The effect of intravenous vitamin C on clinical outcomes in patients with sepsis or septic shock: A meta-analysis of randomized controlled trials

Abstract

ObjectivesVitamin C deficiency is common among patients with sepsis and has been associated with poor clinical outcomes. Nevertheless, the effect of intravenous (IV) vitamin C for the treatment of sepsis remains controversial. The purpose of this meta-analysis was to evaluate the effect of IV vitamin C in patients with sepsis or septic shock.MethodsElectronic databases (PubMed, Embase, Scopus, and Cochrane Library) were searched from inception through May 25, 2022 for randomized controlled trials evaluating the effect of IV vitamin C treatment in patients with sepsis. The primary outcome was short-term mortality, and secondary outcomes including the duration of vasopressor, length of intensive care unit (ICU) stay, and Sequential Organ Failure Assessment (SOFA) score after vitamin C treatment. Subgroup analyses were performed based on the type of disease, dose and duration of IV vitamin C.ResultsA total of 10 studies were included, with a total sample of 755 septic patients. The IV vitamin C was associated with a significant reduction in the short-term mortality (OR 0.51, 95% CI 0.37–0.69, I2 = 0%) and duration of vasopressor (MD −27.88, 95% CI −49.84 to −5.92, I2 = 95%). The length of ICU stay (MD −0.68, 95% CI −2.13 to 0.78, I2 = 74%) and SOFA score (MD −0.05, 95% CI −1.69 to 1.58, I2 = 86%) were not significantly different between two groups.ConclusionIn patients with sepsis or septic shock, the IV vitamin C reduced the short-term mortality rate and duration of vasopressor, with no effect on the length of ICU stay and SOFA score. Further trials are required to explore the optimal dosage and duration of IV vitamin C.Systematic Review Registrationhttps://inplasy.com/inplasy-2022-6-0013/, identifier INPLASY202260013.

Impact of intravenous vitamin C as a monotherapy on mortality risk in critically ill patients: A meta-analysis of randomized controlled trials with trial sequential analysis

“…Secondary outcomes included durations of vasopressor use and mechanical ventilation time, risk of renal replacement therapy, ICU/hospital LOS as well as changes in circulating C-reactive protein (CRP) concentration and sequential organ failure assessment (SOFA) score. Subgroup analyses were performed based on the indications of IVVC treatment and dosage of IVVC (i.e., low vs. high) with cut-off value being set at 100 mg/kg/day or 10000 mg/day as previously reported ( 17 ).…”

“…Focusing on the critically ill population receiving intravenous vitamin C (IVVC) as a monotherapy, previous meta-analyses suggested that the use of IVVC may reduce the risk of mortality without a positive impact on the length of stay (LOS) in hospital or intensive care unit (ICU) ( 16 , 17 ). However, the inclusion of a limited number of patients for analysis in the two meta-analyses [i.e., 467 patients ( 16 ) and 755 patients ( 17 )] may impair the robustness of evidence.…”

“…Focusing on the critically ill population receiving intravenous vitamin C (IVVC) as a monotherapy, previous meta-analyses suggested that the use of IVVC may reduce the risk of mortality without a positive impact on the length of stay (LOS) in hospital or intensive care unit (ICU) ( 16 , 17 ). However, the inclusion of a limited number of patients for analysis in the two meta-analyses [i.e., 467 patients ( 16 ) and 755 patients ( 17 )] may impair the robustness of evidence. In contrast, a recent large-scale randomized controlled trial (RCTs) involving 872 patients with sepsis even reported a slight increase in the risk of mortality/persistent organ dysfunction at 28 days in those with IVVC monotherapy compared to those without ( 23 ).…”

“…Several metaanalyses reported no beneficial effect of vitamin C on the risk of mortality in cardiac surgical patients and those with COVID-19 infection (14,15). For patients with sepsis/septic shock or critical illnesses, the association between mortality and the use of vitamin C was also controversial (16)(17)(18)(19)(20)(21)(22). Such conflicting findings may be attributed to the variations among individual studies including study design (i.e., prospective or retrospective), the choice of study population (e.g., critical vs. non-critical), the use of vitamin C as monotherapy or part of a combined regimen, as well as the selected dosage and route of administration.…”

Immunmodulation durch Ernährung bei kritisch kranken Patienten

“…Mehrere Metaanalysen haben keine Reduktion der Mortalität kritisch kranker Patienten unter Vitamin-C-Gabe aufzeigen können [119,174,215]. Andere aktuelle Metaanalysen geben Hinweise auf einen möglichen dosisabhängigen Effekt von Vitamin C. In den Subgruppen der hochdosierten Gabe von Vitamin C (6-25 g/Tag) haben sich signifikante Assoziationen zu einer verminderten Mortalität gezeigt [61,156,225]. In weiteren systematischen Übersichtsarbeiten ergaben sich unter Vitamin-C-Supplementation Hinweise auf eine Verbesserung des Sequential Organ Failure Assessment (SOFA) Score sowie Assoziationen zu einem Rückgang der erforderlichen Dosis an Vasopressoren, ohne Einfluss auf die Mortalität der Patienten [13,66,172,222].…”