Midodrine initiation criteria, dose titration, and adverse effects when administered to treat shock: A systematic review and semi-quantitative analysis

Objective: Systematically examine the literature describing midodrine to treat shock and to summarize current administration and dosing strategies.
Data sources: Structured literature search conducted in MEDLINE (PubMed) from inception through May 10, 2023.
Study Selection and Data Extraction: Abstracts and full texts were assessed for inclusion by two blinded, independent reviewers. English-language publications describing use of midodrine in adult patients with shock were included. Data were extracted by two blinded, independent abstractors using a standardized extraction tool. Quality assessments were completed by paired reviewers using JBI methodology.
Data Synthesis: Fifteen of 698 (2%) screened manuscripts were included with 1,714 patients with a variety of shock types. Seven studies (47%) were retrospective, two (13%) prospective observational, and six (40%) randomized controlled studies. Midodrine was initiated to facilitate intravenous vasopressor (IVP) weaning in most (11, 73%) studies; only two (13%) reported IVP weaning protocol use. Starting doses were 10 mg every 8 hours (4, 27%) or three times a day (3, 20%), 20 mg every 8 hours (2, 13%); six studies (40%) did not report initial midodrine dosing. A midodrine titration protocol was reported in 6 (40%) studies. Thirteen (87%) studies evaluated for bradycardia, identified in 6 (46%) studies among 204 patients; only one (0.5%) patient required midodrine discontinuation. Three (20%) studies reported on hypertension with an incidence of 7-11%. Four (27%) studies assessed for ischemia; 5/1128 (0.4%) patients experienced mesenteric ischemia requiring midodrine discontinuation.
Relevance to Patient care and Clinical Practice: This review explores the pragmatic details involved in initiating, titrating, and weaning midodrine for the bedside clinician and identifies rates of adverse events and complications.
Conclusions: Published literature describing midodrine use for shock is heterogeneous and comprised primarily of low or very low quality data. Future controlled trials addressing the shortcomings identified in this systematic review are warranted.