Liposomal Bupivacaine in Implant Based Breast Reconstruction

Study Overview
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Brief Summary
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Objectives: To evaluate the effect of liposomal bupivacaine on postoperative pain levels. To evaluate the effect of liposomal bupivacaine on postoperative opioid consumption and opioid related adverse events. To evaluate the effect of liposomal bupivacaine on length of hospital stay. To evaluate the effect of liposomal bupivacaine on patient satisfaction with postoperative pain control. To evaluate the effect of liposomal bupivacaine on overall patient satisfaction.

Detailed Description
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Objectives: To evaluate the effect of liposomal bupivacaine on postoperative pain levels. To evaluate the effect of liposomal bupivacaine on postoperative opioid consumption and opioid related adverse events. To evaluate the effect of liposomal bupivacaine on length of hospital stay. To evaluate the effect of liposomal bupivacaine on patient satisfaction with postoperative pain control. To evaluate the effect of liposomal bupivacaine on overall patient satisfaction. The objective of this project is to evaluate the role of liposomal bupivacaine in postoperative pain control following tissue expander and implant based breast reconstruction. This unique formulation of bupivacaine lends this drug a longer duration of action and reduced plasma bupivacaine concentrations compared to plain bupivacaine. This agent has been demonstrated to be safe, well tolerated, and effective in a number of different clinical applications. However, its role has yet to be evaluated in the context of breast reconstruction. Thus, the authors propose the first, randomized, controlled clinical trial of liposomal bupivacaine for postoperative pain management following tissue expander and implant based breast reconstruction. Patients will be stratified into two study groups. Patients in the Group 1 (Bupivacaine) will be treated intraoperatively with injections of 0.5% bupivacaine and epinephrine 1:200,000, with 50 mg delivered to perform a field block of each pocket. This is the current standard of care. Patients in the Group 2 (Liposomal Bupivacaine) will be treated intraoperatively with injections of 1.33% liposomal bupivacaine, with 133 mg delivered to perform a field block of each breast pocket. This is the experimental intervention. Postoperatively, the investigators will assess pain levels, opioid consumption, opioid related adverse events, length of stay, and satisfaction. The findings from this study will allow the authors to better elucidate the role of liposomal bupivacaine in expander/implant based breast reconstruction. In doing so, they may allow the authors to identify the ideal pain regimen for these patients. This holds important implications, with the potential to reduce postoperative pain, opioid consumption, opioid related adverse events, length of stay, and patient satisfaction.

Official Title
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Liposomal Bupivacaine in Implant Based Breast Reconstruction

Conditions
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Breast Cancer, Postoperative Pain

Intervention / Treatment
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* Drug: Liposomal bupivacaine
* Drug: Bupivacaine with epinephrine
* Drug: Morphine sulfate
* Drug: Hydrocodone/acetaminophen
* Drug: Diazepam


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women undergoing immediate unilateral or bilateral tissue-expander breast reconstruction following skin-sparing or nipple-sparing mastectomy Exclusion Criteria: Women who are unable to give informed consent to participate in this study Women with a documented history of hypersensitivity reactions to local-anesthetic agents Women with a diagnosis of chronic pain disorders such as fibromyalgia, chronic migraine headaches, or psychiatric disorders other than depression or anxiety Women who are currently pregnant Women undergoing tissue expander based breast reconstruction with a muscle flap in combination with a tissue expander Women with impaired hepatic function

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Bupivacaine with epinephrine injections<br>Patients in the control arm of the study will be treated intra-operatively with standard of care, 0.5% bupivacaine and epinephrine injection (1:200,000), with 50 mg delivered into each breast pocket to perform a field block of the breast pocket (see below). Postoperatively, these patients will be treated with standard postoperative pain control, including narcotics as needed, such as morphine sulfate and hydrocodone/acetaminophen, and muscle relaxants, such as diazepam. | Drug: Bupivacaine with epinephrine<br>* Bupivacaine, like other local anesthetics reduces the flow of sodium in and out of nerves. This decreases the initiation and transfer of nerve signals in the area in which the drug is injected. This leads first to a loss of sensation of pain, temperature, touch, and deep pressure. This drug is the current standard of care for local, postoperative local anesthesia following breast reconstruction. Epinephrine, a vasoconstrictor, is included in bupivacaine formulations to improve the duration of local anesthesia.<br>* Other names: Sensorcaine;Drug: Morphine sulfate<br>* Morphine is an opiate pain medication administered intravenously for severe, breakthrough post-operative pain.<br>* Other names: Roxanol;Drug: Hydrocodone/acetaminophen<br>* Hydrocodone acetaminophen is a combination of an opiate pain medication (hydrocodone) and a non-steroidal anti-inflammatory drug (acetaminophen) given orally to patients for moderate post-operative pain.<br>* Other names: Norco;Drug: Diazepam<br>* Diazepam is a benzodiazepine medication that is administered orally to treat muscle spasms in patient's following expander and implant-based breast reconstruction.<br>* Other names: Valium;|
| Experimental: Liposomal bupivacaine<br>Patients in the experimental arm of the study will be treated intra-operatively with 1.33% liposomal bupivacaine, with 133 mg delivered to perform a field block of each breast pocket. Postoperatively, these patients will be treated with standard postoperative pain control, including narcotics as needed, such as morphine sulfate and hydrocodone/acetaminophen, and muscle relaxants, such as diazepam. | Drug: Liposomal bupivacaine<br>* Liposomal Bupivacaine is an aqueous suspension of multivesicular liposomes containing bupivacaine. After injection into soft tissue, bupivacaine is slowly released from the multivesicular liposomes, extending this drug's duration of action.<br>* Other names: Exparel;Drug: Morphine sulfate<br>* Morphine is an opiate pain medication administered intravenously for severe, breakthrough post-operative pain.<br>* Other names: Roxanol;Drug: Hydrocodone/acetaminophen<br>* Hydrocodone acetaminophen is a combination of an opiate pain medication (hydrocodone) and a non-steroidal anti-inflammatory drug (acetaminophen) given orally to patients for moderate post-operative pain.<br>* Other names: Norco;Drug: Diazepam<br>* Diazepam is a benzodiazepine medication that is administered orally to treat muscle spasms in patient's following expander and implant-based breast reconstruction.<br>* Other names: Valium;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Effect of Liposomal Bupivacaine on Average Postoperative Pain Levels on Postoperative Day 1. | Postoperative pain levels were determined with a numeric rating scale (NRS), rating pain from 0 - 10, where 0 = no pain, 10 = worst possible pain. Higher scores indicate a worse outcome. Pain levels were determined during routine vital signs every 4 hours post-operatively. | Average Pain Scores 24 hours Post-Operatively | 
| The Effect of Liposomal Bupivacaine on Antiemetic Consumption | The effect of liposomal bupivacaine on antiemetic consumption was assessed in mg of ondansetron consumed over first 24 hours post-operatively. | 24 hours | 
| The Effect of Liposomal Bupivacaine on Postoperative Opioid Consumption | Postoperative opioid consumption will be determined in each group. Opioid consumption post-operatively will be determined for patients in each group in standardized units of morphine milligram dosing equivalents per hour. | 24 hours | 
| The Effect of Liposomal Bupivacaine on Postoperative Diazepam Consumption | Benzodiazepine consumption, in mg of diazepam, was recorded for all patients and compared over the first 24 hours post-operatively. | 24 hours | 
| The Effect of Liposomal Bupivacaine on Length of Hospital Stay | Length of hospital stay will be determined for patients in each group, in total hours. | 24-60 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Postoperative analgesia, Breast reconstruction, Bupivacaine, Liposomal bupivacaine