Study design and protocol
The current investigation was a prospective observational study recruiting all adult patients who received elective non-cardiac surgery under general anaesthesia between September 2015 and February 2018 at a single tertiary referral hospital. During the period, pEEG was introduced to our department and allowed to use freely by anesthesiologists’ decision. All patients were divided into Entropy (i.e., with intraoperative pEEG) and non-Entropy (i.e., without intraoperative pEEG) groups. Information about demographic characteristics (e.g., age, gender, body mass index) as well as a history of alcohol drinking, dementia, and use of psychiatric medication were collected and recorded. The surgeries that the participants underwent were divided into two categories, namely, joint (including knee, hip, spine) surgery and non-joint (all surgical sites excluded knee, hip, spine) surgery.
Participants
Patient recruitment criteria for the current study were the same as those described in our previous report[22]. The inclusion criteria were adult patients (i.e., age 60 or over) regardless of gender who received postoperative IVPCA for at least three consecutive days within the study period. The exclusion criteria were (1) patients still under sedation after surgery (e.g., those to be transferred to the ICU), (2) non-Chinese speakers, (3) those with preoperative cognitive impairment and/or dementia. The protocol and procedures of the present study were reviewed and approved by the Institutional Review Board (IRB) of Chi Mei Medical Center, Tainan, Taiwan (Approval number: IRB10009-012) and registered in a publicly accessible database [University Hospital Medical Information Network (UMIN), Japan; http://www.umin.ac.jp/ctr/index.htm; Trial ID: UMIN000022711]. Taking the routine nature of the procedures of the current study into consideration, the IRB waived the requirement for a written consent from the participants.
Outcomes (primary and secondary)
The primary aim of this study was to investigate whether pEEG-guided anesthesia could decrease the incidence rate of POD in elective non-cardiac surgical patients aged 60 or older who received postoperative IVPCA. In addition, we compared the occurrence, duration, and phenomenological characteristics of POD from postoperative day one to day three between patients with and those without.
Although pEEG monitoring was originally designed for the adjustment of the hypnotic dosage of anaesthetics, pEEG-guided anesthesia was found to be associated with decreased analgesic requirements, less postoperative nausea/vomiting (PONV) and reduced postoperative pain in patients undergoing non-cardiac surgery[23-25].Accordingly,the secondary outcomes of the present study were the differences in analgesic dosage, pain score, and the incidence of PONV between patients with and without pEEG-guided anesthesia.
Equipment and procedures
Processed electroencephalogram (pEEG) was acquired with a standard equipment(M-Entropy™, GE Healthcare, Helsinki, Finland) that was designed for the computation of two parameters: State Entropy (SE) and Response Entropy (RE). SE (range 0–91) reflects the cortical state of the patient with a range of 40-60 suggesting adequate anaesthesia depth during surgery, while RE (range 0-100) measures the activity of facial muscle which is an early indication of emergency when quickly rising[26]. Three electrodes were placed on the forehead of the participants according to the manufacturer’s instructions.
Intravenous patient controlled analgesia (IVPCA) was achieved by the use of a standard intravenous pump (CADD®-Solis Ambulatory Infusion Pump, Smith Medical ASD. Inc., Oakdale , USA) that delivered intravenous morphine at an initial loading dose of 5mg, followed by a bolus dose of 1 mg without a continuous background infusion. Repeated dosage was set at an interval of at least 10 minutes.
Postoperative monitoring and evaluation parameters
For patients receiving IVPCA, assessments of delirium, effectiveness of analgesia, and side effects (e.g., postoperative nausea/vomiting) in postoperative patients were performed twice a day by the nursing staff of the acute pain service team (APS) that comprised 38 attending anesthesiologists, eight residents, pain nurses, and pharmacists[22, 27]. Attending anesthesiologists provided additional evaluations for problematic patients[22].
Evaluation of delirium was conducted with NuDESC, which is a five-item rating scale that assesses disorientation, inappropriate behaviour, inappropriate communication, illusion/hallucinations, and psychomotor retardation. A psychiatrist or neurologist was consulted to make the diagnosis of delirium if NuDESC ≥1. The severity of postoperative rest/movement-evoked pain was assessed and recorded using 11-points VNRS (0: no pain; 10: the worst imaginable pain) with a score of ≦3 being considered adequate pain control. In addition, the side effects of IVPCA including nausea, vomiting were examined and recorded during each visit[22, 27].
Statistical analysis
Data were analyzed using the STATA 12.0 (Stata Corp, College station, TX, USA) statistical software. Univariate logistic analysis was used to identify predictors for the differences between Entropy and non-Entropy groups. The significance of difference was presented as odds ratio (OR) and 95% confidence intervals (CI). An entry criterion for multivariate selection was set as p <0.1. Multivariate logistic regression with backward elimination procedure was used to achieve the final model, and p <0.05 was set as the exit criterion. Categorical variables were measured by chi-square test or Fisher’s exact test. A p value of <0.05 was considered significant.