Thiamine Deficiency Underrecognized in Sepsis Patients

NASHVILLE—Thiamine deficiency may be prevalent in critically ill patients with sepsis, according to research presented at the Society of Critical Care Medicine’s 2009 Critical Care Congress. In addition, low thiamine levels were found to be associated with high lactic acid levels when accounting for liver injury as a confounder, reported Dr. Michael W. Donnino, MD, of the Emergency and Critical Care Medicine department at the Beth Israel Deaconess Medical Center.

“Without thiamine, anaerobic metabolism predominates, adenosine triphosphate cannot be generated, lactic acid builds up, and tissue hypoxia ensues—all of which leads to cardiovascular collapse or death,” he explained. “Septic shock also may be characterized by a buildup of pyruvate and lactic acidosis. However, whether patients with septic shock display overt or subclinical thiamine deficiency remains unknown.”

SUSPECTED INFECTION EVALUATED

In a prospective, observational, nonintervention study, Dr. Donnino and colleagues measured plasma thiamine levels in critically ill patients from a tertiary medical center and evaluated potential links between thiamine and lactic acid.

Patients met criteria of inclusion if they were 18 years and older, were suspected of an infection, and had evidence of tissue hypoperfusion (ie, lactic acid level > 3 mmol/dL or systolic blood pressure < 90 mm Hg requiring vasopressor support). Absolute thiamine deficiency was determined using previously established laboratory values (< 9 nmol/L).

LIVER ENZYMES A POSSIBLE CONFOUNDER

A total of 30 patients were enrolled in the study. Three patients had absolute thiamine deficiency upon admission and an additional three patients within the first 72 hours, for an overall absolute thiamine deficiency rate of 20%. None of the 30 healthy control patients had thiamine deficiency, Dr. Donnino noted. Age, sex, laboratory values, and white blood cell count were similar between thiamine-deficient patients and those who were not. “For unclear reasons, the thiamine-deficient group had slightly lower statistically significant potassium than nondeficient patients,” Dr. Donnino noted. Sources of infection were similar between each group, with pneumonia and urinary tract infections affecting 33% and 17%, respectively, of all sepsis patients.

Initially, Dr. Donnino and colleagues did not identify a negative correlation between thiamine and lactic acid levels. However, one patient with a bone marrow malignancy who had severe liver failure during his septic episode had thiamine levels approximately four times higher than the norm. This observation prompted the researchers to investigate further and eventually identify a link between high liver enzyme levels and high thiamine levels. After adjustment for age, sex, and comorbid disease, and exclusion of patients with liver dysfunction, there was a strong statistically significant negative correlation between thiamine and lactic acidosis levels in thiamine-deficient patients with normal liver function.

To further assess changes in thiamine levels over time in critically ill patients, the investigators conducted a separate analysis evaluating changes in thiamine levels in patients before and after undergoing coronary artery bypass surgery. “There was a statistically significant decrease in thiamine level overall and in almost every patient,” Dr. Donnino noted. “We concluded that thiamine levels do indeed decrease over time with a stressor. They were still significantly lower at 24 hours.”

THIAMINE ADMINISTRATION AS A TREATMENT OPTION

According to Dr. Donnino, the potentially skewed study population of a tertiary care center was a limitation to this study. Whether thiamine could be used as a metabolic resuscitator in septic shock patients warrants further research, as does the potential link between thiamine levels and liver function, Dr. Donnino added.

—Frederique H. Theuvenin

Suggested Reading
Donnino M. Gastrointestinal beriberi: a previously unrecgonized syndrome. Ann Intern Med. 2004;141(11):898-899.

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