MID-STEP (MIDodrine for Sepsis Treatment and Early vasoPressor Weaning) Trial

Inclusion criteria:

Patients diagnosed with sepsis within 24 hours of meeting all of the following criteria will be eligible to participate in the study:

* Sepsis-3 criteria: acute hospital admission for suspected infection with new or worsening organ dysfunction measured by the increase in Sequential Organ failure Assessment (SOFA) score of 2 points or more.
* IV vasopressor use or persistent hypotension (MAP \< 65 mm Hg) after initial fluid resuscitation in the ED or ICU (30 mL/kg unless deemed excessive by the treating clinician).

Exclusion criteria:

* High-dose vasopressors (norepinephrine equivalent \> 0.3 μg/kg/min)
* Inadequately controlled source of infection
* Cardiogenic or obstructive (massive pulmonary embolism) shock
* Clinical suspicion or confirmed diagnosis of bowel obstruction, bowel ischemia, or ileus
* Contraindication to enteral intake (ileus, vomiting, gastrointestinal bleeding, endoscopic procedures etc.)
* Recent myocardial infarction (STEMI or NSTEMI Type 1 within the past 3 months)
* Recent treatment for peripheral vascular disease (within the past 3 months) or acute limb ischemia
* Current use of monoamine oxidase inhibitors
* Recent stroke (within the past 3 months)
* Prior use of midodrine as a home medication
* Known allergy to midodrine
* Comfort care measures
* Pregnancy
* Bradycardia (heart rate \< 50 beats/min)
* Untreated pheochromocytoma
* Untreated thyrotoxicosis
* Acute Angle-Closure Glaucoma
* Cirrhosis or liver failure with Child-Pugh Score \> 12
* Venous blood lactate \> 4
* Treating emergency or critical care physician unwilling to enroll patient in trial
* Inability to give consent for participation and no representative or surrogate available to consent