Evaluation Of The Influence Of Anesthetic Interventions On The Evolution Of Hepatic Neoplastic Processes
- Conditions
- Hepato-cellular CarcinomaNeutrophil Extracellular Trap FormationAnesthesiaLidocaine Infusion
- Interventions
- Procedure: AnesthesiaProcedure: Anesthesia induction with TCIProcedure: sevoflurane anesthesiaDrug: Intraoperative analgesiaDrug: Non-opioid analgesicsDevice: Bispectral Index (BIS)Procedure: Intraoperative mechanical ventilationProcedure: Blood sampling
- Registration Number
- NCT07207304
- Lead Sponsor
- Iuliu Hatieganu University of Medicine and Pharmacy
- Brief Summary
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
- Detailed Description
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.
Secondary objective:
* To evaluate the impact of anesthesia type-TIVA versus inhalational-on NET formation.
* To assess the role of NETs in the progression of neoplastic disease and correlate their levels with clinical outcomes.
* To evaluate the effect of perioperative lidocaine administration on the generation of NETs.
Study type: prospective, interventional, longitudinal, randomized Methodology - presentation of work protocols
1. Logistical organization stage - ethics committee agreement; includes identification of laboratories and methods of collecting biological products (blood) for plasma concentration measurements, study-specific forms (informed consent form, data culture form)
2. Patient Enrollment Phase and Completion of Study Groups:
2.1 Formation of four study groups, each around of 50 patients diagnosed with hepatocellular carcinoma or hepatic metastases, according to the type of anesthesia administered during surgery: Group 1 - TIVA (propofol) + lidocaine Group 2 - TIVA (propofol) + placebo Group 3 - Sevoflurane + lidocaine Group 4 - Sevoflurane + placebo
2.2 Inclusion Criteria: Patients eligible for the study are those aged between 18 and 80 years, diagnosed with hepatocellular carcinoma or hepatic metastases, and scheduled for elective surgery (hepatectomy or metastasectomy).
2.3 Exclusion Criteria: The following patients will be excluded from the study: those undergoing emergency surgery; patients on chronic immunosuppressive therapy; individuals with contraindications to any of the study medications; patients with psychiatric disorders (depression, bipolar disorder, schizophrenia); individuals with autoimmune diseases or corticosteroid-dependent bronchial asthma; patients with congenital or acquired coagulation disorders; chronic users of anticoagulants and/or antiplatelet agents; HIV-positive patients; pregnant women; and those receiving antiarrhythmic therapy (verapamil, propafenone, amiodarone) that may interfere with lidocaine's antiarrhythmic action.
3. Biological Sample Analysis for NETosis Quantification To quantify NETosis (which cannot be measured directly), surrogate biomarkers will be used that correlate reliably with NET formation. Promising markers include MPO-DNA complexes, cell-free DNA (cfDNA), and citrullinated histone H3 (H3Cit), all of which reflect the extent of NET generation.
4. Patient Follow-Up Patients will be followed for one year to assess overall survival and progression-free survival. Follow-up methods will include direct contact, telephone, and email. Data will be collected regarding general health status, disease progression, timing and presence of tumor recurrence, and any hospitalizations occurring after the surgical intervention along with the reasons for medical visits. Results of follow-up investigations (CT, ultrasound, and laboratory tests) requested by the attending surgeon or oncologist will be collected.
5. Data Processing and Study Completion
5.1 Analysis of H3Cit, MPO-DNA, and cfDNA concentrations in correlation with the type of anesthesia and surgical technique used.
5.2 Evaluation of associations between conventional inflammatory markers and progression of hepatocellular carcinoma or hepatic metastases.
5.3 Determination of the type of correlation between inflammatory markers and NETosis.
5.4 Comparison of plasma concentrations of local anesthetics with values reported in the literature (where antineoplastic effects were observed).
5.5 Statistical analysis and establishment of correlations between the local anesthetic used and cancer recurrence.
Brief Description of Study Procedures This is a prospective, randomized, interventional, single-center clinical trial including patients with hepatocellular carcinoma or hepatic metastases undergoing elective surgery. Tumor staging will be performed according to AJCC (American Joint Committee on Cancer) and BCLC (Barcelona Clinic Liver Cancer) criteria. Patients with ASA physical status I, II, or III will be included. Ethics approvals will be obtained from the UMF Cluj and IRGH Ethics Committees. All participants will sign written informed consent.
Inclusion criteria:
Patients aged 18-80 years with hepatocellular carcinoma or hepatic metastases undergoing elective liver resection (hepatectomy or metastasectomy).
Exclusion criteria:
Patients undergoing emergency surgery; chronic immunosuppressive therapy users; individuals with contraindications to any of the study medications; patients with psychiatric disorders (depression, bipolar disorder, schizophrenia); individuals with autoimmune diseases or corticosteroid-dependent bronchial asthma; patients with congenital or acquired coagulation disorders; chronic users of anticoagulants and/or antiplatelet agents; HIV-positive individuals; pregnant women; and patients on antiarrhythmic drugs (verapamil, propafenone, amiodarone) that could interfere with lidocaine's antiarrhythmic action.
Anesthetic protocol:
Low molecular weight heparin will be administered 12 hours prior to surgery, along with preoperative fasting as per recommendations. Premedication will include midazolam 1 mg IV. Induction will consist of fentanyl 2-3 mcg/kg, propofol 1-1.5 mg/kg, and rocuronium 0.5-0.6 mg/kg for muscle relaxation. Lidocaine 1% at 1.5 mg/kg IV bolus will also be administered at induction.
Maintenance of anesthesia:
Inhalational group: Sevoflurane administered at an EtSevo of 1-1.5 MAC, adjusted in steps of 0.25-0.5 MAC depending on BIS levels (target range 40-59).
TIVA group: Propofol administered using the Schneider pharmacokinetic model, starting with an effect-site concentration of 4 µg/ml, adjusted according to BIS (target 40-59).
All patients will receive mechanical ventilation with volume- or pressure-controlled modes, FiO₂ of 40-60% to maintain SpO₂ ≥94%, in a semi-closed circuit, with a fresh gas flow of 2-2.5 L/min, tidal volume of 6-7 mL/kg ideal body weight, and PEEP adjusted based on patient and surgical specifics.
Intraoperative analgesia:
Administer fentanyl 0.5-1 µg/kg as needed (e.g., if blood pressure or heart rate increases \>20% from baseline, or signs of sympathetic activation such as mydriasis, lacrimation, sweating).
Thirty minutes before the end of surgery, nefopam 40 mg and ketoprofen 100 mg IV will be administered, depending on comorbidities.
Lidocaine infusion:
A continuous infusion of 1% lidocaine at 2 mg/kg/hour will be administered intraoperatively, up to a maximum of 200 mg/hour, from intubation until awakening.
Postoperative analgesia:
Morphine at 0.1-0.2 mg/kg IV will be administered 30 minutes prior to awakening from anesthesia.
Intraoperative monitoring:
Standard ASA monitoring (blood pressure, heart rate, temperature, peripheral oxygen saturation, end-tidal CO₂), BIS (target 40-55), and total fentanyl and lidocaine consumption will be recorded.
Blood sampling:
10 mL of peripheral venous blood will be collected preoperatively and 6 hours postoperatively to determine the levels of MPO-DNA and cfDNA, both strongly correlated with NETosis. Samples will be centrifuged at 1000 rpm, and plasma stored at -80°C. Additional inflammatory markers will be measured, including C-reactive protein (CRP), total leukocyte count, blood glucose, procalcitonin, and interleukins IL-6, IL-8, IL-10, and IL-17 for selected cases.
Patients will be followed for one year to monitor the incidence of metastases and postoperative complications.
Ethical Considerations All patients will be enrolled based on written informed consent and will be monitored according to the Research Ethics Guidelines of the "Iuliu Hațieganu" University of Medicine and Pharmacy, as well as the recommendations and requirements of the Research Ethics Committee, in compliance with international regulations and human rights protections.
The study will be approved by the Ethics Committees of UMF Cluj and IRGH.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 153
- Diagnosed with: hepatocellular carcinoma, or hepatic metastases
- Scheduled for elective liver surgery:
- Undergoing emergency surgery
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Hepatocellular carcinoma (HCC) resection performed under total intravenous anesthesia (TIVA) Anesthesia 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. Hepatocellular carcinoma (HCC) resection performed under total intravenous anesthesia (TIVA) Anesthesia induction with TCI 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. Hepatocellular carcinoma (HCC) resection performed under total intravenous anesthesia (TIVA) Intraoperative analgesia 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. Hepatocellular carcinoma (HCC) resection performed under total intravenous anesthesia (TIVA) Non-opioid analgesics 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. Hepatocellular carcinoma (HCC) resection performed under total intravenous anesthesia (TIVA) Morphine (+) 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. Hepatocellular carcinoma (HCC) resection performed under total intravenous anesthesia (TIVA) Bispectral Index (BIS) 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. Hepatocellular carcinoma (HCC) resection performed under total intravenous anesthesia (TIVA) Intraoperative mechanical ventilation 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. Hepatocellular carcinoma (HCC) resection performed under total intravenous anesthesia (TIVA) Blood sampling 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. HCC resection performed under sevoflurane anesthesia 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. HCC resection performed under sevoflurane anesthesia 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. HCC resection performed under sevoflurane anesthesia Intraoperative analgesia 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. HCC resection performed under sevoflurane anesthesia Non-opioid analgesics 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. HCC resection performed under sevoflurane anesthesia Morphine (+) 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. HCC resection performed under sevoflurane anesthesia Bispectral Index (BIS) 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. HCC resection performed under sevoflurane anesthesia Intraoperative mechanical ventilation 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. HCC resection performed under sevoflurane anesthesia Blood sampling 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. HCC resection performed under TIVA + Lidocaine infusion Anesthesia 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 2 mg/kg/hour will be maintained until emergence from anesthesia, not exceeding a maximum dose of 200 mg/hour. HCC resection performed under TIVA + Lidocaine infusion Anesthesia induction with TCI 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 2 mg/kg/hour will be maintained until emergence from anesthesia, not exceeding a maximum dose of 200 mg/hour. HCC resection performed under TIVA + Lidocaine infusion 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 2 mg/kg/hour will be maintained until emergence from anesthesia, not exceeding a maximum dose of 200 mg/hour. HCC resection performed under TIVA + Lidocaine infusion Intraoperative analgesia 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 2 mg/kg/hour will be maintained until emergence from anesthesia, not exceeding a maximum dose of 200 mg/hour. HCC resection performed under TIVA + Lidocaine infusion Non-opioid analgesics 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 2 mg/kg/hour will be maintained until emergence from anesthesia, not exceeding a maximum dose of 200 mg/hour. HCC resection performed under TIVA + Lidocaine infusion Morphine (+) 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 2 mg/kg/hour will be maintained until emergence from anesthesia, not exceeding a maximum dose of 200 mg/hour. HCC resection performed under TIVA + Lidocaine infusion Bispectral Index (BIS) 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 2 mg/kg/hour will be maintained until emergence from anesthesia, not exceeding a maximum dose of 200 mg/hour. HCC resection performed under TIVA + Lidocaine infusion Intraoperative mechanical ventilation 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 2 mg/kg/hour will be maintained until emergence from anesthesia, not exceeding a maximum dose of 200 mg/hour. HCC resection performed under TIVA + Lidocaine infusion Blood sampling 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 2 mg/kg/hour will be maintained until emergence from anesthesia, not exceeding a maximum dose of 200 mg/hour. HCC resection performed under sevoflurane anesthesia + Lidocaine infusion Anesthesia 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. HCC resection performed under sevoflurane anesthesia + Lidocaine infusion sevoflurane anesthesia 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. HCC resection performed under sevoflurane anesthesia + Lidocaine infusion 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. HCC resection performed under sevoflurane anesthesia + Lidocaine infusion Intraoperative analgesia 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. HCC resection performed under sevoflurane anesthesia + Lidocaine infusion Non-opioid analgesics 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. HCC resection performed under sevoflurane anesthesia + Lidocaine infusion Morphine (+) 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. HCC resection performed under sevoflurane anesthesia + Lidocaine infusion Bispectral Index (BIS) 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. HCC resection performed under sevoflurane anesthesia + Lidocaine infusion Intraoperative mechanical ventilation 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. HCC resection performed under sevoflurane anesthesia + Lidocaine infusion Blood sampling 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.
- Primary Outcome Measures
Name Time Method Survival outcomes after hepatocellular carcinoma resection. 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 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.
- Secondary Outcome Measures
Name Time Method Opioid use In the first 24 hours postoperatively We will evaluate the intraoperative and early postoperative opioid requirements by recording the total amount of opioids administered during surgery and in the first 24 hours postoperatively. In the initial analysis, we will compare the opioid consumption between patients who received continuous intravenous lidocaine infusion and those who did not, irrespective of the anesthetic technique used. Subsequently, we will assess potential differences in opioid requirements across all four study groups.
Quantification of the inflammatory response Preoperatively and at 6, 12, and 24 hours postoperatively Samples will be collected for the analysis of inflammatory markers, C-reactive protein (CRP), total leukocyte count, blood glucose levels, and procalcitonin will be evaluated. In selected cases, interleukin levels (IL-6, IL-8, IL-10, and IL-17) will also be measured. We will analyze the relationship between the dynamics of classical inflammatory markers and NETosis across the four patient groups.
Length of hospital stay From the immediate postoperative period until discharge We will analyze whether differences in the length of hospital stay are associated with perioperative factors such as the type of anesthesia administered, the total intraoperative and early postoperative opioid consumption, and specific surgical characteristics, including the extent of liver resection and intraoperative complications. Additionally, we will assess the impact of early postoperative events-such as the incidence of postoperative delirium, postoperative nausea and vomiting (PONV), impaired mobilization due to inadequate pain control, and opioid-related adverse effects-on prolonged hospitalization.
Trial Locations
- Locations (1)
Regional Institute of Gastroenterology and Hepatology Octavian Fodor
🇷🇴Cluj-Napoca, Cluj, Romania
Regional Institute of Gastroenterology and Hepatology Octavian Fodor🇷🇴Cluj-Napoca, Cluj, Romania