Abstract
ObjectiveNeurological outcome prediction is crucial early after cardiac arrest. Serum biomarkers released from brain cells after hypoxic-ischaemic injury may aid in outcome prediction. The only serum biomarker presently recommended in the European Resuscitation Council prognostication guidelines is neuron-specific enolase (NSE), but NSE has limitations. In this study, we therefore analyzed the outcome predictive accuracy of the serum biomarkers glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase-L1 (UCH-L1) in patients after cardiac arrest. MethodsSerum GFAP and UCH-L1 were collected at 24, 48 and 72 h after cardiac arrest. The primary outcome was neurological function at 6-month follow-up assessed by the cerebral performance category scale (CPC), dichotomized into good (CPC1-2) and poor (CPC3-5). Prognostic accuracies were tested with receiver-operating characteristics by calculating the area under the receiver-operating curve (AUROC) and compared to the AUROC of NSE. Results717 patients were included in the study. GFAP and UCH-L1 discriminated between good and poor neurological outcome at all time-points when used alone (AUROC GFAP 0.88–0.89; UCH-L1 0.85–0.87) or in combination (AUROC 0.90–0.91). The combined model was superior to GFAP and UCH-L1 separately and NSE (AUROC 0.75–0.85) at all time-points. At specificities ≥95%, the combined model predicted poor outcome with a higher sensitivity than NSE at 24 h and with similar sensitivities at 48 and 72 h. ConclusionGFAP and UCH-L1 predicted poor neurological outcome with high accuracy. Their combination may be of special interest for early prognostication after cardiac arrest where it performed significantly better than the currently recommended biomarker NSE.
Highlights
An estimated 56 individuals per 100,000 are treated by emergency medical services for out-of-hospital cardiac arrest annually across European countries.[1]
The combined model was superior to glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase-L1 (UCH-L1) separately and neuron-specific enolase (NSE) (AUROC 0.75À0.85) at all time-points
GFAP and UCH-L1 predicted poor neurological outcome with high accuracy. Their combination may be of special interest for early prognostication after cardiac arrest where it performed significantly better than the currently recommended biomarker NSE
Summary
An estimated 56 individuals per 100,000 are treated by emergency medical services for out-of-hospital cardiac arrest annually across European countries.[1] Similar statistics apply to the United States, Australia and New Zealand.[2,3] Successfully resuscitated patients frequently suffer from hypoxic-ischaemic brain injury which continues to be the principal cause of adverse outcome and death in this group of patients after admission to intensive care.[4] Death often follows withdrawal of life sustaining therapy (WLST), guided by ethical principles due to presumed poor prognosis.[5] In order to minimize the risk of erroneous pessimistic prognoses, the European Resuscitation Council (ERC) and the European Society of Intensive Care Medicine (ESICM) recommend a multimodal prognostication model including the serum biomarker of brain injury neuron-specific enolase (NSE).[6] Several other serum biomarkers, e.g., S100 calcium-binding protein (S100), tau protein and neurofilament light chain (NFL), have recently been investigated as prognostic markers after hypoxic-ischaemic brain injury following cardiac arrest, but only NSE is recommended in the ERC/ESICM algorithm and as a part of a multimodal approach.6À10
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