Breast Cancer, Postoperative Pain
Conditions
Keywords
Breast reconstruction, Bupivacaine, Liposomal bupivacaine, Postoperative analgesia
Brief summary
Objectives: 1. To evaluate the effect of liposomal bupivacaine on postoperative pain levels. 2. To evaluate the effect of liposomal bupivacaine on postoperative opioid consumption and opioid related adverse events. 3. To evaluate the effect of liposomal bupivacaine on length of hospital stay. 4. To evaluate the effect of liposomal bupivacaine on patient satisfaction with postoperative pain control. 5. To evaluate the effect of liposomal bupivacaine on overall patient satisfaction.
Detailed description
Objectives: 1. To evaluate the effect of liposomal bupivacaine on postoperative pain levels. 2. To evaluate the effect of liposomal bupivacaine on postoperative opioid consumption and opioid related adverse events. 3. To evaluate the effect of liposomal bupivacaine on length of hospital stay. 4. To evaluate the effect of liposomal bupivacaine on patient satisfaction with postoperative pain control. 5. 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.
Interventions
DRUGLiposomal bupivacaine
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.
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.
DRUGMorphine sulfate
Morphine is an opiate pain medication administered intravenously for severe, breakthrough post-operative pain.
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.
DRUGDiazepam
Diazepam is a benzodiazepine medication that is administered orally to treat muscle spasms in patient's following expander and implant-based breast reconstruction.
Sponsors
Loma Linda University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 99 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Effect of Liposomal Bupivacaine on Average Postoperative Pain Levels on Postoperative Day 1. | Average Pain Scores 24 hours Post-Operatively | 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. |
| The Effect of Liposomal Bupivacaine on Antiemetic Consumption | 24 hours | The effect of liposomal bupivacaine on antiemetic consumption was assessed in mg of ondansetron consumed over first 24 hours post-operatively. |
| The Effect of Liposomal Bupivacaine on Postoperative Opioid Consumption | 24 hours | 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. |
| The Effect of Liposomal Bupivacaine on Postoperative Diazepam Consumption | 24 hours | Benzodiazepine consumption, in mg of diazepam, was recorded for all patients and compared over the first 24 hours post-operatively. |
| The Effect of Liposomal Bupivacaine on Length of Hospital Stay | 24-60 hours | Length of hospital stay will be determined for patients in each group, in total hours. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Bupivacaine With Epinephrine Injections Patients in the control arm will be treated intra-operatively with standard of care, 0.25% bupivacaine and epinephrine injection (1:200,000), with 50 mg delivered to each breast pocket. Postoperatively, pain will be treated with narcotics as needed, such as morphine sulfate and hydrocodone/acetaminophen, and muscle relaxants, such as diazepam.
Bupivacaine with epinephrine: Bupivacaine is a local anesthetic. This drug is the current standard of care for local anesthesia following breast reconstruction.
Morphine sulfate: Morphine is an opiate pain medication administered intravenously for severe post-operative pain.
Hydrocodone/acetaminophen: Hydrocodone acetaminophen is a combination of an opiate (hydrocodone) and a non-steroidal anti-inflammatory drug (acetaminophen) given orally to patients for moderate post-operative pain.
Diazepam: Diazepam is a benzodiazepine medication that is administered orally to treat muscle spasms. | 12 |
| Liposomal Bupivacaine Patients in the experimental arm of the study will be treated intra-operatively with 1.33% liposomal bupivacaine, with 133 mg delivered to each breast pocket. Postoperatively, pain will be treated with narcotics as needed, such as morphine sulfate and hydrocodone/acetaminophen, and muscle relaxants, such as diazepam.
Liposomal bupivacaine: Liposomal Bupivacaine is a suspension of multivesicular liposomes containing bupivacaine. After injection, bupivacaine is slowly released from the liposomes, extending this drug's duration of action.
Morphine sulfate: Morphine is an opiate pain medication administered intravenously for severe post-operative pain.
Hydrocodone/acetaminophen: Hydrocodone acetaminophen is a combination of an opiate (hydrocodone) and a non-steroidal anti-inflammatory drug (acetaminophen) given orally to patients for moderate post-operative pain.
Diazepam: Diazepam is a benzodiazepine medication that is administered orally to treat muscle spasms. | 12 |
| Total | 24 |
Baseline characteristics
| Characteristic | Liposomal Bupivacaine | Bupivacaine With Epinephrine Injections | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 3 Participants | 5 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants | 9 Participants | 19 Participants |
| Age, Continuous | 48.7 years STANDARD_DEVIATION 11.1 | 56.2 years STANDARD_DEVIATION 12.6 | 52.4 years STANDARD_DEVIATION 12.9 |
| Region of Enrollment United States | 12 Participants | 12 Participants | 24 Participants |
| Sex: Female, Male Female | 12 Participants | 12 Participants | 24 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 12 | 0 / 12 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 |
Outcome results
Primary
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.
Time frame: 24 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bupivacaine With Epinephrine Injections | The Effect of Liposomal Bupivacaine on Antiemetic Consumption | 7.33 mg of ondansetron | Standard Deviation 6.57 |
| Liposomal Bupivacaine | The Effect of Liposomal Bupivacaine on Antiemetic Consumption | 5.75 mg of ondansetron | Standard Deviation 4.94 |
Primary
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.
Time frame: Average Pain Scores 24 hours Post-Operatively
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bupivacaine With Epinephrine Injections | The Effect of Liposomal Bupivacaine on Average Postoperative Pain Levels on Postoperative Day 1. | 3.66 score on a scale | Standard Deviation 0.33 |
| Liposomal Bupivacaine | The Effect of Liposomal Bupivacaine on Average Postoperative Pain Levels on Postoperative Day 1. | 3.68 score on a scale | Standard Deviation 1.35 |
Primary
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.
Time frame: 24-60 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bupivacaine With Epinephrine Injections | The Effect of Liposomal Bupivacaine on Length of Hospital Stay | 46.7 hrs | Standard Deviation 21.1 |
| Liposomal Bupivacaine | The Effect of Liposomal Bupivacaine on Length of Hospital Stay | 29.8 hrs | Standard Deviation 15.3 |
Primary
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.
Time frame: 24 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bupivacaine With Epinephrine Injections | The Effect of Liposomal Bupivacaine on Postoperative Diazepam Consumption | 0.35 mg of diazepam/hr | Standard Deviation 0.19 |
| Liposomal Bupivacaine | The Effect of Liposomal Bupivacaine on Postoperative Diazepam Consumption | 0.18 mg of diazepam/hr | Standard Deviation 0.21 |
Primary
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.
Time frame: 24 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bupivacaine With Epinephrine Injections | The Effect of Liposomal Bupivacaine on Postoperative Opioid Consumption | 1.31 Morphine equivalent dosage per hour | Standard Deviation 0.72 |
| Liposomal Bupivacaine | The Effect of Liposomal Bupivacaine on Postoperative Opioid Consumption | .76 Morphine equivalent dosage per hour | Standard Deviation 0.55 |