Midodrine improves clinical and economic outcomes in patients with septic shock: a randomized controlled clinical trial

Adly, Dina Hussein El; Bazan, Naglaa Samir; Borolossy, Radwa Maher El; Anan, Islam Fawzy; Fakher, Mohamed; Wakeel, Lamia Mohamed El

doi:10.1007/s11845-021-02903-w

Cited by 8 publications

(23 citation statements)

References 22 publications

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“…However, this study was not blinded and was small in size, thus limiting its validity. 17 Ahmed et al evaluated midodrine specifically for the use of blood pressure support in 90 patients with neurogenic shock and also determined that the use of midodrine was associated with decreased duration of intravenous vasopressor support and decreased ICU LoS. Again, however, this study was unblinded and of small sample size, which also limits its validity.…”

Section: Discussionmentioning

confidence: 93%

“…Further, more recently published randomised controlled trials (RCTs) have found results that conflict with the MIDAS trial, further questioning the role of midodrine for vasopressor dependent hypotension. [17][18][19] While a recently published meta-analysis examining the role of midodrine in resolving shock did not find any difference in intravenous vasopressor duration, ICU or hospital lengths of stay or mortality, the review did not provide any subgroup analysis or use Grading of Recommendations, Assessment, Development and Evaluations (GRADE) recommendations or trial sequential analysis (TSA) methods. 20 Further, it was conducted prior to the publication of most recent evidence.…”

Section: Strengths and Limitations Of This Studymentioning

confidence: 99%

“…Recently, there have been several RCTs that have evaluated the use of midodrine as an adjunctive therapy to intravenous vasopressor dependent hypotension. [16][17][18][19] The MIDAS trial randomised 136 undifferentiated hypotensive patients to either midodrine or placebo evaluating the median time from study drug initiation until discontinuation of intravenous vasopressors. The study investigators determined that there was no significant difference between groups.…”

Section: Subgroup Analysesmentioning

confidence: 99%

“…16 More recently, there have been smaller published RCTs that have shown conflicting results. [17][18][19] Adly et al evaluated the use of midodrine in 60 patients with septic shock and clinical stability on low-dose intravenous vasopressors for at least 24 hours and determined that midodrine was associated with significantly shortened duration of intravenous vasopressor support and significant decreased mortality. However, this study was not blinded and was small in size, thus limiting its validity.…”

Section: Subgroup Analysesmentioning

confidence: 99%

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Midodrine therapy for vasopressor dependent shock in the intensive care unit: a protocol for a systematic review and meta-analysis

et al. 2022

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IntroductionIntensive care unit (ICU) lengths of stay are modified by ongoing need for haemodynamic support in critically ill patients. This is most commonly provided by intravenous vasopressor therapy. Midodrine has been used as an oral agent for haemodynamic support in patients with orthostatic hypotension or cirrhosis. However, its efficacy in treating shock in the ICU, particularly for patients weaning from intravenous vasopressors, remains uncertain. The objective of this systematic review is to determine the efficacy of midodrine in vasopressor dependent shock.Methods and analysisWe will search Ovid MEDLINE, Ovid Embase, CINAHL and Cochrane Library for observational trials and randomised controlled trials evaluating midodrine in critically ill patients from inception to 21 April 2022. We will also review unpublished data and relevant conference abstracts. Outcomes will include ICU length of stay, duration of intravenous vasopressor support, ICU mortality, hospital mortality, hospital length of stay and rates of ICU readmission. Data will be analysed in aggregate, where appropriate. We will evaluate risk of bias using the modified Cochrane tool and certainty of evidence using Grading of Recommendations, Assessment, Development and Evaluations methodology. We will perform trial sequential analysis for the outcome of ICU length of stay.Ethics and disseminationEthics approval is not required as primary data will not be collected. Findings of this review will be disseminated through peer-related publication and will inform future clinical trials.PROSPERO registration numberCRD42021260375.

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Section: Discussionmentioning

confidence: 93%

Section: Strengths and Limitations Of This Studymentioning

confidence: 99%

Section: Subgroup Analysesmentioning

confidence: 99%

Section: Subgroup Analysesmentioning

confidence: 99%

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Midodrine therapy for vasopressor dependent shock in the intensive care unit: a protocol for a systematic review and meta-analysis

et al. 2022

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“…A randomized trial comparing oral midodrine with intravenous norepinephrine found that 30 mg/day of midodrine reduced 73 mg of norepinephrine during six days in septic shock [40], which gave a correction factor of 0.4 to midodrine dose in μg/kg/min.…”

Section: Proposed Updated Norepinephrine Equivalent Scorementioning

confidence: 99%

An updated “norepinephrine equivalent” score in intensive care as a marker of shock severity

et al. 2023

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Vasopressors and fluids are the cornerstones for the treatment of shock. The current international guidelines on shock recommend norepinephrine as the first-line vasopressor and vasopressin as the second-line vasopressor. In clinical practice, due to drug availability, local practice variations, special settings, and ongoing research, several alternative vasoconstrictors and adjuncts are used in the absence of precise equivalent doses. Norepinephrine equivalence (NEE) is frequently used in clinical trials to overcome this heterogeneity and describe vasopressor support in a standardized manner. NEE quantifies the total amount of vasopressors, considering the potency of each such agent, which typically includes catecholamines, derivatives, and vasopressin. Intensive care studies use NEE as an eligibility criterion and also an outcome measure. On the other hand, NEE has several pitfalls which clinicians should know, important the lack of conversion of novel vasopressors such as angiotensin II and also adjuncts such as methylene blue, including a lack of high-quality data to support the equation and validate its predictive performance in all types of critical care practice. This review describes the history of NEE and suggests an updated formula incorporating novel vasopressors and adjuncts.

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The Use of Midodrine as an Adjunctive Therapy to Liberate Patients from Intravenous Vasopressors: A Systematic Review and Meta-analysis of Randomized Controlled Studies

et al. 2023

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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 2 = 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. Supplementary Information The online version contains supplementary material available at 10.1007/s40119-023-00301-0.

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Midodrine improves clinical and economic outcomes in patients with septic shock: a randomized controlled clinical trial

Cited by 8 publications

References 22 publications

Midodrine therapy for vasopressor dependent shock in the intensive care unit: a protocol for a systematic review and meta-analysis

Midodrine therapy for vasopressor dependent shock in the intensive care unit: a protocol for a systematic review and meta-analysis

An updated “norepinephrine equivalent” score in intensive care as a marker of shock severity

The Use of Midodrine as an Adjunctive Therapy to Liberate Patients from Intravenous Vasopressors: A Systematic Review and Meta-analysis of Randomized Controlled Studies

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