Direct and indirect associations of stress hyperglycemia with delirium in older adults with community-acquired pneumonia: limited mediation by neutrophil-lymphocyte ratio and procalcitonin

Stress hyperglycaemia is common among older adults hospitalised with community-acquired pneumonia (CAP) and is associated with delirium; however, the underlying inflammatory pathways remain unclear. We investigated whether the neutrophil-to-lymphocyte ratio (NLR) and procalcitonin (PCT) mediate the relation between the stress-hyperglycaemia ratio (SHR) and delirium. This single-centre retrospective cohort included 412 patients aged ≥ 65 years admitted for CAP. Delirium was assessed daily with the Confusion Assessment Method. Logistic regression models yielded odds ratios (ORs) for delirium, whereas linear regression models for NLR and PCT provided standardised beta coefficients (β_std). All continuous variables (SHR, NLR and PCT) were z-scored prior to mediation analysis. Delirium developed in 99 patients (24.0%). After adjustment for age, sex and comorbidities, SHR (OR = 9.13, 95% CI 4.44–18.96), NLR (OR = 1.12 per unit, 95% CI 1.06–1.19) and PCT (OR = 1.14 per ng/mL, 95% CI 1.06–1.21) were independent predictors of delirium. The total standardised effect of SHR on delirium was β_std = 0.321, of which 80.6% was direct (β_std = 0.259, 95% CI 0.149–0.427). The NLR-mediated pathway accounted for 19.4% of the association (β_std = 0.062, 95% CI 0.024–0.107). Pathways involving PCT—alone or in sequence with NLR—were not significant. In older CAP patients, stress hyperglycaemia substantially elevates delirium risk, predominantly through a direct mechanism only partly (≈ 20%) mediated by systemic inflammation reflected by NLR. Prompt detection and management of acute hyperglycaemia may therefore offer a practical approach to delirium prevention. Prospective multicentre studies are needed to confirm causality and to test glucose- and inflammation-modulating interventions.