Abstract

Introduction: As early as 3h after cardiac arrest (CA), the blood level of various cytokines increases and may be associated with outcome of post cardiac arrest syndrome (PCAS). However, it remains uncertain whether blood levels of these cytokines including IL-6 have significance as predictors of outcome following cardiac arrest. Objective: To demonstrate any association between circulating IL-6 level, one of major pro-inflammatory cytokines, and mortality in PCAS of humans. Methods: This was a multicenter observational study conducted between 2006-09 in Chiba, Japan, involving non-trauma CA adult patients. All patients admitted to acute care units were included. Patient characteristics were extracted following an Utstein template. The primary outcome was mortality through the end of the study. IL-6 blood levels were measured on admission, at 6hr, and 24hr after CA. Patients were classified into three groups (high, middle, and low) according to IL-6 levels at each time point. We evaluated the association of IL-6 levels with survival using the Kaplan-Meier method. A Cox proportional hazard model with a step-wise selection procedure was used to identify independent variables associated with overall survival. Results: A total of 227 patients were included in this study. Survival time in “High IL-6” group was shorter than “Low” group. There were significant differences in blood level of IL-6 in the three groups, high (>811pg/mL), mid (811-93pg/mL), and low (<93pg/mL), only at 6hr (long rank; high vs. low p<0.001, high vs. mid p=0.07, and mid vs. low p=0.001 on admission; p<0.001, p<0.001, and p<0.001 at 6hr, respectively; p<0.001, p<0.001, and p=0.936 at 24hr, respectively). Three factors were identified as independent predictors of early death; no bystander CPR (hazard ratio [95% confidential interval], 2.59 [1.10-6.10], p=0.03), a lack of therapeutic hypothermia (2.68 [1.70-4.22], p<0.001), and IL-6 levels at 6hr (high, reference; mid, 0.41 [0.25-0.66], p<0.001; low, 0.11 [0.06-0.20], p<0.001). Conclusions: IL-6 measured at 6hr can predict mortality. It should be studied further to see if it can help direct therapeutic decision-making and whether it can define optimal populations for study in clinical trials.

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