The association of the plasma iron and neuron-specific enolase combination and the 28-day neurological outcome after cardiopulmonary resuscitation: a prospective study of iron metabolism disturbances

<b>BACKGROUND:</b> 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. <b>METHODS:</b> 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. <b>RESULTS:</b> 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 (<i>P</i><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 [<i>OR</i>] 0.607, 95% confidence interval [<i>CI</i>] 0.455-0.808) and an NSE concentration ≥20.5 ng/mL (<i>OR</i> 1.020, 95% <i>CI</i> 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%). <b>CONCLUSION:</b> 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.