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

NCT07131033 | Active Not Recruiting Phase 1

• 1 other identifier: CLanXie
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Laparoscopic Cholecystectomy; Alleviate Postoperative Fatigue Syndrome

Keywords

esketamine; magnesium sulfate; postoperative fatigue syndrome; Laparoscopic Cholecystectomy

Outcome Measures

Primary Outcomes (2)

• Christensen's Fatigue Scale

  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.

  Preoperative day 1 (PRE1), postoperative day 1 (POD1), postoperative day 2 (POD2), postoperative day 7 (POD7), postoperative day 30 (POD30)

• Identity-Consequence Fatigue Scale

  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.

  Preoperative day 1 (PRE1), postoperative day 1 (POD1), postoperative day 2 (POD2), postoperative day 7 (POD7), postoperative day 30 (POD30)

Secondary Outcomes (9)

• The Quality of Recovery-15（QoR-15）

  Preoperative day 1 (PRE1), postoperative day 1 (POD1), postoperative day 2 (POD2)

• Numeric Rating Scale（NRS）

  5 minutes after extubation, postoperative day 1 (POD1), postoperative day 2 (POD2)

• Richmond Agitation and Sedation Scale(RASS)

  5 minutes after extubation, postoperative day 1 (POD1), postoperative day 2 (POD2)

• Mean arterial blood pressure(MAP)

  Perioperative:entering the operating room, before induction of anesthesia, before intubation, immediately after intubation, start of surgery, end of surgery, at extubation

• sleep duration

  Preoperative day 1 (PRE1), postoperative day 1 (POD1), postoperative day 2 (POD2)

Study Arms (4)

Esketamine

EXPERIMENTAL

Patients were given intravenous esketamine 0.25 mg/kg 10 min before induction of anaesthesia, followed by continuous pumping at 0.25 mg/(kg-h) until the end of the operation.

Drug: Esketamine

Magnesium Sulfate

EXPERIMENTAL

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.

Drug: Magnesium sulfate

Esketamine and Magnesium Sulfate

EXPERIMENTAL

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 0.25 mg/kg/h and magnesium sulfate at 10 mg/kg/h via separate channels until surgery completion.

Drug: Esketamine and Magnesium sulfate

Control

PLACEBO COMPARATOR

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.

Drug: Saline

Interventions

Esketamine DRUG

Patients were given intravenous esketamine 0.25 mg/kg 10 min before induction of anaesthesia, followed by continuous pumping at 0.25 mg/(kg-h) until the end of the operation.

Esketamine

Magnesium sulfate DRUG

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.

Magnesium Sulfate

Esketamine and Magnesium sulfate DRUG

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 0.25 mg/kg/h and magnesium sulfate at 10 mg/kg/h via separate channels until surgery completion.

Esketamine and Magnesium Sulfate

Saline DRUG

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.

Control

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age between 18 and 65 years
• American Society of Anesthesiologists (ASA) classification I-II
• Patients scheduled for LC under general anaesthesia and with a procedure duration of less than 60 minutes.

You may not qualify if:

• Patients who do not sign the informed consent;
• 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 difficult airways during anesthesia induction requiring a change in the conventional intubation method;
• patients with sinus bradycardia or atrioventricular block;
• patients with concurrent cholangitis, biliary obstruction, or pancreatitis.

Sponsors & Collaborators

• The Second People's Hospital of Huai'an: lead

Study Sites (1)

The Affiliated Huaian Hospital of Xuzhou Medical University, Huai'an Second Hospital

Huaian, China

Location

Related Publications (9)

• 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.

  PMID: 29755330 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.

  PMID: 19189174 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.

  PMID: 24975098 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.

  PMID: 25940183 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.

  PMID: 33007645 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.

  PMID: 38789968 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.

  PMID: 37424809 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.

  PMID: 23669270 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.

  PMID: 37242238 BACKGROUND

MeSH Terms

Interventions

Esketamine; Magnesium Sulfate; Sodium Chloride

Intervention Hierarchy (Ancestors)

Magnesium Compounds; Inorganic Chemicals; Sulfates; Sulfuric Acids; Sulfur Acids; Sulfur Compounds; Chlorides; Hydrochloric Acid; Chlorine Compounds; Sodium Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: chief physician

Study Record Dates

• First Submitted: August 13, 2025
• First Posted: August 19, 2025
• Study Start: May 6, 2025
• Primary Completion: August 31, 2025
• Study Completion: September 30, 2025
• Last Updated: August 19, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)