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

Study Overview
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Brief Summary
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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.

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

Conditions
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Hepatocellular Carcinoma, Transcatheter Arterial Chemoembolization, Pain

Intervention / Treatment
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* Drug: Esketamine
* Drug: Sufentanil


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Esketamine-PCIA(patient controlled intravenous analgesia)<br>PCIA formula#100ml analgesic solution was prepared by adding 2.5 mg/kg Esketamine and 8mg ondansetron into normal saline. | Drug: Esketamine<br>* 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.<br>* Other names: patient controlled intravenous analgesia;|
| Active Comparator: Sufentanil-PCIA(patient controlled intravenous analgesia)<br>PCIA formula#100ml analgesic solution was prepared by adding 2 μ g/kg sufentanil and 8mg ondansetron into normal saline. | Drug: Sufentanil<br>* 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.<br>* Other names: patient controlled intravenous analgesia;|

What is the study measuring?
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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 |