Evaluation Of The Influence Of Anesthetic Interventions On The Evolution Of Hepatic Neoplastic Processes
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 153
- 试验地点
- 2
- 主要终点
- Survival outcomes after hepatocellular carcinoma resection.
研究概览
简要总结
Evaluation Of The Influence Of Anesthetic Interventions On The Evolution Of Hepatic Neoplastic Processes
The goal of this clinical trial is to evaluate of the involvement of Neutrophil extracellular traps in the evolution of hepatocellular cancer. The main questions it aims to answer are:
- How does the type of anesthesia used in hepatobiliary oncological surgery influence postoperative evolution and the immune response?
- How does the type of anesthesia, TIVA versus inhalational influence the generation of neutrophil extracellular traps (NETs)? Researchers will compare the evolution of the patients assigned to 4 study groups depending on the anesthetic intervention performed.
Participants will:
- will be evaluated pre and postanesthesia, blood samples will be collected for analysis of the inflammatory response
- will be followed up one year for establishing the outcome
详细描述
Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality worldwide, with rising incidence in the context of chronic liver disease, viral hepatitis, non-alcoholic fatty liver disease, and cirrhosis. Surgical resection, whether curative or cytoreductive, is a cornerstone of management in selected patients with HCC or secondary hepatic malignancies. However, accumulating evidence highlights that perioperative factors, especially those related to anesthetic management may influence not only immediate postoperative recovery but also long-term oncologic outcomes. Debates persist regarding the optimal anesthesia for oncologic patients. While some studies favored total intravenous anesthesia (TIVA), recent retrospective studies show no significant difference between inhalational and intravenous techniques. However, adjunct therapies, such as perioperative lidocaine, may influence recurrence and outcomes.
Recent investigations into cancer biology have emphasized the role of systemic inflammation, immune dysregulation, and neutrophil behavior in promoting tumor progression, immune escape, and metastatic dissemination. A novel contributor to this inflammatory pro-tumorigenic environment is NETosis, the formation of neutrophil extracellular traps (NETs). NETs are composed of chromatin fibers (e.g., MPO, elastase, citrullinated histones), which, beyond their physiological role in infection containment, are increasingly implicated in cancer-related processes such as angiogenesis, tumor invasion, thrombosis, and immune suppression.
Research goal The aim of the study is to evaluate the involvement of NETosis in the progression of hepatocellular carcinoma.
Main objective:
To assess the influence of the type of anesthesia used in hepatobiliary oncologic surgery on postoperative evolution and immune response.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
盲法说明
The laboratory physician who processed the samples was blinded to the group assignment of each sample.
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosed with: hepatocellular carcinoma, or hepatic metastases
- •Scheduled for elective liver surgery:
排除标准
- •Undergoing emergency surgery
- •Barcelona-Clinic Liver Cancer stage C;
- •Child-Pugh Class C
- •Receiving chronic immunosuppressive therapy
- •Having contraindications to any of the study medications
- •Diagnosed with psychiatric disorders, such as: depression, bipolar disorder, schizophrenia, having autoimmune diseases
- •Suffering from corticosteroid-dependent bronchial asthma
- •Diagnosed with congenital or acquired coagulation disorders
研究组 & 干预措施
Hepatocellular carcinoma (HCC) resection performed under total intravenous anesthesia (TIVA)
Patients will receive total intravenous anesthesia (TIVA) with 1% propofol, administered using the Schneider pharmacokinetic model. The initial target effect-site concentration will be 4 µg/mL, titrated intraoperatively to maintain a BIS value between 40 and 59.
干预措施: Anesthesia (Procedure)
Hepatocellular carcinoma (HCC) resection performed under total intravenous anesthesia (TIVA)
Patients will receive total intravenous anesthesia (TIVA) with 1% propofol, administered using the Schneider pharmacokinetic model. The initial target effect-site concentration will be 4 µg/mL, titrated intraoperatively to maintain a BIS value between 40 and 59.
干预措施: Anesthesia induction with TCI (Procedure)
HCC resection performed under sevoflurane anesthesia + Lidocaine infusion
Patients in this group will receive sevoflurane-based general anesthesia. Anesthesia will be maintained with sevoflurane at an end-tidal concentration of 1.0-1.5 MAC, titrated in increments or decrements of 0.25-0.5 MAC based on BIS monitoring (target range 40-59). A 1.5 mg/kg intravenous bolus of 1% lidocaine will be administered at induction, followed by a continuous intravenous infusion of 1% lidocaine at 2 mg/kg/hour, not exceeding 200 mg/hour, until emergence from anesthesia.
干预措施: Intraoperative mechanical ventilation (Procedure)
Hepatocellular carcinoma (HCC) resection performed under total intravenous anesthesia (TIVA)
Patients will receive total intravenous anesthesia (TIVA) with 1% propofol, administered using the Schneider pharmacokinetic model. The initial target effect-site concentration will be 4 µg/mL, titrated intraoperatively to maintain a BIS value between 40 and 59.
干预措施: Intraoperative analgesia (Drug)
Hepatocellular carcinoma (HCC) resection performed under total intravenous anesthesia (TIVA)
Patients will receive total intravenous anesthesia (TIVA) with 1% propofol, administered using the Schneider pharmacokinetic model. The initial target effect-site concentration will be 4 µg/mL, titrated intraoperatively to maintain a BIS value between 40 and 59.
干预措施: Non-opioid analgesics (Drug)
Hepatocellular carcinoma (HCC) resection performed under total intravenous anesthesia (TIVA)
Patients will receive total intravenous anesthesia (TIVA) with 1% propofol, administered using the Schneider pharmacokinetic model. The initial target effect-site concentration will be 4 µg/mL, titrated intraoperatively to maintain a BIS value between 40 and 59.
干预措施: Bispectral Index (BIS) (Device)
Hepatocellular carcinoma (HCC) resection performed under total intravenous anesthesia (TIVA)
Patients will receive total intravenous anesthesia (TIVA) with 1% propofol, administered using the Schneider pharmacokinetic model. The initial target effect-site concentration will be 4 µg/mL, titrated intraoperatively to maintain a BIS value between 40 and 59.
干预措施: Intraoperative mechanical ventilation (Procedure)
Hepatocellular carcinoma (HCC) resection performed under total intravenous anesthesia (TIVA)
Patients will receive total intravenous anesthesia (TIVA) with 1% propofol, administered using the Schneider pharmacokinetic model. The initial target effect-site concentration will be 4 µg/mL, titrated intraoperatively to maintain a BIS value between 40 and 59.
干预措施: Blood sampling (Procedure)
HCC resection performed under sevoflurane anesthesia
Patients will receive volatile anesthesia with sevoflurane, maintained at an end-tidal concentration (EtSevo) corresponding to 1.0-1.5 MAC. The concentration will be adjusted in increments or decrements of 0.25-0.5 MAC to maintain a BIS value between 40 and 59.
干预措施: Anesthesia (Procedure)
HCC resection performed under sevoflurane anesthesia
Patients will receive volatile anesthesia with sevoflurane, maintained at an end-tidal concentration (EtSevo) corresponding to 1.0-1.5 MAC. The concentration will be adjusted in increments or decrements of 0.25-0.5 MAC to maintain a BIS value between 40 and 59.
干预措施: Intraoperative analgesia (Drug)
HCC resection performed under sevoflurane anesthesia
Patients will receive volatile anesthesia with sevoflurane, maintained at an end-tidal concentration (EtSevo) corresponding to 1.0-1.5 MAC. The concentration will be adjusted in increments or decrements of 0.25-0.5 MAC to maintain a BIS value between 40 and 59.
干预措施: Non-opioid analgesics (Drug)
HCC resection performed under sevoflurane anesthesia
Patients will receive volatile anesthesia with sevoflurane, maintained at an end-tidal concentration (EtSevo) corresponding to 1.0-1.5 MAC. The concentration will be adjusted in increments or decrements of 0.25-0.5 MAC to maintain a BIS value between 40 and 59.
干预措施: sevoflurane anesthesia (Procedure)
HCC resection performed under sevoflurane anesthesia
Patients will receive volatile anesthesia with sevoflurane, maintained at an end-tidal concentration (EtSevo) corresponding to 1.0-1.5 MAC. The concentration will be adjusted in increments or decrements of 0.25-0.5 MAC to maintain a BIS value between 40 and 59.
干预措施: Bispectral Index (BIS) (Device)
HCC resection performed under sevoflurane anesthesia
Patients will receive volatile anesthesia with sevoflurane, maintained at an end-tidal concentration (EtSevo) corresponding to 1.0-1.5 MAC. The concentration will be adjusted in increments or decrements of 0.25-0.5 MAC to maintain a BIS value between 40 and 59.
干预措施: Intraoperative mechanical ventilation (Procedure)
HCC resection performed under sevoflurane anesthesia
Patients will receive volatile anesthesia with sevoflurane, maintained at an end-tidal concentration (EtSevo) corresponding to 1.0-1.5 MAC. The concentration will be adjusted in increments or decrements of 0.25-0.5 MAC to maintain a BIS value between 40 and 59.
干预措施: Blood sampling (Procedure)
HCC resection performed under TIVA + Lidocaine infusion
Patients in this group will receive TIVA with 1% propofol administered via TCI using the Schneider pharmacokinetic model. A 1.5 mg/kg intravenous bolus of 1% lidocaine will be administered at induction. Following intubation, a continuous infusion of 1% lidocaine at 1 mg/kg/hour will be maintained until emergence from anesthesia, not exceeding a maximum dose of 200 mg/hour.
干预措施: Anesthesia (Procedure)
HCC resection performed under TIVA + Lidocaine infusion
Patients in this group will receive TIVA with 1% propofol administered via TCI using the Schneider pharmacokinetic model. A 1.5 mg/kg intravenous bolus of 1% lidocaine will be administered at induction. Following intubation, a continuous infusion of 1% lidocaine at 1 mg/kg/hour will be maintained until emergence from anesthesia, not exceeding a maximum dose of 200 mg/hour.
干预措施: Anesthesia induction with TCI (Procedure)
HCC resection performed under TIVA + Lidocaine infusion
Patients in this group will receive TIVA with 1% propofol administered via TCI using the Schneider pharmacokinetic model. A 1.5 mg/kg intravenous bolus of 1% lidocaine will be administered at induction. Following intubation, a continuous infusion of 1% lidocaine at 1 mg/kg/hour will be maintained until emergence from anesthesia, not exceeding a maximum dose of 200 mg/hour.
干预措施: Intraoperative analgesia (Drug)
HCC resection performed under TIVA + Lidocaine infusion
Patients in this group will receive TIVA with 1% propofol administered via TCI using the Schneider pharmacokinetic model. A 1.5 mg/kg intravenous bolus of 1% lidocaine will be administered at induction. Following intubation, a continuous infusion of 1% lidocaine at 1 mg/kg/hour will be maintained until emergence from anesthesia, not exceeding a maximum dose of 200 mg/hour.
干预措施: Non-opioid analgesics (Drug)
HCC resection performed under TIVA + Lidocaine infusion
Patients in this group will receive TIVA with 1% propofol administered via TCI using the Schneider pharmacokinetic model. A 1.5 mg/kg intravenous bolus of 1% lidocaine will be administered at induction. Following intubation, a continuous infusion of 1% lidocaine at 1 mg/kg/hour will be maintained until emergence from anesthesia, not exceeding a maximum dose of 200 mg/hour.
干预措施: Bispectral Index (BIS) (Device)
HCC resection performed under TIVA + Lidocaine infusion
Patients in this group will receive TIVA with 1% propofol administered via TCI using the Schneider pharmacokinetic model. A 1.5 mg/kg intravenous bolus of 1% lidocaine will be administered at induction. Following intubation, a continuous infusion of 1% lidocaine at 1 mg/kg/hour will be maintained until emergence from anesthesia, not exceeding a maximum dose of 200 mg/hour.
干预措施: Intraoperative mechanical ventilation (Procedure)
HCC resection performed under TIVA + Lidocaine infusion
Patients in this group will receive TIVA with 1% propofol administered via TCI using the Schneider pharmacokinetic model. A 1.5 mg/kg intravenous bolus of 1% lidocaine will be administered at induction. Following intubation, a continuous infusion of 1% lidocaine at 1 mg/kg/hour will be maintained until emergence from anesthesia, not exceeding a maximum dose of 200 mg/hour.
干预措施: Blood sampling (Procedure)
HCC resection performed under sevoflurane anesthesia + Lidocaine infusion
Patients in this group will receive sevoflurane-based general anesthesia. Anesthesia will be maintained with sevoflurane at an end-tidal concentration of 1.0-1.5 MAC, titrated in increments or decrements of 0.25-0.5 MAC based on BIS monitoring (target range 40-59). A 1.5 mg/kg intravenous bolus of 1% lidocaine will be administered at induction, followed by a continuous intravenous infusion of 1% lidocaine at 2 mg/kg/hour, not exceeding 200 mg/hour, until emergence from anesthesia.
干预措施: Anesthesia (Procedure)
HCC resection performed under sevoflurane anesthesia + Lidocaine infusion
Patients in this group will receive sevoflurane-based general anesthesia. Anesthesia will be maintained with sevoflurane at an end-tidal concentration of 1.0-1.5 MAC, titrated in increments or decrements of 0.25-0.5 MAC based on BIS monitoring (target range 40-59). A 1.5 mg/kg intravenous bolus of 1% lidocaine will be administered at induction, followed by a continuous intravenous infusion of 1% lidocaine at 2 mg/kg/hour, not exceeding 200 mg/hour, until emergence from anesthesia.
干预措施: Intraoperative analgesia (Drug)
HCC resection performed under sevoflurane anesthesia + Lidocaine infusion
Patients in this group will receive sevoflurane-based general anesthesia. Anesthesia will be maintained with sevoflurane at an end-tidal concentration of 1.0-1.5 MAC, titrated in increments or decrements of 0.25-0.5 MAC based on BIS monitoring (target range 40-59). A 1.5 mg/kg intravenous bolus of 1% lidocaine will be administered at induction, followed by a continuous intravenous infusion of 1% lidocaine at 2 mg/kg/hour, not exceeding 200 mg/hour, until emergence from anesthesia.
干预措施: Non-opioid analgesics (Drug)
HCC resection performed under sevoflurane anesthesia + Lidocaine infusion
Patients in this group will receive sevoflurane-based general anesthesia. Anesthesia will be maintained with sevoflurane at an end-tidal concentration of 1.0-1.5 MAC, titrated in increments or decrements of 0.25-0.5 MAC based on BIS monitoring (target range 40-59). A 1.5 mg/kg intravenous bolus of 1% lidocaine will be administered at induction, followed by a continuous intravenous infusion of 1% lidocaine at 2 mg/kg/hour, not exceeding 200 mg/hour, until emergence from anesthesia.
干预措施: Bispectral Index (BIS) (Device)
HCC resection performed under sevoflurane anesthesia + Lidocaine infusion
Patients in this group will receive sevoflurane-based general anesthesia. Anesthesia will be maintained with sevoflurane at an end-tidal concentration of 1.0-1.5 MAC, titrated in increments or decrements of 0.25-0.5 MAC based on BIS monitoring (target range 40-59). A 1.5 mg/kg intravenous bolus of 1% lidocaine will be administered at induction, followed by a continuous intravenous infusion of 1% lidocaine at 2 mg/kg/hour, not exceeding 200 mg/hour, until emergence from anesthesia.
干预措施: Blood sampling (Procedure)
Hepatocellular carcinoma (HCC) resection performed under total intravenous anesthesia (TIVA)
Patients will receive total intravenous anesthesia (TIVA) with 1% propofol, administered using the Schneider pharmacokinetic model. The initial target effect-site concentration will be 4 µg/mL, titrated intraoperatively to maintain a BIS value between 40 and 59.
干预措施: Morphine (+) (Drug)
HCC resection performed under sevoflurane anesthesia
Patients will receive volatile anesthesia with sevoflurane, maintained at an end-tidal concentration (EtSevo) corresponding to 1.0-1.5 MAC. The concentration will be adjusted in increments or decrements of 0.25-0.5 MAC to maintain a BIS value between 40 and 59.
干预措施: Morphine (+) (Drug)
HCC resection performed under TIVA + Lidocaine infusion
Patients in this group will receive TIVA with 1% propofol administered via TCI using the Schneider pharmacokinetic model. A 1.5 mg/kg intravenous bolus of 1% lidocaine will be administered at induction. Following intubation, a continuous infusion of 1% lidocaine at 1 mg/kg/hour will be maintained until emergence from anesthesia, not exceeding a maximum dose of 200 mg/hour.
干预措施: Lidocaine Infusion (Drug)
HCC resection performed under TIVA + Lidocaine infusion
Patients in this group will receive TIVA with 1% propofol administered via TCI using the Schneider pharmacokinetic model. A 1.5 mg/kg intravenous bolus of 1% lidocaine will be administered at induction. Following intubation, a continuous infusion of 1% lidocaine at 1 mg/kg/hour will be maintained until emergence from anesthesia, not exceeding a maximum dose of 200 mg/hour.
干预措施: Morphine (+) (Drug)
HCC resection performed under sevoflurane anesthesia + Lidocaine infusion
Patients in this group will receive sevoflurane-based general anesthesia. Anesthesia will be maintained with sevoflurane at an end-tidal concentration of 1.0-1.5 MAC, titrated in increments or decrements of 0.25-0.5 MAC based on BIS monitoring (target range 40-59). A 1.5 mg/kg intravenous bolus of 1% lidocaine will be administered at induction, followed by a continuous intravenous infusion of 1% lidocaine at 2 mg/kg/hour, not exceeding 200 mg/hour, until emergence from anesthesia.
干预措施: sevoflurane anesthesia (Procedure)
HCC resection performed under sevoflurane anesthesia + Lidocaine infusion
Patients in this group will receive sevoflurane-based general anesthesia. Anesthesia will be maintained with sevoflurane at an end-tidal concentration of 1.0-1.5 MAC, titrated in increments or decrements of 0.25-0.5 MAC based on BIS monitoring (target range 40-59). A 1.5 mg/kg intravenous bolus of 1% lidocaine will be administered at induction, followed by a continuous intravenous infusion of 1% lidocaine at 2 mg/kg/hour, not exceeding 200 mg/hour, until emergence from anesthesia.
干预措施: Lidocaine Infusion (Drug)
HCC resection performed under sevoflurane anesthesia + Lidocaine infusion
Patients in this group will receive sevoflurane-based general anesthesia. Anesthesia will be maintained with sevoflurane at an end-tidal concentration of 1.0-1.5 MAC, titrated in increments or decrements of 0.25-0.5 MAC based on BIS monitoring (target range 40-59). A 1.5 mg/kg intravenous bolus of 1% lidocaine will be administered at induction, followed by a continuous intravenous infusion of 1% lidocaine at 2 mg/kg/hour, not exceeding 200 mg/hour, until emergence from anesthesia.
干预措施: Morphine (+) (Drug)
结局指标
主要结局
Survival outcomes after hepatocellular carcinoma resection.
时间窗: one year postoperatively
Patients will be followed for a period of one year to assess overall survival and progression-free survival. Follow-up will be conducted via direct contact, telephone, or e-mail. Information will be collected regarding the patient's general health status, disease progression, the presence and timing of tumor recurrence, as well as any hospitalizations occurring postoperatively, including the reason for medical consultation. Additionally, results from relevant investigations-such as computed tomography (CT), ultrasound, and blood tests-recommended by the treating surgeon or oncologist will be requested and reviewed.
NETosis quantification
时间窗: Preoperatively and after 6 hours postoperatively
For each patient, 10 mL of blood will be collected from a peripheral vein both preoperatively and 6 hours postoperatively to determine the concentrations of MPO-DNA (myeloperoxidase-DNA complexes), H3Cit (citrullinated histone H3), and cfDNA (cell-free DNA). These biomarkers are closely associated with the formation of neutrophil extracellular traps (NETs). We aim to analyze the potential relationship between the dynamics of NETosis formation, the duration of anesthesia, and postoperative patient outcomes.
次要结局
- Opioid use(In the first 24 hours postoperatively)
- Quantification of the inflammatory response(Preoperatively and at 6, 12, and 24 hours postoperatively)
- Length of hospital stay(From the immediate postoperative period until discharge)
研究者
Șargarovschi Sergiu
Assistant professor
Iuliu Hatieganu University of Medicine and Pharmacy