Application of Intravenous Vitamin C in Adult Patients with Sepsis: A Meta-Analysis of Randomized Controlled Trials

Background: The efficacy of intravenous vitamin C among sepsis patients is uncertain according to recent randomized controlled trials (RCTs). We conducted a meta-analysis to evaluate the efficacy of vitamin C application in adults with sepsis. Methods: We performed a systematic literature search in PubMed, Web of Science, Embase and the Cochrane Library. Eligible studies were RCTs that investigated the application of intravenous vitamin C in adult patients with sepsis. We assessed the risk of bias of the included studies using the Cochrane risk of bias tool and the certainty of evidence according to the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach, for each outcome. Results: : Fourteen trials involving a total of 1823 patients were included. We found that there was no significant effect of vitamin C on 28-day mortality [risk ratio (RR) 0.87, 95% confidence interval (CI) 0.73 to 1.04, p = 0.12, TSA-adjusted CI 0.70 to 1.08, low quality evidence], but among patients who were treated with vitamin C monotherapy instead of combination therapy, the mortality was reduced (RR 0.66, 95% CI 0.49 to 0.88, p = 0.004). Vitamin C was associated with a significant improvement of 72-h ΔSOFA score (SMD = 0.20, 95% CI 0.07 to 0.32, p = 0.002, I 2 =11%, moderate quality evidence). Conclusions: : In this meta-analysis of patients with sepsis, the use of vitamin C was not associated with reduction in 28-day mortality, but vitamin C may have a positive effect in improving organ function. As the certainty of evidence was low, Larger RCTs were needed.