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

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.

Inclusion Criteria: * Age between 18 and 65 years * American Society of Anesthesiologists (ASA) classification I-II * body mass index (BMI) of 18.5 - 30 kg/㎡ * Patients scheduled for elective LC under general anesthesia with an anticipated surgical duration of \< 2 hours * possessing normal cognitive and communication abilities * volunteering to participate and providing written informed consent. Exclusion Criteria: * patients with severe diseases of major organs such as the heart, brain, lungs, liver, and kidneys; * patients with adverse drug reactions to esketamine or magnesium sulfate; * patients with uncontrolled hypertension or hyperthyroidism; * patients with endocrine and metabolic diseases or neurological diseases; * pregnant or lactating women; * long-term users of sedatives, analgesics, or long-term alcohol abusers; * patients with a history of mental illness, language communication barriers, or inability to understand the content of the experiment; * patients with sinus bradycardia or atrioventricular block; * patients with concurrent cholangitis, biliary obstruction, or pancreatitis. Elimination and withdrawal criteria included: * unexpected severe difficult airway during anesthesia induction necessitating alternative intubation techniques; * conversion to open laparotomy due to anatomical variations or surgical complications; * severe or refractory hemodynamic instability requiring frequent or high-dose vasoactive agents, thus precluding adherence to the study protocol; * actual surgical duration exceeding 2 hours; * loss to follow-up, voluntary withdrawal, or substantial loss of core data during the postoperative period.