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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 -
Cardiology and Therapy Mar 2023Studies evaluating the role of midodrine as an adjunctive therapy to liberate patients with shock from intravenous (IV) vasopressors have yielded mixed results. The aim...
BACKGROUND
Studies evaluating the role of midodrine as an adjunctive therapy to liberate patients with shock from intravenous (IV) vasopressors have yielded mixed results. The aim of our study was to evaluate the efficacy and safety of midodrine as an adjunctive therapy to liberate patients with shock from IV vasopressors.
METHODS
Electronic searches of the MEDLINE, EMBASE, and Cochrane databases through April 2022 for randomized controlled trials (RCTs) that evaluated the use of midodrine versus control in patients with shock and a low dose of IV vasopressors. The primary outcome was total IV vasopressor time, while the secondary outcomes included time-to-IV vasopressor discontinuation, IV vasopressor restart, intensive care unit (ICU) length of stay (LOS), hospital LOS, and incidence of bradycardia.
RESULTS
The final analysis included four RCTs with a total of 314 patients: 158 in the midodrine group and 156 in the control group, with a weighted mean age of 64 years (54.2% men). There was no significant difference in the total IV vasopressor time between the midodrine and control groups (standardized mean difference [SMD] - 0.53; 95% confidence interval [CI] - 1.38 to 0.32, p = 0.22; I = 92%). Also, there were no significant differences between the two groups in the time-to-IV vasopressor discontinuation (SMD - 0.05; 95% CI - 0.57 to 0.47, p = 0.09), IV vasopressor restart (19.3 vs. 28.3%; risk ratio [RR] 0.74; 95% 0.25-2.20, p = 0.59), ICU LOS (SMD - 0.49; 95% CI - 1.30 to 0.33, p = 0.24), and hospital LOS (SMD 0.01; 95% CI - 0.27 to 0.29, p = 0.92). However, compared with the control group, the midodrine group had a higher risk of bradycardia (15.3 vs. 2.1% RR 5.56; 95% CI 1.54-20.05, p = 0.01).
CONCLUSIONS
Among patients with vasopressor-dependent shock, midodrine was not associated with early liberation of vasopressor support or shorter ICU or hospital length of stay. Adding midodrine increased the risk of bradycardia. Further large RCTs are needed to better evaluate the efficacy and safety of midodrine in liberating patients from IV vasopressors.
PubMed: 36670331
DOI: 10.1007/s40119-023-00301-0 -
Digestive Diseases and Sciences May 2020Type 1 hepatorenal syndrome (HRS) is a fatal complication of cirrhosis. Treatments trend toward HRS reversal, but few show clear mortality benefit. We sought to quantify... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Type 1 hepatorenal syndrome (HRS) is a fatal complication of cirrhosis. Treatments trend toward HRS reversal, but few show clear mortality benefit. We sought to quantify the progress-or lack thereof-in improving outcomes of type 1 HRS over time.
METHODS
We performed a systematic review and meta-analysis for randomized controlled trials (RCTs) comparing type 1 HRS outcomes including (a) overall survival (liver transplant-free survival if reported) and (b) HRS reversal. Each study arm was analyzed separately to look at changes in outcomes over time. RCTs published comparing medical treatments for type 1 HRS were searched using several databases through July 31, 2019.
RESULTS
Fourteen RCTs (28 arms) involving 778 participants enrolled between 2002 and 2018 were included. Twelve RCTs measured HRS reversal. In conjunction with albumin (or plasma expander), the most common medications used were terlipressin (13 arms), antibiotics (7), norepinephrine (6), dopamine (4), and midodrine/octreotide (3). Pooled survival rate was 34.6% (95% CI 26.4-43.8), and pooled HRS reversal rate was 42.8% (95% CI 34.2-51.9). Regression analyzing the incremental effect of the year the RCT was initiated showed that more recent studies were not associated with improved survival (OR 1.02, 95% CI 0.94-1.11, p = 0.66) or HRS reversal rates (OR 1.03, 95% CI 0.96-1.11, p = 0.41). There was no survival improvement when RCTs with endpoints assessed ≤ or > 1 month were analyzed separately with respective OR of 1.07 (95% CI 0.95-1.20, p = 0.26) and 0.97 (95% CI 0.85-1.12, p = 0.70).
CONCLUSION
Outcomes have not improved for patients with type 1 HRS since 2002. There is a need to improve prevention and treatment of type 1 HRS.
Topics: Adult; Albumins; Anti-Bacterial Agents; Dopamine; Drug Therapy, Combination; Female; Hepatorenal Syndrome; Humans; Male; Middle Aged; Midodrine; Norepinephrine; Octreotide; Plasma Substitutes; Randomized Controlled Trials as Topic; Regression Analysis; Survival Rate; Terlipressin; Treatment Outcome; Vasoconstrictor Agents; Young Adult
PubMed: 31571102
DOI: 10.1007/s10620-019-05858-2 -
Journal of Intensive Care Medicine Nov 2020To evaluate the effects of midodrine in addition to intravenous vasopressor therapy on outcomes in adults recovering from shock. (Meta-Analysis)
Meta-Analysis
PURPOSE
To evaluate the effects of midodrine in addition to intravenous vasopressor therapy on outcomes in adults recovering from shock.
MATERIALS AND METHODS
PubMed, Scopus, Clinicaltrials.gov, and published abstracts were searched from inception to November 2018 for studies comparing outcomes in shock after midodrine initiation versus no midodrine.
RESULTS
Three studies with 2533 patients were included. Patients in whom midodrine was added to intravenous vasopressor therapy compared to intravenous vasopressor therapy alone experienced similar intensive care unit (ICU; mean difference [MD]: 1.38 days, 95% confidence interval [CI]: -3.48 to 6.23, I = 93%) and hospital lengths of stay (MD: 4.37 days, 95% CI: -3.45 to 12.19, I = 93%) and intravenous vasopressor duration after midodrine initiation (MD: 7.28 days, 95% CI: -0.86 to 15.41, I = 97%). Mortality was similar between groups (odds ratio: 0.74, 95% CI: 0.44-1.27, I = 65%). Qualitative assessment of reporting biases revealed minimal location bias, moderate selective outcome reporting bias, no selective analysis reporting bias, and no conflict of interest bias.
CONCLUSIONS
Midodrine had no effect on ICU or hospital length of stay. These results were highly susceptible to the study heterogeneity and availability. Future investigation into standardized initiation of midodrine at an adequate dosage with an expedited titration strategy is needed in order to assess the utility of this strategy in shock management.
Topics: Administration, Intravenous; Adult; Humans; Intensive Care Units; Midodrine; Shock; Vasoconstrictor Agents
PubMed: 31030630
DOI: 10.1177/0885066619843279 -
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 -
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 -
American Journal of Therapeutics May 2023
Meta-Analysis
Topics: Humans; Midodrine; Randomized Controlled Trials as Topic; Shock; Vasoconstrictor Agents
PubMed: 37278709
DOI: 10.1097/MJT.0000000000001610 -
American Journal of Therapeutics
Meta-Analysis
Topics: Humans; Midodrine; Syncope, Vasovagal
PubMed: 35703495
DOI: 10.1097/MJT.0000000000001513 -
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 -
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