OBJECTIVES: We sought to determine trends in use of IV vitamin C for hospitalized patients with sepsis in the context of evolving evidence, including a single-center before-after study in late 2016 and several trials in 2019-2021.

DESIGN: Retrospective cohort study.

SETTING: One thousand one hundred fifteen U.S. hospitals contributing to the Premier Healthcare Database, 2008-2021.

PATIENTS: Eleven million three hundred seventy-five thousand three hundred twenty-six adult inpatients with sepsis.

INTERVENTIONS: IV vitamin C, at any point of the hospital stay.

MEASUREMENTS AND MAIN RESULTS: Patients had a median (interquartile range [IQR]) age of 71 years (59-81 yr) and a median (IQR) of 5 comorbidities (4-7 comorbidities); 53.0% were female; on hospital day 1, 6.9% were mechanically ventilated and 7.5% received a vasopressor. Overall, 32,131 patients (0.3%) received IV vitamin C at any point during hospitalization. During the study period, administration fell from 2008, quarter 1 (0.5%) through 2017, quarter 1 (< 0.1%), then rose and peaked in 2020, quarter 1 (0.6%), and fell through 2021, quarter 4 (0.1%). Examining three time periods defined by predetermined cutpoints (2015 quarter 4, when International Classification of Diseases coding for sepsis changed, and 2020 quarter 1, when the COVID-19 pandemic began), vitamin C use also varied (p < 0.001): 0.2% (2008 quarter 1 to 2015 quarter 3); 0.3% (2015 quarter 4 to 2019 quarter 4); and 0.3% (2020-2021). Temporal trends were similar in sicker subcohorts defined by early mechanical ventilation, early vasopressor use, and diagnosis of COVID-19 (2020-2021). A multilevel logistic regression model with data from 91 hospitals that contributed at least 1 sepsis case per quarter showed a similar utilization pattern, with substantial between-hospital variability (median odds ratio, 7.78; 95% CI, 5.45-11.58).

CONCLUSIONS: IV vitamin C prescription for hospitalized patients with sepsis in the United States was overall infrequent over the 14-year study period, rising after the publication of a before-after study and declining in the COVID-19 pandemic as clinical trial results emerged.