Mega-dose sodium ascorbate: a pilot, single-dose, physiological effect, double-blind, randomized, controlled trial

Abstract

Background Mega-dose sodium ascorbate (NaAscorbate) appears beneficial in experimental sepsis. However, its physiological effects in patients with septic shock are unknown. Methods We conducted a pilot, single-dose, double-blind, randomized controlled trial. We enrolled patients with septic shock within 24 h of diagnosis. We randomly assigned them to receive a single mega-dose of NaAscorbate (30 g over 1 h followed by 30 g over 5 h) or placebo (vehicle). The primary outcome was the total 24 h urine output (UO) from the beginning of the study treatment. Secondary outcomes included the time course of the progressive cumulative UO, vasopressor dose, and sequential organ failure assessment (SOFA) score. Results We enrolled 30 patients (15 patients in each arm). The mean (95% confidence interval) total 24-h UO was 2056 (1520–2593) ml with placebo and 2948 (2181–3715) ml with NaAscorbate (mean difference 891.5, 95% confidence interval [− 2.1 to 1785.2], P = 0.051). Moreover, the progressive cumulative UO was greater over time on linear mixed modelling with NaAscorbate (P < 0.001). Vasopressor dose and SOFA score changes over time showed faster reductions with NaAscorbate (P < 0.001 and P = 0.042). The sodium level, however, increased more over time with NaAscorbate (P < 0.001). There was no statistical difference in other clinical outcomes. Conclusion In patients with septic shock, mega-dose NaAscorbate did not significantly increase cumulative 24-h UO. However, it induced a significantly greater increase in UO and a greater reduction in vasopressor dose and SOFA score over time. One episode of hypernatremia and one of hemolysis were observed in the NaAscorbate group. These findings support further cautious investigation of this novel intervention. Trial registration Australian New Zealand Clinical Trial Registry (ACTRN12620000651987), Date registered June/5/2020.

High-dose vitamin C improves norepinephrine level in patients with septic shock: A single-center, prospective, randomized controlled trial

“…[11] Megadose vitamin C (30 g over 1 h followed by 30 g over 5 h) induced a significant increase in urine volume and a greater reduction in the vasopressor dose and SOFA score over time than other agents. [19] In our study, the dosage of vitamin C was 50 mg/kg/d for 4 days in the low-dose group and 150 mg/kg/d for 4 days in the high-dose group, which was consistent with the doses used in many trials. We also detected an increase in the urine volume in the vitamin C group.…”

“…[ 8 – 10 ] A very high-dose of vitamin C (30 g over 1 h followed by 30 g over 5 h) limits the dose and duration of vasopressor treatment and results in rapid reductions over time. [ 19 ] However, a pilot RCT revealed no significant decrease in the mean dose or duration of vasopressor infusion of intravenous vitamin C (25 mg/kg every 6 h). [ 20 ] These inconsistent findings may be related to differences in the vitamin C dosage and duration of administration.…”

Acute Management of Sepsis beyond 24 Hours

“…65 Ongoing research suggests that the utilization of sodium ascorbate in preference to ascorbic acid may be of interest. 66 Nonetheless, considering the dearth of dependable clinical data, routine administration of antioxidants to septic patients is currently not recommended.…”