Vitamin C supplementation in the critically ill: A systematic review and meta-analysis

Background: Low plasma levels of vitamin C are associated with adverse outcomes, including increased mortality, in critically ill patients. Several trials have suggested that the administration of intravenous vitamin C in this setting may have beneficial effects, such as reducing the incidence of organ failure and improving survival. However, these studies have generally involved combination therapies consisting of vitamin C along with other antioxidants, confounding the effects of vitamin C alone. The primary objective of this meta-analysis is to investigate the effects of isolated intravenous supplementation of vitamin C in adults with critical illness. Methods: A database search was conducted for studies on the use of intravenous vitamin C in adult patients with critical illness. The primary outcome assessed was mortality at the longest follow-up time available. Secondary outcomes were the duration of mechanical ventilation, duration of vasopressor support, fluid requirements, and urine output in the first 24 h of intensive care unit admission. Results: Five studies (four randomized controlled trials and one retrospective review) enrolling a total of 142 patients were included in this meta-analysis. Compared with controls, the administration of intravenous vitamin C was associated with a decreased need for vasopressor support (standardized mean difference -0.71; 95% confidence interval (-1.16 to -0.26); p = 0.002) and decreased duration of mechanical ventilation (standardized mean difference -0.5; 95% confidence interval (-0.93 to -0.06); p = 0.03), but no difference was found in mortality (odds ratio 0.76; 95% confidence interval (0.27 to 2.16); p = 0.6). Trends were also noted toward decreased fluid requirements and increased urine output. No adverse effects were reported. Conclusion: The administration of intravenous vitamin C may lead to vasopressor sparing effects and a reduced need for mechanical ventilation in the critically ill, without affecting overall mortality. However, these results should be interpreted in light of the limitations of the primary literature and should serve as a preview of upcoming trials in this area.