Abstract
BackgroundPrevious randomized trials of vitamin C, hydrocortisone, and thiamine on sepsis were limited by short-term vitamin C administration, heterogeneous populations, and the failure to evaluate each component’s effect. The purpose of this study was to determine whether vitamin C alone for ≥ 5 days or in combination with corticosteroids and/or thiamine was associated with decreased mortality across the sepsis population and subpopulation.MethodsNationwide population-based study conducted using the Korean National Health Insurance Service database. A total of 384,282 adult patients with sepsis who were admitted to the intensive care unit were enrolled from January 2017 to December 2019. The primary outcome was hospital mortality, while the key secondary outcome was 90-day mortality.ResultsThe mean [standard deviation] age was 69.0 [15.4] years; 57% were male; and 36,327 (9%) and 347,955 did and did not receive vitamin C, respectively. After propensity score matching, each group involved 36,327 patients. The hospital mortality was lower by − 0.9% in the treatment group (17.1% vs 18.0%; 95% confidence interval, − 1.3 to − 0.5%; p < 0.001), a significant but extremely small difference. However, mortality decreased greater in patients who received vitamin C for ≥ 5 days (vs 1–2 or 3–4 days) (15.8% vs 18.8% vs 18.3%; p < 0.001). Further, vitamin C was associated with a lower hospital mortality in patients with older age, multiple comorbidities, pneumonia, genitourinary infection, septic shock, and mechanical ventilation. Consistent findings were found for 90-day mortality. Moreover, vitamin C alone or in combination with thiamine was significantly associated with decreased hospital mortality.ConclusionsIntravenous vitamin C of ≥ 5 days was significantly associated with decreased hospital and 90-day mortality in sepsis patients. Vitamin C combined with corticosteroids and/or thiamine in specific sepsis subgroups warrants further study.
Highlights
Previous randomized trials of vitamin C, hydrocortisone, and thiamine on sepsis were limited by shortterm vitamin C administration, heterogeneous populations, and the failure to evaluate each component’s effect
Numerous randomized trials of vitamin C alone or in combination with hydrocortisone and thiamine for sepsis have been conducted, neither treatment was associated with significantly improved outcomes [7,8,9,10]
Vitamin C levels were not available, and patients in this study were not screened based on their vitamin C status. In this nationwide cohort study of patients with sepsis, intravenous vitamin C is associated with a lower hospital mortality
Summary
Previous randomized trials of vitamin C, hydrocortisone, and thiamine on sepsis were limited by shortterm vitamin C administration, heterogeneous populations, and the failure to evaluate each component’s effect. Numerous randomized trials of vitamin C alone or in combination with hydrocortisone and thiamine for sepsis have been conducted, neither treatment was associated with significantly improved outcomes [7,8,9,10] These trials had insufficient power for detecting differences in mortality and limited the use of vitamin C to a maximum of 4 days. A recent network metaanalysis evaluated larger samples to estimate the effect of vitamin C, corticosteroids, and thiamine alone or in combination on mortality and other outcomes [13] This analysis did not assess the treatment duration and may be limited by heterogeneity of the published studies
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