Ascorbic Acid Infusions

Reference

NIH – COVID-19 Treatment Guidelines

• Vitamin C (ascorbic acid) is a water-soluble vitamin that is thought to have beneficial effects in patients with severe and critical illnesses. It is an antioxidant and free radical scavenger that has anti-inflammatory properties, influences cellular immunity and vascular integrity, and serves as a cofactor in the generation of endogenous catecholamines.1,2 Because humans may require more vitamin C in states of oxidative stress, vitamin C supplementation has been evaluated in numerous disease states, including serious infections and sepsis. Because serious COVID-19 may cause sepsis and acute respiratory distress syndrome (ARDS), the potential role of high doses of vitamin C in ameliorating inflammation and vascular injury in patients with COVID-19 is being studied.
• Recommendation for Non-Critically Ill Patients With COVID-19
  There are insufficient data for the COVID-19 Treatment Guidelines Panel (the Panel) to recommend either for or against the use of vitamin C for the treatment of COVID-19 in non-critically ill patients.
  Rationale:
  Because patients who are not critically ill with COVID-19 are less likely to experience oxidative stress or severe inflammation, the role of vitamin C in this setting is unknown.
• Recommendation for Critically Ill Patients With COVID-19
  There are insufficient data for the Panel to recommend either for or against the use of vitamin C for the treatment of COVID-19 in critically ill patients.
  Rationale:
  There are no completed controlled trials of vitamin C in patients with COVID-19, and the available observational data are sparse and inconclusive. Studies of vitamin C in sepsis patients and ARDS patients have reported variable efficacy and few safety concerns.
• Clinical Data on Vitamin C in Critically Ill Patients Without COVID-19
  Intravenous Vitamin C Alone:
  A small, three-arm pilot study compared two regimens of intravenous (IV) vitamin C to placebo in 24 critically ill patients with sepsis. Over the 4-day study period, patients who received vitamin C 200 mg/kg per day and those who received vitamin C 50 mg/kg per day had lower sequential organ failure assessment (SOFA) scores and levels of proinflammatory markers than patients who received placebo.3

  In a randomized controlled trial in critically ill patients with sepsis-induced ARDS (n = 167), patients who received IV vitamin C 200 mg/kg per day for 4 days had SOFA scores and levels of inflammatory markers that were similar to those observed in patients who received placebo. However, 28-day mortality was lower in the treatment group (29.8% vs. 46.3%; P = 0.03), coinciding with more days alive and free of the hospital and the intensive care unit.4 A post hoc analysis of the study data reported a difference in median SOFA scores between the treatment group and placebo group at 96 hours; however, this difference was not present at baseline or 48 hours.

https://www.covid19treatmentguidelines.nih.gov/adjunctive-therapy/vitamin-c/

Reference

ClinicalTrials.gov

• Link
• Previous research has shown that high dose intravenous vitamin C (HDIVC) may benefit patients with sepsis, acute lung injury (ALI), and the acute respiratory distress syndrome (ARDS). However, it is not known if early administration of HDIVC could prevent progression to ARDS.
• We hypothesize that HDIVC is safe and tolerable in Coronavirus disease 2019 (COVID-19) subjects given early or late in the disease course and may reduce the risk of respiratory failure requiring mechanical ventilation and development of ARDS along with reductions in supplemental oxygen demand and inflammatory markers

Drug: ascorbic acid
50 mg/kg L-ascorbic acid infusion given every 6 hours for 4 days (16 total doses)

Reference

ClinicalTrials.gov

• Link

• Despite an organized treatment approach outlined in expert-consensus guidelines for sepsis with fluid resuscitation to treat hypovolemia, antibiotics to target the infectious insult, and vasopressors for hypotension, mortality rates for sepsis remain high and the incidence continues to rise, making sepsis the most expensive inpatient disease.

  1. Recent research has described the therapeutic benefits associated with ascorbic acid treatment for sepsis.
  2. Researchers objectives are to perform a randomized-controlled clinical trial investigating the ability of ascorbic acid(vitamin C) administration to decrease organ dysfunction in severe sepsis. The widespread occurrence of microvascular dysfunction in sepsis leading to tissue hypoxia, mitochondrial dysfunction, and ATP depletion, gives rise to organ failure.
  3. Patients with organ failure and sepsis (severe sepsis) are at a higher risk of death than patients with organ failure alone. Critically ill patients may have an increased requirement for ascorbic acid in sepsis and these patients frequently have levels below normal. Ascorbic acid administration, has been shown to correlate inversely with organ failure (human literature) and directly with survival (animal studies).
• Intravenous ascorbic acid therapy decreases organ failure by providing a protective effect on several microvascular functions including improving capillary blood flow, decreasing microvascular permeability, and improving arteriolar responsiveness to vasoconstrictors. Defining the utility of novel agents to augment researchers care for severe sepsis is an important task as investigators continue the institutional focus on sepsis care.

Patients will receive 67 mg/kg IV ascorbic acid in 100 ml normal saline over 30 minutes every 8 hours (200 mg/kg/day) for 72 hours.

Reference

Mikirova N, Casciari J, Riordan N, Hunninghake R. Clinical experience with intravenous administration of ascorbic acid: achievable levels in blood for different states of inflammation and disease in cancer patients. J Transl Med. 2013;11:191. Published 2013 Aug 15. doi:10.1186/1479-5876-11-191

• Consequently, higher doses provide higher plasma concentrations, but the effect is not linear. This is probably because IVC is administered as a slow “drip” over a dose-dependent time period (15 grams are administered over 0.5 hours, while 100 grams are administered over a 3.5 hours), giving the body more time to clear some of the ascorbate through the kidneys at higher doses.
• Vitamin C is an antioxidant that increases extracellular collagen production and is important for immune cell functioning.
• The intravenous administration of vitamin C involves the slow infusion of vitamin C at doses on the order of 0.1 to 1.0 grams per kilogram body mass and has become increasingly popular among complementary and alternative medicine practitioners.
• When vitamin C is given by intravenous infusion, peak concentrations over 10 mM, two orders of magnitude above what is observed with oral supplementation, can be attained without significant adverse effects to the recipient.

Reference

Walker SE, Iazzetta J, Law S, et al. Administration of Intravenous Ascorbic Acid-Practical Considerations for Clinicians. Nutrients. 2019;11(9):1994. Published 2019 Aug 23. doi:10.3390/nu11091994

• Emerging data suggest that intravenous ascorbic acid (AA) may be beneficial in patients with sepsis. Clinicians require data on stability of diluted AA for safe administration. We evaluated the stability of AA diluted in normal saline (NS) or 5% dextrose in water (D5W) solutions over 14 days at 25 °C and at 4 °C, protected from light, using concentrations of 37 mg/mL and 77 mg/mL (Sandoz) and 40 mg/mL and 92 mg/mL (Mylan). We also assessed stability of a 40 mg/mL solution (Mylan) at 25 °C exposed to light for 75 h.
• Evaluation of the Need to Protect from Light
  During the 75 h evaluation period, AA exposed to fluorescent room light at 25 °C nominally degraded faster than samples protected from light (Table 3). AA stored in the administration sets degraded to 95.15% remaining when exposed to light, compared to 96.79% remaining when protected from light (p = 0.948 for difference in degradation rate to 75 h). Similar rates of degradation were observed in PVC minibags (p = 0.681 for difference in degradation rate).
• This study demonstrates that AA solutions at concentrations between 37 and 92 mg/mL, diluted in either NS or D5W and stored in PVC minibags, are physically, chemically and visually stable for at least 14 days refrigerated at 4 °C with protection from light. Clinicians in acute care settings may consider using AA solutions stored under these conditions. By contrast, when stored at room temperature (25 °C), AA solutions remained stable for 10 days, but discolouration was apparent after 2 days, possibly indicating degradation products of uncertain safety.

Reference

Trissel’s™ 2 Clinical Pharmaceutics Database (Parenteral Compatibility

• Accessed: December 02, 2020
• Findings: Ascorbic acid: concentrations: 1mg/mL and 10 mg/mL.
  Solution: NS. Compatible. 10 mg/mL:  3 to 6% loss at 24 hours room temperature.
• Ascorbic acid: concentrations: 1mg/mL and 10 mg/mL.
  Solution: D5W.. Compatible.  10 mg/mL: No ascorbic acid loss occurred within the study period.