Abstract
Preliminary data have produced conflicting results regarding whether initial vitamin C levels in patients with severe sepsis correlate with mortality outcomes. We hypothesized that low plasma ascorbic acid or thiamine levels in severe sepsis patients admitted from the Emergency Department (ED) to the Intensive Care Unit (ICU) would be associated with increased mortality and an increased incidence of shock. Retrospective analysis of a prospective database of severe sepsis patients admitted to the ICU at an urban, academic medical center. Ascorbic acid and thiamine levels were analyzed in relation to survivors vs. non-survivors and shock vs. non-shock patients. 235 patients were included; mean age, 59.4 years ± 16.8 years; male, 128 (54.5%); in-hospital mortality, 16.6% (39/235); mean APACHE3 score, 61.8 ± 22.8; mean ascorbic acid level (reference range 0.40–2.10 mg/dL), 0.23 mg/dL (95% CI 0.07–4.02); and the mean thiamine level (reference range 14.6–29.5 nmol/L), 6.0 nmol/L (95% CI 4.0–9.5). When survivors were compared to non-survivors, survivors were more likely to be male (57.7% [113/196] vs. 38.5% [15/39]) and have lower APACHE3 scores (58.2 ± 22.6 vs. 79.9 ± 16.0). For the total cohort of 235 patients, there was no statistically significant relationship between a patient’s initial ascorbic acid or thiamine level and either survival or development of shock. In this analysis of early plasma samples from patients with severe sepsis admitted from the ED to the ICU, we found that mean ascorbic acid and thiamine levels were lower than normal range but that there was no relationship between these levels and outcomes, including 28 day mortality and development of shock.
Highlights
Sepsis, the syndrome of life-threatening dysregulated immune response to infectious pathogens, is both common and deadly[1,2]
No statistically significant relationship was found between thiamine levels, tertiles of vitamin C levels, survival in-hospital, at 28 days, 60 days, or 1 year or the development of shock in unadjusted (Table 5) and adjusted analyses. In this analysis of early plasma samples from critically ill patients with severe sepsis admitted to the medical ICU (MICU) from the Emergency Department (ED), we found that the mean vitamin C and thiamine levels were low but that there was no relationship between these initial plasma vitamin C or thiamine levels and outcomes, including mortality and the development of shock, in the total cohort
This is similar to other studies, which have demonstrated that vitamin C levels[36,37,38,39,40,41,42] and thiamine levels[28] are low in a significant percentage of critically ill patients
Summary
The syndrome of life-threatening dysregulated immune response to infectious pathogens, is both common and deadly[1,2]. In the CITRUS-ALI trial, there were no differences in the primary outcomes of change in organ dysfunction or markers of inflammation in septic Intensive Care Unit (ICU) patients with acute Thiamine, another essential micronutrient, is a necessary cofactor for the transfer of pyruvate, a breakdown product of glucose metabolism, into the Kreb’s cycle during aerobic metabolism to produce adenosine triphosphate (ATP). A randomized, double-blind trial of thiamine administration to septic shock patients demonstrated no difference in 24-h lactate levels, shock reversal, severity of illness, or m ortality[29]. These preliminary studies have produced conflicting results, they have generated enthusiasm about combining vitamin C, thiamine, and hydrocortisone, which is thought to be synergistic with these essential nutrients, as a low cost treatment for septic shock. The results of two additional studies yielded similar results: the ACTS trial, a randomized, double-blind trial of HAT, demonstrated no difference between the treatment group and p lacebo[32]; the VICTAS trial, the largest trial to date, enrolling 501 patients randomized to HAT vs. placebo, demonstrated no difference in vasopressor and ventilator free days or in-hospital mortality[33]
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