Meta-analysis assessing the effectiveness of intravenous vitamin C in patients with sepsis and septic shock

Abstract

Sepsis continues to be leading cause of mortality among patients admitted to intensive care unit (ICU), with about 48.9 million cases of sepsis diagnosed and 11 million deaths worldwide in 2017 [1]. Despite significant advances in the understanding of the pathophysiology of sepsis, the mainstay management still relies on active fluid resuscitation for hemodynamic support, early administration of antibiotics, and identification of source and infection control [2]. Vitamin C has been suggested as a possible therapy that attenuates the pathophysiology of sepsis [2]. Multiple randomized controlled trials (RCTs) addressing effectiveness and safety of vitamin C have reported varied conclusions [3]. Previously, published meta-analysis were limited by the sample size and highlighted the need of further studies with a larger number of patients to provide further evidence [3]. The recent publication of results from LOVIT (Lessening Organ Dysfunction with Vitamin C), the largest trial to date addressing this question, justifies re-examination of the evidence [4].PubMed and Scopus databases were searched for relevant studies by two investigators (MAT, UA) using the following keywords: "ascorbic, " "Vitamin C, " "ascorbic acid, " "sepsis, " "septic shock. " Studies were included if they were: (1) RCT (2) comprised of adult patients with Sepsis or septic shock (3) treatment arm: high-dose intravenous (IV) vitamin C (≥1.5 g every 6 hours or 25 mg/kg every 6 hours) either as monotherapy or combination therapy with thiamine and hydrocortisone, (4) control arm: placebo or standard regiment. Outcomes of interest were ICU mortality, 30-day and 90-day mortality, change in Sequential Organ Failure Assessment score (delta SOFA) within 72 hours. Subgroup analyses were conducted for vitamin C as monotherapy versus combination therapy. Review articles, non-randomized studies, conference abstracts and studies published prior to 2010 were excluded. Odds ratios (ORs) or weighted mean difference (WMD) with 95% confidence intervals (CI) were calculated using random effects model. Statistical heterogeneity in studies was assessed by I 2 statistics. A P<0.05 was considered significant.The initial literature search identified 854 unique studies, 14 trials with 2,793 patients met the eligibility criteria [3][4][5]. The preferred reporting items for systematic reviews and meta-analyses (PRISMA) flowchart of the study selection is shown in Supplementary Figure 1. Baseline study characteristics are shown in Supplementary Table 1. IV vitamin C in combination with thiamine and hydrocortisone significantly reduced SOFA score at 72 hours (7 RCTs, 1,318 patients; WMD: -0.52, 95% CI: -1.01 to -0.03, P=0.037, I 2 =53%) (Figure 1D). For

Randomized Clinical Trial of Antioxidant Therapy Patients with Septic Shock and Organ Dysfunction in the ICU: SOFA Score Reduction by Improvement of the Enzymatic and Non-Enzymatic Antioxidant System

“…A more recent meta-analysis reported that Vit C showed no evident clinical improvement and therefore effectiveness of the therapy was not recommended [59]. It is important to mention that in some studies, the basal levels of Vit C have been found to be below the reference value in patients with septic shock [60].…”