Efficacy of High-Dose Vitamin C Infusion on Outcomes in Sepsis Requiring Mechanical Ventilation: A Double-Blind Randomized Controlled Trial

Abstract

Background. Critically ill patients have an increased requirement for vitamin C in sepsis and these patients have low levels of vitamin C. The researchers validated the efficacy of high-dose vitamin C intravenous infusion (IVI) in patients with sepsis requiring mechanical ventilation. Methods. Forty patients were randomly assigned to 2 groups (20 each) in a 1 : 1 ratio in accordance with the vitamin C treatment regimen: Group I (GI): patients received 1.5 g/6 h vitamin C in 50 ml of dextrose 5% in water (D5W) IVI over 30 minutes for 4 consecutive days; Group II (GII): patients received 100 mg vitamin C/day as a first single dose in 50 ml of D5W IVI over 30 minutes and the other three subsequent doses were 50 ml of plain D5W IVI over 30 minutes for 4 consecutive days. Primary outcomes were the change in sequential organ failure assessment (SOFA) score at day 7, the incidence of ventilator-associated pneumonia (VAP), and the plasma vitamin C level. The glutathione peroxidase (GPX) activity, C-reactive protein (CRP) level, duration of vasopressor therapy, and 28-day mortality were secondary outcomes. Results. The change in SOFA score at day 7 showed a significant difference between GI and GII ( p < 0.001 ). The incidence of early VAP was significantly lower in GI ( p = 0.044 ). Vitamin C levels showed a significant rise in GI at day 1 and day 4 ( p < 0.001 and p < 0.001 , respectively). GPX activity of day 4 and day 7 was significantly higher in GI ( p = 0.005 and p = 0.014 , respectively). CRP levels of day 4 and day 7 were significantly higher in GII ( p < 0.001 and p < 0.001 , respectively). There was a significant difference in 28-day mortality ( p = 0.038 ) and duration of vasopressor therapy ( p = 0.033 ) in GI compared to GII. Conclusion. The early use of high-dose vitamin C intravenous infusion in patients with sepsis requiring mechanical ventilation in combination with the standard treatment for sepsis lowered the incidence of VAP, increased the antioxidant status, and improved the illness severity. Trial Registration. This trial is registered with ClinicalTrials.gov Identifier (NCT04029675).

The Outcome of IV Vitamin C Therapy in Patients with Sepsis or Septic Shock: A Meta-Analysis of Randomized Controlled Trials

“…Adverse effects of vitamin C were rare. Driny et al believed that vitamin C was safe, tolerable and would not cause patients withdraw from the study [35]. On the basis of this study, Fowler et al reported that different doses of vitamin C would not lead to any serious adverse events [7].…”

“…We acknowledge some limitations. First of all, 10 RCTs [16, 23,24,27,[29][30][31][34][35][36] were all single center studies with small sample size, which may result in selective bias or introduce small sample effect, so as to obtain a large bene cial therapeutic effect conclusion. Second, RCTs in this meta-analysis used different doses of vitamin C. Most RCTs administered 1.5 g vitamin C every 6 hours or 25 mg/kg every 6 hours, whereas other RCTs administered 50 mg/kg every 6 hours or 200 mg/kg daily.…”

“…11 studies were further removed during the assessment of the full text. Ultimately, 18 eligible RCTs [15][16][17][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36] enrolling 2980 patients were included in this meta-analysis. The PRISMA 2020 owchart of this study is presented in Fig.…”

“…7). Six studies reported IVVC level [16,26,31,33,35,36], and the vitamin C level was associated with a signi cantly increase (MD, 771; 95% CI, 155.47 to 642.43; p = 0.001; I 2 = 99%) (Fig. 8).…”

Potential Antioxidant Multitherapy against Complications Occurring in Sepsis

“…However, these results were based on analyses that did not consider multiple comparisons and should therefore be considered exploratory [ 6 ]. It has been reported that vitamin C reduces 28-day mortality and dosage and duration of norepinephrine in intermittent intervals [ 50 ], also reducing the risk of pulmonary morbidity and organ failure [ 51 ]. Lamontagne et al reported no statistical differences between placebo and supplemented group [ 50 ].…”