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INTRODUCTION:Midodrine is increasingly used in critically ill patients with septic shock to facilitate weaning intravenous (IV) vasopressors and discharge from the intensive care unit. Despite a trend of increasing use, current data demonstrate mixed efficacy in liberation from vasopressors or reduction in length of stay (LOS). Our study aimed to evaluate real-world data on the effect of midodrine on LOS in patients admitted for septic shock.METHODS: Our analysis used de-identified data from the Trisus Medication Compare platform (The Craneware Group, Deerfield Beach, FL) to identify adults with septic shock (ICD-10 code R65.21) and a dispensation for any vasopressor between 1/1/2019-3/31/2022. The primary objective was to compare average in-hospital LOS in patients receiving midodrine versus not. Subgroup analyses were performed in patients requiring invasive mechanical ventilation (IMV), renal replacement therapy (RRT), and two or more vasopressors. Secondary outcomes included 30-day all-cause readmission, bradycardia, and catheter-related bloodstream infection. Continuous and discrete outcomes were assessed using Kruskal-Wallis and Chi-square tests, respectively.

Study ObjectiveSignificant practice variation exists when selecting between hydrocortisone and vasopressin as second line agents in patients with septic shock in need of escalating doses of norepinephrine. The goal of this study was to assess differences in clinical outcomes between these two agents.DesignMulticenter, retrospective, observational study.SettingTen Ascension Health hospitals.PatientsAdult patients with presumed septic shock receiving norepinephrine prior to study drug initiation between December 2015 and August 2021.InterventionVasopressin (0.03–0.04 units/min) or hydrocortisone (200–300 mg/day).Measurements and Main ResultsA total of 768 patients were included with a median (interquartile range) SOFA score of 10 (8–13), norepinephrine dose of 0.3 mcg/kg/min (0.1–0.5 mcg/kg/min), and lactate of 3.8 mmol/L (2.4–7.0 mmol/L) at initiation of the study drug. A significant difference in 28‐day mortality was noted favoring hydrocortisone as an adjunct to norepinephrine after controlling for potential confounding factors (OR 0.46 [95% CI, 0.32–0.66]); similar results were seen following propensity score matching. Compared to vasopressin, hydrocortisone initiation was also associated with a higher rate of hemodynamic responsiveness (91.9% vs. 68.2%, p < 0.01), improved resolution of shock (68.8% vs. 31.5%, p < 0.01), and reduced recurrence of shock within 72 h (8.7% vs. 20.7%, p < 0.01).ConclusionsAddition of hydrocortisone to norepinephrine was associated with a lower 28‐day mortality in patients with septic shock, compared to the addition of vasopressin.