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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 -
Neurology Sep 2014Symptomatic orthostatic hypotension (SOH) and recurrent reflex syncope (RRS) can be disabling. Midodrine has been proposed in the management of patients with these... (Review)
Review
OBJECTIVE
Symptomatic orthostatic hypotension (SOH) and recurrent reflex syncope (RRS) can be disabling. Midodrine has been proposed in the management of patients with these conditions but its impact on patient important outcomes remains uncertain. We performed a systematic review to evaluate the efficacy and safety of midodrine in patients with SOH and RRS.
METHODS
We searched multiple electronic databases without language restriction from their inception to June 2013. We included randomized controlled trials of patients with SOH or RRS that compared treatment with midodrine against a control and reported data on patient important outcomes. We graded the quality of evidence according to the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach.
RESULTS
Eleven trials involving 593 patients were included in this review. Three studies addressed health-related quality of life in patients with RRS, showing improvement with midodrine: risk difference 14% (95% confidence interval [CI] -3.5 to 31.6), very low confidence. Seven studies addressed symptom improvement and provided poolable data showing improvement with midodrine in patients with SOH: risk difference 32.8% (95% CI 13.5-48), low confidence; and RRS: risk difference 63.3% (95% CI 47.6-68.2), very low confidence. Five studies reported syncope recurrence in patients with RRS showing improvement with midodrine: risk difference 37% (95% CI 20.8%-47.4%), moderate confidence. The most frequent side effects in the midodrine arm were pilomotor reactions (33.6%, risk ratio 4.58 [95% CI 2.03-10.37]).
CONCLUSIONS
Evidence warranting low/moderate confidence suggests that midodrine improves clinical important outcomes in patients with SOH and RRS.
Topics: Humans; Hypotension, Orthostatic; Midodrine; Quality of Life; Reflex; Secondary Prevention; Syncope
PubMed: 25150287
DOI: 10.1212/WNL.0000000000000815 -
Effects of midodrine in patients with ascites due to cirrhosis: Systematic review and meta-analysis.Journal of Digestive Diseases Jan 2016Midodrine has been reported to improve systemic and renal hemodynamics in patients with cirrhotic ascites. However, the results of clinical trials are conflicting. The... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Midodrine has been reported to improve systemic and renal hemodynamics in patients with cirrhotic ascites. However, the results of clinical trials are conflicting. The aim of this study is to evaluate the effects of midodrine on cirrhotic ascites through a meta-analysis and systematic review.
METHODS
We searched PubMed (January 1966-December 2014), EMBASE (January 1966-December 2014), the Cochrane Library (Issue 11, 2014), ScienceDirect (January 1966-December 2014), and the China National Knowledge Infrastructure (January 1979-December 2014) databases using the terms 'midodrine' AND 'cirrhosis' AND 'ascites' AND 'paracentesis' for all relevant randomized controlled trials using midodrine for treatment of cirrhotic ascites.
RESULTS
In all, 10 trials with a total of 462 patients were included. As a novel therapy for cirrhotic ascites, midodrine was not found to improve survival [odds ratio (OR) 0.81, 95% confidence interval (CI) 0.23-2.91]; although it might improve response rates (OR 3.36, 95% CI 1.47-7.69) and reduce plasma renin activity (MD -3.10, 95% CI -5.37 to -0.84). When midodrine was used as an alternative to albumin in large-volume paracentesis, the mortality was higher for midodrine than for albumin (OR 10.76, 95% CI 1.35-85.97). However, there was no statistically significant difference in the development of paracentesis-induced circulatory dysfunction between midodrine group and albumin group (OR 1.69, 95% CI 0.43-6.72).
CONCLUSIONS
Midodrine may have treatment effects on cirrhotic ascites. Better powered and well-designed trials are required to assess the extent of the efficacy of midodrine in specifically targeted patients.
Topics: Bias; Data Interpretation, Statistical; Humans; Liver Cirrhosis; Midodrine; Sensitivity and Specificity; Vasoconstrictor Agents
PubMed: 26630543
DOI: 10.1111/1751-2980.12304 -
European Review For Medical and... May 2023This study aims to assess the efficacy and safety of midodrine on treating patients with septic shock. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
This study aims to assess the efficacy and safety of midodrine on treating patients with septic shock.
MATERIALS AND METHODS
Literature search was conducted in PubMed, the Cochrane Library, and Embase. The Mantel-Haenszel method was used to calculate pooled relative risks (RRs) and 95% confidence intervals (95% CI). The mean differences (MD) or standardized mean difference (SMD) were calculated using the inverse variance for continuous variables. Data analysis was performed using Review Manager 5.3.
RESULTS
A total of 6 studies were finally included in this meta-analysis. Adding midodrine to patients with septic shock was associated with a reduction in hospital mortality [risk ratio (RR) 0.76; 95% CI, 0.57-1.00; p=0.05] and intensive care unit (ICU) mortality (RR 0.59; 95% CI, 0.41-0.87; p=0.008). However, there were no significant differences in the duration of intravenous vasopressors [standardized mean difference (SMD) -0.18; 95% CI, -0.47-0.11; p=0.23], intravenous vasopressor reinstitution (RR 0.58; 95% CI, 0.19-1.80; p=0.35), the length of ICU stay [mean difference (MD) -0.53 days; 95% CI, -2.24-1.17; p=0.54], and the length of hospital stay (MD -2.40 days; 95% CI, -5.26-0.46; p=0.10) between midodrine group and intravenous vasopressor alone group.
CONCLUSIONS
The additional use of midodrine might reduce hospital mortality and ICU mortality in patients with septic shock. More high-quality randomized controlled trials are needed to verify this conclusion.
Topics: Humans; Shock, Septic; Midodrine; Intensive Care Units; Hospital Mortality; Length of Stay; Prognosis
PubMed: 37203847
DOI: 10.26355/eurrev_202305_32331 -
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 -
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