Effect of Locally Administered Morphine and Bupivicaine on Acute and Chronic Postmastectomy Pain

Study Overview
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Brief Summary
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This study investigate the effect of addition morphine to locally instillation bupivacaine on developing chronic neuropathic pain acute postoperative pain after breast cancer surgery and on the probability of developing chronic neuropathic pain.

Detailed Description
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Breast cancer is one of the most common cancer diagnoses in women and a significant cause of mortality and morbidity worldwide.Surgical treatment indicated in most patients. Persistent pain and sensory disturbances following surgery is a significant clinical problem with an average prevalence of 20-23.9%. Post-mastectomy chronic pain syndrome (PMPS) is defined as pain of neuropathic character located in the area of surgery and/or the ipsilateral arm, present at least 4 days per week, and with an average intensity of at least 3 on a numeric rating scale from 0 to 10. The pathological mechanisms may be related to patient characteristics, surgical technique and adjuvant therapy. Although the genesis of pain is multi-factorial, sectioning of the intercostobrachial nerve (a cutaneous branch of T1-2) is the nerve lesion diagnosed most often. Uncontrolled acute postoperative pain is defined as an important risk factor for the development of chronic pain. Local anesthetics have been investigated in cancer breast patients through many routes; paravertebral blocks, thoracic epidurals, wound infiltration, topical lidocaine patch, and the topical application of EMLA( Eutectic Mixture of Local Anesthetics) cream on operation site. Most of above studies suggested a better outcome in terms of reduced postoperative pain and improved patient satisfaction. Opioids exert a local analgesic effect is based on several observations: • Nociceptive afferent nerve fibers contain peripheral opioid receptors which are silent except in the presence of local inflammation. • Morphine and its metabolites are largely undetectable systemically when applied topically to skin ulcers, suggesting the analgesic effect is local • Peripheral opioid injections for local analgesia, such as intra-articular morphine after knee surgery, have been found to be effective in several trials. An effective topical opioid analgesic that could be applied to inflamed or open skin lesions would be a useful option for some patients where other options for pain relief have been exhausted.

Official Title
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Effect of Locally Administered Morphine and Bupivicaine on Acute and Chronic Postmastectomy Pain

Conditions
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Acute Pain, Chronic Pain

Intervention / Treatment
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* Drug: local instillation of morphine to surgical wound


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: female patients with cancer breast scheduled for modified radical mastectomy with axillary dissection Exclusion Criteria: allergy to the study drugs significant cardiac, respiratory, renal or hepatic disease drug or alcohol abuse psychiatric illness that would interfere with perception and assessment of pain

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 60 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: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: local instillation of morphine 5 mg<br>5 ml plain bupivacaine 0.5% and 5 mg morphine .Study drugs will be diluted by saline 0.9% to 20 ml volume and irrigated onto the surgical field before skin closure and suction drain will be closed for 30 min after skin closure. | Drug: local instillation of morphine to surgical wound<br>* comparison between different drug doses effects on pain<br>* Other names: morphine sulphate;|
| Active Comparator: local instillation of morphine 10 mg<br>5 ml plain bupivacaine 0.5% and 10 mg morphine .Study drugs will be diluted by saline 0.9% to 20 ml volume and irrigated onto the surgical field before skin closure and suction drain will be closed for 30 min after skin closure. | Drug: local instillation of morphine to surgical wound<br>* comparison between different drug doses effects on pain<br>* Other names: morphine sulphate;|
| Active Comparator: local instillation of morphine 15 mg<br>5 ml plain bupivacaine 0.5% and 15 mg morphine .Study drugs will be diluted by saline 0.9% to 20 ml volume and irrigated onto the surgical field before skin closure and suction drain will be closed for 30 min after skin closure. | Drug: local instillation of morphine to surgical wound<br>* comparison between different drug doses effects on pain<br>* Other names: morphine sulphate;|
| Placebo Comparator: local instillation of local anesthetics<br>5 ml plain bupivacaine 0.5% .Study drugs will be diluted by saline 0.9% to 20 ml volume and irrigated onto the surgical field before skin closure and suction drain will be closed for 30 min after skin closure. | Drug: local instillation of morphine to surgical wound<br>* comparison between different drug doses effects on pain<br>* Other names: morphine sulphate;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| changes in acute pain intensity from the baseline | Visual analogue pain scale score at rest (VAS-R) and during movement or ipsilateral arm abduction (VAS-M), will be assessed at the same points score ranging from 0 to 10 (zero = no pain and 10 = the worst pain imaginable). | at 2,4,6,12,24,36 and 48 hour postoperatively | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postoperative adverse effects | nausea, vomiting respiratory depression, itching and sedation | 2,4,6,12,24,36 and 48 hour postoperatively. | 
| The probability of developing chronic neuropathic pain | postoperative examination in pain clinic using LANSS (Leeds Assessment of Neuropathic Symptoms and Signs) scale | after one month and after two months postoperatively | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Local morphine, Postmastectomy pain