Vitamin C Infusion for Treatment in Sepsis Induced Acute Lung Injury

• Status: Completed
• Trial end date: 2018-01-08
• Target enrollment: 0
• Participant gender: All

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).

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Virginia Commonwealth University
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI)
• Treatments: Ascorbic Acid; Vitamins

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)