Effects of Esketamine on Acute Abdominal Pain After TACE in Patients With Hepatocellular Carcinoma

Effects of Esketamine on Acute Abdominal Pain After TACE in Patients With Hepatocellular Carcinoma:a Prospective Study TACE(Transcatheter Arterial Chemoembolization)

Pain is the main complication after TACE(Transcatheter Arterial Chemoembolization) for hepatocellular carcinoma, and its pathogenesis is not clear.The pain may be related to partial liver tissue swelling after blocking the tumor blood supply artery embolization agent, transient hepatic swelling causing tension or strain on the liver capsule, and chemical irritation by the anticancer drug-Lipiodol mixture,the inadvertent embolization of normal organs and individual sensitivity to pain. Ketamine produces anesthetic and analgesic effects mainly by inhibiting NMDA receptor(N-methyl-D-aspartic acid receptor), and previous studies have shown that low concentrations of ketamine have obvious analgesic effects. Not only that, ketamine also produces analgesic effects by inhibiting opioid receptors via G-protein coupling. In addition, ketamine can bind to monoaminergic receptors in the central and peripheral nervous system, showing an anticholinergic effect and producing an antispasmodic effect. Ketamine also inhibits inflammatory pain by reducing nitric oxide production by inhibiting nitric oxide synthase. Esketamine is about three to four times more potent than ketamine. Therefore,esketamine requires a lower dose, about half the dose of ketamine, to produce anesthetic and analgesic effects, with fewer side effects.

Study Overview

• Status: Recruiting
• Conditions: Pain; Hepatocellular Carcinoma; Transcatheter Arterial Chemoembolization
• Intervention / Treatment: Drug: Esketamine; Drug: Sufentanil

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Chongqing
    • Chongqing, Chongqing, China, 400010
      • Recruiting
      • The Second Affiliated Hospital, Chongqing Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 18 to 80
• Participate in this study and sign informed consent
• Voluntarily receive preoperative intravenous analgesia
• Patients receiving TACE treatment
• HCC (hepatocellular carcinoma)patients with primary liver cancer BCLC(Barcelona Clinic Liver Cancer) stage A-C, liver function A-B

Exclusion Criteria:

• Patients who were unable to cooperate or refused to participate in the trial
• Pregnant women
• Patients with or having a history of serious mental disorders
• Patients with poorly controlled or untreated hypertension (arterial hypertension, resting systolic / diastolic blood pressure more than 180/100mg)
• Patients with unstable angina pectoris or myocardial infarction within 6 months or congestive heart failure
• Patients with intracranial hypertension or glaucoma
• Patients with hyperthyroidism without treatment or insufficient treatment
• Patients with severe respiratory dysfunction
• Allergy or existing contraindication to chemotherapeutic drugs, opioids or ketamine drugs

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Esketamine-PCIA(patient controlled intravenous analgesia); PCIA formula#100ml analgesic solution was prepared by adding 2.5 mg/kg Esketamine and 8mg ondansetron into normal saline.	Drug: Esketamine; PCIA formula#100ml analgesic solution was prepared by adding 2.5 mg/kg Esketamine and 8mg ondansetron into normal saline. 30min before TACE treatment, the first dose of 2ml was slowly injected intravenously. No obvious adverse reactions were observed for 10min.The PCIA pump was commenced at the beginning of TACE. Parameter setting of intravenous analgesia pump: the total volume is 100ml; The duration is 2ml / h; The single dose is 2ml each time; The limit quantity is 10ml / h; The locking time was 10min and the analgesia lasted for 48h. The target value of analgesia in this study was NRS (Numerical Rating Scale)< 4; If NRS ≥ 4, when the effect is still poor after adding drugs by pressing the analgesic pump, the investigators will give the remedial drug(dolantin 50mg im st) according to the patient's condition.; Other Names: patient controlled intravenous analgesia
Active Comparator: Sufentanil-PCIA(patient controlled intravenous analgesia); PCIA formula#100ml analgesic solution was prepared by adding 2 μ g/kg sufentanil and 8mg ondansetron into normal saline.	Drug: Sufentanil; PCIA formula#100ml analgesic solution was prepared by adding 2 μ g/kg sufentanil and 8mg ondansetron into normal saline. 30min before TACE treatment, the first dose of 2ml was slowly injected intravenously.No obvious adverse reactions were observed for 10min. The PCIA pump was commenced at the beginning of TACE. Parameter setting of intravenous analgesia pump: the total volume is 100ml; The duration is 2ml / h; The single dose is 2ml each time; The limit quantity is 10ml / h; The locking time was 10min and the analgesia lasted for 48h. The target value of analgesia in this study was NRS (Numerical Rating Scale)< 4; If NRS ≥ 4, when the effect is still poor after adding drugs by pressing the analgesic pump, the investigators will give the remedial drug(dolantin 50mg im st) according to the patient's condition.; Other Names: patient controlled intravenous analgesia

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain Intensity at 4hours after the beginning of TACE operation	Pain intensity is assessed by numerical rating scale pain scores(0-10,0 represents painless,10 represents intolerable pain;higher scores mean a worse outcome)	From 0 to 4hours after the beginning of TACE
Pain Intensity at 8hours after the beginning of TACE operation	Pain intensity is assessed by numerical rating scale pain scores(0-10,0 represents painless,10 represents intolerable pain;higher scores mean a worse outcome)	From 4hours to 8hours after the beginning of TACE operation
Pain Intensity at 12hours after the beginning of TACE operation	Pain intensity is assessed by numerical rating scale pain scores(0-10,0 represents painless,10 represents intolerable pain;higher scores mean a worse outcome)	From 8hours to 12hours after the beginning of TACE operation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain Intensity at 18hours after the beginning of TACE operation	Pain intensity is assessed by numerical rating scale pain scores(0-10,0 represents painless,10 represents intolerable pain;higher scores mean a worse outcome)	From 12hours to 18hours after the beginning of TACE operation
Pain Intensity at 24hours after the beginning of TACE operation	Pain intensity is assessed by numerical rating scale pain scores(0-10,0 represents painless,10 represents intolerable pain;higher scores mean a worse outcome)	From 18hours to 24hours after the beginning of TACE operation
Pain Intensity at 30hours after the beginning of TACE operation	Pain intensity is assessed by numerical rating scale pain scores(0-10,0 represents painless,10 represents intolerable pain;higher scores mean a worse outcome)	From 24hours to 30hours after the beginning of TACE operation
Pain Intensity at 36hours after the beginning of TACE operation	Pain intensity is assessed by numerical rating scale pain scores(0-10,0 represents painless,10 represents intolerable pain;higher scores mean a worse outcome)	From 30hours to 36hours after the beginning of TACE operation
Pain Intensity at 42hours after the beginning of TACE operation	Pain intensity is assessed by numerical rating scale pain scores(0-10,0 represents painless,10 represents intolerable pain;higher scores mean a worse outcome)	From 36hours to 42hours after the beginning of TACE operation
Pain Intensity at 48hours after the beginning of TACE operation	Pain intensity is assessed by numerical rating scale pain scores(0-10,0 represents painless,10 represents intolerable pain;higher scores mean a worse outcome)	From 42hours to 48hours after the beginning of TACE operation
Maximum Pain Intensity in the First 4hours after the beginning of TACE operation	Pain intensity is assessed by numerical rating scale pain scores(0-10,0 represents painless,10 represents intolerable pain;higher scores mean a worse outcome)	From the beginning of TACE operation to 4hours after the beginning of TACE operation
Maximum Pain Intensity in the Second 4hours after the beginning of TACE operation	Pain intensity is assessed by numerical rating scale pain scores(0-10,0 represents painless,10 represents intolerable pain;higher scores mean a worse outcome)	From 4hours to 8hours after the beginning of TACE operation
Maximum Pain Intensity in the Third 4hours after the beginning of TACE operation	Pain intensity is assessed by numerical rating scale pain scores(0-10,0 represents painless,10 represents intolerable pain;higher scores mean a worse outcome)	From 8hours to 12hours after the beginning of TACE operation
Analgesic Consumption	Analgesic consumption is assessed by the total amount of pain remedy with dolantin when the analgesic effect is poor.	From 0 to 48 hours after the beginning of TACE operation

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ramsay Sedation Score at 1 hour after the beginning of TACE operation	Grade 1 (soberness- the patient is anxious, uneasy or irritable)# Grade 2 (soberness- the patient is cooperative, has good orientation or is quiet)# Grade 3 (soberness- the patient only responds to commands)# Grade 4 (sleep-the patient responds quickly to light tapping between eyebrows or strong sound stimulation)# Grade 5 (sleep-the patient responds slowly to light tapping between the eyebrows or strong sound stimulation) and Grade 6 (sleep-the patient has no response to light tapping between eyebrows or strong sound stimulation). Grade 1 indicates no sedation ; Grade 2 and 3 indicate good sedation ; Grade 4 to 6 indicate poor sedation.	From 0 to 1hour after the beginning of TACE operation
Ramsay Sedation Score at 2 hours after the beginning of TACE operation	Grade 1 (soberness- the patient is anxious, uneasy or irritable)# Grade 2 (soberness- the patient is cooperative, has good orientation or is quiet)# Grade 3 (soberness- the patient only responds to commands)# Grade 4 (sleep-the patient responds quickly to light tapping between eyebrows or strong sound stimulation)# Grade 5 (sleep-the patient responds slowly to light tapping between the eyebrows or strong sound stimulation) and Grade 6 (sleep-the patient has no response to light tapping between eyebrows or strong sound stimulation). Grade 1 indicates no sedation ; Grade 2 and 3 indicate good sedation ; Grade 4 to 6 indicate poor sedation.	From 1hour to 2hours after the beginning of TACE operation
Ramsay Sedation Score at 3 hours after the beginning of TACE operation	Grade 1 (soberness- the patient is anxious, uneasy or irritable)# Grade 2 (soberness- the patient is cooperative, has good orientation or is quiet)# Grade 3 (soberness- the patient only responds to commands)# Grade 4 (sleep-the patient responds quickly to light tapping between eyebrows or strong sound stimulation)# Grade 5 (sleep-the patient responds slowly to light tapping between the eyebrows or strong sound stimulation) and Grade 6 (sleep-the patient has no response to light tapping between eyebrows or strong sound stimulation). Grade 1 indicates no sedation ; Grade 2 and 3 indicate good sedation ; Grade 4 to 6 indicate poor sedation.	From 2hours to 3hours after the beginning of TACE operation
The Quality of Sleep on the Day Just before TACE Treatment	The Richards-Campbell Sleep Questionnaire (RCSQ) is assessed by the quality of patients' sleep quality.0~25 points indicate poor sleep quality;76~100 points indicate good sleep quality (0-100, 0 represents the worst sleep quality; 100 represents the best sleep quality ;higher scores mean a better outcome)	From the day just before TACE treatment to the operation day
The Quality of Sleep on the Operation Day	The Richards-Campbell Sleep Questionnaire (RCSQ) is assessed by the quality of patients' sleep quality.0~25 points indicate poor sleep quality;76~100 points indicate good sleep quality (0-100, 0 represents the worst sleep quality; 100 represents the best sleep quality ;higher scores mean a better outcome)	From the operation day to first day after TACE treatment
The Quality of Sleep on the First Day after TACE Treatment	The Richards-Campbell Sleep Questionnaire (RCSQ) is assessed by the quality of patients' sleep quality.0~25 points indicate poor sleep quality;76~100 points indicate good sleep quality (0-100, 0 represents the worst sleep quality; 100 represents the best sleep quality ;higher scores mean a better outcome)	From the first day after TACE treatment to the second day after TACE treatment
Degree of Satisfaction	Degree of satisfaction is assessed by patient using numerical rating scale (0-10, 0 represents unsatisfactory; 10 represents complete satisfaction;higher scores mean a better outcome)	From 0 to 24 hours after the beginning of TACE operation
Quality-of-Life Assessment at the the beginning of TACE operation	Quality-of-life contains patients' quality of sleep，fatigue, spiritual well-being, and appetite.The scores were categorized as follows: 1，worst；2，bad；3， mild；4， normal；5，very good.	From the beginning of TACE operation to 0 hour after the beginning of TACE operation
Quality-of-Life Assessment at 24hours after the beginning of TACE operation	Quality-of-life contains patients' quality of sleep，fatigue, spiritual well-being, and appetite.The scores were categorized as follows: 1，worst；2，bad；3， mild；4， normal；5，very good.	From 0 to 24 hours after the beginning of TACE operation
Adverse Reaction	Adverse reaction is recorded according to follow-up visits after TACE treatment	From 0 to 48 hours after the beginning of TACE operation

Collaborators and Investigators

• Sponsor: The Second Affiliated Hospital of Chongqing Medical University

Study record dates

Study Major Dates

• Study Start (Actual): January 5, 2023
• Primary Completion (Anticipated): June 30, 2023
• Study Completion (Anticipated): July 30, 2023

Study Registration Dates

• First Submitted: January 2, 2023
• First Submitted That Met QC Criteria: January 2, 2023
• First Posted (Actual): January 4, 2023

Study Record Updates

• Last Update Posted (Actual): March 29, 2023
• Last Update Submitted That Met QC Criteria: March 28, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Pain; Neurologic Manifestations; Signs and Symptoms, Digestive; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Abdominal Pain; Abdomen, Acute; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Analgesics, Opioid; Narcotics; Psychotropic Drugs; Antidepressive Agents; Adjuvants, Anesthesia; Esketamine; Sufentanil
• Other Study ID Numbers: pain after TACE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The individual participant data for this study is available from the sponsor on reasonable request through email.
• IPD Sharing Access Criteria: Within one year
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

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