• David A Wacker, Susan L Burton, John P Berger, A J Hegg, Jamie Heisdorffer, Qi Wang, Emily J Medcraft, and Ronald A Reilkoff.
• Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Internal Medicine, University of Minnesota Medical School, Minneapolis, MN.
• Crit. Care Med. 2022 May 1; 50 (5): e458e467e458-e467.

ObjectivesTo determine whether IV vitamin C therapy reduces 28-day mortality in patients with septic shock.DesignMulticenter, double-blinded, randomized controlled trial.SettingOne academic medical ICU and four community ICUs.PatientsOf 167 adult patients within 24 hours of vasopressor initiation for septic shock, 126 consented to participation, and 124 received study drug and were included in analysis.InterventionsIV vitamin C (10 mg/mL in normal saline) administered as a 1,000-mg bolus over 30 minutes followed by continuous infusion of 250 mg/hr for 96 hours or placebo of equal volumes of normal saline.Measurements And Main ResultsOf 124 subjects receiving study drug and included in analysis, 60 received vitamin C and 64 placebo. The primary outcome of all-cause 28-day mortality (vitamin C, 26.7%; placebo, 40.6%; p = 0.10) was lower in the vitamin C arm but did not reach statistical significance. Initiation of renal replacement therapy was higher in the vitamin C arm (vitamin C, 16.7%; placebo, 3.3%; p = 0.015), as was volume of fluid administration within 6 hours of study drug initiation (vitamin C, 1.07 L; placebo, 0.76 L; p = 0.03). There were no statistically significant differences in other secondary outcomes. In post hoc subgroup analysis, there was a decrease in 28-day mortality in the vitamin C arm among patients requiring positive-pressure ventilation at the time of enrollment (vitamin C, 36.3%; placebo, 60.0%; p = 0.05). This trial is registered at clinicaltrials.gov under identifier NCT03338569.ConclusionsVitamin C monotherapy failed to significantly reduce mortality in septic shock patients as hypothesized. Our findings do not support its routine clinical use for this purpose.Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine and Wolters Kluwer Health, Inc.

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