Burnout and Biological Biomarkers in Emergency and Acute-Care Healthcare Workers: A Systematic Scoping Review with Evidence Mapping

<i>Background and Objectives</i>: Burnout is highly prevalent among emergency and acute care healthcare workers (HCWs), yet biological correlates remain debated because candidate biomarkers are strongly shaped by circadian timing, shift work, sleep loss, and overlapping affective symptoms. We mapped post-2018 evidence of biological biomarkers assessed alongside validated burnout measures in emergency department (ED), emergency medical services (EMS), and related acute care settings. Specifically, we asked whether reproducible biological correlates of burnout can be identified in emergency and acute-care healthcare workers when biomarker endpoint class and sampling context are systematically considered. <i>Materials and Methods</i>: We conducted a systematic scoping review with evidence mapping (PRISMA-ScR). PubMed/MEDLINE and the MDPI platform were searched for English-language studies published from 2018 onward (through January 2026). Eligible quantitative studies enrolled ED/EMS or acute care HCWs, assessed burnout using validated instruments, and reported at least one biological biomarker. Evidence was charted by biomarker domain and endpoint class (basal measures, stress reactivity paradigms, and chronic indices such as hair-based markers). <i>Results</i>: Overall, 19 studies were included in mapping/synthesis. Biomarker selection clustered around the hypothalamic-pituitary-adrenal axis (cortisol; n = 10/19), with fewer studies focused on autonomic function (heart rate variability; n = 2/19) and immune-inflammatory markers (n = 2/19), and single-study coverage for oxidative stress (n = 1/19), cardiometabolic candidates (n = 1/19), cellular aging (n = 1/19), neuroglial/multi-system candidates (n = 1/19), and feasibility-oriented multi-marker designs (n = 1/19). Reported associations with burnout were heterogeneous in direction and magnitude, but were more interpretable when endpoint class, timing anchors, and shift/sleep-related covariates were explicitly reported. Rates of confounder adjustment were low across studies (e.g., only 3/19 reported multivariable adjustment, and none systematically measured sleep or circadian factors), substantially limiting interpretability. <i>Conclusions</i>: The 2018+ literature does not support a single reproducible biomarker for burnout in emergency and acute care workforces. Evidence instead suggests multi-system dysregulation that is highly sensitive to endpoint class, sampling timing, and contextual confounding. Future studies should prioritize timing-anchored repeated-measures protocols across shift and recovery windows, jointly model sleep/circadian factors and depressive symptoms, and evaluate multi-marker panels and intervention responsiveness.