Neurally
Mediated Hypotension
Baschetti R. Chronic fatigue syndrome and neurally mediated hypotension [Letter]. Journal of the American Medical Association 1996; 275(5): 359.
Beard TC. Chronic fatigue syndrome and neurally mediated hypotension [Letter]. Journal of the American Medical Association 1996; 275(5): 359.
Bloomfield DM, Elizabeth S. Kaufman ES, Bigger JT, Fleiss J, Rolnitzky L, Steinman R. Passive head-Up tilt and actively standing up produce similar overall changes in autonomic balance. American Heart Journal 1997; 134(2): 316-21.
Summary: The primary objective of this study was to compare, in normal subjects, the average change in autonomic balance during a 5-minute period by using two methods of changing posture: actively standing up and passive head-up tilt. We hypothesized that the average effect of these two methods of changing posture on autonomic balance would not significantly differ. After collecting supine baseline measurements, subjects were first tilted head up to 60 degrees for 15 minutes, then returned to the supine position for 5 minutes, before they stood up for 5 minutes. Comparing the average (over a 5-minute period) autonomic response to head-up tilt with that of standing, there were no significant differences in the decrease in average R-R intervals (-18% vs -18%, p = not significant), the drop in high-frequency power (-73% vs -69%, p = not significant), or the increase in the low-frequency/high-frequency ratio (+252% vs +298%, p = not significant). The changes in autonomic balance that occur during the first 5 minutes of passive 60-degree head-up tilt are nearly identical to the change in autonomic balance that occurs during the first 5 minutes of quiet standing.
Bou-Holaigah I, Calkins H, Flynn JA, Tunin C, Chang HC, Kan JS, Rowe PC. Provocation of hypotension and pain during upright tilt table testing in adults with fibromyalgia. Clinical and Experimental Rheumatology 1997; 15(3): 239-46.
Abstract: OBJECTIVE: Fibromyalgia is a common but poorly understood problem characterized by widespread pain and chronic fatigue. Because chronic fatigue has been associated with neurally mediated hypotension, we examined the prevalence of abnormal responses to upright tilt table testing in 20 patients with fibromyalgia and 20 healthy controls. METHODS: Each subject completed a symptom questionnaire and underwent a three stage upright tilt table test (stage 1:45 minutes at 70 degrees tilt; stage 2, 15 minutes at 70 degrees tilt with isoproterenol 1-2 micrograms/min; stage 3, 10 minutes at 70 degrees tilt with isoproterenol 3-4 micrograms/min). An abnormal response to upright tilt was defined by syncope or presyncope in association with a drop in systolic blood pressure of at least 25 mm Hg and no associated increase in heart rate. RESULTS: During stage 1 of upright tilt, 12 of 20 fibromyalgia patients (60%), but no controls had an abnormal drop in blood pressure (P < 0.001). Among those with fibromyalgia, all 18 who tolerated upright tilt for more than 10 minutes reported worsening or provocation of their typical widespread fibromyalgia pain during stage 1. In contrast, controls were asymptomatic (P < 0.001). CONCLUSION: These results identify a strong association between fibromyalgia and neurally mediated hypotension. Further studies will be needed to determine whether the autonomic response to upright stress plays a primary role in the pathophysiology of pain and other symptoms in fibromyalgia.
Bou-Holaigah I, Rowe PC, Kan J, Calkins H. The relationship between neurally mediated hypotension and the chronic fatigue syndrome. Journal of the American Medical Association 1995; 274(12): 961-7.
Abstract: OBJECTIVE-To compare the clinical symptoms and response evoked by upright tilt-table testing in healthy individuals and in a sample of those satisfying strict criteria for chronic fatigue syndrome. DESIGN-Case-comparison study with mean (SD) follow-up of 24 (5) weeks. SETTING-Tertiary care hospital. PATIENTS AND OTHER PARTICIPANTS-A sample of 23 patients with chronic fatigue syndrome (five men and 18 women; mean age, 34 years), each of whom fulfilled the strict diagnostic criteria of the Centers for Disease Control and Prevention, was recruited from regional chronic fatigue support groups and from the investigators' clinical practices. There were 14 healthy controls (four men and 10 women; mean age, 36 years). INTERVENTIONS-Each subject completed a symptom questionnaire and underwent a three-stage upright tilt-table test (stage 1, 45 minutes at 70 degrees tilt; stage 2, 15 minutes at 70 degrees tilt with 1 to 2 micrograms/min of isoproterenol; and stage 3, 10 minutes at 70 degrees with 3 to 4 micrograms/min of isoproterenol). Patients were offered therapy with fludrocortisone, beta-adrenergic blocking agents, and disopyramide, alone or in combination, directed at neurally mediated hypotension. MAIN OUTCOME MEASURES-Response to upright tilt and scores on symptom questionnaires prior to and during follow-up. RESULTS-An abnormal response to upright tilt was observed in 22 of 23 patients with chronic fatigue syndrome vs four of 14 controls (P < .001). Seventy percent of chronic fatigue syndrome patients, but no controls, had an abnormal response during stage 1 (P < .001). Nine patients reported complete or nearly complete resolution of chronic fatigue syndrome symptoms after therapy directed at neurally mediated hypotension. CONCLUSIONS-We conclude that chronic fatigue syndrome is associated with neurally mediated hypotension and that its symptoms may be improved in a subset of patients by therapy directed at this abnormal cardiovascular reflex.
Calkins H, Kan J, Rowe PC. Chronic fatigue syndrome and neurally mediated hypotension [Letter]. Journal of the American Medical Association 1996; 275(5): 360.
De Lorenzo F, Hargreaves J, Kakkar VV. Pathogenesis and management of delayed orthostatic hypotension in patients with chronic fatigue syndrome. Clinical Autonomic Research 1997; 7(4): 185-90.
Abstract: The relationship between orthostatic hypotension and chronic fatigue syndrome (CFS) has been reported previously. To study the pathogenesis and management of delayed orthostatic hypotension in patients with CFS, a case comparison study with follow-up of 8 weeks has been designed. A group of 78 patients with CFS (mean age 40 years; 49% men and 51% women), who fulfilled the Centre for Disease Control and Prevention criteria were studied. There were 38 healthy controls (mean age 43 years; 47% men and 53% women). At entry to the study each subject underwent an upright tilt-table test, and clinical and laboratory evaluation. Patients with orthostatic hypotension were offered therapy with sodium chloride (1200 mg) in a sustained-release formulation for 3 weeks, prior to resubmission to the tilt-table testing, and clinical and laboratory evaluation. An abnormal response to upright tilt was observed in 22 of 78 patients with CFS. After sodium chloride therapy for 8 weeks, tilt-table testing was repeated on the 22 patients with an abnormal response at baseline. Of these 22 patients, 10 redeveloped orthostatic hypotension, while 11 did not show an abnormal response to the test and reported an improvement of CFS symptoms. However, those CFS patients who again developed an abnormal response to tilt-test had a significantly reduced plasma renin activity (0.79 pmol/ml per h) compared both with healthy controls (1.29 pmol/ml per h) and with those 11 chronic fatigue patients (1.0 pmol/ml per h) who improved after sodium chloride therapy (p = 0.04). In conclusion, in our study CFS patients who did not respond to sodium chloride therapy were found to have low plasma renin activity. In these patients an abnormal renin-angiotensin-aldosterone system could explain the pathogenesis of orthostatic hypotension and the abnormal response to treatment.
De Lorenzo F, Hargreaves J, Kakkar VV. Possible relationship between chronic fatigue and postural tachycardia syndromes. Clinical Autonomic Research 1996; 6: 263-264.
Abstract: Postural tachycardia syndrome refers to the development of symptoms such as light-headedness, visual blurring, palpitations and weakness on assuming an upright posture; these symptoms are relieved by resuming a supine posture. This syndrome is occasionally associated with idiopathic hypovolemia, impaired vasomotor tone, deconditioning and autonomic neuropathy, but has not been reported in association with chronic fatigue syndrome (CFS). We describe five patients who satisfied the CFS criteria of the Centres for Disease Control and Prevention. Upright tilt-table testing induced significant hypotension and increased heart rate in all five patients, consistent with clinical and autonomic manifestation of postural tachycardia syndrome.
De Lorenzo F, Kakkar VV. Twenty-four-hour urine analysis in patients with orthostatic hypotension and chronic fatigue syndrome [Letter]. Australian and New Zealand Journal of Medicine 1996; 26(6): 849-850.
Freeman R, Komaroff AL. Does the chronic fatigue syndrome involve the autonomic nervous system? American Journal of Medicine 1997; 102(4): 357-64.
Abstract: PURPOSE: To investigate the role of the autonomic nervous system in the symptoms of patients with chronic fatigue syndrome (CFS) and delineate the pathogenesis of the orthostatic Intolerance and predisposition to neurally mediated syncope reported in this patient group. PATIENTS AND METHODS: Twenty-three CFS patients and controls performed a battery of autonomic function tests. The CFS patients completed questionnaires pertaining to autonomic and CFS symptoms, their level of physical activity, and premorbid and coexisting psychiatric disorders. The relationship between autonomic test results, cardiovascular deconditioning, and psychiatric disorders was examined with multivariate statistics and the evidence that autonomic changes seen in CFS might be secondary to a postviral, idiopathic autonomic neuropathy was explored. RESULTS: The CFS subjects had a significant increase in baseline (P < 0.01) and maximum heart rate (HR) on standing and tilting (both P < 0.0001). Tests of parasympathetic nervous system function (the expiratory inspiratory ratio, P < 0.005; maximum minus minimum HR difference, P < 0.05), were significantly less in the CFS group as were measures of sympathetic nervous system function (systolic blood pressure decrease with tilting, P < 0.01; diastolic blood pressure decrease with tilting, P < 0.05; and the systolic blood pressure decrease during phase II of a Valsalva maneuver, P < 0.05). Twenty-five percent of CFS subjects had a positive tilt table test. The physical activity index was a significant predictor of autonomic test results (resting, sitting, standing, and tilted HR, P < 0.05 to P < 0.009); and the blood pressure decrease in phase II of the Valvalsa maneuver, P < 0.05) whereas premorbid and coexistent psychiatric conditions were not. The onset of autonomic symptoms occurred within 4 weeks of a viral infection in 46% of patients-a temporal pattern that is consistent with a postviral, idiopathic autonomic neuropathy. CONCLUSION: Patients with CFS show alterations in measures of sympathetic and parasympathetic nervous system function. These results, which provide the physiological basis for the orthostatic intolerance and other symptoms of autonomic function in this patient group, may be explained by cardiovascular deconditioning, a postviral idiopathic autonomic neuropathy, or both.
Klonoff DC. Chronic fatigue syndrome and neurally mediated hypotension [Letter]. Journal of the American Medical Association 1996; 275(5): 359-60.
Landau WM, Nelson DA. Clinical neuromythology XV. Feinting science: neurocardiogenic syncope and collateral vasovagal confusion. Neurology 1996; 46: 609.
Martínez-Lavín M, Hermosillo AG, Mendoza C, Ortiz R, Cajigas JC, Pineda C, Nava A, Vallejo M. Orthostatic sympathetic derangement in subjects with fibromyalgia. Journal of Rheumatology 1997; 24(4): 714-18.
Abstract: OBJECTIVE: To assess the sympathetic-parasympathetic balance in individuals with fibromyalgia (FM), and its response to orthostatic stress, by power spectral analysis of heart rate variability. METHODS: We studied 19 women with FM and 19 age matched controls. A high resolution electrocardiogram was obtained in supine and standing postures after achieving a stable heart rate. Spectral analysis of R-R intervals was done by the fast Fourier transform algorithm. RESULTS: Analyses of the different frequency components revealed significant difference between the 2 groups in the low frequency (0.050-0.150 Hz) band, which reflects modulation of the sympathetic nervous system. Controls displayed an increased power spectral density upon standing (+0.081 ± 0.217 Hz); individuals with FM had a discordant response (-0.057 ± 0.097 Hz) (p = 0.018). CONCLUSION: In FM, there is a deranged sympathetic response to orthostatic stress. This abnormality may have implications regarding the pathogenesis of FM.
Rowe PC, Bou-Holaigah I, Kan JS, Calkins H. Is neurally mediated hypotension an unrecognised cause of chronic fatigue? Lancet 1995; 345: 623-4.
Abstract: Neurally mediated hypotension is now recognised as a common cause of otherwise unexplained recurrent syncope, but has not been reported in association with chronic fatigue. We describe seven consecutive non-syncopal adolescents with chronic post-exertional fatigue, four of whom satisfied strict criteria for chronic fatigue syndrome. Upright tilt-table testing induced significant hypotension in all seven (median systolic blood pressure 65 mm Hg, range 37-75), consistent with the physiology of neurally mediated hypotension. Four had prompt improvement in their chronic fatigue when treated with atenolol or disopyramide. These observations suggest an overlap in the symptoms of chronic fatigue syndrome and neurally mediated hypotension.
Rowe PC, Bou-Holaigah I, Kan JS, Calkins H. Is neurally mediated hypotension an unrecognised cause of chronic fatigue? [Letter]. Lancet 1995; 345: 1113.
Streeten DHP, Anderson GH, Richardson R, Thomas FD. Abnormal orthostatic changes in blood pressure and heart rate in subjects with intact sympathetic nervous function: evidence for excessive venous pooling. Journal of Laboratory and Clinical Medicine 1988; 111: 326-335.
Streeten DHP, Anderson GH, Scullard TF. Excessive gravitational blood pooling caused by impaired venous tone is the predominant non-cardiac mechanism of orthostatic intolerance. Clinical Science 1996; 90: 277-285.
Abstract: 1. In a group of 40 patients with orthostatic intolerance due to hypotension and/or tachycardia, we have compared the pathogenetic roles of impaired contractility of the arterioles and the veins by measuring contractile responsiveness of the arterioles, reflected by increases in diastolic blood pressure and of the veins reflected by measurements of reduction in venous diameter during intravenous noradrenaline infusions. 2. Compared with 27 healthy subjects, patients with diffuse autonomic insufficiency showed striking supersensitivity in diastolic blood pressure (six out of eight) and venous constrictive responses (seven out of eight patients) to noradrenaline, consistent with impaired arteriolar and venous innervation. 3. In contrast, the patients with hyperadrenergic orthostatic hypotension (n = 16) and orthostatic tachycardia (n = 16) showed diastolic blood pressure responses to noradrenaline that were almost invariably within the 95% confidence limits of the changes in normal subjects but supersensitive constrictive responses of foot veins in 22 of 32 subjects and subnormal venous responses in two individuals. The rate of noradrenaline infusion calculated to cause 50% of maximal venous constriction (the ED50) was significantly lower in the patients [mean (SEM) 6.8 (1.9) ng/min] than in the normal subjects [mean (SEM) 23.2 (3.0) ng/min, P < 0.025]. 4. The finding of significantly supersensitive foot vein constrictive responses to noradrenaline infusion in the patients of all three groups and supersensitive blood pressure responses exclusively in the patients with diffuse autonomic insufficiency indicates that venous pooling in the legs was the predominant pathogenetic mechanism of orthostatic intolerance in all three types of patients studied. 5. Correction of the orthostatic hypotension and/or tachycardia by external compression in virtually all patients confirmed this conclusion.
Streeten DHP, Anderson GH. Delayed orthostatic intolerance. Archives of Internal Medicine 1992; 152: 1066-1072.
Abstract: In seven patients who presented with lightheadedness, fatigue, "weakness," and sometimes syncope, blood pressure was found not to fall after standing for 3 to 4 minutes but to fall severely, frequently with syncope or presyncopal symptoms, after 13 to 30 minutes when measured every minute with an automatic device. This delayed orthostatic hypotension could be corrected with inflation of a pressure suit to 45 mm Hg. Its mechanism was further investigated with measurements of plasma catecholamines, plasma cortisol and aldosterone responses to corticotropin, and the effects of norepinephrine infusions on blood pressure and venous contractility. There was normal or excessive orthostatic norepinephrine release in all patients, evidence of impaired venous innervation in the legs in some, and various disorders in the other patients. Since therapeutic improvement in the orthostatic hypotension greatly reduced the symptoms, we concluded that orthostatic hypotension occurring after more than 10 minutes of standing is a potentially debilitating and often correctable disorder.
Streeten DHP, Anderson GH. Is neurally mediated hypotension an unrecognised cause of chronic fatigue? [Letter]. Lancet 1995: 345: 1113.
Walden RJ. Is neurally mediated hypotension an unrecognised cause of chronic fatigue? [Letter]. Lancet 1995; 345: 1112.
Wessely S. Is neurally mediated hypotension an unrecognised cause of chronic fatigue? [Letter]. Lancet 1995; 345: 1112.