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• W3136552636 abstract "To the Editor: The recent preclinical study by Lankadeva et al (1), in which septic sheep were treated with “mega-dose” IV vitamin C (0.5 g/kg for 0.5 hr followed by 0.5 g/kg/hr for 6.5 hr), indicated dramatic improvement in both physiologic parameters and clinical condition. This dose is equivalent to 150-g vitamin C for a 40-kg animal (or 300 g per an 80-kg person). Although “mega-dose” IV vitamin C has been used for decades as an adjunctive therapy in oncology patients (2), “mega-doses” (e.g., 50 g and above) are not commonly used in septic patients. To date, most trials in patients with sepsis and shock have used IV vitamin C doses of around 6–7 g/d (3), with some trials using doses of up to 15–25 g/d (4,5). Based on the initially positive findings of the sheep study and while this study was still underway, a critical patient with coronavirus disease 2019 acute respiratory distress syndrome, acute kidney injury, and hypotension was also administered “mega-dose” IV vitamin C (60 g total; 30 g over 0.5 hr followed by 30 g over 6.5 hr). The patient was rapidly weaned off norepinephrine and mean arterial pressure increased without requiring vasopressors or fluid resuscitation. Renal and respiratory function parameters also improved. The clinicians are now proposing a randomized controlled trial of “mega-dose” vitamin C for patients with septic shock (ACTRN12620000651987p; 60 g total; 30-g IV for 1 hr followed by 30 g infused over 5 hr). Why might “mega-dose” vitamin C be more effective than “high-dose” vitamin C, which has to date shown variable results in different trials (4,6,7)? In the oncology literature, one school of thought is that pharmacologic doses of vitamin C are required to penetrate into poorly vascularized solid tumor tissue (8,9). It is known that inflammation, a hallmark of sepsis, can downregulate the cellular sodium-dependent vitamin C transporters (10,11). Thus, although low gram doses of vitamin C may saturate the plasma of critically ill patients (12,13), whether this translates to equivalent saturation of septic tissues is as yet unknown. Thus, “mega-dose” vitamin C may be able to bypass transporter-regulated uptake of vitamin C and “force” vitamin C into depleted tissues, thereby facilitating its myriad intracellular functions. This premise needs to be tested in highly inflammatory states such as sepsis. Trials in critically ill patients typically use divided doses of vitamin C administered as two to four bolus infusions per day. Due to rapid renal clearance of excess vitamin C, bolus infusions result in only a transient peak of vitamin C in plasma (13). The mega-dose studies mentioned above (1) (ACTRN12620000651987p) use continuous infusion for a period of up to 7 hours. Continuous infusion of low gram doses of vitamin C can take between 12 and 24 hours to achieve maximal plasma status (13), whereas continuous infusion of “mega-dose” vitamin C would presumably reach maximal status many hours earlier; every hour counts with critically ill patients in shock. As yet, there is no consensus as to the most effect dose of vitamin C in critically ill septic patients. As such, dose-finding studies are still required." @default.
• W3136552636 created "2021-03-29" @default.
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• W3136552636 date "2021-03-18" @default.
• W3136552636 modified "2023-10-18" @default.
• W3136552636 title "Is “Mega-Dose” IV Vitamin C Required for Septic and Critical Coronavirus Disease 2019 Patients?" @default.
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• W3136552636 doi "https://doi.org/10.1097/ccm.0000000000004873" @default.
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