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 intolerance.

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 1995^2,5 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
There 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 legs—evidence of blood pooling in the lower part of the body.⁶

Testing
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 patient’s blood pressure first while lying down and then while standing.

For CFIDS patients, however, the diagnosis of OI isn’t 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 don’t 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 CFIDS News) and collaborated with CFIDS clinician Dr. David Bell, believed a prolonged standing test is more representative of a patient’s 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.

Inadequate circulation
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.

Researchers 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

Heart rate 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

Treatment
Effective treatment 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 patient’s 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 to NMH.¹³

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 haven’t been tested in CFIDS patients. Intravenous saline can help reduce symp-toms, especially following acute exacerbations.

Research needed
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.

References

1. Low PA, et al. Postural tachycardia syndrome (POTS). Neurology.  1995;45:S19-25.
2. Bou-Holaigah I, et al. The relationship between neurally mediated hypotension and the chronic fatigue syndrome. JAMA. 1995;274:961-7.
3. Freeman R, et al. Does the chronic fatigue syndrome involve the autonomic nervous system? Am J Med. 1997;102:357-64.
4. Stewart JM, et al. Orthostatic intolerance in adolescent chronic fatigue syndrome. Pediatrics. 1999;103:116-21.
5. Rowe PC, et al. Is neurally mediated hypotension an unrecognized cause of chronic fatigue? Lancet. 1995;345:623-4.
6. Stewart JM, et al. Patterns of orthostatic intolerance: the orthostatic tachycardia syndrome and adolescent chronic fatigue. J Pediatr. 1999;135:218-25.
7. Streeten DH, et al. The role of delayed orthostatic hypotension in the pathogenesis of chronic fatigue. Clin Auton Res. 1998;8:119-24.
8. 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.
9. Streeten DH, et al. Circulating blood volume in chronic fatigue syndrome. J CFS. 1998;4:3-11.
10. Stewart JM, et al. Vascular perturbations in the chronic orthostatic intolerance of the postural orthostatic tachycardia syndrome. J Appl Physiol. 2000;89:1505-12.
11. Jacob G, et al. Effects of standing on cerebrovascular resistance in patients with idiopathic orthostatic intolerance. Am J Med. 1999;106:59-64.
12. LaManca JJ, et al. Cardiovascular response during head-up tilt in chronic fatigue syndrome. Clin Physiol. 1999;19:111-20.
13. 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.
14. Calkins H. Pharmacologic approaches to therapy for vasovagal syncope. Am J Cardiol. 1999;84:20Q-25Q.