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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 -
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 -
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 -
The Lancet. Gastroenterology &... Feb 2017Several drugs have been studied to improve outcomes for patients with hepatorenal syndrome, but trials have reported variable efficacy. We aimed to compare the efficacy... (Comparative Study)
Comparative Study Meta-Analysis Review
BACKGROUND
Several drugs have been studied to improve outcomes for patients with hepatorenal syndrome, but trials have reported variable efficacy. We aimed to compare the efficacy of different management strategies for type 1 hepatorenal syndrome.
METHODS
For this systematic review and network meta-analysis, we searched Ovid MEDLINE In-Process & Other Non-Indexed Citations, Ovid MEDLINE, Ovid Embase, Ovid Cochrane Central Register of Controlled Trials, Scopus, and Web of Science for papers published up to June 9, 2016. We selected randomised controlled trials of adults (>18 years) with decompensated cirrhosis and type 1 hepatorenal syndrome that compared the efficacy of active vasoactive drugs (terlipressin, midodrine, octreotide, noradrenaline, and dopamine; alone or in combination) with placebo or each other. The primary outcome was reduction in short-term mortality. Secondary outcomes were reversal of hepatorenal syndrome, relapse of hepatorenal syndrome after initial reversal, and adverse events. We did pairwise and network meta-analyses to produce odds ratios (ORs) and 95% CIs. We used the GRADE criteria to appraise quality of evidence.
FINDINGS
We identified 13 randomised controlled trials done in 739 adults with type 1 hepatorenal syndrome. All participants received supportive therapy with albumin. Moderate-quality evidence might support the use of terlipressin over placebo for reduction of short-term mortality (OR 0·65, 95% CI 0·41-1·05), whereas only low-quality evidence supported the use of noradrenaline, midodrine plus octreotide, and dopamine plus furosemide over placebo to reduce mortality, and no ORs for any of the comparisons versus placebo were significant. Moderate-quality evidence supported the use of terlipressin over midodrine plus octreotide (OR 26·25, 95% CI 3·07-224·21) to reverse hepatorenal syndrome, with low-quality evidence supporting the use of noradrenaline over placebo (4·17, 1·37-12·50) and over midodrine plus octreotide (10·00, 1·49-50·00) for this outcome. A median of 16% (range 5-20) of terlipressin-treated patients, and 33% (range 6-40) noradrenaline-treated patients with reversal of hepatorenal syndrome had recurrence on discontinuation of therapy. A median of 8% (range 4-22) terlipressin-treated patients required discontinuation of therapy due to serious adverse events.
INTERPRETATION
Terlipressin with albumin might reduce short-term mortality compared with placebo in patients with type 1 hepatorenal syndrome. Terlipressin with albumin and noradrenaline with albumin are both superior to midodrine plus octreotide with albumin for reversal of hepatorenal syndrome. Pragmatic clinical trials of terlipressin with albumin are warranted to evaluate real-world effectiveness and safety in patients with type 1 hepatorenal syndrome.
FUNDING
None.
Topics: Dopamine; Drug Therapy, Combination; Gastrointestinal Agents; Hepatorenal Syndrome; Humans; Lypressin; Midodrine; Network Meta-Analysis; Norepinephrine; Octreotide; Terlipressin; Treatment Outcome; Vasoconstrictor Agents
PubMed: 28403995
DOI: 10.1016/S2468-1253(16)30157-1 -
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 -
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 -
The Annals of Pharmacotherapy Dec 2018The comparative effects of droxidopa and midodrine on standing systolic blood pressure (sSBP) and risk of supine hypertension in patients with neurogenic orthostatic... (Comparative Study)
Comparative Study Meta-Analysis
Standing and Supine Blood Pressure Outcomes Associated With Droxidopa and Midodrine in Patients With Neurogenic Orthostatic Hypotension: A Bayesian Meta-analysis and Mixed Treatment Comparison of Randomized Trials.
BACKGROUND
The comparative effects of droxidopa and midodrine on standing systolic blood pressure (sSBP) and risk of supine hypertension in patients with neurogenic orthostatic hypotension (NOH) are unknown.
OBJECTIVE
To perform a Bayesian mixed-treatment comparison meta-analysis of droxidopa and midodrine in the treatment of NOH.
METHODS
The PubMed, CENTRAL, and EMBASE databases were searched up to November 16, 2016. Study selection consisted of randomized trials comparing droxidopa or midodrine with placebo and reporting on changes in sSBP and supine hypertension events. Data were pooled to perform a comparison among interventions in a Bayesian fixed-effects model using vague priors and Markov chain Monte Carlo simulation with Gibbs sampling, calculating pooled mean changes in sSBP and risk ratios (RRs) for supine hypertension with associated 95% credible intervals (CrIs).
RESULTS
Six studies (4 administering droxidopa and 2 administering midodrine) enrolling a total of 783 patients were included for analysis. The mean change from baseline in sSBP was significantly greater for both drugs when compared with placebo (droxidopa 6.2 mm Hg [95% CrI = 2.4-10] and midodrine 17 mm Hg [95% CrI = 11.4-23]). Comparative analysis revealed a significant credible difference between droxidopa and midodrine. The RR for supine hypertension was significantly greater for midodrine, but not droxidopa, when compared with placebo (droxidopa RR = 1.4 [95% CrI = 0.7-2.7] and midodrine RR = 5.1 [95% CrI = 1.6-24]). Conclusion and Relevance: In patients with NOH, both droxidopa and midodrine significantly increase sSBP, the latter to a greater extent. However, midodrine, but not droxidopa, significantly increases risk of supine hypertension.
Topics: Antiparkinson Agents; Bayes Theorem; Blood Pressure; Droxidopa; Humans; Hypertension; Hypotension, Orthostatic; Midodrine; Network Meta-Analysis; Odds Ratio; Randomized Controlled Trials as Topic; Standing Position; Supine Position; Treatment Outcome; Vasoconstrictor Agents
PubMed: 29972032
DOI: 10.1177/1060028018786954 -
Journal of Clinical Gastroenterology Apr 2018Hepatorenal syndrome (HRS) is a serious complication of advanced chronic liver disease. Different pharmacological therapies have variable efficacy. We performed a... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Hepatorenal syndrome (HRS) is a serious complication of advanced chronic liver disease. Different pharmacological therapies have variable efficacy. We performed a systematic review and meta-analysis to compare the efficacy of various drugs in the treatment of HRS.
STUDY
Randomized controlled trials comparing active drug with placebo or comparing 2 different drugs were included in this analysis. Primary study outcome was reversal of HRS. Secondary outcomes were HRS relapse and patient survival. Subgroup analysis was performed on patients with type 1 HRS.
RESULTS
Thirteen randomized controlled trial were eligible for analysis. Terlipressin plus albumin was more efficacious than placebo plus albumin (odds ratio=4.72; 95% confidence interval, 1.72-12.93; P=0.003) or midodrine plus albumin and octreotide (odds ratio=5.94; 95% confidence interval, 1.69-20.85; P=0.005), for HRS reversal. However, no significant difference was noted comparing terlipressin plus albumin versus noradrenaline plus albumin, octreotide plus albumin versus placebo plus albumin or noradrenaline plus albumin versus midodrine plus albumin and octreotide. None of the comparisons showed difference on HRS relapse or patient survival. Subgroup analysis revealed that terlipressin was more effective than placebo for type 1 HRS reversal, but no significant differences were noted between any other comparisons, and none of the comparisons showed difference on HRS relapse or patient survival.
CONCLUSIONS
Intravenous infusion of terlipressin is the most effective medical therapy for reversing HRS. Intravenous infusion of noradrenaline is an acceptable alternative. Studies are needed as basis for developing pharmacological strategies to reduce relapse of HRS and improve patient survival.
Topics: Albumins; Drug Therapy, Combination; Hepatorenal Syndrome; Humans; Infusions, Intravenous; Midodrine; Octreotide; Randomized Controlled Trials as Topic; Terlipressin; Vasoconstrictor Agents
PubMed: 28991106
DOI: 10.1097/MCG.0000000000000913 -
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 -
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