Midodrine for Vasopressor Weaning in Septic Shock Patients on Moderate to High-Dose Vasopressors

Introduction: Midodrine, an oral alpha-1 agonist indicated for orthostatic hypotension, is used off-label to shorten intravenous (IV) vasopressor weaning and expedite intensive care unit (ICU) discharge. However, there is mixed evidence regarding its benefit in decreasing vasopressor requirements in patients with septic shock (SS) on low dose vasopressors. Furthermore, no data exists on the benefits or risks in patients requiring moderate-to-high (MH) doses of vasopressors. The objective of this study is to evaluate effect of midodrine on duration of vasopressor requirements when added to patients with SS on MH dose vasopressors.


Methods: This study was a retrospective cohort study within the Houston Methodist System from January 1, 2023, to June 31, 2024. Patients with SS on MH doses of continuous vasopressors who received adjunctive midodrine were compared to patients who received MH vasopressors alone. We included adult patients (> 18 years old) with an ICD-10 code (R65.21) for septic shock, that were admitted to one of seven hospitals in the health system, on MH doses of continuous vasopressors. Exclusion criteria were end stage renal disease, severe heart disease, non-distributive shock, atrioventricular block, and midodrine administration within 24 hours prior to admission.


Results: A total of 250 patients were included, with 125 in the adjunct midodrine group, and 125 patients in the vasopressors only group. For the primary endpoint, the time from initiation of MH dose vasopressors to discontinuation was longer in the adjunctive midodrine group than the vasopressors only group (median [IQR] 4.1 [2.1-9.4] vs. 1.8 [1.1-4.0], p< 0.001). For secondary outcomes, midodrine was also associated with a longer ICU length of stay (LOS), (median [IQR] 16.9 [8.9-37.0], vs. 8.0 [3.9-15.3], p< 0.001), hospital LOS (median [IQR] 23.2 [11.9-47.4] vs.13.0 [7.8-19.5], and new organ dysfunction (n [%], 75 [60] vs. 37 [29.6], p < 0.001). There was no difference in the incidences of adverse events or mortality.


Conclusions: Adjunctive midodrine in patients with SS on MH dose vasopressors was associated with longer vasopressor duration and longer LOS. These findings suggest caution in using midodrine in patients with SS until further evidence is available.