Administration of Parenteral Vitamin C in Patients With Severe Infection: Protocol for a Systematic Review and Meta-analysis

Arnav Agarwal¹, John Basmaji², Shannon M Fernando^{3

4}, Fang Zhou Ge⁵, Yingqi Xiao^{6

7}, Haseeb Faisal⁸, Kimia Honarmand², Mathieu Hylands⁹, Vincent I Lau¹⁰, Kimberley Lewis¹¹, Rachel Couban¹², François Lamontagne^#^{13

14}, Neill Kj Adhikari^#^{9

15}

Affiliations

¹ Division of General Internal Medicine, Department of Medicine, McMaster University, Hamilton, ON, Canada.
² Division of Critical Care, Department of Medicine, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada.
³ Division of Critical Care, Department of Medicine, University of Ottawa, Ottawa, ON, Canada.
⁴ Department of Emergency Medicine, University of Ottawa, Ottawa, ON, Canada.
⁵ Michael G DeGroote School of Medicine, McMaster University, Hamilton, ON, Canada.
⁶ Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, ON, Canada.
⁷ Department of Nursing, West China School of Nursing, West China Hospital, Sichuan University, Chengdu, China.
⁸ Faculty of Medicine, McMaster University, Hamilton, ON, Canada.
⁹ Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, ON, Canada.
¹⁰ Department of Critical Care Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada.
¹¹ Department of Medicine, McMaster University, Hamilton, ON, Canada.
¹² Department of Anesthesia, McMaster University, Hamilton, ON, Canada.
¹³ Department of Medicine, Université de Sherbrooke, Sherbrooke, QC, Canada.
¹⁴ Centre de Recherche du Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, QC, Canada.
¹⁵ Department of Critical Care Medicine, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.

^# Contributed equally.

PMID: 34910661
PMCID: PMC8734609
DOI: 10.2196/33989

Administration of Parenteral Vitamin C in Patients With Severe Infection: Protocol for a Systematic Review and Meta-analysis

Arnav Agarwal et al. JMIR Res Protoc. 2022.

. 2022 Jan 6;11(1):e33989.

doi: 10.2196/33989.

Authors

Affiliations

¹ Division of General Internal Medicine, Department of Medicine, McMaster University, Hamilton, ON, Canada.
² Division of Critical Care, Department of Medicine, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada.
³ Division of Critical Care, Department of Medicine, University of Ottawa, Ottawa, ON, Canada.
⁴ Department of Emergency Medicine, University of Ottawa, Ottawa, ON, Canada.
⁵ Michael G DeGroote School of Medicine, McMaster University, Hamilton, ON, Canada.
⁶ Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, ON, Canada.
⁷ Department of Nursing, West China School of Nursing, West China Hospital, Sichuan University, Chengdu, China.
⁸ Faculty of Medicine, McMaster University, Hamilton, ON, Canada.
⁹ Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, ON, Canada.
¹⁰ Department of Critical Care Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada.
¹¹ Department of Medicine, McMaster University, Hamilton, ON, Canada.
¹² Department of Anesthesia, McMaster University, Hamilton, ON, Canada.
¹³ Department of Medicine, Université de Sherbrooke, Sherbrooke, QC, Canada.
¹⁴ Centre de Recherche du Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, QC, Canada.
¹⁵ Department of Critical Care Medicine, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.

^# Contributed equally.

PMID: 34910661
PMCID: PMC8734609
DOI: 10.2196/33989

Abstract

Background: Severe infections are characterized by inflammation and oxidative damage. Ascorbic acid (vitamin C) administration may attenuate oxidative damage and, in turn, reduce vascular endothelial injury in pulmonary and systemic vasculature.

Objective: We aim to describe a protocol for a living systematic review that will evaluate the effectiveness and safety of parenteral vitamin C administration in adults with severe infections, including those with COVID-19.

Methods: We searched Ovid MEDLINE, Embase, CINAHL, the Centers for Disease Control and Prevention COVID-19 database, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov from inception to March 30, 2021, for randomized controlled trials evaluating parenteral vitamin C versus no parenteral vitamin C in hospitalized adults with severe infection. Eligible studies will include at least 1 arm involving any dose of parenteral vitamin C alone or in combination with other cointerventions and at least 1 arm not involving parenteral vitamin C. The primary outcomes of interest will include in-hospital, 30-day, and 90-day mortality. Title and abstract screening, full-text screening, data extraction, and risk of bias evaluation via a modified Risk of Bias 2.0 tool will be conducted independently and in pairs. We will perform random effects modeling for meta-analyses, in which study weights will be generated by using the inverse variance method. We will assess certainty in effect estimates by using the Grading of Recommendations Assessment, Development and Evaluation methodology. Meta-analyses will be updated iteratively as new trial evidence becomes available.

Results: Among the 1386 citations identified as of March 30, 2021, a total of 17 eligible randomized controlled trials have been identified as of September 2021. We are in the process of updating the search strategy and associated data analyses.

Conclusions: The results will be of importance to critical care physicians and hospitalists who manage severe infection and COVID-19 in daily practice, and they may directly inform international clinical guidance. Although our systematic review will incorporate the most recent trial evidence, ongoing trials may change our confidence in the estimates of effects, thereby necessitating iterative updates in the form of a living review.

Trial registration: PROSPERO CRD42020209187; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=209187.

International registered report identifier (irrid): RR1-10.2196/33989.

Keywords: COVID-19; SARS-CoV-2; ascorbic acid; critical care; effectiveness; infection; infectious disease; inflammation; meta-analysis; oxidation; parenteral; protocol; review; safety; sepsis; severe infection; treatment; vitamin; vitamin C.

©Arnav Agarwal, John Basmaji, Shannon M Fernando, Fang Zhou Ge, Yingqi Xiao, Haseeb Faisal, Kimia Honarmand, Mathieu Hylands, Vincent I Lau, Kimberley Lewis, Rachel Couban, François Lamontagne, Neill KJ Adhikari. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 06.01.2022.

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Conflict of interest statement

Conflicts of Interest: NKJA and FL are coprincipal investigators of LOVIT (Lessening Organ dysfunction with VITamin C), a randomized trial of vitamin C for sepsis (trial number: NCT03680274), and LOVIT-COVID (Lessening Organ dysfunction with VITamin C-COVID), a randomized trial of vitamin C for COVID-19 (trial number: NCT04401150). The remaining authors have no conflicts of interest to declare.

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Administration of Parenteral Vitamin C in Patients With Severe Infection: Protocol for a Systematic Review and Meta-analysis

Affiliations

Administration of Parenteral Vitamin C in Patients With Severe Infection: Protocol for a Systematic Review and Meta-analysis

Authors

Affiliations

Abstract

Conflict of interest statement

References

LinkOut - more resources

Full Text Sources

Miscellaneous