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Randomized Controlled Trial
. 2023 Oct 12;27(1):371.
doi: 10.1186/s13054-023-04644-x.

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

Fumitaka Yanase  1   2 , Sofia Spano  1 , Akinori Maeda  1 , Anis Chaba  1 , Thummaporn Naorungroj  1 , Connie Pei Chen Ow  3 , Yugeesh R Lankadeva  3   4 , Clive N May  3   4 , Ashenafi H Betrie  3 , Darius J R Lane  3 , Glenn M Eastwood  1   2 , Mark P Plummer  5 , Rinaldo Bellomo  6   7   8   9   10
Affiliations
Randomized Controlled Trial

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

Fumitaka Yanase et al. Crit Care. .

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.

Keywords: Sepsis; Septic shock; Sequential organ failure score; Sodium ascorbate; Vasopressors; Vitamin C.

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Conflict of interest statement

YRL, CNM and RB own a patent for the use of mega-dose sodium ascorbate in the treatment of sepsis.

Figures

Fig. 1
Fig. 1
Trial screening and randomization flow chart
Fig. 2
Fig. 2
Panel a: Total urine output 24 h after start of trial drug infusion. Panel b Progressive cumulative urinary output over time
Fig. 3
Fig. 3
Serum sodium changes from baseline over time
Fig. 4
Fig. 4
Plasma ascorbate concentration during the first 24 h
Fig. 5
Fig. 5
Norepinephrine equivalent changes from baseline to 24 h
Fig. 6
Fig. 6
SOFA score changes from baseline to 72 h
See this image and copyright information in PMC

References

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