Implanted System for Orthostatic Hypotension in Multiple-System Atrophy.

Orthostatic hypotension is a cardinal feature of multiple-system atrophy. The upright posture provokes syncopal episodes that prevent patients from standing and walking for more than brief periods. We implanted a system to restore regulation of blood pressure and enable a patient with multiple-system atrophy to stand and walk after having lost these abilities because of orthostatic hypotension. This system involved epidural electrical stimulation delivered over the thoracic spinal cord with accelerometers that detected changes in body position. (Funded by the Defitech Foundation.).

Effectiveness and safety of traditional Chinese medicine in the treatment of senile hypotension: A protocol for systematic review and meta-analysis.

BACKGROUND: Senile hypotension refers to those whose blood pressure (BP) is lower than 90/60 mm Hg. The consequences can not only cause insufficient cardio-cerebral perfusion, but severe cases may also cause angina pectoris and stroke. At present, Western medicine has no ideal therapeutic drugs for senile hypotension. The aim of this systematic review is to assess the effectiveness and safety of traditional Chinese medicine (TCM) therapy for senile hypotension. METHODS: Two reviewers will electronically search the following databases: the Cochrane Central Register of Controlled Trials; PubMed; EMBASE; China National Knowledge Infrastructure; Chinese Biomedical Literature Database; Chinese Scientific Journal Database (VIP database); and Wan-Fang Database from the inception, without restriction of publication status and languages. Additional searching including researches in progress, the reference lists and the citation lists of identified publications. Study selection, data extraction, and assessment of study quality will be performed independently by 2 reviewers. If it is appropriate for a meta-analysis, RevMan 5.4 statistical software will be used; otherwise, a descriptive analysis will be conducted. Data will be synthesized by either the fixed-effects or random-effects model according to a heterogeneity test. The results will be presented as risk ratio (RR) with 95% confidence intervals (CIs) for dichotomous data and weight mean difference (WMD) or standard mean difference 95% CIs for continuous data. RESULTS: This study will provide a comprehensive review of the available evidence for the treatment of TCM with senile hypotension. CONCLUSIONS: The conclusions of our study will provide an evidence to judge whether TCM is an effective and safe intervention for patients with senile hypotension. ETHICS AND DISSEMINATION: This systematic review will be disseminated in a peer-reviewed journal or presented at relevant conferences. It is not necessary for a formal ethical approval because the data are not individualized. TRIAL REGISTRATION NUMBER: INPLASY2020110091.

Lessons learned from the pilot study of an orthostatic hypotension intervention in the subacute phase following spinal cord injury.

Context: Following spinal cord injury (SCI) at the cervical or upper-thoracic level, orthostatic hypotension (OH) is observed in 13-100% of patients. This study aimed to test the feasibility of conducting a randomized controlled trial combining a dynamic tilt-table (Erigo®) and functional electrical stimulation (FES) to mitigate OH symptoms in the subacute phase after SCI. Design: Pilot study. Setting: A tertiary rehabilitation hospital. Participants: Inpatients who had a C4-T6 SCI (AIS A-D) less than 12 weeks before recruitment, and reported symptoms of OH in their medical chart. Interventions: Screening sit-up test to determine eligibility, then 1 assessment session and 3 intervention sessions with Erigo® and FES for eligible participants. Outcome measures: Recruitment rate, duration of assessment and interventions, resources used, blood pressure, and Calgary Presyncope Form (OH symptoms). Results: Amongst the 232 admissions, 148 inpatient charts were reviewed, 11 inpatients met all inclusion criteria, 7 participated in a screening sit-up test, and 2 exhibited OH. Neither of the two participants recruited in the pilot study was able to fully complete the assessment and intervention sessions due to scheduling issues (i.e. limited available time). Conclusion: This pilot study evidenced the non-feasibility of the clinical trial as originally designed, due to the low recruitment rate and the lack of available time for research in participant's weekday schedule. OH in the subacute phase after SCI was less prevalent and less incapacitating than expected. Conventional management and spontaneous resolution of symptoms appeared sufficient to mitigate OH in most patients with subacute SCI.

The efficacy of nonpharmacologic intervention for orthostatic hypotension associated with aging.

OBJECTIVE: To determine the efficacy and safety of nonpharmacologic interventions for orthostatic hypotension (OH) secondary to aging. METHODS: A total of 150 orthostatic challenges were performed in 25 older people (age 60-92 years) to determine cardiovascular responses to bolus water drinking, compression stockings, abdominal compression, and physical countermaneuvers. Primary outcome was response rate as assessed by proportion of participants whose systolic blood pressure (SBP) drop improved by ≥10 mm Hg. RESULTS: The response rate to bolus water drinking was 56% (95% confidence interval [CI] 36.7-74.2), with standing SBP increasing by 12 mm Hg (95% CI 4-20). Physical countermaneuvers were efficacious in 44% (95% CI 25.8-63.3) but had little effect on standing SBP (+7.5 mm Hg [95% CI -1 to 16]). Abdominal compression was efficacious in 52% (95% CI 32.9-70.7) and improved standing SBP (+10 mm Hg [95% CI 2-18]). Compression stockings were the least efficacious therapy (32% [95% CI 16.1-51.4]) and had little effect on standing SBP (+6 mm Hg [95% CI -1, 13]). No intervention improved symptoms during standing. There were no adverse events. CONCLUSIONS: Bolus water drinking should become the standard first-line nonpharmacologic intervention, whereas compression stockings should be disregarded in this population. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for older people with OH, bolus water drinking is superior to other nonpharmacologic interventions in decreasing SBP drop.

Blood Pressure Responses to Endovascular Stimulation: A Potential Therapy for Autonomic Disorders With Vasodilatation.

BACKGROUND: We have previously shown that sympathetic ganglia stimulation via the renal vein rapidly increases blood pressure. This study further investigated the optimal target sites and effective energy levels for stimulation of the renal vasculatures and nearby sympathetic ganglia for rapid increase in blood pressure. METHODS: The pre-study protocol for endovascular stimulations included 2 minutes of stimulation (1-150 V and 10 pulses per second) and at least 2 minutes of rest during poststimulation. If blood pressure and/or heart rate were changed during the stimulation, time to return to baseline was allowed prior to the next stimulation. RESULTS: In 11 acute canine studies, we performed 85 renal artery, 30 renal vein, and 8 hepatic vasculature stimulations. The mean arterial pressure (MAP) rapidly increased during stimulation of renal artery (95 ± 18 mmHg vs. 103 ± 15 mmHg; P < 0.0001), renal vein (90 ± 16 mmHg vs. 102 ± 20 mmHg; P = 0.001), and hepatic vasculatures (74 ± 8 mmHg vs. 82 ± 11 mmHg; P = 0.04). Predictors of a significant increase in MAP were energy >10 V focused on the left renal artery, bilateral renal arteries, and bilateral renal veins (especially the mid segment). Overall, heart rate was unchanged, but muscle fasciculation was observed in 22.0% with an output >10 V (range 15-150 V). Analysis after excluding the stimulations that resulted in fasciculation yielded similar results to the main findings. CONCLUSIONS: Stimulation of intra-abdominal vasculatures promptly increased the MAP and thus may be a potential treatment option for hypotension in autonomic disorders. Predictors of optimal stimulation include energy delivery and the site of stimulation (for the renal vasculatures), which informs the design of subsequent research.

Nonpharmacologic management of orthostatic hypotension: a systematic review.

OBJECTIVE: To systematically review the literature on nonpharmacologic treatment of orthostatic hypotension. DATA SOURCES: MEDLINE, Cumulative Index to Nursing and Allied Health Literature, Embase, Cochrane Central Register of Controlled Trials, and SPORTDiscus were searched for human studies written in the English language between January 1980 and April 2013. Reference lists of relevant articles were reviewed for citations to expand the data set. STUDY SELECTION: Prospective experimental studies assessing nonpharmacologic interventions for management of orthostatic drop in blood pressure in various patient populations were included. All studies identified through the literature search were reviewed independently in duplicate. Of the 642 studies, 23 met the selection criteria. DATA EXTRACTION: Two reviewers independently extracted data for analysis, including systolic and diastolic blood pressure and orthostatic symptoms in response to postural challenge before and after the intervention. All 23 studies were assessed in duplicate for risk of bias using the Physiotherapy Evidence Database scale for randomized controlled trials and the Downs and Black tool for nonrandomized trials. DATA SYNTHESIS: There were 8 identified nonpharmacologic interventions for management of orthostatic hypotension under 2 general categories: physical modalities (exercise, functional electrical stimulation, compression, physical countermaneuvers, compression with physical countermaneuvers, sleeping with head up) and dietary measures (water intake, meals). Owing to the clinically diverse nature of the studies, statistical comparison (meta-analysis) was deemed inappropriate. Instead, descriptive comparisons were drawn. Levels of evidence were assigned. CONCLUSIONS: Strong levels of evidence were found for 4 of the 8 interventions: functional electrical stimulation in spinal cord injury, compression of the legs and/or abdomen, physical countermaneuvers in various patient populations, and eating smaller and more frequent meals in chronic autonomic failure. However, this conclusion is based on a limited number of studies with small sample sizes. Further research into all interventions is warranted.

Bionic baroreceptor corrects postural hypotension in rats with impaired baroreceptor.

BACKGROUND: Impairment of the arterial baroreflex causes orthostatic hypotension. Arterial baroreceptor sensitivity degrades with age. Thus, an impaired baroreceptor plays a pivotal role in orthostatic hypotension in most elderly patients. There is no effective treatment for orthostatic hypotension. The aims of this investigation were to develop a bionic baroreceptor (BBR) and to verify whether it corrects postural hypotension. METHODS AND RESULTS: The BBR consists of a pressure sensor, a regulator, and a neurostimulator. In 35 Sprague-Dawley rats, we vascularly and neurally isolated the baroreceptor regions and attached electrodes to the aortic depressor nerve for stimulation. To mimic impaired baroreceptors, we maintained intracarotid sinus pressure at 60 mm Hg during activation of the BBR. Native baroreflex was reproduced by matching intracarotid sinus pressure to the instantaneous pulsatile aortic pressure. The encoding rule for translating intracarotid sinus pressure into stimulation of the aortic depressor nerve was identified by a white noise technique and applied to the regulator. The open-loop arterial pressure response to intracarotid sinus pressure (n=7) and upright tilt-induced changes in arterial pressure (n=7) were compared between native baroreceptor and BBR conditions. The intracarotid sinus pressure-arterial pressure relationships were comparable. Compared with the absence of baroreflex, the BBR corrected tilt-induced hypotension as effectively as under native baroreceptor conditions (native, -39±5 mm Hg; BBR, -41±5 mm Hg; absence, -63±5 mm Hg; P<0.05). CONCLUSIONS: The BBR restores the pressure buffering function. Although this research demonstrated feasibility of the BBR, further research is needed to verify its long-term effect and safety in larger animal models and humans.

Cardiovascular response to functional electrical stimulation and dynamic tilt table therapy to improve orthostatic tolerance.

Orthostatic hypotension is a common condition for individuals with stroke or spinal cord injury. The inability to regulate the central nervous system will result in pooling of blood in the lower extremities leading to orthostatic intolerance. This study compared the use of functional electrical stimulation (FES) and passive leg movements to improve orthostatic tolerance during head-up tilt. Four trial conditions were assessed during head-up tilt: (1) rest, (2) isometric FES of the hamstring, gastrocnemius and quadriceps muscle group, (3) passive mobilization using the Erigo dynamic tilt table; and (4) dynamic FES (combined 2 and 3). Ten healthy male subjects experienced 70 degrees head-up tilt for 15 min under each trial condition. Heart rate, blood pressure and abdominal echograms of the inferior vena cava were recorded for each trial. Passive mobilization and dynamic FES resulted in an increase in intravascular blood volume, while isometric FES only resulted in elevating heart rate. No significant differences in blood pressure were observed under each condition. We conclude that FES combined with passive stepping movements may be an effective modality to increase circulating blood volume and thereby tolerance to postural hypotension in healthy subjects.

Bionic epidural stimulation restores arterial pressure regulation during orthostasis.

A bionic baroreflex system (BBS) is a computer-assisted intelligent feedback system to control arterial pressure (AP) for the treatment of baroreflex failure. To apply this system clinically, an appropriate efferent neural (sympathetic vasomotor) interface has to be explored. We examined whether the spinal cord is a candidate site for such interface. In six anesthetized and baroreflex-deafferentiated cats, a multielectrode catheter was inserted into the epidural space to deliver epidural spinal cord stimulation (ESCS). Stepwise changes in ESCS rate revealed a linear correlation between ESCS rate and AP for ESCS rates of 2 pulses/s and above (r2, 0.876-0.979; slope, 14.3 +/- 5.8 mmHg.pulses(-1).s; pressure axis intercept, 35.7 +/- 25.9 mmHg). Random changes in ESCS rate with a white noise sequence revealed dynamic transfer function of peripheral effectors. The transfer function resembled a second-order, low-pass filter with a lag time (gain, 16.7 +/- 8.3 mmHg.pulses(-1).s; natural frequency, 0.022 +/- 0.007 Hz; damping coefficient, 2.40 +/- 1.07; lag time, 1.06 +/- 0.41 s). On the basis of the transfer function, we designed an artificial vasomotor center to attenuate hypotension. We evaluated the performance of the BBS against hypotension induced by 60 degrees head-up tilt. In the cats with baroreflex failure, head-up tilt dropped AP by 37 +/- 5 mmHg in 5 s and 59 +/- 11 mmHg in 30 s. BBS with optimized feedback parameters attenuated hypotension to 21 +/- 2 mmHg in 5 s (P < 0.05) and 8 +/- 4 mmHg in 30 s (P < 0.05). These results indicate that ESCS-mediated BBS prevents orthostatic hypotension. Because epidural stimulation is a clinically feasible procedure, this BBS can be applied clinically to combat hypotension associated with various pathophysiologies.

[Effective "home remedies" in orthostatic hypotension. A glass of water before getting up and a brick under the bed]. / Wirksame "Hausmittel" gegen die orthostatische Hypotonie. Ein Glas Wasser vor dem Aufstehen und ein Ziegelstein unterm Bett.

The symptoms of orthostatic hypotension can be considerably improved by non-pharmacological treatment, and patients with such symptoms should not initially be given medication. Many patients, for example, show a pronounced increase in blood pressure shortly after drinking water, and this phenomenon can be utilized to ameliorate symptoms. In patients who respond inadequately, treatment with pharmacological agents is indicated. The most appropriate drug needs to be selected individually on the basis of its action and tolerability. All medications suitable for treating orthostatic hypotension can appreciably increase the blood pressure in the prone patient.

Syncope.

Syncope is a common clinical presentation. Although most commonly benign, it may herald a pathology with a poor prognosis. The work-up of syncope includes a careful history, physical examination, electrocardiogram, risk stratification, and appropriately directed testing. The key factor in the investigation of syncope is the presence (or absence) of structural heart disease or an abnormal electrocardiogram. The most useful investigation in unexplained syncope with a normal heart is the tilt table test for evaluating predisposition to neurocardiogenic (vasovagal) syncope. In the setting of structural heart disease or an abnormal electrocardiogram, electrophysiologic studies play a more important role. The utility of noninvasive cardiac monitoring for symptom-rhythm correlation may be limited by infrequent symptoms. The availability of external and implantable loop recorders allows prolonged periods of monitoring to increase diagnostic yield. The management of patients with syncope may be complex. Early referral to a cardiac electrophysiologist is warranted in patients who are at high risk.

Functional electrical stimulation effect on orthostatic hypotension after spinal cord injury.

OBJECTIVE: To investigate the possibility of using functional electrical stimulation (FES) to control orthostatic hypotension in patients with spinal cord injury (SCI) and to clarify the mechanism of the response. DESIGN: Subjects were tilted by 10 degree increments with varying intensities of lower-extremity FES. Stimulation over muscles was compared to stimulation over noncontractile sites. SETTING: Physical therapy department of a major rehabilitation center. PATIENTS: Six patients with SCI above T6 (3 with recent injury recruited consecutively from an inpatient spinal cord rehabilitation unit, and 3 from the community with longstanding injury, recruited as volunteers). MAIN OUTCOME MEASURES: Blood pressure, heart rate, and perceived presyncope score recorded at each tilt angle and analyzed using a multivariate analysis of variance statistical methodology. RESULTS: Systolic and diastolic blood pressure increased with increasing stimulation intensities (systolic, p = .001; diastolic, p = .0019) and decreased with increasing angle of tilt (p < .001) regardless of the site of stimulation. Subjects tolerated higher angles of incline with electrical stimulation than without (p = .03). CONCLUSIONS: FES causes a dose-dependent increase in blood pressure independent of stimulation site that may be useful in treating orthostatic hypotension.

Role of physical countermaneuvers in the management of orthostatic hypotension: efficacy and biofeedback augmentation.

OBJECTIVE: To evaluate the efficacy of various physical countermaneuvers in reducing orthostatic hypotension and its associated symptoms and to assess the efficacy of biofeedback training in enhancing the effectiveness of physical countermaneuvers. MATERIAL AND METHODS: In nine study subjects with neurogenic orthostatic hypotension, four training sessions on physical countermaneuvers were performed after tilt-up, three with visual feedback on the effect of physical countermaneuvers on blood pressure and other cardiovascular variables. Blood pressure change and orthostatic symptoms during tilt-up were determined, as were the changes in total peripheral resistance, stroke index, and heart rate. RESULTS: The five female and four male patients had a mean age of 53 years and a mean duration of symptoms of 4.2 years. On an orthostatic symptom scale of 0 to 10, these patients had a mean symptom score of 7.3. The increment in systolic blood pressure was better for some maneuvers (such as leg crossing and a combination) than others (such as neck flexion and abdominal contraction). Three patterns of responses to biofeedback were found. Simple maneuvers such as squatting did not improve with training; visual feedback was needed for maneuvers such as thigh contraction, and performance declined without biofeedback; the third pattern, seen in maneuvers such as leg crossing, showed continued improvement with training, even without biofeedback. A survey at 3 to 4 months after training revealed continued use of physical maneuvers (3.8 +/- 3.1 per day), increased standing time with each episode of presyncopal symptoms (8.3 +/- 5.8 minutes), and continued global symptomatic improvement. Total peripheral resistance, but not heart rate or stroke index, showed significant regression with blood pressure improvement. CONCLUSION: Physical countermaneuvers are efficacious in reducing orthostatic hypotension, can be augmented by use of biofeedback, and may significantly improve the functional outcome. The major mechanism of improvement is an increase in total peripheral resistance, presumably by reducing the vascular capacitance.

[Therapy recommendations for children and youths with orthostatic circulatory dysfunction]. / Therapieempfehlungen für Kinder und Jugendliche mit orthostatischer Kreislauffehlregulation.

After recapitulating the symptoms, differential diagnosis, pathophysiology, and diagnostics of orthostatic syndrome in childhood specific recommendations for therapy are given. We emphasize self-treatment by physical training. We summarized the complex therapeutical programme in a leaflet for the young patients and their relatives.