By Vicki C. Walker
In addition to
fighting a daily physical battle with fatigue
and other symptoms, persons with chronic fatigue and immune dysfunction syndrome (CFIDS) often find that
they can no longer drive, stand in line at the grocery store or even do their own laundry because of orthostatic
Orthostatic intolerance (OI) is the development of symptoms such as lightheadedness
or dizziness while standing or sitting upright and has been associated with CFIDS in both adults and children.1,2,3,4
The connection between OI and CFIDS was first introduced in 19952,5 by Rowe and associates
at Johns Hopkins University, who identified one form of OI, neurally mediated hypotension (NMH), in 96%
of CFIDS patients tested.
Since 1995, scientists have learned far more about the broader problem
of OI in CFIDS. It is now thought that most CFIDS patients have some form of OI.2,4,6
Types of OI
are many types of OI, but two forms
have been linked with CFIDS 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) above normal, or to more than 120
bpm total, during the first 10 minutes of standing.1
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, profuse sweating and pallor.
Many patients also develop swollen, bluish legsóevidence of blood pooling in the lower part of the body.6
Most doctors are
familiar with orthostatic hypotension
(OH), which can result in fainting (called syncope) very quickly after standing and can be diagnosed with
a simple in-office test of taking the patientís blood pressure first while lying down and then while standing.
CFIDS patients, however, the diagnosis of OI isnít so simple. Unlike individuals with OH, CFIDS patients
with NMH or POTS often have a delayed form7 of orthostatic intolerance, meaning that heart
rate and blood pressure changes donít develop for many minutes after standing. This makes the standard
in-office test for acute orthostatic hypotension ineffective in diagnosis.
CFIDS patients typically
undergo a head-up tilt table test (HUT)2 as an outpatient in a hospital or cardiology office
to get a definitive diagnosis of OI. Unfortunately, the HUT reproduces the symptoms of NMH and POTS, so
patients often feel worse during
and after the test. Some patients benefit from receiving an intravenous
saline infusion following the test to reduce the occurrence of prolonged symptoms.
The late Dr.
David Streeten, a researcher who studied circulatory problems for decades prior to his death (see
and collaborated with CFIDS clinician Dr. David Bell, believed a prolonged standing test is more representative
of a patientís daily symptoms and experiences than the HUT.8 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 both tests
be done under close medical supervision, as serious complications, including periods of very slow heart
rate, can occur during the test.
There are several hypothesized
causes of NMH and POTS relevant to CFIDS; regardless of the cause, both conditions 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 body9 (much like dehydration or hemorrhage) or their blood
may pool excessively in the extremities.6,10
When healthy people stand, gravity causes
blood to fall to the legs and abdomen, resulting in a decrease in blood flow to the brain.11
Patients with OI experience more pooling and reduced brain blood flow than normal while standing. In a
study of adolescents, blood pooling in the legs was greatest in CFIDS patients and second highest in POTS
patients without CFIDS.4
When blood volume is low in the heart (as happens during pooling),
the brain releases chemicals that alter the pulse and blood pressure in an effort to get the blood flowing
upwards again. When this chemical response is exaggerated, as in NMH and POTS, patients can develop low
blood pressure (hypotension), a rapid heart rate (tachycardia) and orthostatic symptoms like dizziness,
confusion and sweating. CFIDS patients can have either NMH or POTS, and many have both conditions.
have identified several abnormalities in CFIDS patients that are consistent with autonomic nervous system
problems such as NMH and POTS. Adults and adolescents with CFIDS have shown elevated heart rates at rest
and during a tilt test compared to healthy and sedentary controls.3,4,12
variability seems to be significantly reduced in CFS compared to controls,5,6,11 resulting
in the inability to modify heart rate appropriately when faced with orthostatic stress. This also suggests
impairment of the autonomic nervous system.10
Inflation of military antishock trousers
(MAST pants) reversed orthostatic symptoms in CFIDS patients after they had been standing several minutes.8
Unfortunately, MAST pants are neither comfortable nor widely accessible, but this study showed the benefit
of compression treatment in CFIDS patients and lends greater support to the theory that POTS in CFIDS
is more often due to pooling problems rather than low blood volume.8
for NMH and POTS in CFIDS
patients must be individualized. Although treatment for both conditions helps to alleviate some symptoms,
it rarely fully resolves the CFIDS.
The first line of treatment should be nonmedical interventions,
such as increased water and salt consumption (up to 10-15 g sodium daily), tilting the head of the patientís
bed up a few degrees and wearing compression garments such as support hose, girdles
or abdominal binders.
It is also important to avoid activities that can make OI worse, such as standing in long lines or in
warm environments; eating large, heavy meals or becom-ing dehydrated.
If these measures do not
improve symptoms, physicians can prescribe drugs to improve low blood volume (usually fludro-cortisone)
and/or help constrict blood vessels and reduce blood pooling (such as methylphenidate, dextroamphetamine
and midodrine). Sometimes drugs to block the release or effects of epinephrine and norepinephrine are
also used. Selective serotonin reuptake inhibitors (SSRIs) have been prescribed for POTS, and one randomized
trial demonstrated the effectiveness of paroxetine
(Paxil) for patients with recurrent syncope due
Randomized trials in patients with recurrent syncope due to NMH have shown
that the cardiac medications atenolol, midodrine and enalapril may help,14 although they havenít
been tested in CFIDS patients. Intravenous saline can help reduce symp-toms, especially following acute
Further research is required to determine how OI contributes
to CFIDS. It is clear from past studies that the two conditions are associated, but the degree and meaning
of that association is still a focus of vigorous research. Hopefully these investigations will soon yield
answers that will help improve the quality of life of many individuals with CFIDS.
- Low PA, et al. Postural tachycardia syndrome (POTS). Neurology.
Bou-Holaigah I, et al. The relationship between neurally mediated
hypotension and the chronic fatigue syndrome. JAMA. 1995;274:961-7.
Freeman R, et al. Does the chronic fatigue syndrome involve the
autonomic nervous system? Am J Med. 1997;102:357-64.
Stewart JM, et al. Orthostatic intolerance in adolescent chronic
fatigue syndrome. Pediatrics. 1999;103:116-21.
Rowe PC, et al. Is neurally mediated hypotension an unrecognized
cause of chronic fatigue? Lancet. 1995;345:623-4.
Stewart JM, et al. Patterns of orthostatic intolerance: the orthostatic
tachycardia syndrome and adolescent chronic fatigue. J Pediatr. 1999;135:218-25.
Streeten DH, et al. The role of delayed orthostatic hypotension
in the pathogenesis of chronic fatigue. Clin Auton Res. 1998;8:119-24.
Streeten DH, et al. The roles of orthostatic hypotension, orthostatic
tachycardia, and subnormal erythrocyte volume in the pathogenesis of the chronic fatigue syndrome. Am
J Med Sci. 2000;320:1-8.
Streeten DH, et al. Circulating blood volume in chronic fatigue
syndrome. J CFS. 1998;4:3-11.
Stewart JM, et al. Vascular perturbations in the chronic orthostatic
intolerance of the postural orthostatic tachycardia syndrome. J Appl Physiol. 2000;89:1505-12.
Jacob G, et al. Effects of standing on cerebrovascular resistance
in patients with idiopathic orthostatic intolerance. Am J Med. 1999;106:59-64.
LaManca JJ, et al. Cardiovascular response during head-up tilt
in chronic fatigue syndrome. Clin Physiol. 1999;19:111-20.
Di Girolamo E, et al. Effects of paroxetine hydrochloride, a selective
serotonin reuptake inhibitor, on refractory vasovagal syncope: a randomized, double-blind, placebo-controlled
study. J Am Coll Cardiol. 1999;33:1227-30.
Calkins H. Pharmacologic approaches to therapy for vasovagal syncope.
Am J Cardiol. 1999;84:20Q-25Q.
Vicki Walker is Research and Public
Policy Project Manager for The
CFIDS Association of America.