• Ryota Sato, Daisuke Hasegawa, Narut Prasitlumkum, Miki Ueoka, Kazuki Nishida, Kunihiko Takahashi, Michitaka Nasu, and Siddharth Dugar.
• Department of Critical Care Medicine, Respiratory Institute, Cleveland Clinic, Cleveland, OH.
• Crit. Care Med. 2021 Dec 1; 49 (12): 212121302121-2130.

ObjectivesThe aim of this study was to conduct a systematic review and meta-analysis of randomized controlled trials to investigate whether IV high-dose vitamin C improves the short-term mortality of patients with sepsis.DesignThis study is a systematic review and meta-analysis of randomized controlled trials. We searched EMBASE, the Cochrane Central Register of Controlled Trials, and MEDLINE for randomized controlled trials that met inclusion criteria. The protocol was registered at the University hospital Medical Information Network Clinical Trials Registry (UMIN000040528). All analyses were presented with the use of random-effects models. The primary outcome was short-term mortality defined as 28-day, 30-day, or in-hospital mortality.PatientsTwo authors independently evaluated the following eligibility criteria: 1) randomized controlled trial, 2) patients with sepsis aged ≥18 years, and 3) received intravenous high-dose vitamin C in addition to standard of care, or standard of care alone. Then, two authors independently extracted the selected patient and study characteristics and outcomes from studies that met above eligibility criteria.Measurements And Main ResultsEleven randomized controlled trials (n = 1,737 patients) were included in this meta-analysis. High-dose IV vitamin C was not associated with a significantly lower short-term mortality (risk ratio, 0.88; 95% CI, 0.73-1.06; p = 0.18; I2 = 29%) but was associated with a significantly shorter duration of vasopressor use (standardized mean difference, -0.35; 95% CI, -0.63 to -0.07; p < 0.01; I2 = 80%) and a significantly greater decline in the Sequential Organ Failure Assessment score at 72-96 hours (standardized mean difference, -0.20; 95% CI, -0.32 to -0.08; p < 0.01; I2 = 16%). One study reported significant association with hypernatremia, but adverse effects were rare, and high-dose vitamin C is deemed relatively safe.ConclusionsIn this meta-analysis, the use of IV high-dose vitamin C in patients with sepsis was not associated with lower short-term mortality although it was associated with significantly shorter duration of vasopressor use and greater decline in the Sequential Organ Failure Assessment score at 72-96 hours.Copyright © 2021 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

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