Role of AScorbic acid Infusion in critically ill patients with Transfusion Related Acute Lung Injury (ASTRALI)

Introduction: In critically ill patients, Transfusion Related Acute Lung Injury (TRALI) remains the leading cause of transfusion-related fatalities in critical care setting and associated with inflammation and oxidative stress state. Recent research raised the potential efficacy of high dose intravenous ascorbic acid in critically ill patients. Objective: The aim of this trial was to investigate the effect of high dose intravenous ascorbic acid (VC) as a targeted therapy for TRALI in terms of serum proinflammatory (interleukin-8, interleukin-1β, C-reactive protein), anti-inflammatory (interleukin-10), oxidative stress (superoxide dismutase, malondialdehyde) markers, and plasma VC levels. Secondary outcomes were oxygenation (PaO2/FiO2 ratio), vasopressor use, duration of mechanical ventilation, ICU length of stay, 7-days mortality and 28-days mortality. Methods: Eighty critically ill patients with TRALI (n=80) were randomized to receive 2.5gm/6hr intravenous vitamin C for 96 hours (ASTRALI group) or placebo. Patients were followed-up to measure the outcomes initially (T0) and at the end of treatment (T96). Results: When compared to control group, ASTRALI group at T96, showed significantly higher median of interleukin-10 (31.6 ± 25.8 Vs. 17.7 ± 12.0 pg/mL, p<0.0001) levels and superoxide dismutase (12876 ± 4627 U/L Vs. 5895 ± 6632 U/L, p<0.0001) activities, lower median C-reactive protein (76 ± 50 Vs. 89 ± 56 mg/L, p=0.033), interleukin-8 (11.8 ± 7.3, 35.5 ± 19.8 pg/mL, p<0.0001), and malondialdehyde (0.197 ± 0.034 Vs. 0.234 ± 0.074 µM/L, p=0.002) levels. Conclusion: High dose ascorbic acid was associated with significantly reduced oxidative stress, reduced pro-inflammatory markers except IL-1β, elevated anti-inflammatory marker, and elevated plasma VC levels

Should ascorbic acid be a primary therapy for sepsis in prehospital settings?

Background: Prehospital emergency medical services (EMS) are believed to be responsible for the initial treatment of 68 000 septic patients annually in the UK, 88% of whom have severely low ascorbic acid levels, which can lead to organ dysfunction, increasing the likelihood of mortality. Objective: This review aims to determine if early therapeutic use of ascorbic acid (vitamin C) could reduce the deterioration of septic patients and therefore overall mortality. Method: A literature review was conducted using the mySearch, PubMed and Cochrane Library databases. Each was systematically searched for human studies that addressed the use of ascorbic acid as a primary method of treatment during varying stages of sepsis and whether it reduced associated mortality. Studies not published in English or that were more the 5 years old at the time were excluded. The quality of evidence in the remaining articles were appraised using the GRADE method and further assessed for quality with an adjusted Downs and Black scoring tool. Results: Nineteen articles were found, three of which met the inclusion criteria. All addressed the use of ascorbic acid as a therapy in the treatment of sepsis; none were conducted in a prehospital setting. Conclusion: Intravenous ascorbic acid appears to be a safe and effective therapy in treating septic patients, with the potential to reduce mortality rates if given prophylactically. However, a series of clinical trials would need to be conducted to measure the extent of any improvement and therefore clinical value in the prehospital environment.

Evaluation of Ascorbic Acid Adjuvant Therapy and Oxidative Stress Parameters in Burns Patients

Background: Burns trauma is associated with considerable morbidity and mortality. Resuscitation of burns patients with high-dose of Ascorbic acid has shown potential for mitigating the injury, but the optimal dose for this indication is unknown. Aim: This study aimed to evaluate the impact of adjuvant therapy with intravenous Ascorbic acid (6g over 24 hours) on indicators of oxidative stress in patients with major burns. Materials and Methods: We conducted a randomized placebo-controlled study on patients with major burns who presented at the National Orthopaedic Hospital, Enugu, Nigeria between August 2017 and July 2020. Each patient in the treatment group received intravenous Ascorbic acid, 6g over 24 hours, while those in the placebo group received Normal saline in the resuscitation fluid. Oxidative stress evaluation was based on measurement of total antioxidant capacity and malondialdehyde in the participants. The level of statistical significance was determined by a p value of <0.05. Results: The study was conducted on 37 burns patients and 15 healthy subjects. At presentation, the burns patients had significantly lower total antioxidant capacity; P=0.006, and higher serum malondialdehyde; P=0.040, compared to the healthy volunteers. The decrease in serum malondialdehyde in the burns patients treated with high-dose Ascorbic acid; 0.9±0.8 nmol/mL, was greater than that in those treated with placebo; 0.3±1.4 nmol/mL. Similarly the increase in total antioxidant capacity in the burns patients treated with high-dose Ascorbic acid; 151.7±116.5 µmol/L was greater than that in those treated with placebo; 58.4±219.1 µmol/L. However these effects weren’t statistically significant. Conclusion: Intravenous Ascorbic acid at a dose of 6g over 24 hours did not significantly alter the indicators of oxidative stress in the burns patients, under the prevailing conditions of the study.

Administration of Intravenous Ascorbic Acid—Practical Considerations for Clinicians

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. Concentrations were measured using liquid chromatographic separation with ultraviolet light detection on days 0, 0.33, 1, 1.33, 2, 3, 4, 7, 10 and 14. By day 14, solutions at 4 °C retained >97.72% of the initial concentration; at 25 °C, solutions retained >88.02% of the initial concentration, but visual changes were evident after day 2. Multiple linear regression demonstrated that study day and temperature (p < 0.001) but not solution type (p = 0.519), concentration (p = 0.677) or manufacturer (p = 0.808) were associated with the percentage remaining. At 75 h, degradation rates were similar in solutions protected from vs. exposed to light. In conclusion, AA solutions are stable for at least 14 days at 4 °C, with protection from light.