This study protocol was approved by the Medical Institutional Ethics Committee of Ningbo No. 2 hospital and Zhejiang province. This investigation was a single-center, prospective observational study which was conducted in the Department of anesthesiology from July 2015 to July 2017. Consecutive elderly osteoarthritis patients who were scheduled to undergo hip replacement under epidural anesthesia were enrolled. All the enrolled patients provided written informed consent before the surgery. Inclusion criteria: (1) aged between 65 and 80 years; (2) American Society of Anesthesiologists (ASA) grade II or III; (3) undergoing first-time unilateral total hip joint replacement under epidural anesthesia. The exclusion criteria: (1) with preexisting neurological disease or psychiatric disorder; (2) preoperative Mini-Mental State Examination (MMSE) score <24; (3) with a history of cardiovascular or neurosurgical surgery; (4) with alcohol or drug dependence; (5) inability to read or speak, with vision or hearing impairment; (5) with low compliance; (6) loss to follow-up or with no completed data.
Neuropsychological assessment and POCD definition
Neuropsychological assessment at baseline (one day before the surgery) and postoperative day 7 was conducted following the guidance of previous consensus statement (11). As widely described by previous reports, the test battery included Digit span test, MMSE, Trail making test (part A), Word recognition memory tests, Verbal fluency test and Symbol digit test (12). According to the guidance of International Study of Postoperative Cognitive Dysfunction (ISPOCD1 and ISPOCD2), a Z score for each test was calculated (3, 13). In this study, patients were defined as suffering POCD while at least two Z scores ≥ 1.96 (14).
Clinical data collection
The following perioperative clinical data were recorded: (1) demographic data including age, gender, Body Mass Index (BMI), ASA physical status, smoking habits; (2) Preoperative comorbidities including diabetes, hypercholesterolemia, hypertension, peripheral vascular disease, history of myocardial infarct; (3) preoperative medications including angiotensin-converting enzyme (ACE) inhibitors,β-blockers, and statins; (4) other clinical data including preoperative MMSE, duration of surgery and anesthesia, recovery time, estimated blood loss, blood transfusion.
Fasting blood samples from all the enrolled patients were obtained at one day before the surgery (baseline). Serum samples were obtained after centrifugation (3000 rpm, 10min, 4°C) and then stored at -80°C for further laboratory tests. The inflammatory biomarkers including C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) were measured by the enzyme-linked immuno sorbent assay (ELISA) method using kits (R&D Systems, Minneapolis, MN, USA). The serum expression of pNF-H was detected using human pNF-H ELISA kit (BioVendor, Modrice, Czech Republic) following the guidance of the manufacturer's protocol. The obtained serum samples were diluted three fold before the pNF-H detection. A level of >70.5 pg/mL was accepted as pNF-H positivity according to previous reports (5). The preoperative blood analyses (including hemoglobin, white blood cell) and blood biochemical examinations (including albumin, creatinine, urea) were also detected by the laboratory in our hospital.
GraphPad Prism 5.0 (GraphPad Inc., CA, USA) and SPSS 19.0 (SPSS, Inc., IA, USA) were utilized for the data analysis. Continuous and categorical data were presented as mean and standard error (S.E.M), number (n) and percentage (%), respectively. Mann-Whitney U test, t test, Chi-square test and Fisher exact test were used for data analyses as appropriate. Risk factors for POCD were evaluated by univariate and multivariate logistic regression analyses. All statistical analyses were bilateral probability and a P value of <0.05 was considered statistically different.