Introduction
infection, postoperative delirium, tissue damage, TNF-α
INFLAMMATION, INFECTION
Dexmedetomidine is a highly selective alpha-2-adrenoreceptor agonist with specific sympatholytic effects that is commonly used for sedation, analgesia, and anxiolysis in the intensive care unitDexmedetomidine has been shown to reduce the incidence of postoperative delirium (POD) when used during surgery or in the intensive care unitThe CAIP acts as an immunological reflex that links the nervous and immune systems. Consisting of the efferent part of the vagus nerve, the neurotransmitter acetylcholine (ACh), and the alpha 7 subunit of the nicotinic acetylcholine receptor (α7nAChR), the CAIP mediates the cholinergic regulation of inflammation. Following tissue damage or infection, it becomes activated by the release of pro-inflammatory cytokines and in turn controls the immune response via ACh, which binds to the α7nAChR on immune cellsIn mice with LPS-induced inflammation, pre-emptive administration of dexmedetomidine attenuated NF-κB activation and the production of TNF-α, IL-6, and IL-1β at both the mRNA and protein levels in the spleenThe acetylcholine hydrolysing enzymes acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) degrade ACh. AChE is found in all excitable tissues, in most erythrocytes, in immune cells, and in placental tissue and hydrolyzes ACh with a very high affinity. AChE is inhibited at high acetylcholine concentrations. BChE (also called as “pseudo” or “plasma” cholinesterase) is found ubiquitously throughout the body, particularly in the liver, blood serum, pancreas and central nervous system. In the brain, BChE is located mainly in glial and endothelial cells. It hydrolyses with a lower affinity ACh and non-choline esters, and is not inhibited by higher ACh concentrationsThe regulation of AChE and BChE is still the subject of ongoing research. However, previous results from cell cultures and animal experiments indicate that during inflammation, the expression and activity in particular of AChE is modulated in a cell-specific manner by a direct interaction with the α7nAChR, but also by the binding of NF-κB to the AChE promoter geneAn association between cholinesterase enzyme activity and the occurrence of POD has been proposed by several studies, suggesting that lower activity even preoperatively puts patients at risk for PODDexmedetomidine is a particularly interesting drug in this context, as it has an anti-inflammatory effect on the one hand and an anti-delirogenic potential on the other. Moreover, to the best of our knowledge, there have been no clinical reports of a possible effect of dexmedetomidine on cholinesterase activities.Based on all these considerations, we hypothesise that dexmedetomidine has an influence on peripheral cholinesterase activities, potentially related to its anti-delirogenic and anti-inflammatory effects. To examine this hypothesis, we used data from the NEUPRODEX trial, a double-blind randomised controlled trial, which showed that perioperative administration of dexmedetomidine resulted in a significantly lower incidence of POD