Relevance of peripheral cholinesterase activity on postoperative delirium in adult surgical patients (CESARO)

BACKGROUND The cholinergic system is considered to play a key role in the development of postoperative delirium (POD), which is a common complication after surgery. OBJECTIVES To determine whether peri-operative acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activities are associated with the development of POD in in-hospital surgical patients, and raise hypotheses on cholinergic regulatory mechanisms in POD. DESIGN A prospective multicentre observational study by the Peripheral Cholinesterase-activity on Neurocognitive Dysfunctions in Surgical Patients (CESARO) study group. SETTING Nine German hospitals. PATIENTS Patients of at least 18 years of age scheduled for inpatient elective surgery for a variety of surgical procedures. A total of 650 patients (mean age 61.5 years, 52.8% male) were included. METHODS Clinical variables, and peripheral AChE and BuChE activities, were assessed throughout the peri-operative period using bedside point-of-care measurements (one pre-operative and two postoperative measurements). POD screening was conducted postoperatively for at least 24 h and up to the third postoperative day using a validated screening tool (nursing delirium screening scale). RESULTS In all, 179 patients (27.5%) developedPODwithin the early postoperative phase. There was a lower BuChE activity in patients with delirium compared with patients without delirium pre-operatively (Cohen's r = 0.07, P = 0.091), on postoperative day 1 (Cohen's r = 0.12, P = 0.003) and on postoperative day 2 (Cohen's r = 0.12, P = 0.002). In contrast, there was a significantly higher AChE activity in patients with delirium compared with patients without delirium preoperatively (Cohen's r = 0.10, P = 0.012), on postoperative day 1 (Cohen's r = 0.11, P = 0.004) and on postoperative day 2 (Cohen's r = 0.13, P = 0.002). After adjusting for covariates in multiple logistic regression, a significant association between both BuChE and AChE activities and POD was not found. However, in the multivariable analysis using the Generalized Estimating Equation, cholinesterase activities showed that a decrease of BuChE activity by 100UL(-1) increased the risk of a delirium by approximately 2.1% (95% CI 1.6 to 2.8%) and for each 1Ug(-1) of haemoglobin increase in AChE activity, there was a 1.4% (95% CI 0.6 to 2.2%) increased risk of POD. CONCLUSION Peri-operative peripheral cholinesterase activities may be related to the development of POD, but the clinical implications remain unclear. Further studies, in homogeneous patient groups with a strict protocol for measurement time points, are needed to investigate the relationship between cholinesterase activities and POD