Safety of High-Dose Vitamin C in Critically Ill Patients: A Systematic Review and Meta-analysis

Abstract

\n Objective:High-Dose Intravenous Vitamin C (HDIVC) is currently a controversial therapy for sepsis and ARDS. The published evidence regarding its efficacy in critically ill patients has shown conflicting results, and in fact, case reports have raised concerns for nephrotoxicity. The objective of this meta-analysis is to critically appraise the latest evidence regarding the safety of HDIVC in critically ill patients.Data Sources: Structured literature search on PubMed, PubMed Central, Scopus, Embase, and Google Scholar.Study Selection: Cross-sectional studies, case-control studies, cohort studies, randomized controlled trials, and case series with 20 or more critically ill patients who have received intravenous ascorbic acid (vitamin C), published till February 25, 2021. We identified 53 studies in our qualitative analysis and 48 studies in our quantitative analysis among a standardized search of 18,312 studies.Data Synthesis:We pooled data and calculated Odds Ratios (OR) and Mean Differences (MD) with their 95% confidence intervals to assess explanatory variables. Based on a random effect model from 33 studies, pooled hospital mortality outcomes showed a 19% reduction in odds for overall hospital mortality among the HDIVC group (OR, 0.81; 95% CI, 0.66-0.98). Mortality at 28/30-days, ICU mortality, length of hospital stay (LOS), new-onset AKI, and Renal Replacement Therapy (RRT) for AKI did not differ significantly across treatment and control groups. Pooled data from 30 studies disclosed 0.76 fewer ICU days in the HDIVC group than the placebo/ standard of care (SOC) group, 95% CI, -1.34 to -0.19. This significance persisted when we included RCTs only in the analysis (MD, -0.70; 95% CI, -1.39 to -0.02).Conclusions:Our results suggest that HDIVC treatment is renally safe and did not increase adverse kidney events, or mortality. It was associated with a slight reduction in ICU length of stay in critically ill patients.