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Meta-Analysis
. 2021 Jan 6;25(1):17.
doi: 10.1186/s13054-020-03438-9.

Mortality in septic patients treated with vitamin C: a systematic meta-analysis

Sean S Scholz  1 , Rainer Borgstedt  2 , Nicole Ebeling  2 , Leoni C Menzel  3 , Gerrit Jansen  2 , Sebastian Rehberg  2
Affiliations
Meta-Analysis

Mortality in septic patients treated with vitamin C: a systematic meta-analysis

Sean S Scholz et al. Crit Care. .

Abstract

Background: Supplementation of vitamin C in septic patients remains controversial despite eight large clinical trials published only in 2020. We aimed to evaluate the evidence on potential effects of vitamin C treatment on mortality in adult septic patients.

Methods: Data search included PubMed, Web of Science, and the Cochrane Library. A meta-analysis of eligible peer-reviewed studies was performed in accordance with the PRISMA statement. Only studies with valid classifications of sepsis and intravenous vitamin C treatment (alone or combined with hydrocortisone/thiamine) were included.

Results: A total of 17 studies including 3133 patients fulfilled the predefined criteria and were analyzed. Pooled analysis indicated no mortality reduction in patients treated with vitamin C when compared to reference (risk difference - 0.05 [95% CI - 0.11 to - 0.01]; p = 0.08; p for Cochran Q = 0.002; I2 = 56%). Notably, subgroup analyses revealed an improved survival, if vitamin C treatment was applied for 3-4 days (risk difference, - 0.10 [95% CI - 0.19 to - 0.02]; p = 0.02) when compared to patients treated for 1-2 or > 5 days. Also, timing of the pooled mortality assessment indicated a reduction concerning short-term mortality (< 30 days; risk difference, - 0.08 [95% CI - 0.15 to - 0.01]; p = 0.02; p for Cochran Q = 0.02; I2 = 63%). Presence of statistical heterogeneity was noted with no sign of significant publication bias.

Conclusion: Although vitamin C administration did not reduce pooled mortality, patients may profit if vitamin C is administered over 3 to 4 days. Consequently, further research is needed to identify patient subgroups that might benefit from intravenous supplementation of vitamin C.

Keywords: Ascorbic acid; Mortality; Sepsis; Septic shock.

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Conflict of interest statement

All authors report no competing interests.

Figures

Fig. 1
Fig. 1
PRISMA flow diagram showing search and selection strategies
Fig. 2
Fig. 2
Pooled mortality regarding the longest available time period within each study, risk difference, vitamin C treatment versus control; M-H Mantel–Haenszel, CI confidence interval
Fig. 3
Fig. 3
Pooled mortality regarding the longest available time period within each study including subgroup analysis on treatment duration, risk difference, vitamin C treatment versus Control; M-H Mantel–Haenszel, CI confidence interval
See this image and copyright information in PMC

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