High-resolution plasma metabolomics and thiamine status in critically Ill adult patients.

INTRODUCTION: Thiamine (Vitamin B1) is an essential micronutrient and is classically considered a co-factor in energy metabolism. The association between thiamine status and whole-body metabolism in critical illness has not been studied. OBJECTIVES: To determine association between whole blood thiamine pyrophosphate (TPP) concentrations and plasma metabolites and connected metabolic pathways using high resolution metabolomics (HRM) in critically ill patients. METHODS: Cross-sectional study performed at Erciyes University Hospital, Kayseri, Turkey and Emory University, Atlanta, GA, USA. Participants were critically ill adults with an expected length of intensive care unit stay longer than 48 h and receiving chronic furosemide therapy. A total of 76 participants were included. Mean age was 69 years (range 33-92 years); 65% were female. Blood for TPP and metabolomics was obtained on the day of ICU admission. Whole blood TPP was measured by HPLC and plasma HRM was performed using liquid chromatography/mass spectrometry. Data was analyzed using regression analysis of TPP levels against all plasma metabolomic features in metabolome-wide association studies (MWAS). MWAS using the highest and lowest TPP concentration tertiles was performed as a secondary analysis. RESULTS: Specific metabolic pathways associated with whole blood TPP levels in regression and tertile analysis included pentose phosphate, fructose and mannose, branched chain amino acid, arginine and proline, linoleate, and butanoate pathways. CONCLUSIONS: Plasma HRM revealed that thiamine status, determined by whole blood TPP concentrations, was significantly associated with metabolites and metabolic pathways related to metabolism of energy, carbohydrates, amino acids, lipids, and the gut microbiome in adult critically ill patients.

High-Resolution Plasma Metabolomics and Thiamine Status in Critically Ill Adult Patients.

Background and Aim: Thiamine (Vitamin B1) is an essential micronutrient and a co-factor for metabolic functions related to energy metabolism. We determined the association between whole blood thiamine pyrophosphate (TPP) concentrations and plasma metabolites using high resolution metabolomics in critically ill patients. Methods: Cross-sectional study performed in Erciyes University Hospital, Kayseri, Turkey and Emory University, Atlanta, GA, USA. Participants were ≥ 18 years of age, with an expected length of ICU stay longer than 48 hours, receiving furosemide therapy for at least 6 months before ICU admission. Results: Blood for TPP and metabolomics was obtained on the day of ICU admission. Whole blood TPP concentrations were measured using high-performance liquid chromatography (HPLC). Liquid chromatography/mass spectrometry was used for plasma high-resolution metabolomics. Data was analyzed using regression analysis of TPP levels against all plasma metabolomic features in metabolome-wide association studies. We also compared metabolomic features from patients in the highest TPP concentration tertile to patients in the lowest TPP tertile as a secondary analysis. We enrolled 76 participants with a median age of 69 (range, 62.5-79.5) years. Specific metabolic pathways associated with whole blood TPP levels, using both regression and tertile analysis, included pentose phosphate, fructose and mannose, branched chain amino acid, arginine and proline, linoleate, and butanoate pathways. Conclusions: Plasma high-resolution metabolomics analysis showed that whole blood TPP concentrations are significantly associated with metabolites and metabolic pathways linked to the metabolism of energy, amino acids, lipids, and the gut microbiome in adult critically ill patients.

Evaluation of whole blood thiamine pyrophosphate concentrations in critically ill patients receiving chronic diuretic therapy prior to admission to Turkish intensive care units: A pragmatic, multicenter, prospective study.

BACKGROUND/OBJECTIVES: Thiamine plays a pivotal role in energy metabolism. The aim of the study was to determine serial whole blood TPP concentrations in critically ill patients receiving chronic diuretic treatment before ICU admission and to correlate TPP levels with clinically determined serum phosphorus concentrations. SUBJECTS/METHODS: This observational study was performed in 15 medical ICUs. Serial whole blood TPP concentrations were measured by HPLC at baseline and at days 2, 5 and 10 after ICU admission. RESULTS: A total of 221 participants were included. Of these, 18% demonstrated low TPP concentrations upon admission to the ICU, while 26% of participants demonstrated low levels at some point during the 10-day study period. Hypophosphatemia was detected in 30% of participants at some point during the 10-day period of observation. TPP levels were significantly and positively correlated with serum phosphorus levels at each time point (P < 0.05 for all). CONCLUSIONS: Our results show that 18% of these critically ill patients exhibited low whole blood TPP concentrations on ICU admission and 26% had low levels during the initial 10 ICU days, respectively. The modest correlation between TPP and phosphorus concentrations suggests a possible association due to a refeeding effect in ICU patients requiring chronic diuretic therapy.