The Effect of Intravenous Lidocaine on THBS2 and Angiogenic Factors Expression in Women Undergoing Cervical Cancer Surgery

Study Overview
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Brief Summary
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The purpose of this study is to investigate the efficacy of intravenous lidocaine on THBS2, MMPs and VEGF-C in serum in cervical cancer patients undergoing radical hysterectomy under general anesthesia.

Detailed Description
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The surgical stress response to tumour removal causes bloodstream release of a variety of pro-inflammatory cytokines and other molecules which may affect perioperative immune response and other conditions conducive to residual tumour cell survival that could later emerge as clinical recurrences or metastasis. Lidocaine has analgesic and anti-inflammatory effects, and may also have specific anticancer properties. Blood serum expression of these molecules (metalloproteinases, vascular endothelial growth factor [VEGF], epidermal growth factor）, play a important role in the metastatic process and tumor progression. lidocaine could affect the course and growth of metastatic tumors by changing the cancer cells, the tumor microenvironment, or both. We tested the hypothesis that women undergoing cervical cancer resection with these techniques (intravenous lidocaine) have reduced postoperative serum expression of metastasis biomarkers, and may change the outcomes of cancer patients.

Official Title
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Effects of Intravenous Lidocaine on Serum THBS2, MMPS and VEGF-C in Patients Undergoing Radical Hyterectomy Surgery After General Anesthesia

Conditions
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Cervical Cancer, Metastatic Cancer

Intervention / Treatment
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* Drug: Lidocaine
* Other: Normal saline (NS)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients were scheduled by following cervical cancer surgery under general anesthesia Aged 18-65 years ASA physical status Ⅱ-Ⅲ Exclusion Criteria: Severe heart, pulmonary, hepatic and renal insufficiency History of neurological diseases Autoimmune disorders Antiarrhythmic drugs (amiodarone, verapamil, propafenone) Patients' decision to withdraw anytime from the study, and refusal to participate before surgery and at postoperative follow-up Allergy to one of the used medications Psychiatric illness, psychological disorder, and drug or alcohol abuse Unwillingness to comply with the protocol or procedures Preoperative treatment of chemotherapy, radiation, NSAID and hormonal therapy History of anesthesia and surgery in two weeks Coexisting other cancers and intraoperative presence of liver metastasis Perioperative treatment of blood transfusion

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lidocaine<br>Intravenous bolus of 1.5 mg/kg of lidocaine followed by a continuous infusion of 3.0 mg/kg for the first hour, 1.5 mg/kg for the second hour, 0.7 mg/kg for the next 22h. | Drug: Lidocaine<br>* Intravenous bolus of 1.5 mg/kg of lidocaine followed by a continuous infusion of 3.0 mg/kg for the frst hour, 1.5 mg/kg for the second hour, 0.7 mg/kg for the next 22h.<br>|
| Placebo Comparator: Normal saline<br>Normal saline administered as a bolus and an infusion with identical volume and rate changes as the treatment group. | Other: Normal saline (NS)<br>* Patients are received equal volumes of saline intravenously until the end of the surgery<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes from Baseline THBS2 before anaesthetic induction and 48 hours after surgery | Blood samples (5 ml) were drawn from each patient before anaesthetic induction, at the end of the operation, 24h and 48 h after operation | Baseline and 48 hours after operation | 
| Changes from Baseline MMP-2 before anaesthetic induction and 48 hours after surgery | Blood samples (5 ml) were drawn from each patient before anaesthetic induction, at the end of the operation, 24h and 48 h after operation | Baseline and 48 hours after operation | 
| Changes from Baseline MMP-9 before anaesthetic induction and 48 hours after surgery | Blood samples (5 ml) were drawn from each patient before anaesthetic induction, at the end of the operation, 24h and 48 h after operation | Baseline and 48 hours after operation | 
| Changes from Baseline VEGF-C before anaesthetic induction and 48 hours after surgery | Blood samples (5 ml) were drawn from each patient before anaesthetic induction, at the end of the operation, 24h and 48 h after operation | Baseline and 48 hours after operation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Monitoring the severity of postoperative pain with verbalre sponse pain score during the first 48hours postoperatively | the severity of pain measured using Visual Analogue Score (VAS) on postoperative days at the moment, 12, 24 and 48 hours after surgery | at the end of operation and 48 hours after operation | 
| Resumption of bowel function | Record the time to first flatus and the first defecation | at the end of operation and 48 hours after operation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cervical cancer, Tumor progression, Lidocaine, Metalloproteinases, vascular endothelial growth factor, epidermal growth factor, thrombospondin2