Thiamine, Ascorbic Acid, and Hydrocortisone As a Metabolic Resuscitation Cocktail in Sepsis: A Meta-Analysis of Randomized Controlled Trials With Trial Sequential Analysis*

Assouline, Benjamin; Faivre, Anna; Verissimo, Thomas; Sangla, Frédéric; Berchtold, Lena; Giraud, Raphaël; Bendjelid, Karim; Sgardello, Sebastian; Elia, Nadia; Pugin, Jérôme; Seigneux, Sophie de; Legouis, David

doi:10.1097/ccm.0000000000005262

Cited by 42 publications

(32 citation statements)

References 49 publications

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“…In recent years, multiple randomized controlled trials (RCTs) evaluating the effect of intravenous (IV) vitamin C with or without hydrocortisone and thiamine have been completed. Several recently published meta-analyses (14)(15)(16)(17)(18)(19)(20) assessed the combination of hydrocortisone, ascorbic acid, and thiamine (HAT) treatment in septic patients. The results indicated that the HAT treatment improved the Sequential Organ Failure Assessment (SOFA) score and reduced the duration of vasopressor, but was not associated with lower short-term mortality.…”

Section: Introductionmentioning

confidence: 99%

The effect of intravenous vitamin C on clinical outcomes in patients with sepsis or septic shock: A meta-analysis of randomized controlled trials

Zhu

Zhang

et al. 2022

Front. Nutr.

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ObjectivesVitamin C deficiency is common among patients with sepsis and has been associated with poor clinical outcomes. Nevertheless, the effect of intravenous (IV) vitamin C for the treatment of sepsis remains controversial. The purpose of this meta-analysis was to evaluate the effect of IV vitamin C in patients with sepsis or septic shock.MethodsElectronic databases (PubMed, Embase, Scopus, and Cochrane Library) were searched from inception through May 25, 2022 for randomized controlled trials evaluating the effect of IV vitamin C treatment in patients with sepsis. The primary outcome was short-term mortality, and secondary outcomes including the duration of vasopressor, length of intensive care unit (ICU) stay, and Sequential Organ Failure Assessment (SOFA) score after vitamin C treatment. Subgroup analyses were performed based on the type of disease, dose and duration of IV vitamin C.ResultsA total of 10 studies were included, with a total sample of 755 septic patients. The IV vitamin C was associated with a significant reduction in the short-term mortality (OR 0.51, 95% CI 0.37–0.69, I2 = 0%) and duration of vasopressor (MD −27.88, 95% CI −49.84 to −5.92, I2 = 95%). The length of ICU stay (MD −0.68, 95% CI −2.13 to 0.78, I2 = 74%) and SOFA score (MD −0.05, 95% CI −1.69 to 1.58, I2 = 86%) were not significantly different between two groups.ConclusionIn patients with sepsis or septic shock, the IV vitamin C reduced the short-term mortality rate and duration of vasopressor, with no effect on the length of ICU stay and SOFA score. Further trials are required to explore the optimal dosage and duration of IV vitamin C.Systematic Review Registrationhttps://inplasy.com/inplasy-2022-6-0013/, identifier INPLASY202260013.

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Section: Introductionmentioning

confidence: 99%

The effect of intravenous vitamin C on clinical outcomes in patients with sepsis or septic shock: A meta-analysis of randomized controlled trials

Zhu

Zhang

et al. 2022

Front. Nutr.

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“…However, there are only 9 RCTs presenting time to intervention initiation in our meta-analysis, resulting in difficulty in judgement the effect of initiation time. Recent meta-analyses [11,13,[41][42][43]] also failed to find improved mortality among patients with sepsis, no matter combined therapy or monotherapy. Different inclusion criterion, duration, patient populations and timing of administration explain the heterogeneity of different research results to some extent.…”

Section: Discussionmentioning

confidence: 99%

The outcome of IV vitamin C therapy in patients with sepsis or septic shock: a meta-analysis of randomized controlled trials

Liang

Su²,

Shao

et al. 2023

Crit Care

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Background To update a meta-analysis of randomized controlled trials (RCTs) and further explore the outcome of IV vitamin C (IVVC) administration in sepsis or septic shock patients. Methods This study is a meta-analysis of RCTs. The RCTs of vitamin C therapy in sepsis or septic shock were searched in PubMed, EMBASE and Clinical Trials.gov from inception to January 16, 2023. We registered the protocol with PROSPERO (CRD42022354875). The primary outcome was delta Sequential Organ Failure Assessment (SOFA) score at 72–96 h. Two reviewers independently assessed RCTs according to eligibility criteria: (1) study type: RCT; (2) patient population: patients ≥ 18 years with sepsis or septic shock; (3) intervention: IVVC at any doses as monotherapy or combined with thiamine or and hydrocortisone compared with standard of care, no intervention or placebo (defined as control group); (4) the RCT described short-term mortality or SOFA score. Then, two authors independently extracted related information from RCTs. Results Eighteen RCTs (n = 3364 patients) were identified in this meta-analysis. There were significant effects in the delta SOFA score from baseline to 72–96 h (MD, − 0.62; 95% CI, − 1.00 to − 0.25; p = 0.001) and the duration of vasopressor use (MD, − 15.07; 95% CI, − 21.59 to − 8.55; p < 0.00001) with IVVC therapy. Treatment with IVVC was not shown to improve short-term mortality (OR, 0.89; 95% CI, 0.77 to 1.04; p = 0.14); nevertheless, dose at 25–100 mg/kg/d subgroup associated with a significant reduction in short-term mortality (OR, 0.80; 95% CI, 0.65 to 0.97; p = 0.03). An increase adverse event was observed in IVVC therapy (OR, 1.98; 95% CI, 1.06 to 3.68; p = 0.03). Conclusion In this meta-analysis, IVVC in sepsis or septic shock patients significantly improved delta SOFA score and reduced the duration of vasopressor use, whereas it was not associated with reduction in short-term mortality and had higher adverse events.

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“…A diet containing ascorbic acid combined with hydrocortisone and thiamine improves sepsis features and consequences [ 79 ]. The utilization of combined hydrocortisone, ascorbic acid, and thiamine therapy appears to be safe and provides potential benefits for the management of sepsis and septic shock, but some aspects remain controversial since their actions seem to be modest in decreasing mortality [ 80 , 81 , 82 ]. The consumption of polyphenolic antioxidant flavonoids regulates gene expression.…”

Section: Discussionmentioning

confidence: 99%

Effect of Dietary Supplements with ω-3 Fatty Acids, Ascorbic Acid, and Polyphenolic Antioxidant Flavonoid on Gene Expression, Organ Failure, and Mortality in Endotoxemia-Induced Septic Rats

et al. 2023

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Sepsis syndrome develops through enhanced secretion of pro-inflammatory cytokines and the generation of reactive oxygen species (ROS). Sepsis syndrome is characterized by vascular hyperpermeability, hypotension, multiple organ dysfunction syndrome (MODS), and increased mortality, among others. Endotoxemia-derived sepsis is an important cause of sepsis syndrome. During endotoxemia, circulating endotoxin interacts with endothelial cells (ECs), inducing detrimental effects on endothelium function. The endotoxin induces the conversion of ECs into fibroblasts, which are characterized by a massive change in the endothelial gene-expression pattern. This downregulates the endothelial markers and upregulates fibrotic proteins, mesenchymal transcription factors, and extracellular matrix proteins, producing endothelial fibrosis. Sepsis progression is modulated by the consumption of specific nutrients, including ω-3 fatty acids, ascorbic acid, and polyphenolic antioxidant flavonoids. However, the underlying mechanism is poorly described. The notion that gene expression is modulated during inflammatory conditions by nutrient consumption has been reported. However, it is not known whether nutrient consumption modulates the fibrotic endothelial gene-expression pattern during sepsis as a mechanism to decrease vascular hyperpermeability, hypotension, MODS, and mortality. Therefore, the aim of this study was to investigate the impact of the consumption of dietary ω-3 fatty acids, ascorbic acid, and polyphenolic antioxidant flavonoid supplements on the modulation of fibrotic endothelial gene-expression patterns during sepsis and to determine the effects on sepsis outcomes. Our results indicate that the consumption of supplements based on ω-3 fatty acids and polyphenolic antioxidant flavonoids was effective for improving endotoxemia outcomes through prophylactic ingestion and therapeutic usage. Thus, our findings indicated that specific nutrient consumption improves sepsis outcomes and should be considered in treatment.

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Thiamine, Ascorbic Acid, and Hydrocortisone As a Metabolic Resuscitation Cocktail in Sepsis: A Meta-Analysis of Randomized Controlled Trials With Trial Sequential Analysis*

Cited by 42 publications

References 49 publications

The effect of intravenous vitamin C on clinical outcomes in patients with sepsis or septic shock: A meta-analysis of randomized controlled trials

The effect of intravenous vitamin C on clinical outcomes in patients with sepsis or septic shock: A meta-analysis of randomized controlled trials

The outcome of IV vitamin C therapy in patients with sepsis or septic shock: a meta-analysis of randomized controlled trials

Effect of Dietary Supplements with ω-3 Fatty Acids, Ascorbic Acid, and Polyphenolic Antioxidant Flavonoid on Gene Expression, Organ Failure, and Mortality in Endotoxemia-Induced Septic Rats

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