Pre-operative biomarkers and imaging tests as predictors of post-operative delirium in non-cardiac surgical patients: a systematic review

BACKGROUND: Post-operative delirium (POD) is a common post-operative complication in elderly individuals and imposes a significant health and financial burden. Identifying predictive biomarkers may help understand the pathophysiology of POD. Our objective is to summarize the evidence of pre-operative biomarkers and imaging tests to predict POD in patients undergoing non-cardiac surgery. METHODS: A systematic search of English language articles in MEDLINE, EMBASE, Cochrane Database, PsychINFO, PubMed and ClinicalTrials. Gov up to January 2018 was performed. Studies that used biomarkers or imaging tests to predict POD and a validated POD assessment tool were included. Animal studies, paediatric, cardiac and intracranial surgery were excluded. Risk of bias was assessed using the Quality In Prognosis Study tool. RESULTS: Thirty-four prospective cohort studies involving 4424 patients were included. Nineteen studies described serum tests [Interleukin-6, Insulin-like Growth Factor 1, C-Reactive Protein (CRP), cholinesterases, apolipoprotein-E genotype, leptin, hypovitaminosis, hypoalbuminaemia, gamma-amino butyric acid], 10 described cerebral-spinal fluid tests (monoamine precursor, melatonin, acute phase proteins, S100B and neurofibrillary tangles), and 5 described imaging tests. Two studies had high risk of bias due to unclear outcome measurement and study participation. CRP was significantly associated with POD in 5 studies. Other biomarkers were either examined by only a single study or two or more studies with conflicting results. CONCLUSION: CRP is the most promising biomarker associated with POD. However, we are still in the early stages in identifying biomarkers and imaging tests that may further understanding of the pathophysiology of POD.