Effect of Esketamine on Abdominal Pain During TACE-HAIC in Patients With Hepatocellular Carcinoma (TACE-HAIC)

Effect of Esketamine on Abdominal Pain During TACE-HAIC in Patients With Hepatocellular Carcinoma: a Prospective Study TACE-HAIC (Transcatheter Arterial Chemoembolization Combined With Hepatic Artery Infusion Chemotherapy )

Previous studies have confirmed that limb pain caused by oxaliplatin chemotherapy is related to spinal cord central sensitization - induced hyperalgesia through oxaliplatin activating spinal cord NMDA receptor(N-methyl-D-aspartic acid receptor). The investigators speculate that this may be the same as the mechanism of severe abdominal pain caused by HAIC(Hepatic Artery Infusion Chemotherapy) during oxaliplatin infusion. The analgesic effect of Esketamine is mainly related to its inhibition of NMDA receptor in spinal cord. Therefore, this study hypothesized that Esketamine can inhibit the sensitization of spinal cord center by inhibiting NMDA receptor, so as to alleviate severe abdominal pain during HAIC perfusion, and reduce abdominal pain caused by ischemia and inflammation by TACE(transcatheter arterial chemoembolization) by improving organ perfusion and anti-inflammatory effect, Therefore, it is expected that Esketamine can better alleviate acute severe abdominal pain caused by TACE-HAIC (transcatheter arterial chemoembolization combined with Hepatic Artery Infusion Chemotherapy )treatment than sufentanil, decrease the dosage of opioids, and reduce the incidence and degree of chronic abdominal pain after treatment.

Hepatocellular Carcinoma, Transarterial Chemoembolization, Hepatic Arterial Infusion Chemotherapy, Pain

PCIA formula：100ml analgesic solution was prepared by adding 2.5 mg/kg Esketamine and 8mg ondansetron into normal saline.

PCIA formula：100ml analgesic solution was prepared by adding 2 μ g/kg sufentanil and 8mg ondansetron into normal saline.

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. After that, the intravenous analgesia pump was started. 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.

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. After that, the intravenous analgesia pump was started. 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.

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)

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)

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)

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)

Analgesic consumption is assessed by the total amount of pain remedy with dolantin when the analgesic effect is poor after pressing analgesic pump for 3 times or more

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)

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)

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)

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)

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)

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)

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)

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)

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)

Ramsay Sedation score is assessed by: 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.

Ramsay Sedation score is assessed by: 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.

Ramsay Sedation score is assessed by: 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.

Ramsay Sedation score is assessed by: 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.

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)

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)

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)

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)

Inclusion Criteria: Participate in this study and sign informed consent Voluntarily receive postoperative intravenous controlled analgesia Patients receiving TACE-HAIC treatment HCC (hepatocellular carcinoma)patients with primary liver cancer BCLC(Barcelona Clinic Liver Cancer) stage B and C, liver function A Age 18 to 80 Exclusion Criteria: Patients who were unable to cooperate or refused to participate in the trial Pregnant women Patients with sensory abnormalities such as diabetes neuropathy 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 Can not follow with the study procedure

The individual participant data for this study is available from the sponsor on reasonable request through email.