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European Geriatric Medicine Aug 2023The aim of this clinical review was to summarise the existing knowledge on the adverse effects of alpha-blockers and centrally acting antihypertensives, the effect these... (Review)
Review
PURPOSE
The aim of this clinical review was to summarise the existing knowledge on the adverse effects of alpha-blockers and centrally acting antihypertensives, the effect these may have on falls risk, and guide deprescribing of these medications.
METHODS
Literature searches were conducted using PubMed and Embase. Additional articles were identified by searching reference lists and reference to personal libraries. We discuss the place of alpha-blockers and centrally acting antihypertensives in the treatment of hypertension and methods for deprescribing.
RESULTS
Alpha-blockers and centrally acting antihypertensives are no longer recommended for the treatment of hypertension unless all other agents are contraindicated or not tolerated. These medications carry a significant falls risk and non-falls risk-associated side effects. Tools to aid and guide de-prescribing and monitoring of the withdrawal of these medication classes are available to assist the clinician including information on reducing the risk of withdrawal syndromes.
CONCLUSIONS
Centrally acting antihypertensives and alpha-blockers increase the risk of falls through a variety of mechanisms-principally by increasing the risk of hypotension, orthostatic hypotension, arrhythmias and sedation. These agents should be prioritised for de-prescribing in older frailer individuals. We identify a number of tools and a withdrawal protocol to aid the clinician in identifying and de-prescribing these medications.
Topics: Humans; Aged; Antihypertensive Agents; Accidental Falls; Hypertension; Hypotension; Adrenergic alpha-Antagonists
PubMed: 37436689
DOI: 10.1007/s41999-023-00813-x -
Critical Care and Resuscitation :... Dec 2022Midodrine is a peripherally acting, oral α-agonist that is increasingly used in intensive care units despite conflicting evidence for its effectiveness. It has... (Review)
Review
Midodrine is a peripherally acting, oral α-agonist that is increasingly used in intensive care units despite conflicting evidence for its effectiveness. It has pharmacological effects on blood vessels as well as pupillary, cardiac, renal, gastrointestinal, genitourinary, lymphatic and skin tissue. It has approval for use as a treatment for orthostatic hypotension, but a surge in interest over the past decade has prompted its use for a growing number of off-label indications. In critically ill patients, midodrine has been used as either an adjunctive oral therapy to wean vasoplegic patients off low dose intravenous vasopressor infusions, or as an oral vasopressor agent to prevent or minimise the need for intravenous infusion. Clinical trials have mostly focused on midodrine as an intravenous vasopressor weaning agent. Early retrospective studies supported its use for this indication, but more recent randomised controlled trials have largely refuted this practice. Key questions remain on its role in managing critically ill patients before intensive care admission, during intensive care stay, and following discharge. This narrative review presents a comprehensive overview of midodrine use for the critical care physician and highlights why lingering questions around ideal patient selection, dosing, timing of initiation, and efficacy of midodrine for critically ill patients remain unanswered.
PubMed: 38047013
DOI: 10.51893/2022.4.R -
Frontiers in Integrative Neuroscience 2023Visual disturbance is common symptom in Parkinson's disease (PD), and defective pupil light reflex (PLR) is an anticipated contributing factor that may be associated to...
INTRODUCTION
Visual disturbance is common symptom in Parkinson's disease (PD), and defective pupil light reflex (PLR) is an anticipated contributing factor that may be associated to the presence of autonomic dysfunction, which is a common non-motor feature of PD. Studies investigating the intercorrelation between PLR and dysautonomia in PD are limited.
METHODS
The aim of this study was to investigate differences of PLR parameters, measured by eye-tracker, between patients with PD, with and without signs of dysautonomia, and healthy controls (HC). In total, 43 HC and 50 patients with PD were recruited and PLR parameters were measured with Tobii Pro Spectrum, during a long (1,000 ms) and a short (100 ms) light stimulus. Presence of orthostatic hypotension (OH) was used as proxy marker of dysautonomia. Linear mixed-effects model and non-parametric comparative statistics were applied to investigate differences among groups.
RESULTS
Peak constriction velocity was slower in PD compared with HC, after adjustment for age and sex in the mixed model, and the difference was greater in the subgroup of PD with OH (unadjusted). Dilation amplitude and velocity were also gradually slower in HC vs. PD without OH vs. PD with OH (unadjusted for confounders). In the mixed model, age was significant predictor of dilation response.
DISCUSSION
Our results support previous observations on defective PLR in PD, evaluated with eye-tracker, and show a possible association with autonomic dysfunction. Further studies with more patients and rigorous evaluation of autonomic dysfunction are needed to validate these findings.
PubMed: 37727653
DOI: 10.3389/fnint.2023.1249554 -
Movement Disorders Clinical Practice Sep 2023Multiple system atrophy (MSA) is a devastating disease characterized by a variable combination of motor and autonomic symptoms. Previous studies identified numerous...
BACKGROUND
Multiple system atrophy (MSA) is a devastating disease characterized by a variable combination of motor and autonomic symptoms. Previous studies identified numerous clinical factors to be associated with shorter survival.
OBJECTIVE
To enable personalized patient counseling, we aimed at developing a risk model of survival based on baseline clinical symptoms.
METHODS
MSA patients referred to the Movement Disorders Unit in Innsbruck, Austria, between 1999 and 2016 were retrospectively analyzed. Kaplan-Meier curves and multivariate Cox regression analysis with least absolute shrinkage and selection operator penalty for variable selection were performed to identify prognostic factors. A nomogram was developed to estimate the 7 years overall survival probability. The performance of the predictive model was validated and calibrated internally using bootstrap resampling and externally using data from the prospective European MSA Study Group Natural History Study.
RESULTS
A total of 210 MSA patients were included in this analysis, of which 124 patients died. The median survival was 7 years. The following clinical variables were found to significantly affect overall survival and were included in the nomogram: age at symptom onset, falls within 3 years of onset, early autonomic failure including orthostatic hypotension and urogenital failure, and lacking levodopa response. The time-dependent area under curve for internal and external validation was >0.7 within the first 7 years of the disease course. The model was well calibrated showing good overlap between predicted and actual survival probability at 7 years.
CONCLUSION
The nomogram is a simple tool to predict survival on an individual basis and may help to improve counseling and treatment of MSA patients.
PubMed: 37772304
DOI: 10.1002/mdc3.13822 -
Journal of Arrhythmia Apr 2024Long-COVID syndrome has become a new health concern. Many major clinical centers have experienced more patients with symptoms suggestive of autonomic dysfunction,...
BACKGROUND
Long-COVID syndrome has become a new health concern. Many major clinical centers have experienced more patients with symptoms suggestive of autonomic dysfunction, especially postural orthostatic tachycardia syndrome (POTS) following COVID-19. However, there is a lack of information regarding the incidence and associated factors in Asian population.
METHODS
A retro-prospective study was conducted to evaluate patients with symptoms suggestive of POTS or other autonomic dysfunctions. These symptoms last at least 3 months after PCR-proven COVID-19. Exclusion criteria were age under 18 years old, pregnancy, and pre-COVID-19 autonomic dysfunction symptoms. Patients with a symptom severity score greater than two were assessed with blood tests, 24-h Holter, 24-h ambulatory blood pressure, echocardiogram, and head-up tilt table (HUTT).
RESULTS
Seven hundred ninety-three patients were interviewed at 146 ± 37 days after COVID-19. The majority of patients were middle-aged females (53%). Of those, 15 patients had the symptom severity score greater than 2. Out of those 15 patients, 12 had positive HUTT (1 demonstrating POTS, 10 neurocardiogenic syncope, and 1 orthostatic hypotension). Among those with positive HUTT patients, C-reactive protein (CRP) was significantly higher (OR 1.01; -value 0.041). Fatigue and dyspnea on exertion were the two most complaint symptoms.
CONCLUSIONS
This study shows the incidence of autonomic dysfunction and POTS is 1.5% (12/793) and 0.1% POTS (1/793), respectively, in a primary care setting (among general post-COVID-19 patients). The most common symptoms for these patients were fatigue and dyspnea.
PubMed: 38586859
DOI: 10.1002/joa3.13001 -
Journal of Neurology, Neurosurgery, and... Mar 2024variants increase the risk of developing Parkinson disease (PD) and influence its outcome. Deep brain stimulation (DBS) is a recognised therapeutic option for advanced...
BACKGROUND
variants increase the risk of developing Parkinson disease (PD) and influence its outcome. Deep brain stimulation (DBS) is a recognised therapeutic option for advanced PD. Data on DBS long-term outcome in carriers are scarce.
OBJECTIVE
To elucidate the impact of variants on long-term DBS outcome in a large Italian cohort.
METHODS
We retrospectively recruited a multicentric Italian DBS-PD cohort and assessed: (1) prevalence; (2) pre-DBS clinical features; and (3) outcomes of motor, cognitive and other non-motor features up to 5 years post-DBS.
RESULTS
We included 365 patients with PD, of whom 73 (20%) carried variants. 5-year follow-up data were available for 173 PD, including 32 mutated subjects. GBA-PD had an earlier onset and were younger at DBS than non-GBA-PD. They also had shorter disease duration, higher occurrence of dyskinesias and orthostatic hypotension symptoms.At post-DBS, both groups showed marked motor improvement, a significant reduction of fluctuations, dyskinesias and impulsive-compulsive disorders (ICD) and low occurrence of most complications. Only cognitive scores worsened significantly faster in GBA-PD after 3 years. Overt dementia was diagnosed in 11% non-GBA-PD and 25% GBA-PD at 5-year follow-up.
CONCLUSIONS
Evaluation of long-term impact of variants in a large Italian DBS-PD cohort supported the role of DBS surgery as a valid therapeutic strategy in GBA-PD, with long-term benefit on motor performance and ICD. Despite the selective worsening of cognitive scores since 3 years post-DBS, the majority of GBA-PD had not developed dementia at 5-year follow-up.
Topics: Humans; Parkinson Disease; Retrospective Studies; Deep Brain Stimulation; Dyskinesias; Dementia; Italy
PubMed: 37879897
DOI: 10.1136/jnnp-2023-332387 -
Cureus Jul 2023Spontaneous intracranial hypotension (SIH) remains a rare and difficult clinical entity to diagnose and treat. Epidural blood patch (EBP) of the dural sac is the...
OBJECTIVE
Spontaneous intracranial hypotension (SIH) remains a rare and difficult clinical entity to diagnose and treat. Epidural blood patch (EBP) of the dural sac is the mainstay definitive treatment for refractory cases and has mixed efficacy. We sought to evaluate the recent efficacy and outcomes of EBP for SIH at our institution.
METHODS
Twenty-three patients (14 women, 9 men, mean age 49) were seen and treated for SIH between Summer 2009 and Spring 2018 at the same institution. All patients underwent brain MRI with and without gadolinium contrast and T2-weighted spine MRI. Targeted EBP was placed one or two vertebral levels below areas of suspected leak, while the patient was positioned in the lateral decubitus position. Patients were seen in the outpatient setting within a week following initial EBP and repeat EBP was offered to patients with persistent symptoms. Patients were followed if symptoms persisted or for 6 months following clinical relief of symptoms.
RESULTS
22/23 (95.7%) patients presented with complaints of orthostatic headache, and 3 (13%) patients presented with altered mental status (AMS) or focal neurologic deficit. Brain MRI demonstrated pachymeningeal enhancement in 16/23 (69.6%) patients, and 5/23 (21.7%) patients had a subdural hematoma (SDH) present. Dural leaks were successfully identified in 18/23 (78.3%) patients. 12/23 (52.2%) patients had symptomatic relief with initial EBP, and 5/23 (21.7%) patients received further EBPs for persistent disease with all achieving relief after repeat EBP. 5/12 (41.7%) of patients had recurrent symptoms after initial relief with EBP, and 4/5 (80%) were successfully treated with a second EBP. The mean initial EBP volume and number of EBPs per patient were 21.7 mL (median 20 mL, 7-40 mL) and 3.54 (median 1, 1-13) respectively. There was one complication from initial EBP (cervical dural tear requiring operative closure) treated with open surgical management successfully. In total, 18/23 (78.2%) patients are currently asymptomatic with regard to their SIH. The mean follow-up in this cohort was 2.6 years (median 1.8 years, 1.8 months-9.27 years).
CONCLUSIONS
EBP is a viable and effective option for the treatment of recurrent SIH caused by cerebrospinal fluid (CSF) leaks.
PubMed: 37546124
DOI: 10.7759/cureus.41457 -
Cureus Sep 2023Levothyroxine (LT) is the synthetic form of thyroxine (T4), a thyroid hormone analog used to treat hypothyroidism. LT overdose rarely results in severely poor outcomes....
Levothyroxine (LT) is the synthetic form of thyroxine (T4), a thyroid hormone analog used to treat hypothyroidism. LT overdose rarely results in severely poor outcomes. General guidelines for treating exogenous thyrotoxicosis depend on the severity of symptoms. There is no standardized protocol; however, drug discontinuation, beta-blockers (specifically propranolol), and cholestyramine effectively manage overdose when needed, with most cases resolving independently without medical intervention. Here, we present the case of a 26-year-old female with a history of supraventricular tachycardia, anxiety, depression, and Hashimoto thyroiditis who was accidentally overprescribed LT (300 mcg for one and a half months) that resulted in symptoms of lethargy, tremors, body temperature dysregulation, orthostatic hypotension, and diarrhea. This case, with limited evidence, suggests that excessive LT exacerbated the patient's underlying psychiatric symptoms, encouraging suicidal ideation.
PubMed: 37809152
DOI: 10.7759/cureus.44787 -
Cancers Apr 2024Orthostatic hypotension (OH) is associated with a higher risk of mortality in the general population; however, it has not been studied in the cancer population. This...
BACKGROUND
Orthostatic hypotension (OH) is associated with a higher risk of mortality in the general population; however, it has not been studied in the cancer population. This study aimed to assess the prevalence of OH in cancer patients compared to that in the noncancer population.
METHODS
A total of 411 patients (mean age 63.5 ± 10.6 years) were recruited: patients with active cancer ( = 223) and patients hospitalised for other reasons, but without a cancer diagnosis ( = 188). Medical histories were collected and an orthostatic challenge test was performed. OH was defined as a blood pressure (BP) decrease upon standing of ≥20 mmHg for the systolic or ≥10 mmHg for the diastolic BP after 1 or 3 min; or a systolic BP decrease <90 mmHg.
RESULTS
The prevalence of OH in the subjects with cancer was significantly higher than in the subjects without cancer (28.7% vs. 16.5%, respectively, = 0.003). OH was the most common in the lung cancer patients (57.5%). In a single-variable analysis, the predictors of OH were cancer presence, age ≥ 65 years, and body mass index (BMI) ≥ 30 kg/m. In the multivariable model, the strongest independent predictor of OH was cancer status, which doubled the risk of OH, and BMI ≥ 30 kg/m and diabetes.
CONCLUSIONS
Cancer patients are characterised by a high prevalence of OH. In this population, the recommendation of routine orthostatic challenge tests should be considered.
PubMed: 38672623
DOI: 10.3390/cancers16081541 -
Journal of the American Heart... Nov 2023Background Rapidly consuming water may offer practical orthostatic hypotension therapy. However, its efficacy across disorders remains uncertain. This study aims to... (Meta-Analysis)
Meta-Analysis
Background Rapidly consuming water may offer practical orthostatic hypotension therapy. However, its efficacy across disorders remains uncertain. This study aims to assess the impact of rapid 350- to 500-mL water intake on systolic and diastolic blood pressure (BP) and heart rate (HR) through a systematic review and meta-analysis. Methods and Results We systematically reviewed MEDLINE and Embase up to June 2023, including randomized controlled trials and prospective cohort studies. Using random-effects meta-analysis, we calculated pooled mean differences (MDs) for maximum hemodynamic effects of rapid 350- to 500-mL water bolus consumption. Participants with orthostatic hypotension experienced increased systolic BP (MD, 24.18 [95% CI, 15.48-32.88]) and diastolic BP (MD, 11.98 [95% CI, 8.87-15.09]) with decreased HR (MD, -3.46 [95% CI, -5.21 to -1.71]). Similar results were observed in multiple system atrophy and pure autonomic failure subgroup analysis. Healthy participants showed modest increases in systolic BP (MD, 2.33 [95% CI, 1.02-3.64]) and diastolic BP (MD, 2.73 [95% CI, 1.15-4.30]), but HR changes were not significant (MD, -2.06 [95% CI, -5.25 to 1.13]). Water had no significant hemodynamic effects in patients with seated or supine postural tachycardia syndrome, although standing effects were unassessed. Our data do not exclude water's potential standing effect in postural tachycardia syndrome. Conclusions In patients with orthostatic hypotension, rapid water intake elevated short-term systolic BP and diastolic BP, with mild HR reduction when seated or supine. Healthy participants exhibited similar but milder effects. However, patients with postural tachycardia syndrome did not experience these changes in seated or supine positions. Further research is needed to evaluate the promising impact of rapid water ingestion on patients with postural tachycardia syndrome in a standing position, which was not addressed in our study.
Topics: Humans; Hypotension, Orthostatic; Postural Orthostatic Tachycardia Syndrome; Prospective Studies; Hemodynamics; Blood Pressure; Water
PubMed: 37929748
DOI: 10.1161/JAHA.122.029645