Clinical paperSerum tau as a predictor for neurological outcome after cardiopulmonary resuscitation
Introduction
Despite advances in the critical care management of patients after out-of-hospital and in-hospital cardiac arrest (CA) including targeted temperature management (TTM),1, 2 favourable long-term outcomes only range between 7 and 22%.3, 4, 5, 6
Neuro-prognostication remains difficult and is currently based on a multimodal approach including clinical assessment, electroencephalography, somatosensory evoked potentials (SSEP), neuroimaging and blood derived biomarkers.7, 8 Neuron–specific enolase (NSE) is still considered as the gold standard9, 10 and is used beside S-100B,11, 12, 13, 14 and others including secretoneurin (SN),15 glial fibrillary acidic protein (GFAP),12, 16 brain- derived neurotrophic factor (BDNF)12 and neurofilament light chain (NF-L).17
Recently serum tau levels showed a high accuracy in predicting poor outcome after out-of-hospital cardiac arrest (OHCA) independent if mild hypothermia (MTH) (33 °C) or normothermia (NT) (°36 °C) was applied.18 In two smaller observational studies, delayed increase of serum tau was associated with poor outcome in hypothermic patients.19, 20 Tau is a microtubule-associated axonal protein with a stabilizing function under physiological conditions. Following axonal disruption, tau can be detected in brain extracellular fluid,21 cerebrospinal fluid (CSF)22, 23, 24 and serum.25, 26, 27, 28 Whereas brain extracellular tau is only elevated for 48 h after traumatic brain injury, prolonged and sustained elevated serum levels have been reported in severe subarachnoid hemorrhage (SAH) patients21 and CA patients19, 20 with poor outcome. Because of prolonged elevated serum tau levels despite of the relatively short half-life of tau protein (115 h),29 we speculate there is ongoing axonal injury possibly triggered by inflammatory processes. The association of tau in the brain extracellular fluid with elevated IL-6 levels in SAH patients30 and the association of elevated tau fragments with systemic inflammatory markers31 support our considerations.
Therefore, we hypothesized that serum tau elevation beyond 72 h may occur in patients with poor neurological outcome after successful cardiopulmonary resuscitation (CPR) possibly indicating ongoing axonal damage.
The aim of our study was to investigate serum tau kinetics and predictive performance of serum tau over an extended observation period to better understand ongoing pathophysiological processes and improve prognostication, independent if MTH or NT is applied.
Section snippets
Study design
This is a secondary analysis of our previously published study investigating SN after successful CPR.15 This prospective observational single centre trial included 152 consecutive adult patients (age ≥ 18 years) with an in-hospital or out-of-hospital cardiac arrest with presumed cardiac cause admitted to the medical intensive care unit (ICU) of the University Hospital of Innsbruck from September 2008 to April 2013 after successful CPR. The presence of a neuroendocrine tumor, stroke,
Results
The median age was 64 (IQR 53–75) years, and 26% (34/132) were female. Ninety patients (68%) received bystander resuscitation and 17 patients (13%) encountered in-hospital CA. The initial rhythm was ventricular fibrillation in 75 patients (57%) (Table 1). In 68 patients (52%) poor neurological outcome (CPC 3–5) was recorded at hospital discharge, of whom 11 received the maximal ICU care, in 10 and 47 patients therapy was withheld or withdrawn, respectively. (ESM Fig. 1)
Patients with beneficial
Discussion
In the present study, we analysed serum tau in patients after successful CPR treated with MTH or NT over an extended observation period of 168 h. Serum tau showed significantly higher levels in patients with poor (vs. good) neurological outcome with a peak at 72–96 h. Best performance for prognostication could be also demonstrated at 72–96 h. Application of MTH seemed to have minor influence on serum tau levels.
In patients with poor neurological outcome serum tau levels peaked at 72–96 h after
Conclusions
In our study, we could show that peak levels and best prognostication of serum tau is achieved at 72–96 h after CPR in a population consisting of hypothermic and normothermic patients. Sustained elevations beyond 72 h after CPR might be a sign of ongoing neuroinflammatory processes in hypoxic ischemic injury. The influence of MTH seems to be negligible. Further studies are needed to support repeated biomarker assessment beyond 72 h after cardiac arrest.
Conflicts of interest
None.
Acknowledgement
None.
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Resuscitation highlights in 2020
2021, ResuscitationCitation Excerpt :In a sub-study of the TTM trial, the serum biomarkers glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase-L1 (UCH-L1) were found to predict poor neurological outcome with high accuracy.96 At specificities ≥95%, the combination of both biomarkers predicted poor outcome with a higher sensitivity than NSE at 24 h and with similar sensitivities at 48 and 72 h. Serum tau has also been investigated as predictor of neurological outcome after cardiac arrest and in one study was shown to provide the best prognostic discrimination of poor neurological outcome at 72–96 h after CPR.97 In many centres it is now routine practice to obtain a computed tomography (CT) brain scan soon after admission of a patient with ROSC after OHCA.
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