Trial reportBMC anesthesiology2025
Integrated analysis of metabolomics combined and net-work pharmacology reveals the effects of dexmedetomidine on early postoperative cognitive dysfunction in elderly patients: randomized controlled trial.
Trial report in BMC anesthesiology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundPostoperative cognitive dysfunction (POCD) negatively impacts patients' post-surgery recovery, and, in severe cases, raises the risk of mortality. Nonetheless, the underlying mechanism of POCD remains incompletely elucidated, and there is a notable dearth of effective treatment strategies.
methodsA randomized allocation was conducted among a total of 90 patients who underwent arthroplasty surgery, with 45 patients assigned to the dexmedetomidine group and 45 patients assigned to the control group. The Dexmedetomidine (DEX) group received an intravenous infusion of 1 µg/kg dexmedetomidine for 10 min, followed by a maintenance dose of 0.4 µg/kg/h for 30 min before surgery completion; the control (CON) group received 0.9% normal saline, which was continuously pumped in the same way at the same volume and speed for the same time. We used ultrahigh-performance liquid chromatography coupled with Q Exactive mass spectrometry and network pharmacology to screen the targets and pathways through which DEX protects against early POCD. Finally, the obtained key targets were verified by molecular docking and q-PCR.
resultsThe incidence of early POCD was lower in the DEX group than in the CON group one day after surgery (6.67% vs. 26.67%). Metabolomic analysis revealed 34 differentially abundant metabolites between the DEX and CON groups and revealed that DEX impacted early POCD by regulating glycerophospholipid metabolism, the sphingolipid signaling pathway, linoleic acid metabolism, purine metabolism, pyrimidine metabolism, etc. Network analysis further demonstrated that DEX affects the levels of several metabolites, such as phosphatidylcholine, adenosine, L-DOPA, and sphinganine, through the regulation of core target genes, including DRD2 and CYP3A4. Molecular docking showed high affinities between key targets and DEX. The q-PCR results showed that the expression of DRD2 was upregulated, while that of CYP3A4 was downregulated in the DEX group.
conclusionsDEX regulates DRD2 and CYP3A4, influencing glycerophospholipid metabolism, the sphingolipid signaling pathway, linoleic acid metabolism, purine metabolism, pyrimidine metabolism, etc., and regulates metabolites such as phosphatidylcholine, adenosine, L-DOPA, and sphinganine to exert protective effects on early POCD.
trial registrationThe study protocol was registered with the Chinese Clinical Trial Registry on 08 January 2022 (Registration number: ChiCTR2200055399).
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