Compression Therapy in Patients With Orthostatic Hypotension a Systematic Review
Abstract
Background: orthostatic hypotension (OH) affects up to 30% of adults over 65 and frequently contributes to falls and syncopal episodes. Current guidelines suggest a wide range of treatments, but systematic reviews of the evidence base of operations for such recommendations are lacking.
Methods: nosotros performed a systematic review to assess the evidence for all non-pharmacological and pharmacological interventions for OH. Our search included the following databases: MEDLINE; EMBASE; CINAHL; and the Cochrane library. Nosotros searched gray literature and references from included studies and other reviews. Nosotros included randomised, placebo-controlled trials, which measured postural drop as an event. Study quality was assessed using pre-specified measures of bias.
Results: overall, 36 trials (21 interventions) were included. Nosotros identified a heterogeneous population and a wide diversity of study methods, precluding meta-assay. Most trials were of poor quality with high risk of bias. Changes in postural drop and symptoms were frequently inconsistent. Compression bandages, indomethacin, oxilofrine, potassium chloride and yohimbine improved the postural drib. Several vasoactive drugs—including midodrine and pyridostigmine—improved the standing blood pressure, but overall worsened the postural drop.
Conclusions: many commonly recommended interventions for OH accept a limited evidence base supporting their use. High quality, randomised, controlled trials are needed to underpin clinical practise for this condition.
Introduction
Orthostatic hypotension (OH) is common, affecting up to xxx% of the general population over 65 [1], and upward to lxx% of people living in nursing homes [ 2]. The following consensus definition of OH was devised by the American Autonomic Society and the American Academy of Neurology, and subsequently endorsed by the European Federation of Autonomic Societies and the Earth Federation of Neurology: '…a sustained reduction of systolic blood pressure level of at least 20 mmHg or diastolic blood pressure of 10 mmHg within 3 min of standing or head-up tilt to at least 60° on a tilt table' [ 2]. OH is strongly associated with hypertension [ 3, 4, 5, 6, 7, 8], increasing historic period [ 3, 4, v, six, ix] and diabetes mellitus [ 5, 10] equally well as weather condition causing autonomic failure. In add-on to its unpleasant and disabling symptoms, OH is also associated with an increased incidence of cerebrovascular disease [ eleven, 12, 13], myocardial infarction [ eleven], coronary centre disease [ 3, 6, 13], eye failure [ 10], cardiovascular bloodshed [ 3], all crusade mortality [ 3, 9, xiii] and falls [ 8, eleven, xiv]. OH has been associated with cognitive impairment in at least one trial [ 15], but this association was less conclusive in two others [16, 17].
A wide range of non-pharmacological and pharmacological therapies have been used to treat OH. A number of review manufactures and guidelines have been published offering advice on the optimal management of this complicated condition [18, xix, xx, 21, 22, 23, 24, 25, 26], merely rigorous, systematic reviews of the available evidence for treatment of OH are currently defective. Nosotros therefore undertook a systematic review of the efficacy of therapeutic options for managing OH, and set the following objectives: to systematically review the evidence for pharmacological and non-pharmacological treatments of OH; to quantify the extent of reduction in blood pressure level fall by various treatments; and to assess the impact of treatments on standing time, orthostatic symptoms and functional power.
Methods
Search strategy and selection criteria
We used a pre-specified protocol, on the basis of recommendations set up out past the Cochrane Collaboration. The following criteria had to be met for a trial to be considered eligible for inclusion: trials had to be of a randomised, controlled design, and had to compare an intervention with placebo; and could be of either the parallel grouping or the crossover blueprint. Nosotros did non fix any language restrictions, but excluded studies involving astronauts and healthy volunteers. We excluded trials that concentrated on postal service-prandial hypotension and neurally mediated hypotension ('vasovagal syncope') as opposed to OH. We considered both pharmacological and non-pharmacological interventions.
Data source and written report search
We searched the following databases: MEDLINE; EMBASE; the Cumulative Alphabetize to Nursing and Allied Health Literature (CINAHL); the Cochrane Library; Psychinfo; the British Nursing Index; and Current Controlled Trials website. We searched for articles published betwixt 1950 and February 2012. We searched for gray literature using Google, and manus-searched the reference lists of articles we identified, in addition to those in narrative review articles. We utilised the following search terms: [orthostatic hypotension OR postural hypotension] AND [randomised OR randomized OR placebo] AND [interventions as listed below].
Interventions
The interventions examined were derived from previous narrative reviews of OH [18, nineteen, 20, 21, 22, 23, 24, 25], and included: fluid, hydration, water; salt, sodium chloride; bed tilt, elevating bed; counter manoeuvres/maneuvers; compression stocking/hose/bandage/garment, intestinal compression; antihypertensives (all available classes were listed); fludrocortisone; erythropoietin; sympathomimetics [midodrine, dihydroxyphenylserine (l-DOPS, dl-DOPS), yohimbine, ephedrine, pseudoephedrine, dihydroergotamine]; acetylcholinesterase inhibition, pyridostigmine; selective serotonin reuptake inhibitor/SSRI; serotonin-norepinephrine reuptake inhibitor/SNRI; vasopressin analogue; methylphenidate; dextroamphetamine; caffeine; dopamine receptor antagonist (metoclopramide, domperidone); and indomethacin.
Outcomes
The chief outcome measures of interest were change in office blood pressure (lying and standing/tilted systolic and diastolic claret pressure level, and postural drib) and change in orthostatic symptoms. We extracted data on continuing time, functional ability, adverse events and compliance. The following was also recorded: duration of study; source of funding; inclusion and exclusion criteria; sex; age; weight; crusade of OH; co-morbidities; medication; method for recording blood pressure; quality of life; functional condition; habitation place; dose, frequency and duration of intervention or placebo; participant period (numbers that were screened, eligible, assigned to each arm and completed the written report); and mortality data. The change in blood pressure and postural drop was calculated (if feasible) for studies not explicitly stating these outcomes.
Data extraction and quality cess
Information were entered onto a proforma to ensure consistent recording. The starting time 20 papers were analysed by both authors to ensure consistency, with the remainder analysed by ane writer. Foreign linguistic communication articles were translated prior to data extraction. Any discrepancies were resolved by consensus. Studies were also assessed for quality, concentrating on comparability of each arm, forcefulness of randomisation and allocation darkening, effectiveness of patient and staff blinding, detailing of withdrawals and strength of analysis (i.e. use of intention to treat). This was subsequently scored with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) organisation, allowing an easily understood quality of prove 'rating' to be given for each intervention. Course initially allocates a 'loftier' quality score to randomised controlled trials, with the potential to 'step down' the quality of testify to 'medium', 'depression' or 'very low' (dependent on the force of evidence). The overall form should exist reduced by one level for each of the post-obit criteria constitute to be nowadays: serious limitations to study design; important inconsistency; indirectness of prove; imprecise or sparse data; and publication bias. If the limitations of study design are very serious then the quality of evidence may be downgraded by two steps [ 27].
Data analysis
Meta-assay could non be undertaken, due to the heterogeneity of participants, report designs, study interventions and reported outcome measures. Instead, results were grouped by intervention in descriptive course.
Results
Trial pick and report demographics
The initial search strategy yielded 1,466 titles, from which 204 abstracts were identified equally potentially relevant. Papers that did not encounter the inclusion criteria were then excluded. The main reasons for exclusion were: lack of randomisation and placebo-control; subjects were salubrious volunteers or astronauts; or trials were concerned with the management of hypertension. Lxx-viii papers were then obtained and read in particular. Studies were eliminated if they were concerned with syncope for reasons other than OH, or if the lying and the standing claret pressure were non the focus of assessment. A full of 36 studies (37 papers) were finally included, examining 21 different interventions (Figure i). The results of i trial of yohimbine were published in 2 separate journals.
Figure i.
Trial selection flow diagram.
Figure one.
Trial pick menstruation diagram.
Overall, 1,268 patients were included. Their age range was 26–88 years, with a mean age of 58.viii (SD xiii.three) years. Twelve of the 36 studies involved subjects with a mean or median historic period of greater than 65 years, whereas but 4 studies involved patients with a mean or median age of greater than 75 years. Birthday, xi different populations were identified throughout the 36 studies, with 4 studies inadequately characterising the underlying crusade of OH. Fifteen of the 36 trials included a heterogeneous mix of patients, rather than concentrating on i specific illness process. In total, 32 different methods for recording postural drop were identified; variations were predominantly in the timing of the continuing claret pressure, with unclear timings in v studies. Viii studies utilised tilt-table testing. Xiv of the 36 trials used a single dose of therapy only, and in one trial the duration of treatment was unclear. Details are given in Table1.
Table 1.
Participant characteristics and study blueprint by therapy [28–64]
| Author (year) | n | Study type | Population | Hateful age | Sex (% 1000) | BP recording | Control | Intervention | Duration |
|---|---|---|---|---|---|---|---|---|---|
| Amezinium | |||||||||
| Belz et al. (1981) [28] | 12 | Crossover | 'Orthostatic dizziness' | 26 | 17 | Tilt table testing | Placebo | Amezinium 30 mg | Once-off |
| Camphor-crataegus berry combination (CCC); i drop = D-camphor ane mg and Crataegus berry extract 38.92 mg | |||||||||
| Belz et al. (2002) [29] | 48 | Crossover | 'OH' (pooled information of two smaller trials) | 26 | 69 | Tilt tabular array testing | Placebo twenty drops | CCC 5 drops or 20 drops or 80 drops | Once-off on sugar cube |
| Kroll et al. (2005) [30] | 38 | Parallel group | 'OH' | 68 | 58 | Fifty&South BP | Placebo 25 drops TDS | CCC 25 drops TDS | ane/52 each |
| Clonidine or nitroglycerin | |||||||||
| Shibao et al. (2006) [31] | 23 | Crossover (incomplete) | Chief autonomic failure (MSA/PAF) | 66 | 78 | L&S BP | Placebo tablet or patch | Clonidine 0.1 mg tab or Nitroglycerin 0.one mg/h patch | Tab once-off Patch ten h |
| Compression bandages | |||||||||
| Podoleanu et al. (2006) [ 32] | 21 | Crossover | Progressive OH (no symptoms first 3 min) | 70 | 43 | Tilt table testing | Sham bandages (5 mmHg ankle and hip for 10 min. Abdo added last ten min) | Active bandages (40–60 mmHg ankles and 30–40 mmHg hips for 10 min. xx–30 mmHg abdo added terminal 10 min) | Once-off |
| Dihydroergotamine (DHE) and DHE Plus (with etilefrine) | |||||||||
| Lang (1976) [33] | 40 | Crossover | 'Nursing home residents with OH' | 59–88 | ? | L&S BP | Placebo TDS | DHE ii mg TDS | 2/52 each |
| Muth and Jansen (1980) [34] | 42 | Crossover | 'Old persons' infirmary' | 75 | 45 | 50&S BP | Placebo TDS | DHE Plus (DHE 2 mg and etilefrine 20 mg) TDS | 2/52 placebo 8/52 DHE+ |
| Hamouz and Knaup (1983) [35] | 30 | Parallel group | Psych inpatients, on neuroleptic therapy | 48 | 37 | Fifty&S BP | Placebo TDS | DHE Plus (DHE ii mg and etilefrine twenty mg) TDS | 2/52 each |
| Hoeldtke et al. (1986) [36] | 8 | Crossover | OH due to DM/alcohol/idiopathic | 52 | 50 | L&S BP | Placebo (sub-cut) | DHE 6.5 mcg/kg or 13 mcg/kg (sub-cut) | Once-off |
| Thulesius and Berlin (1986) [37] | 58 | Parallel grouping | Psych inpatients, on neuroleptics/tri-cyclics | 55 | 50 | Fifty&South BP | Placebo BD | DHE 5 mg BD | i/52 each |
| Dihydroxyphenylserine (l-DOPS and dl-DOPS) | |||||||||
| Hoeldtke et al. (1984) [38] | 6 | Crossover | 'Severe OH' (DM/idiopathic) | 35–81 | 83 | L&S BP | Placebo | dl-DOPS 600 mg or 800 mg | Once-off |
| Freeman et al. (1999) [39] | 10 | Crossover | 'Astringent OH' (MSA/PAF) | lx | 70 | Tilt table testing | Placebo | dl-DOPS 1,000 mg | Once-off |
| Akizawa et al. (2002) [40] | 149 | Parallel grouping | Haemodialysis ×iii/calendar week | 62 | 48 | L&S BP post dialysis | Placebo, xxx min pre-HD | l-DOPS 200 mg or 400 mg, thirty min pre-Hard disk | 4/52 each |
| Iida et al. (2002) [41] | 86 | Parallel group | Haemodialysis ×iii/week | 60 | 51 | 50&S BP postal service dialysis | Placebo, 30 min pre-Hard disk drive | l-DOPS 400 mg 30 min pre-HD | iv/52 each |
| Kaufmann et al. (2003) [42] | nineteen | Crossover | 'Severe OH' (MSA/PAF). All on fludrocortisone | 64 | 79 | L&South BP | Placebo | l-DOPS, variable, mean 1,137 mg | One time-off |
| Fludrocortisone or norfenefrine | |||||||||
| Campbell et al. (1975) [43] | 6 | Crossover | DM with autonomic neuropathy | 52 | 100 | Tilt table testing | Placebo BD | Fludrocortisone 0.one mg BD | 3/52 each |
| Volk and Stoll (1976) [44] | xiii | Parallel group | Psych inpatients, on neuroleptics/tri-cyclics | 37 | 46 | L&S BP. Graded how pathological: 1 (non); ii (slightly); 3 (moderately); 4 (severely) | Placebo 2 tab/day | Fludrocortisone 0.iii mg/mean solar day for ane/52, then 0.2 mg/day for one/52 (2 tabs each time) or norfenefrine 30 mg/day (2 tabs) | ii/52 each |
| Glypressin | |||||||||
| Rittig et al. (1991) [45] | 7 | Crossover | Parkinsonism with OH | 66 | 57 | Tilt tabular array testing | Placebo (4) | Glypressin 5 mcg/kg or 7.five mcg/kg or 10 mcg/kg (4) | Once-off |
| Indomethacin | |||||||||
| Abate et al. (1979) [ 46] | 12 | Not clear | Idiopathic Parkinsonism with OH | 72 | 58 | Not stated | Placebo TDS | Indomethacin fifty mg TDS | Unclear |
| Abate et al. (1980) [ 47] | 22 | ? crossover (not articulate) | 'Dizziness/fainting due to OH' | 76 | 68 | L&S BP | Placebo TDS | Indomethacin l mg TDS | 1/52 each |
| Midodrine | |||||||||
| Jankovic et al. (1993) [ 48] | 97 | Parallel group | Autonomic failure, mixed causes. Modernistic-to-sev OH | 61 | 55 | L&S BP | Placebo TDS | Midodrine 2.5 mg or v mg or 10 mg TDS | iv/52 each |
| Fouad-Tarazi et al. (1995) [ 49] | 8 | Crossover | Ane MSA, 7 idiopathic. No response other therapy | lx | 50 | L&S BP | Placebo TDS | Midodrine eight.four mg TDS (ephedrine arm) | four/7 placebo 6–10/7 midodrine |
| Depression and Vocalist (1997) [ fifty] | 162 | Parallel group | MSA/PD/DM/PAF | 59 | fifty | L&S BP | Placebo TDS | Midodrine 10 mg TDS | iii/52 each |
| Wright et al. (1997) [ 51] | 25 | Crossover | MSA/PD/DM/PAF | 62 | 44 | L&S BP | Placebo | Midodrine 2.v or 10 or 20 mg | Once-off |
| Octreotide | |||||||||
| Bordet et al. (1995) [52] | 9 | Crossover | MSA | 71 | 33 | Tilt tabular array testing | Placebo | Octreotide 100 mcg | Once-off |
| Oxilofrine | |||||||||
| Pohl and Kriech (1991) [ 53] | 59 | Parallel grouping | 'Orthostatic circulatory disorders' | 43 | 31 | L&Due south BP | Placebo TDS | Oxilofrine 32 mg TDS | 2/52 each |
| Pacing | |||||||||
| Sahul et al. (2004) [54] | 6 | Crossover | Autonomic dysfunction (PD/MSA/PAF/DM) | seventy | 17 | Tilt table testing | Unpaced (wire in situ) | Paced ninety or 110 bpm | Once-off |
| Pindolol | |||||||||
| Cleophas et al. (1986) [55] | 10 | Crossover | DM >twenty years. Demographics for eleven patients | 55 | 63 | Fifty&S BP | Placebo TDS | Pindolol five mg TDS | 1/52 each |
| Dejgard and Hilsted (1988) [56] | 8 | Crossover | T1DM with autonomic failure. | 47 | 50 | 50&S BP | Placebo TDS | Pindolol 5 mg TDS | 10/52 each |
| Potassium chloride (KCl) | |||||||||
| Heseltine et al. (1990) [ 57] | 10 | Crossover | Idiopathic OH | fourscore | threescore | Fifty&Due south BP | Placebo 30 ml daily | KCl 60 mmol (thirty ml) daily | four/52 each |
| Pyridostigmine [NB: two arms with midodrine; yohimbine arm (Shibao et al., 2010) reported beneath] | |||||||||
| Singer et al. (2006) [ 58] | 58 | Crossover | MSA/PAF/DM, autoimmune, unspecified | 59 | 52 | Fifty&Due south BP | Placebo | Pyridostigmine 60 mg, alone/with midodrine 2.5 or 5 mg | Once-off |
| Shibao et al. (2010) [ 59] | 31 | Crossover | 'Astringent OH' (PD/MSA/PAF) | 66 | 45 | Sitting and standing BP | Placebo | Pyridostigmine 60 mg | In one case-off |
| Sleeping head-upwards (SHU) | |||||||||
| Fan et al. (2011) [60] | 100 | Parallel group | 'Symptomatic OH' | 76 (Med) | 44 | Fifty&S BP | Advice only | SHU 5° (six in.) overnight and communication | 6/52 each |
| Xamoterol | |||||||||
| Leslie et al. (1991) [61] | 11 | Crossover | IDDM, autonomic neuropathy | 53 | 64 | L&S BP | Placebo BD | Xamoterol 200 mg BD | 4/52 each |
| Yohimbine [NB: pyridostigmine arm (Shibao et al., 2010) reported in a higher place] | |||||||||
| Des Lauriers et al. (1980), Lecrubier et al. (1981) [ 62, 63] | 12 | Parallel group (same data) | Psych inpatient, on clomipramine >v days | ? | ? | Fifty&S BP | Placebo TDS | Yohimbine 4 mg TDS | 1/52 each |
| Lacomblez et al. (1989) [ 64] | 12 | Crossover | Psych inpatients, on clomipramine 2–seven days | 44 | 25 | L&S BP | Placebo TDS | Yohimbine 4 mg TDS | iii days and 1 dose each |
| Shibao et al. (2010) [ 59] | 31 | Crossover | 'Severe OH' (PD/MSA/PAF) | 66 | 45 | Sitting and standing BP | Placebo | Yohimbine 5.4 mg | Once-off |
| Author (year) | northward | Study type | Population | Mean age | Sex activity (% M) | BP recording | Control | Intervention | Elapsing |
|---|---|---|---|---|---|---|---|---|---|
| Amezinium | |||||||||
| Belz et al. (1981) [28] | 12 | Crossover | 'Orthostatic dizziness' | 26 | 17 | Tilt table testing | Placebo | Amezinium 30 mg | In one case-off |
| Camphor-crataegus drupe combination (CCC); 1 drop = D-camphor 1 mg and Crataegus berry extract 38.92 mg | |||||||||
| Belz et al. (2002) [29] | 48 | Crossover | 'OH' (pooled information of two smaller trials) | 26 | 69 | Tilt table testing | Placebo 20 drops | CCC 5 drops or xx drops or 80 drops | Once-off on sugar cube |
| Kroll et al. (2005) [30] | 38 | Parallel group | 'OH' | 68 | 58 | L&Southward BP | Placebo 25 drops TDS | CCC 25 drops TDS | ane/52 each |
| Clonidine or nitroglycerin | |||||||||
| Shibao et al. (2006) [31] | 23 | Crossover (incomplete) | Primary autonomic failure (MSA/PAF) | 66 | 78 | L&S BP | Placebo tablet or patch | Clonidine 0.1 mg tab or Nitroglycerin 0.ane mg/h patch | Tab one time-off Patch 10 h |
| Compression bandages | |||||||||
| Podoleanu et al. (2006) [ 32] | 21 | Crossover | Progressive OH (no symptoms outset three min) | 70 | 43 | Tilt table testing | Sham bandages (5 mmHg talocrural joint and hip for 10 min. Abdo added last 10 min) | Agile bandages (twoscore–sixty mmHg ankles and 30–40 mmHg hips for ten min. twenty–30 mmHg abdo added concluding x min) | Once-off |
| Dihydroergotamine (DHE) and DHE Plus (with etilefrine) | |||||||||
| Lang (1976) [33] | 40 | Crossover | 'Nursing habitation residents with OH' | 59–88 | ? | 50&S BP | Placebo TDS | DHE 2 mg TDS | 2/52 each |
| Muth and Jansen (1980) [34] | 42 | Crossover | 'Old persons' hospital' | 75 | 45 | Fifty&S BP | Placebo TDS | DHE Plus (DHE 2 mg and etilefrine 20 mg) TDS | 2/52 placebo 8/52 DHE+ |
| Hamouz and Knaup (1983) [35] | thirty | Parallel group | Psych inpatients, on neuroleptic therapy | 48 | 37 | L&S BP | Placebo TDS | DHE Plus (DHE two mg and etilefrine xx mg) TDS | 2/52 each |
| Hoeldtke et al. (1986) [36] | viii | Crossover | OH due to DM/alcohol/idiopathic | 52 | 50 | 50&S BP | Placebo (sub-cut) | DHE half dozen.5 mcg/kg or 13 mcg/kg (sub-cutting) | One time-off |
| Thulesius and Berlin (1986) [37] | 58 | Parallel group | Psych inpatients, on neuroleptics/tri-cyclics | 55 | 50 | Fifty&S BP | Placebo BD | DHE five mg BD | 1/52 each |
| Dihydroxyphenylserine (l-DOPS and dl-DOPS) | |||||||||
| Hoeldtke et al. (1984) [38] | 6 | Crossover | 'Severe OH' (DM/idiopathic) | 35–81 | 83 | Fifty&S BP | Placebo | dl-DOPS 600 mg or 800 mg | Once-off |
| Freeman et al. (1999) [39] | ten | Crossover | 'Severe OH' (MSA/PAF) | 60 | 70 | Tilt tabular array testing | Placebo | dl-DOPS 1,000 mg | In one case-off |
| Akizawa et al. (2002) [forty] | 149 | Parallel grouping | Haemodialysis ×three/week | 62 | 48 | L&S BP post dialysis | Placebo, 30 min pre-HD | fifty-DOPS 200 mg or 400 mg, 30 min pre-Hard disk | 4/52 each |
| Iida et al. (2002) [41] | 86 | Parallel group | Haemodialysis ×3/week | sixty | 51 | L&South BP postal service dialysis | Placebo, xxx min pre-Hard disk | l-DOPS 400 mg 30 min pre-HD | 4/52 each |
| Kaufmann et al. (2003) [42] | nineteen | Crossover | 'Severe OH' (MSA/PAF). All on fludrocortisone | 64 | 79 | L&S BP | Placebo | l-DOPS, variable, mean 1,137 mg | One time-off |
| Fludrocortisone or norfenefrine | |||||||||
| Campbell et al. (1975) [43] | 6 | Crossover | DM with autonomic neuropathy | 52 | 100 | Tilt tabular array testing | Placebo BD | Fludrocortisone 0.1 mg BD | iii/52 each |
| Volk and Stoll (1976) [44] | 13 | Parallel group | Psych inpatients, on neuroleptics/tri-cyclics | 37 | 46 | Fifty&S BP. Graded how pathological: 1 (non); 2 (slightly); 3 (moderately); 4 (severely) | Placebo ii tab/solar day | Fludrocortisone 0.3 mg/solar day for 1/52, then 0.2 mg/mean solar day for ane/52 (two tabs each time) or norfenefrine 30 mg/day (2 tabs) | 2/52 each |
| Glypressin | |||||||||
| Rittig et al. (1991) [45] | 7 | Crossover | Parkinsonism with OH | 66 | 57 | Tilt table testing | Placebo (4) | Glypressin 5 mcg/kg or vii.5 mcg/kg or 10 mcg/kg (4) | Once-off |
| Indomethacin | |||||||||
| Abate et al. (1979) [ 46] | 12 | Not clear | Idiopathic Parkinsonism with OH | 72 | 58 | Non stated | Placebo TDS | Indomethacin 50 mg TDS | Unclear |
| Abate et al. (1980) [ 47] | 22 | ? crossover (not articulate) | 'Dizziness/fainting due to OH' | 76 | 68 | L&S BP | Placebo TDS | Indomethacin 50 mg TDS | 1/52 each |
| Midodrine | |||||||||
| Jankovic et al. (1993) [ 48] | 97 | Parallel grouping | Autonomic failure, mixed causes. Mod-to-sev OH | 61 | 55 | L&Due south BP | Placebo TDS | Midodrine two.five mg or 5 mg or 10 mg TDS | 4/52 each |
| Fouad-Tarazi et al. (1995) [ 49] | 8 | Crossover | I MSA, seven idiopathic. No response other therapy | 60 | 50 | Fifty&S BP | Placebo TDS | Midodrine viii.iv mg TDS (ephedrine arm) | iv/7 placebo 6–10/vii midodrine |
| Low and Singer (1997) [ 50] | 162 | Parallel group | MSA/PD/DM/PAF | 59 | 50 | L&S BP | Placebo TDS | Midodrine 10 mg TDS | iii/52 each |
| Wright et al. (1997) [ 51] | 25 | Crossover | MSA/PD/DM/PAF | 62 | 44 | L&S BP | Placebo | Midodrine 2.5 or 10 or xx mg | One time-off |
| Octreotide | |||||||||
| Bordet et al. (1995) [52] | nine | Crossover | MSA | 71 | 33 | Tilt table testing | Placebo | Octreotide 100 mcg | Once-off |
| Oxilofrine | |||||||||
| Pohl and Kriech (1991) [ 53] | 59 | Parallel group | 'Orthostatic circulatory disorders' | 43 | 31 | L&S BP | Placebo TDS | Oxilofrine 32 mg TDS | 2/52 each |
| Pacing | |||||||||
| Sahul et al. (2004) [54] | six | Crossover | Autonomic dysfunction (PD/MSA/PAF/DM) | seventy | 17 | Tilt table testing | Unpaced (wire in situ) | Paced xc or 110 bpm | Once-off |
| Pindolol | |||||||||
| Cleophas et al. (1986) [55] | 10 | Crossover | DM >20 years. Demographics for xi patients | 55 | 63 | 50&Due south BP | Placebo TDS | Pindolol 5 mg TDS | 1/52 each |
| Dejgard and Hilsted (1988) [56] | eight | Crossover | T1DM with autonomic failure. | 47 | fifty | L&Due south BP | Placebo TDS | Pindolol five mg TDS | 10/52 each |
| Potassium chloride (KCl) | |||||||||
| Heseltine et al. (1990) [ 57] | 10 | Crossover | Idiopathic OH | 80 | 60 | L&South BP | Placebo 30 ml daily | KCl threescore mmol (30 ml) daily | 4/52 each |
| Pyridostigmine [NB: two arms with midodrine; yohimbine arm (Shibao et al., 2010) reported below] | |||||||||
| Singer et al. (2006) [ 58] | 58 | Crossover | MSA/PAF/DM, autoimmune, unspecified | 59 | 52 | L&Southward BP | Placebo | Pyridostigmine 60 mg, lonely/with midodrine 2.five or 5 mg | Once-off |
| Shibao et al. (2010) [ 59] | 31 | Crossover | 'Severe OH' (PD/MSA/PAF) | 66 | 45 | Sitting and standing BP | Placebo | Pyridostigmine 60 mg | One time-off |
| Sleeping head-upward (SHU) | |||||||||
| Fan et al. (2011) [60] | 100 | Parallel group | 'Symptomatic OH' | 76 (Med) | 44 | L&S BP | Advice but | SHU 5° (half-dozen in.) overnight and advice | 6/52 each |
| Xamoterol | |||||||||
| Leslie et al. (1991) [61] | 11 | Crossover | IDDM, autonomic neuropathy | 53 | 64 | L&Southward BP | Placebo BD | Xamoterol 200 mg BD | 4/52 each |
| Yohimbine [NB: pyridostigmine arm (Shibao et al., 2010) reported higher up] | |||||||||
| Des Lauriers et al. (1980), Lecrubier et al. (1981) [ 62, 63] | 12 | Parallel group (same data) | Psych inpatient, on clomipramine >v days | ? | ? | 50&Southward BP | Placebo TDS | Yohimbine 4 mg TDS | 1/52 each |
| Lacomblez et al. (1989) [ 64] | 12 | Crossover | Psych inpatients, on clomipramine 2–7 days | 44 | 25 | L&Southward BP | Placebo TDS | Yohimbine 4 mg TDS | iii days and one dose each |
| Shibao et al. (2010) [ 59] | 31 | Crossover | 'Astringent OH' (PD/MSA/PAF) | 66 | 45 | Sitting and standing BP | Placebo | Yohimbine v.4 mg | Once-off |
L&S BP, lying and standing claret pressure level; OH; orthostatic hypotension; MSA, multiple system atrophy; PAF, pure autonomic failure; PD, Parkinson's disease; DM, diabetes mellitus; T1DM, blazon i diabetes mellitus; IDDM, insulin dependent diabetes mellitus (distinction not always made between these 3); 1/7, i twenty-four hour period; two/52, 2 weeks.
Table 1.
Participant characteristics and study design by therapy [28–64]
| Author (year) | n | Study type | Population | Hateful age | Sex (% Chiliad) | BP recording | Command | Intervention | Duration |
|---|---|---|---|---|---|---|---|---|---|
| Amezinium | |||||||||
| Belz et al. (1981) [28] | 12 | Crossover | 'Orthostatic dizziness' | 26 | 17 | Tilt table testing | Placebo | Amezinium thirty mg | Once-off |
| Camphor-crataegus drupe combination (CCC); i drop = D-camphor 1 mg and Crataegus berry extract 38.92 mg | |||||||||
| Belz et al. (2002) [29] | 48 | Crossover | 'OH' (pooled data of two smaller trials) | 26 | 69 | Tilt tabular array testing | Placebo 20 drops | CCC v drops or 20 drops or fourscore drops | Once-off on saccharide cube |
| Kroll et al. (2005) [30] | 38 | Parallel group | 'OH' | 68 | 58 | L&Due south BP | Placebo 25 drops TDS | CCC 25 drops TDS | one/52 each |
| Clonidine or nitroglycerin | |||||||||
| Shibao et al. (2006) [31] | 23 | Crossover (incomplete) | Chief autonomic failure (MSA/PAF) | 66 | 78 | L&S BP | Placebo tablet or patch | Clonidine 0.i mg tab or Nitroglycerin 0.1 mg/h patch | Tab one time-off Patch x h |
| Compression bandages | |||||||||
| Podoleanu et al. (2006) [ 32] | 21 | Crossover | Progressive OH (no symptoms first iii min) | lxx | 43 | Tilt table testing | Sham bandages (five mmHg ankle and hip for 10 min. Abdo added final 10 min) | Active bandages (40–60 mmHg ankles and 30–40 mmHg hips for x min. 20–xxx mmHg abdo added final x min) | Once-off |
| Dihydroergotamine (DHE) and DHE Plus (with etilefrine) | |||||||||
| Lang (1976) [33] | xl | Crossover | 'Nursing dwelling residents with OH' | 59–88 | ? | L&Due south BP | Placebo TDS | DHE 2 mg TDS | 2/52 each |
| Muth and Jansen (1980) [34] | 42 | Crossover | 'Old persons' hospital' | 75 | 45 | 50&S BP | Placebo TDS | DHE Plus (DHE 2 mg and etilefrine 20 mg) TDS | 2/52 placebo 8/52 DHE+ |
| Hamouz and Knaup (1983) [35] | 30 | Parallel grouping | Psych inpatients, on neuroleptic therapy | 48 | 37 | L&S BP | Placebo TDS | DHE Plus (DHE ii mg and etilefrine 20 mg) TDS | 2/52 each |
| Hoeldtke et al. (1986) [36] | 8 | Crossover | OH due to DM/alcohol/idiopathic | 52 | fifty | L&S BP | Placebo (sub-cut) | DHE 6.v mcg/kg or 13 mcg/kg (sub-cut) | One time-off |
| Thulesius and Berlin (1986) [37] | 58 | Parallel group | Psych inpatients, on neuroleptics/tri-cyclics | 55 | 50 | L&S BP | Placebo BD | DHE 5 mg BD | one/52 each |
| Dihydroxyphenylserine (l-DOPS and dl-DOPS) | |||||||||
| Hoeldtke et al. (1984) [38] | 6 | Crossover | 'Astringent OH' (DM/idiopathic) | 35–81 | 83 | Fifty&S BP | Placebo | dl-DOPS 600 mg or 800 mg | In one case-off |
| Freeman et al. (1999) [39] | 10 | Crossover | 'Severe OH' (MSA/PAF) | 60 | 70 | Tilt table testing | Placebo | dl-DOPS 1,000 mg | In one case-off |
| Akizawa et al. (2002) [40] | 149 | Parallel group | Haemodialysis ×3/week | 62 | 48 | L&S BP post dialysis | Placebo, 30 min pre-Hard disk | 50-DOPS 200 mg or 400 mg, 30 min pre-Hd | 4/52 each |
| Iida et al. (2002) [41] | 86 | Parallel group | Haemodialysis ×3/week | 60 | 51 | L&S BP postal service dialysis | Placebo, 30 min pre-HD | l-DOPS 400 mg 30 min pre-Hard disk | 4/52 each |
| Kaufmann et al. (2003) [42] | xix | Crossover | 'Severe OH' (MSA/PAF). All on fludrocortisone | 64 | 79 | Fifty&S BP | Placebo | 50-DOPS, variable, hateful 1,137 mg | In one case-off |
| Fludrocortisone or norfenefrine | |||||||||
| Campbell et al. (1975) [43] | half dozen | Crossover | DM with autonomic neuropathy | 52 | 100 | Tilt table testing | Placebo BD | Fludrocortisone 0.1 mg BD | three/52 each |
| Volk and Stoll (1976) [44] | 13 | Parallel group | Psych inpatients, on neuroleptics/tri-cyclics | 37 | 46 | L&S BP. Graded how pathological: 1 (non); 2 (slightly); iii (moderately); 4 (severely) | Placebo two tab/day | Fludrocortisone 0.3 mg/twenty-four hour period for ane/52, then 0.2 mg/twenty-four hour period for 1/52 (ii tabs each time) or norfenefrine 30 mg/day (two tabs) | ii/52 each |
| Glypressin | |||||||||
| Rittig et al. (1991) [45] | vii | Crossover | Parkinsonism with OH | 66 | 57 | Tilt table testing | Placebo (IV) | Glypressin v mcg/kg or 7.5 mcg/kg or 10 mcg/kg (4) | Once-off |
| Indomethacin | |||||||||
| Abate et al. (1979) [ 46] | 12 | Non articulate | Idiopathic Parkinsonism with OH | 72 | 58 | Not stated | Placebo TDS | Indomethacin 50 mg TDS | Unclear |
| Abate et al. (1980) [ 47] | 22 | ? crossover (non articulate) | 'Dizziness/fainting due to OH' | 76 | 68 | 50&S BP | Placebo TDS | Indomethacin 50 mg TDS | 1/52 each |
| Midodrine | |||||||||
| Jankovic et al. (1993) [ 48] | 97 | Parallel group | Autonomic failure, mixed causes. Modern-to-sev OH | 61 | 55 | 50&Due south BP | Placebo TDS | Midodrine ii.five mg or five mg or 10 mg TDS | 4/52 each |
| Fouad-Tarazi et al. (1995) [ 49] | 8 | Crossover | I MSA, seven idiopathic. No response other therapy | 60 | 50 | L&S BP | Placebo TDS | Midodrine 8.4 mg TDS (ephedrine arm) | four/7 placebo six–x/7 midodrine |
| Low and Singer (1997) [ 50] | 162 | Parallel group | MSA/PD/DM/PAF | 59 | 50 | L&S BP | Placebo TDS | Midodrine 10 mg TDS | 3/52 each |
| Wright et al. (1997) [ 51] | 25 | Crossover | MSA/PD/DM/PAF | 62 | 44 | L&South BP | Placebo | Midodrine 2.5 or ten or 20 mg | Once-off |
| Octreotide | |||||||||
| Bordet et al. (1995) [52] | ix | Crossover | MSA | 71 | 33 | Tilt table testing | Placebo | Octreotide 100 mcg | In one case-off |
| Oxilofrine | |||||||||
| Pohl and Kriech (1991) [ 53] | 59 | Parallel grouping | 'Orthostatic circulatory disorders' | 43 | 31 | L&S BP | Placebo TDS | Oxilofrine 32 mg TDS | 2/52 each |
| Pacing | |||||||||
| Sahul et al. (2004) [54] | 6 | Crossover | Autonomic dysfunction (PD/MSA/PAF/DM) | 70 | 17 | Tilt table testing | Unpaced (wire in situ) | Paced ninety or 110 bpm | Once-off |
| Pindolol | |||||||||
| Cleophas et al. (1986) [55] | ten | Crossover | DM >xx years. Demographics for eleven patients | 55 | 63 | 50&S BP | Placebo TDS | Pindolol 5 mg TDS | 1/52 each |
| Dejgard and Hilsted (1988) [56] | 8 | Crossover | T1DM with autonomic failure. | 47 | 50 | L&S BP | Placebo TDS | Pindolol 5 mg TDS | x/52 each |
| Potassium chloride (KCl) | |||||||||
| Heseltine et al. (1990) [ 57] | 10 | Crossover | Idiopathic OH | 80 | lx | L&S BP | Placebo 30 ml daily | KCl 60 mmol (30 ml) daily | four/52 each |
| Pyridostigmine [NB: two arms with midodrine; yohimbine arm (Shibao et al., 2010) reported beneath] | |||||||||
| Singer et al. (2006) [ 58] | 58 | Crossover | MSA/PAF/DM, autoimmune, unspecified | 59 | 52 | Fifty&Due south BP | Placebo | Pyridostigmine lx mg, alone/with midodrine 2.5 or v mg | In one case-off |
| Shibao et al. (2010) [ 59] | 31 | Crossover | 'Astringent OH' (PD/MSA/PAF) | 66 | 45 | Sitting and standing BP | Placebo | Pyridostigmine 60 mg | In one case-off |
| Sleeping head-up (SHU) | |||||||||
| Fan et al. (2011) [sixty] | 100 | Parallel group | 'Symptomatic OH' | 76 (Med) | 44 | L&S BP | Advice merely | SHU 5° (6 in.) overnight and advice | 6/52 each |
| Xamoterol | |||||||||
| Leslie et al. (1991) [61] | 11 | Crossover | IDDM, autonomic neuropathy | 53 | 64 | 50&Due south BP | Placebo BD | Xamoterol 200 mg BD | 4/52 each |
| Yohimbine [NB: pyridostigmine arm (Shibao et al., 2010) reported above] | |||||||||
| Des Lauriers et al. (1980), Lecrubier et al. (1981) [ 62, 63] | 12 | Parallel group (same data) | Psych inpatient, on clomipramine >5 days | ? | ? | 50&Southward BP | Placebo TDS | Yohimbine four mg TDS | 1/52 each |
| Lacomblez et al. (1989) [ 64] | 12 | Crossover | Psych inpatients, on clomipramine two–7 days | 44 | 25 | Fifty&S BP | Placebo TDS | Yohimbine iv mg TDS | iii days and one dose each |
| Shibao et al. (2010) [ 59] | 31 | Crossover | 'Severe OH' (PD/MSA/PAF) | 66 | 45 | Sitting and continuing BP | Placebo | Yohimbine 5.4 mg | Once-off |
| Author (twelvemonth) | n | Study type | Population | Mean age | Sex (% K) | BP recording | Control | Intervention | Duration |
|---|---|---|---|---|---|---|---|---|---|
| Amezinium | |||||||||
| Belz et al. (1981) [28] | 12 | Crossover | 'Orthostatic dizziness' | 26 | 17 | Tilt table testing | Placebo | Amezinium 30 mg | Once-off |
| Camphor-crataegus drupe combination (CCC); ane drop = D-camphor 1 mg and Crataegus berry extract 38.92 mg | |||||||||
| Belz et al. (2002) [29] | 48 | Crossover | 'OH' (pooled information of ii smaller trials) | 26 | 69 | Tilt table testing | Placebo 20 drops | CCC 5 drops or xx drops or 80 drops | Once-off on sugar cube |
| Kroll et al. (2005) [xxx] | 38 | Parallel grouping | 'OH' | 68 | 58 | L&S BP | Placebo 25 drops TDS | CCC 25 drops TDS | 1/52 each |
| Clonidine or nitroglycerin | |||||||||
| Shibao et al. (2006) [31] | 23 | Crossover (incomplete) | Chief autonomic failure (MSA/PAF) | 66 | 78 | L&Due south BP | Placebo tablet or patch | Clonidine 0.1 mg tab or Nitroglycerin 0.1 mg/h patch | Tab once-off Patch ten h |
| Compression bandages | |||||||||
| Podoleanu et al. (2006) [ 32] | 21 | Crossover | Progressive OH (no symptoms showtime 3 min) | seventy | 43 | Tilt tabular array testing | Sham bandages (5 mmHg ankle and hip for x min. Abdo added last 10 min) | Active bandages (40–60 mmHg ankles and 30–40 mmHg hips for 10 min. 20–30 mmHg abdo added last x min) | Once-off |
| Dihydroergotamine (DHE) and DHE Plus (with etilefrine) | |||||||||
| Lang (1976) [33] | 40 | Crossover | 'Nursing home residents with OH' | 59–88 | ? | L&S BP | Placebo TDS | DHE 2 mg TDS | 2/52 each |
| Muth and Jansen (1980) [34] | 42 | Crossover | 'Old persons' hospital' | 75 | 45 | 50&S BP | Placebo TDS | DHE Plus (DHE 2 mg and etilefrine xx mg) TDS | 2/52 placebo 8/52 DHE+ |
| Hamouz and Knaup (1983) [35] | 30 | Parallel group | Psych inpatients, on neuroleptic therapy | 48 | 37 | Fifty&S BP | Placebo TDS | DHE Plus (DHE 2 mg and etilefrine twenty mg) TDS | two/52 each |
| Hoeldtke et al. (1986) [36] | 8 | Crossover | OH due to DM/alcohol/idiopathic | 52 | 50 | L&S BP | Placebo (sub-cutting) | DHE 6.5 mcg/kg or 13 mcg/kg (sub-cutting) | Once-off |
| Thulesius and Berlin (1986) [37] | 58 | Parallel group | Psych inpatients, on neuroleptics/tri-cyclics | 55 | 50 | L&S BP | Placebo BD | DHE 5 mg BD | 1/52 each |
| Dihydroxyphenylserine (l-DOPS and dl-DOPS) | |||||||||
| Hoeldtke et al. (1984) [38] | 6 | Crossover | 'Severe OH' (DM/idiopathic) | 35–81 | 83 | Fifty&S BP | Placebo | dl-DOPS 600 mg or 800 mg | Once-off |
| Freeman et al. (1999) [39] | x | Crossover | 'Astringent OH' (MSA/PAF) | threescore | seventy | Tilt table testing | Placebo | dl-DOPS 1,000 mg | Once-off |
| Akizawa et al. (2002) [40] | 149 | Parallel grouping | Haemodialysis ×3/week | 62 | 48 | L&S BP post dialysis | Placebo, 30 min pre-HD | fifty-DOPS 200 mg or 400 mg, thirty min pre-Hard disk drive | 4/52 each |
| Iida et al. (2002) [41] | 86 | Parallel grouping | Haemodialysis ×3/calendar week | sixty | 51 | L&Due south BP post dialysis | Placebo, 30 min pre-Hard disk | l-DOPS 400 mg xxx min pre-Hard disk drive | 4/52 each |
| Kaufmann et al. (2003) [42] | 19 | Crossover | 'Severe OH' (MSA/PAF). All on fludrocortisone | 64 | 79 | 50&Due south BP | Placebo | l-DOPS, variable, mean 1,137 mg | Once-off |
| Fludrocortisone or norfenefrine | |||||||||
| Campbell et al. (1975) [43] | 6 | Crossover | DM with autonomic neuropathy | 52 | 100 | Tilt tabular array testing | Placebo BD | Fludrocortisone 0.ane mg BD | iii/52 each |
| Volk and Stoll (1976) [44] | 13 | Parallel group | Psych inpatients, on neuroleptics/tri-cyclics | 37 | 46 | L&S BP. Graded how pathological: ane (not); 2 (slightly); 3 (moderately); 4 (severely) | Placebo 2 tab/mean solar day | Fludrocortisone 0.iii mg/24-hour interval for 1/52, then 0.2 mg/solar day for i/52 (2 tabs each fourth dimension) or norfenefrine thirty mg/day (2 tabs) | 2/52 each |
| Glypressin | |||||||||
| Rittig et al. (1991) [45] | 7 | Crossover | Parkinsonism with OH | 66 | 57 | Tilt table testing | Placebo (IV) | Glypressin 5 mcg/kg or 7.5 mcg/kg or x mcg/kg (4) | Once-off |
| Indomethacin | |||||||||
| Abate et al. (1979) [ 46] | 12 | Not clear | Idiopathic Parkinsonism with OH | 72 | 58 | Not stated | Placebo TDS | Indomethacin 50 mg TDS | Unclear |
| Allay et al. (1980) [ 47] | 22 | ? crossover (not clear) | 'Dizziness/fainting due to OH' | 76 | 68 | L&S BP | Placebo TDS | Indomethacin 50 mg TDS | 1/52 each |
| Midodrine | |||||||||
| Jankovic et al. (1993) [ 48] | 97 | Parallel group | Autonomic failure, mixed causes. Modern-to-sev OH | 61 | 55 | L&S BP | Placebo TDS | Midodrine 2.5 mg or five mg or 10 mg TDS | 4/52 each |
| Fouad-Tarazi et al. (1995) [ 49] | eight | Crossover | One MSA, seven idiopathic. No response other therapy | lx | fifty | L&S BP | Placebo TDS | Midodrine 8.4 mg TDS (ephedrine arm) | iv/seven placebo half dozen–10/vii midodrine |
| Low and Vocalist (1997) [ 50] | 162 | Parallel group | MSA/PD/DM/PAF | 59 | 50 | Fifty&S BP | Placebo TDS | Midodrine x mg TDS | 3/52 each |
| Wright et al. (1997) [ 51] | 25 | Crossover | MSA/PD/DM/PAF | 62 | 44 | L&Southward BP | Placebo | Midodrine 2.5 or ten or 20 mg | Once-off |
| Octreotide | |||||||||
| Bordet et al. (1995) [52] | 9 | Crossover | MSA | 71 | 33 | Tilt table testing | Placebo | Octreotide 100 mcg | Once-off |
| Oxilofrine | |||||||||
| Pohl and Kriech (1991) [ 53] | 59 | Parallel group | 'Orthostatic circulatory disorders' | 43 | 31 | 50&S BP | Placebo TDS | Oxilofrine 32 mg TDS | 2/52 each |
| Pacing | |||||||||
| Sahul et al. (2004) [54] | 6 | Crossover | Autonomic dysfunction (PD/MSA/PAF/DM) | 70 | 17 | Tilt table testing | Unpaced (wire in situ) | Paced 90 or 110 bpm | Once-off |
| Pindolol | |||||||||
| Cleophas et al. (1986) [55] | x | Crossover | DM >20 years. Demographics for 11 patients | 55 | 63 | 50&S BP | Placebo TDS | Pindolol 5 mg TDS | 1/52 each |
| Dejgard and Hilsted (1988) [56] | eight | Crossover | T1DM with autonomic failure. | 47 | 50 | L&S BP | Placebo TDS | Pindolol five mg TDS | 10/52 each |
| Potassium chloride (KCl) | |||||||||
| Heseltine et al. (1990) [ 57] | 10 | Crossover | Idiopathic OH | eighty | threescore | L&South BP | Placebo 30 ml daily | KCl sixty mmol (30 ml) daily | 4/52 each |
| Pyridostigmine [NB: two arms with midodrine; yohimbine arm (Shibao et al., 2010) reported below] | |||||||||
| Vocalizer et al. (2006) [ 58] | 58 | Crossover | MSA/PAF/DM, autoimmune, unspecified | 59 | 52 | L&S BP | Placebo | Pyridostigmine 60 mg, solitary/with midodrine 2.5 or 5 mg | One time-off |
| Shibao et al. (2010) [ 59] | 31 | Crossover | 'Astringent OH' (PD/MSA/PAF) | 66 | 45 | Sitting and standing BP | Placebo | Pyridostigmine 60 mg | Once-off |
| Sleeping head-up (SHU) | |||||||||
| Fan et al. (2011) [threescore] | 100 | Parallel group | 'Symptomatic OH' | 76 (Med) | 44 | L&S BP | Advice only | SHU 5° (6 in.) overnight and communication | half-dozen/52 each |
| Xamoterol | |||||||||
| Leslie et al. (1991) [61] | 11 | Crossover | IDDM, autonomic neuropathy | 53 | 64 | L&S BP | Placebo BD | Xamoterol 200 mg BD | four/52 each |
| Yohimbine [NB: pyridostigmine arm (Shibao et al., 2010) reported above] | |||||||||
| Des Lauriers et al. (1980), Lecrubier et al. (1981) [ 62, 63] | 12 | Parallel grouping (aforementioned data) | Psych inpatient, on clomipramine >5 days | ? | ? | L&S BP | Placebo TDS | Yohimbine 4 mg TDS | 1/52 each |
| Lacomblez et al. (1989) [ 64] | 12 | Crossover | Psych inpatients, on clomipramine ii–vii days | 44 | 25 | 50&Southward BP | Placebo TDS | Yohimbine 4 mg TDS | 3 days and 1 dose each |
| Shibao et al. (2010) [ 59] | 31 | Crossover | 'Severe OH' (PD/MSA/PAF) | 66 | 45 | Sitting and standing BP | Placebo | Yohimbine 5.4 mg | Once-off |
L&S BP, lying and continuing blood pressure; OH; orthostatic hypotension; MSA, multiple system atrophy; PAF, pure autonomic failure; PD, Parkinson's disease; DM, diabetes mellitus; T1DM, type i diabetes mellitus; IDDM, insulin dependent diabetes mellitus (distinction non always made betwixt these iii); 1/7, ane twenty-four hour period; 2/52, 2 weeks.
Study quality
The quality of study blueprint and reporting was variable: randomisation artillery were well balanced in 22/36 (61%) of trials; randomisation was well-described in only 3/36 (8%) and stated in thirty/36 (83%) [with a gamble of disclosure in 5/30 (17%) of these]; patient blinding was effectively described in 12/36 (33%) of trials, and but stated in a farther 18/36 (50%); staff blinding was effectively described in just 5/36 (xiv%) of studies, and stated in a further 23/36 (64%); 13/36 (36%) of trials analysed data on an intention to care for basis, whereas 13/36 (36%) did non, and it was unclear in 10/36 (28%); 12/36 (33%) of studies detailed their withdrawals, whereas 20/36 (56%) fabricated no mention of withdrawals. Tabular array2 specifies the overall GRADE quality of evidence score for each intervention, and details how each score was reached.
Table ii.
Commentary on effect on postural drib and symptoms, comparing active arm to placebo arm [28– 64]
| Treatment | Studies (n) | Patients (n) | Effect on postural drop (active versus placebo) | Result on symptoms (active versus placebo) | Class quality of evidence [ 27] |
|---|---|---|---|---|---|
| Amezinium [28] | 1 | 12 | Worsened | ? | Moderate (§) |
| Camphor-crataegus berry compound (CCC) [29, thirty] | two | 86 | No effect | ? | Very depression (**, ‡) |
| No effect | Variable outcome | ||||
| Clonidine [31] | 1 | 23 | Pocket-sized improvement | ? | Very low (**, §) |
| Compression bandages [ 32] | 1 | 21 | Significant improvement | Pregnant comeback | Very depression (**, §) |
| Dihydroergotamine (DHE/DHE Plus) [33–37] | 5 | 178 | Significant improvement | Significant improvement | Very depression (**, †, ‡, §) |
| Minor improvement | Minor improvement | ||||
| Modest improvement | No effect | ||||
| Insufficient data | No upshot | ||||
| No effect | ? | ||||
| Dihydroxyphenylserine (l-DOPS/dl-DOPS) [38–42] | 5 | 270 | No effect/minor improvement | ? | Very low (*, †, ‡, §) |
| Minor comeback | No effect | ||||
| Bereft data | Variable effect | ||||
| No effect | Minor improvement | ||||
| No event | ? | ||||
| Fludrocortisone [43, 44] | 2 | 19 | Insufficient data | ? | Very low (*, ‡, §) |
| Bereft information | ? | ||||
| Glypressin [45] | i | 7 | Worsened | ? | Very depression (**, §) |
| Indomethacin [ 46, 47] | 2 | 34 | Significant improvement | ? | Low (*, §) |
| Significant improvement | ? | ||||
| Midodrine [ 48–51] | 4 | 292 | Worsened | Variable upshot | Very low (*, †, ‡, §) |
| No effect | Small improvement | ||||
| No issue | No effect | ||||
| Worsened | Variable effect | ||||
| Nitroglycerine [31] | 1 | 23 | No result | ? | Very low (**, §) |
| Norfenefrine [44] | 1 | 13 | Insufficient data | ? | Low (*, §) |
| Octreotide [52] | 1 | 9 | Worsened | ? | Moderate (§) |
| Oxilofrine [ 53] | 1 | 59 | Pregnant comeback | Variable effect | Moderate (*) |
| Pacing [54] | 1 | half dozen | Insufficient information | No effect | Very low (**, §) |
| Pindolol [55, 56] | two | 18 | Insufficient information | Minor improvement | Low (*, §) |
| No issue | No effect | ||||
| Potassium chloride [ 57] | 1 | 10 | Meaning comeback | Significant improvement | Low (*, §) |
| Pyridostigmine [ 58, 59] | 2 | 89 | Worsened | ? | Very low (**, †) |
| No effect | Worsened | ||||
| Sleeping head-upwards [lx] | 1 | 100 | Minor improvement | No effect | Moderate (*) |
| Xamoterol [61] | 1 | eleven | Worsened | ? | Moderate (§) |
| Yohimbine [ 59, 62–64] | three | 55 | Significant improvement | Pocket-sized improvement | Very low (**, †, ‡, §) |
| Pregnant comeback | No event (both worsened) | ||||
| Pocket-size improvement (only diastolic BP given) | Small-scale comeback |
| Handling | Studies (n) | Patients (n) | Effect on postural driblet (active versus placebo) | Effect on symptoms (active versus placebo) | GRADE quality of evidence [ 27] |
|---|---|---|---|---|---|
| Amezinium [28] | 1 | 12 | Worsened | ? | Moderate (§) |
| Camphor-crataegus berry compound (CCC) [29, 30] | ii | 86 | No consequence | ? | Very low (**, ‡) |
| No issue | Variable issue | ||||
| Clonidine [31] | 1 | 23 | Minor improvement | ? | Very low (**, §) |
| Pinch bandages [ 32] | 1 | 21 | Significant improvement | Significant improvement | Very low (**, §) |
| Dihydroergotamine (DHE/DHE Plus) [33–37] | v | 178 | Significant improvement | Significant improvement | Very low (**, †, ‡, §) |
| Minor improvement | Small-scale improvement | ||||
| Minor improvement | No consequence | ||||
| Insufficient data | No event | ||||
| No issue | ? | ||||
| Dihydroxyphenylserine (l-DOPS/dl-DOPS) [38–42] | 5 | 270 | No effect/pocket-size improvement | ? | Very low (*, †, ‡, §) |
| Small-scale comeback | No outcome | ||||
| Insufficient data | Variable issue | ||||
| No effect | Minor improvement | ||||
| No effect | ? | ||||
| Fludrocortisone [43, 44] | 2 | 19 | Insufficient information | ? | Very low (*, ‡, §) |
| Insufficient data | ? | ||||
| Glypressin [45] | 1 | seven | Worsened | ? | Very low (**, §) |
| Indomethacin [ 46, 47] | 2 | 34 | Pregnant improvement | ? | Low (*, §) |
| Pregnant improvement | ? | ||||
| Midodrine [ 48–51] | 4 | 292 | Worsened | Variable effect | Very low (*, †, ‡, §) |
| No consequence | Minor comeback | ||||
| No event | No effect | ||||
| Worsened | Variable upshot | ||||
| Nitroglycerine [31] | 1 | 23 | No outcome | ? | Very low (**, §) |
| Norfenefrine [44] | 1 | thirteen | Insufficient data | ? | Low (*, §) |
| Octreotide [52] | 1 | ix | Worsened | ? | Moderate (§) |
| Oxilofrine [ 53] | one | 59 | Significant improvement | Variable event | Moderate (*) |
| Pacing [54] | 1 | 6 | Insufficient data | No effect | Very low (**, §) |
| Pindolol [55, 56] | 2 | 18 | Bereft data | Minor improvement | Low (*, §) |
| No outcome | No event | ||||
| Potassium chloride [ 57] | 1 | ten | Significant improvement | Pregnant improvement | Low (*, §) |
| Pyridostigmine [ 58, 59] | 2 | 89 | Worsened | ? | Very depression (**, †) |
| No effect | Worsened | ||||
| Sleeping head-up [60] | 1 | 100 | Pocket-sized improvement | No upshot | Moderate (*) |
| Xamoterol [61] | 1 | 11 | Worsened | ? | Moderate (§) |
| Yohimbine [ 59, 62–64] | iii | 55 | Pregnant improvement | Pocket-size improvement | Very depression (**, †, ‡, §) |
| Significant improvement | No effect (both worsened) | ||||
| Minor improvement (simply diastolic BP given) | Pocket-size improvement |
For the postural driblet: no consequence, inverse drib past −4 to +4 mmHg; minor comeback, reduced drop by five–ix mmHg; significant improvement, reduced drop past x mmHg or more; worsened, increased drib by 5 mmHg or more; insufficient data, baseline drib not bachelor. For symptoms statements are subjective assessments of how agile arm compared with the placebo arm. No mention of symptom change or inadequate data to comment recorded as '?'. GRADE cess: * serious written report limitations; ** very serious study limitations; † inconsistent results; ‡ indirectness of testify; § imprecision. No bear witness of publication bias was identified.
Table 2.
Commentary on outcome on postural drop and symptoms, comparing active arm to placebo arm [28– 64]
| Treatment | Studies (n) | Patients (n) | Effect on postural drop (active versus placebo) | Effect on symptoms (active versus placebo) | GRADE quality of evidence [ 27] |
|---|---|---|---|---|---|
| Amezinium [28] | one | 12 | Worsened | ? | Moderate (§) |
| Camphor-crataegus berry compound (CCC) [29, thirty] | two | 86 | No effect | ? | Very depression (**, ‡) |
| No effect | Variable effect | ||||
| Clonidine [31] | 1 | 23 | Small improvement | ? | Very depression (**, §) |
| Compression bandages [ 32] | 1 | 21 | Significant improvement | Meaning comeback | Very low (**, §) |
| Dihydroergotamine (DHE/DHE Plus) [33–37] | five | 178 | Significant improvement | Pregnant improvement | Very low (**, †, ‡, §) |
| Modest improvement | Small-scale comeback | ||||
| Minor improvement | No effect | ||||
| Insufficient information | No effect | ||||
| No result | ? | ||||
| Dihydroxyphenylserine (l-DOPS/dl-DOPS) [38–42] | 5 | 270 | No effect/minor improvement | ? | Very low (*, †, ‡, §) |
| Minor improvement | No effect | ||||
| Insufficient data | Variable issue | ||||
| No effect | Minor comeback | ||||
| No effect | ? | ||||
| Fludrocortisone [43, 44] | 2 | xix | Insufficient data | ? | Very low (*, ‡, §) |
| Insufficient data | ? | ||||
| Glypressin [45] | ane | 7 | Worsened | ? | Very depression (**, §) |
| Indomethacin [ 46, 47] | two | 34 | Meaning comeback | ? | Low (*, §) |
| Significant improvement | ? | ||||
| Midodrine [ 48–51] | 4 | 292 | Worsened | Variable outcome | Very low (*, †, ‡, §) |
| No effect | Minor comeback | ||||
| No event | No effect | ||||
| Worsened | Variable outcome | ||||
| Nitroglycerine [31] | i | 23 | No event | ? | Very low (**, §) |
| Norfenefrine [44] | 1 | thirteen | Insufficient data | ? | Depression (*, §) |
| Octreotide [52] | one | nine | Worsened | ? | Moderate (§) |
| Oxilofrine [ 53] | 1 | 59 | Significant comeback | Variable consequence | Moderate (*) |
| Pacing [54] | 1 | 6 | Insufficient data | No effect | Very depression (**, §) |
| Pindolol [55, 56] | two | 18 | Insufficient data | Pocket-sized comeback | Depression (*, §) |
| No effect | No consequence | ||||
| Potassium chloride [ 57] | i | 10 | Pregnant improvement | Significant improvement | Low (*, §) |
| Pyridostigmine [ 58, 59] | ii | 89 | Worsened | ? | Very low (**, †) |
| No outcome | Worsened | ||||
| Sleeping head-up [threescore] | 1 | 100 | Modest comeback | No result | Moderate (*) |
| Xamoterol [61] | 1 | 11 | Worsened | ? | Moderate (§) |
| Yohimbine [ 59, 62–64] | 3 | 55 | Significant comeback | Minor comeback | Very low (**, †, ‡, §) |
| Meaning comeback | No effect (both worsened) | ||||
| Minor improvement (only diastolic BP given) | Minor improvement |
| Handling | Studies (northward) | Patients (n) | Result on postural driblet (agile versus placebo) | Effect on symptoms (active versus placebo) | Course quality of evidence [ 27] |
|---|---|---|---|---|---|
| Amezinium [28] | i | 12 | Worsened | ? | Moderate (§) |
| Camphor-crataegus berry compound (CCC) [29, 30] | two | 86 | No effect | ? | Very low (**, ‡) |
| No effect | Variable effect | ||||
| Clonidine [31] | 1 | 23 | Pocket-sized improvement | ? | Very depression (**, §) |
| Compression bandages [ 32] | ane | 21 | Significant comeback | Meaning improvement | Very low (**, §) |
| Dihydroergotamine (DHE/DHE Plus) [33–37] | 5 | 178 | Meaning comeback | Significant improvement | Very depression (**, †, ‡, §) |
| Pocket-sized improvement | Minor comeback | ||||
| Minor improvement | No upshot | ||||
| Bereft data | No effect | ||||
| No effect | ? | ||||
| Dihydroxyphenylserine (fifty-DOPS/dl-DOPS) [38–42] | five | 270 | No outcome/minor improvement | ? | Very low (*, †, ‡, §) |
| Minor comeback | No issue | ||||
| Bereft data | Variable effect | ||||
| No result | Minor improvement | ||||
| No effect | ? | ||||
| Fludrocortisone [43, 44] | 2 | 19 | Insufficient data | ? | Very low (*, ‡, §) |
| Insufficient information | ? | ||||
| Glypressin [45] | 1 | seven | Worsened | ? | Very depression (**, §) |
| Indomethacin [ 46, 47] | 2 | 34 | Significant improvement | ? | Low (*, §) |
| Meaning improvement | ? | ||||
| Midodrine [ 48–51] | 4 | 292 | Worsened | Variable result | Very depression (*, †, ‡, §) |
| No event | Small-scale improvement | ||||
| No effect | No issue | ||||
| Worsened | Variable effect | ||||
| Nitroglycerine [31] | 1 | 23 | No effect | ? | Very low (**, §) |
| Norfenefrine [44] | one | 13 | Insufficient data | ? | Low (*, §) |
| Octreotide [52] | ane | 9 | Worsened | ? | Moderate (§) |
| Oxilofrine [ 53] | 1 | 59 | Meaning improvement | Variable consequence | Moderate (*) |
| Pacing [54] | 1 | six | Insufficient data | No upshot | Very low (**, §) |
| Pindolol [55, 56] | 2 | 18 | Insufficient data | Modest improvement | Low (*, §) |
| No effect | No issue | ||||
| Potassium chloride [ 57] | 1 | x | Significant improvement | Pregnant improvement | Depression (*, §) |
| Pyridostigmine [ 58, 59] | 2 | 89 | Worsened | ? | Very low (**, †) |
| No effect | Worsened | ||||
| Sleeping head-upwards [60] | 1 | 100 | Pocket-size improvement | No upshot | Moderate (*) |
| Xamoterol [61] | 1 | 11 | Worsened | ? | Moderate (§) |
| Yohimbine [ 59, 62–64] | iii | 55 | Meaning improvement | Minor improvement | Very low (**, †, ‡, §) |
| Pregnant improvement | No effect (both worsened) | ||||
| Minor improvement (only diastolic BP given) | Modest improvement |
For the postural drib: no effect, changed drop by −4 to +4 mmHg; minor comeback, reduced drop by v–9 mmHg; significant improvement, reduced driblet by 10 mmHg or more; worsened, increased driblet by five mmHg or more; insufficient data, baseline driblet not available. For symptoms statements are subjective assessments of how active arm compared with the placebo arm. No mention of symptom alter or inadequate information to comment recorded equally '?'. Class cess: * serious written report limitations; ** very serious report limitations; † inconsistent results; ‡ indirectness of testify; § imprecision. No bear witness of publication bias was identified.
Effect on postural driblet
Details and specific figures for the event of each intervention on the lying and standing claret pressure, and the postural drop, are given in Supplementary data (Appendix one) available at Age and Ageing online. A single baseline value is given for two or more artillery in studies where private measurements were not available for each arm separately. The overall effect for each intervention is summarised in Tabular array2.
Clonidine and sleeping caput-upwardly produced minor improvements in the postural drop (although the postural drop with clonidine remained very large). The following therapies consistently produced an improvement in postural drop of greater than 10 mmHg: compression bandages; indomethacin; oxilofrine; potassium chloride; and yohimbine. Both midodrine and pyridostigmine displayed an inconsistent trend towards worsening of the postural drop. The following therapies consistently resulted in worsening of the postural drop: amezinium; glypressin; octreotide; and xamoterol. Those interventions that worsened the postural drop tended to do and so by raising the lying claret pressure level considerably more than the standing claret force per unit area, with the overall issue of widening the gap between the two.
It is important to acknowledge that many of the included trials are pocket-size in size and lack long-term follow-up data. With this in mind, it is difficult to depict potent positive conclusions nearly whatsoever of the interventions examined in this review.
Consequence on symptoms
A variety of methods for recording changes in participants' symptoms were used throughout the included trials, making comparison between interventions difficult. Specific details are given in Supplementary data (Appendix i) bachelor at Age and Ageing online. This information is also summarised in Table2. A total of fourteen trials either did not examine symptoms or did not publish responses for both arms. The following therapies had insufficient information to comment on their outcome on symptoms: fludrocortisone; indomethacin; glypressin; clonidine; nitroglycerine; amezinium; xamoterol; and octreotide. Neither pacing nor sleeping head-up had any impact on symptoms. There was an inconsistent trend towards improvement with the post-obit interventions: midodrine; dihydroxyphenylserine; dihydrergotamine; pindolol; oxilofrine; and camphor-crataegus berry compound. A pocket-sized improvement in symptoms was seen in two trials of yohimbine, although another reported worsening of symptoms in both arms. Both compression bandages and potassium chloride resulted in a meaning improvement in symptoms. I trial of pyridostigmine reported a worsening of symptoms with intervention, whereas another was unclear—the changes in symptoms were given at merely i h postal service-dose. No trials commented on functional ability and few used validated tools for assessing changes in quality of life.
Side effects and adverse events
The majority of studies (22 of the 36) either did not comment on side effects and adverse events, or commented on simply the active arm. The trials that did comment often gave results that conflicted with each other. Details are given in Supplementary data (Appendix 1) available at Age and Ageing online.
Word
Key findings
This systematic review demonstrates that several common treatments for OH have not been examined in randomised, placebo-controlled trials. These include: drinking water; increasing salt intake; and discontinuing antihypertensives. In addition, a number of interventions that frequently appear in guidelines take either no issue on the postural fall in blood pressure, or even worsen the fall in blood force per unit area. Changes in postural fall in blood pressure (whether an improvement or deterioration) are ofttimes not associated with a corresponding change in symptoms. In that location are very few information on how treatments affect functional ability, and few trials examine quality of life.
Strengths and weaknesses
Equally with any systematic review, it is possible that non all relevant published or unpublished studies were identified by the search strategy. However, we were able to obtain all papers that were deemed advisable for the review, including those published in not-English languages (eight non-English language articles were included in the terminal review). The strength of our findings is express past small written report size, variable quality of written report design, and heterogeneity of participants, interventions and measured outcomes. Any positive results should therefore exist interpreted with caution, specially when information on symptom change, quality of life and functional power is lacking. The considerable age of many of the studies made it impractical for us to obtain further information not bachelor in the printed papers. Additionally, using results from trials of once-off intervention to influence routine clinical do is problematic, peculiarly in relation to symptoms. More than positively, we investigated a wide range of interventions, and did non exclude foreign language studies, thus assuasive us to capture as much of the available literature as possible. For this review, we accept concentrated on changes in the postural drib (given that this is the measure out used to make the diagnosis of OH), but it may be that other consequence measures are every bit valid; farther enquiry is needed to establish which measure best correlates with symptoms and quality of life in OH.
Study findings in context
The range of patient groups studied in the included papers confirms that OH is not a single affliction procedure, but rather a symptom or sign to be found in a diverseness of unlike illnesses and age groups. Few trials take concentrated on participants without autonomic failure, which may limit the generalisability of any results to the large number of sufferers who do not have autonomic failure, e.g. older adults with generalised vascular disease [ 20, 65, 66]. It may exist that these individuals require a different approach to managing their condition, and mayhap measures to improve cardiovascular health and role merit investigation.
This review should highlight to clinicians that many of the usually recommended therapeutic interventions for OH do non accept a large, high-quality bear witness base of operations to support their use. Additionally, the evidence base from which electric current guidelines are written is of poor quality. It may exist that doctors with an interest in looking afterward older people with OH would wish to re-evaluate their own practice in view of the findings of this review. Information technology is difficult for the authors to brand any strong recommendations in calorie-free of the findings of the review.
The paucity of big, high-quality RCTs confirms that OH remains very much an underinvestigated condition. We would recommend that clinicians who expect later patients with OH should actively try to enrol their patients in trials that seek to better understand the nature of this complex condition, and how best it should be managed.
Conclusion
There is a lack of good quality, randomised, placebo-controlled trials to requite firm guidance on how best to manage OH. Several unremarkably recommended treatments have not been subjected to rigorous investigation, and of those that have, some may actually worsen the postural fall in blood pressure level. There is also limited information on how therapies bear upon symptoms.
Large, well-designed, randomised, placebo-controlled trials that focus on changes in lying and standing blood pressure level, postural driblet, symptoms, quality of life and functional power are required. There is a need to establish whether currently accepted treatments are effective, too as testing novel approaches. Until this piece of work is undertaken, it remains unclear how best to treat those individuals affected past this complex and unpleasant condition.
-
Many trials of treatments for OH are of low quality and express clinical utility.
-
Several vasoactive interventions, as recommended by narrative review articles, may worsen the postural drop in blood force per unit area.
-
There is limited evidence on how treatments for OH bear on symptoms, functional power and quality of life.
-
Well-designed, randomised, placebo-controlled trials of treatments for OH (focusing on symptoms and quality of life) are needed.
Conflicts of involvement
None declared.
Funding
Dr Witham is funded by the Chief Scientist Function, Scottish Government as a Clinician Scientist.
References
The very long listing of references supporting this review has meant that only the most important are listed here, and are represented by assuming type throughout the text. The total list of references is given in Supplementary data (Appendix 2) bachelor at Age and Ageing online.
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