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 (within the past 3 months). * Recent treatment for peripheral vascular disease (within the past 3 months). * 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. * Fludrocortisone acetate as a current home medication. * Bradycardia (heart rate \< 50 beats/min). * Untreated pheochromocytoma. * Untreated thyrotoxicosis. * Open-angle glaucoma. * 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.