SepsisThiamine deficiency in critically ill patients with sepsis☆,☆☆,★
Introduction
Thiamine is an essential component of cellular metabolism, and the lack of this vitamin results in a potentially life-threatening biochemical lesion [1], [2], [3], [4], [5]. Specifically, thiamine is a cofactor for pyruvate dehydrogenase, the enzyme responsible for the conversion of pyruvate into acetyl–coenzyme A (CoA). Lack of adequate thiamine results in the failure of pyruvate to enter the tricarboxylic acid cycle, thus preventing aerobic metabolism (Fig. 1). This biochemical lesion may lead to profound lactic acidosis (anaerobic metabolism), inability to create adenosine triphosphate, inability to use oxygen, high-output cardiac failure, cardiovascular collapse, and death when untreated (cardiac beriberi) [1], [4]. The prevalence of absolute thiamine deficiency (TD) in critically ill patients suffering from sepsis remains unknown, and the potential for relative TD remains unexplored. If absolute or relative TD was present in septic patients, the manifestations would be essentially indistinguishable from the underlying primary disease. Moreover, mitochondrial dysfunction has been well described in septic patients; however, absolute or relative TD has not been considered as a potential contributor to this injury pattern [6].
One retrospective investigation in an adult intensive care unit used an indirect measurement of TD (ie, erythrocyte transketolase), finding that those with decreased erythrocyte transketolase levels displayed increased mortality [7]. However, this investigation was retrospective and used an indirect measurement of thiamine; in addition, a correlation to known manifestations of TD (ie, lactic acidosis) was not evaluated. To date, no study has evaluated direct thiamine levels in critically ill patients with sepsis. Moreover, no previous investigation has evaluated the association of the continuum of thiamine levels regardless of absolute deficiency with clinical variables such as lactate (ie, the concept of relative TD).
The primary objective of the current study was to determine the prevalence of absolute TD in critically ill patients with sepsis. The secondary objective of the study was to determine the association between thiamine levels and lactic acidosis. We hypothesized that absolute TD would be prevalent in critically ill patients. Because thiamine is an essential cofactor for conversion of pyruvate to acetyl-CoA (aerobic metabolism), we further hypothesized that thiamine levels would be negatively associated with lactic acidosis. To test our hypotheses, we performed a prospective, observational study in which thiamine levels were measured in critically ill patients with septic shock.
Section snippets
Design
This was a prospective, observational study conducted at an urban tertiary care center with 50 000 emergency department visits per year and intensive care units with a total of approximately 50 beds. The study was approved by the institutional review board, and informed written consent was obtained.
Inclusion criteria
Inclusion criteria consisted of age greater than 18 years, suspected infection, and evidence of tissue hypoperfusion. Evidence of hypoperfusion was defined as lactic acid level greater than 4 mmol/L
Results
Thirty study patients and 30 control patients were enrolled between November 2006 and November 2007. The baseline demographics and laboratory values of the study population are represented in Table 1. Controls had mean age of 41 ± 22 years, were 50% female, and had a median thiamine level of 21 with an interquartile range of 16 to 25. None of the 30 controls (0/30, 0%) exhibited absolute TD. Of the 30 study patients, 24 required vasopressor support. Of the non–vasopressor-dependent group, 3 had
Discussion
We evaluated thiamine levels in critically ill patients with sepsis and found that a relatively high percentage presented with and/or developed TD within 72 hours of enrollment. Specifically, 10% of patients were deficient on presentation, with another 10% developing TD over the next 72 hours. Despite the findings of absolute TD, only 1 of 6 deficient patients received thiamine during their hospital course, indicating a lack of clinical recognition of this pathologic state. In addition to the
Limitations
The study is limited by several factors. First, the population of patients in this study may not reflect that of septic patients throughout all centers or other parts of the country. Our hospital is a tertiary care center that often admits patients with advanced disease processes that may be more likely to manifest nutritional deficiencies. We acknowledge that underlying comorbid disease may vary considerably between centers. Our sample size is small, and findings would need to be confirmed in
Conclusions
Absolute TD may be prevalent in critically ill septic patients and appears to be underrecognized when present. In the absence of liver dysfunction, lower thiamine levels are statistically significantly associated with higher lactic acid levels.
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Cited by (0)
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This project was funded from National Institutes of Health (NIH) grant P30 DK040561.
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This study was presented at the Society of Critical Care Medicine Meeting held in Nashville, TN (January 2009).
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Conflicts of interest/disclosures: This study was fully funded through the NIH (Grant P30 DK040561) and conceived/designed by the Principal Investigator (Michael Donnino). The NIH grant funded all of the thiamine assays that were run by Quest Diagnostics. Peter Chou is affiliated with Quest Diagnostics, and his contributions to the study consisted of oversight of the methods for running the thiamine assays and authoring said portions of the methods section of the manuscript. He had no involvement in the conception and execution of the study per se.