Long-term Outcomes of Breast Cancer Patients After Wound Infiltration Analgesia

Study Overview
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Brief Summary
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In the study that was conducted from 05.01.2009 - 31.12.2012. 120 patients were examined. By drawing random numbers, the patients were randomized into 3 groups for postoperative analgesia: Diclofenac 2 mg/kg/day - control, Wound infiltration via wound catheter with catheter tip placed in the axilla, 3*0.5 mg/kg 0.5% levobupivacaine bolus dose. 0.05 mg/kg/h 0.5% levobupivacaine continuously via wound infiltration catheter with catheter tip placed in the axilla. The drug was delivered using a PCA pump for 24 hours. The aim was to compare early postoperative outcomes - pain control on a visual analog scale of 1-10, hand grip strength, and quality of life after surgery and after 1 year. Long-term survival was examined subsequently, from the hospital register.

Detailed Description
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Before the operation, the patients were randomized into 3 groups: the first group received diclofenac for postoperative analgesia. On the first day, they received 2 x 75 mg intravenously, and then 3 x 50 mg tablets. For the wound infiltration with levobupivacaine, a perforated catheter was placed at the end of the surgical procedure by the surgeon in both groups of patients. The tip of the catheter was in the axillary fossa, where the dissection was performed. Patients in the levobupivacaine bolus group (N=39) received three times a day bolus doses of 0.5 mg/kg 0.5% levobupivacaine (Chirocaine, Abbot S.p.A., Latina, Italy) through the catheter. The dose of levobupivacaine was prescribed by the doctor, and the drug was delivered by the nurse. In levobupivacaine, PCA group (N=40) women had the same catheter placed, but received 0.05 mg/kg/h 0.5% levobupivacaine continuously for 24 hours via a catheter placed in the axilla. Levobupivacaine was delivered by PCA pump (CADD - Legacy® PCA Pump, Model 6300, Smiths Medical MD, Inc., St. Paul, USA). These patients were allowed to add a dose of 7.5 mg 0.5% levobupivacaine in case of pain by pressing the patient's button on the PCA pump, with a lock-out period of 4 hours. Postoperative pain was measured with a visual analog scale (VAS). All patients had the option of additional analgesia, using NSAIDs for pain <4 or meperidine for VAS >4. After the surgery, the patients received oncological chemoradiotherapy, depending on the type and stage of cancer.

Official Title
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Long-term Outcomes of Breast Cancer Patients Receiving Levobupivacaine Wound Infiltration or Diclofenac for Postoperative Pain Relief

Conditions
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Postoperative Analgesia, Hand Strength, Health Related Quality of Life, Chronic Shoulder Pain, Breast Cancer Female, Surgical Wound Infiltration, Lymph Node Dissection

Intervention / Treatment
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* Drug: Diclofenac Sodium
* Drug: Levobupivacaine bolus analgesia
* Drug: Levobupivacaine PCA group


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Breast cancer patients whose disease requires axillary lymph node dissection who consented to participate in the study aged 30 - 75 The patient is able to understand all three methods of analgesia Patients can receive any of the study drugs Able to understand and complete questionnaires on quality of life and shoulder pain Exclusion Criteria: Age <30 years - >75 years Patients who refused to participate in the study (at any stage of the study) Patients who after histological analysis did not require axillary lymph node dissection Patients with known intolerance to study drugs Patients who unintentionally removed wound infiltration catheters. Patients who required surgical reintervention during the study period Patients having adverse reactions to any study drug.

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 75 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Diclofenac<br>All patients underwent quadrantectomy or mastectomy with axillary lymph node dissection. They received diclofenac 2 x 75 mg intravenously on the first day after surgery. During the 3 subsequent days, from day 2 to day 4 postoperatively patients were given 3 x 50 mg diclofenac tablets orally. The medicine was delivered by the nurse, and the patients drank tablets in front of her. | Drug: Diclofenac Sodium<br>* A group of patients with breast cancer who were randomized to the diclofenac group by drawing random numbers was given 2 x 75 mg of drug IV on the first PO day and then 3 x 50 mg tablets orally for postoperative analgesia. All patients were assessed before the surgical procedure: hand grip strength, shoulder disability, and health-related quality of life were measured. Pain relief was assessed by the visual analog scale (VAS) from 0-10. Rescue analgesia was offered for pain >4 on the VAS, meperidine 20-30 mg for VAS >or = 4<br>* Other names: Nonsteroidal antiinflammatory drug;|
| Experimental: Levobupivacaine bolus analgesia<br>Group Levobupivacaine Bolus received 0.5 mg/kg 0.5% Levobupivacaine HCl every 8 h via wound catheter. The dose of levobupivacaine was prescribed by the doctor and the drug was delivered by the nurse. | Drug: Levobupivacaine bolus analgesia<br>* The levobupivacaine dose was calculated by a doctor. A wound infiltration catheter was inserted at the end of the surgical procedure by a surgeon. A first dose of local anesthetic was delivered at the end of the surgical procedure to test catheter placement. Bolus doses of local anesthetics based on the patients' body weight were thereafter delivered by the nurse in 8 hours intervals. All patients were assessed before the surgical procedure and hand grip strength, shoulder disability, and health-related quality of life were measured. Pain relief was assessed by the visual analog scale (VAS) from 0-10. Rescue analgesia was offered for pain >4 on the VAS, meperidine 20-30 mg for VAS >or = 4.<br>* Other names: Postoperative wound infiltration with bolus applications of local anesthetic, Chirocaine 0.5%;|
| Experimental: Levobupivacaine PCA group<br>Group Levobupivacaine patient-controlled analgesia (PCA) received 0.05 mg/kg 0.5% Levobupivacaine HCl continuously via wound catheter delivered by CADD - Legacy® PCA Pump. These patients were allowed to add a dose of 7.5 mg 0.5% levobupivacaine in case of pain by pressing the patient's button on the PCA pump, with a lock-out period of 4 hours. | Drug: Levobupivacaine PCA group<br>* The levobupivacaine dose was calculated by a doctor. A wound infiltration catheter was inserted at the end of the surgical procedure by a surgeon. Levobupivacaine was delivered by PCA pump (CADD - Legacy® PCA Pump, Model 6300, Smiths Medical MD, Inc., St. Paul, USA). A drug delivery was started at the end of the surgical procedure. All patients were assessed before the surgical procedure: hand grip strength, shoulder disability, and health-related quality of life were measured. Pain relief was assessed by the visual analog scale (VAS) from 0-10. Rescue analgesia was offered for persisting pain >4 on the VAS, and meperidine 20-30 mg for VAS >or = 4.<br>* Other names: Postoperative continuous wound infiltration analgesia with local anesthetic, Chirocaine 0.5%;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postoperative analgesia | Pain after mastectomy was evaluated by self-reports from patients using a Visual Analog Scale (VAS) from 0 - no pain up to 10 - the worst pain imaginable. | from 1-4 days postoperative, day of surgery is day 1 | 
| Hand grip strength | Hand grip strength (HGS) was measured preoperatively, 4 days after surgery and at follow-up after 1 year, using a handheld dynamometer (Dynatest®, Rud. Reister Gmbh&CaKG, Jungingen, Germany) and expressed in bars. Mean expected normal values for female patients are in the range between 0.4-0.6 bar. | Before surgery, on day 4 after surgery, and one year after surgery | 
| Shoulder disability | Shoulder pain was assessed using the Shoulder Disability Questionnaire (SDQ), and shoulder pain was assessed in 16 typical situations such as writing, opening a door, sleeping on the operated side, or carrying a load. The maximal score was all positive ( 16 in 16, 100%), suggesting that pain was present in all 16 clinical situations, and the minimum score is 0 (0 positive responses /16 situations, 0% - no disability in any situation. | Before surgery and after one year at surgical control. | 
| Health related quality of life | Health-related quality of life was assessed using the Croatian version of the SF-36 questionnaire. There were eight domains examined: physical health, role limitation due to physical problems, pain, general health perception, energy / vitality, social functioning, limitations due to emotional problems, and general mental health. This instrument summarizes health perception from the patient's perspective. SF-36 scores range from 0 (worst) to 100 (best) (5). | Before surgery and after one year at surgical control. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Long-term survival - 5 years after surgery | Survival after 5 years from the surgery will be checked through the hospital registry, or for those who died through the official population records and death registers of the Republic of Croatia. Patients' outcomes are dichotomous and are presented as alive or dead 5 years after surgery. | Five years after surgery | 
| Long term survival - 10 years after surgery | Survival after 10 years from the surgery will be checked through the hospital registry, or for those who died through the official population records and death registers of the Republic of Croatia. Patients' outcomes are dichotomous and are presented as alive or dead 10 years after surgery. | Ten years after surgery until data were collected | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute Postoperative Pain, Breast Cancer, Postoperative analgesia, Patient-Controlled Analgesia, Levobupivacaine, Diclofenac, Hand Grip Strength, Quality of life, Treatment Outcome