Vitamin C Infusion for Treatment in Sepsis Induced Acute Lung Injury
Condition: Acute Lung Injury; Sepsis
MeSH terms: Sepsis; Toxemia; Lung Injury; Acute Lung Injury; Wounds and Injuries
Intervention: Ascorbic Acid; Placebo: 5% Dextrose in water
Intervention description: Intervention; Placebo
Intervention MeSH terms: Ascorbic Acid
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 170.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      Hypothesis 1A: Vitamin C infusion will significantly attenuate sepsis-induced systemic organ
      failure as measured by Sequential Organ Failure Assessment (SOFA) score,

      Hypothesis 1B: Vitamin C infusion will attenuate sepsis-induced lung injury as assessed by
      the oxygenation index and the VE40

      Hypothesis 1C: Vitamin C infusion will attenuate biomarkers of inflammation (C-Reactive
      Protein, Procalcitonin), vascular injury (Thrombomodulin, Angiopoietin-2), alveolar
      epithelial injury (Receptor for Advanced Glycation Products), while inducing the onset of a
      fibrinolytic state (Tissue Factor Pathway Inhibitor).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have suspected or proven infection, and meet 2 out of 4 of the criteria
             for Systemic Inflammatory Response (SIRS) due to infection, and be accompanied by at
             least 1 criterion for sepsis-induced organ dysfunction, and meet all 5 criteria for
             Acute Respiratory Distress Syndrome (ARDS).

          -  Suspected or proven infection: (e.g., thorax, urinary tract, abdomen, skin, sinuses,
             central venous catheters, and central nervous system, see Appendix A).

          -  The presence of a systemic inflammatory response: Defined as: fever: >38ºC (any route)
             or hypothermia: <36ºC (core temp only), tachycardia: heart rate > 90 beats/min or
             receiving medications that slow heart rate or paced rhythm, leukocytosis: >12,000
             WBC/µL or leukopenia: <4,000 WBC/µL or >10% band forms. Respiratory rate > 20 breaths
             per minute or PaCO2 < 32 or invasive mechanical ventilation.

          -  The presence of sepsis associated organ dysfunction: (any of the following thought to
             be due to infection)

          -  Sepsis associated hypotension (systolic blood pressure (SBP) < 90 mm Hg or an SBP
             decrease > 40 mm Hg unexplained by other causes or use of vasopressors for blood
             pressure support (epinephrine, norepinephrine, dopamine =/> 5mcg, phenylephrine,
             vasopressin)

          -  Arterial hypoxemia (PaO2/FiO2 < 300) or supplemental O2 > 6LPM.

          -  Lactate > upper limits of normal laboratory results

          -  Urine output < 0.5 ml/kg/hour for > two hours despite adequate fluid resuscitation

          -  Platelet count < 100,000 per mcL

          -  Coagulopathy (INR > 1.5)

          -  Bilirubin > 2 mg/dL

          -  Glasgow Coma Scale < 11 or a positive CAM ICU score

          -  ARDS characterized by all the following criteria

          -  Lung injury of acute onset, within 1 week of an apparent clinical insult and with
             progression of respiratory symptoms

          -  Bilateral opacities on chest imaging not explained by other pulmonary pathology (e.g.
             pleural effusions, lung collapse, or nodules)

          -  Respiratory failure not explained by heart failure or volume overload

          -  Decreased arterial PaO2/FiO2 ratio ≤ 300 mm Hg

          -  Minimum PEEP of 5 cmH2O (may be delivered noninvasively with CPAP to diagnose mild
             ARDS

        Exclusion Criteria:

          -  Known allergy to Vitamin C

          -  inability to obtain consent;

          -  age < 18 years;

          -  No indwelling venous or arterial catheter in patients requiring insulin in a manner
             that requires glucose being checked more than twice daily (e.g. continuous infusion,
             sliding scale);

          -  presence of diabetic ketoacidosis;

          -  more than 48 hrs since meeting ARDS criteria;

          -  patient or surrogate or physician not committed to full support (not excluded if
             patient would receive all supportive care except for cardiac resuscitation);

          -  pregnancy or breast feeding,

          -  moribund patient not expected to survive 24 hours;

          -  home mechanical ventilation (via tracheotomy or noninvasive) except for CPAP/BIPAP
             used only for sleep-disordered breathing;

          -  home O2 > 2LPM, except for with CPAP/BIPAP

          -  diffuse alveolar hemorrhage (vasculitis);

          -  interstitial lung disease requiring continuous home oxygen therapy;

          -  Active kidney stone

          -  Non English speaking;

          -  Ward of the state (inmate, other)