Esketamine Combined With Magnesium Sulfate for Postoperative Fatigue Syndrome in Patients Undergoing Laparoscopic Cholecystectomy

Summary

Laparoscopic cholecystectomy (LC), while minimally invasive, triggers postoperative fatigue syndrome (POFS) through mechanisms including ischemia-reperfusion injury, neuroendocrine stress (sustained cortisol elevation), and inflammation-driven mitochondrial dysfunction (IDO-mediated kynurenine production). Esketamine, an NMDA receptor antagonist, counteracts POFS by blocking central sensitization, suppressing neuroinflammation (e.g., microglial IL-6 release), and enhancing neuroplasticity via BDNF/TrkB upregulation. Magnesium sulfate complements this by antagonizing NMDA/voltage-gated calcium channels to reduce inflammation and calcium overload, while optimizing cellular energy metabolism as an ATPase cofactor and alleviating muscle spasms. Crucially, their combination holds synergistic potential: esketamine targets central fatigue pathways, while magnesium addresses peripheral metabolic and muscular components. This study aims to determine their individual and interactive effects on POFS, recovery quality, and sleep outcomes in LC patients, establishing an efficient, safe strategy to accelerate postoperative rehabilitation.

Timeline

Start

2025-09-01

Primary completion

2026-06-01

Completion

2026-06-01

Publications

• Background Lacourt TE, Vichaya EG, Chiu GS, Dantzer R, Heijnen CJ. The High Costs of Low-Grade Inflammation: Persistent Fatigue as a Consequence of Reduced Cellular-Energy Availability and Non-adaptive Energy Expenditure. Front Behav Neurosci. 2018 Apr 26;12:78. doi: 10.3389/fnbeh.2018.00078. eCollection 2018.
• Background Zargar-Shoshtari K, Hill AG. Postoperative fatigue: a review. World J Surg. 2009 Apr;33(4):738-45. doi: 10.1007/s00268-008-9906-0.
• Background Zhuang CL, Mao XY, Liu S, Chen WZ, Huang DD, Zhang CJ, Chen BC, Shen X, Yu Z. Ginsenoside Rb1 improves postoperative fatigue syndrome by reducing skeletal muscle oxidative stress through activation of the PI3K/Akt/Nrf2 pathway in aged rats. Eur J Pharmacol. 2014 Oct 5;740:480-7. doi: 10.1016/j.ejphar.2014.06.040. Epub 2014 Jun 27.
• Background Chen W, Liu S, Chen F, Zhou C, Zhuang C, Shao S, Yu J, Huang D, Chen B, Yu Z. [Relationship between NMDA receptor and postoperative fatigue syndrome and its associated central mechanism]. Zhonghua Wei Chang Wai Ke Za Zhi. 2015 Apr;18(4):376-81. Chinese.
• Background Wang X, Lin C, Lan L, Liu J. Perioperative intravenous S-ketamine for acute postoperative pain in adults: A systematic review and meta-analysis. J Clin Anesth. 2021 Feb;68:110071. doi: 10.1016/j.jclinane.2020.110071. Epub 2020 Oct 26.
• Background Lin X, Feng X, Sun L, Wang Y, Wu X, Lu S, Shao L, Wang W, Yang L, Geng W, Lin H. Effects of esketamine on postoperative fatigue syndrome in patients after laparoscopic resection of gastric carcinoma: a randomized controlled trial. BMC Anesthesiol. 2024 May 24;24(1):185. doi: 10.1186/s12871-024-02513-w.
• Background Sun L, Zhao Y, Li Y, Zhai W, Gao F, Yin Q, Cheng W, Wang Z, Zeng Y. Effect of continuous subanesthetic esketamine infusion on postoperative fatigue in patients undergoing laparoscopic radical resection for colorectal cancer: a randomized controlled study. Am J Cancer Res. 2023 Jun 15;13(6):2554-2563. eCollection 2023.
• Background De Oliveira GS Jr, Castro-Alves LJ, Khan JH, McCarthy RJ. Perioperative systemic magnesium to minimize postoperative pain: a meta-analysis of randomized controlled trials. Anesthesiology. 2013 Jul;119(1):178-90. doi: 10.1097/ALN.0b013e318297630d.
• Background Fritzen R, Davies A, Veenhuizen M, Campbell M, Pitt SJ, Ajjan RA, Stewart AJ. Magnesium Deficiency and Cardiometabolic Disease. Nutrients. 2023 May 17;15(10):2355. doi: 10.3390/nu15102355.

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