Elsevier

European Journal of Pharmacology

Volume 868, 5 February 2020, 172889
European Journal of Pharmacology

Efficacy of vitamin C in patients with sepsis: An updated meta-analysis

https://doi.org/10.1016/j.ejphar.2019.172889 Get rights and content

Abstract

Previous studies have suggested the beneficial effects of vitamin C in patients with sepsis. However, the results could not be reproduced in the subsequent studies. This meta-analysis aimed to reevaluate the value of vitamin C treatment in patients with sepsis. Electronic databases were searched from inception to August 2019 for the studies comparing the effect of vitamin C versus non-vitamin C infusion in patients with sepsis. Data from 10 studies (4 randomized controlled trials [RCTs] and 6 retrospective studies) involving 1671 patients (495 in the vitamin C treatment group and 1176 in the control group) were included. The use of vitamin C did not reduce the risk of 28-day (OR = 0.84, P = 0.611, I2 = 56.3%), intensive care unit (ICU; OR = 0.79, P = 0.319, I2 = 46.2%), or in-hospital mortality (OR = 0.76, P = 0.251, I2 = 51.0%). No difference in the duration of vasopressor usage and the length of ICU or hospital stay was present. The subgroup analysis for two RCTs suggested that vitamin C treatment showed reduced 28-day mortality (OR = 0.22, P = 0.014, I2 = 35.7%), whereas this beneficial effect did not occur in subgroup analysis for three retrospective studies (OR = 1.11, P = 0.527, I2 = 0%). Retrospective meta-analysis could not reveal the beneficial effect of vitamin C on patients with sepsis. Therefore, in order to clarify the role of vitamin C in sepsis the high-quality RCTs will be required in the future study.

Introduction

Sepsis is a life-threatening critical disease triggered by a dysregulated immuno-inflammatory response to an infection (Hotchkiss et al., 2016; Singer et al., 2016). It is a major health care problem affecting 31.5 million people globally each year, including 19.4 million people with severe sepsis (Fleischmann et al., 2016). In spite of earlier diagnosis and improvement in management, sepsis was still associated with high mortality. Data from high-income countries indicated that the number of sepsis-related deaths was 2.8 million per year (Cecconi et al., 2018). In addition, patients with sepsis suffer from numerous other complications, reducing their quality of life (Yende et al., 2016; Ou et al., 2016). Given the great danger of sepsis, more effective therapeutic approaches were required.

A significant low vitamin C level was common in patients with sepsis (Belsky et al., 2018). Vitamin C, also known as ascorbic acid, is an important antioxidant that participates in several kinds of biosynthetic and metabolic processes in the human body (Marik, 2018a, Marik, 2018b). Supplementation of exogenous vitamin C might be a potential treatment for sepsis. In animal studies, the infusion of vitamin C reduced organ injury and prevented the deleterious consequences in a septic condition (Gao et al., 2017; Fisher et al., 2014). Therefore, a large number of clinical studies were performed to investigate the therapeutic effect of vitamin C in patients with sepsis. A meta-analysis conducted by Li (2018) demonstrated that the use of vitamin C could significantly reduce the mortality caused by sepsis. However, these results could not be reproduced in the subsequent studies (Mitchell et al., 2019; Ahn et al., 2019; Litwak et al., 2019; Shin et al., 2019). Thus, the role of vitamin C in patients with sepsis remains controversial. Due to the contrasting results, this updated meta-analysis, including newly published studies, was performed to further assess the value of vitamin C in patients with sepsis.

Section snippets

Search strategy and study selection

The PubMed, Web of Science, ClinicalTrials.gov , and Cochrane Library databases were searched from inception to August 2019 for relevant studies. The following search terms were used: (vitamin C or ascorbic acid) and (sepsis or septic). Also, the reference lists in the included studies and previous relevant meta-analyses were reviewed. The language was restricted to English.

The studies comparing the effect of vitamin C versus non-vitamin C infusion in patients with sepsis were included. The

Study characteristics

The flow diagram of screening strategy for inclusion in the meta-analysis is displayed in Fig. 1. A total of 946 references were identified according to the search strategy: PubMed (n = 281), Web of Science (n = 531), ClinicalTrials.gov (n = 20), and Cochrane Library (n = 114). Among these, 188 were excluded because they were duplicate studies and 657 were excluded because they did not associate with the research topic, after reviewing their titles and abstracts. The remaining 102 studies were

Discussion

The present systematic review and meta-analysis of the currently available published data reassessed the impact of vitamin C on patients with sepsis. The infusion of vitamin C did not have any beneficial effect on mortality in patients with sepsis. In addition, the use of vitamin C did not reduce the length of ICU or hospital stay and the duration of vasopressor administration. The incidence of AKI and renal replacement therapy for AKI did not increase in patients treated with vitamin C.

Sepsis

Funding

This study was supported by Medical science and Technology Research Funding of Guangdong (grant no. A2019409), the Fundamental Research Funds for the Central Universities (grant no. 2019MS136) and National Clinical Key Specialty Construction Project of China (2012-649, 2013-544). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Authors' contributions

Tie-he Qin and Shou-hong Wang conceived and designed the study. Xiao-long Liao, Wei-xin Guo and Jian-Yi Wen performed abstract screening and data extraction. Xue-biao Wei and Zhong-hua Wang analyzed the data and drafted the manuscript. All authors revised and approved the final manuscript.

Declaration of competing interest

There were no competing interests among authors.

Acknowledgements

None.

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