ArticleJournal of pain research2026
Effects of Esketamine and Magnesium Sulfate on Postoperative Fatigue Syndrome in Patients Undergoing Laparoscopic Cholecystectomy: A Randomized, Double-Blind, Placebo-Controlled, 2×2 Factorial Trial.
Article in Journal of pain research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07131033 (Effects of Perioperative Intravenous Infusion Esketamine Combined With Magnesium Sulfate for Postoperative Fatigue Syndrome in Patients Undergoing Laparoscopic Cholecystectomy), which is not on this map. Not yet cited in PubMed.
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Effects of Perioperative Intravenous Infusion Esketamine Combined With Magnesium Sulfate for Postoperative Fatigue Syndrome in Patients Undergoing Laparoscopic Cholecystectomy: A 2×2 Factorial Randomized Controlled Trial
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6 authors.
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Abstract
Purpose: This 2×2 factorial trial aimed to evaluate the main effects and interaction of esketamine and magnesium sulfate on postoperative fatigue syndrome (POFS) in patients undergoing laparoscopic cholecystectomy (LC). Patients and Methods: In this randomized, double-blind, 2×2 factorial trial, 128 patients scheduled for elective LC were randomized to receive intravenous esketamine (0.25 mg/kg load, 0.125 mg/kg/h maintenance), magnesium sulfate (30 mg/kg load, 10 mg/kg/h maintenance), both, or placebo. The primary outcome was the Christensen Fatigue Scale (CFS) score on postoperative day 1 (POD 1). Secondary outcomes included longitudinal CFS and Identity-Consequence Fatigue Scale (ICFS) scores, Quality of Recovery-15 (QoR-15), pain scores, intraoperative hemodynamics, anesthetic consumption, and safety profiles. All randomized participants were included in the primary intention-to-treat analysis. Main effects and interactions were evaluated using generalized linear models (GLM), generalized estimating equations, and linear mixed-effects models. ClinicalTrials.gov: NCT07131033 (registered August 13, 2025). Results: Of the 128 randomized patients, 10 were excluded, leaving 118 in the per-protocol set, which was used only as a descriptive sensitivity analysis. Based on the prespecified factorial GLM, both esketamine and magnesium sulfate exhibited significant main effects in reducing POD 1 CFS scores (esketamine: mean difference [MD], -1.12; 95% confidence interval [CI], -1.69 to -0.55; Conclusion: In this 2×2 factorial trial, perioperative esketamine was associated with reduced acute postoperative fatigue and improved early recovery after laparoscopic cholecystectomy, whereas the magnesium sulfate effect was significant in the GLM model but not confirmed by the corrected longitudinal analysis. Both agents had anesthetic-sparing and early analgesic effects, and no significant esketamine-magnesium interaction was detected for the primary outcome. Magnesium sulfate was also associated with intraoperative hemodynamic changes.
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