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

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.

Ex Vivo Evaluation of the Sepsis Triple Therapy High-Dose Vitamin C in Combination with Vitamin B1 and Hydrocortisone in a Human Peripheral Blood Mononuclear Cells (PBMCs) Model

“…Meanwhile, different meta-analyses have been conducted on vitamin C in sepsis and critically ill patients. The results are controversial; while some see a reduction in mortality, a shorter hospital stay and/or a reduced need for vasopressors, these effects are not confirmed in other analyses [ 65 , 66 ]. Of note is a meta-analysis that sees effects depending on the chosen vitamin C dose [ 63 ].…”

Measuring vitamin C in critically ill patients: clinical importance and practical difficulties—Is it time for a surrogate marker?

“…A recently published meta-analysis on mortality performed subgroup analyses and found a beneficial effect of vitamin C on short-term mortality (< 30 days). Additionally, survival was improved by a treatment duration of 3-4 days [13]. The results of vitamin C alone versus combination therapy were not different.…”

Effects of Hydrocortisone Combined with Vitamin C and Vitamin B1 Versus Hydrocortisone Alone on Microcirculation in Patients with Septic Shock: A Prospective, Double-Blind, Randomized, Controlled Trial

“…In the ACTS trial, the combination therapy did not result in a statistically signi cant reduction in the SOFA score during the rst 72 hours after enrollment and the 30-day mortality [12]. However, the subsequent meta-analysis showed that vitamin C alone or in combination with hydrocortisone/thiamine (treatment 3 to 4 days) reduces the 30-day mortality in patients with septic shock [5]. The heterogeneity of these results may be related to the differences in the e cacy of the combination therapy for different septic shock subtypes.…”

“…However, this study has some shortcomings, such as the small sample size and before-after study design. Since the publication of this study, the use of combination therapy has increased gradually [4], and numerous studies have begun to explore the effect of combination therapy on the prognosis of septic shock patients [5][6][7][8][9][10][11][12][13][14]. But these studies have produced inconsistent results and a lack of mechanistic research.…”