Overview
This study aims to investigate whether different doses of locally infiltrated lidocaine affect inflammation, neurological biomarkers, and cognitive function in patients undergoing major head and neck cancer surgery.
Major head and neck cancer surgery can cause substantial physical stress, inflammation, and changes in cognitive function after surgery. Lidocaine is a commonly used local anesthetic that may also have anti-inflammatory and protective effects on the nervous system. However, little is known about whether the dose of lidocaine injected into the surgical area influences these responses.
This prospective, randomized pilot study will include 20 adult patients undergoing head and neck cancer resection followed by microvascular free-flap reconstruction at University Medical Centre Ljubljana, Slovenia.
Participants will be randomly assigned to receive either 150 mg or 300 mg of lidocaine infiltrated into the surgical area at the beginning of surgery. Both groups will receive the same total volume of infiltration solution and the same dose of adrenaline.
Blood samples will be collected before surgery, six hours after surgical incision, and on postoperative days 1, 2, and 6 to measure inflammatory and neurological biomarkers. Cognitive function will be assessed before surgery, on postoperative day 6, and three months after surgery.
The study will explore whether the higher dose of lidocaine is associated with differences in inflammatory responses, neurological biomarkers, and postoperative cognitive function. The findings will help inform the design of larger future clinical studies.
Description
Major head and neck cancer surgery, particularly oncological resection followed by microvascular free-flap reconstruction, is associated with substantial physiological stress, systemic inflammation, and an increased risk of postoperative neurological and cognitive disturbances. These effects may be especially pronounced in patients with pre-existing comorbidities and reduced physiological reserves.
Lidocaine is a widely used local anesthetic with established analgesic properties and potential anti-inflammatory, immunomodulatory, and neuroprotective effects. Experimental and clinical studies have demonstrated its effects on inflammatory cytokine release, neutrophil activation, and endothelial permeability. However, most available perioperative evidence concerns intravenous lidocaine administration, while the potential systemic and neurological effects of local surgical-field infiltration remain insufficiently investigated.
This prospective, randomized, two-arm pilot study aims to explore whether different doses of locally infiltrated lidocaine influence perioperative inflammatory responses, biomarkers associated with neuronal and glial injury, and postoperative cognitive function in patients undergoing major head and neck cancer surgery.
The study will be conducted at University Medical Centre Ljubljana, Slovenia, and will include 20 adult patients undergoing oncological head and neck resection with microvascular soft-tissue free-flap reconstruction. Participants will be randomized into two groups receiving either 300 mg or 150 mg of lidocaine infiltrated into the surgical field. Both infiltration solutions will have an identical total volume of 50 mL and contain the same amount of adrenaline (0.5 mg), allowing comparison between the two lidocaine doses.
General anesthesia will be standardized using total intravenous anesthesia (TIVA) with propofol and remifentanil, administered by manual infusion or target-controlled infusion (TCI). Intraoperative monitoring will include invasive arterial blood pressure, oxygen saturation, heart rate, body temperature, urine output, and processed electroencephalographic monitoring of anesthetic depth.
The inflammatory response will be assessed by measuring serum concentrations of interleukin-6 (IL-6), interleukin-8 (IL-8), and interleukin-10 (IL-10). Biomarkers associated with neuronal, glial, and neurovascular injury will include neuron-specific enolase (NSE), S100β protein, glial fibrillary acidic protein (GFAP), and matrix metalloproteinase-9 (MMP-9).
Five blood samples of 7 mL each (two 3.5 mL serum collection tubes per sampling time point) will be collected immediately before surgery, six hours after surgical incision, and at 08:00 on postoperative days 1, 2, and 6. The total blood volume collected for research purposes will be 35 mL per participant.
Cognitive function will be evaluated using the Mini-Mental State Examination (MMSE) before surgery, on postoperative day 6, and three months after surgery.
The study will explore differences in perioperative biomarker trajectories between the two lidocaine-dose groups and investigate potential associations between systemic inflammatory responses, neurological biomarkers, and postoperative cognitive function.
Given the limited sample size, the study is designed as an exploratory pilot investigation rather than a definitive efficacy trial. The primary scientific purpose is to characterize perioperative biological responses, estimate the magnitude and variability of potential dose-related effects, and generate preliminary evidence to inform the selection of outcome measures and sample size for a larger randomized clinical study.
Eligibility
Inclusion Criteria:
- Adult patients aged 18 years or older.
- Patients scheduled for oncological resection of head and neck cancer followed by microvascular soft-tissue free-flap reconstruction.
- Body mass index (BMI) \< 30 kg/m².
- No known hypersensitivity to amide-type local anesthetics or components of the infiltration solutions.
- Ability and willingness to provide written informed consent for participation in the study.
Exclusion Criteria:
- Refusal to participate or inability to provide written informed consent.
- Known hypersensitivity to lidocaine or any component of the infiltration solution.
- Heart failure with a left ventricular ejection fraction \< 50%.
- Cardiac conduction disorders without an implanted pacemaker.
- Uncontrolled epilepsy.
- Hepatic or renal insufficiency.
- Pregnancy or breastfeeding.
- Pre-existing neurological diseases.
- Psychiatric disorders.
- Preoperative Mini-Mental State Examination (MMSE) score \< 23 points.
