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