• Jayshil J Patel, Alfonso Ortiz-Reyes, Rupinder Dhaliwal, John Clarke, Aileen Hill, Christian Stoppe, Zheng-Yii Lee, and Daren K Heyland.
• Division of Pulmonary and Critical Care Medicine, Medical College of Wisconsin, Milwaukee, WI.
• Crit. Care Med. 2022 Mar 1; 50 (3): e304e312e304-e312.

ObjectivesTo conduct a systematic review and meta-analysis to evaluate the impact of IV vitamin C on outcomes in critically ill patients.Data SourcesSystematic search of MEDLINE, EMBASE, CINAHL, and the Cochrane Register of Controlled Trials.Study SelectionRandomized controlled trials testing IV vitamin C in critically ill patients.Data AbstractionTwo independent reviewers abstracted patient characteristics, treatment details, and clinical outcomes.Data SynthesisFifteen studies involving 2,490 patients were identified. Compared with placebo, IV vitamin C administration is associated with a trend toward reduced overall mortality (relative risk, 0.87; 95% CI, 0.75-1.00; p = 0.06; test for heterogeneity I2 = 6%). High-dose IV vitamin C was associated with a significant reduction in overall mortality (relative risk, 0.70; 95% CI, 0.52-0.96; p = 0.03), whereas low-dose IV vitamin C had no effect (relative risk, 0.94; 95% CI, 0.79-1.07; p = 0.46; test for subgroup differences, p = 0.14). IV vitamin C monotherapy was associated with a significant reduction in overall mortality (relative risk, 0.64; 95% CI, 0.49-0.83; p = 0.006), whereas there was no effect with IV vitamin C combined therapy. No trial reported an increase in adverse events related to IV vitamin C.ConclusionsIV vitamin C administration appears safe and may be associated with a trend toward reduction in overall mortality. High-dose IV vitamin C monotherapy may be associated with improved overall mortality, and further randomized controlled trials are warranted.Copyright © 2021 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

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