Lidocaine Infiltration and Neuroimmunomodulation in Head and Neck Cancer Surgery
Lidocaine and Neuroimmunomodulation: The Effect of Local Anesthetic Concentration in Head and Neck Cancer Resections
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.
Descripción general del estudio
Estado
Estado
Condiciones
Condiciones
Intervención / Tratamiento
Intervención / Tratamiento
Descripción detallada
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.
Tipo de estudio
Tipo de estudio
Inscripción (Estimado)
Inscripción
Fase
Fase
- Fase 4
Contactos y Ubicaciones
Estudio Contacto
Estudio Contacto
- Nombre: Liljana Markova, MD, PhD
- Número de teléfono: +38640802662
- Correo electrónico: liljana.markova@kclj.si
Copia de seguridad de contactos de estudio
- Nombre: Eleonora Ivanova, MD
- Número de teléfono: +386 31 289 803
- Correo electrónico: eleonora.ivanova@kclj.si
Ubicaciones de estudio
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Ljubljana, Eslovenia, 1000
- Reclutamiento
- University Medical Centre Ljubljana
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Criterios de participación
Criterio de elegibilidad
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
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.
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Ciencia básica
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Único
Número de brazos
Armas e Intervenciones
Grupo de participantes/brazoGrupo de participantes/brazo |
Intervención / TratamientoIntervención / Tratamiento |
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Experimental: Higher-Dose Lidocaine (300 mg)
Participants assigned to this group will receive surgical-field infiltration with 30 mL of 1% lidocaine (300 mg), 0.5 mg of adrenaline, and 20 mL of 0.9% sodium chloride solution. The total infiltration volume will be 50 mL. The infiltration will be administered at the beginning of surgery for head and neck cancer resection with microvascular free-flap reconstruction. |
Lidocaine hydrochloride 1% solution will be administered by local infiltration into the surgical field at the beginning of head and neck cancer surgery. Participants will be randomized to receive one of two doses: Higher-dose group: 30 mL of 1% lidocaine (300 mg), combined with 0.5 mg of adrenaline and 20 mL of 0.9% sodium chloride solution. Lower-dose group: 15 mL of 1% lidocaine (150 mg), combined with 0.5 mg of adrenaline and 35 mL of 0.9% sodium chloride solution. Both groups will receive a total infiltration volume of 50 mL and an identical adrenaline dose (0.5 mg). The intervention will be administered once, at the beginning of surgery. |
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Experimental: Lower-Dose Lidocaine (150 mg)
Participants assigned to this group will receive surgical-field infiltration with 15 mL of 1% lidocaine (150 mg), 0.5 mg of adrenaline, and 35 mL of 0.9% sodium chloride solution. The total infiltration volume will be 50 mL. The infiltration will be administered at the beginning of surgery for head and neck cancer resection with microvascular free-flap reconstruction. |
Lidocaine hydrochloride 1% solution will be administered by local infiltration into the surgical field at the beginning of head and neck cancer surgery. Participants will be randomized to receive one of two doses: Higher-dose group: 30 mL of 1% lidocaine (300 mg), combined with 0.5 mg of adrenaline and 20 mL of 0.9% sodium chloride solution. Lower-dose group: 15 mL of 1% lidocaine (150 mg), combined with 0.5 mg of adrenaline and 35 mL of 0.9% sodium chloride solution. Both groups will receive a total infiltration volume of 50 mL and an identical adrenaline dose (0.5 mg). The intervention will be administered once, at the beginning of surgery. |
¿Qué mide el estudio?
Medidas de resultado primarias
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Change in Serum Interleukin-6 (IL-6) Concentration
Periodo de tiempo: Immediately before surgery (baseline), 6 hours after surgical incision, and at 08:00 on postoperative days 1, 2, and 6.
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Changes in serum interleukin-6 (IL-6) concentration relative to the preoperative baseline will be assessed at four postoperative time points. IL-6 concentrations and absolute changes from baseline will be expressed in picograms per milliliter (pg/mL). The magnitude and temporal pattern of changes will be compared between patients receiving 150 mg and 300 mg of infiltrated lidocaine. |
Immediately before surgery (baseline), 6 hours after surgical incision, and at 08:00 on postoperative days 1, 2, and 6.
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Change in Serum Interleukin-8 (IL-8) Concentration
Periodo de tiempo: Immediately before surgery (baseline), 6 hours after surgical incision, and at 08:00 on postoperative days 1, 2, and 6.
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Changes in serum interleukin-8 (IL-8) concentration relative to the preoperative baseline will be assessed at four postoperative time points. IL-8 concentrations and absolute changes from baseline will be expressed in picograms per milliliter (pg/mL). The magnitude and temporal pattern of changes will be compared between patients receiving 150 mg and 300 mg of infiltrated lidocaine. |
Immediately before surgery (baseline), 6 hours after surgical incision, and at 08:00 on postoperative days 1, 2, and 6.
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Change in Serum Interleukin-10 (IL-10) Concentration
Periodo de tiempo: Immediately before surgery (baseline), 6 hours after surgical incision, and at 08:00 on postoperative days 1, 2, and 6.
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Changes in serum interleukin-10 (IL-10) concentration relative to the preoperative baseline will be assessed at four postoperative time points. IL-10 is an anti-inflammatory cytokine involved in the regulation of immune responses. IL-10 concentrations and absolute changes from baseline will be expressed in picograms per milliliter (pg/mL). The magnitude and temporal pattern of changes will be compared between patients receiving 150 mg and 300 mg of infiltrated lidocaine. |
Immediately before surgery (baseline), 6 hours after surgical incision, and at 08:00 on postoperative days 1, 2, and 6.
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Change in Serum Neuron-Specific Enolase (NSE) Concentration
Periodo de tiempo: Immediately before surgery (baseline), 6 hours after surgical incision, and at 08:00 on postoperative days 1, 2, and 6.
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Changes in serum neuron-specific enolase (NSE) concentration relative to the preoperative baseline will be assessed at four postoperative time points. NSE is a biomarker associated with neuronal injury and neurological stress. NSE concentrations and absolute changes from baseline will be expressed in nanograms per milliliter (ng/mL). The magnitude and temporal pattern of changes will be compared between patients receiving 150 mg and 300 mg of infiltrated lidocaine. |
Immediately before surgery (baseline), 6 hours after surgical incision, and at 08:00 on postoperative days 1, 2, and 6.
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Change in Serum S100 Beta (S100β) Protein Concentration
Periodo de tiempo: Immediately before surgery (baseline), 6 hours after surgical incision, and at 08:00 on postoperative days 1, 2, and 6.
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Changes in serum S100 beta (S100β) protein concentration relative to the preoperative baseline will be assessed at four postoperative time points. S100β is a biomarker associated with glial cell injury and neurological stress. S100β concentrations and absolute changes from baseline will be expressed in micrograms per liter (µg/L). The magnitude and temporal pattern of changes will be compared between patients receiving 150 mg and 300 mg of infiltrated lidocaine. |
Immediately before surgery (baseline), 6 hours after surgical incision, and at 08:00 on postoperative days 1, 2, and 6.
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Change in Serum Glial Fibrillary Acidic Protein (GFAP) Concentration
Periodo de tiempo: Immediately before surgery (baseline), 6 hours after surgical incision, and at 08:00 on postoperative days 1, 2, and 6.
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Changes in serum glial fibrillary acidic protein (GFAP) concentration relative to the preoperative baseline will be assessed at four postoperative time points. GFAP is a biomarker associated with astrocytic injury and neurological stress. GFAP concentrations and absolute changes from baseline will be expressed in picograms per milliliter (pg/mL). The magnitude and temporal pattern of changes will be compared between patients receiving 150 mg and 300 mg of infiltrated lidocaine. |
Immediately before surgery (baseline), 6 hours after surgical incision, and at 08:00 on postoperative days 1, 2, and 6.
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Change in Serum Matrix Metalloproteinase-9 (MMP-9) Concentration
Periodo de tiempo: Immediately before surgery (baseline), 6 hours after surgical incision, and at 08:00 on postoperative days 1, 2, and 6.
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Changes in serum matrix metalloproteinase-9 (MMP-9) concentration relative to the preoperative baseline will be assessed at four postoperative time points. MMP-9 is involved in extracellular matrix remodeling, inflammatory processes, and neurovascular responses. MMP-9 concentrations and absolute changes from baseline will be expressed in nanograms per milliliter (ng/mL). The magnitude and temporal pattern of changes will be compared between patients receiving 150 mg and 300 mg of infiltrated lidocaine. |
Immediately before surgery (baseline), 6 hours after surgical incision, and at 08:00 on postoperative days 1, 2, and 6.
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Medidas de resultado secundarias
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Change in Cognitive Function Assessed by the Mini-Mental State Examination (MMSE)
Periodo de tiempo: Preoperatively (baseline), on postoperative day 6, and at 3 months after surgery.
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Changes in cognitive function relative to the preoperative baseline will be assessed using the Mini-Mental State Examination (MMSE), with scores ranging from 0 to 30 points; higher scores indicate better cognitive performance. Assessments will be performed preoperatively, on postoperative day 6, and at 3 months. For patients unable to speak after surgery due to surgical or airway-related limitations, written responses may be accepted instead of verbal responses where feasible. Adaptations will be documented. Changes in MMSE scores will be compared between the 150 mg and 300 mg lidocaine groups. |
Preoperatively (baseline), on postoperative day 6, and at 3 months after surgery.
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Colaboradores e Investigadores
Patrocinador
Patrocinador
Investigadores
Investigadores
- Investigador principal: Liljana Markova, MD, PhD, University Medical Centre Ljubljana
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Actual)
Inicio del estudio
Finalización primaria (Estimado)
Finalización primaria
Finalización del estudio (Estimado)
Finalización del estudio
Fechas de registro del estudio
Enviado por primera vez
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Publicado por primera vez
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización publicada
Última actualización enviada que cumplió con los criterios de control de calidad
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
Otros números de identificación del estudio
- 20250227
Información sobre medicamentos y dispositivos, documentos del estudio
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