Baseline measurements of cellular respiration affect the response to thiamine treatment in post-arrest patients.

Abstract

Thiamine (vitamin B1) is an essential cofactor in mitochondrial oxidative metabolism. Recent trials evaluating thiamine as a metabolic resuscitator in post-cardiac arrest patients have shown variable results, possibly due to differences in baseline mitochondrial function. We hypothesized that baseline mitochondrial respiration predicts a greater response to thiamine supplementation. This is a post hoc analysis of two randomized trials of thiamine administration in cardiac arrest patients (THICA, THACA). Mitochondrial function was assessed in peripheral blood mononuclear cells (PBMCs) using the Seahorse XF Analyzer to measure oxygen consumption rates (OCRs). Patients were stratified above or below the cohort median for each OCR variable. The primary outcome was change in lactate over 24 h. Seventy-four patients (40 thiamine vs. 34 placebo) had baseline OCR measurements and were included in the analysis. In the overall cohort, thiamine did not significantly reduce lactate compared to placebo (geometric mean ratio [GMR] = 0.83; 95% CI 0.64-1.09; p = 0.19). However, among patients with maximal or spare respiration above the median, thiamine treatment was associated with significantly lower lactate levels at 24 h (GMR = 0.61; 95% CI 0.44-0.83; p = 0.003 and GMR = 0.53; 95% CI 0.38-0.75; p < 0.001, respectively). Thiamine supplementation was associated with reduced lactate in patients with preserved mitochondrial functional reserve. Baseline mitochondrial respiration may serve as a biomarker to identify critically ill patients most likely to benefit from metabolic resuscitation therapies.