In a secondary analysis from a randomised, double-blind placebo-controlled trial Dexmedetomidine blocks cholinergic dysregulation in delirium pathogenesis in patients with major surgery

Abstract

Dexmedetomidine is an alpha-2 adrenoreceptor agonist with anti-inflammatory and anti-delirogenic properties. Pathogenesis of postoperative delirium (POD) includes cholinergic dysfunction and deregulated inflammatory response to surgical trauma. Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are discussed as biomarkers for both POD and severity in acute inflammation. To show whether there is a link between blood cholinesterase activities and dexmedetomidine, we performed a secondary analysis of a randomised, double-blind, placebo-controlled trial that recently showed a lower incidence of POD in the dexmedetomidine group. Abdominal or cardiac surgical patients aged ≥ 60 years were randomised to receive dexmedetomidine or placebo intra- and postoperatively in addition to standard general anaesthesia. We analysed the course of perioperative cholinesterase activities of 56 patients, measured preoperatively and twice postoperatively. Dexmedetomidine resulted in no change in AChE activity and caused a rapid recovery of BChE activity after an initial decrease, while placebo showed a significant decrease in both cholinesterase activities. There were no significant between-group differences at any point in time. From these data it can be assumed that dexmedetomidine could alleviate POD via altering the cholinergic anti-inflammatory pathway (CAIP). We advocate for further investigations to show the direct connection between dexmedetomidine and cholinesterase activity.

Figure 1

CONSORT flow chart.

Figure 2

Activities of cholinesterases. (A) Activities of acetylcholinesterase (AChE) (B) Activities of butyrylcholinesterase (BChE) before (preOP), 15 min after (postOP day 0) and one day after surgery (postOP day 1) compared between patients receiving standard general anaesthesia (Placebo, blue, n = 30) or general anaesthesia combined with perioperative dexmedetomidine (Dex, red, n = 26). The Boxplots show median and IQR (lower and upper hinges). P-values compare values of all three points in time within each group, using the Friedman rank analysis.

Figure 3

Activities of cholinesterases. (A) Activities of acetylcholinesterase (AChE) (B) Activities of butyrylcholinesterase (BChE) before (preOP), 15 min after (postOP day 0) and one day after surgery (postOP day 1) compared between patients without delirium (no delirium, blue, n = 42) or patients with delirium (delirium, red, n = 14). The Boxplots show median and IQR (lower and upper hinges). P-values compare values of all three points in time within each group, using the Friedman rank analysis.