Serum markers of brain injury can predict good neurological outcome after out-of-hospital cardiac arrest

Abstract

Purpose The majority of unconscious patients after cardiac arrest (CA) do not fulfill guideline criteria for a likely poor outcome, their prognosis is considered “indeterminate”. We compared brain injury markers in blood for prediction of good outcome and for identifying false positive predictions of poor outcome as recommended by guidelines. Methods Retrospective analysis of prospectively collected serum samples at 24, 48 and 72 h post arrest within the Target Temperature Management after out-of-hospital cardiac arrest (TTM)-trial. Clinically available markers neuron-specific enolase (NSE) and S100B, and novel markers neurofilament light chain (NFL), total tau, ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) and glial fibrillary acidic protein (GFAP) were analysed. Normal levels with a priori cutoffs specified by reference laboratories or defined from literature were used to predict good outcome (no to moderate disability, Cerebral Performance Category scale 1–2) at 6 months. Results Seven hundred and seventeen patients were included. Normal NFL, tau and GFAP had the highest sensitivities (97.2–98% of poor outcome patients had abnormal serum levels) and NPV (normal levels predicted good outcome in 87–95% of patients). Normal S100B and NSE predicted good outcome with NPV 76–82.2%. Normal NSE correctly identified 67/190 (35.3%) patients with good outcome among those classified as “indeterminate outcome” by guidelines. Five patients with single pathological prognostic findings despite normal biomarkers had good outcome. Conclusion Low levels of brain injury markers in blood are associated with good neurological outcome after CA. Incorporating biomarkers into neuroprognostication may help prevent premature withdrawal of life-sustaining therapy. Supplementary Information The online version contains supplementary material available at 10.1007/s00134-021-06481-4.

GFAp and tau protein as predictors of neurological outcome after out-of-hospital cardiac arrest: A post hoc analysis of the COMACARE trial

“…[47] The high performance of NfL was also noted in the TTM trial cohort. [48,49] Currently, a clinically validated highly sensitive method exists for Nfl in a handful of countries, whereas such is not available for GFAp and tau. [50] For GFAp, however, the point-ofcare testing has been approved for research purposes (through Abbott i-STAT).…”

Brain injury after cardiac arrest: pathophysiology, treatment, and prognosis

“…A limited number of studies, using the highly sensitive SIMOA-technology, indicate that NFL has superior prognostic performance compared to the other biomarkers [ 107 – 109 ] and also to other available methods [ 108 ]. In a recent study [ 110 ] investigating the ability of six biomarkers to predict good neurological outcome after arrest, NFL was the most consistent predictor, having the second best sensitivity and specificity. While NFL is gradually being introduced into clinical practice for other diagnoses, much development and validation is necessary before it can become a standard assay for PCABI.…”

“…Two or more concordant unfavourable test results are required to prognosticate poor neurological outcome, while in case of discordance between tests indicating poor prognosis and others indicating good prognosis, a prognostic reassessment is recommended. Signs indicating a potentially good outcome include: an early (within 24 h) return of favourable EEG background (continuous, reactive, and without epileptiform activity) [ 124 , 125 ], low blood levels of NSE within 72 h from ROSC [ 105 , 110 ], and absence of diffusion changes on brain MRI.…”

“…The ERC-ESICM 2021 guidelines suggests caution and reassessment when predictors of poor outcome coexist with signs indicating a potential for recovery. These signs include a ‘benign’ EEG (continuous, reactive, non-suppressed background without epileptiform discharges), absence of diffusion changes on brain MRI and low blood values of biomarkers [ 110 , 112 , 144 ]. However, there are no currently recommended strategies to predict good neurological outcome after cardiac arrest.…”

Can serum markers of brain injury predict neurological outcome after out-of-hospital cardiac arrest? Author’s reply

“…We investigated whether levels of brain injury markers could be used to predict good neurological outcome according to the Cerebral Performance Category Scale (CPC) at 6 months after cardiac arrest [2]. Li and Wang question the necessity of predictors of a good outcome since the majority of cardiac arrest survivors from the TTM-trial belonged to this category [3].…”