Safety, Pharmacodynamics, and Efficacy of High- Versus Low-Dose Ascorbic Acid in Severely Burned Adults

Abstract

<jats:title>Abstract</jats:title> <jats:p>In sepsis and burns, ascorbic acid (AA) is hypothesized advantageous during volume resuscitation. There is uncertainty regarding its safety and dosing. This study evaluated high dose AA (HDAA: 66 mg/kg/h for 24 hours) versus low dose AA (LDAA: 3.5 g/days) administration during the first 24 hours in severely burned adults. We conducted a retrospective study comparing fluid administration before and after switching from low dose to HDAA in severely burned adults. A total of 38 adults with burns &amp;gt;20% TBSA, who received either HDAA or LDAA were included in this retrospective study. AA serum concentrations were quantified at 0, 24, and 72 hours postburn. HDAA impact on hemodynamics, acid–base homeostasis, acute kidney injury, vasopressor use, resuscitation fluid requirement, urinary output, and the incidence of adverse effects was evaluated; secondary clinical outcomes were analyzed. AA plasma levels were 10-fold elevated in the LDAA and 150-fold elevated in the HDAA group at 24 hours and decreased in both groups afterwards. HDAA was not associated with a significantly increased risk of any complications. A significant reduction in colloid fluid requirements was noted (LDAA: 947 ± 1722 ml/24 hours vs HDAA: 278 ± 667 ml/24 hours, P = 0.029). Other hemodynamic and resuscitation measures, as well as secondary clinical outcomes were comparable between groups. HDAA was associated with higher AA levels and lower volumes of colloids in adults with severe burns. The rate of adverse events was not significantly higher in patients treated with HDAA. Future studies should consider prolonged administration of AA.</jats:p>

Oxidative Stress and Hyper-Inflammation as Major Drivers of Severe COVID-19 and Long COVID: Implications for the Benefit of High-Dose Intravenous Vitamin C

“…Due to its water solubility an excess is eliminated rapidly by the kidneys. A daily dose of 200 mg/kg body weight iv is assumed to be well tolerated (Fowler et al, 2014;Nagel et al, 2020), and is currently being tested for efficacy in randomized trials in sepsis, COVID-19 and burns [LOVIT: Lessening Organ dysfunction with VITamin C (NCT03680274), LOVIT-COVID (NCT04401150), REMAP-CAP, VICToRY: VItamin C in Thermal injury (NCT04138394)].…”

Effects of administration of ascorbic acid and low‐dose hydrocortisone after infusion of sublethal doses of lipopolysaccharide to horses

“…90,91 In addition, effects of AA have been investigated in human burn patients, with high doses (66 mg/[kg h] for 24 hours) associated with a significant reduction in colloid fluid requirements compared to lower doses. 92 Taken together, it is possible that higher doses of AA in endotoxic horses could elicit stronger anti-inflammatory and antioxidant effects, as well as improve the cortisol response to illness.…”

Nutrition after severe burn injury

“…Transposed in human burn practice, a treatment with high intravenous doses of vitamin C (66 mg/kg/hour during the first 24 h) was associated with reduced fluid requirements and subsequent edema in a first small study [13]. This reduced volume administration has further been reproduced later in different small nonrandomized controlled trials using the same regimen: in a small pseudo-randomized trial including only 30 severe burn patients [14], in a retrospective study including 38 adults [15] and more recently in a retrospective case-controlled study including a total of 75 patients [16 ▪ ]. Using moderate doses (>10 g/day), a treatment with vitamin C during the first 48 h has been associated with beneficial effect on hospital mortality in another recent retrospective study including a high number of severe burn patients [17].…”