Protective mechanism of dexmedetomidine on early postoperative cognitive dysfunction in elderly: a metabonomic study

To investigate the protective mechanism of dexmedetomidine（Dex）on early postoperative cognitive function in the elderly by determining cognitive function-related metabolites during the early postoperative period following intervention.

A randomized, single-blind, placebo-controlled study was conducted on 48 elderly patients undergoing joint replacement surgery（including hip and knee replacement surgeries）due to arthritis in Army medical center from January to May 2022. They were 10 males and 38 females, at an average age of 71.38（ranging from 65 to 89）years. They were randomly divided into a Dex group（n=32）and a control group（CON group, receiving 0.9% saline at an equal rate and volume via same way, n=16）in a ratio of 2∶1. Mini-Mental State Examination（MMSE）was performed to evaluate cognitive function before and 1 d after the surgery. Metabolomic analysis was carried out on the serum samples harvested on the day of surgery and 1 d after using ultra-high-performance liquid chromatography-quadrupole-Orbitrap high-resolution mass spectrometry（UHPLC-QE-MS）in order to screen for differential metabolites and their pathways.

Postoperative cognitive dysfunction（POCD）was defined as a decrease in MMSE score by ≥2 points when compared to the preoperative score. The incidence of POCD was 6.25% and 37.5%, respectively, in the Dex group and CON group, with statistical significance（Chi-square=5.419, P=0.02）. Metabolomics analysis revealed 70 differential metabolites, including significantly down-regulated compounds such as ethyl dodecanote, prostaglandin D2, Indoxyl sulfate, Epibrassinolide, Diacylglycerol（18∶4/15∶0/0∶0）, Ganoderide H. Up-regulated metabolites included, L-Alloisoleucine, L-Norleucine, Betaine, 3,3,5-triiodo-L-thyronine-beta-D-glucuronoside, Phosphatidylcholine（22∶6/16∶1）, Phosphatidylcholine（22∶5/14∶0）, Phosphatidylcholine（18∶4/18∶1）, Cephalin（20∶3/14∶1）, Glycerophosphocholine, L-Serine, Gamma-Aminobutyric acid. The main pathways involved were glycerophospholipid metabolism, aminoacyl-tRNA biosynthesis, and pathways related to glycine, serine, and threonine metabolism, as well as pathways related to alanine, aspartate, and glutamate metabolism.

Dex protects early postoperative cognitive function by participating in various biological pathways such as lipid metabolism, amino acid metabolism, suppressing inflammatory reactions, alleviating oxidative stress, improving synaptic structure and function, and regulating cellular energy metabolism.