Additive Impact of Interleukin 6 and Neuron Specific Enolase for Prognosis in Patients With Out-of-Hospital Cardiac Arrest - Experience From the HAnnover COoling REgistry

Abstract

Background: Patients after out-of-hospital cardiac arrest (OHCA) are at increased risk for mortality and poor neurological outcome. We assessed the additive impact of interleukin 6 (IL-6) at admission to neuron-specific enolase (NSE) at day 3 for prognosis of 30-day mortality and long-term neurological outcome in OHCA patients.

Methods: A total of 217 patients from the HAnnover COoling REgistry with return of spontaneous circulation (ROSC) after OHCA and IL-6 measurement immediately after admission during 2017-2020 were included to investigate the prognostic value and importance of IL-6 in addition to NSE obtained on day 3. Poor neurological outcome was defined by cerebral performance category (CPC) ≥ 3 after 6 months.

Results: Patients with poor outcome showed higher IL-6 values (30-day mortality: 2,224 ± 524 ng/l vs 186 ± 15 ng/l, p < 0.001; CPC ≥ 3 at 6 months: 1,440 ± 331 ng/l vs 180 ± 24 ng/l, p < 0.001). IL-6 was an independent predictor of mortality (HR = 1.013/ng/l; 95% CI 1.007-1.019; p < 0.001) and poor neurological outcome (HR = 1.004/ng/l; 95% CI 1.001-1.007; p = 0.036). In ROC-analysis, AUC for IL-6 was 0.98 (95% CI 0.96-0.99) for mortality, but only 0.76 (95% CI 0.68-0.84) for poor neurological outcome. The determined cut-off value for IL-6 was 431 ng/l for mortality (NPV 89.2%). In patients with IL-6 > 431 ng/l, the combination with NSE < 46 μg/l optimally identified those individuals with potential for good neurological outcome (CPC ≤ 2).

Conclusion: Elevated IL-6 levels at admission after ROSC were closely associated with 30-day mortality. The combination of IL-6 and NSE provided clinically important additive information for predict poor neurological outcome at 6 months.

Keywords: interleukin 6; neurological outcome; neuron-specific enolase; out-of-hospital cardiac arrest; prognosis.

FIGURE 1

Distribution of interleukin 6 according to 30-day survival (A) for survivors and non-survivors and according to neurological outcome (B) for patients with good (CPC ≤ 2) and poor outcome (CPC ≥ 3), respectively. For both p was < 0.05.

FIGURE 2

Survival proportions of interleukin 6 according to quartiles of HACORE population. p was < 0.0001 in log-rank test.

FIGURE 3

ROC curves for NSE and IL-6 for 30-day survival (A) and poor neurological outcome (B). For both p was < 0.001.

FIGURE 4

Survival proportions of combined determined cut-off values for mortality for IL-6 and NSE. p was < 0.0001 in log-rank test.

FIGURE 5

Neurological outcome according to CPC class in the corresponding groups depending to the determined cut-off values for mortality without patients dying during the first 3 days.