Vasopressors are medications that are given intravenously to increase the blood pressure of patients with illnesses that cause dangerous blood pressure drops. When a doctor prescribes a vasopressor, they ask that the dose be adjusted to achieve a specific blood pressure. This kind of medical support with intravenous (IV) vasopressors are usual treatments in intensive care unit (ICU) settings. Oral vasopressors, such as midodrine, have been historically used to maintain blood pressure in non-critically ill patients. In this study, the investigators will be using midodrine to reduce the need for IV vasopressors as blood pressure improves during the stay in the ICU

The LIBERATE pilot study will evaluate the role of midodrine for patients with low blood pressure in the ICU. The investigators are planning on enrolling up to 20 study participants to evaluate this question in the General Systems ICU at the University of Alberta Hospital.

Purpose: Resuscitation and hemodynamic support with intravenous (IV) vasopressors is a prime indication of treatment in intensive care unit (ICU) settings. Hemodynamic support is typically provided with intravenous (IV) vasopressors. However, these have been shown to have significant negative effects including increased central venous catheter line associated infections, venous thromboembolic disease, impaired mobility and gastrointestinal injury and ischemia. Oral vasopressors, such as midodrine, have been historically used for hemodynamic support in non-critically ill patients, but their study in patients as IV pressor sparing therapy has been limited.

Hypothesis: to evaluate the expanded role of midodrine for any vasoplegic patients in the ICU.

Justification: In 2018, there were 1,613 admissions to the adult general systems ICU (GSICU) at the University of Alberta Hospital (UAH). Patients were sick, with a mean Acute Physiology and Chronic Health Evaluation II (APACHE) score of 21.3, with 36.4% requiring vasopressors on admission, accounting for 1942 patient-days (data from eCritical TRACER database). In the environment strained healthcare resources and limited ICU capacity, the ability to safely wean patients from IV vasopressors with transition to oral hemodynamic supporting agents would greatly improve how patients navigate through the healthcare system. This in turn will improve patient-centered case.

Primary Objective:

To determine if recruitment for LIBERATE is achievable and feasible To compare the effect of enteral midodrine vs placebo on duration of vasopressor support

Secondary Objective: To compare the effect of enteral midodrine vs. placebo on:

ICU length of stay 90-day all-cause mortality Rate of re-initiation of IV vasopressors Rates of ICU re-admission Adverse events Research Method/Procedures: The LIBERATE Trial is a single centre, concealed-allocation parallel-group blinded pilot RCT. Patients will be randomly assigned to midodrine (enteral, 10mg every 8h) or placebo (microcrystalline cellulose) for the duration of their IV vasopressor therapy and 24h following the discontinuation of their IV vasopressor therapy. The recruitment target is 60 patients (i.e., 30 patients per arm) with full follow-up to ensure feasibility. Study personnel at the clinical sites will document the ICU length of stay. Daily assessment will occur for re-initiation of IV vasopressors and ICU re-admission. Patients will be followed at 90 days for mortality.

Plan for Data Analysis: Analyses of the primary and secondary outcomes will involve summary measures obtained by aggregating the endpoints using Stata software package (StataCorp, Texas, USA). Baseline comparisons will be performed using chi-squared test for equal proportions with results to be reported as numbers, percentages, and 95% confidence intervals. Continuous normally distributed variables will be compared using paired t-tests and reported as means with 95% confidence intervals, while non-normally distributed will be compared using Wilcoxon rank sum tests and reported as medians and interquartile ranges.

Inclusion Criteria:

• Age > 18 years old
• ICU admission
• Ongoing vasopressor support
• Decreasing vasopressor dose

Exclusion Criteria:

• Greater than 24 hours from peak vasopressor dose
• Contraindication to enteral medications
• Previously on midodrine in last 7 days
• Expected death or withdrawal of life-sustaining therapies
• Pregnancy
• Known allergy to Midodrine

As this is a pilot study, all results will be used to inform the development of a larger scale, multi centre RCT.