To the editor
Pharmacokinetic and dose-response data suggest a vitamin C (vit C) dose largely exceeding 3 g daily in critically ill patients. We recently proposed higher vit C dosing in cardiac arrest patients who require continuous renal replacement therapy (CRRT). In a reaction, Spoelstra-de Man et al. rebutted that increasing the vit C dose above 2 g/day during continuous veno-venous hemofiltration (CVVH) was unnecessary when normal plasma vit C concentrations are targeted. They based their standpoint on calculating less vit C removal during CVVH than by a normally functioning kidney.
We want to warn for too much oversimplification! First, Spoelstra-de Man et al. used CVVH, which is a sheer convective technique as opposed to continuous venovenous hemodialysis (CVVHD) and continuous veno-venous hemodiafiltration (CVVHDF). Being largely eliminated by diffusion, vit C will be more extensively cleared by CVVHD(F) than by CVVH.  Second, vit C plasma concentrations in the single CVVH-treated patient studied were approximately 200 μmol/L at CVVH initiation and were recorded for 48 h. Vit C, however, is consistently deficient upon intensive care (IC) admission and levels continue to fall dramatically during the acute phase of surgery or critical illness. In a patient with reduced vit C levels and normal renal function, the kidney will adapt and drive back vit C losses. In severely ill patients with low baseline or declining vit C levels, CRRT will continue to remove vit C regardless of plasma levels. Kamel et al. observed a pronounced vit C deficiency in 80% of patients receiving CRRT for a mean duration of 2 weeks despite a daily intravenous supplement of 500 to 1000 mg initiated within 7 days prior to measuring vit C levels. At least one-third of the patients in this study were on CVVHD or CVVHDF. This underscores that more aggressive vit C supplementation is mandatory when CRRT runs for a prolonged time period and, in particular, when renal epuration modes that facilitate vit C elimination are applied. Third, vit C levels corresponding with a neat clinical effect in IC patients have not been determined. For instance, doubling target concentrations from 100 to 200 μmol/L would result in a daily CRRT-induced vit C loss of 1.7 g. Unless proven otherwise, we hold on to our recommendation to supplement up to 12 g vit C in patients undergoing CVVHD, CVVHDF or prolonged CVVH.
Honore PM De Bels D Preseau T Redant S Attou R Spapen HD. Adjuvant vitamin C in cardiac arrest patients undergoing renal replacement therapy: an appeal for a higher high-dose. Crit Care 2018; 22: 207.
Spoelstra-de Man AME De Groot HJ Elbers PWG Oudemans-Van Straaten HM . Response to “Adjuvant vitamin C in cardiac arrest patients undergoing renal replacement therapy: an appeal for a higher high-dose”. Crit Care 2018; 22: 350
Fehrman-Ekholm I Lotsander A Logan K Dunge D Odar-Cederlöf I Kallner A. Concentrations of vitamin C vitamin B12 and folic acid in patients treated with hemodialysis and on-line hemodiafiltration or hemofiltration. Scand J Urol Nephrol 2008; 42: 74-80.
- Export Citation
Fehrman-Ekholm I, Lotsander A, Logan K, Dunge D, Odar-Cederlöf I, Kallner A. Concentrations of vitamin C, vitamin B12 and folic acid in patients treated with hemodialysis and on-line hemodiafiltration or hemofiltration. Scand J Urol Nephrol 2008; 42: 74-80.)| false 10.1080/00365590701514266 18210337
Carr AC Rosengrave PC Bayer S Chambers S Mehrtens J Shaw GM. Hypovitaminosis C and vitamin C deficiency in critically ill patients despite recommended enteral and parenteral intakes. Crit Care 2017; 21: 300.
Kamel AY Dave NJ Zhao VM Griffith DP Connor MJ Jr Ziegler TR. Micronutrient Alterations During Continuous Renal Replacement Therapy in Critically Ill Adults: A Retrospective Study. Nutr Clin Pract 2018; 33: 439-46.