Novel serum biomarkers for predicting neurological outcomes in postcardiac arrest patients treated with targeted temperature management

Abstract

Objective To determine the clinical feasibility of novel serum biomarkers in out-of-hospital cardiac arrest (OHCA) patients treated with target temperature management (TTM). Methods This study was a prospective observational study conducted on OHCA patients who underwent TTM. We measured conventional biomarkers, neuron‑specific enolase and S100 calcium-binding protein (S-100B), as well as novel biomarkers, including tau protein, neurofilament light chain (NFL), glial fibrillary acidic protein (GFAP), and ubiquitin C-terminal hydrolase-L1 (UCH-L1), at 0, 24, 48, and 72 h after the return of spontaneous circulation identified by SIMOA immunoassay. The primary outcome was poor neurological outcome at 6 months after OHCA. Results A total of 100 patients were included in this study from August 2018 to May 2020. Among the included patients, 46 patients had good neurologic outcomes at 6 months after OHCA. All conventional and novel serum biomarkers had the ability to discriminate between the good and poor neurological outcome groups (p < 0.001). The area under the curves of the novel serum biomarkers were highest at 72 h after cardiac arrest (CA) (0.906 for Tau, 0.946 for NFL, 0.875 for GFAP, and 0.935 for UCH-L1). The NFL at 72 h after CA had the highest sensitivity (77.1%, 95% CI 59.9–89.6) in predicting poor neurological outcomes while maintaining 100% specificity. Conclusion Novel serum biomarkers reliably predicted poor neurological outcomes for patients with OHCA treated with TTM when life-sustaining therapy was not withdrawn. Cutoffs from two large existing studies (TTM and COMACARE substudy) were externally validated in our study. The predictive power of the novel biomarkers was the highest at 72 h after CA.

Developments in Post-Resuscitation Care for Out-of-Hospital Cardiac Arrests in Adults—A Narrative Review

“…It is reported that a 100% specificity for unfavorable neurological outcomes was achieved between 1 h [60] and up to 72 h [61][62][63] after ROSC. This bundle of prognostication can be extended by other biomarkers that are currently not recommended such as tau protein, neurofilament light chain, glial fibrillary acidic protein and ubiquitin C-terminal hydrolase-L1, which have recently been described to discriminate between favorable and unfavorable neurological outcomes [64].…”

Confounding factors in article stating that Ubiquitin C terminal hydrolase predicts poor neurological outcome after cardiac arrest

“…Song et al conclude that novel serum biomarkers predict poor neurological outcome after cardiac arrest (CA) with high accuracy [ 1 ]. Cutoffs from two large existing studies (TTM and COMACARE substudy) were externally validated in their study [ 1 ]. According to Song et al, the predictive power of novel biomarkers was the highest 72 h after CA [ 2 ].…”

“…In their analysis, the predictive performance of Ubiquitin C terminal hydrolase (UCHL) was seen in patients with poor outcome [ 1 ]; higher values of UCHL were observed in these patients [ 1 ]. Nearly half of critically ill patients—especially those with shock—had or developed acute kidney injury (AKI) and 20–25% needed renal replacement therapy (RRT) within the first week of hospitalization [ 2 ].…”

“…Nearly half of critically ill patients—especially those with shock—had or developed acute kidney injury (AKI) and 20–25% needed renal replacement therapy (RRT) within the first week of hospitalization [ 2 ]. In Song’s study, the out-of-hospital cardiac arrest (OHCA) group was very sick on admission with lactate between 6 and 9 mmol/L [ 1 ]. Therefore, we could make the assumption that 20–25% of these patients would require RRT or continuous RRT (CRRT).…”

“…New highly adsorptive membranes (HAMs) are able to adsorb molecules with molecular weights greater than 35 kDA, further increasing the removal of UCHL [ 5 ]. Not taking into account the effect of RRT and CRRT on UCHL can mislead evaluations and conclusions by artificially reducing the level of UHCL and underestimating its effects in each group (good versus poor neurological outcome) [ 1 ]. Nevertheless, only a study looking into UCHL clearance could precisely quantify the loss of it by RRT and the potential impact on the results of the study.…”