Effect of high-dose Ascorbic acid on vasopressor′s requirement in septic shock

Zabet, Mohadeseh Hosseini; Mohammadi, Mostafa; Ramezani, Masoud; Khalili, Hossein

doi:10.4103/2279-042x.179569

Cited by 222 publications

(127 citation statements)

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“…Finally, we perused the reference lists of the selected trials and relevant reviews, from which we discovered two more trials. We identified nine trials satisfying our selection criteria [11][12][13][14][15][16][17][18][19]. We did not include two further trials that reported "ventilator-free days" since we were unable to convert this to our outcome of interest, "duration of mechanical ventilation" [20,21].…”

Section: Methodsmentioning

confidence: 99%

Vitamin C may reduce the duration of mechanical ventilation in critically ill patients: a meta-regression analysis

2020

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Background: Our recent meta-analysis indicated that vitamin C may shorten the length of ICU stay and the duration of mechanical ventilation. Here we analyze modification of the vitamin C effect on ventilation time, by the control group ventilation time (which we used as a proxy for severity of disease in the patients of each trial). Methods: We searched MEDLINE, Scopus, and the Cochrane Central Register of Controlled Trials and reference lists of relevant publications. We included controlled trials in which the administration of vitamin C was the only difference between the study groups. We did not limit our search to randomized trials and did not require placebo control. We included all doses and all durations of vitamin C administration. One author extracted study characteristics and outcomes from the trial reports and entered the data in a spreadsheet. Both authors checked the data entered against the original reports. We used meta-regression to examine whether the vitamin C effect on ventilation time depends on the duration of ventilation in the control group.Results: We identified nine potentially eligible trials, eight of which were included in the meta-analysis. We pooled the results of the eight trials, including 685 patients in total, and found that vitamin C shortened the length of mechanical ventilation on average by 14% (P = 0.00001). However, there was significant heterogeneity in the effect of vitamin C between the trials. Heterogeneity was fully explained by the ventilation time in the untreated control group. Vitamin C was most beneficial for patients with the longest ventilation, corresponding to the most severely ill patients. In five trials including 471 patients requiring ventilation for over 10 h, a dosage of 1-6 g/day of vitamin C shortened ventilation time on average by 25% (P < 0.0001). Conclusions: We found strong evidence that vitamin C shortens the duration of mechanical ventilation, but the magnitude of the effect seems to depend on the duration of ventilation in the untreated control group. The level of baseline illness severity should be considered in further research. Different doses should be compared directly in future trials.

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Section: Methodsmentioning

confidence: 99%

Vitamin C may reduce the duration of mechanical ventilation in critically ill patients: a meta-regression analysis

2020

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“…In a phase I safety trial, intravenous ascorbic acid infusion was safe, well-tolerated, and associated with improvement in multiple organ dysfunction and decreased biomarkers of inflammation and endothelial injury (281). Additionally, a small RCT investigating high dose ascorbic acid administration in patients with septic shock reported a reduction in 28-day mortality (283), while a larger trial in patients with sepsis-associated ARDS reported a significant reduction in 28-day all-cause mortality In response to ACTH release from the corticotrophs of the anterior pituitary gland, the adrenal gland rapidly secretes ascorbic acid, an essential cofactor required for adrenal steroidogenesis in mitochondria, contributing to increased glucocorticoids synthesis. (Bottom) Cells: glucocorticoids, in a time-and concentration-dependent manner, increase the expression of mSVCT2, facilitating the uptake of ascorbic acid into the cell.…”

Section: Vitamin Cmentioning

confidence: 99%

General Adaptation in Critical Illness: Glucocorticoid Receptor-alpha Master Regulator of Homeostatic Corrections

Meduri

Chrousos

2020

Front. Endocrinol.

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In critical illness, homeostatic corrections representing the culmination of hundreds of millions of years of evolution, are modulated by the activated glucocorticoid receptor alpha (GRα) and are associated with an enormous bioenergetic and metabolic cost. Appreciation of how homeostatic corrections work and how they evolved provides a conceptual framework to understand the complex pathobiology of critical illness. Emerging literature place the activated GRα at the center of all phases of disease development and resolution, including activation and re-enforcement of innate immunity, downregulation of pro-inflammatory transcription factors, and restoration of anatomy and function. By the time critically ill patients necessitate vital organ support for survival, they have reached near exhaustion or exhaustion of neuroendocrine homeostatic compensation, cell bio-energetic and adaptation functions, and reserves of vital micronutrients. We review how critical illness-related corticosteroid insufficiency, mitochondrial dysfunction/damage, and hypovitaminosis collectively interact to accelerate an anti-homeostatic active process of natural selection. Importantly, the allostatic overload imposed by these homeostatic corrections impacts negatively on both acute and long-term morbidity and mortality. Since the bioenergetic and metabolic reserves to support homeostatic corrections are time-limited, early interventions should be directed at increasing GRα and mitochondria number and function. Present understanding of the activated GC-GRα's role in immunomodulation and disease resolution should be taken into account when re-evaluating how to administer glucocorticoid treatment and co-interventions to improve cellular responsiveness. The activated GRα interdependence with functional mitochondria and three vitamin reserves (B1, C, and D) provides a rationale for co-interventions that include prolonged glucocorticoid treatment in association with rapid correction of hypovitaminosis.

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“…This study was a pilot clinical study. In the published article,[8] authors mentioned mechanisms that have been proposed previously by Carr et al . [7] and others[46] for the probable role of Vitamin C in severe sepsis and septic shock, including antioxidant and anti-inflammatory properties of Vitamin C, cortisol sparing effect, inhibitory effect on nitric oxide synthase and increasing catecholamines synthesis in the brain and adrenal medulla.…”

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confidence: 99%

“…In drafting of our very recent article, [8] related original articles were referred to, but the review article of Carr et al . [7] was missed.…”

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confidence: 99%

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Ascorbic acid in septic shock

Khalili

2016

J Res Pharm Pract

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Effect of high-dose Ascorbic acid on vasopressor′s requirement in septic shock

Cited by 222 publications

References 46 publications

Vitamin C may reduce the duration of mechanical ventilation in critically ill patients: a meta-regression analysis

Vitamin C may reduce the duration of mechanical ventilation in critically ill patients: a meta-regression analysis

General Adaptation in Critical Illness: Glucocorticoid Receptor-alpha Master Regulator of Homeostatic Corrections

Ascorbic acid in septic shock

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