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Meta-Analysis
. 2021 Oct 12;13(10):3564.
doi: 10.3390/nu13103564.

Vitamin C in Critically Ill Patients: An Updated Systematic Review and Meta-Analysis

Dhan Bahadur Shrestha  1 , Pravash Budhathoki  2 , Yub Raj Sedhai  3 , Sujit Kumar Mandal  4 , Shreeja Shikhrakar  5 , Saurab Karki  6 , Ram Kaji Baniya  7 , Markos G Kashiouris  8 , Xian Qiao  9 , Alpha A Fowler  8
Affiliations
Meta-Analysis

Vitamin C in Critically Ill Patients: An Updated Systematic Review and Meta-Analysis

Dhan Bahadur Shrestha et al. Nutrients. .

Abstract

Background: Vitamin C is a water-soluble antioxidant vitamin. Oxidative stress and its markers, along with inflammatory markers, are high during critical illness. Due to conflicting results of the published literature regarding the efficacy of vitamin C in critically ill patients, and especially the concerns for nephrotoxicity raised by some case reports, this meta-analysis was carried out to appraise the evidence and affirmation regarding the role of vitamin C in critically ill patients.

Methods: We searched the database thoroughly to collect relevant studies that assessed intravenous vitamin C use in critically ill patients published until 25 February 2021. We included randomized controlled trials and observational studies with 20 or more critically ill patients who have received intravenous ascorbic acid (vitamin C). After screening 18,312 studies from different databases, 53 were included in our narrative synthesis, and 48 were included in the meta-analysis. We used the Covidence software for screening of the retrieved literature. Review Manager (RevMan) 5.4 was used for the pooling of data and Odds Ratios (OR) and Mean difference (MD) as measures of effects with a 95% confidence interval to assess for explanatory variables.

Results: Pooling data from 33 studies for overall hospital mortality outcomes using a random-effect model showed a 19% reduction in odds of mortality among the vitamin C group (OR, 0.81; 95% CI, 0.66-0.98). Length of hospital stay (LOS), mortality at 28/30 days, ICU mortality, new-onset AKI and Renal Replacement Therapy (RRT) for AKI did not differ significantly across the two groups. Analysis of data from 30 studies reporting ICU stay disclosed 0.76 fewer ICU days in the vitamin C group than the placebo/standard of care (SOC) group (95% CI, -1.34 to -0.19). This significance for shortening ICU stay persisted even when considering RCTs only in the analysis (MD, -0.70; 95% CI, -1.39 to -0.02).

Conclusion: Treatment of critically ill patients with intravenous vitamin C was relatively safe with no significant difference in adverse renal events and decreased in-hospital mortality. The use of vitamin C showed a significant reduction in the length of ICU stays in critically ill patients.

Keywords: acute kidney injury; ascorbic acid; critical illness; intensive care units; oxidative stress; vitamins.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Cochrane ROB 2.0 of the included trials.
Figure 2
Figure 2
PRISMA Flow Diagram.
Figure 3
Figure 3
Forest plot showing overall hospital mortality using random-effect model.
Figure 4
Figure 4
Forest plot showing 28-days mortality using fixed-effect model.
Figure 5
Figure 5
Forest plot showing mean difference of LoHS using random-effect model.
Figure 6
Figure 6
Forest plot showing mean difference of length of ICU stays using a random-effect model.
Figure 7
Figure 7
Forest plot showing the new occurrence of AKI using a fixed-effect model.
Figure 8
Figure 8
Forest plot showing requirement of RRT for AKI using a random-effect model.
See this image and copyright information in PMC

References

    1. Fisher B.J., Kraskauskas D., Martin E.J., Farkas D., Wegelin J.A., Brophy D., Ward K.R., Voelkel N.F., Fowler A.A., Natarajan R. Mechanisms of attenuation of abdominal sepsis induced acute lung injury by ascorbic acid. Am. J. Physiol. Lung Cell. Mol. Physiol. 2012;303:L20–L32. doi: 10.1152/ajplung.00300.2011. - DOI - PubMed
    1. Fisher B.J., Seropian I.M., Kraskauskas D., Thakkar J.N., Voelkel N.F., Fowler A.A., Natarajan R. Ascorbic acid attenuates lipopolysaccharide-induced acute lung injury. Crit. Care Med. 2011;39:1454–1460. doi: 10.1097/CCM.0b013e3182120cb8. - DOI - PubMed
    1. Fowler A.A., Syed A.A., Knowlson S., Sculthorpe R., Farthing D., DeWilde C., Farthing C.A., Larus T.L., Martin E., Brophy D.F., et al. Phase I safety trial of intravenous ascorbic acid in patients with severe sepsis. J. Transl. Med. 2014;12:1–10. doi: 10.1186/1479-5876-12-32. - DOI - PMC - PubMed
    1. Truwit J., Hite R., Morris P., DeWilde C., Jama A.P. Effect of Vitamin C Infusion on Organ Failure and Biomarkers of Inflammation and Vascular Injury in Patients with Sepsis and Severe Acute Respiratory Failure: The CITRIS. [(accessed on 26 January 2021)]. Available online: http://jamanetwork.com. - PMC - PubMed
    1. Marik P.E., Khangoora V., Rivera R., Hooper M.H., Catravas J. Hydrocortisone, Vitamin C, and Thiamine for the Treatment of Severe Sepsis and Septic Shock: A Retrospective Before-After Study. Chest. 2017;151:1229–1238. doi: 10.1016/j.chest.2016.11.036. - DOI - PubMed

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