Tag: neurally mediated hypotension

Home orthostatic training in chronic fatigue syndrome–a randomized, placebo-controlled feasibility study

Abstract:

BACKGROUND: Orthostatic (Tilt)-training is an effective treatment for neurally mediated hypotension (NMH). NMH is a frequent finding in chronic fatigue syndrome (CFS). We evaluated home orthostatic training (HOT) in CFS in a randomized placebo-controlled feasibility study.

METHODS: Thirty-eight patients with CFS (Fukuda Criteria) were randomly allocated to daily tilt training (n = 19) or sham training (n = 19) for 6 months. Haemodynamic responses to standing were performed in all subjects using continuous technology (Taskforce) at enrolment, week 1, 4 and 24. Symptom response and compliance were assessed using diaries.

RESULTS: Two patients (one from each arm) withdrew from the study. Fourteen patients in each group complied completely or partially, and patients found the training manageable and achievable. Compared to the sham group, blood pressure while standing dropped to 8.0 mmHg less in the HOT group at 4 weeks (95% CI: 1.0 to 15.0, P = 0.03). At 4 weeks, the HOT group had higher total peripheral resistance compared to the sham group; mean difference 70.2, 95% CI: -371.4 to 511.8. Changes were maintained at 6 months. There was no significant difference in fatigue between groups at 4 weeks (mean difference 1.4, 95% CI: -13.5 to 16.2), but there was a trend towards improvement in fatigue at 6 months. Compliers had lower fatigue compared to non-compliers.

CONCLUSIONS: A placebo-controlled study of HOT in CFS is feasible. HOT is well tolerated and generally complied with. A likely physiological rationale for HOT in CFS is related to reductions in orthostatic intolerance. An adequately powered study including strategies to enhance compliance is warranted.

 

Source: Sutcliffe K, Gray J, Tan MP, Pairman J, Wilton K, Parry SW, Newton JL. Home orthostatic training in chronic fatigue syndrome–a randomized, placebo-controlled feasibility study. Eur J Clin Invest. 2010 Jan;40(1):18-24. doi: 10.1111/j.1365-2362.2009.02225.x. Epub 2009 Nov 12. https://www.ncbi.nlm.nih.gov/pubmed/19912315

 

A matched case control study of orthostatic intolerance in children/adolescents with chronic fatigue syndrome

Abstract:

This study aimed to define cardiovascular and heart rate variability (HRV) changes following head-up tilt (HUT) in children/adolescents with chronic fatigue syndrome (CFS) in comparison to age- and gender-matched controls.

Twenty-six children/adolescents with CFS (11-19 y) and controls underwent 70-degree HUT for a maximum of 30 min, but returned to horizontal earlier at the participant’s request with symptoms of orthostatic intolerance (OI) that included lightheadedness.

Using electrocardiography and beat-beat finger blood pressure, a positive tilt was defined as OI with 1) neurally mediated hypotension (NMH); bradycardia (HR <75% of baseline), and hypotension [systolic pressure (SysP) drops >25 mm Hg)] or 2) postural orthostatic tachycardia syndrome (POTS); HR increase >30 bpm, or HR >120 bpm (with/without hypotension).

Thirteen CFS and five controls exhibited OI generating a sensitivity and specificity for HUT of 50.0% and 80.8%, respectively. POTS without hypotension occurred in seven CFS subjects but no controls. POTS with hypotension and NMH occurred in both. Predominant sympathetic components to HRV on HUT were measured in CFS tilt-positive subjects.

In conclusion, CFS subjects were more susceptible to OI than controls, the cardiovascular response predominantly manifest as POTS without hypotension, a response unique to CFS suggesting further investigation is warranted with respect to the pathophysiologic mechanisms involved.

 

Source: Galland BC, Jackson PM, Sayers RM, Taylor BJ. A matched case control study of orthostatic intolerance in children/adolescents with chronic fatigue syndrome. Pediatr Res. 2008 Feb;63(2):196-202. https://www.ncbi.nlm.nih.gov/pubmed/18091356

 

Fludrocortisone acetate to treat neurally mediated hypotension in chronic fatigue syndrome: a randomized controlled trial

Abstract:

CONTEXT: Patients with chronic fatigue syndrome (CFS) are more likely than healthy persons to develop neurally mediated hypotension (NMH) in response to prolonged orthostatic stress.

OBJECTIVE: To examine the efficacy of fludrocortisone acetate as monotherapy for adults with both CFS and NMH.

DESIGN: Randomized, double-blind, placebo-controlled trial conducted between March 1996 and February 1999.

SETTING: Two tertiary referral centers in the United States.

PATIENTS: One hundred individuals aged 18 to 50 years who satisfied Centers for Disease Control and Prevention criteria for CFS and had NMH provoked during a 2-stage tilt-table test. Eighty-three subjects had adequate outcome data to assess efficacy.

INTERVENTION: Subjects were randomly assigned to receive fludrocortisone acetate, titrated to 0.1 mg/d (n = 50) or matching placebo (n = 50) for 9 weeks, followed by 2 weeks of observation after discontinuation of therapy.

MAIN OUTCOME MEASURE: Proportion of subjects in each group with at least a 15-point improvement on a 100-point global wellness scale.

RESULTS: Baseline demographic and illness characteristics between the groups were similar; CFS had been present for at least 3 years in 71%. Using an intention-to-treat analysis, 7 subjects (14%) treated with fludrocortisone experienced at least a 15-point improvement in their wellness scores compared with 5 (10%) among placebo recipients (P =.76). No differences were observed in several other symptom scores or in the proportion with normal follow-up tilt test results at the end of the treatment period.

CONCLUSIONS: In our study of adults with CFS, fludrocortisone as monotherapy for NMH was no more efficacious than placebo for amelioration of symptoms. Failure to identify symptomatic improvement with fludrocortisone does not disprove the hypothesis that NMH could be contributing to some of the symptoms of CFS. Further studies are needed to determine whether other medications or combination therapy are more effective in treating orthostatic intolerance in patients with CFS.

Comment in:

Orthostatic hypotension and chronic fatigue syndrome. [JAMA. 2001]

Orthostatic hypotension and chronic fatigue syndrome. [JAMA. 2001]

Orthostatic hypotension and chronic fatigue syndrome. [JAMA. 2001]

 

Source: Rowe PC, Calkins H, DeBusk K, McKenzie R, Anand R, Sharma G, Cuccherini BA, Soto N, Hohman P, Snader S, Lucas KE, Wolff M, Straus SE. Fludrocortisone acetate to treat neurally mediated hypotension in chronic fatigue syndrome: a randomized controlled trial. JAMA. 2001 Jan 3;285(1):52-9. http://www.ncbi.nlm.nih.gov/pubmed/11150109

 

Results of isoproterenol tilt table testing in monozygotic twins discordant for chronic fatigue syndrome

Abstract:

BACKGROUND: The pathogenesis of chronic fatigue syndrome (CFS) is unknown. Neurally mediated hypotension (NMH) has been suggested as a common comorbid condition or a potential underlying cause.

METHODS: We conducted a cotwin control study of 21 monozygotic twins who were discordant for CFS. One twin met the 1994 Centers for Disease Control and Prevention criteria for CFS, and the other twin was healthy and denied chronic fatigue. The twins were selected from a volunteer twin registry in which at least 1 member reported persistent fatigue. As part of a 7-day clinical evaluation, all 21 twin pairs were evaluated with a 3-stage tilt table test with isoproterenol hydrochloride for the assessment of NMH. The presence of NMH was defined as syncope or presyncope associated with a decrease of 25 mm Hg in blood pressure and no associated increase in heart rate.

RESULTS: A positive tilt table test result was observed in 4 twins with CFS (19%) and in 4 healthy twins (19%). This difference was not statistically significant (matched pair odds ratio, 1.0; 95% confidence interval, 0.2-5.4; P>.90). Compared with the healthy twins, the twins with CFS reported more severe symptoms of CFS and NMH both in the week before and during the tilt table test.

CONCLUSIONS: These results do not support a major role for NMH in CFS. They highlight the importance of selecting well-matched control subjects, as well as the unique value of the monozygotic cotwin control design in the study of this illness. Arch Intern Med. 2000;160:3461-3468.

 

Source: Poole J, Herrell R, Ashton S, Goldberg J, Buchwald D. Results of isoproterenol tilt table testing in monozygotic twins discordant for chronic fatigue syndrome. Arch Intern Med. 2000 Dec 11-25;160(22):3461-8. http://www.ncbi.nlm.nih.gov/pubmed/11112240

 

Neurally mediated hypotension in fatigued Gulf War veterans: a preliminary report

Abstract:

BACKGROUND: Many patients with chronic fatigue syndrome (CFS) have neurally mediated hypotension when subjected to head-up tilt, suggesting autonomic nervous system dysfunction. Some Gulf War veterans have symptoms similar to CFS. Whether they also tend to have neurally mediated hypotension is unknown.

METHODS: We performed 3-stage tilt-table testing on 14 Gulf War veterans with chronic fatigue, 13 unfatigued control Gulf War veterans, and 14 unfatigued control subjects who did not serve in the Gulf War. Isoproterenol was used in stages 2 and 3 of the tilt protocol.

RESULTS: More fatigued Gulf War veterans than unfatigued control subjects had hypotensive responses to tilt (P < 0.036). A positive response to the drug-free stage 1 of the tilt was observed in 4 of 14 fatigued Gulf War veterans versus 1 of 27 unfatigued control subjects (P < 0.012). Heart rate and heart rate variation during stage 1 was significantly greater in the fatigued group (P < 0.05).

CONCLUSION: We conclude that more fatigued Gulf War veterans have neurally mediated hypotension than unfatigued control subjects, similar to observations in CFS. Autonomic nervous system dysfunction may be present in some fatigued Gulf War veterans.

 

Source: Davis SD, Kator SF, Wonnett JA, Pappas BL, Sall JL. Neurally mediated hypotension in fatigued Gulf War veterans: a preliminary report. Am J Med Sci. 2000 Feb;319(2):89-95. http://www.ncbi.nlm.nih.gov/pubmed/10698092

 

Syncope: etiology, management, and when to refer

Abstract:

An abnormality of blood pressure control is by far the most likely cause of syncope in children; however, syncope in children may be due to primary cardiac dysrhythmias, particularly in the presence of structural heart disease. An appropriate work-up should include an ECG with a 60-second rhythm strip at first presentation. Tilt testing can usually wait until after a second occurrence on non-pharmacologic therapy. Patients who require more than a history and ECG by the algorithm in the Figure should probably be referred to a cardiologist familiar with the evaluation of syncope. The common form of neurally mediated syncope is also probably related to both breath-holding spells in toddlers, and to many of the cases of chronic fatigue syndrome.

 

Source: Saul JP. Syncope: etiology, management, and when to refer. J S C Med Assoc. 1999 Oct;95(10):385-7. http://www.ncbi.nlm.nih.gov/pubmed/10550969

 

Orthostatic intolerance and chronic fatigue syndrome associated with Ehlers-Danlos syndrome

Abstract:

OBJECTIVE: To report chronic fatigue syndrome (CFS) associated with both Ehlers-Danlos syndrome (EDS) and orthostatic intolerance.

STUDY DESIGN: Case series of adolescents referred to a tertiary clinic for the evaluation of CFS. All subjects had 2-dimensional echocardiography, tests of orthostatic tolerance, and examinations by both a geneticist and an ophthalmologist.

RESULTS: Twelve patients (11 female), median age 15.5 years, met diagnostic criteria for CFS and EDS, and all had either postural tachycardia or neurally mediated hypotension in response to orthostatic stress. Six had classical-type EDS and 6 had hypermobile-type EDS.

CONCLUSIONS: Among patients with CFS and orthostatic intolerance, a subset also has EDS. We propose that the occurrence of these syndromes together can be attributed to the abnormal connective tissue in dependent blood vessels of those with EDS, which permits veins to distend excessively in response to ordinary hydrostatic pressures. This in turn leads to increased venous pooling and its hemodynamic and symptomatic consequences. These observations suggest that a careful search for hypermobility and connective tissue abnormalities should be part of the evaluation of patients with CFS and orthostatic intolerance syndromes.

 

Source: Rowe PC, Barron DF, Calkins H, Maumenee IH, Tong PY, Geraghty MT. Orthostatic intolerance and chronic fatigue syndrome associated with Ehlers-Danlos syndrome. J Pediatr. 1999 Oct;135(4):494-9. http://www.ncbi.nlm.nih.gov/pubmed/10518084

 

Relationship Between Chronic Fatigue Syndrome and Neurally Mediated Hypotension

Abstract:

Chronic fatigue syndrome is a chronic debilitating disease that afflicts 4/1000 of the general population. The pathophysiologic basis for this condition is unknown, and no known consistently effective therapy has been identified. Recent studies have reported a link between the chronic fatigue syndrome and neurally mediated hypotension, a common abnormality of blood pressure regulation. In nonrandomized studies, treatment directed at neurally mediated hypotension has been effective in treating the symptoms of the chronic fatigue syndrome in two-thirds of patients. Prospective randomized trials are now in progress.

 

Source: Calkins H, Rowe PC. Relationship Between Chronic Fatigue Syndrome and Neurally Mediated Hypotension. Cardiol Rev. 1998 May;6(3):125-134. http://www.ncbi.nlm.nih.gov/pubmed/10348934

 

Orthostatic intolerance in the chronic fatigue syndrome

Abstract:

This study aims to investigate the prevalence and pathophysiology of orthostatic intolerance (OI) and its potential contribution to symptoms of a group of unselected patients with chronic fatigue syndrome (CFS).

Seventy five patients (65 women, 10 men) with CFS were evaluated. During an initial visit, a clinical suspicion as to the likelihood of observing laboratory evidence of OI was assigned. Laboratory investigation consisted of beat-to-beat recordings of heart rate, blood pressure (Finapres), and stroke volume (impedance cardiograph) while supine and during 80 degrees head-up tilt (HUT), during rhythmic deep breathing (6 breaths/min) and during the Valsalva maneuver. The responses of 48 age-matched healthy controls who had no history of OI were used to define the range of normal responses to these three maneuvers.

Forty percent of patients with CFS had OI during head-up tilt. Sixteen exhibited neurally-mediated syncope alone, seven tachycardia (> 35 bpm averaged over the whole of the head-up tilt) and six a mixture of tachycardia and syncope. Eight of 48 controls exhibited neurally-mediated syncope. The responses to the Valsalva maneuver and to deep breathing were similar in controls and patients. On average, the duration of disease and patient age were significantly less and the onset of symptoms was more often subacute in patients with OI than in those without OI.

We conclude that there exists a clinically identifiable subgroup of patients with CFS and OI that differs from control subjects and from those with CFS without OI for whom treatment specifically aimed at improving orthostatic tolerance may be indicated.

 

Source: Schondorf R, Benoit J, Wein T, Phaneuf D. Orthostatic intolerance in the chronic fatigue syndrome. J Auton Nerv Syst. 1999 Feb 15;75(2-3):192-201. http://www.ncbi.nlm.nih.gov/pubmed/10189122

 

Neurally mediated hypotension and autonomic dysfunction measured by heart rate variability during head-up tilt testing in children with chronic fatigue syndrome

Abstract:

Recent investigations suggest a role for neurally mediated hypotension (NMH) in the symptomatology of chronic fatigue syndrome (CFS) in adults. Our previous observations in children with NMH and syncope (S) unrelated to CFS indicate that the modulation of sympathetic and parasympathetic tone measured by indices of heart rate variability (HRV) is abnormal in children who faint during head-up tilt (HUT). In order to determine the effects of autonomic tone on HUT in children with CFS we performed measurements of HRV during HUT in 16 patients aged 11-19 with CFS.

Data were compared to 26 patients evaluated for syncope and with 13 normal control subjects. After 30 minutes supine, patients were tilted to 80 degrees for 40 minutes or until syncope occurred. Time domain indices included RR interval, SDNN, RMSSD, and pNN50. An autoregressive model was used to calculate power spectra. LFP (.04-.15 Hz), HFP (.15-.40Hz), and TP (.01-.40Hz). Data were obtained supine (baseline) and after HUT.

Thirteen CFS patients fainted (CFS+, 5/13 pure vasodepressor syncope) and three patients did not (CFS-). Sixteen syncope patients fainted (S+, all mixed vasodepressor-cardioinhibitory) and 10 did not (S-). Four control patients fainted (Control+, all mixed vasodepressor-cardioinhibitory) and nine did not (Control-). Baseline indices of HRV were not different between Control+ and S+, and between Control- and S-, but were depressed in S+ compared to S-. HRV indices were strikingly decreased in CFS patients compared to all other groups.

With tilt, SDNN, RMSSD, and pNN50 and spectral indices decreased in all groups, remaining much depressed in CFS compared to S or control subjects. With HUT, sympathovagal indices (LFP/HFP, nLFP, and nHFP) were relatively unchanged in CFS, which contrasts with the increase in nLFP with HUT in all other groups. With syncope RMSSD, SDNN, LFP, TP, and HFP increased in S+ (and Control+), suggesting enhanced vagal heart rate regulation. These increases were not observed in CFS+ patients.

CFS is associated with NMH during HUT in children. All indices of HRV are markedly depressed in CFS patients, even when compared with already low HRV in S+ or Control+ patients. Sympathovagal balance does not shift toward enhanced sympathetic modulation of heart rate with HUT and there is blunting in the overall HRV response with syncope during HUT. Taken together these data may indicate autonomic impairment in patients with CFS.

 

Source: Stewart J, Weldon A, Arlievsky N, Li K, Munoz J. Neurally mediated hypotension and autonomic dysfunction measured by heart rate variability during head-up tilt testing in children with chronic fatigue syndrome. Clin Auton Res. 1998 Aug;8(4):221-30. http://www.ncbi.nlm.nih.gov/pubmed/9791743