scholarly journals Neurogenic Orthostatic Hypotension. Lessons From Synucleinopathies

2020 ◽  
Author(s):  
Juan Francisco Idiaquez ◽  
Juan Idiaquez ◽  
Juan Carlos Casar ◽  
Italo Biaggioni
Keyword(s):  
Blood Pressure ◽  
Orthostatic Hypotension ◽  
Treatment Options ◽  
Lewy Body Dementia ◽  
Cerebral Hypoperfusion ◽  
Neurogenic Orthostatic Hypotension ◽  
Compression Garments ◽  
Novel Treatments ◽  
Mild Disease ◽  
Noradrenergic Fibers

Abstract Maintenance of upright blood pressure critically depends on the autonomic nervous system and its failure leads to neurogenic orthostatic hypotension (NOH). The most severe cases are seen in neurodegenerative disorders caused by abnormal α-synuclein deposits: multiple system atrophy (MSA), Parkinson’s disease, Lewy body dementia, and pure autonomic failure (PAF). The development of novel treatments for NOH derives from research in these disorders. We provide a brief review of their underlying pathophysiology relevant to understand the rationale behind treatment options for NOH. The goal of treatment is not to normalize blood pressure but rather to improve quality of life and prevent syncope and falls by reducing symptoms of cerebral hypoperfusion. Patients not able to recognize NOH symptoms are at a higher risk for falls. The first step in the management of NOH is to educate patients on how to avoid high-risk situations and providers to identify medications that trigger or worsen NOH. Conservative countermeasures, including diet and compression garments, should always precede pharmacologic therapies. Volume expanders (fludrocortisone and desmopressin) should be used with caution. Drugs that enhance residual sympathetic tone (pyridostigmine and atomoxetine) are more effective in patients with mild disease and in MSA patients with spared postganglionic fibers. Norepinephrine replacement therapy (midodrine and droxidopa) is more effective in patients with neurodegeneration of peripheral noradrenergic fibers like PAF. NOH is often associated with other cardiovascular diseases, most notably supine hypertension, and treatment should be adapted to their presence.

Standing and Supine Blood Pressure Outcomes Associated With Droxidopa and Midodrine in Patients With Neurogenic Orthostatic Hypotension: A Bayesian Meta-analysis and Mixed Treatment Comparison of Randomized Trials

2018 ◽  
Vol 52 (12) ◽  
pp. 1182-1194 ◽  
Author(s):  
Jack J. Chen ◽  
Yi Han ◽  
Jonathan Tang ◽  
Ivan Portillo ◽  
Robert A. Hauser ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Orthostatic Hypotension ◽  
Fixed Effects ◽  
Randomized Trials ◽  
Meta Analysis ◽  
Mixed Treatment Comparison ◽  
Neurogenic Orthostatic Hypotension ◽  
Supine Hypertension ◽  
Treatment Comparison ◽  
Mixed Treatment

Background: The comparative effects of droxidopa and midodrine on standing systolic blood pressure (sSBP) and risk of supine hypertension in patients with neurogenic orthostatic hypotension (NOH) are unknown. Objective: To perform a Bayesian mixed-treatment comparison meta-analysis of droxidopa and midodrine in the treatment of NOH. Methods: The PubMed, CENTRAL, and EMBASE databases were searched up to November 16, 2016. Study selection consisted of randomized trials comparing droxidopa or midodrine with placebo and reporting on changes in sSBP and supine hypertension events. Data were pooled to perform a comparison among interventions in a Bayesian fixed-effects model using vague priors and Markov chain Monte Carlo simulation with Gibbs sampling, calculating pooled mean changes in sSBP and risk ratios (RRs) for supine hypertension with associated 95% credible intervals (CrIs). Results: Six studies (4 administering droxidopa and 2 administering midodrine) enrolling a total of 783 patients were included for analysis. The mean change from baseline in sSBP was significantly greater for both drugs when compared with placebo (droxidopa 6.2 mm Hg [95% CrI = 2.4-10] and midodrine 17 mm Hg [95% CrI = 11.4-23]). Comparative analysis revealed a significant credible difference between droxidopa and midodrine. The RR for supine hypertension was significantly greater for midodrine, but not droxidopa, when compared with placebo (droxidopa RR = 1.4 [95% CrI = 0.7-2.7] and midodrine RR = 5.1 [95% CrI = 1.6-24]). Conclusion and Relevance: In patients with NOH, both droxidopa and midodrine significantly increase sSBP, the latter to a greater extent. However, midodrine, but not droxidopa, significantly increases risk of supine hypertension.

scholarly journals Neurogenic Orthostatic Hypotension: State of the Art and Therapeutic Strategies

2020 ◽  
Vol 14 ◽  
pp. 117954682095341
Author(s):  
Dinesh K Kalra ◽  
Anvi Raina ◽  
Sumit Sohal
Keyword(s):  
Blood Pressure ◽  
Orthostatic Hypotension ◽  
Clinical Features ◽  
Autonomic Dysfunction ◽  
State Of The Art ◽  
Therapeutic Strategies ◽  
Review Article ◽  
Neurogenic Orthostatic Hypotension ◽  
Standing Blood Pressure ◽  
Secondary Causes

Neurogenic orthostatic hypotension (nOH) is a subtype of orthostatic hypotension in which patients have impaired regulation of standing blood pressure due to autonomic dysfunction. Several primary and secondary causes of this disease exist. Patients may present with an array of symptoms making diagnosis difficult. This review article addresses the epidemiology, pathophysiology, causes, clinical features, and management of nOH. We highlight various pharmacological and non-pharmacological approaches to treatment, and review the recent guidelines and our approach to nOH.

scholarly journals Orthostatic arterial hypotension

2017 ◽  
Vol 12 (2) ◽  
pp. 12-15
Author(s):  
Camelia C. DIACONU ◽  
◽  
Denisa BUCUR ◽  
Daniel BERCEANU ◽  
Ovidiu Gabriel BRATU ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Elderly Patients ◽  
Orthostatic Hypotension ◽  
Pharmacological Treatment ◽  
Elderly Population ◽  
Autonomic Failure ◽  
Clinical Manifestations ◽  
The Elderly ◽  
Cerebral Hypoperfusion ◽  
Blurred Vision

Orthostatic hypotension is a persistent decrease of systolic blood pressure by at least 20 mm Hg and/or diastolic blood pressure by at least 10 mm Hg in the first 3 minutes upon standing. Orthostatic hypotension is more common in the elderly patients, being one of relatively frequent causes of hospitalization in the elderly population. Orthostatic hypotension may be primary or secondary, acute or chronic. Its etiology is represented in most cases by the primary or secondary autonomic failure. Clinical manifestations of orthostatic hypotension occur after the transition from supine to standing, and are due to cerebral hypoperfusion. These consist of nausea, dizziness, generalized weakness, postural instability, fatigue, blurred vision. Cardiological and neurological consult are necessary for diagnosis. Pharmacological treatment of orthostatic hypotension is often unsatisfactory, imposing combination with non-pharmacological measures.

scholarly journals The effects of caffeine in adults with neurogenic orthostatic hypotension: a systematic review

2021 ◽  
Author(s):  
Jake Ryan Gibbon ◽  
James Frith
Keyword(s):  
Systematic Review ◽  
Blood Pressure ◽  
Orthostatic Hypotension ◽  
Case Reports ◽  
Meta Analysis ◽  
Evidence Base ◽  
Original Research ◽  
Neurogenic Orthostatic Hypotension ◽  
Serious Adverse Events ◽  
Evidence Based Treatments

Abstract Purpose To systematically review the evidence base for the effectiveness and safety of caffeine for the treatment of neurogenic orthostatic hypotension in adults. Methods Eight electronic databases were searched in January 2021. Original research studies or case reports involving adults with neurogenic orthostatic hypotension were included if caffeine was an intervention and outcomes included symptoms, blood pressure or adverse effects. Relevant studies were screened and underwent qualitative analysis. Insufficient reporting precluded meta-analysis. Results Five studies were identified: four crossover studies and one case report summation. Study size ranged from 5 to 16 participants. Participants had neurogenic orthostatic hypotension, with a mean standing systolic blood pressure of 86 mmHg. Two studies evaluated caffeine alone. Three studies administered caffeine in combination with ergotamine. Caffeine dose ranged from 100 to 300 mg. Nature and timing of outcomes measured varied between studies, with measurements being recorded from 30 to 480 min after intervention. Caffeine/ergotamine improved symptoms in one study and reduced orthostatic blood pressure drop in two studies. Caffeine/ergotamine increased seated blood pressure in three studies, whilst the results for caffeine alone were inconsistent. No serious adverse events were reported. All studies demonstrated high risk of bias. Conclusion Caffeine should only be considered as a treatment for adults with neurogenic orthostatic hypotension when evidence-based treatments have been exhausted. Systematic review registration PROSPERO ID: CRD42020124589. Date of registration: 30/10/2020

scholarly journals Safety and efficacy of ampreloxetine in symptomatic neurogenic orthostatic hypotension: a phase 2 trial

2021 ◽  
Author(s):  
Horacio Kaufmann ◽  
Ross Vickery ◽  
Whedy Wang ◽  
Jitendra Kanodia ◽  
Cyndya A. Shibao ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Systolic Blood Pressure ◽  
Orthostatic Hypotension ◽  
Controlled Study ◽  
Neurogenic Orthostatic Hypotension ◽  
Median Dose ◽  
Double Blind ◽  
Supine Blood Pressure ◽  
Part C ◽  
Standing Blood Pressure

Abstract Purpose In neurogenic orthostatic hypotension, blood pressure falls when upright owing to impaired release of norepinephrine, leading to dizziness. Ampreloxetine, a selective norepinephrine reuptake inhibitor, increases circulating norepinephrine levels. This study explored the safety of ampreloxetine and its effect on blood pressure and symptoms in patients with neurogenic orthostatic hypotension. Methods A multicenter ascending-dose trial (range 1–20 mg, Part A) was followed by a 1 day, double-blind, randomized, placebo-controlled study (median dose 15 mg, Part B). Eligible patients then enrolled in a 20-week, open-label, steady-state extension phase (median dose 10 mg, Part C) followed by a 4-week withdrawal. Assessments included the Orthostatic Hypotension Symptom Assessment Scale (item 1), supine/seated/standing blood pressure, and safety. Results Thirty-four patients (age 66 ± 8 years, 22 men) were enrolled. Part A: The proportion of participants with a positive response (i.e., increase from baseline in seated systolic blood pressure of ≥ 10 mmHg) was greater with the 5 and 10 mg ampreloxetine doses than with placebo or other active ampreloxetine doses. Part B: Seated blood pressure increased 15.7 mmHg 4 h after ampreloxetine and decreased 14.2 mmHg after placebo [least squares mean difference (95% CI) 29.9 mmHg (7.6–52.3); P = 0.0112]. Part C: Symptoms of dizziness/lightheadedness improved 3.1 ± 3.0 points from baseline and standing systolic blood pressure increased 11 ± 12 mmHg. After 4 weeks of withdrawal, symptoms returned to pretreatment levels. The effect of ampreloxetine on supine blood pressure was minimal throughout treatment duration. Conclusion Ampreloxetine was well tolerated and improved orthostatic symptoms and seated/standing blood pressure with little change in supine blood pressure. Trial registration NCT02705755 (first posted March 10, 2016).

Initial orthostatic hypotension and cerebral blood flow regulation: effect of α1-adrenoreceptor activity

2013 ◽  
Vol 304 (2) ◽  
pp. R147-R154 ◽  
Author(s):  
Nia C. S. Lewis ◽  
Philip N. Ainslie ◽  
Greg Atkinson ◽  
Helen Jones ◽  
Emily J. M. Grant ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Orthostatic Hypotension ◽  
Relative Difference ◽  
Cerebral Hypoperfusion ◽  
Adrenergic Blockade ◽  
Absolute Level ◽  
Arterial Blood ◽  
Placebo Trial ◽  
Initial Orthostatic Hypotension ◽  
End Tidal

We examined the hypothesis that α1-adrenergic blockade would lead to an inability to correct initial orthostatic hypotension (IOH) and cerebral hypoperfusion, leading to symptoms of presyncope. Twelve normotensive humans (aged 25 ± 1 yr; means ± SE) attempted to complete a 3-min upright stand, 90 min after the administration of either α1-blockade (prazosin, 1 mg/20 kg body wt) or placebo. Continuous beat-to-beat measurements of middle cerebral artery velocity (MCAv; Doppler), blood pressure (finometer), heart rate, and end-tidal Pco2were obtained. Compared with placebo, the α1-blockade reduced resting mean arterial blood pressure (MAP) (−15%; P < 0.01); MCAv remained unaltered ( P ≥ 0.28). Upon standing, although the absolute level of MAP was lower following α1-blockade (39 ± 10 mmHg vs. 51 ± 14 mmHg), the relative difference in IOH was negligible in both trials (mean difference in MAP: 2 ± 2 mmHg; P = 0.50). Compared with the placebo trial, the declines in MCAv and PetCO2during IOH were greater in the α1-blockade trial by 12 ± 4 cm/s and 4.4 ± 1.3 mmHg, respectively ( P ≤ 0.01). Standing tolerance was markedly reduced in the α1-blockade trial (75 ± 17 s vs. 180 ± 0 s; P < 0.001). In summary, while IOH was little affected by α1-blockade, the associated decline in MCAv was greater in the blockade condition. Unlike in the placebo trial, the extent of IOH and cerebral hypoperfusion failed to recover toward baseline in the α1-blockade trial leading to presyncope. Although the development of IOH is not influenced by the α1-adrenergic receptor pathway, this pathway is critical in the recovery from IOH to prevent cerebral hypoperfusion and ultimately syncope.

Mechanisms underlying the impairment in orthostatic tolerance after nocturnal recumbency in patients with autonomic failure

2001 ◽  
Vol 101 (6) ◽  
pp. 609-618 ◽  
Author(s):  
Stefano OMBONI ◽  
Adrianus A.J. SMIT ◽  
Johannes J. VAN LIESHOUT ◽  
Jos J. SETTELS ◽  
Gerard J. LANGEWOUTERS ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Cardiac Output ◽  
Stroke Volume ◽  
Orthostatic Hypotension ◽  
Peripheral Resistance ◽  
Pulse Contour Analysis ◽  
Pressure Profile ◽  
Neurogenic Orthostatic Hypotension ◽  
Contour Analysis ◽  
Standing Blood Pressure

In the present study, we have assessed in patients with neurogenic orthostatic hypotension the haemodynamics underlying the reduced tolerance to standing after prolonged recumbency at night. In 10 patients with neurogenic orthostatic hypotension (age 33-68 years), of which seven were being treated with fludrocortisone and/or sleeping in the 12° head-up tilt position, 24h continuous non-invasive finger blood pressure was recorded by a Portapres device. Beat-to-beat blood pressure, heart rate, stroke volume, cardiac output and total peripheral vascular resistance obtained by pulse contour analysis were assessed during 5min of standing in the evening (at 22.30 hours) and in the morning (at 06.30hours). On average, the inverse of the normal 24h blood pressure profile was found, with a large diversity in blood pressure profiles among patients. Supine blood pressure values were similar, but standing blood pressure values were lower in the morning than in the evening (P < 0.01). This resulted from larger falls in stroke volume and cardiac output upon standing in the morning compared with the evening, while total peripheral resistance did not change. There was no relationship between the decrease in body weight during the night (mean 0.9kg; range 0.2-1.6kg) and the evening-morning difference in standing blood pressure. We conclude that, in patients with neurogenic orthostatic hypotension, the impaired tolerance to standing in the morning is due to larger falls in stroke volume and cardiac output. Not only nocturnal polyuria, but also a redistribution of body fluid, are likely mechanisms underlying the pronounced decreases in stroke volume and cardiac output after prolonged recumbency at night.

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