Vitamin C Pharmacokinetics in Critically Ill Patients

Grooth, Harm-Jan de; Manubulu-Choo, Wai-Ping; Zandvliet, Anthe S.; Man, Angelique M. E. Spoelstra de; Girbes, Armand R.J.; Swart, Eleonora L.; Straaten, Heleen M. Oudemans–van

doi:10.1016/j.chest.2018.02.025

Cited by 142 publications

(147 citation statements)

References 34 publications

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“…The average person, in good health, maintains normal plasma vitamin C levels with a daily intake of about 0.1 g/day. However, much higher doses, in the order of grams per day, are needed for critically ill patients to reach normal plasma vitamin C levels [2][3][4][5]. Without supplementation, plasma vitamin C levels are particularly low in critically ill patients [6][7][8][9][10], indicating that the body may have a greater need for vitamin C when under severe stress such as illness requiring intensive care.…”

Section: Introductionmentioning

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: Introductionmentioning

confidence: 99%

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

2020

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“…Based on these and other data, any effective AA treatment regimen for critically ill patients must be administered IV rather than orally. In 20 critically ill patients with multiple organ dysfunction, 2000 mg AA per day given IV restored normal AA plasma concentrations, but only a daily dose of 10,000 mg IV AA elevated plasma AA concentrations to above 1000 μmol/L, the optimal concentration for free radical scavenging effects [20,[22][23][24]. In 24 critically ill patients with sepsis, Fowler et al demonstrated that IV administration of 200 mg/kg per day (as compared to 50 mg/kg/d) in four bolus doses effectively and consistently elevated steady-state plasma concentrations to above 1000 μmol/L within 24 h of the first dose [23].…”

Section: Ascorbic Acid (Vitamin C)mentioning

confidence: 94%

“…While not universally defined, normal AA concentrations range from 21 μmol/L (0.37 mg/dL) to 100 μmol/L (1.76 mg/dL) [17,20,21]. In a small cohort of healthy volunteers, mean peak plasma concentrations of AA reached 134.8 ± 20.6 μmol/L after oral administration of 1250 mg AA.…”

Section: Ascorbic Acid (Vitamin C)mentioning

confidence: 99%

High-Dose Intravenous Ascorbic Acid: Ready for Prime Time in Traumatic Brain Injury?

et al. 2019

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Traumatic brain injury (TBI) is one of the leading public health problems in the USA and worldwide. It is the number one cause of death and disability in children and adults between ages 1-44. Despite efforts to prevent TBIs, the incidence continues to rise. Secondary brain injury occurs in the first hours and days after the initial impact and is the most effective target for intervention. Inflammatory processes and oxidative stress play an important role in the pathomechanism of TBI and are exacerbated by impaired endogenous defense mechanisms, including depletion of antioxidants. As a reducing agent, free radical scavenger, and co-factor in numerous biosynthetic reactions, ascorbic acid (AA, vitamin C) is an essential nutrient that rapidly becomes depleted in states of critical illness. The administration of high-dose intravenous (IV) AA has demonstrated benefits in numerous preclinical models in the areas of trauma, critical care, wound healing, and hematology. A safe and inexpensive treatment, high-dose IV AA administration gained recent attention in studies demonstrating an associated mortality reduction in septic shock patients. High-quality data on the effects of high-dose IV AA on TBI are lacking. Historic data in a small number of patients demonstrate acute and profound AA deficiency in patients with central nervous system pathology, particularly TBI, and a strong correlation between low AA concentrations and poor outcomes. While replenishing deficient AA stores in TBI patients should improve the brain's ability to tolerate oxidative stress, high-dose IV AA may prove an effective strategy to prevent or mitigate secondary brain injury due to its ability to impede lipid peroxidation, scavenge reactive oxygen species, suppress inflammatory mediators, stabilize the endothelium, and reduce brain edema. The existing preclinical data and limited clinical data suggest that high-dose IV AA may be effective in lowering oxidative stress and decreasing cerebral edema. Whether this translates into improved clinical outcomes will depend on identifying the ideal target patient population and possible treatment combinations, factors that need to be evaluated in future clinical studies. With its excellent safety profile and low cost, high-dose IV AA is ready to be evaluated in the early treatment of TBI patients to mitigate secondary brain injury and improve outcomes.

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“…The results between the two methods were determined to be equivalent for total vitamin C. Over the range measured (4-133 μmol/L) a small bias (3.7 μmol/L) was observed for the HPLC-UV method, which did not exist at concentrations of clinical interest, <28.4 μmol/L. It is unclear whether this bias would increase at levels >133 μmol/L as these concentrations are likely to be observed in high-dose vitamin C trials [14,52,78].…”

Section: Literature Searchmentioning

confidence: 99%

“…This was re-enforced by the findings in the second National Health and Nutrition Examination Survey in the US (1976)(1977)(1978)(1979)(1980) [57]. Currently there does not appear to be standardised normal, or expected, reference indices for serum/plasma vitamin C. Many of the published indices range from 23 to 100 μmol/L [2,14,44,78,88]. One epidemiological study on European populations reported a vitamin C reference range of 6.25-116.81 μmol/L across five countries [89].…”

Section: Post-analytical Conceptsmentioning

confidence: 99%

Vitamin C measurement in critical illness: challenges, methodologies and quality improvements

Collie

Greaves

Jones

et al. 2019

Clinical Chemistry and Laboratory Medicine (CCLM)

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Background: There is renewed interest in high-dose vitamin C interventions in clinical medicine due to its antioxidant properties, safe use and cost-effectiveness. Yet, randomised control trials (RCTs) employing these interventions are failing to include robust analytical methodology and proper sample handling and processing techniques. Consequently, comparisons between studies becomes impossible as there is no metrological traceability and results may be prone to pre-analytical errors. Content: Through published vitamin C stability studies, method comparison papers and data from vitamin C external quality assurance programs, an assessment was made on the functionality of current methods for critically ill patient samples. Summary: Data was obtained from two external quality assurance programs, two papers assessing sample stability and interlaboratory agreement and a publication on vitamin C method comparisons. A shift from spectrophotometric and enzymatic methodologies to high performance liquid chromatography (HPLC) greatly improved the variability and interlaboratory agreement. Therefore, the current analytical performance of vitamin C HPLC methodologies are acceptable for the requirements of a high-dose vitamin C RCTs. Outlook: Recommendations across the total testing process of vitamin C have been provided to improve the quality of the results. The harmonisation of sample handling and processing procedures will further improve the reliability of current analytical methodologies.

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Vitamin C Pharmacokinetics in Critically Ill Patients

Cited by 142 publications

References 34 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

High-Dose Intravenous Ascorbic Acid: Ready for Prime Time in Traumatic Brain Injury?

Vitamin C measurement in critical illness: challenges, methodologies and quality improvements

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