Sean S Scholz1, Rainer Borgstedt2, Nicole Ebeling2, Leoni C Menzel3, Gerrit Jansen2, Sebastian Rehberg2. 1. Department of Anaesthesiology, Intensive Care, Emergency Medicine, Transfusion Medicine and Pain Therapy, Protestant Hospital of the Bethel Foundation, University Hospital OWL, University of Bielefeld, Campus Bielefeld-Bethel, Burgsteig 13, Haus Gilead I, 33617, Bielefeld, Germany. sean.scholz@evkb.de. 2. Department of Anaesthesiology, Intensive Care, Emergency Medicine, Transfusion Medicine and Pain Therapy, Protestant Hospital of the Bethel Foundation, University Hospital OWL, University of Bielefeld, Campus Bielefeld-Bethel, Burgsteig 13, Haus Gilead I, 33617, Bielefeld, Germany. 3. Institute for Diagnostic and Interventional Radiology, Protestant Hospital of the Bethel Foundation, Bielefeld, Germany.
Abstract
BACKGROUND: Supplementation of vitamin C in septic patients remains controversial despite eight large clinical trials published only in 2020. We aimed to evaluate the evidence on potential effects of vitamin C treatment on mortality in adult septic patients. METHODS: Data search included PubMed, Web of Science, and the Cochrane Library. A meta-analysis of eligible peer-reviewed studies was performed in accordance with the PRISMA statement. Only studies with valid classifications of sepsis and intravenous vitamin C treatment (alone or combined with hydrocortisone/thiamine) were included. RESULTS: A total of 17 studies including 3133 patients fulfilled the predefined criteria and were analyzed. Pooled analysis indicated no mortality reduction in patients treated with vitamin C when compared to reference (risk difference - 0.05 [95% CI - 0.11 to - 0.01]; p = 0.08; p for Cochran Q = 0.002; I2 = 56%). Notably, subgroup analyses revealed an improved survival, if vitamin C treatment was applied for 3-4 days (risk difference, - 0.10 [95% CI - 0.19 to - 0.02]; p = 0.02) when compared to patients treated for 1-2 or > 5 days. Also, timing of the pooled mortality assessment indicated a reduction concerning short-term mortality (< 30 days; risk difference, - 0.08 [95% CI - 0.15 to - 0.01]; p = 0.02; p for Cochran Q = 0.02; I2 = 63%). Presence of statistical heterogeneity was noted with no sign of significant publication bias. CONCLUSION: Although vitamin C administration did not reduce pooled mortality, patients may profit if vitamin C is administered over 3 to 4 days. Consequently, further research is needed to identify patient subgroups that might benefit from intravenous supplementation of vitamin C.
BACKGROUND: Supplementation of vitamin C in septic patients remains controversial despite eight large clinical trials published only in 2020. We aimed to evaluate the evidence on potential effects of vitamin C treatment on mortality in adult septic patients. METHODS: Data search included PubMed, Web of Science, and the Cochrane Library. A meta-analysis of eligible peer-reviewed studies was performed in accordance with the PRISMA statement. Only studies with valid classifications of sepsis and intravenous vitamin C treatment (alone or combined with hydrocortisone/thiamine) were included. RESULTS: A total of 17 studies including 3133 patients fulfilled the predefined criteria and were analyzed. Pooled analysis indicated no mortality reduction in patients treated with vitamin C when compared to reference (risk difference - 0.05 [95% CI - 0.11 to - 0.01]; p = 0.08; p for Cochran Q = 0.002; I2 = 56%). Notably, subgroup analyses revealed an improved survival, if vitamin C treatment was applied for 3-4 days (risk difference, - 0.10 [95% CI - 0.19 to - 0.02]; p = 0.02) when compared to patients treated for 1-2 or > 5 days. Also, timing of the pooled mortality assessment indicated a reduction concerning short-term mortality (< 30 days; risk difference, - 0.08 [95% CI - 0.15 to - 0.01]; p = 0.02; p for Cochran Q = 0.02; I2 = 63%). Presence of statistical heterogeneity was noted with no sign of significant publication bias. CONCLUSION: Although vitamin C administration did not reduce pooled mortality, patients may profit if vitamin C is administered over 3 to 4 days. Consequently, further research is needed to identify patient subgroups that might benefit from intravenous supplementation of vitamin C.
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