- Open Access
Dosing adjuvant vitamin C in critically ill patients undergoing continuous renal replacement therapy: We are not there yet!
Critical Care volume 23, Article number: 5 (2019)
The original article was published in Critical Care 2018 22:320
We read with great interest the recent letter to Critical Care by Marik and Hooper . Vitamin C (vit C) is increasingly recognized as a crucial compound to alleviate morbidity in critically ill patients. Vit C concentrations, however, are usually far below normal and even close to “scurvy levels” in this population. Vit C also is substantially cleared by continuous renal replacement therapy (CRRT). Significant vit C deficiency was observed in 80% of patients subjected to various types of CRRT despite receiving a daily intravenous (IV) supplement of 500 to 1000 mg . Therefore, high-dose (from 6 to 12 g) vit C substitution during CRRT seems justified .
Marik and Hooper argued against such dose increase in patients receiving CRRT. To support their statement, they provided serum vit C dosages in a small number of septic patients who received 6 g vit C IV while undergoing continuous veno-venous hemofiltration (CVVH). Vit C trough and peak levels were largely above normal and comparable to levels obtained in patients not receiving CVVH .
We want to warn against oversimplification. Marik and Hooper measured vit C within 30 min after the end of vit C infusion. It would have been more relevant to measure vit C after 24 to 48 h of CVVH treatment. Up to 50% of vit C is cleared in a time-dependent manner during a 4-h session of intermittent hemodialysis or hemodiafiltration [4, 5], which suggests that continuous techniques may exacerbate vit C losses. Vit C also is eliminated by both diffusion (dialysis) and convection (filtration). During hemodiafiltration, diffusion is responsible for two thirds of the vit C loss whereas convection accounts only for one third . CVVH is a sheer convective technique in contrast with other often-used CRRT modes in the critically ill, such as continuous veno-venous hemodialysis (CVVHD) and continuous veno-venous hemodiafiltration (CVVHDF). Marik and Hooper thus report the most modest way of CRRT-induced vit C elimination. It is reasonable to think that more diffusion-based CRRT techniques may yield other results.
We agree with Marik and Hooper that 6 g/day vit C IV is sufficient for patients without acute kidney injury and not requiring CRRT. However, vit C measurements should be performed after prolonged CVVH sessions to ensure that a 6 g daily supplement can keep levels within normal range. More studies are needed in patients receiving CVVHD or CVVHDF to exclude overlooking too great a vit C loss.
Continuous renal replacement therapy
Continuous veno-venous hemofiltration
Continuous veno-venous hemodialysis
Continuous veno-venous hemodiafiltration
- Vit C:
Marik PE, Hooper MH. Adjuvant Vitamin C in critically ill patients undergoing renal replacement therapy: What's the right dose? Crit Care. 2018;22:320. https://doi.org/10.1186/s13054-018-2190-y. No abstract available.
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. https://doi.org/10.1177/0884533617716618 Epub 2017 Dec 18.
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. https://doi.org/10.1186/s13054-018-2115-9.
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. https://doi.org/10.1080/00365590701514266.
Morena M, Cristol JP, Bosc JY, Tetta C, Forret G, Leger CL, et al. Convective and diffusive losses of vitamin C during haemodiafiltration session: a contributive factor to oxidative stress in haemodialysis patients. Nephrol Dial Transplant. 2002;17:422–7.
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See related letter by Marik and Hooper https://ccforum.biomedcentral.com/articles/10.1186/s13054-018-2190-y.