Abstract 207: Soluble Urokinase-Type Plasminogen Activator Receptor in Comatose Survivors After Out-of-Hospital Cardiac Arrest Treated With Targeted Temperature Management

Abstract

Introduction: Exposure to whole-body ischemia/reperfusion after out-of-hospital cardiac arrest (OHCA) triggers a systemic inflammatory response where soluble urokinase plasminogen activator receptor (suPAR) is released. Aims: This study investigated serial levels of suPAR in patients treated with differentiated target temperature management (TTM) and the associations with mortality and neurological outcome. Methods: In this single center sub-study of the randomized Targeted Temperature Management for 24 vs 48h (TTH-trial), we included 82 patients and measured serial levels of suPAR at 24, 48 and 72 h. We assessed all-cause mortality and neurological function evaluated by the Cerebral Performance Categories at six months after OHCA. Levels of suPAR between TTH groups were evaluated in repeated measures mixed models. Mortality was assessed by the Kaplan-Meier method. Good neurological outcome at six months was assessed by logistic regression analyses. The predictive value of suPAR was evaluated with the area under the receiver operating characteristic (ROC) curve. Results: Levels of suPAR were significantly different between TTH-groups (p interaction =0.04) with the highest difference at 48h, 4.7 ng/mL (95%CI: 4.1-5.4 ng/mL) in the TTH24 group compared to 2.8 ng/mL (95%CI: 2.2-3.5 ng/mL) in the TTH48 group, p<0.0001. Levels of suPAR above the median value (2.6 ng/mL) was significantly associated with increased all-cause mortality at any timepoint (p log-rank <0.05). The interaction of suPAR levels and TTH group was not significant (p interaction =NS). A two-fold increase in levels of suPAR were significantly associated with a decreased odds ratio of a good neurological outcome in both unadjusted and adjusted analyses without interaction of TTH group (p interaction =NS). AUC at 24h was 0.78 (95%CI: 0.67-88, p<0.0001). The optimal cutoff value for suPAR in predicting 180 mortality was 2.6 ng/mL (sensitivity: 0.75, specificity: 0.63). Conclusion: Prolonged TTM of 48 hours vs. 24 hours was associated with lower levels of suPAR. High levels of suPAR were associated with increased mortality and lower odds for good neurological outcome at six months with no significant interaction of TTH group. The biomarker suPAR was a modest predictor of outcome.