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

Laparoscopic cholecystectomy (LC), although minimally invasive, is frequently associated with postoperative fatigue syndrome (POFS), which can delay recovery and prolong convalescence. Esketamine, an NMDA receptor antagonist, has demonstrated potential benefits in reducing postoperative fatigue and pain through central sensitization blockade and anti-inflammatory effects. Magnesium sulfate, another NMDA receptor antagonist and physiological calcium channel blocker, offers complementary analgesic, anti-inflammatory, and cardiovascular-modulating properties. This randomized, double-blind, 2 × 2 factorial trial aims to evaluate the independent and combined effects of perioperative esketamine and magnesium sulfate on postoperative fatigue, recovery quality, pain, and intraoperative hemodynamics in patients undergoing LC, with the goal of identifying an effective and safe strategy to accelerate early 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.