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The Cochrane Database of Systematic... Oct 2011Neurally mediated reflex syncope is the most common cause of transient loss of consciousness. In patients not responding to non-pharmacological treatment,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Neurally mediated reflex syncope is the most common cause of transient loss of consciousness. In patients not responding to non-pharmacological treatment, pharmacological or pacemaker treatment might be considered.
OBJECTIVES
To examine the effects of pharmacological therapy and pacemaker implantation in patients with vasovagal syncope, carotid sinus syncope and situational syncope.
SEARCH STRATEGY
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) on The Cochrane Library (Issue 1, 2008), PubMed (1950 until February 2008), EMBASE on OVID (1980 until February 2008) and CINAHL on EBSCOhost (1937 until February 2008). No language restrictions were applied.
SELECTION CRITERIA
We included parallel randomized controlled trials and randomized cross-over trials of pharmacological treatment (beta-blockers, fludrocortisone, alpha-adrenergic agonists, selective serotonine reuptake inhibitors, ACE inhibitors, disopyramide, anticholinergic agents or salt tablets) or dual chamber pacemaker treatment. Studies were included if pharmacological or pacemaker treatment was compared with any form of standardised control treatment (standard treatment), placebo treatment, or (other) pharmacological or pacemaker treatment. We did not include non-randomized studies.
DATA COLLECTION AND ANALYSIS
Two reviewers independently assessed the risk of bias. Using a standardised data extraction form, they extracted characteristics and results of the various studies. In a consensus meeting they discussed any disagreements that had occurred during data extraction. If no agreement could be reached, a third reviewer was asked to make a decision. Summary estimates with 95% confidence intervals of treatment effect were calculated using relative risks, rate ratios or weighted means differences depending on the type of outcome reported.
MAIN RESULTS
We included 46 randomized studies, 40 on vasovagal syncope and six on carotid sinus syncope. No studies on situational syncope matched the criteria for inclusion in our review. Studies in general were small with a median sample size of 42. A wide range of control treatments were used with 22 studies using a placebo arm. Blinding of patients and treating physicians was applied in eight studies. Results varied considerably between studies and between types of outcomes.For vasovagal syncope, the occurrence of syncope upon provocational head-up tilt testing was lower upon treatment with beta-blockers, ACE-inhibitors and anticholinergic agents compared to standard treatment. For carotid sinus syncope, the occurrence of syncope upon carotid sinus massage was lower on midodrine treatment compared to placebo treatment in one study.
AUTHORS' CONCLUSIONS
There is insufficient evidence to support the use of any of the pharmacological or pacemaker treatments for vasovagal syncope and carotid sinus syncope. Larger studies using patient relevant outcomes are needed.
Topics: Carotid Artery Diseases; Carotid Sinus; Humans; Pacemaker, Artificial; Randomized Controlled Trials as Topic; Syncope; Syncope, Vasovagal
PubMed: 21975744
DOI: 10.1002/14651858.CD004194.pub3 -
Archives of Physical Medicine and... May 2009To review systematically the evidence for the management of orthostatic hypotension (OH) in patients with spinal cord injuries (SCIs). (Review)
Review
OBJECTIVE
To review systematically the evidence for the management of orthostatic hypotension (OH) in patients with spinal cord injuries (SCIs).
DATA SOURCES
A key word literature search was conducted of original and review articles as well as practice guidelines using Medline, CINAHL, EMBASE, and PsycInfo, and manual searches of retrieved articles from 1950 to July 2008, to identify literature evaluating the effectiveness of currently used treatments for OH.
STUDY SELECTION
Included randomized controlled trials (RCTs), prospective cohort studies, case-control studies, pre-post studies, and case reports that assessed pharmacologic and nonpharmacologic intervention for the management of OH in patients with SCI.
DATA EXTRACTION
Two independent reviewers evaluated the quality of each study, using the Physiotherapy Evidence Database score for RCTs and the Downs and Black scale for all other studies. Study results were tabulated and levels of evidence assigned.
DATA SYNTHESIS
A total of 8 pharmacologic and 21 nonpharmacologic studies were identified that met the criteria. Of these 26 studies (some include both pharmacologic and nonpharmacologic interventions), only 1 pharmacologic RCT was identified (low-quality RCT producing level 2 evidence), in which midodrine was found to be effective in the management of OH after SCI. Functional electrical stimulation was one of the only nonpharmacologic interventions with some evidence (level 2) to support its utility.
CONCLUSIONS
Although a wide array of physical and pharmacologic measures are recommended for the management of OH in the general population, very few have been evaluated for use in SCI. Further research needs to quantify the efficacy of treatment for OH in subjects with SCI, especially of the many other pharmacologic interventions that have been shown to be effective in non-SCI conditions.
Topics: Combined Modality Therapy; Female; Follow-Up Studies; Humans; Hypotension, Orthostatic; Injury Severity Score; Male; Midodrine; Paraplegia; Physical Therapy Modalities; Quadriplegia; Randomized Controlled Trials as Topic; Risk Assessment; Severity of Illness Index; Spinal Cord Injuries; Treatment Outcome; Vasoconstrictor Agents
PubMed: 19406310
DOI: 10.1016/j.apmr.2009.01.009 -
Journal of Child Neurology Dec 2020Postural orthostatic tachycardia syndrome has been recognized for decades, but treatment is largely based on anecdotal experience and expert opinion. Pharmacologic...
PURPOSE
Postural orthostatic tachycardia syndrome has been recognized for decades, but treatment is largely based on anecdotal experience and expert opinion. Pharmacologic treatment is inconsistent and unstandardized. We did a systematic review to identify controlled studies from which informed treatment decisions can be made.
METHOD
Through a standard systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we identified all English-language studies of a medication treatment for postural orthostatic tachycardia syndrome that included a comparison or control group and followed outcomes for at least 1 week of treatment.
RESULTS
A total of 626 studies were identified by the search criteria, and 8, involving a total of 499 patients, met the criteria. No studies were adequately similar to allow for meta-analysis. Of the identified 8 studies, 2 were randomized controlled trials and 4 had been subjected to peer review. In individual studies, there was some favorable effect with fludrocortisone, beta blockers, midodrine, and selective serotonin reuptake inhibitors.
CONCLUSION
There is a paucity of high-quality data about effectiveness of medication in the treatment of postural orthostatic tachycardia syndrome. Nonetheless, 2 randomized trials and 6 other reports show some favorable effects of medication.
Topics: Adrenergic beta-Antagonists; Anti-Inflammatory Agents; Fludrocortisone; Humans; Postural Orthostatic Tachycardia Syndrome; Selective Serotonin Reuptake Inhibitors; Treatment Outcome
PubMed: 32838632
DOI: 10.1177/0883073820948679 -
The Cochrane Database of Systematic... Jul 2005Adrenergic drugs have been used for the treatment of urinary incontinence. However, they have generally been considered to be ineffective or to have side effects which... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Adrenergic drugs have been used for the treatment of urinary incontinence. However, they have generally been considered to be ineffective or to have side effects which may limit their clinical use.
OBJECTIVES
To determine the effectiveness of adrenergic agonists in the treatment of urinary incontinence in adults.
SEARCH STRATEGY
We searched the Cochrane Incontinence Group specialised trials register (searched 9 March 2005) and the reference lists of relevant articles.
SELECTION CRITERIA
Randomised or quasi-randomised controlled trials in adults with urinary incontinence which included an adrenergic agonist drug in at least one arm of the trial.
DATA COLLECTION AND ANALYSIS
Two reviewers independently assessed eligibility, trial quality and extracted data. Data were processed as described in the Cochrane Reviewers' Handbook.
MAIN RESULTS
Twenty-two eligible randomised trials were identified, of which 11 were crossover trials. The trials included 1099 women with 673 receiving an adrenergic drug (phenylpropanolamine in 11 trials, midodrine in two, norepinephrine in three, clenbuterol in another three, terbutaline in one, eskornade in one and Ro-115-1240 in one). No trials included men. The limited evidence suggested that an adrenergic agonist drug is better than placebo in reducing the number of pad changes and incontinence episodes, as well as improving subjective symptoms. In two small trials, the drugs also appeared to be better than pelvic floor muscle training, possibly reflecting relative acceptability of the treatments to women but perhaps due to differential withdrawal of women from the trial groups. There was not enough evidence to evaluate the use of higher compared to lower doses of adrenergic agonists nor the relative merits of an adrenergic agonist drug compared with oestrogen, whether used alone or in combination. Over a quarter of women reported adverse effects. There were similar numbers of adverse effects with adrenergics, placebo or alternative drug treatment. However, when these were due to recognised adrenergic stimulation (insomnia, restlessness and vasomotor stimulation) they were only severe enough to stop treatment in 4% of women.
AUTHORS' CONCLUSIONS
There was weak evidence to suggest that use of an adrenergic agonist was better than placebo treatment. There was not enough evidence to assess the effects of adrenergic agonists when compared to or combined with other treatments. Further larger trials are needed to identify when adrenergics may be useful. Patients using adrenergic agonists may suffer from minor side effects, which sometimes cause them to stop treatment. Rare but serious side effects, such as cardiac arrhythmias and hypertension, have been reported.
Topics: Adrenergic Agonists; Adult; Clenbuterol; Female; Humans; Midodrine; Phenylpropanolamine; Randomized Controlled Trials as Topic; Urinary Incontinence; Urinary Incontinence, Stress
PubMed: 16034867
DOI: 10.1002/14651858.CD001842.pub2 -
International Journal of Clinical... Jul 2013The 'short' and 'long-term' benefits of pharmacological interventions to treat orthostatic hypotension (OH) remain unclear. The aim was to systematically examine the... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
The 'short' and 'long-term' benefits of pharmacological interventions to treat orthostatic hypotension (OH) remain unclear. The aim was to systematically examine the published literature on the effectiveness of different drug regimens for the treatment of OH.
DESIGN
Systematic review.
SETTING
MEDLINE (1950-Week 7, 2011), EMBASE (1980-Week 7, 2011), CINAHL (1981-Week 7, 2011) databases and hand-searching of bibliographies were used to identify suitable papers.
PARTICIPANTS
Studies selected were those, which investigated drug treatment of OH in a single- or double-blind randomised controlled trial (RCT) in humans over 18 years of age.
MEASUREMENTS
Data were extracted from suitable full-text articles by three investigators independently.
RESULTS
The 13 trials met the criteria for systematic review amongst which was considerable variation in the size of postural blood pressure (BP) change with active treatment. However, there was evidence that commonly used drugs midodrine or fludrocortisone therapy did increase standing or head-up-tilt (HUT) systolic blood pressure in certain patient groups.
CONCLUSION
The evidence that pharmacological therapy is of benefit for the treatment of OH is limited by the lack of good quality clinical trial evidence. Further well-designed RCTs of pharmacological treatment of OH investigating the impact on postural symptoms as well as actual BP changes are needed.
Topics: Adult; Aged; Cardiovascular Agents; Double-Blind Method; Female; Fludrocortisone; Humans; Hypotension, Orthostatic; Male; Middle Aged; Midodrine; Octreotide; Pyridostigmine Bromide; Randomized Controlled Trials as Topic; Single-Blind Method; Treatment Outcome; Young Adult
PubMed: 23758443
DOI: 10.1111/ijcp.12122 -
American Journal of TherapeuticsOrthostatic hypotension (OH) is a potentially debilitating condition caused by dysfunction of the autonomic nervous system, which is essential for the physiologic...
BACKGROUND
Orthostatic hypotension (OH) is a potentially debilitating condition caused by dysfunction of the autonomic nervous system, which is essential for the physiologic response to orthostatic posture. In addition to OH, autonomic dysfunction may also be associated with the development of concurrent supine hypertension (SH).
AREAS OF UNCERTAINTY
This paradoxical effect speaks to the complexity of the pathogenesis of autonomic disease and greatly complicates management of these patients. Clinicians are faced with a dilemma because aggressive treatment of orthostatic intolerance can worsen supine hypertension and attempts to control supine hypertension can worsen orthostatic intolerance.
DATA SOURCES
Systematic review of the published literature.
PREVENTION OF SUPINE HYPERTENSION
Patients should aim to avoid known stressors, perform physical maneuvers (eg, slowly getting up from bed, sleeping with head of bed elevated), manage underlying related conditions (eg, diabetes mellitus), and exercise.
MANAGEMENT OF SUPINE HYPERTENSION
With failure of conservative management, patients may advance to pharmacologic therapy. It is important to understand the underlying suspected etiology of the syndrome of supine hypertension and OH (SH-OH) to select promising pharmacologic agents. This article reviews medical treatment options to work toward achieving a better quality of life for patients afflicted with this disease. Although clonidine and beta-blockers can be used to treat hypertension without causing significant hypotension, midodrine, pyridostigmine, and droxidopa may be helpful in preventing OH.
CONCLUSION
The etiology and severity of autonomic dysfunction vary widely between patients, suggesting a need for an individualized treatment approach. Achieving perfect blood pressure control is not a realistic goal. Rather, treatment should be aimed at improving the patient's quality of life and decreasing their risk of injury and organ damage.
Topics: Droxidopa; Humans; Hypertension; Hypotension, Orthostatic; Midodrine; Quality of Life
PubMed: 31524637
DOI: 10.1097/MJT.0000000000001054 -
Journal of Neurotrauma May 2024Cognitive impairment is a common complication following spinal cord injury (SCI) and imposes a significant negative impact on adjustment, functional independence,... (Review)
Review
Cognitive impairment is a common complication following spinal cord injury (SCI) and imposes a significant negative impact on adjustment, functional independence, physical and mental health, and quality of life. It is unclear whether interventions for cognitive impairment following SCI are effective. A systematic review of controlled trials was performed to evaluate the effect of interventions on cognitive functions in adults with SCI using search engines: Embase, The Cochrane Library, MEDLINE, Scopus, CINAHL, and Web of Science up to December 2023. Two reviewers independently screened the articles, and study findings were synthesized and summarized. The risk of bias was evaluated using the Cochrane Risk of Bias 2.0 tool. Eight moderate-quality studies were found that investigated the effects of physical exercise/activity-based therapy plus cognitive training or intermittent hypoxia, diet modification and dietary supplements, tibial nerve or cortical stimulation, and drug therapy on cognitive function in SCI. Physical exercise/activity-based therapy plus cognitive training showed most promise for improving cognitive functions, while drug therapy, diet modification, and dietary supplements showed potential for improving cognitive function. However, about half of the participants experienced heightened instability in blood pressure following the administration of midodrine, and one participant reported gastrointestinal side effects after taking omega-3 fatty acids. There was no evidence of improvement in cognitive function for stimulation techniques. The current review highlights the scarcity of research investigating the effectiveness of interventions that target cognitive function after SCI. Further, the effects of these eight studies are uncertain due to concerns about the quality of designs and small sample sizes utilized in the trials, as well as the employment of insensitive neurocognitive tests when applied to adults with SCI. This review highlights a significant gap in knowledge related to SCI cognitive rehabilitation.
PubMed: 38623777
DOI: 10.1089/neu.2024.0032 -
The Cochrane Database of Systematic... Sep 2019Hepatorenal syndrome is defined as renal failure in people with cirrhosis in the absence of other causes. In addition to supportive treatment such as albumin to restore...
BACKGROUND
Hepatorenal syndrome is defined as renal failure in people with cirrhosis in the absence of other causes. In addition to supportive treatment such as albumin to restore fluid balance, the other potential treatments include systemic vasoconstrictor drugs (such as vasopressin analogues or noradrenaline), renal vasodilator drugs (such as dopamine), transjugular intrahepatic portosystemic shunt (TIPS), and liver support with molecular adsorbent recirculating system (MARS). There is uncertainty over the best treatment regimen for hepatorenal syndrome.
OBJECTIVES
To compare the benefits and harms of different treatments for hepatorenal syndrome in people with decompensated liver cirrhosis.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, Science Citation Index Expanded, World Health Organization International Clinical Trials Registry Platform, and trial registers until December 2018 to identify randomised clinical trials on hepatorenal syndrome in people with cirrhosis.
SELECTION CRITERIA
We included only randomised clinical trials (irrespective of language, blinding, or publication status) in adults with cirrhosis and hepatorenal syndrome. We excluded randomised clinical trials in which participants had previously undergone liver transplantation.
DATA COLLECTION AND ANALYSIS
Two authors independently identified eligible trials and collected data. The outcomes for this review included mortality, serious adverse events, any adverse events, resolution of hepatorenal syndrome, liver transplantation, and other decompensation events. We performed a network meta-analysis with OpenBUGS using Bayesian methods and calculated the odds ratio (OR), rate ratio, hazard ratio (HR), and mean difference (MD) with 95% credible intervals (CrI) based on an available-case analysis, according to National Institute of Health and Care Excellence Decision Support Unit guidance.
MAIN RESULTS
We included a total of 25 trials (1263 participants; 12 interventions) in the review. Twenty-three trials (1185 participants) were included in one or more outcomes. All the trials were at high risk of bias, and all the evidence was of low or very low certainty. The trials included participants with liver cirrhosis of varied aetiologies as well as a mixture of type I hepatorenal syndrome only, type II hepatorenal syndrome only, or people with both type I and type II hepatorenal syndrome. Participant age ranged from 42 to 60 years, and the proportion of females ranged from 5.8% to 61.5% in the trials that reported this information. The follow-up in the trials ranged from one week to six months. Overall, 59% of participants died during this period and about 35% of participants recovered from hepatorenal syndrome. The most common interventions compared were albumin plus terlipressin, albumin plus noradrenaline, and albumin alone.There was no evidence of a difference in mortality (22 trials; 1153 participants) at maximal follow-up between the different interventions. None of the trials reported health-related quality of life. There was no evidence of differences in the proportion of people with serious adverse events (three trials; 428 participants), number of participants with serious adverse events per participant (two trials; 166 participants), proportion of participants with any adverse events (four trials; 402 participants), the proportion of people who underwent liver transplantation at maximal follow-up (four trials; 342 participants), or other features of decompensation at maximal follow-up (one trial; 466 participants). Five trials (293 participants) reported number of any adverse events, and five trials (219 participants) reported treatment costs. Albumin plus noradrenaline had fewer numbers of adverse events per participant (rate ratio 0.51, 95% CrI 0.28 to 0.87). Eighteen trials (1047 participants) reported recovery from hepatorenal syndrome (as per definition of hepatorenal syndrome). In terms of recovery from hepatorenal syndrome, in the direct comparisons, albumin plus midodrine plus octreotide and albumin plus octreotide had lower recovery from hepatorenal syndrome than albumin plus terlipressin (HR 0.04; 95% CrI 0.00 to 0.25 and HR 0.26, 95% CrI 0.07 to 0.80 respectively). There was no evidence of differences between the groups in any of the other direct comparisons. In the network meta-analysis, albumin and albumin plus midodrine plus octreotide had lower recovery from hepatorenal syndrome compared with albumin plus terlipressin.
FUNDING
two trials were funded by pharmaceutical companies; five trials were funded by parties who had no vested interest in the results of the trial; and 18 trials did not report the source of funding.
AUTHORS' CONCLUSIONS
Based on very low-certainty evidence, there is no evidence of benefit or harm of any of the interventions for hepatorenal syndrome with regards to the following outcomes: all-cause mortality, serious adverse events (proportion), number of serious adverse events per participant, any adverse events (proportion), liver transplantation, or other decompensation events. Low-certainty evidence suggests that albumin plus noradrenaline had fewer 'any adverse events per participant' than albumin plus terlipressin. Low- or very low-certainty evidence also found that albumin plus midodrine plus octreotide and albumin alone had lower recovery from hepatorenal syndrome compared with albumin plus terlipressin.Future randomised clinical trials should be adequately powered; employ blinding, avoid post-randomisation dropouts or planned cross-overs (or perform an intention-to-treat analysis); and report clinically important outcomes such as mortality, health-related quality of life, adverse events, and recovery from hepatorenal syndrome. Albumin plus noradrenaline and albumin plus terlipressin appear to be the interventions that should be compared in future trials.
Topics: Adult; Bayes Theorem; Female; Hepatorenal Syndrome; Humans; Liver Cirrhosis; Liver Transplantation; Male; Middle Aged; Network Meta-Analysis; Quality of Life; Randomized Controlled Trials as Topic; Vasoconstrictor Agents
PubMed: 31513287
DOI: 10.1002/14651858.CD013103.pub2 -
Open Heart Jun 2024Neurocardiogenic syncope is a common condition with significant associated psychological and physical morbidity. The effectiveness of therapeutic options for... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Neurocardiogenic syncope is a common condition with significant associated psychological and physical morbidity. The effectiveness of therapeutic options for neurocardiogenic syncope beyond placebo remains uncertain.
METHODS
The primary endpoint was the risk ratio (RR) of spontaneously recurring syncope following any therapeutic intervention. We also examined the effect of blinding on treatment efficacy. We identified all randomised trials which evaluated the effect of any pharmacological, device-based or supportive intervention on patients with a history of syncope. A systematic search was conducted on Medline, Embase, PubMed databases and Cochrane Central Register for Controlled Trials from 1950 to 25 April 2023. Event rates, their RRs and 95% CIs were calculated, and a random-effects meta-analysis was conducted for each intervention. Data analysis was performed in R using RStudio.
RESULTS
We identified 47 eligible trials randomising 3518 patients. Blinded trials assessing syncope recurrence were neutral for beta blockers, fludrocortisone and conventional dual-chamber pacing but were favourable for selective serotonin reuptake inhibitors (SSRIs) (RR 0.40, 95% CI 0.26 to 0.63, p<0.001), midodrine (RR 0.70, 95% CI 0.53 to 0.94, p=0.016) and closed-loop stimulation (CLS) pacing (RR 0.15, 95% CI 0.07 to 0.35, p<0.001). Unblinded trials reported significant benefits for all therapy categories other than beta blockers and consistently showed larger benefits than blinded trials.
CONCLUSIONS
Under blinded conditions, SSRIs, midodrine and CLS pacing significantly reduced syncope recurrence. Future trials for syncope should be blinded to avoid overestimating treatment effects.
PROSPERO REGISTRATION NUMBER
CRD42022330148.
Topics: Humans; Syncope, Vasovagal; Randomized Controlled Trials as Topic; Treatment Outcome; Recurrence
PubMed: 38890128
DOI: 10.1136/openhrt-2024-002669