Treatment Of Orthostatic Hypotension Research Articles

Treatment of orthostatic hypotension during acute inpatient rehabilitation after spinal cord injury: usual care versus anti-hypotensive therapy.

To compare pharmacological treatment of hypotension and orthostatic hypotension (OH) initiated based upon a blood pressure (BP) threshold, regardless of symptoms (TXT), to usual care pharmacological treatment of symptomatic hypotension (UC), during acute inpatient rehabilitation (AIR) following spinal cord injury (SCI). Block randomization, based on the neurological level of injury as: cervical lesions (C1-C8); high thoracic lesions (T1-T5) and low thoracic lesions (T6-T12), was used to determine responses to the primary question "was the therapy session affected by low BP or concern for low BP development?". Study participants and therapists were unaware of group assignment. A total of 66 participants enrolled; 25 (38%) in the TXT group, 29 (44%) in the UC group, and 12 (18%) withdrew. Responses to the primary question were recorded for 32 participants, 15 in the TXT and 17 in the UC group. There was an average of 81±51 therapy sessions/participant in the TXT and 60±27 sessions/participant in the UC group. Of those therapy sessions, low BP or concerns for low BP affected an average of 9±8 sessions/participant in the TXT group and 10±12 sessions/participant in the UC group. Neither the total number of therapy sessions (p=0.16) nor group assignment (p=0.83) significantly predicted the number of sessions affected by low BP. These data are not conclusive but indicate that the treatment of asymptomatic hypotension and OH does not increase time spent in therapy compared to usual care treatment of symptomatic hypotension and OH in newly injured patients with SCI.

Orthostatic Hypotension in Hypertensive Adults: Harry Goldblatt Award for Early Career Investigators 2021.

Orthostatic hypotension affects roughly 10% of individuals with hypertension and is associated with several adverse health outcomes, including dementia, cardiovascular disease, stroke, and death. Among adults with hypertension, orthostatic hypotension has also been shown to predict patterns of blood pressure dysregulation that may not be appreciated in the office setting, including nocturnal nondipping. Individuals with uncontrolled hypertension are at particular risk of orthostatic hypotension and may meet diagnostic criteria for the condition with a smaller relative reduction in blood pressure compared with normotensive individuals. Antihypertensive medications are commonly de-prescribed to address orthostatic hypotension; however, this approach may worsen supine or seated hypertension, which may be an important driver of adverse events in this population. There is significant variability between guidelines for the diagnosis of orthostatic hypotension with regards to timing and position of blood pressure measurements. Clinically relevant orthostatic hypotension may be missed when standing measurements are delayed or when taken after a seated rather than supine position. The treatment of orthostatic hypotension in patients with hypertension poses a significant management challenge for clinicians; however, recent evidence suggests that intensive blood pressure control may reduce the risk of orthostatic hypotension. A detailed characterization of blood pressure variability is essential to tailoring a treatment plan and can be accomplished using both in-office and out-of-office monitoring.

Oral and intravenous hydration in the treatment of orthostatic hypotension and postural tachycardia syndrome.

Hydration with water and salt is the mainstay of treatment for autonomic nervous system disorders that impair orthostatic tolerance. The goal is to expand intravascular volume to compensate for the downward displacement of blood volume that occurs when standing and thereby sustain cerebral perfusion and restore quality of life. Despite strong consensus recommendations for salt supplementation as standard treatment of these disorders, published evidence of benefit is relatively weak, and no randomized clinical trials have occurred. This review summarizes the physiological rationale for hydration and evaluates the literature on oral and intravenous hydration in the treatment of neurogenic orthostatic hypotension, postural tachycardia syndrome, and recurrent vasovagal syncope. We conclude that oral salt replacement is indicated for treatment of neurogenic orthostatic hypotension because these patients have excessive renal sodium excretion, and for treatment of chronic orthostatic intolerance because these patients are often hypovolemic. As not all patients are able to tolerate sufficient oral hydration, there is also a role for intravenous volume-loading in severe cases of postural tachycardia syndrome. We offer guidance, based on review of the literature and the clinical judgment of a cardiologist and neurologist with experience treating autonomic disorders, regarding the option of ongoing intravenous hydration for treatment of severe, refractory cases of postural tachycardia syndrome.

Диабетическая кардиальная автономная нейропатия: каковы перспективы в лечении?

Кардиальная автономная нейропатия (КАН) является серьезным и частым осложнением сахарного диабета. Несмотря на ее связь с повышенным риском сердечно-сосудистой смертности и различными симптомами и нарушениями, значимость КАН сложно переоценить. Изменение образа жизни, интенсивный гликемический контроль позволяют предотвратить развитие или прогрессирование КАН. Патогенетическое лечение КАН включает: сбалансированную диету и физическую активность; оптимизацию гликемического контроля; лечение дислипопротеинемии; коррекцию метаболических нарушений в миокарде; профилактику и лечение тромбоза; применение ингибиторов альдозоредуктазы; применение дигомо-гамма-линоленовой кислоты (ДГЛК); применение ацетил-L-карнитина, антиоксидантов, в первую очередь α-липоевой кислоты (α-ЛК), применение ω-3 и ω-6 полиненасыщенных жирных кислот (ω-3 и ω-6 ПНЖК), вазодилататоров, жирорастворимого витамина B1, аминогуанидина; заместительную терапию ростовыми факторами, в тяжелых случаях — лечение ортостатической гипотензии. Многообещающим является применение средств, которые повышают кровоток в vasa vasorum, в том числе аналогов простациклина, блокаторов тромбоксана А2, а также препаратов, которые способствуют усилению и/или нормализации функции Na+-,К+-АТФазы (ингибиторы фосфодиэстеразы), α-ЛК, ДГЛК, ω-3 ПНЖК, а также одновременное назначение α-ЛК, ω-3 ПНЖК и ДГЛК.

The Pressor Response to the Drinking of Cold Water and Cold Carbonated Water in Healthy Younger and Older Adults.

Purpose: Water drinking has been proposed for the treatment of orthostatic hypotension because it can increase blood pressure in patients. This study aimed to investigate whether drinking water with a cold or carbonation stimulus would cause a more effective pressor response, and whether it would be greater in older than in younger adults.Methods: We assessed blood pressure and heart rate from non-invasive arterial pressure (a volume-clamp method) and type II electrocardiography in 13 healthy young adults (6 females, 7 males; mean age, 19.9 ± 1.1 years) and nine healthy older adults (all females; mean age, 71.4 ± 4.2 years) who drank 200 mL of cold, cold carbonated, and room temperature water.Results: The pressor response to the drinking of cold and cold carbonated water was greater than that to room temperature water in both younger and older participants (p < 0.05; changes in systolic blood pressure of room temperature water, cold water and cold carbonated water in young: 15.31 ± 9.66, 22.56 ± 11.51 and 32.6 ± 17.98 mmHg, respectively; changes in systolic blood pressure of room temperature water, cold water and cold carbonated water in elderly: 21.84 ± 14.31, 41.53 ± 19.82 and 48.16 ± 16.77 mmHg, respectively). In addition, the pressor response to cold and cold carbonated water was persistent during the recovery period by about 5–10 mmHg (p < 0.05). Furthermore, the pressor response during the drinking and recovery periods was greater in the older than in the younger participants (p < 0.05).Conclusion: Our data suggest that even smaller amounts of water are able to elicit a sustained pressor response, in particular if the water is cold and carbonated. We speculate that the pressor effect may render cold and carbonated water an appropriate first aid method against certain forms of acute hypotension.

Pure autonomic failure-A localized alpha synucleinopathy with a potential for conversion to more extensive alpha synucleinopathies

Pure autonomic failure (PAF) is an alpha synucleinopathy with predominant involvement of the autonomic ganglia and peripheral nerves. The hallmark clinical feature is orthostatic hypotension. However, genitourinary, sudomotor, and cardiac involvement is also common. Many patients also develop supine hypertension. Almost a quarter of patients can phenoconvert or evolve into Parkinson's disease, multiple system atrophy, and Lewy body dementia in the future. Early severe bladder involvement, higher supine noradrenaline level, early motor involvement, and dream enactment behavior increase the risk of phenoconversion. The diagnosis is confirmed via autonomic function testing and serum noradrenaline measurement. The treatment is mainly supportive. The non-pharmacological treatment includes adequate fluid, dietary salt, compression stockings, and abdominal binders. The drug therapies to improve blood pressure include midodrine, fludrocortisone, pyridostigmine, and droxidopa. The diagnostic criteria need to be updated to incorporate the recent understandings. The treatment of orthostatic hypotension and supine hypertension is mainly based on case series and anecdotal reports. Randomized control trials are needed to ascertain the best treatment strategies for PAF.

Droxidopa for Treatment of Refractory Orthostatic Hypotension in Patients with AL Amyloidosis: A Case Series

BackgroundOrthostatic hypotension due to autonomic dysfunction is a well-known complication of light chain (AL) amyloidosis, which can become progressively debilitating and difficult to manage. Treatment of the underlying plasma cell dyscrasia will eventually decrease further amyloid deposition. Management of orthostatic hypotension secondary to AL amyloidosis improves quality of life and facilitates delivery of plasma cell therapy. Pharmacologic interventions include fludrocortisone, sympathomimetic agents such as midodrine, droxidopa, the acetylcholinesterase inhibitor pyridostigmine or the norepinephrine transporter (NET) inhibitor atomoxetine. Fludrocortisone is often poorly tolerated in amyloid patients because it may exacerbate edema. Droxidopa is a synthetic amino acid analog that is directly metabolized to norepinephrine by dopa-decarboxylase, which increases blood pressure (BP) by inducing peripheral arterial and venous vasoconstriction.AimsTo assess the effectiveness of droxidopa in patients with AL amyloidosis with severe orthostatic hypotension refractory to midodrine. Also, to describe effective dose of droxidopa, duration of therapy, adverse effects and reasons for discontinuation.MethodsA regional retrospective study was done in patients with AL amyloidosis with severe, refractory orthostatic hypotension who received droxidopa. Retrospective data was reviewed from 2018 to 2021 at a single academic center in the United States.ResultsFive patients with AL amyloidosis were included in the study; three patients had lambda-restricted plasma cell dyscrasia and two had multiple myeloma (MM) associated AL amyloidosis (both kappa light chain restricted). Of the five patients, all had cardiac, renal, autonomic nervous system and peripheral nervous system involvement and two of the five had gastrointestinal involvement as well. Given their poor performance status and advanced organ involvement, none of the patients were eligible for high-dose intravenous melphalan with autologous peripheral blood stem cell transplantation (HDM/SCT), and thus were treated with cyclophosphamide, bortezomib and dexamethasone (CyBorD). All patients achieved very good partial response to complete hematologic response. The main findings are summarized in table 1.All patients had severe, symptomatic orthostatic hypotension that was objectively defined as a decrease in systolic blood pressure by 20 millimeters of mercury (mmHg) or a decrease in diastolic blood pressure of 10 mmHg from supine to either sitting or standing in the clinic or at home (Freeman R consensus statement on the definition of orthostatic hypotension, 2011). Initial treatment for all patients included midodrine, ranging from 5 to 30mg TID based on individual tolerance. Three of the patients also were initially treated with fludrocortisone 0.05 to 0.2mg daily (use limited by fluid retention). Only one patient was on pyridostigmine 30mg TID (case 5). Given persistence of symptoms despite therapy, droxidopa was started at 100mg TID in all patients, and the dose was titrated as tolerated. None required the maximal approved dose of 600mg TID.The indication to start droxidopa was based on refractory, symptomatic orthostatic hypotension in all five patients. After initiation of droxidopa, all except for one patient reported improvement both in symptoms of lightheadedness as well as measurements of orthostatic blood pressure values. By the end of this study, three patients continued treatment with droxidopa (cases 1-3); one was weaned-off after resolution of symptoms (case 5) and one was discontinued due to supine hypertension (case 4).ConclusionData shows that droxidopa is an effective treatment of orthostatic hypotension refractory to midodrine in patients with AL amyloidosis. Slow titration may be important to minimize rapid changes in blood pressure. Further studies are warranted to assess droxidopa's safety and compare with other treatments for orthostatic hypotension. [Display omitted] DisclosuresHughes: Amgen: Speakers Bureau; Rigel: Other: Advisory Board, Research Funding; Abbvie: Speakers Bureau; Karyopharm: Other: Advisory Board, Speakers Bureau. Sanchorawala: Celgene: Research Funding; Takeda: Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Prothena: Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Membership on an entity's Board of Directors or advisory committees; Caelum: Membership on an entity's Board of Directors or advisory committees, Research Funding; Regeneron: Membership on an entity's Board of Directors or advisory committees; Proclara: Membership on an entity's Board of Directors or advisory committees; Oncopeptide: Research Funding; Karyopharm: Research Funding; Sorrento: Research Funding; Pfizer: Honoraria. Sloan: Nuvectis: Consultancy; Abbvie: Consultancy; Stemline: Consultancy; Astrazeneca: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees; Pharmacosmos: Membership on an entity's Board of Directors or advisory committees.

Fludrocortisone for orthostatic hypotension.

Orthostatic hypotension is an excessive fall in blood pressure (BP) while standing and is the result of a decrease in cardiac output or defective or inadequate vasoconstrictor mechanisms. Fludrocortisone is a mineralocorticoid that increases blood volume and blood pressure. Fludrocortisone is considered the first- or second-line pharmacological therapy for orthostatic hypotension alongside mechanical and positional measures such as increasing fluid and salt intake and venous compression methods. However, there has been no Cochrane Review of the benefits and harms of this drug for this condition. To identify and evaluate the benefits and harms of fludrocortisone for orthostatic hypotension. We searched the following databases on 11 November 2019: Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, Embase and CINAHL. We also searched trials registries. We included all studies evaluating the benefits and harms of fludrocortisone compared to placebo, another drug for orthostatic hypotension, or studies without comparators, including randomized controlled trials (RCTs), quasi-RCTs and observational studies. We included studies in people with orthostatic hypotension due to a chronic peripheral neuropathy, a central autonomic neuropathy, or autonomic failure from other causes, but not medication-induced orthostatic hypotension or orthostatic hypotension from acute volume depletion or blood loss. We usedCochrane methodological procedures for most of the review. We developed and used a tool to prioritize observational studies that offered the best available evidence where there are gaps in the evidencefrom RCTs. We assessed the certainty of evidence for fludrocortisone versus placebo using GRADE. We included 13 studies of 513 participants, including three cross-over RCTs and 10 observational studies (three cohort studies, six case series and one case-control study). The included RCTs were small (total of 28 participants in RCTs), short term (two to three weeks), only examined fludrocortisone for orthostatic hypotension in people with two conditions (diabetes and Parkinson disease), and had variable risk of bias (two had unclear risk of bias and one had low risk of bias). Heterogeneity in participant populations, comparators and outcome assessment methods prevented meta-analyses of the RCTs. We found very low-certainty evidence about the effects of fludrocortisone versus placebo on drop in BP in people with diabetes (-26 mmHg versus -39 mmHg systolic; -7 mmHg versus -11 mmHg diastolic; 1 cross-over study, 6 participants). For people with Parkinson disease, we found very-low certainty evidence about the effects of fludrocortisone on drop in BP compared to pyridostigmine (-14 mmHg versus -22.1 mmHg diastolic; P = 0.036; 1 cross-over study, 9 participants) and domperidone (no change after treatment in either group;1 cross-over study, 13 participants). For orthostatic symptoms, we found very low-certainty evidence for fludrocortisone versus placebo in people with diabetes (4 out of 5 analyzed participants had improvements in orthostatic symptoms, 1 cross-over study, 6 participants), for fludrocortisone versus pyridostigmine in people with Parkinson disease (orthostatic symptoms unchanged;1 cross-over study, 9 participants) or fludrocortisone versus domperidone (improvement to 6 for both interventions on the Composite Autonomic Symptom Scale-Orthostatic Domain (COMPASS-OD);1 cross-over study, 13 participants). Evidence on adverse events was also very low-certainty in both populations, but indicated side effects were minimal. Observational studies filled some gaps in evidence by examining the effects in larger groups of participants, with more diverse conditions, over longer periods of time. One cohort study (341 people studied retrospectively) found fludrocortisone may not be harmful in the long term for familial dysautonomia. However, it is unclear if this translates to long-term improvements in BP drop or a meaningful improvement in orthostatic symptoms. The evidence is very uncertain about the effects of fludrocortisone on blood pressure, orthostatic symptoms or adverse events in people with orthostatic hypotension and diabetes or Parkinson disease. There is a lack of information on long-term treatment and treatment of orthostatic hypotension in other disease states. There is a need for standardized reporting of outcomes and for standardization of measurements of blood pressure in orthostatic hypotension.

Abstract 043: Local Passive Heat in the Treatment of Nocturnal Supine Hypertension in Autonomic Failure

Supine hypertension affects about half of patients with primary autonomic failure (AF), complicates the treatment of orthostatic hypotension (OH) and induces nocturnal polyuria, resulting in worsening of morning OH. We previously showed that short exposure to local passive heat (40-42°C applied for ≤2 hours over abdomen and pelvis with a heating pad) acutely decreased systolic blood pressure (BP) by -25±5 mmHg in AF patients with supine hypertension due to decreases in stroke volume (-29±5%) and cardiac output (-30±5%). In this study, we hypothesized that local passive heat therapy applied overnight would lower nocturnal BP and polyuria, and improve early morning OH in these patients. Ten AF patients with supine hypertension (age 76±2 years, 6 men, supine systolic BP 168±3 mmHg) received passive heat (38°C with a water-perfused heating pad placed under the torso) or placebo, in a 2-night crossover study. Supine BP was monitored every 2 hr from 8pm-8am. Heat therapy was applied from 10pm-6am. Morning orthostatic tolerance was assessed at 8 am. Systolic BP significantly decreased during overnight heat therapy compared to placebo (Figure; P&lt;0.01 by mixed-effects model) with a maximal reduction of 30±6 mmHg at 4 hours of heat. Despite lowering nighttime BP, heat therapy did not decrease nocturnal diuresis or improve morning OH. In conclusion, low levels of local heat therapy applied overnight effectively lowers BP in AF patients with nocturnal supine hypertension. Thus, local heat therapy offers a novel non-pharmacologic approach to treat this condition, but future studies are needed to assess the long-term safety of this approach.

Lewy body dementia: therapeutic propositions according to evidence based medicine and practice

Lewy body dementia (LBD) may present with two clinical forms: dementia with Lewy bodies (DLB) and Parkinson's disease with dementia. LBD is characterized by a profound deficiency of acetylcholine and a deficiency of dopamine. The cholinergic deficit is implicated in major attention disorders and fluctuations. Acetylcholinesterase inhibitors (donepezil or rivastigmine) were studied in several double-blind placebo-controlled studies. The meta-analyzes show a moderate benefit on the cognitive level and on some psychiatric manifestations including hallucinations. A disabling parkinsonian syndrome can be treated with L-dopa as in Parkinson's disease. However, the results are often limited because the increase in doses is restricted by cognitive and psychobehavioral disorders. Hallucinations may require antipsychotic treatment and the best documented drug is clozapine. Some other antipsychotics were assessed but in few therapeutic trials, and appear less efficacious, and with bad tolerance. Finally, the last of LBD cardinal disorders, REM sleep behavior disorders can be improved by melatonin. Other manifestations of LBD are troublesome. Some therapeutic trials with modafinil were proposed to improve diurnal hypersomnia. Anxiety and depression are often difficult to be treated. For antidepressant drugs, the first choice seems to be selective serotonin receptor inhibitors. Treatment for orthostatic hypotension, constipation, and swallowing dysfunction has also been more or less documented. In each case, non-drug management is considered (cognitive stimulation, physiotherapy, speech therapy, etc.). Finally, a therapeutic strategy is suggested, based on the medical and clinical experience. This strategy underlines the importance to improve cholinergic deficit and sleep disturbances. It also stresses the importance of a careful revision of all drugs administered to the patients with a peculiar attention to the anticholinergic treatment.

Obituary: Sir Roger Bannister (1929–2018)

Obituary: Sir Roger Bannister (1929–2018)

State of the art for diagnosis and treatment of orthostatic hypotension

This paper presents state of the art of the problem of diagnosis and treatment of orthostatic hypotension (OH). It focuses on the developed algorithms for diagnostics of classical orthostatic hypotension (COH), initial orthostatic hypotension (IOH) and delayed orthostatic hypotension (DOH). It describes the necessary methods for the differential diagnosis of the OH causes. Comparative analysis of the European Society of Cardiology and American College of Cardiology/American Heart Association/Society of Cardiac Rhythm was performed. The treatment options for different groups of patients with orthostatic hypotension are described.

Fludrocortisone for orthostatic hypotension

Background Orthostatic hypotension is an excessive fall in blood pressure (BP) while standing and is the result of a decrease in cardiac output or defective or inadequate vasoconstrictor mechanisms. Fludrocortisone is a mineralocorticoid that increases blood volume and blood pressure. Fludrocortisone is considered the first- or second-line pharmacological therapy for orthostatic hypotension alongside mechanical and positional measures such as increasing fluid and salt intake and venous compression methods. However, there has been no Cochrane Review of the benefits and harms of this drug for this condition. Objectives To identify and evaluate the benefits and harms of fludrocortisone for orthostatic hypotension. Search methods We searched the following databases on 11 November 2019: Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, Embase and CINAHL. We also searched trials registries. Selection criteria We included all studies evaluating the benefits and harms of fludrocortisone compared to placebo, another drug for orthostatic hypotension, or studies without comparators, including randomized controlled trials (RCTs), quasi-RCTs and observational studies. We included studies in people with orthostatic hypotension due to a chronic peripheral neuropathy, a central autonomic neuropathy, or autonomic failure from other causes, but not medication-induced orthostatic hypotension or orthostatic hypotension from acute volume depletion or blood loss. Data collection and analysis We used Cochrane methodological procedures for most of the review. We developed and used a tool to prioritize observational studies that offered the best available evidence where there are gaps in the evidence from RCTs. We assessed the certainty of evidence for fludrocortisone versus placebo using GRADE. Main results We included 13 studies of 513 participants, including three cross-over RCTs and 10 observational studies (three cohort studies, six case series and one case-control study). The included RCTs were small (total of 28 participants in RCTs), short term (two to three weeks), only examined fludrocortisone for orthostatic hypotension in people with two conditions (diabetes and Parkinson disease), and had variable risk of bias (two had unclear risk of bias and one had low risk of bias). Heterogeneity in participant populations, comparators and outcome assessment methods prevented meta-analyses of the RCTs. We found very low-certainty evidence about the effects of fludrocortisone versus placebo on drop in BP in people with diabetes (-26 mmHg versus -39 mmHg systolic; -7 mmHg versus -11 mmHg diastolic; 1 cross-over study, 6 participants). For people with Parkinson disease, we found very-low certainty evidence about the effects of fludrocortisone on drop in BP compared to pyridostigmine (-14 mmHg versus -22.1 mmHg diastolic; P = 0.036; 1 cross-over study, 9 participants) and domperidone (no change after treatment in either group; 1 cross-over study, 13 participants). For orthostatic symptoms, we found very low-certainty evidence for fludrocortisone versus placebo in people with diabetes (4 out of 5 analyzed participants had improvements in orthostatic symptoms, 1 cross-over study, 6 participants), for fludrocortisone versus pyridostigmine in people with Parkinson disease (orthostatic symptoms unchanged; 1 cross-over study, 9 participants) or fludrocortisone versus domperidone (improvement to 6 for both interventions on the Composite Autonomic Symptom Scale-Orthostatic Domain (COMPASS-OD); 1 cross-over study, 13 participants). Evidence on adverse events was also very low-certainty in both populations, but indicated side effects were minimal. Observational studies filled some gaps in evidence by examining the effects in larger groups of participants, with more diverse conditions, over longer periods of time. One cohort study (341 people studied retrospectively) found fludrocortisone may not be harmful in the long term for familial dysautonomia. However, it is unclear if this translates to long-term improvements in BP drop or a meaningful improvement in orthostatic symptoms. Authors' conclusions The evidence is very uncertain about the effects of fludrocortisone on blood pressure, orthostatic symptoms or adverse events in people with orthostatic hypotension and diabetes or Parkinson disease. There is a lack of information on long-term treatment and treatment of orthostatic hypotension in other disease states. There is a need for standardized reporting of outcomes and for standardization of measurements of blood pressure in orthostatic hypotension.

神経症的不登校を伴った起立性低血圧(直後型)の病態と治療経過について

神経症的不登校を伴った起立性低血圧(直後型)の病態と治療経過について

Hipotensiunea arterială ortostatică

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.

Efficacy of Servo-Controlled Splanchnic Venous Compression in the Treatment of Orthostatic Hypotension: A Randomized Comparison With Midodrine.

Splanchnic venous pooling is a major hemodynamic determinant of orthostatic hypotension, but is not specifically targeted by pressor agents, the mainstay of treatment. We developed an automated inflatable abdominal binder that provides sustained servo-controlled venous compression (40 mm Hg) and can be activated only on standing. We tested the efficacy of this device against placebo and compared it to midodrine in 19 autonomic failure patients randomized to receive either placebo, midodrine (2.5-10 mg), or placebo combined with binder on separate days in a single-blind, crossover study. Systolic blood pressure (SBP) was measured seated and standing before and 1-hour post medication; the binder was inflated immediately before standing. Only midodrine increased seated SBP (31±5 versus 9±4 placebo and 7±5 binder, P=0.003), whereas orthostatic tolerance (defined as area under the curve of upright SBP [AUCSBP]) improved similarly with binder and midodrine (AUCSBP, 195±35 and 197±41 versus 19±38 mm Hg×minute for placebo; P=0.003). Orthostatic symptom burden decreased with the binder (from 21.9±3.6 to 16.3±3.1, P=0.032) and midodrine (from 25.6±3.4 to 14.2±3.3, P<0.001), but not with placebo (from 19.6±3.5 to 20.1±3.3, P=0.756). We also compared the combination of midodrine and binder with midodrine alone. The combination produced a greater increase in orthostatic tolerance (AUCSBP, 326±65 versus 140±53 mm Hg×minute for midodrine alone; P=0.028, n=21) and decreased orthostatic symptoms (from 21.8±3.2 to 12.9±2.9, P<0.001). In conclusion, servo-controlled abdominal venous compression with an automated inflatable binder is as effective as midodrine, the standard of care, in the management of orthostatic hypotension. Combining both therapies produces greater improvement in orthostatic tolerance. URL: https://www.clinicaltrials.gov. Unique identifier: NCT00223691.

Droxidopa for orthostatic hypotension: a systematic review and meta-analysis.

The systematic review and meta-analysis aims to determine the efficacy and safety of droxidopa in the treatment of orthostatic hypotension, following its recent approvals in the United States. MEDLINE, EMBASE, PubMed, Cochrane Controlled Trials Register, Web of Science, ProQuest, and the WHO Clinical Trials Registry were searched. Studies were included if they randomized adults with orthostatic hypotension to droxidopa or to control, and outcomes related to symptoms, daily activity, blood pressure, or adverse events. Data were extracted independently by two reviewers. Risk of bias was judged against the Cochrane risk of bias tool and quality of evidence measured using Grading of Recommendations Assessment, Development and Evaluation criteria. A fixed-effects model was used for pooled analysis. Of 224 identified records, four studies met eligibility, with a pooled sample size of 494. Study duration was between 1 and 8 weeks. Droxidopa was effective at reducing dizziness [mean difference -0.97 (95% confidence interval -1.51, -0.42)], overall symptoms [-0.52 (-0.98, -0.06)] and difficulty with activity [-0.86 (-1.34, -0.38)]. Droxidopa was also effective at improving standing SBP [3.9 (0.1, 7.69)]. Rates of adverse events were similar between droxidopa and control groups, including supine hypertension [odds ratio 1.93 (0.87, 4.25)]. Droxidopa is well tolerated and effective at reducing the symptoms associated with neurogenic orthostatic hypotension without increasing the risk of supine hypertension. PROSPERO ID CRD42015024612.

P454: Safety, efficacy and tolerability of Droxidopa in the treatment of orthostatic hypotension: a retrospective review

P454: Safety, efficacy and tolerability of Droxidopa in the treatment of orthostatic hypotension: a retrospective review

Midodrine

Midodrine

Complexity of impaired parasympathetic heart rate regulation in diabetes.

The autonomic nervous system is crucial for blood pressure and heart rate regulation. Sympathetic efferent fibers elicit vasoconstriction, raise heart rate and cardiac contractility, and promote sodium reabsorption through direct renal tubular actions and renin-angiotensin system activation. Parasympathetic efferent fibers rapidly reduce heart rate. Both autonomic branches are tightly controlled by baroreflex, stabilizing blood pressure in a feedback fashion (1). Severe autonomic failure due to sympathetic and parasympathetic dysfunction typically occurs in patients with long-standing and poorly controlled diabetes. The condition is associated with profound orthostatic hypotension, postprandial hypotension, a fixed heart rate, and exercise intolerance. Positron emission tomography or single photon emission tomography imaging with tracers taken up by adrenergic sympathetic nerve endings suggest that autonomic efferent nerves are irreversibly damaged in these patients (2,3). There are no causative treatments for late-stage disease and symptomatic treatment is difficult. Clinicians caring for autonomic failure patients are faced with the therapeutic dilemma that blood pressure is often markedly elevated in the supine position (4). Yet, antihypertensive treatment exacerbates orthostatic hypotension. Conversely, treatment of orthostatic hypotension with pressor agents might hasten cardiovascular and renal disease progression. The condition carries a poor prognosis. More subtle changes in cardiovascular autonomic regulation are common early in the course of type 1 or type 2 diabetes. Typically, impaired parasympathetic heart rate control precedes sympathetic dysfunction. Simple bedside tests, such as respiratory sinus arrhythmia assessment during deep breathing, are often diagnostic (5). Heart rate variability and noninvasive baroreflex sensitivity measurements are also useful diagnostic tools, particularly in epidemiologic …