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Intensive Care Medicine Oct 2020ICU discharge is often delayed by a requirement for intravenous vasopressor medications to maintain normotension. We hypothesised that the administration of midodrine,... (Randomized Controlled Trial)
Randomized Controlled Trial
Effect of midodrine versus placebo on time to vasopressor discontinuation in patients with persistent hypotension in the intensive care unit (MIDAS): an international randomised clinical trial.
PURPOSE
ICU discharge is often delayed by a requirement for intravenous vasopressor medications to maintain normotension. We hypothesised that the administration of midodrine, an oral α-adrenergic agonist, as adjunct to standard treatment shortens the duration of intravenous vasopressor requirement.
METHODS
In this multicentre, randomised, controlled trial including three tertiary referral hospitals in the US and Australia, we enrolled adult patients with hypotension requiring a single-agent intravenous vasopressor for ≥ 24 h. Subjects received oral midodrine (20 mg) or placebo every 8 h in addition to standard care until cessation of intravenous vasopressors, ICU discharge, or occurrence of adverse events. The primary outcome was time to vasopressor discontinuation. Secondary outcomes included time to ICU discharge readiness, ICU and hospital lengths of stay, and ICU readmission rates.
RESULTS
Between October 2012 and June 2019, 136 participants were randomised, of whom 132 received the allocated intervention and were included in the analysis (modified intention-to-treat approach). Time to vasopressor discontinuation was not different between midodrine and placebo groups (median [IQR], 23.5 [10-54] vs 22.5 [10.4-40] h; difference, 1 h; 95% CI - 10.4 to 12.3 h; p = 0.62). No differences in secondary endpoints were observed. Bradycardia occurred more often after midodrine administration (5 [7.6%] vs 0 [0%], p = 0.02).
CONCLUSION
Midodrine did not accelerate liberation from intravenous vasopressors and was not effective for the treatment of hypotension in critically ill patients.
Topics: Adult; Australia; Humans; Hypotension; Intensive Care Units; Midodrine; Vasoconstrictor Agents
PubMed: 32885276
DOI: 10.1007/s00134-020-06216-x -
Hepatology (Baltimore, Md.) Aug 2015Hepatorenal syndrome (HRS), a serious complication of cirrhosis, is associated with high mortality without treatment. Terlipressin with albumin is effective in the... (Comparative Study)
Comparative Study Randomized Controlled Trial
UNLABELLED
Hepatorenal syndrome (HRS), a serious complication of cirrhosis, is associated with high mortality without treatment. Terlipressin with albumin is effective in the reversal of HRS. Where terlipressin is not available, as in the United States, midodrine and octreotide with albumin are used as an alternative treatment of HRS. The aim was to compare the effectiveness of terlipressin plus albumin versus midodrine and octreotide plus albumin in the treatment of HRS in a randomized controlled trial. Twenty-seven patients were randomized to receive terlipressin with albumin (TERLI group) and 22 to receive midodrine and octreotide plus albumin (MID/OCT group). The TERLI group received terlipressin by intravenous infusion, initially 3 mg/24 hours, progressively increased to 12 mg/24 hours if there was no response. The MID/OCT group received midodrine orally at an initial dose of 7.5 mg thrice daily, with the dose increased to a maximum of 12.5 mg thrice daily, together with octreotide subcutaneously: initial dose 100 μg thrice daily and up to 200 μg thrice daily. Both groups received albumin intravenously 1 g/kg of body weight on day 1 and 20-40 g/day thereafter. There was a significantly higher rate of recovery of renal function in the TERLI group (19/27, 70.4%) compared to the MID/OCT group (6/21, 28.6%), P = 0.01. Improvement in renal function and lower baseline Model for End-Stage Liver Disease score were associated with better survival.
CONCLUSION
Terlipressin plus albumin is significantly more effective than midodrine and octreotide plus albumin in improving renal function in patients with HRS.
Topics: Aged; Albumins; Analysis of Variance; Drug Therapy, Combination; Female; Follow-Up Studies; Hepatorenal Syndrome; Humans; Infusions, Intravenous; Kaplan-Meier Estimate; Kidney Function Tests; Liver Function Tests; Lypressin; Male; Middle Aged; Midodrine; Octreotide; Predictive Value of Tests; Survival Analysis; Terlipressin; Treatment Outcome
PubMed: 25644760
DOI: 10.1002/hep.27709 -
Drug and Therapeutics Bulletin May 2016Midodrine (Bramox-Brancaster Pharma Limited) was authorised in the UK by the Medicines and Healthcare products Regulatory Agency (MHRA) in March 2015 for "the treatment... (Review)
Review
Midodrine (Bramox-Brancaster Pharma Limited) was authorised in the UK by the Medicines and Healthcare products Regulatory Agency (MHRA) in March 2015 for "the treatment of severe orthostatic hypotension due to autonomic dysfunction in adults when corrective factors have been ruled out and other forms of treatment are inadequate".(1) Previously, midodrine had only been available in the UK as an unlicensed product used on a named-patient basis. It is the first drug to be licensed in the UK for the treatment of orthostatic hypotension. Here we consider the evidence for midodrine in the treatment of severe orthostatic hypotension and how it fits with current management strategies.
Topics: Contraindications; Drug Interactions; Humans; Hypotension, Orthostatic; Midodrine
PubMed: 27173783
DOI: 10.1136/dtb.2016.5.0399 -
American Journal of Health-system... Jun 2022Prolonged duration of intravenous (IV) vasopressor dependence in critically ill adult patients with vasodilatory shock results in increased length of stay in both the... (Review)
Review
PURPOSE
Prolonged duration of intravenous (IV) vasopressor dependence in critically ill adult patients with vasodilatory shock results in increased length of stay in both the intensive care unit (ICU) and hospital, translating to higher risk of infection, delirium, immobility, and cost. Acceleration of vasopressor liberation can aid in reducing these risks. Midodrine is an oral α 1-adrenergic receptor agonist that offers a potential means of liberating patients from IV vasopressor therapy. This clinical review summarizes primary literature and proposes a clinical application for midodrine in the recovery phase of vasodilatory shock.
SUMMARY
Five studies with a total of over 1,000 patients conducted between 2011 and 2021 were identified. In observational studies, midodrine administration was demonstrated to lead to faster time to liberation from IV vasopressor therapy and shorter ICU length of stay in patients recovering from vasodilatory shock. These findings were not replicated in a prospective, multicenter, randomized controlled trial. In this review, literature evaluating midodrine use for IV vasopressor liberation is summarized and study limitations are discussed.
CONCLUSION
On the basis of this review of current literature, recommendations are provided on selecting appropriate candidates for adjunctive midodrine in the recovery phase of vasodilatory shock and considerations are discussed for safely and effectively initiating, titrating, and discontinuing therapy.
Topics: Administration, Intravenous; Adult; Humans; Hypotension; Intensive Care Units; Midodrine; Multicenter Studies as Topic; Prospective Studies; Randomized Controlled Trials as Topic; Vasoconstrictor Agents
PubMed: 35235946
DOI: 10.1093/ajhp/zxac069 -
American Journal of Therapeutics 2019
Topics: Adrenergic alpha-1 Receptor Agonists; Aged; Bradycardia; Digoxin; Drug Interactions; Electrocardiography; Glomerular Filtration Rate; Half-Life; Humans; Hypertension; Kidney; Male; Midodrine; Renal Insufficiency, Chronic; Tachycardia, Supraventricular
PubMed: 31498780
DOI: 10.1097/MJT.0000000000000856 -
Cureus Feb 2024Sepsis and septic shock represent critical conditions, often necessitating vasopressor support in the intensive care unit (ICU). Midodrine, an oral vasopressor, has... (Review)
Review
Sepsis and septic shock represent critical conditions, often necessitating vasopressor support in the intensive care unit (ICU). Midodrine, an oral vasopressor, has gathered attention as a potential adjunct to vasopressor therapy, aiming to facilitate weaning and improve clinical outcomes. However, the efficacy of midodrine remains questionable, with conflicting evidence from clinical trials and meta-analyses. This article provides a comprehensive review of the literature on midodrine's role in ICU settings by gathering evidence from multicenter trials, retrospective studies, and meta-analyses. While some studies suggest a limited benefit of midodrine in expediting vasopressor weaning and reducing ICU/hospital stays, others report potential advantages, particularly in reducing mortality rates among septic shock patients. Ongoing efforts aim to address knowledge gaps surrounding midodrine's efficacy and safety.
PubMed: 38558716
DOI: 10.7759/cureus.55192 -
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 -
Cardiology in the Young May 2021Vasovagal syncope is the most common cause of syncope in childhood and its treatment is not at a satisfactory level yet. We aimed to investigate patients who were...
BACKGROUND
Vasovagal syncope is the most common cause of syncope in childhood and its treatment is not at a satisfactory level yet. We aimed to investigate patients who were diagnosed with vasovagal syncope, did not benefit from conventional treatment, received midodrine treatment, and to evaluate their response to midodrine treatment.
METHODS
Files of 24 patients who were diagnosed with recurrent vasovagal syncope, did not benefit from non-pharmacological treatments, and received midodrine treatment during June 2017-October 2019 were retrospectively analysed.
RESULTS
In total, 24 patients received a treatment dose of midodrine at 5 mg/day (2.5 mg BID) included in the study. The mean number of syncope was 5.75 ± 2.67 prior to treatment. Following treatment, the mean number of syncope was 0.42 ± 0.89. It was observed that syncope episodes did not recur in 17 patients, but it recurred in 4 out of 7 patients in the first 3 months of the treatment and did not recur in the following months. The episodes improved in two patients with an increase in the treatment dose, but the syncope episodes continued in only one patient.
CONCLUSION
It was concluded that midodrine treatment was effective and safe in adolescents with recurrent vasovagal syncope.
Topics: Adolescent; Child; Humans; Midodrine; Recurrence; Retrospective Studies; Syncope, Vasovagal
PubMed: 33407967
DOI: 10.1017/S1047951120004746 -
The Annals of Pharmacotherapy Apr 2009To review studies evaluating the use of midodrine and octreotide in hemodynamic complications of cirrhosis, including ascites and hepatorenal syndrome. (Review)
Review
OBJECTIVE
To review studies evaluating the use of midodrine and octreotide in hemodynamic complications of cirrhosis, including ascites and hepatorenal syndrome.
DATA SOURCES
Searches of MEDLINE (1966-September 2008) and EMBASE (1974-September 2008) were conducted using the terms midodrine, octreotide, hepatorenal syndrome, ascites, cirrhosis, and paracentesis-induced circulatory dysfunction. Literature review was limited to English-language, human studies.
STUDY SELECTION AND DATA EXTRACTION
Studies identified from data sources were considered for review. Studies were excluded if primary therapy involved any of the following: transjugular intrahepatic portosystemic shunt procedure, medications other than midodrine or octreotide, or patients included for treatment or prevention of portal hypertension and/or variceal bleeding. Pharmacokinetic/pharmacodynamic studies and studies using retrospective data collection were excluded. Seven studies were included in this review.
DATA SYNTHESIS
Midodrine and octreotide in combination or alone have shown conflicting results for systemic and renal hemodynamics and renal function in patients with cirrhosis-related complications. Patients with ascites being treated with midodrine, alone or in combination with octreotide, showed significant changes in systemic hemodynamics, without a correlating change in renal perfusion. Studies comparing the use of midodrine with use of albumin for the prevention of paracentesis-induced circulatory dysfunction (PICD) showed no incidence of PICD in either treatment group. In hepatorenal syndrome, patients using midodrine with octreotide showed significant changes in systemic hemodynamics and improvements in renal perfusion. This regimen's effect on survival is yet to be determined.
CONCLUSIONS
Available evidence shows inconsistent results for the effectiveness and safety of midodrine and octreotide use in cirrhotic patients. Because of the contradictory results, longer treatment duration and increased number of study participants are necessary to determine the proper use of midodrine and octreotide in these patients.
Topics: Ascites; Hemodynamics; Hepatorenal Syndrome; Humans; Liver Cirrhosis; Midodrine; Octreotide; Treatment Outcome; Vascular Diseases
PubMed: 19299324
DOI: 10.1345/aph.1L373 -
Journal of Population Therapeutics and... Aug 2017Midodrine is an oral, peripherally acting alpha-adrenergic agonist. After gaining Food and Drug Administration (FDA) approval in 1996 for orthostatic hypotension, its... (Review)
Review
Midodrine is an oral, peripherally acting alpha-adrenergic agonist. After gaining Food and Drug Administration (FDA) approval in 1996 for orthostatic hypotension, its use has evolved to target vasoplegic conditions such as intradialytic hypotension in the end-stage renal disease population, refractory ascites in cirrhotic patients to support diuresis, and in hepatorenal syndrome. Upon oral ingestion, the drug undergoes enzymatic hydrolysis to an active metabolite, desglymidodrine. Its use has been well tolerated at 2.5 mg, 5 mg, and 10 mg oral doses. The most frequently occurring side effects relate directly to its sympathomimetic profile and include piloerection, scalp pruritis, generalized paresthesias, and urinary retention. The vasoplegic profile of sepsis would be a potential target for midodrine therapy. While its use to mediate recovery from septic shock has been suggested, there is a paucity of clinical data supporting its use. Such therapy may be uniquely appropriate in septic patients who are not candidates for intensive care unit (ICU) level of care.
Topics: Adrenergic alpha-Agonists; Humans; Hypotension; Intensive Care Units; Midodrine; Prodrugs; Pruritus
PubMed: 28873293
DOI: 10.22374/1710-6222.24.3.4