A 2023 review article aims to understand how midodrine might improve patient outcomes by sparing the use of intravenous vasopressors (IVP), addressing an unmet need in the management of septic shock. Using midodrine as a vasopressor-sparing agent stems from its ability to increase blood pressure by stimulating alpha-1 adrenergic receptors, leading to vasoconstriction. Being an oral medication, midodrine could potentially offer a more convenient and safer alternative or supplement to IV vasopressors, allowing for an earlier transition from intensive care settings and reducing the duration of IV vasopressor use. The summary highlights the importance of careful consideration and thorough clinical evaluation to determine whether incorporating midodrine into treatment protocols for septic shock could offer tangible benefits in terms of efficacy, patient safety, and healthcare resource utilization. [1]
Several studies aimed to assess the role of midodrine in the treatment of septic shock (See Table 1). Although some studies, limited by small sample size and/or retrospective nature, indicated a statistically significant difference in decreased IVP duration associated with midodrine use, the majority of studies have evaluated midodrine Q8 hours in the recovery phase of shock. However, midodrine half-life is shorter at 3 to 4 hours. As such, given the possibility of large swings in plasma concentrations of the medication, the results should be interpreted with caution. The MIDAS trial (N= 132) is referred to as the largest randomized clinical trial evaluating midodrine as an adjunct to standard treatment in shortening the duration of IVP requirement for patients with vasodilatory shock in the intensive care unit (ICU). This study did not reveal a significant difference in the midodrine group in regards to time to discontinuation of IVPs, time to ICU discharge readiness, or ICU or hospital length of stay when compared to placebo (See Table 2). Overall, given the sparse data on the use of midodrine as an adjunctive IVP-sparing treatment option in septic shock, no definitive conclusion can be made concerning the effectiveness of midodrine for avoiding vasopressor infusions in hypotensive, critically-ill patients. [1]
A 2019 review article aimed to assess the clinical efficacy, safety, and potential role in therapy for catecholamine-sparing agents in vasodilatory shock. Regarding midodrine, the authors highlighted that at the time of this publication, only four published studies had examined its potential as a catecholamine-sparing agent in managing vasodilatory shock. The initial evaluation of midodrine’s catecholamine-sparing effects was conducted through a prospective observational study, which noted a substantial reduction in vasopressor infusion rates during the initial four doses of midodrine among surgical intensive care unit (ICU) patients. Subsequent retrospective studies examined patients treated with adjunctive midodrine alongside vasopressors compared to those treated with vasopressors alone. One such study, involving patients with cardiovascular, trauma, or sepsis-related hypotension, reported a 97.3% reduction in median phenylephrine equivalent rate within 24 hours of midodrine initiation; however, the duration of vasopressor treatment was not directly compared between the groups. [2]
The largest identified study compared midodrine with vasopressors alone and assessed the duration of intravenous vasopressor administration and ICU length of stay in medical ICU patients with septic shock. Findings from this study revealed significant reductions in both parameters with adjunctive midodrine therapy. Another descriptive study documented midodrine utilization in 1,119 patients admitted to a single center's surgical or medical ICU, with approximately 50% of patients on vasopressors at baseline having them weaned off within 24 hours of midodrine initiation. However, total duration of vasopressor therapy and ICU length of stay were not compared due to the absence of a control group. Based on these findings, the authors suggest that midodrine presents as a potential adjunctive therapy in the management of vasodilatory shock, and offers the possibility of facilitating vasopressor discontinuation and ICU discharge. However, due to study design limitations within the assessed studies, it remains uncertain whether the decline in vasopressor rates is directly attributed to midodrine therapy. Therefore, further research is warranted to elucidate the specific effects of midodrine in this context. [2]