High dose intravenous vitamin C treatment in Sepsis: associations with acute kidney injury and mortality

Abstract

Background The effects of vitamin C on clinical outcomes in critically ill patients remain controversial due to inconclusive studies. This retrospective observational cohort study evaluated the effects of vitamin C therapy on acute kidney injury (AKI) and mortality among septic patients. Methods Electronic medical records of 1390 patients from an academic hospital who were categorized as Treatment (received at least one dose of 1.5 g IV vitamin C, n = 212) or Comparison (received no, or less than 1.5 g IV vitamin C, n = 1178) were reviewed. Propensity score matching was conducted to balance a number of covariates between groups. Multivariate logistic regressions were conducted predicting AKI and in-hospital mortality among the full sample and a sub-sample of patients seen in the ICU. Results Data revealed that vitamin C therapy was associated with increases in AKI (OR = 2.07 95% CI [1.46–2.93]) and in-hospital mortality (OR = 1.67 95% CI [1.003–2.78]) after adjusting for demographic and clinical covariates. When stratified to examine ICU patients, vitamin C therapy remained a significant risk factor of AKI (OR = 1.61 95% CI [1.09–2.39]) and provided no protective benefit against mortality (OR = 0.79 95% CI [0.48–1.31]). Conclusion Ongoing use of high dose vitamin C in sepsis should be appraised due to observed associations with AKI and death.

Impact of intravenous vitamin C as a monotherapy on mortality risk in critically ill patients: A meta-analysis of randomized controlled trials with trial sequential analysis

“…Another interesting finding of the current study was a non-significant trend toward a higher risk of renal replacement therapy linked to the use of IVVC compared with that in the control group based on data from four available trials that adopted relatively large IVVC dosages (i.e., 200 mg/kg/day, 6 g/day, 24 g/day) ( 23 , 33 , 35 , 37 ) despite not fitting the criteria for a high dosage in this study. Despite the lack of robustness of evidence based on the small number of studies, our finding may be in line with that of a previous cohort study on 1,390 critically ill patients showing that IVVC with a dosage ≥1.5 g four times a day was associated with an increased risk of acute kidney and in-hospital mortality compared with those receiving no treatment or a single dose less than 1.5 g ( 43 ).…”

Pharmacologic Ascorbic Acid as Early Therapy for Hospitalized Patients with COVID-19: A Randomized Clinical Trial

“…Similarly, in sepsis studies, estimated peak plasma concentrations are predicted to be less than 5% of the peak concentrations predicted from the dose in our COVID trial [ 15 , 23 , 37 ]. Doses used in sepsis studies were initially selected to rapidly reverse AA deficiency unrelated to the generation of hydrogen peroxide, although the use of even these comparatively lower AA doses in a sepsis population might confer increased risk because of concurrent acute kidney injury in sepsis [ 38 , 39 ].…”

Potential Antioxidant Multitherapy against Complications Occurring in Sepsis

“…However, other negative effects regarding antioxidant monotherapies have been brought up, in particular concerning the cardiovascular and renal systems. With respect to the renal system, it seems that vitamin C is associated with increases in AKI and in-hospital mortality [ 68 , 69 ] and an early administration of NAC not only does not attenuate the endothelial damage during sepsis, but it can aggravate it, leading to sepsis-induced organ failure and, in particular, cardiovascular failure [ 70 ]. Moreover, it seems that NAC administration can directly damage the cardiovascular system, leading to cardiac depression, reduction of cardiac index, left ventricular stroke work index, and mean arterial pressure [ 67 ].…”

“…Vitamin C used alone as monotherapy has shown controversial results in patients with sepsis, where no significant differences in markers of organ dysfunction have been observed [ 7 ]. Indeed, other clinical trials have suggested an increased incidence of sepsis-induced AKI [ 68 ] and increased risk of mortality [ 74 ]. In the case of selenium, clinical studies have not shown that this antioxidant has a significant effect in reducing mortality in patients with sepsis [ 71 , 72 , 75 ], despite showing a substantial increase in the GSH-Px enzyme as part of the antioxidant defense system [ 71 , 75 , 76 ].…”