Vitamin C, Thiamine, and Steroids in Sepsis

Inclusion Criteria:

   - Suspected or confirmed infection as evidenced by ordering of blood cultures and
   administration of at least one antimicrobial agent

   - Anticipated or confirmed intensive care unit (ICU) admission

   - Acute respiratory or cardiovascular organ dysfunction attributed to sepsis as
   evidenced by at least one of the following requirements:

      1. Vasopressor Requirement - Continuous infusion of norepinephrine, epinephrine,
      vasopressin, dopamine, phenylephrine or other vasopressor agents at any dose for
      greater than 1 hour and required to maintain a mean arterial pressure ≥ 65 mm Hg
      despite intravenous crystalloid infusion of at least 1000cc

      2. Respiratory Support Requirement - Acute hypoxemic respiratory failure defined as
      persistent hypoxemia (partial pressure of arterial oxygen (PaO2)/fraction of
      inspired oxygen (FiO2) ≤ 300 or blood oxygen saturation (SpO2)/FiO2 ≤ 315)
      requiring (1) intubation and mechanical ventilation, or (2) positive pressure
      ventilation via tight-fitting face mask (i.e. continuous positive airway pressure
      (CPAP) or bilevel positive airway pressure (BiPAP) or (3) high flow nasal cannula
      ≥ 40 liter per minute (LPM) flow and FiO2 ≥ 0.40

Exclusion Criteria:

   - Weight < 40 kilograms (kg)

   - Prior enrollment in this study

   - Qualifying organ dysfunction no longer present at the time subject would be randomized

   - Cardiovascular or respiratory organ failure caused by an illness other than sepsis

   - First episode of qualifying organ dysfunction during the current emergency department
   (ED) or ICU admission occurred > 24 hours before the subject could be randomized

   - Limitations of care (defined as refusal of cardiovascular and respiratory support
   modes) including "do not intubate" (DNI) status

   - Current hospitalization > 30 days at time of randomization

   - Chronic hypoxemia requiring supplemental non-invasive oxygen (nasal cannula or NIPPV)
   or home mechanical ventilation

   - Chronic cardiovascular failure requiring home mechanical hemodynamic support (e.g.,
   LVAD) or home chemical hemodynamic support (e.g., milrinone)

   - Known allergy or contraindication to vitamin C, thiamine, and/or corticosteroids
   (including previously or currently diagnosed primary hyperoxaluria and/or oxalate
   nephropathy, or known/suspected ethylene glycol ingestion, or known
   glucose-6-phosphate dehydrogenase (G6PD) deficiency)

   - Use of vitamin C at a dose of > 1 gram daily within the 24 hours preceding first
   episode of qualifying organ dysfunction during a given ED or ICU admission

   - Chronic disease/illness that, in the opinion of the site investigator, have an
   expected lifespan of < 30 days unrelated to current sepsis diagnosis (e.g., stage IV
   malignancy, neurodegenerative disease, etc.)

   - Pregnancy or known active breastfeeding

   - Prisoner or Incarceration

   - Current participation in another interventional research study

   - Inability or unwillingness of subject or legal surrogate/representative to give
   written informed consent