Parenteral Vitamin C in Patients with Severe Infection: A Systematic Review

Agarwal, Arnav; Basmaji, John; Fernando, Shannon M.; Ge, Fang Zhou; Xiao, Yingqi; Faisal, Haseeb; Honarmand, Kimia; Hylands, Mathieu; Lau, Vincent; Lewis, Kimberley; Couban, Rachel; Lamontagne, François; Adhikari, Neill K. J.

doi:10.1056/evidoa2200105

Cited by 29 publications

(42 citation statements)

References 86 publications

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“…The most recent updated SRMA demonstrated beneficial effects on 30-day and hospital mortality in 4366 patients, while a detrimental effect was observed at 90 days in an analysis including only a subset of 1722 patients and for which LOVIT contributed to 58% [ 10 ].…”

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confidence: 99%

Intravenous vitamin C in adults with sepsis in the intensive care unit: still LOV’IT?

et al. 2022

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confidence: 99%

Intravenous vitamin C in adults with sepsis in the intensive care unit: still LOV’IT?

et al. 2022

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“…The findings of the LOVIT trial are tempered by those of a concurrently published meta-analysis of 41 randomized controlled trials of intravenous vitamin C in adults with severe infection ( n = 4,915), including the LOVIT trial, which reported low certainty evidence that vitamin C might reduce mortality (risk ratio, 0.88; 95% CI, 0.73–1.06 for in-hospital mortality) 8 . Disparate results were reported in sensitivity analyses that were limited to blinded trials deemed at low risk of bias 8 . The heterogeneity in treatment effect and lack of biological evidence of harm with intravenous vitamin C are confounding.…”

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confidence: 99%

“…Vitamin C is a major anti-oxidant with additional pleiotropic anti-inflammatory, anticoagulant and immunomodulatory effects that becomes depleted in response to oxidative stress, providing a rationale for examining the effects of vitamin C in sepsis 7 . Randomized trials evaluating the effectiveness of intravenous vitamin C for sepsis, either alone or in combination with other therapies such as glucocorticoids and thiamine, an approach known as ‘metabolic resuscitation’, have yielded varying results 8 .…”

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confidence: 99%

“…Putative biochemical mechanisms for possible harm of intravenous vitamin C include the composition of the treatment. In LOVIT, vitamin C was administered as ascorbic acid with a pH as low as 5.0 and delivered at a dose 3–4 fold higher than in previous randomized trials 8 . Whether administering this volume of titratable acid is harmful in the setting of sepsis and in the presence of a compromised buffering system is unclear.…”

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Restrictive fluid therapy and high-dose vitamin C in sepsis

Plummer

Bellomo

2022

Nat Rev Nephrol

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“…Statistical heterogeneity in studies was assessed by I 2 statistics. A P<0.05 was considered significant.The initial literature search identified 854 unique studies, 14 trials with 2,793 patients met the eligibility criteria [3][4][5]. The preferred reporting items for systematic reviews and meta-analyses (PRISMA) flowchart of the study selection is shown in Supplementary Figure 1.…”

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confidence: 99%

Meta-analysis assessing the effectiveness of intravenous vitamin C in patients with sepsis and septic shock

Tariq¹,

Amin

Ali

2022

Acute Crit Care

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Sepsis continues to be leading cause of mortality among patients admitted to intensive care unit (ICU), with about 48.9 million cases of sepsis diagnosed and 11 million deaths worldwide in 2017 [1]. Despite significant advances in the understanding of the pathophysiology of sepsis, the mainstay management still relies on active fluid resuscitation for hemodynamic support, early administration of antibiotics, and identification of source and infection control [2]. Vitamin C has been suggested as a possible therapy that attenuates the pathophysiology of sepsis [2]. Multiple randomized controlled trials (RCTs) addressing effectiveness and safety of vitamin C have reported varied conclusions [3]. Previously, published meta-analysis were limited by the sample size and highlighted the need of further studies with a larger number of patients to provide further evidence [3]. The recent publication of results from LOVIT (Lessening Organ Dysfunction with Vitamin C), the largest trial to date addressing this question, justifies re-examination of the evidence [4].PubMed and Scopus databases were searched for relevant studies by two investigators (MAT, UA) using the following keywords: "ascorbic, " "Vitamin C, " "ascorbic acid, " "sepsis, " "septic shock. " Studies were included if they were: (1) RCT (2) comprised of adult patients with Sepsis or septic shock (3) treatment arm: high-dose intravenous (IV) vitamin C (≥1.5 g every 6 hours or 25 mg/kg every 6 hours) either as monotherapy or combination therapy with thiamine and hydrocortisone, (4) control arm: placebo or standard regiment. Outcomes of interest were ICU mortality, 30-day and 90-day mortality, change in Sequential Organ Failure Assessment score (delta SOFA) within 72 hours. Subgroup analyses were conducted for vitamin C as monotherapy versus combination therapy. Review articles, non-randomized studies, conference abstracts and studies published prior to 2010 were excluded. Odds ratios (ORs) or weighted mean difference (WMD) with 95% confidence intervals (CI) were calculated using random effects model. Statistical heterogeneity in studies was assessed by I 2 statistics. A P<0.05 was considered significant.The initial literature search identified 854 unique studies, 14 trials with 2,793 patients met the eligibility criteria [3][4][5]. The preferred reporting items for systematic reviews and meta-analyses (PRISMA) flowchart of the study selection is shown in Supplementary Figure 1. Baseline study characteristics are shown in Supplementary Table 1. IV vitamin C in combination with thiamine and hydrocortisone significantly reduced SOFA score at 72 hours (7 RCTs, 1,318 patients; WMD: -0.52, 95% CI: -1.01 to -0.03, P=0.037, I 2 =53%) (Figure 1D). For

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Parenteral Vitamin C in Patients with Severe Infection: A Systematic Review

Cited by 29 publications

References 86 publications

Intravenous vitamin C in adults with sepsis in the intensive care unit: still LOV’IT?

Intravenous vitamin C in adults with sepsis in the intensive care unit: still LOV’IT?

Restrictive fluid therapy and high-dose vitamin C in sepsis

Meta-analysis assessing the effectiveness of intravenous vitamin C in patients with sepsis and septic shock

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