Intravenous vitamin C as micronutrient therapy in patients with sepsis or septic shock: an updated systematic review and meta-analysis of randomized controlled trials

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Objective The adjunctive therapeutic value of vitamin C in sepsis or septic shock patients remains controversial. This study aimed to evaluate the therapeutic efficacy and safety of intravenous administration of vitamin C in sepsis or septic shock patients through meta-analysis. Methods Relevant literature was searched in PubMed, Embase, and Scopus databases and other related databases. The primary outcome was 28-day mortality. Secondary outcomes included duration and total dose of vasopressors, change in sequential organ failure assessment (SOFA) scores from baseline to the earliest reported time point between 72 and 96 h (ΔSOFA), hospital length of stay, intensive care unit length of stay, urine output in the 24-h, and incidence of adverse events. Results Fourteen randomized controlled trials enrolling 1,958 patients were eligible for assessment. Meta-analysis demonstrated that intravenous vitamin C reduced 28-day mortality in sepsis or septic shock patients compared to the control group (RR 0.70; 95% CI 0.53 to 0.93; P = 0.02; I 2 = 52%), based on low quality of evidence, and subgroup analysis showed the benefit was driven by single-center studies, not observed in multicenter trials. Vitamin C shortened the duration of vasopressor use (SMD = −0.42, 95% CI −0.77 to −0.08, P = 0.02) and was associated with a greater reduction in SOFA score (MD = −1.04, 95% CI −1.83 to −0.25, P = 0.01), but did not reduce vasopressor dose, length of stay, or 24-h urine output. No significant adverse events were reported. Conclusion This meta-analysis suggests that intravenous vitamin C might be associated with reduced mortality in sepsis, but the benefit was not confirmed in low-risk-of-bias multicenter trials and was primarily driven by single-center studies. Intravenous vitamin C appeared safe. Given the exploratory nature of these subgroup analyses and the data-driven thresholds used, high-quality, multicenter RCTs are warranted. Systematic review registration http://www.crd.york.ac.uk/PROSPERO/view/CRD4204261367808 , identifier CRD4204261367808.