November 10, 2021

An article review from the ESICM Journal Review Club


Most unconscious patients after cardiac arrest do not fulfil guideline criteria for poor neurological outcome, and their prognosis is considered “indeterminate”. In this study, the authors compared brain injury markers in blood to predict good outcome and identify false positive predictions of poor outcome.

They retrospectively analysed prospectively collected serum samples at 24, 48 and 72 hours post-arrest within the target temperature management (TTM) trial from 717 patients.

The markers that were taken into consideration for this study were: NSE, S100B, NFL, total tau, UCH-L1, GFAP.

Normal levels of these markers were used to predict good outcome (defined as CPC scale 1-2) at 6 months after cardiac arrest.

The authors found that all examined markers had the potential to identify patients with good neurological outcome from 24 hours after cardiac arrest.
In addition, normal levels of NSE correctly identified one-third of good-outcome patients classified as indeterminate outcomes according to the ERC/ESICM algorithm.



• Prospective and multicenter design
• Large sample size
• Conservative protocol for neurological prognostication
• Strict criteria for withdrawal of life-sustaining therapy (WLST)
• Face-to-face evaluation of outcome and a priori cut-offs for brain injury markers
• Laboratory technicians blinded to clinical information
• Biomarker levels not available for clinical decision making


• A more conservative approach to WLST may have led to additional good outcomes
• Biomarker levels may be influenced by sepsis, trauma or other factors triggering the initial event
• All patients received a strict protocol of targeted temperature management to levels below 37°C and protocolised sedation for at least 36 hours which might not be applied in all ICUs.


In a large sample of patients, established and novel serum markers of brain injury predicted good neurological outcome as early as 24 hours after cardiac arrest. Thus, normal levels of these markers can be used to identify patients with limited neurological damage in which continuation of life support therapy can be lifesaving.

Unfortunately, routinary use is not common in most ICUs as many markers are only available for experimental settings. The use of these biomarkers should always be integrated with all other signs of prognostication as per ERC/ESICM guidelines.


This article review was prepared and submitted by Dr Annalisa Lerose, MD, Azienda Ospedaliero Universitaria Integrata di Verona, Italy on behalf of ESICM Journal Review Club.


Moseby-Knappe, M. et al. Serum markers of brain injury can predict good neurological outcome after out-of-hospital cardiac arrest. Intensive Care Med 47, 984–994 (2021).

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