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

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.

Study Overview

• Status: Completed
• Conditions: Chronic Pain; Acute Pain
• Intervention / Treatment: Drug: local instillation of morphine to surgical wound

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 120
• Phase: Phase 2

Contacts and Locations

Study Locations

• Egypt
  • Assiut, Egypt, 171516
    • Assiut University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: local instillation of morphine 5 mg; 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; comparison between different drug doses effects on pain; Other Names: morphine sulphate
Active Comparator: local instillation of morphine 10 mg; 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; comparison between different drug doses effects on pain; Other Names: morphine sulphate
Active Comparator: local instillation of morphine 15 mg; 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; comparison between different drug doses effects on pain; Other Names: morphine sulphate
Placebo Comparator: local instillation of local anesthetics; 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; comparison between different drug doses effects on pain; Other Names: morphine sulphate

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Assiut University
• Investigators: Principal Investigator: Shereen M Mohamed, MD, Lecturer of anesthesia, ICU and pain management- South Egypt Cancer Institute- Assuit University

Publications and helpful links

General Publications

• Mohamed SA, Abdel-Ghaffar HS, Kamal SM, Fares KM, Hamza HM. Effect of Topical Morphine on Acute and Chronic Postmastectomy Pain: What Is the Optimum Dose? Reg Anesth Pain Med. 2016 Nov/Dec;41(6):704-710. doi: 10.1097/AAP.0000000000000496.

Study record dates

Study Major Dates

• Study Start: January 1, 2015
• Primary Completion (Actual): August 1, 2015
• Study Completion (Actual): December 1, 2015

Study Registration Dates

• First Submitted: May 28, 2015
• First Submitted That Met QC Criteria: June 2, 2015
• First Posted (Estimate): June 4, 2015

Study Record Updates

• Last Update Posted (Estimate): December 30, 2015
• Last Update Submitted That Met QC Criteria: December 29, 2015
• Last Verified: December 1, 2015

More Information

Terms related to this study

• Keywords: Local morphine; Postmastectomy pain
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Chronic Pain; Acute Pain; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Morphine
• Other Study ID Numbers: 209