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Cureus Aug 2023Hepatorenal syndrome (HRS), defined by the extreme manifestation of renal impairment in patients with cirrhosis, is characterized by reduced renal blood flow and... (Review)
Review
Hepatorenal syndrome (HRS), defined by the extreme manifestation of renal impairment in patients with cirrhosis, is characterized by reduced renal blood flow and glomerular filtration rate. It is diagnosed with reduced kidney function confirming the absence of intrinsic kidney disease, such as hematuria or proteinuria. HRS is potentially reversible with liver transplantation or vasoconstrictor drugs. The condition carries a poor prognosis with high mortality rates, particularly in patients with advanced cirrhosis. The latest management for HRS involves a combination of pharmacological and non-pharmacological interventions, aiming to improve renal function and reduce the risk of mortality. Pharmacological treatments include vasoconstrictors, such as terlipressin and midodrine, and albumin infusion, which have been shown to improve renal function and reduce mortality in HRS patients. Non-pharmacological interventions, including invasive procedures such as transjugular intrahepatic portosystemic shunt (TIPS), plasma exchange, liver transplantation, and renal replacement therapy, may also be considered. Though TIPS has been shown to be effective in improving renal function in HRS patients, liver transplantation remains at the top of the consideration for the treatment of end-stage liver disease and HRS. Recent studies have placed importance on early recognition and prompt intervention in HRS patients, as delaying treatment can result in poorer outcomes. Although there are numerous reviews that summarize various aspects of HRS, the recent advancements in the management and pathophysiology of HRS are still insufficient. Therefore, in this review, we summarized a brief pathophysiology and highlighted recent advancements in the management of HRS with a quick review of the latest articles.
PubMed: 37680416
DOI: 10.7759/cureus.43073 -
The Cochrane Database of Systematic... Sep 2017Hepatorenal syndrome is defined as severe renal failure occurring in people with cirrhosis and ascites. Systematic reviews of randomised clinical trials found that,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Hepatorenal syndrome is defined as severe renal failure occurring in people with cirrhosis and ascites. Systematic reviews of randomised clinical trials found that, compared with placebo, terlipressin may reduce mortality and improve renal function in people with hepatorenal syndrome, but we need current evidence from systematic reviews on the benefits and harms of terlipressin versus other vasoactive drugs.
OBJECTIVES
To evaluate the beneficial and harmful effects of terlipressin versus other vasoactive drugs for people with hepatorenal syndrome.
SEARCH METHODS
We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE, Embase, and Science Citation Index Expanded; conducted manual searches of references in relevant literature; and wrote to experts and pharmaceutical companies (date of last search November 2016).
SELECTION CRITERIA
Randomised clinical trials comparing terlipressin versus any other type of vasoactive drugs for hepatorenal syndrome. We allowed albumin and other cointerventions if provided equally in the comparison groups.
DATA COLLECTION AND ANALYSIS
Three authors independently extracted data. The primary outcomes were mortality, hepatorenal syndrome (persistent hepatorenal syndrome despite treatment), and serious adverse events. We conducted meta-analyses and present the results as risk ratios (RR) with 95% confidence intervals (CI). We performed sensitivity, subgroup, and Trial Sequential Analyses and evaluated bias control based on the Cochrane Hepato-Biliary Group domains.
MAIN RESULTS
We included 10 randomised clinical trials with 474 participants. The trials compared terlipressin versus noradrenaline (seven trials), octreotide (one trial), midodrine and octreotide (one trial), or dopamine (one trial). All participants in both groups received albumin as cointervention. We classified two trials at low risk of bias and eight trials at high risk of bias in the assessment of mortality and all trials at high risk of bias for remaining outcomes. In five trials, investigators specifically stated that they did not receive funding from for-profit organisations. We had no information about the funding source from the remaining five trials.Terlipressin was not superior or inferior compared with other vasoactive drugs in regard to mortality when including the two trials with a low risk of bias (RR 0.92, 95% CI 0.63 to 1.36; 94 participants, very low quality evidence) or when including all 10 trials (RR 0.96, 95% CI 0.88 to 1.06; 474 participants; I² = 0%; very low quality evidence). One meta-analysis including nine trials suggested a beneficial effect of terlipressin on hepatorenal syndrome (RR 0.79, 95% CI 0.63 to 0.99; 394 participants; I² = 26%; very low quality evidence). Due to the high mortality of hepatorenal syndrome, the registration of other serious adverse events is uncertain, but comparing terlipressin and other vasoactive drugs we found no significant difference (RR 0.96, 95% CI 0.88 to 1.06; 474 participants; I² = 0%; very low quality evidence). Several trials did not report systematically of adverse events, but terlipressin seemed to increase the risks of diarrhoea or abdominal pain, or both (RR 3.50, 95% CI 1.19 to 10.27; 221 participants; 5 trials, I² = 0%). However, Trial Sequential Analyses found insufficient evidence to support or refute any differences between interventions for all outcomes. Considering reversal of hepatorenal syndrome, subgroup analyses on the type of other vasoactive drugs found that terlipressin was superior compared with midodrine and octreotide (RR 0.47, 95% CI 0.30 to 0.72) or octreotide alone (RR 0.56, 95% CI 0.33 to 0.96), but each subgroup only included one small trial. None of the remaining subgroup or sensitivity analyses found differences between terlipressin and other vasoactive drugs. We downgraded the evidence to very low quality because of the high risk of bias, imprecision, and the results of the Trial Sequential Analyses.
AUTHORS' CONCLUSIONS
This review found insufficient evidence to support or refute beneficial or harmful effects of terlipressin and albumin versus other vasoactive drugs and albumin. Additional research is needed to evaluate if clinically meaningful differences exist between interventions.
Topics: Antihypertensive Agents; Dopamine; Hepatorenal Syndrome; Humans; Lypressin; Midodrine; Norepinephrine; Octreotide; Randomized Controlled Trials as Topic; Terlipressin; Vasoconstrictor Agents
PubMed: 28953318
DOI: 10.1002/14651858.CD011532.pub2 -
Clinical Cardiology Jun 2010The association of clinostatic hypertension (CH) and orthostatic hypotension (OH) is described as the "Hyp-Hyp phenomenon," and it has been found in about 5.5% of... (Review)
Review
BACKGROUND
The association of clinostatic hypertension (CH) and orthostatic hypotension (OH) is described as the "Hyp-Hyp phenomenon," and it has been found in about 5.5% of hypertensive patients and in up to 50% of patients with OH. The importance of CH/OH in clinical practice is mainly due to the presence of troublesome symptoms, end-organ damage, and difficulties in its clinical management.
HYPOTHESIS
The review focuses on the clinical problem of CH and review the international literature for the best management, including the diagnostic work-up and the taylored treatment for this kind of patients.
METHODS
A systematic review of the literature was conducted through MEDLINE research to focus the main controversial issues about CH/OH. Included topics: (1) the diagnostic work-up, (2) the association with dysautonomic failure and syncope, and (3) the treatment options and prevention of end-organ damage.
RESULTS
Current standard reference for OH diagnosis includes functional assessment of the cardiac vagal nervous system and the sympathetic adrenergic system. The association with dysautonomic failure and with syncope needs further investigation. Pharmacologic treatment of OH is aimed at controlling symptoms rather than restoring normotension. Midodrine is the only medication that has been put to multicenter placebo-controlled trial and subsequently approved by the U.S. Food and Drug Administration (FDA) for OH treatment. Short-acting oral antihypertensive agents at bedtime should be considered in patients with severe, sustained CH.
CONCLUSIONS
Data obtained from the literature review showed that clinical diagnosis of the Hyp-Hyp phenomenon is relatively simple, but it remains more difficult to establish the causal disease. In our opinion, it is advisable to define simple diagnostic standards for the selection of patients at risk of dysautonomic impairment so that a subsequent highly specific diagnostic work-up could be initiated.
Topics: Antihypertensive Agents; Autonomic Nervous System; Blood Pressure; Humans; Hypertension; Hypotension, Orthostatic; Midodrine; Predictive Value of Tests; Treatment Outcome; Vasoconstrictor Agents
PubMed: 20552588
DOI: 10.1002/clc.20722 -
European Urology Jan 2008Stress urinary incontinence (SUI) occurs in men and women. Pharmacologic treatment of female SUI has been beneficiary but the role of drug treatment in male SUI is... (Review)
Review
OBJECTIVE
Stress urinary incontinence (SUI) occurs in men and women. Pharmacologic treatment of female SUI has been beneficiary but the role of drug treatment in male SUI is controversial. This review evaluates the drug classes, the effects of these drugs in trials with male SUI, and the levels of evidence of the individual trials.
METHODS
A systematic literature review was conducted searching for studies on male SUI published between 1966 and 2007. In retrieved articles, reference lists were hand-searched to identify additional articles. The level of evidence was judged according to the Oxford classification.
RESULTS
This search found nine articles providing evidence that alpha-adrenoceptor agonists (ephedrine, phenylpropanolamine, midodrine), beta2-adrenoceptor agonists (clenbuterol), and serotonin-noradrenaline reuptake inhibitors (imipramine, duloxetine) have a potentially beneficial effect on male SUI. Most trials used only small numbers of patients and a mixed study population (men and women). The evidence level of most studies was low due to the lack of randomisation (case series or cohort studies, level 4). In contrast, the first high-level study to provide evidence in the treatment of male SUI was with duloxetine, a selective serotonin and noradrenaline reuptake inhibitor (randomised controlled study, level 1b). However, only one well-designed study has been published so far.
CONCLUSIONS
One high-level study with duloxetine in combination with pelvic floor muscle training shows preliminary but promising results in the treatment of male SUI. These results have to be confirmed in larger and well-designed trials to allow definite recommendations for the pharmacologic treatment of male SUI.
Topics: Adrenergic alpha-Agonists; Adrenergic beta-Agonists; Humans; Male; Selective Serotonin Reuptake Inhibitors; Treatment Outcome; Urinary Incontinence, Stress
PubMed: 17920183
DOI: 10.1016/j.eururo.2007.09.037 -
Cureus Jul 2023Hepatorenal syndrome (HRS), a consequence of liver cirrhosis, is the development of renal failure, which carries a grave prognosis. Reversing acute renal failure with... (Review)
Review
BACKGROUND
Hepatorenal syndrome (HRS), a consequence of liver cirrhosis, is the development of renal failure, which carries a grave prognosis. Reversing acute renal failure with various vasoconstrictor therapies at an appropriate time favors a good prognosis, especially when a liver transplant is not feasible.
OBJECTIVE
This study aims to compare various treatment modalities to deduce an effective way to manage HRS.
METHODS
The authors conducted a literature search in PubMed, Google Scholar, the Cochrane Library, and Science Direct in October 2022, using regular and MeSH keywords. A total of 1072 articles were identified. The PRISMA guidelines were used, the PICO framework was addressed, and the inclusion criteria were set based on studies from the past 10 years. After quality assessment, 14 studies were included for in-depth analysis in this review. Results: A total of 14 studies were included after quality assessment, including randomized controlled trials, systematic reviews, meta-analyses, and observational cohort studies. Nine hundred and forty-one patients represented this review's experimental and observational studies, apart from the other systematic reviews analyzed. Nine studies discovered that Terlipressin, especially when administered with albumin, was more effective than other conventional treatment modalities, including norepinephrine and midodrine, in terms of improving mortality and reversing the HRS. Four studies suggested that terlipressin exhibited similar effectiveness but found no significant difference. In contrast, one study found that norepinephrine was superior to terlipressin when particularly considering the adverse effects.
CONCLUSION
Terlipressin, one of the most widely used vasoconstrictor agents across the world, seems to be effective in reversing renal failure in HRS. Although adverse effects are seen with this agent, it is still beneficial when compared to other medications. Further studies with larger sample sizes may be warranted.
PubMed: 37621788
DOI: 10.7759/cureus.42367 -
American Journal of Therapeutics
Meta-Analysis
Topics: Humans; Midodrine; Syncope, Vasovagal
PubMed: 35703495
DOI: 10.1097/MJT.0000000000001513 -
The Cochrane Database of Systematic... Jul 2013The use of acupuncture for stress urinary incontinence is increasing in frequency, especially in Asian area. However, its effectiveness and side effects have not been... (Review)
Review
BACKGROUND
The use of acupuncture for stress urinary incontinence is increasing in frequency, especially in Asian area. However, its effectiveness and side effects have not been evaluated.
OBJECTIVES
To assess the effectiveness and side effects of acupuncture for stress urinary incontinence in adults.
SEARCH METHODS
We searched the Cochrane Incontinence Group Specialised Register (searched 28 January 2013), EMBASE, AMED, Chinese Biomedical Literature Database (CBM), Chinese Acupuncture Trials Register and China National Knowledge Infrastructure (CNKI) (all searched 20 February 2013). In addition, we searched the reference lists of relevant articles and contacted authors and trialists in the field.
SELECTION CRITERIA
Randomised and quasi-randomised controlled trials of acupuncture interventions without other treatments for the management of stress urinary incontinence for adults.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed eligibility, trial quality and extracted data. We meta-analysed data where appropriate.
MAIN RESULTS
We identified 17 possibly eligible studies but only one small trial with 60 women met our inclusion criteria. The trial compared acupuncture versus midodrine, a drug for treating hypotension. The risk of bias was high as there was no concealment of randomised allocation, and there was no blinding of assessment of outcome. In addition, it was not possible to blind participants or health providers to the interventions. The statistical methods were not described.More women improved in the acupuncture group (73% with acupuncture versus 33% with midodrine; risk ratio (RR) 2.20, 95% confidence interval (CI) 1.27 to 3.81) but the cure rates were low and not statistically significantly different (13% versus 7%; RR 2.00, 95% CI 0.40 to 10.11). There were adverse events in the drug group only.
AUTHORS' CONCLUSIONS
The effect of acupuncture for stress urinary incontinence for adults is uncertain. There is not enough evidence to determine whether acupuncture is more effective than drug treatment.
Topics: Acupuncture Therapy; Adrenergic alpha-1 Receptor Agonists; Adult; Female; Humans; Midodrine; Randomized Controlled Trials as Topic; Urinary Incontinence, Stress
PubMed: 23818069
DOI: 10.1002/14651858.CD009408.pub2 -
Age and Ageing Sep 2012orthostatic 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... (Meta-Analysis)
Meta-Analysis Review
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 for such recommendations are lacking.
METHODS
we 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. We searched grey literature and references from included studies and other reviews. We included randomised, placebo-controlled trials, which measured postural drop as an outcome. Study quality was assessed using pre-specified measures of bias.
RESULTS
overall, 36 trials (21 interventions) were included. We identified a heterogeneous population and a wide variety of study methods, precluding meta-analysis. 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 drop. 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 have a limited evidence base supporting their use. High quality, randomised, controlled trials are needed to underpin clinical practice for this condition.
Topics: Adult; Aged; Aged, 80 and over; Blood Pressure; Cardiovascular Agents; Compression Bandages; Female; Humans; Hypotension, Orthostatic; Male; Middle Aged; Treatment Outcome; Vasoconstrictor Agents
PubMed: 22591985
DOI: 10.1093/ageing/afs061 -
The Cochrane Database of Systematic... 2003Adrenergic 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 trials register (January 2002) and the reference lists of relevant articles. Date of the most recent searches: January 2002.
SELECTION CRITERIA
Randomised or quasi-randomised controlled trials which include an adrenergic agonist drug in at least one arm for adults with urinary incontinence.
DATA COLLECTION AND ANALYSIS
Two reviewers independently assessed eligibility, trial quality and extracted data. Data were processed as described in the Cochrane Collaboration Handbook.
MAIN RESULTS
Fifteen randomised trials were identified, which included 832 women, of whom 506 received an adrenergic drug (phenylpropanolamine in 11 trials, Midodrine in two and Clenbuterol in another two). Of these, six were crossover trials. No trials included men. The limited evidence suggested that an adrenergic agonist drug is better than placebo in reducing number of pad changes and incontinence episodes, as well as improvement in subjective symptoms. The drugs also appeared to be better than pelvic floor muscle training in two small trials, 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.
REVIEWER'S CONCLUSIONS
There was weak evidence to suggest that use of an adrenergic agonist is better than placebo treatment. There was not enough evidence to assess the effects of adrenergic agonists when compared to or combined with other treatments. Patients using adrenergic agonists may suffer from minor side effects, only occasionally leading them to stop treatment. Rare but serious side effects such as cardiac arrhythmias and hypertension have been reported, however.
Topics: Adrenergic Agonists; Adult; Clenbuterol; Female; Humans; Midodrine; Phenylpropanolamine; Randomized Controlled Trials as Topic; Urinary Incontinence; Urinary Incontinence, Stress
PubMed: 12804414
DOI: 10.1002/14651858.CD001842 -
Alimentary Pharmacology & Therapeutics Mar 2017Hepatorenal syndrome type 1 (HRS1) is a functional, rapidly progressive, potentially reversible form of acute kidney injury occurring in patients with cirrhosis.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Hepatorenal syndrome type 1 (HRS1) is a functional, rapidly progressive, potentially reversible form of acute kidney injury occurring in patients with cirrhosis. Characterised by intense renal arterial vasoconstriction, it carries a very poor prognosis. There is a significant unmet need for a widely approved, safe and effective pharmacological treatment.
AIM
To re-evaluate efficacy and safety of pharmacological treatments for HRS1, in the light of recently published randomised controlled trials (RCTs).
METHODS
MEDLINE (OvidSP), EMBASE, PubMed and Cochrane registers were searched for RCTs reporting efficacy and adverse events related to pharmacological treatment of HRS1. Search terms included: 'hepatorenal syndrome', 'terlipressin', 'noradrenaline', 'octreotide', 'midodrine', 'vasopressin', 'dopamine', 'albumin' and synonyms. Comparison of vasoactive drugs vs. placebo/no treatment, and two active drugs were included. Meta-analysis was performed for HRS1 reversal, creatinine improvement, mortality and adverse events.
RESULTS
Twelve RCTs enrolling 700 HRS1 patients were included. Treatment with terlipressin and albumin led to HRS1 reversal more frequently than albumin alone or placebo (RR: 2.54, 95% CI: 1.51-4.26). Noradrenaline was effective in reversing HRS1, but trials were small and nonblinded. Overall, there was mortality benefit with terlipressin (RR: 0.79, 95% CI: 0.63-1.01), but sensitivity analysis including only trials with low risk of selection bias weakened this relationship (RR: 0.87, 95% CI: 0.71-1.06). Notably, there was a significant risk of adverse events with terlipressin therapy (RR: 4.32, 95% CI: 0.75-24.86).
CONCLUSIONS
Terlipressin treatment is superior to placebo for achieving HRS1 reversal, but mortality benefit is less clear. Terlipressin is associated with significant adverse events, but infusion regimens may be better tolerated. There is continued need for safe and effective treatment options for hepatorenal syndrome.
Topics: Albumins; Creatinine; Hepatorenal Syndrome; Humans; Liver Cirrhosis; Lypressin; Prognosis; Randomized Controlled Trials as Topic; Terlipressin; Treatment Outcome; Vasoconstrictor Agents
PubMed: 28052382
DOI: 10.1111/apt.13912