This was an observational prospective cohort pilot study, which was approved by our Institutional Review Board and was registered by the Clinical Research Information Service (clinical trial registration number: ChiCTR1800015606). The study was approved by the Ethics Committee of Beijing Chao-Yang Hospital affiliated to Capital Medical University. All patients received CABG from May 2018 to April 2019. All participants were informed of the study purpose and design and provided written consent before study enrolment. Patients who met all inclusion criteria and did not fall into any exclusion criteria were included in the study. Registered patients were asked to stay in close contact with the researchers. The inclusion criteria of the patients were: received CABG in Beijing Chao-Yang Hospital affiliated to Capital Medical University; aged 60–85 years old and with grade American society of anesthesiologists (ASA) classification Ⅱ-Ⅲ. The following patients were excluded: (1) those with a history of neurological diseases, mental illness or abnormal personality; (2) unable to communicate well, confused thinking, and failing to cooperate with investigators; (3) those with PND before operation; (4) those who need to take a sedative or depressive drugs during the perioperative period; (5) with central nervous system disease, psychological disease or long-term use of antidepressant drugs; (6) unable to effectively communicate with the researchers. 38 patients were excluded and 82 patients completed the study.
All patients were fasting for 8 hours before the operation. The patients received oxygen supply with the Zeus anesthesia machine (Draeger, Germany) mask. Five lead electrocardiographs (ECG) and pulse oxygen saturation (SpO2) were collected to monitor vital signs. Radial artery puncture and catheterization with local anesthesia were performed to monitoring invasive blood pressure. Induction: etomidate 0.1–0.3 mg/kg, sufentanil 1–2 µg/kg and rocuronium bromide 1 mg/kg. Ventilation with endotracheal intubation performed 5 to 10 minutes after induction with 8 mL/kg of tidal volume, the inspiratory-to-expiratory ratio of 2:1, and respiratory rate of 10–14 times/min. End-tidal carbon dioxide (ETCO2) was maintained between 35–45 mmHg, propofol 3–8 mg.kg− 1.h− 1 was injected intravenously, bispectral index (BIS) value was maintained at about between 40–60. A three-cavity central venous catheter was inserted through the right subclavian vein, and a swan-ganz floating catheter was inserted through the right internal jugular vein puncture to connect the vigilance heart output monitor (Edwards company, USA) and monitor the pulmonary arterial pressure and blood temperature. The operating room temperature 25–27℃, humidity 40–53%.
To measure TNF-α, IL-1 (interleukin-1), IL-6 (interleukin-6), S100β, MDA (malondialdehyde) and T-AOC (total antioxidant capacity) levels, 5 mL venous blood samples were obtained at four time points: 5 min before operation (T0), end of surgery (T1), the first day after surgery (T2), the third day after surgery (T3). Plasma was separated by centrifugation at 3000 rpm for 10 min and stored at − 80 °C for further analysis.
Medical And Demographic Characteristics Of Patients
The clinical characteristics of the patients were recorded, including age, sex, height, weight, education years, preoperative diagnosis, ASA classification, intraoperative bleeding volume and urinary volume, operation time, the time from the end of surgery to extubation and the days of the intensive care unit (ICU).
According to the criteria that were used in the ISPOCD1 and ISPOCD2 studies , we used a validated battery of 5 neuropsychological tests, including Hopkins verbal learning test (HVLT), trail making test A (TMTA), digit span test (DST), revised brief visuospatial memory test (BVMT-R) and digit symbol-coding test (DSCT), to assess global cognitive status, short-term and intermediate-term memory, attention, concentration, and psychomotor skills. One day before the surgical procedure (T0), for every patient we asked the investigator to perform neuropsychological tests to assess him/her in a quiet room at 9 a.m. Neuropsychological tests were repeated on the 7th day after surgery (T4) in the same standardized fashion. A battery of tests of approximately 40 min duration was administered by the investigator.
Diagnose Of Pnd
The diagnostic standard of PND is the Z-score method . We calculate the Z-score as follows: we record the difference of the mean value of postoperative and preoperative scores in the control group and obtain the standard deviation (SD) of the score difference in the control group. For every patient, we calculate the difference between the patient's postoperative and preoperative values and then compare with the mean score of the difference of the control group, then divide SD to obtain the Z-score. In this experiment, we use the critical value of 0.05. This suggests that if the Z-score is higher than1.96 (two standard deviations), we conclude that the result is significant. If the Z-score of two or more tests is higher than 1.96, we can conclude that PNCD occurred to the patient.
Preparation Of Blood Samples
5 mL venous blood was collected at T0, T1, T2, and T3. The serum was prepared via centrifugation (Z 400; Hermle Labortechnik GmbH, Wehingen, Germany) at 3000 rpm for 10 min. The concentration of TNF-α, IL-6, IL-1, and S100β were tested using an enzyme-linked immunosorbent assay (ELISA) method (Deyi Clinical Laboratory, Beijing, China) according to the manufacturer's instructions. The concentration of MDA and T-AOC was tested using a colorimetric method (Nanjing Jiancheng Bioengineering Institute, China).
Data management and statistical analyses were performed in SPSS Statistics software version 25 (IBM Corp., Armonk, NewYork, United States). The data were presented as means ± standard error (SEM) for continuous variables if normally distributed, as median (minimum, maximum) if not, and as percentages (%) for categorical variables. Statistical differences between the two groups were obtained using the t-test or Wilcoxon rank-sum test, as appropriate for continuous data. The chi-square test or Fisher exact test was used for categorical data. A binary logistic regression analysis was conducted to assess which factors were significantly associated with PND. All P values were based on two-sided tests, and P values of < 0.05 were considered statistically significant. All participants provided written informed consent and ethical approval was provided by the local medical ethics committee of the Beijing Chaoyang Hospital, Capital Medical University.