Objectives
To assess the ability of the biomarkers neuron-specific enolase (NSE), tau, neurofilament
light chain (NFL), and glial fibrillary acidic protein (GFAP) to predict postoperative
cognitive dysfunction (POCD) at discharge in patients who underwent cardiac surgery.
Design
Post hoc analyses (with tests being prespecified before data analyses) from a randomized
clinical trial.
Setting
Single-center study from a primary heart center in Denmark.
Participants
Adult patients undergoing elective or subacute on-pump coronary artery bypass grafting
and/or aortic valve replacement.
Interventions
Blood was collected before induction of anesthesia, after 24 hours, after 48 hours,
and at discharge from the surgical ward. The International Study of Postoperative
Cognitive Dysfunction test battery was applied to diagnose POCD at discharge and after
three months. Linear mixed models of covariance were used to assess whether repeated
measurements of biomarker levels were associated with POCD. Receiver operating characteristic
(ROC) curves were applied to assess the predictive value of each biomarker measurement
for POCD.
Measurements and Main Results
A total of 168 patients had biomarkers measured at baseline, and 47 (28%) fulfilled
the POCD criteria at discharge. Patients with POCD at discharge had significantly
higher levels of tau (p = 0.02) and GFAP (p = 0.01) from baseline to discharge. The biomarker measurements achieving the highest
area under the ROC curve for prediction of POCD at discharge were NFL measured at
discharge (AUC, 0.64; 95% confidence interval [CI], 0.54-0.73), GFAP measured 48 hours
after induction (AUC, 0.64; 95% CI, 0.55-0.73), and GFAP measured at discharge (AUC,
0.64; 95% CI, 0.54-0.74), corresponding to a moderate predictive ability.
Conclusions
Postoperative serum levels of tau and GFAP were significantly elevated in cardiac
surgery patients with POCD at discharge, however, the biomarkers achieved only modest
predictive abilities for POCD at discharge. Postoperative levels of NSE were not associated
with POCD at discharge.
Key Words
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References
- Neurobehavioural sequelae of cardiopulmonary bypass.Lancet. 1999; 353: 1601-1606
- Neurocognitive dysfunction after coronary artery bypass surgery: A systematic review.J Thorac Cardiovasc Surg. 2000; 120: 632-639
- Longitudinal assessment of neurocognitive function after coronary-artery bypass surgery.N Engl J Med. 2001; 344: 395-402
- Silent brain injury after cardiac surgery: A review: Cognitive dysfunction and magnetic resonance imaging diffusion-weighted imaging findings.J Am Coll Cardiol. 2012; 60: 791-797
- Preoperative cognitive impairment and postoperative delirium predict decline in activities of daily living after cardiac surgery—A prospective, observational cohort study.Geriatr. 2020; 5: 1-12
- Long-term consequences of postoperative cognitive dysfunction.Anesthesiology. 2009; 110: 548-555
- The assessment of postoperative cognitive function.Acta Anaesthesiol Scand. 2001; 45: 275-289
- Neuron-specific enolase as a predictor of death or poor neurological outcome after out-of-hospital cardiac arrest and targeted temperature management at 33°C and 36°C.J Am Coll Cardiol. 2015; 65: 2104-2114
- Serologic markers of brain injury and cognitive function after cardiopulmonary bypass.Ann Surg. 2006; 244: 593-600
- A literature review of the feasibility of glial fibrillary acidic protein as a biomarker for stroke and traumatic brain injury.Mol Diagn Ther. 2012; 16: 79-92
- Glial fibrillary acidic protein in children with congenital heart disease undergoing cardiopulmonary bypass.Cardiol Young. 2014; 24: 623-631
- Brain injury biomarkers in the setting of cardiac surgery: Still a world to explore.Brain Inj. 2016; 30: 10-17
- Cardiac surgery is associated with biomarker evidence of neuronal damage.J Alzheimers Dis. 2020; 75: 1211-1220
- S100B protein and neuron-specific enolase as predictors of cognitive dysfunction after coronary artery bypass graft surgery.Eur J Anaesthesiol. 2016; 33: 681-689
- Perfusion Pressure Cerebral Infarct (PPCI) trial - the importance of mean arterial pressure during cardiopulmonary bypass to prevent cerebral complications after cardiac surgery: Study protocol for a randomised controlled trial.Trials. 2016; 17: 247
- High-target versus low-target blood pressure management during cardiopulmonary bypass to prevent cerebral injury in cardiac surgery patients: A randomized controlled trial.Circulation. 2018; 137: 1770-1780
- Long-term survival and cognitive function according to blood pressure management during cardiac surgery. A follow-up.Acta Anaesthesiol Scand. 2020; 64: 936-944
- Domain-specific cognitive dysfunction after cardiac surgery. A secondary analysis of a randomized trial.Acta Anaesthesiol Scand. 2019; 63: 730-738
- Associations between mean arterial pressure during cardiopulmonary bypass and biomarkers of cerebral injury in patients undergoing cardiac surgery: Secondary results from a randomized controlled trial.Interact Cardiovasc Thorac Surg. 2021; 32: 229-235
- Long-term postoperative cognitive dysfunction in the elderly: ISPOCD1 study.Lancet. 1998; 351: 857-861
- Short-term practice effects and variability in cognitive testing in a healthy elderly population.Exp Gerontol. 2012; 47: 432-436
- Proteins in cerebrospinal fluid and blood: Barriers, CSF flow rate and source-related dynamics.Restor Neurol Neurosci. 2003; 21: 1-19
- Neuron specific enolase and S-100B as predictors of outcome after cardiac arrest and induced hypothermia.Resuscitation. 2009; 80: 784-789
- Tau proteins in serum predict neurological outcome after hypoxic brain injury from cardiac arrest: Results of a pilot study.Resuscitation. 2013; 84: 351-356
- Neurofilaments as biomarkers in neurological disorders.Nat Rev Neurol. 2018; 14: 577-589
- Post-cardiac arrest serum levels of glial fibrillary acidic protein for predicting neurological outcome.Resuscitation. 2014; 85: 1654-1661
- Brain injury after adult cardiac surgery.Acta Anaesthesiol Stand. 2004; 48: 4-19
- Blood-brain barrier disruption after cardiac surgery.Am J Neuroradiol. 2013; 34: 518-523
- New insights into the pathophysiology of postoperative cognitive dysfunction.Acta Anaesthesiol Scand. 2010; 54: 951-956
- Brain complications and neurocognitive outcome after cardiac valve surgery.Stroke. 2014; 45: AWP49
- The relevance of postoperative cognitive decline in daily living: Results of a 1-year follow-up.J Cardiothorac Vasc Anesth. 2016; 2: 297-303
- Defining neuropsychological dysfunction after coronary artery bypass grafting.Ann Thorac Surg. 1996; 61: 1342-1347
- Recommendations for the nomenclature of cognitive change associated with anaesthesia and surgery - 2018.Br J Anaesth. 2018; 121: 991-993
- Do multiple outcome measures require p-value adjustment?.BMC Med Res Methodol. 2002; 2: 1-4
- No adjustments are needed for multiple comparisons.Epidemiology. 1990; 1: 43-46
Article info
Publication history
Published online: May 16, 2021
Footnotes
The study was funded by the Danish Heart Foundation (24-R97-A5179-22868 and 15-R99-A6034-22905); the Research Foundations at Rigshospitalet (E-22329-01), University of Copenhagen, Denmark; the Lundbeck Foundation (R186-2015-2132); the Swedish Research Council (#2017-00915; #2018-02532); the Alzheimer Drug Discovery Foundation (ADDF), United States (#201809-2016615; #201809-2016862); the European Research Council (#681712); the Swedish Alzheimer Foundation (#AF-742881), Hjärnfonden, Sweden (#FO2017-0243); and the Swedish state under the agreement between the Swedish government and the County Councils, the ALF-agreement (#ALFGBG-715986; #ALFGBG-720931), and European Union Joint Program for Neurodegenerative Disorders (JPND2019-466-236). HZ is a Wallenberg Scholar.
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