New inflammatory biomarker as a predictor of poor neurological outcome early after out-of-hospital cardiac arrest

Background

Neurological prognosis after out-of-hospital cardiac arrest (OHCA) remains a major clinical challenge. New early biomarkers are needed to accurate neuroprognostication. There is an early systemic inflammatory response which may contribute to secondary brain injury and impact on neurological outcome.

Objective

To evaluate neurological outcome prediction accuracy of inflammatory indices derived from biomarkers and blood cell counts early after OHCA.

Methods

This prospective study included consecutive patients with OHCA treated between 2019 and 2025. Neurological outcome at hospital discharge was assessed using the Cerebral Performance Category (CPC) scale, defining good neurological outcome (GNO) as CPC 1–2 and poor neurological outcome (PNO) as CPC 3–5.

Basic and cardiac arrest characteristics and lab test results at arrival and 24 hours were compared across groups. Odds ratio (OR) for PNO of biologically plausible inflammatory biomarkers such as IL-6, and neutrophil-to-lymphocyte (NLR24h) and IL-6/Ly24h ratios, were explored. Discriminative ability of the best new biomarkers to predict PNO whereas assessed using receiver operating characteristic (ROC) curves.

Results

A total of 173 patients were included; 83 (48%) had PNO and 90 (52%) GNO. No significant differences were observed in main baseline characteristics. Patients with PNO had less shockable first rhythm (55 [66%] vs 79 [89%]; p=0.001) and longer time to return of spontaneous circulation (ROSC) (32 [24-49] vs. 20 [14-27]; p<0.001).

In laboratory results, pH (7.10 [6.90–7.18] vs. 7.19 [7.06–7.26]; p<0.001) and Ly24h (1000 [700–1500] vs. 1300 [990–1700]; p=0.004) were lower in PNO, whereas lactate (66 [40–90] vs. 42 [22–64]; p<0.001), IL-6 (265 [179–566] vs. 138 [74–255]; p=0.001), NLR24h (12 [8-18] vs. 8.6 [5.6–13.3]; p<0.001), and C-reactive protein (CRP)/Ly24h (0.005 [0.003–0.009] vs. 0.003 [0.002–0.006]; p=0.005) were higher. CRP (5.4 [3.2-8.9] vs. 4.4 [2.2-7.7]; p=0.09) and neutrophil count at 24h (12300 [8400-16300] vs. 10810 [8270-11758]; p=0.15) were non-significantly higher in PNO patients (Table 1A).

Each decrease in Ly24h (OR 0.999 [0.998-0.999]; p=0.017) and each increase of IL-6 (OR 1.002 [1.000–1.004], p=0.021), NLR24h (OR 1.084 [1.031-1.138], p=0.001), IL-6/Ly24h (12.839 [2.654-62.100], p=0.002) ratios were associated with a higher probability of PNO (Table 1B).

After adjustment for ROSC, witnessed arrest, admission lactate, sex, age, and initial rhythm, IL-6/Ly24h remained independently associated with PNO (adjusted OR 14.35 [2.26–91.12]; p=0.005). ROC analysis showed an area under the curve (AUC) of 0.85 [0.76–0.93], outperforming IL-6 (0.69 [0.58–0.81]) and unadjusted IL-6/Ly24h (0.77 [0.68–0.87]).

Conclusions

In a prospective cohort of patients with OHCA, IL-6/Ly24h was independently associated with PNO. This biomarker integrates persistent systemic inflammation and early immune dysregulation and may complement traditional prognostic models.