The Effect of Intraoperative Infusion of Esketamine on Cholestatic Pruritus in Patients Undergoing Hepatobiliary Surgery

The Effect of Intraoperative Infusion of Esketamine on Cholestatic Pruritus in Patients Undergoing Hepatobiliary Surgery: A Single-center Randomized Controlled Study

To explore the effect of esketamine on cholestatic pruritus in patients undergoing hepatobiliary surgery

Study Overview

• Status: Not yet recruiting
• Conditions: Cholestatic Pruritus
• Intervention / Treatment: Drug: Esketamine; Drug: normal Saline

Detailed Description

Cholestatic pruritus is a common and refractory symptom in patients undergoing hepatobiliary surgery, often caused by impaired bile excretion due to bile duct stones, biliary tumors, or bile duct strictures. Patients typically present with moderate to severe pruritus, initially or most severely affecting the palms and soles, which significantly impairs quality of life and is frequently accompanied by sleep disturbances, anxiety, and depression. Esketamine, as an NMDA receptor antagonist, exhibits anti-hyperalgesic effects and inhibits central sensitization. Recent studies suggest that it may also alleviate refractory pruritus. This study aims to investigate the effect of intraoperative continuous infusion of esketamine on cholestatic pruritus in patients undergoing hepatobiliary surgery

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Guolin Wang, Study Director; Phone Number: +8615822855556; Email: wangguolinghad@hotmail.com

Study Locations

• China
  • Tianjin, China
    • Tianjin Medical University General Hospital, Tianjin, 300052
    • Contact: Guolin Wang, Study Director; Phone Number: +8615822855556; Email: wangguolinghad@hotmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 1. Inclusion Criteria:

  1. Patients with cholestasis caused by bile duct stones, gallbladder stones, bile duct strictures, pancreatic head cancer, cholangiocarcinoma, or periampullary carcinoma, etc.
  2. Manifestations of cholestatic pruritus, typically with the palms and soles as the initial or most severely affected sites, which may extend to the limbs and trunk; possibly accompanied by jaundice (yellowing of the skin and sclera), dark urine (e.g., tea-colored), and clay-colored stools; often with a tendency to worsen at night.
  3. Report of pruritus with an NRS score ≥ 4 (moderate to severe pruritus) twice within one week.
  4. Scheduled for elective hepatobiliary surgery under general anesthesia, including but not limited to: partial hepatectomy, common bile duct exploration, choledocholithotomy, biliary-enteric anastomosis (e.g., Roux-en-Y anastomosis), pancreaticoduodenectomy (Whipple procedure), and radical resection of hilar cholangiocarcinoma.
  5. American Society of Anesthesiologists (ASA) physical status classification I-III.
  6. Age ≥ 18 years, body mass index (BMI) between 18 and 30 kg/m², regardless of gender.
  7. Patients have fully understood the nature of the study, voluntarily agree to participate, and have signed the informed consent form.

Exclusion Criteria:

1. Known allergy to any component of the study drug or history of allergic constitution;
2. History of allergy to general anesthetics, opioids, or non-steroidal anti-inflammatory drugs;
3. History of neurological disease; history of chronic pain; substance abuse or alcoholism; long-term use of opioids; administration of opioids within 48 hours prior to surgery;
4. ASA physical status classification IV;
5. Coronary heart disease, bronchial asthma, severe hypertension, severe hematologic dysfunction, renal dysfunction, or marked electrolyte abnormalities;
6. History of gastrointestinal diseases (peptic ulcer, Crohn's disease, ulcerative colitis);
7. Respiratory insufficiency or respiratory failure;
8. Preoperative diagnosis of severe liver failure of Child-Pugh class C or presence of hepatic encephalopathy;
9. Other pruritic disorders: uremic pruritus, polycythemia vera, cutaneous T-cell lymphoma, hypereosinophilia, drug eruption and drug-induced pruritus, as well as other pruritic diseases that may be easily confused, such as atopic dermatitis, pemphigoid, scabies, delusional parasitosis, dermatitis artefacta, etc.;
10. Pregnant or breastfeeding women;
11. BMI < 18 kg/m² or BMI > 30 kg/m²;
12. Poor compliance or inability to complete the study according to the protocol;
13. Participation in another drug clinical trial within the past 4 weeks;
14. Any other condition that, in the opinion of the investigators, makes the patient unsuitable for enrollment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Patients receiving esketamine intervention; Patients undergoing hepatobiliary surgery and suffering from cholestatic pruritus received continuous infusion of esketamine during the operation.	Drug: Esketamine; Continuous intraoperative infusion of esketamine at 0.3 mg/kg/h
Placebo Comparator: Patients receiving an equal volume of saline; Patients undergoing hepatobiliary surgery and suffering from cholestatic pruritus received continuous infusion of an equal volume of normal saline during the operation as a placebo control.	Drug: normal Saline; Patients undergoing hepatobiliary surgery and suffering from cholestatic pruritus received continuous infusion of an equal volume of normal saline during the operation as a placebo control.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
NRS scores for pruritus assessed in the morning and evening on postoperative day 1	The patient evaluated the intensity of pruritus with 11 numbers ranging from 0 to 10, and the higher the number, the more severe the condition. The higher the number, the more severe the itching. 0: No sensation. 1-3: Mild itching. 4-6: Moderate itching. 7-9: Severe itching. 10: Extremely severe itching.	The morning and evening of the first day after the operation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The NRS scores for pruritus in the morning and evening on the second and third days after the operation.	The patient evaluated the intensity of pruritus with 11 numbers ranging from 0 to 10, and the higher the number, the more severe the condition. The higher the number, the more severe the itching. 0: No sensation. 1-3: Mild itching. 4-6: Moderate itching. 7-9: Severe itching. 10:Extremely severe itching.	On the morning and evening of the second and third days after the operation
The incidence of sleep disorders on postoperative days 1-3	Patients completed the sleep quality scale(AIS, Athens Insomnia Scale) on the first, second and third day after surgery. The AIS has a total of 8 items, with scores ranging from 0 to 24 points, and a total score of 6 points or higher indicates a diagnosis of insomnia. The investigators asked the patients to fill out this questionnaire after the first, second and third postoperative nights to evaluate the changes in sleep quality. The investigators recorded AIS scores as statistical indicators.	The first, second and third days after the surgery
Postoperative anxiety	Patients completed the anxiety rating scales (HADS-A, Hospital Anxiety and Depression Scale-Anxiety subscale) on the day before surgery. HADS-A consists of 7 items, each question in the questionnaire was scored on a scale of 0-3, and a total score of 8 points or higher is diagnosed as anxiety. And the investigators asked the patients to fill out this questionnaire on the 1-3 days after surgery again to evaluate the changes in anxiety. The investigators recorded HADS-A scores as statistical indicators	1 day before surgery ,1 -3 days after surgery
Postoperative depression	Patients completed the depression rating scales (HADS-D, Hospital Anxiety and Depression Scale-Depression subscale) on the day before surgery. HADS-D consists of 7 items, each question in the questionnaire was scored on a scale of 0-3, and a total score of 8 points or higher is diagnosed as depression. And the investigators asked the patients to fill out this questionnaire on the 1-3 days after surgery again to evaluate the changes in depression. The investigators recorded HADS-D scores as statistical indicators.	1 day before surgery ,1 -3 days after surgery
Pain Score (NRS)	The pain score at rest or after movement was evaluated by pain 11-point numerical rating scale (NRS): 0 = no pain, 10 = greatest imaginable pain.	1-3 days after surgery
5-D itch scale at 72 hours after surgery	The duration, severity, outcome trend, life impairment, and pruritus site (5-D) were used to evaluate the patient's pruritus. Each dimension was scored from 1 to 5, with a total score ranging from 5 to 25. The higher the score, the more severe the itching	72 hours after surgery
Liver function tests (LFTs)	Alanine Transaminase, ALT; Aspartate Aminotransferase, AST; Total Bilirubin, TBil; Direct Bilirubin, DBIL; Alkaline phosphatase, ALP; Gamma-glutamyltransferase, GGT	Preoperative baseline and postoperative day one
Postoperative Complications	Nausea and vomiting; Dizziness; Nightmare; Respiratory depression; hallucinations	Within 72 hours postoperatively

Collaborators and Investigators

• Sponsor: Tianjin Medical University General Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): August 15, 2026
• Primary Completion (Estimated): April 20, 2027
• Study Completion (Estimated): April 20, 2027

Study Registration Dates

• First Submitted: April 14, 2026
• First Submitted That Met QC Criteria: August 11, 2026
• First Posted (Actual): August 12, 2026

Study Record Updates

• Last Update Posted (Actual): August 12, 2026
• Last Update Submitted That Met QC Criteria: August 11, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: esketamine; cholestatic pruritus
• Additional Relevant MeSH Terms: Pharmaceutical Preparations; Crystalloid Solutions; Isotonic Solutions; Solutions; Esketamine; Saline Solution
• Other Study ID Numbers: IRB2025-YX-497-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No