Evaluation Of The Influence Of Anesthetic Interventions On The Evolution Of Hepatic Neoplastic Processes

Patients diagnosed with hepatocellular carcinoma will be randomly assigned to one of four groups. They will receive standard anesthesia with maintenance based on either sevoflurane or propofol. Two of the groups will additionally receive intravenous lidocaine, administered from induction until the end of surgery. Blood samples will be collected preoperatively and six hours postoperatively to measure citrullinated histone H3 (H3Cit), a reliable biomarker of NETosis. Additional inflammatory markers will also be analyzed. All patients will be followed for a period of one year

During induction, patients will receive fentanyl (2-3 µg/kg), propofol (1-1.5 mg/kg) as a bolus or via TCI, and rocuronium (0.5-0.6 mg/kg) to facilitate anesthesia induction and ensure adequate neuromuscular relaxation for endotracheal intubation. Anesthesia will be maintained using TIVA with 1% propofol administered via TCI, guided by the Schneider pharmacokinetic model. The initial target effect-site concentration will be 4 µg/mL and will be titrated intraoperatively to maintain a BIS value between 40 and 59.

"During induction, patients will receive fentanyl (2-3 µg/kg), propofol (1-1.5 mg/kg), and rocuronium (0.5-0.6 mg/kg) to facilitate anesthesia induction and ensure adequate neuromuscular relaxation for endotracheal intubation.~For patients in the inhalation anesthesia group, maintenance will be performed using sevoflurane. The end-tidal concentration of sevoflurane (EtSevo) will be maintained between 1.0 and 1.5 MAC, with adjustments in increments or decrements of 0.25-0.5 MAC, depending on the BIS value, which will be maintained between 40 and 59."

During induction, a 1.5 mg/kg intravenous bolus of 1% lidocaine will also be administered. In the maintenance phase of anesthesia, a continuous infusion of 1% lidocaine at 2 mg/kg/hour-up to a maximum of 200 mg/hour-will be administered, starting after endotracheal intubation and continued until emergence from anesthesia.

Intraoperative analgesia will be ensured by administering fentanyl 0.5-1 µg/kg as needed, based on clinical signs of inadequate analgesia (e.g., an increase in blood pressure or heart rate exceeding 20% of baseline, mydriasis, lacrimation, or diaphoresis)

Thirty minutes before the end of surgery, nefopam 40 mg, paracetamol 1 g, and ketoprofen 100 mg will be administered intravenously, depending on the patient's comorbidities, surgical particularities, extent of resection, and residual liver volume.

Postoperative analgesia will be provided with morphine at a dose of 0.1-0.2 mg/kg, administered 30 minutes before emergence from anesthesia. The administration will be performed intravenously, with the dose adjusted based on patient weight and clinical condition. Additional bolus doses may be given in the post-anesthesia care unit (PACU), guided by the patient's reported pain intensity using the Visual Analog Scale (VAS). In the PACU, morphine will be titrated starting with 2-5 mg IV given slowly over 4-5 minutes, with repeated doses every 5-10 minutes if needed, while closely monitoring respiratory rate, level of consciousness, and hemodynamic stability. For ongoing pain management, intermittent IV bolus dosing (typically 0.05-0.1 mg/kg every 4 hours as required) may be used, taking into account factors such as patient comorbidities, type of surgery, and residual hepatic function.

Bispectral index (BIS) monitoring will be used to guide the depth of anesthesia. The target BIS value will be maintained between 40 and 59 throughout the procedure to ensure adequate hypnosis while avoiding excessive anesthetic depth. BIS values will be continuously recorded and adjustments to anesthetic agents will be made accordingly.

Intraoperative mechanical ventilation will be performed using a lung-protective strategy. Patients will be ventilated with a volume-controlled mode, using a tidal volume of 6-8 mL/kg of predicted body weight, a respiratory rate adjusted to maintain end-tidal CO₂ (EtCO₂) between 35-45 mmHg, and a positive end-expiratory pressure (PEEP) of minimum 6 cmH₂O. Fraction of inspired oxygen (FiO₂) will be set to maintain peripheral oxygen saturation (SpO₂) above 94%. Recruitment maneuvers may be applied periodically or as clinically indicated.

A total of 10 mL of peripheral venous blood will be collected from each patient at two time points: preoperatively (baseline) and 6 hours after surgery. These samples will be used to quantify the concentration of neutrophil extracellular trap (NET)-associated biomarkers, including myeloperoxidase-DNA complexes (MPO-DNA) and cell-free DNA (cfDNA), which are closely associated with NET formation. Following collection, samples will be centrifuged at 1000 rpm, and the resulting plasma will be aliquoted and stored at -80 °C for later analysis. In parallel, additional inflammatory and metabolic markers will be measured, including C-reactive protein (CRP), total leukocyte count, blood glucose, procalcitonin, and interleukin levels (IL-6, IL-8, IL-10, and IL-17) in selected patients. All participants will be monitored for a period of one year to assess the incidence of postoperative complications and cancer recurrence, including metastasis.