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

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; I² = 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.