Vitamin C-based regimens for sepsis and septic shock: Systematic review and meta-analysis of randomized clinical trials.

Purpose: to critically appraise and synthesize the evidence on the effects of vitamin C-based regimens for patients with sepsis or septic shock.

Methods: a broad search was performed on May 2021 to identify randomized clinical trials (RCTs) assessing vitamin C-based regimens as adjuvant therapy for adults with sepsis or septic shock. We used the Cochrane Risk of Bias table to assess the methodological quality of the included RCTs and the GRADE approach to evaluate the evidence certainty.

Results: We included 20 RCTs (2124 participants). Evidence from low to very low certainty showed that vitamin C compared to placebo may reduce all-cause mortality up to 28 days (relative risk [RR] 0.60, 95% confidence interval (CI) 0.45 to 0.80, 4 RCTs, 335 participants). Considering the other comparisons (vitamin C alone or combined with thiamine and/or hydrocortisone, compared to placebo, standard care or hydrocortisone), there were a little to no difference or very uncertain evidence for adverse events, SOFA score, ICU length of stay, acute kidney injury, mechanical ventilation- and vasoactive drugs-free days up to 28 days.

Conclusion: Further RCTs with higher methodological quality, an increased number of participants and assessing clinically relevant outcomes are needed to provide better decision-making guidance.

Prospero Register: CRD42021251786.