Study design
This is a prospective randomized controlled study, which was approved by the Ethics Committee of Shenzhen University First Affiliated Hospital/Shenzhen Second People’s Hospital in August 2017, and was registered at Chictr.org.cn. (ID: ChiCTR-INR-17012557). Informed written consent was obtained from all patients, and the study was based on the principles of the Declaration of Helsinki for medical research involving human subjects.
Participants
From Sept. 2017 to March 2018, 120 patients were included in this study. ASA I/II patient aged 16-65 years scheduled for shoulder arthroscopy in beach chair position were randomized into either group C or group O, described below, using computer generated random numbers. The random allocation sequence was conducted by a team member who was not related to operation and patient assessment. And the same member prepared opaque envelopes in which the intervention information was concealed. Before interscalene brachial plexus block, these envelopes were opened. Patients were excluded from the study if with a cardiac pacemaker, communication difficulties, history of mental illness, craniocerebral surgery, coagulation dysfunction, diabetes mellitus with peripheral neuropathy, or participating in other clinical trials.
Interventions
All patients were monitored in the operating room as per standard procedure, with non-invasive blood pressure (NIBP), heart rate (HR), electrocardiogram (ECG), pulse oximetry (SpO2) and invasive blood pressure (IBP). These data were automatically collected and recorded in our electronic medical record system (Medicalsystem, Co. Ltd., Suzhou, China). At the same time, patients were monitored with BIS (A-2000XP BIS, Aspect Medical system, Dublin, Ireland).
Ultrasound-guided interscalene brachial plexus block was performed before anesthesia induction. All patients received TCI propofol (the initial target concentrations in the plasma was 3 to 4 mcg ml-1) by BCP-100 infusion system and remifentanil (the initial target concentrations in the effect-side was 4ng/ml) by normal TCI pump until the BIS maintained at <60 for 30 seconds, followed by propofol administration either by open-loop in the group O or closed-loop in the group C. The parameters of TIVA-TCI described by Marsh et al.[7] and Minto et al.[8] were used for propofol and remifentanil, respectively.
The rocuronium was used after loss of consciousness, and the induction dose was 0.6 mg/kg. Endotracheal intubation was performed after muscle relaxation.
The patients were randomized into two groups, namely group O and group C, according to methods to adjust propofol TCI target concentration during maintenance phase of general anesthesia. In group O, the target concentration of propofol was regulated manually by anesthesiologists based on their clinical experience, and in group C it was regulated automatically by the closed-loop infusion system (BCP-100, Beijing Silugao Medical Technology Co. Ltd., Beijing, China), in order to maintain BIS value at about 50 (40 to 60). The system used in this study was based on PID control as described above. It would judge the average value of BIS within 5 seconds in closed-loop mode. If the average value exceeded the set range, the system referred to the trend of the average value to decide whether to increase or decrease the concentration. And in the process of increasing or decreasing the concentration, the system referred to the trend of propofol concentration to determine whether to stop or accelerate the procedure. Both groups were treated with remifentanil, and the target concentration (3 to 5 ng ml-1) was determined by the clinical judgment of the anesthesiologists.
Surgery was performed in beach chair position. Intraoperative blood pressure was controlled within 30% of the base value. When the blood pressure was lower than 30% of baseline value, phenylephrine was administered at 20~40mcg or 0.02~0.1mcg kg-1 min-1. Nitroglycerin was administered when blood pressure was higher than 30% of the base value. Atropine 0.5 mg was administered when heart rate was below 50bpm. No inhalation anesthetic was used and 5 mg tropisetron was administered at about 15 minutes before the end of the operation.
The infusion of intravenous anesthetics was stopped at the end of the operation in both groups. When the patient established regular breathing with adequate ventilation, and be able to obey commands, extubation was performed.
An MMSE was assessed at the preoperative patient’s visit and the day after surgery by a blinded anesthesiologist. Blood samples were taken before anesthesia, after extubation and the day after operation, respectively. After centrifugation (15 minutes at 2000 rpm), serum samples were stored at -70°C for long-term storage. Serum GFAP and S100B levels were measured in duplicate manner for each sample using a commercial ELISA.
Data collection
Outcomes
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Statistical analysis
SPSS 17.0 was used for statistical analysis. . Categorical variables, expressed as numbers (frequencies), were compared using the c2 test or one-way ANOVA followed by Fisher test. Continuous variables were presented as means (standard deviation) or medians (25th percentile; 75th percentile). And comparisons between the two groups were performed using unpaired Student’s t-tests or Manne-Whitney U-tests as appropriate. P-value <0.05 was considered statistically significant.