Abstract
BACKGROUND: Iron metabolism dyshomeostasis is associated with ferroptosis and ischemia-reperfusion injury. We aim to investigate post-cardiac arrest changes in plasma iron metabolism-related parameters and their prognostic value for 28-day neurological outcomes. METHODS: In this prospective observational cohort study, plasma iron metabolism-related parameters (iron, ferritin, hepcidin, soluble transferrin receptor [sTfR], total iron binding capacity [TIBC], and transferrin saturation), interleukin-6, and neuron-specific enolase (NSE) were assessed in 120 patients after restoration of spontaneous circulation (ROSC) on days 1 and 3 of intensive care unit (ICU) admission and in 40 healthy controls. The primary outcome was poor 28-day neurological prognosis. RESULTS: Compared to controls, post-ROSC patients exhibited significant plasma iron metabolism disturbances, including decreased iron, TIBC, transferrin saturation, with elevated hepcidin, ferritin, sTfR, interleukin-6, and NSE on day 1 after ICU admission (P<0.05 for all). On day 28 post-ROSC, patients with poor neurological outcomes (71/120) presented more pronounced alterations than those with good neurological outcomes. Binary logistic analysis revealed that a plasma iron concentration ≤11.2 µmol/L (odds ratio [OR] 0.607, 95% confidence interval [CI] 0.455-0.808) and an NSE concentration ≥20.5 ng/mL (OR 1.020, 95% CI 1.005-1.035) on day 1 of ICU admission were associated with 28-day poor neurological outcomes. The plasma iron-NSE combination showed better predictive performance (area under the curve=0.935, sensitivity 89.8%, specificity 84.5%). CONCLUSION: Early post-ROSC plasma iron metabolism disturbances combined with NSE elevation were associated with the 28-day neurological prognosis, suggesting the therapeutic potential of targeting the iron metabolism pathway.