IRB-HSR# 13957: IV Lidocaine for Patients Undergoing Primary Breast Cancer Surgery:

Study Overview
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Brief Summary
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The purpose of this study is to determine whether a local anesthetic drug (lidocaine) given during anesthesia intravenously (IV) through a needle in your vein,), can: Help decrease pain after surgery. Have you need less pain medication. Have less side effects like nausea and vomiting following your surgery. Help to prevent chronic pain. Affect recurrence of cancer after surgery.

Detailed Description
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Pain after breast surgery is usually treated with narcotics; however, these are associated with a high incidence of side effects such as itching, nausea and vomiting, constipation, urinary retention and dizziness. Another modality for pain control is regional anesthesia; thoracic paravertebral blocks [TPVB] using local anesthetics are particularly appealing for breast surgery. They provide good pain control, possibly blunting surgical stress response, and decrease the need for anesthetic agent. However, TPVB are not widely used, and the inherent risk associated with their placement, such as pneumothorax, nerve injury, bleeding and infection, makes them less appealing to patients. From a pain management point of view, paravertebral blocks may be the optimal approach for reducing pain and opiate consumption after breast cancer surgery. In addition, retrospective data suggest a reduction in cancer recurrence if this technique is used. Unfortunately, this effective technique is not widely performed because of the risk of pneumothorax and is only used in some centers. Our intent is to study an alternative approach with fewer risks. In this study, we will test the ability of intravenous lidocaine to provide pain relief after breast surgery. We base our hypothesis on a number of previous trials showing significant benefits of intravenous local anesthetics in the setting of abdominal surgery1-4. Approximately 30 to 50% of patients will develop chronic pain following mastectomy5,6. It has been suggested that adequately treating pain in the immediate perioperative period will prevent chronic pain. Specifically, application of EMLA (local anesthetic) cream perioperatively during breast surgery has been shown to reduce the incidence of chronic pain development7. Perioperative administration of intravenous lidocaine may offer similar benefits. Therefore, we will study the incidence of chronic pain in our population after 6 months. Finally, anesthetic choice during primary surgical intervention for cancer may affect recurrence and metastasis. A recent retrospective study suggests a profound reduction in recurrence in breast cancer patients receiving regional + general anesthesia as compared with general alone9. Similar data have been published in abstract form regarding recurrence after prostate surgery10. Also, Christopherson et al studied the long-term survival of 177 patients after resection of colon cancer in a trial of general anesthesia with and without epidural anesthesia and analgesia supplementation for resection of colon cancer. Epidural supplementation was associated with enhanced survival among patients without metastases before 1.46 years8. Although the mechanisms of this beneficial effect are unclear, attenuation of the surgical stress response, modulation of the inflammatory system, and/or decreased requirement for volatile anesthetics and opiates by regional anesthesia are possible mechanisms11. For example, the neural inputs activated during surgical stress may result in activation of promalignant pathways. Morphine has been shown to promote angiogenesis in a model of breast cancer, a key step in tumor development12. In addition, opiates interfere with natural killer cell function13. It is conceivable that the beneficial effect on recurrence might derive from low systemic level of local anesthetics attained during regional anesthesia. A number of studies have demonstrated significant reduction in opiate requirements and a decrease in the magnitude of stress response when local anesthetics are used intravenously1,3,4. If so, systemic administration would be a safer and a simpler way to reach the same goal. We therefore will compare the effect of local anesthetics given intravenously as compared with placebo on cancer recurrence rate.

Official Title
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IRB-HSR# 13957: IV Lidocaine for Patients Undergoing Primary Breast Cancer Surgery: Effects on Postoperative Recovery and Cancer Recurrence

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Placebo
* Drug: Lidocaine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: informed consent age older than 18 to 80 years (inclusive) scheduled for mastectomy because of breast cancer American Society of Anesthesiologists (ASA) physical classification classes I - III Exclusion Criteria: Allergy to local anesthetics, fentanyl or morphine severe cardiovascular disease (myocardial infarction within 6 months), profoundly decreased left ventricular function (ejection fraction <40%) or high-grade arrhythmias severe liver disease (known AST or ALT or billirubin >2.5 times the upper limit of normal) renal impairment (creatinine clearance less than 60) pregnant or breast feeding patient is enrolled in another study or have been in one in the last 30 days

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>ALL subjects will receive lidocaine up to 1.5mg/kg IV (in the vein) as a rapid injection. Then the continuous IV infusion of the study medication (containing lidocaine 8 mg/ml or placebo) will be started and will continue for up to two hours in the recovery room. | Drug: Placebo<br>* ALL subjects will receive lidocaine up to 1.5mg/kg IV (in the vein) as a rapid injection. Then the continuous IV infusion of the study medication (containing lidocaine 8 mg/ml or placebo) will be started and will continue for up to two hours in the recovery room.<br>* Other names: xylocaine;|
| Experimental: Lidocaine<br>ALL subjects will receive lidocaine up to 1.5mg/kg IV (in the vein) as a rapid injection. Then the continuous IV infusion of the study medication (containing lidocaine 8 mg/ml or placebo) will be started and will continue for up to two hours in the recovery room. | Drug: Lidocaine<br>* ALL subjects will receive lidocaine up to 1.5mg/kg IV (in the vein) as a rapid injection. Then the continuous IV infusion of the study medication (containing lidocaine 8 mg/ml or placebo) will be started and will continue for up to two hours in the recovery room.<br>* Other names: xylocaine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| opiate consumption | We hypothesize that intraoperative use of intravenous lidocaine (as compared with placebo) will result in: decreased opiate consumption (primary endpoint), less pain, less fatigue and earlier postoperative discharge. | hospital discharge/ days 0-7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| chronic pain | We hypothesize that patients receiving IV lidocaine will report less pain than those in the placebo group at 6 months following surgery. | 6 months after surgery | 
| cancer recurrence | We hypothesize that patients in the IV lidocaine group will have a lower rate of cancer recurrence than those in the placebo group at 5 years following surgery. | yearly for 5 years after surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Breast Cancer