Impact of intravenous vitamin C as a monotherapy on mortality risk in critically ill patients: A meta-analysis of randomized controlled trials with trial sequential analysis

Kuo-Chuan Hung; Min-Hsiang Chuang; Jen-Yin Chen; Chih-Wei Hsu; Chong-Chi Chiu; Ying-Jen Chang; Chia-Wei Lee; I-Wen Chen; Cheuk-Kwan Sun

doi:10.3389/fnut.2023.1094757

Impact of intravenous vitamin C as a monotherapy on mortality risk in critically ill patients: A meta-analysis of randomized controlled trials with trial sequential analysis

Front Nutr. 2023 Mar 24:10:1094757. doi: 10.3389/fnut.2023.1094757. eCollection 2023.

Authors

Kuo-Chuan Hung^{1

2}, Min-Hsiang Chuang³, Jen-Yin Chen², Chih-Wei Hsu⁴, Chong-Chi Chiu^{5

6

7}, Ying-Jen Chang², Chia-Wei Lee⁸, I-Wen Chen⁹, Cheuk-Kwan Sun^{6

10}

Affiliations

¹ School of Medicine, College of Medicine, National Sun Yat-sen University, Kaohsiung City, Taiwan.
² Department of Anesthesiology, Chi Mei Medical Center, Tainan City, Taiwan.
³ Department of Internal Medicine, Chi Mei Medical Center, Tainan City, Taiwan.
⁴ Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung City, Taiwan.
⁵ Department of General Surgery, E-Da Cancer Hospital, I-Shou University, Kaohsiung City, Taiwan.
⁶ School of Medicine, College of Medicine, I-Shou University, Kaohsiung City, Taiwan.
⁷ Department of Medical Education and Research, E-Da Cancer Hospital, I-Shou University, Kaohsiung City, Taiwan.
⁸ Department of Neurology, Chi Mei Medical Center, Tainan City, Taiwan.
⁹ Department of Anesthesiology, Chi Mei Medical Center, Liouying, Tainan City, Taiwan.
¹⁰ Department of Emergency Medicine, E-Da Hospital, I-Shou University, Kaohsiung City, Taiwan.

Abstract

Background: This meta-analysis aimed at investigating the pooled evidence regarding the effects of intravenous vitamin C (IVVC) on mortality rate in critically ill patients.

Methods: Databases including Medline, Embase, and Cochrane Library were searched from inception to October, 2022 to identify RCTs. The primary outcome was the risk of overall mortality. Subgroup analyses were performed based on IVVC dosage (i.e., cut-off value: 100 mg/kg/day or 10000 mg/day). Trial sequential analysis (TSA) was used to examine the robustness of evidence.

Results: A total of 12 trials including 1,712 patients were analyzed. Although meta-analysis demonstrated a lower risk of mortality in patients with IVVC treatment compared to those without [risk ratio (RR): 0.76, 95% CI: 0.6 to 0.97, p = 0.02, I ² = 36%, 1,711 patients), TSA suggested the need for more studies for verification. Moreover, subgroup analyses revealed a reduced mortality risk associated with a low IVVC dosage (RR = 0.72, p = 0.03, 546 patients), while no beneficial effect was noted with high IVVC dosage (RR = 0.74, p = 0.13, I ² = 60%, 1,165 patients). The durations of vasopressor [mean difference (MD): -37.75 h, 404 patients) and mechanical ventilation (MD: -47.29 h, 388 patients) use were shorter in the IVVC group than those in the controls, while there was no significant difference in other prognostic outcomes (e.g., length of stay in intensive care unit/hospital) between the two groups.

Conclusion: Although intravenous vitamin C as a monotherapy reduced pooled mortality, durations of vasopressor use and mechanical ventilation, further research is required to support our findings and to identify the optimal dosage of vitamin C in the critical care setting.

Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022371090.

Keywords: critically illness; mortality; sepsis; septic shock; vitamin C.

Publication types

Systematic Review