Alleviate Postoperative Fatigue Syndrome, Laparoscopic Cholecystectomy
Conditions
Keywords
esketamine, magnesium sulfate, postoperative fatigue syndrome, Laparoscopic Cholecystectomy
Brief summary
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.
Detailed description
This randomized, double-blind trial investigated the effects of esketamine and magnesium sulfate on postoperative fatigue syndrome in patients undergoing laparoscopic cholecystectomy. Using computer-generated randomization and sealed envelopes, 128 patients were allocated in a 1:1:1:1 ratio to four groups: Group E received intravenous esketamine (0.25 mg/kg over 10 min pre-induction followed by 0.125 mg/kg/h); Group M received magnesium sulfate (30 mg/kg over 10 min pre-induction followed by 10 mg/kg/h); Group EM received both drugs concurrently at the specified doses; and Group C received volume-matched normal saline. Patients, attending anesthesiologists, and outcome assessors remained blinded to group assignment throughout the study, with intraoperative management handled by a separate non-investigating anesthesiologist to preserve blinding integrity. The patients were routinely fasted for 8 h and abstained from drinking for 2 h preoperatively. No premedication was administered. After admission, patients were routinely administered oxygen by mask, peripheral venous access was opened, and standard monitoring was applied, including noninvasive blood pressure, pulse oximetry, electrocardiogram, body temperature, and bispectral index (BIS). Additionally, a noninvasive hemodynamic monitoring system (NICAP-T20A, Mailian Medical Technology Co., Ltd., Changsha, China) was used to continuously record cardiac output (CO) and systemic vascular resistance (SVR). Anesthesia was induced with propofol 1.5 to 2.0 mg/kg, sufentanil 0.5 μg/kg, and rocuronium bromide 0.6 mg/kg. Subsequently, 4 mg of intravenous betamethasone was administered. Following 3 minutes of mask ventilation, tracheal intubation was performed. Mechanical ventilation was controlled using an oxygen-air mixture (flow rate, 2.0 L/min; FiO₂, 50%) with a tidal volume of 6 to 8 mL/kg and an inspiratory-to-expiratory ratio of 1:2. End-tidal carbon dioxide was maintained at 35 to 40 mmHg. During anesthesia maintenance, remifentanil 0.1 to 0.5 μg/kg/min and propofol 4 to 12 mg/kg/h were continuously infused in all four groups. A four-channel microinfusion pump was used for synchronous intravenous infusion. Each drug was administered through an independent channel to avoid drug interactions, and the study drugs were continuously infused during the operation until the end of surgery. The appropriate depth of anesthesia (BIS 40-60) was maintained by adjusting the infusion rate of propofol and remifentanil. Vasoactive drugs (ephedrine, phenylephrine) were administered as needed to regulate blood pressure. After the operation, the patient was immediately transferred to the PACU. The trachea was extubated upon the recovery of consciousness, adequate muscle strength, and stable spontaneous respiration. Patients were discharged to the ward if no adverse events occurred during a 30-minute observation period and the Steward recovery score was ≥ 4. In the PACU, 30 mg of ketorolac tromethamine was administered intravenously for analgesia if the patient's NRS score was \> 3 or if the patient requested analgesia.
Interventions
DRUGEsketamine
Patients were given intravenous esketamine 0.25 mg/kg 10 min before induction of anaesthesia, followed by continuous pumping at 0.125 mg/(kg-h) until the end of the operation.
DRUGMagnesium sulfate
Patients were injected with 30 mg/kg of magnesium sulphate intravenously 10 min before the induction of anaesthesia, followed by continuous pumping at 10 mg/(kg-h) until the end of the operation.
DRUGEsketamine and Magnesium sulfate
Patients received a simultaneous intravenous infusion of esketamine (0.25 mg/kg) and magnesium sulfate (30 mg/kg) over 10 minutes before anesthesia induction, followed by continuous infusion of esketamine at 0.125 mg/kg/h and magnesium sulfate at 10 mg/kg/h via separate channels until surgery completion.
DRUGSaline
Patients in the control group received an equivalent volume of normal saline infused intravenously over 10 minutes before anesthesia induction, followed by continuous saline infusion at a matched flow rate via a separate channel until surgery completion.
Sponsors
The Second People's Hospital of Huai'an
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
The randomization sequence was generated by a computer and handed over in sealed opaque sequentially numbered envelopes. The envelope was opened by anaesthetist not involved in the study and drugs were dispensed as per the allocation card. The configured drugs were then handed over to experienced anaesthetists who were not aware of the subgroups
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Christensen's Fatigue Scale | postoperative day 1 (POD1) | The Christensen Fatigue Scale, a widely used unidimensional tool for assessing postoperative fatigue syndrome, relies on patients' subjective ratings of fatigue and daily activity ability on a 1-10 scale, with no multiple subdimensions or specific items. Scoring criteria are: 1-2 points (normal, fatigue only with excessive activity, normal sleep); 3-5 points (able to perform daily activities, occasional slightly strenuous activity); 6-8 points (maintaining only partial daily activities, difficulty with walking/climbing stairs, need for sleep); 9-10 points (unable to perform daily activities, extreme need for sleep). A score \> 2 points indicates fatigue, while ≥ 6 points may signal clinically noticeable postoperative fatigue syndrome. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Christensen's Fatigue Scale | Preoperative day 1 (PRE1), postoperative day 1 (POD1), postoperative day 2 (POD2), postoperative day 7 (POD7), postoperative day 30 (POD30) | The Christensen Fatigue Scale, a widely used unidimensional tool for assessing postoperative fatigue syndrome, relies on patients' subjective ratings of fatigue and daily activity ability on a 1-10 scale, with no multiple subdimensions or specific items. Scoring criteria are: 1-2 points (normal, fatigue only with excessive activity, normal sleep); 3-5 points (able to perform daily activities, occasional slightly strenuous activity); 6-8 points (maintaining only partial daily activities, difficulty with walking/climbing stairs, need for sleep); 9-10 points (unable to perform daily activities, extreme need for sleep). A score \> 2 points indicates fatigue, while ≥ 6 points may signal clinically noticeable postoperative fatigue syndrome. |
| Identity-Consequence Fatigue Scale | Preoperative day 1 (PRE1), postoperative day 1 (POD1), postoperative day 2 (POD2), postoperative day 7 (POD7), postoperative day 30 (POD30) | The 31-item Identity-Consequence Fatigue Scale (ICFS), which is a multidimensional self-report questionnaire designed to comprehensively assess fatigue, captures fatigue's complexity by exploring its interactions with one's sense of identity and consequent impacts on daily functioning, emotional states, and social interactions. For scoring, items typically use Likert-type scales (with slight variations in response options across items), some requiring reverse scoring for consistent interpretation. Total scores are summed, with the minimum and maximum values of the total score to be specified based on the scale's scoring criteria; higher scores indicate more severe (worse) fatigue. This comprehensive 31-item structure enables detailed exploration of fatigue, suiting research needing a thorough understanding of its multifaceted nature. |
| The Quality of Recovery-15（QoR-15） | Preoperative day 1 (PRE1), postoperative day 1 (POD1), postoperative day 2 (POD2), postoperative day 7 (POD7), postoperative day 30 (POD30) | The QoR-15 scale is divided into five dimensions: physical comfort (5 items), self-care (2 items), psychological support (2 items), emotional state (4 items), and pain (2 items), with each item rated on a scale of 0-10, and the total score ranging from 0-150, with the higher the score the better the quality of recovery, and a score of 118 and above indicating surgery. |
| Numeric Rating Scale（NRS） | 5 minutes after extubation, postoperative day 1 (POD1), postoperative day 2 (POD2) | NRS is a rating used to assess a patient's level of pain, which is assessed by the patient based on self-perception on a scale from 0 to 10. A score of 0 represents no pain and a score of 10 represents the most pain. |
| Richmond Agitation and Sedation Scale(RASS) | 5 minutes after extubation, postoperative day 1 (POD1), postoperative day 2 (POD2) | The Richmond Agitation-Sedation Scale (RASS) is a widely used tool to assess the level of sedation and agitation in patients. It ranges from +4 to -5, with specific descriptors for each score: +4 indicates combative behavior; +3 is extremely agitated; +2 means agitated and restless ; +1 denotes restless but calm; 0 represents alert and calm; -1 is drowsy; -2 indicates light sedation; -3 means moderate sedation; -4 is deep sedation ; and -5 represents unarousable. This scale helps clinicians objectively evaluate and adjust sedation levels to ensure patient comfort and safety. |
| perioperative hemodynamic fluctuations | At seven predefined time points: upon operating room arrival (T0), post-induction (T1), post-intubation (T2), at skin incision (T3), immediately after pneumoperitoneum establishment (T4), 10 minutes post-pneumoperitoneum (T5), and at the end of surgery ( | Mean arterial blood pressure (MAP); Heart Rate (HR); CardiacOutput (CO); Systemic Vascular Resistance (SVR) |
| Discontinuation time, extubation time | Postoperative | Patient awakening time and extubation time (time from stopping medication to awakening and extubation) |
| Drug use | Perioperative | The names and dosages of the patients' intraoperative anaesthetic drugs (propofol and remifentanil), vasoactive drugs, and postoperative analgesic drugs were recorded. |
| Incidence of adverse reactions | postoperative day 1 (POD1), postoperative day 2 (POD2) | respiratory depression, postoperative coughing, incidence of postoperative nausea and vomiting, postoperative hoarseness, sore throat, hallucinations, drowsiness, nightmares, blurred vision, sensory abnormalities, dissociative symptoms, cognitive decline, muscle strength reduction |
Countries
China
Outcome results
None listed