The First Affiliated Hospital of Xiamen University
Phase
Phase 1/2
Started
2025-06-29
Last updated
2025-09-11
Condition(s) studied
Hepatic NeoplasmHepatic Cancer
Investigational drug(s) / intervention(s)
Intravenous esketamine using Dixon's up-and-down sequential methodIntravenous the dose of esketamine ED95Intravenous fentanyl 1 μg∙kg-1
Intravenous esketamine using Dixon's up-and-down sequential method: Using Dixon's up-and-down sequential method, esketamine will be titrated intravenously from an initial 0.3 mg∙kg-1 dose with 0.02 mg∙kg-1 adjustments based on intraprocedural responses to pain (Positive: purposeful somatic movement or the complaint of pain; Negative: no movement or no complaint of pain). The titration sequence will continue until six crossover inflection points are observed.
Intravenous the dose of esketamine ED95: The intervention group will be injected with the dose of esketamine ED95.
Intravenous fentanyl 1 μg∙kg-1: The control group will be injected with fentanyl 1 μg∙kg-1.
Study summary
Effective pain management during percutaneous thermal ablation of liver tumors outside the operating room remains a significant challenge. While hepatic hilar nerve block (HHNB) provides partial analgesia, its incomplete efficacy often requires opioid supplementation, potentially increasing perioperative risks. Esketamine, an N-methyl-D-aspartate receptor antagonist, exhibits unique dual analgesic-sedative properties that may address this therapeutic gap, thus obviating the necessity for opioids. This prospective dose-finding study aimed to establish the median effective dose (ED50) and 95% effective dose (ED95) of esketamine for opioid-free analgesia during ultrasound-guided thermal ablation of liver tumors under HHNB. Afterwards, the investigators will conduct an RCT study to evaluate the safety of the dose of esketamine ED95 through the incidence of respiratory depression.
Eligibility
Sex
ALL
Min age
18 Years
Max age
80 Years
Healthy volunteers
No
Inclusion Criteria:
* Aged 18 - 80 years;
* ASA physical status Ⅰ or Ⅲ;
* Body mass index (BMI) 18 - 28 kg∙m-2;
* Scheduled for elective ultrasound-guided thermal ablation of solitary liver tumors under HHNB.
Exclusion Criteria:
(i) Pharmacological contraindications:
* Known hypersensitivity to study medications (esketamine, midazolam);
* Opioid or benzodiazepine dependence;
* Using analgesics within the last 24 h preoperatively;
* Participation in other investigational drug trials within 90 days. (ii) Clinical comorbidities and surgery history:
* Multifocal hepatic lesions requiring concurrent ablation;
* Patients after liver transplantation;
* Active upper respiratory tract infection within 14 days;
* Severe cardiopulmonary diseases (New York Heart Association \[NYHA\] class Ⅲ-Ⅳ, FEV1/FVC \< 70%);
* Decompensated hepatic insufficiency (Child-Pugh C);
* Uncontrolled hypertension (≥180/110 mmHg), elevated intracranial/intraocular pressure, or hyperthyroidism;
* Major neuropsychiatric disorders (epilepsy, schizophrenia, major depressive disorder, cognitive impairment).
(iii) Procedural Risk Factors:
* Anticipated difficult airway (Mallampati Ⅲ-Ⅳ, thyromental distance \< 6 cm) or anatomical airway obstruction;
* Inadequate preoperative fasting (solid intake \< 8 hours, clear fluids \< 2 hours).
Primary outcome measure(s)
thermal ablation-induced somatic responses to pain — Day 1 (During the surgery at the first stage of the research) Positive: Body movement or complaint of pain. Negative: No body movement or no reported pain. This scale will be administered during the surgery at the first stage of the research.
Incidence of respiratory depression — Day 1 (T2-T5 of the second stage of the research) By comparing with the control group, evaluate the safety of ED95 of esketamine by the incidence of respiratory depression at T2-T5 of the second stage of the research.
The primary outcome is the incidence of respiratory depression, which is defined as SpO2 \<90% or EtCO2 \>55 mmHg.
T2: 60 seconds after esketamine injection; T3: 5 minutes after HHNB; T4: During thermal ablation of liver tumors; and T5: In the PACU.
Trial sites (1)
Facility
City
Region
Status
Department of Anesthesiology, The First Affiliated Hospital of Xiamen University, 55 Zhenhai Road, Xiamen, China
Xiamen
Fujian
More The First Affiliated Hospital of Xiamen University trials in China
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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