Metabolomic profiling using 1H NMR spectroscopy in emergency department patients with sepsis: association with SOFA severity scores and in-hospital mortality. A prospective observational study

Metabolomics offers mechanistic insights into the pathophysiology of sepsis and may complement conventional severity scoring. This prospective study evaluated the serum metabolomic profile of patients with sepsis presenting to the Emergency Department (ED) and its relationship with Sequential Organ Failure Assessment (SOFA) scores and in-hospital mortality. One hundred and fifty-five adults (≥18 years) meeting Sepsis-3 criteria were enrolled consecutively from a tertiary care ED between July 2023 and July 2024. Serum samples were collected at two standardised time points: admission (T1, 0 h) and 72 hours (T2). Samples were analysed using 1H NMR spectroscopy on an 800 MHz Bruker Avance III spectrometer. SOFA scores were recorded at T1 and T2. The primary outcome was in-hospital mortality. Associations between metabolites, SOFA scores, and mortality were examined using univariable non-parametric tests, Spearman correlation, and a parsimonious multivariable logistic regression model. All metabolite p-values are exploratory given the absence of formal multiplicity correction. Of 155 patients, 98 had sepsis and 57 had septic shock; 38 (24.5%) died in hospital. Baseline characteristics did not differ significantly between survivors and non-survivors. At T2, non-survivors had significantly lower levels of methanol (10.6 vs 18.1 µM, p=0.02), mannose (52.6 vs 72.1 µM, p=0.044), isoleucine (p=0.015), leucine (p=0.027), and valine (p=0.02), and higher pyruvate (56.2 vs 27.4 µM, p=0.011). No significant metabolite differences were observed at T1. SOFA score was associated with in-hospital mortality (OR 1.36, 95% CI 1.06–1.74, p=0.017; AUC 0.70, 95% CI 0.55–0.84). Distinct metabolic alterations at 72 hours — but not at ED admission — particularly in branched-chain amino acids, mannose, methanol, and pyruvate, were associated with in-hospital mortality in sepsis patients. These findings suggest that early metabolic trajectories may complement ongoing risk stratification after initial ED resuscitation, but require validation in larger, multicentre cohorts before clinical translation.