Background/Purpose: Intravenous (IV) vasopressor agents are mainstay therapy for the management of refractory hypotension in critically ill patients in the intensive care unit (ICU). Patients remain in the ICU for vasopressor administration and monitoring which results in increased length of stay (LOS). Midodrine is an oral alpha-1 adrenergic agonist that causes vasoconstriction and increased blood pressure. It is commonly utilized off-label as an adjunctive therapy to help wean off vasopressors and decrease ICU LOS. Although midodrine offers many benefits, a study by Rizvi, et al stated that inappropriate continuation at hospital discharge resulted in a 1.6-fold higher risk of 1-year mortality compared to patients that were appropriately discontinued. The purpose of this study is to identify opportunities to optimize midodrine use by quantifying the time to discontinuation of vasopressors in critically ill patients when adjunctive oral midodrine is prescribed.

Methodology: A single center study was conducted at Baptist Hospital of Miami from October 2018 to September 2019 and March to April 2020, respectively. Adult, non-pregnant, patients admitted to the ICU concomitantly receiving vasopressors and midodrine were included. The primary outcomes included time to vasopressor discontinuation after midodrine initiation, percentage of patients appropriately transitioned off of midodrine upon transfer out of ICU and upon hospital discharge in each study period. Secondary outcomes were time from midodrine initiation to ICU discharge determination, ICU LOS, duration of vasopressor prior to midodrine, median duration of midodrine utilization in both phases as well as pharmacy interventions in phase II.

Results: A total of 137 patients (phase I = 73, phase II = 64) were screened per inclusion and exclusion criteria. From these, 104 patients (phase I = 60, phase II = 44) were evaluated for study outcomes. Expired patients (phase I = 45, phase II = 20) were not included in data analysis. In terms of primary outcomes, time to vasopressor discontinuation after midodrine initiation increased from 3 days (phase I) to 4 days (phase II), p = 0.832. The percent of patients taken off of midodrine improved at ICU transfer from 40% (phase I) to 79% (phase II), p = 0.019 and upon hospital discharge from 60% (phase I) to 92% (phase II), p = 0.037. On the contrary, the time from midodrine initiation to ICU discharge significantly increased from 5 days to 12 days in phase I vs. phase II (p = 0.002). Additionally, the ICU LOS was prolonged from 12 days in phase I to 23 days in phase II (p = 0.006). The time on vasopressor prior to midodrine initiation was prolonged in phase I at 5 days compared to phase II at 4 days (p = 0.587). In addition, the average duration of midodrine therapy was 12 days in phase I compared to 9 days in phase II (p = 0.267). A total of 28 pharmacy interventions were performed with 100% acceptance rate in phase II.

Conclusions: Vasopressors were discontinued sooner in phase I versus phase II after midodrine was initiated, however, the average duration of vasopressor use was 8 days in both phases. Patients in phase I were continued on midodrine for a longer compared to phase II (phase I = 12 days vs. phase II = 9 days). Additionally, pharmacist interventions in phase II led to an improved percentage of patients transitioned off of midodrine when on ICU and hospital discharge. On the contrary, patients in phase I had a significantly shorter ICU LOS compared to phase II, which may be potentially attributed to the COVID-19 pandemic and mechanical ventilation requirements. Overall patients in phase I were started on midodrine later than patients in phase II, which may be limited with the observation that patients in phase I had higher acuity level as demonstrated by an average APACHE IV score of 62 in phase I vs. 43 in phase II as well as higher mortality rate of 75% in phase I compared to 45% in phase II. Through this study, pharmacist’s role in therapy optimization and appropriate discontinuation of midodrine upon ICU and/or hospital discharge is evident.

Publication Date


Presented At:

BHSF Pharmacy Residency Conference

Content Type



Claudia Martin Diaz - Pharmacy Resident PGY1

Author Credentials

Claudia Martin Diaz, Pharm.D.

Heidi Clarke, Pharm.D., BCCCP

Payal Patel, Pharm.D., BCCCP

Radhan Gopalani, Pharm.D., BCPS

Stephanie Palma, Pharm.D., BCPS

Open Access

Available to all.