
Dr. David Streeten, a researcher who studied circulatory problems, and who collaborated with CFS clinician Dr. David S. Bell, favored the use of a prolonged standing test as more representative of a patient's daily symptoms and experiences than the HUT.16 Blood pressure and heart rate are measured every few minutes
while patients lie quietly for 30 minutes and again as they stand quiet and motionless for 60 minutes,
or until severe symptoms develop. It is very important that either this test or the HUT be done under
close medical supervision, as serious complications, including brief periods of very slow heart rate,
can occur during the test.
There are several hypothesized causes of NMH and POTS relevant to CFS; regardless of the cause, all lead to
inadequate blood circulation that may reduce the amount of blood getting back to the heart and brain.
Patients may have low blood volume throughout the body17,18,19 or their blood may pool excessively in the extremities10,11 or both.
When healthy people stand, gravity causes about 750 ml of blood to fall to the abdomen and legs, resulting in a decrease in blood flow to the brain.20 In patients with POTS, cerebral blood flow decreases more prominently while standing.21 In one study of adolescents, the amount of blood that pooled in the legs was highest in CFS patients and second highest in POTS patients, as determined by measuring the circumference of their calves while lying down and again while standing.7
When the heart receives less blood from the limbs during standing, the brain releases chemicals and alters the pulse and blood pressure in an effort to get the blood flowing upwards again. When this chemical response is accentuated, as in NMH and POTS, patients can develop a rapid heart rate (tachycardia), low blood pressure (hypotension) and orthostatic symptoms (see "Types of OI" above). CFS patients can have either NMH or POTS, and some have both conditions.
Researchers have identified several physiological abnormalities in CFS patients that are consistent with autonomic nervous system problems such as NMH and POTS. In five studies, adults and adolescents with CFS had elevated heart rates at rest compared to healthy and sedentary controls,5,7,9,22,23, although two studies found no difference.2,24Heart rate further increased when patients underwent a tilt test, a finding consistent with POTS.5,7,23
In addition, three studies - one in adults5 and two in adolescents11,6 - found that heart rate variability is significantly reduced in CFS compared to controls. This means that instead of having a heart rate that changes appropriately when faced with orthostatic stress, many CFS patients have reduced modulation of their heart rate, suggesting impairment of the autonomic nervous system.11 In contrast, one study of adults with CFS found that heart rate variability is similar to that in controls.25
Effective treatment for NMH and POTS in CFS must be individualized. In general, treatment for POTS and NMH helps
greatly to alleviate some symptoms, but rarely fully resolves the CFS.
The first line of treatment should be non-medical interventions, such as increasing fluids and salt, tilting the head of the bed up a few degrees, wearing compression garments (such as support hose, girdles or abdominal binders), and learning to avoid and cope with things that can make OI worse (such as standing in long lines, being in warm environments and eating large, heavy meals).
If these are not effective, doctors may introduce pharmaceutical treatments
such as fludrocortisone (Florinef) to treat low blood volume, and vasoconstrictor medications, including
methylphenidate (Ritalin), dextroamphetamine (Dexedrine) and midodrine (ProAmatine) to treat blood pooling (Tnderal or Tenormin), and sometimes drugs to block the release or effect of epinephrine and norepinephrine. Selective serotonin reuptake inhibitors (SSRIs) have been used with some success in patients with POTS, and one randomized
trial has demonstrated the efficacy of paroxetine (Paxil) for those with recurrent syncope due to NMH.26
It is unclear whether these medications will work in CFIDS. Intravenous saline can help reduce symptoms, especially following HUT or other acute exacerbations of symptoms. Common syncope treatments beta-blockers and clonidine may be less effective in POTS and may reflect different causes for POTS and simple fainting.
Further research is required to determine how orthostatic intolerance is involved in CFS. It is clear from past
studies that OI is associated with CFS, but the degree and meaning of that association is still a focus of vigorous research, including studies being funded by the CFIDS Association of America.
- Low PA, Opfer-Gehrking TL, Textor SC, et al. Postural
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- Bou-Holaigah I, Rowe PC, Kan J, Calkins H. The relationship
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H, Rowe PC. Relationship Between Chronic Fatigue Syndrome and Neurally Mediated Hypotension. Cardiol Rev.
- Schondorf R, Freeman R. The importance of orthostatic intolerance in the chronic
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- Freeman R, Komaroff AL. Does the chronic fatigue
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- Stewart JM. Autonomic
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- Stewart JM, Gewitz MH, Weldon A, Arlievsky N, Li K, Munoz J. Orthostatic intolerance
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- Rowe PC, Bou-Holaigah I, Kan
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- Stewart J, Weldon A, Arlievsky N, Li K, Munoz J. Neurally mediated hypotension and autonomic dysfunction
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- Stewart JM, Gewitz MH, Weldon A, Munoz J. Patterns of orthostatic
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- Stewart J.M., Weldon A. Vascular perturbations in the chronic orthostatic intolerance of the postural
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- Bannister RH eal. Consensus
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- Jacob G, Atkinson D, Jordan
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- Rowell LB. Human Cardiovascular Control. New York: Oxford; 1993.
- Schondorf R, Benoit J, Wein T, Phaneuf D. Orthostatic intolerance in the chronic fatigue syndrome. J Auton
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- LaManca JJ, Peckerman A, Walker J, et al. Cardiovascular response
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- Alexander ME, Berde
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