- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01204242
IRB-HSR# 13957: IV Lidocaine for Patients Undergoing Primary Breast Cancer Surgery:
IRB-HSR# 13957: IV Lidocaine for Patients Undergoing Primary Breast Cancer Surgery: Effects on Postoperative Recovery and Cancer Recurrence
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.
Study Overview
Detailed Description
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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
Virginia
-
Charlottesville, Virginia, United States, 22908
- University of Virginia Health System
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Placebo Comparator: Placebo
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. |
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.
Other Names:
|
Experimental: Lidocaine
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. |
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.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
opiate consumption
Time Frame: hospital discharge/ days 0-7
|
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
Time Frame: 6 months after surgery
|
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
Time Frame: yearly for 5 years after surgery
|
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
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Mohammed Tiouririne, MD, UVA Dept of Anesthesiology
Publications and helpful links
General Publications
- Exadaktylos AK, Buggy DJ, Moriarty DC, Mascha E, Sessler DI. Can anesthetic technique for primary breast cancer surgery affect recurrence or metastasis? Anesthesiology. 2006 Oct;105(4):660-4. doi: 10.1097/00000542-200610000-00008.
- Apfel CC, Korttila K, Abdalla M, Kerger H, Turan A, Vedder I, Zernak C, Danner K, Jokela R, Pocock SJ, Trenkler S, Kredel M, Biedler A, Sessler DI, Roewer N; IMPACT Investigators. A factorial trial of six interventions for the prevention of postoperative nausea and vomiting. N Engl J Med. 2004 Jun 10;350(24):2441-51. doi: 10.1056/NEJMoa032196.
- Christopherson R, James KE, Tableman M, Marshall P, Johnson FE. Long-term survival after colon cancer surgery: a variation associated with choice of anesthesia. Anesth Analg. 2008 Jul;107(1):325-32. doi: 10.1213/ane.0b013e3181770f55.
- Wallace MS, Wallace AM, Lee J, Dobke MK. Pain after breast surgery: a survey of 282 women. Pain. 1996 Aug;66(2-3):195-205. doi: 10.1016/0304-3959(96)03064-3.
- Herroeder S, Pecher S, Schonherr ME, Kaulitz G, Hahnenkamp K, Friess H, Bottiger BW, Bauer H, Dijkgraaf MG, Durieux ME, Hollmann MW. Systemic lidocaine shortens length of hospital stay after colorectal surgery: a double-blinded, randomized, placebo-controlled trial. Ann Surg. 2007 Aug;246(2):192-200. doi: 10.1097/SLA.0b013e31805dac11. Erratum In: Ann Surg. 2009 Apr;249(4):701. Dijkgraaf, Omarcel G W [corrected to Dijkgraaf, Marcel G W].
- Jung BF, Ahrendt GM, Oaklander AL, Dworkin RH. Neuropathic pain following breast cancer surgery: proposed classification and research update. Pain. 2003 Jul;104(1-2):1-13. doi: 10.1016/s0304-3959(03)00241-0. No abstract available.
- Groudine SB, Fisher HA, Kaufman RP Jr, Patel MK, Wilkins LJ, Mehta SA, Lumb PD. Intravenous lidocaine speeds the return of bowel function, decreases postoperative pain, and shortens hospital stay in patients undergoing radical retropubic prostatectomy. Anesth Analg. 1998 Feb;86(2):235-9. doi: 10.1097/00000539-199802000-00003.
- Fassoulaki A, Sarantopoulos C, Melemeni A, Hogan Q. EMLA reduces acute and chronic pain after breast surgery for cancer. Reg Anesth Pain Med. 2000 Jul-Aug;25(4):350-5. doi: 10.1053/rapm.2000.7812. Erratum In: Reg Anesth Pain Med 2002 Jan-Feb;27(1):116.
- Kaba A, Laurent SR, Detroz BJ, Sessler DI, Durieux ME, Lamy ML, Joris JL. Intravenous lidocaine infusion facilitates acute rehabilitation after laparoscopic colectomy. Anesthesiology. 2007 Jan;106(1):11-8; discussion 5-6. doi: 10.1097/00000542-200701000-00007.
- Cassuto J, Wallin G, Hogstrom S, Faxen A, Rimback G. Inhibition of postoperative pain by continuous low-dose intravenous infusion of lidocaine. Anesth Analg. 1985 Oct;64(10):971-4.
- Biki B MD, Sessler DI, Mascha E, Buggy DJ: Can Anaesthetic Technique for Radical Prostatectomy Surgery Affect Recurrence or Metastasis?, ASA Annual Meeting American Society of Anesthesiologists. San Francisco, 2007
- Ben-Eliyahu S, Page GG, Yirmiya R, Shakhar G. Evidence that stress and surgical interventions promote tumor development by suppressing natural killer cell activity. Int J Cancer. 1999 Mar 15;80(6):880-8. doi: 10.1002/(sici)1097-0215(19990315)80:63.0.co;2-y.
- Farooqui M, Li Y, Rogers T, Poonawala T, Griffin RJ, Song CW, Gupta K. COX-2 inhibitor celecoxib prevents chronic morphine-induced promotion of angiogenesis, tumour growth, metastasis and mortality, without compromising analgesia. Br J Cancer. 2007 Dec 3;97(11):1523-31. doi: 10.1038/sj.bjc.6604057. Epub 2007 Oct 30.
- Eisenstein TK, Hilburger ME. Opioid modulation of immune responses: effects on phagocyte and lymphoid cell populations. J Neuroimmunol. 1998 Mar 15;83(1-2):36-44. doi: 10.1016/s0165-5728(97)00219-1.
- Terkawi AS, Durieux ME, Gottschalk A, Brenin D, Tiouririne M. Effect of intravenous lidocaine on postoperative recovery of patients undergoing mastectomy: a double-blind, placebo-controlled randomized trial. Reg Anesth Pain Med. 2014 Nov-Dec;39(6):472-7. doi: 10.1097/AAP.0000000000000140.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Skin Diseases
- Neoplasms
- Neoplasms by Site
- Breast Diseases
- Breast Neoplasms
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Arrhythmia Agents
- Central Nervous System Depressants
- Peripheral Nervous System Agents
- Sensory System Agents
- Anesthetics
- Membrane Transport Modulators
- Anesthetics, Local
- Voltage-Gated Sodium Channel Blockers
- Sodium Channel Blockers
- Lidocaine
Other Study ID Numbers
- 13957
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
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