Levobupivacaine Prolonged Wound Infusion for Postoperative Pain Relief After Breast Surgery

The aim of the study is to evaluate efficacy and safety of long term (14 days) wound infusion with levobupivacaine in patients with breast cancer undergoing mastectomy with immediate breast reconstruction: this is a double blind, randomized, parallel group study. The study moves from the concept that nociceptive stimulus last further than 48 hours after surgical intervention: long term analgesia is necessary to provide a real benefit to the patient and provide central sensitization. Intralesional catheter is placed at the end of surgery. In the first 24 postoperative hours we provide continuous wound infusion with levobupivacaine 0,25% 5ml/h with morphine Patient Controlled Analgesia (PCA) when NRS >4. From the second postoperative day morphine PCA is removed and patients are randomized to receive levobupivacaine 0,25% or saline, released with 5 ml boluses and lock-out of 2 hours, with rescue analgesia with tramadol 37,5 mg + acetaminophen 325 mg oral fix combination (Patrol). Intralesional catheter is taken off 14 days after surgical intervention or after 36 hours of non-use.

Pain evaluation (NRS at rest and movement) and oral rescue doses consumption are performed; pain physicians also care about any catheter-related or drug-related side effect, registering number of total boluses. Patients are provided with a home diary for pain scores to be filled and brought back when surgical visit is performed. A phone interview at 1 and 3 month is performed to investigate pain chronicization.

Surgical evaluation is provided, also to establish any catheter-related infective or healing complication.

Physiatric evaluation before the intervention and 1 and 3 months is provided to ensure rehabilitation process.

A validated questionnaire (short form 36/ SF-36) must be filled by all patients, to understand differences in return to a normal quality of life and to social activities between the two groups.

Study Overview

• Status: Unknown
• Conditions: Chronic Pain; Acute Pain; Mastectomy; Wound Infusion
• Intervention / Treatment: Drug: Levobupivacaine PCIA (Patient Controlled Intrawound Analgesia); Drug: Levobupivacaine continuous infusion; Device: intrawound infusion catheter; Drug: morphine; Drug: Patrol; Drug: saline

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 4

Contacts and Locations

Study Locations

• Italy
  • Pavia, Italy, 27100
    • Recruiting
    • Department of Anesthesia - Pain Therapy Service
    • Contact: Allegri Massimo, MD; Phone Number: +390382502627; Email: massimo.allegri@unipv.it
    • Sub-Investigator: Bugada Dario, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• F; age 18 to 70
• American Society of Anesthesiologists (ASA) I e II;
• breast cancer ( DIN 2 e 3, o LIN 2 e 3 sec. Tavassoli) scheduled for nipple-sparing mastectomy, simple mastectomy, skin-sparing mastectomy, skin-reducing mastectomy c, lymphnode biopsy and axillary dissection;
• immediate sub-pectoral prosthetic reconstruction;
• signed informed consent.

Exclusion Criteria:

• preexisting pectoral, axillar, thoracic homolateral pain
• habitual opioid consumption;
• drug-alcoholics addiction ;
• ICU postoperative recovery;
• kidney failure (creatinin > 2 g/dl, creatinin <clearance 30 ml/h) and/or hepatic failure (cholinesterase < 2000 UI);
• cardiac arrhythmias o;
• Epilepsy;
• Psychiatric, cognitive disorders, mental retardation;
• Coagulopathies (INR > 2, activated partial thromboplastin time - aPTT>44 sec);
• platelet count less than 100.000/mm3;
• BMI > 30;
• Allergies to study drugs.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Levobupivacaine; Levobupivacaine Patient Controlled Infusion 5 ml 0,25%, lock out 2 hours	Drug: Levobupivacaine PCIA (Patient Controlled Intrawound Analgesia); patient controlled infusion from the 2nd day after surgery; Drug: Levobupivacaine continuous infusion; Continuous infusion Levobupivacaine 0,25% 5ml/h for 24 hs in all patients; Device: intrawound infusion catheter; placed by surgeon at the end surgery in all patients; Drug: morphine; PCA with morphine: 0,5 mg/ml bolus 1 mg lock-out 5 min max 20 mg in 4 hs - for the first 24 hs as rescue analgesia; Drug: Patrol; tramadol-paracetamol 37,5/325 mg oral fix combination-rescue analgesia from 2nd day (after morphine PCA removal)
Placebo Comparator: Saline; patient controlled infusion 5 ml bolus, lock out 2 hours	Drug: Levobupivacaine continuous infusion; Continuous infusion Levobupivacaine 0,25% 5ml/h for 24 hs in all patients; Device: intrawound infusion catheter; placed by surgeon at the end surgery in all patients; Drug: morphine; PCA with morphine: 0,5 mg/ml bolus 1 mg lock-out 5 min max 20 mg in 4 hs - for the first 24 hs as rescue analgesia; Drug: Patrol; tramadol-paracetamol 37,5/325 mg oral fix combination-rescue analgesia from 2nd day (after morphine PCA removal); Drug: saline; patient controlled infusion from the 2nd day after surgery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
reduction in oral Tramadol-Paracetamol combination consumption from 2nd to 14th day after mastectomy	from day 2 to 14

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
reduction in pain values at rest and movement in treatment group		14 days
incidence of drug-related side effects	local anesthetic toxicity, opioid side effects	up to 14 days
incidence of catheter-related surgical complications	infections, healing retardation	up to 1 month
earlier upper limb rehabilitation	physiatric evaluations	up to 1 month
earlier return to social activities and good quality of life	validated SF-36 questionnaire	up to 1 month
different chronic pain incidence	phone interview at 1 and 3 months	up to 3 months

Collaborators and Investigators

• Sponsor: IRCCS Policlinico S. Matteo
• Investigators: Principal Investigator: Allegri Massimo, MD, Pain Therapy Service IRCCS Policlinico S Matteo Pavia Italy

Study record dates

Study Major Dates

• Study Start: January 1, 2013
• Primary Completion (Anticipated): September 1, 2017
• Study Completion (Anticipated): December 1, 2017

Study Registration Dates

• First Submitted: January 11, 2014
• First Submitted That Met QC Criteria: January 11, 2014
• First Posted (Estimate): January 14, 2014

Study Record Updates

• Last Update Posted (Actual): March 3, 2017
• Last Update Submitted That Met QC Criteria: March 1, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• 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; Anesthetics; Analgesics, Opioid; Narcotics; Anesthetics, Local; Morphine; Levobupivacaine
• Other Study ID Numbers: 2011-006331-35