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Critical Care Medicine Oct 2022Hepatorenal syndrome (HRS) is associated with high rates of morbidity and mortality. Evidence examining commonly used drug treatments remains uncertain. We assessed the... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Hepatorenal syndrome (HRS) is associated with high rates of morbidity and mortality. Evidence examining commonly used drug treatments remains uncertain. We assessed the comparative effectiveness of inpatient treatments for HRS by performing a network meta-analysis of randomized clinical trials (RCTs).
DATA SOURCES
We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Medline In-Process & Other Non-Indexed Citations, Scopus, and Web of Science from inception.
STUDY SELECTION AND DATA EXTRACTION
Pairs of reviewers independently identified eligible RCTs that enrolled patients with type 1 or 2 HRS. Pairs of reviewers independently extracted data.
DATA SYNTHESIS
We assessed risk of bias using the Cochrane tool for RCTs and certainty of evidence using the Grading of Recommendations, Assessment, Development and Evaluations approach. Our main outcomes are all-cause mortality, HRS reversal, and serious adverse events. Of 3,079 citations, we included 26 RCTs examining 1,736 patients. Based on pooled analysis, terlipressin increases HRS reversal compared with placebo (142 reversals per 1,000 [95% CI, >87.7 to >210.9]; high certainty). Norepinephrine (112.7 reversals per 1,000 [95% CI, 52.6 to >192.3]) may increase HRS reversal compared with placebo (low certainty). The effect of midodrine+octreotide (67.8 reversals per 1,000 [95% CI, <2.8 to >177.4]; very low) on HRS reversal is uncertain. Terlipressin may reduce mortality compared with placebo (93.7 fewer deaths [95% CI, 168.7 to <12.5]; low certainty). Terlipressin probably increases the risk of serious adverse events compared with placebo (20.4 more events per 1,000 [95% CI, <5.1 to >51]; moderate certainty).
CONCLUSIONS
Terlipressin increases HRS reversal compared with placebo. Terlipressin may reduce mortality. Until access to terlipressin improves, initial norepinephrine administration may be more appropriate than initial trial with midodrine+octreotide. Our review has the potential to inform future guideline and practice in the treatment of HRS.
Topics: Hepatorenal Syndrome; Humans; Midodrine; Network Meta-Analysis; Norepinephrine; Octreotide; Terlipressin; Treatment Outcome; Vasoconstrictor Agents
PubMed: 35777925
DOI: 10.1097/CCM.0000000000005595 -
Europace : European Pacing,... Jul 2022Vasovagal syncope (VVS) is a common clinical condition that lacks effective medical therapies despite being associated with significant morbidity. Current guidelines... (Meta-Analysis)
Meta-Analysis
AIMS
Vasovagal syncope (VVS) is a common clinical condition that lacks effective medical therapies despite being associated with significant morbidity. Current guidelines suggest that midodrine, a prodrug for an α1-adrenergic receptor agonist, might suppress VVS but supporting studies have utilized heterogeneous methods and yielded inconsistent results. To evaluate the efficacy of midodrine to prevent syncope in patients with recurrent VVS by conducting a systematic review and meta-analysis of published studies.
METHODS AND RESULTS
Relevant randomized controlled trials were identified from the MEDLINE, Embase, CENTRAL, and CINAHL databases without language restriction from inception to June 2021. All studies were conducted in clinical syncope populations and compared the benefit of midodrine vs. placebo or non-pharmacological standard care. Weighted relative risks (RRs) were estimated using random effects meta-analysis techniques. Seven studies (n = 315) met inclusion criteria. Patients were 33 ± 17 years of age and 31% male. Midodrine was found to substantially reduce the likelihood of positive head-up-tilt (HUT) test outcomes [RR = 0.37 (0.23-0.59), P < 0.001]. In contrast, the pooled results of single- and double-blind clinical trials (I2 = 54%) suggested a more modest benefit from midodrine for the prevention of clinical syncope [RR = 0.51 (0.33-0.79), P = 0.003]. The two rigorous double-blind, randomized, placebo-controlled clinical trials included 179 VVS patients with minimal between-study heterogeneity (I2 = 0%) and reported a risk reduction with midodrine [RR = 0.71 (0.53-0.95), P = 0.02].
CONCLUSIONS
Midodrine is effective in preventing syncope induced by HUT testing and less, but still significant, RR reduction in randomized, double-blinded clinical trials.
Topics: Double-Blind Method; Female; Humans; Male; Midodrine; Randomized Controlled Trials as Topic; Syncope; Syncope, Vasovagal; Tilt-Table Test
PubMed: 35025999
DOI: 10.1093/europace/euab323 -
Cureus Jul 2022Ascites is the most common complication of liver cirrhosis. Midodrine is a vasoconstrictor that improves splanchnic and systemic hemodynamics, reduces ascites, and... (Review)
Review
Ascites is the most common complication of liver cirrhosis. Midodrine is a vasoconstrictor that improves splanchnic and systemic hemodynamics, reduces ascites, and improves clinical outcomes. Here, we aimed to examine the role of midodrine in cirrhosis-related ascites. Scopus, Embase, PubMed, and PubMed Central databases were searched for relevant randomized controlled trials comparing midodrine with other interventions in patients with cirrhotic ascites on November 25, 2020, using appropriate keywords like "midodrine", "ascitic cirrhosis", "peritoneal paracentesis" and suitable Boolean operators. Odds ratio (OR) and mean difference (MD) were used to analyze pool data as appropriate with a 95% confident interval (CI). A total of 14 studies were included in our analysis including 1199 patients. The addition of midodrine resulted in statistically significant improvement in mean arterial pressure (MAP) (MD, 3.95 mmHg; 95% CI, 1.53-6.36) and MELD (Model for End-Stage Liver Disease) score (MD, -1.27; 95% CI, -2.49 to -0.04) compared to standard medical treatment (SMT). There was also a significant improvement in plasma renin activity and plasma aldosterone concentration. However, there was no significant improvement in mortality or serum creatinine compared to SMT. In addition, there was no statistically significant improvement in MAP, plasma renin activity, plasma aldosterone concentration, MELD score, overall mortality, and paracentesis-induced circulatory dysfunction comparing midodrine with albumin. Midodrine alone leads to significant improvement in various clinical parameters in patients with cirrhotic ascites compared to standard medical care. At the same time, it was found to be non-inferior to albumin. Therefore, further well-designed studies need to be carried out on midodrine in addition to albumin for optimal clinical benefits among patients with ascites due to cirrhosis.
PubMed: 36060403
DOI: 10.7759/cureus.27483 -
Cureus May 2023The literature on pharmacologic treatments for postural orthostatic tachycardia syndrome (POTS) is inconsistent and unstandardized. Therefore, we aimed to evaluate... (Review)
Review
The literature on pharmacologic treatments for postural orthostatic tachycardia syndrome (POTS) is inconsistent and unstandardized. Therefore, we aimed to evaluate choices in pharmacologic treatment options for POTS and the challenges encountered in the studies. We searched numerous databases like PubMed, Scopus, Embase, Web of Science, and Google Scholar for literature published before April 8, 2023. The search was done to retrieve potential peer-reviewed articles that explored drug therapy in POTS. Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines were used to conduct the systematic review. Of the 421 potential articles assessed, 17 met the inclusion criteria. Results demonstrated that pharmacologic treatment options for POTS were effective in reducing symptoms of POTS, but most of the studies were underpowered. Several were terminated due to various reasons. Midodrine ivabradine, bisoprolol, fludrocortisone, droxidopa, desmopressin, propranolol, modafinil, methylphenidate, and melatonin have been studied with positive impact but sample sizes that were low in the range of 10-50 subjects. Therefore, we concluded the treatment options effectively improve symptoms of POTS and increase orthostatic tolerance, but more evidence is needed as most studies had a low sample size and thus are underpowered.
PubMed: 37313107
DOI: 10.7759/cureus.38887 -
Therapeutic Advances in... 2022Clozapine is the most effective medication for treatment-refractory schizophrenia but is associated with significant adverse drug effects, including hypotension and... (Review)
Review
BACKGROUND
Clozapine is the most effective medication for treatment-refractory schizophrenia but is associated with significant adverse drug effects, including hypotension and dizziness, which have a negative impact on quality of life and treatment compliance. Available evidence for the management of clozapine-induced hypotension is scant.
OBJECTIVES
Due to limited guidance on the safety and efficacy of pharmacological treatments for clozapine-induced hypotension, we set out to systematically review and assess the evidence for the management of clozapine-induced hypotension and provide guidance to clinicians, patients, and carers.
DESIGN
We undertook a systematic review of the safety and efficacy of interventions for clozapine-induced hypotension given the limited available evidence.
DATA SOURCES AND METHODS
PubMed, Embase, PsycINFO, CINAHL, and the Cochrane trial Registry were searched from inception to November 2021 for literature on the treatment strategies for clozapine-induced hypotension and dizziness using a PROSPERO pre-registered search strategy. For orthostatic hypotension, we developed a management framework to assist in the choice of intervention.
RESULTS
We identified nine case studies and four case series describing interventions in 15 patients. Hypotension interventions included temporary clozapine dose reduction, non-pharmacological treatments, and pharmacological treatments. Midodrine, fludrocortisone, moclobemide and Bovril combination, and etilefrine were associated with improvement in symptoms or reduction in orthostatic hypotension. Angiotensin II, arginine vasopressin, and noradrenaline successfully restored and maintained mean arterial pressure in critical care situations. A paradoxical reaction of severe hypotension was reported with adrenaline use.
CONCLUSION
Orthostatic hypotension is a common side effect during clozapine titration. Following an assessment of the titration schedule, salt and fluid intake, and review of hypertensive and nonselective α1-adrenergic agents, first-line treatment should be a temporary reduction in clozapine dose or non-pharmacological interventions. If orthostatic hypotension persists, fludrocortisone should be trialled with monitoring of potassium levels and sodium and fluid intake. Midodrine may be considered second-line or where fludrocortisone is contraindicated or poorly tolerated. For patients on clozapine with hypotension in critical care settings, the use of adrenaline to maintain mean arterial pressure should be avoided.
REGISTRATION
PROSPERO (Registration No. CRD42020191530).
PubMed: 35633931
DOI: 10.1177/20451253221092931 -
Critical Care Research and Practice 2021To evaluate the efficacy and safety of midodrine use in intensive care units (ICU) to facilitate weaning off intravenous vasopressors (IVV). (Review)
Review
PURPOSE
To evaluate the efficacy and safety of midodrine use in intensive care units (ICU) to facilitate weaning off intravenous vasopressors (IVV).
METHODS
We searched PubMed/MEDLINE, Cochrane library, and Google Scholar (inception through October 18, 2020) for studies evaluating adjuvant use of midodrine to IVV in the ICU. The outcomes of interest were ICU length of stay (LOS), hospital LOS, mortality, IVV reinstitution, ICU readmission, and bradycardia. Estimates were pooled using the random-effects model. We reported effect sizes as standardized mean difference (SMD) for continuous outcomes and risk ratios (RRs) for other outcomes with a 95% confidence interval (CI).
RESULTS
A total of 6 studies were found that met inclusion criteria and had sufficient data for our quantitative analysis (1 randomized controlled trial and 5 retrospective studies). A total of 2,857 patients were included: 600 in the midodrine group and 2,257 patients in the control group. Midodrine use was not associated with a significant difference in ICU LOS (SMD 0.16 days; 95% CI -0.23 to 0.55), hospital LOS (SMD 0.03 days; 95% CI -0.33 to 0.0.39), mortality (RR 0.87; 95% CI 0.52 to 1.46), IVV reinstitution (RR 0.47; 95% CI 0.17 to 1.3), or ICU readmission (RR 1.03; 95% CI 0.71 to 1.49) when compared to using only IVV. However, there were higher trends of bradycardia with midodrine use that did not reach significance (RR 7.64; 95% CI 0.23 to 256.42).
CONCLUSION
This meta-analysis suggests that midodrine was not associated with a significant decrease in ICU LOS, hospital LOS, mortality, or ICU readmissions.
PubMed: 34055408
DOI: 10.1155/2021/5588483 -
Journal of Cardiovascular Pharmacology Jul 2023Postural orthostatic tachycardia syndrome (POTS) is a clinical syndrome of inappropriate increase in heart rate on standing that has been recently also associated with...
Postural orthostatic tachycardia syndrome (POTS) is a clinical syndrome of inappropriate increase in heart rate on standing that has been recently also associated with Coronavirus Disease 2019 (COVID-19) as part of the postacute sequelae of COVID-19 (PASC) or long-COVID. We herein aimed to systematically review reported cases of POTS after COVID-19 and determine the characteristics of the subjects, the diagnostic approach used, and the treatment strategies. We searched the literature according to the following criteria: (1) diagnosis of POTS according to standard definition; (2) timely association with a probable or definite diagnosis of COVID-19; and (3) a description of the individual subject(s). We identified 21 reports meeting criteria between March 2020 and September 2022, including 68 subjects (51 females and 17 males, 3:1 ratio) with a mean age of 34 ± 12 years, with reports deriving from the United States, Norway, Sweden, Israel, Ireland, United Kingdom, Singapore, and Japan. Most cases had mild COVID-19 symptoms. The most common POTS symptoms were palpitations, chest pain, lightheadedness, and debilitating fatigue. The diagnosis was established by means of head-up tilt table or active stand test. Nonpharmacologic treatments (fluids, sodium intake, and compression stockings) were virtually always used, but largely ineffective. Subjects received different treatments, the most common being beta-adrenergic blockers (ie, propranolol), mineral corticosteroids (ie, fludrocortisone), midodrine, and ivabradine. Symptoms tended to improve over time, but most patients remained symptomatic for several months. In conclusion, POTS after COVID-19 is a clinical condition affecting young individuals, and disproportionately young women, occurring as part of PASC-long-COVID, often debilitating, which can be easily diagnosed with a thorough clinical assessment and measuring changes in orthostatic heart rate and blood pressure. POTS after COVID-19 seems to be poorly responsive to nonpharmacological treatments but with symptoms improving with pharmacological interventions. Given the limited data available, additional research is urgently needed with respect to its epidemiology, pathophysiology, and treatments.
Topics: Male; Humans; Female; Young Adult; Adult; Middle Aged; Postural Orthostatic Tachycardia Syndrome; Post-Acute COVID-19 Syndrome; COVID-19; Adrenergic beta-Antagonists; Midodrine; Heart Rate
PubMed: 37094584
DOI: 10.1097/FJC.0000000000001432 -
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 -
Heart Rhythm Mar 2023Vasovagal syncope (VVS) is a transient loss of consciousness that currently imposes a high burden on health care systems with limited evidence of the comparative... (Meta-Analysis)
Meta-Analysis Review
Vasovagal syncope (VVS) is a transient loss of consciousness that currently imposes a high burden on health care systems with limited evidence of the comparative efficacy of available pharmacologic interventions. This study aims to compare all pharmacologic therapies suggested in randomized controlled trials (RCTs) through systematic review and network meta-analysis. A systematic search in PubMed, Embase, Web of Science, and Cochrane Library was conducted to identify RCTs evaluating pharmacologic therapies for patients with VVS. The primary outcome was spontaneous VVS recurrence. The secondary outcome was a positive head-up tilt test (HUTT) after receiving intervention, regarded as a lower level of evidence. Pooled risk ratio (RR) with 95% confidence interval (CI) was calculated using random-effect network meta-analysis. Pairwise meta-analysis for comparison with placebo was also performed when applicable. The surface under the cumulative ranking curve analysis was conducted to rank the treatments for each outcome. Twenty-eight studies with 1744 patients allocated to different medications or placebo were included. Network meta-analysis of the reduction in the primary outcome showed efficacy for midodrine (RR 0.55; 95% CI 0.35-0.85) and fluoxetine (especially in patients with concomitant anxiety) (RR 0.36; 95% CI 0.16-0.84). In addition, midodrine and atomoxetine were superior to other treatment options, considering positive HUTT (RR 0.37; 95% CI 0.23-0.59; and RR 0.49; 95% CI 0.28-0.86, respectively). Overall, midodrine was the only agent shown to reduce spontaneous syncopal events. Fluoxetine also seems to be beneficial but should be studied further in RCTs. Our network meta-analysis did not find evidence of the efficacy of any other medication.
Topics: Humans; Fluoxetine; Midodrine; Syncope, Vasovagal; Network Meta-Analysis; Randomized Controlled Trials as Topic
PubMed: 36509319
DOI: 10.1016/j.hrthm.2022.12.010 -
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